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Sample records for carcinoma pathogenic role

  1. The Role of Pathogenic Autoantibodies in Autoimmunity

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    Merrill J. Rowley

    2015-11-01

    Full Text Available The serological presence of autoantibodies is diagnostic of autoimmunity, and these autoantibodies may be present for many years before the presentation of autoimmune disease (AID. Although a pathogenic role has been demonstrated for various autoantibodies reactive with cell surface and extracellular autoantigens, studies using monoclonal antibodies (mAb show not all antibodies in the polyclonal response are pathogenic. Differences depend on Fab-mediated diversity in epitope specificity, Fc-mediated effects based on immunoglobulin (Ig class and subclass, activation of complement, and the milieu in which the reaction occurs. These autoantibodies often occur in organ-specific AID and this review illustrates their pathogenic and highly specific effects. The role of autoantibodies associated with intracellular antigens is less clear. In vitro they may inhibit or adversely affect well-defined intracellular biochemical pathways, yet, in vivo they are separated from their autoantigens by multiple cellular barriers. Recent evidence that Ig can traverse cell membranes, interact with intracellular proteins, and induce apoptosis has provided new evidence for a pathogenic role for such autoantibodies. An understanding of how autoantibodies behave in the polyclonal response and their role in pathogenesis of AID may help identify populations of culprit B-cells and selection of treatments that suppress or eliminate them.

  2. Prognostic impact of BRCA1 pathogenic and BRCA1/BRCA2 unclassified variant mutations in patients with ovarian carcinoma

    NARCIS (Netherlands)

    Majdak, EJ; Debniak, J; Milczek, T; Cornelisse, CJ; Devilee, P; Emerich, J; Jassem, J; De Bock, GH

    2005-01-01

    BACKGROUND. The clinical relevance of BRCA1/2 alterations in ovarian carcinoma patients is debatable. Our aim was to determine factors influencing the risk of recurrence and death in ovarian carcinoma patients with BRCA pathogenic and unclassified variant mutations. METHODS. A consecutive series of

  3. Diagnostic role of barium enema in carcinoma rectum

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    Asghar, M.

    2003-01-01

    Objective: The main aim of this barium enema study was to evaluate its role in patients suspected to have rectal pathologies with complaints of change in bowel habit, anorexia/weight loss, bleeding per rectum and acute/sub-acute colonic obstruction. Results: barium enema study as screening test for colo-rectal carcinoma was undertaken. Contrast outlined the colonic growth in 35 cases, out of which the cases of carcinoma colon were 24 including 13 patients suffering from carcinoma rectum. The percentage of carcinoma colon to total colonic growth was 68% while, carcinoma rectum to total carcinoma colon was 54%. Conclusion: On the basis of these investigations, it is concluded that patient's compliance is important factor in the early detection of colonic neoplasia. Though results of colonoscopy are more reliable but in practice, barium enema (double contrast) is performed initially to outline the lesion and then colonoscopy for biopsy purpose. (author)

  4. The role of social cognition in parasite and pathogen avoidance.

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    Kavaliers, Martin; Choleris, Elena

    2018-07-19

    The acquisition and use of social information are integral to social behaviour and parasite/pathogen avoidance. This involves social cognition which encompasses mechanisms for acquiring, processing, retaining and acting on social information. Social cognition entails the acquisition of social information about others (i.e. social recognition) and from others (i.e. social learning). Social cognition involves assessing other individuals and their infection status and the pathogen and parasite threat they pose and deciding about when and how to interact with them. Social cognition provides a framework for examining pathogen and parasite avoidance behaviours and their associated neurobiological mechanisms. Here, we briefly consider the relationships between social cognition and olfactory-mediated pathogen and parasite avoidance behaviours. We briefly discuss aspects of (i) social recognition of actual and potentially infected individuals and the impact of parasite/pathogen threat on mate and social partner choice; (ii) the roles of 'out-groups' (strangers, unfamiliar individuals) and 'in-groups' (familiar individuals) in the expression of parasite/pathogen avoidance behaviours; (iii) individual and social learning, i.e. the utilization of the pathogen recognition and avoidance responses of others; and (iv) the neurobiological mechanisms, in particular the roles of the nonapeptide, oxytocin and steroid hormones (oestrogens) associated with social cognition and parasite/pathogen avoidance.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'. © 2018 The Author(s).

  5. Insight of Genus Corynebacterium: Ascertaining the Role of Pathogenic and Non-pathogenic Species.

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    Oliveira, Alberto; Oliveira, Leticia C; Aburjaile, Flavia; Benevides, Leandro; Tiwari, Sandeep; Jamal, Syed B; Silva, Arthur; Figueiredo, Henrique C P; Ghosh, Preetam; Portela, Ricardo W; De Carvalho Azevedo, Vasco A; Wattam, Alice R

    2017-01-01

    This review gathers recent information about genomic and transcriptomic studies in the Corynebacterium genus, exploring, for example, prediction of pathogenicity islands and stress response in different pathogenic and non-pathogenic species. In addition, is described several phylogeny studies to Corynebacterium , exploring since the identification of species until biological speciation in one species belonging to the genus Corynebacterium . Important concepts associated with virulence highlighting the role of Pld protein and Tox gene. The adhesion, characteristic of virulence factor, was described using the sortase mechanism that is associated to anchorage to the cell wall. In addition, survival inside the host cell and some diseases, were too addressed for pathogenic corynebacteria, while important biochemical pathways and biotechnological applications retain the focus of this review for non-pathogenic corynebacteria. Concluding, this review broadly explores characteristics in genus Corynebacterium showing to have strong relevance inside the medical, veterinary, and biotechnology field.

  6. Role of chemotherapy in nasopharyngeal carcinoma

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    Fabiola Paiar

    2012-06-01

    Full Text Available Nasopharyngeal carcinoma (NPC is a unique malignant head and neck cancer with clinical, demographic, and geographic features distinct from other head and neck epithelial malignancies. Non-keratinizing, poorly differentiated, and undifferentiated WHO types 2 and 3 is the most common subtypes of NPC. NPC is also characterized by its relatively high sensitivity to radiation, so that in the last decades radiotherapy (RT has been the cornerstone of treatment. However, in the majority of cases NPC is discovered at locally advanced stage. The results are disappointing when RT alone is offered. The 5-year survival rates have been reported to be about 34-52%. The poor prognosis for advanced NPC led to increasing interests in exploring the use of chemotherapy (CT. NPC has been considered to be not only radiosensitive but also chemo-sensitive and has shown high response rate to various chemotherapeutic agents. Certainly, the treatment strategies for NPC will continue to change and evolve as a better understanding is gained of the molecular and immune mechanisms that drive this disease. We reviewed the current literature focusing on the role of CT and new-targeted agents.

  7. The role of thionins in rice defence against root pathogens.

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    Ji, Hongli; Gheysen, Godelieve; Ullah, Chhana; Verbeek, Ruben; Shang, Chenjing; De Vleesschauwer, David; Höfte, Monica; Kyndt, Tina

    2015-10-01

    Thionins are antimicrobial peptides that are involved in plant defence. Here, we present an in-depth analysis of the role of rice thionin genes in defence responses against two root pathogens: the root-knot nematode Meloidogyne graminicola and the oomycete Pythium graminicola. The expression of rice thionin genes was observed to be differentially regulated by defence-related hormones, whereas all analysed genes were consistently down-regulated in M. graminicola-induced galls, at least until 7 days post-inoculation (dpi). Transgenic lines of Oryza sativa cv. Nipponbare overproducing OsTHI7 revealed decreased susceptibility to M. graminicola infection and P. graminicola colonization. Taken together, these results demonstrate the role of rice thionin genes in defence against two of the most damaging root pathogens attacking rice. © 2015 BSPP AND JOHN WILEY & SONS LTD.

  8. The Multifaceted Role of Podoplanin Expression in Hepatocellular Carcinoma

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    Cioca, Andreea; Ceausu, Amalia R.; Marin, Irina; Raica, Marius; Cimpean, Anca Maria

    2017-01-01

    The role of podoplanin in hepatocellular carcinoma (HCC) is not clear yet. The aim of our study was to evaluate the expression of podoplanin in HCC and to determine its role in hepatocarcinogenesis. We performed immunohistochemistry with monoclonal D2-40 antibody, on paraffin-embedded tissue sections of 72 patients diagnosed with HCC. Lymphatic vessels density (LVD) was increased in patients who had vascular invasion at the time of diagnosis (P=0.018) and in those with associated cirrhosis (P...

  9. The role of EMMPRIN expression in ovarian epithelial carcinomas.

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    Zhao, Yang; Chen, Shuo; Gou, Wen-feng; Niu, Zhe-feng; Zhao, Shuang; Xiao, Li-jun; Takano, Yasuo; Zheng, Hua-chuan

    2013-09-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) was reported to involve in the invasion and metastasis of malignancies by regulating the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in stromal and cancer cells. The study aimed to clarify the role of EMMPRIN expression in tumorigenesis and progression of ovarian epithelial carcinomas. EMMPRIN siRNA were transfected into ovarian carcinoma cells with the phenotypes and their related molecules examined. EMMPRIN expression was determined in ovarian normal tissue, benign and borderline tumors, and epithelial carcinomas by real-time PCR, western blot, and immunohistochemistry. EMMPRIN siRNA treatment resulted in a lower growth, G 1 arrest, apoptotic induction, decreased migration, and invasion. The transfectants showed reduced expression of Wnt5a, Akt, p70s6k, Bcl-xL, survivin, VEGF, and MMP-9 than mock and control cells at both mRNA and protein levels. According to real-time PCR and western blot, EMMPRIN mRNA or protein level was higher in ovarian borderline tumor and carcinoma than normal ovary and benign tumors (PEMMPRIN expression was positively correlated with FIGO staging, dedifferentiation, Ki-67 expression, the lower cumulative and relapse-free survival rate (PEMMPRIN protein and mRNA might be involved in the pathogenesis, differentiation, and progression of ovarian carcinomas, possibly by modulating cellular events, such as proliferation, cell cycle, apoptosis, migration, and invasion.

  10. Role of gut pathogens in development of irritable bowel syndrome

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    Madhusudan Grover

    2014-01-01

    Full Text Available Acute infectious gastroenteritis is one of the most commonly identifiable risk factors for the development of irritable bowel syndrome (IBS. A number of bacterial, viral and parasitic pathogens have been found to be associated with the development of IBS and other functional gastrointestinal (GI disorders. Epidemiological studies have identified demographic and acute enteritis-related risk factors for the development of post-infectious-IBS (PI-IBS. Immune dysregulation, alterations in barrier function, serotonergic and mast cell activation have been identified as potential pathophysiological mechanisms. Additionally, variations in host genes involved in barrier function, antigen presentation and cytokine response have been associated with PI-IBS development. However, it is unknown whether specific pathogens have unique effects on long-term alterations in gut physiology or different pathogens converge to cause common alterations resulting in similar phenotype. The role of microbial virulence and pathogenicity factors in development of PI-IBS is also largely unknown. Additionally, alterations in host gut sensation, motility, secretion, and barrier function in PI-IBS need to be elucidated. Finally, both GI infections and antibiotics used to treat these infections can cause long-term alterations in host commensal microbiota. It is plausible that alteration in the commensal microbiome persists in a subset of patients predisposing them to develop PI-IBS.

  11. The role of mast cells in oral squamous cell carcinoma

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    Gudiseva, Swetha; Chitturi, Raviteja; Anumula, Vamsikrishna; Poosarla, Chandrashekar; Baddam, Venkat Ramana Reddy

    2017-01-01

    The mast cells are initial effective lineage in both humoral and adaptive immunity. They are ubiquitous in skin, mucosa, and in function. They contain biologically essential and dynamic mediators in healthy and harmful conditions of tissue. Mast cell malfunctioning could be attributed to various chronic allergic diseases. Considerately, emerging evidence of mast cell involvement in various cancers shows them to have both positive and negative roles in tumour growth. It mostly indulges in tumour progression and metastasis via angiogenesis, extracellular matrix degradation, and mitogenic activity in the tumour microenvironment. The current paper reviewed research papers on mast cells in oral squamous cell carcinoma through the PubMed database from 1980 to the present date. The present paper is an attempt to summarise the research reports on the role of mast cells in oral squamous cell carcinoma. Further to this note, this paper also outlines the role of mast cells in normal physiological processes and tumour biology. PMID:28435394

  12. The role of mast cells in oral squamous cell carcinoma

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    Swetha Gudiseva

    2017-03-01

    Full Text Available The mast cells are initial effective lineage in both humoral and adaptive immunity. They are ubiquitous in skin, mucosa, and in function. They contain biologically essential and dynamic mediators in healthy and harmful conditions of tissue. Mast cell malfunctioning could be attributed to various chronic allergic diseases. Considerately, emerging evidence of mast cell involvement in various cancers shows them to have both positive and negative roles in tumour growth. It mostly indulges in tumour progression and metastasis via angiogenesis, extracellular matrix degradation, and mitogenic activity in the tumour microenvironment. The current paper reviewed research papers on mast cells in oral squamous cell carcinoma through the PubMed database from 1980 to the present date. The present paper is an attempt to summarise the research reports on the role of mast cells in oral squamous cell carcinoma. Further to this note, this paper also outlines the role of mast cells in normal physiological processes and tumour biology.

  13. Trichomonas vaginalis: pathogenicity and potential role in human reproductive failure.

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    Mielczarek, Ewelina; Blaszkowska, Joanna

    2016-08-01

    Trichomonas vaginalis, which colonizes the genitourinary tract of men and women, is a sexually transmitted parasite causing symptomatic or asymptomatic trichomoniasis. The host-parasite relationship is very complex, and clinical symptoms cannot likely be attributed to a single pathogenic effect. Among the many factors responsible for interactions between T. vaginalis and host tissues, contact-dependent and contact-independent mechanisms are important in pathogenicity, as is the immune response. This review focuses on the potential virulence properties of T. vaginalis and its role in female and male infertility. It highlights the association between T. vaginalis infection and serious adverse health consequences experienced by women, including infertility, preterm birth and low-birth-weight infants. Long-term clinical observations and results of in vitro experimental studies indicate that in men, trichomoniasis has been also associated with infertility through inflammatory damage to the genitourinary tract or interference with sperm function. These results contribute significantly to improving our knowledge of the role of parasitic virulence factors in the development of infection and its role in human infertility.

  14. Protozoa lectins and their role in host-pathogen interactions.

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    Singh, Ram Sarup; Walia, Amandeep Kaur; Kanwar, Jagat Rakesh

    2016-01-01

    Lectins are proteins/glycoproteins of non-immune origin that agglutinate red blood cells, lymphocytes, fibroblasts, etc., and bind reversibly to carbohydrates present on the apposing cells. They have at least two carbohydrate binding sites and their binding can be inhibited by one or more carbohydrates. Owing to carbohydrate binding specificity of lectins, they mediate cell-cell interactions and play role in protozoan adhesion and host cell cytotoxicity, thus are central to the pathogenic property of the parasite. Several parasitic protozoa possess lectins which mediate parasite adherence to host cells based on their carbohydrate specificities. These interactions could be exploited for development of novel therapeutics, targeting the adherence and thus helpful in eradicating wide spread of protozoan diseases. The current review highlights the present state knowledge with regard to protozoal lectins with an emphasis on their haemagglutination activity, carbohydrate specificity, characteristics and also their role in pathogenesis notably as adhesion molecules, thereby aiding the pathogen in disease establishment. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. The Criteria to Confirm the Role of Epstein-Barr Virus in Nasopharyngeal Carcinoma Initiation

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    Ai-Di Gu

    2012-10-01

    Full Text Available Epstein-Barr virus (EBV is associated with nasopharyngeal carcinoma (NPC, but it remains obscure whether EBV is a viral cause of, or only an accompaniment of, NPC. We will discuss the accumulated evidence pointing to the relationship between EBV infection and NPC initiation from epidemiologic, pathogenic, molecular oncogenic, and experimental animal studies. We believe that convincing evidence from these perspectives must be provided before we can ascertain the causal role of EBV infection in NPC. Specifically, (1 epidemiological studies should reveal EBV infection as a risk factor; (2 the introduction of EBV into an animal model should produce NPC; (3 in the animal model NPC, the main molecular event(s or the involved signaling pathway(s should be identical to that in human NPC; and (4 finally and most importantly, prevention of EBV infection or clearance of EBV from infected individuals must be able to reduce the incidence rate of NPC.

  16. Role of cytologic grading in prognostication of invasive breast carcinoma

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    Khan Nazoora

    2009-01-01

    Full Text Available Background: Evaluation of cytologic features is indispensable in the preoperative diagnosis and grading of infiltrating ductal breast carcinoma (CA in fine-needle aspiration cytology (FNAC material and this method can also provide additional information regarding intrinsic features of the tumor as well as its prognosis. Aim: This study has been done to evaluate comparatively the cytologic and histomorphologic grading of infiltrating ductal carcinoma of breast with specific reference to lymph node metastasis and its role in prognostication. Materials and Methods: Forty three patients who underwent FNAC and mastectomy for infiltrating ductal carcinoma were cytologically and histologically graded (employing Robinson′s cytologic grading system and Elston′s modification of Bloom-Richardson system, respectively. Statistical analysis was done employing ′z′ test and c2 test to compare the two grading system and to examine the degree of correlation between the cytologic and histologic grades. Multiple regression analysis was done to assess the significance of every cytologic and histologic parameter. All 43 cases, graded cyto-histologically were also evaluated for presence or absence of metastasis to the regional lymph nodes employing c2 test. Results: With histologic grade taken as the standard, cytology was found to be fairly comparable, for grading breast carcinoma (overall sensitivity 89.1%, specificity 100%. Further comparison of the two grading systems by Z-test showed that difference between the cytologic and histologic grading was insignificant in all the three grade (p > 0.05. Of the six parameters studied, cell dissociation, nucleoli and chromatin pattern were the most influential features (p < 0.001. The statistically significant difference (p < 0.001 was found in incidences of axillary lymph node metastatic rate in three cytologic grades (15.4% in grade I vs. 83.3% in grade III as well. Conclusions: Apart from being simple and

  17. The non-canonical roles of clathrin and actin in pathogen internalization, egress and spread.

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    Humphries, Ashley C; Way, Michael

    2013-08-01

    The role of clathrin in pathogen entry has received much attention and has highlighted the adaptability of clathrin during internalization. Recent studies have now uncovered additional roles for clathrin and have put the spotlight on its role in pathogen spread. Here, we discuss the manipulation of clathrin by pathogens, with specific attention to the processes that occur at the plasma membrane. In the majority of cases, both clathrin and the actin cytoskeleton are hijacked, so we also examine the interplay between these two systems and their role during pathogen internalization, egress and spread.

  18. Role of FNA cytology in the management of carcinoma breast

    International Nuclear Information System (INIS)

    Tariq, G.R.; Haleem, A.; Zaidi, A.H.; Afzal, M.; Abbasi, S.

    2005-01-01

    Objective: To evaluate the utility and role of fine needle aspiration cytology (FNAC) in essential surgical management of carcinoma breast. Patients and Methods: The study included one hundred cases of carcinoma of breast-97 females and 3 males, confirmed on histopathological examination and surgically treated at PNS Shifa, CMH Pano Aqil and PNS Rahat. FNA cytology was the primary tool of investigation in all. The benefit of the procedure was evaluated considering the ease of the procedure, cost, safety, reliability as screening procedure and its effect on sparing the patients from excision or incision biopsy and thus additional anesthesia. Results: Sensitivity of the procedure was 78%, specificity 100%, predictive value 100% and overall diagnostic accuracy 72%. Out of 78 cases, diagnosed as positive for malignancy on FNAC and later confirmed by histopathological examination, 58 underwent frozen section examination followed by definitive surgery (modified radical mastectomy). Remaining 20 cases underwent additional core biopsy. Out of these, 12 cases underwent definitive surgery without frozen section and 8 patients underwent frozen section examination followed by definitive surgery. A single case required general anesthesia (GA) while the patients undergoing core biopsy required a local anesthesia (LA) as well. Cases remaining undiagnosed by FNA-cytology (22 cases) required either an excision biopsy (17 cases) or incision biopsy (5 cases) under GA followed by definitive surgery, thus requiring general anesthesia twice during the management. Conclusion: FNA-cytology can positively affect the surgical management of carcinoma breast. It can be utilized to select the patients for frozen selection examination and can thus spare the patients from additional procedure of excision or incision biopsy under separate anesthesia. It may be adopted as a routine procedure in surgical outpatient. (author)

  19. Characterization and isolation of an extracellular serine protease from the tomato pathogen Colletotrichum coccodes, and it's role in pathogenicity

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    Redman, Regina S.; Rodriguez, Rusty J.

    2002-01-01

    Extracellular enzymes play an important role in the pathogenicity and virulence of phytopathogenic fungi. Several isolates of Colletotrichum coccodes causal agent of anthracnose on tomato, were screened to determine the relationship between protease activity and virulence. A direct relationship was observed between extracellular protease activity and the induction of disease symptoms of fruit and mortality in plants. Isolate Cc155 exhibited the highest protease activity after five days of growth in protease induction medium and produced an extracellular serine protease (sp78) that was 78 kDa, auto-degradative, glucose repressible, and non-glycosylated. To determine the role of sp78 in pathogenicity, a UV-induced extracellular protease deficient mutant (np155) was generated from the wildtype isolate Cc155. Np155 maintained growth rates comparable to Cc155 and produced wildtype levels of extracellular cellulase but did not produce extracellular protease. Unlike Cc155, np155 caused no disease symptoms on tomato fruit and 0% mortality on tomato seedlings. These results suggest that extracellular protease activity is required for pathogenicity and virulence of C. coccodes and that the elimination of protease activity transforms a virulent pathogen to a non-pathogenic endophyte.

  20. The multifaceted role of podoplanin expression in hepatocellular carcinoma

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    Andreea Cioca

    2017-02-01

    Full Text Available The role of podoplanin in hepatocellular carcinoma (HCC is not clear yet. The aim of our study was to evaluate the expression of podoplanin in HCC and to determine its role in hepatocarcinogenesis. We performed immunohistochemistry with monoclonal D2-40 antibody, on paraffin-embedded tissue sections of 72 patients diagnosed with HCC. Lymphatic vessels density (LVD was increased in patients who had vascular invasion at the time of diagnosis (P=0.018 and in those with associated cirrhosis (P=0.006. Tumor cells showing podoplanin expression were correlated with histological grade (P=0.040. Podoplanin-expressing cancer associated fibroblasts (CAFs were correlated with both LVD (P=0.019 and tumor cells (P=0.015. Our results sustain the dual role of podoplanin in HCC by its involvement in both HCC tumorigenesis, lymphatic neovascularization and tumor invasion invasiveness. A possible crosstalk between epithelial and stromal tumor cells in HCC tumor microenvironment may be mediated by podoplanin, but this hypothesis needs further studies to elucidate this interrelation.

  1. The multifaceted role of podoplanin expression in hepatocellular carcinoma.

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    Cioca, Andreea; Ceausu, Amalia R; Marin, Irina; Raica, Marius; Cimpean, Anca M

    2017-02-13

    The role of podoplanin in hepatocellular carcinoma (HCC) is not clear yet. The aim of our study was to evaluate the expression of podoplanin in HCC and to determine its role in hepatocarcinogenesis. We performed immunohistochemistry with monoclonal D2-40 antibody, on paraffin-embedded tissue sections of 72 patients diagnosed with HCC. Lymphatic vessels density (LVD) was increased in patients who had vascular invasion at the time of diagnosis (P=0.018) and in those with associated cirrhosis (P=0.006). Tumor cells showing podoplanin expression were correlated with histological grade (P=0.040). Podoplanin-expressing cancer associated fibroblasts (CAFs) were correlated with both LVD (P=0.019) and tumor cells (P=0.015). Our results sustain the dual role of podoplanin in HCC by its involvement in both HCC tumorigenesis, lymphatic neovascularization and tumor invasion invasiveness. A possible crosstalk between epithelial and stromal tumor cells in HCC tumor microenvironment may be mediated by podoplanin, but this hypothesis needs further studies to elucidate this interrelation.

  2. Production of cross-kingdom oxylipins by pathogenic fungi: An update on their role in development and pathogenicity.

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    Fischer, Gregory J; Keller, Nancy P

    2016-03-01

    Oxylipins are a class of molecules derived from the incorporation of oxygen into polyunsaturated fatty acid substrates through the action of oxygenases. While extensively investigated in the context of mammalian immune responses, over the last decade it has become apparent that oxylipins are a common means of communication among and between plants, animals, and fungi to control development and alter host-microbe interactions. In fungi, some oxylipins are derived nonenzymatically while others are produced by lipoxygenases, cyclooxygenases, and monooxygenases with homology to plant and human enzymes. Recent investigations of numerous plant and human fungal pathogens have revealed oxylipins to be involved in the establishment and progression of disease. This review highlights oxylipin production by pathogenic fungi and their role in fungal development and pathogen/host interactions.

  3. The role of glutathione transferases in renal cell carcinoma

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    Ćorić Vesna

    2016-01-01

    Full Text Available Mounting evidence suggest that members of the subfamily of cytosolic glutathione S-transferases (GSTs possess roles far beyond the classical glutathione-dependent enzymatic conjugation of electrophilic metabolites and xenobiotics. Namely, monomeric forms of certain GSTs are capable of forming protein: protein interactions with protein kinases and regulate cell apoptotic pathways. Due to this dual functionality of cytosolic GSTs, they might be implicated in both the development and the progression of renal cell carcinoma (RCC. Prominent genetic heterogeneity, resulting from the gene deletions, as well as from SNPs in the coding and non-coding regions of GST genes, might affect GST isoenzyme profiles in renal parenchyma and therefore serve as a valuable indicator for predicting the risk of cancer development. Namely, GSTs are involved in the biotransformation of several compounds recognized as risk factors for RCC. The most potent carcinogen of polycyclic aromatic hydrocarbon diol epoxides, present in cigarette smoke, is of benzo(apyrene (BPDE, detoxified by GSTs. So far, the relationship between GST genotype and BPDE-DNA adduct formation, in determining the risk for RCC, has not been evaluated in patients with RCC. Although the association between certain individual and combined GST genotypes and RCC risk has been debated in a the literature, the data on the prognostic value of GST polymorphism in patients with RCC are scarce, probably due to the fact that the molecular mechanism supporting the role of GSTs in RCC progression has not been clarified as yet.

  4. Baculovirus enhancins and their role in viral pathogenicity. Chapter 9

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    James M. Slavicek

    2012-01-01

    Baculoviruses are a large group of viruses pathogenic to arthropods, primarily insects from the order Lepidoptera and also insects in the orders Hymenoptera and Diptera. Baculoviruses have been used to control insect pests on agricultural crops and forests around the world. Efforts have been ongoing for the last two decades to develop strains of baculoviruses with...

  5. The functional role of long non-coding RNA in digestive system carcinomas.

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    Wang, Guang-Yu; Zhu, Yuan-Yuan; Zhang, Yan-Qiao

    2014-09-01

    In recent years, long non-coding RNAs (lncRNAs) are emerging as either oncogenes or tumor suppressor genes. Recent evidences suggest that lncRNAs play a very important role in digestive system carcinomas. However, the biological function of lncRNAs in the vast majority of digestive system carcinomas remains unclear. Recently, increasing studies has begun to explore their molecular mechanisms and regulatory networks that they are implicated in tumorigenesis. In this review, we highlight the emerging functional role of lncRNAs in digestive system carcinomas. It is becoming clear that lncRNAs will be exciting and potentially useful for diagnosis and treatment of digestive system carcinomas, some of these lncRNAs might function as both diagnostic markers and the treatment targets of digestive system carcinomas.

  6. The Role of the Immune Response in Merkel Cell Carcinoma

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    Triozzi, Pierre L.; Fernandez, Anthony P.

    2013-01-01

    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies

  7. The Role of the Immune Response in Merkel Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Triozzi, Pierre L., E-mail: triozzp@ccf.org [Taussig Cancer Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States); Fernandez, Anthony P. [Departments of Dermatology and Anatomic Pathology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 (United States)

    2013-02-28

    Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies.

  8. Role of sex steroid receptors in pathobiology of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Mamta Kalra; Jary Mayes; Senait Assefa; Anil K Kaul; Rashmi Kaul

    2008-01-01

    The striking gender disparity observed in the incidence of hepatocellular carcinoma (HCC) suggests an important role of sex hormones in HCC pathogenesis. Though the studies began as early as in 1980s, the precise role of sex hormones and the significance of their receptors in HCC still remain poorly understood and perhaps contribute to current controversies about the potential use of hormonal therapy in HCC. A comprehensive review of the existing literature revealed several shortcomings associated with the studies on estrogen receptor (ER) and androgen receptor (AR) in normal liver and HCC. These shortcomings include the use of less sensitive receptor ligand binding assays and immunohistochemistry studies for ERα alone until 1996 when ERβ isoform was identified. The animal models of HCC utilized for studies were primarily based on chemical-induced hepatocarcinogenesis with less similarity to virus-induced HCC pathogenesis. However, recent in vitro studies in hepatoma cells provide newer insights for hormonal regulation of key cellular processes including interaction of ER and AR with viral proteins. In light of the above facts, there is an urgent need for a detailed investigation of sex hormones and their receptors in normal liver and HCC. In this review, we systematically present the information currently available on androgens, estrogens and their receptors in normal liver and HCC obtained from in vitro, in vivo experimental models and clinical studies. This information will direct future basic and clinical research to bridge the gap in knowledge to explore the therapeutic potential of hormonal therapy in HCC. 2008 The WJG Press. All rights reserved.

  9. The role of hyperparasitism in microbial pathogen ecology and evolution.

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    Parratt, Steven R; Laine, Anna-Liisa

    2016-08-01

    Many micro-organisms employ a parasitic lifestyle and, through their antagonistic interactions with host populations, have major impacts on human, agricultural and natural ecosystems. Most pathogens are likely to host parasites of their own, that is, hyperparasites, but how nested chains of parasites impact on disease dynamics is grossly neglected in the ecological and evolutionary literature. In this minireview we argue that the diversity and dynamics of micro-hyperparasites are an important component of natural host-pathogen systems. We use the current literature from a handful of key systems to show that observed patterns of pathogen virulence and disease dynamics may well be influenced by hyperparasites. Exploring these factors will shed light on many aspects of microbial ecology and disease biology, including resistance-virulence evolution, apparent competition, epidemiology and ecosystem stability. Considering the importance of hyperparasites in natural populations will have applied consequences for the field of biological control and therapeutic science, where hyperparastism is employed as a control mechanism but not necessarily ecologically understood.

  10. Hantaviruses in the Americas and Their Role as Emerging Pathogens

    Directory of Open Access Journals (Sweden)

    Fernando Torres-Pérez

    2010-11-01

    Full Text Available The continued emergence and re-emergence of pathogens represent an ongoing, sometimes major, threat to populations. Hantaviruses (family Bunyaviridae and their associated human diseases were considered to be confined to Eurasia, but the occurrence of an outbreak in 1993–94 in the southwestern United States led to a great increase in their study among virologists worldwide. Well over 40 hantaviral genotypes have been described, the large majority since 1993, and nearly half of them pathogenic for humans. Hantaviruses cause persistent infections in their reservoir hosts, and in the Americas, human disease is manifest as a cardiopulmonary compromise, hantavirus cardiopulmonary syndrome (HCPS, with case-fatality ratios, for the most common viral serotypes, between 30% and 40%. Habitat disturbance and larger-scale ecological disturbances, perhaps including climate change, are among the factors that may have increased the human caseload of HCPS between 1993 and the present. We consider here the features that influence the structure of host population dynamics that may lead to viral outbreaks, as well as the macromolecular determinants of hantaviruses that have been regarded as having potential contribution to pathogenicity.

  11. An Anti-Oncogenic Role for Decorin in Mammary Carcinoma

    National Research Council Canada - National Science Library

    Iozzo, Renato V

    2004-01-01

    .... In the preliminary data that support the basis of this proposal, we discovered that decorin causes a functional inactivation of the oncogenic ErbB2 protein in mammary carcinoma cells overexpressing ErbB2...

  12. Food-borne pathogens, health and role of dietary phytochemicals.

    Science.gov (United States)

    Shetty, K; Labbe, R G

    1998-12-01

    Infectious diseases transmitted by food have become a major public health concern in recent years. In the USA alone, there are an estimated 6-33 million cases each year. The list of responsible agents continues to grow. In the past 20 years some dozen new pathogens that are primarily food-borne have been identified. Fruits and vegetables, often from the global food market, have been added to the traditional vehicles of food-borne illness; that is, undercooked meat, poultry, seafood, or unpasteurized milk. Such products are minimally processed and have fewer barriers to microbial growth such as salt, sugar or preservatives. The evolution of the epidemiology of food-borne illness requires a rethinking of traditional, though still valid, solutions for their prevention. Among various strategies to prevent food-borne pathogens, use of dietary phytochemicals is promising. The major obstacle in the use of dietary phytochemical is the consistency of phytochemicals in different foods due to their natural genetic variation. We have developed a novel tissue-culture-based selection strategy to isolate elite phenolic phytochemical-producing clonal lines of species belonging to the family Lamiaceae. Among several species we have targeted elite clonal lines of thyme (Thymus vulgaris) and oregano (Origanum vulgare) against Escherichia coli and Clostridium perfrigens in fresh and processed meats. We are also evaluating high phenolic profile-containing clonal lines of basil (Ocimum basilicum) to inhibit gastric ulcer-causing Helicobacter pylori. Other elite lines of the members of the family Lamiaceae, rosemary (Rosmarinus officinalis) and salvia (Salvia officinalis) also hold promise against a wide range of food pathogens such as Salmonella species in poultry products and Vibrio species in seafood.

  13. DJ-1 and androgen receptor immunohistochemical expression in prostatic carcinoma: A possible role in carcinogenesis

    International Nuclear Information System (INIS)

    Osman, W.M.; Abd El Atti, R.M.; Abou Gabal, H.H.

    2013-01-01

    Background and Aim: Androgen plays a fundamental role in the growth and differentiation of prostate. Androgen receptor (AR) expression may represent a potential marker of prognosis in prostate cancer. However, there have been variable results regarding its ability to predict clinical progression. Despite the oncogenic properties of DJ-1, its significance in prostate cancer development and progression is not well understood. This research shed some light on the possible role of immunohistochemical expression of DJ-1 in clinically localized prostatic carcinoma in relation to the established role of AR and other clinico pathologic parameters. Materials and Methods: The immunohistochemical expression of AR and DJ-1 was evaluated in 129 samples including benign hyperplasia (n = 60) and prostatic carcinoma (n = 69). Results: The mean value of AR immunostaining was significantly higher in prostatic carcinomas than in benign hyperplasia (P = 0.001). A significant inverse correlation was found between AR immunostaining and the grade of prostatic carcinomas. A significantly higher median DJ-1 score was found in prostatic carcinoma than in benign hyperplasia (P = 0.0001). There was a significant direct correlation between AR and DJ-1 score (P = 0.0001). AR is more sensitive in predicting prostatic carcinoma than DJ-1 but DJ-1 is more specific than AR. Conclusion: AR nuclear expression was consistently present in benign and adenocarcinoma epithelium. But, there may be limited clinical use for AR expression in localized carcinoma due to its constant heterogeneity. DJ-1 with its oncogenic properties, specificity for prostatic carcinoma and homogenous expression gives an ideal complementary role to AR in the detection and treatment of prostatic carcinomas.

  14. Role of Neurokinin 3 Receptor Signaling in Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Obata, Kyoichi; Shimo, Tsuyoshi; Okui, Tatsuo; Matsumoto, Kenichi; Takada, Hiroyuki; Takabatake, Kiyofumi; Kunisada, Yuki; Ibaragi, Soichiro; Yoshioka, Norie; Kishimoto, Koji; Nagatsuka, Hitoshi; Sasaki, Akira

    2017-11-01

    The neurokinin 3 receptor (NK-3R) is differentially expressed in the central nervous system including cases of human oral squamous cell carcinoma. However, the role of NK-3R signaling in oral squamous cell carcinoma is not well known. NK-3R expression in surgically resected oral squamous cell carcinoma was examined immunohistochemically and the strength of the expression was quantified. We evaluated the function of NK-3R signaling using NK-3R antagonist in human oral squamous cell carcinoma bone invasion mouse model. NK-3R was significantly expressed in tumor cells that had invaded the bone matrix compared to the oral side tumor cells. SB222200, a selective antagonist of NK-3R, significantly suppressed the radiographic osteolytic lesion and tumorigenesis. NK-3R signaling is a potential target for the treatment of oral squamous cell carcinoma in cases of bone destruction. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  15. Prognostic role of sirt1 in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Song, S.; Zhang, H.

    2014-01-01

    To determine the clinical significance of silent mating type information regulation 2 homolog 1 (SIRT1) expression in Hepatocellular Carcinoma (HCC) and its association with P53 and Yes-associated protein 2 (YAP2) expression. Study Design: Observational study. Place and Duration of Study: Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun, China, from January 2000 to January 2010. Methodology: Tissue microarray technique and immunohistochemistry were conducted to detect the expression of SIRT1, P53 and YAP2 proteins in 300 self-paired HCC samples. Associations with clinicopathologic manifestations were analyzed, overall survival analysis and multivariate analysis were performed. Results: By tissue microarray technique and immunohistochemistry on 300 self-paired HCC samples, it was found that SIRT1, P53 and YAP2 were significantly overexpressed in HCC tumor tissues compared with adjacent non-tumor tissues. SIRT1 immunostaining localized both in the nucleus (145/300, 48.3%) and the cytoplasm (70/300, 23.3%), and the overexpression of nuclear SIRT1 was positively related to the overexpression of P53 and YAP2. Survival analysis showed that nuclear SIRT1, P53 and YAP2 overexpression predicted poor overall survival while cytoplasmic SIRT1 overexpression predicted longer overall survival. Multivariate analysis showed nuclear SIRT1 and P53 overexpression as independent tumor promoters while cytoplasmic SIRT1 overexpression as an independent tumor suppressor. Conclusion: SIRT1 was overexpressed in HCC and the expression was positively related to P53 and YAP2 expression. As the nuclear SIRT1 functions as a tumor promoter and cytoplasmic SIRT1 functions as a tumor suppressor, the role of SIRT1 in HCC should be reconsidered. (author)

  16. Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review

    Science.gov (United States)

    Woods, Robbie SR; O’Regan, Esther M; Kennedy, Susan; Martin, Cara; O’Leary, John J; Timon, Conrad

    2014-01-01

    Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPV-related oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities. PMID:24945004

  17. Immunological disturbances and their role in treatment for cervical carcinoma

    International Nuclear Information System (INIS)

    Grinevich, Yu.A.; Dzyubko, N.Ya.; Kokhanevich, E.V.

    1983-01-01

    The study is concerned with immunologic status (cell-mediated and humoral immunity) as a factor influencing the choice of scheme of treatment for carcinoma of cervix uteri. The indexes of immunocompetence should be taken into account in planning the differential treatment of precancer and early forms of carcinoma of cervix uteri. Radiation treatment exerts an immunosuppressive effect. However, immunologic indexes are not affected considerably by laser destruction or surgery. Cryodestruction has a beneficial effect on cell-mediated immunity. Considering these effects as well as the long-term results of different orocedures of treatment, laser coagulation, cryogenic destruction or diathermoconization should be recommended for management of carcinoma in situ of cervix uteri, and extensive extirpation of the uterus, unattended by radiation, for Tla

  18. USGS role and response to highly pathogenic avian influenza

    Science.gov (United States)

    Harris, M. Camille; Miles, A. Keith; Pearce, John M.; Prosser, Diann J.; Sleeman, Jonathan M.; Whalen, Mary E.

    2015-09-09

    Avian influenza viruses are naturally occurring in wild birds such as ducks, geese, swans, and gulls. These viruses generally do not cause illness in wild birds, however, when spread to poultry they can be highly pathogenic and cause illness and death in backyard and commercial farms. Outbreaks may cause devastating agricultural economic losses and some viral strains have the potential to infect people directly. Furthermore, the combination of avian influenza viruses with mammalian viruses can result in strains with the ability to transmit from person to person, possibly leading to viruses with pandemic potential. All known pandemic influenza viruses have had some genetic material of avian origin. Since 1996, a strain of highly pathogenic avian influenza (HPAI) virus, H5N1, has caused infection in wild birds, losses to poultry farms in Eurasia and North Africa, and led to the deaths of several hundred people. Spread of the H5N1 virus and other influenza strains from China was likely facilitated by migratory birds. In December 2014, HPAI was detected in poultry in Canada and migratory birds in the United States. Since then, HPAI viruses have spread to large parts of the United States and will likely continue to spread through migratory bird flyways and other mechanisms throughout North America. In the United States, HPAI viruses have severely affected the poultry industry with millions of domestic birds dead or culled. These strains of HPAI are not known to cause disease in humans; however, the Centers for Disease Control and Prevention (CDC) advise caution when in close contact with infected birds. Experts agree that HPAI strains currently circulating in wild birds of North America will likely persist for the next few years. This unprecedented situation presents risks to the poultry industry, natural resource management, and potentially human health. Scientific knowledge and decision support tools are urgently needed to understand factors affecting the persistence

  19. Pathogenic factors of Pseudomonas aeruginosa – the role of biofilm in pathogenicity and as a target for phage therapy

    Directory of Open Access Journals (Sweden)

    Fairoz Al-Wrafy

    2017-02-01

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen that can cause several acute and chronic infections in humans, and it has become an important cause of nosocomial infections and antibiotic resistance. Biofilm represents an important virulence factor for these bacteria, plays a role in P. aeruginosa infections and avoidance of immune defence mechanisms, and has the ability to protect the bacteria from antibiotics. Alginate, Psl and Pel, three exopolysaccharides, are the main components in biofilm matrix, with many biological functions attributed to them, especially with respect to the protection of the bacterial cell from antibiotics and the immune system. Pseudomonas infections, biofilm formation and development of resistance to antibiotics all require better understanding to achieve the best results using alternative treatment with phage therapy. This review describes the P. aeruginosa pathogenicity and virulence factors with a special focus on the biofilm and its role in infection and resistance to antibiotics and summarizes phage therapy as an alternative approach in treatment of P. aeruginosa infections.

  20. Role of radiation in the management of carcinoma of larynx

    International Nuclear Information System (INIS)

    Anand, A.K.; Sharma, S.C.; Patel, F.D.; Ayyagari, S.; Gupta, S.D.

    1991-01-01

    488 Cases of carcinoma of larynx treated at Postgraduate Institute of Medical Education and Research, Chandigarh, during the years 1974-79, were retrospectively analysed. Distribution of cases with respect to age, sex, anatomical site, stage, clinical presentation and treatment were evaluated. (author). 4 tabs

  1. Role of pelvic lymphadenectomy in stage 1A endometrial carcinoma ...

    African Journals Online (AJOL)

    Hossam Hassan Aly Hassan El Sokkary

    2013-10-31

    Oct 31, 2013 ... phadenectomy in managing stage 1A diagnosed preoperatively, we try to evaluate this need. Objective: To ... Methods: 60 Cases of endometrial carcinoma diagnosed by fractional curettage and proved to be stage 1A .... The strongest argument for routine staging is the avoidance of pelvic radiation therapy ...

  2. Could Uric acid have a Pathogenic Role in Chronic Allograft ...

    African Journals Online (AJOL)

    Introduction: Chronic allograft dysfunction (CAD) is the primary cause of chronic graft failure after kidney transplantation. The pathogenesis of CAD involves both antigen-dependent and antigen-independent mechanisms. Serum uric acid could have a role in both mechanisms. Review: Hyperuricemia in subjects with renal ...

  3. Roles of Arabidopsis WRKY3 and WRKY4 Transcription Factors in Plant Responses to Pathogens

    Directory of Open Access Journals (Sweden)

    Fan Baofang

    2008-06-01

    Full Text Available Abstract Background Plant WRKY DNA-binding transcription factors are involved in plant responses to biotic and abiotic responses. It has been previously shown that Arabidopsis WRKY3 and WRKY4, which encode two structurally similar WRKY transcription factors, are induced by pathogen infection and salicylic acid (SA. However, the role of the two WRKY transcription factors in plant disease resistance has not been directly analyzed. Results Both WRKY3 and WRKY4 are nuclear-localized and specifically recognize the TTGACC W-box sequences in vitro. Expression of WRKY3 and WRKY4 was induced rapidly by stress conditions generated by liquid infiltration or spraying. Stress-induced expression of WRKY4 was further elevated by pathogen infection and SA treatment. To determine directly their role in plant disease resistance, we have isolated T-DNA insertion mutants and generated transgenic overexpression lines for WRKY3 and WRKY4. Both the loss-of-function mutants and transgenic overexpression lines were examined for responses to the biotrophic bacterial pathogen Pseudomonas syringae and the necrotrophic fungal pathogen Botrytis cinerea. The wrky3 and wrky4 single and double mutants exhibited more severe disease symptoms and support higher fungal growth than wild-type plants after Botrytis infection. Although disruption of WRKY3 and WRKY4 did not have a major effect on plant response to P. syringae, overexpression of WRKY4 greatly enhanced plant susceptibility to the bacterial pathogen and suppressed pathogen-induced PR1 gene expression. Conclusion The nuclear localization and sequence-specific DNA-binding activity support that WRKY3 and WRKY4 function as transcription factors. Functional analysis based on T-DNA insertion mutants and transgenic overexpression lines indicates that WRKY3 and WRKY4 have a positive role in plant resistance to necrotrophic pathogens and WRKY4 has a negative effect on plant resistance to biotrophic pathogens.

  4. Treatment of primary tracheal carcinoma. The role of external and endoluminal radiotherapy

    International Nuclear Information System (INIS)

    Harms, W.; Wannenmacher, M.; Becker, H.; Herth, F.; Gagel, B.

    2000-01-01

    Background and Purpose: In a retrospective study the role of radiation therapy for the treatment of primary tracheal carcinoma was investigated. Patients and Methods: Between 1984 and 1997, 25 patients with primary tracheal carcinoma were treated with external beam radiotherapy (17 squamous-cell carcinoma [SCC], 8 adenoid cystic carcinoma [ACC], median dose SCC 60 Gy, ACC 55 Gy). An additional brachytherapy boost was carried out in 10/25 patients (median dose SCC 18 Gy, ACC 15 Gy). Ten patients underwent operative treatment. Results: The median survival (Kaplan-Meier) for patients with SCC was 33 months (ACC 94.2). The 1-, 2- and 5-year survival rates (Kaplan-Meier) for patients with SCC were 64.7% (ACC 85.7%), 64.7% (ACC 85.7%), and 26% (ACC 85.7%). Patients with ACC and patients with a complete remission after treatment had a significantly better survival probability (log rank test, p [de

  5. Pathogenic and Diagnostic Potential of BLCA-1 and BLCA-4 Nuclear Proteins in Urothelial Cell Carcinoma of Human Bladder

    Directory of Open Access Journals (Sweden)

    Matteo Santoni

    2012-01-01

    Full Text Available Transitional cell carcinoma (TCC of the bladder is one of the most common malignancies of genitourinary tract. Patients with bladder cancer need a life-long surveillance, directly due to the relatively high recurrence rate of this tumor. The use of cystoscopy represents the gold standard for the followup of previously treated patients. Nevertheless, several factors, including cost and invasiveness, render cystoscopy not ideal for routine controls. Advances in the identification of specific alterations in the nuclear structure of bladder cancer cells have opened novel diagnostic landscapes. The members of nuclear matrix protein family BLCA-1 and BLCA-4, are currently under evaluation as bladder cancer urinary markers. They are involved in tumour cell proliferation, survival, and angiogenesis. In this paper, we illustrate the role of BLCA-1 and BLCA-4 in bladder carcinogenesis and their potential exploitation as biomarkers in this cancer.

  6. Diversity and role of cave-dwelling hematophagous insects in pathogen transmission in the Afrotropical region.

    Science.gov (United States)

    Obame-Nkoghe, Judicaël; Leroy, Eric-Maurice; Paupy, Christophe

    2017-04-12

    The progressive anthropization of caves for food resources or economic purposes increases human exposure to pathogens that naturally infect cave-dwelling animals. The presence of wild or domestic animals in the immediate surroundings of caves also may contribute to increasing the risk of emergence of such pathogens. Some zoonotic pathogens are transmitted through direct contact, but many others require arthropod vectors, such as blood-feeding insects. In Africa, hematophagous insects often play a key role in the epidemiology of many pathogens; however, their ecology in cave habitats remains poorly known. During the last decades, several investigations carried out in Afrotropical caves suggested the medical and veterinary importance particularly of insect taxa of the Diptera order. Therefore, the role of some of these insects as vectors of pathogens that infect cave-dwelling vertebrates has been studied. The present review summarizes these findings, brings insights into the diversity of cave-dwelling hematophagous Diptera and their involvement in pathogen transmission, and finally discusses new challenges and future research directions.

  7. Immunotherapy in Merkel cell carcinoma: role of Avelumab

    Directory of Open Access Journals (Sweden)

    Palla AR

    2018-03-01

    Full Text Available Amruth R Palla, Donald Doll Department of Internal Medicine, Division of Hematology and Oncology, Ellis Fischel Cancer Center, University of Missouri, Columbia, MO, USA Abstract: Merkel cell carcinoma (MCC, a rare skin cancer, is associated with high mortality, especially in a metastatic setting. Though conventional chemotherapy with platinum and etoposide has had high response rates, many of the patients have had early relapse without any effective therapy thereafter. Recently, immune check point inhibitors have shown very good durable responses, leading to the approval of a programmed death-ligand 1 inhibitor Avelumab for these patients. We briefly review the epidemiology and immune basis of the pathogenesis of MCC, which therefore explains the excellent response to check point inhibitors, and throw light on future directions of immunotherapy for this cancer. Keywords: Merkel cell carcinoma, T cell, PD-L1, Avelumab, immunotherapy, check point inhibitors, neuroendocrine tumor

  8. Immunotherapy in Merkel cell carcinoma: role of Avelumab

    OpenAIRE

    Palla,Amruth; Doll,Donald

    2018-01-01

    Amruth R Palla, Donald Doll Department of Internal Medicine, Division of Hematology and Oncology, Ellis Fischel Cancer Center, University of Missouri, Columbia, MO, USA Abstract: Merkel cell carcinoma (MCC), a rare skin cancer, is associated with high mortality, especially in a metastatic setting. Though conventional chemotherapy with platinum and etoposide has had high response rates, many of the patients have had early relapse without any effective therapy thereafter. Recently, imm...

  9. Role of everolimus in the treatment of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Saby George

    2009-08-01

    Full Text Available Saby George1, Ronald M Bukowski21University of Texas Health Sciences Center, MC-8221, Division of Hematology and Oncology, San Antonio, Texas, USA; 2CCF Lerner College of Medicine Division of Hematology and Oncology, Cleveland, Ohio, USAAbstract: The therapeutic options in metastatic renal cell carcinoma have been recently expanded by the discovery of the VHL gene, the mutation of which is associated with development of clear cell carcinoma, and overexpression of the angiogenesis pathway, resulting in a very vascular tumor. This breakthrough in science led to the development of a variety of small molecules inhibiting the VEGF-dependent angiogenic pathway, such as sunitinib and sorafenib. These agents prolong overall and progression-free survival, respectively. The result was the development of robust front-line therapies which ultimately fail and are associated with disease progression. In this setting, there existed an unmet need for developing second-line therapies for patients with refractory metastatic renal cell carcinoma (MRCC. Everolimus (RAD 001 is an oral inhibitor of the mammalian target of rapamycin (mTOR pathway. The double-blind, randomized, placebo-controlled phase III trial of everolimus (RECORD-1 conducted in MRCC patients after progression on sunitinib or sorafenib, or both, demonstrated a progression-free survival benefit favoring the study drug (4.9 months vs 1.9 months, HR 0.33, 95% CI 0.25 to 0.43, P ≤ 0 0.001. Everolimus thus established itself as a standard of care in the second-line setting for patients with MRCC who have failed treatment with VEGF receptor inhibitors.Keywords: mTOR inhibitor, mammalian target of rapamycin inhibitor, signal transduction inhibitor, renal cell carcinoma, targeted therapy

  10. Role of Cereal Secondary Metabolites Involved in Mediating the Outcome of Plant-Pathogen Interactions

    Directory of Open Access Journals (Sweden)

    Lauren A. Du Fall

    2011-12-01

    Full Text Available Cereal crops such as wheat, rice and barley underpin the staple diet for human consumption globally. A multitude of threats to stable and secure yields of these crops exist including from losses caused by pathogens, particularly fungal. Plants have evolved complex mechanisms to resist pathogens including programmed cell death responses, the release of pathogenicity-related proteins and oxidative bursts. Another such mechanism is the synthesis and release of secondary metabolites toxic to potential pathogens. Several classes of these compounds have been identified and their anti-fungal properties demonstrated. However the lack of suitable analytical techniques has hampered the progress of identifying and exploiting more of these novel metabolites. In this review, we summarise the role of the secondary metabolites in cereal crop diseases and briefly touch on the analytical techniques that hold the key to unlocking their potential in reducing yield losses.

  11. Role of proline and pyrroline-5-carboxylate metabolism in plant defense against invading pathogens

    Science.gov (United States)

    Qamar, Aarzoo; Mysore, Kirankumar S.; Senthil-Kumar, Muthappa

    2015-01-01

    Pyrroline-5-carboxylate (P5C) is an intermediate product of both proline biosynthesis and catabolism. Recent evidences indicate that proline-P5C metabolism is tightly regulated in plants, especially during pathogen infection and abiotic stress. However, role of P5C and its metabolism in plants has not yet been fully understood. Studies indicate that P5C synthesized in mitochondria has a role in both resistance (R)-gene-mediated and non-host resistance against invading pathogens. Proline dehydrogenase and delta-ornithine amino transferase-encoding genes, both involved in P5C synthesis in mitochondria are implicated in defense response of Nicotiana benthamiana and Arabidopsis thaliana against bacterial pathogens. Such defense response is proposed to involve salicylic acid-dependent pathway, reactive oxygen species (ROS) and hypersensitive response (HR)-associated cell death. Recently HR, a form of programmed cell death (PCD), has been proposed to be induced by changes in mitochondrial P5C synthesis or the increase in P5C levels per se in plants inoculated with either a host pathogen carrying suitable avirulent (Avr) gene or a non-host pathogen. Consistently, A. thaliana mutant plants deficient in P5C catabolism showed HR like cell death when grown in external P5C or proline supplemented medium. Similarly, yeast and plant cells under oxidative stress were shown to increase ROS production and PCD due to increase in P5C levels. Similar mechanism has also been reported as one of the triggers for apoptosis in mammalian cells. This review critically analyzes results from various studies and enumerates the pathways for regulation of P5C levels in the plant cell, especially in mitochondria, during pathogen infection. Further, mechanisms regulating P5C- mediated defense responses, namely HR are outlined. This review also provides new insights into the differential role of proline-P5C metabolism in plants exposed to pathogen infection. PMID:26217357

  12. Cytodiagnosis of myxoid adrenocortical carcinoma and role of immunocytochemistry to differentiate it from renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Santosh Kumar Mondal

    2014-01-01

    Full Text Available Adrenocortical carcinoma (ACC is a rare malignancy and cytodiagnosis of this tumor is not routinely encountered by a cytopathologist. Here, we report a case of ACC initially diagnosed by computed tomography (CT-guided fine needle aspiration cytology (FNAC with the help of immunocytochemistry. A 48-year-old lady presented with flank pain and abdominal mass for the last 6 months. A CT scan of her abdomen revealed a large mass arising from the upper part of the left kidney. CT-guided FNAC was performed. Cytologic smears showed pleomorphic large cells arranged discretely and in small aggregates against a myxoid background. The cells had a high nucleocytoplasmic ratio, anisonucleosis and conspicuous nucleoli. Based on cytomorphology, differential diagnoses of ACC and renal cell carcinoma (RCC were made. On immunocytochemistry, the tumor cells were synaptophysin, inhibin, vimentin and Melan-A positive but cytokeratin and epithelial membrane antigen negative. Thus, a cytodiagnosis of myxoid ACC was made and histopathologic examination was suggested. Subsequent histologic examination and immunohistochemistry proved the case to be myxoid ACC.

  13. Potential role of bacteria packaging by protozoa in the persistence and transmission of pathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Alix M Denoncourt

    2014-05-01

    Full Text Available Many pathogenic bacteria live in close association with protozoa. These unicellular eukaryotic microorganisms are ubiquitous in various environments. A number of protozoa such as amoebae and ciliates ingest pathogenic bacteria, package them usually in membrane structures, and then release them into the environment. Packaged bacteria are more resistant to various stresses and are more apt to survive than free bacteria. New evidence indicates that protozoa and not bacteria control the packaging process. It is possible that packaging is more common than suspected and may play a major role in the persistence and transmission of pathogenic bacteria. To confirm the role of packaging in the propagation of infections, it is vital that the molecular mechanisms governing the packaging of bacteria by protozoa be identified as well as elements related to the ecology of this process in order to determine whether packaging acts as a Trojan Horse.

  14. Immunotherapy in Merkel cell carcinoma: role of Avelumab.

    Science.gov (United States)

    Palla, Amruth R; Doll, Donald

    2018-01-01

    Merkel cell carcinoma (MCC), a rare skin cancer, is associated with high mortality, especially in a metastatic setting. Though conventional chemotherapy with platinum and etoposide has had high response rates, many of the patients have had early relapse without any effective therapy thereafter. Recently, immune check point inhibitors have shown very good durable responses, leading to the approval of a programmed death-ligand 1 inhibitor Avelumab for these patients. We briefly review the epidemiology and immune basis of the pathogenesis of MCC, which therefore explains the excellent response to check point inhibitors, and throw light on future directions of immunotherapy for this cancer.

  15. [Care of Merkel cell carcinoma and role of the radiotherapy].

    Science.gov (United States)

    Rehailia-Blanchard, Amel; Pigné, Grégoire; Guy, Jean-Baptiste; Vallard, Alexis; El Meddeb Hamrouni, Anis; Rancoule, Chloé; Magné, Nicolas

    2017-01-01

    Merkel cell carcinoma is a rare neuro-endocrine tumor of skin with a poor prognosis. Data available in literature are scarce. Current treatment for locoregional disease is based on combined treatment by surgery and radiotherapy. However these treatments are controversial. The aim of the present review is to sum up the different available studies and to compare national and international guidelines. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  16. The role of strigolactones during plant interactions with the pathogenic fungus Fusarium oxysporum.

    Science.gov (United States)

    Foo, Eloise; Blake, Sara N; Fisher, Brendan J; Smith, Jason A; Reid, James B

    2016-06-01

    Strigolactones (SLs) do not influence spore germination or hyphal growth of Fusarium oxysporum. Mutant studies revealed no role for SLs but a role for ethylene signalling in defence against this pathogen in pea. Strigolactones (SLs) play important roles both inside the plant as a hormone and outside the plant as a rhizosphere signal in interactions with mycorrhizal fungi and parasitic weeds. What is less well understood is any potential role SLs may play in interactions with disease causing microbes such as pathogenic fungi. In this paper we investigate the influence of SLs on the hemibiotrophic pathogen Fusarium oxysporum f.sp. pisi both directly via their effects on fungal growth and inside the plant through the use of a mutant deficient in SL. Given that various stereoisomers of synthetic and naturally occuring SLs can display different biological activities, we used (+)-GR24, (-)-GR24 and the naturally occurring SL, (+)-strigol, as well as a racemic mixture of 5-deoxystrigol. As a positive control, we examined the influence of a plant mutant with altered ethylene signalling, ein2, on disease development. We found no evidence that SLs influence spore germination or hyphal growth of Fusarium oxysporum and that, while ethylene signalling influences pea susceptibility to this pathogen, SLs do not.

  17. The role of sequential chemoradiation for local advanced oropharyngeal carcinoma

    International Nuclear Information System (INIS)

    Masterson, Liam; Tanweer, Faiz

    2013-01-01

    This study aims to assess survival, prognostic indicators, and pattern of failure for advanced oropharyngeal cancer treated by induction chemotherapy followed by concomitant chemoradiation (sequential CRT). A retrospective review of 80 consecutive patients who underwent chemoradiation [doublet cisplatin and 5-fluorouracil (PF)] for local advanced oropharyngeal carcinoma at a tertiary center from March 2003 to July 2008 is reported. Seven studies utilizing a similar protocol were reviewed, and all outcomes are collated. At a median follow-up of 32 months, the 3-year overall survival was 75%. Tumor size (p<0.001), age at presentation (p<0.002), and failure to complete the full course of induction chemotherapy (p<0.01) were all found to be significant factors affecting survival. Induction chemotherapy followed by concomitant chemoradiation utilizing doublet PF is an effective treatment for local advanced oropharyngeal carcinoma. At present, the addition of a taxane to the PF regimen cannot be assumed to provide benefit until further evidence emerges from a representative controlled trial. (author)

  18. Serous tubal intraepithelial carcinoma: its potential role in primary peritoneal serous carcinoma and serous cancer prevention.

    Science.gov (United States)

    Carlson, Joseph W; Miron, Alexander; Jarboe, Elke A; Parast, Mana M; Hirsch, Michelle S; Lee, Yonghee; Muto, Michael G; Kindelberger, David; Crum, Christopher P

    2008-09-01

    A diagnosis of primary peritoneal serous carcinoma (PPSC) requires exclusion of a source in other reproductive organs. Serous tubal intraepithelial carcinoma (STIC; stage 0) has been described in asymptomatic women with BRCA mutations and linked to a serous cancer precursor in the fimbria. This study examined the frequency of STIC in PPSC and its clinical outcome in BRCA-positive women. Presence or absence of STIC was recorded in consecutive cases meeting the 2001 WHO criteria for PPSC, including 26 patients with nonuniform sampling of the fallopian tubes (group 1) and 19 patients with complete tubal examination (group 2; sectioning and extensively examining the fimbriated end, or SEE-FIM protocol). In selected cases, STIC or its putative precursor and the peritoneal tumor were analyzed for p53 mutations (exons 1 to 11). Outcome of STIC was ascertained by literature review. Thirteen (50%) of 26 PPSCs in group 1 involved the endosalpinx, with nine STICs (35%). Fifteen (79%) of 19 cases in group 2 contained endosalpingeal involvement, with nine STICs (47%). STIC was typically fimbrial and unifocal, with variable invasion of the tubal wall. In five of five cases, the peritoneal and tubal lesion shared an identical p53 mutation. Of 10 reported STICs in BRCA-positive women, all patients were without disease on follow-up. The fimbria is the source of nearly one half of PPSCs, suggesting serous malignancy originates in the tubal mucosa but grows preferentially at a remote peritoneal site. The generally low risk of recurrence in stage 0 (STIC) disease further underscores STIC as a possible target for early serous cancer detection and prevention.

  19. The etiologic role of HPV in vulvar squamous cell carcinoma fine tuned.

    NARCIS (Netherlands)

    Nieuwenhof, H.P. van de; Kempen, L.C.L.T. van; Hullu, J.A. de; Bekkers, R.L.M.; Bulten, J.; Melchers, W.J.G.; Massuger, L.F.A.G.

    2009-01-01

    PURPOSE: High-risk human papilloma virus (HPV) plays a role in the development of a subset of vulvar squamous cell carcinomas. Uncertainty exists about the true impact of HPV in this tumor type because conflicting reports have been published with diverging prevalence rates. This study was done to

  20. Medullary breast carcinoma: The role of radiotherapy as primary treatment

    International Nuclear Information System (INIS)

    Fourquet, A.; Vilcoq, J.R.; Zafrani, B.; Schlienger, P.; Campana, F.; Jullien, D.

    1987-01-01

    The results are reported of a selected series of 41 patients with medullary carcinoma of the breast, treated with primary radiotherapy with (24 patients) or without (17 patients) adjuvant chemotherapy. Complete responses to radiotherapy occurred with moderate doses (67% of the patients had a complete response after a dose of 55-60 Gy) and were increased by the addition of an irradiation boost. The 6-year actuarial free of local recurrence survival, metastase-free survival and survival rates were 86, 83, and 83%, respectively. The 6-year actuarial probability of living with breast preserved was 72%. Recurrences and survivals were not influenced by the tumor size or clinical axillary node status. Adjuvant chemotherapy had no effect on the rate of recurrence or survival. 14 refs.; 3 tabs

  1. Functional Roles and Therapeutic Applications of Exosomes in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Laura Santangelo

    2017-01-01

    Full Text Available Exosomes are important in intercellular communication. They assure the horizontal transfer of specific functional contents (i.e., proteins, lipids, RNA molecules, and circulating DNA from donor to recipient cells. Notably, tumor-derived exosomes (TDEs appear to be an important vehicle of specific signals in cancer, impacting on tumor growth and metastasis. Recent researches point to the characterization of exosomes in Hepatocellular Carcinoma (HCC, the major adult liver malignancy. In this review, we summarize current findings on HCC exosomes, focusing on the identification of noncoding RNAs as exosome-enriched functional regulators and new potential biomarkers. The great potential of exosomes in future HCC diagnostic and therapeutic approaches is underlined.

  2. The Role of Everolimus in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Malek Meskawi

    2015-12-01

    Full Text Available Everolimus (RAD001 is an orally administered agent that inhibits the mammalian target of rapamycin serine-threonine kinase. A phase III pivotal trial on everolimus, published in 2008, provided the first evidence for the efficacy of sequential therapy for patients with metastatic clear cell renal cell carcinoma (RCC. In this study, everolimus was used after failure of one or several previous lines of therapy, and it demonstrated a 3-month survival benefit relative to placebo. Currently, based on the level 1 evidence, everolimus represents the molecule of choice for third-line therapy after failure of previous two tyrosine kinase inhibitors (TKIs. However, second-line use after failure of one TKI is challenged by two new molecules (nivolumab and cabozantinib, which proved to have better efficacy with similar toxicity profile. In non-clear cell metastatic RCC, the current evidence recommends everolimus as a second-line therapy after failure of previous first-line sunitinib.

  3. The hygiene hypothesis in autoimmunity: the role of pathogens and commensals.

    Science.gov (United States)

    Bach, Jean-François

    2018-02-01

    The incidence of autoimmune diseases has been steadily rising. Concomitantly, the incidence of most infectious diseases has declined. This observation gave rise to the hygiene hypothesis, which postulates that a reduction in the frequency of infections contributes directly to the increase in the frequency of autoimmune and allergic diseases. This hypothesis is supported by robust epidemiological data, but the underlying mechanisms are unclear. Pathogens are known to be important, as autoimmune disease is prevented in various experimental models by infection with different bacteria, viruses and parasites. Gut commensal bacteria also play an important role: dysbiosis of the gut flora is observed in patients with autoimmune diseases, although the causal relationship with the occurrence of autoimmune diseases has not been established. Both pathogens and commensals act by stimulating immunoregulatory pathways. Here, I discuss the importance of innate immune receptors, in particular Toll-like receptors, in mediating the protective effect of pathogens and commensals on autoimmunity.

  4. Human gallbladder carcinoma: Role of neurotrophins, MIB-1, CD34 and CA15-3.

    Science.gov (United States)

    Artico, M; Bronzetti, E; Alicino, V; Ionta, B; Bosco, S; Grande, C; Bruno, M; Tranquilli Leali, F M; Ionta, G; Fumagalli, L

    2010-03-11

    Gallbladder carcinoma is the most common biliary tract tumor and the fifth most common gastrointestinal tract cancer .The prognosis of gallbladder carcinoma is poor and less than 5% of the patients are still alive five years postoperatively. Gallbladder specimens were obtained during surgical operations performed in eleven patients for resection of a gallbladder carcinoma, and during five autopsies (control cases selected among patients who died from for other causes, excluding those suffering from biliary or hepatic diseases). Immunohistochemical characterization and distribution of neurotrophins, with their respective receptors, were analyzed. The actual role played by these neurotrophic factors in the general regulation, vascular permeability, algic responsiveness, release of locally active substances and potential tumorigenesis in the gallbladder and biliary ducts compartment remains controversial. Our study revealed an increased immunohistochemical expression of NGF and TrKA in the epithelium and in the epithelial glands of the gallbladder carcinoma together with an evident immunoreactivity for BDNF in the same neoplastic areas. An evident immunoreactivity for NGF, TrKA and BDNF was observed in control specimens of gallbladder obtained during autopsies, whereas a weak or quite absent immunoreactivity was observed in the same specimens for NT4, TrKC and p75. On the contrary an appreciable immunoreactivity for p75 was observed in the specimens harvested from patients with gallbladder carcinoma. We also investigated the expression of some known tumor markers such as MIB-1 (anti Ki-67), CD34 and CA15-3, to identify a possible correlation between the expression of these molecular factors and the prognosis of gallbladder carcinoma. They resulted highly expressed in the stroma (CD34 and CA 15-3) and in the epithelium/epithelial glands (MIB-1) of the neoplastic areas and appeared to be almost absent in the control cases, suggesting that these markers, taken together

  5. Human gallbladder carcinoma: Role of neurotrophins, MIB-1, CD34 and CA15-3

    Directory of Open Access Journals (Sweden)

    M. Artico

    2010-03-01

    Full Text Available Gallbladder carcinoma is the most common biliary tract tumor and the fifth most common gastrointestinal tract cancer .The prognosis of gallbladder carcinoma is poor and less than 5% of the patients are still alive five years postoperatively.1 Gallbladder specimens were obtained during surgical operations performed in eleven patients for resection of a gallbladder carcinoma, and during five autopsies (control cases selected among patients who died from for other causes, excluding those suffering from biliary or hepatic diseases. Immunohistochemical characterization and distribution of neurotrophins, with their respective receptors, were analyzed. The actual role played by these neurotrophic factors in the general regulation, vascular permeability, algic responsiveness, release of locally active substances and potential tumorigenesis in the gallbladder and biliary ducts compartment remains controversial. Our study revealed an increased immunohistochemical expression of NGF and TrKA in the epithelium and in the epithelial glands of the gallbladder carcinoma together with an evident immunoreactivity for BDNF in the same neoplastic areas. An evident immunoreactivity for NGF, TrKA and BDNF was observed in control specimens of gallbladder obtained during autopsies, whereas a weak or quite absent immunoreactivity was observed in the same specimens for NT4, TrKC and p75. On the contrary an appreciable immunoreactivity for p75 was observed in the specimens harvested from patients with gallbladder carcinoma. We also investigated the expression of some known tumor markers such as MIB-1 (anti Ki-67, CD34 and CA15-3, to identify a possible correlation between the expression of these molecular factors and the prognosis of gallbladder carcinoma. They resulted highly expressed in the stroma (CD34 and CA 15-3 and in the epithelium/epithelial glands (MIB-1 of the neoplastic areas and appeared to be almost absent in the control cases, suggesting that these markers

  6. The role of a cytosolic superoxide dismutase in barley-pathogen interactions

    KAUST Repository

    Lightfoot, Damien

    2016-03-19

    Reactive oxygen species (ROS), including superoxide (O2-HO2) and hydrogen peroxide (H2O2), are differentially produced during resistance responses to biotrophic pathogens and during susceptible responses to necrotrophic and hemi-biotrophic pathogens. Superoxide dismutase (SOD) is responsible for the catalysis of the dismutation of O2-HO2 to H2O2, regulating the redox status of plant cells. Increased SOD activity has been correlated previously with resistance in barley to the hemi-biotrophic pathogen Pyrenophora teres f. teres (Ptt, the causal agent of the net form of net blotch disease), but the role of individual isoforms of SOD has not been studied. A cytosolic CuZnSOD, HvCSD1, was isolated from barley and characterized as being expressed in tissue from different developmental stages. HvCSD1 was up-regulated during the interaction with Ptt and to a greater extent during the resistance response. Net blotch disease symptoms and fungal growth were not as pronounced in transgenic HvCSD1 knockdown lines in a susceptible background (cv. Golden Promise), when compared with wild-type plants, suggesting that cytosolic O2-HO2 contributes to the signalling required to induce a defence response to Ptt. There was no effect of HvCSD1 knockdown on infection by the hemi-biotrophic rice blast pathogen Magnaporthe oryzae or the biotrophic powdery mildew pathogen Blumeria graminis f. sp. hordei, but HvCSD1 also played a role in the regulation of lesion development by methyl viologen. Together, these results suggest that HvCSD1 could be important in the maintenance of the cytosolic redox status and in the differential regulation of responses to pathogens with different lifestyles.

  7. The role of postradiotherapy neck dissection in supraglottic carcinoma

    International Nuclear Information System (INIS)

    Chan, Annie W.; Ancukiewicz, Marek; Carballo, Natalia; Montgomery, William; Wang, C.C.

    2001-01-01

    Purpose: To evaluate our policy of performing neck dissection based on regional response after definitive radiotherapy in patients with supraglottic carcinoma and to identify the prognostic factors in this group of patients. Methods and Materials: Between 1970 and 1995, 121 patients with node-positive squamous cell carcinoma of the supraglottic larynx were treated with definitive radiotherapy. Sixty-nine percent of patients presented with 1997 AJCC Stage IV disease. The N-stage distribution was N1, 49; N2, 62; and N3, 10. The median size of the lymph nodes was 3 cm (range, 0.5-8 cm). Forty-five patients received once-a-day treatment with a median total dose of 65 Gy (range, 58.0-70.8 Gy) in 1.8-2.0 Gy per fraction over 48 days, and 76 patients received split-course accelerated hyperfractionation with a median total dose of 67.2 Gy (range, 63.2-73.6 Gy) in 1.6 Gy twice a day over 43 days. Patients whose lymph nodes were not clinically detectable at 4-6 weeks after the completion of radiotherapy (complete response) were followed without any neck dissection. Patients with persistent neck adenopathy (partial response) underwent neck dissection whenever possible. Mean follow-up of the living patients was 6.5 years. Results: Regional response was related to the size of lymph nodes at presentation. Eighty-seven percent of patients with nodal size of 3 cm or less had a complete response, whereas 43% of patients with nodal size greater than 3 cm had a partial response. The rate of regional control at 3 years for all patients in the study was 66%. The 3-year ultimate regional control rate after salvage neck dissection was 75%. A relapse in both the primary and regional sites was the most common pattern of relapse, accounting for 39% of all the failures. Local failure was associated with subsequent regional relapse with a relative risk of 4.3. For patients with completeresponse in whom postradiotherapy neck dissection was withheld, the regional control rates were 75% and 86

  8. The role of radiotherapy for locally advanced gallbladder carcinoma

    International Nuclear Information System (INIS)

    Shin, Hyun Soo; Seong, Jin Sil

    2000-01-01

    A retrospective review of 72 patients with locally advanced gallbladder carcinoma, between January 1900 and December 1996, was performed. Survival results and prognostic factors are analyzed for the patients treated with a various modalities. The patients were classified by treatment modality: group 1 included to 27 patients treated with palliative surgery alone, and group 2 for 11 patient treated with palliative surgery and radiotherapy; group 3 for 18 patients not treated by any treatment modality, and group 4 for 16 patients treated with radiotherapy alone. Age distribution ranged from 35 to 80 years with a mean of 63 years. The stage was classified by TNM and Nevin's staging system; all patients had an advanced stage more than III. Palliative surgery was done in 3B patients and adjuvant radiation therapy (Rl1 was followed in 11. For 34 patients, in whom no resection was tried, definitive RT was done in 16. Radiation delivered to tumor site and draining nodes up to 45-612 Gy using 10 MY linear accelerator. Chemotherapy was given to 25 patients with 5-FU based regimens. Median survival time was 10.3 months and 3-year survival rates (3-YSR) were 13.0% in all patients. Survival rates according to the treatment modalities were as followed; in palliative surgery alone, 3-YSR was 2.5%; in palliative surgery and adjuvant RT, 3-YSR was 45.5%; in no treatment group, 3YSR were 8.3%; and definitive RT was 13.1%. It was better survival in additional RT after palliative surgery group than palliative surgery alone (p=0.0009). It was better survival in definitive RT group than no treatment group (p=0.022). Significant prognostic factors by multivariate analysis were treatment modalities, the type of tumor and TNM stage. Significant prognostic factors by multivariate analysis were treatment modalities, the type of tumor and the presence of jaundice. It is suggested that RT could be potentially effective as adjuvant treatment modalities after palliative surgery or primary

  9. Emerging Role of Immunotherapy in Advanced Urothelial Carcinoma.

    Science.gov (United States)

    Koshkin, Vadim S; Grivas, Petros

    2018-04-11

    Advanced urothelial carcinoma (aUC) has long been treated preferably with cisplatin-based chemotherapy, but many patients are cisplatin-ineligible whereas for those who progress on a platinum-based regimen treatment options are limited. We review key recent data regarding immune checkpoint inhibitors that are changing this treatment landscape. Since May 2016, five different agents targeting the PD-1/PD-L1 pathway (atezolizumab, pembrolizumab, nivolumab, avelumab, durvalumab) have received FDA approval for the treatment of aUC in the platinum-refractory setting, while pembrolizumab and atezolizumab are FDA-approved for cisplatin-ineligible patients in the first-line setting. Clinical outcomes and safety profiles of these agents appear relatively comparable across separate trials; however, only pembrolizumab is supported by level I evidence from a large randomized phase III trial showing overall survival benefit over conventional cytotoxic salvage chemotherapy in the platinum-refractory setting. Pembrolizumab has the highest level of evidence in platinum-refractory aUC, whereas pembrolizumab and atezolizumab have comparable level of evidence in the frontline setting in cisplatin-ineligible patients. Ongoing research is evaluating novel agents, various rational combinations, and sequences, as well as predictive and prognostic biomarkers.

  10. Merkel cell carcinoma: Outcome and role of radiotherapy

    International Nuclear Information System (INIS)

    Salvador Alonso, R.; Lahbabi, I.; Ben Hassel, M.; Boisselier, P.; Crevoisier, R. de; Chaari, N.; Lesimple, T.; Chevrier, S.

    2008-01-01

    Merkel cell carcinoma (M.C.C.) are rare neuroendocrine malignant tumor of the skin, occurring in elderly patients. It affects primarily the sun-exposed areas of the skin, with approximately 50% of all tumors occurring in the face and neck and 40% in the extremities. Immunohistochemical markers (C.K.20+, C.K.7- and T.T.F.1-) are used to distinguish between M.C.C. and other tumors. M.C.C. have a tendency to rapid local progression, frequent spread to regional lymph nodes and distant metastases. Due to the rarity of the disease, the optimal treatment has not been fully defined. Localized stages (stages I and II) are treated by surgical excision of the primary tumor (with 2 to 3 cm margin) and lymphadenectomy in case of node-positive disease, followed by external beam radiotherapy (E.B.R.T.) to a total dose of 50 to 60 Gy in the tumor bed. Adjuvant E.B.R.T. has been shown to decrease markedly locoregional recurrences and to increase survival in recent studies. Treatment of lymph nodes area is more controversial. Chemotherapy is recommended only for metastatic disease. (authors)

  11. The role of fruit bats in the transmission of pathogenic leptospires in Australia

    DEFF Research Database (Denmark)

    Tulsiani, Suhella; Cobbold, R N; Graham, G C

    2011-01-01

    Although antileptospiral antibodies and leptospiral DNA have been detected in Australian fruit bats, the role of such bats as infectious hosts for the leptospires found in rodents and humans remains unconfirmed. A cohort-design, replicated survey was recently conducted in Far North Queensland, Au...... serovars), as disseminators of pathogens to rodent populations. Stringent quantitative risk analysis of the present and similar data, to explore their implications in terms of disease prevalence and wildlife population dynamics, is recommended....

  12. The role of natural environments in the evolution of resistance traits in pathogenic bacteria

    OpenAIRE

    Martinez, Jose L.

    2009-01-01

    Antibiotics are among the most valuable compounds used for fighting human diseases. Unfortunately, pathogenic bacteria have evolved towards resistance. One important and frequently forgotten aspect of antibiotics and their resistance genes is that they evolved in non-clinical (natural) environments before the use of antibiotics by humans. Given that the biosphere is mainly formed by micro-organisms, learning the functional role of antibiotics and their resistance elements in nature has releva...

  13. The role of human papillomavirus in oral squamous cell carcinoma: myth and reality.

    Science.gov (United States)

    Kansy, Katinka; Thiele, Oliver; Freier, Kolja

    2014-06-01

    As the traditional risk factors for oral squamous cell carcinoma, especially tobacco, decline, new potential causative agents become the focus of research. Since the discovery of human papillomavirus (HPV) and its importance in carcinogenesis in cervical cancer, a lot of research has been undertaken to define its role in different types of cancer. In the present study, we evaluate the role of high-risk HPV types in initiation and progression of oral squamous cell carcinoma (OSCC) using a systematic review of the current literature. A literature research with the search term "HPV oral squamous cell carcinoma" was performed via PubMed. Results were screened systematically for relevance and classified into the following categories: molecular biology, genetics, clinical aspects, and prevalence. Articles were then further analyzed to assess quality. The literature research led to 527 results, with an overall HPV prevalence of 30.1 % in OSCCs. The most frequently identified subtypes were HPV-16 and HPV-18 (25.4 and 18.1 %, respectively). Prognostic relevance of HPV was discussed controversially. HPV detection via polymerase chain reaction is the most established method today. Molecular changes according to carcinogenic pathways described for cervix carcinoma were not routinely found in OSCC. In general, no definite role of high-risk HPV is currently deducible from the literature. High-risk subtypes 16 and 18 are present in the genome in approximately one third of OSCC. Its role as a causative agent is less clear than the role in oropharyngeal tumors. The infection might not be the cause of carcinogenesis in a significant number of patients but may become proportionally more important with the decrease of the classical risk factors of tobacco and alcohol.

  14. Shedding light on the role of photosynthesis in pathogen colonization and host defense

    KAUST Repository

    Garavaglia, Betiana S.; Thomas, Ludivine; Gottig, Natalia; Zimaro, Tamara; Garofalo, Cecilia G.; Gehring, Christoph A; Ottado, Jorgelina

    2010-01-01

    The role of photosynthesis in plant defense is a fundamental question awaiting further molecular and physiological elucidation. To this end we investigated host responses to infection with the bacterial pathogen Xanthomonas axonopodis pv. citri, the pathogen responsible for citrus canker. This pathogen encodes a plant-like natriuretic peptide (XacPNP) that is expressed specifically during the infection process and prevents deterioration of the physiological condition of the infected tissue. Proteomic assays of citrus leaves infected with a XacPNP deletion mutant (DeltaXacPNP) resulted in a major reduction in photosynthetic proteins such as Rubisco, Rubisco activase and ATP synthase as a compared with infection with wild type bacteria. In contrast, infiltration of citrus leaves with recombinant XacPNP caused an increase in these host proteins and a concomitant increase in photosynthetic efficiency as measured by chlorophyll fluorescence assays. Reversion of the reduction in photosynthetic efficiency in citrus leaves infected with DeltaXacPNP was achieved by the application of XacPNP or Citrus sinensis PNP lending support to a case of molecular mimicry. Finally, given that DeltaXacPNP infection is less successful than infection with the wild type, it appears that reducing photosynthesis is an effective plant defense mechanism against biotrophic pathogens.

  15. Shedding light on the role of photosynthesis in pathogen colonization and host defense

    KAUST Repository

    Garavaglia, Betiana S.

    2010-09-01

    The role of photosynthesis in plant defense is a fundamental question awaiting further molecular and physiological elucidation. To this end we investigated host responses to infection with the bacterial pathogen Xanthomonas axonopodis pv. citri, the pathogen responsible for citrus canker. This pathogen encodes a plant-like natriuretic peptide (XacPNP) that is expressed specifically during the infection process and prevents deterioration of the physiological condition of the infected tissue. Proteomic assays of citrus leaves infected with a XacPNP deletion mutant (DeltaXacPNP) resulted in a major reduction in photosynthetic proteins such as Rubisco, Rubisco activase and ATP synthase as a compared with infection with wild type bacteria. In contrast, infiltration of citrus leaves with recombinant XacPNP caused an increase in these host proteins and a concomitant increase in photosynthetic efficiency as measured by chlorophyll fluorescence assays. Reversion of the reduction in photosynthetic efficiency in citrus leaves infected with DeltaXacPNP was achieved by the application of XacPNP or Citrus sinensis PNP lending support to a case of molecular mimicry. Finally, given that DeltaXacPNP infection is less successful than infection with the wild type, it appears that reducing photosynthesis is an effective plant defense mechanism against biotrophic pathogens.

  16. Role and regulation of the orphan AphA protein of quorum sensing in pathogenic Vibrios.

    Science.gov (United States)

    Lu, Renfei; Osei-Adjei, George; Huang, Xinxiang; Zhang, Yiquan

    2018-03-01

    Quorum sensing (QS), a cell-to-cell communication process, is widely distributed in the bacterial kingdom. Bacteria use QS to control gene expression in response to cell density by detecting the signal molecules called autoinducers. AphA protein is the master QS regulator of vibrios operating at low cell density. It regulates the expression of a variety of genes, especially those encoding virulence factors, flagella/motility and biofilm formation. The role and regulation of AphA in vibrios, especially in human pathogenic vibrios, are summarized in this review. Clarification of the roles of AphA will help us to understand the pathogenesis of vibrios.

  17. Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab

    International Nuclear Information System (INIS)

    Bukowski, Ronald M

    2010-01-01

    The biology and pathogenesis of clear cell carcinoma of the kidney has been extensively investgated, and the role of von Hipple-Landau gene inactivation and tumor associated angiogenesis is now recognized. Development of vascular endothelial growth factor inhibitors and phase 3 clinical trials utilizing this class of agents has produced a new treatment paradigm for patients with metastatic renal cell carcinoma (RCC). One of the active regimens identified is the combination of bevacizumab and interferon-α. Recently published reports provided evidence of the clinical and biologic activity of this therapy. The current manuscript reviews the background and rationale for the activity of bevacizumab in RCC, and results from recent clinical trials with this agent alone or in combination with targeted agents or cytokines. The role of this therapy in contrast to other targeted agents is reviewed, and the potential utility as well as questions raised by recent studies are discussed

  18. Role of pelvic lymphadenectomy in stage 1A endometrial carcinoma ...

    African Journals Online (AJOL)

    Introduction: Endometrial cancer is the commonest gynecological cancer mostly affecting women in the postmenopausal age group. There is a debate regarding the need of pelvic lymphadenectomy in managing stage 1A diagnosed preoperatively, we try to evaluate this need. Objective: To evaluate the role of pelvic ...

  19. The radiologist's role in the management of papillary renal cell carcinoma.

    Science.gov (United States)

    Corral de la Calle, M Á; Encinas de la Iglesia, J; Martín López, M R; Fernández Pérez, G C; Águeda Del Bas, D S

    Papillary carcinoma is the second most common renal cell carcinoma. It has a better prognosis than the more frequent clear cell carcinoma, although this does not hold true for advanced cases, because no specific treatment exists. It presents as a circumscribed peripheral tumor (small and homogeneously solid or larger and cystic/hemorrhagic) or as an infiltrating lesion that invades the veins, which has a worse prognosis. Due to their low vascular density, papillary renal cell carcinomas enhance less than other renal tumors, and this facilitates their characterization. On computed tomography, they might not enhance conclusively, and in these cases they are impossible to distinguish from hyperattenuating cysts. Contrast-enhanced ultrasonography and magnetic resonance imaging are more sensitive for detecting vascularization. Other characteristics include a specific vascular pattern, hypointensity on T2-weighted images, restricted water diffusion, and increased signal intensity in opposed phase images. We discuss the genetic, histologic, clinical, and radiological aspects of these tumors in which radiologists play a fundamental role in management. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Characterising the role of GABA and its metabolism in the wheat pathogen Stagonospora nodorum.

    Directory of Open Access Journals (Sweden)

    Oliver Mead

    Full Text Available A reverse genetics approach was used to investigate the role of γ-aminobutyric acid metabolism in the wheat pathogenic fungus Stagonospora nodorum. The creation of mutants lacking Sdh1, the gene encoding succinic semialdehyde dehydrogenase, resulted in strains that grew poorly on γ-aminobutyric acid as a nitrogen source. The sdh1 mutants were more susceptible to reactive oxygen stress but were less affected by increased growth temperatures. Pathogenicity assays revealed that the metabolism of γ-aminobutyric acid is required for complete pathogenicity. Growth assays of the wild-type and mutant strains showed that the inclusion of γ-aminobutyric acid as a supplement in minimal media (i.e., not as a nitrogen or carbon source resulted in restricted growth but increased sporulation. The addition of glutamate, the precursor to GABA, had no effect on either growth or sporulation. The γ-aminobutyric acid effect on sporulation was found to be dose dependent and not restricted to Stagonospora nodorum with a similar effect observed in the dothideomycete Botryosphaeria sp. The positive effect on sporulation was assayed using isomers of γ-aminobutyric acid and other metabolites known to influence asexual development in Stagonospora nodorum but no effect was observed. These data demonstrate that γ-aminobutyric acid plays an important role in Stagonospora nodorum in responding to environmental stresses while also having a positive effect on asexual development.

  1. Immunohistochemical analysis of the role and relationship between Notch-1 and Oct-4 expression in urinary bladder carcinoma.

    Science.gov (United States)

    Abdou, Asmaa Gaber; El-Wahed, Moshira Mohammed Abd; Kandil, Mona Abd-Elhalim; Samaka, Rehab Monir; Elkady, Noha

    2013-10-01

    Most tumors contain a minor population of cancer stem cells that are responsible for tumor heterogeneity, resistance to therapy and recurrence. Oct-4 is a transcription factor responsible for self-renewal of stem cells, whereas the Notch family of receptors and ligands may play a pivotal role in the regulation of stem cell maintenance and differentiation. This study aimed at an evaluation of Oct-4 and Notch-1 expression in both carcinoma and stromal cells of 83 cases of primary bladder carcinoma and to study the relationship between them. Notch-1 was expressed in carcinoma and stromal cells of all malignant cases, where expression in both cell types was correlated with parameters indicating differentiation, such as low grade (p bladder carcinoma, such as poor differentiation (p = 0.001), high proliferation (p bladder carcinoma, where they may cooperate in the progression of bladder carcinoma by acquiring aggressive features, such as a liability for recurrence and dissemination. Notch-1 is also expressed in both carcinoma cells and stromal cells of bladder carcinoma. Although they could share in enhancing differentiation, stromal expression of Notch-1 may have a bad impact, possibly through up-regulation of the active nuclear form of Oct-4 in carcinoma cells. © 2013 APMIS Published by Blackwell Publishing Ltd.

  2. Role of carbon-11 choline PET/CT in the management of uterine carcinoma. Initial experience

    International Nuclear Information System (INIS)

    Sofue, Keitaro; Sawada, Morio; Arai, Yasuaki; Tateishi, Ukihide; Inoue, Tomio; Maeda, Tetsuo; Sugimura, Kazuro; Terauchi, Takashi; Kano, Daisuke

    2009-01-01

    The present study was conducted to clarify the role of carbon-11 choline ( 11 C-choline) positron emission tomography (PET)/computed tomography (CT) in the management of uterine carcinoma. Twenty-two patients who underwent 11 C-choline PET/CT and pelvic MRI were evaluated retrospectively. The images were reviewed by a board-certified radiologist and a nuclear medicine specialist who were unaware of any clinical information, and a consensus was reached. Diagnostic accuracy of PET/CT was evaluated for staging. The reference standard consisted of histological examination (n=17) and follow-up conventional CT (n=5). In five patients with cervical carcinoma, 11 C-choline PET/CT was performed before and after treatment that consisted of cisplatin infusion and subsequent radiotherapy. Standardized uptake value (SUV) was compared with unidimensional and volumetric measurements that were made on magnetic resonance images (MRI) before and after treatment. Based on PET/CT interpretations, the reviewers correctly classified tumor (T) stage in 8 patients (47%), nodes (N) stage in 21 patients (96%), metastasis (M) stage in 20 patients (91%), and tumor, nodes and metastasis (TNM) stage in 15 patients (88%). Tumor size, volume, and SUV decreased after treatment in five patients with cervical carcinoma. Using the Pearson correlation test, a significant correlation was found between the reduction rate of SUV and reduction rate of tumor volume. 11 C-choline PET/CT is an accurate means for the management of patients with uterine carcinoma. The combination of 11 C-choline PET/CT and MRI increases the accuracy of staging in patients with uterine carcinoma. (author)

  3. Metastatic clear cell carcinoma of the kidney: therapeutic role of bevacizumab

    Directory of Open Access Journals (Sweden)

    Ronald M Bukowski

    2010-03-01

    Full Text Available Ronald M BukowskiCleveland Clinic Taussig Cancer Center, CCF Lerner College of Medicine of CWRU Cleveland, OH, USAAbstract: The biology and pathogenesis of clear cell carcinoma of the kidney has been extensively investgated, and the role of von Hipple-Landau gene inactivation and tumor associated angiogenesis is now recognized. Development of vascular endothelial growth factor inhibitors and phase 3 clinical trials utilizing this class of agents has produced a new treatment paradigm for patients with metastatic renal cell carcinoma (RCC. One of the active regimens identified is the combination of bevacizumab and interferon-α. Recently published reports provided evidence of the clinical and biologic activity of this therapy. The current manuscript reviews the background and rationale for the activity of bevacizumab in RCC, and results from recent clinical trials with this agent alone or in combination with targeted agents or cytokines. The role of this therapy in contrast to other targeted agents is reviewed, and the potential utility as well as questions raised by recent studies are discussed.Keywords: metastatic renal cell carcinoma, bevacizumab, interferon-α

  4. The nonstructural proteins of Nipah virus play a key role in pathogenicity in experimentally infected animals.

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    Misako Yoneda

    Full Text Available Nipah virus (NiV P gene encodes P protein and three accessory proteins (V, C and W. It has been reported that all four P gene products have IFN antagonist activity when the proteins were transiently expressed. However, the role of those accessory proteins in natural infection with NiV remains unknown. We generated recombinant NiVs lacking V, C or W protein, rNiV(V-, rNiV(C-, and rNiV(W-, respectively, to analyze the functions of these proteins in infected cells and the implications in in vivo pathogenicity. All the recombinants grew well in cell culture, although the maximum titers of rNiV(V- and rNiV(C- were lower than the other recombinants. The rNiV(V-, rNiV(C- and rNiV(W- suppressed the IFN response as well as the parental rNiV, thereby indicating that the lack of each accessory protein does not significantly affect the inhibition of IFN signaling in infected cells. In experimentally infected golden hamsters, rNiV(V- and rNiV(C- but not the rNiV(W- virus showed a significant reduction in virulence. These results suggest that V and C proteins play key roles in NiV pathogenicity, and the roles are independent of their IFN-antagonist activity. This is the first report that identifies the molecular determinants of NiV in pathogenicity in vivo.

  5. Role of retinoic acid receptors in squamous-cell carcinoma in human esophagus

    DEFF Research Database (Denmark)

    Bergheim, I.; Wolfgarten, E.; Bollschweiler, E.

    2005-01-01

    BACKGROUND: Worldwide, cancer in the esophagus ranks among the 10 most common cancers. Alterations of retinoic acid receptors (e.g. RARalpha, beta, gamma, and RXRalpha, beta, gamma) expression is considered to play an important role in development of squamous-cell carcinoma (SCC), which is the most...... common esophageal cancer. Alcohol consumption and smoking, which can alter retinoic acid receptor levels, have been identified as key risk factors in the development of carcinoma in the aero-digestive tract. Therefore, the aim of the present study was to evaluate protein levels of retinoic acid receptors...... were found for RARalpha, beta, and RXRbeta protein levels between normal esophageal tissue of patients and that of controls. CONCLUSION: In conclusion, results of the present study suggest that alterations of retinoic acid receptors protein may contribute in the development of SCC in esophagus...

  6. C-type lectins: their network and roles in pathogen recognition and immunity.

    Science.gov (United States)

    Mayer, Sabine; Raulf, Marie-Kristin; Lepenies, Bernd

    2017-02-01

    C-type lectins (CTLs) represent the most complex family of animal/human lectins that comprises 17 different groups. During evolution, CTLs have developed by diversification to cover a broad range of glycan ligands. However, ligand binding by CTLs is not necessarily restricted to glycans as some CTLs also bind to proteins, lipids, inorganic molecules, or ice crystals. CTLs share a common fold that harbors a Ca 2+ for contact to the sugar and about 18 invariant residues in a phylogenetically conserved pattern. In vertebrates, CTLs have numerous functions, including serum glycoprotein homeostasis, pathogen sensing, and the initiation of immune responses. Myeloid CTLs in innate immunity are mainly expressed by antigen-presenting cells and play a prominent role in the recognition of a variety of pathogens such as fungi, bacteria, viruses, and parasites. However, myeloid CTLs such as the macrophage inducible CTL (Mincle) or Clec-9a may also bind to self-antigens and thus contribute to immune homeostasis. While some CTLs induce pro-inflammatory responses and thereby lead to activation of adaptive immune responses, other CTLs act as inhibitory receptors and dampen cellular functions. Since CTLs are key players in pathogen recognition and innate immunity, targeting CTLs may be a promising strategy for cell-specific delivery of drugs or vaccine antigens and to modulate immune responses.

  7. The role of the arbuscular mycorrhiza-associated rhizobacteria in the biocontrol of soilborne phyto pathogens

    Energy Technology Data Exchange (ETDEWEB)

    Lioussanne, L.

    2010-07-01

    The mutualistic symbiosis of most land plants with arbuscular mycorrhizal (AM) fungi has been shown to favor mineral and water nutrition and to increase resistance to abiotic and biotic stresses. This review reports the main mechanisms involved in the control of the disease symptoms and of the intraradical proliferation of soilborne phytopathogens by root colonization with AM fungi, with a special emphasis on the role of the rhizobacteria shown to be specifically associated with the AM extraradical network and the mycorrhizosphere (the soil zone with particular characteristics under the influence of the root/AM association). The mycorrhizosphere would constitute an environment conducive to microorganisms antagonistic to pathogen proliferation. Moreover, attempts to identify rhizobacteria from AM structures and/or the mycorrhizosphere often lead to the isolation of organisms showing strong properties of antagonism on various soilborne pathogens. The ability of AM fungi to control soilborne diseases would be strongly related to their capacity to specifically stimulate the establishment of rhizobacteria unfavorable to pathogen development within the mycorrhizosphere before root infection. Current knowledge concerning the mechanisms involved in AM/rhizobacteria interactions are also described in this review. (Author) 101 refs.

  8. The specific role of radiotherapy in the management of prostate carcinoma at different stages of tumor development

    International Nuclear Information System (INIS)

    Huber, J.

    1987-01-01

    The study described here was based on the case reports of 135 patients of the Radiological Department at Kiel's University Hospital, who were treated for carcinomas of the prostate at any time during the period between 1965 and 1980. It was the aim of these evaluations to define the particular role of radiotherapy in the management of carcinomas of the prostate and to compare it to that of other methods of treatment (hormones, surgery). Percutaneous local irradiation of the carcinoma or irradiation of metastases were the criteria of inclusion into this retrospective study. The stage of the tumour was a decisive factor in the final analysis of the results. (orig.) [de

  9. An antifungal role of hydrogen sulfide on the postharvest pathogens Aspergillus niger and Penicillium italicum.

    Directory of Open Access Journals (Sweden)

    Liu-Hui Fu

    Full Text Available In this research, the antifungal role of hydrogen sulfide (H2S on the postharvest pathogens Aspergillus niger and Penicillium italicum growing on fruits and under culture conditions on defined media was investigated. Our results show that H2S, released by sodium hydrosulfide (NaHS effectively reduced the postharvest decay of fruits induced by A. niger and P. italicum. Furthermore, H2S inhibited spore germination, germ tube elongation, mycelial growth, and produced abnormal mycelial contractions when the fungi were grown on defined media in Petri plates. Further studies showed that H2S could cause an increase in intracellular reactive oxygen species (ROS in A. niger. In accordance with this observation we show that enzyme activities and the expression of superoxide dismutase (SOD and catalase (CAT genes in A. niger treated with H2S were lower than those in control. Moreover, H2S also significantly inhibited the growth of Saccharomyces cerevisiae, Rhizopus oryzae, the human pathogen Candida albicans, and several food-borne bacteria. We also found that short time exposure of H2S showed a microbicidal role rather than just inhibiting the growth of microbes. Taken together, this study suggests the potential value of H2S in reducing postharvest loss and food spoilage caused by microbe propagation.

  10. Anticardiolipin antibodies in classic pediatric hemolytic-uremic syndrome: a possible pathogenic role.

    Science.gov (United States)

    Ardiles, L G; Olavarría, F; Elgueta, M; Moya, P; Mezzano, S

    1998-01-01

    Anticardiolipin (aCL) antibodies have been associated with thrombocytopenia, hemolytic anemia and an increased risk of thrombosis in different vascular locations, even in the absence of lupus. The classic hemolytic-uremic syndrome is a postinfectious acute renal failure characterized by hemolytic anemia, thrombocytopenia and the presence of widespread glomerular thrombosis in the kidney, with pathogenic mechanisms that remain to be identified. In order to establish the frequency of aCL antibodies in this syndrome and to identify a possible role in the pathogenesis and clinical manifestations, 17 patients were studied during the reactant phase of the disease looking for an association between the presence of aCL antibodies (isotypes IgG, IgA and IgM) and the main clinical variables of the syndrome. In 8 patients IgG aCL was present, 2 patients had IgM aCL, and 1 had IgA antibodies on the solid-phase ELISA aCL assays, but no association could be demonstrated with the clinical variables studied. Although it might correspond to an epiphenomenon related to the triggering intestinal infection, a pathogenic role cannot be discarded and additional studies should be performed.

  11. Bovine mastitis disease/pathogenicity: evidence of the potential role of microbial biofilms.

    Science.gov (United States)

    Gomes, Fernanda; Saavedra, Maria José; Henriques, Mariana

    2016-04-01

    Bovine mastitis (BM) is a disease with high incidence worldwide and one of the most relevant bovine pathologies and the most costly to the dairy industry. BM is an inflammation of the udder and represents one of the most difficult veterinary diseases to control. Biofilm formation is considered a selective advantage for pathogens causing mastitis, facilitating bacterial persistence in the udder. In fact, recently some authors drew attention to the biofilm formation ability presented by several mastitis causing pathogens and to its possible relation with recurrent mastitis infections and with the increased resistance to antimicrobial agents and host immune defence system. Actually, up to now, several researchers reported the potential role of cells in this mode of growth in the previous facts mentioned. As a consequence of the presence of biofilms, the infection here focused is more difficult to treat and eradicate, making this problem a more relevant pressing issue. Thus, we believe that a deeper knowledge of these structures in mastitis can help to determine the best control strategy to be used in veterinary practice in order to reduce losses in the dairy industry and to ensure milk safety and quality. The aim of this paper was to review the existing research and consequently to provide an overview of the role of biofilms in BM infections. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Role of glycogen synthase kinase-3 beta in the inflammatory response caused by bacterial pathogens

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    Cortés-Vieyra Ricarda

    2012-06-01

    Full Text Available Abstract Glycogen synthase kinase 3β (GSK3β plays a fundamental role during the inflammatory response induced by bacteria. Depending on the pathogen and its virulence factors, the type of cell and probably the context in which the interaction between host cells and bacteria takes place, GSK3β may promote or inhibit inflammation. The goal of this review is to discuss recent findings on the role of the inhibition or activation of GSK3β and its modulation of the inflammatory signaling in monocytes/macrophages and epithelial cells at the transcriptional level, mainly through the regulation of nuclear factor-kappaB (NF-κB activity. Also included is a brief overview on the importance of GSK3 in non-inflammatory processes during bacterial infection.

  13. Role of glycogen synthase kinase-3 beta in the inflammatory response caused by bacterial pathogens.

    Science.gov (United States)

    Cortés-Vieyra, Ricarda; Bravo-Patiño, Alejandro; Valdez-Alarcón, Juan J; Juárez, Marcos Cajero; Finlay, B Brett; Baizabal-Aguirre, Víctor M

    2012-06-12

    Glycogen synthase kinase 3β (GSK3β) plays a fundamental role during the inflammatory response induced by bacteria. Depending on the pathogen and its virulence factors, the type of cell and probably the context in which the interaction between host cells and bacteria takes place, GSK3β may promote or inhibit inflammation. The goal of this review is to discuss recent findings on the role of the inhibition or activation of GSK3β and its modulation of the inflammatory signaling in monocytes/macrophages and epithelial cells at the transcriptional level, mainly through the regulation of nuclear factor-kappaB (NF-κB) activity. Also included is a brief overview on the importance of GSK3 in non-inflammatory processes during bacterial infection.

  14. Role of computed tomography (CT scan in staging of cervical carcinoma

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    T V Prasad

    2014-01-01

    Full Text Available Background & objectives: Staging of cervical carcinoma is done clinically using International Federation of Obstetrics and Gynecology (FIGO guidelines. It is based on physical examination findings and also includes results of biopsy, endoscopy and conventional radiological tests like chest radiograph, intravenous urography and barium enema. These conventional radiological investigations have largely been replaced by computed tomography (CT and magnetic resonance imaging (MRI at present. FIGO staging system does not consider CT and MRI mandatory; however, use of these modalities are encouraged. This prospective study was conducted to determine the role of CT in staging work up in women diagnosed with cervical carcinoma. Methods: Fifty three women diagnosed with cervical carcinoma were evaluated with contrast enhanced CT scan of abdomen and pelvis. CT scan images were especially evaluated to determine tumour size, invasion of parmetrium, pelvic walls, rectum, urinary bladder and ureters, pelvic or retroperitoneal lymphadenopathy and distant metastases. CT findings were associated with clinical findings and staging, including findings from cystoscopy and sigmoidoscopy. Results: There was a poor agreement between clinical and CT staging of cervical carcinoma. Primary tumour was demonstrated on CT in 36 (70% of 53 patients. CT underestimated the parametrial, vaginal and pelvic wall invasion when compared with physical examination. CT overestimated the urinary bladder and rectal invasion when compared with cysto-sigmoidoscopy, however, CT had 100 per cent negative predictive value (NPV to exclude bladder and rectal involvement. CT detection of lymph node enlargement and lung metastases influenced the management. Interpretation & conclusions: Our findings show that CT scan does not reliably correlate with clinical FIGO staging of cervical cancer. However, it can detect urinary obstruction as well as nodal or distant metastases and thus improves the

  15. Frequency of carcinoma of prostate in clinically benign prostatic hyperplasia and role of different screening tests

    International Nuclear Information System (INIS)

    Rasool, M.; Saeed, M.; Ali, S.; Saleem, M.S.; Saleem, M.S.

    2012-01-01

    Objectives: To assess the frequency of carcinoma in clinically benign prostatic hyperplasia and role. of digital rectal examination (DRE) and prostatic specific antigen (PSA) in assessment of these patients. Data source: Patients admitted to the Department of Urology and Renal Transplantation with lower urinary tract symptoms (LUTS) due to enlarged prostate. Design of study: Descriptive Study Place and Duration of Study: Department of Urology and Renal Transplantation, Quaid-e-Azam Medical College Bahawal Victoria Hospital, Bahawalpur, from January 2007 to December 2010. Patients and Methods: Patients presenting with lower urinary tract symptoms over the age of 50 years were evaluated on International Prostate Symptoms Score (IPSS), clinically examined and post-voiding residual urine determined on abdominal ultrasonography. The selection criteria were; Refractory retention of urine, Severe IPSS, absence of signs of malignancy on Digital Rectal Examination (DRE) and post-voiding residual urine more than 100 mI. Thus a total 300 patients were selected. Patient's blood sample was sent to laboratory to assess Prostate Specific Antigen (PSA) level pre-operatively. All these patients underwent either transurethral resection of prostate (TURP) or transvesical prostatectomy (TVP) and prostatic tissue was sent for histopathology. Results: In this study, 13.33% patients were found to have carcinoma of prostate in spite of being clinically benign prostates in all patients, irrespective of PSA range. The PSA value was found 4ngjml. In this study, 9.95% patients had carcinoma prostate in spite having normal PSA and benign prostate on DRE while with rising PSA levels and normal DRE, chances of malignancy detection increases (66.67% ). Conclusion: We conclude that although frequency is low the possibility of malignancy in clinically benign enlarged prostate should be borne in mind whenever subjecting the patient for screening, assessment and treatment. DRE alone is insufficient

  16. Methyl esterification of pectin plays a role during plant-pathogen interactions and affects plant resistance to diseases.

    Science.gov (United States)

    Lionetti, Vincenzo; Cervone, Felice; Bellincampi, Daniela

    2012-11-01

    The cell wall is a complex structure mainly composed by a cellulose-hemicellulose network embedded in a cohesive pectin matrix. Pectin is synthesized in a highly methyl esterified form and is de-esterified in muro by pectin methyl esterases (PMEs). The degree and pattern of methyl esterification affect the cell wall structure and properties with consequences on both the physiological processes of the plants and their resistance to pathogens. PME activity displays a crucial role in the outcome of the plant-pathogen interactions by making pectin more susceptible to the action of the enzymes produced by the pathogens. This review focuses on the impact of pectin methyl esterification in plant-pathogen interactions and on the dynamic role of its alteration during pathogenesis. Copyright © 2012 Elsevier GmbH. All rights reserved.

  17. Metastatic squamous cell carcinoma of the gingiva appearing as a solitary branchial cyst carcinoma: diagnostic role of PET/CT.

    Science.gov (United States)

    Zhang, Xiong-Xin; Zhao, Kui; Zhou, Shui-Hong; Wang, Qin-Ying; Liu, Jian-Hua; Lu, Zhong-Jie

    2014-01-01

    We herein present a case of a left cervical cystic mass, for which the initial pathological diagnosis was branchial cleft cyst carcinoma (following complete mass excision). Thorough postoperative examinations, including with FDG positron emission tomography/computed tomography (PET/CT), revealed a primary tumor in the retromolar region of the left mandible. A 52-year-old female presented with a 2-month history of a painless, progressively enlarged left-sided neck mass. Fine-needle aspiration biopsy suggested a branchial cleft cyst. Physical examination revealed a 3 × 3-cm smooth, tender mass in the upper-left neck and anterior border of the sternocleidomastoid muscle. Examination using nasendoscopy and a strobolaryngoscope revealed no abnormalities of the nasal cavity, nasopharynx, oropharynx, hypopharynx or larynx. MRI of the neck revealed a solitary, round, cystic mass under the left parotid gland. The mass was excised completely. Pathologic results indicated a branchial cleft cyst carcinoma. According to the diagnostic criteria for a branchial cleft cystic carcinoma, PET/CT was performed to detect the occult primary site. PET/CT revealed high FDG uptake in the tooth root of the left mandible. Frozen sections of the mass were indicative of moderate, differentiated squamous cell carcinoma. The carcinoma in the retromolar region of the left mandible was locally excised under general anesthesia. A partial left maxillectomy, partial mandibulectomy, and left radical neck dissection were performed. The patient received postoperative concurrent chemoradiotherapy, and was disease-free at the 8-month follow-up. True branchial cleft cyst carcinoma is rare: once diagnosed, it should be distinguished from metastatic cystic cervical lymph and occult primary carcinoma. FDG PET/CT is useful in the identification of occult primary tumor.

  18. Role of soil, crop debris, and a plant pathogen in Salmonella enterica contamination of tomato plants.

    Directory of Open Access Journals (Sweden)

    Jeri D Barak

    Full Text Available BACKGROUND: In the U.S., tomatoes have become the most implicated vehicle for produce-associated Salmonellosis with 12 outbreaks since 1998. Although unconfirmed, trace backs suggest pre-harvest contamination with Salmonella enterica. Routes of tomato crop contamination by S. enterica in the absence of direct artificial inoculation have not been investigated. METHODOLOGY/PRINCIPAL FINDINGS: This work examined the role of contaminated soil, the potential for crop debris to act as inoculum from one crop to the next, and any interaction between the seedbourne plant pathogen Xanthomonas campestris pv. vesicatoria and S. enterica on tomato plants. Our results show S. enterica can survive for up to six weeks in fallow soil with the ability to contaminate tomato plants. We found S. enterica can contaminate a subsequent crop via crop debris; however a fallow period between crop incorporation and subsequent seeding can affect contamination patterns. Throughout these studies, populations of S. enterica declined over time and there was no bacterial growth in either the phyllosphere or rhizoplane. The presence of X. campestris pv. vesicatoria on co-colonized tomato plants had no effect on the incidence of S. enterica tomato phyllosphere contamination. However, growth of S. enterica in the tomato phyllosphere occurred on co-colonized plants in the absence of plant disease. CONCLUSIONS/SIGNIFICANCE: S. enterica contaminated soil can lead to contamination of the tomato phyllosphere. A six week lag period between soil contamination and tomato seeding did not deter subsequent crop contamination. In the absence of plant disease, presence of the bacterial plant pathogen, X. campestris pv. vesicatoria was beneficial to S. enterica allowing multiplication of the human pathogen population. Any event leading to soil contamination with S. enterica could pose a public health risk with subsequent tomato production, especially in areas prone to bacterial spot disease.

  19. The role of CT in the diagnosis of bronchogenic carcinoma not detected by plain radiograph

    International Nuclear Information System (INIS)

    Choi, Byoung Wook; Choe, Kyu Ok; Lee, Je Hyuk; Ryu, Seok Jong

    2000-01-01

    To evaluate the role of CT and CT features in the diagnosis of bronchogenic carcinomas not detected by plain radiography. Eighteen patients [19 primary cancer lesions, M:F=16:2, aged 43-75 (mean, 56.3) years] with lung cancer initially not detected by plain radiography were involved in this study. CT scanning was performed in all cases, and fibrobronchoscopy, and sputum cytology, each in 17. Lesions were divided into two groups: the central type, if on or proximal to the segmental bronchus, and the peripheral type, if distal to this. Plain radiographs were analysed for possible causes of occultness and for clinical characteristics including cell type, location, and size. We focused on the CT findings, comparing cases undetected by CT with those undetected by bronchoscopy. In the central type, the cause of occultness, as seen on plain radiographs, was small size, no secondary findings, or confusing shadow from hilar vessels. In the peripheral type, the cause was overlapping shadow due to normal structures of the chest, or combined diseases. Eight lesions were first detected by sputum cytology, 6 by bronchoscopy, and 5 by CT. Fourteen lesions were the central type (main bronchus 2, lobar bronchus 7, segmental bronchus 5), and five were peripheral. Central-type lesions were either squamous cell carcinoma (n=11), adenocarcinoma (n=1), small cell carcinoma (n=1), or large cell carcinoma (n=1). The peripheral type were either squamous cell carcinoma (n=2), adenocarcinoma (n=2), or large cell carcinoma (n=1). Size ranged from 0.2 to 4(mean, 2; central 1.7, peripheral 2.8) cm. Surgical resection was possible in 15 patients (16 cancers, including 13 at stage I). Only two were at a stage which rendered them unresectable. CT revealed 13 cancers, including all those which were peripheral. The finding were endobronchial nodule (n=4), bronchial wall thickening (n=1), perihilar mass (n=3), parenchymal mass (n=2), and subpleural mass (n=3). In six central-type cases [endobronchial

  20. The role of hypoxia, p53, and apoptosis in human cervical carcinoma pathogenesis

    International Nuclear Information System (INIS)

    Kim, Charlotte Y.; Tsai, Mitchell H.; Osmanian, Cynthia; Calkins, Dennise P.; Graeber, Thomas G.; Greenspan, David L.; Kennedy, Andrew S.; Rinker, Lillian H.; Varia, Mahesh A.; DiPaolo, Joseph A.; Peehl, Donna M.; Raleigh, James A.; Giaccia, Amato J.

    1997-01-01

    Objective: Low oxygen tension in the tumor microenvironment may have an important role during tumor growth, and is of particular prognostic significance in human cervical carcinoma. Because some human papillomavirus (HPV) infections are associated with cervical neoplasia, the relationship between hypoxia and apoptosis in primary cervical epithelial cells containing HPV16 E6 and E7, intact HPV 16 genome, and HPV positive cervical carcinoma cell lines, was examined. In addition, the relationship between hypoxia and apoptosis in spontaneous human cervical carcinomas was determined in situ. Materials and Methods: Primary normal human cervical epithelial cells were infected with retroviral vectors containing HPV16 E6 and E7 or transfected with a plasmid containing the whole HPV 16 genome. Clones were selected in neomycin containing medium. Exponentially growing cells were incubated under aerobic conditions (20% O 2 ), anaerobic conditions (0.02% O 2 ), or irradiated with 6 Gy. Analysis of apoptotic cells was performed by staining with Hoechst dye and propidium iodide and viewing with a fluorescent microscope. To determine the level of expression of the apoptotic modulators p53 and Bax, immunoblots were performed on whole cell extracts from treated cells. A clinical tumor hypoxia study was conducted at the University of North Carolina utilizing pimonidazole, a 2-nitroimidazole compound which binds irreversibly to cellular macromolecules under low oxygen conditions. Nine patients were enrolled with biopsy proven squamous cell carcinoma of the cervix and no prior treatment. Biopsies of the gross tumor were obtained after pimonidazole infusion. Contiguous histological sections were analyzed for hypoxia using a immunohistochemical technique and for apoptosis using TUNEL. Results: In vitro, hypoxia uncoupled p53 from E6 mediated degradation, and stimulated both p53 induction and apoptosis in primary cervical epithelial cells infected with the HPV E6 and E7 genes. In contrast

  1. Prognostic role of microRNA-150 in various carcinomas: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Wang W

    2016-03-01

    Full Text Available Wei Wang, Xinshuai Wang, Yali Zhang, Dan Wang, Hui Gao, Lijuan Wang, Shegan Gao Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, People’s Republic of China Objective: MicroRNA-150 (miR-150 was revealed to be an attractive prognostic biomarker in recent studies. However, the prognostic significance of miR-150 expression in cancer remains inconclusive. The aim of this study was to summarize the global predicting role of miR-150 in survival in patients with various carcinomas.Methods: Eligible studies were identified through multiple search strategies. Data were extracted from the studies by investigating the relationship between miR-150 expression and survival in patients with cancer. A meta-analysis of the hazard ratio (HR was then performed to evaluate the prognostic role of miR-150 in different tumors. Pooled HRs of miR-150 for overall survival and progression-free survival were calculated to measure the effect of miR-150 expression on prognosis.Results: This meta-analysis included nine published studies concerning various carcinomas. Our results indicate that an elevated miR-150 expression is associated with an enhanced overall survival in the digestive tract cancer subgroup (HR =0.57, 95% confidence interval [CI]: 0.37–0.90 and a poor progression-free survival in various cancers (HR =3.08, 95% CI: 2.00–4.75.Conclusion: miR-150 may have the potential to become a new useful prognostic factor to monitor cancer prognosis and progression. However, given the current insufficient relevant data, further clinical studies are needed. Keywords: microRNA-150, carcinomas, prognosis, meta-analysis

  2. Role of endoscopic ultrasound in diagnosis and management of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Koduru P

    2015-10-01

    Full Text Available Pramoda Koduru,1 Rei Suzuki,2 Sundeep Lakhtakia,3 Mohan Ramchandani,3 Dadang Makmun,4 Manoop S Bhutani,1 1Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Department of Gastroenterology and Rheumatology, Fukushima University School of Medicine, Fukushima, Japan; 3Asian Institute of Gastroenterology, Hyderabad, India; 4University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia Abstract: Hepatocellular carcinoma (HCC is an aggressive tumor and a leading cause of cancer-related deaths globally. The mortality rate remains high despite many advances in treatment. HCC is frequently diagnosed late in its course due to lack of classical symptoms at earlier stages. Endoscopic ultrasound (EUS has emerged as an important diagnostic tool for the diagnostic evaluation, staging, and treatment of gastrointestinal tract disorders. EUS-guided fine needle aspiration has been a valuable addition to EUS by being able to obtain tissue under direct visualization. Here, we review the potential role of EUS in the diagnosis and management of HCC. EUS seems to be a safe and reliable alternative method for obtaining tissue for diagnosis of liver cancer, especially for lesions that are inaccessible by traditional methods. EUS could play an important role in the diagnosis and management of HCC. Keywords: endoscopic ultrasound, fine needle aspiration, hepatocellular carcinoma, hepatoma

  3. Essential role of STX6 in esophageal squamous cell carcinoma growth and migration

    Energy Technology Data Exchange (ETDEWEB)

    Du, Jin [Department of Cardiothoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029 (China); Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028 (China); Liu, Xiang [Department of Cardiothoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029 (China); Wu, Yanhu, E-mail: wuyanhu@njmu.edu.cn [Department of Cardiothoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029 (China); Zhu, Jinfu; Tang, Yihu [Department of Cardiothoracic Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029 (China)

    2016-03-25

    Abnormalities in endosomes, or dysregulation in their trafficking, play an important role directly in many diseases including oncogenesis. Syntaxin-6 (STX6) is involved in diverse cellular functions in a variety of cell types and has been shown to regulate many intracellular membrane trafficking events such as endocytosis, recycling and anterograde and retrograde trafficking. However, its expression pattern and biological functions in esophageal squamous cell carcinoma (ESCC) remained unknown. Here, we have found that the expression of STX6 was up-regulated in ESCC samples, its expression was significantly correlated with tumor size, histological differentiation, lymph node metastasis and depth. On one hand, STX6 silencing inhibited ESCC cells viability and proliferation in a p53-dependent manner. On the other hand, STX6 effect integrin trafficking and regulate ESCC cells migration. Taken together, our study revealed the oncogenic roles of STX6 in the progression of ESCC, and it might be a valuable target for ESCC therapy.

  4. Role of fascin in the proliferation and invasiveness of esophageal carcinoma cells

    International Nuclear Information System (INIS)

    Xie, J.J.; Xu, L.Y.; Zhang, H.H.; Cai, W.J.; Mai, R.Q.; Xie, Y.M.; Yang, Z.M.; Niu, Y.D.; Shen, Z.Y.; Li, E.M.

    2005-01-01

    Fascin, an actin-bundling protein, induces membrane protrusions and increases cell motility in various transformed cells. The overexpression of fascin in esophageal squamous cell carcinoma (ESCC) has been described only recently, but the roles and mechanism still remained unclear. Here, by using RNA interference (RNAi), we have stably silenced the expression of the fascin in EC109 cells, an ESCC cell line. Down-regulation of fascin resulted in a suppression of cell proliferation and as well as a decrease in cell invasiveness. Furthermore, we revealed that fascin might have functions in regulating tumor growth in vivo. The effect of fascin on cell invasiveness correlated with the activation of matrix metalloproteases such as MMP-2 and MMP-9. We examined that fascin down-expression also led to a decrease of c-erbB-2 and β-catenin at the protein level. These results suggested that fascin might play crucial roles in regulating neoplasm progression of ESCC

  5. Interleukin-37 expression and its potential role in oral leukoplakia and oral squamous cell carcinoma.

    Science.gov (United States)

    Lin, Lin; Wang, Jiayi; Liu, Dongjuan; Liu, Sai; Xu, Hao; Ji, Ning; Zhou, Min; Zeng, Xin; Zhang, Dunfang; Li, Jing; Chen, Qianming

    2016-05-26

    Interleukin 37 (IL-37) has been reported to play a significant role in innate immune response and to be involved in several kinds of cancers. However, the investigation of association between IL-37 and oral mucosa carcinogenesis hasn't been clearly established. The aim of the study was to assess IL-37 expression and explore its role in oral mucosa carcinogenesis. The expression of IL-37 increased from normal control (NC) to Oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC). Moreover, statistically highly significant difference was present between scores of OLK with and without mild/moderate dysplasia (P oral mucosa carcinogenesis. Overall, IL-37 can be used as a biomarker for early oral tumorigenesis and for malignant transformation risk assessment of premalignant lesions.

  6. The battle in the apoplast: further insights into the roles of proteases and their inhibitors in plant-pathogen interactions

    Directory of Open Access Journals (Sweden)

    Mansoor eKarimi Jashni

    2015-08-01

    Full Text Available Upon host penetration, fungal pathogens secrete a plethora of effectors to promote disease, including proteases that degrade plant antimicrobial proteins, and protease inhibitors (PIs that inhibit plant proteases with antimicrobial activity. Conversely, plants secrete proteases and PIs to protect themselves against pathogens or to mediate recognition of pathogen proteases and PIs, which leads to induction of defense responses. Many examples of proteases and PIs mediating effector-triggered immunity in host plants have been reported in the literature, but little is known about their role in compromising basal defense responses induced by microbe-associated molecular patterns. Recently, several reports appeared in literature on secreted fungal proteases that modify or degrade pathogenesis-related proteins, including plant chitinases or PIs that compromise their activities. This prompted us to review the recent advances on proteases and PIs involved in fungal virulence and plant defense. Proteases and PIs from plants and their fungal pathogens play an important role in the arms race between plants and pathogens, which has resulted in co-evolutionary diversification and adaptation shaping pathogen lifestyles.

  7. The role of surgery in renal cell carcinoma with pancreatic metastasis

    Directory of Open Access Journals (Sweden)

    Ying-Hsu Chang

    2015-04-01

    Full Text Available Metastasis of renal cell carcinoma to the pancreas is uncommon and, in most cases, presents as a single pancreatic mass that shows a more favorable prognosis than primary pancreatic tumors. We examined patients with renal cell carcinoma metastatic to the pancreas, and discuss the clinical findings, treatment administered, and final outcomes. The present study is a retrospective analysis of renal cell carcinoma patients with pancreatic metastasis. Pancreatic tumor specimens were obtained by surgical excision, surgical biopsy, fine-needle biopsy, or endoscopic ultrasound biopsy. The surgical approaches included distal splenopancreatectomy, total pancreatectomy, or distal pancreatectomy. The physician determined the postoperative treatment regimen with interferon-α or targeted therapy on the basis of patient's performance. A total of six patients with median age of 50 years were included in the study. The median time from the primary nephrectomy to the development of pancreatic metastasis was 16 years. In the biopsy-only group, the mean stable disease period was 16.5 months. In the patients treated with surgery combined with interferon-α or targeted therapy, the mean stable disease period was 29.5 months. The patients treated with repeat mastectomy showed a mean stable disease period of 33.3 months. Aggressive surgical management is more effective than observation or immunotherapy. Recent advances in the design of targeted therapies may provide alternative treatment strategies. Combination therapy may play an important role in the future. Considering patient compliance and cost-effectiveness, resection of pancreatic metastasis is currently the first choice of treatment.

  8. The role of CRISPR-Cas systems in virulence of pathogenic bacteria.

    Science.gov (United States)

    Louwen, Rogier; Staals, Raymond H J; Endtz, Hubert P; van Baarlen, Peter; van der Oost, John

    2014-03-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) genes are present in many bacterial and archaeal genomes. Since the discovery of the typical CRISPR loci in the 1980s, well before their physiological role was revealed, their variable sequences have been used as a complementary typing tool in diagnostic, epidemiologic, and evolutionary analyses of prokaryotic strains. The discovery that CRISPR spacers are often identical to sequence fragments of mobile genetic elements was a major breakthrough that eventually led to the elucidation of CRISPR-Cas as an adaptive immunity system. Key elements of this unique prokaryotic defense system are small CRISPR RNAs that guide nucleases to complementary target nucleic acids of invading viruses and plasmids, generally followed by the degradation of the invader. In addition, several recent studies have pointed at direct links of CRISPR-Cas to regulation of a range of stress-related phenomena. An interesting example concerns a pathogenic bacterium that possesses a CRISPR-associated ribonucleoprotein complex that may play a dual role in defense and/or virulence. In this review, we describe recently reported cases of potential involvement of CRISPR-Cas systems in bacterial stress responses in general and bacterial virulence in particular.

  9. Evidence for a pathogenic role of nitric oxide in inflammation-induced osteoporosis.

    Science.gov (United States)

    Armour, K E; Van'T Hof, R J; Grabowski, P S; Reid, D M; Ralston, S H

    1999-12-01

    Inflammatory disease is associated with increased production of nitric oxide (NO) and activation of the inducible nitric oxide synthase (iNOS) pathway. Several studies have addressed the role of NO as a mediator of cytokine effects on bone cell activity in vitro. Stimulatory and inhibitory actions have been found, however, depending on the concentrations produced and model system used. In view of this, it has been difficult to predict whether increased production of NO during inflammation is likely to increase bone loss or prevent it. We have investigated the pathogenic role of NO in an animal model of inflammation-induced osteoporosis (IMO). NO production was increased in IMO when compared with controls (+344%; p turnover, but L-NMMA had no effect on bone mass in control animals. This study has important implications for many inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, and inflammatory bowel disease which are associated with increased NO production and osteoporosis. Our data not only suggest that iNOS activation and increased NO production contribute to the pathogenesis of osteoporosis in these situations, but also suggest that NOS inhibitors could be of therapeutic value in the prevention and treatment of such bone loss.

  10. Role of periodontal pathogenic bacteria in RANKL-mediated bone destruction in periodontal disease.

    Science.gov (United States)

    Kajiya, Mikihito; Giro, Gabriela; Taubman, Martin A; Han, Xiaozhe; Mayer, Marcia P A; Kawai, Toshihisa

    2010-11-08

    Accumulated lines of evidence suggest that hyperimmune responses to periodontal bacteria result in the destruction of periodontal connective tissue and alveolar bone. The etiological roles of periodontal bacteria in the onset and progression of periodontal disease (PD) are well documented. However, the mechanism underlying the engagement of periodontal bacteria in RANKL-mediated alveolar bone resorption remains unclear. Therefore, this review article addresses three critical subjects. First, we discuss earlier studies of immune intervention, ultimately leading to the identification of bacteria-reactive lymphocytes as the cellular source of osteoclast-induction factor lymphokine (now called RANKL) in the context of periodontal bone resorption. Next, we consider (1) the effects of periodontal bacteria on RANKL production from a variety of adaptive immune effector cells, as well as fibroblasts, in inflamed periodontal tissue and (2) the bifunctional roles (upregulation vs. downregulation) of LPS produced from periodontal bacteria in a RANKL-induced osteoclast-signal pathway. Future studies in these two areas could lead to new therapeutic approaches for the management of PD by down-modulating RANKL production and/or RANKL-mediated osteoclastogenesis in the context of host immune responses against periodontal pathogenic bacteria.

  11. Pathogenic mechanisms in lysosomal disease: a reappraisal of the role of the lysosome.

    Science.gov (United States)

    Walkley, Steven U

    2007-04-01

    The view that lysosomes simply represent end organelles in the serial degradation of polymeric molecules derived from the cell surface and its interior has led to major misconceptions about the nature of lysosomal storage diseases and the pathogenic cascades that characterize them. Accordingly, lysosomal storage bodies are often considered 'inert', inducing cell dysfunction and death primarily through mechanical overcrowding of normal organelles or by other non-specific means leading to generalized cytotoxicity. However, modern studies of lysosomes and their component proteins provide evidence to support a far greater role for these organelles in cell metabolism. In intimate association with endosomal, autophagosomal and related vesicular systems, the greater lysosomal system can be conceptualized as a vital recycling centre that serves as a central metabolic coordinator, influencing literally every aspect of the cell, from signal transduction to regulation of gene expression. This broader view of the role of lysosomes in cells not only provides insight into how single gene defects impacting on lysosomal function can result in the plethora of complex cellular transformations characteristic of these diseases, but also suggests new and innovative therapies that may hold considerable promise for ameliorating disease progression.

  12. The Role of CRISPR-Cas Systems in Virulence of Pathogenic Bacteria

    Science.gov (United States)

    Staals, Raymond H. J.; Endtz, Hubert P.; van Baarlen, Peter; van der Oost, John

    2014-01-01

    SUMMARY Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) genes are present in many bacterial and archaeal genomes. Since the discovery of the typical CRISPR loci in the 1980s, well before their physiological role was revealed, their variable sequences have been used as a complementary typing tool in diagnostic, epidemiologic, and evolutionary analyses of prokaryotic strains. The discovery that CRISPR spacers are often identical to sequence fragments of mobile genetic elements was a major breakthrough that eventually led to the elucidation of CRISPR-Cas as an adaptive immunity system. Key elements of this unique prokaryotic defense system are small CRISPR RNAs that guide nucleases to complementary target nucleic acids of invading viruses and plasmids, generally followed by the degradation of the invader. In addition, several recent studies have pointed at direct links of CRISPR-Cas to regulation of a range of stress-related phenomena. An interesting example concerns a pathogenic bacterium that possesses a CRISPR-associated ribonucleoprotein complex that may play a dual role in defense and/or virulence. In this review, we describe recently reported cases of potential involvement of CRISPR-Cas systems in bacterial stress responses in general and bacterial virulence in particular. PMID:24600041

  13. Role of Arginine decarboxylase (ADC) in Arabidopsis thaliana defence against the pathogenic bacterium Pseudomonas viridiflava.

    Science.gov (United States)

    Rossi, F R; Marina, M; Pieckenstain, F L

    2015-07-01

    Polyamine biosynthesis starts with putrescine production through the decarboxylation of arginine or ornithine. In Arabidopsis thaliana, putrescine is synthesised exclusively by arginine decarboxylase (ADC), which exists as two isoforms (ADC1 and 2) that are differentially regulated by abiotic stimuli, but their role in defence against pathogens has not been studied in depth. This work analysed the participation of ADC in Arabidopsis defence against Pseudomonas viridiflava. ADC activity and expression, polyamine levels and bacterial resistance were analysed in null mutants of each ADC isoform. In non-infected wild-type (WT) plants, ADC2 expression was much higher than ADC1. Analysis of adc mutants demonstrated that ADC2 contributes to a much higher extent than ADC1 to basal ADC activity and putrescine biosynthesis. In addition, adc2 mutants showed increased basal expression of salicylic acid- and jasmonic acid-dependent PR genes. Bacterial infection induced putrescine accumulation and ADC1 expression in WT plants, but pathogen-induced putrescine accumulation was blocked in adc1 mutants. Results suggest a specific participation of ADC1 in defence, although basal resistance was not decreased by dysfunction of either of the two ADC genes. In addition, and as opposed to WT plants, bacterial infection increased ADC2 expression and ADC activity in adc1 mutants, which could counterbalance the lack of ADC1. Results demonstrate a major contribution of ADC2 to total ADC activity and the specific induction of ADC1 in response to infection. A certain degree of functional redundancy between the two isoforms in relation to their contribution to basal resistance is also evident. © 2015 German Botanical Society and The Royal Botanical Society of the Netherlands.

  14. Discoidin domain receptor 1: New star in cancer-targeted therapy and its complex role in breast carcinoma.

    Science.gov (United States)

    Jing, Hui; Song, Jingyuan; Zheng, Junnian

    2018-03-01

    Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase activated by various types of collagens that performs a critical role in cell attachment, migration, survival and proliferation. The functions of DDR1 in various types of tumor have been studied extensively. However, in breast carcinoma, the roles of collagen-evoked DDR1 remain ill defined. Although a number of studies have reported that DDR1 promotes apoptosis and inhibits migration in breast carcinoma, it has also been reported to be associated with tumor cell survival, chemoresistance to genotoxic drugs and the facilitation of invasion. The present review summarizes current progress and the complex effects of DDR1 in the field of breast carcinoma, and presents DDR1 as a promising therapeutic target.

  15. Role of radical resection in patients with gallbladder carcinoma and jaundice.

    Science.gov (United States)

    Feng, Fei-ling; Liu, Chen; Li, Bin; Zhang, Bai-he; Jiang, Xiao-qing

    2012-03-01

    Gallbladder carcinoma (GBC) is a commonly-seen malignancy of the biliary tract characterized by difficult early diagnosis, rapid growth, early metastasis, and poor prognosis. Nearly half of GBC patients also have jaundice, which is a mark of the advanced stage of GBC. The role of radical resection in patients of gallbladder carcinoma with jaundice is still a matter of uncertainty, which we attempted to clarify in this study. Totally, 251 GBC patients who received treatment at the Eastern Hepatobiliary Surgery Hospital (EHBH) from December 2002 to January 2010 were recruited into this study. We divided them into group A (jaundice group, n=117) and group B (non-jaundice group, n=134). Clinical records and follow-up data were collected and retrospectively analyzed in both groups. Compared with group A, patients in group B had a longer median survival time ((6.0±0.5) months vs. (15.0±2.6) months, Pjaundice (n=111), was still longer than that in patients with jaundice (n=116) (Pjaundice patients and non-jaundice patients; (12.0±4.3) months vs. (18.0±3.0) months (P>0.05). GBC with jaundice usually implies advanced stage disease and a poor prognosis for the patients. However, our findings indicate that as long as the patient's condition allows, radical resection is still feasible for GBC patients with jaundice, and may achieve a prognosis close to those GBC patients without jaundice.

  16. Anaplastic carcinoma of the pancreas: Is there a role for palliative surgical procedure?

    Directory of Open Access Journals (Sweden)

    Rajan Vaithianathan

    2014-01-01

    Full Text Available Anaplastic carcinoma (AC or undifferentiated carcinoma of the pancreas is a rare variant among the malignant pancreatic neoplasms. These tumors have a poor prognosis with survival measured in months. The role of surgical palliation to improve the quality of life is not well defined in these patients. We report a case of AC of pancreas in a 65-year-old male patient. Patient had upper abdominal pain with frequent bilious vomiting. Computed tomography scan of the abdomen showed a mass in the body of pancreas with possible infiltration of duodenojejunal flexure (DJF. Laparotomy revealed an inoperable mass with posterior fixity and involvement of the DJF. Patient underwent a palliative duodenojejunostomy. Tissue biopsy from the tumor showed pleomorphic type AC with giant cells. Patient had good symptomatic relief from profuse vomiting and progressed well at follow up. AC of pancreas is a rare and aggressive malignancy with dismal outlook. If obstructive symptoms are present due to duodenal involvement, a palliative bypass may be a worthwhile surgical option in selected cases.

  17. Prognostic role of serum prostatic acid phosphatase for 103Pd-based radiation for prostatic carcinoma

    International Nuclear Information System (INIS)

    Dattoli, Michael; Wallner, Kent; True, Lawrence; Sorace, Richard; Koval, John; Cash, Jennifer; Acosta, Rudolph; Biswas, Mohendra; Binder, Michael; Sullivan, Brent; Lastarria, Emilio; Kirwan, Novelle; Stein, Douglas

    1999-01-01

    Purpose: To establish the prognostic role of serum enzymatic prostatic acid phosphatase (PAP) in patients treated with palladium ( 103 Pd) and supplemental external beam irradiation (EBRT) for clinically localized, high-risk prostate carcinoma. Methods and Materials: One hundred twenty-four consecutive patients with Stage T2a-T3 prostatic carcinoma were treated from 1992 through 1995. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (100 patients), Gleason score 7-10 (40 patients), pretreatment prostate specific antigen (PSA) > 15 ng/ml (32 patients), or elevated serum PAP (25 patients). Patients received 41 Gy conformal EBRT to a limited pelvic field, followed 4 weeks later by a 103 Pd boost (prescription dose 80 Gy). Biochemical failure was defined as a PSA greater than 1 ng/ml (normal < 4 ng/ml). Results: The overall, actuarial freedom from biochemical failure at 4 years after treatment was 79%. In Cox-proportional hazard multivariate analysis, the strongest predictor of failure was elevated pretreatment acid phosphatase (p = 0.02), followed by Gleason score (p = 0.1), and PSA (p = 0.14). Conclusion: PAP was the strongest predictor of long-term biochemical failure. It may be a more accurate indicator of micrometastatic disease than PSA, and as such, we suggest that it be reconsidered for general use in radiation-treated patients

  18. The predictive role of E2-EPF ubiquitin carrier protein in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Chen, Miao-Fen; Lee, Kuan-Der; Lu, Ming-Shian; Chen, Chih-Cheng; Hsieh, Ming-Ju; Liu, Yun-Hen; Lin, Paul-Yang; Chen, Wen-Cheng

    2009-03-01

    The ubiquitin proteasome pathway has been implicated in carcinogenesis. However, the role of E2-EPF ubiquitin carrier protein (UCP) in esophageal cancer remains relatively unstudied. In the study, we examined the mRNA level of circulating tumor cells from 60 esophageal cancer patients by membrane arrays consisting of a panel of potential markers including UCP, compared to 40 normal populations. The predictive capacity of UCP was also assessed by immunohistochemical staining of a retrospective series of 84 biopsied esophageal squamous cell carcinomas in relation to clinical outcome. In addition, we studied in vitro biological changes including tumor growth, metastatic capacity, and the sensitivity to irradiation and cisplatin, after experimental manipulation of UCP expression in esophageal cancer cells. By the data of 25-gene membrane array analysis, UCP was the only factor significantly associated with the extent of tumor burden in esophageal cancer patients. Our immunochemistry findings further indicate that UCP positivity was linked to poor response to neoadjuvant therapy and worse survival. In cell culture, inhibited UCP significantly decrease tumor growth and the capacity for metastasis. The epithelial-mesenchymal transition (EMT) induced by VHL/HIF-1alpha-TGF-beta1 pathway might be the underlying mechanism responsible to the more aggressive tumor growth in UCP-positive esophageal cancer. Our results suggest that UCP was significantly associated with poor prognosis of esophageal cancer and may be a new molecular target for therapeutic intervention for esophageal squamous cell carcinoma.

  19. Purification of antilisterial peptide (SubtilosinA from novel Bacillus tequilensis FR9 and demonstrate their pathogen invasion protection ability using human carcinoma cell line.

    Directory of Open Access Journals (Sweden)

    Rizwana Parveen Rani

    2016-12-01

    Full Text Available This study focuses on isolation, screening and characterization of novel probiotics from gastrointestinal tract of free-range chicken (Gallus gallus domesticus. Fifty seven colonies were isolated and three isolates (FR4, FR9 and FR12 were selected and identified as Lactobacillus gasseri FR4, Bacillus tequilensis FR9 and L. animalis FR12 by 16S rRNA sequencing. Three strains were able to survive in stimulated acidic and bile conditions and inhibit the growth of pathogens. Especially, FR9 exhibited maximum inhibition against Listeria monocytogenes and none of them exhibited hemolytic activity. Native-PAGE revealed the presence of low molecular weight (3.4-5.0 KDa antimicrobial peptide. The peptide was further purified by Sephadex G-50 column and RP-HPLC using C18 column. N-terminal amino acid sequencing of antimicrobial peptide showed 100% consensus to antilisterial peptide SubtilosinA and SboA gene was amplified from FR9 genome. FR9 showed maximum aggregation activity, EPS production (85.46 mg/L and cholesterol assimilation (63.12 ± 0.05 µg/mL. Strong adhesion property (12.6% and pathogen invasion protection ability was revealed by B. tequilensis FR9 towards HCT-116 human colon carcinoma cell line. This is the first study to demonstrate antilisterial SubtilosinA production of B. tequilensis. Our results indicate that B. tequilensis FR9 strain furnish the essential characteristics of a potential probiotics and might be incorporated into human and animal food supplements.

  20. Evaluating the Role of Immunological Cells (Tissue Eosinophils and Mast Cells) in Progression of Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Saxena, S; Singh, A; Singh, P; Sundaragiri, K S; Sankhla, B; Bhargava, A

    2018-04-01

    Mast cells and eosinophils are increased in oral squamous cell carcinoma. The significance of such an association has been variably thought to be either a potential diagnostic tool for stromal invasion or as a prognostic indicator. The aim of the study was to study the mast cells and eosinophils between normal oral mucosa, leukoplakia and oral squamous cell carcinoma and to study the significance of mast cells in the progression of the lesion. A retrospective study was done on archival tissue received from January 2015 to December 2015, in the Department of Oral Pathology, RUHS College of Dental Sciences, Jaipur, Rajasthan, India. Seventy (70) cases were studied (30 cases each of leukoplakia and carcinoma and 10 cases of control group), sections were stained with toluidine blue solution to reveal mast cells. Eosinophils were studied in Haematoxylin & Eosin stained sections. Mast cell density significantly increased from: normal mucosa to oral leukoplakia to carcinoma, suggesting a role of the mast cells in the development of these lesions. The higher eosinophil counts in carcinoma group compared to dysplasia group proved that they might have a role in stromal invasion. The assessment of these could become, in the future, useful for therapeutic approaches in this subset of the patient.

  1. Salivary gland carcinomas: prognostic factors for local control and distant metastasis, the role of radiotherapy

    International Nuclear Information System (INIS)

    Terhaard, C.H.J.; Lubsen, H.; Tweel, I. van der; Hilgers, F.J.M.; Eijkenboom, W.M.H.; Marres, H.A.M.; Tjho-Heslinga, R.E.; Jong, J.M.A. de; Roodenburg, J.L.N.

    1997-01-01

    Purpose: The Dutch Head and Neck Oncology Cooperative Group, in which head and neck groups of all University hospitals and the two cancer institutes are represented, initiated a retrospective study concerning salivary gland carcinomas. A majority of Dutch patients with head and neck carcinomas are treated in the participating centres, and the follow-up is precise. Prognostic factors for local control and survival were studied, with special interest in the role of treatment and the role of histologic type. Methods and materials: Results were obtained of 568 patients with a mean follow-up time of 5 years. The parotid gland was involved in 59%, the submandibular gland in 14%, oral cavity in 24% and 3% was located elsewhere. Mean age was 59 years (range 8-100 yr), 48% was female. T-stage was T 1 in 27%, T 2 in 44%, T 3 in 19% and T 4 in 11%. Positive necknodes were seen in 15%, 3% was initially M 1 . Histologic type was acinic cell carcinoma in 12%, mucoepidermoid ca. in 16%, adenoid cystic ca. in 26%, adenoca. in 24%, carcinoma in pleomorphic adenoma in 8%, squamous cell ca. in 6% and undifferentiated ca. in 7%. Resection margins were radical in 37%, close in 20% and irradical in 40% (3% unknown). Surgery was the primary treatment in 501 patients, combined with postoperative radiotherapy (50-70 Gy, mean dose 62 Gy) in 389 patients. Radiotherapy was the primary treatment in 40 patients (18 M 1 , 30% N+), 20 patients were not treated and 7 patients were treated otherwise. For statistical analysis the Cox PH regression analysis was used (SPSS-PC+). Results: Actuarial local control after 8 years was 80% for surgery alone and 92% for the combined modality (in which more advanced cases prevaled). Independent factors for local control in the surgery±radiotherapy group were: I:T-stage (T 3 vs T 1-2 : RR 3.7; T 4 vs T 1-2 : RR 11.7), II: anatomic site (oral cavity vs parotid and submandibular gland: RR 0.2) and III: treatment modality (surgery alone vs surgery

  2. Role of Waterborne Pathogens in the Food Supply Chain: Implications to Risk Management with Local and Global Perspectives

    Science.gov (United States)

    Microbial risk assessment (MRA) in the food industry is used to support HACCP – which largely focuses on bacterial pathogen control in processing foodstuffs Potential role of microbially-contaminated water used in food production is not as well understood Emergence...

  3. The role of micro-RNAs in hepatocellular carcinoma: from molecular biology to treatment.

    Science.gov (United States)

    D'Anzeo, Marco; Faloppi, Luca; Scartozzi, Mario; Giampieri, Riccardo; Bianconi, Maristella; Del Prete, Michela; Silvestris, Nicola; Cascinu, Stefano

    2014-05-19

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third leading cause of cancer deaths. microRNAs (miRNAs) are evolutionary conserved small non-coding RNA that negatively regulate gene expression and protein translation. Recent evidences have shown that they are involved in many biological processes, from development and cell-cycle regulation to apoptosis. miRNAs can behave as tumor suppressor or promoter of oncogenesis depending on the cellular function of their targets. Moreover, they are frequently dysregulated in HCC. In this review we summarize the latest findings of miRNAs regulation in HCC and their role as potentially diagnostic and prognostic biomarkers for HCC. We highlight development of miRNAs as potential therapeutic targets for HCC.

  4. The Role of Free Tissue Transfer in Merkel Cell Carcinoma of the Head and Neck

    International Nuclear Information System (INIS)

    Londino, A. V.; Miles, B. A.

    2012-01-01

    Merkel cell carcinoma (MCC) is an uncommon neuroendocrine malignancy with a propensity for the head and neck. It typically presents a symptomatically in elderly Caucasians and is characterized by early local and regional spread. There is currently limited data on the appropriate algorithm for treatment of MCC. However, multimodal therapy with wide surgical excision with or without radiation therapy has become standard of care. The location of the primary tumor and intensive adjuvant therapy is often required, provides a challenge to the reconstructive head and neck surgeon. Occasionally, free tissue transfer reconstructive techniques are employed in the reconstruction of MCC defects. This paper will discuss the role of free tissue transfer as a reconstructive option after surgery for advanced head and neck MCC

  5. Is There a Role for Oncotype Dx Testing in Invasive Lobular Carcinoma?

    Science.gov (United States)

    Conlon, Niamh; Ross, Dara S; Howard, Jane; Catalano, Jeffrey P; Dickler, Maura N; Tan, Lee K

    2015-01-01

    Oncotype Dx Breast Cancer Assay is a 21-gene assay used in estrogen receptor (ER)-positive breast cancer to predict benefit from chemotherapy (CT). Tumors are placed into one of three risk categories based on their recurrence score (RS). This paper explores the impact of tumor histopathologic features and Oncotype Dx RS on the treatment plan for invasive lobular carcinoma (ILC). Invasive lobular carcinoma cases submitted for Oncotype Dx testing were identified from a clinical data base. The histopathologic and immunohistochemical features and RS subcategory of each tumor, and treatment regimen and medical oncologic assessments of each patient were reviewed. A total of 135 cases of ILC had RS testing, which represented 15% of all ILC diagnosed at the institution over the time period. 80% of ILC was of the classical subtype and all tumors were ER positive and human epidermal growth factor receptor 2 (HER-2) negative by immunohistochemistry. Sixty three percent of cases were low risk (LR), 35.5% were intermediate risk (IR) and 1.5% were high risk (HR). Both HR cases were pleomorphic ILC. Sixty eight percent of classical ILC had a LR score, while 70% of pleomorphic ILC had an IR score. Patients in the IR category were significantly more likely to undergo CT than patients in the LR category (54% versus 18%; p < 0.0001). In the LR category, those undergoing CT were significantly younger and more likely to have positive lymph nodes (p < 0.05). Qualitative analysis of medical oncologic assessments showed that RS played a role in decision-making on CT in 74% of cases overall. At our institution, Oncotype Dx RS currently plays a role in the management of a proportion of ILC and impacts on treatment decisions. © 2015 Wiley Periodicals, Inc.

  6. Oral cavity squamous cell carcinoma: Role of pretreatment imaging and its influence on management

    International Nuclear Information System (INIS)

    Arya, S.; Rane, P.; Deshmukh, A.

    2014-01-01

    Squamous cell carcinoma (SCC) is the commonest malignancy in the oral cavity. The oral cavity has several subsites. Knowledge of the patterns of disease spread at each subsite with the impact on treatment and prognosis provides a deeper understanding of the role of imaging. Information from imaging helps accurate staging, assess resectability, and plan multimodality treatment. Mandibular erosion, posterior soft tissue extent, and perineural spread influence treatment and prognosis in gingival, buccal, and retromolar trigone (RMT) cancers. Multidetector computed tomography (MDCT) with multiplanar reformations and bone and soft tissue algorithms provides the highest specificity for bone erosion. Hard palate SCC is optimally imaged with contrast-enhanced magnetic resonance imaging (MRI) to detect perineural spread. In oral tongue and floor of the mouth (FOM) SCC, extrinsic muscle invasion, extension across the midline, extent of posterior and inferior spread, and proximity to the hyoid are issues that impact therapeutic options. Contrast-enhanced MRI is the optimal imaging method for staging the primary due to its superior soft tissue resolution. In oral tongue SCCs with tumour thickness ≤4 mm, elective neck dissection can be avoided. For nodal staging (N-staging), all imaging methods are comparable, but fall short of surgical staging. Sentinel lymph node biopsy has a promising role in N-staging. Positron emission tomography (PET)/integrated PET/CT has no role in evaluating the clinically negative neck. PET/CT has a role in pretreatment evaluation of advanced oral cavity SCC for depicting distant metastases and for mapping nodal extent in the clinically positive neck. Diffusion-weighted MRI, dynamic contrast-enhanced MRI, and CT perfusion have a potential role as baseline pretreatment studies for response assessment to chemoradiation in advanced oral cavity SCC. - Highlights: • Brief outline of treatment principles in oral cavity squamous cell carcinoma (OCSCC

  7. Immunomodulatory role for membrane vesicles released by THP-1 macrophages and respiratory pathogens during macrophage infection.

    Science.gov (United States)

    Volgers, Charlotte; Benedikter, Birke J; Grauls, Gert E; Savelkoul, Paul H M; Stassen, Frank R M

    2017-11-13

    During infection, inflammation is partially driven by the release of mediators which facilitate intercellular communication. Amongst these mediators are small membrane vesicles (MVs) that can be released by both host cells and Gram-negative and -positive bacteria. Bacterial membrane vesicles are known to exert immuno-modulatory and -stimulatory actions. Moreover, it has been proposed that host cell-derived vesicles, released during infection, also have immunostimulatory properties. In this study, we assessed the release and activity of host cell-derived and bacterial MVs during the first hours following infection of THP-1 macrophages with the common respiratory pathogens non-typeable Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa. Using a combination of flow cytometry, tunable resistive pulse sensing (TRPS)-based analysis and electron microscopy, we demonstrated that the release of MVs occurs by both host cells and bacteria during infection. MVs released during infection and bacterial culture were found to induce a strong pro-inflammatory response by naive THP-1 macrophages. Yet, these MVs were also found to induce tolerance of host cells to secondary immunogenic stimuli and to enhance bacterial adherence and the number of intracellular bacteria. Bacterial MVs may play a dual role during infection, as they can both trigger and dampen immune responses thereby contributing to immune defence and bacterial survival.

  8. The Roles of Hemagglutinin Phe-95 in Receptor Binding and Pathogenicity of Influenza B Virus

    Science.gov (United States)

    Ni, Fengyun; Mbawuike, Innocent Nnadi; Kondrashkina, Elena; Wang, Qinghua

    2014-01-01

    Diverged ~4,000 years ago, influenza B virus has several important differences from influenza A virus, including lower receptor-binding affinity and highly restricted host range. Based on our prior structural studies, we hypothesized that a single-residue difference in the receptor-binding site of hemagglutinin (HA), Phe-95 in influenza B virus versus Tyr-98 in influenza A/H1~H15, is possibly a key determinant for the low receptor-binding affinity. Here we demonstrate that the mutation Phe95→Tyr in influenza B virus HA restores all three hydrogen bonds made by Tyr-98 in influenza A/H3 HA and has the potential to enhance receptor binding. However, the full realization of this potential is influenced by the local environment into which the mutation is introduced. The binding and replication of the recombinant viruses correlate well with the receptor-binding capabilities of HA. These results are discussed in relation to the roles of Phe-95 in receptor binding and pathogenicity of influenza B virus. PMID:24503069

  9. The role of iron uptake in pathogenicity and symbiosis in Photorhabdus luminescens TT01

    Directory of Open Access Journals (Sweden)

    Joyce Susan A

    2010-06-01

    Full Text Available Abstract Background Photorhabdus are Gram negative bacteria that are pathogenic to insect larvae whilst also having a mutualistic interaction with nematodes from the family Heterorhabditis. Iron is an essential nutrient and bacteria have different mechanisms for obtaining both the ferrous (Fe2+ and ferric (Fe3+ forms of this metal from their environments. In this study we were interested in analyzing the role of Fe3+ and Fe2+ iron uptake systems in the ability of Photorhabdus to interact with its invertebrate hosts. Results We constructed targeted deletion mutants of exbD, feoABC and yfeABCD in P. luminescens TT01. The exbD mutant was predicted to be crippled in its ability to obtain Fe3+ and we show that this mutant does not grow well in iron-limited media. We also show that this mutant was avirulent to the insect but was unaffected in its symbiotic interaction with Heterorhabditis. Furthermore we show that a mutation in feoABC (encoding a predicted Fe2+ permease was unaffected in both virulence and symbiosis whilst the divalent cation transporter encoded by yfeABCD is required for virulence in the Tobacco Hornworm, Manduca sexta (Lepidoptera but not in the Greater Wax Moth, Galleria mellonella (Lepidoptera. Moreover the Yfe transporter also appears to have a role during colonization of the IJ stage of the nematode. Conclusion In this study we show that iron uptake (via the TonB complex and the Yfe transporter is important for the virulence of P. luminescens to insect larvae. Moreover this study also reveals that the Yfe transporter appears to be involved in Mn2+-uptake during growth in the gut lumen of the IJ nematode. Therefore, the Yfe transporter in P. luminescens TT01 is important during colonization of both the insect and nematode and, moreover, the metal ion transported by this pathway is host-dependent.

  10. Role of commercial probiotic strains against human pathogen adhesion to intestinal mucus.

    Science.gov (United States)

    Collado, M C; Meriluoto, J; Salminen, S

    2007-10-01

    The aims of this study present were to assess and to evaluate in vitro the abilities of commercial probiotic strains derived from fermented milk products and related sources currently marketed in European countries, to inhibit, compete and displace the adhesion of selected potential pathogens to immobilized human mucus. The adhesion was assessed by measuring the radioactivity of bacteria adhered to the human mucus. We tested 12 probiotic strains against eight selected pathogens. All strains tested were able to adhere to mucus. All probiotic strains tested were able to inhibit and displace (P<0.05) the adhesion of Bacteroides, Clostridium, Staphylococcus and Enterobacter. In addition, the abilities to inhibit and to displace adhered pathogens depended on both the probiotic and the pathogen strains tested suggesting that several complementary mechanisms are implied in the processes. Our results indicate the need for a case-by-case assessment in order to select strains with the ability to inhibit or displace a specific pathogen. Probiotics could be useful to correct deviations observed in intestinal microbiota associated with specific diseases and also, to prevent pathogen infections. The competitive exclusion properties of probiotics as well as their ability to displace and inhibit pathogens are the most importance for therapeutic manipulation of the enteric microbiota. The application of such strategies could contribute to expand the beneficial properties on human health against pathogen infection.

  11. Role of hydrogen peroxide during the interaction between the hemibiotrophic fungal pathogen Septoria tritici and wheat

    NARCIS (Netherlands)

    Shetty, N.P.; Mehrabi, R.; Lütken, H.; Haldrup, A.; Kema, G.H.J.

    2007-01-01

    Hydrogen peroxide (H2O2) is reported to inhibit biotrophic but benefit necrotrophic pathogens. Infection by necrotrophs can result in a massive accumulation of H2O2 in hosts. Little is known of how pathogens with both growth types are affected (hemibiotrophs). The hemibiotroph, Septoria tritici,

  12. Role of RPLND and Metastasectomy in the Management of Oligometastatic Renal Cell Carcinoma.

    Science.gov (United States)

    Nagaraja, H; Srivatsa, N; Hemalatha, S; Shweta, S; Raghunath, S K

    2018-03-01

    Although lymphadenectomy is currently accepted as most accurate and reliable staging procedure for lymph node metastases, its therapeutic benefit in renal cell carcinoma (RCC) still remains controversial. Although the new, targeted therapy paradigms have changed the treatment of patients with advanced RCC and offer prolonged survival, cure is extremely uncommon in the absence of surgical resections. In this paper, the current role of metastasectomy is reviewed. Review the available literature concerning the role of retroperitoneal lymph node dissection and metastasectomy in outcome of oligometastatic RCC. A PubMed search was conducted to identify original articles, review articles, and editorials addressing the role of retroperitoneal lymph node dissection and metastasectomy in outcome of oligometastatic RCC. Keywords included renal tumors, renal cell cancer, kidney cancer, lymphadenectomy, metastasectomy, and oligometastases. While there is no randomized study available, recent large observational studies have better defined the prognosis of patients with metastatic RCC with or without metastasectomy and RPLND. To date, the available evidence suggests that RPLND and metastasectomy may be beneficial when technically feasible in patients with locally advanced (unfavorable clinical and pathologic characteristics) and oligometastatic disease. A proportion of patients will achieve long-term survival with aggressive surgical resection.

  13. Role of cyclophilin B in tumorigenesis and cisplatin resistance in hepatocellular carcinoma in humans.

    Science.gov (United States)

    Kim, Yeonghwan; Jang, Miran; Lim, Sangbin; Won, Hyeran; Yoon, Kyung-Sik; Park, Jae-Hoon; Kim, Hyo Jong; Kim, Byung-Ho; Park, Won-Sang; Ha, Joohun; Kim, Sung-Soo

    2011-11-01

    Cyclophilin B (CypB) performs diverse roles in living cells, but its role in hepatocellular carcinoma (HCC) is largely unclear. To reveal its role in HCC, we investigated the induction of CypB under hypoxia and its functions in tumor cells in vitro and in vivo. Here, we demonstrated that hypoxia-inducible factor 1α (HIF-1α) induces CypB under hypoxia. Interestingly, CypB protected tumor cells, even p53-defective HCC cells, against hypoxia- and cisplatin-induced apoptosis. Furthermore, it regulated the effects of HIF-1α, including those in angiogenesis and glucose metabolism, via a positive feedback loop with HIF-1α. The tumorigenic and chemoresistant effects of CypB were confirmed in vivo using a xenograft model. Finally, we showed that CypB is overexpressed in 78% and 91% of the human HCC and colon cancer tissues, respectively, and its overexpression in these cancers reduced patient survival. These results indicate that CypB induced by hypoxia stimulates the survival of HCC via a positive feedback loop with HIF-1α, indicating that CypB is a novel candidate target for developing chemotherapeutic agents against HCC and colon cancer. Copyright © 2011 American Association for the Study of Liver Diseases.

  14. The regulatory role of heparin on c-Met signaling in hepatocellular carcinoma cells.

    Science.gov (United States)

    İşcan, Evin; Güneş, Aysim; Korhan, Peyda; Yılmaz, Yeliz; Erdal, Esra; Atabey, Neşe

    2017-06-01

    The role of heparin as an anticoagulant is well defined; however, its role in tumorigenesis and tumor progression is not clear yet. Some studies have shown that anticoagulant treatment in cancer patients improve overall survival, however, recent clinical trials have not shown a survival benefit in cancer patients receiving heparin treatment. In our previous studies we have shown the inhibitory effects of heparin on Hepatocyte Growth Factor (HGF)-induced invasion and migration in hepatocellular carcinoma (HCC) cells. In this study, we showed the differential effects of heparin on the behaviors of HCC cells based on the presence or absence of HGF. In the absence of HGF, heparin activated HGF/c-Met signaling and promoted motility and invasion in HCC cells. Heparin treatment led to c-Met receptor dimerization and activated c-Met signaling in an HGF independent manner. Heparin-induced c-Met activation increased migration and invasion through ERK1/2, early growth response factor 1 (EGR1) and Matrix Metalloproteinases (MMP) axis. Interestingly, heparin modestly decreased the proliferation of HCC cells by inhibiting activatory phosphorylation of Akt. The inhibition of c-Met signaling reversed heparin-induced increase in motility and invasion and, proliferation inhibition. Our study provides a new perspective into the role of heparin on c-Met signaling in HCC.

  15. Characterization of indigoidine biosynthetic genes in Erwinia chrysanthemi and role of this blue pigment in pathogenicity.

    Science.gov (United States)

    Reverchon, Sylvie; Rouanet, Carine; Expert, Dominique; Nasser, William

    2002-02-01

    In the plant-pathogenic bacterium Erwinia chrysanthemi production of pectate lyases, the main virulence determinant, is modulated by a complex network involving several regulatory proteins. One of these regulators, PecS, also controls the synthesis of a blue pigment identified as indigoidine. Since production of this pigment is cryptic in the wild-type strain, E. chrysanthemi ind mutants deficient in indigoidine synthesis were isolated by screening a library of Tn5-B21 insertions in a pecS mutant. These ind mutations were localized close to the regulatory pecS-pecM locus, immediately downstream of pecM. Sequence analysis of this DNA region revealed three open reading frames, indA, indB, and indC, involved in indigoidine biosynthesis. No specific function could be assigned to IndA. In contrast, IndB displays similarity to various phosphatases involved in antibiotic synthesis and IndC reveals significant homology with many nonribosomal peptide synthetases (NRPS). The IndC product contains an adenylation domain showing the signature sequence DAWCFGLI for glutamine recognition and an oxidation domain similar to that found in various thiazole-forming NRPS. These data suggest that glutamine is the precursor of indigoidine. We assume that indigoidine results from the condensation of two glutamine molecules that have been previously cyclized by intramolecular amide bond formation and then dehydrogenated. Expression of ind genes is strongly derepressed in the pecS background, indicating that PecS is the main regulator of this secondary metabolite synthesis. DNA band shift assays support a model whereby the PecS protein represses indA and indC expression by binding to indA and indC promoter regions. The regulatory link, via pecS, between indigoidine and virulence factor production led us to explore a potential role of indigoidine in E. chrysanthemi pathogenicity. Mutants impaired in indigoidine production were unable to cause systemic invasion of potted Saintpaulia ionantha

  16. The Plant Ribosome-Inactivating Proteins Play Important Roles in Defense against Pathogens and Insect Pest Attacks

    Directory of Open Access Journals (Sweden)

    Feng Zhu

    2018-02-01

    Full Text Available Ribosome-inactivating proteins (RIPs are toxic N-glycosidases that depurinate eukaryotic and prokaryotic rRNAs, thereby arresting protein synthesis during translation. RIPs are widely found in various plant species and within different tissues. It is demonstrated in vitro and in transgenic plants that RIPs have been connected to defense by antifungal, antibacterial, antiviral, and insecticidal activities. However, the mechanism of these effects is still not completely clear. There are a number of reviews of RIPs. However, there are no reviews on the biological functions of RIPs in defense against pathogens and insect pests. Therefore, in this report, we focused on the effect of RIPs from plants in defense against pathogens and insect pest attacks. First, we summarize the three different types of RIPs based on their physical properties. RIPs are generally distributed in plants. Then, we discuss the distribution of RIPs that are found in various plant species and in fungi, bacteria, algae, and animals. Various RIPs have shown unique bioactive properties including antibacterial, antifungal, antiviral, and insecticidal activity. Finally, we divided the discussion into the biological roles of RIPs in defense against bacteria, fungi, viruses, and insects. This review is focused on the role of plant RIPs in defense against bacteria, fungi, viruses, and insect attacks. The role of plant RIPs in defense against pathogens and insects is being comprehended currently. Future study utilizing transgenic technology approaches to study the mechanisms of RIPs will undoubtedly generate a better comprehending of the role of plant RIPs in defense against pathogens and insects. Discovering additional crosstalk mechanisms between RIPs and phytohormones or reactive oxygen species (ROS against pathogen and insect infections will be a significant subject in the field of biotic stress study. These studies are helpful in revealing significance of genetic control that can

  17. Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

    Directory of Open Access Journals (Sweden)

    Fecher LA

    2015-11-01

    Full Text Available Leslie A Fecher,1,3 William H Sharfman2 1Department of Internal Medicine and Dermatology, Indiana University Health Simon Cancer Center, Indianapolis, IN, USA; 2The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA, 3Department of Internal Medicine and Dermatology, University of Michigan, MI, USA Abstract: Cutaneous basal cell carcinoma (BCC is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449, a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. Keywords: basal cell carcinoma, hedgehog, smoothened, vismodegib, Gorlin, basal cell nevus syndrome

  18. Do Human Papilloma Viruses Play Any Role in Oral Squamous Cell Carcinoma in North Indians?

    Science.gov (United States)

    Singh, Vineeta; Husain, Nuzhat; Akhtar, Naseem; Kumar, Vijay; Tewari, Shikha; Mishra, Sridhar; Misra, Sanjeev; Khan, M Y

    2015-01-01

    Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy among males in India. While tobacco and alcohol are main aetiological factors, human papilloma virus (HPV) presence has surprisingly increased in head and neck Squamous Cell Carcinoma (HNSCC) in the past two decade but its frequency in OSCCS is still uncertain. We aim to explore the frequency of HPV and its major genotypes in North Indian patients and their association with clinicopathological and histopathological features and p16 expression pattern. The study group comprised 250 histologically proven cases of OSCC. HPV was detected by real time PCR in tumor biopsy specimens and confirmed by conventional PCR with PGMY09/ PGMY11 primers. Genotyping for high-risk types 16/ 18 was conducted by type specific PCR. p16 expression was assessed by immunohistochemsitry. HPV presence was confirmed in 23/250 (9.2%) OSCC cases, of which 30.4% had HPV 16 infection, 17.4%were positive for HPV 18 and 26.1% had co-infections. HPV presence was significantly associated with male gender (p=0.02) and habit of pan masala chewing (p=0.01). HPV positive cases also had a history of tobacco consumption in 91.3% cases. p16 over expression was observed in 39.1% of HPV positive cases but this was not significantly different from negative cases (p=0.54). The frequency of HPV in OSCC is low in North-India and majority of cases are associated with a tobacco habit. It appears that tobacco shows a confounding effect in HPV positive cases and use of p16 protein as a reliable marker to assess the potential etiological role of HPV in OSCC in our population is not suggested.

  19. Role of India's wildlife in the emergence and re-emergence of zoonotic pathogens, risk factors and public health implications.

    Science.gov (United States)

    Singh, B B; Gajadhar, A A

    2014-10-01

    Evolving land use practices have led to an increase in interactions at the human/wildlife interface. The presence and poor knowledge of zoonotic pathogens in India's wildlife and the occurrence of enormous human populations interfacing with, and critically linked to, forest ecosystems warrant attention. Factors such as diverse migratory bird populations, climate change, expanding human population and shrinking wildlife habitats play a significant role in the emergence and re-emergence of zoonotic pathogens from India's wildlife. The introduction of a novel Kyasanur forest disease virus (family flaviviridae) into human populations in 1957 and subsequent occurrence of seasonal outbreaks illustrate the key role that India's wild animals play in the emergence and reemergence of zoonotic pathogens. Other high priority zoonotic diseases of wildlife origin which could affect both livestock and humans include influenza, Nipah, Japanese encephalitis, rabies, plague, leptospirosis, anthrax and leishmaniasis. Continuous monitoring of India's extensively diverse and dispersed wildlife is challenging, but their use as indicators should facilitate efficient and rapid disease-outbreak response across the region and occasionally the globe. Defining and prioritizing research on zoonotic pathogens in wildlife are essential, particularly in a multidisciplinary one-world one-health approach which includes human and veterinary medical studies at the wildlife-livestock-human interfaces. This review indicates that wild animals play an important role in the emergence and re-emergence of zoonotic pathogens and provides brief summaries of the zoonotic diseases that have occurred in wild animals in India. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. The role of relA and spoT in Yersinia pestis KIM5 pathogenicity.

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    Wei Sun

    2009-08-01

    Full Text Available The ppGpp molecule is part of a highly conserved regulatory system for mediating the growth response to various environmental conditions. This mechanism may represent a common strategy whereby pathogens such as Yersinia pestis, the causative agent of plague, regulate the virulence gene programs required for invasion, survival and persistence within host cells to match the capacity for growth. The products of the relA and spoT genes carry out ppGpp synthesis. To investigate the role of ppGpp on growth, protein synthesis, gene expression and virulence, we constructed a Delta relA Delta spoT Y. pestis mutant. The mutant was no longer able to synthesize ppGpp in response to amino acid or carbon starvation, as expected. We also found that it exhibited several novel phenotypes, including a reduced growth rate and autoaggregation at 26 degrees C. In addition, there was a reduction in the level of secretion of key virulence proteins and the mutant was > 1,000-fold less virulent than its wild-type parent strain. Mice vaccinated subcutaneously (s.c. with 2.5x10(4 CFU of the Delta relA Delta spoT mutant developed high anti-Y. pestis serum IgG titers, were completely protected against s.c. challenge with 1.5x10(5 CFU of virulent Y. pestis and partially protected (60% survival against pulmonary challenge with 2.0x10(4 CFU of virulent Y. pestis. Our results indicate that ppGpp represents an important virulence determinant in Y. pestis and the Delta relA Delta spoT mutant strain is a promising vaccine candidate to provide protection against plague.

  1. The role of Fusarium oxysporum effector protein Avr2 in resistance and pathogenicity

    NARCIS (Netherlands)

    Ma, L.

    2012-01-01

    Lisong Ma onderzocht de moleculaire interactie tussen tomaat en de verwelking veroorzakende schimmel Fusarium oxyspourm f.sp. lycopersici (Fol). Hierbij identificeerde ze de functionele aspecten van de effectoreiwitten Six (Secreted un Xylem). Planten worden onafgebroken blootgesteld aan pathogene

  2. The role of primary radiotherapy for squamous cell carcinoma of the supraglottic larynx

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Won Taek; Kim, Dong Won; Kwon, Byung Hyun; Nam, Ji Ho [College of Medicine, Pusan National Univ, Pusan (Korea, Republic of); Hur, Won Joo [College of Medicine, Donga Univ, Pusan (Korea, Republic of)

    2000-12-01

    was done. Four patients were died from distant metastasis,: three in lung, one in brain. Double primary tumor was found in 2 cases, one in lung (metachronous), another in thyroid (synchronous). Ulcerative lesions were revealed as unfavorable prognostic factor (p=0.0215), and radiation dose (more or less than 702 Gy) was an important factor on survival (p=0.0302). The role of radiotherapy in the treatment of supraglottic carcinoma is to improve the survival- val and to preserve the laryngeal function. Based on our data and other studies, early and moderately advanced supraglottic carcinomas could be successfully treated with either conservative surgery or radiotherapy alone. Both modalities showed similar results in survival and vocal preservation. For the advanced cases, radiotherapy alone. is inadequate for curative aim and surgery combined with radiotherapy should be done in operable patients. When patients refuse operation or want to preserve vocal function, or for the patients with inoperable medical conditions, combined chemoradiotherapy (concurrent) or altered fractionated radiotherapy with or without radiosensitizer should be taken into consideration in future.

  3. The role of primary radiotherapy for squamous cell carcinoma of the supraglottic larynx

    International Nuclear Information System (INIS)

    Kim, Won Taek; Kim, Dong Won; Kwon, Byung Hyun; Nam, Ji Ho; Hur, Won Joo

    2000-01-01

    was done. Four patients were died from distant metastasis,: three in lung, one in brain. Double primary tumor was found in 2 cases, one in lung (metachronous), another in thyroid (synchronous). Ulcerative lesions were revealed as unfavorable prognostic factor (p=0.0215), and radiation dose (more or less than 702 Gy) was an important factor on survival (p=0.0302). The role of radiotherapy in the treatment of supraglottic carcinoma is to improve the survival- val and to preserve the laryngeal function. Based on our data and other studies, early and moderately advanced supraglottic carcinomas could be successfully treated with either conservative surgery or radiotherapy alone. Both modalities showed similar results in survival and vocal preservation. For the advanced cases, radiotherapy alone. is inadequate for curative aim and surgery combined with radiotherapy should be done in operable patients. When patients refuse operation or want to preserve vocal function, or for the patients with inoperable medical conditions, combined chemoradiotherapy (concurrent) or altered fractionated radiotherapy with or without radiosensitizer should be taken into consideration in future

  4. Potential role of bacteria packaging by protozoa in the persistence and transmission of pathogenic bacteria

    OpenAIRE

    Denoncourt, Alix M.; Paquet, Valérie E.; Charette, Steve J.

    2014-01-01

    Many pathogenic bacteria live in close association with protozoa. These unicellular eukaryotic microorganisms are ubiquitous in various environments. A number of protozoa such as amoebae and ciliates ingest pathogenic bacteria, package them usually in membrane structures, and then release them into the environment. Packaged bacteria are more resistant to various stresses and are more apt to survive than free bacteria. New evidence indicates that protozoa and not bacteria control the packaging...

  5. Advanced Renal Cell Carcinoma: Role of the Radiologist in the Era of Precision Medicine.

    Science.gov (United States)

    Shinagare, Atul B; Krajewski, Katherine M; Braschi-Amirfarzan, Marta; Ramaiya, Nikhil H

    2017-08-01

    For the past decade, advanced renal cell carcinoma (RCC) has been at the forefront of oncologic innovation. Our rapidly evolving understanding of the molecular and genetic basis of RCC has revolutionized the management of advanced RCC; 10 novel molecular targeted agents and immune checkpoint inhibitor have received U.S. Food and Drug Administration approval for treatment of advanced RCC in a little over a decade. Amid this progress, imaging has assumed a central role in metastatic surveillance and follow-up of advanced RCC. State-of-the-art knowledge of the molecular basis of RCC and its treatment and imaging will help ensure that the radiology community remains relevant and central in the care of patients with advanced RCC. This article will review developments in management of advanced RCC from a radiologist's perspective to highlight our clinical role. It will describe how the underlying molecular mechanisms of RCC provide specific targets for novel anticancer agents. The relationship between the mechanisms of action of these novel anticancer agents and the imaging appearance of tumor response will be discussed, along with the available tumor response criteria and their strengths and weaknesses, thus assisting radiologists in response assessment in the setting of clinical trials or routine practice. The class- and drug-specific toxicities and complications associated with the novel anticancer agents will be summarized, since these are frequently missed or misinterpreted and require the radiologist's input in prompt detection and management. The potential role of radiogenomics and texture analysis in the management of advanced RCC will also be discussed. © RSNA, 2017.

  6. Role of mannitol metabolism in the pathogenicity of the necrotrophic fungus Alternaria brassicicola

    Directory of Open Access Journals (Sweden)

    Benoit eCalmes

    2013-05-01

    Full Text Available In this study, the physiological functions of fungal mannitol metabolism in the pathogenicity and protection against environmental stresses were investigated in the necrotrophic fungus Alternaria brassicicola. Mannitol metabolism was examined during infection of Brassica oleracea leaves by sequential HPLC quantification of the major soluble carbohydrates and expression analysis of genes encoding two proteins of mannitol metabolism, i.e. a mannitol dehydrogenase (AbMdh, and a mannitol-1-phosphate dehydrogenase (AbMpd. Knockout mutants deficient for AbMdh or AbMpd and a double mutant lacking both enzyme activities were constructed. Their capacity to cope with various oxidative and drought stresses and their pathogenic behaviour were evaluated. Metabolic and gene expression profiling indicated an increase in mannitol production during plant infection. Depending on the mutants, distinct pathogenic processes, such as leaf and silique colonization, sporulation, survival on seeds, were impaired by comparison to the wild-type. This pathogenic alteration could be partly explained by the differential susceptibilities of mutants to oxidative and drought stresses. These results highlight the importance of mannitol metabolism with respect to the ability of A. brassicicola to efficiently accomplish key steps of its pathogenic life cycle.

  7. State of the art toward defining the role of radiation therapy in the management of small cell bronchogenic carcinoma

    International Nuclear Information System (INIS)

    Salazar, O.M.; Creech, R.H.

    1980-01-01

    This review article with 70 references discusses the state of the art in defining the role of radiotherapy in managing small cell bronchogenic carcinoma (SCBC). It reviews the history of therapeutic approaches to SCBC. Several issues of particular interest to limited disease are discussed. They are: local radiation therapy for limited disease, combined radiation therapy and chemotherapy in limited disease, combination chemotherapy alone for limited disease, and an overview of the treatment of limited disease. A section on extensive disease discusses the role of radiation therapy and chemotherapy, chemotherapy only for extensive disease, and an overview of the treatment of extensive disease. An additional section discusses the use of elective brain irradiation in small cell bronchogenic carcinoma

  8. Multiple Roles of Autophagy in the Sorafenib Resistance of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Ting Sun

    2017-11-01

    Full Text Available Hepatocellular carcinoma (HCC is the second leading cause of cancer-related death worldwide, and prognosis remains unsatisfactory since the disease is often diagnosed at the advanced stages. Currently, the multikinase inhibitor sorafenib is the only drug approved for the treatment of advanced HCC. However, primary or acquired resistance to sorafenib develops, generating a roadblock in HCC therapy. Autophagy is an intracellular lysosomal pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology. Current understanding of the role of autophagy in the progression of cancer and the response to cancer therapy remains controversial. Sorafenib is able to induce autophagy in HCC, but the effect of autophagy is indistinct. Some studies established that sorafenib-induced autophagy serves as a pro-survival response. However, other studies found that sorafenib-induced autophagy improves the lethality of sorafenib against HCC cells. The mechanisms underlying autophagy and sorafenib resistance remain elusive. The purpose of this review is to summarize the progress of research focused on autophagy and sorafenib resistance and to update current knowledge of how cellular autophagy impacts sorafenib sensitivity in HCC treatment.

  9. Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

    Science.gov (United States)

    Fecher, Leslie A; Sharfman, William H

    2015-01-01

    Cutaneous basal cell carcinoma (BCC) is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449), a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA)-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. PMID:26604681

  10. Clinical role in biopsy after interstitial irradiation to squamous cell carcinoma of tongue

    International Nuclear Information System (INIS)

    Sato, Tomoichi

    1995-01-01

    The clinical role of biopsy after interstitial irradiation therapy was evaluated in 44 patients with squamous cell carcinoma of tongue on which biopsy was done in our hospital. More residual tumors were observed in the induration-positive groups compared to those of the induration-negative groups. No tumor was histologically observed in 71.4% of the induration-positive groups. On the adjacent and covering mucous membranes, epithelial dysplasia was detected in 15 patients, 1 of them was Grade III and 9 were Grade IV. Two patients had recurrence. In the initial stage of interstitial irradiation, reaction of stoma showed decrease of edema, inflammatory cell infiltration, regeneration and dilation of vessels after 6 weeks. The regeneration of collagen fiber increased within 3-14 weeks after irradiation, followed by decrease of its activity. After interstitial irradiation, 2 of 9 Grade IIb patients treated by surgery and 2 by re-interstitial irradiation survived. One of 3 Grade III patients manifested recurrence and was treated by surgery. All patients were alive. Fourteen of 17 Grade IV patients under careful observation were still alive. Eleven of 15 patients treated by total neck dissection after interstitial irradiation survived. Four Grade IV patients showed recurrence. Two-year primary lesion control rate was 91.2% and the survival rate for 5 year was 74.0%. (S.Y.). 54 refs

  11. Clinical role in biopsy after interstitial irradiation to squamous cell carcinoma of tongue

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Tomoichi [Kanagawa Dental Coll., Yokosuka (Japan)

    1995-03-01

    The clinical role of biopsy after interstitial irradiation therapy was evaluated in 44 patients with squamous cell carcinoma of tongue on which biopsy was done in our hospital. More residual tumors were observed in the induration-positive groups compared to those of the induration-negative groups. No tumor was histologically observed in 71.4% of the induration-positive groups. On the adjacent and covering mucous membranes, epithelial dysplasia was detected in 15 patients, 1 of them was Grade III and 9 were Grade IV. Two patients had recurrence. In the initial stage of interstitial irradiation, reaction of stoma showed decrease of edema, inflammatory cell infiltration, regeneration and dilation of vessels after 6 weeks. The regeneration of collagen fiber increased within 3-14 weeks after irradiation, followed by decrease of its activity. After interstitial irradiation, 2 of 9 Grade IIb patients treated by surgery and 2 by re-interstitial irradiation survived. One of 3 Grade III patients manifested recurrence and was treated by surgery. All patients were alive. Fourteen of 17 Grade IV patients under careful observation were still alive. Eleven of 15 patients treated by total neck dissection after interstitial irradiation survived. Four Grade IV patients showed recurrence. Two-year primary lesion control rate was 91.2% and the survival rate for 5 year was 74.0%. (S.Y.). 54 refs.

  12. Role of superoxide dismutase in hepatitis B virus-related hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Xiaolian Zhang

    2016-01-01

    Full Text Available Background: Reactive oxygen species (ROS play important roles in hepatocarcinogenesis. Superoxide dismutase (SOD is involved in the repair of ROS. Serum alpha-fetoprotein (AFP is the “golden marker” for diagnosing hepatocellular carcinoma (HCC, and one major shortcoming of its use is that it is insensitive for the early detection of HCC. Therefore, we evaluated serum SOD levels and their association with AFP in hepatitis B virus (HBV-related HCC. Materials and Methods: A total of 279 subjects were divided into three groups: 99 HBV patients with HCC, 73 HBV patients without HCC, and 107 sex- and age-matched healthy controls. Serum levels of SOD were assayed using colorimetry, while AFP levels were measured by electrochemiluminescence immunoassay. Results: A highly significant elevation was found in AFP in HBV-with HCC patients compared to HBV-without HCC patients and control subjects (P < 0.001. Alternatively, serum SOD levels were significantly decreased in patients with HCC compared to HBV patients without HCC and healthy controls (P < 0.001. Furthermore, serum SOD was negatively correlated with AFP (r = −0.505, P < 0.001 in HBV-with HCC patients. Conclusion: SOD and AFP might be simultaneously evaluated to improve the HCC detection rate.

  13. A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yuzhu Jiang; Seon-Hee Yim; Hai-Dong Xu; Seung-Hyun Jung; So Young Yang; Hae-Jin Hu; Chan-Kwon Jung; Yeun-Jun Chung

    2011-01-01

    AIM: To explore the expression pattern of E2F5 in primary hepatocellular carcinomas (HCCs) and elucidate the roles of E2F5 in hepatocarcinogenesis. METHODS: E2F5 expression was analyzed in 120 primary HCCs and 29 normal liver tissues by immunohistochemistry analysis. E2F5-small interfering RNA was transfected into HepG2, an E2F5-overexpressed HCC cell line. After E2F5 knockdown, cell growth capacity and migrating potential were examined. RESULTS: E2F5 was significantly overexpressed in primary HCCs compared with normal liver tissues (P = 0.008). The E2F5-silenced cells showed significantly reduced proliferation (P = 0.004). On the colony formation and soft agar assays, the number of colonies was significantly reduced in E2F5-silenced cells (P = 0.004 and P = 0.009, respectively). E2F5 knockdown resulted in the accumulation of G0/G1 phase cells and a reduction of S phase cells. The number of migrating/invading cells was also reduced after E2F5 knockdown (P = 0.021). CONCLUSION: To our knowledge, this is the first evidence that E2F5 is commonly overexpressed in primary HCC and that E2F5 knockdown significantly repressed the growth of HCC cells.

  14. SREBP-1 Has a Prognostic Role and Contributes to Invasion and Metastasis in Human Hepatocellular Carcinoma

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    Chao Li

    2014-04-01

    Full Text Available Sterol regulatory element-binding protein 1 (SREBP-1 is a well-known nuclear transcription factor involved in lipid synthesis. Recent studies have focused on its functions in tumor cell proliferation and apoptosis, but its role in cell migration and invasion, especially in hepatocellular carcinoma (HCC, is still unclear. In this study, we found that the expression of SREBP-1 in HCC tissues was significantly higher than those in matched tumor-adjacent tissues (p < 0.05. SREBP-1 was expressed at significantly higher levels in patients with large tumor size, high histological grade and advanced tumor-node-metastasis (TNM stage (p < 0.05. The positive expression of SREBP-1 correlated with a worse 3-year overall and disease-free survival of HCC patients (p < 0.05. Additionally, SREBP-1 was an independent factor for predicting both 3-year overall and disease-free survival of HCC patients (p < 0.05. In vitro studies revealed that downregulation of SREBP-1 inhibited cell proliferation and induced apoptosis in both HepG2 and MHCC97L cells (p < 0.05. Furthermore, wound healing and transwell assays showed that SREBP-1 knockdown prominently inhibited cell migration and invasion in both HepG2 and MHCC97L cells (p < 0.05. These results suggest that SREBP-1 may serve as a prognostic marker in HCC and may promote tumor progression by promoting cell growth and metastasis.

  15. The role of radiotherapy and chemotherapy in the treatment of merkel cell carcinoma

    International Nuclear Information System (INIS)

    Fenig, Eyal; Katz, Alan; Brenner, Baruch; Rakovsky, Erica; Sulkes, Aaron

    1996-01-01

    Purpose/Objective: To determine the role of radiation therapy and chemotherapy in the treatment of Merkel Cell Carcinoma (MCC), a highly aggressive skin tumor. Materials and Methods: A retrospective analysis of 27 patients treated at the Rabin Medical Center in Israel is presented. Data on 40 patients, including 13 additional patients from the Israel Cancer Registry, were analyzed for prognostic factors using uni- and multivariate analysis. Results: Univariate analysis revealed regional lymph node involvement and coexistence of secondary primary as unfavorable prognostic factors. In multivariate analysis only lymph node involvement showed borderline statistical significance. Radiation therapy was highly effective when given as consolidation after surgery or chemotherapy. In 11 patients irradiated prophylactically only one in-field relapse (9%) occurred. Radiation therapy yielded responses in 15 of 15 measurable sites (5CR, 10 PR). Chemotherapy produced responses in 18 of 26 treatments (70%), mostly CR (41%). However, in the absence of radiation therapy the responses were of short duration. Conclusion: Our data support combined treatment with chemotherapy followed by irradiation for advanced loco-regional disease. Further large scale investigations are warranted to confirm this approach

  16. Role of surgery in breast metastasis from carcinoma of the cervix

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    Parveen Yadav

    2011-01-01

    Full Text Available Carcinoma of the cervix is the most common malignancy among women in India. Although metastatic disease is common, metastasis to breast is rare. A limited number of case reports are published in the world literature. Most of the previous reports of metastatic cervical carcinoma to breast are either autopsy series or widely disseminated disease where no treatment options were available. A rare case of cervical carcinoma presenting as metastasis in breast is reported here where palliative mastectomy improved the general condition of the patient. A female patient aged 58 years was diagnosed and treated for cervical carcinoma, FIGO stage 2B. Four months after the treatment which included both external beam and intracavitory radiotherapy, the patient presented with breast and lung metastasis. Palliative mastectomy was done which improved the general condition of the patient. Metastatic carcinoma of the cervix can present as a case of breast carcinoma. In an appropriate setting, this possibility should be kept in mind. Palliative mastectomy should be offered for patients of cervical carcinoma with metastasis to breast when needed.

  17. Sperm associated antigen 9 plays an important role in bladder transitional cell carcinoma.

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    Deepika Kanojia

    Full Text Available BACKGROUND: Majority of bladder cancer deaths are caused due to transitional cell carcinoma (TCC which is the most prevalent and chemoresistant malignancy of urinary bladder. Therefore, we analyzed the role of Sperm associated antigen 9 (SPAG9 in bladder TCC. METHODOLOGY AND FINDINGS: We examined SPAG9 expression and humoral response in 125 bladder TCC patients. Four bladder cancer cell lines were assessed for SPAG9 expression. In addition, we investigated the effect of SPAG9 ablation on cellular proliferation, cell cycle, migration and invasion in UM-UC-3 bladder cancer cells by employing gene silencing approach. Our SPAG9 gene and protein expression analysis revealed SPAG9 expression in 81% of bladder TCC tissue specimens. High SPAG9 expression (>60% SPAG9 positive cells was found to be significantly associated with superficial non-muscle invasive stage (P = 0.042 and low grade tumors (P = 0.002 suggesting SPAG9 putative role in early spread and tumorigenesis. Humoral response against SPAG9 was observed in 95% of patients found positive for SPAG9 expression. All four bladder cancer cell lines revealed SPAG9 expression. In addition, SPAG9 gene silencing in UM-UC-3 cells resulted in induction of G0-G1 arrest characterized by up-regulation of p16 and p21 and consequent down-regulation of cyclin E, cyclin D and cyclin B, CDK4 and CDK1. Further, SPAG9 gene silencing also resulted in reduction in cellular growth, and migration and invasion ability of cancer cells in vitro. CONCLUSIONS: Collectively, our data in clinical specimens indicated that SPAG9 is potential biomarker and therapeutic target for bladder TCC.

  18. Expression and Role of GPR87 in Urothelial Carcinoma of the Bladder

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    Yoshiyuki Kakehi

    2013-06-01

    Full Text Available The orphan GPR87 has recently been matched with its ligand LPA, which is a lipid mediator with multiple physiological functions, including cancer cell proliferation. This study aimed to clarify the role of GPR87 in urothelial carcinoma of the bladder. GPR87 expression was assessed in seven human bladder cancer cell lines. A replication-deficient recombinant adenoviral vector expressing shRNA targeting GPR87 (Ad-shGPR87, was constructed. Gene silencing was carried out using Ad-shGPR87. Immunohistochemical analysis was performed for transurethral resection of bladder tumor samples from 71 patients with non-muscle-invasive bladder cancer. We observed GPR87 expression in five of the seven cell lines, and silencing GPR87 gene expression significantly reduced cell viability. GPR87 expression was positive in 38 (54% of 71 tumors. Ki-67 index was associated with positive GPR87 staining status (p < 0.0001. Patients with GPR87-positive tumors had shorter intravesical recurrence-free survival than those with GPR87-negative tumors (p = 0.010. Multivariate analysis revealed that GPR87 staining status was an independent prognostic parameter for intravesical recurrence (p = 0.041. Progression from non-muscle-invasive to muscle-invasive tumor was more frequently observed in patients with GPR87-positive tumors, although this trend did not reach statistical significance (p = 0.056. These results warrant further prospective studies to clarify the role of GPR87 expression in intravesical recurrence and progression in bladder cancer.

  19. The role of zinc in the interplay between pathogenic streptococci and their hosts

    NARCIS (Netherlands)

    Shafeeq, Sulman; Kuipers, Oscar P.; Kloosterman, Tomas G.

    Recent studies on pathogenic streptococci have revealed that zinc is a pivotal metal ion in their interaction with the host. In these streptococci, systems exist that ensure optimal use of zinc from the surrounding milieu, as well as export of zinc when concentrations exceed tolerance levels. Zinc

  20. Roles of Forkhead-box Transcription Factors in Controlling Development, Pathogenicity, and Stress Response in Magnaporthe oryzae

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    Jaejin Park

    2014-06-01

    Full Text Available Although multiple transcription factors (TFs have been characterized via mutagenesis to understand their roles in controlling pathogenicity and infection-related development in Magnaporthe oryzae, the causal agent of rice blast, if and how forkhead-box (FOX TFs contribute to these processes remain to be characterized. Four putative FOX TF genes were identified in the genome of M. oryzae, and phylogenetic analysis suggested that two of them (MoFKH1 and MoHCM1 correspond to Ascomycota-specific members of the FOX TF family while the others (MoFOX1 and MoFOX2 are Pezizomycotina-specific members. Deletion of MoFKH1 (ΔMofkh1 resulted in reduced mycelial growth and conidial germination, abnormal septation and stress response, and reduced virulence. Similarly, ΔMohcm1 exhibited reduced mycelial growth and conidial germination. Conidia of ΔMofkh1 and ΔMohcm1 were more sensitive to one or both of the cell cycle inhibitors hydroxyurea and benomyl, suggesting their role in cell cycle control. On the other hand, loss of MoFOX1 (ΔMofox1 did not show any noticeable changes in development, pathogenicity, and stress response. Deletion of MoFOX2 was not successful even after repeated attempts. Taken together, these results suggested that MoFKH1 and Mo-HCM1 are important in fungal development and that MoFKH1 is further implicated in pathogenicity and stress response in M. oryzae.

  1. The role and regulation of catalase in respiratory tract opportunistic bacterial pathogens.

    Science.gov (United States)

    Eason, Mia M; Fan, Xin

    2014-09-01

    Respiratory tract bacterial pathogens are the etiologic agents of a variety of illnesses. The ability of these bacteria to cause disease is imparted through survival within the host and avoidance of pathogen clearance by the immune system. Respiratory tract pathogens are continually bombarded by reactive oxygen species (ROS), which may be produced by competing bacteria, normal metabolic function, or host immunological responses. In order to survive and proliferate, bacteria have adapted defense mechanisms to circumvent the effects of ROS. Bacteria employ the use of anti-oxidant enzymes, catalases and catalase-peroxidases, to relieve the effects of the oxidative stressors to which they are continually exposed. The decomposition of ROS has been shown to provide favorable conditions in which respiratory tract opportunistic bacterial pathogens such as Haemophilus influenzae, Mycobacterium tuberculosis, Legionella pneumophila, and Neisseria meningitidis are able to withstand exposure to highly reactive molecules and yet survive. Bacteria possessing mutations in the catalase gene have a decreased survival rate, yet may be able to compensate for the lack of catalatic activity if peroxidatic activity is present. An incomplete knowledge of the mechanisms by which catalase and catalase-peroxidases are regulated still persists, however, in some bacterial species, a regulatory factor known as OxyR has been shown to either up-regulate or down-regulate catalase gene expression. Yet, more research is still needed to increase the knowledge base in relation to this enzyme class. As with this review, we focus on major respiratory tract opportunistic bacterial pathogens in order to elucidate the function and regulation of catalases. The importance of the research could lead to the development of novel treatments against respiratory bacterial infections. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. The role of Tl-201 total body scintigraphy in follow up of thyroid carcinoma

    International Nuclear Information System (INIS)

    Hoefnagel, C.A.; Delprat, C.C.; Marcuse, H.R.

    1985-01-01

    To evaluate the reliability of the procedure T1-201 total body scintigraphy was performed in 294 patients (449 studies) after total thyroidectomy for thyroid carcinoma. Results were correlated with I-131-scintigraphy and tumor-marker levels (Tgb or Calcitonin/CEA). T1-201 total body scintigraphy was negative in 196 patients with no evidence of disease. T1-201-scintigraphy correctly detected tumor localizations in 24 of 30 patients with I-131-positive metastases. In 28 patients T2-201 total body scintigraphy revealed metastases which did not concentrate I-131. Histology/cytology confirmed thyroid carcinoma metastases in 16 patients and other pathology in 5 cases. 9 of 18 patients with medullary thyroid carcinoma (I-131-negative) had elevated Calcitonin/CEA-levels. The T1-201 scintigram was positive in 8 of these patients. Comparison of T1-201, I-131 and tumor markers showed that only combined use of these parameters provide complete reliability. The authors conclude that T1-201 total body scintigraphy is useful in follow up of thyroid carcinoma, especially when a discrepancy of the other parameters exists and particularly in medullary carcinoma. In long term follow up of patients who are unsuspected of disease after successful therapy for thyroid carcinoma one can rely on T1-201 total body scintigraphy in combination with tumor marker assays

  3. The Role of PI3K/Akt/mTOR Signaling in Gastric Carcinoma

    International Nuclear Information System (INIS)

    Matsuoka, Tasuku; Yashiro, Masakazu

    2014-01-01

    The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is one of the key signaling pathways induced by various receptor-tyrosine kinases. Accumulating evidence shows that this pathway is an important promoter of cell growth, metabolism, survival, metastasis, and resistance to chemotherapy. Genetic alterations in the PI3K/Akt/mTOR pathway in gastric carcinoma have often been demonstrated. Many kinds of molecular targeting therapies are currently undergoing clinical testing in patients with solid tumors. However, with the exception of the ErbB2-targeting antibody, targeting agents, including PI3K/Akt/mTOR inhibitors, have not been approved for treatment of patients with gastric carcinoma. This review summarizes the current knowledge on PI3K/Akt/mTOR signaling in the pathogenesis of gastric carcinoma and the possible therapeutic targets for gastric carcinoma. Improved knowledge of the PI3K/Akt/mTOR pathway in gastric carcinoma will be useful in understanding the mechanisms of tumor development and for identifying ideal targets of anticancer therapy for gastric carcinoma

  4. The Role of PI3K/Akt/mTOR Signaling in Gastric Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Matsuoka, Tasuku [Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Yashiro, Masakazu, E-mail: m9312510@med.osaka-cu.ac.jp [Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Oncology Institute of Geriatrics and Medical Science, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)

    2014-07-07

    The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is one of the key signaling pathways induced by various receptor-tyrosine kinases. Accumulating evidence shows that this pathway is an important promoter of cell growth, metabolism, survival, metastasis, and resistance to chemotherapy. Genetic alterations in the PI3K/Akt/mTOR pathway in gastric carcinoma have often been demonstrated. Many kinds of molecular targeting therapies are currently undergoing clinical testing in patients with solid tumors. However, with the exception of the ErbB2-targeting antibody, targeting agents, including PI3K/Akt/mTOR inhibitors, have not been approved for treatment of patients with gastric carcinoma. This review summarizes the current knowledge on PI3K/Akt/mTOR signaling in the pathogenesis of gastric carcinoma and the possible therapeutic targets for gastric carcinoma. Improved knowledge of the PI3K/Akt/mTOR pathway in gastric carcinoma will be useful in understanding the mechanisms of tumor development and for identifying ideal targets of anticancer therapy for gastric carcinoma.

  5. The aetiological role of human papillomavirus in oesophageal squamous cell carcinoma: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Surabhi S Liyanage

    Full Text Available BACKGROUND: The aetiological role of human papillomavirus (HPV in oesophageal squamous cell carcinoma (OSCC has been widely researched for more than three decades, with conflicting findings. In the absence of a large, adequately powered single case-control study, a meta-analysis of all available case-control studies is the most rigorous way of identifying any potential association between HPV and OSCC. We present the first global meta-analysis of case-control studies investigating the role of HPV in OSCC. METHODS: Case-control studies investigating OSCC tissue for presence of HPV DNA were identified. 21 case-control studies analyzing a total of 1223 cases and 1415 controls, met our inclusion criteria. HPV detection rates were tabulated for each study and all studies were assessed for quality. The random effects method was used to pool the odds ratios (OR. RESULTS: From all OSCC specimens included in this meta-analysis, 35% (426/1223 were positive for HPV DNA. The pooled OR for an HPV-OSCC association was 3.04 (95% CI 2.20 to 4.20. Meta-regression analysis did not find a significant association between OR and any of the quality domains. Influence analysis was non-significant for the effect of individual studies on the pooled estimate. Studies conducted in countries with low to medium OSCC incidence showed a stronger relationship (OR 4.65, 95% CI 2.47 to 8.76 than regions of high OSCC incidence (OR 2.65, 95% CI 1.80 to 3.91. CONCLUSIONS: Uncertainty around the aetiological role of HPV in OSCC is due largely to the small number and scale of appropriately designed studies. Our meta-analysis of these studies suggests that HPV increases the risk of OSCC three-fold. This study provides the strongest evidence to date of an HPV-OSCC association. The importance of these findings is that prophylactic vaccination could be of public health benefit in prevention of OSCC in countries with high OSCC incidence.

  6. EGFR kinase-dependent and kinase-independent roles in clear cell renal cell carcinoma.

    Science.gov (United States)

    Cossu-Rocca, Paolo; Muroni, Maria R; Sanges, Francesca; Sotgiu, Giovanni; Asunis, Anna; Tanca, Luciana; Onnis, Daniela; Pira, Giovanna; Manca, Alessandra; Dore, Simone; Uras, Maria G; Ena, Sara; De Miglio, Maria R

    2016-01-01

    Epidermal growth factor receptor (EGFR) is associated with progression of many epithelial malignancies and represents a significant therapeutic target. Although clear cell renal cell carcinoma (CCRCC) has been widely investigated for EGFR molecular alterations, genetic evidences of EGFR gene activating mutations and/or gene amplification have been rarely confirmed in the literature. Therefore, until now EGFR-targeted therapies in clinical trials have been demonstrated unsuccessful. New evidence has been given about the interactions between EGFR and the sodium glucose co-transporter-1 (SGLT1) in maintaining the glucose basal intracellular level to favour cancer cell growth and survival; thus a new functional role may be attributed to EGFR, regardless of its kinase activity. To define the role of EGFR in CCRCC an extensive investigation of genetic changes and functional kinase activities was performed in a series of tumors by analyzing the EGFR mutational status and expression profile, together with the protein expression of downstream signaling pathways members. Furthermore, we investigated the co-expression of EGFR and SGLT1 proteins and their relationships with clinic-pathological features in CCRCC. EGFR protein expression was identified in 98.4% of CCRCC. Furthermore, it was described for the first time that SGLT1 is overexpressed in CCRCC (80.9%), and that co-expression with EGFR is appreciable in 79.4% of the tumours. Moreover, the activation of downstream EGFR pathways was found in about 79.4% of SGLT1-positive CCRCCs. The mutational status analysis of EGFR failed to demonstrate mutations on exons 18 to 24 and the presence of EGFR-variantIII (EGFRvIII) in all CCRCCs analyzed. FISH analysis revealed absence of EGFR amplification, and high polysomy of chromosome 7. Finally, the EGFR gene expression profile showed gene overexpression in 38.2% of CCRCCs. Our study contributes to define the complexity of EGFR role in CCRCC, identifying its bivalent kinase

  7. Role of endoscopic biliary drainage in advanced hepatocellular carcinoma with jaundice.

    Science.gov (United States)

    Woo, Hyun Young; Han, Sung Yong; Heo, Jeong; Kim, Dong Uk; Baek, Dong Hoon; Yoo, So Yong; Kim, Chang Won; Kim, Suk; Song, Geun Am; Cho, Mong; Kang, Dae Hwan

    2017-01-01

    Patients with advanced hepatocellular carcinoma (HCC) with jaundice have an extremely poor prognosis. Although biliary drainage can resolve obstructive jaundice, signs of obstruction may not be evident. This study evaluated the role of endoscopic biliary drainage in patients with advanced HCC and obstructive jaundice. From 2010 to 2015, 74 patients underwent endoscopic biliary drainage for obstructive jaundice due to advanced HCC. Jaundice resolution was defined as complete response and total bilirubin concentration below 3 mg/dl. The technical success rate in the 74 patients was 92.1% (70/76). Of the 70 patients who underwent successful biliary drainage, 48 (68.6%) and 22 (31.4%) were Child-Pugh classes B and C, respectively, and 10 (14.3%) and 60 (85.7%) were BCLC stages B and C, respectively. Intrahepatic bile duct (IHD) dilatation was observed in 35 patients (50%). After drainage, the complete response rate was 35.7% (25/70). The mean time to resolution was 17.4 ±8.5 days. However, jaundice was re-aggravated in 74.3% (15/25) after a mean 103.5 ±96.4 days. Multivariate analysis showed that the absence of ascites, presence of IHD dilatation, normal range of prothrombin time, and lower MELD score were significantly associated with complete response. The overall survival rate was 15.7% (11/70) and the median survival time is 28 days (95% confidence interval 2.6-563 days). Complete response and HCC treatment after drainage were significantly associated with survival. Effective endoscopic biliary drainage is an important palliative treatment in patients with advanced HCC and obstructive jaundice, especially those with IHD dilatation and preserved liver function, as determined by ascites, prothrombin time, and MELD score.

  8. Role of radiofrequency ablation in unresectable hepatocellular carcinoma: An Indian experience

    International Nuclear Information System (INIS)

    Kalra, Naveen; Kang, Mandeep; Bhatia, Anmol; Duseja, Ajay K; Dhiman, Radha K; Arya, Virendra K; Rajwanshi, Arvind; Chawla, Yogesh K; Khandelwal, Niranjan

    2013-01-01

    To evaluate the role of radiofrequency ablation (RFA) as an ablative technique in patients with unresectable hepatocellular carcinoma (HCC). A tertiary care center, prospective study. The subjects comprised 31 patients (30 males, one female; age range 32-75 years) with HCC (41 lesions) who were treated with image-guided RFA. The follow-up period ranged from 3 months to 6 years, and included a multiphasic computed tomography (CT) at 1, 3 and 6 months post-RFA, and every 6 months thereafter. Patient outcome was evaluated and the tumor recurrence, survival and complications were assessed. Discrete categorical data were presented as n (%) and continuous data as mean ± SD. Pearson correlation coefficient was used to determine the relationship between the different variables. Kaplan–Meier survival curve and Log-rank test were used to test the significance of difference between the survival time of the different groups. The ablation success rate was 80.5% (33/41 HCC lesions). 12.2% (5/41) of the lesions were managed with repeat RFA due to tumor residue. 4.9% (2/41) of the lesions were managed with repeated RFA and transarterial chemoembolization. Eight patients had tumor recurrence (five patients (16.1%) had local recurrence and three patients (9.6%) had distant recurrence). Eleven patients died within 3.5-20 months post-RFA. The survival rate at 1 year in patients who completed at least 1 year of follow-up was 63.3%. There was one major complication (1/31, 3.2%) in a patient with a subcapsular lesion and ascites. This patient developed hemoperitoneum in the immediate postprocedure period and was managed with endovascular treatment. She, however, had hepatic decompensation and died 48 h post-RFA. RFA is an effective and safe treatment for small unresectable HCC

  9. Expression and role of oncogenic miRNA-224 in esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    He, Xiaoyan; Zhang, Zhimei; Li, Ming; Li, Shuo; Ren, Lihua; Zhu, Hong; Xiao, Bin; Shi, Ruihua

    2015-01-01

    Aberrant expression of miR-224 is associated with tumor development and progression. This study investigated the role of miR-224 in esophageal squamous cell carcinoma (ESCC) ex vivo and in vitro. A total of 103 esophageal intraepithelial neoplasia, ESCC tissue specimens, and their matched distant normal tissues were collected to test miR-224 expression using qRT-PCR analysis. Western blot was used to quantify the level of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1) and PHLPP2 in ESCC tissues. Cell viability, apoptosis, invasion, and colony formation assays were used to assess the altered phenotypes of esophageal cancer cell lines after miR-224 expression or inhibition. A luciferase reporter assay was used to confirm miR-224 binding to PHLPP1 and PHLPP2 mRNA. miR-224 was significantly overexpressed in esophageal intraepithelial neoplasia and ESCC tissues, while the expression of PHLPP1 and PHLPP2 proteins, the target genes of miR-224, was downregulated in ESCC tissues. miR-224 expression was associated with advanced clinical TNM stage, pathologic grade, and the level of PHLPP1 and PHLPP2 proteins in ESCC tissues. Ectopic overexpression of miR-224 promoted proliferation, migration, and invasion, but suppressed apoptosis of ESCC cells. miR-224 was able to bind to the 3′ untranslated region (3′-UTR) of PHLPP1 and PHLPP2 mRNA to suppress their expression. The current study demonstrated that miR-224 acts as an oncogenic miRNA in ESCC, possibly by targeting PHLPP1 and PHLPP2. The online version of this article (doi:10.1186/s12885-015-1581-6) contains supplementary material, which is available to authorized users

  10. Role of CXC chemokine ligand 13 in oral squamous cell carcinoma associated osteolysis in athymic mice.

    Science.gov (United States)

    Pandruvada, Subramanya N M; Yuvaraj, Sambandam; Liu, Xiang; Sundaram, Kumaran; Shanmugarajan, Srinivasan; Ries, William L; Norris, James S; London, Steven D; Reddy, Sakamuri V

    2010-05-15

    Oral squamous cell carcinomas (OSCC) are malignant tumors with a potent activity of local bone invasion; however, the molecular mechanisms of tumor osteolysis are unclear. In this study, we identified high level expression of chemokine ligand, CXCL13 and RANK ligand (RANKL) in OSCC cells (SCC1, SCC12 and SCC14a). OSCC cell-conditioned media (20%) induced osteoclast differentiation which was inhibited by OPG in peripheral blood monocyte cultures indicating that OSCC cells produce soluble RANKL. Recombinant hCXCL13 (10 ng/ml) significantly enhanced RANKL-stimulated osteoclast differentiation in these cultures. Trans-well migration assay identified that CXCL13 induces chemotaxis of peripheral blood monocytes in vitro which was inhibited by addition of anti-CXCR5 receptor antibody. Zymogram analysis of conditioned media from OSCC cells revealed matrix metalloproteinase-9 (MMP-9) activity. Interestingly, CXCL13 treatment to OSCC cells induced CXCR5 and MMP-9 expression suggesting an autocrine regulatory function in OSCC cells. To examine the OSCC tumor cell bone invasion/osteolysis, we established an in vivo model for OSCC by subcutaneous injection of OSCC cells onto the surface of calvaria in NCr-nu/nu athymic mice, which developed tumors in 4-5 weeks. muCT analysis revealed numerous osteolytic lesions in calvaria from OSCC tumor-bearing mice. Histochemical staining of calvarial sections from these mice revealed a significant increase in the numbers of TRAP-positive osteoclasts at the tumor-bone interface. Immunohistochemical analysis confirmed CXCL13 and MMP-9 expression in tumor cells. Thus, our data implicate a functional role for CXCL13 in bone invasion and may be a potential therapeutic target to prevent osteolysis associated with OSCC tumors in vivo.

  11. The role of bioactive substances in controlling foodborne pathogens derived from Metasequoia glyptostroboides Miki ex Hu.

    Science.gov (United States)

    Bajpai, Vivek K; Na, Minkyun; Kang, Sun Chul

    2010-07-01

    In an attempt to isolate bioactive substances, ethyl acetate cone extract of Metasequoia glyptostroboides was subjected to a column chromatographic analysis that resulted in isolation of an abietane type diterpenoid, taxoquinone. Its structure was elucidated by spectroscopic means. In further, taxoquinone showed potential antibacterial effect as diameters of zones of inhibition against foodborne pathogenic bacteria such as Listeria monocytogenes ATCC 19166, Salmonella typhimurium KCTC 2515, Salmonella enteritidis KCTC 2021, Escherichia coli ATCC 8739, E. coli O157:H7 ATCC 43888, Enterobacter aerogenes KCTC2190, Staphylococcus aureus ATCC 6538 and S. aureus KCTC 1916, which were found in the range of 10.6-15.8mm. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of taxoquinone against the employed bacterial pathogens were found in the range of 62.5-250 and 125-500 microg/ml. Also the compound had strong antibacterial effect on the viable counts of the tested bacteria. Further, scanning electron microscopic study demonstrated potential detrimental effect of taxoquinone on the morphology of E. coli ATCC 8739. These findings indicate that bioactive compound taxoquinone present in M. glyptostroboides could be used as a promising antibacterial agent in food industry to inhibit the growth of certain important foodborne pathogens. 2010 Elsevier Ltd. All rights reserved.

  12. Biofilms in drinking water and their role as reservoir for pathogens.

    Science.gov (United States)

    Wingender, Jost; Flemming, Hans-Curt

    2011-11-01

    Most microorganisms on Earth live in various aggregates which are generally termed "biofilms". They are ubiquitous and represent the most successful form of life. They are the active agent in biofiltration and the carriers of the self-cleaning potential in soils, sediments and water. They are also common on surfaces in technical systems where they sometimes cause biofouling. In recent years it has become evident that biofilms in drinking water distribution networks can become transient or long-term habitats for hygienically relevant microorganisms. Important categories of these organisms include faecal indicator bacteria (e.g., Escherichia coli), obligate bacterial pathogens of faecal origin (e.g., Campylobacter spp.) opportunistic bacteria of environmental origin (e.g., Legionella spp., Pseudomonas aeruginosa), enteric viruses (e.g., adenoviruses, rotaviruses, noroviruses) and parasitic protozoa (e.g., Cryptosporidium parvum). These organisms can attach to preexisting biofilms, where they become integrated and survive for days to weeks or even longer, depending on the biology and ecology of the organism and the environmental conditions. There are indications that at least a part of the biofilm populations of pathogenic bacteria persists in a viable but non-culturable (VBNC) state and remains unnoticed by the methods appointed to their detection. Thus, biofilms in drinking water systems can serve as an environmental reservoir for pathogenic microorganisms and represent a potential source of water contamination, resulting in a potential health risk for humans if left unnoticed. Copyright © 2011 Elsevier GmbH. All rights reserved.

  13. Functional role and prognostic significance of CD157 in ovarian carcinoma.

    Science.gov (United States)

    Ortolan, Erika; Arisio, Riccardo; Morone, Simona; Bovino, Paola; Lo-Buono, Nicola; Nacci, Giulia; Parrotta, Rossella; Katsaros, Dionyssios; Rapa, Ida; Migliaretti, Giuseppe; Ferrero, Enza; Volante, Marco; Funaro, Ada

    2010-08-04

    CD157, an ADP-ribosyl cyclase-related cell surface molecule, regulates leukocyte diapedesis during inflammation. Because CD157 is expressed in mesothelial cells and diapedesis resembles tumor cell migration, we investigated the role of CD157 in ovarian carcinoma. We assayed surgically obtained ovarian cancer and mesothelial cells and both native and engineered ovarian cancer cell lines for CD157 expression using flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR), and for adhesion to extracellular matrices, migration, and invasion using cell-based assays. We investigated invasion of human peritoneal mesothelial cells by serous ovarian cancer cells with a three-dimensional coculture model. Experiments were performed with or without CD157-blocking antibodies. CD157 expression in tissue sections from ovarian cancer patients (n = 88) was examined by immunohistochemistry, quantified by histological score (H score), and categorized as at or above or below the median value of 60, and compared with clinical parameters. Statistical tests were two-sided. CD157 was expressed by ovarian cancer cells and mesothelium, and it potentiated the adhesion, migration, and invasion of serous ovarian cancer cells through different extracellular matrices. CD157-transfected ovarian cancer cells migrated twice as much as CD157-negative control cells (P = .001). Blockage of CD157 inhibited mesothelial invasion by serous ovarian cancer cells in a three-dimensional model. CD157 was expressed in 82 (93%) of the 88 epithelial ovarian cancer tissue specimens. In serous ovarian cancer, patients with CD157 H scores of 60 or greater had statistically significantly shorter disease-free survival and overall survival than patients with lower CD157 H scores (CD157 H score > or =60 vs or =60 vs <60: median overall survival = 45 months, 95% CI = 21.21 to 68.79 vs unreached, P = .024). Multivariable Cox regression showed that CD157 is an independent prognostic factor for recurrence

  14. The role of IgG4 (+) plasma cells in the association of Hashimoto's thyroiditis with papillary carcinoma.

    Science.gov (United States)

    Taşli, Funda; Ozkök, Güliz; Argon, Asuman; Ersöz, Didem; Yağci, Ayşe; Uslu, Adam; Erkan, Nazif; Salman, Tarik; Vardar, Enver

    2014-12-01

    Hashimoto's thyroiditis (HT) is considered to be a risk factor for the formation of papillary carcinoma. The association of IgG4-related sclerosing disease with tumor is reported to be as sporadic cases in many organs. In this study, it was intended to re-classify the HT diagnosed cases on the basis of the existence of IgG4 (+) plasma cells; to investigate the clinicopathologic and histopathologic features of the both groups; and in addition, to evaluate the papillary carcinoma prevalence in IgG4 (+) and IgG4 (-) HT cases as well as the prognostic parameters between these groups. Totally 59 cases between the years 2008-2013, 29 of which contain Hashimoto thyroiditis diagnosis in total thyroidectomy materials, and 30 of which contain the diagnosis of HT+papillary carcinoma, were included in the study. The materials were immunohistochemically applied IgG and IgG4; and the cases were classified in two groups as IgG4-positive HT and IgG4-negative HT containing cases, on the basis of IgG4/IgG rate. All histopathologic and clinicopathologic parameters between these two groups, as well as their association with papillary carcinoma were investigated. Thirty eight (64.4%) of total 59 cases were NonIgG4 thyroiditis, and 21 (35.5%) were IgG4 thyroiditis. Tumors were detected in 14 (36.8%) of the NonIgG4 thyroiditis cases, and in 16 (76.1%) of the IgG4 thyroiditis cases. The association of IgG4 thyroiditis with tumor is statistically significant (p thyroiditis cases. Perithyroidal extension was detected in six of the cases with tumor, and five of the six cases were IgG4 thyroiditis cases. The association of IgG4 (+) HT cases with increased papillary carcinoma prevalence is suggestive of that IgG4 (+) plasma cells can play a role in carcinogenesis in papillary carcinomas developed in HTs, without a chronic sclerosing ground. In addition, although the number of cases is limited, the high-association of IgG4 (+) plasma cells with adverse prognostic parameters such as

  15. Ductal carcinoma in situ within fibroadenoma: Microcalcifications identified on mammography play a crucial role in diagnosis

    International Nuclear Information System (INIS)

    You, Jai Kyung; Kim, Yee Jeong; Kim, Bo Mi; Kim, Eun Kyung

    2016-01-01

    Fibroadenoma is a common, benign tumor of the breast, which is rarely associated with an increased risk of carcinoma. We report a case of ductal carcinoma in situ within a fibroadenoma in a 38-year-old woman. The lesion was a 1 cm, circumscribed, ovoid mass with internal calcifications evident on mammography and ultrasound, which is commonly found in fibroadenoma, but the calcifications were fine and linear, which is uncommon. This type of calcification is classified as suspicious by the American College of Radiology Breast Imaging-Reporting And Data System, and it is often correlated with comedo necrosis of ductal carcinoma, and, so, requires immediate pathologic confirmation. In our case, careful analysis of the unusual calcifications led to appropriate intervention and diagnosis. Radiologists should be aware that fibroadenomas can be malignant, and they should look for suspicious microcalcifications within a fibroadenoma

  16. Ductal carcinoma in situ within fibroadenoma: Microcalcifications identified on mammography play a crucial role in diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    You, Jai Kyung; Kim, Yee Jeong; Kim, Bo Mi [NHIS Ilsan Hospital, Goyang (Korea, Republic of); Kim, Eun Kyung [Dept. of Diagnostic Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-06-15

    Fibroadenoma is a common, benign tumor of the breast, which is rarely associated with an increased risk of carcinoma. We report a case of ductal carcinoma in situ within a fibroadenoma in a 38-year-old woman. The lesion was a 1 cm, circumscribed, ovoid mass with internal calcifications evident on mammography and ultrasound, which is commonly found in fibroadenoma, but the calcifications were fine and linear, which is uncommon. This type of calcification is classified as suspicious by the American College of Radiology Breast Imaging-Reporting And Data System, and it is often correlated with comedo necrosis of ductal carcinoma, and, so, requires immediate pathologic confirmation. In our case, careful analysis of the unusual calcifications led to appropriate intervention and diagnosis. Radiologists should be aware that fibroadenomas can be malignant, and they should look for suspicious microcalcifications within a fibroadenoma.

  17. The role of metalloendopeptidases in oropharyngeal carcinomas assessed by tissue microarray.

    Science.gov (United States)

    Ribeiro, Daniel A; Nascimento, Fabio D; Fracalossi, Ana Carolina C; Noguti, Juliana; Oshima, Celina T F; Ihara, Silvia S M; Franco, Marcello F

    2011-01-01

    The goal of this study was to investigate the expression of some metalloendopeptidases in squamous cell carcinomas of the oropharynx as well as its relation to histological differentiation, staging of disease, and prognosis. Paraffin blocks from 21 primary tumors were obtained from archives of the Department of Pathology, Paulista Medical School, Federal University of Sao Paulo, UNIFESP/EPM. Immunohistochemistry was used to detect the expression of EP24.15 and EP24.16 by means of tissue microarrays. Expression of EP24.15 or EP24.16 was not correlated with the stage of disease, histopathological grading or recurrence in squamous cell carcinomas of the oropharynx. In summary, our results support the notion that EP24.15 and EP24.16 are expressed in carcinoma of the oropharynx; however, these do not appear to be suitable biomarkers for histological grading, disease stage or recurrence as depicted by tissue microarrays and immunohistochemistry.

  18. The role of thyrotropin suppression in patients with differentiated thyroid carcinoma.

    LENUS (Irish Health Repository)

    Deasy, J

    2010-07-01

    Thyroid carcinoma is the commonest endocrine malignancy. The majority of these are differentiated thyroid carcinomas, which have a good overall prognosis. Treatment includes surgical excision, radio-iodine ablation and long-term thyrotropin suppression. The degree and length of suppression required, as well as the potential side-effect remain controversial. Therefore, the aim of this study was to establish the degree of thyrotropin suppression achieved in a cohort of patients with differentiated thyroid carcinoma. A retrospective review was performed of a prospectively maintained database. All patients with a diagnosis of differentiated thyroid carcinoma between January 1998 and January 2008 were identified. Demographic data, pathological stage and the treatment that the patient received was documented. TSH and free T4 levels were identified at specific time points post-operatively. Eighty-eight patients with differentiated thyroid carcinoma were identified. Seventy patients (79.5%) were female. The mean age was 55, with a range of 18 to 79 years. The majority of patients underwent a total thyroidectomy (n=79; 89.7%) and of those 29 (32.9%) had an associated modified neck dissection. Accurate follow-up was available on forty-nine patients. TSH and free T4 were measured at 3 and 6 months, as well as at 1 and 2 years post-operatively. Adequate TSH suppression was taken at a level < 0.1 mU\\/L. The majority of patients (69.5%) had achieved adequate TSH suppression at 2 years. However, 65% of these same patients had a high free T4 at 2 years indicating a degree of hyperthyroidism. This study has demonstrated that TSH suppression is being adequately achieved in the majority of patients with differentiated thyroid carcinoma. However, this must be carefully weighed against the potential detrimental side-effects of long-term sub-clinical hyperthyroidism.

  19. A novel role for the TIR domain in association with pathogen-derived elicitors.

    Directory of Open Access Journals (Sweden)

    Tessa M Burch-Smith

    2007-03-01

    Full Text Available Plant innate immunity is mediated by Resistance (R proteins, which bear a striking resemblance to animal molecules of similar function. Tobacco N is a TIR-NB-LRR R gene that confers resistance to Tobacco mosaic virus, specifically the p50 helicase domain. An intriguing question is how plant R proteins recognize the presence of pathogen-derived Avirulence (Avr elicitor proteins. We have used biochemical cell fraction and immunoprecipitation in addition to confocal fluorescence microscopy of living tissue to examine the association between N and p50. Surprisingly, both N and p50 are cytoplasmic and nuclear proteins, and N's nuclear localization is required for its function. We also demonstrate an in planta association between N and p50. Further, we show that N's TIR domain is critical for this association, and indeed, it alone can associate with p50. Our results differ from current models for plant innate immunity that propose detection is mediated solely through the LRR domains of these molecules. The data we present support an intricate process of pathogen elicitor recognition by R proteins involving multiple subcellular compartments and the formation of multiple protein complexes.

  20. Drivers of bacterial genomes plasticity and roles they play in pathogen virulence, persistence and drug resistance.

    Science.gov (United States)

    Patel, Seema

    2016-11-01

    Despite the advent of next-generation sequencing (NGS) technologies, sophisticated data analysis and drug development efforts, bacterial drug resistance persists and is escalating in magnitude. To better control the pathogens, a thorough understanding of their genomic architecture and dynamics is vital. Bacterial genome is extremely complex, a mosaic of numerous co-operating and antagonizing components, altruistic and self-interested entities, behavior of which are predictable and conserved to some extent, yet largely dictated by an array of variables. In this regard, mobile genetic elements (MGE), DNA repair systems, post-segregation killing systems, toxin-antitoxin (TA) systems, restriction-modification (RM) systems etc. are dominant agents and horizontal gene transfer (HGT), gene redundancy, epigenetics, phase and antigenic variation etc. processes shape the genome. By illegitimate recombinations, deletions, insertions, duplications, amplifications, inversions, conversions, translocations, modification of intergenic regions and other alterations, bacterial genome is modified to tackle stressors like drugs, and host immune effectors. Over the years, thousands of studies have investigated this aspect and mammoth amount of insights have been accumulated. This review strives to distillate the existing information, formulate hypotheses and to suggest directions, that might contribute towards improved mitigation of the vicious pathogens. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. The role of oxidative stress and periodontal disease in squamous cell carcinomas of the oral cavity – a review

    Directory of Open Access Journals (Sweden)

    Simina Boia1,

    2016-12-01

    Full Text Available OBJECTIVES AND BACKGROUND This multidisciplinary and retrospective study of the Periodontal, Ear nose and throat, Oral-Maxillofacial and Biochemical literature aims, highlights and recalls the important role of the oxidative stress (OS and periodontal disease in the development of squamous cell carcinomas of the oral cavity (OSCC. MATERIALS AND METHODS In the present study we analyzed a total number of 670 cases, collected from specialized scientific papers belonging to several authors of international level. These scientific papers are focused on highlighting the most common lipid peroxidation marker, Malondialdehyde (MDA, of both periodontal disease and squamous cell carcinoma of the oral cavity from serum or saliva samples that are biochemically collected and analyzed. RESULTS In all analyzed studies, we found that oxidative stress alters the composition of saliva. Also the depletion of antioxidants was remarked in the groups of subjects diagnosed with OSCC and those affected by periodontal disease. Scientific studies that investigated smokers, revealed the fact that these patients also show increased levels of reactive oxygen species. Thus, it is very likely that oxidative damage is intensified by smoking. CONCLUSIONS The purpose of this review was to emphasize the importance of oxidative stress in the development of periodontal disease as a first stage towards the development of squamous cell carcinomas and to represent the essential foundation of more extensive future investigations. REFERENCES 1. Rashmi M, Saumya B. Evaluation of salivary and serum lipid peroxidation, and glutathione in oral leukoplakia and oral squamous cell carcinoma. Journal of Oral Science. 2014;56:135-142. 2. Tóthová L, Kamodyová N, Červenka T, Celec P. Salivary markers of oxidative stress in oral diseases. Front. Cell. Infect. Microbiol. 2015. 3. Bahar G, Feinmesser R, Shpitzer T, Popovtzer A, Nagler RM, Salivary analysis in oral cancer patients: DNA and protein

  2. NADPH-dependent thioredoxin reductase C plays a role in nonhost disease resistance against Pseudomonas syringae pathogens by regulating chloroplast-generated reactive oxygen species

    Directory of Open Access Journals (Sweden)

    Yasuhiro Ishiga

    2016-04-01

    Full Text Available Chloroplasts are cytoplasmic organelles for photosynthesis in eukaryotic cells. In addition, recent studies have shown that chloroplasts have a critical role in plant innate immunity against invading pathogens. Hydrogen peroxide is a toxic by-product from photosynthesis, which also functions as a signaling compound in plant innate immunity. Therefore, it is important to regulate the level of hydrogen peroxide in response to pathogens. Chloroplasts maintain components of the redox detoxification system including enzymes such as 2-Cys peroxiredoxins (2-Cys Prxs, and NADPH-dependent thioredoxin reductase C (NTRC. However, the significance of 2-Cys Prxs and NTRC in the molecular basis of nonhost disease resistance is largely unknown. We evaluated the roles of Prxs and NTRC using knock-out mutants of Arabidopsis in response to nonhost Pseudomonas syringae pathogens. Plants lacking functional NTRC showed localized cell death (LCD accompanied by the elevated accumulation of hydrogen peroxide in response to nonhost pathogens. Interestingly, the Arabidopsis ntrc mutant showed enhanced bacterial growth and disease susceptibility of nonhost pathogens. Furthermore, the expression profiles of the salicylic acid (SA and jasmonic acid (JA-mediated signaling pathways and phytohormone analyses including SA and JA revealed that the Arabidopsis ntrc mutant shows elevated JA-mediated signaling pathways in response to nonhost pathogen. These results suggest the critical role of NTRC in plant innate immunity against nonhost P. syringae pathogens.

  3. Modeling and roles of meteorological factors in outbreaks of highly pathogenic avian influenza H5N1.

    Directory of Open Access Journals (Sweden)

    Paritosh K Biswas

    Full Text Available The highly pathogenic avian influenza A virus subtype H5N1 (HPAI H5N1 is a deadly zoonotic pathogen. Its persistence in poultry in several countries is a potential threat: a mutant or genetically reassorted progenitor might cause a human pandemic. Its world-wide eradication from poultry is important to protect public health. The global trend of outbreaks of influenza attributable to HPAI H5N1 shows a clear seasonality. Meteorological factors might be associated with such trend but have not been studied. For the first time, we analyze the role of meteorological factors in the occurrences of HPAI outbreaks in Bangladesh. We employed autoregressive integrated moving average (ARIMA and multiplicative seasonal autoregressive integrated moving average (SARIMA to assess the roles of different meteorological factors in outbreaks of HPAI. Outbreaks were modeled best when multiplicative seasonality was incorporated. Incorporation of any meteorological variable(s as inputs did not improve the performance of any multivariable models, but relative humidity (RH was a significant covariate in several ARIMA and SARIMA models with different autoregressive and moving average orders. The variable cloud cover was also a significant covariate in two SARIMA models, but air temperature along with RH might be a predictor when moving average (MA order at lag 1 month is considered.

  4. Role of 18F-FDG PET/CT in Posttreatment Evaluation of Anal Carcinoma.

    Science.gov (United States)

    Houard, Clémence; Pinaquy, Jean-Baptiste; Mesguich, Charles; Henriques de Figueiredo, Bénédicte; Cazeau, Anne-Laure; Allard, Jean-Baptiste; Laharie, Hortense; Bordenave, Laurence; Fernandez, Philippe; Vendrely, Véronique

    2017-09-01

    The aim of this study was to evaluate the relevance of PET/CT and 18 F-FDG as a strategy for response evaluation after chemoradiotherapy for anal cancer. For this, the performance of posttreatment 18 F-FDG PET/CT, the impact on patient care, and the predictive value of metabolic response were assessed. Methods: This was a retrospective and multicenter analysis of 87 patients treated by chemoradiotherapy for anal squamous cell carcinoma between October 2007 and October 2013. All patients underwent systematic posttreatment 18 F-FDG PET/CT and were followed with at least a clinical examination every 4 mo for 2 y and every 6 mo thereafter. Disease progression was confirmed by biopsy for all patients in the case of local recurrence before surgery. Kaplan-Meier and Cox regression models were used to test for associations between metabolic or clinical endpoints and progression-free survival (PFS) or cause-specific survival (CSS). Results: The median follow-up was 25 mo. 18 F-FDG PET/CT was performed 1-8 mo (median, 4 mo) after completion of chemoradiotherapy. Overall, 25 patients relapsed and 13 died. The posttherapy 18 F-FDG PET/CT did not show any abnormal 18 F-FDG uptake (complete metabolic response [CMR]) in 55 patients whereas 32 displayed incomplete response (non-CMR): 15 patients with partial response and 17 with disease progression. The sensitivity of 18 F-FDG PET/CT to detect residual tumor tissue was 92% (95% confidence interval [CI], 75%-97%), specificity was 85% (95% CI, 75%-92%), positive predictive value was 72% (95% CI, 61%-90%), and negative predictive value was 96.4% (95% CI, 90%-98.7%). The 2-y PFS was 96% (95% CI, 90-100) for patients with CMR and 28% (95% CI, 14-47) for non-CMR patients ( P PET/CT changed patient management in 14 cases (16%), with relevant modifications in 12 (14%). A Cox proportional hazards model of survival outcome indicated that a CMR was the only significant predictor of PFS and CSS ( P PET/CT shows good accuracy in posttreatment

  5. Recurrent bladder carcinoma: clinical and prognostic role of 18 F-FDG PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Alongi, Pierpaolo [San Raffaele G. Giglio Institute, Department of Radiological Sciences, Nuclear Medicine Unit, Cefalu (Italy); Caobelli, Federico [Basel University Hospital, Department of Nuclear Medicine, Basel (Switzerland); Gentile, Roberta; Baldari, Sergio [University of Messina, Nuclear Medicine Unit, Department of Biomedical Sciences and Morphological and Functional Images, Messina (Italy); Stefano, Alessandro; Russo, Giorgio; Gilardi, Maria Carla [IBFM-CNR, Cefalu (Italy); Albano, Domenico [Universita degli Studi di Palermo, DIBIMEF - Sezione di Scienze Radiologiche, Palermo (Italy); Midiri, Massimo [San Raffaele G. Giglio Institute, Department of Radiological Sciences, Nuclear Medicine Unit, Cefalu (Italy); Universita degli Studi di Palermo, DIBIMEF - Sezione di Scienze Radiologiche, Palermo (Italy)

    2017-02-15

    A small number of studies evaluated the detection rate of lesions from bladder carcinoma (BC) of 18 F-FDG PET/CT in the restaging process. However, the prognostic role of FDG PET/CT still remains unclear. The aim of the present study was to evaluate the accuracy, the effect upon treatment decision, and the prognostic value of FDG PET/CT in patients with suspected recurrent BC. Forty-one patients affected by BC underwent FDG PET/CT for restaging purpose. The diagnostic accuracy of visually interpreted FDG PET/CT was assessed compared to histology (n = 8), other diagnostic imaging modalities (contrast-enhanced CT in 38/41 patients and MRI in 15/41) and clinical follow-up (n = 41). Semiquantitative PET values (SUVmax, SUVmean, SUL, MTV, TLG) were calculated using a graph-based method. Progression-free survival (PFS) and overall survival (OS) were assessed by using Kaplan-Meier curves. The risk of progression (hazard ratio, HR) was computed by Cox regression analysis by considering all the available variables. PET was considered positive in 21 of 41 patients. Of these, recurrent BC was confirmed in 20 (95 %). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG PET/CT were 87 %, 94 %, 95 %, 85 %, 90 %. AUC was 0.9 (95 %IC 0.8-1). Bayesian positive and negative likelihood ratios were 14.5 and 0.13, respectively. FDG PET/CT findings modified the therapeutic approach in 16 patients (modified therapy in 10 PET-positive patients, watch-and-wait in six PET-negative patients). PFS was significantly longer in patients with negative scan vs. those with pathological findings (85 % vs. 24 %, p < 0.05; HR = 12.4; p = 0.001). Moreover, an unremarkable study was associated with a longer OS (88 % vs. 47 % after 2 years and 87 % vs. 25 % after 3 years, respectively, p < 0.05). Standardized uptake value (SUV)max > 6 and total lesion glycolysis (TLG) > 8.5 were recognized as the most accurate thresholds to predict PFS (2-year PFS 62 % for

  6. Role of percutaneous nephrostomy in advanced cervical carcinoma with obstructive uropathy: A case series

    Directory of Open Access Journals (Sweden)

    Kamlesh Mishra

    2009-01-01

    Full Text Available Aims and Objective: Over 70% of the cases present in advanced stages of the disease and are associated with poor prognosis and high mortality rates. In many of them, it is difficult to offer definitive treatment as they present in uremia due to associated obstructive uropathy. There are no clear-cut guidelines for performing percutaneous nephrostomy (PCN in patients of advanced cervical cancer. The results are unpredictable in terms of benefits achieved in these cases. Thus, we evaluated our experiences with PCN in the management of cervical cancer patients presenting with obstructive uropathy. Material and Methods: 15 patients of cervical cancer with obstructive uropathy and deranged renal functions were retrospectively evaluated for the role of PCN in their management Results: PCN was done in 15 patients of advanced cervical cancer. The mean age of patients was 44.5 years. Twelve (80% patients presented primarily with advanced cervical carcinoma and obstructive uropathy. Three (20% were already treated. Symptomatic improvement and significant fall of mean serum creatinine value from 7.5 mg% to 0.9 mg% over a period of 1-3 weeks was noted post PCN. Out of 12 patient with primary untreated advanced disease, curative treatment was possible in 3, palliative radiotherapy/chemo-therapy in 7 and only symptomatic treatment in 2 cases, after obstructive uropathy was managed with PCN insertion. Out of 3 already treated patients, 2 were disease free after curative radiotherapy/surgery. PCN was done to prevent permanent kidney damage in them. One patient was defaulter of curative radiotherapy. She had progressive residual disease. Complications like hemorrhage (20%, infection (26%, reinsertion for dislodgment/misplacement (53%, percutaneous leak or perinephric leak (20%, blockage of PCN (33% were noticed. Conclusion: In spite of inherent, albeit manageable complications, PCN is a simple and safe technique. One of the major benefits observed was

  7. Role of novel anticancer drug Roscovitine on enhancing radiosensitivity in carcinoma cell lines

    International Nuclear Information System (INIS)

    Noaman, E.; Sayed, H.M.; Medhat, A.M.; Morcos, N.Y.S.

    2010-01-01

    The present study was conducted to evaluate the radiosensitization effect of Roscovitine (cyclin dependent kinase inhibitor) in carcinoma cell lines. Three cell lines are used liver carcinoma cell line (HepG2), brain carcinoma cell line (U251), Lung carcinoma cell line (H460) in this study cells were treated with Roscovitine in different concentrations ranging from 0.1 ?M to 100 ?M before exposure to radiation doses ranging from 0.5 Gy to 20 Gy according to each experiment. The cell viability by MTT assay, the cell cycle analysis by flow cytometry and DNA fragmentation repair mechanism by diphenylamine were measured after Roscovitine treatment with or without radiation exposure to explore the sensitization effect of Roscovitine. The present study conclude that Roscovitine a good candidate as radiosensitizer for modifying the ionizing radiation (IR) response in cancer cells, beside its cyclin dependent kinase inhibitor function, Roscovitine can generate DNA Double strand Breaks and cooperate to enhance IR induce DNA damages. Roscovitine is currently in clinical trials, although our findings suggest that the combination of Roscovitine with IR appears to be a very promising especially for liver, brain and lung cancer treatment, further investigation is needed to evaluate the therapeutic index before tested in clinical trials

  8. Role of novel anticancer drug Roscovitine on enhancing radiosensitivity in carcinoma cell lines

    International Nuclear Information System (INIS)

    Mohamed, H.M.S.

    2009-01-01

    The present study was conducted to evaluate the radiosensitization effect of Roscovitine (cyclin dependent kinase inhibitor) in carcinoma cell lines. Three cell lines are used (HepG2 liver carcinoma cell line, U251 brain carcinoma cell line, H460 Lung carcinoma cell line) in this study .cells were treated with Roscovitine in different concentrations ranging from 0.1μM to 100 μM before exposure to radiation doses ranging from 0.5 Gy to 20 Gy according to each experiment. The cell viability by MTT assay, The cell cycle analysis by flow cytometry and DNA fragmentation repair mechanism by diphenylamine were measured after Roscovitine treatment with or without radiation to explore the sensitization effect of Roscovitine. The present study conclude that Roscovitine a good candidate as radiosensitizer for modifying the ionizing radiation (IR) response in cancer cells, beside its cyclin dependent kinase inhibitor function, roscovitine can generate DNA Double strand Breaks and cooperate to enhance IR induce DNA damages . Roscovitine is currently in clinical trials, although our findings suggest that the combination of Roscovitine with IR appears to be a very promising especially for liver, brain and lung cancer treatment, further investigation is needed to evaluate the therapeutic index before tested in clinical trial

  9. Painless thyroiditis associated to thyroid carcinoma: role of initial ultrasonography evaluation.

    Science.gov (United States)

    Valentini, Raisa Bressan; Macedo, Bruno Mussoi de; Izquierdo, Rogério Friedrich; Meyer, Erika Laurini Souza

    2016-04-01

    Even though it is a rare event, most associations of thyroid carcinoma with subacute thyroiditis described in the literature are related to its granulomatous form (Quervain's thyroiditis). We present a patient with subacute lymphocytic thyroiditis (painless thyroiditis) and papillary thyroid cancer that was first suspected in an initial ultrasound evaluation. A 30-year old female patient who was referred to the emergency room due to hyperthyroidism symptoms was diagnosed with painless thyroiditis established by physical examination and laboratory findings. With the presence of a palpable painless thyroid nodule an ultrasound was prescribed and the images revealed a suspicious thyroid nodule, microcalcification focus in the heterogeneous thyroid parenquima and cervical lymphadenopathy. Fine needle aspiration biopsy was taken from this nodule; cytology was assessed for compatibility with papillary thyroid carcinoma. Postsurgical pathology evaluation showed a multicentric papillary carcinoma and lymphocytic infiltration. Subacute thyroiditis, regardless of type, may produce transitory ultrasound changes that obscure the coexistence of papillary carcinoma. Due to this, initial thyroid ultrasound evaluation should be delayed until clinical recovery. We recommended a thyroid ultrasound exam for initial evaluation of painless thyroiditis, particularly in patients with palpable thyroid nodule. Further cytological examination is recommended in cases presenting with suspect thyroid nodule and/or non-nodular hypoechoic (> 1 cm) or heterogeneous areas with microcalcification focus.

  10. Soft tissue buccal carcinoma - a role of MDCT and PET/CT during the staging procedure

    International Nuclear Information System (INIS)

    Al-Amin, M.; Zlatareva, D.; Dineva, S.; Hadjidekov, V.; Kostadinova, I.; Al-Amin, B.

    2013-01-01

    Full text: Introduction: The incidence of buccal mucosa carcinoma is 8-10 % of cancers developing in the oral mucosa. Most often it develops on prior pre-neoplasia: leucoplakia, lichen. Characterized by painless in the early growth. The tumor is widely and quickly grows into the underlying tissues. Contracture are common. Histologically settled mostly squamous cell carcinoma and rarely glandular small salivary glands. What you will learn: A case study about a patient referred by a dentist with a painless swelling of the face on the right, with tightly - elastin texture appeared about 3 months ago is presented . Patient has difficulty swallowing, talking and breathing and limited mouth opening. Discussion: A MDCT study with intravenous contrast medium was performed for findings staging. It is found a heterodense tumor formation, involving the nasopharynx and oropharynx right without infiltration of main blood vessels with destruction of almost the entire branch of the mandible, with an interruption of the processus caronoideus integrity as well as the lateral wall and floor of the right maxillary sinus. The diagnose is buccal tumor formation in stage T4 N2V, Mx. The patient was referred to a specialized hospital for active treatment in maxillofacial surgery, where a biopsy was done and the histological result is: moderately differentiated buccal and gingival squamous cell carcinoma. From X-ray study of the lungs and heart several pulmonary nodules are identified and there is a possibility for metastatic lesions. Patient was referred for restaging and conducting whole body PET/CT. It is found a metabolically active tumor formation with data for regional lymphatic dissemination in the right. Conclusion: Squamous cell carcinoma is the most common cancer of the oral cavity (90-95 %). Buccal carcinoma represents 9.8% of cancer of the oral cavity and maxillofacial area. Treatment is complex. The five-year survival in T3 and T4 stages is 20-30%

  11. Role of microRNA-7 and selenoprotein P in hepatocellular carcinoma.

    Science.gov (United States)

    Tarek, Marwa; Louka, Manal Louis; Khairy, Eman; Ali-Labib, Randa; Zakaria Zaky, Doaa; Montasser, Iman F

    2017-05-01

    There is an obvious need to diagnose hepatocellular carcinoma using novel non-invasive and sensitive biomarkers. In this regard, the aim of this study was to evaluate and correlate both relative quantification of microRNA-7 using quantitative real time polymerase chain reaction and quantitative analysis of selenoprotein P using enzyme-linked immunosorbent assay in sera of hepatocellular carcinoma patients, chronic liver disease patients, as well as normal healthy subjects in order to establish a new diagnostic biomarker with a valid non-invasive technique. In addition, this study aimed to investigate whether changes in selenium supply affect microRNA-7 expression and selenoprotein P levels in human hepatocarcinoma cell line (HepG2). The results showed a highly significant decrease in serum microRNA-7 relative quantification values and selenoprotein P levels in malignant group in comparison with benign and control groups. The best cutoff for serum microRNA-7 and selenoprotein P to discriminate hepatocellular carcinoma group from benign and control groups was 0.06 and 4.30 mg/L, respectively. Furthermore, this study showed that changes in selenium supply to HepG2 cell line can alter the microRNA-7 profile and are paralleled by changes in the concentration of its target protein (selenoprotein P). Hence, serum microRNA-7 and selenoprotein P appear to be potential non-invasive diagnostic markers for hepatocellular carcinoma. Moreover, the results suggest that selenium could be used as an anticancer therapy for hepatocellular carcinoma by affecting both microRNA-7 and selenoprotein P.

  12. Is there a role of whole-body bone scan in patients with esophageal squamous cell carcinoma

    Science.gov (United States)

    2012-01-01

    Background Correct detection of bone metastases in patients with esophageal squamous cell carcinoma is pivotal for prognosis and selection of an appropriate treatment regimen. Whole-body bone scan for staging is not routinely recommended in patients with esophageal squamous cell carcinoma. The aim of this study was to investigate the role of bone scan in detecting bone metastases in patients with esophageal squamous cell carcinoma. Methods We retrospectively evaluated the radiographic and scintigraphic images of 360 esophageal squamous cell carcinoma patients between 1999 and 2008. Of these 360 patients, 288 patients received bone scan during pretreatment staging, and sensitivity, specificity, positive predictive value, and negative predictive value of bone scan were determined. Of these 360 patients, surgery was performed in 161 patients including 119 patients with preoperative bone scan and 42 patients without preoperative bone scan. Among these 161 patients receiving surgery, 133 patients had stages II + III disease, including 99 patients with preoperative bone scan and 34 patients without preoperative bone scan. Bone recurrence-free survival and overall survival were compared in all 161 patients and 133 stages II + III patients, respectively. Results The diagnostic performance for bone metastasis was as follows: sensitivity, 80%; specificity, 90.1%; positive predictive value, 43.5%; and negative predictive value, 97.9%. In all 161 patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0.009, univariately). In multivariate comparison, absence of preoperative bone scan (P = 0.012, odds ratio: 5.053) represented the independent adverse prognosticator for bone recurrence-free survival. In 133 stages II + III patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0

  13. Role of LPAR3, PKC and EGFR in LPA-induced cell migration in oral squamous carcinoma cells

    International Nuclear Information System (INIS)

    Brusevold, Ingvild J; Tveteraas, Ingun H; Aasrum, Monica; Ødegård, John; Sandnes, Dagny L; Christoffersen, Thoralf

    2014-01-01

    Oral squamous cell carcinoma is an aggressive neoplasm with serious morbidity and mortality, which typically spreads through local invasive growth. Lysophosphatidic acid (LPA) is involved in a number of biological processes, and may have a role in cancer cell migration and invasiveness. LPA is present in most tissues and can activate cells through six different LPA receptors (LPAR1-6). Although LPA is predominantly promigratory, some of the receptors may have antimigratory effects in certain cells. The signalling mechanisms of LPA are not fully understood, and in oral carcinoma cells the specific receptors and pathways involved in LPA-stimulated migration are unknown. The oral carcinoma cell lines E10, SCC-9, and D2 were investigated. Cell migration was studied in a scratch wound assay, and invasion was demonstrated in organotypic three dimensional co-cultures. Protein and mRNA expression of LPA receptors was studied with Western blotting and qRT-PCR. Activation of signalling proteins was examined with Western blotting and isoelectric focusing, and signalling mechanisms were further explored using pharmacological agents and siRNA directed at specific receptors and pathways. LPA stimulated cell migration in the two oral carcinoma cell lines E10 and SCC-9, but was slightly inhibitory in D2. The receptor expression profile and the effects of specific pharmacological antagonist and agonists indicated that LPA-stimulated cell migration was mediated through LPAR3 in E10 and SCC-9. Furthermore, in both these cell lines, the stimulation by LPA was dependent on PKC activity. However, while LPA induced transactivation of EGFR and the stimulated migration was blocked by EGFR inhibitors in E10 cells, LPA did not induce EGFR transactivation in SCC-9 cells. In D2 cells, LPA induced EGFR transactivation, but this was associated with slowing of a very high inherent migration rate in these cells. The results demonstrate LPA-stimulated migration in oral carcinoma cells through LPAR3

  14. Is there a role of whole-body bone scan in patients with esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Li, Shau-Hsuan; Huang, Yung-Cheng; Huang, Wan-Ting; Lin, Wei-Che; Liu, Chien-Ting; Tien, Wan-Yu; Lu, Hung-I

    2012-01-01

    Correct detection of bone metastases in patients with esophageal squamous cell carcinoma is pivotal for prognosis and selection of an appropriate treatment regimen. Whole-body bone scan for staging is not routinely recommended in patients with esophageal squamous cell carcinoma. The aim of this study was to investigate the role of bone scan in detecting bone metastases in patients with esophageal squamous cell carcinoma. We retrospectively evaluated the radiographic and scintigraphic images of 360 esophageal squamous cell carcinoma patients between 1999 and 2008. Of these 360 patients, 288 patients received bone scan during pretreatment staging, and sensitivity, specificity, positive predictive value, and negative predictive value of bone scan were determined. Of these 360 patients, surgery was performed in 161 patients including 119 patients with preoperative bone scan and 42 patients without preoperative bone scan. Among these 161 patients receiving surgery, 133 patients had stages II + III disease, including 99 patients with preoperative bone scan and 34 patients without preoperative bone scan. Bone recurrence-free survival and overall survival were compared in all 161 patients and 133 stages II + III patients, respectively. The diagnostic performance for bone metastasis was as follows: sensitivity, 80%; specificity, 90.1%; positive predictive value, 43.5%; and negative predictive value, 97.9%. In all 161 patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0.009, univariately). In multivariate comparison, absence of preoperative bone scan (P = 0.012, odds ratio: 5.053) represented the independent adverse prognosticator for bone recurrence-free survival. In 133 stages II + III patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0.003, univariately) and overall survival (P = 0

  15. A role for antioxidants in acclimation of marine derived pathogenic fungus (NIOCC 1) to salt stress

    Digital Repository Service at National Institute of Oceanography (India)

    Ravindran, C.; Varatharajan, G.R.; Rajasabapathy, R.; Vijayakanth, S.; HarishKumar, A.; Meena, R.M.

    stresses were analyzed and discussed for their possible role in the stress mechanism. The marine derived fungus was identified as Phialosimplex genus, which is associated with infections in dogs. Thus the present study elucidates that the scavenging...

  16. A novel role for the NLRC4 inflammasome in mucosal defenses against the fungal pathogen Candida albicans.

    Directory of Open Access Journals (Sweden)

    Jeffrey Tomalka

    2011-12-01

    Full Text Available Candida sp. are opportunistic fungal pathogens that colonize the skin and oral cavity and, when overgrown under permissive conditions, cause inflammation and disease. Previously, we identified a central role for the NLRP3 inflammasome in regulating IL-1β production and resistance to dissemination from oral infection with Candida albicans. Here we show that mucosal expression of NLRP3 and NLRC4 is induced by Candida infection, and up-regulation of these molecules is impaired in NLRP3 and NLRC4 deficient mice. Additionally, we reveal a role for the NLRC4 inflammasome in anti-fungal defenses. NLRC4 is important for control of mucosal Candida infection and impacts inflammatory cell recruitment to infected tissues, as well as protects against systemic dissemination of infection. Deficiency in either NLRC4 or NLRP3 results in severely attenuated pro-inflammatory and antimicrobial peptide responses in the oral cavity. Using bone marrow chimeric mouse models, we show that, in contrast to NLRP3 which limits the severity of infection when present in either the hematopoietic or stromal compartments, NLRC4 plays an important role in limiting mucosal candidiasis when functioning at the level of the mucosal stroma. Collectively, these studies reveal the tissue specific roles of the NLRP3 and NLRC4 inflammasome in innate immune responses against mucosal Candida infection.

  17. The role of lymph node dissection in the contemporary management of renal cell carcinoma: A critical appraisal of the evidence.

    Science.gov (United States)

    Brito, Joseph; Gershman, Boris

    2017-11-01

    The role of lymph node dissection (LND) in the management of renal cell carcinoma has been controversial. Older studies provided initial support to a potential survival benefit in resection of lymph node metastases, and several predictive models were developed to identify patients with lymph node involvement. However, the only randomized trial on the subject did not report a survival benefit to LND in the nonmetastatic setting. Several studies have recently reexplored the therapeutic benefit of LND. In both nonmetastatic and metastatic settings, LND does not appear to be associated with a survival benefit. Moreover, it does not appear that LND confers a survival advantage to patients at increased risk of lymph node metastases, such as those with preoperative radiographic lymphadenopathy or across increasing probability of lymph node disease. Among patients with clinically isolated lymph node metastases, the majority develop disease progression following surgical resection, suggesting a high prevalence of occult systemic disease. Lymph node metastases appear to have prognostic value in both nonmetastatic and metastatic settings. LND may, therefore, have an increasingly important staging role in the management of renal cell carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Code blue: Acinetobacter baumannii, a nosocomial pathogen with a role in the oral cavity

    Science.gov (United States)

    Richards, A.M.; Kwaik, Y. Abu; Lamont, R.J.

    2015-01-01

    SUMMARY Actinetobacter baumannii is an important nosocomial pathogen that can cause a wide range of serious conditions including pneumonia, meningitis, necrotizing fasciitis and sepsis. It is also a major cause of wound infections in military personnel injured during the conflicts in Afghanistan and Iraq, leading to its popular nickname of ‘Iraqibacter’. Contributing to its success in clinical settings is resistance to environmental stresses such as desiccation and disinfectants. Moreover, in recent years there has been a dramatic increase in the number of A. baumannii strains with resistance to multiple antibiotic classes. Acinetobacter baumannii is an inhabitant of oral biofilms, which can act as a reservoir for pneumonia and chronic obstructive pulmonary disease. Subgingival colonization by A. baumannii increases the risk of refractory periodontitis. Pathogenesis of the organism involves adherence, biofilm formation and iron acquisition. In addition, A. baumannii can induce apoptotic cell death in epithelial cells and kill hyphal forms of Candida albicans. Virulence factors that have been identified include pili, the outer membrane protein OmpA, phospholipases and extracellular polysaccharide. Acinetobacter baumannii can sense blue light through a blue-light sensing using flavin (BLUF) domain protein, BlsA. The resulting conformational change in BlsA leads to changes in gene expression, including virulence genes. PMID:25052812

  19. Role of Soluble Innate Effector Molecules in Pulmonary Defense against Fungal Pathogens

    Directory of Open Access Journals (Sweden)

    Soledad R. Ordonez

    2017-10-01

    Full Text Available Fungal infections of the lung are life-threatening but rarely occur in healthy, immunocompetent individuals, indicating efficient clearance by pulmonary defense mechanisms. Upon inhalation, fungi will first encounter the airway surface liquid which contains several soluble effector molecules that form the first barrier of defense against fungal infections. These include host defense peptides, like LL-37 and defensins that can neutralize fungi by direct killing of the pathogen, and collectins, such as surfactant protein A and D, that can aggregate fungi and stimulate phagocytosis. In addition, these molecules have immunomodulatory activities which can aid in fungal clearance from the lung. However, existing observations are based on in vitro studies which do not reflect the complexity of the lung and its airway surface liquid. Ionic strength, pH, and the presence of mucus can have strong detrimental effects on antifungal activity, while the potential synergistic interplay between soluble effector molecules is largely unknown. In this review, we describe the current knowledge on soluble effector molecules that contribute to antifungal activity, the importance of environmental factors and discuss the future directions required to understand the innate antifungal defense in the lung.

  20. Role of Soluble Innate Effector Molecules in Pulmonary Defense against Fungal Pathogens

    Science.gov (United States)

    Ordonez, Soledad R.; Veldhuizen, Edwin J. A.; van Eijk, Martin; Haagsman, Henk P.

    2017-01-01

    Fungal infections of the lung are life-threatening but rarely occur in healthy, immunocompetent individuals, indicating efficient clearance by pulmonary defense mechanisms. Upon inhalation, fungi will first encounter the airway surface liquid which contains several soluble effector molecules that form the first barrier of defense against fungal infections. These include host defense peptides, like LL-37 and defensins that can neutralize fungi by direct killing of the pathogen, and collectins, such as surfactant protein A and D, that can aggregate fungi and stimulate phagocytosis. In addition, these molecules have immunomodulatory activities which can aid in fungal clearance from the lung. However, existing observations are based on in vitro studies which do not reflect the complexity of the lung and its airway surface liquid. Ionic strength, pH, and the presence of mucus can have strong detrimental effects on antifungal activity, while the potential synergistic interplay between soluble effector molecules is largely unknown. In this review, we describe the current knowledge on soluble effector molecules that contribute to antifungal activity, the importance of environmental factors and discuss the future directions required to understand the innate antifungal defense in the lung. PMID:29163395

  1. Full Length Article Role of glypican-3 immunocytochemistry in differentiating hepatocellular carcinoma from metastatic carcinoma of the liver utilizing fine needle aspiration cytology

    International Nuclear Information System (INIS)

    Zaakook, M.; Abu Sinna, E.; Ayoub, M.; El-Sheikh, S.

    2013-01-01

    Purpose: Evaluation of the sensitivity and specificity of glypican3 (GPC3) in differentiating hepatocellular carcinoma (HCC) from metastatic carcinomas of the liver in cell block material. Patients and methods: Sixty cell blocks were prepared from liver FNAs performed in the radiodiagnosis department, National Cancer Institute, in the period between August 2011 and May 2012. Cases diagnosed as hepatocellular carcinoma, or metastatic carcinoma were included in the study. Cell block sections were stained with anti GPC-3. Sensitivity, specificity, and positive and negative predictive values, of GPC3 were calculated. The final diagnosis was based on the triple approach of clinical data, radiological findings, as well as cytomorphologic features aided by GPC-3 results. Results: 70% of cases were diagnosed as HCC, and 30% as metastatic carcinomas. 95.2% of HCC cases expressed GPC3. Poorly differentiated cases showed the highest GPC3 sensitivity (100%), followed by moderately differentiated cases (96.5%), while well differentiated cases expressed GPC3 in 90% of cases. 83.3% of metastatic carcinomas were negative for GPC3. In this study, sensitivity of GPC-3 in HCC was 95.2%, specificity was 83.3%, positive and negative predictive values were 93% and 88.2% respectively, and total accuracy was 91.7%. Conclusion: Immunocytochemical staining for GPC3 in cell block material is a highly sensitive and specific method capable of distinguishing HCC from the vast majority of metastatic carcinomas of the liver

  2. ROLE OF CT IN DIFFERENTIATION OF MUCINOUS AND NON-MUCINOUS CARCINOMAS OF THE RECTUM

    Directory of Open Access Journals (Sweden)

    Piyush Joshi

    2017-01-01

    Full Text Available BACKGROUND Colorectal carcinomas can broadly be classified as either non-mucinous or mucinous. Usually, mucinous adenocarcinomas present at a more advanced stage, have more aggressive local spread and have an increased incidence of lymph node involvement. Those cancers occurring in the rectum are considered more aggressive and require careful planning for treatment. Screening Computed Tomography (CT is widely used for the initial evaluation of these tumours. The aim of the study is to retrospectively analyse the CT images of rectal adenocarcinomas and suggest parameters to aid differentiation of mucinous and non-mucinous tumours. MATERIALS AND METHODS The CT images of 24 cases of mucinous and 26 cases of non-mucinous adenocarcinoma were retrospectively reviewed and evaluated for parameters like morphology, wall thickness, size, pattern and degree of enhancement and the presence or absence of calcification. Also, evaluated was involvement of adjacent structures, lymph nodes and distant metastases. RESULTS All the parameters were analysed for significance using the chi-square test. Mucinous adenocarcinomas of the rectum showed a greater propensity for eccentric bowel thickening, heterogenous enhancement and calcification with a p value less than 0.05. Heterogenous enhancement showed the greatest sensitivity (75% and calcification the greatest specificity (83.3%. The other parameters did not show any difference between the two groups. CONCLUSION CT features most likely to suggest rectal mucinous carcinoma are heterogenous contrast enhancement, eccentric wall thickening and intratumoural calcification. As mucinous carcinomas follow an aggressive course, if a diagnosis of mucinous carcinoma of the rectum can be suggested on the staging CT, it may influence patient management.

  3. Management of Merkel cell carcinoma: Role of radiotherapy in elderly patients

    International Nuclear Information System (INIS)

    Assouline, A.; Krzisch, C.; Assouline, A.; Levy, A.; Mazeron, J.J.; Mazeron, J.J.; Chargari, C.

    2010-01-01

    Purpose Merkel cell carcinoma carcinoma (M.C.C.) or primary cutaneous neuroendocrine carcinoma is a rare and aggressive malignancy affecting elderly. Optimal therapeutic strategy has not yet been established in elderly patients. Patients and methods From March 1996 to March 2007, 29 patients with Merkel cell carcinoma of were treated at the University Hospital of Amiens, France. Adjuvant radiotherapy (R.T.) was performed for 14 patients (50%) on the tumor bed with margins of 3 to 5 cm, an average dose of 46 Gy (30-60 Gy), by 2 Gy per fraction. Ten of them also received R.T. to the lymph node area at mean dose of 44.3 Gy (26-50 Gy). Duration of R.T. was 35 days. A retrospective analysis was conducted to better evaluate survival and prognostic factors. Results Median overall survival (O.S.) was 18.9 months (3-122) and the median time to progression (M.T.P.) 5.5 months (1-26). At 5 years, O.S. for irradiated patients was 47% (IC95: 12-82%) versus 27% (IC95: 5-49%) in cases of surgery alone (p = 0.032). The most frequent sites of recurrence were nodal (34.5%), local (24.1%) and metastatic (17.2%). For patients over 70 years, eight (36.5%) were free of disease at last news, 8 (36.5%) had died from cancer and six from other causes (27%). In this subgroup, M.T.P. was 6 months (2-19) and median O.S. of 19 months (4-87). There was no acute toxicity greater than grade 2. Conclusion Although limited by a retrospective analysis, this report suggests an advantage of postoperative R.T. for patients with M.C.C.. It combined low toxicity and improvement of survival. Prospective multicenter trials are needed to clarify and validate the optimal strategy. (authors)

  4. Clinical role of early dynamic FDG-PET/CT for the evaluation of renal cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nakajima, Reiko; Abe, Koichiro; Sakai, Shuji [Tokyo Women' s Medical University, Department of Diagnostic Imaging and Nuclear Medicine, Tokyo (Japan); Kondo, Tsunenori; Tanabe, Kazunari [Tokyo Women' s Medical University, Department of Urology, Tokyo (Japan)

    2016-06-15

    We studied the usefulness of early dynamic (ED) and whole-body (WB) FDG-PET/CT for the evaluation of renal cell carcinoma (RCC). One hundred patients with 107 tumours underwent kidney ED and WB FDG-PET/CT. We visually and semiquantitatively evaluated the FDG accumulation in RCCs in the ED and WB phases, and compared the accumulation values with regard to histological type (clear cell carcinoma [CCC] vs. non-clear cell carcinoma [N-CCC]), the TNM stage (high stage [3-4] vs. low stage [1-2]), the Fuhrman grade (high grade [3-4] vs. low grade [1-2]) and presence versus absence of venous (V) and lymphatic (Ly) invasion. In the ED phase, visual evaluation revealed no significant differences in FDG accumulation in terms of each item. However, the maximum standardized uptake value and tumour-to-normal tissue ratios were significantly higher in the CCCs compared to the N-CCCs (p < 0.001). In the WB phase, in contrast, significantly higher FDG accumulation (p < 0.001) was found in RCCs with a higher TNM stage, higher Furman grade, and the presence of V and Ly invasion in both the visual and the semiquantitative evaluations. ED and WB FDG-PET/CT is a useful tool for the evaluation of RCCs. (orig.)

  5. Emerging role of microRNAs in the treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Callegari E

    2015-05-01

    Full Text Available Elisa Callegari,1 Marco Domenicali,2 Laura Gramantieri,3 Massimo Negrini,1 Silvia Sabbioni4 1Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, 2Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 3Center for Applied Biomedical Research, S Orsola-Malpighi University Hospital, Bologna, 4Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy Abstract: Hepatocellular carcinoma is the third leading cause of cancer deaths worldwide. Currently available curative options, such as surgery and transplantation, are not available to patients with advanced stages of disease. Among the potential new treatments being investigated are microRNA (miRNA-based therapies. A number of preclinical studies have reported antitumor activities of miRNA mimics or anti-miRNA molecules. Optimal in vivo delivery of miRNA molecules is crucial to their action. To this end, significant progress has been made in the development of nanoparticles for in vivo delivery of miRNA molecules. Delivery of these molecules, alone or in combination with other drugs, promises to open new possibilities for therapeutic approaches to hepatocellular carcinoma. Keywords: hepatocellular carcinoma, microRNA, nanocarriers, therapy 

  6. Role of concurrent chemoradiation in inoperable carcinoma esophagus: A prospective study

    Directory of Open Access Journals (Sweden)

    Virendra Bhandari

    2014-01-01

    Full Text Available Introduction: The treatment of choice in cancer esophagus is controversial. Radiation therapy oncology group, Eastern cooperative oncology group and Cochrane studies have shown superiority of concurrent chemoradiation in inoperable carcinoma esophagus. In these studies full dose cisplatin was given every 3 weeks along with radiotherapy and hence had some toxicity. So, we started treating inoperable carcinoma esophagus patients with low dose weekly cisplatin given concurrently with radiotherapy aiming at low toxicity and similar results. Materials and Methods: A total of 31 cases of inoperable cases of carcinoma esophagus were treated with once weekly cisplatin 30 mg/m 2 along with radiotherapy 60 Gy in 30 fractions in 6 weeks on Telecobalt/Linear accelerator. Results : w0 e could achieve lower toxicity with 80%, 35% and 19% with 1, 2, and 3 year′s survival with a median survival of 18 months. So, we conclude that this regimen is better than 3 weekly chemotherapy regimen as is better tolerated with less toxicity and similar outcome.

  7. The role of bleomycin combination in radiation therapy for squamous cell carcinoma in the oral cavity

    International Nuclear Information System (INIS)

    Masaki, Norie

    1986-01-01

    In an effort to improve tumor control by radiation therapy, a treatment regimen consisting of concurrent combination of bleomycin (90 mg/3 weeks) and radiation (30 Gy/3 weeks) was applied. Between 1972 and 1981, 287 patients with squamous cell carcinoma in the oral cavity were subjected to this bleomycin-radiation combination regimen. All except 4 patients experienced marked response after treatment using the bleomycin-radiation combination alone. One hundred thirty-four patients (47 %) obtained CR and 149 (53 %) PR. Higher CR rates were obtained in patients with carcinoma of the lower gum (62 %), of the upper gum (68 %), and of the cheek mucosa (43 %), compared to patients with carcinoma of the floor of the mouth (21 %), and of the tongue (15 %). In each of the tumor sites, small lesions (T1, T2) obtained higher CR rates, compared with large lesions (T3, T4). Of the 134 patients who experienced CR, 83 were observed without any further treatment after bleomycin-radiation combination alone. Local recurrence-free rates of these patients were 72 % for T1, T2 lesions and 48 % for T3, T4 lesions. Local control rates were increased to 85 % and 78 %, respectively, with successful salvage treatment involving surgery or interstitial radiotherapy for post-irradiation failures. (author)

  8. Clinical role of early dynamic FDG-PET/CT for the evaluation of renal cell carcinoma.

    Science.gov (United States)

    Nakajima, Reiko; Abe, Koichiro; Kondo, Tsunenori; Tanabe, Kazunari; Sakai, Shuji

    2016-06-01

    We studied the usefulness of early dynamic (ED) and whole-body (WB) FDG-PET/CT for the evaluation of renal cell carcinoma (RCC). One hundred patients with 107 tumours underwent kidney ED and WB FDG-PET/CT. We visually and semiquantitatively evaluated the FDG accumulation in RCCs in the ED and WB phases, and compared the accumulation values with regard to histological type (clear cell carcinoma [CCC] vs. non-clear cell carcinoma [N-CCC]), the TNM stage (high stage [3-4] vs. low stage [1-2]), the Fuhrman grade (high grade [3-4] vs. low grade [1-2]) and presence versus absence of venous (V) and lymphatic (Ly) invasion. In the ED phase, visual evaluation revealed no significant differences in FDG accumulation in terms of each item. However, the maximum standardized uptake value and tumour-to-normal tissue ratios were significantly higher in the CCCs compared to the N-CCCs (p PET/CT is a useful tool for the evaluation of RCCs. • ED and WB FDG-PET/ CT helps to assess patients with RCC • ED FDG-PET/CT enabled differentiation between CCC and N-CCC • FDG accumulation in the WB phase reflects tumour aggressiveness • Management of RCC is improved by ED and WB FDG-PET/CT.

  9. Heat Shock Proteins: Pathogenic Role in Atherosclerosis and Potential Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Arman Kilic

    2012-01-01

    Full Text Available Heat shock proteins (HSPs are a highly conserved group of proteins that are constitutively expressed and function as molecular chaperones, aiding in protein folding and preventing the accumulation of misfolded proteins. In the arterial wall, HSPs have a protective role under normal physiologic conditions. In disease states, however, HSPs expressed on the vascular endothelial cell surface can act as targets for detrimental autoimmunity due to their highly conserved sequences. Developing therapeutic strategies for atherosclerosis based on HSPs is challenged by the need to balance such physiologic and pathologic roles of these proteins. This paper summarizes the role of HSPs in normal vascular wall processes as well as in the development and progression of atherosclerosis. The potential implications of HSPs in clinical therapies for atherosclerosis are also discussed.

  10. Microbial and viral pathogens in colorectal cancer.

    LENUS (Irish Health Repository)

    Collins, Danielle

    2011-05-01

    The heterogenetic and sporadic nature of colorectal cancer has led to many epidemiological associations with causes of this disease. As our understanding of the underlying molecular processes in colorectal-cancer develops, the concept of microbial-epithelial interactions as an oncogenic trigger might provide a plausible hypothesis for the pathogenesis of colorectal cancer. By contrast with other cancers of the gastrointestinal tract (gastric carcinoma, mucosa-associated lymphoid-tissue lymphoma), a direct causal link between microbial infection (bacteria and viruses) and colorectal carcinoma has not been established. Studies support the involvement of these organisms in oncogenesis, however, in colorectal cancer, clinical data are lacking. Here, we discuss current evidence (both in vitro and clinical studies), and focus on a putative role for bacterial and viral pathogens as a cause of colorectal cancer.

  11. Microbial and viral pathogens in colorectal cancer.

    LENUS (Irish Health Repository)

    Collins, Danielle

    2012-02-01

    The heterogenetic and sporadic nature of colorectal cancer has led to many epidemiological associations with causes of this disease. As our understanding of the underlying molecular processes in colorectal-cancer develops, the concept of microbial-epithelial interactions as an oncogenic trigger might provide a plausible hypothesis for the pathogenesis of colorectal cancer. By contrast with other cancers of the gastrointestinal tract (gastric carcinoma, mucosa-associated lymphoid-tissue lymphoma), a direct causal link between microbial infection (bacteria and viruses) and colorectal carcinoma has not been established. Studies support the involvement of these organisms in oncogenesis, however, in colorectal cancer, clinical data are lacking. Here, we discuss current evidence (both in vitro and clinical studies), and focus on a putative role for bacterial and viral pathogens as a cause of colorectal cancer.

  12. Calcineurin plays key roles in the dimorphic transition and virulence of the human pathogenic zygomycete Mucor circinelloides.

    Science.gov (United States)

    Lee, Soo Chan; Li, Alicia; Calo, Silvia; Heitman, Joseph

    2013-01-01

    Many pathogenic fungi are dimorphic and switch between yeast and filamentous states. This switch alters host-microbe interactions and is critical for pathogenicity. However, in zygomycetes, whether dimorphism contributes to virulence is a central unanswered question. The pathogenic zygomycete Mucor circinelloides exhibits hyphal growth in aerobic conditions but switches to multi-budded yeast growth under anaerobic/high CO₂ conditions. We found that in the presence of the calcineurin inhibitor FK506, Mucor exhibits exclusively multi-budded yeast growth. We also found that M. circinelloides encodes three calcineurin catalytic A subunits (CnaA, CnaB, and CnaC) and one calcineurin regulatory B subunit (CnbR). Mutations in the latch region of CnbR and in the FKBP12-FK506 binding domain of CnaA result in hyphal growth of Mucor in the presence of FK506. Disruption of the cnbR gene encoding the sole calcineurin B subunit necessary for calcineurin activity yielded mutants locked in permanent yeast phase growth. These findings reveal that the calcineurin pathway plays key roles in the dimorphic transition from yeast to hyphae. The cnbR yeast-locked mutants are less virulent than the wild-type strain in a heterologous host system, providing evidence that hyphae or the yeast-hyphal transition are linked to virulence. Protein kinase A activity (PKA) is elevated during yeast growth under anaerobic conditions, in the presence of FK506, or in the yeast-locked cnbR mutants, suggesting a novel connection between PKA and calcineurin. cnaA mutants lacking the CnaA catalytic subunit are hypersensitive to calcineurin inhibitors, display a hyphal polarity defect, and produce a mixture of yeast and hyphae in aerobic culture. The cnaA mutants also produce spores that are larger than wild-type, and spore size is correlated with virulence potential. Our results demonstrate that the calcineurin pathway orchestrates the yeast-hyphal and spore size dimorphic transitions that contribute to

  13. Role of Mitochondrial DNA Copy Number Alteration in Human Renal Cell Carcinoma

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    Chen-Sung Lin

    2016-05-01

    Full Text Available We investigated the role of mitochondrial DNA (mtDNA copy number alteration in human renal cell carcinoma (RCC. The mtDNA copy numbers of paired cancer and non-cancer parts from five resected RCC kidneys after radical nephrectomy were determined by quantitative polymerase chain reaction (Q-PCR. An RCC cell line, 786-O, was infected by lentiviral particles to knock down mitochondrial transcriptional factor A (TFAM. Null target (NT and TFAM-knockdown (TFAM-KD represented the control and knockdown 786-O clones, respectively. Protein or mRNA expression levels of TFAM; mtDNA-encoded NADH dehydrogenase subunit 1 (ND1, ND6 and cytochrome c oxidase subunit 2 (COX-2; nuclear DNA (nDNA-encoded succinate dehydrogenase subunit A (SDHA; v-akt murine thymoma viral oncogene homolog 1 gene (AKT-encoded AKT and v-myc myelocytomatosis viral oncogene homolog gene (c-MYC-encoded MYC; glycolytic enzymes including hexokinase II (HK-II, glucose 6-phosphate isomerase (GPI, phosphofructokinase (PFK, and lactate dehydrogenase subunit A (LDHA; and hypoxia-inducible factors the HIF-1α and HIF-2α, pyruvate dehydrogenase kinase 1 (PDK1, and pyruvate dehydrogenase E1 component α subunit (PDHA1 were analyzed by Western blot or Q-PCR. Bioenergetic parameters of cellular metabolism, basal mitochondrial oxygen consumption rate (mOCRB and basal extracellular acidification rate (ECARB, were measured by a Seahorse XFe-24 analyzer. Cell invasiveness was evaluated by a trans-well migration assay and vimentin expression. Doxorubicin was used as a chemotherapeutic agent. The results showed a decrease of mtDNA copy numbers in resected RCC tissues (p = 0.043. The TFAM-KD clone expressed lower mtDNA copy number (p = 0.034, lower mRNA levels of TFAM (p = 0.008, ND1 (p = 0.007, and ND6 (p = 0.017, and lower protein levels of TFAM and COX-2 than did the NT clone. By contrast, the protein levels of HIF-2α, HK-II, PFK, LDHA, AKT, MYC and vimentin; trans-well migration activity (p = 0

  14. Role of stroma and Wound Healing in carcinoma response to ionizing radiation

    International Nuclear Information System (INIS)

    Arshad, Adnan

    2014-01-01

    Wound healing and carcinogenesis are defined as complex, adaptive processes which are controlled by intricate communications between the host and the tissue microenvironment. A number of phenotypic similarities are shared by wounds and cancers in cellular signaling and gene expression. Radiotherapy is the second most effective modality of cancer treatment after surgery and can be used, either alone or in combination with chemotherapy. Recent findings suggest that radiotherapy apart from tumor cell death also rapidly and persistently modifies the tissue microenvironment. These modifications affect cell phenotype, tissue metabolism, bidirectional exchanges and signaling events between cells. The complex interactions between stromal cells and cancer cells are of immense interest and in The First Part of My Thesis, I tried to explore the crosstalk between stromal and carcinoma cells in response to radiotherapy by genetic modulation of the stroma and irradiation. We found that fibroblasts, irrespective of their RhoB status, do not modulate intrinsic radiosensitivity of TC-1 but produce diffusible factors able to modify tumor cell fate. Then we found that Wt and RhoB deficient fibroblasts stimulated TC-1 migration through distinct mechanisms respectively, TGF-β1 and MMP-mediated. We also found that co-irradiation of fibroblasts and TC-1 abrogated the pro-migratory phenotype by repression of TGF-β and MMP secretion. This result is highly relevant to the clinical situation and suggests that conversely to, the current view; irradiated stroma would not enhance carcinoma migration and could be manipulated to promote anti-tumor immune response. Secondly, our in vivo experiments, tends to confirm the in vitro data showing that irradiated tumor bed does not stimulate tumor growth and escape. Our results also challenges the view that irradiated stroma would promote migration of carcinoma cells as we show that independently from their genotype co-irradiation of fibroblasts and

  15. The role of habitat filtering in the leaf economics spectrum and plant susceptibility to pathogen infection

    Science.gov (United States)

    Welsh, Miranda E; Cronin, James P.; Mitchell, Charles E.

    2016-01-01

    1.The Leaf Economics Spectrum (LES) describes global covariation in the traits of plant leaves. The LES is thought to arise from biophysical constraints and habitat filtering (ecological selection against unfit trait combinations along environmental gradients). However, the role of habitat filtering in generating the LES has not been tested experimentally.

  16. The Role of CRISPR-Cas Systems in Virulence of Pathogenic Bacteria

    NARCIS (Netherlands)

    Louwen, R.; Staals, R.H.J.; Endtz, H.P.; Baarlen, van P.; Oost, van der J.

    2014-01-01

    Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) genes are present in many bacterial and archaeal genomes. Since the discovery of the typical CRISPR loci in the 1980s, well before their physiological role was revealed, their variable sequences have been

  17. Role for β-catenin and HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions

    Science.gov (United States)

    Irazoqui, Javier E.; Ng, Aylwin; Xavier, Ramnik J.; Ausubel, Frederick M.

    2008-01-01

    We used the model nematode Caenorhabditis elegans infected with the human pathogen Staphylococcus aureus to identify components of epithelial immunity. Transcriptional profiling and reverse genetic analysis revealed that mutation of the C. elegans β-catenin homolog bar-1 or the downstream homeobox gene egl-5 results in a defective response and hypersensitivity to S. aureus infection. Epistasis analysis showed that bar-1 and egl-5 function in parallel to previously described C. elegans immune-response pathways. Overexpression of human homologs of egl-5 modulated NF-κB-dependent TLR2 signaling in epithelial cells. These data suggest that β-catenin and homeobox genes play an important and conserved role in innate immune defense. PMID:18981407

  18. Role for beta-catenin and HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions.

    Science.gov (United States)

    Irazoqui, Javier E; Ng, Aylwin; Xavier, Ramnik J; Ausubel, Frederick M

    2008-11-11

    We used the model nematode Caenorhabditis elegans infected with the human pathogen Staphylococcus aureus to identify components of epithelial immunity. Transcriptional profiling and reverse genetic analysis revealed that mutation of the C. elegans beta-catenin homolog bar-1 or the downstream homeobox gene egl-5 results in a defective response and hypersensitivity to S. aureus infection. Epistasis analysis showed that bar-1 and egl-5 function in parallel to previously described C. elegans immune-response pathways. Overexpression of human homologs of egl-5 modulated NF-kappaB-dependent TLR2 signaling in epithelial cells. These data suggest that beta-catenin and homeobox genes play an important and conserved role in innate immune defense.

  19. The role of 'atypical' Brucella in amphibians: are we facing novel emerging pathogens?

    Science.gov (United States)

    Mühldorfer, K; Wibbelt, G; Szentiks, C A; Fischer, D; Scholz, H C; Zschöck, M; Eisenberg, T

    2017-01-01

    To discuss together the novel cases of Brucella infections in frogs with the results of published reports to extend our current knowledge on 'atypical' brucellae isolated from amphibians and to discuss the challenges we face on this extraordinary emerging group of pathogens. Since our first description, an additional 14 isolates from four different frog species were collected. Novel isolates and a subset of Brucella isolates previously cultured from African bullfrogs were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), Fourier transform-infrared (FT-IR) spectroscopy and broth microdilution susceptibility testing. MALDI-TOF MS worked very efficiently for an accurate bacterial identification to the genus level. Within the cluster analysis, 'atypical' brucellae grouped distant from Brucella melitensis and were even more separated by FT-IR spectroscopy with respect to their geographical origin. Minimum inhibitory concentrations of 14 antimicrobial substances are provided as baseline data on antimicrobial susceptibility. The case history of Brucella infections in amphibians reveals a variety of pathologies ranging from localized manifestations to systemic infections. Some isolates seem to be capable of causing high mortality in zoological exhibitions putting higher demands on the management of endangered frog species. There is considerable risk in overlooking and misidentifying 'atypical' Brucella in routine diagnostics. Brucella have only recently been described in cold-blooded vertebrates. Their presence in frog species native to Africa, America and Australia indicates a more common occurrence in amphibians than previously thought. This study provides an extensive overview of amphibian brucellae by highlighting the main features of their clinical significance, diagnosis and zoonotic potential. © 2016 The Society for Applied Microbiology.

  20. Role of periodontal pathogenic bacteria in RANKL-mediated bone destruction in periodontal disease

    OpenAIRE

    Mikihito Kajiya; Gabriela Giro; Martin A. Taubman; Xiaozhe Han; Marcia P.A. Mayer; Toshihisa Kawai

    2010-01-01

    Accumulated lines of evidence suggest that hyperimmune responses to periodontal bacteria result in the destruction of periodontal connective tissue and alveolar bone. The etiological roles of periodontal bacteria in the onset and progression of periodontal disease (PD) are well documented. However, the mechanism underlying the engagement of periodontal bacteria in RANKL-mediated alveolar bone resorption remains unclear. Therefore, this review article addresses three critical subjects. First, ...

  1. The conserved clag multigene family of malaria parasites: essential roles in host-pathogen interaction.

    Science.gov (United States)

    Gupta, Ankit; Thiruvengadam, Girija; Desai, Sanjay A

    2015-01-01

    The clag multigene family is strictly conserved in malaria parasites, but absent from neighboring genera of protozoan parasites. Early research pointed to roles in merozoite invasion and infected cell cytoadherence, but more recent studies have implicated channel-mediated uptake of ions and nutrients from host plasma. Here, we review the current understanding of this gene family, which appears to be central to host-parasite interactions and an important therapeutic target. Published by Elsevier Ltd.

  2. Conservation and restoration of forest trees impacted by non-native pathogens: the role of genetics and tree improvement

    Science.gov (United States)

    R.A. Sniezko; L.A. Winn

    2017-01-01

    North American native tree species in forest ecosystems, as well as managed forests and urban plantings, are being severely impacted by pathogens and insects. The impacts of these pathogens and insects often increase over time, and they are particularly acute for those species affected by non-native pathogens and insects. For restoration of affected tree species or for...

  3. Emerging role of bacteria in oral carcinogenesis: a review with special reference to perio-pathogenic bacteria.

    Science.gov (United States)

    Perera, Manosha; Al-Hebshi, Nezar Noor; Speicher, David J; Perera, Irosha; Johnson, Newell W

    2016-01-01

    Oral cancer, primarily oral squamous cell carcinoma (OSCC), continues to be a major global health problem with high incidence and low survival rates. While the major risk factors for this malignancy, mostly lifestyle related, have been identified, around 15% of oral cancer cases remain unexplained. In light of evidence implicating bacteria in the aetiology of some cancer types, several epidemiological studies have been conducted in the last decade, employing methodologies ranging from traditional culture techniques to 16S rRNA metagenomics, to assess the possible role of bacteria in OSCC. While these studies have demonstrated differences in microbial composition between cancerous and healthy tissues, they have failed to agree on specific bacteria or patterns of oral microbial dysbiosis to implicate in OSCC. On the contrary, some oral taxa, particularly Porphyromonas gingivalis and Fusobacterium nucleatum, show strong oral carcinogenic potential in vitro and in animal studies. Bacteria are thought to contribute to oral carcinogenesis via inhibition of apoptosis, activation of cell proliferation, promotion of cellular invasion, induction of chronic inflammation, and production of carcinogens. This narrative review provides a critical analysis of and an update on the association between bacteria and oral carcinogenesis and the possible mechanisms underlying it.

  4. Expression and role of fibroblast activation protein-alpha in microinvasive breast carcinoma

    Directory of Open Access Journals (Sweden)

    Hua Xing

    2011-11-01

    Full Text Available Abstract Background Diagnosis of ductal carcinoma in situ (DCIS in breast cancer cases is challenging for pathologist due to a variety of in situ patterns and artefacts, which could be misinterpreted as stromal invasion. Microinvasion is detected by the presence of cytologically malignant cells outside the confines of the basement membrane and myoepithelium. When malignant cells invade the stroma, there is tissue remodeling induced by perturbed stromal-epithelial interactions. Carcinoma-associated fibroblasts (CAFs are main cells in the microenvironment of the remodeled tumor-host interface. They are characterized by the expression of the specific fibroblast activation protein-alpha (FAP-α, and differ from that of normal fibroblasts exhibiting an immunophenotype of CD34. We hypothesized that staining for FAP-α may be helpful in determining whether DCIS has microinvasion. Methods 349 excised breast specimens were immunostained for smooth muscle actin SMA, CD34, FAP-α, and Calponin. Study material was divided into 5 groups: group 1: normal mammary tissues of healthy women after plastic surgery; group 2: usual ductal hyperplasia (UDH; group 3: DCIS without microinvasion on H & E stain; group 4: DCIS with microinvasion on H & E stain (DCIS-MI, and group 5: invasive ductal carcinoma (IDC. A comparative evaluation of the four immunostains was conducted. Results Our results demonstrated that using FAP-α and Calponin adjunctively improved the sensitivity of pathological diagnosis of DCIS-MI by 11.29%, whereas the adjunctive use of FAP-α and Calponin improved the sensitivity of pathological diagnosis of DCIS by 13.6%. Conclusions This study provides the first evidence that immunostaining with FAP-α and Calponin can serve as a novel marker for pathologically diagnosing whether DCIS has microinvasion.

  5. Role of magnetic resonance diffusion-weighted imaging in evaluating response after chemoembolization of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Yuan Zheng; Ye Xiaodan; Dong Sheng; Xu Lichao; Xu Xueyuan; Liu Shiyuan; Xiao Xiangsheng

    2010-01-01

    Objective: To investigate the value of hepatocellular carcinoma pretreatment apparent diffusion coefficients (ADCs) and its ADCs changes after treatment in predicting and early monitoring the response after chemoembolization. Materials and methods: Twenty-five responding and nine nonresponding hepatocellular carcinoma lesions were prospectively evaluated with magnetic resonance diffusion-weighted imaging in 24 h before and in 48 h after chemoembolization. Quantitative ADC maps were calculated with images with b values of 0 and 500 s/mm 2 . Results: Nonresponding lesions had a significantly higher pretreatment mean ADC than did responding lesions (1.726 ± 0.323 x 10 -3 mm 2 /s vs.1.294 ± 0.185 10 -3 mm 2 /s, P ≤ 0.001). The results of receiver operator characteristic (ROC) analysis for identification of nonresponding lesions showed that threshold ADC value of 1.618 x 10 -3 mm 2 /s had 96.0% sensitivity and 77.8% specificity. After transarterial chemoembolization, responding lesions had a significant increase in %ADC values than did nonresponding lesions (32.63% vs. 5.24%, P = 0.025). The results of ROC analysis for identification of responding lesions showed that threshold %ADC value of 16.21% had 72% sensitivity and 100% specificity. No significant change was observed in normal liver parenchyma (P = 0.862) and spleen (P = 0.052). Conclusion: High pretreatment mean ADC value of hepatocellular carcinoma was predictive of poor response to chemoembolization. A significant increase in %ADC value was observed in lesions that responded to chemoembolization.

  6. Treatment of Recurrent Bronchial Carcinoma: The Role of High-Dose-Rate Endoluminal Brachytherapy

    International Nuclear Information System (INIS)

    Hauswald, Henrik; Stoiber, Eva; Rochet, Nathalie; Lindel, Katja; Grehn, Christian; Becker, Heinrich D.; Debus, Juergen; Harms, Wolfgang

    2010-01-01

    Purpose: This study's aim was to assess outcome and toxicity of high-dose-rate endoluminal brachytherapy (HDREB) for recurrent bronchial carcinoma. Methods and Materials: From 1987 to 2005, 41 patients were treated with HDREB for symptomatic recurrent bronchial carcinoma. All patients had previously undergone external beam radiotherapy (EBRT) with a median dose of 56 Gy (range, 30-70 Gy). The median HDREB dose applied was 15 Gy (range, 5-29 Gy). The median time interval between primary EBRT and reirradiation was 9 months (range, 2-54 months). Results: After a median follow-up of 6.7 months, the 6-, 12-, and 24-month overall survival rates were 58%, 18%, and 7%, respectively. The median overall survival time was 6.7 months. Local remission was achieved in 73% of patients (n = 30). A total of 24% of patients (n = 10) showed no response or progressive disease within 8 weeks after treatment. In 1 patient, treatment response was not documented. The 6-, 12-, and 24-month local control rates were 38%, 17%, and 3%, respectively. The median local progression-free survival time was 4 months (range, 1-23 months). Prognostic factors were a total dose of ≥15 Gy of HDREB (p = 0.029) and a Karnofsky performance score of ≥80% (p = 0.0012). The cause of death was locoregional progression in 27% of patients (n = 11), distant metastases in 24% of patients (n = 10), fatal hemorrhage in 15% of patients (n = 6), and other causes in 29% of patients (n = 12). None of the patients with locally controlled disease showed grade 3 or 4 late effects. Conclusions: Palliative treatment of symptomatic, locally recurrent bronchial carcinoma with HDREB can effectively relieve symptoms in the majority of patients while causing only few complications. Still, time to progression is short.

  7. Role of magnetic resonance diffusion-weighted imaging in evaluating response after chemoembolization of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Yuan Zheng, E-mail: yuanzheng0404@163.co [Department of Radiology, Affiliated Changzheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai 200003 (China); Ye Xiaodan [Department of Radiology, Affiliated Changzheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai 200003 (China); Department of Radiology, Affiliated Shanghai Chest Hospital, Shanghai Jiaotong University, 241 West Huai Hai Road, Shanghai 200030 (China); Dong Sheng, E-mail: dongsheng2828@hotmail.co [Department of Radiology, Affiliated Changzheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai 200003 (China); Xu Lichao; Xu Xueyuan; Liu Shiyuan; Xiao Xiangsheng [Department of Radiology, Affiliated Changzheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai 200003 (China)

    2010-07-15

    Objective: To investigate the value of hepatocellular carcinoma pretreatment apparent diffusion coefficients (ADCs) and its ADCs changes after treatment in predicting and early monitoring the response after chemoembolization. Materials and methods: Twenty-five responding and nine nonresponding hepatocellular carcinoma lesions were prospectively evaluated with magnetic resonance diffusion-weighted imaging in 24 h before and in 48 h after chemoembolization. Quantitative ADC maps were calculated with images with b values of 0 and 500 s/mm{sup 2}. Results: Nonresponding lesions had a significantly higher pretreatment mean ADC than did responding lesions (1.726 {+-} 0.323 x 10{sup -3} mm{sup 2}/s vs.1.294 {+-} 0.185 10{sup -3} mm{sup 2}/s, P {<=} 0.001). The results of receiver operator characteristic (ROC) analysis for identification of nonresponding lesions showed that threshold ADC value of 1.618 x 10{sup -3} mm{sup 2}/s had 96.0% sensitivity and 77.8% specificity. After transarterial chemoembolization, responding lesions had a significant increase in %ADC values than did nonresponding lesions (32.63% vs. 5.24%, P = 0.025). The results of ROC analysis for identification of responding lesions showed that threshold %ADC value of 16.21% had 72% sensitivity and 100% specificity. No significant change was observed in normal liver parenchyma (P = 0.862) and spleen (P = 0.052). Conclusion: High pretreatment mean ADC value of hepatocellular carcinoma was predictive of poor response to chemoembolization. A significant increase in %ADC value was observed in lesions that responded to chemoembolization.

  8. Role of computed tomography in the evaluation and management of carcinoma of the prostate

    International Nuclear Information System (INIS)

    Giri, P.G.S.; Walsh, J.W.; Hazra, T.A.; Texter, J.H.; Koontz, W.W.

    1982-01-01

    Between January 1978 to March 1980, 25 patients with biopsy-proven prostate carcinoma were evaluated by computerized tomography (CT). CT differed from clinical stage in 7 of 25 patients (28%). In 6 of the 7 patients, change in stage resulted because of demonstration of extracapsular extension and/or pelvic lymph node involvement. Twelve of the 25 patients (48%) underwent surgery with histological confirmation of CT findings. CT identified nodal involvement accurately in 10 of 12 patients (83%). We recommend use of CT for initial staging, treatment planning and assessment of response in the management of prostate cancer

  9. The Role of Ceramide Synthases in the Pathogenicity of Cryptococcus neoformans.

    Science.gov (United States)

    Munshi, Mansa A; Gardin, Justin M; Singh, Ashutosh; Luberto, Chiara; Rieger, Robert; Bouklas, Tejas; Fries, Bettina C; Del Poeta, Maurizio

    2018-02-06

    Cryptococcus neoformans (C. neoformans) is estimated to cause about 220,000 new cases every year in patients with AIDS, despite advances in antifungal treatments. C. neoformans possesses a remarkable ability to disseminate through an immunocompromised host, making treatment difficult. Here, we examine the mechanism of survival of C. neoformans under varying host conditions and find a role for ceramide synthase in C. neoformans virulence. This study also provides a detailed lipidomics resource for the fungal lipid research community in addition to discovering a potential target for antifungal therapy. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Role of GPER1, EGFR and CXCR1 in differentiating between malignant follicular thyroid carcinoma and benign follicular thyroid adenoma

    Science.gov (United States)

    Zhao, Le; Zhu, Xiao-Yun; Jiang, Rong; Xu, Man; Wang, Ni; Chen, George G; Liu, Zhi-Min

    2015-01-01

    It is extremely difficult to discriminate between follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FTA) before surgery, because the morphologies of carcinoma cells and adenoma cells obtained by fine needle aspiration biopsy (FNAB) are similar. Molecular markers may be helpful on this issue. The purpose of this study was to assess the role of GPER1, EGFR and CXCR1 in differential diagnosis between FTC and FTA. GPER1, EGFR and CXCR1 mRNA expression levels were examined in 15 FTCs and 10 FTAs using real-time RT-PCR. FTC showed to have significantly increased mRNA levels of the three molecules compared to FTA (P FTA, respectively. Statistical analysis showed that GPER1, EGFR and CXCR1 protein expression were correlated with one another in FTC and concomitant high expression of the three molecules had stronger correlation with the occurrence of FTC than did each alone. The positive predictive values (PPV) for concomitant high expression of the three molecules for discriminating between FTC and FTA were 91.0% for GPER1/EGFR, 93.8% for GPER1/CXCR1, 92.3% for EGFR/CXCR1 and 98.2% for GPER1/EGFR/CXCR1, respectively. These results indicated that the evaluation of GPER1, EGFR and CXCR1 concomitant high expression may be helpful in differential diagnosis between FTC and FTA. PMID:26617848

  11. L-Arginine Increases Cytotoxicity in Irradiated Ehrlich Carcinoma Cell Line: Possible Potential Role of Nitric Oxide

    International Nuclear Information System (INIS)

    Noaman, E.

    2008-01-01

    Cancer cells possess nitric oxide syntheses (NOS) which metabolize L-Arginine (L-Arg) for producing nitric oxide (NO) The present study investigates the relations between NO and ionizing radiation in the Ehrlich ascites carcinoma (EAC) cell line. NOS activity was stimulated by exposure of cells to L-Arg just after irradiation. L-Arg (5 m M) supply led to an increase in ionizing radiation induced cytotoxicity (% of viability 18± 3 %) whereas, neither L-Arg itself nor ionizing irradiation caused cell death at the doses used in this study. Also, cells were treated either with L-Thio citrulline (L-Thio), an irreversible inhibitor of NOS or with exogenous superoxide dismutase (SOD) and catalase. L-Thio and SOD prevented L-Arg mediated deleterious effects on Irradiated cells, whereas catalase was ineffective. Intracellular antioxidant enzyme activity was also determined. Ionizing radiation + L-Arg stress altered the activity of catalase (66 % decrease) and glutathione peroxidase (83 % decrease). Our findings demonstrated that L-Arg induces increase the radiation-mediated deleterious effects in Ehrlich ascites carcinoma cells cytotoxicity and that the ratio NO/ O 2 plays a key role in these processes. NO could participate the deleterious effect of irradiation, in conjugation with others reactive oxygen species (ROS) produced during the oxidation of intracellular components by ionizing radiation (dose 6 Gy)

  12. Prophylactic Role of Averrhoa carambola (Star Fruit) Extract against Chemically Induced Hepatocellular Carcinoma in Swiss Albino Mice.

    Science.gov (United States)

    Singh, Ritu; Sharma, Jyoti; Goyal, P K

    2014-01-01

    Liver cancer remains one of the severe lethal malignancies worldwide and hepatocellular carcinoma (HCC) is the most common form. The current study was designed to evaluate the prophylactic role of the fruit of Averrhoa carambola (star fruit or Kamrak) on diethylnitrosamine- (DENA-) induced (15 mg/kg b.wt.; single i.p. injection) and CCl4-promoted (1.6 g/kg b.wt. in corn oil thrice a week for 24 weeks) liver cancer in Swiss albino mice. Administration of ACE was made orally at a dose of 25 mg/kg b.wt/day for 5 consecutive days and it was withdrawn 48 hrs before the first administration of DENA (preinitiational stage). CCl4 was given after 2 weeks of DENA administration. A cent percent tumor incidence was noted in carcinogen treated animals while ACE administration resulted in a considerable reduction in tumor incidence, tumor yield, and tumor burden. Further, ACE treatment brings out a significant reduction in lipid peroxidation (P carambola against hepatocellular carcinoma in mice; therefore, it could be employed for the further screening as a good chemopreventive natural supplement against cancer.

  13. CT colonography: Diagnostic role of contrast enhancement of benign polyps and colorectal carcinoma

    International Nuclear Information System (INIS)

    Stoinova, V.; Nedevska, M.

    2006-01-01

    Full text: The aim of this study was to compare pre- and postcontrast CT attenuation values of benign colorectal polyps and carcinoma lesions detected by CT colonography, and to investigate whether contrast enhancement of these lesions can be potentially used for differentiation from residual fluid and feces. We retrospectively reviewed CT colonographic dataset of 120 patients. 35 benign polyps and 22 colorectal carcinomas were included in our study. All lesions were confirmed by colonoscopic biopsy or surgery. The difference in attenuation value between precontrast and postcontrast studies of polyps was statistically significant; the same was true for colorectal cancers. In the precontrast phase no statistically significant difference was observed between stool, polyps and cancers. The mean attenuation value of solid fecal residuals was 37 HU before and after contrast enhancement. Residual fluid do not take up contrast and the density does not change in the contrast-enhanced phase. The difference between postcontrast density of polyps and cancers with respect to density of stools and residual fluid was significant. The use of contrast medium could be helpful in CT colonography for discriminating polypoid benign lesions and colorectal cancer from fecal and fluid residuals

  14. The role of immunosuppression in squamous cell carcinomas arising in seborrheic keratosis.

    Science.gov (United States)

    Conic, Ruzica Z; Napekoski, Karl; Schuetz, Heidi; Piliang, Melissa; Bergfeld, Wilma; Atanaskova Mesinkovska, Natasha

    2017-06-01

    Seborrheic keratoses (SK) are common skin neoplasms considered to be benign. Reports of associated squamous cell carcinoma arising within seborrheic keratosis (SCC-SK) have been described. To describe the histopathologic characteristics of SCC-SK and identify predisposing factors in formation of these rare lesions. There were 162 cases of SCC-SK in a span of a decade (2003-2014). All of the histopathologic specimens and medical records were reviewed. Data from these patients were compared to a control group with seborrheic keratosis who were matched by age, sex, and location of lesion from the same time period (n = 162). SCC-SK has the classic histopathologic features of SK, such as hyperkeratosis, parakeratosis, papillomatosis, and pseudohorn cysts. The areas of squamous cell carcinoma were characterized by areas of squamous dysplasia (100%), hypogranulosis (79.6%), squamous eddies (79.6%), solar elastosis (80.9%), and brown pigmentation (59.9%). Patients with a history of immunosuppression had an increased risk for developing SCC-SK (19% vs 3%; P < .01), particularly when inhibition was transplant-associated (10% vs 0%; P < .01). This was a single center, retrospective study. SCC-SK occurs more often in elderly men with a history of immunosuppression associated with organ transplants. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  15. The role of X-CT volumetry in radiotherapy of carcinoma of the uterine cervix

    International Nuclear Information System (INIS)

    Miura, Kentaro; Itami, Jun; Ogata, Hitoshi

    1987-01-01

    Computed tomography(X-CT) of squamous cell carcinoma of the uterine cervix was done before and after radiotherapy in forty cases. Changes on X-CT images and its relationship to local control are discussed. Volume of the cervix measured by X-CT is turned out to be a very important factor in radiotherapy of carcinoma of the uterine cervix. 2 cases whose volumes of the cervix exceed 100 cc before radiotherapy failed to obtain local control (p 0.005). After radiotherapy in 6 cases whose volumes of the cervix were more than 20 cc, 5 cases of all failed in local and in 33 cases whose volumes of the cervix were less than 20 cc, 32 cases of all obtained 1 year local control (p < 0.001). In about half cases in which contrast medium was administered low density areas in cervix were observed, in most of all this low density area disappeared after radiotherapy. In the cases in which this low density remained, 3 out of 4 cases failed locally. (author)

  16. Role of LOX3 Gene in Alleviating Adverse Effects of Drought and Pathogens in Rice

    Institute of Scientific and Technical Information of China (English)

    LIU Nan-nan; JIANG Ling; ZHANG Wen-wei; LIU Ling-long; ZHAI Hu-qu; WAN Jian-min

    2008-01-01

    Lipoxygenase 3 (LOX3) is a major component of the LOX isozymes in mature rice seeds. To investigate the role of LOX3 gene under stresses, a plant expression vector containing antisense cDNA of LOX3 was constructed. Rice varieties Wuyunjing 7 and Kasalath were transformed by the Agrobacterium-mediated method and transgenic rice plants were generated. PCR and Southern blot results showed that the antisense LOX3 gene was integrated into the rice genome. Analyses of embryo LOX3 deletion and semi-quantitative RT-PCR confirmed the antisense suppression of LOX3 gene in transgenic plants. The T2 antisense plants of LOX3 were sensitive to drought stress, rice blast and bacterial blight compared with non-transgenic plants. These results suggest that the LOX3 gene might function in response to stresses.

  17. 3-Methylthiopropionic Acid of Rhizoctonia solani AG-3 and Its Role in the Pathogenicity of the Fungus

    Directory of Open Access Journals (Sweden)

    Frederick Kankam

    2016-04-01

    Full Text Available Studies were conducted to determine the role of 3-methylthioproprionic acid (MTPA in the pathogenicity of potato stem canker, Rhizoctonia solani, and the concentrations required to inhibit growth of R. solani under laboratory and plant house-based conditions. The experiments were laid out in a completely randomized design with five treatments and five replications. The treatments were 0, 1, 2, 4, and 8 mM concentrations of MTPA. The purified toxin exhibited maximal activity at pH 2.5 and 30°C. MTPA at 1, 2, 4, and 8 mM levels reduced plant height, chlorophyll content, haulm fresh weight, number of stolons, canopy development, and tuber weight of potato plants, as compared to the control. MTPA significantly affected mycelial growth with 8 mM causing the highest infection. The potato seedlings treated with MTPA concentrations of 1.0–8.0 mM induced necrosis of up to 80% of root system area. Cankers were resulted from the injection of potato seedling stems with 8.0 mM MTPA. The results showed the disappearance of cell membrane, rough mitochondrial and cell walls, change of the shape of chloroplasts, and swollen endoplasmic reticulum. Seventy-six (76 hours after toxin treatment, cell contents were completely broken, cytoplasm dissolved, and more chromatin were seen in the nucleus. The results suggested that high levels of the toxin concentration caused cell membrane and cytoplasm fracture. The integrity of cellular structure was destroyed by the phytotoxin. The concentrations of the phytotoxin were significantly correlated with pathogenicity and caused damage to the cell membrane of potato stem base tissue.

  18. CXCR4 expression in feline mammary carcinoma cells: evidence of a proliferative role for the SDF-1/CXCR4 axis

    Directory of Open Access Journals (Sweden)

    Ferrari Angelo

    2012-03-01

    Full Text Available Abstract Background Mammary tumours frequently develop in female domestic cats being highly malignant in a large percentage of cases. Chemokines regulate many physiological and pathological processes including organogenesis, chemotaxis of inflammatory cells, as well as tumour progression and metastasization. In particular, the chemokine/receptor pair SDF-1/CXCR4 has been involved in the regulation of metastatic potential of neoplastic cells, including breast cancer. The aim of this study was the immunohistochemical defininition of the expression profile of CXCR4 in primary and metastatic feline mammary carcinomas and the evaluation of the role of SDF-1 in feline mammary tumour cell proliferation. Results A total of 45 mammary surgical samples, including 33 primary tumours (31 carcinomas and 2 adenomas, 6 metastases, and 4 normal mammary tissues were anlyzed. Tumor samples were collected from a total number of 26 animals, as in some cases concurrent occurrence of neoplasm in more than one mammary gland was observed. Tissues were processed for standard histological examination, and all lesions were classified according to the World Health Organization criteria. CXCR4 expression in neoplastic cells was evaluated by immunohistochemistry. The level of CXCR4 immunoreactivity was semi-quantitatively estimated as CXCR4 score evaluating both the number of positive cells and the intensity of staining. Six primary, fibroblast-free primary cultures were obtained from fresh feline mammary carcinomas and characterized by immunofluorescence for CXCR4 and malignant mammary cell marker expression. SDF-1-dependent in vitro proliferative effects were also assayed. CXCR4 expression was observed in 29 out of 31 malignant tissues with a higher CXCR4 score observed in 4 out of 6 metastatic lesions than in the respective primary tumours. In 2 benign lesions analyzed, only the single basaloid adenoma showed a mild positive immunostaining against CXCR4. Normal tissue did

  19. The Janus-faced roles of Krüppel-like factor 4 in oral squamous cell carcinoma cells.

    Science.gov (United States)

    Li, Wenwen; Liu, Man; Su, Ying; Zhou, Xinying; Liu, Yao; Zhang, Xinyan

    2015-12-29

    Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor that regulates many essential processes, including development and cell differentiation, proliferation, and apoptosis. Along with these roles in normal cells and tissues, KLF4 has important tumor suppressive and oncogenic functions in some malignancies. However, the roles of KLF4 in oral squamous cell carcinoma remain unclear. This study investigated the epigenetic alterations and possible roles of KLF4 in oral cancer carcinogenesis. Notably, KLF4 expression was significantly decreased in human oral cancer tissues compared with healthy controls, and KLF4 promoter hypermethylation contributed to the suppression of KLF4 expression. KLF4 expression was associated with tumor grade. Its expression was much lower in poorly differentiated oral cancers than in well-differentiated cancer cells. KLF4 exerted its antitumor activity in vitro and/or in vivo by inhibiting cell proliferation, cell cycle progression, cell colony formation and by inducing apoptosis. In addition, KLF4 over-expression promoted oral cancer cell migration and invasion in vitro. Knockdown of KLF4 promoted oral cancer cells growth and colony formation, and simultaneously inhibited cell migration and invasion. Mechanistic studies revealed that MMP-9 might contribute to KLF4-mediated cell migration and invasion. These results provide evidence that KLF4 might play Janus-faced roles in oral cancer carcinogenesis, acting both as a tumor suppressor and as an oncogene.

  20. The role and progress of interventional therapy in the prevention and treatment of postoperative hepatocellular carcinoma recurrence

    International Nuclear Information System (INIS)

    Xiao Yunping; Xiao Enhua

    2008-01-01

    The articles concerning intensive effect and progress of interventional therapy for hepatocellular carcinoma (HCC) recurrence were comprehensively reviewed. Along with unceasing abundance of all interventional methods (including transcatheter arterial chemoemblization (TACE), percutaneous dehydrated ethanol injection, radio frequency ablation, percutaneous microwave therapy, argon-helium cryoablation, high-intensity focused ultrasound and radionuclide interventional therapy, etc), combined interventional therapies mainly TACE were increasingly appreciated in postoperative HCC recurrence, but still have to be further standardized. With further emerging and maturing of new technologies, such as antiangiogenesis, gene therapy and targeted therapy on HCC metastatic and recurrence specific cycle; the effect of combined therapy will be further promoted. Interventional therapy will play an important role in the prevention and treatment of postoperative HCC recurrence in the foreseen furture. (authors)

  1. The increasing roles of epigenetics in breast cancer: Implications for pathogenicity, biomarkers, prevention and treatment.

    Science.gov (United States)

    Basse, Clémence; Arock, Michel

    2015-12-15

    Nowadays, the mechanisms governing the occurrence of cancer are thought to be the consequence not only of genetic defects but also of epigenetic modifications. Therefore, epigenetic has become a very attractive and increasingly investigated field of research in order to find new ways of prevention and treatment of neoplasia, and this is particularly the case for breast cancer (BC). Thus, this review will first develop the main known epigenetic modifications that can occur in cancer and then expose the future role that control of epigenetic modifications might play in prevention, prognostication, follow-up and treatment of BC. Indeed, epigenetic biomarkers found in peripheral blood might become new tools to detect BC, to define its prognostic and to predict its outcome, whereas epi-drugs might have an increasing potential of development in the next future. However, if DNA methyltransferase inhibitors and histone desacetylase inhibitors have shown encouraging results in BC, their action remains nonspecific. Thus, additional clinical studies are needed to evaluate more precisely the effects of these molecules, even if they have provided encouraging results in cotreatment and combined therapies. This review will also deal with the potential of RNA interference (RNAi) as epi-drugs. Finally, we will focus on the potential prevention of BC through epigenetic based on diet and we will particularly develop the possible place of isothiocyanates from cruciferous vegetables or of Genistein from soybean in a dietary program that might potentially reduce the risk of BC in large populations. © 2014 UICC.

  2. Prophylactic Role of Averrhoa carambola (Star Fruit Extract against Chemically Induced Hepatocellular Carcinoma in Swiss Albino Mice

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    Ritu Singh

    2014-01-01

    Full Text Available Liver cancer remains one of the severe lethal malignancies worldwide and hepatocellular carcinoma (HCC is the most common form. The current study was designed to evaluate the prophylactic role of the fruit of Averrhoa carambola (star fruit or Kamrak on diethylnitrosamine- (DENA- induced (15 mg/kg b.wt.; single i.p. injection and CCl4-promoted (1.6 g/kg b.wt. in corn oil thrice a week for 24 weeks liver cancer in Swiss albino mice. Administration of ACE was made orally at a dose of 25 mg/kg b.wt/day for 5 consecutive days and it was withdrawn 48 hrs before the first administration of DENA (preinitiational stage. CCl4 was given after 2 weeks of DENA administration. A cent percent tumor incidence was noted in carcinogen treated animals while ACE administration resulted in a considerable reduction in tumor incidence, tumor yield, and tumor burden. Further, ACE treatment brings out a significant reduction in lipid peroxidation (P<0.001 along with an elevation in the activities of enzymatic antioxidants (superoxide dismutase, P<0.001, and catalase, P<0.001, nonenzymatic antioxidant (reduced glutathione, P<0.001, and total proteins (P<0.001 when compared to the carcinogen treated control. These results demonstrate that ACE prevents the DENA/CCl4 induced adverse physical and biochemical alterations during hepatic carcinogenesis in mice. This study suggests the prophylactic role of Averrhoa carambola against hepatocellular carcinoma in mice; therefore, it could be employed for the further screening as a good chemopreventive natural supplement against cancer.

  3. Proangiogenic hematopoietic cells of monocytic origin: roles in vascular regeneration and pathogenic processes of systemic sclerosis.

    Science.gov (United States)

    Yamaguchi, Yukie; Kuwana, Masataka

    2013-02-01

    New blood vessel formation is critical, not only for organ development and tissue regeneration, but also for various pathologic processes, such as tumor development and vasculopathy. The maintenance of the postnatal vascular system requires constant remodeling, which occurs through angiogenesis, vasculogenesis, and arteriogenesis. Vasculogenesis is mediated by the de novo differentiation of mature endothelial cells from endothelial progenitor cells (EPCs). Early studies provided evidence that bone marrow-derived CD14⁺ monocytes can serve as a subset of EPCs because of their expression of endothelial markers and ability to promote neovascularization in vitro and in vivo. However, the current consensus is that monocytic cells do not give rise to endothelial cells in vivo, but function as support cells, by promoting vascular formation and repair through their immediate recruitment to the site of vascular injury, secretion of proangiogenic factors, and differentiation into mural cells. These monocytes that function in a supporting role in vascular repair are now termed monocytic pro-angiogenic hematopoietic cells (PHCs). Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by excessive fibrosis and microvasculopathy, along with poor vascular formation and repair. We recently showed that in patients with SSc, circulating monocytic PHCs increase dramatically and have enhanced angiogenic potency. These effects may be induced in response to defective vascular repair machinery. Since CD14⁺ monocytes can also differentiate into fibroblast-like cells that produce extracellular matrix proteins, here we propose a new hypothesis that aberrant monocytic PHCs, once mobilized into circulation, may also contribute to the fibrotic process of SSc.

  4. Galectin-3 functions as an alarmin: pathogenic role for sepsis development in murine respiratory tularemia.

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    Bibhuti B Mishra

    Full Text Available Sepsis is a complex immune disorder with a mortality rate of 20-50% and currently has no therapeutic interventions. It is thus critical to identify and characterize molecules/factors responsible for its development. We have recently shown that pulmonary infection with Francisella results in sepsis development. As extensive cell death is a prominent feature of sepsis, we hypothesized that host endogenous molecules called alarmins released from dead or dying host cells cause a hyperinflammatory response culminating in sepsis development. In the current study we investigated the role of galectin-3, a mammalian β-galactoside binding lectin, as an alarmin in sepsis development during F. novicida infection. We observed an upregulated expression and extracellular release of galectin-3 in the lungs of mice undergoing lethal pulmonary infection with virulent strain of F. novicida but not in those infected with a non-lethal, attenuated strain of the bacteria. In comparison with their wild-type C57Bl/6 counterparts, F. novicida infected galectin-3 deficient (galectin-3(-/- mice demonstrated significantly reduced leukocyte infiltration, particularly neutrophils in their lungs. They also exhibited a marked decrease in inflammatory cytokines, vascular injury markers, and neutrophil-associated inflammatory mediators. Concomitantly, in-vitro pre-treatment of primary neutrophils and macrophages with recombinant galectin-3 augmented F. novicida-induced activation of these cells. Correlating with the reduced inflammatory response, F. novicida infected galectin-3(-/- mice exhibited improved lung architecture with reduced cell death and improved survival over wild-type mice, despite similar bacterial burden. Collectively, these findings suggest that galectin-3 functions as an alarmin by augmenting the inflammatory response in sepsis development during pulmonary F. novicida infection.

  5. Frequency of Somatic TP53 Mutations in Combination with Known Pathogenic Mutations in Colon Adenocarcinoma, Non–Small Cell Lung Carcinoma, and Gliomas as Identified by Next-Generation Sequencing

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    Zahra Shajani-Yi

    2018-03-01

    Full Text Available The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer. It encodes p53, a DNA-binding transcription factor that regulates multiple genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis, and senescence. TP53 is associated with human cancer by mutations that lead to a loss of wild-type p53 function as well as mutations that confer alternate oncogenic functions that enable them to promote invasion, metastasis, proliferation, and cell survival. Identifying the discrete TP53 mutations in tumor cells may help direct therapies that are more effective. In this study, we identified the frequency of individual TP53 mutations in patients with colon adenocarcinoma (48%, non–small cell lung carcinoma (NSCLC (36%, and glioma/glioblastoma (28% at our institution using next-generation sequencing. We also identified the occurrence of somatic mutations in numerous actionable genes including BRAF, EGFR, KRAS, IDH1, and PIK3CA that occurred concurrently with these TP53 mutations. Of the 480 tumors examined that contained one or more mutations in the TP53 gene, 219 were colon adenocarcinomas, 215 were NSCLCs, and 46 were gliomas/glioblastomas. Among the patients positive for TP53 mutations diagnosed with colon adenocarcinoma, 50% also showed at least one mutation in pathogenic genes of which 14% were BRAF, 33% were KRAS, and 3% were NRAS. Forty-seven percent of NSCLC patients harboring TP53 mutations also had a mutation in at least one actionable pathogenic variant with the following frequencies: BRAF: 4%, EGFR: 10%, KRAS: 28%, and PIK3CA: 4%. Fifty-two percent of patients diagnosed with glioma/glioblastoma with a positive TP53 mutation had at least one concurrent mutation in a known pathogenic gene of which 9% were CDKN2A, 41% were IDH1, and 11% were PIK3CA.

  6. Progression of understanding for the role of Epstein-Barr virus and management of nasopharyngeal carcinoma.

    Science.gov (United States)

    Nakanishi, Yosuke; Wakisaka, Naohiro; Kondo, Satoru; Endo, Kazuhira; Sugimoto, Hisashi; Hatano, Miyako; Ueno, Takayoshi; Ishikawa, Kazuya; Yoshizaki, Tomokazu

    2017-09-01

    Nasopharyngeal carcinoma (NPC) is very common in southern China and Southeast Asia. In regions where NPC is endemic, undifferentiated subtypes constitute most cases and are invariably associated with Epstein-Barr virus (EBV) infection, whereas the differentiated subtype is more common in other parts of the world. Undifferentiated NPC is a unique malignancy with regard to its epidemiology, etiology, and clinical presentation. Clinically, NPC is highly invasive and metastatic, but sensitive to both chemotherapy and radiotherapy (RT). Overall prognosis has dramatically improved over the past three decades because of advances in management, including the improvement of RT technology, the broader application of chemotherapy, and more accurate disease staging. Despite the excellent local control with modern RT, distant failure remains a challenging problem. Advances in molecular technology have helped to elucidate the molecular pathogenesis of NPC. This article reviews the contribution of EBV gene products to NPC pathogenesis and the current management of NPC.

  7. Role of Sentinel Lymph Node Biopsy in the Management of Merkel Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Eric P. Arruda

    2012-01-01

    Full Text Available Merkel cell carcinoma (MCC is a rare and typically aggressive form of skin cancer. It most commonly affects the elderly and has a predilection for the sun-exposed skin of the head and neck region. Other etiological factors include immune suppression, organ transplantation, and polyoma virus infection. MCC has a propensity to spread to regional lymphatics with a high locoregional recurrence rate. Since its discovery in 1972, treatment paradigms have shifted, with no consensus on optimal management strategies. Currently, standard of care includes surgical intervention to the primary and locoregional site with adjuvant radiotherapy for high-risk disease. In this paper, we discuss the history, pathology, and epidemiology of this rare disease with a focus on the evidentiary basis of treatment protocols. The use of sentinel lymph node biopsy as a management option will be the focus of this paper.

  8. Unmet needs in squamous cell carcinoma of the lung: potential role for immunotherapy.

    Science.gov (United States)

    Stinchcombe, Thomas E

    2014-05-01

    Squamous cell carcinoma of the lung accounts for 20-30% of non-small cell lung cancers (NSCLC). Despite the differences in disease characteristics between squamous and non-squamous NSCLC, both have historically been treated similarly in the clinic. Recently approved drugs have revealed differences in activity and safety profiles across histologic subtypes and have applicability in treating non-squamous, but not typically squamous, NSCLC. Exploration of immune checkpoints--co-inhibitory molecules used to regulate immune responses--has resulted in novel immunotherapies designed to interrupt signaling through the cytotoxic T lymphocyte-associated antigen-4 or programmed cell death protein-1 pathways on lymphocytes. Modulation of these pathways can lead to restored antitumor immune responses, and preliminary evidence shows that agents targeting these pathways have activity in lung cancer, including squamous NSCLC.

  9. Role of Sentinel Lymph Node Biopsy in the Management of Merkel Cell Carcinoma

    International Nuclear Information System (INIS)

    Arruda, E.P.; Higgins, K.M.; Higgins, K. M.; Higgins, K. M.

    2012-01-01

    Merkel cell carcinoma (MCC) is a rare and typically aggressive form of skin cancer. It most commonly affects the elderly and has a predilection for the sun-exposed skin of the head and neck region. Other etiological factors include immune suppression, organ transplantation, and polyoma virus infection. MCC has a propensity to spread to regional lymphatics with a high locoregional recurrence rate. Since its discovery in 1972, treatment paradigms have shifted, with no consensus on optimal management strategies. Currently, standard of care includes surgical intervention to the primary and locoregional site with adjuvant radiotherapy for high-risk disease. In this paper, we discuss the history, pathology, and epidemiology of this rare disease with a focus on the evidentiary basis of treatment protocols. The use of sentinel lymph node biopsy as a management option will be the focus of this paper.

  10. Essential Role of the ESX-5 Secretion System in Outer Membrane Permeability of Pathogenic Mycobacteria

    KAUST Repository

    Ates, Louis S.

    2015-05-04

    Mycobacteria possess different type VII secretion (T7S) systems to secrete proteins across their unusual cell envelope. One of these systems, ESX-5, is only present in slow-growing mycobacteria and responsible for the secretion of multiple substrates. However, the role of ESX-5 substrates in growth and/or virulence is largely unknown. In this study, we show that esx-5 is essential for growth of both Mycobacterium marinum and Mycobacterium bovis. Remarkably, this essentiality can be rescued by increasing the permeability of the outer membrane, either by altering its lipid composition or by the introduction of the heterologous porin MspA. Mutagenesis of the first nucleotide-binding domain of the membrane ATPase EccC5 prevented both ESX-5-dependent secretion and bacterial growth, but did not affect ESX-5 complex assembly. This suggests that the rescuing effect is not due to pores formed by the ESX-5 membrane complex, but caused by ESX-5 activity. Subsequent proteomic analysis to identify crucial ESX-5 substrates confirmed that all detectable PE and PPE proteins in the cell surface and cell envelope fractions were routed through ESX-5. Additionally, saturated transposon-directed insertion-site sequencing (TraDIS) was applied to both wild-type M. marinum cells and cells expressing mspA to identify genes that are not essential anymore in the presence of MspA. This analysis confirmed the importance of esx-5, but we could not identify essential ESX-5 substrates, indicating that multiple of these substrates are together responsible for the essentiality. Finally, examination of phenotypes on defined carbon sources revealed that an esx-5 mutant is strongly impaired in the uptake and utilization of hydrophobic carbon sources. Based on these data, we propose a model in which the ESX-5 system is responsible for the transport of cell envelope proteins that are required for nutrient uptake. These proteins might in this way compensate for the lack of MspA-like porins in slow

  11. Essential Role of the ESX-5 Secretion System in Outer Membrane Permeability of Pathogenic Mycobacteria.

    Directory of Open Access Journals (Sweden)

    Louis S Ates

    2015-05-01

    Full Text Available Mycobacteria possess different type VII secretion (T7S systems to secrete proteins across their unusual cell envelope. One of these systems, ESX-5, is only present in slow-growing mycobacteria and responsible for the secretion of multiple substrates. However, the role of ESX-5 substrates in growth and/or virulence is largely unknown. In this study, we show that esx-5 is essential for growth of both Mycobacterium marinum and Mycobacterium bovis. Remarkably, this essentiality can be rescued by increasing the permeability of the outer membrane, either by altering its lipid composition or by the introduction of the heterologous porin MspA. Mutagenesis of the first nucleotide-binding domain of the membrane ATPase EccC5 prevented both ESX-5-dependent secretion and bacterial growth, but did not affect ESX-5 complex assembly. This suggests that the rescuing effect is not due to pores formed by the ESX-5 membrane complex, but caused by ESX-5 activity. Subsequent proteomic analysis to identify crucial ESX-5 substrates confirmed that all detectable PE and PPE proteins in the cell surface and cell envelope fractions were routed through ESX-5. Additionally, saturated transposon-directed insertion-site sequencing (TraDIS was applied to both wild-type M. marinum cells and cells expressing mspA to identify genes that are not essential anymore in the presence of MspA. This analysis confirmed the importance of esx-5, but we could not identify essential ESX-5 substrates, indicating that multiple of these substrates are together responsible for the essentiality. Finally, examination of phenotypes on defined carbon sources revealed that an esx-5 mutant is strongly impaired in the uptake and utilization of hydrophobic carbon sources. Based on these data, we propose a model in which the ESX-5 system is responsible for the transport of cell envelope proteins that are required for nutrient uptake. These proteins might in this way compensate for the lack of Msp

  12. Essential Role of the ESX-5 Secretion System in Outer Membrane Permeability of Pathogenic Mycobacteria

    KAUST Repository

    Ates, Louis S.; Ummels, Roy; Commandeur, Susanna; van der Weerd, Robert; Sparrius, Marion; Weerdenburg, Eveline; Alber, Marina; Kalscheuer, Rainer; Piersma, Sander R.; Abdallah, Abdallah; Abd El Ghany, Moataz; Abdel-Haleem, Alyaa M.; Pain, Arnab; Jimé nez, Connie R.; Bitter, Wilbert; Houben, Edith N.G.

    2015-01-01

    Mycobacteria possess different type VII secretion (T7S) systems to secrete proteins across their unusual cell envelope. One of these systems, ESX-5, is only present in slow-growing mycobacteria and responsible for the secretion of multiple substrates. However, the role of ESX-5 substrates in growth and/or virulence is largely unknown. In this study, we show that esx-5 is essential for growth of both Mycobacterium marinum and Mycobacterium bovis. Remarkably, this essentiality can be rescued by increasing the permeability of the outer membrane, either by altering its lipid composition or by the introduction of the heterologous porin MspA. Mutagenesis of the first nucleotide-binding domain of the membrane ATPase EccC5 prevented both ESX-5-dependent secretion and bacterial growth, but did not affect ESX-5 complex assembly. This suggests that the rescuing effect is not due to pores formed by the ESX-5 membrane complex, but caused by ESX-5 activity. Subsequent proteomic analysis to identify crucial ESX-5 substrates confirmed that all detectable PE and PPE proteins in the cell surface and cell envelope fractions were routed through ESX-5. Additionally, saturated transposon-directed insertion-site sequencing (TraDIS) was applied to both wild-type M. marinum cells and cells expressing mspA to identify genes that are not essential anymore in the presence of MspA. This analysis confirmed the importance of esx-5, but we could not identify essential ESX-5 substrates, indicating that multiple of these substrates are together responsible for the essentiality. Finally, examination of phenotypes on defined carbon sources revealed that an esx-5 mutant is strongly impaired in the uptake and utilization of hydrophobic carbon sources. Based on these data, we propose a model in which the ESX-5 system is responsible for the transport of cell envelope proteins that are required for nutrient uptake. These proteins might in this way compensate for the lack of MspA-like porins in slow

  13. Peritoneal Adhesion and Angiogenesis in Ovarian Carcinoma Are Inversely Regulated by Hyaluronan: The Role of Gonadotropins

    Directory of Open Access Journals (Sweden)

    Yael Chagit Tzuman

    2010-01-01

    Full Text Available Ovarian carcinoma is the leading cause of death among gynecologic cancers. Although transformation of the outer ovarian epithelium was linked with ovulation, the disease is significantly more prevalent and severe in postmenopausal women. We postulated that menopause could augment ovarian cancer progression through the effects of gonadotropins on multifocal seeding to the mesothelial layer lining the peritoneum. This seeding is mediated by integrins as well as by CD44 interaction with hyaluronan (HA. Here, we report the effect of gonadotropins on HA synthesis and degradation and on peritoneal adhesion. A significant concentration- and time-dependent induction in expression levels of HA synthases (HASs and hyaluronidases (Hyals was observed in vitro on stimulation of human epithelial ovarian carcinoma cells by gonadotropins. Hormonal regulation of HA-mediated adhesion was manifested in vivo as well, by fluorescence microscopy of stained MLS multicellular tumor spheroids. The number of spheroids adhered to the mesothelium of ovariectomized CD-1 nude mice 9.5 hours after intraperitoneal insertion was significantly higher than in nonovariectomized mice. Inhibition of HA synthesis by 6-diazo-5-oxo-1-norleucine (DON both in spheroids and ovariectomized mice significantly reduced the number of adhered spheroids. Thus, the change in the hormonal environment during menopause assists in HA-dependent adherence of ovarian cancer spheroids onto the peritoneum. However, HA is antiangiogenic and it can significantly suppress tumor progression. Accordingly, angiogenesis of the adhered spheroids was significantly elevated in DON-treated tumors. These results can explain the selective pressure that can lead to simultaneously increased tumor expression of both HASs and Hyals.

  14. Role of plasma EBV DNA levels in predicting recurrence of nasopharyngeal carcinoma in a western population

    International Nuclear Information System (INIS)

    Ferrari, Daris; Alterio, Daniela; Foa, Paolo; Codecà, Carla; Bertuzzi, Cecilia; Broggio, Francesca; Crepaldi, Francesca; Luciani, Andrea; Floriani, Irene; Ansarin, Mohssen; Chiesa, Fausto

    2012-01-01

    Loco-regionally advanced nasopharyngeal carcinomas can be cured by the combination of chemotherapy and radiotherapy. In Eastern countries, plasma levels of viral Epstein-Barr deoxyribonucleic acid (DNA) are accurate in predicting recurrence, but few data are available in Western populations. The aim of this prospective study was to evaluate the relationship between viral Epstein-Barr DNA copy numbers in plasma and the response rate, progression-free survival and overall survival in a cohort of Western patients with stage IIb-IVb nasopharyngeal cancer. We evaluated plasma samples from 36 consecutive patients treated with induction chemotherapy followed by chemoradiation. EBV copy numbers were determined after DNA extraction using real-time quantitative polymerase chain reaction. Survival curves were estimated using the Kaplan–Meier method. Circulating Epstein-Barr virus DNA levels were measured before treatment, at the end of concomitant chemo- and radiotherapy, and during the follow-up period. Pre-treatment levels significantly correlated with the initial stage and probability of relapse. Their increase was 100% specific and 71.3% sensitive in detecting loco-regional or metastatic recurrence (an overall accuracy of 94.4%). Three-year progression-free and overall survival were respectively 78.2% and 97.1%. The results of this study confirm that patients from a Western country affected by loco-regionally advanced nasopharyngeal carcinoma have high plasma Epstein-Barr virus DNA levels at diagnosis. The monitoring of plasma levels is sensitive and highly specific in detecting disease recurrence and metastases

  15. Breast MRI of ductal carcinoma in situ. Is there MRI role?

    International Nuclear Information System (INIS)

    Francescutti, G.E.; Londero, V.; Berra, I.; Del Frate, C.; Zuiani, C.; Bazzocchi, M.

    2002-01-01

    Background. The purpose of this study is to report our personal experience of 22 cases of ductal carcinoma in situ (DCIS) studied with magnetic resonance imaging (MRI). Patients and methods. From September 1995 to December 2001, 22 women diagnosed with DCIS lesions underwent contrast enhanced MRI within 7 days after mammographic examination. Dynamic MRI was performed with a 1 T system, using a three dimensional fast low angle shot (FLASH) pulse sequence before and after contrast media administration. We evaluated the morphologic features of the enhancement, the enhancement rate and the signal time intensity curve. Pathology was obtained in all cases. Results. The results of histopatological examination included: 15 DCIS and 7 DCIS with associated microinvasive component or microfoci of invasive ductal carcinoma (IDC). On MRI, 21 of 22 (95%) DCIS lesions showed contrast enhancement. Fourteen out of 15 pure DCIS lesions demonstrated respectively a low (3), undeterminate (5), and strong (6) enhancement. Morphologically, the enhancing lesion was focal in 7, segmental in 4, and with linear branching in 3 cases. Wash out was found in 4 cases, plateau curve in 8 and Type I curve in 2 cases. Multifocality was present in 5 cases. All DCIS with associated microinvasion demonstrated contrast enhancement: 1/7 cases showed a low enhancement, 2/7 showed an indeterminate enhancement and 4/7 showed a strong enhancement. Morphologically, the enhancing lesion was focal in 3/9, segmental in 5 and with linear branching in 1 case. The wash out was demonstrated in 3/7 cases, plateau curve in 3 and Type 1 curve in 1 case. Multifocality was present in 3 cases. Conclusions. In conclusion, the sensitivity of MRI for DCIS detection is lower than that achieved for invasive breast cancer; however, contrast-enhanced MRI can depict foci of DCIS that are mammographically occult. The MRI technique is of complementary value for a better description of tumor size and detection of additional

  16. Role of microRNAs in hepatocellular carcinoma: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Callegari E

    2013-09-01

    Full Text Available Elisa Callegari,1 Bahaeldin K Elamin,1,2 Silvia Sabbioni,3,5 Laura Gramantieri,4 Massimo Negrini1,5 1Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale, Università di Ferrara, Ferrara, Italy; 2Department of Microbiology, Faculty of Medical Laboratory Sciences, University of Khartoum, Sudan; 3Dipartimento di Scienze della Vita e Biotecnologie, Università di Ferrara, Ferrara, 4Centro di Ricerca Biomedica Applicata e Dipartimento di Medicina Interna, Policlinico S Orsola-Malpighi e Università di Bologna, Bologna, 5Tecnopolo "Laboratorio per le Tecnologie delle Terapie Avanzate", Università di Ferrara, Ferrara, Italy Abstract: Hepatocellular carcinoma (HCC is one of the most deadly tumors, and current treatments for the disease are often ineffective. The discovery of the involvement of microRNAs (miRNAs in hepatocarcinogenesis represents an important area of investigation for the development of their clinical applications. These molecules may act as oncogenes or tumor suppressors by directly or indirectly controlling the expression of key proteins involved in cancer-associated pathways. On the clinical side, because of their tumor-specific expression and stability in tissues and in the circulation, miRNAs have been proposed as novel diagnostic tools for classification and prognostic stratification of HCC. In recent years, the therapeutic potential of miRNAs has been demonstrated in various preclinical studies. Anti-miRNA oligonucleotides and miRNA mimics have been found to have antitumor activity. Moreover, by exploiting tumor-specific expression of miRNA, efforts have been aimed at improving targeting of tumor cells by replicative oncolytic viruses while sparing normal cells. These areas are expected to be explored further in the upcoming years to assess the clinical value of miRNA-based approaches in HCC and cancer in general. Keywords: hepatocellular carcinoma, microRNA, micromarkers, oncolytic viruses

  17. Role of ultrasonography in detecting mammographically occult breast carcinoma in women with dense breasts.

    Science.gov (United States)

    Corsetti, V; Ferrari, A; Ghirardi, M; Bergonzini, R; Bellarosa, S; Angelini, O; Bani, C; Ciatto, S

    2006-04-01

    The purpose of this study was to assess the usefulness of routine ultrasonography in women with negative mammography and dense breasts [Breast Imaging Reporting and Data System (BIRADS D3-4)]. We applied a protocol involving routine ultrasonography in a consecutive series of subjects with negative mammography and dense breasts. After evaluation by internal and external reviewers of cancers detected by ultrasonography performed to confirm negative mammography, we determined the additional cancer detection rate of ultrasonography and the cost of the protocol. Out of 17,883 total mammographies, 167 cancers were diagnosed (detection rate: 0.93%). Out of 257 suspicious mammographies, 138 cancers were detected. Out of 17,626 negative mammographies, 6,449 (36.5%) were classified as "dense breast" and underwent ultrasonography: 29 cancers were detected (detection rate: 0.44%, or 17.3% of total cancers). Out of 25 cancer cases reviewed, negative mammography and asymptomatic status was confirmed in 15 (detection rate 0.23%, or 8.9% of total cancers). The cancer detection rate was 0.11%, 0.22%, 0.32% and 0.14% for age groups 59, respectively. The cost per additional carcinoma detected by ultrasonography alone was euro 25,847.85 whereas that per examined woman was euro 21.68. The study confirms the possibility that ultrasonography can detect mammographically occult breast carcinoma in dense breasts. The evidence is insufficient to recommend this policy in routine screening practice but suggests that, at least in current clinical practice, adding ultrasonography in dense breasts may be useful despite the substantial costs.

  18. The role of epithelial-mesenchymal transition in squamous cell carcinoma of the oral cavity.

    Science.gov (United States)

    Zidar, Nina; Boštjančič, Emanuela; Malgaj, Marija; Gale, Nina; Dovšak, Tadej; Didanovič, Vojko

    2018-02-01

    Epithelial-mesenchymal transition (EMT) has emerged as a possible mechanism of cancer metastasizing, but strong evidence for EMT involvement in human cancer is lacking. Our aim was to compare oral spindle cell carcinoma (SpCC) as an example of EMT with oral conventional squamous cell carcinoma (SCC) with and without nodal metastases to test the hypothesis that EMT contributes to metastasizing in oral SCC. Thirty cases of oral SCC with and without nodal metastasis and 15 cases of SpCC were included. Epithelial (cytokeratin, E-cadherin), mesenchymal (vimentin, N-cadherin), and stem cell markers (ALDH-1, CD44, Nanog, Sox-2) and transcription repressors (Snail, Slug, Twist) were analyzed immunohistochemically. We also analyzed the expression of microRNAs miR-141, miR-200 family, miR-205, and miR-429. SpCC exhibited loss of epithelial markers and expression of mesenchymal markers or coexpression of both up-regulation of transcription repressors and down-regulation of the investigated microRNAs. SCC showed only occasional focal expression of mesenchymal markers at the invasive front. No other differences were observed between SCC with and without nodal metastases except for a higher expression of ALDH-1 in SCC with metastases. Our results suggest that SpCC is an example of true EMT but do not support the hypothesis that EMT is involved in metastasizing of conventional SCC. Regarding oral SCC progression and metastasizing, we have been facing a shift from the initial enthusiasm for the EMT concept towards a more critical approach with "EMT-like" and "partial EMT" concepts. The real question, though, is, is there no EMT at all?

  19. The Role of Radiotherapy in the Treatment of Extrahepatic Bile Duct Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Hyun Soo; Kim, Gwi Eon; Lee, Hyung Sik; Suh, Chang Ok; Loh, John Ku; Lee, Jong Tae [Yonsei National University College of Medicine, Seoul (Korea, Republic of)

    1991-12-15

    Twenty-seven patients with unresectable extrahepatic bile duct carcinoma (n=21) or with microscopic evidence of tumor rest after aggressive surgery for extrahepatic bile duct carcinoma(n=6) between 1985 and 1990 were given radiotherapy consisting intentionally external radiotherapy and /or intraluminal therapy using Gamma-Med 12i (192-lr) high dose rate (HDR) remote control afterloading system following bile drainage procedures and Gianturco stent insertion. The objectives of this study has been to assess the feasibility and effects on survival of a combination of external radiotherapy and brachytherapy with which we hope to achieve optimal loco-regional control for patients with unresectable extrahepatic bile duct tumors. Sixteen patients were men and eleven were women, and the mean age was 58 years (34-70 ). 10MV X-ray was used for radiation therapy, with the total dose ranging from 45 Gy to 55 Gy, and intraluminal brachytherapy performed after external radiotherapy, with the dose of total 15 Gy. The minimum follow up was 12 months. Failure were predominantly local-regional, without distant failure. Median survival was 10 months; 2-year actuarial survival rates was 21%. Median survival for common hepatic duct(CHD) cancer was 9 months; for common bile duct (CBD) cancer, was 16 months. And median survival for incomplete surgery/external radiotherapy group and external/intraluminal radiotherapy group was 10 months; for external radiotherapy alone group, was 6 months. Use of chemotherapy and/or hyperthermia were not affected in survival. Therefore, our result is that the survival rates in the group of external/intraluminal radiotherapy were comparable with ones in the group of incomplete resection/external radiotherapy, and so we believe that the aggressive local and regional radiotherapy can improve the quality of life and the survival length.

  20. Possible role of the scintigraphic estimation of the relative liver perfusion in the choice of treatment of liver carcinomas

    International Nuclear Information System (INIS)

    Artiko, V.; Obradovic, V.; Davidovic, B.; Petrovic, N.; Vlajkoviae, M.; Kostic, K.

    2005-01-01

    Full text: In the pre-evaluation and diagnosis of the patients with liver tumors, significant nuclear medicine methods used are: radiocolloid, blood pool, hepatobiliary scintigraphy, angioscintigraphy with radiolabeled microspheres as well as 'first pass' radionuclide angiography, which can precede all of the above mentioned methods, during single injection application. The aim of the study is evaluation of the possible role of the scintigraphic estimation of the relative liver perfusion in the choice of treatment of liver carcinomas. The study was performed in 120 patients: 24 controls (C), 35 with benign liver tumors (BT), 35 with hepatocellular carcinomas (HCC), 19 with metastases of colorectal carcinomas (MCC) as well as 7 with metastases of other tumors (MOT-bronchus, lung carcinoma and lymphoma). 7/35 HCC had cavernous portal vein developed after tumor thrombosis, 2 had complete thrombosis and 5 had incomplete thrombosis (thrombosis of the either of portal venous branches (3) and incomplete portal venous thrombosis -2). 2/19 patients with MCC had cavernous portal vein developed after tumor thrombosis, 3 had complete portal venous occlusion and 4 incomplete thrombosis (thrombosis of the either of branches). The study was performed with ROTA scintillation camera and Micro Delta computer, during 60 sec (1f/sec) from i.v.application of 740 MBq 99mTc-pertecnetate. TA curves were generated using liver ROI, spleen ROI and left kidney ROI, and curves were generated. Hepatic perfusion index was calculated using slope analysis (Portal slope Ps and arterial slope As) method according to following formula HPI=Ps/(Ps+As). Complementary methods used were Doppler ultrasonography, CT, MRI, tumor marker assays (CEA, Ca19-9, AFP) laboratory analyses, pathohistological finding and clinical diagnosis. In C, HPI was 0.68±0.06 which did not differ from the value in BT (0.64 ±0.08) (p>0.05). However, in HCC ( X=0.26±0.20), and LM (X=0.40±0.28), HPI values were significantly

  1. DNA aneuploidy in colorectal adenomas: Role in the adenoma-carcinoma sequence Aneuploidía del ADN en adenomas colónicos: Papel en la secuencia adenoma-carcinoma

    Directory of Open Access Journals (Sweden)

    M. Alcántara Torres

    2005-01-01

    Full Text Available Introduction: aneuploidy has been observed in 6-27% of lesions known to be precursors of colorectal cancer, such as adenomas or ulcerative colitis. It has been suggested that aneuploidy may predispose to malignancy in these cases. However, its role in the adenoma-carcinoma sequence has not been definitely established. The objective of this study was to assess the incidence of aneuploidy in colon adenomas, as well as to study its possible role in the adenoma-carcinoma sequence. Material and methods: the study was performed on a series of 57 large bowel adenomas measuring 10 mm or more, collected from 54 consecutive patients. All specimens were obtained either by endoscopic or by surgical resection. There were 49 adenomas with low-grade dysplasia, two with high-grade dysplasia, two intramucous carcinomas, and four microinvasive carcinomas. A flow cytometric DNA analysis was performed in fresh specimens following Vindelov´s method. Results: aneuploid DNA was detected in five out of 49 low-grade dysplasia adenomas (10%, in all four high-grade dysplasia adenomas or intramucous carcinomas (100%, and in three out of four microinvasive carcinomas (75%. The association between aneuploidy and high-grade dysplasia adenomas, intramucous, or microinvasive carcinoma was statistically significant (p Introducción: en patología benigna de intestino grueso precursora del cáncer colorrectal, como adenomas o colitis ulcerosa, se ha observado aneuploidía en el 6-27% de los casos y se ha sugerido que su presencia predispone al desarrollo de malignidad. Sin embargo, su papel en la secuencia adenoma-carcinoma no se ha demostrado de forma concluyente. El objetivo de nuestro trabajo fue valorar la incidencia de aneuploidía en adenomas colónicos, con y sin signos de malignidad, y estudiar su posible papel en la secuencia adenoma-carcinoma. Material y métodos: el estudio se realizó en una serie de 57 adenomas de intestino grueso, de 10 o más mil

  2. The Double-Edged Sword in Pathogenic Trypanosomatids: The Pivotal Role of Mitochondria in Oxidative Stress and Bioenergetics

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    Rubem Figueiredo Sadok Menna-Barreto

    2014-01-01

    Full Text Available The pathogenic trypanosomatids Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. are the causative agents of African trypanosomiasis, Chagas disease, and leishmaniasis, respectively. These diseases are considered to be neglected tropical illnesses that persist under conditions of poverty and are concentrated in impoverished populations in the developing world. Novel efficient and nontoxic drugs are urgently needed as substitutes for the currently limited chemotherapy. Trypanosomatids display a single mitochondrion with several peculiar features, such as the presence of different energetic and antioxidant enzymes and a specific arrangement of mitochondrial DNA (kinetoplast DNA. Due to mitochondrial differences between mammals and trypanosomatids, this organelle is an excellent candidate for drug intervention. Additionally, during trypanosomatids’ life cycle, the shape and functional plasticity of their single mitochondrion undergo profound alterations, reflecting adaptation to different environments. In an uncoupling situation, the organelle produces high amounts of reactive oxygen species. However, these species role in parasite biology is still controversial, involving parasite death, cell signalling, or even proliferation. Novel perspectives on trypanosomatid-targeting chemotherapy could be developed based on better comprehension of mitochondrial oxidative regulation processes.

  3. [The role of natural environment in spreading of hantavirus--model of the correlation between host, pathogen and human infections].

    Science.gov (United States)

    Baumann, Anna; Dudek, Dorota; Sadkowska-Todys, Małgorzata

    2007-01-01

    The environmental changes caused by humans influence ecosystem and thus have significant impact on occurrence of emerging and re-emerging diseases. The hantavirus infection belong to the one of them. The aim of this paper was to present current knowledge about relationship between hantavirus, their natural host and the spread of the infection to people. Rodents constitute both the natural host of the hantaviruses and the reservoir of hantavirus for environment. Circulation of the virus in the rodent population is crucial to maintain the virus in the environment. The individual characteristics of rodents influence on risk of infection with hantavirus. However, this relationship is still unexplained. Risk of pathogen exposure often increases with age and behavioral differences associated with the sex of the susceptible individual. Mating behaviors seem to play an important role in the spread of the virus among rodents. Human incidence of hantavirus infection has in general been found to correlate to the population size of rodent host especially in the model of nephropathia epidemica (NE; a mild form of HFRS), Puumala virus (PUU) and bank voles. The occurrence of hantavirus infections in humans is assumed to rise as a secondary effect from altered population sizes of rodents in a changing environment due to e.g. mast years, forest fragmentation, global warming.

  4. Animal model of acid-reflux esophagitis: pathogenic roles of acid/pepsin, prostaglandins, and amino acids.

    Science.gov (United States)

    Takeuchi, Koji; Nagahama, Kenji

    2014-01-01

    Esophagitis was induced in rats within 3 h by ligating both the pylorus and transitional region between the forestomach and glandular portion under ether anesthesia. This esophageal injury was prevented by the administration of acid suppressants and antipepsin drug and aggravated by exogenous pepsin. Damage was also aggravated by pretreatment with indomethacin and the selective COX-1 but not COX-2 inhibitor, whereas PGE2 showed a biphasic effect depending on the dose; a protection at low doses, and an aggravation at high doses, with both being mediated by EP1 receptors. Various amino acids also affected this esophagitis in different ways; L-alanine and L-glutamine had a deleterious effect, while L-arginine and glycine were highly protective, both due to yet unidentified mechanisms. It is assumed that acid/pepsin plays a major pathogenic role in this model of esophagitis; PGs derived from COX-1 are involved in mucosal defense of the esophagus; and some amino acids are protective against esophagitis. These findings also suggest a novel therapeutic approach in the treatment of esophagitis, in addition to acid suppressant therapy. The model introduced may be useful to test the protective effects of drugs on esophagitis and investigate the mucosal defense mechanism in the esophagus.

  5. Transforming growth factor-β: activation by neuraminidase and role in highly pathogenic H5N1 influenza pathogenesis.

    Directory of Open Access Journals (Sweden)

    Christina M Carlson

    2010-10-01

    Full Text Available Transforming growth factor-beta (TGF-β, a multifunctional cytokine regulating several immunologic processes, is expressed by virtually all cells as a biologically inactive molecule termed latent TGF-β (LTGF-β. We have previously shown that TGF-β activity increases during influenza virus infection in mice and suggested that the neuraminidase (NA protein mediates this activation. In the current study, we determined the mechanism of activation of LTGF-β by NA from the influenza virus A/Gray Teal/Australia/2/1979 by mobility shift and enzyme inhibition assays. We also investigated whether exogenous TGF-β administered via a replication-deficient adenovirus vector provides protection from H5N1 influenza pathogenesis and whether depletion of TGF-β during virus infection increases morbidity in mice. We found that both the influenza and bacterial NA activate LTGF-β by removing sialic acid motifs from LTGF-β, each NA being specific for the sialic acid linkages cleaved. Further, NA likely activates LTGF-β primarily via its enzymatic activity, but proteases might also play a role in this process. Several influenza A virus subtypes (H1N1, H1N2, H3N2, H5N9, H6N1, and H7N3 except the highly pathogenic H5N1 strains activated LTGF-β in vitro and in vivo. Addition of exogenous TGF-β to H5N1 influenza virus-infected mice delayed mortality and reduced viral titers whereas neutralization of TGF-β during H5N1 and pandemic 2009 H1N1 infection increased morbidity. Together, these data show that microbe-associated NAs can directly activate LTGF-β and that TGF-β plays a pivotal role protecting the host from influenza pathogenesis.

  6. Elucidating the role of the phenylacetic acid metabolic complex in the pathogenic activity of Rhizoctonia solani anastomosis group 3.

    Science.gov (United States)

    Bartz, Faith E; Glassbrook, Norman J; Danehower, David A; Cubeta, Marc A

    2012-01-01

    The soil fungus Rhizoctonia solani produces phytotoxic phenylacetic acid (PAA) and hydroxy (OH-) and methoxy (MeO-) derivatives of PAA. However, limited information is available on the specific role that these compounds play in the development of Rhizoctonia disease symptoms and concentration(s) required to induce a host response. Reports that PAA inhibits the growth of R. solani conflict with the established ability of the fungus to produce and metabolize PAA. Experiments were conducted to clarify the role of the PAA metabolic complex in Rhizoctonia disease. In this study the concentration of PAA and derivatives required to induce tomato root necrosis and stem canker, in the absence of the fungus, and the concentration that inhibits mycelial growth of R. solani were determined. The effect of exogenous PAA and derivatives of PAA on tomato seedling growth also was investigated. Growth of tomato seedlings in medium containing 0.1-7.5 mM PAA and derivatives induced necrosis of up to 85% of root system. Canker development resulted from injection of tomato seedling stems with 7.5 mM PAA, 3-OH-PAA, or 3-MeO-PAA. PAA in the growth medium reduced R. solani biomass, with 50% reduction observed at 7.5 mM. PAA, and derivatives were quantified from the culture medium of 14 isolates of R. solani belonging to three distinct anastomosis groups by GC-MS. The quantities ranged from below the limit of detection to 678 nM, below the concentrations experimentally determined to be phytotoxic. Correlation analyses revealed that isolates of R. solani that produced high PAA and derivatives in vitro also caused high mortality on tomato seedlings. The results of this investigation add to the body of evidence that the PAA metabolic complex is involved in Rhizoctonia disease development but do not indicate that production of these compounds is the primary or the only determinant of pathogenicity.

  7. Expression and role of VEGFA and miR-381 in portal vein tumor thrombi in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Jing; Wu, Shuzhi; Huang, Tianren

    2018-06-01

    The aim of the present study was to examine the expression and role of vascular endothelial growth factor A (VEGFA) and microRNA (miRNA or miR)-381 in tumor thrombi from patients with hepatocellular carcinoma and portal vein tumor thrombus (PVTT). Tumor thrombi and adjacent paired tissues were collected from 39 patients with hepatocellular carcinoma with PVTT. VEGFA expression levels were assessed using reverse transcription-quantitative polymerase chain reaction and western blotting. miRNAs that may regulate VEGFA expression were predicted using bioinformatics analysis and confirmed via a dual luciferase reporter assay. The effects of VEGFA and its upstream miRNA on proliferation of the proliferation of EAhy926 human venous endothelial cells were analyzed using an MTT assay. Compared with the paired adjacent tissues, VEGFA was significantly upregulated at both the mRNA and protein level in tumor thrombi (P<0.05). VEGFA was predicted to be a target of miR-381 and this was confirmed experimentally. miR-381 expression was significantly downregulated in tumor thrombi from patients with PVTT compared with paired adjacent tissues (P<0.05). In addition, transfection with antagomirs against miR-381 or short interfering RNA against VEGFA significantly inhibited EAhy926 cell proliferation (P<0.05). In conclusion, the results of the present study indicate that VEGFA is upregulated in tumor thrombi whereas miR-381 is downregulated. VEGFA is regulated by miR-381 and both may be associated with the development of PVTT.

  8. Insights into the role of components of the tumor microenvironment in oral carcinoma call for new therapeutic approaches

    International Nuclear Information System (INIS)

    Salo, Tuula; Vered, Marilena; Bello, Ibrahim O.; Nyberg, Pia; Bitu, Carolina Cavalcante; Zlotogorski Hurvitz, Ayelet; Dayan, Dan

    2014-01-01

    The research on oral cancer has focused mainly on the cancer cells, their genetic changes and consequent phenotypic modifications. However, it is increasingly clear that the tumor microenvironment (TME) has been shown to be in a dynamic state of inter-relations with the cancer cells. The TME contains a variety of components including the non-cancerous cells (i.e., immune cells, resident fibroblasts and angiogenic vascular cells) and the ECM milieu [including fibers (mainly collagen and fibronectin) and soluble factors (i.e., enzymes, growth factors, cytokines and chemokines)]. Thus, it is currently assumed that TME is considered a part of the cancerous tissue and the functionality of its key components constitutes the setting on which the hallmarks of the cancer cells can evolve. Therefore, in terms of controlling a malignancy, one should control the growth, invasion and spread of the cancer cells through modifications in the TME components. This mini review focuses on the TME as a diagnostic approach and reports the recent insights into the role of different TME key components [such as carcinoma-associated fibroblasts (CAFs) and inflammation (CAI) cells, angiogenesis, stromal matrix molecules and proteases] in the molecular biology of oral carcinoma. Furthermore, the impact of TME components on clinical outcomes and the concomitant need for development of new therapeutic approaches will be discussed. - Highlights: • Tumor depth and budding, hypoxia and TME cells associate with worse prognosis. • Pro-tumoral CAFs and CAI cells aid proliferation, invasion and spread hypoxia. • Some ECM-bound factors exert pro-angiogenic or pro-tumor activities. • Tumor spread is greatly dependent on ECM proteolysis, mediated by TME cells. • Direct targeting of TME components for treatment is still experimental

  9. Insights into the role of components of the tumor microenvironment in oral carcinoma call for new therapeutic approaches

    Energy Technology Data Exchange (ETDEWEB)

    Salo, Tuula, E-mail: Tuula.salo@oulu.fi [Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, and Medical Research Center, Oulu (Finland); Oulu University Central Hospital, Oulu (Finland); Institute of Dentistry, University of Helsinki, Helsinki (Finland); Vered, Marilena [Institute of Pathology, The Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan (Israel); Department of Oral Pathology and Oral Medicine, School of Dentistry, Tel Aviv University, Tel Aviv 69978 (Israel); Bello, Ibrahim O. [Department of Oral Medicine and Diagnostic Sciences, King Saud University, Riyadh (Saudi Arabia); Nyberg, Pia [Oulu University Central Hospital, Oulu (Finland); Bitu, Carolina Cavalcante [Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, and Medical Research Center, Oulu (Finland); Zlotogorski Hurvitz, Ayelet [Department of Oral Pathology and Oral Medicine, School of Dentistry, Tel Aviv University, Tel Aviv 69978 (Israel); Department of Oral and Maxillofacial Surgery, Rabin Medical Center, Beilinson Campus, Petah Tikva (Israel); Dayan, Dan [Department of Oral Pathology and Oral Medicine, School of Dentistry, Tel Aviv University, Tel Aviv 69978 (Israel)

    2014-07-15

    The research on oral cancer has focused mainly on the cancer cells, their genetic changes and consequent phenotypic modifications. However, it is increasingly clear that the tumor microenvironment (TME) has been shown to be in a dynamic state of inter-relations with the cancer cells. The TME contains a variety of components including the non-cancerous cells (i.e., immune cells, resident fibroblasts and angiogenic vascular cells) and the ECM milieu [including fibers (mainly collagen and fibronectin) and soluble factors (i.e., enzymes, growth factors, cytokines and chemokines)]. Thus, it is currently assumed that TME is considered a part of the cancerous tissue and the functionality of its key components constitutes the setting on which the hallmarks of the cancer cells can evolve. Therefore, in terms of controlling a malignancy, one should control the growth, invasion and spread of the cancer cells through modifications in the TME components. This mini review focuses on the TME as a diagnostic approach and reports the recent insights into the role of different TME key components [such as carcinoma-associated fibroblasts (CAFs) and inflammation (CAI) cells, angiogenesis, stromal matrix molecules and proteases] in the molecular biology of oral carcinoma. Furthermore, the impact of TME components on clinical outcomes and the concomitant need for development of new therapeutic approaches will be discussed. - Highlights: • Tumor depth and budding, hypoxia and TME cells associate with worse prognosis. • Pro-tumoral CAFs and CAI cells aid proliferation, invasion and spread hypoxia. • Some ECM-bound factors exert pro-angiogenic or pro-tumor activities. • Tumor spread is greatly dependent on ECM proteolysis, mediated by TME cells. • Direct targeting of TME components for treatment is still experimental.

  10. The Pathologic Finding of Combined Lobular Carcinoma In Situ and Invasive Lobular Cancer May Indicate more than Just a High-Risk Marker Role of Lobular Carcinoma In Situ.

    Science.gov (United States)

    Jean-Louis, Christopher J; Masdon, Joshua; Smith, Betsy; Battles, Oscar; Dale, Paul

    2017-05-01

    may in fact have a precursory role in development of invasive lobular carcinoma of the breast. Additional studies to further investigate this relationship between LCIS and ILC, including genomic analysis, are presently underway.

  11. Role and mechanism of PKC on radiosensitization in pancreatic carcinoma cell line Panc-1

    International Nuclear Information System (INIS)

    Qiao Qiao; Zhang Shuo; Chen Yanzhi; Li Guang

    2008-01-01

    Objective: To explore the effect of PKC on radiosensitization in pancreatic carcinoma cell line Panc-1, and its mediating mechanism. Methods: Panc-1 cells were treated with the specific activator of PKC (phorbol 12-myristate 13-acetate, PMA) and the specific inhibitor of PKC (chelerythrine, CH) to observe the SF2 changes. Cell survival was determined by clonogenic assay. The apoptosis rates of the cells were analyzed by flow cytometry with Annexin V/PI staining. The expression of apoptosis related protein Bcl-2 and Bax after the treatment of CH and/or irradiation was determined by immunocytochemistry. Results: The SF 2 values of radiation group, PMA group and CH group were 0.78 ± 0.02, 0.92 ± 0.11 and 0.19 ± 0.20, respectively. CH can significantly increase the sensitivity of Panc-1 to irradiation. SERs of Panc-1 cells were 1.05, 1.24 and 1.77 after the treatment of 0.5, 2 and 8 μmol/L of CH, respectively. The result of flow cytometry analysis showed that PMA decreased the apoptosis index with irradiation, while CH significantly increased the apoptosis index. Expression of Bax protein was increased significantly (P<0.05) while that of Bcl-2 was not influenced; however, the ratio of Bax/Bcl-2 was increased. Conclusions: PKC regulates the radiosensitivity of Panc-1 by mediating the apoptosis of tumor cells. (authors)

  12. Role of Bax in resveratrol-induced apoptosis of colorectal carcinoma cells

    International Nuclear Information System (INIS)

    Mahyar-Roemer, Mojgan; Köhler, Hans; Roemer, Klaus

    2002-01-01

    The natural plant polyphenol resveratrol present in some foods including grapes, wine, and peanuts, has been implicated in the inhibition, delay, and reversion of cellular events associated with heart diseases and tumorigenesis. Recent work has suggested that the cancer chemoprotective effect of the compound is primarily linked to its ability to induce cell division cycle arrest and apoptosis, the latter possibly through the activation of pro-apoptotic proteins such as Bax. The expression, subcellular localization, and importance of Bax for resveratrol-provoked apoptosis were assessed in human HCT116 colon carcinoma cells and derivatives with both bax alleles inactivated. Low to moderate concentrations of resveratrol induced co-localization of cellular Bax protein with mitochondria, collapse of the mitochondrial membrane potential, activation of caspases 3 and 9, and finally, apoptosis. In the absence of Bax, membrane potential collapse was delayed, and apoptosis was reduced but not absent. Resveratrol inhibited the formation of colonies by both HCT116 and HCT116 bax -/- cells. Resveratrol at physiological doses can induce a Bax-mediated and a Bax-independent mitochondrial apoptosis. Both can limit the ability of the cells to form colonies

  13. Scintimammography: The new role of Technetium-99 m Sestamibi imaging for the diagnosis of breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Khalkhali, I.; Diggles, L. E.; Cutrone, J. A.; Mishkin, F. S. [Los Angeles Medical Center, Torrance (United States). Dept. of Radiology; Iraniha, S. [Los Angeles Medical Center, Torrance (United States). Surgery

    1997-09-01

    Technetium-99-Sestamibi scintimammography has emerged as a new procedure for the imaging of breast tumors, Currently, a large clinical experience has been developed and the results published. At the present time, the major drawback of this procedure appears to be its low sensitivity for the detection of breast carcinomas smaller than 1 cm in diameter. There are other biologic and technical issues that remain to be overcome to optimally image the breasts. Some of these include: development of a dedicated breast imager using nuclear medicine techniques, development of stereotactic needle localization of the abnormalities that demonstrate focal increase uptake in women with normal mammogram and breast physical examination, manufacturing of a breast compression device so that they can immobilize the breast in place for more adequate imaging, overcoming the issue of unilateral or bilateral diffuse breast uptake that is noted in 7 - 10 percent of the cases and finally determination of optimal dose and imaging factors. This review includes their experience at Harbor-University of California, Los Angeles Medical Center with the use of this agent for breast imaging since 1992.

  14. A Novel Role of Silibinin as a Putative Epigenetic Modulator in Human Prostate Carcinoma

    Directory of Open Access Journals (Sweden)

    Ioannis Anestopoulos

    2016-12-01

    Full Text Available Silibinin, extracted from milk thistle (Silybum marianum L., has exhibited considerable preclinical activity against prostate carcinoma. Its antitumor and chemopreventive activities have been associated with diverse effects on cell cycle, apoptosis, and receptor-dependent mitogenic signaling pathways. Here we hypothesized that silibinin’s pleiotropic effects may reflect its interference with epigenetic mechanisms in human prostate cancer cells. More specifically, we have demonstrated that silibinin reduces gene expression levels of the Polycomb Repressive Complex 2 (PRC2 members Enhancer of Zeste Homolog 2 (EZH2, Suppressor of Zeste Homolog 12 (SUZ12, and Embryonic Ectoderm Development (EED in DU145 and PC3 human prostate cancer cells, as evidenced by Real Time Polymerase Chain Reaction (RT-PCR. Furthermore immunoblot and immunofluorescence analysis revealed that silibinin-mediated reduction of EZH2 levels was accompanied by an increase in trimethylation of histone H3 on lysine (Κ-27 residue (H3K27me3 levels and that such response was, in part, dependent on decreased expression levels of phosphorylated Akt (ser473 (pAkt and phosphorylated EZH2 (ser21 (pEZH2. Additionally silibinin exerted other epigenetic effects involving an increase in total DNA methyltransferase (DNMT activity while it decreased histone deacetylases 1-2 (HDACs1-2 expression levels. We conclude that silibinin induces epigenetic alterations in human prostate cancer cells, suggesting that subsequent disruptions of central processes in chromatin conformation may account for some of its diverse anticancer effects.

  15. Scintimammography: The new role of Technetium-99 m Sestamibi imaging for the diagnosis of breast carcinoma

    International Nuclear Information System (INIS)

    Khalkhali, I.; Diggles, L. E.; Cutrone, J. A.; Mishkin, F. S.; Iraniha, S.

    1997-01-01

    Technetium-99-Sestamibi scintimammography has emerged as a new procedure for the imaging of breast tumors, Currently, a large clinical experience has been developed and the results published. At the present time, the major drawback of this procedure appears to be its low sensitivity for the detection of breast carcinomas smaller than 1 cm in diameter. There are other biologic and technical issues that remain to be overcome to optimally image the breasts. Some of these include: development of a dedicated breast imager using nuclear medicine techniques, development of stereotactic needle localization of the abnormalities that demonstrate focal increase uptake in women with normal mammogram and breast physical examination, manufacturing of a breast compression device so that they can immobilize the breast in place for more adequate imaging, overcoming the issue of unilateral or bilateral diffuse breast uptake that is noted in 7 - 10 percent of the cases and finally determination of optimal dose and imaging factors. This review includes their experience at Harbor-University of California, Los Angeles Medical Center with the use of this agent for breast imaging since 1992

  16. DLEC1 Expression Is Modulated by Epigenetic Modifications in Hepatocelluar Carcinoma Cells: Role of HBx Genotypes

    International Nuclear Information System (INIS)

    Niu, Dandan; Feng, Huixing; Chen, Wei Ning

    2010-01-01

    Deleted in Lung and Esophageal Cancer 1 (DLEC1) is a functional tumor suppressor gene (TSG). It has been found to be silenced in a variety of human cancers including hepatocellular carcinoma (HCC). The silencing of DLEC1 can be modulated by epigenetic modifications, such as DNA hypermethylation and histone hypoacetylation. In the case of HCC, hepatitis B virus X protein (HBx) has been implicated in methylation of target promoters resulting in the down-regulation of tumor suppressor genes, which in turn contributes to the development of HCC. In the present study, we first established a cell system in which epigenetic modifications can be modulated using inhibitors of either DNA methylation or histone deacetylation. The cell system was used to reveal that the expression of DLEC1 was upregulated by HBx in a genotype-dependent manner. In particular, HBx genotype A was found to decrease DNA methylation of the DLEC1 promoter. Our results have provided new insights on the impact of HBx in HCC development by epigenetic modifications

  17. Clinical experience and critical evaluation of the role of sorafenib in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Zustovich F

    2011-05-01

    Full Text Available Fable Zustovich1, Giuseppe Lombardi1, Davide Pastorelli1, Patrizia Farina1, Massimo Dal Bianco2, Luca De Zorzi2, Maurizia Dalla Palma1, Ornella Nicoletto1, Vittorina Zagonel11Oncologia Medica 1, Istituto Oncologico Veneto-IRCCS, Padova, Italy; 2UO Urologia, Ospedale Sant'Antonio, ULSS 16, Padova, ItalyAbstract: Renal cell carcinoma (RCC is a common malignancy worldwide with approximately 95,000 new cases per year and ranks as the sixth cause of cancer deaths. Until recently, the slightly active and very toxic cytokines were available for patients with advanced RCC. Advances have been made in understanding the molecular biology of renal cancer. The introduction of targeted agents has led to promising possibilities for treating these highly vascularized tumors. Angiogenesis inhibition is likely to represent the main potential therapeutic target. Sorafenib is an oral multikinase inhibitor with activity against tyrosine kinase receptors that are responsible for blood vessel development and has shown to be active in treating advanced RCC. In this review, we summarize the pharmacology, mode of action, pharmacokinetics, and safety of sorafenib use in therapy for advanced RCC.Keywords: sorafenib, pharmacokinetics, angiogenesis 

  18. The Role of Pretreatment FDG-PET in Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy

    International Nuclear Information System (INIS)

    Liu, Wen-Shan; Wu, Ming-Fang; Tseng, Hsien-Chun; Liu, Jung-Tung; Weng, Jui-Hung; Li, Yueh-Chun; Lee, Jong-Kang

    2012-01-01

    Purpose: Pretreatment with 2- [ 18 F] fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) was evaluated as a predictor of local failure-free survival (LFFS), disease-free survival (DFS), and overall survival (OS) in patients with nonkeratinizing nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT) alone or concurrently with chemotherapy (CCRT). Patients and Methods: Seventy-five M0 NPC patients who received FDG-PET before treatment were analyzed. The primary tumor FDG uptake was measured as the maximum standardized uptake value (SUVmax). The LFFS, DFS, and OS were calculated by the Kaplan-Meier method, and the differences were evaluated on log-rank test. The prognostic significance was assessed by univariate and multivariate analyses. Results: Eighteen patients received IMRT alone and 57 received CCRT. The mean SUVmax was significantly higher in 12 patients with locoregional or distant failure than in those without failure (p 18 F-FDG uptake (SUVmax >5) indicates poor outcome in patients with NPC.

  19. LEPREL1 Expression in Human Hepatocellular Carcinoma and Its Suppressor Role on Cell Proliferation

    Directory of Open Access Journals (Sweden)

    Jianguo Wang

    2013-01-01

    Full Text Available Background. Hepatocellular carcinoma (HCC is one of the most aggressive malignancies worldwide. It is characterized by its high invasive and metastatic potential. Leprecan-like 1 (LEPREL1 has been demonstrated to be downregulated in the HCC tissues in previous proteomics studies. The present study is aimed at a new understanding of LEPREL1 function in HCC. Methods. Quantitative RT-PCR, immunohistochemical analysis, and western blot analysis were used to evaluate the expression of LEPREL1 between the paired HCC tumor and nontumorous tissues. The biology function of LEPREL1 was investigated by Cell Counting Kit-8 (CCK8 assay and colony formation assay in HepG2 and Bel-7402 cells. Results. The levels of LEPREL1 mRNA and protein were significantly lower in the HCC tissues as compared to those of the nontumorous tissues. Reduced LEPREL1 expression was not associated with conventional clinical parameters of HCC. Overexpression of LEPREL1 in HepG2 and Bel-7402 cells inhibited cell proliferation (P<0.01 and colony formation (P<0.05. LEPREL1 suppressed tumor cell proliferation through regulation of the cell cycle by downregulation of cyclins. Conclusions. Clinical parameters analysis suggested that LEPREL1 was an independent factor in the development of HCC. The biology function experiments showed that LEPREL1 might serve as a potential tumor suppressor gene by inhibiting the HCC cell proliferation.

  20. Role of chemotherapy and molecularly targeted agents in the treatment of adenoid cystic carcinoma of the lacrimal gland.

    Science.gov (United States)

    Le Tourneau, Christophe; Razak, Albiruni R A; Levy, Christine; Calugaru, Valentin; Galatoire, Olivier; Dendale, Rémi; Desjardins, Laurence; Gan, Hui K

    2011-11-01

    Adenoid cystic carcinoma (ACC) is the most common malignant epithelial cancer of the lacrimal gland. Despite a slow rate of growth, ACCs are ultimately associated with poor clinical outcome. Given the rarity of this disease, most recommendations regarding therapy are guided by expert opinion and retrospective data rather than level 1 evidence. Surgery and postoperative radiation therapy are commonly used as initial local treatment. In patients at high risk of recurrence, concomitant platinum-based chemotherapy may be added to postoperative radiotherapy in an attempt to enhance radio-sensitivity. While encouraging responses have been reported with intra-arterial neoadjuvant chemotherapy, this strategy is associated with substantial toxicity and should be considered investigational. For patients with metastatic disease not amenable to surgery or radiotherapy, chemotherapy may have a role based on its modest efficacy in non-lacrimal ACC. Similarly, molecular targeted agents may have a role, although the agents tested to date in non-lacrimal ACC have been disappointing. A better understanding of the biology of ACC will be crucial to the future success of developing targeted agents for this disease.

  1. Negative Correlation between miR-200c and Decorin Plays an Important Role in the Pathogenesis of Colorectal Carcinoma

    Directory of Open Access Journals (Sweden)

    Ren-Yi Tang

    2017-01-01

    Full Text Available Aim. To demonstrate the regulatory role of miRNA in colorectal carcinoma (CRC and reveal the transcript markers that may be associated with CRC clinical outcomes. Method. Herein, we analyzed both mRNA and miRNA gene expression profiles of 255 CRC tumor samples from The Cancer Genome Atlas project to reveal the regulatory association between miRNA and mRNA. Also, the potential role of gene coexpression network in CRC has been explored. Results. The negative correlation between miR-200c and DCN (Decorin was calculated in CRC, indicating that DCN could be a potential target of miR-200c. Clinical features indicated that colon polyp history and overall survival were significantly related to the expression level of miR-200c. Three coexpression networks have been constructed, and genes involved in the networks are related to cell cycle, NOTCH, and mTOR signaling pathways. Conclusion. Our result provides a new insight into cancer related mRNA coexpression network in CRC research.

  2. A Study to investigate the role of p27 and Cyclin E immunoexpression as a prognostic factor in early breast carcinoma

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    Chetty Runjan

    2011-03-01

    Full Text Available Abstract Background Cyclin E and p27 expression is easy to assess in human tissues by standard immunohistochemical techniques. Immunohistochemistry is cost effective, relatively easy to perform and will play more of a role in the future management of cancer. The aim of this study was to investigate the role of p27 and cyclin E immunoexpression as a prognostic factor in early breast carcinoma. Methods Cyclin E and p27 immunohistochemistry was performed on sixty six cases of breast carcinoma submitted over a five year period to the Division of Anatomical Pathology, Groote Schuur hospital; Whittaker and Associates; and PathCare. All tumours included in this study were less than 5 cm in diameter (pT1 and pT2 stage and all the patients had wide local excisions performed. Follow up information was obtained from patient folders in the Department of Radiation Oncology. Results There was no significant association of cyclin E and p27 expression with distant metastasis free survival (MFS for all invasive carcinomas in contrast to grade, lymph node spread and vascular invasion. However, there was a statistically significant direct association of cyclin E with distant metastases in all invasive carcinomas, in the subgroup of infiltrating duct carcinomas (IDC and in the node negative group when cyclin E was stratified as negative and positive (low/high. In this study of early breast carcinoma, only 9/66 cases showed cyclin E expression. Of these, four patients had distant metastases, one patient had a local recurrence and four patients were alive at last follow-up. Furthermore, cyclin E expression was significantly associated with grade, lymph node spread, oestrogen receptor status and histological type. None of the lobular carcinomas showed cyclin E positivity and only one case of lobular carcinoma presented with distant metastases. 59/66 cases were positive (low/high for p27 while seven cases were negative, 22 cases showed low expression and 37 cases

  3. Role of Definitive Radiation Therapy in Carcinoma of Unknown Primary in the Abdomen and Pelvis

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    Kelly, Patrick; Das, Prajnan; Varadhachary, Gauri R.; Fontanilla, Hiral P.; Krishnan, Sunil; Delclos, Marc E.; Jhingran, Anuja; Eifel, Patricia J.; Crane, Christopher H.

    2012-01-01

    Objectives: Carcinoma of unknown primary (CUP) in the abdomen and pelvis is a heterogeneous group of cancers with no standard treatment. Considered by many to be incurable, these patients are often treated with chemotherapy alone. In this study, we determined the effectiveness of radiation therapy in combination with chemotherapy in patients with CUP in the abdomen and pelvis. Patients and Methods: Medical records were reviewed for 37 patients with CUP treated with radiation therapy for disease located in the soft tissues and/or nodal basins of the abdomen and pelvis at University of Texas M.D. Anderson Cancer between 2002 and 2009. All patients underwent chemotherapy, either before or concurrent with radiation therapy. Patients were selected for radiation therapy on the basis of histologic type, disease extent, and prior therapy response. Twenty patients underwent definitive radiation therapy (defined as radiation therapy targeting all known disease sites with at least 45 Gy) and 17 patients underwent palliative radiation therapy. Only 6 patients had surgical resection of their disease. Patient and treatment characteristics were extracted and the endpoints of local disease control, progression-free survival (PFS), overall survival (OS), and treatment-related toxicity incidence were analyzed. Results: The 2-year PFS and OS rates for the entire cohort were 32% and 57%, respectively. However, in patients treated with definitive radiation therapy, the rates were 48% and 76%, and 7 patients lived more than 3 years after treatment with no evidence of disease progression. Nevertheless, radiation-associated toxicity was significant in this cohort, as 40% experienced Grade 2 or higher late toxicities. Conclusions: The use of definitive radiation therapy should be considered in selected patients with CUP in the soft tissues or nodal basins of the abdomen and pelvis.

  4. Clear cell carcinoma of the ovary: Is there a role of histology-specific treatment?

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    Takano Masashi

    2012-06-01

    Full Text Available Abstract Several clinical trials to establish standard treatment modality for ovarian cancers included a high abundance of patients with serous histologic tumors, which were quite sensitive to platinum-based chemotherapy. On the other hand, ovarian tumor with rare histologic subtypes such as clear cell or mucinous tumors have been recognized to show chemo-resistant phenotype, leading to poorer prognosis. Especially, clear cell carcinoma of the ovary (CCC is a distinctive tumor, deriving from endometriosis or clear cell adenofibroma, and response rate to platinum-based therapy is extremely low. It was implied that complete surgical staging enabled us to distinguish a high risk group of recurrence in CCC patients whose disease was confined to the ovary (pT1M0; however, complete surgical staging procedures could not lead to improved survival. Moreover, the status of peritoneal cytology was recognized as an independent prognostic factor in early-staged CCC patients, even after complete surgical staging. In advanced cases with CCC, the patients with no residual tumor had significantly better survival than those with the tumor less than 1 cm or those with tumor diameter more than 1 cm. Therefore, the importance of achieving no macroscopic residual disease at primary surgery is so important compared with other histologic subtypes. On the other hand, many studies have shown that conventional platinum-based chemotherapy regimens yielded a poorer prognosis in patients with CCC than in patients with serous subtypes. The response rate by paclitaxel plus carboplatin (TC was slightly higher, ranging from 22% to 56%, which was not satisfactory enough. Another regimen for CCC tumors is now being explored: irinotecan plus cisplatin, and molecular targeting agents. In this review article, we discuss the surgical issues for early-staged and advanced CCC including possibility of fertility-sparing surgery, and the chemotherapy for CCC disease.

  5. The role of whole brain radiotherapy and stereotactic radiosurgery on brain metastases from renal cell carcinoma

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    Goyal, Lav K.; Suh, John H.; Reddy, Chandana A.; Barnett, Gene H.

    2000-01-01

    Purpose: We reviewed our experience with patients who have undergone stereotactic radiosurgery (SRS) for brain metastases secondary to renal cell carcinoma (RCC). Analysis was performed to determine the survival, local control, distant brain failure (DBF), and then to define which tumors may not require upfront whole-brain radiotherapy (WBRT). Methods and Materials: Twenty-nine patients with 66 tumors underwent SRS from 1991 to 1998. Median follow-up from time of brain metastases diagnoses relative to each tumor was 12.5 months and 6.8 months from the time of SRS. Median SRS dose was 1,800 cGy to the 60% isodose line. Three patients had undergone SRS for previously treated tumors. Results: Median survival time from diagnosis was 10.0 months. Overall survival was not affected by age, addition of WBRT, number of lesions, tumor volume, or the presence of systemic disease. Of the 23 patients with follow-up neuroimaging, 4 of 47 (9%) tumors recurred. The addition of WBRT did not improve local control. Of the 13 patients who presented with a single lesion, 3 went on to develop DBF (23%), while 6 of the 10 patients who presented with multiple metastases developed DBF (60%). Conclusion: Patients with brain metastases secondary to RCC treated by SRS alone have excellent local control. The decision of whether or not to add WBRT to SRS should depend on whether the patient has a high likelihood of developing DBF. Our study suggests that patients who present with multiple brain lesions may be more likely to benefit from the addition of WBRT because they appear to be more than twice as likely to develop DBF as compared to patients with a single lesion

  6. Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma

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    M Hashem Abdel

    2011-11-01

    Full Text Available Abstract Background Hepatitis C virus (HCV is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has the highest reported rates of HCV infection (predominantly genotype 4 in the world; this study investigated effects of HCV genotype-4 (HCV-4 on prevalence of insulin resistance in chronic hepatitis C (CHC and HCC in Egyptian patients. Methods Fifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples. Results HCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p = 0.23. Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p Conclusions IR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development.

  7. Merkel cell carcinoma: the role of radiation therapy in general management

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    Bischof, M.; Kampen, M. van; Huber, P.; Wannenmacher, M.

    1999-01-01

    Background: Merkel cell carcinoma (MCC) is a rare malignant, locally aggressive tumor of the skin. Because few data exist about the clinical course of irradiated patients, we reviewed the 17 patients treated at our institution since 1982. Patients and Methods: The median age at diagnosis was 71 years (range 47 to 88 years). Twelve patients presented with lymph node involvement (Stage II), 5 patients with negative lymph nodes (Stage I). Five patients were irradiated immediately after initial surgical excision of the primary tumor. Eleven patients underwent a surgical treatment of recurrence prior to the first irradiation. Only 1 patient received primary radiotherapy. A median dose of 52.8 Gy (range 40 to 60 Gy) in the region of the primary tumor and a median dose of 49.5 Gy (range 30 to 54 Gy) in the regional lymph nodes were delivered. Results: The median overall survival after first diagnosis was 45 months. Three-year overall survival was 57%, 5-year cause-specific survival was 73% (Kaplan Meier). Local control could be achieved in the 5 patients irradiated immediately after surgical treatment of the primary tumor. In contrast, an in-field recurrence occurred in 5 of 12 patients irradiated after surgical excision of relapsed disease. Five patients developed distant metastases. None of these patients was irradiated immediately after surgical excision of the primary tumor. Conclusions: With respect to our experience, a local control can be achieved with an immediate postoperative radiotherapy of the primary tumor site and the adjacent lymph nodes. (orig.) [de

  8. Treg subsets in inflammatory bowel disease and colorectal carcinoma: Characteristics, role, and therapeutic targets

    NARCIS (Netherlands)

    van Herk, Egbert H.; te Velde, Anje A.

    2016-01-01

    T regulatory cells (Tregs) play an important role in the regulation of autoimmunity, autoinflammation, allergic diseases, infection, and the tumor environment. Different subsets are characterized that use a number of regulatory mechanisms. Tregs can influence the progression of inflammatory bowel

  9. Patients' potential role in the transmission of health care-associated infections: prevalence of contamination with bacterial pathogens and patient attitudes toward hand hygiene.

    Science.gov (United States)

    Istenes, Nancy; Bingham, James; Hazelett, Susan; Fleming, Eileen; Kirk, Jane

    2013-09-01

    Transmission of health care-associated infections (HAIs) has been primarily attributed to health care workers, and hand hygiene is considered the most important means to reduce transmission. Whereas hand hygiene research has focused on reducing health care worker hand contamination and improving hand hygiene compliance, contamination of patients' hands and their role in the transmission of HAIs remains unknown. Patients' hands were sampled by a "glove juice" recovery method and enumerated for the presence of common health care-associated pathogens. Patient demographics and other covariates were collected to determine their association with patient hand contamination. Patient attitudes and practices toward hand hygiene were also surveyed and analyzed. Of the 100 patients in the study, 39% of hands were contaminated with at least 1 pathogenic organism, and 8% were contaminated with 2 or more pathogens 48 hours after admission. Patient admission from or discharge to an outside institution and self-reported functional limitations were the only covariates that were significantly associated with hand contamination. Pathogenic organisms can be frequently detected on hands of acute care patients. Future studies are needed to better understand the relationship between patient hand contamination and the acquisition of HAIs in addition to the role patient hand hygiene can play in reducing HAIs. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  10. A prebiotic role of Ecklonia cava improves the mortality of Edwardsiella tarda-infected zebrafish models via regulating the growth of lactic acid bacteria and pathogen bacteria.

    Science.gov (United States)

    Lee, WonWoo; Oh, Jae Young; Kim, Eun-A; Kang, Nalae; Kim, Kil-Nam; Ahn, Ginnae; Jeon, You-Jin

    2016-07-01

    In this study, the beneficial prebiotic roles of Ecklonia cava (E. cava, EC) were evaluated on the growth of lactic acid bacteria (LAB) and pathogen bacteria and the mortality of pathogen-bacteria infected zebrafish model. The result showed that the original E. cava (EC) led to the highest growth effects on three LABs (Lactobacillus brevis, L. brevis; Lactobacillus pentosus, L. pentosus; Lactobacillus plantarum; L. plantarum) and it was dose-dependent manners. Also, EC, its Celluclast enzymatic (ECC) and 100% ethanol extracts (ECE) showed the anti-bacterial activities on the fish pathogenic bacteria such as (Edwardsiella tarda; E. tarda, Streptococcus iniae; S. iniae, and Vibrio harveyi; V. harveyi). Interestingly, EC induced the higher production of the secondary metabolites from L. plantarum in MRS medium. The secondary metabolites produced by EC significantly inhibited the growth of pathogen bacteria. In further in vivo study, the co-treatment of EC and L. plantarum improved the growth and mortality of E. tarda-infected zebrafish as regulating the expression of inflammatory molecules such as iNOS and COX2. Taken together, our present study suggests that the EC plays an important role as a potential prebiotic and has a protective effect against the infection caused by E. tarda injection in zebrafish. Also, our conclusion from this evidence is that EC can be used and applied as a useful prebiotic. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Haemophilus influenzae Isolated From Men With Acute Urethritis: Its Pathogenic Roles, Responses to Antimicrobial Chemotherapies, and Antimicrobial Susceptibilities.

    Science.gov (United States)

    Ito, Shin; Hatazaki, Kyoko; Shimuta, Ken; Kondo, Hiromi; Mizutani, Kosuke; Yasuda, Mitsuru; Nakane, Keita; Tsuchiya, Tomohiro; Yokoi, Shigeaki; Nakano, Masahiro; Ohinishi, Makoto; Deguchi, Takashi

    2017-04-01

    There have been few comprehensive studies on Haemophilus influenza-positive urethritis. In this retrospective study, we enrolled 68 men with H. influenzae-positive urethritis, including coinfections with Neisseria gonorrhoeae, Chlamydia trachomatis, and/or genital mycoplasmas: 2, 3, 20, and 43 treated with ceftriaxone, levofloxacin, sitafloxacin, and extended-release azithromycin (azithromycin-SR), respectively. We assessed microbiological outcomes in 54 men and clinical outcomes in 46 with H. influenzae-positive monomicrobial nongonococcal urethritis. We determined minimum inhibitory concentrations (MICs) of 6 antimicrobial agents for 59 pretreatment isolates. H. influenzae was eradicated from the men treated with ceftriaxone, levofloxacin, or sitafloxacin. The eradication rate with azithromycin-SR was 85.3%. The disappearance or alleviation of urethritis symptoms and the decreases in leukocyte counts in first-voided urine were significantly associated with the eradication of H. influenzae after treatment. For the isolates, ceftriaxone, levofloxacin, sitafloxacin, azithromycin, tetracycline, and doxycycline MICs were ≤0.008-0.25, 0.008-0.5, 0.001-0.008, 0.12-1, 0.25-16, and 0.25-2 μg/mL, respectively. The azithromycin MICs for 3 of 4 strains persisting after azithromycin-SR administration were 1 μg/mL. H. influenzae with an azithromycin MIC of 1 μg/mL increased chronologically. H. influenzae showed good responses to the chemotherapies for urethritis. The significant associations of the clinical outcomes of the chemotherapies with their microbiological outcomes suggested that H. influenzae could play pathogenic roles in urethritis. All isolates, except for one with decreased susceptibility to tetracyclines, were susceptible to the examined agents. However, the increase in H. influenzae with an azithromycin MIC of 1 μg/mL might threaten efficacies of azithromycin regimens on H. influenzae-positive urethritis.

  12. DPAGT1-CDG: Functional analysis of disease-causing pathogenic mutations and role of endoplasmic reticulum stress.

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    Patricia Yuste-Checa

    Full Text Available Pathogenic mutations in DPAGT1 are manifested as two possible phenotypes: congenital disorder of glycosylation DPAGT1-CDG (also known as CDG-Ij, and limb-girdle congenital myasthenic syndrome (CMS with tubular aggregates. UDP-N-acetylglucosamine-dolichyl-phosphate N-acetylglucosamine phosphotransferase (GPT, the protein encoded by DPAGT1, is an endoplasmic reticulum (ER-resident protein involved in an initial step in the N-glycosylation pathway. The aim of the present study was to examine the effect of six variants in DPAGT1 detected in patients with DPAGT1-CDG, and the role of endoplasmic reticulum stress, as part of the search for therapeutic strategies to use against DPAGT1-CDG. The effect of the six mutations, i.e., c.358C>A (p.Leu120Met, c.791T>G (p.Val264Gly, c.901C>T (p.Arg301Cys, c.902G>A (p.Arg301His, c.1154T>G (p.Leu385Arg, and of the novel mutation c.329T>C (p.Phe110Ser, were examined via the analysis of DPAGT1 transcriptional profiles and GTP levels in patient-derived fibroblasts. In addition, the transient expression of different mutations was analysed in COS-7 cells. The results obtained, together with those of bioinformatic studies, revealed these mutations to affect the splicing process, the stability of GTP, or the ability of this protein to correctly localise in the ER membrane. The unfolded protein response (UPR; the response to ER stress was found not to be active in patient-derived fibroblasts, unlike that seen in cells from patients with PMM2-CDG or DPM1-CDG. Even so, the fibroblasts of patients with DPAGT1-CDG seemed to be more sensitive to the stressor tunicamycin. The present work improves our knowledge of DPAGT1-CDG and provides bases for developing tailored splicing and folding therapies.

  13. Mucosal-Associated Invariant T Cell Interactions with Commensal and Pathogenic Bacteria: Potential Role in Antimicrobial Immunity in the Child

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    Liana Ghazarian

    2017-12-01

    Full Text Available Mucosal-associated invariant T (MAIT cells are unconventional CD3+CD161high T lymphocytes that recognize vitamin B2 (riboflavin biosynthesis precursor derivatives presented by the MHC-I related protein, MR1. In humans, their T cell receptor is composed of a Vα7.2-Jα33/20/12 chain, combined with a restricted set of Vβ chains. MAIT cells are very abundant in the liver (up to 40% of resident T cells and in mucosal tissues, such as the lung and gut. In adult peripheral blood, they represent up to 10% of circulating T cells, whereas they are very few in cord blood. This large number of MAIT cells in the adult likely results from their gradual expansion with age following repeated encounters with riboflavin-producing microbes. Upon recognition of MR1 ligands, MAIT cells have the capacity to rapidly eliminate bacterially infected cells through the production of inflammatory cytokines (IFNγ, TNFα, and IL-17 and cytotoxic effector molecules (perforin and granzyme B. Thus, MAIT cells may play a crucial role in antimicrobial defense, in particular at mucosal sites. In addition, MAIT cells have been implicated in diseases of non-microbial etiology, including autoimmunity and other inflammatory diseases. Although their participation in various clinical settings has received increased attention in adults, data in children are scarce. Due to their innate-like characteristics, MAIT cells might be particularly important to control microbial infections in the young age, when long-term protective adaptive immunity is not fully developed. Herein, we review the data showing how MAIT cells may control microbial infections and how they discriminate pathogens from commensals, with a focus on models relevant for childhood infections.

  14. Roles for miR-375 in Neuroendocrine Differentiation and Tumor Suppression via Notch Pathway Suppression in Merkel Cell Carcinoma.

    Science.gov (United States)

    Abraham, Karan J; Zhang, Xiao; Vidal, Ricardo; Paré, Geneviève C; Feilotter, Harriet E; Tron, Victor A

    2016-04-01

    Dysfunction of key miRNA pathways regulating basic cellular processes is a common driver of many cancers. However, the biological roles and/or clinical applications of such pathways in Merkel cell carcinoma (MCC), a rare but lethal cutaneous neuroendocrine (NE) malignancy, have yet to be determined. Previous work has established that miR-375 is highly expressed in MCC tumors, but its biological role in MCC remains unknown. Herein, we show that elevated miR-375 expression is a specific feature of well-differentiated MCC cell lines that express NE markers. In contrast, miR-375 is strikingly down-regulated in highly aggressive, undifferentiated MCC cell lines. Enforced miR-375 expression in these cells induced NE differentiation, and opposed cancer cell viability, migration, invasion, and survival, pointing to tumor-suppressive roles for miR-375. Mechanistically, miR-375-driven phenotypes were caused by the direct post-transcriptional repression of multiple Notch pathway proteins (Notch2 and RBPJ) linked to cancer and regulation of cell fate. Thus, we detail a novel molecular axis linking tumor-suppressive miR-375 and Notch with NE differentiation and cancer cell behavior in MCC. Our findings identify miR-375 as a putative regulator of NE differentiation, provide insight into the cell of origin of MCC, and suggest that miR-375 silencing may promote aggressive cancer cell behavior through Notch disinhibition. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. Downregulation of tropomyosin-1 in squamous cell carcinoma of esophagus, the role of Ras signaling and methylation.

    Science.gov (United States)

    Zare, Maryam; Jazii, Ferdous Rastgar; Soheili, Zahra-Soheila; Moghanibashi, Mohamad-Mehdi

    2012-10-01

    Tropomyosins (TMs) are a family of cytoskeletal proteins that bind to and stabilize actin microfilaments. Non-muscle cells express multiple isoforms of TMs including three high molecular weight (HMW) isoforms: TM1, TM2, and TM3. While reports have indicated downregulation of TMs in transformed cells and several human cancers, nevertheless, little is known about the underlying mechanism of TMs suppression. In present study the expression of HMW TMs was investigated in squamous cell carcinoma of esophagus (SCCE), relative to primary cell cultures of normal esophagus by western blotting and real-time RT-PCR. Our results showed that TM1, TM2, and TM3 were significantly downregulated in cell line of SCCE. Moreover, mRNA level of TPM1 and TPM2 were markedly decreased by 93% and 96%, in tumor cell line relative to esophagus normal epithelial cells. Therefore, downregulation of TMs could play an important role in tumorigenesis of esophageal cancer. To asses the mechanism of TM downregulation in esophageal cancer, the role of Ras dependent signaling and promoter hypermethylation were investigated. We found that inhibition of two Ras effectory downstream pathways; MEK/ERK and PI3K/Akt leads to significant increased expression of TM1 protein and both TPM1 and TPM2 mRNAs. In addition, methyltransferase inhibition significantly upregulated TM1, suggesting the prominent contribution of promoter hypermethylation in TM1 downregulation in esophageal cancer. These data indicate that downregulation of HMW TMs occurs basically in SCCE and the activation of MEK/ERK and PI3K/Akt pathways as well as the epigenetic mechanism of promoter hypermethylation play important role in TM1 suppression in SCCE. Copyright © 2011 Wiley Periodicals, Inc.

  16. Natural History of Untreated Hepatocellular Carcinoma in a US Cohort and the Role of Cancer Surveillance.

    Science.gov (United States)

    Khalaf, Natalia; Ying, Jun; Mittal, Sahil; Temple, Sarah; Kanwal, Fasiha; Davila, Jessica; El-Serag, Hashem B

    2017-02-01

    Determining the natural history and predictors of survival in patients with untreated hepatocellular carcinoma (HCC) in the United States is useful to test existing tumor classifications, identify subgroups of patients likely to benefit from treatment, and estimate lead time related to HCC surveillance. We identified a national cohort of 518 veterans diagnosed with HCC from 2004 through 2011, with follow-up ending in 2014, who received no palliative or curative treatment. We examined the association between postdiagnosis survival and patient factors, tumor characteristics, and prediagnosis surveillance. The mean age at HCC diagnosis was 65.7 years and most patients had hepatitis C (60.6%). Almost all patients (99%) died within the observation period; the median overall survival time was 3.6 months and survival times were 13.4, 9.5, 3.4, and 1.6 months for patients of Barcelona Clinic Liver Cancer stages 0/A, B, C, and D, respectively. In addition, model for end-stage liver disease and levels of α-fetoprotein were predictive of survival. Nearly 28% received prediagnosis HCC surveillance, which was associated with detection of disease at an earlier stage (Barcelona Clinic Liver Cancer 0/A/B; 26.4% vs 14.4%; P = .0006) and slightly longer survival than patients with no surveillance overall (5.2 months vs 3.4 months; P = .021); there was no difference in survival times of patients with 0/A stage who did versus did not receive surveillance (10.3 months vs 10.5 months). Patients with HCCs, including those detected through surveillance, survived for short time periods in the absence of treatment, irrespective of their initial stage at diagnosis. Model for end-stage liver disease scores and levels of α-fetoprotein were prognostic factors, independent of Barcelona Clinic Liver Cancer stage. The lead time related to detection by surveillance was modest (<2 months) and therefore unlikely to explain the survival benefit associated with surveillance in previous studies

  17. Role of Brachytherapy in the Boost Management of Anal Carcinoma With Node Involvement (CORS-03 Study)

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    Moureau-Zabotto, Laurence, E-mail: moureaul@ipc.unicancer.fr [Department of Radiation Therapy, Institut Paoli Calmettes, Marseille (France); Ortholan, Cecile [Department of Radiation Therapy, Monaco (France); Hannoun-Levi, Jean-Michel [Department of Radiation Therapy, Antoine Lacassagne Cancer Center, Nice (France); Teissier, Eric [Azurean Cancer Center, Mougins (France); Cowen, Didier [Department of Radiation Therapy, Timone Academic Hospital and North Academic Hospital, Marseille (France); Department of Radiation Therapy, Val d' Aurelle Cancer Center, Montpellier (France); Salem, Nagi [Department of Radiation Therapy, Institut Paoli Calmettes, Marseille (France); Lemanski, Claire [Catalan Oncology Center, Perpignan (France); Ellis, Steve [French Red Cross Center, Toulon (France); Resbeut, Michel [Department of Radiation Therapy, Institut Paoli Calmettes, Marseille (France); French Red Cross Center, Toulon (France)

    2013-03-01

    Purpose: To assess retrospectively the clinical outcome in anal cancer patients, with lymph node involvement, treated with split-course radiation therapy and receiving a boost through external beam radiation therapy (EBRT) or brachytherapy (BCT). Methods and Materials: From 2000 to 2005, among 229 patients with invasive nonmetastatic anal squamous cell carcinoma, a selected group of 99 patients, with lymph node involvement, was studied. Tumor staging reported was T1 in 4 patients, T2 in 16 patients, T3 in 49 patients, T4 in 16 patients, and T unknown in 14 patients and as N1 in 67 patients and N2/N3 in 32 patients. Patients underwent a first course of EBRT (mean dose, 45.1 Gy) followed by a boost (mean dose, 18 Gy) using EBRT (50 patients) or BCT (49 patients). All characteristics of patients and tumors were well balanced between the BCT and EBRT groups. Prognostic factors of cumulative rate of local recurrence (CRLR), cumulative rate of distant (including nodal) recurrence (CRDR), colostomy-free survival (CFS) rate, and overall survival (OS) rate were analyzed for the overall population and according to the nodal status classification. Results: The median follow-up was 71.5 months. The 5-year CRLR, CRDR, CFS rate, and OS rate were 21%, 19%, 63%, and 74.4%, respectively. In the overall population, the type of node involvement (N1 vs N2/N3) was the unique independent prognostic factor for CRLR. In N1 patients, by use of multivariate analysis, BCT boost was the unique prognostic factor for CRLR (4% for BCT vs 31% for EBRT; hazard ratio, 0.08; P=.042). No studied factors were significantly associated with CRDR, CFS, and OS. No difference with regard to boost technique and any other factor studied was observed in N2/N3 patients for any kind of recurrence. Conclusion: In anal cancer, even in the case of initial perirectal node invasion, BCT boost is superior to EBRT boost for CRLR, without an influence on OS, suggesting that N1 status should not be a contraindication to

  18. Brain metastasis from hepatocellular carcinoma: the role of surgery as a prognostic factor

    International Nuclear Information System (INIS)

    Han, Moon-Soo; Moon, Kyung-Sub; Lee, Kyung-Hwa; Cho, Sung-Bum; Lim, Sa-Hoe; Jang, Woo-Youl; Jung, Tae-Young; Kim, In-Young; Jung, Shin

    2013-01-01

    The incidence of brain metastasis from hepatocellular carcinoma (HCC) is expected to increase as a result of prolonged survival due to the recent advances in HCC treatment. However, there is no definite treatment strategy for brain metastasis from HCC mainly due to its rarity and dismal prognosis. To provide helpful recommendations in treatment of brain metastasis from HCC, the authors aimed to identify prognostic factors that influence survival rates with a review of the recently published data. Thirty-three cases of brain metastasis, whose incidence was 0.65%, were selected from a total of 5015 HCC patients and reviewed retrospectively in terms of clinical and radiological features. Median overall survival time after diagnosis of brain metastasis was 10.4 weeks (95% confidence interval [CI], 5.1-15.7 weeks) with 1-, 6- and 12-month survival rates, of 79%, 24% and 6%, respectively. Median survival of the patients treated with surgical resection or surgical resection followed by whole-brain radiation therapy (WBRT) (25.3 weeks; range, 15.8-34.8 weeks) was longer than that of the patients treated with gamma knife surgery (GKS), WBRT, or GKS followed by WBRT (10.4 weeks; range, 7.5-13.3 weeks) as well as that of patients treated with only steroids (1 week; range, 0.0-3.3 weeks) (p < 0.001). Child-Pugh’s classification A group had a longer median survival time than Child-Pugh’s classification B or C group (14.4 weeks vs 8.4 weeks, p = 0.038). RPA class I & II group had also a longer median survival time than RPA class III group did (13.4 weeks vs 2.4 weeks, p = 0.001). Surgical resection (hazard ratio [HR] 0.23, 95% CI 0.08-0.66, p = 0.006) and good liver function at the time of brain metastasis (HR 0.25, 95% CI 0.09-0.69, p = 0.007) were found to be the powerful prognostic factors for favorable survival in the multivariate analysis. In addition, presence of intratumoral hemorrhage was a statistically significant prognostic factor for survival. Although HCC

  19. Potential Role of Diploscapter sp. Strain LKC25, a Bacterivorous Nematode from Soil, as a Vector of Food-Borne Pathogenic Bacteria to Preharvest Fruits and Vegetables

    Science.gov (United States)

    Gibbs, Daunte S.; Anderson, Gary L.; Beuchat, Larry R.; Carta, Lynn K.; Williams, Phillip L.

    2005-01-01

    Diploscapter, a thermotolerant, free-living soil bacterial-feeding nematode commonly found in compost, sewage, and agricultural soil in the United States, was studied to determine its potential role as a vehicle of Salmonella enterica serotype Poona, enterohemorrhagic Escherichia coli O157:H7, and Listeria monocytogenes in contaminating preharvest fruits and vegetables. The ability of Diploscapter sp. strain LKC25 to survive on agar media, in cow manure, and in composted turkey manure and to be attracted to, ingest, and disperse food-borne pathogens inoculated into soil or a mixture of soil and composted turkey manure was investigated. Diploscapter sp. strain LKC25 survived and reproduced in lawns of S. enterica serotype Poona, E. coli O157:H7, and L. monocytogenes on agar media and in cow manure and composted turkey manure. Attraction of Diploscapter sp. strain LKC25 to colonies of pathogenic bacteria on tryptic soy agar within 10, 20, 30, and 60 min and 24 h was determined. At least 85% of the worms initially placed 0.5 to 1 cm away from bacterial colonies migrated to the colonies within 1 h. Within 24 h, ≥90% of the worms were embedded in colonies. The potential of Diploscapter sp. strain LKC25 to shed pathogenic bacteria after exposure to bacteria inoculated into soil or a mixture of soil and composted turkey manure was investigated. Results indicate that Diploscapter sp. strain LKC25 can shed pathogenic bacteria after exposure to pathogens in these milieus. They also demonstrate its potential to serve as a vector of food-borne pathogenic bacteria in soil, with or without amendment with compost, to the surface of preharvest fruits and vegetables in contact with soil. PMID:15870330

  20. The diagnostic value of long non-coding RNA MIR31HG and its role in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Sun, Kaiyan; Zhao, Xinwei; Wan, Junhu; Yang, Lijun; Chu, Jie; Dong, Shuling; Yin, Huiqing; Ming, Liang; He, Fucheng

    2018-06-01

    This study aimed to assess plasma lncRNA microRNA-31 hist gene (MIR31HG) as a novel diagnostic and therapeutic biomarker for esophageal squamous cell carcinoma (ESCC) and to investigate its role in ESCC. The expression of MIR31HG, Furin and MMP1 was examined via quantitative real-time polymerase chain reaction. MIR31HG expression between plasma and ESCC tissues was compared using Pearson correlation analysis; furthermore, the association between Furin/MMP1 levels and MIR31HG levels in ESCC tissues was analyzed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of plasma MIR31HG. A WST-1 assay was performed to assess cell proliferation. The migratability and invasiveness of cells was determined via Transwell assays. MIR31HG was significantly upregulated in ESCC tissues and plasma (P occurance. Furthermore, knockdown of MIR31HG suppressed the capacity for proliferation, migration, and invasion of ESCC cells (P < 0.01). In addition, silencing of MIR31HG inhibited the expression of Furin and MMP1 in EC9706 and EC1 and the level of Furin/MMP1 in ESCC tissues displayed a significant positive correlation with MIR31HG (P < 0.01). MIR31HG can be used as a novel potential diagnostic biomarker and a potential therapeutic target for ESCC. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. Potential Antioxidant Role of Tridham in Managing Oxidative Stress against Aflatoxin-B1-Induced Experimental Hepatocellular Carcinoma

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    Vijaya Ravinayagam

    2012-01-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most fatal cancers due to delayed diagnosis and lack of effective treatment options. Significant exposure to Aflatoxin B1 (AFB1, a potent hepatotoxic and hepatocarcinogenic mycotoxin, plays a major role in liver carcinogenesis through oxidative tissue damage and p53 mutation. The present study emphasizes the anticarcinogenic effect of Tridham (TD, a polyherbal traditional medicine, on AFB1-induced HCC in male Wistar rats. AFB1-administered HCC-bearing rats (Group II showed increased levels of lipid peroxides (LPOs, thiobarbituric acid substances (TBARs, and protein carbonyls (PCOs and decreased levels of enzymic and nonenzymic antioxidants when compared to control animals (Group I. Administration of TD orally (300 mg/kg body weight/day for 45 days to HCC-bearing animals (Group III significantly reduced the tissue damage accompanied by restoration of the levels of antioxidants. Histological observation confirmed the induction of tumour in Group II animals and complete regression of tumour in Group III animals. This study highlights the potent antioxidant properties of TD which contribute to its therapeutic effect in AFB1-induced HCC in rats.

  2. The role of Rad 51 protein in radioresistance of spheroid model of Du 145 prostate carcinoma cell line

    International Nuclear Information System (INIS)

    Taghizadeh, M.; Khoei, S.; Nikoofar, A. R.; Ghamsari, L.; Goliaei, B.

    2009-01-01

    Rad 51 is a protein with critical role in double strand break repair. Down-regulation of this protein has a significant effect in radiosensitivity of some cell lines like prostate carcinoma. Compared to monolayer cell culture model, the spheroids are more resistant to radiation. The aim of the current study was to determine the Rad 51 protein level in Du 145 spheroids, and monolayer cells before and after exposure to gamma irradiation. Materials and Methods: In the present study, western blot was used to determine the level of Rad 51 protein in Du 145 cell line grown as monolayer and spheroid. Results: Western blot analysis showed that in the spheroid cells, Rad 51 had an elevated level before and after radiation in comparison with monolayer cells. Higher doses of radiation induced elevated expression of Rad 51 protein in both culture models.The level of at protein after exposure to gamma rays had been time-dependent. Conclusion: Rad 51 might act as a mediator of radiation resistance in tumor cells. Repression of Rad 51 activity could be a prominent strategy to overcome radiation resistance of tumors.

  3. The role of scheduled second TACE in early-stage hepatocellular carcinoma with complete response to initial TACE

    Directory of Open Access Journals (Sweden)

    Jung Hee Kim

    2017-03-01

    Full Text Available Background/Aims We investigated the outcomes of early-stage hepatocellular carcinoma (HCC patients who showed a complete response (CR to initial transarterial chemoembolization (TACE, with a focus on the role of scheduled TACE repetition. Methods A total of 178 patients with early-stage HCC who were initially treated with TACE and showed a CR based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST criteria on one month follow-up computed tomography (CT were analyzed. Among them, 90 patients underwent scheduled repetition of TACE in the absence of viable tumor on CT. Results During a median follow-up period of 4.6 years (range: 0.4-8.8 years, mortality was observed in 71 patients (39.9%. The overall recurrence-free and local recurrence-free survival rates at 1 year were 44.4% and 56.2%. In the multivariable model, scheduled repetition of TACE was an independent factor associated with survival (hazard ratio [95% confidence interval]: 0.56 [0.34-0.93], P=0.025. When stratified using Barcelona clinic liver cancer (BCLC stage, scheduled repetition of TACE was associated with a favorable survival rate in BCLC stage A patients, but not in BCLC 0 patients. Conclusions Scheduled repetition of TACE was associated with better survival for early-stage HCC patients showing a CR after initial TACE, especially in BCLC stage A patients.

  4. The Prognostic Role of NEDD9 and P38 Protein Expression Levels in Urinary Bladder Transitional Cell Carcinoma

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    Ola A. Harb

    2017-01-01

    Full Text Available Background. The most common malignant tumor of the urinary bladder is transitional cell carcinoma (TCC. Neural precursor cell-expressed developmentally downregulated protein 9 (NEDD9 is found to be a cell adhesion mediator. P38 Mitogen-Activated Protein Kinase is a serine/threonine kinases member which can mediate carcinogenesis through intracellular signaling. Methods. To assess their prognostic role; NEDD9 and p38 protein were evaluated in sections from 50 paraffin blocks of TCC. Results. The high expressions of NEDD9 and p38 protein were significantly associated with grade, stage, distant metastasis (p<0.001, number of tumors, lymph node metastasis, and tumor size (p<0.001, 0.002; 0.018, <0.001; and 0.004, 0.007, respectively. High NEDD9 and p38 detection had a worse 3-year OS (p=0.041 and <0.001, respectively. By multivariate analysis the NEDD9 and p38 protein expression levels and various clinicopathological criteria including gender, grade, stage of the tumor, and regional lymph node involvement were independent prognostic parameters of TCC of the urinary bladder patients’ outcome. Conclusion. NEDD9 and p38 protein expressions were poor prognostic markers of TCC.

  5. Curcumin-Induced Apoptosis in Human Hepatocellular Carcinoma J5 Cells: Critical Role of Ca+2-Dependent Pathway

    Directory of Open Access Journals (Sweden)

    Wei-Hsun Wang

    2012-01-01

    Full Text Available The antitumor effects of curcumin, a natural biologically active compound extracted from rhizomes of Curcuma longa, have been studied in many cancer cell types including human hepatocellular carcinoma (HCC. Here, we investigated the effects of Ca2+ on curcumin-induced apoptosis in human HCC J5 cells. The abrogation of mitochondrial membrane potential (ΔΨm, the increase of reactive oxygen species (ROS production, and calcium release were demonstrated with flow cytometry as early as 15 minutes after curcumin treatment. In addition, an increase level of cytochrome c in the cytoplasm which led to DNA fragmentation was observed. To verify the role of Ca2+ in curcumin-induced apoptosis, 1,2-bis(o-aminophenoxyethane-N,N,N′,N′-tetraacetic acid (BAPTA, an intracellular calcium chelator, was applied. Cell viability was increased, but ΔΨm, ROS production, activation of caspase 3, and cell death were decreased in J5 cells pretreated with BAPTA for 2 h followed by the treatment of 25 μM curcumin. These results suggest that the curcumin-induced apoptosis in human HCC J5 cells is via mitochondria-dependent pathway and is closely related to the level of intracellular accumulation of calcium.

  6. Do environmental factors play a role in the aetiology of carcinoma in situ testis and the testicular dysgenesis syndrome?

    Science.gov (United States)

    Sonne, S B; Hoei-Hansen, C E; Fisher, J S; Leffers, H; Rajpert-de Meyts, E; Skakkebaek, N E

    2004-01-01

    The hypothesis of the Testicular Dysgenesis Syndrome (TDS), first suggested in 2001, propose that several disorders of the male reproductive system such as infertility, hypospadias, cryptorchidism and testicular cancer are all symptoms of TDS, which is most likely initiated during early foetal development, and may be provoked by external factors such as endocrine disruptors in addition to genetic predisposition. Testicular germ cell tumours (TGCTs), considered the most severe symptom of TDS, have increased in incidence during the last 60 years, to become the most common malignancy in young Caucasian men aged 17-45 years. TGCTs of young men originate from carcinoma in situ (CIS) cells. In the last few years, progress has been made identifying candidate genes involved in the neoplastic development of CIS, which may elucidate the timing of the initiation of CIS, currently thought to originate in foetal life from primordial germ cells or early gonocytes. Histological dysgenetic features are frequently seen in testes affected with the TDS components testis cancer or cryptorchidism. A TDS-like phenotype can be induced in male rats by in utero exposure to high concentrations of dibutyl phthalate (DBP) suggesting that ubiquitously present environmental endocrine disruptors may play a role in the aetiology of human TDS. So far, no animal model has been able to mimick all the symptoms of TDS including TGCTs although CIS-like cells have been found in a spontaneous testicular neoplasm in a rabbit.

  7. AMPK in Pathogens.

    Science.gov (United States)

    Mesquita, Inês; Moreira, Diana; Sampaio-Marques, Belém; Laforge, Mireille; Cordeiro-da-Silva, Anabela; Ludovico, Paula; Estaquier, Jérôme; Silvestre, Ricardo

    2016-01-01

    During host-pathogen interactions, a complex web of events is crucial for the outcome of infection. Pathogen recognition triggers powerful cellular signaling events that is translated into the induction and maintenance of innate and adaptive host immunity against infection. In opposition, pathogens employ active mechanisms to manipulate host cell regulatory pathways toward their proliferation and survival. Among these, subversion of host cell energy metabolism by pathogens is currently recognized to play an important role in microbial growth and persistence. Extensive studies have documented the role of AMP-activated protein kinase (AMPK) signaling, a central cellular hub involved in the regulation of energy homeostasis, in host-pathogen interactions. Here, we highlight the most recent advances detailing how pathogens hijack cellular metabolism by suppressing or increasing the activity of the host energy sensor AMPK. We also address the role of lower eukaryote AMPK orthologues in the adaptive process to the host microenvironment and their contribution for pathogen survival, differentiation, and growth. Finally, we review the effects of pharmacological or genetic AMPK modulation on pathogen growth and persistence.

  8. Role of Omega 3 Fatty Acids Against Ehrlich Ascites Carcinoma-Induced Hepatic and Brain Dysfunctions in Gamma Irradiated Mice

    International Nuclear Information System (INIS)

    El-Gharib, M.M.M.

    2014-01-01

    Cancer is a deadly disease that has touched the lives of many people in the world today. Omega 3 essential fatty acids (ω-3 FAs); found in high concentrations in fish oil, claim a plethora of health benefits. The present study aimed to evaluate the role of ω-3 FAs supplementation either alone or combined with fractionated γ-radiation exposure against Ehrlich solid tumor-induced inflammation, oxidative stress, biochemical alterations and histopathological changes in the liver, brain and tumor tissues of Albino mice. ω-3 FAs were orally administered via gavages to mice for a period of 30 consecutive days at a dose of 300 mg/kg body weight. On the 7th day of experiment, mice were subcutaneously transplanted in the neck region with 0.2 ml of Ehrlich ascites carcinoma cells for solid tumor induction and on the 17th and 25th days, mice were exposed to a fractionated whole body γ-radiation (0.5 Gy/week for two weeks). The results of the present work showed that Ehrlich carcinoma (EC) and/or γ-irradiation led to systemic inflammation (elevated TNF-α, TLC and CRP levels), hepatic oxidative stress (elevated TBARs level, decreased GSH, GSH-Px, CAT and SOD levels) and biochemical alterations in liver (elevated AST, ALT, ALP and LDH activities) and brain (dopamine, EP,NE and serotonin levels) tissues. On the other hand, ω-3 FAs supplementation to the experimentally irradiated EC-bearing mice, significantly reduced tumor size, depressed the concentrations of inflammatory markers, reduced oxidative stress and also ameliorated the biochemical alterations in liver and brain tissues. Histopathological examinations showed that treatment with ω-3 FAs recorded great destruction of tumor tissue, great disappearance of metastatic EC cells from the liver tissue and normal appearance in cerebrum and cerebellum of brain tissue layers in EC-bearing mice. Combined treatment of EC-bearing mice with ω-3 FAs and γ-irradiation showed necrotic cells and remnant tumor cells in tumor

  9. Potential role of mTORC2 as a therapeutic target in clear cell carcinoma of the ovary.

    Science.gov (United States)

    Hisamatsu, Takeshi; Mabuchi, Seiji; Matsumoto, Yuri; Kawano, Mahiru; Sasano, Tomoyuki; Takahashi, Ryoko; Sawada, Kenjiro; Ito, Kimihiko; Kurachi, Hirohisa; Schilder, Russell J; Testa, Joseph R; Kimura, Tadashi

    2013-07-01

    The goal of this study was to examine the role of mTOR complex 2 (mTORC2) as a therapeutic target in ovarian clear cell carcinoma (CCC), which is regarded as an aggressive, chemoresistant histologic subtype. Using tissue microarrays of 98 primary ovarian cancers [52 CCCs and 46 serous adenocarcinomas (SAC)], activation of mTORC2 was assessed by immunohistochemistry. Then, the growth-inhibitory effect of mTORC2-targeting therapy, as well as the role of mTORC2 signaling as a mechanism for acquired resistance to the mTOR complex 1 (mTORC1) inhibitor RAD001 in ovarian CCC, were examined using two pairs of RAD001-sensitive parental (RMG2 and HAC2) and RAD001-resistant CCC cell lines (RMG2-RR and HAC2-RR). mTORC2 was more frequently activated in CCCs than in SACs (71.2% vs. 45.7%). Simultaneous inhibition of mTORC1 and mTORC2 by AZD8055 markedly inhibited the proliferation of both RAD001-sensitive and -resistant cells in vitro. Treatment with RAD001 induced mTORC2-mediated AKT activation in RAD001-sensitive CCC cells. Moreover, increased activation of mTORC2-AKT signaling was observed in RAD001-resistant CCC cells compared with the respective parental cells. Inhibition of mTORC2 during RAD001 treatment enhanced the antitumor effect of RAD001 and prevented CCC cells from acquiring resistance to RAD001. In conclusion, mTORC2 is frequently activated, and can be a promising therapeutic target, in ovarian CCCs. Moreover, mTORC2-targeted therapy may be efficacious in a first-line setting as well as for second-line treatment of recurrent disease developing after RAD001-treatment.

  10. Hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Farooqi, J.I.; Farooqi, R.J.

    2001-01-01

    Hepatocellular carcinoma (HCC) is a common cause of cancer mortality. Hepatitis B and C viruses, aflatoxin and alga toxin in the contaminated drinking water are the major etiological factors. Rapidly progressing medical imaging has resulted in the improved treatment results. Surgical resection has a major role for influencing prognosis of HCC. Local cancer therapies based on the advances in early diagnosis are progressing rapidly. Multimodality combination and sequential treatment has proved effective, unfortunately systemic chemotherapy for HCC remains disappointed. All of these have resulted in the improved prognosis of HCC. (author)

  11. A scoping review of the role of wildlife in the transmission of bacterial pathogens and antimicrobial resistance to the food Chain.

    Science.gov (United States)

    Greig, J; Rajić, A; Young, I; Mascarenhas, M; Waddell, L; LeJeune, J

    2015-06-01

    Wildlife can contribute to environmental contamination with bacterial pathogens and their transfer to the human food chain. Global usage and frequent misuse of antimicrobials contribute to emergence of new antimicrobial resistant (AMR) strains of foodborne pathogens. We conducted a scoping review of published research to identify and characterize the evidence on wildlife's role in transmission of AMR and/or bacterial pathogens to the food chain. An advisory group (AG) of 13 North American experts from diverse disciplines was surveyed to solicit insight in the review scope, priority topics and research characteristics. A pre-tested search strategy was implemented in seven bibliographic databases (1990 to January 2013). Citations were relevance screened, and key characteristics on priority topics extracted independently by two reviewers. Analysis identified topic areas with solid evidence and main knowledge gaps. North America reported 30% of 866 relevant articles. The prevalence of five targeted bacterial pathogens and/or AMR in any pathogen in wildlife was reported in 582 articles. Transmission risk factors for selected bacteria or AMR in any bacteria were reported in 300. Interventions to control transmission were discussed in 124 articles and formally evaluated in 50. The majority of primary research investigated birds, cervids, rodents, feral pigs, opossums, E. coli (n = 329), Salmonella (n = 293) and Campylobacter (n = 124). An association between wildlife and transmission of bacterial pathogens and/or AMR to the food chain was supported in 122 studies. The scoping review identified a significant body of research on the role of wild birds in the prevalence and transmission of E. coli, Salmonella and Campylobacter. There was little research employing molecular methods contributing to the evidence concerning the importance and direction of transmission of wildlife/pathogen combinations. Given the advancements of these methods, future research should focus in this

  12. Role of natural antisense transcripts pertaining to tumor suppressor genes in human carcinomas

    International Nuclear Information System (INIS)

    Pelicci, G.; Pierotti, M.

    2009-01-01

    Overlapping transcripts in opposite orientations can potentially form perfect sense-antisense duplex RNA. Recently, several studies have revealed the extent of natural antisense transcripts (NATs) and their role in important biological phenomena also in higher organisms. In order to test the hypothesis that the function of NATs in man might represent an essential element in the regulation of gene expression, especially at transcriptional level, in this study we planned to look for, systematically examine, and characterize NATs belonging in the human genome to the tumour suppressor class of genes, so to identify physiological (and potentially pathological) modulators in this gene class

  13. Specific role of targeted molecular therapy in treatment of oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Pankaj Gupta

    2017-12-01

    Full Text Available Oral cancer is a potentially fatal disease that constitutes an important portion of tumors that occur in the head and neck region. Oral cancer can affect overall and mental health, appearance, employment, social life, and family living. The disease can cause serious changes in the functioning of the upper aero digestive tract that affects the quality of life in patients. The use of conventional treatment modalities (surgery, radiation, and/or chemotherapy depends on tumor respectability and location as well as whether an organ preservation approach is feasible. However, their role in oral cancer treatment is nonselective and can cause damage to normal tissue. In particular, chemo radiotherapy is associated with systemic toxicities that often reduce patient compliance and prevent timely completion of therapy. The development of targeted therapies to target select pathways involved in carcinogenesis, potentially decrease systemic toxicities and morbidities associated with cancer burden and hence improve the prognosis in cancer patients. In the present article, the role of various targeted molecules in the treatment of oral cancer is discussed.

  14. ROLE OF THE MORPHOMETRIC PARAMETERS OF INTRATUMORAL MICROVESSELS AND THE PROLIFERATIVE ACTIVITY OF TUMOR CELLS IN RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    N. A. Gorban

    2014-08-01

    Full Text Available Tumor cell proliferation and angiogenesis are essential factors for tumor growth, progression, and metastasis.Objective: to assess the relationship between the values of proliferative activity and the morphometric parameters of intratumoral microvessels in metastatic and localized carcinomas of the kidney.Materials and methods. Surgical specimens taken from 54 patients (32 men and 22 women aged 26 to 69 years (mean age 55 ± 1.5 years with the verified diagnosis of clear-cell renal cell carcinoma (RCC were studied.Conclusion. Proliferative activity and angioarchitectonics are an important biological characteristic of a tumor of unequal clinical value in RCC. Metastatic carcinoma has a higher proliferative activity and a low tumor vascularization than those of localized carcinoma.

  15. Germline single nucleotide polymorphisms associated with response of urothelial carcinoma to platinum-based therapy: the role of the host.

    LENUS (Irish Health Repository)

    Gallagher, D J

    2013-09-01

    Variations in urothelial carcinoma (UC) response to platinum chemotherapy are common and frequently attributed to genetic and epigenetic variations of somatic DNA. We hypothesized that variations in germline DNA may contribute to UC chemosensitivity.

  16. Pancreatic metastasis in a case of small cell lung carcinoma: Diagnostic role of fine-needle aspiration cytology and immunocytochemistry

    Directory of Open Access Journals (Sweden)

    Dilip K Das

    2011-01-01

    Full Text Available Small cell lung carcinoma represents a group of highly malignant tumors giving rise to early and widespread metastasis at the time of diagnosis. However, the pancreas is a relatively infrequent site of metastasis by this neoplasm, and there are only occasional reports on its fine needle aspiration (FNA cytology diagnosis. A 66-year-old man presented with extensive mediastinal lymphadenopathy and a mass in the pancreatic tail. Ultrasound-guided FNA smears from the pancreatic mass contained small, round tumor cells with extensive nuclear molding. The cytodiagnosis was metastatic small cell carcinoma. Immunocytochemical staining showed that a variable number of neoplastic cell were positive for cytokeratin, chromogranin A, neurone-specific enolase and synaptophysin but negative for leukocyte common antigen. The trans-bronchial needle aspiration was non-diagnostic, but biopsy was suspicious of a small cell carcinoma. This case represents a rare metastatic lesion in the pancreas from small cell lung carcinoma, diagnosed by FNA cytology.

  17. Prostatic carcinoma. Diagnostic and stating: MR imaging. Cancer de la prostate Diagnostic et bilan: role de l'imagerie

    Energy Technology Data Exchange (ETDEWEB)

    Roy, C; Spittler, G; Jacqmin, D [Centre Hospitalier Universitaire, 67 - Strasbourg (FR); Morel, M [Clinique Saint-Francois, 67 Haguenau (FR)

    1991-01-01

    Prostatic carcinoma is the second most commun cause of cancer death over 60 years. It is suspected by digital examination and prostatic specific antigen dosage. Transrectal ultrasound shows the tumor as an hypoechoic lesion. Sensitivity is good but specificity is low. Transrectal biopsy of prostate guided by transrectal ultrasound made the diagnosis. At present, MR Imaging is the most accurate diagnostic modality for loco-regional staging of prostatic carcinoma.

  18. Characterization of two homeodomain transcription factors with critical but distinct roles in virulence in the vascular pathogen Verticillium dahliae

    Science.gov (United States)

    Vascular wilt caused by Verticillium dahliae is a destructive disease that represents a chronic economic problem for crop production worldwide. In this work, we characterized two new regulators of pathogenicity in this species. Vph1 (VDAG_06555) was identified in a candidate gene approach as a putat...

  19. Small-scale shifting mosaics of two dominant grassland species: the possible role of soil-borne pathogens

    NARCIS (Netherlands)

    Olff, H.; Hoorens, B.; De Goede, R.G.M.; Van der Putten, W.H.; Gleichman, J.M.

    2000-01-01

    We analyzed the dynamics of dominant plant species in a grazed grassland over 17 years, and investigated whether local shifts in these dominant species, leading to vegetation mosaics, could be attributed to interactions between plants and soil-borne pathogens. We found that Festuca rubra and Carer

  20. Small-scale shifting mosaics of two dominant grassland species : the possible role of soil-borne pathogens

    NARCIS (Netherlands)

    Olff, H.; Hoorens, B.; Goede, R.G.M. de; Putten, W.H. van der; Gleichman, J.M.

    2000-01-01

    We analyzed the dynamics of dominant plant species in a grazed grassland over 17 years, and investigated whether local shifts in these dominant species, leading to vegetation mosaics, could be attributed to interactions between plants and soil-borne pathogens. We found that Festuca rubra and Carex

  1. Molecular pathogenesis of H5 highly pathogenic avian influenza: the role of the haemagglutinin cleavage site motif

    Science.gov (United States)

    Luczo, Jasmina M.; Stambas, John; Durr, Peter A.; Michalski, Wojtek P.

    2015-01-01

    Summary The emergence of H5N1 highly pathogenic avian influenza has caused a heavy socio‐economic burden through culling of poultry to minimise human and livestock infection. Although human infections with H5N1 have to date been limited, concerns for the pandemic potential of this zoonotic virus have been greatly intensified following experimental evidence of aerosol transmission of H5N1 viruses in a mammalian infection model. In this review, we discuss the dominance of the haemagglutinin cleavage site motif as a pathogenicity determinant, the host‐pathogen molecular interactions driving cleavage activation, reverse genetics manipulations and identification of residues key to haemagglutinin cleavage site functionality and the mechanisms of cell and tissue damage during H5N1 infection. We specifically focus on the disease in chickens, as it is in this species that high pathogenicity frequently evolves and from which transmission to the human population occurs. With >75% of emerging infectious diseases being of zoonotic origin, it is necessary to understand pathogenesis in the primary host to explain spillover events into the human population. © 2015 The Authors. Reviews in Medical Virology published by John Wiley & Sons Ltd. PMID:26467906

  2. Small-scale shifting mosaics of two dominant grassland species: the possible role of soil-borne pathogens.

    Science.gov (United States)

    Olff, H; Hoorens, B; de Goede, R G M; van der Putten, W H; Gleichman, J M

    2000-10-01

    We analyzed the dynamics of dominant plant species in a grazed grassland over 17 years, and investigated whether local shifts in these dominant species, leading to vegetation mosaics, could be attributed to interactions between plants and soil-borne pathogens. We found that Festuca rubra and Carex arenaria locally alternated in abundance, with different sites close together behaving out of phase, resulting in a shifting mosaic. The net effect of killing all soil biota on the growth of these two species was investigated in a greenhouse experiment using gamma radiation, controlling for possible effects of sterilization on soil chemistry. Both plant species showed a strong net positive response to soil sterilization, indicating that pathogens (e.g., nematodes, pathogenic fungi) outweighed the effect of mutualists (e.g., mycorrhizae). This positive growth response towards soil sterilization appeared not be due to effects of sterilization on soil chemistry. Growth of Carex was strongly reduced by soil-borne pathogens (86% reduction relative to its growth on sterilized soil) on soil from a site where this species decreased during the last decade (and Festuca increased), while it was reduced much less (50%) on soil from a nearby site where it increased in abundance during the last decade. Similarly, Festuca was reduced more (67%) on soil from the site where it decreased (and Carex increased) than on soil from the site where it increased (55%, the site where Carex decreased). Plant-feeding nematodes showed high small-scale variation in densities, and we related this variation to the observed growth reductions in both plant species. Carex growth on unsterilized soil was significantly more reduced at higher densities of plant-feeding nematodes, while the growth reduction in Festuca was independent of plant-feeding nematode densities. At high plant-feeding nematode densities, growth of Carex was reduced more than Festuca, while at low nematode densities the opposite was found

  3. Role of pathogenicity determinant protein C (PdpC in determining the virulence of the Francisella tularensis subspecies tularensis SCHU.

    Directory of Open Access Journals (Sweden)

    Akihiko Uda

    Full Text Available Francisella tularensis subspecies tularensis, the etiological agent of tularemia, is highly pathogenic to humans and animals. However, the SCHU strain of F. tularensis SCHU P0 maintained by passaging in artificial media has been found to be attenuated. To better understand the molecular mechanisms behind the pathogenicity of F. tularensis SCHU, we attempted to isolate virulent bacteria by serial passages in mice. SCHU P5 obtained after 5th passages in mice remained avirulent, while SCHU P9 obtained after 9th passages was completely virulent in mice. Moreover, SCHU P9 grew more efficiently in J774.1 murine macrophages compared with that in the less pathogenic SCHU P0 and P5. Comparison of the nucleotide sequences of the whole genomes of SCHU P0, P5, and P9 revealed only 1 nucleotide difference among P0, P5 and P9 in 1 of the 2 copies of pathogenicity determinant protein C (pdpC gene. An adenine residue deletion was observed in the pdpC1 gene of SCHU P0, P5, and P9 and in the pdpC2 gene of SCHU P0, and P5, while P9 was characterized by the wild type pdpC2 gene. Thus, SCHU P0 and P5 expressed only truncated forms of PdpC protein, while SCHU P9 expressed both wild type and truncated versions. To validate the pathogenicity of PdpC, both copies of the pdpC gene in SCHU P9 have been inactivated by Targetron mutagenesis. SCHU P9 mutants with inactivated pdpC gene showed low intracellular growth in J774.1 cells and did not induce severe disease in experimentally infected mice, while virulence of the mutants was restored by complementation with expression of the intact PdpC. These results demonstrate that PdpC is crucial in determining the virulence of F. tularensis SCHU.

  4. Hepatitis B virus mutation may play a role in hepatocellular carcinoma recurrence: A systematic review and meta-regression analysis.

    Science.gov (United States)

    Zhou, Hua-ying; Luo, Yue; Chen, Wen-dong; Gong, Guo-zhong

    2015-06-01

    A number of studies have confirmed that antiviral therapy with nucleotide analogs (NAs) can improve the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative therapy. However, what factors affected the prognosis of HBV-HCC after removal of the primary tumor and inhibition of HBV replication? A meta-regression analysis was conducted to explore the prognostic factor for this subgroup of patients. MEDLINE, EMBASE, Web of Science, and Cochrane library were searched from January 1995 to February 2014 for clinical trials evaluating the effect of NAs on the prognosis of HBV-HCC after curative therapy. Data were extracted for host, viral, and intervention information. Single-arm meta-analysis was performed to assess overall survival (OS) rates and HCC recurrence. Meta-regression analysis was carried out to explore risk factors for 1-year OS rate and HCC recurrence for HBV-HCC patients after curative therapy and antiviral therapy. Fourteen observational studies with 1284 patients met the inclusion criteria. Influential factors for prognosis of HCC were mainly baseline HBeAg positivity, cirrhotic stage, advanced Tumor-Node-Metastasis (TNM) stage, macrovascular invasion, and antiviral agent type. The 1-year OS rate decreased by more than four times (coefficient -4.45, P<0.001) and the 1-year HCC recurrence increased by more than one time (coefficient 1.20, P=0.003) when lamivudine was chosen for HCC after curative therapy, relative to entecavir for HCC. HBV mutation may play a role in HCC recurrence. Entecavir or tenofovir, a high genetic barrier to resistance, should be recommended for HBV-HCC patients. © 2015 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  5. Challenging Role of Dietary Aflatoxin B1 Exposure and Hepatitis B Infection on Risk of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Basak Kucukcakan

    2015-03-01

    Full Text Available Aflatoxins (AFT are poisonous substances which are classified in Group 1 carcinogenic agents to humans by International Agency for Research on Cancer (IARC. AFT can occur naturally in food commodities (maize, corn, rice as a result of fungal contamination in hot and humid environments. In the food, toxin contamination can remain during manufacturing and long after fungi have stopped being biologically active. Aflatoxin B1 (AFB1 is the most dominant and potent agent from all AFT. In developing countries, high exposure to AFB1 can cause chronic toxicity and usually increases the incidence of Hepatocellular Carcinoma (HCC. However, in these regions hepatitis B is the most common risk factor for HCC cases. Many researches were aimed to enlighten the mechanism and the role of two etiological agents on risk of HCC, but the obtained data was conflicting with each other. It was uncertain that the indicators/biomarkers might be the contribution of the carcinogenic status of the patient; and, the biomarker samples from the subject may only reflect the recent effects of the toxin exposure after consumption of AFB1 contaminated commodities. The studies were facing with the errors of methods which were un-fit to enlighten the possible interaction between Hepatitis B and AFB1 on contribution to HCC. It was pivotal to understand the effect of each risk factor in order to prevent and improve public health in poor and undeveloped regions. Although some of the studies evaluate AFB1 alone as a considerable factor on HCC risk, according to this review it was concluded vice versa. This study was aimed to clarify the main etiological agent of HCC where AFB1 and HBV are endangering public health. In additionally, the purpose was to enlighten the possible synergistic effect between these two factors among HCC pathogenesis. Hence forth, appropriate and right applications could be conducted in undeveloped countries in order to protect public health.

  6. The role of genetic factors in patients with hepatocellular carcinoma and iron overload - a prospective series of 234 patients.

    Science.gov (United States)

    Funakoshi, Natalie; Chaze, Iphigénie; Alary, Anne-Sophie; Tachon, Gaëlle; Cunat, Séverine; Giansily-Blaizot, Muriel; Bismuth, Michael; Larrey, Dominique; Pageaux, Georges-Philippe; Schved, Jean-François; Donnadieu-Rigole, Hélène; Blanc, Pierre; Aguilar-Martinez, Patricia

    2016-05-01

    Iron overload (IO) in HFE-related hereditary haemochromatosis is associated with increased risk of liver cancer. This study aimed to investigate the role of other genes involved in hereditary IO among patients with hepatocellular carcinoma (HCC). Patients with HCC diagnosed in our institution were included in this prospective study. Those with ferritin levels ≥300 μg/L (males) or ≥200 μg/L (females) and/or transferrin saturation ≥50% (males) or ≥45% (females) had liver iron concentration (LIC) evaluated by MRI. HFE C282Y and H63D mutations were screened. Genetic analyses of genes involved in hereditary IO (HFE, HJV/HFE2, HAMP, TFR2, SLC40A1, GNPAT) were performed in patients with increased LIC. A total of 234 patients were included; 215 (92%) had common acquired risk factors of HCC (mainly alcoholism or chronic viral hepatitis). 119 patients had abnormal iron parameters. Twelve (5.1%) were C282Y homozygotes, three were compound C282Y/H63D heterozygotes. LIC was measured by MRI in 100 patients. Thirteen patients with a LIC>70 μmol/g were enrolled in further genetic analyses: two unrelated patients bore the HAMP:c.-153C>T mutation at the heterozygous state, which is associated with increased risk of IO and severe haemochromatosis. Specific haplotypes of SLC40A1 were also studied. Additional genetic risk factors of IO were found in 18 patients (7.7%) among a large series of 234 HCC patients. Screening for IO and the associated at-risk genotypes in patients who have developed HCC, is useful for both determining etiologic diagnosis and enabling family screening and possibly primary prevention in relatives. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. The Role of Radiation Therapy in the Treatment of Adenoid Cystic Carcinoma of the Head and Neck

    International Nuclear Information System (INIS)

    Kim, Won Dong; Park, Charn Il; Kim, Kwang Hyun

    1992-01-01

    Forty eight patients with adenoid cystic carcinoma(ACC) in the head and beck treated between 1979 and 1990 were reviewed according to treatment modalities and clinical courses. The common site of origin was minor salivary gland (69%), mostly had palate and maxillary sinus. 11 patients received radiation therapy(RT) alone and 37 patients received combined surgery and radiation therapy. The follow-up period of the survivors ranged from 4 to 118 months (median 49.5 months). The 5 year local control rate was 69.3%, 67.3% and 83.9% in RT alone, conservative operation(OP)+RT and radical OP+RT group, respectively(p>0.05). The control of local disease was best achieved with radical OP+RT. In postoperative RT, high dose (≥60 Gy) and generous field size (>64cm 2 ) yielded a better local control rate. Actuarial overall survival rate was 79.0%, at 5 years and 19.2% at 10 years. Distant metastases (DM) developed in 40% of patients, mostly in the lung. Disease-free(NED) survival rate was 45.8%, at 5 years and significant differences did not exist according to primary sites and treatment options. Survival rate after the onset of DM was 19.5% at 5 years. Occurrence of DM tends to lower survival significantly. In an effort to find the role of RT in the treatment of ACC, our data suggest that a well-planned postoperative RT employing a high dose and generous field size can produce high local control rate and remaining urgent problem of distant metastasis demands more effective chemotherapy for the purpose of improving survival of ACC patients

  8. OSU-2S/sorafenib synergistic antitumor combination against hepatocellular carcinoma: The role of PKCδ/p53

    Directory of Open Access Journals (Sweden)

    Hany A Omar

    2016-11-01

    Full Text Available Background: Sorafenib (Nexavar® is an FDA-approved systemic therapy for advanced hepatocellular carcinoma (HCC. However, the low efficacy and adverse effects at high doses limit the clinical application of sorafenib and strongly recommend its combination with other agents aiming at ameliorating its drawbacks. OSU-2S, a PKCδ activator, was selected as a potential candidate anticancer agent to be combined with sorafenib to promote the anti-cancer activity through synergistic interaction. Methods: The antitumor effects of sorafenib, OSU-2S and their combination were assessed by MTT assay, caspase activation, Western blotting, migration/invasion assays in four different HCC cell lines. The synergistic interactions were determined by Calcusyn analysis. PKCδ knockdown was used to elucidate the role of PKCδ activation as a mechanism for the synergy. The knockdown/over-expression of p53 was used to explain the differential sensitivity of HCC cell lines to sorafenib and/or OSU-2S. Results: OSU-2S synergistically enhanced the anti-proliferative effects of sorafenib in the four used HCC cell lines with combination indices < 1. This effect was accompanied by parallel increases in caspase 3/7 activity, PARP cleavage, PKCδ activation and HCC cell migration/invasion. In addition, PKCδ knockdown abolished the synergy between sorafenib and OSU-2S. Furthermore, p53 restoration in Hep3B cells through the over-expression rendered them more sensitive to both agents while p53 knockdown from HepG2 cells increased their resistance to both agents. Conclusions: OSU-2S augments the anti-proliferative effect of sorafenib in HCC cell lines, in part, through the activation of PKCδ. The p53 status in HCC cells predicts their sensitivity towards both sorafenib and OSU-2S. The proposed combination represents a therapeutically relevant approach that can lead to a new HCC therapeutic protocol.

  9. The Role of Radiotherapy Alone in Patients With Merkel Cell Carcinoma: Reporting the Australian Experience of 43 Patients

    International Nuclear Information System (INIS)

    Veness, Michael; Foote, Matthew; Gebski, Val; Poulsen, Michael

    2010-01-01

    Purpose: To review the role of radiotherapy (RTx) alone in patients with Merkel cell carcinoma (MCC). Methods and Materials: The records of 43 patients with MCC treated with RTx alone between 1993 and 2007 at the Westmead and Royal Brisbane/Mater Hospitals, Australia, were reviewed. Multivariate analysis was performed by use of Cox regression analysis. Results: The median age was 79 years (range, 48-91 years) in 19 women (44%) and 24 men (56%). All patients were white, and 5 (12%) had immunosuppression. A majority (56%) underwent irradiation at initial diagnosis, with the remainder (44%) treated in the relapse setting. The median duration of follow-up was 39 months. The head and neck comprised the most frequently treated site (47%). The median maximum lesion size was 30 mm (range, 5-130 mm). Relapse developed in 60% of patients, with most being out-of-field relapses. The in-field control rate was 75%. Most out-of-field relapses were to visceral organs. Relapse developed outside the irradiated field in 53% of patients. On multivariate analysis, only nodal status (negative nodes vs. nodes present) was significantly associated with relapse-free survival, with p = 0.005 (hazard ratio, 0.25; 95% confidence interval, 0.96-0.663). Overall survival at 2 and 5 years was 58% and 37%, respectively. Conclusions: Patients with MCC treated with RTx have a high likelihood of obtaining in-field control. Doses of 50 to 55 Gy in 20 to 25 fractions are recommended. A minority of patients are cured, with many dying of systemic relapse. Lower dose fractionation schedules (e.g., 25 Gy in 5 fractions) may be considered in patients with a very poor performance status.

  10. The Essential Role of Radiotherapy in the Treatment of Merkel Cell Carcinoma: A Study From the Rare Cancer Network

    Energy Technology Data Exchange (ETDEWEB)

    Ghadjar, Pirus, E-mail: pirus.ghadjar@insel.ch [Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern (Switzerland); Kaanders, Johannes H. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Institute of Oncology (Netherlands); Poortmans, Philipp [Department of Radiation Oncology, Institute Verbeeten, Tilburg (Netherlands); Zaucha, Renata [Department of Oncology and Radiotherapy, Medical University, Gdansk (Poland); Krengli, Marco [Department of Radiotherapy, University Hospital Maggiore della Carita, Novara (Italy); Lagrange, Jean L. [Service de Radiotherapie, Hopital Henri-Mondor, Creteil (France); Oezsoy, Orhan [Department of Radiation Oncology, CHCVs-RSV, Sion (Switzerland); Nguyen, Tan D. [Department of Radiation Oncology, Institut Jean Godinot, Reims (France); Miralbell, Raymond [Department of Radiation Oncology, Hopitaux Universitaires de Geneve, Geneva (Switzerland); Baize, Adele [Department de Radio-Oncologie, Institut Jules Bordet, Bruxelles (Belgium); Boujelbene, Noureddine [Department of Radiation Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne (Switzerland); Collen, Timothy [Department of Radiation Oncology, Kantonsspital St. Gallen (Switzerland); Scandolaro, Luciano [Radioterapia, Azienda Ospedale Sant' Anna, Como (Italy); Untereiner, Michel [Centre Francois Baclesse, Luxembourg (Luxembourg); Goldberg, Hadassah [Oncology Departement, Rambam Medical Center, Haifa (Israel); Pesce, Gianfranco A. [Department of Radiation Oncology, Oncology Institute of Southern Switzerland, Opedale San Giovanni, Bellinzona (Switzerland); Anacak, Yavuz [Department of Radiation Oncology, EGE University, Izmir (Turkey); Friedrich, Esther E.; Aebersold, Daniel M. [Department of Radiation Oncology, Inselspital, Bern University Hospital, and University of Bern (Switzerland); Beer, Karl T. [Radio Onkologiezentrum Biel (Switzerland)

    2011-11-15

    Purpose: To evaluate the role of postoperative radiotherapy (RT) in Merkel cell carcinoma (MCC). Methods and Materials: A retrospective multicenter study was performed in 180 patients with MCC treated between February 1988 and September 2009. Patients who had had surgery alone were compared with patients who received surgery and postoperative RT or radical RT. Local relapse-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastasis-free survival (DMFS) rates were assessed together with disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates. Results: Seventy-nine patients were male and 101 patients were female, and the median age was 73 years old (range, 38-93 years). The majority of patients had localized disease (n = 146), and the remaining patients had regional lymph node metastasis (n = 34). Forty-nine patients underwent surgery for the primary tumor without postoperative RT to the primary site; the other 131 patients received surgery for the primary tumor, followed by postoperative RT (n = 118) or a biopsy of the primary tumor followed by radical RT (n = 13). Median follow-up was 5 years (range, 0.2-16.5 years). Patients in the RT group had improved LRFS (93% vs. 64%; p < 0.001), RRFS (76% vs. 27%; p < 0.001), DMFS (70% vs. 42%; p = 0.01), DFS (59% vs. 4%; p < 0.001), and CSS (65% vs. 49%; p = 0.03) rates compared to patients who underwent surgery for the primary tumor alone; LRFS, RRFS, DMFS, and DFS rates remained significant with multivariable Cox regression analysis. However OS was not significantly improved by postoperative RT (56% vs. 46%; p = 0.2). Conclusions: After multivariable analysis, postoperative RT was associated with improved outcome and seems to be an important component in the multimodality treatment of MCC.

  11. Role of Brg1 in progression of esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Shahram Torkamandi

    2014-11-01

    Full Text Available Objective(s: Epigenetic regulation of gene expression can be carried out through chromatin remodeling enzymes such as SWI/SNF. Brg1 also known as SMARCA4 is a catalytic subunit of SWI/SNF, which is necessary for MMPs expression. Matrix metalloproteinases (MMPs are known as important player enzymes during tumor progression and metastasis. Aberrant epigenetic modification of chromatin should be precisely clarified to reveal probable unknown pathways in ESCC progression. Probable role of Brg1 in ESCC tumorigenesis and metastasis was studied through the assessment of Brg1 mRNA expression in KYSE30, and further evaluation about the biology of Brg1 was performed through the Brg1 silencing. Materials and Methods: Level of Brg1 mRNA expression in KYSE30 was compared to normal tissues using the real time polymerase chain reaction (PCR. Moreover, KYSE30 cells were transfected with Brg1-siRNA to silence the Brg1. Results: Our results showed for the first time that Brg1 mRNA expression was increased in KYSE30 cell line (ESCC cell line compared with normal esophageal tissue of ESCC patients. Rate of transfection in KYSE30 was also between 40 to 50%, using the pSilencer-Brg1shRNA (1:1 ratio. Conclusion: Our data indicated that chromatin remodeling machinery is a novel aspect in tumor biology of ESCC, and overexpression of Brg1 as an important member of SWI/SNF might be involved in the migration and invasion of ESCC tumoral cells.

  12. Colletotrichum higginsianum Mitogen-Activated Protein Kinase ChMK1: Role in Growth, Cell Wall Integrity, Colony Melanization and Pathogenicity

    Directory of Open Access Journals (Sweden)

    Wei Wei

    2016-08-01

    Full Text Available Colletotrichum higginsianum is an economically important pathogen that causes anthracnose disease in a wide range of cruciferous crops. To facilitate the efficient control of anthracnose disease, it will be important to understand the mechanism by which the cruciferous crops and C. higginsianum interact. A key step in understanding this interaction is characterizing the mitogen-activated protein kinases (MAPK signaling pathway of C. higginsianum. MAPK plays important roles in diverse physiological processes of multiple pathogens. In this study, a Fus3/Kss1-related MAPK gene, ChMK1, from C. higginsianum was analyzed. The results showed that the Fus3/Kss1-related MAPK ChMK1 plays a significant role in cell wall integrity. Targeted deletion of ChMK1 resulted in a hypersensitivity to cell wall inhibitors, reduced conidiation and albinistic colonies. Further, the deletion mutant was also unable to form melanized appressorium, a specialized infection structure that is necessary for successful infection. Therefore, the deletion mutant loses pathogenicity on A. thaliana leaves, demonstrating that ChMK1 plays an essential role in the early infection step. In addition, the ChMK1 deletion mutant showed an attenuated growth rate that is different from that of its homologue in C. lagenarium, indicating the diverse roles that Fus3/Kss1-related MAPKs plays in phytopathogenic fungi. Furthermore, the expression level of three melanin synthesis associated genes were clearly decreased in the albinistic ChMK1 mutant compared to that of the wild type strain, suggesting that ChMK1 is also required for colony melanization in C. higginsianum.

  13. Risk of a Second Kidney Carcinoma Following Childhood Cancer: Role of Chemotherapy and Radiation Dose to Kidneys.

    Science.gov (United States)

    de Vathaire, Florent; Scwhartz, Boris; El-Fayech, Chiraz; Allodji, Rodrigue Sètchéou; Escudier, Bernard; Hawkins, Mike; Diallo, Ibrahima; Haddy, Nadia

    2015-11-01

    Kidney carcinoma is a rare second malignancy following childhood cancer. We sought to quantify risk and assess risk factors for kidney carcinoma following treatment for childhood cancer. We evaluated a cohort of 4,350 patients who were 5-year cancer survivors and had been treated for cancer as children in France and the United Kingdom. Patients were treated between 1943 and 1985, and were followed for an average of 27 years. Radiation dose to the kidneys during treatment was estimated with dedicated software, regardless of the site of childhood cancer. Kidney carcinoma developed in 13 patients. The cumulative incidence of kidney carcinoma was 0.62% (95% CI 0.27%-1.45%) at 40 years after diagnosis, which was 13.3-fold higher (95% CI 7.1-22.3) than in the general population. The absolute excess risk strongly increased with longer duration of followup (p kidney carcinoma was 5.7-fold higher (95% CI 1.4-14.7) if radiotherapy was not performed or less than 1 Gy had been absorbed by the kidney but 66.3-fold higher (95% CI 23.8-142.5) if the radiation dose to the kidneys was 10 to 19 Gy and 14.5-fold higher (95% CI 0.8-63.9) for larger radiation doses to the kidney. Treatment with chemotherapy increased the risk of kidney carcinoma (RR 5.1, 95% CI 1.1-22.7) but we were unable to identify a specific drug or drug category responsible for this effect. Moderate radiation dose to the kidneys during childhood cancer treatment increases the risk of a second kidney carcinoma. This incidence will be further increased when childhood cancer survivors reach old age. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  14. Influenza interaction with cocirculating pathogens and its impact on surveillance, pathogenesis, and epidemic profile: A key role for mathematical modelling.

    Directory of Open Access Journals (Sweden)

    Lulla Opatowski

    2018-02-01

    Full Text Available Evidence is mounting that influenza virus interacts with other pathogens colonising or infecting the human respiratory tract. Taking into account interactions with other pathogens may be critical to determining the real influenza burden and the full impact of public health policies targeting influenza. This is particularly true for mathematical modelling studies, which have become critical in public health decision-making. Yet models usually focus on influenza virus acquisition and infection alone, thereby making broad oversimplifications of pathogen ecology. Herein, we report evidence of influenza virus interactions with bacteria and viruses and systematically review the modelling studies that have incorporated interactions. Despite the many studies examining possible associations between influenza and Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Neisseria meningitidis, respiratory syncytial virus (RSV, human rhinoviruses, human parainfluenza viruses, etc., very few mathematical models have integrated other pathogens alongside influenza. The notable exception is the pneumococcus-influenza interaction, for which several recent modelling studies demonstrate the power of dynamic modelling as an approach to test biological hypotheses on interaction mechanisms and estimate the strength of those interactions. We explore how different interference mechanisms may lead to unexpected incidence trends and possible misinterpretation, and we illustrate the impact of interactions on public health surveillance using simple transmission models. We demonstrate that the development of multipathogen models is essential to assessing the true public health burden of influenza and that it is needed to help improve planning and evaluation of control measures. Finally, we identify the public health, surveillance, modelling, and biological challenges and propose avenues of research for the coming years.

  15. Role of hydrogen peroxide and antioxidant enzymes in the interaction between a hemibiotrophic fungal pathogen, Leptosphaeria maculans, and oilseed rape

    Czech Academy of Sciences Publication Activity Database

    Jindřichová, Barbora; Fodor, J.; Šindelářová, Milada; Burketová, Lenka; Valentová, O.

    2011-01-01

    Roč. 72, č. 2 (2011), s. 149-156 ISSN 0098-8472 R&D Projects: GA ČR GA522/08/1581; GA MŠk MEB040923 Institutional research plan: CEZ:AV0Z50380511 Keywords : hydrogen peroxide * antioxidant enzymes * hemibiotrophic pathogen Subject RIV: GF - Plant Pathology, Vermin, Weed, Plant Protection Impact factor: 2.985, year: 2011

  16. CARCINOMA PROSTATE HISTOPATHOLOGY IN NEEDLE BIOPSIES INCLUDING REVISED GLEASON’S GRADING AND ROLE OF IMMUNOHISTOCHEMICAL MARKERS

    Directory of Open Access Journals (Sweden)

    Rema Priyadarsini

    2017-05-01

    Full Text Available BACKGROUND Adenocarcinoma of prostate is the most common form of cancer in men accounting for 29% of cancers in developed nations and the incidence of prostatic cancer is 6.4% in males of Trivandrum District. MATERIALS AND METHODS All prostatic biopsies taken per rectally and stained by haematoxylin and eosin. In suspected cases of malignancy immunohistochemical markers, the AMACR P504S and high molecular weight cytokeratin 34E12 were done. RESULTS The total number of cases studied were 142. The final diagnosis with histomorphological features show that maximum cases were prostatic carcinoma constituting 45.5% of the samples received. CONCLUSION All prostatic carcinomas were graded by revised Gleason’s grade (ISUP 2005 and the use of immunohistochemical markers in arriving at a definite diagnosis in carcinoma prostate was confirmed.

  17. The role of immunohistochemistry, electron microscopy, and ultrastructural cytochemistry in the diagnosis of mixed carcinoma-neuroendocrine neoplasms.

    Science.gov (United States)

    Graham, A R; Payne, C M; Nagle, R B; Angel, E

    1987-02-01

    We studied four mixed carcinoma-neuroendocrine neoplasms from gastrointestinal tract and pancreas by routine light microscopy (LM), immunohistochemistry (IH), electron microscopy (EM), and ultrastructural cytochemistry (UC). By LM, the individual tumors showed fairly pure neuroendocrine (carcinoid) or epithelial (papillary) patterns, mixed neuroendocrine-carcinoma features and poorly-differentiated tumor in sheets and nests which did not lend itself to morphologic characterization. IH demonstrated mixed expression, within different areas of the same neoplasm, of epithelial antigens (keratins and carcinoembryonic antigen [CEA]) and neuroendocrine markers (neuron-specific enolase [NSE], bombesin and neurohormonal peptides). By EM, each tumor showed ultrastructural features of epithelial and neuroendocrine differentiation which varied substantially in terms of number of cells involved and their distribution; two of the neoplasms showed biphasic differentiation within single cells. The nature of the neurosecretory granules was verified with the uranaffin reaction (UR). This study illustrates the value of combining LM, IH, EM and UC for the identification of mixed carcinoma-neuroendocrine lesions.

  18. Three Fusarium oxysporum mitogen-activated protein kinases (MAPKs) have distinct and complementary roles in stress adaptation and cross-kingdom pathogenicity.

    Science.gov (United States)

    Segorbe, David; Di Pietro, Antonio; Pérez-Nadales, Elena; Turrà, David

    2017-09-01

    Mitogen-activated protein kinase (MAPK) cascades mediate cellular responses to environmental signals. Previous studies in the fungal pathogen Fusarium oxysporum have revealed a crucial role of Fmk1, the MAPK orthologous to Saccharomyces cerevisiae Fus3/Kss1, in vegetative hyphal fusion and plant infection. Here, we genetically dissected the individual and combined contributions of the three MAPKs Fmk1, Mpk1 and Hog1 in the regulation of development, stress response and virulence of F. oxysporum on plant and animal hosts. Mutants lacking Fmk1 or Mpk1 were affected in reactive oxygen species (ROS) homeostasis and impaired in hyphal fusion and aggregation. Loss of Mpk1 also led to increased sensitivity to cell wall and heat stress, which was exacerbated by simultaneous inactivation of Fmk1, suggesting that both MAPKs contribute to cellular adaptation to high temperature, a prerequisite for mammalian pathogens. Deletion of Hog1 caused increased sensitivity to hyperosmotic stress and resulted in partial rescue of the restricted colony growth phenotype of the mpk1Δ mutant. Infection assays on tomato plants and the invertebrate animal host Galleria mellonella revealed distinct and additive contributions of the different MAPKs to virulence. Our results indicate that positive and negative cross-talk between the three MAPK pathways regulates stress adaptation, development and virulence in the cross-kingdom pathogen F. oxysporum. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  19. The role of scintigraphy with 57Co-bleomycin in the detection and staging of planocellular carcinomas

    International Nuclear Information System (INIS)

    Janchar, B.; Shushtarshich, J.; Machkovshek, M.

    1990-01-01

    Opinions of usefullness of 57 Co-bleomycin in the diagnostics of planocellular carcinomas have been differing. This method was reported in early 70-ties but was never generally accepted because of some physical characteristics of 57 Co (half-life of 57 Co 270 days). The authors report two cases in which radiography and imaging with this agent helped to provide correct diagnosis: an unclear case of Pancoast tumor and a case of metastatic involvement of thoracic wall after laryngeal carcinoma. (author) 7 refs.; 4 figs

  20. Anal carcinomas: the role of endoanal ultrasound and magnetic resonance imaging in staging, response evaluation and follow-up

    Energy Technology Data Exchange (ETDEWEB)

    Parikh, Jyoti; Shaw, Aidan; Griffin, Nyree [Guys and St. Thomas' Hospital, Department of Radiology, London (United Kingdom); Grant, Lee A. [Royal Marsden Hospital, Department of Radiology, London (United Kingdom); Schizas, Alexis M.P.; Datta, Vivek; Williams, Andrew B. [Guys and St. Thomas' Hospital, Department of General Surgery, London (United Kingdom)

    2011-04-15

    Anal carcinoma is an important but rare condition, managed in specialist centres. Both endoanal ultrasound and magnetic resonance imaging (MRI) can be used in the locoregional staging and follow-up of patients with anal cancer, and both may assist in treatment planning and prognosis. Recent guidelines published by the European Society for Medical Oncology have recommended MRI as the technique of choice for assessment of locoregional disease. This paper describes the techniques for both endoanal ultrasound and MRI, and compares the relative merits and disadvantages of each in the local assessment of anal carcinoma. (orig.)

  1. The p53 molecule and its prognostic role in squamous cell carcinomas of the head and neck

    DEFF Research Database (Denmark)

    Nylander, K.; Dabelsteen, Erik; Hall, P.A.

    2000-01-01

    and poor patient outcome was found when looking only at patients with laryngeal squamous cell carcinomas. Also, in oral premalignant lesions, expression of p53-positive cells in the suprabasal layers of the epithelium has been seen as an indication of impending malignant development. Concerning......Despite intense research, the 5-year survival rate for patients with squamous cell carcinoma of the head and neck (SCCHN) is still low. Several different factors have been studied in the search for one or more factors that give important prognostic information at the time of diagnosis. Many recent...

  2. Role of domestic ducks in the emergence of a new genotype of highly pathogenic H5N1 avian influenza A viruses in Bangladesh.

    Science.gov (United States)

    Barman, Subrata; Marinova-Petkova, Atanaska; Hasan, M Kamrul; Akhtar, Sharmin; El-Shesheny, Rabeh; Turner, Jasmine Cm; Franks, John; Walker, David; Seiler, Jon; Friedman, Kimberly; Kercher, Lisa; Jeevan, Trushar; Darnell, Daniel; Kayali, Ghazi; Jones-Engel, Lisa; McKenzie, Pamela; Krauss, Scott; Webby, Richard J; Webster, Robert G; Feeroz, Mohammed M

    2017-08-09

    Highly pathogenic avian influenza H5N1 viruses were first isolated in Bangladesh in February 2007. Subsequently, clades 2.2.2, 2.3.4.2 and 2.3.2.1a were identified in Bangladesh, and our previous surveillance data revealed that by the end of 2014, the circulating viruses exclusively comprised clade 2.3.2.1a. We recently determined the status of circulating avian influenza viruses in Bangladesh by conducting surveillance of live poultry markets and waterfowl in wetland areas from February 2015 through February 2016. Until April 2015, clade 2.3.2.1a persisted without any change in genotype. However, in June 2015, we identified a new genotype of H5N1 viruses, clade 2.3.2.1a, which quickly became predominant. These newly emerged H5N1 viruses contained the hemagglutinin, neuraminidase and matrix genes of circulating 2.3.2.1a Bangladeshi H5N1 viruses and five other genes of low pathogenic Eurasian-lineage avian influenza A viruses. Some of these internal genes were closely related to those of low pathogenic viruses isolated from ducks in free-range farms and wild birds in a wetland region of northeastern Bangladesh, where commercially raised domestic ducks have frequent contact with migratory birds. These findings indicate that migratory birds of the Central Asian flyway and domestic ducks in the free-range farms in Tanguar haor-like wetlands played an important role in the emergence of this novel genotype of highly pathogenic H5N1 viruses.

  3. The Role of Stress and Stress Adaptations in Determining the Fate of the Bacterial Pathogen Listeria monocytogenes in the Food Chain

    Science.gov (United States)

    NicAogáin, Kerrie; O’Byrne, Conor P.

    2016-01-01

    The foodborne pathogen Listeria monocytogenes is a highly adaptable organism that can persist in a wide range of environmental and food-related niches. The consumption of contaminated ready-to-eat foods can cause infections, termed listeriosis, in vulnerable humans, particularly those with weakened immune systems. Although these infections are comparatively rare they are associated with high mortality rates and therefore this pathogen has a significant impact on food safety. L. monocytogenes can adapt to and survive a wide range of stress conditions including low pH, low water activity, and low temperature, which makes it problematic for food producers who rely on these stresses for preservation. Stress tolerance in L. monocytogenes can be explained partially by the presence of the general stress response (GSR), a transcriptional response under the control of the alternative sigma factor sigma B (σB) that reconfigures gene transcription to provide homeostatic and protective functions to cope with the stress. Within the host σB also plays a key role in surviving the harsh conditions found in the gastrointestinal tract. As the infection progresses beyond the GI tract L. monocytogenes uses an intracellular infectious cycle to propagate, spread and remain protected from the host’s humoral immunity. Many of the virulence genes that facilitate this infectious cycle are under the control of a master transcriptional regulator called PrfA. In this review we consider the environmental reservoirs that enable L. monocytogenes to gain access to the food chain and discuss the stresses that the pathogen must overcome to survive and grow in these environments. The overlap that exists between stress tolerance and virulence is described. We review the principal measures that are used to control the pathogen and point to exciting new approaches that might provide improved means of control in the future. PMID:27933042

  4. The Role of Stress and Stress Adaptations in Determining the Fate of the Bacterial Pathogen Listeria monocytogenes in the Food Chain.

    Science.gov (United States)

    NicAogáin, Kerrie; O'Byrne, Conor P

    2016-01-01

    The foodborne pathogen Listeria monocytogenes is a highly adaptable organism that can persist in a wide range of environmental and food-related niches. The consumption of contaminated ready-to-eat foods can cause infections, termed listeriosis, in vulnerable humans, particularly those with weakened immune systems. Although these infections are comparatively rare they are associated with high mortality rates and therefore this pathogen has a significant impact on food safety. L. monocytogenes can adapt to and survive a wide range of stress conditions including low pH, low water activity, and low temperature, which makes it problematic for food producers who rely on these stresses for preservation. Stress tolerance in L. monocytogenes can be explained partially by the presence of the general stress response (GSR), a transcriptional response under the control of the alternative sigma factor sigma B (σ B ) that reconfigures gene transcription to provide homeostatic and protective functions to cope with the stress. Within the host σ B also plays a key role in surviving the harsh conditions found in the gastrointestinal tract. As the infection progresses beyond the GI tract L. monocytogenes uses an intracellular infectious cycle to propagate, spread and remain protected from the host's humoral immunity. Many of the virulence genes that facilitate this infectious cycle are under the control of a master transcriptional regulator called PrfA. In this review we consider the environmental reservoirs that enable L. monocytogenes to gain access to the food chain and discuss the stresses that the pathogen must overcome to survive and grow in these environments. The overlap that exists between stress tolerance and virulence is described. We review the principal measures that are used to control the pathogen and point to exciting new approaches that might provide improved means of control in the future.

  5. Role of 30 kDa antigen of enteric bacterial pathogens as a possible arthritogenic factor in post-dysenteric reactive arthritis

    Directory of Open Access Journals (Sweden)

    Malkit Singh

    2013-01-01

    Full Text Available Background: Reactive arthritis (ReA/Reiter′s syndrome (RS may be caused as a sequel of infections caused by enteric bacterial pathogens, although the mechanisms through, which different pathogens cause similar disease are not clear. Aim: This study was done to look for the presence and role of any common bacterial antigen among the pathogens isolated from such patients. Materials and Methods: A total of 51 patients of ReA and 75 controls (three groups of 25 subjects each: Group 1: Patients who did not develop arthritic complications within 3 months after bacillary dysentery/diarrhea; Group 2: Patients with other arthritic diseases and Group 3: Normal healthy subjects were included. The isolated enteric pathogens were tested to detect the immunodominant antigens. Results and Conclusions: A common 30 kDa antigen was found to be specifically present among seven arthritogenic enteric bacterial strains belonging to three genera, Salmonella, Shigella and Hafnia. Post-dysenteric ReA patients′ sera show higher levels of immunoglobulin G, immunoglobulin M and immunoglobulin A antibodies against this antigen as compared to the controls. Lymphocytes of ReA patients recognize this antigen, proliferate and produce interleukin-2 in response to this antigen more than the lymphocytes of controls. 30 kDa antigen may be a common arthritogenic factor associated with post-dysenteric ReA/RS. The association of Hafnia alvei with post-dysenteric ReA is described for the first time. Four cases of mycobacterial ReA had an association with this antigen, suggesting that the arthritogenic antigen of mycobacteria and enteric bacteria may be of a similar nature.

  6. Construction of a recombinant eukaryotic human ZHX1 gene expression plasmid and the role of ZHX1 in hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Jianping; Liu, Dejie; Liang, Xiaohong; Gao, Lifen; Yue, Xuetian; Yang, Yang; Ma, Chunhong; Liu, Jun

    2013-11-01

    The zinc-fingers and homeoboxes protein 1 (ZHX1) consists of 873 amino acid residues, is localized in the cell nucleus and appears to act as a transcriptional repressor. Previous studies have shown that ZHX1 interacts with nuclear factor Y subunit α (NF-YA), DNA methyltransferases (DNMT) 3B and ZHX2, all of which are involved in tumorigenesis. However, the exact role of ZHX1 in tumorigenesis remains unknown. The aim of the current study was to construct a recombinant eukaryotic expression plasmid containing the human ZHX1 (hZHX1) gene and to investigate the biological activities of ZHX1 in hepatocellular carcinoma (HCC). Reverse transcription-polymerase chain reaction (RT‑PCR) was used to amplify the N- and C-terminal fragments (ZHX1‑N and ZHX1‑C, respectively) of the hZHX1 gene. The two PCR fragments were cloned into the pEASY-T1 vector and subcloned into the pcDNA3 plasmid to generate a recombinant pcDNA3‑ZHX1 plasmid. Following identification by enzyme digestion and DNA sequencing, the recombinant pcDNA3‑ZHX1 plasmid was transfected into SMMC-7721 cells. The level of ZHX1 expression was detected by RT-PCR and western blot analysis. Cell growth curve assays were used to evaluate the effect of ZHX1 on cell proliferation. Moreover, the differential expression of ZHX1 between cancer and adjacent cirrhotic liver tissue was investigated by quantitative PCR (qPCR). Enzyme digestion and DNA sequencing confirmed the successful construction of the recombinant plasmid, pcDNA3‑ZHX1. qPCR and western blot analysis demonstrated that ZHX1 was efficiently expressed in SMMC-7721 cells and overexpression of ZHX1 may inhibit the proliferation of SMMC-7721 cells. In addition, reduced ZHX1 expression is widespread among cancer tissues from HCC patients. In conclusion, a recombinant eukaryotic expression plasmid, pcDNA3‑ZHX1, was successfully constructed. In addition, the current results indicate that a low expression of ZHX1 may be responsible for hepatocarcinogenesis.

  7. Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion

    Directory of Open Access Journals (Sweden)

    Shen Qingli

    2010-08-01

    Full Text Available Abstract Background Micro-ribonucleic acid (miRNA-199a-5p has been reported to be decreased in hepatocellular carcinoma (HCC compared to normal tissue. Discoidin domain receptor-1 (DDR1 tyrosine kinase, involved in cell invasion-related signaling pathway, was predicted to be a potential target of miR-199a-5p by the use of miRNA target prediction algorithms. The aim of this study was to investigate the role of miR-199a-5p and DDR1 in HCC invasion. Methods Mature miR-199a-5p and DDR1 expression were evaluated in tumor and adjacent non-tumor liver tissues from 23 patients with HCC undergoing liver resection and five hepatoma cell lines by the use of real-time quantitative RT-PCR (qRT-PCR analysis. The effect of aberrant miR-199a-5p expression on cell invasion was assessed in vitro using HepG2 and SNU-182 hepatoma cell lines. Luciferase reporter assay was employed to validate DDR1 as a putative miR-199a-5p target gene. Regulation of DDR1 expression by miR-199a-5p was assessed by the use qRT-PCR and western blotting analysis. Results A significant down-regulation of miR-199a-5p was observed in 65.2% of HCC tissues and in four of five cell lines. In contrast, DDR1 expression was significantly increased in 52.2% of HCC samples and in two of five cell lines. Increased DDR1 expression in HCC was associated with advanced tumor stage. DDR1 was shown to be a direct target of miR-199a-5p by luciferase reporter assay. Transfection of miR-199a-5p inhibited invasion of HepG2 but not SNU-182 hepatoma cells. Conclusions Decreased expression of miR-199a-5p contributes to increased cell invasion by functional deregulation of DDR1 activity in HCC. However, the effect of miR-199a-5p on DDR1 varies among individuals and hepatoma cell lines. These findings may have significant translational relevance for development of new targeted therapies as well as prognostic prediction for patients with HCC.

  8. The role of PET in initial work-up and evaluation after therapy in patients with carcinoma of unknown primary

    Energy Technology Data Exchange (ETDEWEB)

    Ryoo, Baek Yeol; Kang, Yoon Koo

    1998-12-01

    The carcinoma of unknown primary occupied 5 - 10 % of all malignancies. It is heterogenous in origin and has poor prognosis. The indentification of primary site and definition of involved area are more helpful in the management. The efficacy of positron emission tomography (PET) with fluorine-18- fluorodeoxyglucose (F18-FDG) positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (F18-FDG) was evaluated in several tumors such as breast, pancreas and head and neck cancers. In carcinoma of unknown primary, it was reported that the concentration of FDG was increased in tumor tissues, and that PET with F18-FDG may be much helpful in identifying primary site and defining involved area. The authors evaluated the usefulness of PET with F18-FDG in initial work-up and in evaluation after radical therapy for the patients with carcinoma of unknown primary. The visual analysis of FDG-PET would be helpful in identifying primary site and defining involved area. In detecting recurrent of residual lesions, FDG-PET seemed to be less helpful than conventional diagnostic work-up. But more studies with larger number of cases and longer follow-up were required. The results of this study can be bases for the direction of future studies for the usefulness of PET in carcinoma of unknown primary.

  9. The role of PET in initial work-up and evaluation after therapy in patients with carcinoma of unknown primary

    International Nuclear Information System (INIS)

    Ryoo, Baek Yeol; Kang, Yoon Koo

    1998-12-01

    The carcinoma of unknown primary occupied 5 - 10 % of all malignancies. It is heterogenous in origin and has poor prognosis. The indentification of primary site and definition of involved area are more helpful in the management. The efficacy of positron emission tomography (PET) with fluorine-18- fluorodeoxyglucose (F18-FDG) positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (F18-FDG) was evaluated in several tumors such as breast, pancreas and head and neck cancers. In carcinoma of unknown primary, it was reported that the concentration of FDG was increased in tumor tissues, and that PET with F18-FDG may be much helpful in identifying primary site and defining involved area. The authors evaluated the usefulness of PET with F18-FDG in initial work-up and in evaluation after radical therapy for the patients with carcinoma of unknown primary. The visual analysis of FDG-PET would be helpful in identifying primary site and defining involved area. In detecting recurrent of residual lesions, FDG-PET seemed to be less helpful than conventional diagnostic work-up. But more studies with larger number of cases and longer follow-up were required. The results of this study can be bases for the direction of future studies for the usefulness of PET in carcinoma of unknown primary

  10. Predation scars may influence host susceptibility to pathogens: evaluating the role of corallivores as vectors of coral disease.

    Science.gov (United States)

    Nicolet, K J; Chong-Seng, K M; Pratchett, M S; Willis, B L; Hoogenboom, M O

    2018-03-27

    Infectious diseases not regulated by host density, such as vector-borne diseases, have the potential to drive population declines and extinctions. Here we test the vector potential of the snail Drupella sp. and butterflyfish Chaetodon plebeius for two coral diseases, black band (BBD) and brown band (BrB) disease. Drupella transmitted BrB to healthy corals in 40% of cases immediately following feeding on infected corals, and even in 12% of cases 12 and 24 hours following feeding. However, Drupella was unable to transmit BBD in either transmission treatment. In a field experiment testing the vector potential of naturally-occurring fish assemblages, equivalent numbers of caged and uncaged coral fragments became infected with either BrB, BBD or skeletal eroding band, indicating that corallivorous fish were unlikely to have caused transmission. In aquaria, C. plebeius did not transmit either BBD or BrB, even following extended feeding on both infected and healthy nubbins. A literature review confirmed only four known coral disease vectors, all invertebrates, corroborating our conclusion that polyp-feeding fishes are unlikely to be vectors of coral diseases. This potentially because polyp-feeding fishes produce shallow lesions, not allowing pathogens to invade coral tissues. In contrast, corallivorous invertebrates that create deeper feeding scars increase pathogens transmission.

  11. Diet quality can play a critical role in defense efficacy against parasitoids and pathogens in the Glanville fritillary (Melitaea cinxia).

    Science.gov (United States)

    Laurentz, Minna; Reudler, Joanneke H; Mappes, Johanna; Friman, Ville; Ikonen, Suvi; Lindstedt, Carita

    2012-01-01

    Numerous herbivorous insect species sequester noxious chemicals from host plants that effectively defend against predators, and against parasitoids and pathogens. Sequestration of these chemicals may be expensive and involve a trade off with other fitness traits. Here, we tested this hypothesis. We reared Glanville fritillary butterfly (Melitaea cinxia L.) larvae on plant diets containing low- and high-levels of iridoid glycosides (IGs) (mainly aucubin and catalpol) and tested: 1) whether IGs affect the herbivore's defense against parasitoids (measured as encapsulation rate) and bacterial pathogens (measured as herbivore survival); 2) whether parasitoid and bacterial defenses interact; and 3) whether sequestration of the plant's defense chemicals incurs any life history costs. Encapsulation rates were stronger when there were higher percentages of catalpol in the diet. Implanted individuals had greater amounts of IGs in their bodies as adults. This suggests that parasitized individuals may sequester more IGs, increase their feeding rate after parasitism, or that there is a trade off between detoxification efficiency and encapsulation rate. Larval survival after bacterial infection was influenced by diet, but probably not by diet IG content, as changes in survival did not correlate linearly with the levels of IGs in the diet. However, M. cinxia larvae with good encapsulation abilities were better defended against bacteria. We did not find any life history costs of diet IG concentration for larvae. These results suggest that the sequestering of plant defense chemicals can help herbivorous insects to defend against parasitoids.

  12. Pathogen inactivation techniques.

    Science.gov (United States)

    Pelletier, J P R; Transue, S; Snyder, E L

    2006-01-01

    of investigation. Clearly, regulatory agencies have a major role to play in the evaluation of these new technologies. This chapter will cover the several types of pathogen-reduction systems, mechanisms of action, the inactivation efficacy for specific types of pathogens, toxicology of the various systems and the published research and clinical trial data supporting their potential usefulness. Due to the nature of the field, pathogen reduction is a work in progress and this review should be considered as a snapshot in time rather than a clear picture of what the future will bring.

  13. Exploring new roles for the rpoS gene in the survival and virulence of the fire blight pathogen Erwinia amylovora.

    Science.gov (United States)

    Santander, Ricardo D; Monte-Serrano, Mercedes; Rodríguez-Herva, José J; López-Solanilla, Emilia; Rodríguez-Palenzuela, Pablo; Biosca, Elena G

    2014-12-01

    Erwinia amylovora causes fire blight in economically important plants of the family Rosaceae. This bacterial pathogen spends part of its life cycle coping with starvation and other fluctuating environmental conditions. In many Gram-negative bacteria, starvation and other stress responses are regulated by the sigma factor RpoS. We obtained an E. amylovora rpoS mutant to explore the role of this gene in starvation responses and its potential implication in other processes not yet studied in this pathogen. Results showed that E. amylovora needs rpoS to develop normal starvation survival and viable but nonculturable (VBNC) responses. Furthermore, this gene contributed to stationary phase cross-protection against oxidative, osmotic, and acid stresses and was essential for cross-protection against heat shock, but nonessential against acid shock. RpoS also mediated regulation of motility, exopolysaccharide synthesis, and virulence in immature loquats, but not in pear plantlets, and contributed to E. amylovora survival in nonhost tissues during incompatible interactions. Our results reveal some unique roles for the rpoS gene in E. amylovora and provide new knowledge on the regulation of different processes related to its ecology, including survival in different environments and virulence in immature fruits. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  14. The control of H5 or H7 mildly pathogenic avian influenza: a role for inactivated vaccine.

    Science.gov (United States)

    Halvorson, David A

    2002-02-01

    Biosecurity is the first line of defence in the prevention and control of mildly pathogenic avian influenza (MPAI). Its use has been highly successful in keeping avian influenza (AI) out of commercial poultry worldwide. However, sometimes AI becomes introduced into poultry populations and, when that occurs, biosecurity again is the primary means of controlling the disease. There is agreement that routine serological monitoring, disease reporting, isolation or quarantine of affected flocks, application of strict measures to prevent the contamination of and movement of people and equipment, and changing flock schedules are necessities for controlling AI. There is disagreement as to the disposition of MPAI-infected flocks: some advocate their destruction and others advocate controlled marketing. Sometimes biosecurity is not enough to stop the spread of MPAI. In general, influenza virus requires a dense population of susceptible hosts to maintain itself. When there is a large population of susceptible poultry in an area, use of an inactivated AI vaccine can contribute to AI control by reducing the susceptibility of the population. Does use of inactivated vaccine assist, complicate or interfere with AI control and eradication? Yes, it assists MPAI control (which may reduce the risk of highly pathogenic AI (HPAI)) but, unless steps are taken to prevent it, vaccination may interfere with sero-epidemiology in the case of an HPAI outbreak. Does lack of vaccine assist, complicate or interfere with AI control and eradication? Yes, it assists in identification of sero-positive (convalescent) flocks in a HPAI eradication program, but it interferes with MPAI control (which in turn may increase the risk of emergence of HPAI).A number of hypothetical concerns have been raised about the use of inactivated AI vaccines. Infection of vaccinated flocks, serology complications and spreading of virus by vaccine crews are some of the hypothetical concerns. The discussion of these concerns

  15. Radiosensitivity of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hennequin, C.; Quero, L.; Rivera, S.

    2011-01-01

    The frequency of hepatocellular carcinoma (HCC) is increasing in the western world and the role of radiotherapy is more and more discussed. Classically, hepatocellular carcinoma was considered as a radioresistant tumour: in fact, modern radio-biologic studies, performed on cell lines directly established from patients, showed that hepatocellular carcinoma has the same radiosensitivity than the other epithelial tumours. From clinical studies, its α/β ratio has been estimated to be around 15 Gy. Radiosensitivity of normal hepatic parenchyma is now well evaluated and some accurate NTCP models are available to guide hepatic irradiation. The biology of hepatocellular carcinoma is also better described: the combination of radiotherapy and targeted therapies will be a promising approach in the near future. (authors)

  16. Cryotherapy for hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Awad, Tahany; Thorlund, Kristian; Gluud, Christian

    2009-01-01

    BACKGROUND: Hepatocellular carcinoma is the most common primary malignant cancer of the liver. Evidence for the role of cryotherapy in the treatment of hepatocellular carcinoma is controversial. OBJECTIVES: The aim of this review is to evaluate the potential benefits and harms of cryotherapy...... for the treatment of hepatocellular carcinoma. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS until June 2009. We identified further studies by searching...... of benefit but included for the assessment of harm. Both severe and non-severe adverse events were reported, but the true nature and extent of harm was difficult to asses. AUTHORS' CONCLUSIONS: At present, there is no evidence to recommend or refute cryotherapy for patients with hepatocellular carcinoma...

  17. Antibiotic-Associated Apoptotic Enterocolitis in the Absence of a Defined Pathogen: The Role of Intestinal Microbiota Depletion*

    Science.gov (United States)

    Wurm, Philipp; Spindelboeck, Walter; Krause, Robert; Plank, Johannes; Fuchs, Gottfried; Bashir, Mina; Petritsch, Wolfgang; Halwachs, Bettina; Langner, Cord; Högenauer, Christoph

    2017-01-01

    Objective: Antibiotic therapy is a major risk factor for the development of diarrhea and colitis with varying severity. Often the origin of antibiotic-associated gastrointestinal deterioration remains elusive and no specific infectious agents could be discerned. Patients: We represent three cases of intractable high-volume diarrhea associated with combined antibiotic and steroid therapy in critically ill patients not fitting into established disease entities. Cases presented with severe apoptotic enterocolitis resembling acute intestinal graft-versus-host-disease. Microbiologic workup precluded known enteropathogens, but microbiota analysis revealed a severely depleted gut microbiota with concomitant opportunistic pathogen overgrowth. Interventions: Fecal microbiota transplantation, performed in one patient, was associated with correction of dysbiosis, rapid clinical improvement, and healing of enterocolitis. Conclusions: Our series represents a severe form of antibiotic-associated colitis in critically ill patients signified by microbiota depletion, and reestablishment of a physiologic gastrointestinal microbiota might be beneficial for this condition. PMID:28333760

  18. The multifunctional LigB adhesin binds homeostatic proteins with potential roles in cutaneous infection by pathogenic Leptospira interrogans.

    Directory of Open Access Journals (Sweden)

    Henry A Choy

    Full Text Available Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin, and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury, where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have been mapped to an overlapping domain in LigB comprising repeats 9-11, with repeat 11 possibly enhancing binding by a conformational effect. Leptospirosis

  19. A TALE of transposition: Tn3-like transposons play a major role in the spread of pathogenicity determinants of Xanthomonas citri and other xanthomonads.

    Science.gov (United States)

    Ferreira, Rafael Marini; de Oliveira, Amanda Carolina P; Moreira, Leandro M; Belasque, José; Gourbeyre, Edith; Siguier, Patricia; Ferro, Maria Inês T; Ferro, Jesus A; Chandler, Michael; Varani, Alessandro M

    2015-02-17

    Members of the genus Xanthomonas are among the most important phytopathogens. A key feature of Xanthomonas pathogenesis is the translocation of type III secretion system (T3SS) effector proteins (T3SEs) into the plant target cells via a T3SS. Several T3SEs and a murein lytic transglycosylase gene (mlt, required for citrus canker symptoms) are found associated with three transposition-related genes in Xanthomonas citri plasmid pXAC64. These are flanked by short inverted repeats (IRs). The region was identified as a transposon, TnXax1, with typical Tn3 family features, including a transposase and two recombination genes. Two 14-bp palindromic sequences within a 193-bp potential resolution site occur between the recombination genes. Additional derivatives carrying different T3SEs and other passenger genes occur in different Xanthomonas species. The T3SEs include transcription activator-like effectors (TALEs). Certain TALEs are flanked by the same IRs as found in TnXax1 to form mobile insertion cassettes (MICs), suggesting that they may be transmitted horizontally. A significant number of MICs carrying other passenger genes (including a number of TALE genes) were also identified, flanked by the same TnXax1 IRs and delimited by 5-bp target site duplications. We conclude that a large fraction of T3SEs, including individual TALEs and potential pathogenicity determinants, have spread by transposition and that TnXax1, which exhibits all of the essential characteristics of a functional transposon, may be involved in driving MIC transposition. We also propose that TALE genes may diversify by fork slippage during the replicative Tn3 family transposition. These mechanisms may play a crucial role in the emergence of Xanthomonas pathogenicity. Xanthomonas genomes carry many insertion sequences (IS) and transposons, which play an important role in their evolution and architecture. This study reveals a key relationship between transposons and pathogenicity determinants in

  20. The Immunoexpression of Glucocorticoid Receptors in Breast Carcinomas, Lactational Change, and Normal Breast Epithelium and Its Possible Role in Mammary Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Raja Alyusuf

    2017-01-01

    Full Text Available The role of estrogen and progesterone receptors in breast cancer biology is well established. In contrast, other steroid hormones are less well studied. Glucocorticoids (GCs are known to play a role in mammary development and differentiation; thus, it is of interest to attempt to delineate their immunoexpression across a spectrum of mammary epithelia. Aim. To delineate the distribution pattern of glucocorticoid receptors (GRs in malignant versus nonmalignant epithelium with particular emphasis on lactational epithelium. Materials and Methods. Immunohistochemistry (IHC for GRs was performed on archival formalin-fixed paraffin-embedded tissue blocks of 96 cases comprising 52 invasive carcinomas, 21 cases with lactational change, and 23 cases showing normal mammary tissue histology. Results. Results reveal an overexpression of GRs in mammary malignant epithelium as compared to both normal and lactational groups individually and combined. GR overexpression is significantly more pronounced in HER-2-negative cancers. Discussion. This is the first study to compare GR expression in human lactating epithelium versus malignant and normal epithelium. The article discusses the literature related to the pathobiology of GCs in the breast with special emphasis on breast cancer. Conclusion. The lactational epithelium did not show overexpression of GR, while GR was overexpressed in mammary NST (ductal carcinoma, particularly HER-2-negative cancers.

  1. Role of human papillomavirus in oral squamous cell carcinoma and oral potentially malignant disorders: A review of the literature

    Science.gov (United States)

    Gupta, Shikha; Gupta, Sunita

    2015-01-01

    Human papillomaviruses (HPVs) are epitheliotropic viruses with an affinity for keratinocytes and are principally found in the anogenital tract, urethra, skin, larynx, tracheobronchial and oral mucosa. On the basis of high, but variable frequency of HPV in oral squamous cell carcinoma (OSCC), malignant potential of HPV infection has been hypothesized but not definitely confirmed. The aim of this review was to highlight the genomic structure and possible mechanism of infection and carcinogenesis by HPV in the oral mucosa and to review the frequency of HPV prevalence in OSCC and oral potentially malignant disorders. A computer database search was performed through the use of PubMed from 1994 to 2014. Search keywords used were: HPV and oral cancer, HPV and oral leukoplakia, HPV and oral lichen planus, HPV and OSCC, HPV and verrucous carcinoma, HPV and proliferative verrucous leukoplakia, HPV and oral papilloma. PMID:26097339

  2. Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Diagnostic Evaluation of Carcinoma Urinary Bladder: Comparison with Computed Tomography

    International Nuclear Information System (INIS)

    Chakraborty, Dhritiman; Mittal, Bhagwant Rai; Kashyap, Raghava; Mete, Utham Kumar; Narang, Vikram; Das, Ashim; Bhattacharya, Anish; Khandelwal, Niranjan; Mandal, Arup K.

    2014-01-01

    Bladder carcinoma is the most frequent tumor of the urinary tract and accounts 7% of all malignancies in men and 2% of all malignancies in women. This retrospective study was carried out to assess the diagnostic utility of F18-fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the imaging evaluation of bladder carcinoma. Seventy-seven consecutive patients diagnosed to have carcinoma urinary bladder referred for F18-FDG PET/CT were included in this study. Thirty-four patients were for initial staging after transurethral biopsy and remaining 43 patients were for restaging. All patients also underwent CT scan of the abdomen and pelvis. PET/CT findings were correlated with diagnostic CT scan and histopathological findings. In 30 of the 34 patients for initial staging, both PET/CT and CT confirmed the primary lesion in the bladder. Histopathology report was available in 23 patients. Lymph nodes FDG uptake reported to be metastatic in 10/23 patients while CT detected lymph node metastasis in 12 patients. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy have been calculated to be 87.5%, 80%, 70%, 92%, 82% for PET/CT and 66%, 57%, 50%, 72%, 60% for CT respectively. PET/CT detected metastatic disease in 8 patients whereas CT detected in 4 patients. Of the 43 patients for restaging, local recurrence was detected in 24 patients on both PET/CT and CT. Histopathology report was available in 17 patients. Sensitivity, specificity, PPV, NPV and accuracy were 85%, 60%, 60%, 85%, 70% for PET/CT and 80%, 50%, 40%, 85%, 58% for CT respectively. Nineteen patients were detected to have metastatic disease by PET/CT, whereas CT detected metastases in 11 patients. F-18 FDG PET/CT is a very useful modality in pre-operative staging and monitoring after surgery, chemotherapy or radiotherapy of patients with carcinoma urinary bladder

  3. The Role of Compounds Derived from Natural Supplement as Anticancer Agents in Renal Cell Carcinoma: A Review

    OpenAIRE

    Haque, Inamul; Subramanian, Arvind; Huang, Chao H.; Godwin, Andrew K.; Van Veldhuizen, Peter J.; Banerjee, Snigdha; Banerjee, Sushanta K.

    2017-01-01

    Renal Cell Carcinoma (RCC) is the most prominent kidney cancer derived from renal tubules and accounts for roughly 85% of all malignant kidney cancer. Every year, over 60,000 new cases are registered, and about 14,000 people die from RCC. The incidence of this has been increasing significantly in the U.S. and other countries. An increased understanding of molecular biology and the genomics of RCC has uncovered several signaling pathways involved in the progression of this cancer. Significant ...

  4. [The Role of 5-Aza-CdR on Methylation of Promoter in RASSF1A Gene in Endometrial Carcinoma].

    Science.gov (United States)

    Huang, Li-ping; Chen, Chen; Wang, Xue-ping; Liu, Hui

    2015-05-01

    To explore the effect of demethylating drug 5-Aza-2'-deoxycytidine (5-Aza-CdR) on methtylation status of the Ras-association domain familylA gene (RASSF1A) in human endometrial carcinoma. Randomly'assign the human endometrial carcinoma cell line HEC-1-B into groups and use demethylating drug 5-Aza-CdR of different concentration to treat them. Then Methylation-specific polymerase chain reaction (MSP), real-time PCR, Western blot, TUNEL technology were used to analyze methylation status of RASSF1A promoter CpG islands, RASSF1A mRNA expression, RASSF1A protein expression and apoptosis of HEC-1-B cell. High DNA methylation in RASSF1A gene promoter region, low RASSF1A mRNA level and protein expression and out of control of human endometrial carcinoma cell HEC-1-B apoptosis were observed. 5-Aza-CdR of different concentration could reverse RASSF1A gene's methylation status, recover the expression of mRNA and protein, and control the growth of HEC-1-B by inducing apoptosis. Aberrant methylation of RASSF1A in endometrial cancer as a therapeutic target, demethylating agent 5-Aza-CdR could be an effective way of gene therapy.

  5. Role of brachytherapy in treatment of epidermoid carcinomas of the vallecula after conservative supraglottic laryngectomy followed by irradiation

    International Nuclear Information System (INIS)

    Clippe, Sebastien; Pommier, Pascal; Poupart, Marc; Ceruse, Philippe; Rosenbusch, Thomas; Ramade, Antoine; Montbarbon, Xavier; Gerard, Jean-Pierre; Carrie, Christian; Ardiet, Jean-Michel

    2002-01-01

    Purpose:To evaluate survival and functional results of the treatment of carcinomas of the vallecula using surgery, irradiation, and interstitial brachytherapy. Methods and Materials: Between 1990 and 1998, 36 patients with squamous cell carcinoma of the vallecula were treated with horizontal supraglottic functional laryngectomy, external beam radiotherapy (median dose 54 Gy), and additional interstitial brachytherapy (median dose 16 Gy). Results were compared with a previous series of 22 patients treated without brachytherapy. Results: The median follow-up was 44 months. The 5-year actuarial overall survival rate was 61.3%. The 5-year specific survival rate was 86%, with 2 local failures (local control rate 94.4%) and 4 isolated distant metastases. Ten patients developed a second primary. The overall survival was 34% for 22 patients previously treated without brachytherapy. Severe toxicities occurred in 9 patients: death (related to larynx edema or inhalation, n=1), soft tissue necrosis (n=1), aspiration pneumonia (n=1), mandibular necrosis (n=2), pharyngocutaneous fistula (n=2), and laryngeal edema (n=2). All the patients fed orally with no definitive gastrostomy or tracheotomy. Conclusion: Additional brachytherapy for vallecula carcinoma seems to improve locoregional control and overall survival dramatically. Functional results were also excellent. To our knowledge, this original therapeutic schedule has never been previously described

  6. Capsicum annuum homeobox 1 (CaHB1) is a nuclear factor that has roles in plant development, salt tolerance, and pathogen defense

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Sang-Keun; Yoon, Joonseon [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seou1 151-742 (Korea, Republic of); Choi, Gyung Ja [Screening Division, Korea Research Institute of Chemical Technology, Daejeon 305-600 (Korea, Republic of); Jang, Hyun A; Kwon, Suk-Yoon [Korea Research Institute of Bioscience and Biotechnology, Yusung, Daejeon 305-600 (Korea, Republic of); Choi, Doil, E-mail: doil@snu.ac.kr [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seou1 151-742 (Korea, Republic of)

    2013-12-06

    Highlights: •The CaHB1 is a nuclear factor, belonging to HD-Zip proteins. •SA and ET, as signal molecules, modulate CaHB1-mediated responses. •Overexpression of CaHB1 in tomato resulted in a thicker cell wall. •CaHB1-transgenic tomato confers resistance to Phytophthora infestans. •CaHB1 enhanced tolerance to saline stress in tomato. -- Abstract: Homeodomain-leucine zipper (HD-Zip) family proteins are unique to plants, but little is known about their role in defense responses. CaHB1 is a nuclear factor in peppers, belonging to subfamily II of HD-Zip proteins. Here, we determined the role of CaHB1 in the defense response. CaHB1 expression was induced when pepper plants were challenged with Phytophthora capsici, a plant pathogen to which peppers are susceptible, or environmental stresses such as drought and salt stimuli. CaHB1 was also highly expressed in pepper leaves following application of SA, whereas ethephon and MeJA had a moderate effect. To further investigate the function of CaHB1 in plants, we performed gain-of-function study by overexpression of CaHB1 in tomato. CaHB1-transgenic tomatoes showed significant growth enhancement including increased leaf thickness and enlarged cell size (1.8-fold larger than control plants). Microscopic analysis revealed that leaves from CaHB1-transgenic plants had thicker cell walls and cuticle layers than those from controls. Moreover, CaHB1-transgenic plants displayed enhanced resistance against Phytophthora infestans and increased tolerance to salt stress. Additionally, RT-PCR analysis of CaHB1-transgenic tomatoes revealed constitutive up-regulation of multiple genes involved in plant defense and osmotic stress. Therefore, our findings suggest roles for CaHB1 in development, salt stress, and pathogen defense.

  7. Capsicum annuum homeobox 1 (CaHB1) is a nuclear factor that has roles in plant development, salt tolerance, and pathogen defense

    International Nuclear Information System (INIS)

    Oh, Sang-Keun; Yoon, Joonseon; Choi, Gyung Ja; Jang, Hyun A; Kwon, Suk-Yoon; Choi, Doil

    2013-01-01

    Highlights: •The CaHB1 is a nuclear factor, belonging to HD-Zip proteins. •SA and ET, as signal molecules, modulate CaHB1-mediated responses. •Overexpression of CaHB1 in tomato resulted in a thicker cell wall. •CaHB1-transgenic tomato confers resistance to Phytophthora infestans. •CaHB1 enhanced tolerance to saline stress in tomato. -- Abstract: Homeodomain-leucine zipper (HD-Zip) family proteins are unique to plants, but little is known about their role in defense responses. CaHB1 is a nuclear factor in peppers, belonging to subfamily II of HD-Zip proteins. Here, we determined the role of CaHB1 in the defense response. CaHB1 expression was induced when pepper plants were challenged with Phytophthora capsici, a plant pathogen to which peppers are susceptible, or environmental stresses such as drought and salt stimuli. CaHB1 was also highly expressed in pepper leaves following application of SA, whereas ethephon and MeJA had a moderate effect. To further investigate the function of CaHB1 in plants, we performed gain-of-function study by overexpression of CaHB1 in tomato. CaHB1-transgenic tomatoes showed significant growth enhancement including increased leaf thickness and enlarged cell size (1.8-fold larger than control plants). Microscopic analysis revealed that leaves from CaHB1-transgenic plants had thicker cell walls and cuticle layers than those from controls. Moreover, CaHB1-transgenic plants displayed enhanced resistance against Phytophthora infestans and increased tolerance to salt stress. Additionally, RT-PCR analysis of CaHB1-transgenic tomatoes revealed constitutive up-regulation of multiple genes involved in plant defense and osmotic stress. Therefore, our findings suggest roles for CaHB1 in development, salt stress, and pathogen defense

  8. Mobilisation and remobilisation of a large archetypal pathogenicity island of uropathogenic Escherichia coli in vitro support the role of conjugation for horizontal transfer of genomic islands

    Directory of Open Access Journals (Sweden)

    Hochhut Bianca

    2011-09-01

    Full Text Available Abstract Background A substantial amount of data has been accumulated supporting the important role of genomic islands (GEIs - including pathogenicity islands (PAIs - in bacterial genome plasticity and the evolution of bacterial pathogens. Their instability and the high level sequence similarity of different (partial islands suggest an exchange of PAIs between strains of the same or even different bacterial species by horizontal gene transfer (HGT. Transfer events of archetypal large genomic islands of enterobacteria which often lack genes required for mobilisation or transfer have been rarely investigated so far. Results To study mobilisation of such large genomic regions in prototypic uropathogenic E. coli (UPEC strain 536, PAI II536 was supplemented with the mobRP4 region, an origin of replication (oriVR6K, an origin of transfer (oriTRP4 and a chloramphenicol resistance selection marker. In the presence of helper plasmid RP4, conjugative transfer of the 107-kb PAI II536 construct occured from strain 536 into an E. coli K-12 recipient. In transconjugants, PAI II536 existed either as a cytoplasmic circular intermediate (CI or integrated site-specifically into the recipient's chromosome at the leuX tRNA gene. This locus is the chromosomal integration site of PAI II536 in UPEC strain 536. From the E. coli K-12 recipient, the chromosomal PAI II536 construct as well as the CIs could be successfully remobilised and inserted into leuX in a PAI II536 deletion mutant of E. coli 536. Conclusions Our results corroborate that mobilisation and conjugal transfer may contribute to evolution of bacterial pathogens through horizontal transfer of large chromosomal regions such as PAIs. Stabilisation of these mobile genetic elements in the bacterial chromosome result from selective loss of mobilisation and transfer functions of genomic islands.

  9. Vulvar carcinoma

    International Nuclear Information System (INIS)

    Anderson, John M.; Cassady, J. Robert; Shimm, David S.; Stea, Baldassarre

    1995-01-01

    Purpose: Controversies exist regarding the use of radiation therapy in the treatment of vulvar carcinoma. A retrospective review was performed to evaluate our institution's experience with surgery and radiation for this disease. Methods and Materials: The medical records of 47 patients treated for squamous cell carcinoma of the vulva at our institution (1974-1992) were reviewed for TNM stage (AJCC criteria), treatment modality, and associated 5-year local control and survival based on Kaplan-Meier analysis. Results: Twenty-eight patients (60%) presented with Stage I and II disease and their 5-year survival was 69%. Stage III patients accounted for 12 (25%) of the patients and their 5-year survival was 73%. Seven patients presented with Stage IV disease and five died within 13 months of diagnosis after predominantly palliative therapy. The 40 patients with Stages I, II, and III disease were treated aggressively and were further evaluated for treatment-modality-associated survival and local control. Radiation therapy was used as primary treatment in nine patients, of whom seven were treated with radiation alone and two were treated postoperatively after wide excision. Surgery alone was performed in 31 patients consisting of either radical vulvectomy (20 patients) or wide excision (11 patients). When comparing outcomes of radical vulvectomy vs. radiation therapy, we noted that the 5-year actuarial survivals were comparable (74% for either modality), despite the presence of more favorable prognostic factors in the group treated with radical vulvectomy. Patients treated with wide excision alone had a trend for a poorer 5-year actuarial survival (51%) and local control (50%). Conclusions: Radical vulvectomy offers good locoregional control and survival. This retrospective review further supports the use of radiation therapy with conservative surgery as an alternative treatment option for patients with vulvar carcinoma treated with curative intent. In contrast, the use of

  10. Role of Sterylglucosidase 1 (Sgl1) on the pathogenicity of Cryptococcus neoformans: potential applications for vaccine development.

    Science.gov (United States)

    Rella, Antonella; Mor, Visesato; Farnoud, Amir M; Singh, Ashutosh; Shamseddine, Achraf A; Ivanova, Elitza; Carpino, Nicholas; Montagna, Maria T; Luberto, Chiara; Del Poeta, Maurizio

    2015-01-01

    Cryptococcosis caused by Cryptococcus neoformans and Cryptococcus gattii affects a large population and is a cause of significant morbidity and mortality. Despite its public health burden, there are currently no vaccines against cryptococcosis and new strategies against such infections are needed. In this study, we demonstrate that C. neoformans has the biochemical ability to metabolize sterylglucosides (SGs), a class of immunomodulatory glycolipids. Genetic manipulations that eliminate cryptococccal sterylglucosidase lead to the accumulation of SGs and generate a mutant strain (Δsgl1) that is non-pathogenic in the mouse models of cryptococcosis. Interestingly, this mutant strain acts as a vaccine strain and protects mice against cryptococcosis following infection with C. neoformans or C. gattii. The immunity induced by the Δsgl1 strain is not CD4(+) T-cells dependent. Immunocompromised mice, which lack CD4(+) T-cells, are able to control the infection by Δsgl1 and acquire immunity against the challenge by wild-type C. neoformans following vaccination with the Δsgl1 strain. These findings are particularly important in the context of HIV/AIDS immune deficiency and suggest that the Δsgl1 strain might provide a potential vaccination strategy against cryptococcosis.

  11. Wall ingrowth deposition in phloem parenchyma transfer cells in Arabidopsis: Heteroblastic variations and a potential role in pathogen defence.

    Science.gov (United States)

    Nguyen, Suong T T; McCurdy, David W

    2017-06-03

    Transfer cell (TCs) develop unique wall ingrowth networks which amplify plasma membrane surface area and thus maximize nutrient transporter density at key anatomic sites for nutrient exchange within plants and their external environment. These sites fall into 4 main groups corresponding to 4 categories of trans-membrane flux: absorption/secretion of solutes from or to the external environment, and absorption/secretion of solutes from or to internal, extra-cytoplasmic compartments. Research on TC biology over recent decades has demonstrated correlations between wall ingrowth deposition in TCs and enhanced transport capacity in many major agricultural species such as pea, fava bean, cotton and maize. Consequently, there is general consensus that the existence of wall ingrowth morphology implies an augmentation in membrane transport capacity. However, this may not be entirely applicable for phloem parenchyma (PP) TCs in Arabidopsis. Our recent survey of PP TC abundance and distribution in Arabidopsis veins indicated that PP TC development reflects heteroblastic status. A consequence of this observation is the suggestion that PP TCs, or at least wall ingrowth deposition in these cells, potentially act as a physical barrier to defend access of invading pathogens to sugar-rich sieve elements rather than solely in facilitating the export of photoassimilate from collection phloem in leaves.

  12. Role of RpoS in virulence and stress tolerance of the plant pathogen Erwinia carotovora subsp. carotovora.

    Science.gov (United States)

    Andersson, R A; Kõiv, V; Norman-Setterblad, C; Pirhonen, M

    1999-12-01

    The plant-pathogenic bacterium Erwinia carotovora subsp. carotovora causes plant disease mainly through a number of extracellular plant-cell-wall-degrading enzymes. In this study, the ability of an rpoS mutant of the Er. carotovora subsp. carotovora strain SCC3193 to infect plants and withstand environmental stress was characterized. This mutant was found to be sensitive to osmotic and oxidative stresses in vitro and to be deficient in glycogen accumulation. The production of extracellular enzymes in vitro was similar in the mutant and in the wild-type strains. However, the rpoS mutant caused more severe symptoms than the wild-type strain on tobacco plants and also produced more extracellular enzymes in planta, but did not grow to higher cell density in planta compared to the wild-type strain. When tested on plants with reduced catalase activities, which show higher levels of reactive oxygen species, the rpoS mutant was found to cause lower symptom levels and to have impaired growth. In addition, the mutant was unable to compete with the wild-type strain in planta and in vitro. These results suggest that a functional rpoS gene is needed mainly for survival in a competitive environment and during stress conditions, and not for effective infection of plants.

  13. Reduction of quinones and phenoxy radicals by extracellular glucose dehydrogenase from Glomerella cingulata suggests a role in plant pathogenicity.

    Science.gov (United States)

    Sygmund, Christoph; Klausberger, Miriam; Felice, Alfons K; Ludwig, Roland

    2011-11-01

    The plant-pathogenic fungus Glomerella cingulata (anamorph Colletotrichum gloeosporoides) secretes high levels of an FAD-dependent glucose dehydrogenase (GDH) when grown on tomato juice-supplemented media. To elucidate its molecular and catalytic properties, GDH was produced in submerged culture. The highest volumetric activity was obtained in shaking flasks after 6 days of cultivation (3400 U l⁻¹, 4.2 % of total extracellular protein). GDH is a monomeric protein with an isoelectric point of 5.6. The molecular masses of the glycoforms ranged from 95 to 135 kDa, but after deglycosylation, a single 68 kDa band was obtained. The absorption spectrum is typical for an FAD-containing enzyme with maxima at 370 and 458 nm and the cofactor is non-covalently bound. The preferred substrates are glucose and xylose. Suitable electron acceptors are quinones, phenoxy radicals, 2,6-dichloroindophenol, ferricyanide and ferrocenium hexafluorophosphate. In contrast, oxygen turnover is very low. The GDH-encoding gene was cloned and phylogenetic analysis of the translated protein reveals its affiliation to the GMC family of oxidoreductases. The proposed function of this quinone and phenoxy radical reducing enzyme is to neutralize the action of plant laccase, phenoloxidase or peroxidase activities, which are increased in infected plants to evade fungal attack.

  14. The role of rodents in the ecology of Ixodes ricinus and associated pathogens in Central and Eastern Europe.

    Science.gov (United States)

    Mihalca, Andrei D; Sándor, Attila D

    2013-01-01

    Rodents comprise more species than any other mammal order. Most rodents are considered keystone species in their ecological communities, hence the survival of many other species in the ecosystem depend on them. From medical point of view, this is particularly important for rodent-dependent pathogens. In the particular case of tick-borne diseases, rodents are important as hosts for vector ticks and as reservoir hosts (Lyme borreliosis, human granulocytic anaplasmosis, Crimean-Congo hemorrhagic fever, Tick-borne relapsing fevers, tick-borne rickettsioses, babesiosis). Community and population ecology of rodents was shown to be correlated with disease ecology in the case of many tick-borne diseases. In Eastern Europe, several adult hard-tick species use rodents as their principal hosts: Ixodes apronophorus, I. crenulatus, I. laguri, I. redikorzevi, I. trianguliceps. However, the majority of ticks feeding on rodents are immature stages of ticks which as adults are parasitic on larger mammals. Larvae and nymphs of Ixodes ricinus, the most abundant and medically important tick from Europe, are commonly found on rodents. This is particularly important, as many rodents are synanthropic and, together with other micromammals and birds are often the only available natural hosts for ticks in urban environments. This work reviews the correlated ecology of rodents and I. ricinus.

  15. A Role for Nonsense-Mediated mRNA Decay in Plants: Pathogen Responses Are Induced in Arabidopsis thaliana NMD Mutants

    Science.gov (United States)

    Rayson, Samantha; Arciga-Reyes, Luis; Wootton, Lucie; De Torres Zabala, Marta; Truman, William; Graham, Neil; Grant, Murray; Davies, Brendan

    2012-01-01

    Nonsense-mediated mRNA decay (NMD) is a conserved mechanism that targets aberrant mRNAs for destruction. NMD has also been found to regulate the expression of large numbers of genes in diverse organisms, although the biological role for this is unclear and few evolutionarily conserved targets have been identified. Expression analyses of three Arabidopsis thaliana lines deficient in NMD reveal that the vast majority of NMD-targeted transcripts are associated with response to pathogens. Congruently, NMD mutants, in which these transcripts are elevated, confer partial resistance to Pseudomonas syringae. These findings suggest a biological rationale for the regulation of gene expression by NMD in plants and suggest that manipulation of NMD could offer a new approach for crop protection. Amongst the few non-pathogen responsive NMD-targeted genes, one potential NMD targeted signal, the evolutionarily conserved upstream open reading frame (CuORF), was found to be hugely over-represented, raising the possibility that this feature could be used to target specific physiological mRNAs for control by NMD. PMID:22384098

  16. Identification of a new biocontrol gene in Trichoderma atroviride: the role of an ABC transporter membrane pump in the interaction with different plant-pathogenic fungi.

    Science.gov (United States)

    Ruocco, Michelina; Lanzuise, Stefania; Vinale, Francesco; Marra, Roberta; Turrà, David; Woo, Sheridan Lois; Lorito, Matteo

    2009-03-01

    Successful biocontrol interactions often require that the beneficial microbes involved are resistant or tolerant to a variety of toxicants, including antibiotics produced by themselves or phytopathogens, plant antimicrobial compounds, and synthetic chemicals or contaminants. The ability of Trichoderma spp., the most widely applied biocontrol fungi, to withstand different chemical stresses, including those associated with mycoparasitism, is well known. In this work, we identified an ATP-binding cassette transporter cell membrane pump as an important component of the above indicated resistance mechanisms that appears to be supported by an extensive and powerful cell detoxification system. The encoding gene, named Taabc2, was cloned from a strain of Trichoderma atroviride and characterized. Its expression was found to be upregulated in the presence of pathogen-secreted metabolites, specific mycotoxins and some fungicides, and in conditions that stimulate the production in Trichoderma spp. of antagonism-related factors (toxins and enzymes). The key role of this gene in antagonism and biocontrol was demonstrated by the characterization of the obtained deletion mutants. They suffered an increased susceptibility to inhibitory compounds either secreted by pathogenic fungi or possibly produced by the biocontrol microbe itself and lost, partially or entirely, the ability to protect tomato plants from Pythium ultimum and Rhizoctonia solani attack.

  17. [Pulmonary sarcomatoid carcinoma].

    Science.gov (United States)

    Antoine, Martine; Vieira, Thibault; Fallet, Vincent; Hamard, Cécile; Duruisseaux, Michael; Cadranel, Jacques; Wislez, Marie

    2016-01-01

    Pulmonary sarcomatoid carcinomas are a rare group of tumors accounting for about one percent of non-small cell lung carcinoma (NSCLC). In 2015, the World Health Organization classification united under this name all the carcinomas with sarcomatous-like component with spindle cell or giant cell appearance, or associated with a sarcomatous component sometimes heterologous. There are five subtypes: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. Clinical characteristics are not specific from the other subtypes of NSCLC. Epithelial to mesenchymal transition pathway may play a key role. Patients, usually tobacco smokers, are frequently symptomatic. Tumors are voluminous more often peripherical than central, with strong fixation on FDG TEP CT. Distant metastases are frequent with atypical visceral locations. These tumors have poorer prognosis than the other NSCLC subtypes because of great aggressivity, and frequent chemoresistance. Here we present pathological description and a review of literature with molecular features in order to better describe these tumors and perhaps introduce new therapeutics. Copyright © 2016. Published by Elsevier Masson SAS.

  18. TLR receptors in laryngeal carcinoma - immunophenotypic, molecular and functional studies.

    Directory of Open Access Journals (Sweden)

    Mirosław Szczepański

    2011-04-01

    Full Text Available Toll-like receptors (TLRs have been shown to play crucial role in the recognition of unicellular pathogens. We have shown the expression of three TLRs on tumor cells of human laryngeal carcinoma by means of immunohistochemistry. In the current study we searched presence of TLR1-10 on protein and molecular level in larynx carcinoma cell lines and the impact of respective TLR ligands on TLR expression. Larynx carcinoma cell lines have been used. Cell were subjected to immunocytochemistry. RNA isolated from the cells was tested by RT-PCR. Cells were cultured in the presence of respective TLR ligands. Cells than were harvested and subjected to flow cytometry, using anti TLR1-10 Moabs. The cells were evaluated of membrane and cytoplasmic cell staining. TLR reactivity varied in individual cell lines. RT-PCR allowed to show mRNA for all TLRs tested. After short-term cell culture each cell line exhibited distinct pattern of expression of TLRs following interaction with respective ligand. Cytoplasmic TLR staining had usually higher MFI value than membrane one, but after culture with ligand it became reversed. TLRs 7 and 9 showed highest expression in the majority of tumor cells tested. In conclusion, larynx carcinoma cell lines exhibit rather universal expression of TLRs, both on protein and molecular level. Culture of TLR expressing tumor cells with ligands points out for potential reactivity of tumor cells with TLR agonists, what may have therapeutic implications.

  19. Squamous Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Squamous cell carcinoma Overview Squamous cell carcinoma: This man's skin ... a squamous cell carcinoma on his face. Squamous cell carcinoma: Overview Squamous cell carcinoma (SCC) is a ...

  20. Quorum sensing in the plant pathogen Erwinia carotovora subsp. carotovora: the role of expR(Ecc).

    Science.gov (United States)

    Andersson, R A; Eriksson, A R; Heikinheimo, R; Mäe, A; Pirhonen, M; Kõiv, V; Hyytiäinen, H; Tuikkala, A; Palva, E T

    2000-04-01

    The production of the main virulence determinants of the plant pathogen Erwinia carotovora subsp. carotovora, the extracellular cell wall-degrading enzymes, is partly controlled by the diffusible signal molecule N-(3-oxohexanoyl)-L-homoserine lactone (OHHL). OHHL is synthesized by the product of the expI/carI gene. Linked to expI we found a gene encoding a putative transcriptional regulator of the LuxR-family. This gene, expR(Ecc), is transcribed convergently to the expI gene and the two open reading frames are partially overlapping. The ExpR(Ecc) protein showed extensive amino acid sequence similarity to the repressor EsaR from Pantoea stewartii subsp. stewartii (formerly Erwinia stewartii subsp. stewartii) and to the ExpR(Ech) protein of Erwinia chrysanthemi. Inactivation of the E. carotovora subsp. carotovora expR(Ecc) gene caused no decrease in virulence or production of virulence determinants in vitro. In contrast, there was a slight increase in the maceration capacity of the mutant strain. The effects of ExpR(Ecc) were probably mediated by changes in OHHL levels. Inactivation of expR(Ecc) resulted in increased OHHL levels during early logarithmic growth. In addition, overexpression of expR(Ecc) caused a clear decrease in the production of virulence determinants and part of this effect was likely to be caused by OHHL binding to ExpR(Ecc). ExpR(Ecc) did not appear to exhibit transcriptional regulation of expI, but the effect on OHHL was apparently due to other mechanisms.

  1. Subtle Hepatocellular Carcinoma: A Persisting Role for Alpha-Fetoprotein Monitoring in High-Risk Patients with Cirrhosis

    Directory of Open Access Journals (Sweden)

    Barry Schlansky

    2011-10-01

    Full Text Available Hepatocellular carcinoma (HCC is a common, aggressive malignancy that usually develops in a background of liver cirrhosis. Practice guidelines recommend screening of cirrhotic patients with ultrasound and more detailed imaging (computed tomography or magnetic resonance imaging if abnormalities are detected. The utility of alpha-fetoprotein levels in HCC surveillance is controversial. Although HCC risk differs by etiology of cirrhosis, screening and surveillance guidelines are uniform after cirrhosis is established. We report a case of rapidly progressive HCC occurring in a cirrhotic patient with multiple unique risk factors for neoplasia, detected by a rising alpha-fetoprotein level without imaging features of liver cancer.

  2. The role of TGF-β and its crosstalk with RAC1/RAC1b signaling in breast and pancreas carcinoma.

    Science.gov (United States)

    Melzer, Catharina; Hass, Ralf; von der Ohe, Juliane; Lehnert, Hendrik; Ungefroren, Hendrik

    2017-05-12

    This article focusses on the role of TGF-β and its signaling crosstalk with the RHO family GTPases RAC1 and RAC1b in the progression of breast and pancreatic carcinoma. The aggressive nature of these tumor types is mainly due to metastatic dissemination. Metastasis is facilitated by desmoplasia, a peculiar tumor microenvironment and the ability of the tumor cells to undergo epithelial-mesenchymal transition (EMT) and to adopt a motile and invasive phenotype. These processes are controlled entirely or in part by TGF-β and the small RHO GTPase RAC1 with both proteins acting as tumor promoters in late-stage cancers. Data from our and other studies point to signaling crosstalk between TGF-β and RAC1 and the related isoform, RAC1b, in pancreatic and mammary carcinoma cells. Based on the exciting observation that RAC1b functions as an endogenous inhibitor of RAC1, we propose a model on how the relative abundance or activity of RAC1 and RAC1b in the tumor cells may determine their responses to TGF-β and, ultimately, the metastatic capacity of the tumor.

  3. Analysis of the Role of PET/CT SUVmax in Prognosis and Its Correlation with 
Clinicopathological Characteristics in Resectable Lung Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Hongliang REN

    2016-04-01

    Full Text Available Background and objective Lung cancer is the leading cause of cancer death in men and women in the world, more than one-half of cases are diagnosed at a advanced stage, and the overall 5-year survival rate for lung cancer is 18%. Lung cancer is divided into non-small cell lung carcinoma (NSCLC and small cell lung carcinoma (SCLC. Approximately 80%-85% of cases are NSCLC which includes three main types: adenocarcinoma (40%, squamous cell carcinoma (SCC (20%-30%, and large cell carcinoma (10%. Although therapies that target driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking-related SCC. We need pay more attention to the diagnosis and treatment of SCC. 18F-FDG positron emission tomography (PET/computed tomography (CT has emerged as an accurate staging modality in lung cancer diagnosis. The aim of this study is to investigate the role of maximum standardized uptake value (SUVmax on PET-CT in prognosis and its correlation with clinicopathological characteristics in resectable SCC. Methods One hundred and eighty-two resectable SCC patients who underwent PET/CT imaging between May 2005 and October 2014 were enrolled into this retrospectively study. All the enrolled patients had underwent pulmonary resection with mediastinal lymph node dissection without preoperative chemotherapy or radiotherapy. Survival outcomes were analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model. Correlation between SUVmax and clinicopathological factors was analysed using Pearson correlation analysis and Spearman rank correlation analysis. Results The patients were divided into two groups on the basis of SUVmax 13.0 as cutoff value, and patients with SUVmax more than 13.0 had shorter median overall survival than patients less than 13.0 in univariate analysis (56 months vs 87 months; P=0.022. There was remarkable correlation between SUVmax and gender, tumor size, tumor-node-metastasis (TNM stage

  4. [Analysis of the Role of PET/CT SUVmax in Prognosis and Its Correlation with 
Clinicopathological Characteristics in Resectable Lung Squamous Cell Carcinoma].

    Science.gov (United States)

    Ren, Hongliang; Xu, Wengui; You, Jian; Song, Xiuyu; Huang, Hui; Zhao, Ning; Ren, Xiubao; Zhang, Xinwei

    2016-04-20

    Lung cancer is the leading cause of cancer death in men and women in the world, more than one-half of cases are diagnosed at a advanced stage, and the overall 5-year survival rate for lung cancer is 18%. Lung cancer is divided into non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). Approximately 80%-85% of cases are NSCLC which includes three main types: adenocarcinoma (40%), squamous cell carcinoma (SCC) (20%-30%), and large cell carcinoma (10%). Although therapies that target driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking-related SCC. We need pay more attention to the diagnosis and treatment of SCC. 18F-FDG positron emission tomography (PET)/computed tomography (CT) has emerged as an accurate staging modality in lung cancer diagnosis. The aim of this study is to investigate the role of maximum standardized uptake value (SUVmax) on PET-CT in prognosis and its correlation with clinicopathological characteristics in resectable SCC. One hundred and eighty-two resectable SCC patients who underwent PET/CT imaging between May 2005 and October 2014 were enrolled into this retrospectively study. All the enrolled patients had underwent pulmonary resection with mediastinal lymph node dissection without preoperative chemotherapy or radiotherapy. Survival outcomes were analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model. Correlation between SUVmax and clinicopathological factors was analysed using Pearson correlation analysis and Spearman rank correlation analysis. The patients were divided into two groups on the basis of SUVmax 13.0 as cutoff value, and patients with SUVmax more than 13.0 had shorter median overall survival than patients less than 13.0 in univariate analysis (56 months vs 87 months; P=0.022). There was remarkable correlation between SUVmax and gender, tumor size, tumor-node-metastasis (TNM) stage, neutrophil, NLR, hemoglobin (Pdifference by

  5. RegA Plays a Key Role in Oxygen-Dependent Establishment of Persistence and in Isocitrate Lyase Activity, a Critical Determinant of In vivo Brucella suis Pathogenicity

    Directory of Open Access Journals (Sweden)

    Elias Abdou

    2017-05-01

    Full Text Available For aerobic human pathogens, adaptation to hypoxia is a critical factor for the establishment of persistent infections, as oxygen availability is low inside the host. The two-component system RegB/A of Brucella suis plays a central role in the control of respiratory systems adapted to oxygen deficiency, and in persistence in vivo. Using an original “in vitro model of persistence” consisting in gradual oxygen depletion, we compared transcriptomes and proteomes of wild-type and ΔregA strains to identify the RegA-regulon potentially involved in the set-up of persistence. Consecutive to oxygen consumption resulting in growth arrest, 12% of the genes in B. suis were potentially controlled directly or indirectly by RegA, among which numerous transcriptional regulators were up-regulated. In contrast, genes or proteins involved in envelope biogenesis and in cellular division were repressed, suggesting a possible role for RegA in the set-up of a non-proliferative persistence state. Importantly, the greatest number of the RegA-repressed genes and proteins, including aceA encoding the functional IsoCitrate Lyase (ICL, were involved in energy production. A potential consequence of this RegA impact may be the slowing-down of the central metabolism as B. suis progressively enters into persistence. Moreover, ICL is an essential determinant of pathogenesis and long-term interactions with the host, as demonstrated by the strict dependence of B. suis on ICL activity for multiplication and persistence during in vivo infection. RegA regulates gene or protein expression of all functional groups, which is why RegA is a key regulator of B. suis in adaptation to oxygen depletion. This function may contribute to the constraint of bacterial growth, typical of chronic infection. Oxygen-dependent activation of two-component systems that control persistence regulons, shared by several aerobic human pathogens, has not been studied in Brucella sp. before. This work

  6. Pathogen intelligence

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    Michael eSteinert

    2014-01-01

    Full Text Available Different species inhabit different sensory worlds and thus have evolved diverse means of processing information, learning and memory. In the escalated arms race with host defense, each pathogenic bacterium not only has evolved its individual cellular sensing and behaviour, but also collective sensing, interbacterial communication, distributed information processing, joint decision making, dissociative behaviour, and the phenotypic and genotypic heterogeneity necessary for epidemiologic success. Moreover, pathogenic populations take advantage of dormancy strategies and rapid evolutionary speed, which allow them to save co-generated intelligent traits in a collective genomic memory. This review discusses how these mechanisms add further levels of complexity to bacterial pathogenicity and transmission, and how mining for these mechanisms could help to develop new anti-infective strategies.

  7. The Role of Esophagogastric Anastomotic Technique in Decreasing Benign Stricture Formation in the Surgery of Esophageal Carcinoma

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    Sokouti Mohsen

    2013-03-01

    Full Text Available Introduction: Postoperative stenosis and dysphagia after esophageal carcinoma resection is the major problem. The aim of this study is to compare two types cervical esophagogastric anastomosis in reduction of stricture formation in esophageal cancer surgery. Methods: The subjects of this study were 223 patients undergoing esophageal carcinoma resection during 1998 to 2007. Twenty two patients were excluded from the study because of recurrent malignancy of anastomosis, mortality and losing in follow up period. Two hundred and one patients remained by the end of study were classified into two groups: 98 patients were treated by routinely transverse hand-sewn cervical esophagogastric anastomosis (group 1; and 103 patients were treated by the proposed oblique hand-sewn esophagogastric anastomotic technique (group 2. All the operations were with high abdominal and left cervical incisions (Transhiatal esophagectomy. All patients of both groups were followed up at least 6-month for detection of anastomotic strictures. Results: Postoperative dysphagia occurred in 20 patients of group 1 versus 5 patients of group 2. In working up by rigid esophagoscopy, two patients of group 2 and four patients of group 1 had not true strictures. Anastomotic strictures occurred in 16 cases of group 1, versus 3 cases of group 2. Statistical comparative analysis results of two groups about stricture formation were significant (3% versus 16% P= 0.003. Conclusion: The oblique hand-sewn esophagogastric anastomostic techniques reduce markedly the rate of stricture formation after esophagectomy.

  8. Repeated surgeries in invasive lobular breast cancer with preoperative MRI: Role of additional carcinoma in situ and background parenchymal enhancement.

    Science.gov (United States)

    Preibsch, H; Richter, V; Bahrs, S D; Hattermann, V; Wietek, B M; Bier, G; Kloth, C; Blumenstock, G; Hahn, M; Staebler, A; Nikolaou, K; Wiesinger, B

    2017-05-01

    Analysing the influence of additional carcinoma in situ (CIS) and background parenchymal enhancement (BPE) in preoperative MRI on repeated surgeries in patients with invasive lobular carcinoma (ILC) of the breast. Retrospective analysis of 106 patients (mean age 58.6±9.9years) with 108 ILC. Preoperative tumour size as assessed by MRI, mammography and sonography was recorded and compared to histopathology. In contrast-enhanced MRI, the degree of BPE was categorised by two readers. The influence of additionally detected CIS and BPE on the rate of repeated surgeries was analysed. Additional CIS was present in 45.4% of the cases (49/108). The degree of BPE was minimal or mild in 80% of the cases and moderate or marked in 20% of the cases. In 17 cases (15.7%) at least one repeated surgery was performed. In n=15 of these cases, repeated surgery was performed after BCT (n=9 re-excisions, n=6 conversions to mastectomy), in n=2 cases after initial mastectomy. The initial surgical procedure (p=0.008) and additional CIS (p=0.046) significantly influenced the rate of repeated surgeries, while tumour size, patient age and BPE did not (p=ns). Additional CIS was associated with a higher rate of repeated surgeries, whereas BPE had no influence. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Physiological and Pathogenic Roles of Prolyl Isomerase Pin1 in Metabolic Regulations via Multiple Signal Transduction Pathway Modulations

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    Yusuke Nakatsu

    2016-09-01

    Full Text Available Prolyl isomerases are divided into three groups, the FKBP family, Cyclophilin and the Parvulin family (Pin1 and Par14. Among these isomerases, Pin1 is a unique prolyl isomerase binding to the motif including pSer/pThr-Pro that is phosphorylated by kinases. Once bound, Pin1 modulates the enzymatic activity, protein stability or subcellular localization of target proteins by changing the cis- and trans-formations of proline. Several studies have examined the roles of Pin1 in the pathogenesis of cancers and Alzheimer’s disease. On the other hand, recent studies have newly demonstrated Pin1 to be involved in regulating glucose and lipid metabolism. Interestingly, while Pin1 expression is markedly increased by high-fat diet feeding, Pin1 KO mice are resistant to diet-induced obesity, non-alcoholic steatohepatitis and diabetic vascular dysfunction. These phenomena result from the binding of Pin1 to several key factors regulating metabolic functions, which include insulin receptor substrate-1, AMPK, Crtc2 and NF-κB p65. In this review, we focus on recent advances in elucidating the physiological roles of Pin1 as well as the pathogenesis of disorders involving this isomerase, from the viewpoint of the relationships between signal transductions and metabolic functions.

  10. Role of protein kinase C and epidermal growth factor receptor signalling in growth stimulation by neurotensin in colon carcinoma cells

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    Dajani Olav

    2011-10-01

    Full Text Available Abstract Background Neurotensin has been found to promote colon carcinogenesis in rats and mice, and proliferation of human colon carcinoma cell lines, but the mechanisms involved are not clear. We have examined signalling pathways activated by neurotensin in colorectal and pancreatic carcinoma cells. Methods Colon carcinoma cell lines HCT116 and HT29 and pancreatic adenocarcinoma cell line Panc-1 were cultured and stimulated with neurotensin or epidermal growth factor (EGF. DNA synthesis was determined by incorporation of radiolabelled thymidine into DNA. Levels and phosphorylation of proteins in signalling pathways were assessed by Western blotting. Results Neurotensin stimulated the phosphorylation of both extracellular signal-regulated kinase (ERK and Akt in all three cell lines, but apparently did so through different pathways. In Panc-1 cells, neurotensin-induced phosphorylation of ERK, but not Akt, was dependent on protein kinase C (PKC, whereas an inhibitor of the β-isoform of phosphoinositide 3-kinase (PI3K, TGX221, abolished neurotensin-induced Akt phosphorylation in these cells, and there was no evidence of EGF receptor (EGFR transactivation. In HT29 cells, in contrast, the EGFR tyrosine kinase inhibitor gefitinib blocked neurotensin-stimulated phosphorylation of both ERK and Akt, indicating transactivation of EGFR, independently of PKC. In HCT116 cells, neurotensin induced both a PKC-dependent phosphorylation of ERK and a metalloproteinase-mediated transactivation of EGFR that was associated with a gefitinib-sensitive phosphorylation of the downstream adaptor protein Shc. The activation of Akt was also inhibited by gefitinib, but only partly, suggesting a mechanism in addition to EGFR transactivation. Inhibition of PKC blocked neurotensin-induced DNA synthesis in HCT116 cells. Conclusions While acting predominantly through PKC in Panc-1 cells and via EGFR transactivation in HT29 cells, neurotensin used both these pathways in HCT116

  11. Role of protein kinase C and epidermal growth factor receptor signalling in growth stimulation by neurotensin in colon carcinoma cells

    International Nuclear Information System (INIS)

    Müller, Kristin M; Tveteraas, Ingun H; Aasrum, Monica; Ødegård, John; Dawood, Mona; Dajani, Olav; Christoffersen, Thoralf; Sandnes, Dagny L

    2011-01-01

    Neurotensin has been found to promote colon carcinogenesis in rats and mice, and proliferation of human colon carcinoma cell lines, but the mechanisms involved are not clear. We have examined signalling pathways activated by neurotensin in colorectal and pancreatic carcinoma cells. Colon carcinoma cell lines HCT116 and HT29 and pancreatic adenocarcinoma cell line Panc-1 were cultured and stimulated with neurotensin or epidermal growth factor (EGF). DNA synthesis was determined by incorporation of radiolabelled thymidine into DNA. Levels and phosphorylation of proteins in signalling pathways were assessed by Western blotting. Neurotensin stimulated the phosphorylation of both extracellular signal-regulated kinase (ERK) and Akt in all three cell lines, but apparently did so through different pathways. In Panc-1 cells, neurotensin-induced phosphorylation of ERK, but not Akt, was dependent on protein kinase C (PKC), whereas an inhibitor of the β-isoform of phosphoinositide 3-kinase (PI3K), TGX221, abolished neurotensin-induced Akt phosphorylation in these cells, and there was no evidence of EGF receptor (EGFR) transactivation. In HT29 cells, in contrast, the EGFR tyrosine kinase inhibitor gefitinib blocked neurotensin-stimulated phosphorylation of both ERK and Akt, indicating transactivation of EGFR, independently of PKC. In HCT116 cells, neurotensin induced both a PKC-dependent phosphorylation of ERK and a metalloproteinase-mediated transactivation of EGFR that was associated with a gefitinib-sensitive phosphorylation of the downstream adaptor protein Shc. The activation of Akt was also inhibited by gefitinib, but only partly, suggesting a mechanism in addition to EGFR transactivation. Inhibition of PKC blocked neurotensin-induced DNA synthesis in HCT116 cells. While acting predominantly through PKC in Panc-1 cells and via EGFR transactivation in HT29 cells, neurotensin used both these pathways in HCT116 cells. In these cells, neurotensin-induced activation of ERK

  12. The role of apparent diffusion coefficient value in evaluation of the response to preoperative chemoradiation in rectal carcinoma

    International Nuclear Information System (INIS)

    Sun Yingshi; Zhang Xiaopeng; Tang Lei; Li Jie; Cao Kun; Cui Yong; Qi Liping; Wang Ning

    2010-01-01

    Objective: To assess response of rectal carcinoma to preoperative chemoradiation therapy (CRT) using DWI and tumor ADC values, and to investigate the value of ADC in predicting and monitoring therapeutic effect of CRT. Methods: Twenty-six patients with primary rectal carcinoma undergoing preoperative CRT were recruited to the study. DWI was performed on a 1.5 T MR scanner in all patients at the time point of pre-therapy, the end of the 1st, 2nd week of therapy and pre-operation, respectively. ADC values of the tumors were calculated on the workstation. Randomized block design was applied to analyze cange in ADCs following treatment. Results All patients were divided into T-downstaging group (n=12) and T-non-downstaging group (n=14). In T-downstaging group, the mean tumor ADC values were (1.10 ± 0.13) x10 -3 , (1.32 ± 0.19) x 10 -3 , (1.35 ± 0.13) x 10 -3 , (1.32 ± 1.00) x 10 -3 mm 2 /s at the time point of pretreatment, week 1, week 2, pre-operation, respectively (F =16.420, P -3 mm 2 /s to (1.23 ± 0.13) x 10 -3 mm 2 /s at the time of week 1 (P>0.05). The ADC value in T-non-downstaging group continuously increased to (1.30 ± 0.16) x 10 -3 mm 2 /s at the end of the 2nd week of CRT (F=5.023, P st week as a diagnostic marker of tumor downstaging, when it was set as 11.6%, the sensitivity, specificity, positive predictive value and negative predictive value is 75.0%, 78.6%, 75.0% and 78.6% respectively, the area under curve (Az) was 0.774 (95% confidence interval: 0.583 to 0.964). Conclusions: An early significant increase of mean tumor ADC value in rectal carcinoma has a potential to predict therapeutic effect of CRT. One week after beginning CRT is an early time point to monitor therapy efficacy. (authors)

  13. Nitrate assimilation pathway (NAP): role of structural (nit) and transporter (ntr1) genes in Fusarium oxysporum f.sp. lycopersici growth and pathogenicity.

    Science.gov (United States)

    Gomez-Gil, Lucia; Camara Almiron, Jesus; Rodriguez Carrillo, Patricia Lizett; Olivares Medina, Cindy Nayely; Bravo Ruiz, Gustavo; Romo Rodriguez, Pamela; Corrales Escobosa, Alma Rosa; Gutierrez Corona, Felix; Roncero, M Isabel

    2018-04-01

    The tomato pathogen Fusarium oxysporum f.sp. lycopersici possesses the capability to use nitrate as the only nitrogen source under aerobic and anaerobic conditions and to activate virulence-related functions when cultivated in the presence of nitrate, but not in ammonium. The genome of F. oxysporum f.sp. lycopersici encodes three paralogs nitrate reductase (NR) genes (nit1, nit2 and nit3) and one predicted ortholog of the Aspergillus nidulans high-affinity nitrate/nitrite transporters NtrA and NtrB, named ntr1. We set out to clarify the role of nit1, nit2, nit3 and ntr1 genes in nitrate assimilation and in the virulence of F. oxysporum f.sp. lycopersici. Quantitative RT-PCR analysis revealed that only nit1, nit2 and ntr1 are expressed at significant levels during growth in nitrate as the only nitrogen source. Targeted deletion of nit1 and ntr1, but not of nit2 or nit3, severely impaired growth of F. oxysporum on nitrate as nitrogen source, indicating that Nit1 and Ntr1 proteins are involved in nitrate assimilation by the fungus; biochemical analysis of nit mutants indicated that Nit1 and Nit2 enzymes contribute to about 50 and 30% of the total NR activity, respectively. In addition, a spontaneous chlorate-resistant mutant derived from F. oxysporum 4287, denoted NitFG, was characterized, showing inability to grow in nitrate under aerobic and anaerobic conditions and low levels of NR activity, in spite of its increased transcription levels of nit1 and nit2 genes. Tomato plant infection assays showed that NitFG and ∆ntr1 mutants induced an earlier death in tomato plants, whereas the single mutants ∆nit1, ∆nit2 and ∆nit1∆nit2 double mutant showed a mortality rate similar to the wild-type strain. Taken together, these results indicate that the Nit1 and Ntr1 proteins are important for nitrate assimilation of F. oxysporum f.sp. lycopersici incubated under aerobic and anaerobic conditions and that this metabolic process is not essential for the virulence of

  14. The MqsRA Toxin-Antitoxin System from Xylella fastidiosa Plays a Key Role in Bacterial Fitness, Pathogenicity, and Persister Cell Formation

    Science.gov (United States)

    Merfa, Marcus V.; Niza, Bárbara; Takita, Marco A.; De Souza, Alessandra A.

    2016-01-01

    Through the formation of persister cells, bacteria exhibit tolerance to multidrug and other environmental stresses without undergoing genetic changes. The toxin-antitoxin (TA) systems are involved in the formation of persister cells because they are able to induce cell dormancy. Among the TA systems, the MqsRA system has been observed to be highly induced in persister cells of Xylella fastidiosa (causal agent of citrus variegated chlorosis—CVC) activated by copper stress, and has been described in Escherichia coli as related to the formation of persister cells and biofilms. Thus, we evaluated the role of this TA system in X. fastidiosa by overexpressing the MqsR toxin, and verified that the toxin positively regulated biofilm formation and negatively cell movement, resulting in reduced pathogenicity in citrus plants. The overexpression of MqsR also increased the formation of persister cells under copper stress. Analysis of the gene and protein expression showed that this system likely has an autoregulation mechanism to express the toxin and antitoxin in the most beneficial ratio for the cell to oppose stress. Our results suggest that this TA system plays a key role in the adaptation and survival of X. fastidiosa and reveal new insights into the physiology of phytopathogen-host interactions. PMID:27375608

  15. NpPDR1, a Pleiotropic Drug Resistance-Type ATP-Binding Cassette Transporter from Nicotiana plumbaginifolia, Plays a Major Role in Plant Pathogen Defense1

    Science.gov (United States)

    Stukkens, Yvan; Bultreys, Alain; Grec, Sébastien; Trombik, Tomasz; Vanham, Delphine; Boutry, Marc

    2005-01-01

    Nicotiana plumbaginifolia NpPDR1, a plasma membrane pleiotropic drug resistance-type ATP-binding cassette transporter formerly named NpABC1, has been suggested to transport the diterpene sclareol, an antifungal compound. However, direct evidence for a role of pleiotropic drug resistance transporters in the plant defense is still lacking. In situ immunolocalization and histochemical analysis using the gusA reporter gene showed that NpPDR1 was constitutively expressed in the whole root, in the leaf glandular trichomes, and in the flower petals. However, NpPDR1 expression was induced in the whole leaf following infection with the fungus Botrytis cinerea, and the bacteria Pseudomonas syringae pv tabaci, Pseudomonas fluorescens, and Pseudomonas marginalis pv marginalis, which do not induce a hypersensitive response in N. plumbaginifolia, whereas a weaker response was observed using P. syringae pv syringae, which does induce a hypersensitive response. Induced NpPDR1 expression was more associated with the jasmonic acid than the salicylic acid signaling pathway. These data suggest that NpPDR1 is involved in both constitutive and jasmonic acid-dependent induced defense. Transgenic plants in which NpPDR1 expression was prevented by RNA interference showed increased sensitivity to sclareol and reduced resistance to B. cinerea. These data show that NpPDR1 is involved in pathogen resistance and thus demonstrate a new role for the ATP-binding cassette transporter family. PMID:16126865

  16. NpPDR1, a pleiotropic drug resistance-type ATP-binding cassette transporter from Nicotiana plumbaginifolia, plays a major role in plant pathogen defense.

    Science.gov (United States)

    Stukkens, Yvan; Bultreys, Alain; Grec, Sébastien; Trombik, Tomasz; Vanham, Delphine; Boutry, Marc

    2005-09-01

    Nicotiana plumbaginifolia NpPDR1, a plasma membrane pleiotropic drug resistance-type ATP-binding cassette transporter formerly named NpABC1, has been suggested to transport the diterpene sclareol, an antifungal compound. However, direct evidence for a role of pleiotropic drug resistance transporters in the plant defense is still lacking. In situ immunolocalization and histochemical analysis using the gusA reporter gene showed that NpPDR1 was constitutively expressed in the whole root, in the leaf glandular trichomes, and in the flower petals. However, NpPDR1 expression was induced in the whole leaf following infection with the fungus Botrytis cinerea, and the bacteria Pseudomonas syringae pv tabaci, Pseudomonas fluorescens, and Pseudomonas marginalis pv marginalis, which do not induce a hypersensitive response in N. plumbaginifolia, whereas a weaker response was observed using P. syringae pv syringae, which does induce a hypersensitive response. Induced NpPDR1 expression was more associated with the jasmonic acid than the salicylic acid signaling pathway. These data suggest that NpPDR1 is involved in both constitutive and jasmonic acid-dependent induced defense. Transgenic plants in which NpPDR1 expression was prevented by RNA interference showed increased sensitivity to sclareol and reduced resistance to B. cinerea. These data show that NpPDR1 is involved in pathogen resistance and thus demonstrate a new role for the ATP-binding cassette transporter family.

  17. Evaluating the Trends of Bloodstream Infections among Pediatric and Adult Patients at a Teaching Hospital of Kathmandu, Nepal: Role of Drug Resistant Pathogens

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    Narayan Prasad Parajuli

    2017-01-01

    Full Text Available Bloodstream infections (BSIs are among the significant causes of morbidity and mortality for patients of all age groups. However, very little is known about the trends of bacterial bloodstream infections and antimicrobial susceptibilities among pediatric and adult population from Nepal. In this study, we have investigated the different etiological agents responsible for bloodstream infections among pediatric and adult patients and the role of drug resistant organisms in these infections at a tertiary care teaching hospital of Kathmandu, Nepal. A total of 3,088 blood culture specimens obtained from pediatric and adult patients suspected to have bloodstream infections were processed by standard microbiological methods. Significant bacterial pathogens were identified by morphological, biochemical, and serological methods as suggested by American Society for Microbiology. In vitro antimicrobial susceptibility testing was performed by Kirby-Bauer disk diffusion method and interpreted according to the guidelines of Clinical and Laboratory Standards Institute. Overall, incidence of bloodstream infections among the suspected patients was 7.48%. Pediatric patients (n=90, 9.37% were the significant subgroup of patients affected with bloodstream infections compared to adults (p<0.05, CI-95%. Gram positive (n=49, 54.4% bacteria in pediatric and gram negative bacteria (n=141, 78.7% in adult patients were the most common isolates for BSI. Staphylococcus aureus (n=41, 45.6% in pediatric patients and Salmonella enterica (n=40, 28.3% in adult patients were the leading pathogens. Trends of antimicrobial resistance among isolated bacterial strains were significantly high in adults compared to pediatric patients. Methicillin resistant Staphylococcus aureus (MRSA (31.4%, extended spectrum beta-lactamase (ESBL (12.5%, and metallo-beta-lactamase (MBL (3.9% producing gram negatives were major resistant strains. Our study shows higher rates of bloodstream infections in

  18. Supporting Treatment Decisions in Patients with Differentiated Thyroid Carcinoma (DTC) under Radioiodine-131 Therapy: Role of Biological Dosimetry Assessment

    International Nuclear Information System (INIS)

    Fadel, A.M.; Chebel, G.M.; Di Giorgio, M.; Vallerga, M.B.; Taja, M.R.; Radl, A.; Bubniak, R.V.; Oneto, A.

    2010-01-01

    Radioiodine-131 therapy is applied in patients with differentiated thyroid carcinoma (DTC), within the therapeutic scheme following thyroidectomy, for the ablation of thyroid remnants and treatment of metastatic disease. Several approaches for the selection of a therapeutic dose were applied. The aim of this therapy is to achieve a lethal dose in the tumor tissue, without exceeding the dose of tolerance in healthy tissues (doses greater than 2 Gy in bone marrow could lead to myelotoxicity). In this work, the treatment protocol used incorporates the assessment by biological dosimetry (BD) for estimating doses to whole body and bone marrow, to tailor patient's treatment. Biological Dosimetry prospective studies conducted on samples from patients with cumulative activities, before and after each therapeutic administration, allows to evaluate DNA damage and repair capacity in peripheral blood lymphocytes. (authors)

  19. Early onset sebaceous carcinoma

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    Kaltreider Sara A

    2011-09-01

    Full Text Available Abstract Background Ocular sebaceous carcinoma can masquerade as benign lesions resulting in delay of diagnosis. Early recognition is even more difficult in young patients where the disease rarely occurs. Here, we provide a clinicopathological correlation of ocular sebaceous carcinoma in a young individual lacking history of hereditary cancer or immunosuppression. Findings A detailed histopathological study including p53 DNA sequencing was performed on an aggressive sebaceous carcinoma presenting in a healthy 32 year-old Caucasian woman. She had no history of retinoblastoma, evidence for a hereditary cancer syndrome, or radiation therapy. However, she potentially was at risk for excessive UV light exposure. A detailed review of the literature is also provided. A moderately well differentiated sebaceous carcinoma was established histopathologically arising from the meibomian gland of the upper eyelid. In most areas, the cytoplasm contained small but distinct Oil-red-O positive vacuoles. Direct sequencing of p53 identified a G:C→A:T mutation at a dipyrimidine site. The mutation results in substitution of arginine for the highly conserved glycine at residue 199 located at the p53 dimer-dimer interface. Energy minimization structural modeling predicts that G199R will neutralize negative charges contributed by nearby inter- and intramonomeric glutamate residues. Discussion This study points to the importance of recognizing that sebaceous carcinoma can occur in young patients with no evidence for hereditary cancer risk or radiation therapy. The G199R substitution is anticipated to alter the stability of the p53 tetrameric complex. The role of UV light in the etiology of sebaceous carcinoma deserves further study. Our findings, taken together with those of others, suggest that different environmental factors could lead to the development of sebaceous carcinoma in different patients.

  20. The role of long noncoding RNA-LET in cell proliferation and invasion of nasopharyngeal carcinoma and its mechanism

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    Chen L

    2017-05-01

    Full Text Available Lei Chen,1,* Lingling Sun,1,* Lei Dong,2 Peng Cui,3 Ziwei Xia,4 Chao Li,1 Yu Zhu5 1Department of Otolaryngology, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Pediatrics, Division of Hematology/Oncology, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, GA, USA; 3Department of Multidisciplinary Consultation Center of TCM and Western Medicine, The Affiliated Qingdao Hiser Hospital of Qingdao University, Qingdao, 4Department of Clinical Medicine, The Second Clinical Medical School of Tianjin Medical University, 5Department of Clinical Laboratory, Tianjin Huanhu Hospital, Tianjin Key Laboratory of Cerebral Vessels and Neural Degeneration, Tianjin, People’s Republic of China *These authors contributed equally to this work Abstract: LncRNA-LET, a recently identified long noncoding RNA, has been shown to act as a tumor suppressor; however, its biological function and mechanism have not been fully investigated. Our research found that there was less expression of LET in nasopharyngeal carcinoma (NPC tissues than normal tissues and that LET might inhibit proliferation, adhesion and invasion of NPC in vitro by enhancing its expression. By contrast, decreased LET expression could promote the proliferation, adhesion and invasion of NPC. In addition, the expression profiles of related genes and MAPK/ERK pathway were also regulated effectively via overexpression or silencing of LET. This result provides comprehensive evidence of LET’s antitumor effect on NPC in vitro, which might provide a new approach for clinical treatment. Keywords: LncRNA-LET, proliferation, invasion, nasopharyngeal carcinoma, MAPK/ERK pathway

  1. Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma

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    Trojan J

    2016-09-01

    Full Text Available Jörg Trojan, Oliver Waidmann Medizinische Klinik 1, Universitätsklinikum Frankfurt, Germany Abstract: Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC. In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months. Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1 blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC. Keywords: hepatocellular carcinoma, receptor tyrosine kinase inhibitor, sorafenib, regorafenib, lenvatinib, tivantinib, cabozantinib, ramucirumab, immunotherapy, anti-CTLA-4, anti-PD-1, oncolytic virus

  2. Incidence trends in head and neck squamous cell carcinoma in Slovenia, 1983-2009: role of human papillomavirus infection.

    Science.gov (United States)

    Strojan, Primož; Zadnik, Vesna; Šifrer, Robert; Lanišnik, Boštjan; Didanović, Vojislav; Jereb, Sara; Poljak, Mario; Kocjan, Boštjan J; Gale, Nina

    2015-12-01

    An increase in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) was observed in several population-based registries and has been attributed to human papillomavirus (HPV) infection. In the present study, we aimed to assess the contribution of HPV infection to the burden of mucosal head and neck squamous cell carcinoma (HNSCC) in Slovenia. For this purpose, data from the nationwide Cancer Registry of Slovenia for cases diagnosed between 1983 and 2009 were analyzed to determine time trends of age-adjusted incidence rates and survival in terms of annual percentage change (APC) for HNSCC in potentially HPV-related and HPV-unrelated sites. In addition, determination of p16 protein, HPV DNA and E6/E7 mRNA was performed in a cohort of OPSCC patients identified from the prospective database for the years 2007-2008. In total, 2,862 cases of HNSCC in potentially HPV-related sites and 7,006 cases in potentially HPV-unrelated sites were identified with decreased incidence observed over the time period in both groups (-0.58; 95 % CI -1.28 to -0.13 and -0.90; 95 % CI -1.23 to -0.57). Regardless of the group, incidence trends for both genders showed a significant decrease in men and increase in women. In a cohort of 99 OPSCC patients diagnosed between 2007 and 2008, 20 (20.2 %) patients had HPV positive tumors and exhibited a superior outcome compared to HPV-negative patients. In conclusion, results of the epidemiologic and histopathologic study confirmed that HPV infection had no major impact on the incidence trends in the Slovenian patients with HNSCC and, specifically, OPSCC during the studied period.

  3. The Role of Cyclins and Cyclins Inhibitors in the Multistep Process of HPV-Associated Cervical Carcinoma

    International Nuclear Information System (INIS)

    Bahnassy, A.A.; Mokhtar, N.M.; Zekri, A.; Alam El-Din, H.M.; Aboubaker, A.A.; Kamel, K.; El-Sabah, M.T.

    2006-01-01

    Background: Human papillomavirus (HPV) types 16 and 18 are associated with cervical carcinogenesis. This is possibly achieved through an interaction between HPV oncogenic proteins and some cell cycle regulatory genes. However, the exact pathogenetic mechanisms are not well defined yet. Methods: We investigated 110 subjects (43 invasive squamous cell carcinoma [ISCC], 38 CIN Ill, II CIN II, 18 CIN I) confirmed to be positive for HPV 16 and/or 18 as well as 20 normal cervical tissue (NCT) samples for abnormal expression of cyclin DJ, cyclin E, CDK4, cyclin inhibitors (p2Jwa/; p27, pI6/NK4A) and Ki-67 using immunohistochemistry and differential PCR techniques. Results: There was a significant increase in the expression of Ki-67, cyclin E, CDK4, pJ6/NK4A (p=0003, 0.001,0.001) and a significant decrease in p27K1P/ from NCT to ISCC (p=0.003). There was a significant correlation between altered expression of p27K1P I and p 161NK4A (p KIpl (ρ=0.011) in all studied groups In ISCC, there was significant relationship between standard clinico-pathological prognostic factors and high Ki-67 index, increased cyclin D J and cyclin E, reduced p2 7Kip / and p21 waf Conclusion: I) Aberrations involving p27K/P 1, cyclin E, CDK4 and pJ6/NK4A are considered early events in HPV 16 and IS-associated cervical carcinogenesis (CINI and lI), whereas cyclin DI aberrations are late events (CINIII and ISCC). 2) immunohistochemical tests for pJ61NK4A and cyclin E could help in early diagnosis of cervical carcinoma. 3) Only FIGO stage, cyclin DI, p27K1P1 and Ki-67 are independent prognostic factors that might help in predicting outcome of cervical cancer palients

  4. Biological Role of Paenilarvins, Iturin-Like Lipopeptide Secondary Metabolites Produced by the Honey Bee Pathogen Paenibacillus larvae.

    Science.gov (United States)

    Hertlein, Gillian; Seiffert, Marlene; Gensel, Sebastian; Garcia-Gonzalez, Eva; Ebeling, Julia; Skobalj, Ranko; Kuthning, Anja; Süssmuth, Roderich D; Genersch, Elke

    2016-01-01

    The Gram-positive bacterium Paenibacillus larvae (P. larvae) is the causative agent of a deadly honey bee brood disease called American Foulbrood (AFB). AFB is a notifiable epizootic in most countries and, hence, P. larvae is of considerable relevance for veterinarians and apiculturists alike. Over the last decade, much progress has been made in the understanding of the (patho)biology of P. larvae. Recently, several non-ribosomally produced peptides (NRP) and peptide/polyketide (NRP/PK) hybrids produced by P. larvae were identified. Among these NRPs were iturin-like lipopeptides, the paenilarvins A-C. Iturins are known to exhibit strong anti-fungal activity; for some iturins, cytotoxic activity towards mammalian erythrocytes and human cancer cell lines are described. We here present our results on the analysis of the natural function of the paenilarvins during pathogenesis of P. larvae infections. We demonstrated production of paenilarvins in infected larvae. However, we could neither demonstrate cytotoxicity of paenilarvins towards cultured insect cells nor towards larvae in feeding assays. Accordingly, exposure bioassays performed with larvae infected by wild-type P. larvae and a knockout mutant of P. larvae lacking production of paenilarvins did not substantiate a role for the paenilarvins as virulence factor. Further experiments are necessary to analyze the relevance of the paenilarvins' anti-fungal activity for P. larvae infections in the presence of fungal competitors in the larval midgut or cadaver.

  5. The roles of host and pathogen factors and the innate immune response in the pathogenesis of Clostridium difficile infection

    Science.gov (United States)

    Sun, Xingmin; Hirota, Simon A.

    2014-01-01

    Clostridium difficile (C. difficile) is the most common cause of nosocomial antibiotic-associated diarrhea and the etiologic agent of pseudomembranous colitis. The clinical manifestation of Clostridium difficile infection (CDI) is highly variable, from asymptomatic carriage, to mild self-limiting diarrhea, to the more severe pseudomembranous colitis. Furthermore, in extreme cases, colonic inflammation and tissue damage can lead to toxic megacolon, a condition requiring surgical intervention. C. difficile expresses two key virulence factors; the exotoxins, toxin A (TcdA) and toxin B (TcdB), which are glucosyltransferases that target host-cell monomeric GTPases. In addition, some hypervirulent strains produce a third toxin, binary toxin or C. difficile transferase (CDT), which may contribute to the pathogenesis of CDI. More recently, other factors such as surface layer proteins (SLPs) and flagellin have also been linked to the inflammatory responses observed in CDI. Although the adaptive immune response can influence the severity of CDI, the innate immune responses to C. difficile and its toxins play crucial roles in CDI onset, progression, and overall prognosis. Despite this, the innate immune responses in CDI have drawn relatively little attention from clinical researchers. Targeting these responses may prove useful clinically as adjuvant therapies, especially in refractory and/or recurrent CDI. This review will focus on recent advances in our understanding of how C. difficile and its toxins modulate innate immune responses that contribute to CDI pathogenesis. PMID:25242213

  6. Role of yqiC in the pathogenicity of Salmonella and innate immune responses of human intestinal epithelium

    Directory of Open Access Journals (Sweden)

    Ke-Chuan Wang

    2016-10-01

    Full Text Available The yqiC gene of Salmonella enterica serovar Typhimurium (S. Typhimurium regulates bacterial growth at different temperatures and mice survival after infection. However, the role of yqiC in bacterial colonization and host immunity remains unknown. We infected human LS174T, Caco-2, HeLa, and THP-1 cells with S. Typhimurium wild-type SL1344, its yqiC mutant, and its complemented strain. Bacterial colonization and internalization in the four cell lines significantly reduced on yqiC depletion. Postinfection production of interleukin-8 and human β-defensin-3 in LS174T cells significantly reduced because of yqiC deleted in S. Typhimurium. The phenotype of yqiC mutant exhibited few and short flagella, fimbriae on the cell surface, enhanced biofilm formation, upregulated type-1 fimbriae expression, and reduced bacterial motility. Type-1 fimbriae, flagella, SPI-1, and SPI-2 gene expression was quantified using real-time PCR. The data show that deletion of yqiC upregulated fimA and fimZ expression and downregulated flhD, fliZ, invA, and sseB expression. Furthermore, thin-layer chromatography and high-performance liquid chromatography revealed the absence of menaquinone in the yqiC mutant, thus validating the importance of yqiC in the bacterial electron transport chain. Therefore, YqiC can negatively regulate FimZ for type-1 fimbriae expression and manipulate the functions of its downstream virulence factors including flagella, SPI-1, and SPI-2 effectors.

  7. Lack of evidence for the pathogenic role of iron and HFE gene mutations in Brazilian patients with nonalcoholic steatohepatitis

    Directory of Open Access Journals (Sweden)

    M.M. Deguti

    2003-06-01

    Full Text Available The hypothesis of the role of iron overload associated with HFE gene mutations in the pathogenesis of nonalcoholic steatohepatitis (NASH has been raised in recent years. In the present study, biochemical and histopathological evidence of iron overload and HFE mutations was investigated in NASH patients. Thirty-two NASH patients, 19 females (59%, average 49.2 years, 72% Caucasians, 12% Mulattoes and 12% Asians, were submitted to serum aminotransferase and iron profile determinations. Liver biopsies were analyzed for necroinflammatory activity, architectural damage and iron deposition. In 31 of the patients, C282Y and H63D mutations were tested by PCR-RFLP. Alanine aminotransferase levels were increased in 30 patients, 2.42 ± 1.12 times the upper normal limit on average. Serum iron concentration, transferrin saturation and ferritin averages were 99.4 ± 31.3 g/dl, 33.1 ± 12.7% and 219.8 ± 163.8 µg/dl, respectively, corresponding to normal values in 93.5, 68.7 and 78.1% of the patients. Hepatic siderosis was observed in three patients and was not associated with architectural damage (P = 0.53 or with necroinflammatory activity (P = 0.27. The allelic frequencies (N = 31 found were 1.6 and 14.1% for C282Y and H63D, respectively, which were compatible with those described for the local population. In conclusion, no evidence of an association of hepatic iron overload and HFE mutations with NASH was found. Brazilian NASH patients comprise a heterogeneous group with many associated conditions such as hyperinsulinism, environmental hepatotoxin exposure and drugs, but not hepatic iron overload, and their disease susceptibility could be related to genetic and environmental features other than HFE mutations.

  8. Pathogenicity of the highly leukotoxic JP2 clone of Aggregatibacter actinomycetemcomitans and its geographic dissemination and role in aggressive periodontitis

    Directory of Open Access Journals (Sweden)

    Dorte Haubek

    2014-08-01

    Full Text Available For decades, Aggregatibacter actinomycetemcomitans has been associated with aggressive forms of periodontitis in adolescents. In the middle of the 1990s, a specific JP2 clone of A. actinomycetemcomitans, belonging to the cluster of serotype b strains of A. actinomycetemcomitans and having a number of other characteristics, was found to be strongly associated with aggressive forms of periodontitis, particularly in North Africa. Although several longitudinal studies still point to the bacterial species, A. actinomycetemcomitans as a risk factor of aggressive periodontitis, it is now also widely accepted that the highly leukotoxic JP2 clone of A. actinomycetemcomitans is implicated in rapidly progressing forms of aggressive periodontitis. The JP2 clone strains are highly prevalent in human populations living in Northern and Western parts of Africa. These strains are also prevalent in geographically widespread populations that have originated from the Northwest Africa. Only sporadic signs of a dissemination of the JP2 clone strains to non-African populations have been found despite Africans living geographically widespread for hundreds of years. It remains an unanswered question if a particular host tropism exists as a possible explanation for the frequent colonization of the Northwest African population with the JP2 clone. Two exotoxins of A. actinomycetemcomitans are known, leukotoxin (LtxA and cytolethal distending toxin (Cdt. LtxA is able to kill human immune cells, and Cdt can block cell cycle progression in eukaryotic cells and thus induce cell cycle arrest. Whereas the leukotoxin production is enhanced in JP2 clone strains thus increasing the virulence potential of A. actinomycetemcomitans, it has not been possible so far to demonstrate such a role for Cdt. Lines of evidence have led to the understanding of the highly leukotoxic JP2 clone of A. actinomycetemcomitans as an aetiological factor of aggressive periodontitis. Patients, who are

  9. Pathogenicity of the highly leukotoxic JP2 clone of Aggregatibacter actinomycetemcomitans and its geographic dissemination and role in aggressive periodontitis

    Science.gov (United States)

    Haubek, Dorte; Johansson, Anders

    2014-01-01

    For decades, Aggregatibacter actinomycetemcomitans has been associated with aggressive forms of periodontitis in adolescents. In the middle of the 1990s, a specific JP2 clone of A. actinomycetemcomitans, belonging to the cluster of serotype b strains of A. actinomycetemcomitans and having a number of other characteristics, was found to be strongly associated with aggressive forms of periodontitis, particularly in North Africa. Although several longitudinal studies still point to the bacterial species, A. actinomycetemcomitans as a risk factor of aggressive periodontitis, it is now also widely accepted that the highly leukotoxic JP2 clone of A. actinomycetemcomitans is implicated in rapidly progressing forms of aggressive periodontitis. The JP2 clone strains are highly prevalent in human populations living in Northern and Western parts of Africa. These strains are also prevalent in geographically widespread populations that have originated from the Northwest Africa. Only sporadic signs of a dissemination of the JP2 clone strains to non-African populations have been found despite Africans living geographically widespread for hundreds of years. It remains an unanswered question if a particular host tropism exists as a possible explanation for the frequent colonization of the Northwest African population with the JP2 clone. Two exotoxins of A. actinomycetemcomitans are known, leukotoxin (LtxA) and cytolethal distending toxin (Cdt). LtxA is able to kill human immune cells, and Cdt can block cell cycle progression in eukaryotic cells and thus induce cell cycle arrest. Whereas the leukotoxin production is enhanced in JP2 clone strains thus increasing the virulence potential of A. actinomycetemcomitans, it has not been possible so far to demonstrate such a role for Cdt. Lines of evidence have led to the understanding of the highly leukotoxic JP2 clone of A. actinomycetemcomitans as an aetiological factor of aggressive periodontitis. Patients, who are colonized with the JP2

  10. Essential pathogenic role of endogenous IL-18 in murine diabetes induced by multiple low doses of streptozotocin. Prevention of hyperglycemia and insulitis by a recombinant IL-18-binding protein: Fc construct

    DEFF Research Database (Denmark)

    Nicoletti, Ferdinando; Di Marco, Roberto; Papaccio, Gianpaolo

    2003-01-01

    IL-18 is a cytokine structurally and functionally related to IL-1 that, in synergy with IL-12, stimulates the synthesis of IFN-gamma from T lymphocytes and natural killer cells. Because IFN-gamma plays a key pathogenic role in the development of murine immunoinflammatory diabetes induced by multi...

  11. Role of Pre-therapeutic 18F-FDG PET/CT in Guiding the Treatment Strategy and Predicting Prognosis in Patients with Esophageal Carcinoma

    Directory of Open Access Journals (Sweden)

    Teik Hin Tan

    2016-07-01

    Full Text Available Objective(s: The present study aimed to evaluate the role of pretherapeutic 18fluorine-fluorodeoxyglucose positron emission tomographycomputed tomography (18F-FDG PET-CT and maximum standardized uptake value (SUVmax in guiding the treatment strategy and predicting the prognosis of esophageal carcinoma, using the survival data of thepatients.Methods: The present retrospective, cohort study was performed on 40 consecutive patients with esophageal carcinoma (confirmed by endoscopic biopsy, who underwent pre-operative 18F-FDG PET-CTstaging between January 2009 and June 2014. All the patients underwent contrast-enhanced CT and non-contrasted 18F-FDG PET-CT evaluations.The patients were followed-up over 12 months to assess the changes in therapeutic strategies. Survival analysis was done considering the primary tumor SUVmax, using the Kaplan–Meier product-limit method.Results: In a total of 40 patients, 18F-FDG PET-CT scan led to changes in disease stage in 26n (65.0% cases, with upstaging and downstaging reported in 10n (25.0% and 16n (40.0% patients, respectively. The management strategy changed from palliative to curative in 10 out of 24 patients and from curative to palliative in 7 out of 16 cases. Based on the18F-FDG PET-CT scan alone, the median survival of patients in the palliative group was 4.0n (95 % CI 3.0-5.0 months, whereas the median survival in the curative group has not been reached, based on the 12-month followup.Selection of treatment strategy on the basis of 18F-FDG PET/CT alone was significantly associated with the survival outcomes at nine months (P=0.03 and marginally significant at 12 months (P=0.05. On the basisof SUVmax, the relation between survival and SUVmax was not statistically significant.Conclusion: 18F-FDG PET/CT scan had a significant impact on stage stratification and subsequently, selection of a stage-specific treatment approach and the overall survival outcome in patients with esophageal carcinoma. However, pre

  12. The role of 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography in the management of patients with carcinoma of unknown primary.

    Science.gov (United States)

    Deonarine, P; Han, S; Poon, F W; de Wet, C

    2013-08-01

    Carcinoma of unknown primary is one of the ten most frequent cancers worldwide. Its median survival time is less than 10 months. Detecting primary tumour locations and/or occult metastatic lesions may inform definitive treatment and improve patients' prognosis. We aimed to determine: (1) the sensitivity, specificity and accuracy of (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography; (2) its detection rate of primary tumour locations and occult metastases and (3) factors associated with improved survival times. We retrospectively reviewed all cases in the West of Scotland for the period 1 December 2007 to 31 May 2011 that met all our selection criteria: (1) diagnosis of carcinoma of unknown primary; (2) a thorough but negative 'work-up' and (3) (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography report. Statistical methods included frequencies, Kaplan-Meier graphs and log-rank tests to compare survival times. (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography detected primary tumour sites in 19/51 (37.3%) and occult metastases in 28/51 (54.9%) of eligible patients. Its sensitivity, specificity and accuracy were 79.2%, 70.4% and 74.5%, respectively; 20/51 (39.2%) patients died during the study period with a median survival of 8.4 months (range 21.4, SD ± 6.2). The number of metastatic locations was strongly associated with survival (p = 0.002), but detection of a primary tumour site (p = 0.174) or histopathology (p = 0.301) was not. (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography detected occult metastatic sites in the majority and a primary cancer location in a substantial minority of patients. Our results were comparable with international literature and may indicate that (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography have an early role to improve the accuracy of cancer staging and to optimise carcinoma of unknown

  13. Role of the B Allele of Influenza A Virus Segment 8 in Setting Mammalian Host Range and Pathogenicity.

    Science.gov (United States)

    Turnbull, Matthew L; Wise, Helen M; Nicol, Marlynne Q; Smith, Nikki; Dunfee, Rebecca L; Beard, Philippa M; Jagger, Brett W; Ligertwood, Yvonne; Hardisty, Gareth R; Xiao, Haixia; Benton, Donald J; Coburn, Alice M; Paulo, Joao A; Gygi, Steven P; McCauley, John W; Taubenberger, Jeffery K; Lycett, Samantha J; Weekes, Michael P; Dutia, Bernadette M; Digard, Paul

    2016-10-15

    burden on farming and health care sectors. Host adaptation likely involves multiple viral factors. Here, we investigated the role of IAV segment 8. Segment 8 has evolved into two distinct clades: the A and B alleles. The B-allele genes have previously been suggested to be restricted to avian virus species. We introduced a selection of avian virus A- and B-allele segment 8s into human H1N1 and H3N2 virus backgrounds and found that these reassortant viruses were fully competent in mammalian host systems. We also analyzed the currently available public data on the segment 8 gene distribution and found surprisingly little evidence for specific avian host restriction of the B-clade segment. We conclude that B-allele segment 8 genes are, in fact, capable of supporting infection in mammals and that they should be considered during the assessment of the pandemic risk of zoonotic influenza A viruses. Copyright © 2016 Turnbull et al.

  14. Integrating evolutionary game theory into an agent-based model of ductal carcinoma in situ: Role of gap junctions in cancer progression.

    Science.gov (United States)

    Malekian, Negin; Habibi, Jafar; Zangooei, Mohammad Hossein; Aghakhani, Hojjat

    2016-11-01

    There are many cells with various phenotypic behaviors in cancer interacting with each other. For example, an apoptotic cell may induce apoptosis in adjacent cells. A living cell can also protect cells from undergoing apoptosis and necrosis. These survival and death signals are propagated through interaction pathways between adjacent cells called gap junctions. The function of these signals depends on the cellular context of the cell receiving them. For instance, a receiver cell experiencing a low level of oxygen may interpret a received survival signal as an apoptosis signal. In this study, we examine the effect of these signals on tumor growth. We make an evolutionary game theory component in order to model the signal propagation through gap junctions. The game payoffs are defined as a function of cellular context. Then, the game theory component is integrated into an agent-based model of tumor growth. After that, the integrated model is applied to ductal carcinoma in situ, a type of early stage breast cancer. Different scenarios are explored to observe the impact of the gap junction communication and parameters of the game theory component on cancer progression. We compare these scenarios by using the Wilcoxon signed-rank test. The Wilcoxon signed-rank test succeeds in proving a significant difference between the tumor growth of the model before and after considering the gap junction communication. The Wilcoxon signed-rank test also proves that the tumor growth significantly depends on the oxygen threshold of turning survival signals into apoptosis. In this study, the gap junction communication is modeled by using evolutionary game theory to illustrate its role at early stage cancers such as ductal carcinoma in situ. This work indicates that the gap junction communication and the oxygen threshold of turning survival signals into apoptosis can notably affect cancer progression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Prostate carcinomas

    International Nuclear Information System (INIS)

    Toledano, A.; Chauveinc, L.; Flam, T.; Thiounn, N.; Solignac, S.; Timbert, M.; Rosenwald, J.C.; Cosset, J.M.; Ammor, A.; Bonnetain, F.; Brenier, J.P.; Maingon, P.; Peignaux, K.; Truc, G.; Bosset, M.; Crevoisier, R. de; Tucker, S.; Dong, L.; Cheung, R.; Kuban, D.; Azria, D.; Llacer Moscardo, C.; Ailleres, N.; Allaw, A.; Serre, A.; Fenoglietto, P.; Hay, M.H.; Thezenas, S.; Dubois, J.B.; Pommier, P.; Perol, D.; Lagrange, J.L.; Richaud, P.; Brune, D.; Le Prise, E.; Azria, D.; Beckendorf, V.; Chabaud, S.; Carrie, C.; Bosset, M.; Bosset, J.F.; Maingon, P.; Ammor, A.; Crehangen, G.; Truc, G.; Peignaux, K.; Bonnetain, F.; Keros, L.; Bernier, V.; Aletti, P.; Wolf, D.; Marchesia, V.; Noel, A.; Artignan, X.; Fourneret, P.; Bacconier, M.; Shestaeva, O.; Pasquier, D.; Descotes, J.L.; Balosso, J.; Bolla, M.; Burette, R.; Corbusier, A.; Germeau, F.; Crevoisier, R. de; Dong, L.; Bonnen, M.; Cheung, R.; Tucker, S.; Kuban, D.; Crevoisier, R. de; Melancon, A.; Kuban, D.; Cheung, R.; Dong, L.; Peignaux, K.; Brenier, J.P.; Truc, G.; Bosset, M.; Ammor, A.; Barillot, I.; Maingon, P.; Molines, J.C.; Berland, E.; Cornulier, J. de; Coulet-Parpillon, A.; Cohard, C.; Picone, M.; Fourneret, P.; Artignan, X.; Daanen, V.; Gastaldo, J.; Bolla, M.; Collomb, D.; Dusserre, A.; Descotes, J.L.; Troccaz, J.; Giraud, J.Y.; Quero, L.; Hennequin, C.; Ravery, V.; Desgrandschamps, F.; Maylin, C.; Boccon-Gibod, L.; Salem, N.; Bladou, F.; Gravis, G.; Tallet, A.; Simonian, M.; Serment, G.; Salem, N.; Bladou, F.; Gravis, G.; Simonian, M.; Rosello, R.; Serment, G.

    2005-01-01

    Some short communications on the prostate carcinoma are given here. The impact of pelvic irradiation, conformation with intensity modulation, association of radiotherapy and chemotherapy reduction of side effects, imaging, doses escalation are such subjects studied and reported. (N.C.)

  16. Viruses, Other Pathogenic Microorganisms and Esophageal Cancer.

    Science.gov (United States)

    Xu, Wenji; Liu, Zhongshu; Bao, Quncha; Qian, Zhikan

    2015-05-01

    Esophageal cancer (EC) is the eighth most prevalent malignant tumor and the sixth leading cause of cancer mortality throughout the world. Despite the technical developments in diagnosis and treatment, the 5-year survival rate is still low. The etiology of EC remains poorly understood; multiple risk factors may be involved and account for the great variation in EC incidence in different geographic regions. Infection with carcinogenetic pathogens has been proposed as a risk factor for EC. This review explores the recent studies on the association of human papillomavirus (HPV), Epstein-Barr virus (EBV), Helicobacter pylori and esophageal bacterial biota with EC. Among the above-mentioned pathogens, HPV most likely contributes to esophageal squamous cell carcinoma (ESCC) in high-risk populations. New techniques are being applied to studies on the role of infection in EC, which will inevitably bring novel ideas to the field in the near future. Multiple meta-analyses support the finding of a higher HPV detection rate in regions associated with high risk for ESCC compared to low-risk areas. A potential role of HPV in the rise of esophageal adenocarcinoma (EAC) was proposed recently. However, further studies are required before a firm conclusion can be drawn. Less work has been done in studying the association between EBV and ESCC, and the results are quite controversial. H. pylori infection is found to be inversely related to EC, which is probably due to the reduced incidence of gastroesophageal reflux disease. Analysis of the esophageal bacterial biota revealed distinct clusters of bacteria in normal and diseased esophagi. A type II microbiome rich in Gram-negative bacteria potentially contributes to EAC by inducing chronic inflammation. Novel findings from such studies as these may benefit public health by justifying anti-infection measures to prevent EC.

  17. Anaplastic carcinoma

    International Nuclear Information System (INIS)

    Parikh, D.M.; Agarwal, S.; Rao, R.S.

    1999-01-01

    Thyroid carcinoma (TC) is a slow growing tumor with an indolent course and has an excellent prognosis. However, a sharp contrast exists in the biological behavior of TC, which in its well-differentiated form is associated with long-term survival, but in its undifferentiated form is one of the most lethal neoplasms known. The anaplastic carcinoma (ANC) form has a fulminanat course with poor prognosis and almost invariably, a fatal outcome

  18. Basal Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

  19. Merkel Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Merkel cell carcinoma Overview Merkel cell carcinoma: This rare skin ... hard patch (1) or firm bump (2). Merkel cell carcinoma: Overview What is Merkel cell carcinoma? Merkel ...

  20. Diagnostic and pathogenetic role of café-au-lait macules in nevoid basal cell carcinoma syndrome

    Directory of Open Access Journals (Sweden)

    Ponti Giovanni

    2012-10-01

    Full Text Available Abstract Café au lait spots (CALS are common dermatologic findings that can at the same time arise in a variety of pathologic conditions such as Neurofibromatosis type 1 (NF1, together with numerous hereditary syndromes for which they represent either diagnostic criteria or associated elements (McCune Albright, Silver-Russell, LEOPARD, Ataxia-Telangiectasia. A review of the literature also revealed two cases of association with NBCCS. We report here the case of a female proband with CALS associated to Nevoid Basal Cell Carcinoma Syndrome (NBCCS with known PTCH1 germline mutation (C.1348-2A>G who had been misdiagnosed with NF1 in her childhood because of 5 CALS and cutaneous nodules. The patient presented a giant cell tumor of the skin, palmar and calcaneal epidermoidal cystic nodules, odontogenic keratocystic tumors and deformity of the jaw profile. Her family history brought both her brother and father to our attention because of the presence of KCOTs diagnosed at early age: after genetic testing, the same PTCH1 germline mutation was identified in the three family members. Clinical criteria are used for discerning NF1 diagnosis (size, number and onset age, while there are no definite guidelines concerning CALS except for their presence. In our experience, we have noted an association of CALS with NBCCS; this seems interesting because we already know clinical criteria are a dynamic entity and can be modified by epidemiologic evidences.

  1. The role of combined composite resection and irradiation in the management of carcinoma of the oral cavity and oropharynx

    International Nuclear Information System (INIS)

    Wazer, D.E.; Schmidt-Ullrich, R.; Keisch, M.; Karmody, C.S.; Koch, W.

    1989-01-01

    Squamous cell carcinoma of the oral cavity and oropharynx can invade the mandible requiring an 'en bloc' or composite resection. With this procedure alone, reported local control rates for advanced stage tumors have been suboptimal suggesting the need for adjuvant therapy. The treatment records of 35 patients were reviewed who were treated with composite resection alone, composite resection plus radiotherapy, or composite resection as a salvage procedure for a primary treatment failure. Combined irradiation and composite resection resulted in a higher local control than patients receiving composite resection alone (72% vs. 43%). There was no difference in complication rates between these two treatment groups. Composite resection as a salvage procedure resulted in local control in 38% of patients though this was associated with a 64% rate of complications. This data and a review of the literature suggest that tumors of the oral cavity and oropharynx with extension to the mandible requiring composite resection probably represent a category of tumors with a high risk of local recurrence and may benefit from adjuvant irradiation. (orig.) [de

  2. Surgical resection of a renal cell carcinoma involving the inferior vena cava: the role of the cardiothoracic surgeon

    LENUS (Irish Health Repository)

    Parissis, Haralabos

    2010-11-05

    Abstract Background The techniques for the resection of renal tumors with IVC extension are based on the experience of individual units. We attempt to provide a logical approach of the surgical strategies in a stepwise fashion. Methods Over 6-years 9 patients with renal cell carcinoma invading the IVC, underwent surgery. There were 6 males. The extension was at level IV in 4 and III in 5 cases. CPB used in 8 and hypothermia and circulatory arrest in all patients with level IV disease. The results and an algorithm of the plan of action, as per level of extension are presented. Results Plan of action: For level I-II disease: No Cardiothoracic involvement, For level III: Cardiopulmonary Bypass (CPB) & control of the cavo-atrial junction. For level IV: use of brief periods of Circulatory Arrest & repair of the Cavotomy with a pericardial patch. Postoperative morbidity: prolonged ICU stay, 3 patients (33.3%); tracheostomy, 1 (11.1%); Sepsis, 2 (22.2%); CVA 1, (11.1%). Mortality: 2 patients (22.2%) Conclusions Total clearance of the IVC from an adherent tumor is important, therefore extensive level IV disease presents a surgical challenge. We recommend CPB for level III and brief periods of Total Circulatory Arrest (TCA) for level IV disease.

  3. A Case-Control Study of the Role of Human Papillomavirus in Oesophageal Squamous Cell Carcinoma in Australia

    Directory of Open Access Journals (Sweden)

    Surabhi S. Liyanage

    2014-01-01

    Full Text Available Objective. We investigate the prevalence of human papillomavirus (HPV in oesophageal squamous cell carcinoma (OSCC tissues compared to oesophageal tissue from healthy controls, in an Australian cohort. Methods. We conducted a hospital-based case-control study of 99 patients with OSCC and 100 healthy controls to examine the presence of HPV DNA. Paraffin tissues were tested using the PapType high-risk HPV detection and genotyping kit and with INNO-LiPA HPV Genotyping Extra. The biopsy samples were tested for HPV using a PCR-ELISA method based on the L1 consensus primer set PGMY09-PGMY11. Results. HPV DNA of the oncogenic genotype 16 was detected in 1/99 case specimens, a rate of 1010 per 100,000 (95% CI: 30–5500. All control specimens were negative for HPV. Significantly higher rates of smoking, other aerodigestive cancers, and mortality were seen among cases than controls. A pooled analysis of this study and the only other Australian case-control study found that 9/321 cases and 0/155 controls were positive for HPV. The pooled odds ratio for HPV being a risk factor for OSCC was 9.35 (95% CI: 0.47–190.33. Conclusion. Our results suggest that in this multifactorial cancer HPV may be an additional risk factor; although a larger, better powered study is needed.

  4. Metastatic renal cell carcinoma in the thyroid gland: ultrasonographic features and the diagnostic role of core needle biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ok Kyu; Koo, Ja Seung; Kwak, Jin Young; Moon, Hee Jung; Yoon, Jung Hyun; Kim, Eun Kyung [Severance Hospital, Yonsei University College of Medicine, Seoul(Korea, Republic of)

    2017-07-15

    The aims of this study were to present the ultrasonographic (US) features of metastatic renal cell carcinoma (RCC) in the thyroid gland and to evaluate the diagnostic utility of fine needle aspiration (FNA) and core needle biopsy (CNB). Eight patients with nine metastatic RCC nodules in the thyroid glands who were treated from January 2002 to March 2015 in a single tertiary hospital were consecutively selected and retrospectively reviewed. US features and clinical history were obtained from the institution’s medical database. FNA was performed nine times on eight nodules and CNB was performed six times on six nodules. The diagnostic utility of FNA and CNB was evaluated. All nine nodules showed mass formation without diffuse thyroid involvement. On ultrasonography, metastatic RCC nodules were solid (100%), hypoechoic (100%), and ovalshaped nodules with a well-defined smooth margin (88.9%) and increased vascularity (100%, with 55% showing extensive vascularity). No calcifications were noted in any nodules. Lymph node metastasis and direct extension to nearby structures beyond the thyroid gland were not found. One FNA (11%) was able to confirm metastatic RCC, whereas all six CNBs confirmed metastatic RCC. Metastatic RCC appears as oval-shaped hypoechoic solid nodules with well-defined smooth margins, no calcifications, and increased vascularity on ultrasonography. Characteristic US features along with a previous history of RCC should raise clinical suspicion, and CNB should be performed to make an accurate diagnosis.

  5. Prognostic role of C-reactive protein in patients with nasopharyngeal carcinoma: A meta-analysis and literature review.

    Science.gov (United States)

    Fang, Yi; Xu, Chang; Wu, Peng; Zhang, Ling-Hao; Li, Da-Wei; Sun, Jie-Hao; Li, Wen-Feng; Liao, Zhi-Su

    2017-11-01

    C-reactive protein (CRP) has been shown to be associated with several tumors. However, its association with nasopharyngeal carcinoma (NPC) is not well characterized. We performed a literature review and meta-analysis to assess the prognostic relevance of elevated CRP levels in patients with NPC. A literature search for relevant studies was performed on PubMed (Medline), the Cochrane Library, and Web of Science databases. Hazard ratios (95% confidence intervals) were calculated to assess the association between elevated CRP levels and survival outcomes. Five studies with a combined study population of 5215 patients with NPC were included. Pooled hazard ratios for overall survival and distant metastasis-free survival were 1.84 (95% CI = 1.57-2.17) and 1.81 (95% CI = 1.53-2.14), respectively. Subgroup analyses showed that types of indicators and treatment before inclusion had no significant impact on the observed association. Elevated serum CRP levels in patients with NPC were associated with worse prognosis.

  6. The role of postoperative radiation and chemoradiation in Merkel Cell Carcinoma: A systematic review of the literature

    Directory of Open Access Journals (Sweden)

    Shaakir eHasan

    2013-11-01

    Full Text Available Objective: A systematic review of the literature was undertaken to investigate whether adjuvant radiotherapy and/or chemotherapeutics offered any additional benefit than surgery alone in the treatment of Merkel Cell Carcinoma (MCC. Methods: A PubMed, MEDLINE search was conducted between 1995-2013, to identify reported cases of surgically treated MCC followed by either observation, radiation, or chemoradiation. Patient demographics and outcomes were recorded and compared in a systematic fashion. Results: Thirty-four studies (n = 4475 were included. The median age was 73 years, median follow-up was 36 months and there was a 1.5:1 ratio of men to women. All 4475 patients had surgery, 1975 had no further treatment, 1689 received postoperative RT, and 301 received postoperative chemoRT. The most common site was face/head/neck, 47.8%. Stage 1 was the most common clinical stage at diagnosis (57%. Three-year LC was 20% [median 10%] in the observation cohort, compared to 65% [62%] with postoperative RT and 67% [75%] with postoperative chemoRT; these findings were statistically significant (P

  7. Role of KEAP1/NRF2 and TP53 mutations in lung squamous cell carcinoma development and radiotherapy response prediction

    Science.gov (United States)

    Jeong, Youngtae; Hoang, Ngoc T.; Lovejoy, Alexander; Stehr, Henning; Newman, Aaron M.; Gentles, Andrew J.; Kong, William; Truong, Diana; Martin, Shanique; Chaudhuri, Aadel; Heiser, Diane; Zhou, Li; Say, Carmen; Carter, Justin N.; Hiniker, Susan M.; Loo, Billy W.; West, Robert B.; Beachy, Philip; Alizadeh, Ash A.; Diehn, Maximilian

    2016-01-01

    Lung squamous cell carcinomas (LSCC) pathogenesis remains incompletely understood and biomarkers predicting treatment response remain lacking. Here we describe novel murine LSCC models driven by loss of Trp53 and Keap1, both of which are frequently mutated in human LSCCs. Homozygous inactivation of Keap1 or Trp53 promoted airway basal stem cell (ABSC) self-renewal, suggesting that mutations in these genes lead to expansion of mutant stem cell clones. Deletion of Trp53 and Keap1 in ABSCs, but not more differentiated tracheal cells, produced tumors recapitulating histological and molecular features of human LSCCs, indicating that they represent the likely cell of origin in this model. Deletion of Keap1 promoted tumor aggressiveness, metastasis, and resistance to oxidative stress and radiotherapy (RT). KEAP1/NRF2 mutation status predicted risk of local recurrence after RT in non-small lung cancer (NSCLC) patients and could be non-invasively identified in circulating tumor DNA. Thus, KEAP1/NRF2 mutations could serve as predictive biomarkers for personalization of therapeutic strategies for NSCLCs. PMID:27663899

  8. The Role of Compounds Derived from Natural Supplement as Anticancer Agents in Renal Cell Carcinoma: A Review

    Science.gov (United States)

    Haque, Inamul; Subramanian, Arvind; Huang, Chao H.; Godwin, Andrew K.; Van Veldhuizen, Peter J.; Banerjee, Snigdha; Banerjee, Sushanta K.

    2017-01-01

    Renal Cell Carcinoma (RCC) is the most prominent kidney cancer derived from renal tubules and accounts for roughly 85% of all malignant kidney cancer. Every year, over 60,000 new cases are registered, and about 14,000 people die from RCC. The incidence of this has been increasing significantly in the U.S. and other countries. An increased understanding of molecular biology and the genomics of RCC has uncovered several signaling pathways involved in the progression of this cancer. Significant advances in the treatment of RCC have been reported from agents approved by the Food and Drug Administration (FDA) that target these pathways. These agents have become drugs of choice because they demonstrate clinical benefit and increased survival in patients with metastatic disease. However, the patients eventually relapse and develop resistance to these drugs. To improve outcomes and seek approaches for producing long-term durable remission, the search for more effective therapies and preventative strategies are warranted. Treatment of RCC using natural products is one of these strategies to reduce the incidence. However, recent studies have focused on these chemoprevention agents as anti-cancer therapies given they can inhibit tumor cell grow and lack the severe side effects common to synthetic compounds. This review elaborates on the current understanding of natural products and their mechanisms of action as anti-cancer agents. The present review will provide information for possible use of these products alone or in combination with chemotherapy for the prevention and treatment of RCC. PMID:29301217

  9. The Role of Compounds Derived from Natural Supplement as Anticancer Agents in Renal Cell Carcinoma: A Review.

    Science.gov (United States)

    Haque, Inamul; Subramanian, Arvind; Huang, Chao H; Godwin, Andrew K; Van Veldhuizen, Peter J; Banerjee, Snigdha; Banerjee, Sushanta K

    2017-12-31

    Renal Cell Carcinoma (RCC) is the most prominent kidney cancer derived from renal tubules and accounts for roughly 85% of all malignant kidney cancer. Every year, over 60,000 new cases are registered, and about 14,000 people die from RCC. The incidence of this has been increasing significantly in the U.S. and other countries. An increased understanding of molecular biology and the genomics of RCC has uncovered several signaling pathways involved in the progression of this cancer. Significant advances in the treatment of RCC have been reported from agents approved by the Food and Drug Administration (FDA) that target these pathways. These agents have become drugs of choice because they demonstrate clinical benefit and increased survival in patients with metastatic disease. However, the patients eventually relapse and develop resistance to these drugs. To improve outcomes and seek approaches for producing long-term durable remission, the search for more effective therapies and preventative strategies are warranted. Treatment of RCC using natural products is one of these strategies to reduce the incidence. However, recent studies have focused on these chemoprevention agents as anti-cancer therapies given they can inhibit tumor cell grow and lack the severe side effects common to synthetic compounds. This review elaborates on the current understanding of natural products and their mechanisms of action as anti-cancer agents. The present review will provide information for possible use of these products alone or in combination with chemotherapy for the prevention and treatment of RCC.

  10. The role of adjuvant chemotherapy in nasopharyngeal carcinoma with bulky neck lymph nodes in the era of IMRT.

    Science.gov (United States)

    Xu, Tingting; Shen, Chunying; Ou, Xiaomin; He, Xiayun; Ying, Hongmei; Hu, Chaosu

    2016-04-12

    Nasopharyngeal carcinoma (NPC) patients with N2-3 diseases are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy (CCRT). Our study is aim to determine the optimal treatment strategy of these patients. Patients with histologically proven NPC were retrospectively analyzed according to the AJCC 2002 stage classification system. A total of 547 patients who had N2-3 diseases were enrolled. They were all treated with Intensity-modulated radiation therapy (IMRT) combined with systemic treatments, including radiotherapy alone (RT alone), neoadjuvant chemotherapy followed by radiotherapy (NACT+RT), CCRT, NACT+CCRT, NACT followed by radiotherapy and adjuvant chemotherapy (NACT+RT+AC), CCRT+AC and NACT+CCRT+AC. A subgroup analysis was also conducted. With a median follow-up time of 53.8 months, adjuvant chemotherapy significantly decreased the risk of distant metastasis (HR 0.413, 95% CI 0.194-0.881, p = 0.022) as well as significantly increased the OS (HR 0.398, 95% CI 0.187-0.848, p = 0.017) in patients with N3 disease. The addition of adjuvant chemotherapy seemed to provide benefits to patients with N3 stage NPC and the current study may indicate the need for further randomized investigation.

  11. Inflammation and cancer: role of annexin A1 and FPR2/ALX in proliferation and metastasis in human laryngeal squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Thaís Santana Gastardelo

    Full Text Available The anti-inflammatory protein annexin A1 (ANXA1 has been associated with cancer progression and metastasis, suggesting its role in regulating tumor cell proliferation. We investigated the mechanism of ANXA1 interaction with formylated peptide receptor 2 (FPR2/ALX in control, peritumoral and tumor larynx tissue samples from 20 patients, to quantitate the neutrophils and mast cells, and to evaluate the protein expression and co-localization of ANXA1/FPR2 in these inflammatory cells and laryngeal squamous cells by immunocytochemistry. In addition, we performed in vitro experiments to further investigate the functional role of ANXA1/FPR2 in the proliferation and metastasis of Hep-2 cells, a cell line from larynx epidermoid carcinoma, after treatment with ANXA1(2-26 (annexin A1 N-terminal-derived peptide, Boc2 (antagonist of FPR and/or dexamethasone. Under these treatments, the level of Hep-2 cell proliferation, pro-inflammatory cytokines, ANXA1/FPR2 co-localization, and the prostaglandin signalling were analyzed using ELISA, immunocytochemistry and real-time PCR. An influx of neutrophils and degranulated mast cells was detected in tumor samples. In these inflammatory cells of peritumoral and tumor samples, ANXA1/FPR2 expression was markedly exacerbated, however, in laryngeal carcinoma cells, this expression was down-regulated. ANXA1(2-26 treatment reduced the proliferation of the Hep-2 cells, an effect that was blocked by Boc2, and up-regulated ANXA1/FPR2 expression. ANXA1(2-26 treatment also reduced the levels of pro-inflammatory cytokines and affected the expression of metalloproteinases and EP receptors, which are involved in the prostaglandin signalling. Overall, this study identified potential roles for the molecular mechanism of the ANXA1/FPR2 interaction in laryngeal cancer, including its relationship with the prostaglandin pathway, providing promising starting points for future research. ANXA1 may contribute to the regulation of tumor growth

  12. Pathogens and Disease Play Havoc on the Host Epiproteome—The “First Line of Response” Role for Proteomic Changes Influenced by Disorder

    Directory of Open Access Journals (Sweden)

    Erik H. A. Rikkerink

    2018-03-01

    Full Text Available Organisms face stress from multiple sources simultaneously and require mechanisms to respond to these scenarios if they are to survive in the long term. This overview focuses on a series of key points that illustrate how disorder and post-translational changes can combine to play a critical role in orchestrating the response of organisms to the stress of a changing environment. Increasingly, protein complexes are thought of as dynamic multi-component molecular machines able to adapt through compositional, conformational and/or post-translational modifications to control their largely metabolic outputs. These metabolites then feed into cellular physiological homeostasis or the production of secondary metabolites with novel anti-microbial properties. The control of adaptations to stress operates at multiple levels including the proteome and the dynamic nature of proteomic changes suggests a parallel with the equally dynamic epigenetic changes at the level of nucleic acids. Given their properties, I propose that some disordered protein platforms specifically enable organisms to sense and react rapidly as the first line of response to change. Using examples from the highly dynamic host-pathogen and host-stress response, I illustrate by example how disordered proteins are key to fulfilling the need for multiple levels of integration of response at different time scales to create robust control points.

  13. Potential role of combined FDG PET/CT & contrast enhancement MRI in a rectal carcinoma model with nodal metastases characterized by a poor FDG-avidity.

    Science.gov (United States)

    Farace, Paolo; Conti, Giamaica; Merigo, Flavia; Tambalo, Stefano; Marzola, Pasquina; Sbarbati, Andrea; Quarta, Carmelo; D'Ambrosio, Daniela; Chondrogiannis, Sotirios; Nanni, Cristina; Rubello, Domenico

    2012-04-01

    To investigate the additional role of MRI contrast enhancement (CE) in the primary tumor and the FDG uptake at PET in the lymph-node metastases. A model of colorectal cancer induced by orthotopic HT-29 cells microinjection, producing pelvic lymph node metastases, was assessed using CE-MRI and FDG-PET. Histology and GLUT-1 immunohistochemistry were performed on primary tumors and iliac lymph nodes. Primary tumors were characterized by low FDG-uptake but high CE-MRI, particularly at tumor periphery. Undetectable FDG-uptake characterized the metastatic lymph-nodes. Histology revealed large stromal bundles at tumor periphery and a dense network of stromal fibers and neoplastic cells in the inner portion of the tumors. Both primary tumors and positive lymph nodes showed poor GLUT-1 staining. Our data support the complementary role of MRI-CE and FDG PET in some types of carcinomas characterized by abundant cancer-associated stroma and poor FDG avidity consequent to poor GLUT-1 transported. In these tumors FDG-PET alone may be not completely adequate to obtain an adequate tumor radiotherapy planning, and a combination with dual CE-MRI is strongly recommended. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. Potential role of combined FDG PET/CT and contrast enhancement MRI in a rectal carcinoma model with nodal metastases characterized by a poor FDG-avidity

    International Nuclear Information System (INIS)

    Farace, Paolo; Conti, Giamaica; Merigo, Flavia; Tambalo, Stefano; Marzola, Pasquina; Sbarbati, Andrea; Quarta, Carmelo; D’Ambrosio, Daniela; Chondrogiannis, Sotirios; Nanni, Cristina; Rubello, Domenico

    2012-01-01

    Purpose: To investigate the additional role of MRI contrast enhancement (CE) in the primary tumor and the FDG uptake at PET in the lymph-node metastases. Materials and methods: A model of colorectal cancer induced by orthotopic HT-29 cells microinjection, producing pelvic lymph node metastases, was assessed using CE-MRI and FDG-PET. Histology and GLUT-1 immunohistochemistry were performed on primary tumors and iliac lymph nodes. Results: Primary tumors were characterized by low FDG-uptake but high CE-MRI, particularly at tumor periphery. Undetectable FDG-uptake characterized the metastatic lymph-nodes. Histology revealed large stromal bundles at tumor periphery and a dense network of stromal fibers and neoplastic cells in the inner portion of the tumors. Both primary tumors and positive lymph nodes showed poor GLUT-1 staining. Conclusion: Our data support the complementary role of MRI-CE and FDG PET in some types of carcinomas characterized by abundant cancer-associated stroma and poor FDG avidity consequent to poor GLUT-1 transported. In these tumors FDG-PET alone may be not completely adequate to obtain an adequate tumor radiotherapy planning, and a combination with dual CE-MRI is strongly recommended.

  15. Role of the Genes of Type VI Secretion System in Virulence of Rice Bacterial Brown Stripe Pathogen Acidovorax avenae subsp. avenae Strain RS-2

    Directory of Open Access Journals (Sweden)

    Md. Mahidul Islam Masum

    2017-09-01

    Full Text Available The Type VI secretion system (T6SS is a class of macromolecular machine that is required for the virulence of gram-negative bacteria. However, it is still not clear what the role of T6SS in the virulence of rice bacterial brown stripe pathogen Acidovorax avenae subsp. avenae (Aaa is. The aim of the current study was to investigate the contribution of T6SS in Aaa strain RS2 virulence using insertional deletion mutation and complementation approaches. This strain produced weak virulence but contains a complete T6SS gene cluster based on a genome-wide analysis. Here we compared the virulence-related phenotypes between the wild-type (RS-2 and 25 T6SS mutants, which were constructed using homologous recombination methods. The mutation of 15 T6SS genes significantly reduced bacterial virulence and the secretion of Hcp protein. Additionally, the complemented 7 mutations ΔpppA, ΔclpB, Δhcp, ΔdotU, ΔicmF, ΔimpJ, and ΔimpM caused similar virulence characteristics as RS-2. Moreover, the mutant ΔpppA, ΔclpB, ΔicmF, ΔimpJ and ΔimpM genes caused by a 38.3~56.4% reduction in biofilm formation while the mutants ΔpppA, ΔclpB, ΔicmF and Δhcp resulted in a 37.5~44.6% reduction in motility. All together, these results demonstrate that T6SS play vital roles in the virulence of strain RS-2, which may be partially attributed to the reductions in Hcp secretion, biofilm formation and motility. However, differences in virulence between strain RS-1 and RS-2 suggest that other factors may also be involved in the virulence of Aaa.

  16. Role of the Genes of Type VI Secretion System in Virulence of Rice Bacterial Brown Stripe Pathogen Acidovorax avenae subsp. avenae Strain RS-2.

    Science.gov (United States)

    Masum, Md Mahidul Islam; Yang, Yingzi; Li, Bin; Olaitan, Ogunyemi Solabomi; Chen, Jie; Zhang, Yang; Fang, Yushi; Qiu, Wen; Wang, Yanli; Sun, Guochang

    2017-09-21

    The Type VI secretion system (T6SS) is a class of macromolecular machine that is required for the virulence of gram-negative bacteria. However, it is still not clear what the role of T6SS in the virulence of rice bacterial brown stripe pathogen Acidovorax avenae subsp. avenae (Aaa) is. The aim of the current study was to investigate the contribution of T6SS in Aaa strain RS2 virulence using insertional deletion mutation and complementation approaches. This strain produced weak virulence but contains a complete T6SS gene cluster based on a genome-wide analysis. Here we compared the virulence-related phenotypes between the wild-type (RS-2) and 25 T6SS mutants, which were constructed using homologous recombination methods. The mutation of 15 T6SS genes significantly reduced bacterial virulence and the secretion of Hcp protein. Additionally, the complemented 7 mutations Δ pppA , Δ clpB , Δ hcp , Δ dotU , Δ icmF , Δ impJ , and Δ impM caused similar virulence characteristics as RS-2. Moreover, the mutant Δ pppA , Δ clpB , Δ icmF , Δ impJ and Δ impM genes caused by a 38.3~56.4% reduction in biofilm formation while the mutants Δ pppA , Δ clpB , Δ icmF and Δ hcp resulted in a 37.5~44.6% reduction in motility. All together, these results demonstrate that T6SS play vital roles in the virulence of strain RS-2, which may be partially attributed to the reductions in Hcp secretion, biofilm formation and motility. However, differences in virulence between strain RS-1 and RS-2 suggest that other factors may also be involved in the virulence of Aaa.

  17. DETECTION OF TELOMERASE ACTIVITY IN BREAST CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    Yang Wentao; Xu Liangzhong; Zhang Taiming; Zhu weiping; Li Xiaomei; Jin Aiping

    1998-01-01

    Objective:To investigate the significance of telomerase activity in breast carcinoma with its respect to axillary lymph node status. Methods: Telomerase activity was analyzed in 88 breast carcinomas and 16benign breast lesions, using polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay. Results: Telomerase activity was detected in 75 (85%) of 88 breast carcinomas (including three breast carcinomas in situ which were all positive for telomerase activity), whereas in benign breast lesions analyzed only 2(12.5%) of 16 cases were positive for telomerase activity. The difference between the two groups was statistically significant (P<0.001). Besides,telomerase activity was expressed significantly higher in node-positive breast carcinoma (93%) than in nodenegative ones (77%) (P<0.05). Conclusion: Our results suggest that telomerase activation plays an important role during breast carcinoma development. It is possible that this enzyme may serve as an early indication of breast carcinoma.

  18. Incorporating climate change into pest risk models for forest pathogens: a role for cold stress in an era of global warming?

    Science.gov (United States)

    Robert C. Venette

    2013-01-01

    Climate change may alter the distribution and activity of native and alien pathogens that infect trees and, in severe cases, cause tree death. In this study, potential future changes in climate suitability are investigated for three forest pathogens that occur in western North America: the native Arceuthobium tsugense subsp tsugense...

  19. Imaging of uterine cervix carcinoma

    International Nuclear Information System (INIS)

    Viala, J.

    2000-01-01

    Imaging of uterine cervix carcinoma has evolved during the last decade. Recent developments in magnetic resonance imaging have expanded the role of MRI in evaluating the pathology of uterine cervix carcinoma. MRI is now the modality of choice for tumor staging, evaluating tumor response to treatment, diagnosing recurrences and for evaluating pregnant patients. MRI images will soon be used to calculate dosimetry for brachytherapy with matching and fusion software. (author)

  20. Foodborne pathogens

    Directory of Open Access Journals (Sweden)

    Thomas Bintsis

    2017-06-01

    Full Text Available Foodborne pathogens are causing a great number of diseases with significant effects on human health and economy. The characteristics of the most common pathogenic bacteria (Bacillus cereus, Campylobacter jejuni, Clostridium botulinum, Clostridium perfringens, Cronobacter sakazakii, Esherichia coli, Listeria monocytogenes, Salmonella spp., Shigella spp., Staphylococccus aureus, Vibrio spp. and Yersinia enterocolitica, viruses (Hepatitis A and Noroviruses and parasites (Cyclospora cayetanensis, Toxoplasma gondii and Trichinella spiralis, together with some important outbreaks, are reviewed. Food safety management systems based on to classical hazard-based approach has been proved to be inefficient, and risk-based food safety approach is now suggested from leading researchers and organizations. In this context, a food safety management system should be designed in a way to estimate the risks to human health from food consumption and to identify, select and implement mitigation strategies in order to control and reduce these risks. In addition, the application of suitable food safety education programs for all involved people in the production and consumption of foods is suggested.

  1. Role of Shear Wave Elastography in Evaluating the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B

    Science.gov (United States)

    Jeong, Jae Yoon; Sohn, Joo Hyun; Sohn, Won; Park, Chan Hyuk; Kim, Tae Yeob; Jun, Dae Won; Kim, Yongsoo; Jeong, Woo Kyoung

    2017-01-01

    Background/Aims To investigate the use of measurements of liver stiffness (LS) by two-dimensional real-time shear wave elastography (SWE) for predicting the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Methods We retrospectively collected data on 291 enrolled patients with CHB whose LS had been measured using SWE. Results The mean age of the patients was 46.8 years; males predominated (67%), and 40 of the patients (14%) had clinical cirrhosis. Among the patients, 165 (56.7%) received antiviral treatment. The median LS value was 7.4 kPa, and the median follow-up period was 35.8 months (range, 3.0 to 52.8 months). During follow-up, HCC developed in 13 patients (4.5%), and the cumulative incidence rates of HCC at 1, 2, and 4 years were 1.1%, 3.6%, and 8.4%, respectively. Based on a multivariate analysis, older age (≥50 years) and higher LS value (≥10 kPa) were independently associated with the risk of developing HCC (hazard ratio [HR], 4.53, p=0.023; and HR, 4.08, p=0.022). The cumulative incidence rate of HCC was significantly higher in patients with higher LS values (≥10 kPa) than in those with lower LS values (<10 kPa) (p=0.001). Conclusions Increased LS measured by SWE at any time point regardless of antiviral treatment is associated with an increased risk of HCC in patients with CHB. PMID:28651307

  2. Oropharyngeal Squamous Cell Carcinoma Treated With Radiotherapy or Radiochemotherapy: Prognostic Role of TP53 and HPV Status

    International Nuclear Information System (INIS)

    Fallai, Carlo; Perrone, Federica; Licitra, Lisa; Pilotti, Silvana; Locati, Laura; Bossi, Paolo; Orlandi, Ester; Palazzi, Mauro; Olmi, Patrizia

    2009-01-01

    Purpose: To study the prognostic value of the TP53 mutation and human papilloma virus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC). Methods and materials: The TP53 mutation and HPV status were analyzed in 78 cases of locoregionally advanced OPSCC. The possible correlation of these factors with locoregiownal control, relapse-free survival, disease-specific survival, and overall survival (OS) was also investigated. Results: Of these 78 cases, 22 had disruptive and 22 had non-disruptive (silent) TP53 mutations; the remaining 34 cases had wild-type (WT) TP53. HPV 16 DNA was found in 9 cases (11%), but all HPV-positive (HPV+) cases carried a functional p53 protein, except for 1 case that had a silent mutation. HPV+ patients fared better than HPV-negative (HPV-) patients in terms of all survival parameters, with highly statistically significant differences between the groups. Specifically, no distant metastases were observed in the HPV+ patients, whereas they occurred in 17% of the HPV- patients. However, no difference was observed between the WT TP53 and mutation group, even when this was analyzed in terms of disruptive and non-disruptive mutations. Regardless, treatment with chemotherapy nearly doubled the 5-year OS rates, both in the mutation (42% vs. 22%) and WT (30 vs. 16%) group, but only the mutation group showed improvement in all survival parameters. In addition, the second tumor-free 5-year survival rate was 72% in HPV- cases, but no second tumors were observed in HPV+ and WT p53 cases. Conclusions: Patients with HPV+ OPSCC have an excellent prognosis after radiochemotherapy, but cisplatin-based chemotherapy may not confer a satisfactory outcome, especially in WT cases, thereby justifying the additional or alternative use of taxanes and epidermal growth factor receptors inhibitors. Uncommon distant metastases and second tumors in the HPV+ group may be cause for clinicians to review the follow-up policies in these patients.

  3. The Emerging Role of PD-1/PD-L1-Targeting Immunotherapy in the Treatment of Metastatic Urothelial Carcinoma.

    Science.gov (United States)

    Gwynn, Morgan E; DeRemer, David L

    2018-01-01

    To summarize and evaluate immunotherapy agents targeting programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) recently approved for the treatment of metastatic urothelial carcinomas (UC). A literature review was performed using PubMed (2012 to June 2017), the American Society of Clinical Oncology abstract databases (2012 to June 2017 Annual Meetings/symposia), and the America Association for Cancer Research symposia (2012 to June 2017). A search using clinicaltrials.gov was conducted to identify studies for atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab. English language phase I to III studies assessing PD-1 and PD-L1 in UC were incorporated. Atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab have demonstrated clinical efficacy with tolerable toxicities in patients with metastatic UC with disease progression following platinum-based chemotherapy. Anti-PD-1/PD-L1 therapies may provide overall survival advantage; these are currently being evaluated in ongoing phase 3 studies. Greater objective response rates seem to be observed in PD-L1-positive patients versus PD-L1-negative patients, but methodologies in this assessment differ among clinical trials. The identification of biomarkers that provide greater insight into patients who positively respond to PD-1/PD-L1 therapies are needed. Treatment options for metastatic UC have expanded to include PD-1/PD-L1 therapies. These agents should be strongly considered as second-line therapy over single-agent chemotherapy for patients who fail or progress after platinum-based treatment.

  4. Role of anti-angiogenesis therapy in the management of hepatocellular carcinoma: The jury is still out

    Institute of Scientific and Technical Information of China (English)

    Hong; Sun; Man-Sheng; Zhu; Wen-Rui; Wu; Xiang-De; Shi; Lei-Bo; Xu

    2014-01-01

    As the leading cause of disease-related deaths,cancer is a major public health threat worldwide.Surgical resection is still the first-line therapy for patients with early-stage cancers.However,postoperative relapse and metastasis remain the cause of 90%of deaths of patients with solid organ malignancies,including hepatocellular carcinoma(HCC).With the rapid development of molecular biology techniques in recent years,molecularly targeted therapies using monoclonal antibodies,small molecules,and vaccines have become a milestone in cancer therapeutic by significantly improv-ing the survival of cancer patients,and have opened a window of hope for patients with advanced cancer.Hypervascularization is a major characteristic of HCC.It has been reported that anti-angiogenic treatments,which inhibit blood vessel formation,are highly effective for treating HCC.However,the efficacy and safety of anti-angiogenesis therapies remain controversial.Sorafenib is an oral multikinase inhibitor with antiproliferative and anti-angiogenic effects and is the first molecular target drug approved for the treatment of advanced HCC.While sorafenib has shown promising therapeutic effects,substantial evidence of primary and acquired resistance to sorafenib has been reported.Numerous clinical trials have been conducted to evaluate a large number of molecularly targeted drugs for treating HCC,but most drugs exhibited less efficacy and/or higher toxicity compared to sorafenib.Therefore,understanding the mechanism(s)underlying sorafenib resistance of cancer cells is highlighted for efficiently treating HCC.This concise review aims to provide an overview of anti-angiogenesis therapy in the management of HCC and to discuss the common mechanisms of resistance to anti-angiogenesis therapies.

  5. Role of axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast

    International Nuclear Information System (INIS)

    Zavagno, Giorgio; Capitanio, Giovanni; Ballarin, Andrea; Pierobon, Maria Elena; Marconato, Giorgia; Nitti, Donato; Carcoforo, Paolo; Marconato, Renato; Franchini, Zeno; Scalco, Giuliano; Burelli, Paolo; Pietrarota, Paolo; Lise, Mario; Mencarelli, Roberto

    2005-01-01

    Sentinel lymph node (SLN) biopsy is an effective tool for axillary staging in patients with invasive breast cancer. This procedure has been recently proposed as part of the treatment for patients with ductal carcinoma in situ (DCIS), because cases of undetected invasive foci and nodal metastases occasionally occur. However, the indications for SLN biopsy in DCIS patients are controversial. The aim of the present study was therefore to assess the incidence of SLN metastases in a series of patients with a diagnosis of pure DCIS. A retrospective evaluation was made of a series of 102 patients who underwent SLN biopsy, and had a final histologic diagnosis of pure DCIS. Patients with microinvasion were excluded from the analysis. The patients were operated on in five Institutions between 1999 and 2004. Subdermal or subareolar injection of 30–50 MBq of 99 m-Tc colloidal albumin was used for SLN identification. All sentinel nodes were evaluated with serial sectioning, haematoxylin and eosin staining, and immunohistochemical analysis for cytocheratin. Only one patient (0.98%) was SLN positive. The primary tumour was a small micropapillary intermediate-grade DCIS and the SLN harboured a micrometastasis. At pathologic revision of the specimen, no detectable focus of microinvasion was found. Our findings indicate that SLN metastases in pure DCIS are a very rare occurrence. SLN biopsy should not therefore be routinely performed in patients who undergo resection for DCIS. SLN mapping can be performed, as a second operation, in cases in which an invasive component is identified in the specimen. Only DCIS patients who require a mastectomy should have SLN biopsy performed at the time of breast operation, since in these cases subsequent node mapping is not feasible

  6. Role of Tetrasomy for the Diagnosis of Urothelial Carcinoma Using UroVysion Fluorescent In Situ Hybridization.

    Science.gov (United States)

    Zhou, Amy G; Liu, Yuxin; Cyr, Maryann St; Garver, Joanne; Woda, Bruce A; Cosar, Ediz F; Hutchinson, Lloyd M

    2016-06-01

    -UroVysion fluorescent in situ hybridization (FISH) is routinely used to detect urothelial carcinoma (UC). A positive threshold is defined as chromosome polysomy in 4 or more cells, which also includes tetrasomy, a natural product of cell division. -To evaluate tetrasomy for UC detection and explore the relation to the surgical diagnosis or patient history. -The FISH was performed on 1532 urine samples from patients with cytology results and 4 or more years of follow-up. We created separate polysomy and tetrasomy categories and constructed receiver operating curves to determine appropriate thresholds using biopsy (n = 194) as the gold standard. Standard FISH and a novel assay integrating cytomorphology and FISH (Target-FISH) were compared. Matching tissue biopsies of urine samples with 10 or more tetrasomy cells were analyzed. -No significant threshold was found for tetrasomy cells. Exclusion of tetrasomy from the polysomy category changed the threshold from 8.5 to 4.5 cells, increased specificity (59.2% to 78.9%), but reduced sensitivity (78.9% to 65.9%). In Target-FISH, the same approach yielded a specificity of 93.7% and sensitivity of 65.2%. Similarly, specificity improved significantly for low- and high-grade UC, but sensitivity decreased for low-grade UC. No evidence of UC was observed in 95% (52 of 55) of the patients referred for screening who had 10 or more tetrasomy cells by FISH. Matching biopsies for urines containing 10 or more tetrasomy cells showed few or no tetrasomy cells. -Tetrasomy is a nonspecific finding frequently encountered in urine FISH and should be excluded from the polysomy classification. Target-FISH is an optimal approach, offering the ability to detect rare tetrasomy tumors.

  7. HIF-1α and GLUT-1 Expression in Atypical Endometrial Hyperplasia, Type I and II Endometrial Carcinoma: A Potential Role in Pathogenesis

    Science.gov (United States)

    Abdou, Asmaa Gaber; Wahed, Moshira Mohammed Abdel; Kassem, Hend Abdou

    2016-01-01

    Introduction Hypoxia-Inducible Factor 1α (HIF-1α) is one of the major adaptive responses to hypoxia, regulating the activity of glucose transporter -1 (GLUT-1), responsible for glucose uptake. Aim To evaluate the immunohistochemical expression of both HIF-1α and GLUT-1 in type I and II endometrial carcinoma and their correlation with the available clinicopathologic variables in each type. Materials and Methods A retrospective study was conducted on archival blocks diagnosed from pathology department between April 2010 and August 2014 included 9 cases of atypical hyperplasia and 67 cases of endometrial carcinoma. Evaluation of both HIF-1α and GLUT-1 expression using standard immunohistochemical techniques performed on cut sections from selected paraffin embedded blocks. Statistical Analysis Descriptive analysis of the variables and statistical significances were calculated by non-parametric chi-square test using the Statistical Package for the Social Sciences version 12.0 (SPSS). Results HIF-1α was expressed in epithelial (88.9%, 52.2%, 61.2% and 50%) and stromal (33.3%, 74.6%. 71.4% and 83.3%) components of hyperplasia, total cases of EC, type I and II EC, respectively. GLUT-1 was expressed in the epithelial component of 88.9%, 98.5%, 98% and 100% of hyperplasia, total EC cases, type I and II EC, respectively. The necrosis related pattern of epithelial HIF-1α expression was in favour of type II (p=0.018) and grade III (p=0.038). HIF-1α H-score was associated with high apoptosis in both type I and total cases of EC (p=0.04). GLUT-1 H-score was negatively correlated with apoptotic count (p=0.04) and associated with high grade (p=0.003) and advanced stage in total EC (p=0.004). GLUT-1 H-score was correlated with the pattern of HIF-1α staining in all cases of EC (p= 0.04). Conclusion The role of HIF-1α in epithelial cells may differ from that of stromal cells in EC; however they augment the expression of each other supporting the crosstalk between them. The

  8. A nitrogen response pathway regulates virulence in plant pathogenic fungi: role of TOR and the bZIP protein MeaB.

    Science.gov (United States)

    López-Berges, Manuel S; Rispail, Nicolas; Prados-Rosales, Rafael C; Di Pietro, Antonio

    2010-12-01

    Virulence in plant pathogenic fungi is controlled through a variety of cellular pathways in response to the host environment. Nitrogen limitation has been proposed to act as a key signal to trigger the in planta expression of virulence genes. Moreover, a conserved Pathogenicity mitogen activated protein kinase (MAPK) cascade is strictly required for plant infection in a wide range of pathogens. We investigated the relationship between nitrogen signaling and the Pathogenicity MAPK cascade in controlling infectious growth of the vascular wilt fungus Fusarium oxysporum. Several MAPK-activated virulence functions such as invasive growth, vegetative hyphal fusion and host adhesion were strongly repressed in the presence of the preferred nitrogen source ammonium. Repression of these functions by ammonium was abolished by L-Methionine sulfoximine (MSX) or rapamycin, two specific inhibitors of Gln synthetase and the protein kinase TOR (Target Of Rapamycin), respectively, and was dependent on the bZIP protein MeaB. Supplying tomato plants with ammonium rather than nitrate resulted in a significant delay of vascular wilt symptoms caused by the F. oxysporum wild type strain, but not by the ΔmeaB mutant. Ammonium also repressed invasive growth in two other pathogens, the rice blast fungus Magnaporthe oryzae and the wheat head blight pathogen Fusarium graminearum. Our results suggest the presence of a conserved nitrogen-responsive pathway that operates via TOR and MeaB to control infectious growth in plant pathogenic fungi.

  9. High intensity focused ultrasound (HIFU) therapy for local treatment of hepatocellular carcinoma: Role of partial rib resection

    International Nuclear Information System (INIS)

    Zhu Hui; Zhou Kun; Zhang Lian; Jin Chengbin; Peng Song; Yang Wei; Li Kequan; Su Haibing; Chen Wenzhi; Bai Jin; Wu Feng; Wang, Zhibiao

    2009-01-01

    Objective: It has long been known that high intensity focused ultrasound (HIFU) can kill tissue through coagulative necrosis. However, it is only in recent years that practical clinical applications are becoming possible. Since the ribs have strong reflections to ultrasonic beams, they may affect the deposition of ultrasound energy, decreasing the efficacy of HIFU treatment and increasing the chance of adverse events when the intra-abdominal tumours concealed by ribs are treated. The aim of this study was to evaluate the influence of partial rib resection on the efficacy and safety of HIFU treatment. Methods: This prospective study was approved by the ethics committee at Chongqing University of Medical Sciences. An informed consent form was obtained from each patient and family member. A total of 16 patients with hepatocellular carcinoma (HCC), consisting of 13 males and 3 females, were studied. All patients had the successful HIFU treatment. To create a better acoustic pathway for HIFU treatment, all of the 16 patients had the ribs that shield the tumour mass to be removed. Magnetic resonance imaging (MRI) was used to evaluate the efficacy of HIFU treatment. Results: Sixteen cases had 23 nodules, including 12 cases with a single nodule, 1 case with 2 nodules, 3 cases with 3 nodules. The mean diameter of tumours was 7.0 ± 2.1 cm (5-10 cm). According to TNM classification, 9 patients were diagnosed as stage II, 4 patients were stage III, and 3 patients were stage IV. Follow-up imaging showed an absence of tumour blood supply and shrinkage of all treated lesions. The survival rates at 1, 2, 3, 4, and 5 years were 100%, 83.3%, 69.4%, 55.6%, and 55.6%, respectively. No serious complications were observed in the patients treated with HIFU. Conclusion: Partial rib resection can create a better acoustic pathway of HIFU therapy. Even though it is an invasive treatment, this measure offers patients an improved prospect of complete tumour ablation when no other treatment is

  10. Role of presurgical targeted molecular therapy in renal cell carcinoma with an inferior vena cava tumor thrombus

    Directory of Open Access Journals (Sweden)

    Peng C

    2018-04-01

    Full Text Available Cheng Peng,1,* Liangyou Gu,1,* Lei Wang,2 Qingbo Huang,1 Baojun Wang,1 Gang Guo,1 Yang Fan,1 Yu Gao,1 Xin Ma,1 Xu Zhang1 1Department of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical Academy, Beijing, People’s Republic of China; 2Department of Urology, Chinese PLA 534 Hospital, Luoyang, People’s Republic of China *These authors contributed equally to this work Purpose: The clinical benefit of targeted molecular therapy (TMT in renal cell carcinoma (RCC with an inferior vena cava (IVC tumor thrombus remains controversial. The aim of this study was to investigate the effects of presurgical TMT on the heights and levels of IVC thrombi, and to assess its impact on surgical strategy. Patients and methods: We retrospectively reviewed data from 18 patients with RCC involving IVC tumor thrombi who were treated at our hospital with presurgical TMT followed by an IVC thrombectomy. The changes in heights and levels of the IVC thrombi were compared using computed tomography or magnetic resonance imaging. Clinicopathological factors were also evaluated to assess their association with TMT efficacy. Results: The tumor thrombus levels before TMT were stage I in 1 patient (5.6%, II in 12 patients (66.7%, III in 4 patients (22.2%, and IV in 1 patient (5.6%. After a median of two treatment cycles (range: 1–3, the thrombus height decreased measurably in 11 patients (61.1% with an average shrinkage of 17.7%. The thrombus height remained stable in five patients (27.8% and was enlarged in two (11.1%. Downstaging of the thrombus level occurred in four patients (22.2%; the surgical strategy was modified in three patients (16.7% to avoid cardiopulmonary bypass and complicated liver mobilization under robot-assisted laparoscopy. Furthermore, a higher neutrophil count tended to be associated with a worse clinical TMT-associated outcome (P=0.056. Conclusion: Our data suggest a limited influence of presurgical TMT

  11. Carcinoma multiplex

    International Nuclear Information System (INIS)

    Shah, S. A.; Riaz, U.; Zahoor, I.; Jalil, A.; Zubair, M.

    2013-01-01

    Multiple primaries in a single patient are uncommon, though not very rare. The existence of such cancers in two un-related, non-paired organs is even more un-common. Here, we present a case of 55 years old male who presented to us with a mucoepidermoid carcinoma of the parotid gland and was operated. Later on, he presented with a large cystic swelling in the pelvis which turned out to be pseudomyxoma peritonei. A review of slides and immunohistochemistry indicated it to be adenocarcinoma colon. He presented again with recurrent mucoepidermoid carcinoma of the parotid which was operated successfully with the use of myocutaneous flap for wound closure. He is currently undergoing chemotherapy. In order to establish a separate mono-clonal etiology of both tumours, immunohistochemistry was performed. To the best of our knowledge, carcinoma multiplex in the colon and the parotid has never been reported before. (author)

  12. Temporal activation of anti- and pro-apoptotic factors in human gingival fibroblasts infected with the periodontal pathogen, Porphyromonas gingivalis: potential role of bacterial proteases in host signalling

    Directory of Open Access Journals (Sweden)

    Takehara Tadamichi

    2006-03-01

    Full Text Available Abstract Background Porphyromonas gingivalis is the foremost oral pathogen of adult periodontitis in humans. However, the mechanisms of bacterial invasion and the resultant destruction of the gingival tissue remain largely undefined. Results We report host-P. gingivalis interactions in primary human gingival fibroblast (HGF cells. Quantitative immunostaining revealed the need for a high multiplicity of infection for optimal infection. Early in infection (2–12 h, P. gingivalis activated the proinflammatory transcription factor NF-kappa B, partly via the PI3 kinase/AKT pathway. This was accompanied by the induction of cellular anti-apoptotic genes, including Bfl-1, Boo, Bcl-XL, Bcl2, Mcl-1, Bcl-w and Survivin. Late in infection (24–36 h the anti-apoptotic genes largely shut down and the pro-apoptotic genes, including Nip3, Hrk, Bak, Bik, Bok, Bax, Bad, Bim and Moap-1, were activated. Apoptosis was characterized by nuclear DNA degradation and activation of caspases-3, -6, -7 and -9 via the intrinsic mitochondrial pathway. Use of inhibitors revealed an anti-apoptotic function of NF-kappa B and PI3 kinase in P. gingivalis-infected HGF cells. Use of a triple protease mutant P. gingivalis lacking three major gingipains (rgpA rgpB kgp suggested a role of some or all these proteases in myriad aspects of bacteria-gingival interaction. Conclusion The pathology of the gingival fibroblast in P. gingivalis infection is affected by a temporal shift from cellular survival response to apoptosis, regulated by a number of anti- and pro-apoptotic molecules. The gingipain group of proteases affects bacteria-host interactions and may directly promote apoptosis by intracellular proteolytic activation of caspase-3.

  13. Investigating the Role of the Host Multidrug Resistance Associated Protein Transporter Family in Burkholderia cepacia Complex Pathogenicity Using a Caenorhabditis elegans Infection Model.

    Science.gov (United States)

    Tedesco, Pietro; Visone, Marco; Parrilli, Ermenegilda; Tutino, Maria Luisa; Perrin, Elena; Maida, Isabel; Fani, Renato; Ballestriero, Francesco; Santos, Radleigh; Pinilla, Clemencia; Di Schiavi, Elia; Tegos, George; de Pascale, Donatella

    2015-01-01

    This study investigated the relationship between host efflux system of the non-vertebrate nematode Caenorhabditis elegans and Burkholderia cepacia complex (Bcc) strain virulence. This is the first comprehensive effort to profile host-transporters within the context of Bcc infection. With this aim, two different toxicity tests were performed: a slow killing assay that monitors mortality of the host by intestinal colonization and a fast killing assay that assesses production of toxins. A Virulence Ranking scheme was defined, that expressed the toxicity of the Bcc panel members, based on the percentage of surviving worms. According to this ranking the 18 Bcc strains were divided in 4 distinct groups. Only the Cystic Fibrosis isolated strains possessed profound nematode killing ability to accumulate in worms' intestines. For the transporter analysis a complete set of isogenic nematode single Multidrug Resistance associated Protein (MRP) efflux mutants and a number of efflux inhibitors were interrogated in the host toxicity assays. The Bcc pathogenicity profile of the 7 isogenic C. elegans MRP knock-out strains functionality was classified in two distinct groups. Disabling host transporters enhanced nematode mortality more than 50% in 5 out of 7 mutants when compared to wild type. In particular mrp-2 was the most susceptible phenotype with increased mortality for 13 out 18 Bcc strains, whereas mrp-3 and mrp-4 knock-outs had lower mortality rates, suggesting a different role in toxin-substrate recognition. The use of MRP efflux inhibitors in the assays resulted in substantially increased (>40% on average) mortality of wild-type worms.

  14. Roles of the twin-arginine translocase and associated chaperones in the biogenesis of the electron transport chains of the human pathogen Campylobacter jejuni.

    Science.gov (United States)

    Hitchcock, Andrew; Hall, Stephen J; Myers, Jonathan D; Mulholland, Francis; Jones, Michael A; Kelly, David J

    2010-10-01

    The zoonotic pathogen Campylobacter jejuni NCTC 11168 uses a complex set of electron transport chains to ensure growth with a variety of electron donors and alternative electron acceptors, some of which are known to be important for host colonization. Many of the key redox proteins essential for electron transfer in this bacterium have N-terminal twin-arginine translocase (TAT) signal sequences that ensure their transport across the cytoplasmic membrane in a folded state. By comparisons of 2D gels of periplasmic extracts, gene fusions and specific enzyme assays in wild-type, tatC mutant and complemented strains, we experimentally verified the TAT dependence of 10 proteins with an N-terminal twin-arginine motif. NrfH, which has a TAT-like motif (LRRKILK), was functional in nitrite reduction in a tatC mutant, and was correctly rejected as a TAT substrate by the tatfind and TatP prediction programs. However, the hydrogenase subunit HydA is also rejected by tatfind, but was shown to be TAT-dependent experimentally. The YedY homologue Cj0379 is the only TAT translocated molybdoenzyme of unknown function in C. jejuni; we show that a cj0379c mutant is deficient in chicken colonization and has a nitrosative stress phenotype, suggestive of a possible role for Cj0379 in the reduction of reactive nitrogen species in the periplasm. Only two potential TAT chaperones, NapD and Cj1514, are encoded in the genome. Surprisingly, despite homology to TorD, Cj1514 was shown to be specifically required for the activity of formate dehydrogenase, not trimethylamine N-oxide reductase, and was designated FdhM.

  15. Follicular carcinoma

    International Nuclear Information System (INIS)

    Shah, D.H.; Samuel, A.M.

    1999-01-01

    Follicular thyroid carcinoma (FTC) is considered as a disease of the elderly with a higher incidence in females as compared to papillary thyroid carcinoma (PTC). Some studies have reported its occurrence at an early age, which may be attributed to early diagnosis because of the availability of advanced techniques. The prognosis of the disease is considered poor as compared to that of PTC. The conclusions drawn in this review are based on 663 cases in whom adequate data was available for meaningful analysis followed for a mean period of 9.2 years, median, 7.8 years; range, 1-32 years

  16. GALLBLADDER CARCINOMA

    OpenAIRE

    Blaž Trotovšek; Valentin Sojar; Dragan Stanisavljevič; Aleš Tomažič

    2003-01-01

    Background. Carcinoma of the gallbladder is a tumour with a dismal prognosis and 5-years overall survival rate less than 5%. Among the tumours of the gastrointestinal tract it is fifth in the row and its incidence is approximately 1.2/105. Tumour occurs more often (2–6 times) in women and in people over 50 years old (90%). According to the Slovenian Registry of Cancer for year 1998 the incidence of gallbladder carcinoma was 2.7/105 and it occurred 4 times more often among women. The most impo...

  17. Roles of posttherapy 18F-FDG PET/CT in patients with advanced squamous cell carcinoma of the uterine cervix receiving concurrent chemoradiotherapy.

    Science.gov (United States)

    Liu, Feng-Yuan; Su, Tzu-Pei; Wang, Chun-Chieh; Chao, Angel; Chou, Hung-Hsueh; Chang, Yu-Chen; Yen, T