Sample records for adenocarcinoma potential relevance


    Robert Edwards


    Full Text Available The family of Retinoic acid compounds have long been the subject of intense study and interest as chemo prophylactic agents. This dates back to their therapeutic effect in leukoplakia Where ATRA was shown to lead to the reversal of premalignant lesions and Subsequent reports on their use in metastatic colorectal adenocarcinoma and a vast array of other malignant disorders as well as adjuvant treatment of loco regional head and neck and colorectal adenocarcinoma. All-trans retinoic acid has transformed the treatment and outcome of patients with acute promyelocytic leukemia by differentiating leukemic promyelocytes into mature cells. Retinoid Receptor knock out mouse models also serve as excellent proof for the critical role of retinoids in embryogenesis, specifically their vital role in heart and blood vessel development, CNS specification, fetal lung development and proper limb morphogenesis. Here we show the results of our first phase of in vitro studies of the interaction of ATRA with the Gut homing Receptor, CCR9. Hypoxia up regulates CCR9 expression in CCIC, while ATRA down regulates CCR9 expression in hypoxic CCIC. In contrast, HT29 cells express significantly less CCR9 which is up regulated by hypoxia and further enhanced by ATRA treatment. We conclude that CCIC (representing a colon cancer stem-like line respond differently to ATRA treatment Vs. a less stem-like, more differentiated cancer cell line such as HT-29. These results support a potential clinical use of ATRA early in the natural history of CRC in order to abort or slow down the process of metastasis in colorectal adenocarcinoma which is the ultimate killer of such patients. They also signify the critical significance of the time window and intratumoral heterogeneity in the final outcome of our intervention with ATRA in the treatment of CRC.

  2. Cryptosporidium parvum, a potential cause of colic adenocarcinoma

    Pinon Anthony


    Full Text Available Abstract Background Cryptosporidiosis represents a major public health problem. This infection has been reported worldwide as a frequent cause of diarrhoea. Particularly, it remains a clinically significant opportunistic infection among immunocompromised patients, causing potentially life-threatening diarrhoea in HIV-infected persons. However, the understanding about different aspects of this infection such as invasion, transmission and pathogenesis is problematic. Additionally, it has been difficult to find suitable animal models for propagation of this parasite. Efforts are needed to develop reproducible animal models allowing both the routine passage of different species and approaching unclear aspects of Cryptosporidium infection, especially in the pathophysiology field. Results We developed a model using adult severe combined immunodeficiency (SCID mice inoculated with Cryptosporidium parvum or Cryptosporidium muris while treated or not with Dexamethasone (Dex in order to investigate divergences in prepatent period, oocyst shedding or clinical and histopathological manifestations. C. muris-infected mice showed high levels of oocysts excretion, whatever the chemical immunosuppression status. Pre-patent periods were 11 days and 9.7 days in average in Dex treated and untreated mice, respectively. Parasite infection was restricted to the stomach, and had a clear preferential colonization for fundic area in both groups. Among C. parvum-infected mice, Dex-treated SCID mice became chronic shedders with a prepatent period of 6.2 days in average. C. parvum-inoculated mice treated with Dex developed glandular cystic polyps with areas of intraepithelial neoplasia, and also with the presence of intramucosal adenocarcinoma. Conclusion For the first time C. parvum is associated with the formation of polyps and adenocarcinoma lesions in the gut of Dex-treated SCID mice. Additionally, we have developed a model to compare chronic muris and parvum

  3. Clinically relevant characterization of lung adenocarcinoma subtypes based on cellular pathways: an international validation study.

    Christopher M Bryant

    Full Text Available Lung adenocarcinoma (AD represents a predominant type of lung cancer demonstrating significant morphologic and molecular heterogeneity. We sought to understand this heterogeneity by utilizing gene expression analyses of 432 AD samples and examining associations between 27 known cancer-related pathways and the AD subtype, clinical characteristics and patient survival. Unsupervised clustering of AD and gene expression enrichment analysis reveals that cell proliferation is the most important pathway separating tumors into subgroups. Further, AD with increased cell proliferation demonstrate significantly poorer outcome and an increased solid AD subtype component. Additionally, we find that tumors with any solid component have decreased survival as compared to tumors without a solid component. These results lead to the potential to use a relatively simple pathological examination of a tumor in order to determine its aggressiveness and the patient's prognosis. Additional results suggest the ability to use a similar approach to determine a patient's sensitivity to targeted treatment. We then demonstrated the consistency of these findings using two independent AD cohorts from Asia (N = 87 and Europe (N = 89 using the identical analytic procedures.

  4. Diagnosis potential of near infrared Mueller Matrix imaging for colonic adenocarcinoma

    Wang, Jianfeng; Zheng, Wei; Lin, Kan; Huang, Zhiwei


    Mueller matrix imaging along with polar decomposition method was employed for the colonic adenocarcinoma detection by polarized light in the near-infrared spectral range (700-1100 nm). A high-speed (caner) were acquired. Polar decomposition was further implemented on the 16 images to derive the diattentuation, depolarization, and the retardance images. The decomposed images showed clear margin between the normal and adenocarcinomaous colon tissue samples. The work shows the potential of near-infrared Mueller matrix imaging for the early diagnosis and detection of malignant lesions in the colon.

  5. Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas.

    Julia Slotta-Huspenina

    Full Text Available A high percentage of oesophageal adenocarcinomas show an aggressive clinical behaviour with a significant resistance to chemotherapy. Heat-shock proteins (HSPs and glucose-regulated proteins (GRPs are molecular chaperones that play an important role in tumour biology. Recently, novel therapeutic approaches targeting HSP90/GRP94 have been introduced for treating cancer. We performed a comprehensive investigation of HSP and GRP expression including HSP27, phosphorylated (p-HSP27((Ser15, p-HSP27((Ser78, p-HSP27((Ser82, HSP60, HSP70, HSP90, GRP78 and GRP94 in 92 primary resected oesophageal adenocarcinomas by using reverse phase protein arrays (RPPA, immunohistochemistry (IHC and real-time quantitative RT-PCR (qPCR. Results were correlated with pathologic features and survival. HSP/GRP protein and mRNA expression was detected in all tumours at various levels. Unsupervised hierarchical clustering showed two distinct groups of tumours with specific protein expression patterns: The hallmark of the first group was a high expression of p-HSP27((Ser15, Ser78, Ser82 and low expression of GRP78, GRP94 and HSP60. The second group showed the inverse pattern with low p-HSP27 and high GRP78, GRP94 and HSP60 expression. The clinical outcome for patients from the first group was significantly improved compared to patients from the second group, both in univariate analysis (p = 0.015 and multivariate analysis (p = 0.029. Interestingly, these two groups could not be distinguished by immunohistochemistry or qPCR analysis. In summary, two distinct and prognostic relevant HSP/GRP protein expression patterns in adenocarcinomas of the oesophagus were detected by RPPA. Our approach may be helpful for identifying candidates for specific HSP/GRP-targeted therapies.

  6. Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas.

    Slotta-Huspenina, Julia; Berg, Daniela; Bauer, Karina; Wolff, Claudia; Malinowsky, Katharina; Bauer, Lukas; Drecoll, Enken; Bettstetter, Marcus; Feith, Marcus; Walch, Axel; Höfler, Heinz; Becker, Karl-Friedrich; Langer, Rupert


    A high percentage of oesophageal adenocarcinomas show an aggressive clinical behaviour with a significant resistance to chemotherapy. Heat-shock proteins (HSPs) and glucose-regulated proteins (GRPs) are molecular chaperones that play an important role in tumour biology. Recently, novel therapeutic approaches targeting HSP90/GRP94 have been introduced for treating cancer. We performed a comprehensive investigation of HSP and GRP expression including HSP27, phosphorylated (p)-HSP27((Ser15)), p-HSP27((Ser78)), p-HSP27((Ser82)), HSP60, HSP70, HSP90, GRP78 and GRP94 in 92 primary resected oesophageal adenocarcinomas by using reverse phase protein arrays (RPPA), immunohistochemistry (IHC) and real-time quantitative RT-PCR (qPCR). Results were correlated with pathologic features and survival. HSP/GRP protein and mRNA expression was detected in all tumours at various levels. Unsupervised hierarchical clustering showed two distinct groups of tumours with specific protein expression patterns: The hallmark of the first group was a high expression of p-HSP27((Ser15, Ser78, Ser82)) and low expression of GRP78, GRP94 and HSP60. The second group showed the inverse pattern with low p-HSP27 and high GRP78, GRP94 and HSP60 expression. The clinical outcome for patients from the first group was significantly improved compared to patients from the second group, both in univariate analysis (p = 0.015) and multivariate analysis (p = 0.029). Interestingly, these two groups could not be distinguished by immunohistochemistry or qPCR analysis. In summary, two distinct and prognostic relevant HSP/GRP protein expression patterns in adenocarcinomas of the oesophagus were detected by RPPA. Our approach may be helpful for identifying candidates for specific HSP/GRP-targeted therapies.

  7. ADAM28: a potential oncogene involved in asbestos-related lung adenocarcinomas.

    Wright, Casey M; Larsen, Jill E; Hayward, Nicholas K; Martins, Maria U; Tan, Maxine E; Davidson, Morgan R; Savarimuthu, Santiyagu M; McLachlan, Rebecca E; Passmore, Linda H; Windsor, Morgan N; Clarke, Belinda E; Duhig, Edwina E; Yang, Ian A; Bowman, Rayleen V; Fong, Kwun M


    Asbestos-related lung cancer accounts for 4-12% of all lung cancers worldwide. Since putative mechanisms of carcinogenesis differ between asbestos and tobacco induced lung cancers, tumors induced by the two agents may be genetically distinct. To identify gene expression biomarkers associated with asbestos-related lung tumorigenicity we performed gene expression array analysis on tumors of 36 patients with primary lung adenocarcinoma, comparing 12 patients with lung asbestos body counts above levels associated with urban dwelling (ARLC-AC: asbestos-related lung cancer-adenocarcinoma) with 24 patients with no asbestos bodies (NARLC-AC: non-asbestos related lung cancer-adenocarcinoma). Genes differentially expressed between ARLC-AC and NARLC-AC were identified on fold change and P value, and then prioritized using gene ontology. Candidates included ZNRF3, ADAM28, PPP1CA, IRF6, RAB3D, and PRDX1. Expression of these six genes was technically and biologically replicated by qRT-PCR in the training set and biologically validated in three independent test sets. ADAM28, encoding a disintegrin and metalloproteinase domain protein that interacts with integrins, was consistently upregulated in ARLC across all four datasets. Further studies are being designed to investigate the possible role of this gene in asbestos lung tumorigenicity, its potential utility as a marker of asbestos related lung cancer for purposes of causal attribution, and its potential as a treatment target for lung cancers arising in asbestos exposed persons.

  8. Inverse Relationship Between Leydig Cell Density and Metastatic Potential of Prostatic Adenocarcinoma

    W. John Wang


    Full Text Available Purpose: Evaluate the relationship between metastatic potential of prostatic adenocarcinoma (PC and testicular Leydig cell density. Materials and methods: Tissue samples from 111 men, age 52–85, with PC and bilateral orchiectomy were evaluated for Leydig cell density. The patients were divided into two groups: Group A were patients with metastasis (n=36 and Group B were patients without metastasis (n=75. Leydig cell density was determined by direct manual microscopic cell count on the tissue sections. The means of cell counts by four pathologists, expressed as cell/0.78 mm2 were used for analysis. The normally distributed data were analyzed by two‐tail Student’s t‐test. Thirty‐eight age‐compatible autopsy cases who died of unrelated causes served as normal controls. Results: The mean of Leydig cell count in group A patients was 14.43 (14.43 ± 1.19 SE. Mean of Group B was 47.05 (47.05 ± 4.05 SE whereas normal controls displayed a mean of 48.66 (48.66 ± 2.94 SE. Group A was significantly different from control (p0.75. Conclusions: Patients with metastatic adenocarcinoma of prostate, as a group, have a significantly lower Leydig cell density than patients without metastasis or patients without PC in compatible age groups. The hormonal relationship between this observation is however unknown. One possible explanation is that PC subpopulation with metastatic potential may require different level of endogenous androgen or are androgen‐independent.

  9. Selected flavonoids potentiate the toxicity of cisplatin in human lung adenocarcinoma cells: A role for glutathione depletion

    Kachadourian, Remy; LEITNER, VHEATHER M.; Day, Brian J.


    Adjuvant therapies that enhance the anti-tumor effects of cisplatin are actively being pursued. Growing evidence supports the involvement of mitochondrial dysfunction in the anti-cancer effect of cis-diammineplatinum(II) dichloride (cisplatin, CDDP). We examined the potential of using selective flavonoids that are effective in depleting tumor cells of glu-tathione (GSH) to potentiate cisplatin-mediated cytotoxicity in human lung adenocarcinoma (A549) cells. We found that cisplatin (40 μM, 48-...

  10. Identification of the potential biomarkers for the metastasis of rectal adenocarcinoma.

    Hua, Yang; Ma, Xiukun; Liu, Xianglong; Yuan, Xiangfei; Qin, Hai; Zhang, Xipeng


    Rectal cancer is a common malignant tumor of the digestive tract, with a high incidence and high mortality. This study aimed to identify the potential biomarkers and therapeutic targets for rectal adenocarcinoma (RAC) metastasis. The expression profiling of RAC patients with metastasis and RAC patients without metastasis was downloaded from The Cancer Genome Atlas (TCGA) database. The datasets were used to identify the genes associated with RAC metastasis. Fifty up-regulated genes and seventeen down-regulated genes were identified in the primary tumor loci of RAC metastasis compared with non-metastasis. Sixty-seven dysregulated gens were conducted to construct the protein-protein network, and CCND3 was the hub protein. The dysregulated genes were significantly enriched in pancreatic secretion, cell adhesion molecules pathways, response to vitamin D of biological process, and retinoid binding of molecular function. Quantitative real-time polymerase chain reaction results demonstrated that CCND3, AQP3, PEG10, and RAB27B had the up-regulated tendency in RAC metastasis; ADCY1 had the down-regulated tendency in RAC metastasis. CCND3, AQP3, PEG10, RAB27B, and ADCY1 might play essential roles in the metastasis process of RAC through pancreatic secretion and cell adhesion molecules pathways. The five genes could be potential diagnosis biomarkers or therapeutic targets for RAC metastasis.

  11. Identification of ubiquinol cytochrome c reductase hinge (UQCRH) as a potential diagnostic biomarker for lung adenocarcinoma

    Gao, Feng; Liu, Qicai; Li, Guoping; Dong, Feng; Qiu, Minglian; Lv, Xiaoting; Zhang, Sheng; Guo, Zheng


    Ubiquinol cytochrome c reductase hinge (UQCRH) is a novel protein that localizes in the mitochondrial membrane and induces mitochondrial reactive oxygen species (ROS) generation. It had a high expression rate of 87.10% (108/124) in lung adenocarcinoma. Moreover, serum UQCRH level in patients with lung adenocarcinoma was significantly increased compared with that of pneumonia patients (p < 0.0001) and normal control subjects (p < 0.0001). Receiver operating characteristic curve analysis using ...

  12. Potential Therapeutic Benefit of Combining Gefitinib and Tamoxifen for Treating Advanced Lung Adenocarcinoma

    Chien-Ming Liu


    Full Text Available Introduction. Epidermal growth factor receptor (EGFR mutations are known as oncogene driver mutations and with EGFR mutations exhibit good response to the EGFR tyrosine kinase inhibitor Gefitinib. Some studies have shown that activation of estrogen and estrogen receptor α or β (ERα/β promote adenocarcinoma. We evaluated the relationship between the two receptors and the potential therapeutic benefit with Gefitinib and Tamoxifen. Methods. We assessed the association between EGFR mutations as well as ERα/β expression/location and overall survival in a cohort of 55 patients with LAC from a single hospital. PC9 (EGFR exon 19 deletion mutant; Gefitinib-vulnerable cells and A549 (EGFR wild type; Gefitinib-resistant cells cancer cells were used to evaluate the in vitro therapeutic benefits of combining Gefitinib and Tamoxifen. Results. We found that the cytosolic but not the nuclear expression of ERβ was associated with better OS in LAC tumors but not associated with EGFR mutation. The in vitro study showed that combined Gefitinib and Tamoxifen resulted in increased apoptosis and cytosolic expression of ERβ. In addition, combining both medications resulted in reduced cell growth and increased the cytotoxic effect of Gefitinib. Conclusion. Tamoxifen enhanced advanced LAC cytotoxic effect induced by Gefitinib by arresting ERβ in cytosol.

  13. Proteomic identification of potential prognostic biomarkers in resectable pancreatic ductal adenocarcinoma.

    Iuga, Cristina; Seicean, Andrada; Iancu, Cornel; Buiga, Rareş; Sappa, Praveen K; Völker, Uwe; Hammer, Elke


    Pancreatic cancer is a devastating disease with a mortality rate almost identical with its incidence. In this context, the investigation of the pancreatic cancer proteome has gained considerable attention because profiles of proteins may be able to identify disease states and progression more accurately. Therefore, our objective was to investigate the changes in the proteome of patients suffering from pancreatic ductal adenocarcinoma (PDAC) by a comprehensive quantitative approach. Comparative proteomic profiling by label-free LC-MS/MS analysis of nine matched pairs of tumor and nontumor pancreas samples was used to identify differences in protein levels characteristic for PDAC. In this analysis, 488 proteins were quantified by at least two peptides of which 99 proteins displayed altered levels in PDAC (p 1.3). Screening of data revealed a number of molecules that had already been related to PDAC such as galectin-1 (LEG1), major vault protein, adenylyl cyclase-associated protein 1 (CAP1), but also a potential new prognostic biomarker prolargin (PRELP). The Kaplan-Meier survival analysis revealed a significant correlation of protein abundance of PRELP with postoperative survival of patients with PDAC. For selected proteins the findings were verified by targeted proteomics (SRM), validated by immunohistochemistry and Western blotting and their value as candidate biomarkers is discussed.

  14. Erythropoietin receptor expression is a potential prognostic factor in human lung adenocarcinoma.

    Anita Rózsás

    Full Text Available Recombinant human erythropoietins (rHuEPOs are used to treat cancer-related anemia. Recent preclinical studies and clinical trials, however, have raised concerns about the potential tumor-promoting effects of these drugs. Because the clinical significance of erythropoietin receptor (EPOR signaling in human non-small cell lung cancer (NSCLC also remains controversial, our aim was to study whether EPO treatment modifies tumor growth and if EPOR expression has an impact on the clinical behavior of this malignancy. A total of 43 patients with stage III-IV adenocarcinoma (ADC and complete clinicopathological data were included. EPOR expression in human ADC samples and cell lines was measured by quantitative real-time polymerase chain reaction. Effects of exogenous rHuEPOα were studied on human lung ADC cell lines in vitro. In vivo growth of human ADC xenografts treated with rHuEPOα with or without chemotherapy was also assessed. In vivo tumor and endothelial cell (EC proliferation was determined by 5-bromo-2'-deoxy-uridine (BrdU incorporation and immunofluorescent labeling. Although EPOR mRNA was expressed in all of the three investigated ADC cell lines, rHuEPOα treatment (either alone or in combination with gemcitabine did not alter ADC cell proliferation in vitro. However, rHuEPOα significantly decreased tumor cell proliferation and growth of human H1975 lung ADC xenografts. At the same time, rHuEPOα treatment of H1975 tumors resulted in accelerated tumor endothelial cell proliferation. Moreover, in patients with advanced stage lung ADC, high intratumoral EPOR mRNA levels were associated with significantly increased overall survival. This study reveals high EPOR level as a potential novel positive prognostic marker in human lung ADC.

  15. Metabolites of purine nucleoside phosphorylase (NP in serum have the potential to delineate pancreatic adenocarcinoma.

    Shaiju K Vareed

    Full Text Available Pancreatic Adenocarcinoma (PDAC, the fourth highest cause of cancer related deaths in the United States, has the most aggressive presentation resulting in a very short median survival time for the affected patients. Early detection of PDAC is confounded by lack of specific markers that has motivated the use of high throughput molecular approaches to delineate potential biomarkers. To pursue identification of a distinct marker, this study profiled the secretory proteome in 16 PDAC, 2 carcinoma in situ (CIS and 7 benign patients using label-free mass spectrometry coupled to 1D-SDS-PAGE and Strong Cation-Exchange Chromatography (SCX. A total of 431 proteins were detected of which 56 were found to be significantly elevated in PDAC. Included in this differential set were Parkinson disease autosomal recessive, early onset 7 (PARK 7 and Alpha Synuclein (aSyn, both of which are known to be pathognomonic to Parkinson's disease as well as metabolic enzymes like Purine Nucleoside Phosphorylase (NP which has been exploited as therapeutic target in cancers. Tissue Microarray analysis confirmed higher expression of aSyn and NP in ductal epithelia of pancreatic tumors compared to benign ducts. Furthermore, extent of both aSyn and NP staining positively correlated with tumor stage and perineural invasion while their intensity of staining correlated with the existence of metastatic lesions in the PDAC tissues. From the biomarker perspective, NP protein levels were higher in PDAC sera and furthermore serum levels of its downstream metabolites guanosine and adenosine were able to distinguish PDAC from benign in an unsupervised hierarchical classification model. Overall, this study for the first time describes elevated levels of aSyn in PDAC as well as highlights the potential of evaluating NP protein expression and levels of its downstream metabolites to develop a multiplex panel for non-invasive detection of PDAC.

  16. Outcome of conservative treatment and subsequent assisted reproductive technology for patients with early-stage endometrial adenocarcinoma and poor fertility potential

    TONG Xiao-mei; ZHU Hai-yan; LIN Xiao-na; JIANG Ling-ying; XU Wei-hai; LIU Liu; ZHANG Song-ying


    Conservative treatment with high doses of progestin is an alternative to standard hysterectomy for young patients with early-stage endometrial adenocarcinoma who desire to preserve their fertility.Here we report a patient with well-differentiated early-stage endometrial adenocarcinoma and poor fertility potential who failed to become pregnant in two in vitro fertilization-embryo transfer cycles and suffered a relapse after conservative treatment.This case illustrates that assessment of fertility potential is critical at the time of initial evaluation and conservative treatment planning for patients with endometrial adenocarcinoma.Chin Med J 2012; 125(19):3578-3580

  17. Ion channel gene expression in lung adenocarcinoma: potential role in prognosis and diagnosis.

    Ko, Jae-Hong; Gu, Wanjun; Lim, Inja; Bang, Hyoweon; Ko, Eun A; Zhou, Tong


    Ion channels are known to regulate cancer processes at all stages. The roles of ion channels in cancer pathology are extremely diverse. We systematically analyzed the expression patterns of ion channel genes in lung adenocarcinoma. First, we compared the expression of ion channel genes between normal and tumor tissues in patients with lung adenocarcinoma. Thirty-seven ion channel genes were identified as being differentially expressed between the two groups. Next, we investigated the prognostic power of ion channel genes in lung adenocarcinoma. We assigned a risk score to each lung adenocarcinoma patient based on the expression of the differentially expressed ion channel genes. We demonstrated that the risk score effectively predicted overall survival and recurrence-free survival in lung adenocarcinoma. We also found that the risk scores for ever-smokers were higher than those for never-smokers. Multivariate analysis indicated that the risk score was a significant prognostic factor for survival, which is independent of patient age, gender, stage, smoking history, Myc level, and EGFR/KRAS/ALK gene mutation status. Finally, we investigated the difference in ion channel gene expression between the two major subtypes of non-small cell lung cancer: adenocarcinoma and squamous-cell carcinoma. Thirty ion channel genes were identified as being differentially expressed between the two groups. We suggest that ion channel gene expression can be used to improve the subtype classification in non-small cell lung cancer at the molecular level. The findings in this study have been validated in several independent lung cancer cohorts.

  18. Pioglitazone protects against cisplatin induced nephrotoxicity in rats and potentiates its anticancer activity against human renal adenocarcinoma cell lines.

    Mahmoud, Mona F; El Shazly, Shimaa M


    Cisplatin-induced nephrotoxicity is a serious problem that limits its use in cancer treatment. The present study aimed to investigate the renal protective capacity of pioglitazone to reduce the cisplatin- induced nephrotoxicity. The underlying suggested mechanism(s) and whether this nephroprotective effect (if any) interferes with the cytotoxic effect of cisplatin on cancer cells were also investigated. Pioglitazone, Bisphenol A diglycidyl ether, BADGE, IP injected (Peroxisome proliferator- activated receptor gamma (PPAR-γ) antagonist), or their combination were administered to rats one hour before cisplatin injection. Moreover, their effects on the cell viability of human renal adenocarcinoma cell models (ACHN) were studied. The obtained results showed that pioglitazone improved the renal function, structural changes, renal malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-κB) genes expression in cisplatin injected rats. It increased both renal reduced glutathione (GSH) content and PPAR-γ gene expression. In contrast to the data obtained by prior administration of BADGE. Pioglitazone also potentiated the cytotoxic effect of cisplatin on human renal adenocarcinoma cells and this effect was abolished by BADGE co administration. In conclusion, these results suggested that pioglitazone protected against cisplatin- induced nephrotoxicity through its interaction with PPAR-γ receptors and antioxidant effects. Furthermore, pioglitazone did not interfere but rather potentiated the cytotoxic effects of cisplatin on human renal adenocarcinoma cells.

  19. Hypoxia in human colorectal adenocarcinoma: comparison between extrinsic and potential intrinsic hypoxia markers.

    Goethals, L.; Debucquoy, A.; Perneel, C.; Geboes, K.; Ectors, N.; Schutter, H. De; Penninckx, F.; McBride, W.H.; Begg, A.C.; Haustermans, K.


    PURPOSE: To detect and quantify hypoxia in colorectal adenocarcinomas by use of pimonidazole and iododeoxyuridine (IdUrd) as extrinsic markers and carbonic anhydrase IX (CA IX), microvessel density (MVD), epidermal growth-factor receptor (EGFR), and vascular endothelial growth factor (VEGF) as intri

  20. Seismic liquefaction potential assessment by using relevance vector machine

    Pijush Samui


    Determining the liquefaction potential of soil is important in earthquake engineering.This study proposes the use of the Relevance Vector Machine (RVM) to determine the liquefaction potential of soil by using actual cone penetration test(CPT) data.RVM is based on a Bayesian formulation of a linear model with an appropriate prior that results in a sparse representation.The results are compared with a widely used artificial neural network(ANN) model.Overall,the RVM shows good performance and is proven to be more accurate than the ANN model.It also provides probabilistic output.The model provides a viable tool for earthquake engineers to assess seismic conditions for sites that are susceptible to liquefaction.

  1. Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer.

    Bennett, M W


    BACKGROUND: Despite being immunogenic, gastric cancers overcome antitumour immune responses by mechanisms that have yet to be fully elucidated. Fas ligand (FasL) is a molecule that induces Fas receptor mediated apoptosis of activated immunocytes, thereby mediating normal immune downregulatory roles including immune response termination, tolerance acquisition, and immune privilege. Colon cancer cell lines have previously been shown to express FasL and kill lymphoid cells by Fas mediated apoptosis in vitro. Many diverse tumours have since been found to express FasL suggesting that a "Fas counterattack" against antitumour immune effector cells may contribute to tumour immune escape. AIM: To ascertain if human gastric tumours express FasL in vivo, as a potential mediator of immune escape in stomach cancer. SPECIMENS: Thirty paraffin wax embedded human gastric adenocarcinomas. METHODS: FasL protein was detected in gastric tumours using immunohistochemistry; FasL mRNA was detected in the tumours using in situ hybridisation. Cell death was detected in situ in tumour infiltrating lymphocytes using terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL). RESULTS: Prevalent expression of FasL was detected in all 30 resected gastric adenocarcinomas examined. In the tumours, FasL protein and mRNA were co-localised to neoplastic gastric epithelial cells, confirming expression by the tumour cells. FasL expression was independent of tumour stage, suggesting that it may be expressed throughout gastric cancer progression. TUNEL staining disclosed a high level of cell death among lymphocytes infiltrating FasL positive areas of tumour. CONCLUSIONS: Human gastric adenocarcinomas express the immune downregulatory molecule, FasL. The results suggest that FasL is a prevalent mediator of immune privilege in stomach cancer.

  2. Comprehensive molecular pathology analysis of small bowel adenocarcinoma reveals novel targets with potential for clinical utility.

    Alvi, Muhammad A; McArt, Darragh G; Kelly, Paul; Fuchs, Marc-Aurel; Alderdice, Matthew; McCabe, Clare M; Bingham, Victoria; McGready, Claire; Tripathi, Shailesh; Emmert-Streib, Frank; Loughrey, Maurice B; McQuaid, Stephen; Maxwell, Perry; Hamilton, Peter W; Turkington, Richard; James, Jacqueline A; Wilson, Richard H; Salto-Tellez, Manuel


    Small bowel accounts for only 0.5% of cancer cases in the US but incidence rates have been rising at 2.4% per year over the past decade. One-third of these are adenocarcinomas but little is known about their molecular pathology and no molecular markers are available for clinical use. Using a retrospective 28 patient matched normal-tumor cohort, next-generation sequencing, gene expression arrays and CpG methylation arrays were used for molecular profiling. Next-generation sequencing identified novel mutations in IDH1, CDH1, KIT, FGFR2, FLT3, NPM1, PTEN, MET, AKT1, RET, NOTCH1 and ERBB4. Array data revealed 17% of CpGs and 5% of RNA transcripts assayed to be differentially methylated and expressed respectively (p clinically exploitable markers.

  3. Estrogen, male dominance and esophageal adenocarcinoma: Is there a link?

    Huiqi Yang; Olga A Sukocheva; Damian J Hussey; David I Watson


    Esophageal adenocarcinoma is a cancer with poor prognosis, and its incidence has risen sharply over recent decades. Obesity is a major risk factor for developing this cancer and there is a clear male gender bias in the incidence that cannot be fully explained by known risk factors. It is possible that a difference in the expression of estrogen, or its signaling axes, may contribute to this gender bias. We undertook a comprehensive literature search and analyzed the available data regarding estrogen and estrogen receptor expression, and the possible sex-specific links with esophageal adenocarcinoma development. Potentially relevant associations between visceral vs subcutaneous fat deposition and estrogen expression, and the effect of crosstalk between estrogen and leptin signaling were identified. We also found limited studies suggesting a role for estrogen receptor β expression in esophageal adenocarcinoma development. The current literature supports speculation on an etiological role for estrogen in the male gender bias in esophageal adenocarcinoma, but further studies are required.

  4. Extract relevant features from DEM for groundwater potential mapping

    Liu, T.; Yan, H.; Zhai, L.


    Multi-criteria evaluation (MCE) method has been applied much in groundwater potential mapping researches. But when to data scarce areas, it will encounter lots of problems due to limited data. Digital Elevation Model (DEM) is the digital representations of the topography, and has many applications in various fields. Former researches had been approved that much information concerned to groundwater potential mapping (such as geological features, terrain features, hydrology features, etc.) can be extracted from DEM data. This made using DEM data for groundwater potential mapping is feasible. In this research, one of the most widely used and also easy to access data in GIS, DEM data was used to extract information for groundwater potential mapping in batter river basin in Alberta, Canada. First five determining factors for potential ground water mapping were put forward based on previous studies (lineaments and lineament density, drainage networks and its density, topographic wetness index (TWI), relief and convergence Index (CI)). Extraction methods of the five determining factors from DEM were put forward and thematic maps were produced accordingly. Cumulative effects matrix was used for weight assignment, a multi-criteria evaluation process was carried out by ArcGIS software to delineate the potential groundwater map. The final groundwater potential map was divided into five categories, viz., non-potential, poor, moderate, good, and excellent zones. Eventually, the success rate curve was drawn and the area under curve (AUC) was figured out for validation. Validation result showed that the success rate of the model was 79% and approved the method's feasibility. The method afforded a new way for researches on groundwater management in areas suffers from data scarcity, and also broaden the application area of DEM data.

  5. Adenocarcinoma of the esophagus and Barrett's esophagus

    Bytzer, P; Christensen, P B; Damkier, P


    OBJECTIVE: We described incidence rates of esophageal adenocarcinoma in Denmark in a 20-yr period and determined the proportion of patients diagnosed with esophageal adenocarcinoma who had a previous diagnosis of Barrett's esophagus, making them potential candidates for endoscopic surveillance. M......'s esophagus, but these screening programs are not likely to reduce the death rate from esophageal adenocarcinomas in the general population....

  6. Soluble Human Epidermal Growth Factor Receptor 2 (sHER2 as a Potential Risk Assessment, Screening, and Diagnostic Biomarker of Lung Adenocarcinoma

    Andre T. Baron


    Full Text Available Lung cancer is the leading cause of cancer-related death in the United States. Here, we evaluated the potential clinical utility of soluble human epidermal growth factor receptor 2 (sHER2 for the risk assessment, screening, and diagnosis of non-small cell lung cancer (NSCLC using an unmatched case-control study design. Serum sHER2 concentrations were measured by immunoassay in 244 primary NSCLC cases and 218 healthy controls. Wilcoxon rank-sum tests, logistic regression models, and receiver operating characteristic plots were used to assess whether sHER2 is associated with lung cancer. Median serum sHER2 concentrations are higher in patients with adenocarcinoma than squamous cell carcinoma regardless of gender, and sHER2 is a weak, independent biomarker of adenocarcinoma, but not of squamous cell carcinoma, adjusted for age and gender. The age-adjusted relative risk (odds of adenocarcinoma is 3.95 (95% CI: 1.22, 12.81 and 7.93 (95% CI: 2.26, 27.82 greater for women and men with high sHER2 concentrations (≥6.60 ng/mL vs. low sHER2 concentrations (≤1.85 ng/mL, respectively. When adjusted for each other, sHER2, age, and gender discern healthy controls from patients with primary adenocarcinomas of the lung with 85.9% accuracy. We conclude that even though serum sHER2 is not a strong, stand-alone discriminatory biomarker of adenocarcinoma, sHER2 may be a useful, independent covariate in multivariate risk assessment, screening, and diagnostic models of lung cancer.

  7. Dynamic hyperinflation and pulmonary inflammation: a potentially relevant relationship?

    A. Agusti


    Full Text Available In patients with moderate-to-severe chronic obstructive pulmonary disease (COPD, end-expiratory lung volume increases under conditions of greater minute ventilation (e.g. exercise. This abnormal response is termed dynamic hyperinflation (DH and has now been recognised as a key determinant of symptomatology and exercise intolerance in COPD. Reduced elastic recoil, loss of alveolar attachments and increased airway resistance are the mechanical factors traditionally invoked to explain the occurrence of DH in COPD. An abnormal inflammatory response to, most frequently, tobacco smoking is a key pathophysiological component of COPD, but its potential relationship with DH has not been directly investigated and is poorly understood. The present article discusses, first, the mechanisms by which DH can enhance inflammation in COPD (including cellular stretching, tissue damage and danger signals, hyperventilation and hypoxia. It then reviews how the abnormal inflammatory response that characterises the disease can augment DH (oedema and increased airway resistance, increased mucus production and alveolar destruction. Finally, it speculates that if these relationships eventually prove to be real, then the use of long-acting bronchodilators may help reduce the inflammatory load of these patients and, conversely, the use of anti-inflammatory therapy can contribute to the reduction of DH.

  8. Therapeutic Potential of Andrographolide Isolated from the Leaves of Andrographis paniculata Nees for Treating Lung Adenocarcinomas

    Yu-Tang Tung


    Full Text Available Andrographolide is one of the major diterpene lactones found in Andrographis paniculata Nees and exhibits remarkable inhibitory effects on various cancers. In this study, the antipulmonary cancer effects of andrographolide were studied in a lung tumor mouse model induced by human vascular endothelial growth factor A165 (hVEGF-A165. These results demonstrated that andrographolide significantly reduced the expression of hVEGF-A165 compared with a mock group in the Clara cells of the lungs. In addition, andrographolide also decreased tumor formation by reducing VEGF, EGFR, Cyclin A, and Cyclin B expression on the transcriptional and translational levels. These results indicated that andrographolide treatment on the overexpression of VEGF can arrest the cell cycle, which induced pulmonary tumors in transgenic mice. In conclusion, the antiangiogenesis and chemotherapeutic potential of andrographolide may provide a cure for pulmonary tumors in the future.

  9. Gray level entropy matrix is a superior predictor than multiplex ELISA in the detection of reactive stroma and metastatic potential of high-grade prostatic adenocarcinoma.

    Jia, Xiaopeng; Sun, Yanan; Wang, Baozhi


    Recent reports have indicated that not only the primary glandular tissue but also the surrounding stromal tissue plays an active role in the progression of carcinoma. Such is true for cancer tissues arising in the prostate. However, the precise role of stromal tissue in benign prostatic hyperplasia (BPH) and prostate adenocarcinoma is not well described. We undertook this current investigation to examine the changes in orientation of the extracellular matrix and correlate with prostatic cancer progression. We used a novel form of image analysis called gray level entropy matrix (GLEM) texture analysis to evaluate morphometric changes in stromal tissues. We used normal prostatic tissue obtained from cadaveric specimen and compared with BPH, prostatic intraepithelium neoplastic, hormone responsive prostatic adenocarcinoma and castration-resistant prostatic adenocarcinoma tissues. GLEM showed higher entropy in disease-resistant prostatic tissues, compared with benign forms of all spectra of pathologically diagnosed prostatic tissues (P entropy is reflective of the disorganized morphological organization of the stroma, possibly reflecting the reactive matrix. In contrast, ELISA revealed that although individually correlated with the progressive stages of benign and carcinomatous prostatic tissues and trend correlation between groups, intergroup comparisons failed to arrive at statistical significance of comparisons between markers of neovasculogenesis, vascular endothelial growth factor, epithelial-mesenchymal transition (beta1-integrin, E-cadherin, MMP3) and osteogenic metastasis (RANKL and osteoprotegerin). The results of our study demonstrate the potential of GLEM entropy of gray level pixel in providing quasiquantitative estimate of a reactive stroma in advance stages of prostatic adenocarcinoma and thus can be routinely used in clinical decision making.

  10. Characterization of the cell of origin and propagation potential of the fibroblast growth factor 9-induced mouse model of lung adenocarcinoma.

    Arai, Daisuke; Hegab, Ahmed E; Soejima, Kenzo; Kuroda, Aoi; Ishioka, Kota; Yasuda, Hiroyuki; Naoki, Katsuhiko; Kagawa, Shizuko; Hamamoto, Junko; Yin, Yongjun; Ornitz, David M; Betsuyaku, Tomoko


    Fibroblast growth factor 9 (FGF9) is essential for lung development and is highly expressed in a subset of human lung adenocarcinomas. We recently described a mouse model in which FGF9 expression in the lung epithelium caused proliferation of the airway epithelium at the terminal bronchioles and led to rapid development of adenocarcinoma. Here, we used this model to characterize the effects of prolonged FGF9 induction on the proximal and distal lung epithelia, and examined the propagation potential of FGF9-induced lung tumours. We showed that prolonged FGF9 over-expression in the lung resulted in the development of adenocarcinomas arising from both alveolar type II and airway secretory cells in the lung parenchyma and airways, respectively. We found that tumour cells harboured tumour-propagating cells that were able to form secondary tumours in recipient mice, regardless of FGF9 expression. However, the highest degree of tumour propagation was observed when unfractionated tumour cells were co-administered with autologous, tumour-associated mesenchymal cells. Although the initiation of lung adenocarcinomas was dependent on activation of the FGF9-FGF receptor 3 (FGFR3) signalling axis, maintenance and propagation of the tumour was independent of this signalling. Activation of an alternative FGF-FGFR axis and the interaction with tumour stromal cells is likely to be responsible for the development of this independence. This study demonstrates the complex role of FGF-FGFR signalling in the initiation, growth and propagation of lung cancer. Our findings suggest that analysing the expressions of FGF-FGFRs in human lung cancer will be a useful tool for guiding customized therapy.

  11. Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.

    Katarina Lagergren

    Full Text Available The strong male predominance in oesophageal adenocarcinoma (OAC and Barrett's oesophagus (BO continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute.This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1, receptor beta (ESR2, and aromatase (CYP19A1, and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR, oxytocin protein (OXT, and cyclic ADP ribose hydrolase glycoprotein (CD38, were analysed using a gene-based approach, versatile gene-based test association study (VEGAS.Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058 and an increased risk of OAC and BO combined in males (p = 0.0023. Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035 and in males (p = 0.0012. We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only.Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.

  12. Curcumin inhibits growth potential by G1 cell cycle arrest and induces apoptosis in p53-mutated COLO 320DM human colon adenocarcinoma cells.

    Dasiram, Jade Dhananjay; Ganesan, Ramamoorthi; Kannan, Janani; Kotteeswaran, Venkatesan; Sivalingam, Nageswaran


    Curcumin, a natural polyphenolic compound and it is isolated from the rhizome of Curcuma longa, have been reported to possess anticancer effect against stage I and II colon cancer. However, the effect of curcumin on colon cancer at Dukes' type C metastatic stage III remains still unclear. In the present study, we have investigated the anticancer effects of curcumin on p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage. The cellular viability and proliferation were assessed by trypan blue exclusion assay and MTT assay, respectively. The cytotoxicity effect was examined by lactate dehydrogenase (LDH) cytotoxicity assay. Apoptosis was analyzed by DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis. Cell cycle distribution was performed by flow cytometry analysis. Here we have observed that curcumin treatment significantly inhibited the cellular viability and proliferation potential of p53 mutated COLO 320DM cells in a dose- and time-dependent manner. In addition, curcumin treatment showed no cytotoxic effects to the COLO 320DM cells. DNA fragmentation analysis, Hoechst and propidium iodide double fluorescent staining and confocal microscopy analysis revealed that curcumin treatment induced apoptosis in COLO 320DM cells. Furthermore, curcumin caused cell cycle arrest at the G1 phase, decreased the cell population in the S phase and induced apoptosis in COLO 320DM colon adenocarcinoma cells. Together, these data suggest that curcumin exerts anticancer effects and induces apoptosis in p53 mutated COLO 320DM human colon adenocarcinoma cells derived from Dukes' type C metastatic stage.

  13. Identification of distinct phenotypes of locally advanced pancreatic adenocarcinoma.

    Teo, Minyuen


    A significant number of pancreatic ductal adenocarcinoma present as locally advanced disease. Optimal treatment remains controversial. We sought to analyze the clinical course of locally advanced pancreatic adenocarcinoma (LAPC) in order to identify potential distinct clinical phenotypes.

  14. Prognostic potential of initial CT changes for progression-free survival in gefitinib-treated patients with advanced adenocarcinoma of the lung: a preliminary analysis

    Wu, Yu-Cheng; Hsu, Hsian-He; Chang, Wei-Chou; Ko, Kai-Hsiung; Hsu, Yi-Chih [Tri-Service General Hospital, National Defense Medical Center, Department of Radiology, Taipei (China); Tung, Ho-Jui [Asia University, Department of Healthcare Administration, Taichung (China); Huang, Tsai-Wang; Chang, Hung [Tri-Service General Hospital, National Defense Medical Center, Division of Thoracic Surgery, Department of Surgery, Taipei (China); Ho, Ching-Liang [Tri-Service General Hospital, National Defense Medical Center, Division of hematology-oncology, Department of internal Medicine, Taipei (China)


    We aimed to determine whether initial tumour responses measured during short-term follow-up computed tomography (CT) examinations after baseline examinations would correlate with clinical outcomes in patients with non-small cell lung cancer (NSCLC) who received epidermal growth factor receptor (EGFR)-targeted therapy. A total of 86 gefitinib-treated patients with advanced adenocarcinoma of the lung were retrospectively reviewed. All patients underwent baseline and short-term follow-up CT examinations. The new response criteria (NRC) by Lee et al. were used for the response evaluations. A Cox proportional hazards multiple regression model and Kaplan-Meier survival analyses were used to evaluate correlations between the initial tumour changes and progression-free and overall survival (PFS, OS). Better separation and smaller p values were observed for both PFS and OS when good and poor disease responses (as defined by NRC) were compared after excluding tumours with characteristic morphologies. Early tumour changes correlated with PFS in a size-dependent manner. Moreover, a stronger association was observed between size changes and PFS when characteristic morphology was also considered. Initial changes in tumour size during short-term post-treatment CT examinations could act as a potential prognostic imaging surrogate for PFS in gefitinib-treated patients with advanced adenocarcinoma of the lung. (orig.)

  15. Synchronous gastric adenocarcinoma and pancreatic ductal adenocarcinoma

    Mirko Muroni; Francesco D'Angelo; Massimo Pezzatini; Simone Sebastiani; Samantha Noto; Emanuela Pilozzi; Giovanni Ramacciato


    BACKGROUND: The association between gastric and pancreatic carcinoma is a relatively rare condition. In gastric carcinoma patients, the prevalence of second tumors varies 2.8% to 6.8% according to the reported statistics. Gastric cancer associated with pancreatic cancer is uncommon. METHODS: We report a case of a 73-year-old patient hospitalized for vomiting and weight loss. Esophagogastro-duodenoscopy demonstrated an ulcerative lesion of the gastric antrum. Computed tomography and magnetic resonance showed a gastric thickening in the antral and pyloric portion and a nodular mass (3×1.7 cm) in the uncinate portion of the pancreas. RESULTS: The patient underwent pancreaticoduoden-ectomy according to Whipple regional typeⅠFortner. Histological examination of the specimen demonstrated a moderately differentiated adenocarcinoma of the stomach and a poorly differentiated ductal adenocarcinoma of the pancreas. CONCLUSIONS: Long survival is rare in patients with associated gastric and pancreatic cancer. Surgical resection remains the only potentially curative treatment.

  16. A review of potential factors relevant to coping in patients with advanced cancer

    Thomsen, Thora Grothe; Hansen, Susan Rydahl; Wagner, Lis


    The aim was to identify characteristics that are considered to describe coping in patients with advanced cancer, as seen from a patient perspective. Based on the identified characteristics, the second aim was to identify potential factors that are relevant to coping in patients with advanced cancer....

  17. The Potential Relevance of Cognitive Neuroscience for the Development and Use of Technology-Enhanced Learning

    Howard-Jones, Paul; Ott, Michela; van Leeuwen, Theo; De Smedt, Bert


    There is increasing interest in the application of cognitive neuroscience in educational thinking and practice, and here we review findings from neuroscience that demonstrate its potential relevance to technology-enhanced learning (TEL). First, we identify some of the issues in integrating neuroscientific concepts into TEL research. We caution…

  18. Attentional Modulation of Visual-Evoked Potentials by Threat: Investigating the Effect of Evolutionary Relevance

    Brown, Christopher; El-Deredy, Wael; Blanchette, Isabelle


    In dot-probe tasks, threatening cues facilitate attention to targets and enhance the amplitude of the target P1 peak of the visual-evoked potential. While theories have suggested that evolutionarily relevant threats should obtain preferential neural processing, this has not been examined empirically. In this study we examined the effects of…

  19. Orphan nuclear receptor Nurr1 as a potential novel marker for progression in human pancreatic ductal adenocarcinoma

    Ji, Li; Gong, Chen; Ge, Liangyu; Song, Linping; Chen, Fenfen; Jin, Chunjing; Zhu, Hongyan; Zhou, Guoxiong


    Nuclear receptor related-1 protein (Nurr1) is a novel orphan member of the nuclear receptor superfamily (the NR4A family) involved in tumorigenesis. The aim of the present study was to investigate the expression and possible function of Nurr1 in pancreatic ductal adenocarcinoma (PDAC). The expression pattern of Nurr1 protein was determined using immunohistochemical staining in 138 patients with PDAC. Elevated Nurr1 expression was more commonly observed in PDAC tissues and cell lines compared with healthy controls. Elevated expression was significantly associated with histological differentiation (P=0.041), lymph node metastasis (P=0.021), TNM classification of malignant tumors stage (P=0.031) and poor survival (P=0.001). Further experiments demonstrated that suppression of endogenous Nurr1 expression attenuated cell proliferation, migration and invasion, and induced apoptosis of PDAC cells. In conclusion, these results suggest that Nurr1 has an important role in the progression of PDAC and may be used as a novel marker for therapeutic targets.

  20. The ERK MAP kinase-PEA3/ETV4-MMP-1 axis is operative in oesophageal adenocarcinoma

    Keld, Richard


    Abstract Background Many members of the ETS-domain transcription factor family are important drivers of tumourigenesis. In this context, their activation by Ras-ERK pathway signaling is particularly relevant to the tumourigenic properties of many ETS-domain transcription factors. The PEA3 subfamily of ETS-domain transcription factors have been implicated in tumour metastasis in several different cancers. Results Here, we have studied the expression of the PEA3 subfamily members PEA3\\/ETV4 and ER81\\/ETV1 in oesophageal adenocarcinomas and determined their role in oesophageal adenocarcinoma cell function. PEA3 plays an important role in controlling both the proliferation and invasive properties of OE33 oesophageal adenocarcinoma cells. A key target gene is MMP-1. The ERK MAP kinase pathway activates PEA3 subfamily members and also plays a role in these PEA3 controlled events, establishing the ERK-PEA3-MMP-1 axis as important in OE33 cells. PEA3 subfamily members are upregulated in human adenocarcinomas and expression correlates with MMP-1 expression and late stage metastatic disease. Enhanced ERK signaling is also more prevalent in late stage oesophageal adenocarcinomas. Conclusions This study shows that the ERK-PEA3-MMP-1 axis is upregulated in oesophageal adenocarcinoma cells and is a potentially important driver of the metastatic progression of oesophageal adenocarcinomas.

  1. The ERK MAP kinase-PEA3/ETV4-MMP-1 axis is operative in oesophageal adenocarcinoma

    Gulmann Christian


    Full Text Available Abstract Background Many members of the ETS-domain transcription factor family are important drivers of tumourigenesis. In this context, their activation by Ras-ERK pathway signaling is particularly relevant to the tumourigenic properties of many ETS-domain transcription factors. The PEA3 subfamily of ETS-domain transcription factors have been implicated in tumour metastasis in several different cancers. Results Here, we have studied the expression of the PEA3 subfamily members PEA3/ETV4 and ER81/ETV1 in oesophageal adenocarcinomas and determined their role in oesophageal adenocarcinoma cell function. PEA3 plays an important role in controlling both the proliferation and invasive properties of OE33 oesophageal adenocarcinoma cells. A key target gene is MMP-1. The ERK MAP kinase pathway activates PEA3 subfamily members and also plays a role in these PEA3 controlled events, establishing the ERK-PEA3-MMP-1 axis as important in OE33 cells. PEA3 subfamily members are upregulated in human adenocarcinomas and expression correlates with MMP-1 expression and late stage metastatic disease. Enhanced ERK signaling is also more prevalent in late stage oesophageal adenocarcinomas. Conclusions This study shows that the ERK-PEA3-MMP-1 axis is upregulated in oesophageal adenocarcinoma cells and is a potentially important driver of the metastatic progression of oesophageal adenocarcinomas.

  2. MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma

    Schultz, Nicolai A; Werner, Jens; Willenbrock, Hanni;


    MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro......, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced......-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis...

  3. Do adenocarcinomas of the prostate with Gleason score (GS) ≤6 have the potential to metastasize to lymph nodes?

    Ross, Hillary M; Kryvenko, Oleksandr N; Cowan, Janet E; Simko, Jeffry P; Wheeler, Thomas M; Epstein, Jonathan I


    Although rare, there are cases within reported series of men with Gleason score (GS) ≤6 on radical prostatectomies that show pelvic lymph node (LN) metastases. However, there are no studies on whether pelvic LN metastases occur in tumors with GS ≤6 using the International Society of Urological Pathology (ISUP) updated GS system. We performed a search of the radical prostatectomy databases at 4 large academic centers for cases of GS ≤6. Only prostatectomies submitted and embedded in entirety with pelvic LN dissections were included. A combined total of 14,123 cases were identified, of which 22 cases had a positive LN. Histopathologic review of 19 cases (3 cases unavailable for review) showed higher grade than originally reported by the pathologists in all cases. Of the 17 pre-ISUP reviewed cases, 2 were upgraded to 4+3=7 with both cribriform and poorly formed glands. One case was upgraded to 4+3=7 with tertiary pattern 5 displaying cribriform glands, poorly formed glands, and cords of single cells. Eleven cases were upgraded to 3+4=7 with glomeruloid structures and small to large cribriform glands (1 of these also had features of ductal adenocarcinoma). Two cases had tertiary pattern 4 with small cribriform glands. One case had a prominent colloid component that would currently be graded as 4+5=9 because of large cribriform glands and solid sheets of cells within the mucin. Of the 2 post-ISUP cases, 1 demonstrated tertiary pattern 4, and the other showed GS 3+4=7 with irregular cribriform glands. Undergrading is the primary reason for LN positivity with GS ≤6, which has decreased significantly since the adoption of the ISUP grading system in 2005. Of over 14,000 totally embedded radical prostatectomies from multiple institutions, there was not a single case of a GS ≤6 tumor with LN metastases. In contrast to prevailing assumptions, GS ≤6 tumors do not appear to metastasize to LNs. Rather, Gleason pattern 4 or 5, as better defined by the current ISUP

  4. Metabolic acidosis in renal transplantation: neglected but of potential clinical relevance.

    Messa, Pier Giorgio; Alfieri, Carlo; Vettoretti, Simone


    Chronic metabolic acidosis (CMA) is a common complication of the more advanced stages of chronic kidney diseases (CKD), and is associated with morbidity and mortality of CKD patients and possibly with the progression of renal disease. Nevertheless, there is limited evidence or information on the prevalence, the potential causal factors, the clinical impact and the effects of correction of CMA in kidney transplant recipients. In this review, we briefly look at the more relevant, though scanty, studies which have, over time, addressed the above-mentioned points, with the hope that in the future the interest of transplant nephrologists and surgeons will grow towards this unreasonably neglected issue.

  5. The bioactive potential of red raspberry (Rubus idaeus L.) leaves in exhibiting cytotoxic and cytoprotective activity on human laryngeal carcinoma and colon adenocarcinoma.

    Durgo, Ksenija; Belščak-Cvitanović, Ana; Stančić, Angela; Franekić, Jasna; Komes, Draženka


    In this article, the bioactive potential of red raspberry leaves, a by-product of this widely spread plant, mostly valued for its antioxidant-rich fruits, was determined. The polyphenolic profile and antioxidative properties of red raspberry leaf extract were determined and examined for potential biological activity. Cytotoxic effect, antioxidative/prooxidative effect, and effect on total glutathione concentration were determined in human laryngeal carcinoma (HEp2) and colon adenocarcinoma (SW 480) cell lines. SW 480 cells are more susceptible to raspberry leaf extract in comparison with HEp2 cells. The antioxidative nature of raspberry leaf extract was detected in HEp2 cells treated with hydrogen peroxide, as opposed to SW 480 cells, where raspberry leaf extract induced reactive oxygen species formation. Raspberry leaf extract increased total glutathione level in HEp2 cells. This effect was reinforced after 24 hours of recovery, indicating that induction was caused by products formed during cellular metabolism of compounds present in the extract. Comparison of the results obtained on these two cell lines indicates that cellular response to raspberry extract will depend on the type of the cells that are exposed to it. The results obtained confirmed the biological activity of red raspberry leaf polyphenols and showed that this traditional plant can supplement the daily intake of valuable natural antioxidants, which exhibit beneficial health effects.

  6. Effects of mifepristone on invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 in vitro and in vivo

    Da-Qiang Li; Zhi-Biao Wang; Jin Bai; Jie Zhao; Yuan Wang; Kai Hu; Yong-Hong Du


    AIM: To investigate the effects of mifepristone on the invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 and its mechanisms.METHODS: After incubation with various concentrations of mifepristone (5, 10, 20 μmol/L), the adhesion to artificial basement membrane, Matrigel, and the migration of MKN-45cells were assayed using MTT assay and lranswell cell culture chambers, respectively. Enzyme- linked immunoabsorbent assay (ELISA) and flow cytometry were used to determine the expression of vascular endothelial growth factor (VEGF)and integrin β3 in the cells. After subcutaneous transplantation of MKN-45 cells in nude mice, mifepristone (50 mg/kg.d)was administrated subcutaneously for 8 wk to assess its effects on tumor metastasis. Immunohistochemical analysis was used to detect the expression of VEGF and microvascular density (MVD) in xenografted tumors.RESULTS: Mifepristone dose-dependently inhibited the heterotypic adhesion to Matrigel of MKN-45 cells. The inhibition was accompanied by a significant down-regulation of integrin β3 expression in the cells. After incubation with 5, 10, 20 μmol/L mifepristone, the number of migrated MKN-45 cells was 72±8, 50±6, 41±5 in experiment group, and 94±16 in control group (P<0.01). Meanwhile, secreted VEGF protein of MKN-45 cells in mifepristone-treated group (14.2±2.9, 8.9±3.1, 5.4±2.1 ng/g per liter) was significantly lower than that in control group (22.7±4.3 ng/g per liter,P<0.01). In vivo, mifepristone decreased the number of metastatic foci in lungs of nude mice and down-regulated the expression of VEGF and MlVD in the xenograted tumors.CONCLUSION: Mifepristone can effectively inhibit the invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45in vitro and in vivo through inhibition of heterotypic adhesion to basement membrane,cell migration and angiogenesis.

  7. Metric-space approach to potentials and its relevance to density-functional theory

    Sharp, P. M.; D'Amico, I.


    External potentials play a crucial role in modeling quantum systems, since, for a given interparticle interaction, they define the system Hamiltonian. We use the metric-space approach to quantum mechanics to derive, from the energy conservation law, two natural metrics for potentials. We show that these metrics are well defined for physical potentials, regardless of whether the system is in an eigenstate or if the potential is bounded. In addition, we discuss the gauge freedom of potentials and how to ensure that the metrics preserve physical relevance. Our metrics for potentials, together with the metrics for wave functions and densities from I. D'Amico et al. [Phys. Rev. Lett. 106, 050401 (2011), 10.1103/PhysRevLett.106.050401] paves the way for a comprehensive study of the two fundamental theorems of density-functional theory. We explore these by analyzing two many-body systems for which the related exact Kohn-Sham systems can be derived. First we consider the information provided by each of the metrics, and we find that the density metric performs best in distinguishing two many-body systems. Next we study for the systems at hand the one-to-one relationships among potentials, ground-state wave functions, and ground-state densities defined by the Hohenberg-Kohn theorem as relationships in metric spaces. We find that, in metric space, these relationships are monotonic and incorporate regions of linearity, at least for the systems considered. Finally, we use the metrics for wave functions and potentials in order to assess quantitatively how close the many-body and Kohn-Sham systems are: We show that, at least for the systems analyzed, both metrics provide a consistent picture, and for large regions of the parameter space the error in approximating the many-body wave function with the Kohn-Sham wave function lies under a threshold of 10%.

  8. Choline Transporters in Human Lung Adenocarcinoma: Expression and Functional Implications


    Choline is an essential nutrient for cell survival and proliferation, however, the expression and function of choline transporters have not been well identified in cancer. In this study, we detected the mRNA and protein expression of organic cation transporter OCT3, carnitine/cation transporters OCTN 1 and OCTN2,and choline transporter-like protein CTL1 in human lung adenocarcinoma cell lines A549, H1299 and SPC-A-1.Their expression pattern was further confirmed in 25 human primary adenocarcinoma tissues. The choline uptake in these cell lines was significantly blocked by CTL1 inhibitor, but only partially inhibited by OCT or OCTN inhibitors. The efficacy of these inhibitors on cell proliferation is closely correlated with their abilities to block choline transport. Under the native expression of these transporters, the total choline uptake was notably blocked by specific PI3K/AKT inhibitors. These results describe the expression of choline transporters and their relevant function in cell proliferation of human lung adenocarcinoma, thus providing a potential"choline-starvation" strategy of cancer interference through targeting choline transporters, especially CTL1.

  9. Characterization of mammary adenocarcinomas in male rats after N-methyl-N-nitrosourea exposure--Potential for human male breast cancer model.

    Yoshizawa, Katsuhiko; Yuki, Michiko; Kinoshita, Yuichi; Emoto, Yuko; Yuri, Takashi; Shikata, Nobuaki; Elmore, Susan A; Tsubura, Airo


    The frequency of breast cancer in men is extremely rare, reported to be less than 1% and there is currently no available animal model for male mammary tumors. We compared the characteristics of various immunohistochemical markers in N-methyl-N-nitrosourea (MNU)-induced mammary adenocarcinomas in male and female Crj:CD(SD)IGS rats including: estrogen receptor α (ER), progesterone receptor (PgR), androgen receptor (AR), receptor tyrosine-protein kinase erbB-2 (HER2), GATA binding protein 3 (GATA3), and proliferating cell nuclear antigen (PCNA). Female mammary adenocarcinomas were strongly positive in the nuclei of tumor cells for PCNA and ER (100%) with only 60% and 53% expressing PgR and GATA3, respectively. 100% of male adenocarcinomas also exhibited strongly positive expression in the nuclei of tumor cells for PCNA, with 25% expressing AR and only 8% showing positivity for ER. Male carcinomas did not express PgR or GATA3 and none of the tumors, male or female, were positive for HER2. Based on the observed ER and PgR positivity and HER2 negativity within these tumors, MNU-induced mammary adenocarcinomas in female rats appear to be hormonally dependent, similar to human luminal A type breast cancer. In contrast, MNU-induced mammary adenocarcinomas in male rats showed no reactivity for ER, PgR, HER2 or GATA3, suggesting no hormonal dependency. Both male and female adenocarcinomas showed high proliferating activity by PCNA immunohistochemistry. Based on our literature review, human male breast cancers are mainly dependent on ER and/or PgR, therefore the biological pathogenesis of MNU-induced male mammary cancer in rats may differ from that of male breast cancer in humans.

  10. Synchronous rectal adenocarcinoma and anal canal adenocarcinoma

    GU Jin; LI Jiyou; YAO Yunfeng; LU Aiping; WANG Hongyi


    It is difficult to distinguish a tectal carcinoma with anal metastases from coexistent synchronous anorectal carcinomas.The therapeutic strategy for rectal and anal carcinoma is so different that it should be clearly identified.Here,we report on the case of a 63-year-old man who presented with an upper-third rectal adenocarcinoma.Five months after resection,he developed an adenocarcinoma in the anal canal.The histological slides of both tumors were reviewed and immunohistochemical studies for cytokeratins(CKs)7 and 20 were performed.The index tumor demonstrated CK 7-/CK 20+and the second showed CK7+/CK20+.For this reason,we believe the present case had synchronous adenocarcinomas arising from anal canal and the rectum separately.It is very important to difierentiate the anorectal lesions pathologically because of the impact on the therapeutic options available,especially for the lesion arising in the anal canal.

  11. The combination of a nuclear HMGB1-positive and HMGB2-negative expression is potentially associated with a shortened survival in patients with pancreatic ductal adenocarcinoma.

    Takeda, Toru; Izumi, Hiroto; Kitada, Shohei; Uramoto, Hidetaka; Tasaki, Takashi; Zhi, Li; Guo, Xin; Kawatsu, Yuichiro; Kimura, Tomoko; Horie, Seichi; Nabeshima, Atsunori; Noguchi, Hirotsugu; Wang, Ke-Yong; Sasaguri, Yasuyuki; Kohno, Kimitoshi; Yamada, Sohsuke


    High-mobility group box (HMGB) proteins are ubiquitous, abundant nuclear non-histone chromosomal proteins that play a critical role in binding to distorted DNA structures and subsequently regulating DNA transcription, replication, repair, and recombination. Both HMGB1 and HMGB2 exhibit a high expression in several human cancers and are closely associated with tumor progression and a poor prognosis. However, the expression patterns of these molecules in pancreatic ductal adenocarcinoma (PDAC) remain to be elucidated. As most cases of postoperative relapse of PDAC occur within the first 2 years, the clinical significance of accurate biomarkers is needed. Therefore, we investigated the correlation between the immunohistochemical HMGB1 and HMGB2 expression and the clinicopathological characteristics and prognosis using 62 paraffin-embedded tumor samples obtained from patients with surgically resected PDAC. The HMGB1/2 expression was considered to be positive when 10 % or more of the cancer cells showed positive nuclear, not merely cytoplasmic, staining. Consequently, the expression of HMGB1/2 was observed in 54 (87.1 %) and 31 (50.0 %) patients, respectively. Unexpectedly, a positive HMGB1 expression was found to have a significantly close relationship with a negative HMGB2 expression. The univariate and multivariate analyses demonstrated that the patients with a HMGB1+ and HMGB2- status had markedly lower disease-specific survival rates, especially within the first 2 years postoperatively, whereas those with a HMGB1+ status alone did not. Therefore, the combination of a HMGB1+ and HMGB2- expression potentially predicts a poor prognosis in patients with PDAC, and these new biomarkers may be useful parameters for clinical management in the early postoperative phase.

  12. Clinical relevancy and risks of potential drug–drug interactions in intensive therapy

    Rodrigues, Aline Teotonio; Stahlschmidt, Rebeca; Granja, Silvia; Falcão, Antonio Luis Eiras; Moriel, Patricia; Mazzola, Priscila Gava


    Purpose Evaluate the potential Drug–Drug Interactions (pDDI) found in prescription orders of adult Intensive Care Unit (ICU) of a Brazilian public health system hospital; quantify and qualify the pDDI regarding their severity and risks to the critical patient, using the database from Micromedex®. Methods Prospective study (January–December of 2011) collecting and evaluating 369 prescription orders (convenient sampling), one per patient. Results During the study 1844 pDDIs were identified and distributed in 405 pairs (medication A × medication B combination). There was an average of 5.00 ± 5.06 pDDIs per prescription order, the most prevalent being moderate and important interactions, present in 74% and 67% of prescription orders, respectively. In total, there were 9 contraindicated, 129 important and 204 moderate pDDIs. Among them 52 had as management recommendation to “avoid concomitant use” or “suspension of medication”, while 306 had as recommendation “continuous and adequate monitoring”. Conclusion The high number of pDDIs found in the study combined with the evaluation of the clinical relevancy of the most frequent pDDIs in the ICU shows that moderate and important interactions are highly incident. As the majority of them demand monitoring and adequate management, being aware of these interactions is major information for the safe and individualized risk management. PMID:27134536

  13. Potentially pathogenic Escherichia coli can form a biofilm under conditions relevant to the food production chain.

    Nesse, Live L; Sekse, Camilla; Berg, Kristin; Johannesen, Karianne C S; Solheim, Heidi; Vestby, Lene K; Urdahl, Anne Margrete


    The biofilm-producing abilities of potentially human-pathogenic serotypes of Escherichia coli from the ovine reservoir were studied at different temperatures and on different surfaces. A possible influence of the hydrophobicity of the bacterial cells, as well as the presence of two virulence factors, the Shiga toxin-encoding (Stx) bacteriophage and the eae gene, was also studied. A total of 99 E. coli isolates of serotypes O26:H11, O103:H2, and O103:H25 isolated from sheep feces were included. The results show that isolates of all three E. coli serotypes investigated can produce biofilm on stainless steel, glass, and polystyrene at 12, 20, and 37°C. There was a good general correlation between the results obtained on the different surfaces. E. coli O103:H2 isolates produced much more biofilm than those of the other two serotypes at all three temperatures. In addition, isolates of serotype O26:H11 produced more biofilm than those of O103:H25 at 37°C. The hydrophobicity of the isolates varied between serotypes and was also influenced by temperature. The results strongly indicated that hydrophobicity influenced the attachment of the bacteria rather than their ability to form biofilm once attached. Isolates with the eae gene produced less biofilm at 37°C than isolates without this gene. The presence of a Stx bacteriophage did not influence biofilm production. In conclusion, our results show that potentially human-pathogenic E. coli from the ovine reservoir can form biofilm on various surfaces and at several temperatures relevant for food production and handling.

  14. Self-esteem modulates automatic attentional responses to self-relevant stimuli: evidence from event-related brain potentials

    Jie eChen; Qing eShui; Yiping eZhong


    Previous studies have widely shown that self-esteem modulates the attention bias towards social rejection or emotion-related information. However, little is known about the influences of self-esteem on attention bias towards self-relevant stimuli. We aimed to investigate neural correlates that underlie the modulation effect of self-esteem on self-relevant processing. Event-related potentials (ERP) were recorded for subjects’ own names and close others’ names (the names of their friends) while...

  15. Potential of polarization lidar to provide profiles of CCN- and INP-relevant aerosol parameters

    Mamouri, Rodanthi-Elisavet; Ansmann, Albert


    We investigate the potential of polarization lidar to provide vertical profiles of aerosol parameters from which cloud condensation nucleus (CCN) and ice nucleating particle (INP) number concentrations can be estimated. We show that height profiles of particle number concentrations n50, dry considering dry aerosol particles with radius > 50 nm (reservoir of CCN in the case of marine and continental non-desert aerosols), n100, dry (particles with dry radius > 100 nm, reservoir of desert dust CCN), and of n250, dry (particles with dry radius > 250 nm, reservoir of favorable INP), as well as profiles of the particle surface area concentration sdry (used in INP parameterizations) can be retrieved from lidar-derived aerosol extinction coefficients σ with relative uncertainties of a factor of 1.5-2 in the case of n50, dry and n100, dry and of about 25-50 % in the case of n250, dry and sdry. Of key importance is the potential of polarization lidar to distinguish and separate the optical properties of desert aerosols from non-desert aerosol such as continental and marine particles. We investigate the relationship between σ, measured at ambient atmospheric conditions, and n50, dry for marine and continental aerosols, n100, dry for desert dust particles, and n250, dry and sdry for three aerosol types (desert, non-desert continental, marine) and for the main lidar wavelengths of 355, 532, and 1064 nm. Our study is based on multiyear Aerosol Robotic Network (AERONET) photometer observations of aerosol optical thickness and column-integrated particle size distribution at Leipzig, Germany, and Limassol, Cyprus, which cover all realistic aerosol mixtures. We further include AERONET data from field campaigns in Morocco, Cabo Verde, and Barbados, which provide pure dust and pure marine aerosol scenarios. By means of a simple CCN parameterization (with n50, dry or n100, dry as input) and available INP parameterization schemes (with n250, dry and sdry as input) we finally compute

  16. Oesophageal adenocarcinoma: the new epidemic in men?

    Rutegård, Martin; Lagergren, Pernilla; Nordenstedt, Helena; Lagergren, Jesper


    The last decades have witnessed an unprecedented rise in the incidence of oesophageal adenocarcinoma. This rise has mainly affected men, and current male-to-female sex ratio estimates range from 7-10 to 1. Major risk factors for oesophageal adenocarcinoma are gastro-oesophageal reflux disease and obesity, especially in combination. The prevalence of these risk factors has increased during the last decades, but there does not seem to be a marked differential distribution among men and women. However, reflux among men is more often associated with erosive reflux disease than it is among women. There is also evidence that male-type obesity, with a prominent abdominal distribution of fat, confers a greater risk increase for oesophageal adenocarcinoma than the female equivalent. Due to the marked male predominance and the finding that women tend to develop specialized intestinal metaplasia (Barrett's oesophagus) and adenocarcinoma at a later age than men, interest has been directed towards a potential aetiological role of reproductive factors and sex hormones. Breastfeeding has been found to be a protective factor for the development of adenocarcinoma, while no association has hitherto been established with other reproductive factors. Taken together, the male predominance in the incidence of oesophageal adenocarcinoma may partly be explained by the differential effect of the major risk factors reflux disease and obesity, but the mechanisms whereby this occurs need to be elucidated. Moreover, the association with breastfeeding indicates a need for extensive epidemiological studies to clarify a possible role of sex hormonal influence in the aetiology of oesophageal adenocarcinoma.


    Oliveira, Eduardo


    The purpose of this article is to explore a potential regional branding strategy for the northern part of Portugal, emphasizing the regional tourism potential. Furthermore, it aims to clarify the answers of the following research questions: i) is tourism a strategic domain with the potential to inte

  18. Ogg1 genetic background determines the genotoxic potential of environmentally relevant arsenic exposures.

    Bach, Jordi; Sampayo-Reyes, Adriana; Marcos, Ricard; Hernández, Alba


    Inorganic arsenic (i-As) is a well-established human carcinogen to which millions of people are exposed worldwide. It is generally accepted that the genotoxic effects of i-As after an acute exposure are partially linked to the i-As-induced production of reactive oxygen species, but it is necessary to better determine whether chronic sub-toxic i-As doses are able to induce biologically significant levels of oxidative DNA damage (ODD). To fill in this gap, we have tested the genotoxic and oxidative effects of environmentally relevant arsenic exposures using mouse embryonic fibroblast MEF mutant Ogg1 cells and their wild-type counterparts. Effects were examined by using the comet assay complemented with the use of FPG enzyme. Our findings indicate that MEF Ogg1-/- cells are more sensitive to arsenite-induced acute toxicity, genotoxicity and ODD. Long-term exposure to sub-toxic doses of arsenite generates a detectable increase in ODD and genotoxic DNA damage only in MEF Ogg1-deficient cells. Altogether, the data presented here point out the relevance of ODD and Ogg1 genetic background on the genotoxic risk of i-As at environmentally plausible doses. The persistent accumulation of DNA 8-OH-dG lesions in Ogg1-/- cells during the complete course of the exposure suggests a relevant role in arsenic-associated carcinogenic risk in turn.

  19. Strategies for the prevention of oesophageal adenocarcinoma.

    Almond, L Max; Old, Oliver; Barr, Hugh


    The incidence of oesophageal adenocarcinoma has increased by 500% over the past 30 years [1]. Improved understanding of the mechanisms of neoplastic progression provides an opportunity to reverse this trend. A thorough review of emerging strategies aiming to prevent the formation of oesophageal malignancy is presented. These include dietary modification, chemoprevention, early endoscopic identification and treatment of premalignant disease, and the potential for a non-endoscopic screening test. Oesophageal adenocarcinoma has become a major public health problem in the West and it is essential that clinicians are fully informed of risk reduction strategies so that they can be actively promoted in the community.

  20. Apocrine adenocarcinoma of the vulva

    Babita Kajal


    Full Text Available Cutaneous vulvar carcinomas are predominantly of squamous cell carcinoma type. Primary vulvar adenocarcinomas are rare with a poorly understood histogenesis. They are classified into extramammary Paget’s disease, sweat gland carcinomas, and breast-like adenocarcinomas of the vulva. Adenocarcinomas, originating from Bartholin glands, can also present as vulvar adenocarcinoma. Rare adenocarcinomas with apocrine features have been described in the literature. The origin of these neoplasms from the native apocrine sweat glands or from anogenital mammary-like glands is still debatable. We report herein a case of a 67 year old female with a rare primary apocrine carcinoma of the vulva.

  1. Comparison of Two Old Phytochemicals versus Two Newly Researched Plant-Derived Compounds: Potential for Brain and Other Relevant Ailments

    Chun-Mei Wang


    Full Text Available Among hundreds of formulae of Chinese herbal prescriptions and recently extracted active components from the herbs, some of which had demonstrated their functions on nervous system. For the last decade or more, Gingko biloba and Polygala tenuifolia were widely studied for their beneficial effects against damage to the brain. Two compounds extracted from Apium graveolens and Rhizoma coptidis, butylphthalide and berberine, respectively, received much attention recently as potential neuroprotective agents. In this review, the two traditionally used herbs and the two relatively new compounds will be discussed with regard to their potential advantages in alleviating brain and other relevant ailments.

  2. An investigation into pharmaceutically relevant mutagenicity data and the influence on Ames predictive potential

    McCarren Patrick


    prevalence, and molecular weight. Conclusions Despite extensive work in the area of predicting this particular toxicity, work in designing and publishing more relevant test sets for compounds relevant to drug discovery is still necessary. This work also shows that great care must be taken in using QSAR models to replace experimental evidence. When considering all substructures, a random forest model, which can inherently cover distinct neighborhoods, built on Novartis data and previously reported external data provided a suitable model.

  3. On the relevance of bubbles and potential flows for stellar convection

    Bertolami, Marcelo M Miller; Prat, Vincent; Barsukow, Wasilij; Weiss, Achim


    Recently Pasetto et al. have proposed a new method to derive a convection theory appropriate for the implementation in stellar evolution codes. Their approach is based on the simple physical picture of spherical bubbles moving within a potential flow in dynamically unstable regions, and a detailed computation of the bubble dynamics. Based on this approach the authors derive a new theory of convection which is claimed to be parameter free, non-local and time-dependent. This is a very strong claim, as such a theory is the holy grail of stellar physics. Unfortunately we have identified several distinct problems in the derivation which ultimately render their theory inapplicable to any physical regime. In addition we show that the framework of spherical bubbles in potential flows is unable to capture the essence of stellar convection, even when equations are derived correctly.

  4. Chemical Compounds Toxic to Invertebrates Isolated from Marine Cyanobacteria of Potential Relevance to the Agricultural Industry

    Magbubah Essack


    Full Text Available In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review.

  5. Chemical Compounds Toxic to Invertebrates Isolated from Marine Cyanobacteria of Potential Relevance to the Agricultural Industry

    Essack, Magbubah


    In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review.

  6. Self-esteem modulates automatic attentional responses to self-relevant stimuli: Evidence from event-related brain potentials

    Jie eChen


    Full Text Available Previous studies have widely shown that self-esteem modulates the attention bias towards social rejection or emotion-related information. However, little is known about the influences of self-esteem on attention bias towards self-relevant stimuli. We aimed to investigate neural correlates that underlie the modulation effect of self-esteem on self-relevant processing. Event-related potentials were recorded for subjects’ own names and close others’ names (the names of their friends while subjects performed a three-stimulus oddball task. The results showed larger P2 amplitudes for one’s own name than for close-other’s name in the low self-esteem group, whereas this P2 effect were not observed in the high self-esteem group. In addition, one’s own name elicited equivalent N250 amplitudes and larger P3 amplitudes compared with close-other’s name in both high and low self-esteem groups. However, no interaction effects were observed between self-esteem and self-relevant processing in the N250 and P3 components. Thus, we found that the modulation effects of self-esteem on self-relevant processing occurred at the early P2 stage, but not at the later N250 and P3 stages. These findings reflect that individuals with low self-esteem demonstrate automatic attention towards their own names.

  7. Impairment of the reproductive potential of male fathead minnows by environmentally relevant exposures to 4-nonylphenolf

    Schoenfuss, H.L.; Bartell, S.E.; Bistodeau, T.B.; Cediel, R.A.; Grove, K.J.; Zintek, L.; Lee, K.E.; Barber, L.B.


    The synthetic organic compound 4-nonylphenol (NP) has been detected in many human-impacted surface waters in North America. In this study, we examined the ability of NP to alter reproductive competence in male fathead minnows after a 28 day flow-through exposure in a range of environmentally relevant concentrations bracketing the U.S. Environmental Protection Agency toxicity-based NP chronic exposure criterion of 6.1 ??g NP/L. Exposure to NP at and above the EPA chronic exposure criterion resulted in an induction of plasma vitellogenin (VTG) within 14 days. However, 7 days after the cessation of exposure, VTG concentrations had dropped more than 50% and few males expressed VTG above the detection threshold. All of the morphological endpoints, including gonadosomatic index, hepatosomatic index, secondary sexual characters, and histopathology, were unaltered by all NP treatments. However, when NP-exposed male fish were allowed to compete with control males for access to nest sites and females, most treatments altered the reproductive competence of exposed males. At lower NP concentrations, exposed males out-competed control males, possibly by being primed through the estrogenic NP exposure in a fashion similar to priming by pheromones released from female fathead minnows. At higher NP exposure concentrations, this priming effect was negated by the adverse effects of the exposure and control males out-competed treated males. Results of this study indicate the complexity of endocrine disrupting effects and the need for multiple analysis levels to assess the effects of these compounds on aquatic organisms. ?? 2007 Elsevier B.V. All rights reserved.

  8. Aggregation of the protein TRIOBP-1 and its potential relevance to schizophrenia.

    Nicholas J Bradshaw

    Full Text Available We have previously proposed that specific proteins may form insoluble aggregates as a response to an illness-specific proteostatic dysbalance in a subset of brains from individuals with mental illness, as is the case for other chronic brain conditions. So far, established risk factors DISC1 and dysbindin were seen to specifically aggregate in a subset of such patients, as was a novel schizophrenia-related protein, CRMP1, identified through a condition-specific epitope discovery approach. In this process, antibodies are raised against the pooled insoluble protein fractions (aggregomes of post mortem brain samples from schizophrenia patients, followed by epitope identification and confirmation using additional techniques. Pursuing this epitope discovery paradigm further, we reveal TRIO binding protein (TRIOBP to be a major substrate of a monoclonal antibody with a high specificity to brain aggregomes from patients with chronic mental illness. TRIOBP is a gene previously associated with deafness which encodes for several distinct protein species, each involved in actin cytoskeletal dynamics. The 3' splice variant TRIOBP-1 is found to be the antibody substrate and has a high aggregation propensity when over-expressed in neuroblastoma cells, while the major 5' splice variant, TRIOBP-4, does not. Endogenous TRIOBP-1 can also spontaneously aggregate, doing so to a greater extent in cell cultures which are post-mitotic, consistent with aggregated TRIOBP-1 being able to accumulate in the differentiated neurons of the brain. Finally, upon expression in Neuroscreen-1 cells, aggregated TRIOBP-1 affects cell morphology, indicating that TRIOBP-1 aggregates may directly affect cell development, as opposed to simply being a by-product of other processes involved in major mental illness. While further experiments in clinical samples are required to clarify their relevance to chronic mental illness in the general population, TRIOBP-1 aggregates are thus

  9. Significance of antioxidant potential of plants and its relevance to therapeutic applications.

    Kasote, Deepak M; Katyare, Surendra S; Hegde, Mahabaleshwar V; Bae, Hanhong


    Oxidative stress has been identified as the root cause of the development and progression of several diseases. Supplementation of exogenous antioxidants or boosting endogenous antioxidant defenses of the body is a promising way of combating the undesirable effects of reactive oxygen species (ROS) induced oxidative damage. Plants have an innate ability to biosynthesize a wide range of non-enzymatic antioxidants capable of attenuating ROS- induced oxidative damage. Several in vitro methods have been used to screen plants for their antioxidant potential, and in most of these assays they revealed potent antioxidant activity. However, prior to confirming their in vivo therapeutic efficacy, plant antioxidants have to pass through several physiopharmacological processes. Consequently, the findings of in vitro and in vivo antioxidant potential assessment studies are not always the same. Nevertheless, the results of in vitro assays have been irrelevantly extrapolated to the therapeutic application of plant antioxidants without undertaking sufficient in vivo studies. Therefore, we have briefly reviewed the physiology and redox biology of both plants and humans to improve our understanding of plant antioxidants as therapeutic entities. The applications and limitations of antioxidant activity measurement assays were also highlighted to identify the precise path to be followed for future research in the area of plant antioxidants.

  10. Physics of a partially ionized gas relevant to galaxy formation simulations -- the ionization potential energy reservoir

    Vandenbroucke, Bert; Schroyen, Joeri; Jachowicz, Natalie


    Simulation codes for galaxy formation and evolution take on board as many physical processes as possible beyond the standard gravitational and hydrodynamical physics. Most of this extra physics takes place below the resolution level of the simulations and is added in a sub-grid fashion. However, these sub-grid processes affect the macroscopic hydrodynamical properties of the gas and thus couple to the on-grid physics that is explicitly integrated during the simulation. In this paper, we focus on the link between partial ionization and the hydrodynamical equations. We show that the energy stored in ions and free electrons constitutes a potential energy term which breaks the linear dependence of the internal energy on temperature. Correctly taking into account ionization hence requires modifying both the equation of state and the energy-temperature relation. We implemented these changes in the cosmological simulation code Gadget2. As an example of the effects of these changes, we study the propagation of Sedov-...

  11. The relevance of individual microphysical processes for potential vorticity anomalies in extratropical cyclones

    Crezee, Bas; Joos, Hanna; Wernli, Heini


    Extratropical cyclones have a large impact on daily weather through their accompanying strong winds and precipitation. The latent heating and cooling associated with microphysical processes like condensation, freezing and melting, sublimation and evaporation leads to the formation of distinct cloud diabatic potential vorticity (CDPV) anomalies. Positive low-level CDPV anomalies - which typically are formed along the fronts and close to the cyclone center - have been shown to interact with upper-level PV anomalies thereby potentially enhancing storm intensification. Here a novel method is applied, which calculates backward trajectories from the mature storm stage, integrates cloud diabatic PV changes due to microphysical processes, and constructs a CDPV budget for each individual anomaly. Thereby we quantify the contributions of, e.g., cloud condensation, depositional growth of snow and melting of snow to the individual anomalies and in turn to the near-surface circulation. First, we apply this method to an idealized mid-latitude cyclone. The formation of the relatively small low-level negative CDPV anomalies is dominated each by one specific process, depending on their location relative to the front. For the large positive PV anomaly we find that the strongest contributions are from in-cloud condensation and below-cloud snow melting and rain evaporation. Although contributions of in-cloud depositional growth of ice are rather small, they cover a very large area and are therefore dynamically significant, i.e., they produce a fairly large-scale but low-amplitude anomaly. In addition the results from the idealized simulations are compared to a wintertime cyclone. It will be discussed how well the method works for real cyclones and how closely the results agree with those from the idealized channel model experiment.

  12. New technology and illness self-management: Potential relevance for resource-poor populations in Asia.

    Lucas, Henry


    Advances in technology have made it possible for many standard diagnostic and health monitoring procedures, traditionally carried out by qualified personnel within medical facilities, to be reliably undertaken by patients or carers in their own homes with a minimum of basic training. There has also been a dramatic increase in the number and diversity of both sources of information on health issues and the possibilities for sharing information and experiences over ICT-based social networks. It has been suggested that these developments have the potential to 'empower' patients, reducing their dependence on providers and possibly improving their quality of care by increasing the volume and timeliness of diagnostic data and encouraging active self-management of their condition, for example through lifestyle changes. Perhaps more significantly, it is also seen by many economies with ageing populations as a way to contain high and ever rising healthcare costs. It has also been suggested that a move to greater self-management supported by expert networks and smart phone technology could improve the treatment of many millions of patients with chronic diseases in low and middle income economies that are also confronting the potential cost implications of epidemiological and demographic transitions, combined with the higher expectations of a more educated and knowledgeable population. There is now limited evidence that some fairly basic e- and mHealth interventions, for example in the areas of MNCH, malaria and HIV/AIDS can have a positive impact, even in resource-poor contexts. The aim here is to explore the extent to which further investment in technology could play a role in the development of an effective and affordable health sector strategy for at least some developing economies. It is suggested that the effectiveness of the approach may be highly dependent on the specific health conditions addressed, the nature of existing health systems and the overall socio

  13. Potential of polarization lidar to provide profiles of CCN- and INP-relevant aerosol parameters

    R. E. Mamouri


    Full Text Available We investigate the potential of polarization lidar to provide vertical profiles of aerosol parameters from which cloud condensation nucleus (CCN and ice nucleating particle (INP number concentrations can be estimated. We show that height profiles of number concentrations of aerosol particles with radius > 50 nm (APC50, reservoir of favorable CCN and with radius > 250 nm (APC250, reservoir of favorable INP, as well as profiles of the aerosol particle surface area concentration (ASC, used in INP parameterization can be retrieved from lidar-derived aerosol extinction coefficients (AEC with relative uncertainties of a factor of around 2 (APC50, and of about 25–50 % (APC250, ASC. Of key importance is the potential of polarization lidar to identify mineral dust particles and to distinguish and separate the aerosol properties of basic aerosol types such as mineral dust and continental pollution (haze, smoke. We investigate the relationship between AEC and APC50, APC250, and ASC for the main lidar wavelengths of 355, 532 and 1064 nm and main aerosol types (dust, pollution, marine. Our study is based on multiyear Aerosol Robotic Network (AERONET photometer observations of aerosol optical thickness and column-integrated particle size distribution at Leipzig, Germany, and Limassol, Cyprus, which cover all realistic aerosol mixtures of continental pollution, mineral dust, and marine aerosol. We further include AERONET data from field campaigns in Morocco, Cabo Verde, and Barbados, which provide pure dust and pure marine aerosol scenarios. By means of a simple relationship between APC50 and the CCN-reservoir particles (APCCCN and published INP parameterization schemes (with APC250 and ASC as input we finally compute APCCCN and INP concentration profiles. We apply the full methodology to a lidar observation of a heavy dust outbreak crossing Cyprus with dust up to 8 km height and to a case during which anthropogenic pollution dominated.

  14. Comparing the abuse potential of methylphenidate versus other stimulants: a review of available evidence and relevance to the ADHD patient.

    Kollins, Scott H


    The use of psychostimulants to treat attention-deficit/hyperactivity disorder (ADHD) has been controversial for a number of reasons. In an effort to clarify the extent to which the psychostimulant methylphenidate has abuse potential, the existing published evidence has been reviewed and is summarized here, with an emphasis on delineating a number of related but independent issues that are often confused. Methylphenidate produces behavioral effects associated with abuse potential as assessed by traditional assays, but the relevance of this literature to the clinical use of the drug in the treatment of ADHD is ambiguous at best. Existing neuropharmacologic data suggest that methylphenidate has pharmacokinetic properties that reduce its abuse potential as compared with other stimulant drugs of abuse, such as cocaine.

  15. First aid training in driving schools - uselessness or relevant measure with considerable potential?

    Petr Zámečník


    of the Red Cross and Red Crescent Societies. 1 What is the phone number emergency line; 2 How should you act when you arrive at the place of fresh traffic accident where has not been given any help yet? 3 How will you know that a person has internal bleeding in a car accident? 4 How will you know that a person has a spinal injury in a car accident? Answers were given into context with other parts of questionnaire. There were 370 respondents mostly at the age of eighteen and nineteen who were applying for "B" driving license in four regions from thirteen in the Czech Republic. Survey shows alarming results. Promising number of willing respondents - 92% of young drivers intend to provide first aid in traffic accidents - gives in the light of other responses reason for serious concern. Despite high willingness only 58% of respondents feel competent to provide first aid, fair idea of how to act have 23% of respondents and the most common life-threatening states in a car accident is able to identify only few individuals. Such bad results are probably due to the unsufficient first aid courses in driving schools, which are focused mainly on theory and are lacking of practical training. Therefore there is strong need for change in system of first aid courses in driving schools towards more relevant forms of training.

  16. Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: potential therapeutic relevance

    Goard Carolyn A


    Full Text Available Abstract Background Ovarian carcinoma is a rarely curable disease, for which new treatment options are required. As agents that block HMG-CoA reductase and the mevalonate pathway, the statin family of drugs are used in the treatment of hypercholesterolemia and have been shown to trigger apoptosis in a tumor-specific manner. Recent clinical trials show that the addition of statins to traditional chemotherapeutic strategies can increase efficacy of targeting statin-sensitive tumors. Our goal was to assess statin-induced apoptosis of ovarian cancer cells, either alone or in combination with chemotherapeutics, and then determine these mechanisms of action. Methods The effect of lovastatin on ovarian cancer cell lines was evaluated alone and in combination with cisplatin and doxorubicin using several assays (MTT, TUNEL, fixed PI, PARP cleavage and synergy determined by evaluating the combination index. The mechanisms of action were evaluated using functional, molecular, and pharmacologic approaches. Results We demonstrate that lovastatin induces apoptosis of ovarian cancer cells in a p53-independent manner and synergizes with doxorubicin, a chemotherapeutic agent used to treat recurrent cases of ovarian cancer. Lovastatin drives ovarian tumor cell death by two mechanisms: first, by blocking HMG-CoA reductase activity, and second, by sensitizing multi-drug resistant cells to doxorubicin by a novel mevalonate-independent mechanism. This inhibition of drug transport, likely through inhibition of P-glycoprotein, potentiates both DNA damage and tumor cell apoptosis. Conclusions The results of this research provide pre-clinical data to warrant further evaluation of statins as potential anti-cancer agents to treat ovarian carcinoma. Many statins are inexpensive, off-patent generic drugs that are immediately available for use as anti-cancer agents. We provide evidence that lovastatin triggers apoptosis of ovarian cancer cells as a single agent by a

  17. Pharmaceutical consumption and residuals potentially relevant to nutrient cycling in Greater Accra, Ghana

    Evren Sinar


    Full Text Available Recycling nutrients form sanitary wastes back into agricultural ecosystems offers an option to alleviate soil depletion in regions where the use of mineral fertiliser is limited. Exemplary nutrient and water cycling approaches, including collection, treatment and use of human urine, are established at Valley View University (VVU in Greater Accra, Ghana.Concerns have been recently raised in regard to fate and impact of pharmaceutical residues in soils and interlinked environment. To evaluate in how far emerging knowledge can be transposed onto VVU, urban and rural environments in Greater Accra, spatial disease occurrence and drug consumption patterns were studied. Malaria has been found to represent the most severe health burden in Ghana, but there is also a high prevalence of infectious diseases. Drugs consumed in great quantities and in respect to their residual loads potentially problematic in the environment belong to therapeutic groups of: antibiotics, analgesics, drugs for diabetes, antimalarials, cardiovascular drugs and anthelmintics. Drug consumption revealed to be highest in urban and lowest in rural areas. At VVU the range of consumed drugs is comparable to urban areas except for the negligible use of diabetes and cardiovascular medication as well as contraceptives.

  18. Potential cross-reactivity of monoclonal antibodies against clinically relevant mycobacteria.

    Flores-Moreno, K; Celis-Meneses, J S; Meneses-Ruiz, D M; Castillo-Rodal, A I; Orduña, P; Montiel, B A; López-Vidal, Y


    Tuberculosis is a disease caused by the Mycobacterium tuberculosis complex (MTb). In 2011, global mortality due to tuberculosis was 1·4 million individuals. The only available vaccine is the attenuated M. bovis [bacillus Calmette-Guérin (BCG)] strain, which confers variable protection against pulmonary tuberculosis. Some widely distributed non-tuberculous mycobacteria (NTM), such as M. avium and M. arupense, are also potential pathogens for humans. This work aimed to produce and characterize monoclonal antibodies against the M. bovis BCG Mexico strain of the MTb, M. avium subs. hominissuis and the M. arupense strain from NTM. Hybridomas were produced from splenocytes of BALB/c female mice immunized with radiation-inactivated mycobacteria, and the immunoglobulin (Ig)G2a antibody-producing clones with the highest antigenic recognition were selected. The selected clones, Mbv 2A10 for M. bovis BCG Mexico, Mav 3H1 for M. avium and Mar 2D10 for M. arupense, were used in further studies. Enzyme-linked immunosorbent assay (ELISA) and immune proteomics analyses characterized the clones as having the highest cross-reactivity with mycobacteria. Using mass spectrometry, a number of proteins recognized by the monoclonal antibody (mAb) clones were identified. These proteins had roles in metabolic processes, hypoxia, cell cycle and dormancy. In addition, a Clustal W and Immune Epitope Database (IEDB) in-silico analysis was performed in protein sequences that result in the conserved regions within probability epitopes that could be recognized for Mbv2A10 and Mav3H1 clones.


    Mahjoub, Ahmed; Poston, Michael J.; Hand, Kevin P.; Hodyss, Robert; Blacksberg, Jordana; Carlson, Robert W.; Ehlmann, Bethany L.; Choukroun, Mathieu [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States); Brown, Michael E.; Eiler, John M., E-mail: [California Institute of Technology, Division of Geological and Planetary Sciences, Pasadena, CA 91125 (United States)


    In this work we explore the chemistry that occurs during the irradiation of ice mixtures on planetary surfaces, with the goal of linking the presence of specific chemical compounds to their formation locations in the solar system and subsequent processing by later migration inward. We focus on the outer solar system and the chemical differences for ice mixtures inside and outside the stability line for H{sub 2}S. We perform a set of experiments to explore the hypothesis advanced by Wong and Brown that links the color bimodality in Jupiter's Trojans to the presence of H{sub 2}S in the surface of their precursors. Non-thermal (10 keV electron irradiation) and thermally driven chemistry of CH{sub 3}OH–NH{sub 3}–H{sub 2}O (“without H{sub 2}S”) and H{sub 2}S–CH{sub 3}OH–NH{sub 3}–H{sub 2}O (“with H{sub 2}S”) ices were examined. Mid-IR analyses of ice and mass spectrometry monitoring of the volatiles released during heating show a rich chemistry in both of the ice mixtures. The “with H{sub 2}S” mixture experiment shows a rapid consumption of H{sub 2}S molecules and production of OCS molecules after a few hours of irradiation. The heating of the irradiated “with H{sub 2}S” mixture to temperatures above 120 K leads to the appearance of new infrared bands that we provisionally assign to SO{sub 2}and CS. We show that radiolysis products are stable under the temperature and irradiation conditions of Jupiter Trojan asteroids. This makes them suitable target molecules for potential future missions as well as telescope observations with a high signal-to-noise ratio. We also suggest the consideration of sulfur chemistry in the theoretical modeling aimed at understanding the chemical composition of Trojans and KOBs.

  20. Cutaneous metastasis in anorectal adenocarcinoma

    Krishnendra Varma


    Full Text Available Cutaneous metastasis in anorectal adenocarcinoma is a rare entity. Here, we report the case of a 40-year-old female who presented with yellowish-brown, irregular, solid, elevated rashes over the pubis with a recent history off palliative colostomy for anorectal adenocarcinoma. Clinically, we suspected metastasis that was proved on biopsy. We report this case due to the rare presenting site (i.e., perineum of a metastatic adenocarcinoma.

  1. Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy.

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung


    Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008-2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC.

  2. Glutaminase-deficient mice display hippocampal hypoactivity, insensitivity to pro-psychotic drugs and potentiated latent inhibition: relevance to schizophrenia.

    Gaisler-Salomon, Inna; Miller, Gretchen M; Chuhma, Nao; Lee, Sooyeon; Zhang, Hong; Ghoddoussi, Farhad; Lewandowski, Nicole; Fairhurst, Stephen; Wang, Yvonne; Conjard-Duplany, Agnès; Masson, Justine; Balsam, Peter; Hen, René; Arancio, Ottavio; Galloway, Matthew P; Moore, Holly M; Small, Scott A; Rayport, Stephen


    Dysregulated glutamatergic neurotransmission has been strongly implicated in the pathophysiology of schizophrenia (SCZ). Recently, presynaptic modulation of glutamate transmission has been shown to have therapeutic promise. We asked whether genetic knockdown of glutaminase (gene GLS1) to reduce glutamatergic transmission presynaptically by slowing the recycling of glutamine to glutamate, would produce a phenotype relevant to SCZ and its treatment. GLS1 heterozygous (GLS1 het) mice showed about a 50% global reduction in glutaminase activity, and a modest reduction in glutamate levels in brain regions relevant to SCZ pathophysiology, but displayed neither general behavioral abnormalities nor SCZ-associated phenotypes. Functional imaging, measuring regional cerebral blood volume, showed hippocampal hypometabolism mainly in the CA1 subregion and subiculum, the inverse of recent clinical imaging findings in prodromal and SCZ patients. GLS1 het mice were less sensitive to the behavioral stimulating effects of amphetamine, showed a reduction in amphetamine-induced striatal dopamine release and in ketamine-induced frontal cortical activation, suggesting that GLS1 het mice are resistant to the effects of these pro-psychotic challenges. Moreover, GLS1 het mice showed clozapine-like potentiation of latent inhibition, suggesting that reduction in glutaminase has antipsychotic-like properties. These observations provide further support for the pivotal role of altered glutamatergic synaptic transmission in the pathophysiology of SCZ, and suggest that presynaptic modulation of the glutamine-glutamate pathway through glutaminase inhibition may provide a new direction for the pharmacotherapy of SCZ.

  3. Anti-metastatic Potential of Amide-linked Local Anesthetics: Inhibition of Lung Adenocarcinoma Cell Migration and Inflammatory Src Signaling Independent of Sodium Channel Blockade

    Piegeler, Tobias; Votta-Velis, E. Gina; Liu, Guoquan; Place, Aaron T.; Schwartz, David E.; Beck-Schimmer, Beatrice; Minshall, Richard D.; Borgeat, Alain


    Background Retrospective analysis of patients undergoing cancer surgery suggests the use of regional anesthesia may reduce cancer recurrence and improve survival. Amide-linked local anesthetics have anti-inflammatory properties, although the mechanism of action in this regard is unclear. As inflammatory processes involving Src tyrosine protein kinase and intercellular adhesion molecule-1 are important in tumor growth and metastasis, we hypothesized that amide-linked local anesthetics may inhibit inflammatory Src-signaling involved in migration of adenocarcinoma cells. Methods NCI-H838 lung cancer cells were incubated with Tumor Necrosis Factor-α in absence/presence of ropivacaine, lidocaine, or chloroprocaine (1nM-100μM). Cell migration and total cell lysate Src-activation and Intercellular Adhesion Molecule-1 phosphorylation were assessed. The role of voltage-gated sodium-channels in the mechanism of local anesthetic effects was also evaluated. Results Ropivacaine treatment (100μM) of H838 cells for 20 minutes decreased basal Src activity by 62% (p=0.003), and both ropivacaine and lidocaine co-administered with Tumor Necrosis Factor-α statistically significantly decreased Src-activation and Intercellular Adhesion Molecule-1 phosphorylation, whereas chloroprocaine had no such effect. Migration of these cells at 4 hours was inhibited by 26% (p=0.005) in presence of 1μM ropivacaine and 21% by 1μM lidocaine (p=0.004). These effects of ropivacaine and lidocaine were independent of voltage-gated sodium-channel inhibition. Conclusions This study indicates that amide-, but not ester-linked local anesthetics may provide beneficial anti-metastatic effects. The observed inhibition of NCI-H838 cell migration by lidocaine and ropivacaine was associated with the inhibition of Tumor Necrosis Factor-α-induced Src-activation and Intercellular Adhesion Molecule-1 phosphorylation, providing the first evidence of a molecular mechanism which appears to be independent of their

  4. Asymptomatic ileal adenocarcinoma in the setting of undiagnosed Crohn's disease

    Vikram B Reddy; Harold Aslanian; Namsoo Suh; Walter E Longo


    A 53-year old previously healthy male underwent a screening colonoscopy for detection of a potential colorectal neoplasm. The terminal ileum was intubated and a mass was noted. Examination of the colon was normal. The biopsy of the ileal mass was consistent with an adenocarcinoma arising from the terminal ileum. His father who had never been previously ill from gastrointestinal disease died of natural causes,but was found to have Crohn's disease postmortem.The patient underwent exploratory laparotomy and aright hemicolectomy with a 30 cm section of terminal ileum in continuity. Findings were consistent with ileal adenocarcinoma in the setting of Crohn's disease. Thepatient made an uneventful recovery. The pathology was stage 1 adenocarcinoma. This is a unique case in that on a screening colonoscopy, a favorable ileal adenocarcinoma was discovered in the setting of asymptomatic, undiagnosed ileal Crohn's disease in a patient whose father had Crohn's disease diagnosed postmortem.

  5. Vesical metastasis of gastric adenocarcinoma

    Alberto A. Antunes


    Full Text Available Metastatic vesical tumors are rare, and constitute approximately 1% of all neoplasias affecting this organ. The authors report the case of a 63-year old woman with vesical metastasis of gastric adenocarcinoma. Patient presented signs of cachexia and complained of left lumbar pain and dysuria unresponsive to antibiotic therapy for approximately 5 months. She reported a previous partial gastrectomy due to ulcerative undifferentiated gastric adenocarcinoma 1 year and 9 months before. Cystoscopy revealed an extensive vegetative lesion in bladder, occupying its entire mucosal surface. The biopsy revealed metastatic signet-ring cell adenocarcinoma.

  6. [Ocular metastasis heralding gastric adenocarcinoma].

    Chekrine, T; Tawfiq, N; Bouchbika, Z; Benchakroun, N; Jouhadi, H; Sahraoui, S; Benider, A


    Ocular metastasis is a rare presenting feature of gastric adenocarcinoma. We report a 48-year-old woman who presented with a decrease in visual acuity of the right eye leading to the discovery of an ocular metastasis. Diagnostic work-up identified a gastric adenocarcinoma with pulmonary metastases. She received four cycles of chemotherapy combining epirubicin, cisplatin and fluorouracil. The patient died 6 months after the diagnosis of respiratory failure.

  7. Clinical relevancy and determinants of potential drug–drug interactions in chronic kidney disease patients: results from a retrospective analysis

    Saleem A


    Full Text Available Ahsan Saleem,1,2 Imran Masood,1 Tahir Mehmood Khan3 1Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 2Pharmacy Services Department, Integrated Medical Center, The Aga Khan University Hospital, Lahore, Pakistan; 3School of Pharmacy, Monash University, Sunway Campus, Selangor, Malaysia Background: Chronic kidney disease (CKD alters the pharmacokinetic and pharmacodynamic responses of various renally excreted drugs and increases the risk of drug-related problems, such as drug–drug interactions.Objectives: To assess the pattern, determinants, and clinical relevancy of potential drug–drug interactions (pDDIs in CKD patients.Materials and methods: This study retrospectively reviewed medical charts of all CKD patients admitted in the nephrology unit of a tertiary care hospital in Pakistan from January 2013 to December 2014. The Micromedex Drug-Reax® system was used to screen patient profiles for pDDIs, and IBM SPSS version 20 was used to carry out statistical analysis.Results: We evaluated 209 medical charts and found pDDIs in nearly 78.5% CKD patients. Overall, 541 pDDIs were observed, of which, nearly 60.8% patients had moderate, 41.1% had minor, 27.8% had major, and 13.4% had contraindicated interactions. Among those interactions, 49.4% had good evidence, 44.0% had fair, 6.3% had excellent evidence, and 35.5% interactions had delayed onset of action. The potential adverse outcomes of pDDIs included postural hypotension, QT prolongation, ceftriaxone–calcium precipitation, cardiac arrhythmias, and reduction in therapeutic effectiveness. The occurrence of pDDIs was found strongly associated with the age of <60 years, number of prescribed medicines ≥5, hypertension, and the lengthy hospitalization of patients.Conclusion: The occurrence of pDDIs was high in CKD patients. It was observed that CKD patients with an older age, higher number of prescribed medicines, lengthy hospitalization, and hypertension were at

  8. The prevalence of human papillomavirus in colorectal adenomas and adenocarcinomas

    Baandrup, Louise; Thomsen, Louise T; Olesen, Tina Bech;


    The role of human papillomavirus (HPV) in colorectal cancer has been widely studied with conflicting results. We performed a systematic review and a meta-analysis to estimate the prevalence of HPV in colorectal adenocarcinomas and adenomas, and test the potential association.......The role of human papillomavirus (HPV) in colorectal cancer has been widely studied with conflicting results. We performed a systematic review and a meta-analysis to estimate the prevalence of HPV in colorectal adenocarcinomas and adenomas, and test the potential association....

  9. Gene expression profiling to identify the toxicities and potentially relevant human disease outcomes associated with environmental heavy metal exposure.

    Korashy, Hesham M; Attafi, Ibraheem M; Famulski, Konrad S; Bakheet, Saleh A; Hafez, Mohammed M; Alsaad, Abdulaziz M S; Al-Ghadeer, Abdul Rahman M


    Heavy metals are the most commonly encountered toxic substances that increase susceptibility to various diseases after prolonged exposure. We have previously shown that healthy volunteers living near a mining area had significant contamination with heavy metals associated with significant changes in the expression of some detoxifying genes, xenobiotic metabolizing enzymes, and DNA repair genes. However, alterations of most of the molecular target genes associated with diseases are still unknown. Thus, the aims of this study were to (a) evaluate the gene expression profile and (b) identify the toxicities and potentially relevant human disease outcomes associated with long-term human exposure to environmental heavy metals in mining area using microarray analysis. For this purpose, 40 healthy male volunteers who were residents of a heavy metal-polluted area (Mahd Al-Dhahab city, Saudi Arabia) and 20 healthy male volunteers who were residents of a non-heavy metal-polluted area were included in the study. Total RNA was isolated from whole blood using PAXgene Blood RNA tubes and then reversed transcribed and hybridized to the gene array using the Affymetrix U219 GeneChip. Microarray analysis showed about 2129 genes were identified and differentially altered, among which a shared set of 425 genes was differentially expressed in the heavy metal-exposed groups. Ingenuity pathway analysis revealed that the most altered gene-regulated diseases in heavy metal-exposed groups included hematological and developmental disorders and mostly renal and urological diseases. Quantitative real-time polymerase chain reaction closely matched the microarray data for some genes tested. Importantly, changes in gene-related diseases were attributed to alterations in the genes encoded for protein synthesis. Renal and urological diseases were the diseases that were most frequently associated with the heavy metal-exposed group. Therefore, there is a need for further studies to validate these

  10. Chromodomain-helicase-DNA binding protein 5, 7 and pronecrotic mixed lineage kinase domain-like protein serve as potential prognostic biomarkers in patients with resected pancreatic adenocarcinomas

    Crystal S Seldon; Lauren E Colbert; William A Hall; Sarah B Fisher; David S Yu; Jerome C Landry


    Pancreatic cancer is one of the deadliest cancers with a very poor prognosis. Recently, there has been a significant increase in research directed towards identifying potential biomarkers that can be used to diagnose and provide prognostic information for pancreatic cancer. These markers can be used clinically to optimize and personalize therapy for individual patients. In this review, we focused on 3 biomarkers involved in the DNA damage response pathway and the necroptosis pathway: Chromodomainhelicase-DNA binding protein 5, chromodomain-helicaseDNA binding protein 7, and mixed lineage kinase domain-like protein. The aim of this article is to review present literature provided for these biomarkers and current studies in which their effectiveness as prognostic biomarkers are analyzed in order to determine their future use as biomarkers in clinical medicine. Based on the data presented, these biomarkers warrant further investigation,and should be validated in future studies.

  11. Amplification of the Insulin-Like Growth Factor 1 Receptor Gene Is a Rare Event in Adrenocortical Adenocarcinomas: Searching for Potential Mechanisms of Overexpression

    Tamaya Castro Ribeiro


    Full Text Available Context. IGF1R overexpression appears to be a prognostic biomarker of metastatic pediatric adrenocortical tumors. However, the molecular mechanisms that are implicated in its upregulation remain unknown. Aim. To investigate the potential mechanisms involved in IGF1R overexpression. Patients and Methods. We studied 64 adrenocortical tumors. IGF1R copy number variation was determined in all patients using MLPA and confirmed using real time PCR. In a subgroup of 32 patients, automatic sequencing was used to identify IGF1R allelic variants and the expression of microRNAs involved in IGF1R regulation by real time PCR. Results. IGF1R amplification was detected in an adrenocortical carcinoma that was diagnosed in a 46-year-old woman with Cushing’s syndrome and virilization. IGF1R overexpression was demonstrated in this case. In addition, gene amplification of other loci was identified in this adrenocortical malignant tumor, but no IGF1R copy number variation was evidenced in the remaining cases. Automatic sequencing revealed three known polymorphisms but they did not correlate with its expression. Expression of miR-100, miR-145, miR-375, and miR-126 did not correlate with IGF1R expression. Conclusion. We demonstrated amplification and overexpression of IGF1R gene in only one adrenocortical carcinoma, suggesting that these combined events are uncommon. In addition, IGF1R polymorphisms and abnormal microRNA expression did not correlate with IGF1R upregulation in adrenocortical tumors.

  12. US and MRI Findings of Penile Metastasis from Rectal Adenocarcinoma: A Case Report

    Oh, Ha Yeun [Kangwon National University Hospital, Chuncheon (Korea, Republic of)


    Metastatic tumors of the penis originating from the gastrointestinal tract are rare clinical conditions. We experienced a case of penile metastasis in a 59-year-old man who underwent an abdomino-peritoneal resection for a moderately-differentiated adenocarcinoma of the rectum 4 years earlier. We report penile ultrasonography and magnetic resonance imaging findings on this uncommon metastatic penile tumor from a rectal adenocarcinoma and briefly review radiologic findings and relevant literature

  13. Precision prevention of oesophageal adenocarcinoma.

    Vaughan, Thomas L; Fitzgerald, Rebecca C


    The incidence of oesophageal adenocarcinoma has risen rapidly over the past four decades. Unfortunately, treatments have not kept pace; unless their cancer is identified at a very early stage, most patients will not survive a year after diagnosis. The beginnings of this widespread problem were first recognized over 25 years ago, yet rates have continued to rise against a backdrop of much improved understanding and management of oesophageal adenocarcinoma. We estimate that only ∼7% of the 10,000 cases of oesophageal adenocarcinoma diagnosed annually in the USA are identified through current approaches to cancer control, and trace pathways by which the remaining 93% are 'lost'. On the basis of emerging data on aetiology and predictive factors, together with new diagnostic tools, we suggest a five-tier strategy for prevention and control that begins with a wide population base and triages individuals into progressively higher risk strata, each with risk-appropriate prevention, screening and treatment options.

  14. Unusual presentation of metastatic adenocarcinoma

    Mudan Satvinder


    Full Text Available Abstract Background The most common tumours of the adrenal gland are adenoma, pheochromocytoma, adrenocortical carcinoma, and metastases. Although the imaging features of these tumours are established, the imaging characteristics of uncommon adrenal masses are less well known. In patients with extradrenal tumour, incidental discovery of an adrenal mass necessitates excluding the possibility of metastatic malignancy. Case presentation A 52 year-old female was diagnosed with oesophageal adenocarcinoma and treated with oesophagectomy and adjuvant chemotherapy. Sixteen months later on staging CT scan a 2 × 2 cm adrenal mass was detected, which increased in size over a period of time to 3 × 3 cm in size. Adrenalectomy was performed and histological examination revealed metastatic adenocarcinoma within an adrenal adenoma. Conclusion The present case highlights the unusual behaviour of an oesophageal adenocarcinoma causing metastasis to an adrenocortical adenoma.

  15. Effect of specific or random c-DNA priming on sensitivity of tyrosinase nested RT-PCR : Potential clinical relevance

    Calogero, A; Hospers, GAP; Timmer-Bosscha, H; Mulder, NH; Schraffordt Koops, H.


    The reverse transcriptase polymerase chain reaction (RT-PCR) can be of clinical relevance in identifying malignant melanoma cells in blood or tissues of patients at risk for disseminated melanoma. The diagnostic value of this marker however, is still controversial. The objective of this study was to

  16. Potential causative agents of acute gastroenteritis in households with preschool children : prevalence, risk factors, clinical relevance and household transmission

    Heusinkveld, M.; Mughini-Gras, L.; Pijnacker, R.; Vennema, H.; Scholts, R.; van Huisstede-Vlaanderen, K. W.; Kortbeek, T.; Kooistra-Smid, M.; van Pelt, W.


    Acute gastroenteritis (AGE) morbidity remains high amongst preschool children, posing a significant societal burden. Empirical data on AGE-causing agents is needed to gauge their clinical relevance and identify agent-specific targets for control. We assessed the prevalence, risk factors and associat

  17. Trefoil factor 3 as a novel biomarker to distinguish between adenocarcinoma and squamous cell carcinoma.

    Wang, Xiao-Nan; Wang, Shu-Jing; Pandey, Vijay; Chen, Ping; Li, Qing; Wu, Zheng-Sheng; Wu, Qiang; Lobie, Peter E


    In carcinoma, such as of the lung, the histological subtype is important to select an appropriate therapeutic strategy for patients. However, carcinomas with poor differentiation cannot always be distinguished on the basis of morphology alone nor on clinical findings. Hence, delineation of poorly differentiated adenocarcinoma and squamous cell carcinoma, the 2 most common epithelial-origin carcinomas, is pivotal for selection of optimum therapy. Herein, we explored the potential utility of trefoil factor 3 (TFF3) as a biomarker for primary lung adenocarcinoma and extrapulmonary adenocarcinomas derived from different organs. We observed that 90.9% of lung adenocarcinomas were TFF3-positive, whereas no expression of TFF3 was observed in squamous cell carcinomas. The subtype of lung carcinoma was confirmed by four established biomarkers, cytokeratin 7 and thyroid transcription factor 1 for adenocarcinoma and P63 and cytokeratin 5/6 for squamous cell carcinoma. Furthermore, expression of TFF3 mRNA was observed by quantitative PCR in all of 11 human lung adenocarcinoma cell lines and highly correlated with markers of the adenocarcinomatous lineage. In contrast, little or no expression of TFF3 was observed in 4 lung squamous cell carcinoma cell lines. By use of forced expression, or siRNA-mediated depletion of TFF3, we determined that TFF3 appeared to maintain rather than promote glandular differentiation of lung carcinoma cells. In addition, TFF3 expression was also determined in adenocarcinomas from colorectum, stomach, cervix, esophagus, and larynx. Among all these extrapulmonary carcinomas, 93.7% of adenocarcinomas exhibited TFF3 positivity, whereas only 2.9% of squamous cell carcinomas were TFF3-positive. Totally, 92.9% of both pulmonary and extrapulmonary adenocarcinomas exhibited TFF3 positivity, whereas only 1.5% of squamous cell carcinomas were TFF3-positive. In conclusion, TFF3 is preferentially expressed in adenocarcinoma and may function as an additional

  18. Cutaneous Metastases From Esophageal Adenocarcinoma

    Triantafyllou, Stamatina; Georgia, Doulami; Gavriella-Zoi, Vrakopoulou; Dimitrios, Mpistarakis; Stulianos, Katsaragakis; Theodoros, Liakakos; Georgios, Zografos; Dimitrios, Theodorou


    The aim of this study is to present 2 rare cases of cutaneous metastases originated from adenocarcinoma of the gastro-esophageal junction, thus, underline the need for early diagnosis and possible treatment of suspicious skin lesions among patients with esophageal malignancy. Metastatic cancer to the skin originated from internal malignancies, mostly lung cancer, breast cancer, and colorectal cancer, constitute 0.5 to 9% of all metastatic cancers.5,8,15 Skin metastases, mainly from squamous cell carcinomas of the esophagus, are rarely reported. Cutaneous metastasis is a finding indicating progressiveness of the disease.17 More precisely, median survival is estimated approximately 4.7 months.2,14 This study is a retrospective review of 2 cases of patients with adenocarcinoma of the esophagus and a review of the literature. Two patients aged 60 and 32 years old, respectively, underwent esophagectomy. Both pathologic reports disclosed adenocarcinoma of the gastro-esophageal junction staged T3 N2 M0 (stage IIIB). During follow-up time, the 2 patients were diagnosed with cutaneous metastases originated from the primary esophageal tumor 11 and 4 months after surgery, respectively. The first patient is alive 37 months after diagnosis, while the second one died 16 months after surgery. Cutaneous metastasis caused by esophageal adenocarcinoma is possible. Therefore, follow-up of patients who were diagnosed with esophageal malignancy and underwent esophagectomy is mandatory in order to reveal early surgical stages. PMID:25785344

  19. IQGAP1 in rectal adenocarcinomas

    Holck, Susanne; Nielsen, Hans Jørgen; Hammer, Emilie;


    Treatment of rectal adenocarcinoma includes total mesorectal excision, which is preceded by radiochemotherapy (RCT) in cases of advanced disease. The response to RCT varies from total tumor regression to no effect but this heterogeneous response is unexplained. However, both radiation and treatme...

  20. Interphase cytogenetics of prostatic adenocarcinoma

    J.C. Alers (Janneke)


    textabstractIn the first part of this chapter an overview will be presented on the structural, histological and functional aspects of the normal human prostate. The second part describes the epidemiological and clinicopathological features of prostatic adenocarcinoma. Further, a state of the art of

  1. Met expression is an independent prognostic risk factor in patients with oesophageal adenocarcinoma

    J.B. Tuynman; S.M. Lagarde (Sjoerd); F.J.W. ten Kate (Fiebo); D.J. Richel (Dirk); J.J.B. van Lanschot (Jan)


    textabstractOesophageal adenocarcinoma is an aggressive malignancy with propensity for early lymphatic and haematogenous dissemination. Since conventional TNM staging does not provide accurate prognostic information, novel molecular prognostic markers and potential therapeutic targets are subject of

  2. Incidence rate and pattern of clinically relevant potential drug-drug interactions in a large outpatient population of a developing country

    Ehsan Nabovati


    Full Text Available The objective of this study was to determine incidence rate, type, and pattern of clinically relevant potential drug-drug interactions (pDDIs in a large outpatient population of a developing country. A retrospective, descriptive cross-sectional study was conducted on outpatients’ prescriptions in Khorasan Razavi province, Iran, over 12 months. A list of 25 clinically relevant DDIs, which are likely to occur in the outpatient setting, was used as the reference. Most frequent clinically relevant pDDIs, most common drugs contributing to the pDDIs, and the pattern of pDDIs for each medical specialty were determined. Descriptive statistics were used to report the results. In total, out of 8,169,142 prescriptions, 6,096 clinically relevant pDDIs were identified. The most common identified pDDIs were theophyllines-quinolones, warfarin-nonsteroidal anti-inflammatory drugs, benzodiazepines-azole antifungal agents, and anticoagulants-thyroid hormones. The most common drugs contributing to the identified pDDIs were ciprofloxacin, theophylline, warfarin, aminophylline, alprazolam, levothyroxine, and selegiline. While the incidence rate of clinically relevant pDDIs in prescriptions of general practitioners, internists, and cardiologists was the highest, the average pDDI incidence per 10,000 prescriptions of pulmonologists, infectious disease specialists, and cardiologists was highest. Although a small proportion of the analyzed prescriptions contained drug pairs with potential for clinically relevant DDIs, a significant number of outpatients have been exposed to the adverse effects associated with these interactions. It is recommended that in addition to training physicians and pharmacists, other effective interventions such as computerized alerting systems and electronic prescribing systems be designed and implemented.

  3. Adenocarcinoma arising from vaginal stump: unusual vaginal carcinogenesis 7 years after hysterectomy due to cervical intraepithelial neoplasia.

    Shibata, Takashi; Ikura, Yoshihiro; Iwai, Yasuhiro; Tokuda, Hisato; Cho, Yuka; Morimoto, Noriyuki; Nakago, Satoshi; Oishi, Tetsuya


    Primary vaginal adenocarcinomas are one of the rarest malignant neoplasms, which develop in the female genital tract. Because of the extremely low incidence, their clinical and pathologic characteristics are still obscure. Recently, we experienced a case of vaginal adenocarcinoma that appeared 7 yr after hysterectomy because of cervical intraepithelial neoplasia. The patient, a 65-yr-old obese woman, was diagnosed as having adenocarcinoma in the vaginal stump and was treated by simple tumor excision and radiation. Immunohistochemical and molecular biologic examinations indicated a potential association with human papilloma virus infection in the development of the vaginal adenocarcinoma. There has been no evidence of recurrence for 3 yr after the operation.

  4. Phenolic compounds, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension of commonly used medicinal plants, herbs and spices in Latin America.

    Ranilla, Lena Galvez; Kwon, Young-In; Apostolidis, Emmanouil; Shetty, Kalidas


    Traditionally used medicinal plants, herbs and spices in Latin America were investigated to determine their phenolic profiles, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension. High phenolic and antioxidant activity-containing medicinal plants and spices such as Chancapiedra (Phyllantus niruri L.), Zarzaparrilla (Smilax officinalis), Yerba Mate (Ilex paraguayensis St-Hil), and Huacatay (Tagetes minuta) had the highest anti-hyperglycemia relevant in vitro alpha-glucosidase inhibitory activities with no effect on alpha-amylase. Molle (Schinus molle), Maca (Lepidium meyenii Walp), Caigua (Cyclanthera pedata) and ginger (Zingiber officinale) inhibited significantly the hypertension relevant angiotensin I-converting enzyme (ACE). All evaluated pepper (Capsicum) genus exhibited both anti-hyperglycemia and anti-hypertension potential. Major phenolic compounds in Matico (Piper angustifolium R.), Guascas (Galinsoga parviflora) and Huacatay were chlorogenic acid and hydroxycinnamic acid derivatives. Therefore, specific medicinal plants, herbs and spices from Latin America have potential for hyperglycemia and hypertension prevention associated with Type 2 diabetes.

  5. Relevance of Radiocaesium Interception Potential (RIP) on a worldwide scale to assess soil vulnerability to 137Cs contamination

    Vandebroek, L.; Hees, Van M.; Delvaux, B.; Spaargaren, O.; Thiry, Y.


    The extent of radiocaesium retention in soil is important to quantify the risk of further foodchain contamination. The Radiocaesium Interception Potential (RIP – Cremers et al., 1988, Nature 335, 247–249) is an intrinsic soil parameter which can be used to categorize soils or minerals in terms of th

  6. Hepatoid Adenocarcinoma of the Urachus

    Daniel Fernando Gallego


    Full Text Available Hepatoid adenocarcinoma of the urachus is a rare condition. We present the case of a 51-year-old female who developed abdominal pain and hematuria. Pelvic magnetic resonance imaging (MRI reported an urachal mass with invasion to the bladder that was resected by partial cystectomy. On light microscopy the tumor resembled liver architecture, with polygonal atypical cells in nest formation and trabecular structures. Immunochemistry was positive for alfa-fetoprotein (AFP and serum AFP was elevated. Hepatoid adenocarcinomas have been reported in multiple organs, being most commonly found in the stomach and the ovaries. Bladder compromise has been rarely described in the literature, and it has been associated with poor prognosis, low remission rates, and early metastasis.

  7. Adenocarcinoma of the uterine cervix.

    Rutledge, F N; Galakatos, A E; Wharton, J T; Smith, J P


    From January 1, 1947, through December 31, 1971, 219 patients with primary adenocarcinoma of the intact uterine cervix were treated at the M.D. Anderson Hospital and Tumor Institute. Two modes of therapy were primarily used, namely, irradiationtherapy alone and irradiation therapy plus operation. The 5 year survival resultsare 83.7 per cent for patients with Stage i disease, 48.0 per cent for patients with Stage ii disease, 29.2 per cent for patients with Stage iii disease, and 0.0 per cent for patients with Stage iv disease. The group with irradiation plus operation had a better over-all survival rate. In addition, the incidence of central and pelvic recurrent disease was remarkably lower (fourfold difference). The urologic and bowel complications are discussed. This review lends support for our practice of preoperative irradiation followed by simple (constructive) hysterectomy for selected patients eith adenocarcinoma of the uterine cervix.

  8. Oncocytic Adenocarcinoma of the Orbit.

    Harris, Gerald J; Paul, Sean; Hunt, Bryan C

    Oncocytic adenocarcinoma of the orbit is a rare tumor, with 1 case of nonlacrimal sac, nonlacrimal gland origin, and a poor outcome previously reported. An 85-year-old man with a 2-month history of left-sided epiphora, enlarging eyelid nodules, and diplopia in left gaze was found on imaging to have a poorly circumscribed, nodular mass of uniform radiodensity in the inferomedial orbit. Incisional biopsy revealed morphologic and immunohistochemical features of oncocytic adenocarcinoma with origin in the caruncle suspected, and CT of the neck, chest, abdomen, and pelvis showed no metastases or remote primary tumor source. Based on multidisciplinary consensus, orbital exenteration with adjuvant radiation therapy was performed, and there was no evidence of residual or recurrent tumor 2 years after treatment.

  9. Sulfur isotopic fractionation in vacuum UV photodissociation of hydrogen sulfide and its potential relevance to meteorite analysis.

    Chakraborty, Subrata; Jackson, Teresa L; Ahmed, Musahid; Thiemens, Mark H


    Select meteoritic classes possess mass-independent sulfur isotopic compositions in sulfide and organic phases. Photochemistry in the solar nebula has been attributed as a source of these anomalies. Hydrogen sulfide (H2S) is the most abundant gas-phase species in the solar nebula, and hence, photodissociation of H2S by solar vacuum UV (VUV) photons (especially by Lyman-α radiation) is a relevant process. Because of experimental difficulties associated with accessing VUV radiation, there is a paucity of data and a lack of theoretical basis to test the hypothesis of a photochemical origin of mass-independent sulfur. Here, we present multiisotopic measurements of elemental sulfur produced during the VUV photolysis of H2S. Mass-independent sulfur isotopic compositions are observed. The observed isotopic fractionation patterns are wavelength-dependent. VUV photodissociation of H2S takes place through several predissociative channels, and the measured mass-independent fractionation is most likely a manifestation of these processes. Meteorite sulfur data are discussed in light of the present experiments, and suggestions are made to guide future experiments and models.

  10. Polycomb repressive complex 2 regulates MiR-200b in retinal endothelial cells: potential relevance in diabetic retinopathy.

    Michael Anthony Ruiz

    Full Text Available Glucose-induced augmented vascular endothelial growth factor (VEGF production is a key event in diabetic retinopathy. We have previously demonstrated that downregulation of miR-200b increases VEGF, mediating structural and functional changes in the retina in diabetes. However, mechanisms regulating miR-200b in diabetes are not known. Histone methyltransferase complex, Polycomb Repressive Complex 2 (PRC2, has been shown to repress miRNAs in neoplastic process. We hypothesized that, in diabetes, PRC2 represses miR-200b through its histone H3 lysine-27 trimethylation mark. We show that human retinal microvascular endothelial cells exposed to high levels of glucose regulate miR-200b repression through histone methylation and that inhibition of PRC2 increases miR-200b while reducing VEGF. Furthermore, retinal tissue from animal models of diabetes showed increased expression of major PRC2 components, demonstrating in vivo relevance. This research established a repressive relationship between PRC2 and miR-200b, providing evidence of a novel mechanism of miRNA regulation through histone methylation.

  11. Antioxidant potential and health relevant functionality of traditionally processed Cassia hirsuta L. seeds: an Indian underutilized food legume.

    Vadivel, Vellingiri; Nandety, Aruna; Biesalski, Hans Konrad


    The methanolic extract of Cassia hirsuta L. seed materials, an underutilized food legume collected from India, was analyzed for antioxidant activity and health relevant functionality. The methanolic extract of raw seeds contained a total free phenolic content of 15.82 ± 1.69 g catechin equivalent/100 g extract DM. Encouraging levels of ferric reducing/antioxidant power (FRAP, 1,446 mmol Fe[II]/mg extract), inhibition of ß-carotene degradation (48.81%) and scavenging activity against DPPH (64.40%) and superoxide (43.78%) radicals were exhibited by the raw samples. Further, 83.11% of α-amylase and 62.79% of α-glucosidase enzyme inhibition characteristics under in vitro starch digestion bioassay were also recorded. Sprouting + oil-frying caused an apparent increase on the total free phenolic content and a significant improvement in the antioxidant and free radical scavenging capacity of methanolic extract of C. hirsuta seeds, while soaking + cooking as well as open-pan roasting treatments showed diminishing effects. The analysis of the phenolic profile revealed the presence of gallic acid, p-coumaric acid and (+)-catechin in the methanolic extract of these seeds.

  12. Vitiligo associated with esophageal adenocarcinoma

    Ali Asilian


    Full Text Available Vitiligo is a disease that results in depigmented areas in the skin. It may develop at any age but the average age at onset is 20 years. Association of vitiligo and melanoma has been commonly reported, but malignancies other than melanoma have been rarely associated with vitiligo. We report a 73-year-old patient with new onset vitiligo who developed esophageal adenocarcinoma in the following years.

  13. Optimal lymphadenectomy for esophageal adenocarcinoma.

    Oezcelik, A


    Recently published data have shown that an extended lymphadenectomy during the en bloc esophagectomy leads to a significant increased long-term survival for esophageal adenocarcinoma. On the other hand some studies indicate that the increased survival is based on stage migration and that the surgical complication rate is increased after extended lymphadenectomy. The aim of this review was to give an overview about all aspects of an extended lymphadenectomy in patients with esophageal adenocarcinoma. The review of the literature shows clearly that the number of involved lymph nodes is an independent prognostic factor in patients with esophageal adenocarcinoma. Furthermore, an extended lymphadenectomy leads to an increased long-term survival. Some studies describe that 23 lymph nodes should be removed to predict survival; other studies 18 lymph nodes or 15 lymph nodes. Opponents indicate that the survival benefit is based on stage migration. The studies with a large study population have performed a Cox regression analyzes and identified the number of lymph nodes removed as an independent factor for improved survival, which means it is significant independently from other parameters. Under these circumstances is stage migration not an option to explain the survival benefit. An important difficulty is, that there is no standardized definition of an extended lymphadenectomy, which means the localization and number of removed lymph nodes differ depending from the performing centre. The controversies regarding the survival benefit of the lymphadenectomy is based on the lack of standardisation of the lymphadenectomy. The main goal of further studies should be to generate a clear definition of an extended lymphadenectomy in patients with esophageal adenocarcinoma.

  14. Interphase cytogenetics of prostatic adenocarcinoma

    Alers, Janneke


    textabstractIn the first part of this chapter an overview will be presented on the structural, histological and functional aspects of the normal human prostate. The second part describes the epidemiological and clinicopathological features of prostatic adenocarcinoma. Further, a state of the art of (cyto)genetic aberrations occurring in prostatic cancer is given. The third part of this introduction will discuss methodological aspects of this thesis, i.e., the development and methodology of no...

  15. Incidence of potential drug interactions in a transplant centre setting and relevance of electronic alerts for clinical practice support

    Piera Polidori


    Full Text Available Background Adverse drug events may occur as a result of drug–drug interactions (DDIs. Information technology (IT systems can be an important decision-making tool for healthcare workers to identify DDIs.Objective The aim of the study is to analyse drug prescriptions in our main hospital units, in order to measure the incidence and severity of potential DDIs. The utility of clinical decision-support systems (CDSSs and computerised physician order entry (CPOE in term of alerts adherence was also assessed. DDIs were assessed using a Micromedex healthcare series database.Methods The system, adopted by the hospital, generates alerts for prescriptions with negative interactions and thanks to an ’acknowledgement function’ it is possible to verify physician adherence to alerts. This function, although used previously, became mandatory from September 2010. Physician adherence to alerts and mean monthly incidence of potential DDIs in analysed units, before and after the mandatory ‘acknowledgement function’, were calculated.Results The intensive care unit (ICU registered the greatest incidence of potential DDIs (49.0%, followed by the abdominal surgery unit and dialysis (43.4 and 42.0%, respectively. The cardiothoracic surgery unit (41.6%, step-down unit (38.3% and post-anaesthesia care unit (30.0% were comparable. The operating theatre and endoscopy registered the fewest potential DDIs (28.2 and 22.7%, respectively. Adherence to alerts after the ‘acknowledgement function’ increased by 25.0% in the ICU, 54.0% in the cardiothoracic surgery unit, 52.5% in the abdominal surgery unit, 58.0% in the stepdown unit, 67.0% in dialysis, 51.0% in endoscopy and 48.0% in the post-anaesthesia care unit. In the operating theatre, adherence to alerts decreased from 34.0 to 30.0%. The incidence of potential DDIs after mandatory use of the ’acknowledgement function’ decreased slightly in endoscopy (–2.9%, the abdominal surgery unit (–2.7%, dialysis (

  16. The Soil Microbiota Harbors a Diversity of Carbapenem-Hydrolyzing β-Lactamases of Potential Clinical Relevance.

    Gudeta, Dereje Dadi; Bortolaia, Valeria; Amos, Greg; Wellington, Elizabeth M H; Brandt, Kristian K; Poirel, Laurent; Nielsen, Jesper Boye; Westh, Henrik; Guardabassi, Luca


    The origin of carbapenem-hydrolyzing metallo-β-lactamases (MBLs) acquired by clinical bacteria is largely unknown. We investigated the frequency, host range, diversity, and functionality of MBLs in the soil microbiota. Twenty-five soil samples of different types and geographical origins were analyzed by antimicrobial selective culture, followed by phenotypic testing and expression of MBL-encoding genes in Escherichia coli, and whole-genome sequencing of MBL-producing strains was performed. Carbapenemase activity was detected in 29 bacterial isolates from 13 soil samples, leading to identification of seven new MBLs in presumptive Pedobacter roseus (PEDO-1), Pedobacter borealis (PEDO-2), Pedobacter kyungheensis (PEDO-3), Chryseobacterium piscium (CPS-1), Epilithonimonas tenax (ESP-1), Massilia oculi (MSI-1), and Sphingomonas sp. (SPG-1). Carbapenemase production was likely an intrinsic feature in Chryseobacterium and Epilithonimonas, as it occurred in reference strains of different species within these genera. The amino acid identity to MBLs described in clinical bacteria ranged between 40 and 69%. Remarkable features of the new MBLs included prophage integration of the encoding gene (PEDO-1), an unusual amino acid residue at a key position for MBL structure and catalysis (CPS-1), and overlap with a putative OXA β-lactamase (MSI-1). Heterologous expression of PEDO-1, CPS-1, and ESP-1in E. coli significantly increased the MICs of ampicillin, ceftazidime, cefpodoxime, cefoxitin, and meropenem. Our study shows that MBL producers are widespread in soil and include four genera that were previously not known to produce MBLs. The MBLs produced by these bacteria are distantly related to MBLs identified in clinical samples but constitute resistance determinants of clinical relevance if acquired by pathogenic bacteria.

  17. Fasciola hepatica mucin-encoding gene: expression, variability and its potential relevance in host-parasite relationship.

    Cancela, Martín; Santos, Guilherme B; Carmona, Carlos; Ferreira, Henrique B; Tort, José Francisco; Zaha, Arnaldo


    Fasciola hepatica is the causative agent of fasciolosis, a zoonosis with significant impact both in human and animal health. Understanding the basic processes of parasite biology, especially those related to interactions with its host, will contribute to control F. hepatica infections and hence liver pathology. Mucins have been described as important mediators for parasite establishment within its host, due to their key roles in immune evasion. In F. hepatica, mucin expression is upregulated in the mammalian invasive newly excysted juvenile (NEJ) stage in comparison with the adult stage. Here, we performed sequencing of mucin cDNAs prepared from NEJ RNA, resulting in six different cDNAs clusters. The differences are due to the presence of a tandem repeated sequence of 66 bp encoded by different exons. Two groups of apomucins one with three and the other with four repeats, with 459 and 393 bp respectively, were identified. These cDNAs have open reading frames encoding Ser-Thr enriched proteins with an N-terminal signal peptide, characteristic of apomucin backbone. We cloned a 4470 bp gene comprising eight exons and seven introns that encodes all the cDNA variants identified in NEJs. By real time polymerase chain reaction and high-resolution melting approaches of individual flukes we infer that fhemuc-1 is a single-copy gene, with at least two different alleles. Our data suggest that both gene polymorphism and alternative splicing might account for apomucin variability in the fhemuc-1 gene that is upregulated in NEJ invasive stage. The relevance of this variation in host-parasite interplay is discussed.

  18. Advanced Gastric Neuroendocrine Carcinoma with an Adenocarcinoma Component

    Masashi Miguchi


    Full Text Available In the present study, we observed that the adenocarcinoma component in the mucosa was continuous with neuroendocrine carcinoma (NEC in the deeper layers; this suggests the normal course of NEC carcinogenesis at the histological level. A 72-year-old man was admitted to our hospital with a chief complaint of tarry stools. Endoscopic examination of the upper gastrointestinal tract revealed a 2-cm tumor, with a deep central depression, surrounded by a smooth elevated area, in the middle of the stomach body. A biopsy showed that the tumor was a moderately differentiated gastric adenocarcinoma. The patient underwent total gastrectomy and standard lymph node dissection. The resected tumor was a 3.5 × 2.5 cm type 2 lesion. It comprised two elements at the histological level: (i a moderately differentiated adenocarcinoma in the superficial portion of the mucous membrane layer, and (ii NEC-like cells with dark, round nuclei and scant cytoplasm, presenting a solid and trabecular pattern, in the submucosal and muscularis propria layers. Immunohistochemical findings showed that the NEC-like cells were diffusely positive for chromogranin A, synaptophysin, neural cell adhesion molecule, and neuron-specific enolase, but were negative for carcinoembryonic antigen. The Ki-67 labeling index was 95%. The final pathological diagnosis was gastric NEC with an adenocarcinoma component and a high cellular proliferative potential.

  19. Nonspecific granulomatous prostatitis with prostatic adenocarcinoma

    Murugan Paari


    Full Text Available Granulomatous prostatitis is an infrequently seen entity in routine practice. One of its most common subtypes is nonspecific granulomatous prostatitis (NSGP, the etiology of which is still under debate. Such cases may be mistaken for adenocarcinoma clinically and radiologically. Histological resemblance to adenocarcinoma may arise when there is a xanthogranulomatous pattern or a prominence of epithelioid histiocytes. However, NSGP may rarely coexist with adenocarcinoma and it is critical to sample these cases thoroughly to exclude the presence of malignancy.

  20. Influence of amine structural characteristics on N-nitrosamine formation potential relevant to postcombustion CO2 capture systems.

    Dai, Ning; Mitch, William A


    Concerns have arisen for the possible contamination of air or drinking water supplies downwind of amine-based CO2 capture facilities by potentially carcinogenic N-nitrosamines formed from reactions between flue gas NOx and amine solvents. This study evaluated the influence of amine structure on the potential to form total N-nitrosamines within the absorber and washwater units of a laboratory-scale CO2 capture reactor, and in the solvent after a pressure-cooker treatment as a mimic of desorber conditions. Among 16 amines representing 3 amine classes (alkanolamines, straight-chain and cyclic diamines, and amino acids), the order of the amine was the primary determinant of total N-nitrosamine formation in the absorber unit, with total N-nitrosamine formation in the order: secondary amines ≈ tertiary amines ≫ primary amines. Similar results were observed upon pressure-cooker treatment, due to reactions between nitrite and amines at high temperature. For secondary and tertiary amines, total N-nitrosamine formation under these desorber-like conditions appeared to be more important than in the absorber, but for primary amines, significant formation of total N-nitrosamines was only observed in the absorber. For diamines and amino acids, total N-nitrosamine accumulation rates in washwaters were lowest for primary amines. For alkanolamines, however, total N-nitrosamine accumulation in the washwater was similar regardless of alkanolamine order, due to the combined effects of amine reactivity toward nitrosation and amine volatility. While total N-nitrosamine accumulation rates in washwaters were generally 1-2 orders of magnitude lower than in the absorber, they were comparable to absorber rates for several primary amines. Decarboxylation of the amino acid sarcosine resulted in the accumulation of significant concentrations of N-nitrosodimethylamine and N-nitrodimethylamine in the washwater.

  1. Identification of serum biomarkers for diagnosing stage Ⅰ lung adenocarcinoma by MALDI-TOF mass spectrometry


    Objective To identify specific biomarkers that could improve early diagnosis of lung adenocarcinoma using matrix-assisted laser desorption/ionization (MALDI) technology. Methods Serum samples were isolated from 17 patients with stage Ⅰ lung adenocarcinoma and 17 age-and sex-matched healthy controls,and the serum proteomic profiles were obtained by matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. Results Compared with healthy control group,two highly expressed potenti...

  2. FE65 regulates and interacts with the Bloom syndrome protein in dynamic nuclear spheres - potential relevance to Alzheimer's disease.

    Schrötter, Andreas; Mastalski, Thomas; Nensa, Fabian M; Neumann, Martin; Loosse, Christina; Pfeiffer, Kathy; Magraoui, Fouzi El; Platta, Harald W; Erdmann, Ralf; Theiss, Carsten; Uszkoreit, Julian; Eisenacher, Martin; Meyer, Helmut E; Marcus, Katrin; Müller, Thorsten


    The intracellular domain of the amyloid precursor protein (AICD) is generated following cleavage of the precursor by the γ-secretase complex and is involved in membrane to nucleus signaling, for which the binding of AICD to the adapter protein FE65 is essential. Here we show that FE65 knockdown causes a downregulation of the protein Bloom syndrome protein (BLM) and the minichromosome maintenance (MCM) protein family and that elevated nuclear levels of FE65 result in stabilization of the BLM protein in nuclear mobile spheres. These spheres are able to grow and fuse, and potentially correspond to the nuclear domain 10. BLM plays a role in DNA replication and repair mechanisms and FE65 was also shown to play a role in DNA damage response in the cell. A set of proliferation assays in our work revealed that FE65 knockdown in HEK293T cells reduced cell replication. On the basis of these results, we hypothesize that nuclear FE65 levels (nuclear FE65/BLM containing spheres) may regulate cell cycle re-entry in neurons as a result of increased interaction of FE65 with BLM and/or an increase in MCM protein levels. Thus, FE65 interactions with BLM and MCM proteins may contribute to the neuronal cell cycle re-entry observed in brains affected by Alzheimer's disease.

  3. Dioxins and related compounds in Vietnamese, Vietnamese food and the environment. Potential relevance of hot spots from recent findings

    Paepke, O. [ERGO Research, Hamburg (Germany); Quynh, Hoang Trong [Institute for Oncology, Ha Noi (Viet Nam); Schecter, A. [Univ. of Texas School of Public Health, Dallas Regional Campus, Dallas, TX (United States)


    Agent Orange, a phenoxyherbicide mixture of 2,4,5-trichlorophenoxyaceticacid (2,4,5-T) and 2,4- dichlorophenoxyacetic acid (2,4-D) was sprayed for reasons of defoliation in large amounts on about 10 % of southern Vietnam during the Vietnam war between 1962-1971. 2,4,5-T was contaminated with the highly toxic and persistent 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the low ppm-range (mg/kg). In samples collected between 1970 and 1973 Baughman et al., 1973 documented elevated levels of TCDD from Agent Orange in milk samples from southern Vietnamese woman as well as in fish and shrimp samples from sprayed areas in this region. Studies have documented the intake of 2,3,7,8-TCDD from Agent Orange in Vietnamese and in among US war veterans. This paper gives an overview on recent findings for PCDDs/Fs and dioxin-like PCBs and in various environmental compartments, in humans and in food. Due to the fact that 2,3,7,8-TCDD is the major dioxin congener in 2,4,5-T, many investigators focused mainly on TCDD. We found from our own investigations, that TCDD in case of dioxin contamination is still the predominant dioxin congener, but in certain instances we also found other elevated congeners as well. In some cases mixed chemical contamination of food or humans was found - originating from Agent Orange and other sources. The paper will explain the potential origin of some of the other contaminations found.

  4. Overexpression of vasoactive intestinal peptide receptors and cyclooxygenase-2 in human prostate cancer. Analysis of potential prognostic relevance.

    Fernández-Martínez, Ana B; Carmena, María J; Arenas, M Isabel; Bajo, Ana M; Prieto, Juan C; Sánchez-Chapado, Manuel


    Vasoactive intestinal peptide (VIP) is a potent inductor of cyclooxygenase-2 (COX-2) expression in human prostate cancer cell lines. There are conflicting data regarding the role of COX-2 in the progression of this disease. Here we examined the expression of VIP receptors (VPAC1 and VPAC2) and COX-2 in prostate cancer specimens. Correlations among protein levels and various clinicopathological factors and prognosis of patients were statistically analyzed. For these purposes, formaldehyde-fixed, paraffin-embedded prostate tissue specimens from 63 patients with prostate cancer and 9 control samples were used. The expression of VPAC1 and VPAC2 receptors and COX-2 was analyzed at mRNA levels by quantitative reverse transcriptase-PCR. The corresponding expression at protein level was studied by immunohistochemistry, scored as negative, weak, moderate, or strong, and correlated with different clinicopathological factors by means of multivariate analysis. 88% of prostate cancer tissues overexpressed VPAC1-receptor at mRNA level, 72% VPAC2-receptor and 77% COX-2. Simultaneous overexpression of the three genes was seen in 52% of patients. Similar overexpression patterns were observed at protein level. The correlation between VPAC1 and VPAC2 receptor protein levels was statistically significant. However, no significant correlations existed among protein levels of VPAC receptors and COX-2 with patient age, prostate-specific antigen (PSA) levels, tumor stage, Gleason score and survival time. The overexpression of VPAC1 and VPAC2 receptors and COX-2 in cancer tissue gives them a potential role as targets for diagnosis of prostate cancer but results do not support a clear value as biomarkers for the clinical prognosis of this disease.

  5. Transcriptomic Microenvironment of Lung Adenocarcinoma.

    Bossé, Yohan; Sazonova, Olga; Gaudreault, Nathalie; Bastien, Nathalie; Conti, Massimo; Pagé, Sylvain; Trahan, Sylvain; Couture, Christian; Joubert, Philippe


    Background: Tissues surrounding tumors are increasingly studied to understand the biology of cancer development and identify biomarkers.Methods: A unique geographic tissue sampling collection was obtained from patients that underwent curative lobectomy for stage I pulmonary adenocarcinoma. Tumor and nontumor lung samples located at 0, 2, 4, and 6 cm away from the tumor were collected. Whole-genome gene expression profiling was performed on all samples (n = 5 specimens × 12 patients = 60). Analyses were carried out to identify genes differentially expressed in the tumor compared with adjacent nontumor lung tissues at different distances from the tumor as well as to identify stable and transient genes in nontumor tissues with respect to tumor proximity.Results: The magnitude of gene expression changes between tumor and nontumor sites was similar with increasing distance from the tumor. A total of 482 up- and 843 downregulated genes were found in tumors, including 312 and 566 that were consistently differentially expressed across nontumor sites. Twenty-nine genes induced and 34 knocked-down in tumors were also identified. Tumor proximity analyses revealed 15,700 stable genes in nontumor lung tissues. Gene expression changes across nontumor sites were subtle and not statistically significant.Conclusions: This study describes the transcriptomic microenvironment of lung adenocarcinoma and adjacent nontumor lung tissues collected at standardized distances relative to the tumor.Impact: This study provides further insights about the molecular transitions that occur from normal tissue to lung adenocarcinoma and is an important step to develop biomarkers in nonmalignant lung tissues. Cancer Epidemiol Biomarkers Prev; 26(3); 389-96. ©2016 AACR.

  6. Adenocarcinoma uretral em uma cadela Urethral adenocarcinoma in a bitch

    Marcia Cristina da Silva


    Full Text Available Tumores primários de uretra são raros em animais e há poucos relatos em cães. A ocorrência é maior em cadelas idosas, não havendo predileção por raça. Disúria, estrangúria e hematúria são sinais clínicos associados a esses tumores. É relatado um caso de adenocarcinoma primário de uretra em um cadela Poodle de 12 anos de idade que apresentava aumento de volume no membro pélvico esquerdo. Na necropsia, foram encontradas metástases na articulação femorotibial esquerda, na glândula adrenal e no rim.Urethral primary tumors are rare in animals and there are only few reports in dogs. They are more frequent in old bitches and have no breed predilection. Clinical signs associated with urethral primary tumors include dysuria, strangury and hematuria. We report a case of primary urethral adenocarcinoma in a 12-year-old female Poodle that was presented with localized volume enlargement in the left pelvic limb. At necropsy metastasis were found at the left femorotibial joint, adrenal gland and kidney.

  7. Sigmoid adenocarcinoma with renal metastasis

    Carini Dagnoni


    Full Text Available We report a case of a 75-year-old man submitted to a rectosigmoidectomy and partial cystectomy because of a sigmoid cancer and colovesical fistula. Seven months later and after four cycles of adjuvant chemotherapy, a lesion was detected in the kidney. Histology revealed tubular adenocarcinoma, which meant sigmoid cancer metastasis. Kidney metastases are very rare in colorectal cancer (CRC, but may be generally associated with an unfavorable prognosis. Thus, patients with metastatic CRC and kidney tumors are a diagnostic and therapeutic challenge.

  8. Neurological manifestation of colonic adenocarcinoma

    Uzair Chaudhary


    Full Text Available Paraneoplastic neurologic disorders are extremely rare in cancer patients and are most commonly associated with certain tumors, such as ovarian cancer, small cell lung cancer, and breast cancer. We report here a paraneoplastic neurological syndrome in a 53-year-old man with colonic adenocarcinoma with a solitary liver metastasis. His paraneoplastic syndrome was successfully treated by methylprednisolone and primary oncologic therapies including neoadjuvant chemotherapy and definitive surgery. This is also the first documented case of simultaneous manifestation of a sensory neuropathy and limbic encephalitis with colon cancer.

  9. MYC and gastric adenocarcinoma carcinogenesis

    Danielle Queiroz Calcagno; Mariana Ferreira Leal; Paulo Pimentel Assumpcao; Marilia de Arruda Cardoso Smith; Rommel Rodriguez Burbano


    MYC is an oncogene involved in cell cycle regulation, cell growth arrest, cell adhesion, metabolism, ribosome biogenesis, protein synthesis, and mitochondrial function. It has been described as a key element of several carcinogenesis processes in humans. Many studies have shown an association between MYC deregulation and gastric cancer. MYC deregulation is also seen in gastric preneoplastic lesions and thus it may have a role in early gastric carcinogenesis. Several studies have suggested that amplification is the main mechanism of MYC deregulation in gastric cancer. In the present review, we focus on the deregulation of the MYC oncogene in gastric adenocarcinoma carcinogenesis, including its association with Helicobacter pylori (H pylori) and clinical applications.

  10. Vulvar mucinous adenocarcinoma with neuroendocrine differentiation: A case report and review of the literature

    Rosmalen, M.H. Van; Reijnen, C.; Boll, D.; Pijnenborg, J.M.A.; Wurff, A.A. van der; Piek, J.M.


    BACKGROUND: There are limited cases in literature of patients with mucinous adenocarcinoma of the vulva with neuroendocrine differentiation have. With this new case, we aim to provide an overview of the existing literature and present a tool with relevant markers for the pathologist in the different

  11. Prostatic intraepithelial neoplasia-like ductal prostatic adenocarcinoma: A case suitable for active surveillance?

    Soroush Rais-Bahrami


    Full Text Available In contrast to typical prostatic ductal adenocarcinoma, prostatic intraepithelial neoplasia (PIN-like ductal adenocarcinoma is a rare variant of prostate cancer with low-grade clinical behavior. We report a case of a 66-year-old African-American male with an elevated serum prostate-specific antigen who underwent multiparametric prostate magnetic resonance imaging (MRI and MRI/ultrasound fusion-guided biopsies. Pathology demonstrated low-volume Gleason score 3 + 3 = 6 (Grade Group 1, acinar adenocarcinoma involving one core and PIN-like ductal adenocarcinoma on a separate core. Herein, we discuss the potential role of active surveillance for patients with this rare variant of prostate cancer found in the era of advanced imaging with multiparametric MRI for prostate cancer.

  12. A review of the epidemiology of Barrett's oesophagus and oesophageal adenocarcinoma.

    Schneider, Jennifer L; Corley, Douglas A


    While the incidence rates of many cancers have decreased in past decades, the incidence of oesophageal adenocarcinoma continues to increase. The only known precursor for oesophageal adenocarcinoma is Barrett's oesophagus. Studies conducted have identified white race, male sex, GORD, cigarette smoking, obesity, and the absence of Helicobacter pylori status as risk factors for oesophageal adenocarcinoma. Other potential associations include dietary factors and the absence of non-steroidal anti-inflammatory drug use. Many individual studies have been limited by sample size and several meta-analyses have pooled data from studies to address this limitation. In this review we present a synthesis of these studies and summarize current knowledge of risk factors for both oesophageal adenocarcinoma and Barrett's oesophagus.

  13. A Critical Investigation of the Relevance and Potential of IDPS as a Local Governance Instrument for Pursuing Social Justice in South Africa

    Oliver Njuh Fuo


    Full Text Available Unlike the situation in the past, when local government’s role was limited to service delivery, local government is now constitutionally mandated to play an expanded developmental role. As a “co-responsible” sphere of government, local government is obliged to contribute towards realising the transformative constitutional mandate aimed at social justice. South African scholars and jurists share the view that social justice is primarily concerned with the eradication of poverty and extreme inequalities in access to basic services, and aims to ensure that poor people command sufficient material resources to facilitate their equal participation in socio-political life. In order to enable municipalities to fulfil their broad constitutional mandate, the system of integrated development planning (IDPs came into effect in South Africa in 2000. Each municipality is obliged to design, adopt and implement an integrated development plan in order to achieve its expanded constitutional mandate. The IDP is considered to be the chief legally prescribed governance instrument for South African municipalities. The purpose of this article is to explore and critically investigate the relevance and potential of IDPs in contributing towards the achievement of social justice in South Africa. This article argues inter alia that the multitude of sectors that converge in an IDP makes it directly relevant and gives it enormous potential to contribute towards social justice because, depending on the context, municipalities could include and implement strategies that specifically respond to diverse areas of human need. In this regard, the legal and policy frameworks for IDPs provide a structured scheme that could be used by municipalities to prioritise and meet the basic needs of especially the poor. Despite its potential, it is argued that the ability of IDPs to respond to the basic needs of the poor is largely constrained by a series of implementation challenges

  14. Hearing loss as an unusual consequence of metastatic gastric adenocarcinoma

    CE Owers


    Full Text Available A sixty-one year old man was referred with a history of progressive dysphagia, vomiting and weight loss with some back pain. Upper gastrointestinal endoscopy and biopsies revealed a gastro-oesophageal junction adenocarcinoma. Despite the absence of metastatic disease on computed tomography, positron emission tomography demonstrated multiple vertebral and sternal deposits. He was reviewed in an ENT clinic with a sudden onset of hearing loss accompanied by dizziness, but no focal neurology. Magnetic resonance imaging identified bilateral 2cm lesions at the internal auditory meatus, consistent with a diagnosis of bilateral acoustic neuromas. The patient subsequently died of carcinomatosis and, because of the potential familial significance of bilateral acoustic neuromas, a limited post-mortem examination was carried out. Unexpectedly, this revealed bilateral adenocarcinoma metastases infiltrating the internal auditory meatus affecting the acoustic nerves. The authors believe this a very rare presentation of metastatic gastric disease.

  15. [An unusual secondary localization of bronchial adenocarcinoma].

    Mirallie, E; Courant, O; Sagan, C; Letessier, E; Paineau, J; Visset, J


    The authors report a rare case of metastatic carcinoma of the large bowel, secondary to a primary bronchogenic adenocarcinoma. Abdominal pain developed in a 44-year old man 5 months after lobectomy for lung adenocarcinoma. The diagnosis of a large caecal extraluminal mass was established by means of sonography, scanner and laparoscopy. Palliative resection (brain metastases) was performed. Postoperative histological examination revealed the resected tumor to be identical to the lung adenocarcinoma. The patient eventually died 4 months after resection (complication of intracranial hypertension). Diagnosis and therapeutic features of metastatic extra-thoracic lung carcinoma are discussed.

  16. [Why oesophageal adenocarcinoma is occurring more frequently].

    Doorakkers, Eva; Brusselaers, Nele


    The incidence of oesophageal adenocarcinoma has increased rapidly over the past decades in the Western world. The prognosis is poor with a mean 5-year survival rate of 19% in the Netherlands. Important risk factors that might account for this rising incidence are reflux, obesity and the absence of Helicobacter pylori. Oesophageal adenocarcinoma is 9 times more likely in men than in women. The reason for this much higher incidence of adenocarcinoma in men is still unclear, but sex hormones may play a role.

  17. Association of the DNMT3B polymorphism with colorectal adenomatous polyps and adenocarcinoma.

    Guo, Xiaoqing; Zhang, Liwei; Wu, Mingli; Wang, Na; Liu, Yanfeng; Er, Limian; Wang, Shunping; Gao, Yang; Yu, Weifang; Xue, Hui; Xu, Zhibin; Wang, Shijie


    DNMT3B is an important enzyme to modulate the methylation status in mammalian cells. The aim of this study is to investigate the correlation of the DNMT3B G39179T polymorphism with the susceptibilities of colorectal adenomatous polyps and adenocarcinoma. This case-control study included 146 colorectal adenomatous polyps, 170 colorectal adenocarcinoma patients, and 157 normal controls. DNMT3B polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Family history of colorectal cancer significantly increases the risk of developing colorectal adenomatous polyps and adenocarcinoma. The genotype frequency of DNMT3B polymorphism (T/T and G/T + G/G) in adenocarcinoma patients was significantly different from that in controls (P value = 0.01). Compared with DNMT3B T/T genotype, the G allelotype (G/T + G/G genotype) had lower risk to develop colorectal adenocarcinoma (OR = 0.50, 95% CI = 0.29-0.87); while there was no significant difference between the colorectal adenomatous polyps patients and controls (OR = 0.63, 95% CI = 0.37-1.09), although descending tendency could be found in this polyps group. In the stratification analysis, a significant association was confined to subgroups of age DNMT3B G39179T SNP in different ethnics. DNMT3B G39179T SNP may be a potential genetic susceptibility factor for adenocarcinoma of the colon, especially in younger Chinese Han non-drinker men.

  18. Risk factors for Barrett's oesophagus and oesophageal adenocarcinoma: Results from the FINBAR study

    Lesley A Anderson; RG Peter Watson; Seamus J Murphy; Brian T Johnston; Harry Comber; Jim Mc Guigan; John V Reynolds; Liam J Murray


    AIM: To investigate risk factors associated with Barrett's oesophagus and oesophageal adenocarcinoma.METHODS: This all-Ireland population-based case-control study recruited 224 Barrett's oesophagus patients, 227 oesophageal adenocarcinoma patients and 260 controls. All participants underwent a structured interview with information obtained about potential lifestyle and environmental risk factors.RESULTS: Gastro-oesophageal reflux was associated with Barrett's [OR 12.0 (95% CI 7.64-18.7)] and oesophageal adenocarcinoma [OR 3.48 (95% CI 2.25-5.41)]. Oesophageal adenocarcinoma patients were more likely than controls to be ex- or current smokers [OR 1.72 (95% CI 1.06-2.81) and OR 4.84 (95% CI 2.72-8.61) respectively] and to have a high body mass index [OR 2.69 (95% CI 1.62-4.46)]. No significant associations were observed between these risk factors and Barrett's oesophagus. Fruit but not vegetables were negatively associated with oesophageal adenocarcinoma [OR 0.50 (95% CI 0.30-0.86)].CONCLUSION: A high body mass index, a diet low in fruit and cigarette smoking may be involved in the progression from Barrett's oesophagus to oesophageal adenocarcinoma.

  19. Preoperative evaluation of oesophageal adenocarcinoma.

    Khanna, Lauren G; Gress, Frank G


    The preoperative evaluation of oesophageal adenocarcinoma involves endoscopic ultrasound (EUS), computed tomography (CT), and positron emission tomography (PET). With routine Barrett's oesophagus surveillance, superficial cancers are often identified. EUS, CT and PET have a limited role in the staging of superficial tumours. Standard EUS has limited accuracy, but high frequency ultrasound miniprobes are valuable for assessing tumour stage in superficial tumours. However, the best method for determining depth of invasion, and thereby stage of disease, is endoscopic mucosal resection. In contrast, in advanced oesophageal cancers, a multi-modality approach is crucial. Accurate tumour staging is very important since the treatment of advanced cancers involves a combination of chemotherapy, radiation, and surgery. EUS is very useful for staging of the tumour and nodes. High frequency ultrasound miniprobes provide the ability to perform staging when the lesion is obstructing the oesophageal lumen. CT and PET provide valuable information regarding node and metastasis staging.

  20. MicroRNAs in pancreatic ductal adenocarcinoma

    Jong Y Park; James Helm; Domenico Coppola; Donghwa Kim; Mokenge Malafa; Seung Joon Kim


    Ductal adenocarcinoma of the pancreas is a lethal cancer for which the only chance of long-term survival belongs to the patient with localized disease in whom a potentially curative resection can be done.Therefore,biomarkers for early detection and new therapeutic strategies are urgently needed.miRNAs are a recently discovered class of small endogenous non-coding RNAs of about 22 nucleotides that have gained attention for their role in downregulation of mRNA expression at the posttranscriptional level.miRNAs regulate proteins involved in critical cellular processes such as differentiation,proliferation,and apoptosis.Evidence suggests that deregulated miRNA expression is involved in carcinogenesis at many sites,including the pancreas.Aberrant expression of miRNAs may upregulate the expression of oncogenes or downregulate the expression of tumor suppressor genes,as well as play a role in other mechanisms of carcinogenesis.The purpose of this review is to summarize our knowledge of deregulated miRNA expression in pancreatic cancer and discuss the implication for potential translation of this knowledge into clinical practice.

  1. Immunohistochemical staining of radixin and moesin in prostatic adenocarcinoma

    Becich Michael J


    Full Text Available Abstract Background Some members of the Protein 4.1 superfamily are believed to be involved in cell proliferation and growth, or in the regulation of these processes. While the expression levels of two members of this family, radixin and moesin, have been studied in many tumor types, to our knowledge they have not been investigated in prostate cancer. Methods Tissue microarrays were immunohistochemically stained for either radixin or moesin, with the staining intensities subsequently quantified and statistically analyzed using One-Way ANOVA or nonparametric equivalent with subsequent Student-Newman-Keuls tests for multiple comparisons. There were 11 cases of normal donor prostates (NDP, 14 cases of benign prostatic hyperplasia (BPH, 23 cases of high-grade prostatic intraepithelial neoplasia (HGPIN, 88 cases of prostatic adenocarcinoma (PCa, and 25 cases of normal tissue adjacent to adenocarcinoma (NAC analyzed in the microarrays. Results NDP, BPH, and HGPIN had higher absolute staining scores for radixin than PCa and NAC, but with a significant difference observed between only HGPIN and PCa (p = Conclusions To our knowledge, these studies represent the first reports on the expression profiles of radixin and moesin in prostatic adenocarcinoma. The current study has shown that there were statistically significant differences observed between HGPIN and PCa and HGPIN and NAC in terms of radixin expression. The differences in the moesin profiles by tissue type were not statistically significant. Additional larger studies with these markers may further elucidate their potential roles in prostatic neoplasia progression.

  2. Case Report: Bazex Syndrome Associated With Pulmonary Adenocarcinoma.

    Zhao, Jing; Zhang, Xilin; Chen, Zhuo; Wu, Jian-Hua


    Bazex syndrome, a rare paraneoplastic syndrome characterized by psoriasiform eruptions, palmoplantar keratosis, and symmetric onychodystrophy, is most prevalent with squamous cell carcinomas of the upper aerodigestive tract.Here, we reported an uncommon case of Bazex syndrome about an 83-year-old man with pulmonary adenocarcinoma and osseous metastasis, Physical examination found psoriasiform eruptions on the nose, cheeks, ears, knees, and the dorsa of interphalangeal joints, along with plantar keratosis and symmetric onychodystrophy involving hands and feet. Imaging analyses pulmonary adenocarcinoma with both local metastatic nodules and osseous metastasis.Symptomatic treatment with topical corticosteroids and oral retinoids showed no improvement. A 4-month follow-up showed that Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, successfully reduced primary tumor size and alleviated cutaneous lesions.Our report here highlighted a potential correlation between pulmonary adenocarcinoma and Bazex syndrome, which is characterized by hallmark nail destruction and preferential involvement of body extremities. Moreover, etiological therapy against underlying malignancy is essential for treating paraneoplastic Bazex syndrome.

  3. Rare coexistence of sarcoidosis and lung adenocarcinoma

    Amit Girish Kachalia


    Conclusion: While evidence is still lacking regarding association between sarcoidosis and lung adenocarcinoma, it is important for clinicians to exclude metastatic malignancy in patients exhibiting clinical and radiographic findings consistent with sarcoidosis.

  4. In vitro inhibitory potential of Cynara scolymus, Silybum marianum, Taraxacum officinale, and Peumus boldus on key enzymes relevant to metabolic syndrome.

    Villiger, Angela; Sala, Filippo; Suter, Andy; Butterweck, Veronika


    Boldocynara®, a proprietary dietary supplement product consisting of the plants Cynara scolymus, Silybum marianum, Taraxacum officinale, and Peumus boldus, used to promote functions of the liver and the gallbladder. It was the aim of the present study to look from a different perspective at the product by investigating the in vitro potential of Boldocynara® as a combination product and its individual extracts on key enzymes relevant to metabolic syndrome. Peumus boldus extract exhibited pronounced inhibitory activities on α-glucosidase (80% inhibition at 100 µg/ml, IC50: 17.56 µg/ml). Silybum marianum had moderate pancreatic lipase (PL) inhibitory activities (30% at 100 µg/ml) whereas Cynara scolymus showed moderate ACE inhibitory activity (31% at 100 µg/ml). The combination had moderate to weak effects on the tested enzymes. In conclusion, our results indicate some moderate potential of the dietary supplement Boldocynara® and its single ingredients for the prevention of metabolic disorders.

  5. Maspin expression, subcellular localization and clinicopathological correlation in endometrial hyperplasia and endometrial adenocarcinoma.

    Blandamura, Stella; Alessandrini, Lara; Saccardi, Carlo; Giacomelli, Luciano; Fabris, Alberta; Borghero, Angela; Litta, Pietro


    Maspin expression in endometrial hyperplasia and endometrial endometrioid adenocarcinomas was assessed and its correlation with p53 and Ki67 expressions and clinical outcome, as well as its potential to distinguish typical from atypical endometrial hyperplasia, were assessed in this study. Histological sections from 114 cases of endometrial endometrioid adenocarcinoma, 75 cases of endometrial hyperplasia (typical and atypical), and 23 normal endometrial tissue samples were examined. The most representative hematoxylin-eosin slides were selected and 2-3 micron-thick sections were cut for immunohistochemical staining with maspin, p53, and Ki67 antibodies. While there was no maspin expression in normal endometrial cells, it was present in 14.5% of the patients with endometrial hyperplasia without atypia. Staining for maspin was positive in atypical hyperplasia and endometrial adenocarcinoma in, respectively, 45% and 49.1% of the cases studied. No statistically significant correlations were found between maspin and Ki-67 antibodies or p53 expression. Our findings showed that maspin expression, which generally correlates with a less aggressive behavior, is significantly higher in atypical hyperplasia and in endometrial endometrioid adenocarcinoma. Maspin positivity in endometrial hyperplasia could be used to identify pseudo-atypical hyperplasia and could be considered a potentially useful prognostic parameter in those cases in which adenocarcinomas are well differentiated.

  6. Urothelial-Type adenocarcinoma of the prostate mimicking metastatic colorectal adenocarcinoma

    Brian P. Adley


    Full Text Available Adenocarcinoma arising in urinary bladder or prostatic urethra is uncommon. When they occur, the tumor can be mistaken for metastatic lesions, especially from the colon. Here we report the fifth case of a primary urothelial-type adenocarcinoma arising in the prostate which showed enteric differentiation. The patient was a 55 year-old male whose prostatic needle core biopsy showed a high grade adenocarcinoma which was initially thought to be metastatic colon cancer. A follow-up colonoscopy was unremarkable. Subsequent prostatectomy revealed a high grade adenocarcinoma which was positive for cytokeratins 7 and 20, carcinoembryonic antigen, CDX2, and high molecular weight cytokeratin, and negative for prostate specific antigen, prostate specific acid phosphatase and AMACR. A diagnosis of urothelial-type adenocarcinoma of the prostate was rendered. We review the literature regarding this entity, and discuss the differential diagnosis, emphasizing utility of immunohistochemistry in making the diagnosis. Finally, we speculate on the behavior of these rare tumors.

  7. Reduced retinoid signaling in the skin after systemic retinoid-X receptor ligand treatment in mice with potential relevance for skin disorders.

    Mihály, Johanna; Gericke, Janine; Aydemir, Gamze; Weiss, Kathrin; Carlsen, Harald; Blomhoff, Rune; Garcia, Javier; Rühl, Ralph


    Retinoid-X receptor (RXR)- and retinoic acid receptor (RAR)-mediated signaling is induced by retinoic acids (RA), which are involved in the regulation of skin permeability, differentiation and immune response. Dysregulation of retinoid signaling is present in various skin disorders. Topically and systemically administered synthetic RAR or RXR agonists might influence retinoid-mediated signaling in the skin of RARE reporter animals and gene expression analysis for retinoid, skin homeostasis and skin inflammation marker genes and local retinoid concentrations. Mice were treated orally and topically with synthetic ligands and bioimaging, QRT-PCR and retinoid analysis were performed. Topical application of the synthetic RAR ligand AM580 significantly enhanced retinoid signaling in skin while topical application of the RXR ligand LG268 did not influence retinoic acid receptor response elements (RARE)-mediated signaling. Systemic treatments with LG268 decreased the expression of genes involved in skin homeostasis, RA synthesis and skin RA concentrations, while it increased various markers for skin inflammation and RA degradation, which corresponds to decreased skin RARE signaling. We conclude from these observations that increased systemic concentrations of an RXR -ligand may be one reason for reduced retinoid signaling, -reduced all-trans RA levels in the skin, reduced epidermal homeostasis and increased skin inflammation marker expression with potential relevance for various skin disorders, like atopic dermatitis.

  8. Current perspectives of mi-RNA in oesophageal adenocarcinoma: Roles in predicting carcinogenesis, progression and values in clinical management.

    Amin, Moein; Lam, Alfred King-yin


    Aberrant expressions of micro-ribonucleic acids (miRs) are closely associated with the pathogenesis in many human cancers. In oesophageal adenocarcinomas, altered expressions of different sets of miRs are noted to be associated with the development of adenocarcinoma from Barrett's oesophagus. In different studies, miRs such as miR-192, miR-196 and miR-21 were frequently noted to up-regulated whereas miR-203, miR-205 and miR-let-7 were commonly down-regulated during the development of Barrett's oesophagus to oesophageal adenocarcinoma. In addition, changes in the expression of miRs are associated with the predication of metastasis, prognosis and response to chemo-radiation in the patients with oesophageal adenocarcinoma. Experimental studies in manipulating the miRs in cancer cell lines could provide hints for therapeutics for the cancer. However, the number of studies reported on these aspects of oesophageal adenocarcinoma was limited and the miRs noted needed to be confirmed by additional studies. Overall, the mechanisms of involvements of miRs in pathogenesis and progression of oesophageal adenocarcinoma are complex. Although miRs have the potential to act as prognostic and clinical biomarkers for cancer therapy in oesophageal adenocarcinoma, more works in larger populations and clinical trials are needed to validate these clinical implications.

  9. MicroRNA Expression Analyses in Preoperative Pancreatic Juice Samples of Pancreatic Ductal Adenocarcinoma

    Yoshihiko Sadakari


    Full Text Available Context Cytological assessment of pancreatic juice is commonly used to diagnose pancreatic ductal adenocarcinoma; however, the sensitivity of cytological assessment has been reported to be low. MicroRNAs are small RNAs regulating various cellular processes and have recently been identified as possible markers of malignant diseases including pancreatic ductal adenocarcinoma. Objective The purposes of this study were to prove the existence of microRNAs in pancreatic juice and to determine whether specific microRNAs in pancreatic juice could be used for detecting pancreatic ductal adenocarcinoma. Methods Relative expression levels of microRNA-21 and microRNA-155 in formalin-fixed paraffin-embedded tissues of resected specimens (no. 13 and pancreatic juice samples collected using preoperative endoscopic retrograde cholangiopancreatography (no. 21 were quantified and their expression levels were then compared to pancreatic ductal adenocarcinoma and chronic pancreatitis. Results Relative expression levels of microRNA-21 in tissue and pancreatic juice samples were significantly higher in pancreatic ductal adenocarcinoma than those in chronic pancreatitis (P=0.009 and P=0.021, respectively. The same results were obtained in the expression levels of microRNA-155 in tissue and pancreatic juice between pancreatic ductal adenocarcinoma and chronic pancreatitis (P=0.014 and P=0.021, respectively. Expression levels of microRNA-21 and microRNA-155 did not correlate with the preoperative cytological results of pancreatic juice. Conclusion MicroRNA-21 and microRNA-155 in pancreatic juice have the potential of becoming biomarkers for diagnosing pancreatic ductal adenocarcinoma.

  10. Expression and clinical significance of fibroblast growth factor 1 in gastric adenocarcinoma

    Liu NQ


    Full Text Available Naiqing Liu,1,2,* Jingyu Zhang,2,* Shuxiang Sun,2 Liguang Yang,2 Zhongjin Zhou,2 Qinli Sun,2 Jun Niu11Department of General Surgery, Qilu Hospital Affiliated to Shandong University, Jinan, People’s Republic of China; 2Department of General Surgery, Yishui Central Hospital, Linyi, People’s Republic of China*These authors contributed equally to this workBackground: The clinical significance of fibroblast growth factor 1 (FGF1 has been revealed in several cancers, including ovarian cancer, breast cancer, and bladder cancer. However, the clinical significance of FGF1 in gastric adenocarcinoma has not been explored.Patients and methods: In our experiments, we systematically evaluated FGF1 expression in 178 cases of gastric adenocarcinoma with immunohistochemistry, and subsequently analyzed the correlation between FGF1 expression and clinicopathologic features. Moreover, FGF1 expression in tumor tissue and corresponding adjacent tissue was detected and compared by real-time polymerase chain reaction. The Kaplan–Meier method and the Cox-regression model were used with univariate and multivariate analysis, respectively, to evaluate the prognostic value of FGF1 in gastric adenocarcinoma.Results: Higher FGF1 expression rate is 56.7% (101/178 in gastric adenocarcinoma. FGF1 expression in gastric adenocarcinoma was significantly higher than adjacent tissue (P<0.0001. Expression of FGF1 is significantly associated with lymph node invasion (P<0.001, distant metastasis (P=0.013, and differentiation (P=0.015. Moreover, FGF1 overexpression was closely related to unfavorable overall survival rate (P=0.021, and can be identified to be an independent unfavorable prognostic factor (P=0.004.Conclusion: FGF1 is an independent prognostic factor, indicating that FGF1 could be a potential molecular drug target in gastric adenocarcinoma.Keywords: fibroblast growth factor 1, gastric adenocarcinoma, prognosis, biomarker, lymph node, gene fusion

  11. EGFR Mutation Status in Uighur Lung Adenocarcinoma Patients

    Li SHAN


    Full Text Available Background and objective Epidermal growth factor receptor (EGFR, a transmembrane protein, is a member of the tyrosine kinase family. Gefitinib, an EGFR tyrosine-kinase inhibitors, has shown a high response rate in the treatment of lung cancer in patients with EGFR mutation. However, significant differences in EGFR mutations exist among different ethnic groups. The aim of this study is to investigate the prevalence of EGFR mutations in Uighur lung adenocarcinoma patients by using a rapid and sensitive detection method and to analyze EGFR mutation differences compared with Han lung adenocarcinoma patients. Methods We examined lung adenocarcinoma tissues from 138 patients, including 68 Uighur lung adenocarcinoma patients and 70 Han lung adenocarcinoma patients, for EGFR mutations in exons 18, 19, 20, and 21 by using the amplification refractory mutation system (ARMS PCR method. The mutation differences between Uighur and Han lung adenocarcinoma were compared by using the chi-square test method. Results EGFR mutations were detected in 43 (31.2% of the 138 lung adenocarcinoma patients. EGFR mutations were detected in 11 (16.2% of the 68 Uighur lung adenocarcinoma patients and in 32 (45.7% of the 70 Han lung adenocarcinoma patients. Significant differences were observed in the EGFR mutations between Uighur lung adenocarcinoma patients and Han lung adenocarcinoma patients (P<0.001. Conclusion Our results indicate that the EGFR mutation in Uighur lung adenocarcinoma patients (16.2% is significantly lower than that in Han lung adenocarcinoma patients (45.7%.


    Arockiasamy Babiya Infant


    Full Text Available BACKGROUND Primary adenocarcinoma of cervix constitutes 10-15% of all cases of carcinoma of cervix, which is the second most common carcinoma next to squamous cell carcinoma. Endocervical adenocarcinoma have a considerable morphological overlap with endometrial adenocarcinoma though they differ in their aetiologies, behaviour, and treatments. This makes their diagnosis very difficult particularly in biopsy or curetting specimens or when a fractional dilation and curettage specimens show adenocarcinoma in both components of it. This study was done in the aim to suggest the possible origin of the tumour with the help of immunohistochemistry. AIMS AND OBJECTIVES To identify the incidence, distribution, clinicopathological, histomorphological features of endocervical adenocarcinomas and to determine the immunohistochemical expression of CEA, Vimentin, ER and PR in endometrioid type of adenocarcinoma detected in endocervical biopsies, fractional dilation and curettage specimens (Both the components showing similar morphology, and in hysterectomy specimens to suggest the site of origin of tumour. MATERIALS AND METHODS It is a retrospective descriptive study of cervical adenocarcinomas conducted in the Institute of Obstetrics and Gynaecology, Madras Medical College, Chennai for a period of 4 years during the period between 2009 November to 2013 October. The statistical analysis was performed using statistical package for social science software version 11.5 the clinicopathological profile of the tumour were calculated using Student t-test and chi-square test. OBSERVATION AND RESULTS Among the total 13499 cases received during the study period, 2489 were cervical malignancies comprising 148 adenocarcinoma. It includes 101 mucinous (Endocervical type, 44 endometrioid type, 2 serous type, and 1 clear cell type. Among the 30 cases of endometrioid type, 16 cases showed definite immunophenotype of cervical origin, 9 cases of endometrial origin and in the

  13. Multidetector computed tomography in the preoperative staging of gastric adenocarcinoma

    Barros, Ricardo Hoelz de Oliveira; Penachim, Thiago Jose; Martins, Daniel Lahan; Andreollo, Nelson Adami; Caserta, Nelson Marcio Gomes, E-mail: [Universidade Estadual de Campinas (UNICAMP), Campinas, SP (Brazil)


    Objective: To evaluate the role of multidetector computed tomography in the preoperative investigation of tumor invasion depth and lymph node and metastatic involvement according to the TNM classification, in patients with gastric adenocarcinoma. Materials and Methods: Fifty-four patients with biopsy-confirmed gastric cancer underwent preoperative staging with 64-channel multidetector computed tomography. Two independent radiologists analyzed the images and classified the findings. Sensitivity, specificity, accuracy and overall accuracy were calculated for each observer. The interobserver agreement was also evaluated. Results: The accuracy in the classification of categories T ranged from 74% to 96% for observer 1 and from 80% to 92% for observer 2. The overall accuracy was 70% for both observers. The weighted kappa index was 0.75, consistent with a significant interobserver agreement. The accuracy in the classification of lymph node involvement (category N) ranged from 55% to 79% for observer 1 and from 73% to 82% for observer 2. The evaluation of metastatic involvement showed an overall accuracy of 89.6% for both observers. Conclusion: 64-channel multidetector computed tomography demonstrated clinically relevant accuracy in the preoperative staging of gastric adenocarcinoma as regards invasion depth (T category) and metastatic involvement (M category). (author)

  14. Identifying Patient-Specific Epstein-Barr Nuclear Antigen-1 Genetic Variation and Potential Autoreactive Targets Relevant to Multiple Sclerosis Pathogenesis.

    Monika Tschochner

    Full Text Available Epstein-Barr virus (EBV infection represents a major environmental risk factor for multiple sclerosis (MS, with evidence of selective expansion of Epstein-Barr Nuclear Antigen-1 (EBNA1-specific CD4+ T cells that cross-recognize MS-associated myelin antigens in MS patients. HLA-DRB1*15-restricted antigen presentation also appears to determine susceptibility given its role as a dominant risk allele. In this study, we have utilised standard and next-generation sequencing techniques to investigate EBNA-1 sequence variation and its relationship to HLA-DR15 binding affinity, as well as examining potential cross-reactive immune targets within the central nervous system proteome.Sanger sequencing was performed on DNA isolated from peripheral blood samples from 73 Western Australian MS cases, without requirement for primary culture, with additional FLX 454 Roche sequencing in 23 samples to identify low-frequency variants. Patient-derived viral sequences were used to predict HLA-DRB1*1501 epitopes (NetMHCII, NetMHCIIpan and candidates were evaluated for cross recognition with human brain proteins.EBNA-1 sequence variation was limited, with no evidence of multiple viral strains and only low levels of variation identified by FLX technology (8.3% nucleotide positions at a 1% cut-off. In silico epitope mapping revealed two known HLA-DRB1*1501-restricted epitopes ('AEG': aa 481-496 and 'MVF': aa 562-577, and two putative epitopes between positions 502-543. We identified potential cross-reactive targets involving a number of major myelin antigens including experimentally confirmed HLA-DRB1*15-restricted epitopes as well as novel candidate antigens within myelin and paranodal assembly proteins that may be relevant to MS pathogenesis.This study demonstrates the feasibility of obtaining autologous EBNA-1 sequences directly from buffy coat samples, and confirms divergence of these sequences from standard laboratory strains. This approach has identified a number of

  15. A novel human ghrelin variant (In1-ghrelin and ghrelin-O-acyltransferase are overexpressed in breast cancer: potential pathophysiological relevance.

    Manuel D Gahete

    Full Text Available The human ghrelin gene, which encodes the ghrelin and obestatin peptides, contains 5 exons (Ex, with Ex1-Ex4 encoding a 117 amino-acid (aa preproprotein that is known to be processed to yield a 28-aa (ghrelin and/or a 23-aa (obestatin mature peptides, which possess biological activities in multiple tissues. However, the ghrelin gene also encodes additional peptides through alternative splicing or post-translational modifications. Indeed, we previously identified a spliced mRNA ghrelin variant in mouse (In2-ghrelin-variant, which is regulated in a tissue-dependent manner by metabolic status and may thus be of biological relevance. Here, we have characterized a new human ghrelin variant that contains Ex0-1, intron (In 1, and Ex2 and lacks Ex3-4. This human In1-ghrelin variant would encode a new prepropeptide that conserves the first 12aa of native-ghrelin (including the Ser3-potential octanoylation site but has a different C-terminal tail. Expression of In1-variant was detected in 22 human tissues and its levels were positively correlated with those of ghrelin-O-acyltransferase (GOAT; p = 0.0001 but not with native-ghrelin expression, suggesting that In1-ghrelin could be a primary substrate for GOAT in human tissues. Interestingly, levels of In1-ghrelin variant expression in breast cancer samples were 8-times higher than those of normal mammary tissue, and showed a strong correlation in breast tumors with GOAT (p = 0.0001, ghrelin receptor-type 1b (GHSR1b; p = 0.049 and cyclin-D3 (a cell-cycle inducer/proliferation marker; p = 0.009, but not with native-ghrelin or GHSR1a expression. Interestingly, In1-ghrelin variant overexpression increased basal proliferation of MDA-MB-231 breast cancer cells. Taken together, our results provide evidence that In1-ghrelin is a novel element of the ghrelin family with a potential pathophysiological role in breast cancer.

  16. Herceptin responsive lung adenocarcinoma in the setting of bilateral synchronous lung primaries and breast carcinoma

    Gerard J Fitzmaurice


    Full Text Available The incidence of human epidermal growth factor receptor 2 (Her-2 mutations in lung adenocarcinoma is approximately 3%; however, its significance in the management of these lung cancers remains under investigation. We describe an incidental but unique opportunity to evaluate the response to treatment with herceptin in a patient with bilateral synchronous lung primaries in conjunction with breast carcinoma. Interval imaging following surgical resection of the squamous cell carcinoma while on herceptin treatment delineated the radiological regression of the Her-2 positive lung adenocarcinoma. We feel that this case highlights the potential role for herceptin treatment in Her-2 positive lung adenocarcinomas and demonstrates the importance of screening for these mutations.

  17. Synchronous Malignant Peripheral Nerve Sheath Tumor and Adenocarcinoma of the Prostate: Case Report and Literature Review

    Nikolaos Ferakis


    Full Text Available Malignant Peripheral Nerve Sheath Tumors (MPNSTs of the prostate are extremely rare. A very unusual case of simultaneous adenocarcinoma and MPNST of the prostate is reported. A 60-year-old Caucasian male presented for annual urologic examination. Digital rectal examination revealed a painless, toughish, and asymmetrically enlarged prostate. Serum prostate-specific antigen was 1 ng/mL. Radiologic examinations demonstrated a large mass, which was arising from the left peripheral lobe of the prostate. The patient underwent transrectal ultrasound-guided biopsy of the prostate which revealed a smooth muscle tumor of uncertain malignant potential. Radical retropubic prostatectomy with en bloc removal of the mass and the seminal vesicles was performed and histology demonstrated low-grade MPNST and adenocarcinoma of the prostate. To the best of our knowledge, this is the first report of simultaneous prostatic adenocarcinoma and MPNST in the English literature.

  18. Synchronous Malignant Peripheral Nerve Sheath Tumor and Adenocarcinoma of the Prostate: Case Report and Literature Review

    Bouropoulos, Konstantinos; Farmakis, Antonios


    Malignant Peripheral Nerve Sheath Tumors (MPNSTs) of the prostate are extremely rare. A very unusual case of simultaneous adenocarcinoma and MPNST of the prostate is reported. A 60-year-old Caucasian male presented for annual urologic examination. Digital rectal examination revealed a painless, toughish, and asymmetrically enlarged prostate. Serum prostate-specific antigen was 1 ng/mL. Radiologic examinations demonstrated a large mass, which was arising from the left peripheral lobe of the prostate. The patient underwent transrectal ultrasound-guided biopsy of the prostate which revealed a smooth muscle tumor of uncertain malignant potential. Radical retropubic prostatectomy with en bloc removal of the mass and the seminal vesicles was performed and histology demonstrated low-grade MPNST and adenocarcinoma of the prostate. To the best of our knowledge, this is the first report of simultaneous prostatic adenocarcinoma and MPNST in the English literature. PMID:27872787

  19. Adenocarcinoma of Meckel's cave: case report.

    Tacconi, L; Arulampalam, T; Johnston, F; Symon, L


    A rare localization of adenocarcinoma in Meckel's cave is reported in a 58-year-old woman, who had a 5-month history of pain and altered sensation in the second division of the left trigeminal nerve. Removal of the lesion was achieved by a subtemporal route. Histology showed this to be an adenocarcinoma. The patient underwent investigations for a primary tumor; the investigations were all negative, and the patient was subsequently treated with a course of radiotherapy. At 4-month follow-up, there was no evidence of recurrence, and she remains symptomatically well. The various mechanisms of secondary localization are discussed.

  20. Spinal cord compression due to ethmoid adenocarcinoma.

    Johns, D R; Sweriduk, S T


    Adenocarcinoma of the ethmoid sinus is a rare tumor which has been epidemiologically linked to woodworking in the furniture industry. It has a low propensity to metastasize and has not been previously reported to cause spinal cord compression. A symptomatic epidural spinal cord compression was confirmed on magnetic resonance imaging (MRI) scan in a former furniture worker with widely disseminated metastases. The clinical features of ethmoid sinus adenocarcinoma and neoplastic spinal cord compression, and the comparative value of MRI scanning in the neuroradiologic diagnosis of spinal cord compression are reviewed.

  1. Generalized Lymphadenopathy: Unusual Presentation of Prostate Adenocarcinoma

    Bulent Cetin


    Full Text Available Generalized lymphadenopathy is a rare manifestation of metastatic prostate cancer. Here, we report the case of a 59-year-old male patient with supraclavicular, mediastinal, hilar, and retroperitoneal and inguinal lymphadenopathy, which suggested the diagnosis of lymphoma. There were no urinary symptoms. A biopsy of the inguinal lymph node was compatible with adenocarcinoma, whose prostatic origin was shown by immunohistochemical staining with PSA. The origin of the primary tumor was confirmed by directed prostate biopsy. We emphasize that a suspicion of prostate cancer in men with adenocarcinoma of undetermined origin is important for an adequate diagnostic and therapeutic approach.

  2. Skin Metastasis from an Occult Esophageal Adenocarcinoma

    F Fereidooni


    Full Text Available Metastases to the skin from carcinoma arising in other organs are uncommon, yet they may be the first presentation of neoplastic disease. They usually originate from primary tumours in the breast, lung or colon. Skin metastases from esophageal adenocarcinoma are extremely rare. A unique case of an otherwise healthy patient who presented with a small, painless, mobile, clinically localized facial skin nodule is reported. A biopsy revealed metastatic adenocarcinoma, and subsequent investigations detected the primary tumour in the esophagus, despite no symptoms.


    Praffulla Chandra


    Full Text Available BACKGROUND Primary carcinoma of vagina is a rare entity in Gynaecological oncology. A tumour should be considered as a primary vaginal carcinoma when cervix is uninvolved. Here we are reporting a case of primary vaginal adenocarcinoma with a rare uterine malformation, right renal agenesis and enlarged left kidney. This case was confirmed by meticulous physical examination, histopathology and relevant radiological investigations which excluded the possibility of carcinoma cervix, endometrium and ovary. This patient was treated solely by chemotherapy

  4. Molecular mechanisms of bortezomib resistant adenocarcinoma cells.

    Erika Suzuki

    Full Text Available Bortezomib (Velcade™ is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM. Despite its demonstrated clinical success, some patients are deprived of treatment due to primary refractoriness or development of resistance during therapy. To investigate the role of the duration of proteasome inhibition in the anti-tumor response of bortezomib, we established clonal isolates of HT-29 adenocarcinoma cells adapted to continuous exposure of bortezomib. These cells were ~30-fold resistant to bortezomib. Two novel and distinct mutations in the β5 subunit, Cys63Phe, located distal to the binding site in a helix critical for drug binding, and Arg24Cys, found in the propeptide region were found in all resistant clones. The latter mutation is a natural variant found to be elevated in frequency in patients with MM. Proteasome activity and levels of both the constitutive and immunoproteasome were increased in resistant cells, which correlated to an increase in subunit gene expression. These changes correlated with a more rapid recovery of proteasome activity following brief exposure to bortezomib. Increased recovery rate was not due to increased proteasome turnover as similar findings were seen in cells co-treated with cycloheximide. When we exposed resistant cells to the irreversible proteasome inhibitor carfilzomib we noted a slower rate of recovery of proteasome activity as compared to bortezomib in both parental and resistant cells. Importantly, carfilzomib maintained its cytotoxic potential in the bortezomib resistant cell lines. Therefore, resistance to bortezomib, can be overcome with irreversible inhibitors, suggesting prolonged proteasome inhibition induces a more potent anti-tumor response.

  5. Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis?

    Rensing, K.L.; Houttuijn Bloemendaal, F.M.; Weijers, E.M.; Richel, D.J.; Büller, H.R.; Koolwijk, P.; van der Loos, C.M.; Twickler, T.B.; von der Thüsen, J.H.


    Negative effects on the progression of adenocarcinomas by hyperinsulinaemia and the insulin analogue glargine (A21Gly,B31Arg,B32Arg human insulin) have recently been suggested. Most actions of this insulin analogue have hitherto been explained by direct stimulation of growth potential of neoplastic

  6. Prognostic significance of erythropoietin in pancreatic adenocarcinoma.

    Thilo Welsch

    Full Text Available BACKGROUND: Erythropoietin (Epo administration has been reported to have tumor-promoting effects in anemic cancer patients. We investigated the prognostic impact of endogenous Epo in patients with pancreatic ductal adenocarcinoma (PDAC. METHODOLOGY: The clinico-pathological relevance of hemoglobin (Hb, n = 150, serum Epo (sEpo, n = 87 and tissue expression of Epo/Epo receptor (EpoR, n = 104 was analyzed in patients with PDAC. Epo/EpoR expression, signaling, growth, invasion and chemoresistance were studied in Epo-exposed PDAC cell lines. RESULTS: Compared to donors, median preoperative Hb levels were reduced by 15% in both chronic pancreatitis (CP, p<0.05 and PDAC (p<0.001, reaching anemic grade in one third of patients. While inversely correlating to Hb (r = -0.46, 95% of sEPO values lay within the normal range. The individual levels of compensation were adequate in CP (observed to predicted ratio, O/P = 0.99 but not in PDAC (O/P = 0.85. Strikingly, lower sEPO values yielding inadequate Epo responses were prominent in non-metastatic M0-patients, whereas these parameters were restored in metastatic M1-group (8 vs. 13 mU/mL; O/P = 0.82 vs. 0.96; p<0.01--although Hb levels and the prevalence of anemia were comparable. Higher sEpo values (upper quartile ≥ 16 mU/ml were not significantly different in M0 (20% and M1 (30% groups, but were an independent prognostic factor for shorter survival (HR 2.20, 10 vs. 17 months, p<0.05. The pattern of Epo expression in pancreas and liver suggested ectopic release of Epo by capillaries/vasa vasorum and hepatocytes, regulated by but not emanating from tumor cells. Epo could initiate PI3K/Akt signaling via EpoR in PDAC cells but failed to alter their functions, probably due to co-expression of the soluble EpoR isoform, known to antagonize Epo. CONCLUSION/SIGNIFICANCE: Higher sEPO levels counteract anemia but worsen outcome in PDAC patients. Further trials are required to clarify how overcoming a sEPO threshold

  7. The influence of anthracosis and p16ink4a gene abberant methylation to the oncogenesis and progression of small pulmonary adenocarcinoma

    Daye WANG


    Full Text Available Background and objective Anthracosis is black dust matter deposition in the pulmonary parenchyma, which can cause bronchial deformity and destruction. Previously reported, anthracosis is closely correlated to the oncogenesis and progression of small pulmonary adenocarcinoma and p16ink4a gene aberrant methylation was closely associated with lung carcinogenesis. In this study, we want to characterize the influence of anthracosis and p16ink4a gene aberrant methylation on small adenocarcinoma. Methods DNA was bisulfite modified and then Methylation Specific PCR was used to detect p16ink4a gene aberrant methylation, and black dust matter was extracted from lung tissues, the absolute absorbance (A detected by densitometry was defined as anthracotic index (AI. The histopathologic diagnosis was according to Noguchi's classification for small pulmonary adenocarcinoma. Results For heavy smokers, the mean AI was significantly higher than that of nonsmokers (P=0.005 and the frequency of p16ink4a gene aberrant methylation was also significantly higher than that of nonsmokers (P=0.023. The frequency of p16ink4a gene aberrant methylation of early stage small adenocarcinoma was lower than that of advanced and poor differentiated small adenocarcinoma, otherwise p16ink4a protein expression of early stage small adenocarcinoma was significantly higher than that of poor differentiated small adenocarcinoma (P=0.032. Conclusion AI and p16ink4a gene aberrant methylation detection could be used as a combined potential biomarker of small adenocarcinoma.  

  8. Pancreatic ductal adenocarcinoma screening: New perspectives

    Raffaele Pezzilli; Dario Fabbri; Andrea Imbrogno


    Pancreatic ductal adenocarcinoma accounts for more than 90% of all pancreatic cancers and its incidence has increased significantly worldwide.Patients with pancreatic ductal adenocarcinoma have a poor outcome and more than 95% of the people affected die from the disease within 12 mo after diagnosis.Surgery is the first-line treatment in the case of resectable neoplasm,but only 20% of patients are candidates for this approach.One of the reasons there are few candidates for surgery is that,during the early phases of the disease,the symptoms are poor or non-specific.Early diagnosis is of crucial importance to improve patient outcome; therefore,we are looking for a good screening test.The screening test must identify the disease in an early stage in order to be effective; having said this,a need exists to introduce the concept of "early" ductal adenocarcinoma.It has been reported that at least five additional years after the occurrence of the initiating mutation are required for the acquisition of metastatic ability of pancreatic adenocarcinoma and patients die an average of two years thereafter.We have reviewed the most recent literature in order to evaluate the present and future perspectives of screening programs of this deadly disease.

  9. Epidemiology and risk factors for oesophageal adenocarcinoma.

    Lepage, Côme; Drouillard, Antoine; Jouve, Jean-Louis; Faivre, Jean


    Oesophageal adenocarcinoma will soon cease to be a rare form of cancer for people born after 1940. In many Western countries, its incidence has increased more rapidly than other digestive cancers. Incidence started increasing in the Seventies in England and USA, 15 years later in Western Europe and Australia. The cumulative risk between the ages of 15 and 74 is particularly striking in the UK, with a tenfold increase in men and fivefold increase in women in little more than a single generation. Prognosis is poor with a 5-year relative survival rate of less than 10%. The main known risk factors are gastro-oesophageal reflux, obesity (predominantly mediated by intra-abdominal adipose tissues) and smoking. Barrett's oesophagus is a precancerous lesion, however, the risk of degeneration has been overestimated. In population-based studies the annual risk of adenocarcinoma varied between 0.12% and 0.14% and its incidence between 1.2 and 1.4 per 1000 person-years. Only 5% of subjects with Barrett's oesophagus die of oesophageal adenocarcinoma. On the basis of recent epidemiological data, new surveillance strategies should be developed. The purpose of this review is to focus on the epidemiology and risk factors of oesophageal adenocarcinoma.

  10. [P53 protein in adenocarcinoma of the large intestine].

    Paluszkiewicz, P; Pawłowska-Wakowicz, B; Cybulski, M; Berbeć, H


    P53 gen mutations play significant role in neoplastic transformation of colorectal mucosa. We investigated p53 immunostaining in 80 cases of spontaneous human colorectal adenocarcinomas (with monoclonal DO7 antibody and LSAB+ kit). We found positive, nuclear p53 immunostaining in 64% of nonmucinous adenocarcinoma tissues and in 19% of mucinous adenocarcinomas tissues. P53 protein deposits were most often found in colorectal adenocarcinomas localised in rectum (66.67%) and in advanced (Dukes C, D) colorectal adenocarcinomas (59.38%) as well. There was no statistical significance between the p53 positive immunostaining and the histological differentiation of the colorectal adenocarcinomas. The overall survival of patients with tumours positive for p53 protein was significantly shorter than that of patients with colorectal cancers negative for p53 protein. We conclude that p53 immunohistochemical analysis may be treated as a supplementary prognostic marker for patients with colorectal adenocarcinoma, especially it may be useful for adjuvant therapy selection.

  11. Metastatic Pulmonary Adenocarcinoma 6 Years After Curative Resection for Ampullary Adenocarcinoma. Metastatic Disease from Initial Primary or Metachronous Tumour?

    Alexandros Giakoustidis


    Full Text Available Context With patients surviving longer after pancreatic resection, the challenges now is the management of the unresolved longerterm issues. Case report A 53-year-old woman with painless obstructive jaundice, underwent a pylorous preserving pancreaticoduodenectomy for a pT3N0M0 ampullary adenocarcinoma in 2001 (patchy chronic pancreatitis with mucinous metaplasia of background pancreatic duct epithelium and acinar atrophy were noted. Despite adjuvant chemotherapy, at month 54 she required a pulmonary wedge resection for metastatic adenocarcinoma, followed by a pulmonary relapse at 76 months when she underwent 6 neoadjuvant cycles of gemcitabine/capecitabine and a left pneumonectomy. Finally 7 years after the initial Whipple’s, a single 18F fluorodeoxyglucose (FDG avid pancreatic tail lesion led to completion pancreatectomy for a well-differentiated ductal adenocarcinoma with clear resection margins albeit peripancreatic adipose tissue infiltration. On review all resected tumour cells had identical immunophenotype (CK7+/CK20-/MUC1+/MUC2- as that of the primary. She is currently asymptomatic on follow-up. Conclusions These findings suggest that in selected cases even in the presence of pulmonary metastasis, repeat resections could result in long-term survival of patients with metachronous ampullary cancer. Second, even ampullary tumours maybe should be regarded as index tumors in the presence of ductal precursor lesions in the resection specimen. Three distant metastases, particularly if long after the initial tumour, should instigate a search for metachronous tumour, especially in the presence of field change in the initial specimen. Risk-adapted follow-up protocols with recognition of such factors could result in cost-effective surveillance and potentially improved outcomes.

  12. An Asian population-based survival analysis of patients with distal esophageal and gastric cardia adenocarcinomas

    ZHENG Bin; ZHENG Wei; ZHU Yong,; WU Wei-dong; CHEN Chun


    Background Gastroesophageal junction adenocarcinomas include adenocarcinomas of the distal esophagus(DE)and gastric cardia(GC).It is controversial whether these tumors are the same entity and whether they have the same survival rates.Patients with DE and GC adenocarcinomas have a similar survival rate in the US;however,data are lacking in Asian countries.Therefore,we conducted a retrospective study to understand the implications of the tumor location in the survival of Asian patients.Methods A total of 209 patients with pathologically confirmed DE and GC adenocarcinomas,from 2005 to 2007,were included in the study.We identified patients with adenocarcinomas of the DE(DE group,n=91)and GC(GC group)(n=118).We performed an unadjusted survival analysis using the Kaplan-Meier method,and used a Cox proportional hazards regression model to adjust for potential confounding covariates.Results We found no significant difference between the overall survival of the DE and GC groups.The 3-year survival rates were 44.8% and 53.0%,respectively,and the 5-year survival rates were 27.9% and 30.2%,respectively(P=0.162).We found no significant difference in early staging,advanced staging,different T staging,and different N staging,between the groups.Both advanced post-operative N staging and advanced AJCC staging had a significant adverse effect on survival.Conclusions Patients with DE and GC adenocarcinomas have similar survival rates in the Asian population.Both post-operative N staging and AJCC staging are prognostic factors.

  13. A cross sectional study of p504s, CD133, and Twist expression in the esophageal metaplasia dysplasia adenocarcinoma sequence.

    Ahmad, J; Arthur, K; Maxwell, P; Kennedy, A; Johnston, B T; Murray, L; McManus, D T


    The incidence of esophageal adenocarcinoma has increased dramatically over recent years and Barrett's esophagus is considered the most established risk factor for its development. Endoscopic surveillance of Barrett's esophagus is therefore recommended but hinges on histological interpretation of randomly taken biopsies which is poorly reproducible. The use of biomarkers presents an opportunity to improve our ability to risk-stratify these patients.We examined three biomarkers namely p504s, CD133, and Twist in the setting of Barrett's esophagus, low-grade dysplasia, and esophageal adenocarcinoma to evaluate differential expression between benign, dysplastic, and malignant Barrett's tissue in an exploratory cross-sectional study. Twenty-five cases each of Barrett's esophagus, low-grade dysplasia, and esophageal adenocarcinoma were included along-with 25 cases of esophagectomy resections for Barrett's adenocarcinoma. The biomarkers were immunostained on automated Ventana(®) immunostainer. The biopsies were assessed for biomarker expression by two independent observers. Granular cytoplasmic staining of p504s was observed in dysplastic Barrett's biopsies and esophageal adenocarcinoma but not in Barrett's esophagus. Apical and membranous CD133 expression was also observed in dysplastic Barrett's and esophageal adenocarcinoma. Nuclear Twist expression was seen predominantly in stromal cells. There was increased p504s expression in dysplastic Barrett's esophagus and esophageal adenocarcinoma compared with controls. CD133 expression was detected for the first time in esophageal adenocarcinoma and dysplastic Barrett's esophagus. Twist expression was not convincing enough to be labeled as Barrett's biomarker. p504s and CD133 have the potential to differentiate benign from malignant Barrett's tissue in this exploratory study. Their validity should be established in prospective longitudinal studies.

  14. MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma.

    Mathieu Salaün

    Full Text Available Several matrix metalloproteinases (MMPs are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging.To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma.K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors.In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27, but in none of the non-invasive (0/4 (p=0.001.MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer.

  15. Follistatin is a novel biomarker for lung adenocarcinoma in humans.

    Fangfang Chen

    Full Text Available Follistatin (FST, a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear.The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80, which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40 using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis.These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma.

  16. Adenocarcinoma of the Rectum with Cutaneous Metastases

    Nohad Hanbala


    Full Text Available Cutaneous metastases of rectal carcinoma is a rare event. It occurs in fewer than 4% of all patients with rectal cancer. When present, it typically signifies a disseminated disease with a poor prognosis. Early detection and proper diagnosis of metastatic rectal cancer can significantly alter treatment and prognosis. We report a 70-year-oldmale who underwent rectal resection with permanent colostomy for rectal adenocarcinoma since seven years. The patient recently developed multiple skin nodules, mainly in his face, scalp, and upper trunk, associated with itching. Fine needle aspiration cytology from a face nodule was done which revealed metastatic adenocarcinoma associated with severe inflammation. Cutaneous metastasis of rectaladenocarcinoma is an unusual event that presents mainly in the form of skin nodules and could be the first sign of metastasis. Early diagnosis of cutaneous metastasis in these patients is important because it can alter treatment and prognosis.

  17. Bone and brain metastases from ampullary adenocarcinoma

    Ioannis A Voutsadakis; Stergios Doumas; Konstantinos Tsapakidis; Maria Papagianni; Christos N Papandreou


    Ampullary carcinoma is the second most common cancer of the peri-ampullary area after pancreatic carcinoma and metastasizes mostly intra-abdominally and to the liver. Extra-abdominal metastases are less frequent. In this report we describe the case of a patient with resected adenocarcinoma of the ampulla of Vater who developed skeletal metastases in the lower extremity and brain metastases. We briefly discuss aspects of this comparatively rare gastrointestinal malignancy.

  18. Appendiceal Adenocarcinoma Presenting as a Rectal Polyp

    Erin Fitzgerald


    Full Text Available Appendiceal adenocarcinoma typically presents as an incidentally noted appendiceal mass, or with symptoms of right lower quadrant pain that can mimic appendicitis, but local involvement of adjacent organs is uncommon, particularly as the presenting sign. We report on a case of a primary appendiceal cancer initially diagnosed as a rectal polyp based on its appearance in the rectal lumen. The management of the patient was in keeping with standard practice for a rectal polyp, and the diagnosis of appendiceal adenocarcinoma was made intraoperatively. The operative strategy had to be adjusted due to this unexpected finding. Although there are published cases of appendiceal adenocarcinoma inducing intussusception and thus mimicking a cecal polyp, there are no reports in the literature describing invasion of the appendix through the rectal wall and thus mimicking a rectal polyp. The patient is a 75-year-old female who presented with spontaneous hematochezia and, on colonoscopy, was noted to have a rectal polyp that appeared to be located within a diverticulum. When endoscopic mucosal resection was not successful, she was referred to colorectal surgery for a low anterior resection. Preoperative imaging was notable for an enlarged appendix adjacent to the rectum. Intraoperatively, the appendix was found to be densely adherent to the right lateral rectal wall. An en bloc resection of the distal sigmoid colon, proximal rectum and appendix was performed, with pathology demonstrating appendiceal adenocarcinoma that invaded through the rectal wall. The prognosis in this type of malignancy weighs heavily on whether or not perforation and spread throughout the peritoneal cavity have occurred. In this unusual presentation, an en bloc resection is required for a complete resection and to minimize the risk of peritoneal spread. Unusual appearing polyps do not always originate from the bowel wall. Abnormal radiographic findings adjacent to an area of

  19. Treatment of urachal adenocarcinoma-case report

    Mekić-Abazović Alma


    Full Text Available In this case, we have presented a 55-year old patient with dysuria and bloody urine. He was hospitalized at the Urology Department of County Zenica Hospital due to obstructive uropathy. Diagnostics showed the cause is a large bleeding mass in prostatic part of urethra. After cystectomy, immunohistochemistry revealed urachal adenocarcinoma, rare type of urogenital carcinomas, presented only in 5% of all cancer types. He was treated with dual modality, chemotherapy and radiotherapy

  20. Complete response and prolonged disease-free survival in a patient with recurrent duodenal adenocarcinoma treated with bevacizumab plus FOLFOX6.

    Nagaraj, Gayathri; Zarbalian, Yousef; Flora, Karin; Tan, Benjamin R


    Small bowel adenocarcinoma is an uncommon gastrointestinal malignancy with limited data on effective chemotherapy in the adjuvant setting, as well as for advanced disease. We present a case report of a patient with recurrent duodenal adenocarcinoma after resection and adjuvant chemotherapy who experienced a complete response to bevacizumab with oxaliplatin and 5FU (FOLFOX) followed by bevacizumab/capecitabine maintenance therapy for 2 years. The patient continues to be disease-free 8 years after his recurrence. This case highlights the potential of vascular endothelial growth factor (VEGF) inhibitors to enhance chemotherapeutic regimens for advanced small bowel adenocarcinoma.

  1. Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis.

    Reid, Brian J; Li, Xiaohong; Galipeau, Patricia C; Vaughan, Thomas L


    The public health importance of Barrett's oesophagus lies in its association with oesophageal adenocarcinoma. The incidence of oesophageal adenocarcinoma has risen at an alarming rate over the past four decades in many regions of the Western world, and there are indications that the incidence of this disease is on the rise in Asian populations in which it has been rare. Much has been learned of host and environmental risk factors that affect the incidence of oesophageal adenocarcinoma, and data indicate that patients with Barrett's oesophagus rarely develop oesophageal adenocarcinoma. Given that 95% of oesophageal adenocarcinomas arise in individuals without a prior diagnosis of Barrett's oesophagus, what strategies can be used to reduce late diagnosis of oesophageal adenocarcinoma?

  2. Small interference RNA targeting tissue factor inhibits human lung adenocarcinoma growth in vitro and in vivo

    Wang Jianing


    Full Text Available Abstract Background The human coagulation trigger tissue factor (TF is overexpressed in several types of cancer and involved in tumor growth, vascularization, and metastasis. To explore the role of TF in biological processes of lung adenocarcinoma, we used RNA interference (RNAi technology to silence TF in a lung adenocarcinoma cell line A549 with high-level expression of TF and evaluate its antitumor effects in vitro and in vivo. Methods The specific small interfering RNA (siRNA designed for targeting human TF was transfected into A549 cells. The expression of TF was detected by reverse transcription-PCR and Western blot. Cell proliferation was measured by MTT and clonogenic assays. Cell apoptosis was assessed by flow cytometry. The metastatic potential of A549 cells was determined by wound healing, the mobility and Matrigel invasion assays. Expressions of PI3K/Akt, Erk1/2, VEGF and MMP-2/-9 in transfected cells were detected by Western blot. In vivo, the effect of TF-siRNA on the growth of A549 lung adenocarcinoma xenografts in nude mice was investigated. Results TF -siRNA significantly reduced the expression of TF in the mRNA and protein levels. The down-regulation of TF in A549 cells resulted in the suppression of cell proliferation, invasion and metastasis and induced cell apoptosis in dose-dependent manner. Erk MAPK, PI3K/Akt pathways as well as VEGF and MMP-2/-9 expressions were inhibited in TF-siRNA transfected cells. Moreover, intratumoral injection of siRNA targeting TF suppressed the tumor growth of A549 cells in vivo model of lung adenocarcinoma. Conclusions Down-regulation of TF using siRNA could provide a potential approach for gene therapy against lung adenocarcinoma, and the antitumor effects may be associated with inhibition of Erk MAPK, PI3K/Akt pathways.

  3. Gastric choriocarcinoma admixed with an α-fetoprotein-producing adenocarcinoma and separated adenocarcinoma

    Bang Wool Eom; So-Youn Jung; Hongman Yoon; Myeong-Cherl Kook; Keun Won Ryu; Jun Ho Lee; Young-Woo Kim


    We report a case of gastric choriocarcinoma admixed with an α-fetoprotein (AFP)-producing adenocarcinoma .A 70-year-old man was hospitalized for gastric cancer that was detected during screening by esophagogastroduodenoscopy (EGD). Initial laboratory data showed the increased serum level of AFP and EGD revealed a 5-cm ulcerofungating mass in the greater curvature of the gastric antrum.The patient underwent radical subtotal gastrectomy with D2 lymph node dissection and Billroth Ⅱ gastrojejunostomy. Histopathological evaluation confirmed double primary gastric cancer: gastric choriocarcinoma admixed with an AFP-producing adenocarcinoma and separated adenocarcinoma. At 2 wk postoperatively, his human chorionic gonadotropin and AFP levels had reduced and six cycles of adjuvant chemotherapy were initiated. No recurrence or distant metastasis was observed at 4 years postoperatively.

  4. Small nuclear ribonucleoprotein associated polypeptide N accelerates cell proliferation in pancreatic adenocarcinoma.

    Ma, Jin; Zhang, Zhuo; Wang, Jiancheng


    The spliceosome, the large RNA‑protein molecular complex, is crucial for pre‑mRNA splicing. Several antitumor drugs have been found to tightly bind to the components of the spliceosome and mutations in the spliceosome have been reported in several types of cancer. However, the involvement of the spliceosome in pancreatic adenocarcinoma remains unclear. In the present study, small nuclear ribonucleoprotein associated polypeptide N (SNRPN), a key constituent of spliceosomes, was disrupted in BxPC‑3 pancreatic adenocarcinoma cells using lentivirus‑mediated RNA interference (RNAi). It was found that knockdown of SNRPN reduced the proliferation ability of BxPC‑3 cells, as determined by an MTT assay. Furthermore, cell colony formation was impaired in SNRPN depleted adenocarcinoma cells and cell cycle analysis showed that depletion of SNRPN led to S phase cell cycle arrest and apoptosis. These results suggest that SNRPN is a key player in pancreatic adenocarcinoma cell growth, and targeted loss of SNRPN may be a potential therapeutic method for pancreatic cancer.

  5. Life expectancy with perioperative chemotherapy and chemoradiotherapy for locally advanced gastric adenocarcinoma

    Sadighi S


    Full Text Available "nBackground: Although postoperative chemoradiotherapy should be considered for all patients at high risk for recurrence of adenocarcinoma of the stomach, curative surgery occurs in less than 50% of nonmetastatic gastric cancers. A regimen of docetaxel, cisplatin and infusional fluorouracil improves survival of patients with incurable locally-advanced gastric adenocarcinoma. So we assessed the perioperative regimen of docetaxel, cisplatin and infusions 5FU (TCF and postoperative chemoradiotherapy to improve outcomes in patients with potentially resectable gastric adenocarcinoma. "nMethods: Between March 2005 and March 2008, we 100 enrolled patients with stage II to IV (M0 adenocarcinoma of the stomach who had not been treated previously. Treatment consisted of three preoperative and one postoperative cycles of TCF followed by chemoradiotherapy. The primary end point was overall survival. The secondary end points were progression-free survival and toxicity of treatment. "nResults: A total of 100 patients participated, 83 of whom received neoadjuvant and 17 received adjuvant chemotherapy. Seventy-five patients underwent at least D0 gastrectomy. After chemotherapy, tumor stages were significantly lower than before beginning the protocol. Out of 100 patients, 44 had stage IV before chemotherapy versus 15 after the treatment. Three patients showed complete pathologic response. The median survival time was 25 months. "nConclusion: Docetaxel, cisplatin and 5FU combination chemotherapy is an active preoperative treatment in locally advanced gastric cancer. Perioperative chemoradio-therapy should be considered as an option to lengthen patient survival.

  6. Thioredoxin interacting protein and its association with clinical outcome in gastro-oesophageal adenocarcinoma

    Caroline M. Woolston


    Full Text Available The overall prognosis for operable gastro-oesophageal adenocarcinoma remains poor and therefore neoadjuvant chemotherapy has become the standard of care, in addition to radical surgery. Certain anticancer agents (e.g. anthracyclines and cisplatin generate damaging reactive oxygen species as by-products of their mechanism of action. Drug effectiveness can therefore depend upon the presence of cellular redox buffering systems that are often deregulated in cancer. The expression of the redox protein, thioredoxin interacting protein, was assessed in gastro-oesophageal adenocarcinomas. Thioredoxin interacting protein expression was assessed using conventional immunohistochemistry on a tissue microarray of 140 adenocarcinoma patients treated by primary surgery alone and 88 operable cases treated with neoadjuvant chemotherapy. In the primary surgery cases, high thioredoxin interacting protein expression associated with a lack of lymph node involvement (p=0.005, no perineural invasion (p=0.030 and well/moderate tumour differentiation (p=0.033. In the neoadjuvant tumours, high thioredoxin interacting protein expression was an independent marker for improved disease specific survival (p=0.002 especially in cases with anthracycline-based regimes (p=0.008. This study highlights the potential of thioredoxin interacting protein as a biomarker for response in neoadjuvant treated gastro-oesophageal adenocarcinoma and may represent a useful therapeutic target due to its association with tumour progression.

  7. Novel Drug Targets Based on Association between Inflammation and Pancreatic Ductal Adenocarcinoma

    Muhammad Wasif Saif


    Full Text Available Dear Sir We read with great interest the editorial published by Uomo et al. in the 2010 May issue of JOP. J Pancreas (Online titled: “Inflammation and Pancreatic Ductal Adenocarcinoma: A Potential Scenario for Novel Drug Targets” [1]. There is a growing amount of evidence that inflammation plays a contributory role in the pathogenesis of cancer, including pancreatic carcinogenesis. Inflammatory states are characterized by the formation of reactive oxygen species and the induction of cell cycling for tissue growth and repair [1, 2, 3]. The initiation, promotion and expansion of tumors may be influenced by numerous components that also function in the inflammatory response. Recognized risk factors for pancreatic cancer include cigarette smoking, chronic/hereditary pancreatitis, obesity and type II diabetes. Each risk factor is linked by the fact that the inflammatory state significantly drives its pathology. We agree with the authors that multiple links between inflammation and pancreatic adenocarcinoma has led to development of novel targeted therapy which is under evaluation both in vivo and in vitro studies to fight against pancreatic adenocarcinoma. Pancreatic cancer is one of the leading causes of cancer mortality in the United States. Current therapy for pancreatic cancer involves surgery, chemotherapy, and radiation therapy; however, the 5-year survival rate remains less than 5%. Therefore, developments of novel agents, in particular based on the pathogenesis of pancreatic adenocarcinoma are urgently indicated.

  8. Identification and characterization of SP cells in human lung adenocarcinoma SPC-A1 cells

    Yanliang ZHU


    Full Text Available Background and objective Recently, eloquent studies from some solid tumors have provided proofs that cancers originate from cancer stem cells (CSC. The discovery of CSC has changed our view of carcinogenesis and chemotherapy. The aim of this study is to identify and characterize the CSC population that drives and maintains lung adenocarcinoma growth and metastasis. Methods Side population (SP cell analysis combined with serum-free media (SFM were applied to established human lung adenocarcinoma cell lines. Properties of SP cells were evaluated by their proliferative index, colony-forming efficiency and tumorigenic potential. Results Characteristic SP cells could be detected by FACS in lung adenocarcinoma cell lines. And the proportion of SP cells is greatly increased after serum-free culture.SP cells have a greater proliferative index, a higher colony-forming efficiency and a greater ability to form tumor in vivo .Conclusion SP cells exist in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting.

  9. Src mutation induces acquired lapatinib resistance in ERBB2-amplified human gastroesophageal adenocarcinoma models.

    Yong Sang Hong

    Full Text Available ERBB2-directed therapy is now a routine component of therapy for ERBB2-amplified metastatic gastroesophageal adenocarcinomas. However, there is little knowledge of the mechanisms by which these tumors develop acquired resistance to ERBB2 inhibition. To investigate this question we sought to characterize cell line models of ERBB2-amplified gastroesophageal adenocarcinoma with acquired resistance to ERBB2 inhibition. We generated lapatinib-resistant (LR subclones from an initially lapatinib-sensitive ERBB2-amplified esophageal adenocarcinoma cell line, OE19. We subsequently performed genomic characterization and functional analyses of resistant subclones with acquired lapatinib resistance. We identified a novel, acquired SrcE527K mutation in a subset of LR OE19 subclones. Cells with this mutant allele harbour increased Src phosphorylation. Genetic and pharmacologic inhibition of Src resensitized these subclones to lapatinib. Biochemically, Src mutations could activate both the phosphatidylinositol 3-kinase and mitogen activated protein kinase pathways in the lapatinib-treated LR OE19 cells. Ectopic expression of SrcE527K mutation also was sufficient to induce lapatinib resistance in drug-naïve cells. These results indicate that pathologic activation of Src is a potential mechanism of acquired resistance to ERBB2 inhibition in ERBB2-amplified gastroesophageal cancer. Although Src mutation has not been described in primary tumor samples, we propose that the Src hyperactivation should be investigated in the settings of acquired resistance to ERBB2 inhibition in esophageal and gastric adenocarcinoma.

  10. Corn-derived carbohydrate inositol hexaphosphate inhibits Barrett's adenocarcinoma growth by pro-apoptotic mechanisms.

    McFadden, David W; Riggs, Dale R; Jackson, Barbara J; Cunningham, Cynthia


    Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate that is found in food sources high in fiber content. IP6 has been reported to have significant inhibitory effects against a variety of primary tumors. We hypothesized that IP6 would inhibit the cell growth rate of Barrett's adenocarcinoma in vitro. Two Barrett's-associated adenocarcinoma cell lines, SEG-1 and BIC-1, were treated with IP6 at 0.5, 1.0 and 5.0 mM concentrations. Cell viability was measured by MTT assay. Apoptosis and necrosis were evaluated by the Annexin V FITC assay. Reductions (PIP6 decreased late apoptosis and necrosis in BIC cells, whereas in SEG-1 cells, early apoptosis, late apoptosis and necrosis were all increased by IP6. IP6 decreases cellular growth by pro-apoptotic mechanisms. Our findings suggest that IP6 has the potential to become an effective adjunct for Barrett's adenocarcinoma. Further studies are needed to evaluate safety and clinical utility of this agent in patients with Barrett's adenocarcinoma.

  11. Thioredoxin interacting protein and its association with clinical outcome in gastro-oesophageal adenocarcinoma.

    Woolston, Caroline M; Madhusudan, Srinivasan; Soomro, Irshad N; Lobo, Dileep N; Reece-Smith, Alexander M; Parsons, Simon L; Martin, Stewart G


    The overall prognosis for operable gastro-oesophageal adenocarcinoma remains poor and therefore neoadjuvant chemotherapy has become the standard of care, in addition to radical surgery. Certain anticancer agents (e.g. anthracyclines and cisplatin) generate damaging reactive oxygen species as by-products of their mechanism of action. Drug effectiveness can therefore depend upon the presence of cellular redox buffering systems that are often deregulated in cancer. The expression of the redox protein, thioredoxin interacting protein, was assessed in gastro-oesophageal adenocarcinomas. Thioredoxin interacting protein expression was assessed using conventional immunohistochemistry on a tissue microarray of 140 adenocarcinoma patients treated by primary surgery alone and 88 operable cases treated with neoadjuvant chemotherapy. In the primary surgery cases, high thioredoxin interacting protein expression associated with a lack of lymph node involvement (p=0.005), no perineural invasion (p=0.030) and well/moderate tumour differentiation (p=0.033). In the neoadjuvant tumours, high thioredoxin interacting protein expression was an independent marker for improved disease specific survival (p=0.002) especially in cases with anthracycline-based regimes (p=0.008). This study highlights the potential of thioredoxin interacting protein as a biomarker for response in neoadjuvant treated gastro-oesophageal adenocarcinoma and may represent a useful therapeutic target due to its association with tumour progression.

  12. A novel aminothiazole KY-05009 with potential to inhibit Traf2- and Nck-interacting kinase (TNIK attenuates TGF-β1-mediated epithelial-to-mesenchymal transition in human lung adenocarcinoma A549 cells.

    Jiyeon Kim

    Full Text Available Transforming growth factor (TGF-β triggers the epithelial-to-mesenchymal transition (EMT of cancer cells via well-orchestrated crosstalk between Smad and non-Smad signaling pathways, including Wnt/β-catenin. Since EMT-induced motility and invasion play a critical role in cancer metastasis, EMT-related molecules are emerging as novel targets of anti-cancer therapies. Traf2- and Nck-interacting kinase (TNIK has recently been considered as a first-in-class anti-cancer target molecule to regulate Wnt signaling pathway, but pharmacologic inhibition of its EMT activity has not yet been studied. Here, using 5-(4-methylbenzamido-2-(phenylaminothiazole-4-carboxamide (KY-05009 with TNIK-inhibitory activity, its efficacy to inhibit EMT in cancer cells was validated. The molecular docking/binding study revealed the binding of KY-05009 in the hinge region of TNIK, and the inhibitory activity of KY-05009 against TNIK was confirmed by an ATP competition assay (Ki, 100 nM. In A549 cells, KY-05009 significantly and strongly inhibited the TGF-β-activated EMT through the attenuation of Smad and non-Smad signaling pathways, including the Wnt, NF-κB, FAK-Src-paxillin-related focal adhesion, and MAP kinases (ERK and JNK signaling pathways. Continuing efforts to identify and validate potential therapeutic targets associated with EMT, such as TNIK, provide new and improved therapies for treating and/or preventing EMT-based disorders, such as cancer metastasis and fibrosis.

  13. Association of visceral adiposity with oesophageal and junctional adenocarcinomas.

    Beddy, P


    BACKGROUND: Obesity is associated with an increased incidence of oesophageal and oesophagogastric junction adenocarcinoma, in particular Siewert types I and II. This study compared abdominal fat composition in patients with oesophageal\\/junctional adenocarcinoma with that in patients with oesophageal squamous cell carcinoma and gastric adenocarcinoma, and in controls. METHOD: In total, 194 patients (110 with oesophageal\\/junctional adenocarcinoma, 38 with gastric adenocarcinoma and 46 with oesophageal squamous cell carcinoma) and 90 matched control subjects were recruited. The abdominal fat area was assessed using computed tomography (CT), and the total fat area (TFA), visceral fat area (VFA) and subcutaneous fat area (SFA) were calculated. RESULTS: Patients with oesophageal\\/junctional adenocarcinoma had significantly higher TFA and VFA values compared with controls (both P < 0.001), patients with gastric adenocarcinoma (P = 0.013 and P = 0.006 respectively) and patients with oesophageal squamous cell carcinoma (both P < 0.001). For junctional tumours, the highest TFA and VFA values were seen in patients with Siewert type I tumours (respectively P = 0.041 and P = 0.033 versus type III; P = 0.332 and P = 0.152 versus type II). CONCLUSION: Patients with oesophageal\\/junctional adenocarcinoma, in particular oesophageal and Siewert type I junctional tumours, have greater CT-defined visceral adiposity than patients with gastric adenocarcinoma or oesophageal squamous cell carcinoma, or controls.

  14. Role of Radiotherapy in Aggressive Digital Papillary Adenocarcinoma.

    Feldmeyer, Laurence; Prieto, Victor G; Ivan, Doina; Nagarajan, Priyadharsini; Tetzlaff, Michael T; Curry, Jonathan L; Bell, Diana; Moon, Bryan S; Torres-Cabala, Carlos A; Aung, Phyu P


    Aggressive digital papillary adenocarcinoma (ADPA) is a rare and often misdiagnosed malignant tumor of the sweat glands, most commonly encountered on the extremities. Due to the relatively high metastatic potential of the tumor, aggressive surgical treatment, including amputation, is generally recommended. We present a case of a 36-year-old male with an over 10-year history of a skin lesion on the right hand in the web space between the index and the middle finger. Histologically, the lesion revealed a malignant epithelioid neoplasm with features consistent with ADPA. The lesion was treated with 5-weeks preoperative radiation (total 5000 cGy) followed by surgical resection. There was no evidence of residual disease confirmed by pathological study of re-excision specimen as well as imaging studies. This is, to the best of knowledge, the first report of complete regression of an ADPA after radiotherapy.

  15. Claudin-1, but not claudin-4, exhibits differential expression patterns between well- to moderately-differentiated and poorly-differentiated gastric adenocarcinoma



    Claudins are members of a large family of transmembrane proteins, which are essential in the formation of tight junctions and have previously been associated with the process of tumor progression. Studies have reported the aberrant expression of claudin-1 and claudin-4 in numerous types of cancer. The present study aimed to investigate the expression of claudin-1 and claudin-4 in gastric adenocarcinoma tissue. Surgically resected gastric adenocarcinoma tissue specimens were obtained from 94 patients. Protein expression levels of claudin-1 and claudin-4 were determined using immunohistochemical staining; the association between claudin-1 or claudin-4 expression and various clinicopathological parameters were then analyzed. In gastric adenocarcinoma specimens, the expression rates of claudin-1 and claudin-4 were 43.6 and 87.2%, respectively. Claudin-1 expression demonstrated a significant correlation with histological type (P<0.01) and was significantly higher in well- to moderately-differentiated gastric adenocarcinomas compared with poorly-differentiated tumors. However, no correlation was observed between claudin-4 expression in adenocarcinoma and clinicopathological parameters. In conclusion, downregulation of claudin-1 expression in poorly-differentiated gastric adenocarcinoma may be involved in the biological transformation of tumors. The present findings suggested that claudin-1 may be an important protein associated with histological type and therefore may have potential for use as a prognostic marker for gastric adenocarcinoma. Further studies are required to elucidate the precise mechanism of claudin expression and its involvement in tumor progression. PMID:26170982

  16. Texture analysis for survival prediction of pancreatic ductal adenocarcinoma patients with neoadjuvant chemotherapy

    Chakraborty, Jayasree; Langdon-Embry, Liana; Escalon, Joanna G.; Allen, Peter J.; Lowery, Maeve A.; O'Reilly, Eileen M.; Do, Richard K. G.; Simpson, Amber L.


    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. The five-year survival rate for all stages is approximately 6%, and approximately 2% when presenting with distant disease.1 Only 10-20% of all patients present with resectable disease, but recurrence rates are high with only 5 to 15% remaining free of disease at 5 years. At this time, we are unable to distinguish between resectable PDAC patients with occult metastatic disease from those with potentially curable disease. Early classification of these tumor types may eventually lead to changes in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant treatments. Texture analysis is an emerging methodology in oncologic imaging for quantitatively assessing tumor heterogeneity that could potentially aid in the stratification of these patients. The present study derives several texture-based features from CT images of PDAC patients, acquired prior to neoadjuvant chemotherapy, and analyzes their performance, individually as well as in combination, as prognostic markers. A fuzzy minimum redundancy maximum relevance method with leave-one-image-out technique is included to select discriminating features from the set of extracted features. With a naive Bayes classifier, the proposed method predicts the 5-year overall survival of PDAC patients prior to neoadjuvant therapy and achieves the best results in terms of the area under the receiver operating characteristic curve of 0:858 and accuracy of 83:0% with four-fold cross-validation techniques.

  17. File list: Pol.Lng.05.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Full Text Available Pol.Lng.05.AllAg.Lung_adenocarcinoma mm9 RNA polymerase Lung Lung adenocarcinoma ...

  18. File list: DNS.Lng.05.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Full Text Available DNS.Lng.05.AllAg.Lung_adenocarcinoma mm9 DNase-seq Lung Lung adenocarcinoma ...

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    Full Text Available Unc.Lng.20.AllAg.Lung_adenocarcinoma mm9 Unclassified Lung Lung adenocarcinoma http...:// ...

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    Full Text Available Unc.Lng.10.AllAg.Lung_adenocarcinoma mm9 Unclassified Lung Lung adenocarcinoma http...:// ...

  1. File list: Unc.Lng.50.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Full Text Available Unc.Lng.50.AllAg.Lung_adenocarcinoma mm9 Unclassified Lung Lung adenocarcinoma http...:// ...

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    Full Text Available DNS.Lng.50.AllAg.Lung_adenocarcinoma mm9 DNase-seq Lung Lung adenocarcinoma ...

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    Full Text Available Pol.Lng.50.AllAg.Lung_adenocarcinoma mm9 RNA polymerase Lung Lung adenocarcinoma ...

  4. File list: DNS.Lng.20.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Full Text Available DNS.Lng.20.AllAg.Lung_adenocarcinoma mm9 DNase-seq Lung Lung adenocarcinoma ...

  5. File list: Unc.Lng.05.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Full Text Available Unc.Lng.05.AllAg.Lung_adenocarcinoma mm9 Unclassified Lung Lung adenocarcinoma http...:// ...

  6. File list: DNS.Lng.10.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Full Text Available DNS.Lng.10.AllAg.Lung_adenocarcinoma mm9 DNase-seq Lung Lung adenocarcinoma ...

  7. File list: Pol.Lng.20.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Full Text Available Pol.Lng.20.AllAg.Lung_adenocarcinoma mm9 RNA polymerase Lung Lung adenocarcinoma ...

  8. File list: Pol.Lng.10.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Full Text Available Pol.Lng.10.AllAg.Lung_adenocarcinoma mm9 RNA polymerase Lung Lung adenocarcinoma ...

  9. Two Sides of the Same Coin: ERP and Wavelet Analyses of Visual Potentials Evoked and Induced by Task-Relevant Faces

    Lubbe, van der Rob H.J.; Szumska, Izabela; Fajkowska, Malgorzata


    New analysis techniques of the electroencephalogram (EEG) such as wavelet analysis open the possibility to address questions that may largely improve our understanding of the EEG and clarify its relation with related potentials (ERPs). Three issues were addressed. 1) To what extent can early ERP com

  10. Oregon Trust Agreement Planning Project : Potential Mitigations to the Impacts on Oregon Wildlife Resources Associated with Relevant Mainstem Columbia River and Willamette River Hydroelectric Projects.

    United States. Bonneville Power Administration.


    A coalition of the Oregon wildlife agencies and tribes (the Oregon Wildlife Mitigation Coalition) have forged a cooperative effort to promote wildlife mitigation from losses to Oregon wildlife resources associated with the four mainstream Columbia River and the eight Willamette River Basin hydroelectric projects. This coalition formed a Joint Advisory Committee, made up of technical representatives from all of the tribes and agencies, to develop this report. The goal was to create a list of potential mitigation opportunities by priority, and to attempt to determine the costs of mitigating the wildlife losses. The information and analysis was completed for all projects in Oregon, but was gathered separately for the Lower Columbia and Willamette Basin projects. The coalition developed a procedure to gather information on potential mitigation projects and opportunities. All tribes, agencies and interested parties were contacted in an attempt to evaluate all proposed or potential mitigation. A database was developed and minimum criteria were established for opportunities to be considered. These criteria included the location of the mitigation site within a defined area, as well as other criteria established by the Northwest Power Planning Council. Costs were established for general habitats within the mitigation area, based on estimates from certified appraisers. An analysis of the cost effectiveness of various types of mitigation projects was completed. Estimates of operation and maintenance costs were also developed. The report outlines strategies for gathering mitigation potentials, evaluating them, determining their costs, and attempting to move towards their implementation.

  11. Antioxidant enzymes and lipid peroxidation in endometrium of patients with polyps, myoma, hyperplasia and adenocarcinoma

    Pajović Snežana B


    Full Text Available Abstract Background Oxidative stress and impaired antioxidant system have been proposed as a potential factors involved in the pathophysiology of diverse disease states, including carcinogenesis. In this study, we explored the lipid peroxidation levels and antioxidant enzyme activities in women diagnosed with different forms of gynecological diseases in order to evaluate the antioxidant status in endometrium of such patients. Methods Endometrial tissues of gynecological patients with different diagnoses were collected and subjected to assays for superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and lipid hydroperoxides. Results Superoxide dismutase activity was significantly decreased (50% in average in hyperplastic and adenocarcinoma patients. Activities of both glutathione peroxidase and glutathione reductase were increased 60% and 100% on average, in hyperplastic patients, while in adenocarcinoma patients only glutathione reductase activity was elevated 100%. Catalase activity was significantly decreased in adenocarcinoma patients (47%. Lipid hydroperoxides level was negatively correlated to superoxide dismutase and catalase activities, and positively correlated to glutathione peroxidase and glutathione reductase activities. Conclusions This study provided the first comparison of antioxidant status and lipid peroxidation in endometrial tissues of patients with polyps, myoma, hyperplasia and adenocarcinoma. The results showed that patients with premalignant (hyperplastic and malignant (adenocarcinoma lesions had enhanced lipid peroxidation and altered uterine antioxidant enzyme activities than patients with benign uterine diseases, polyps and myoma, although the extent of disturbance varied with the diagnosis. Further investigation is needed to clarify the mechanisms responsible for the observed alterations and whether lipid hydroperoxide levels and antioxidant enzyme activities in uterus of gynecological patients

  12. Potential relevance of pre-operative quality of life questionnaires to identify candidates for surgical treatment of genital prolapse: a pilot study

    Chauvin Christian


    Full Text Available Abstract Background To evaluate prolapse-related symptoms, quality of life and sexuality of patients with validated questionnaires before and after surgery for genital prolapse and assess relevance of such an evaluation to select women for surgery. Methods From November 2009 to April 2010, 16 patients operated on for genital prolapse of grade greater than or equal to 2 (POP-Q classification were evaluated prospectively by three questionnaires of quality of life Pelvic Floor Distress Inventory (PFDI-20, Pelvic Floor Impact Questionnaire (PFIQ-7 and Pelvic Organ Prolaps/Urinary Incontinence Sexual Questionnaire (PISQ-12. Data were collected the day before surgery and 6 weeks postoperatively. Results Eleven patients had laparoscopic surgery and five vaginal surgery. There was a significant decrease in pelvic heaviness, vaginal discomfort and urinary symptoms after surgery. The score of symptoms of prolapse, the PFDI-20 score was 98.5 preoperatively and 31.8 postoperatively (p Conclusions This study suggests that surgery improves quality of life of patients with genital prolapse. Quality of life questionnaires could help select good candidates for surgery. Further studies are required to determine threshold to standardize indications of surgery.

  13. A systematic review of motivational interviewing in healthcare: the potential of motivational interviewing to address the lifestyle factors relevant to multimorbidity

    Kylie McKenzie


    Full Text Available Internationally, health systems face an increasing demand for services from people living with multimorbidity. Multimorbidity is often associated with high levels of treatment burden. Targeting lifestyle factors that impact across multiple conditions may promote quality of life and better health outcomes for people with multimorbidity. Motivational interviewing (MI has been studied as one approach to supporting lifestyle behaviour change. A systematic review was conducted to assess the effectiveness of MI in healthcare settings and to consider its relevance for multimorbidity. Twelve meta-analyses pertinent to multimorbidity lifestyle factors were identified. As an intervention, MI has been found to have a small-to-medium statistically significant effect across a wide variety of single diseases and for a range of behavioural outcomes. This review highlights the need for specific research into the application of MI to determine if the benefits of MI seen with single diseases are also present in the context of multimorbidity. Journal of Comorbidity 2015;5:162–174

  14. Gastric neo-adenocarcinoma arising in a gastric tube after Ivor Lewis oesophagectomy for oesophageal adenocarcinoma.

    Hanif, Faisal; Kerr, Joana; Going, James J; Fullarton, Grant


    A 69-year-old man, seven years post Ivor-Lewis oesophagectomy for oesophageal adenocarcinoma, was diagnosed to have a moderately differentiated 4 cm, malignant ulcer within the gastric tube remnant on an endoscopic biopsy. His original presentation was with a T1N0 oesophageal adenocarcinoma, histologically intestinal in type with inflammatory features. He presented with anaemia and melena due to a malignant ulcer in the mid body of his gastric tube on an endoscopy which was confirmed to be a gastric neo-adenocarcinoma on biopsy. He underwent right posterolateral thoracotomy and a wedge resection of the gastric tube including the tumour. Pathology confirmed a T3 N0 (0/7 lymph nodes) with clear margins moderately differentiated adenocarcinoma of intestinal phenotype with papillary features and was reported to be a histopathologically new tumour. Proposed surgical treatments in such patients are dependent on patient's fitness for major resection and may vary from Endoscopic Mucosal Resection to partial resection with preservation of right gastroepiploic vessels or total gastrectomy with intestinal interposition via a retromediastinal route. We suggest that regular endoscopic surveillance may be indicated in such post-oesophagectomy patients as the number of patients developing gastric tube cancers may increase with improve survival of those patients.

  15. Ectopic expression of RASSF2 and its prognostic role for gastric adenocarcinoma patients.

    Luo, Deng; Ye, Ting; Li, Tian-Qian; Tang, Peng; Min, Sha-Dong; Zhao, Gong-Fang; Huang, Hua; Chang, Jiang; Wang, Yan; Lv, Lin; Lu, Ming-Liang; Zheng, Meng-Yao


    RASSF2 has recently been identified as a potential tumor suppressor that serves as a Ras effector in various types of human cancers. However, there have been few reports detailing this in gastric cancer. Samples of gastric adenocarcinoma from 276 Chinese patients with follow-up were analyzed for RASSF2 protein expression by immunohistochemistry. RASSF2 was expressed in up to 31.2% (86/276) of this group of gastric carcinoma. The expression of RASSF2 was significantly lower in carcinomas than in normal mucosas (P50.9% reduction in 3-year survival compared to that of patients with RASSF2-positive expression. In late stages, the difference was also significant (χ(2)=6.246, P=0.019), with a 35.5% reduction in 3-year survival. It is suggested that RASSF2 plays an important role in the evolution of gastric adenocarcinoma and should be considered as a potential marker for its prognosis.

  16. Gemcitabine response in pancreatic adenocarcinoma cells is synergistically enhanced by dithiocarbamate derivatives.

    Dalla Pozza, Elisa; Donadelli, Massimo; Costanzo, Chiara; Zaniboni, Tatyana; Dando, Ilaria; Franchini, Marta; Arpicco, Silvia; Scarpa, Aldo; Palmieri, Marta


    Pancreatic adenocarcinoma is a common malignancy that remains refractory to all available therapies, including the gold standard drug gemcitabine (GEM). We investigated the effect of the combination of GEM and each of the ionophore compounds pyrrolidine dithiocarbamate (PDTC) and disulfiram [DSF; 1-(diethylthiocarbamoyldisulfanyl)-N,N-diethylmethanethioamide] on p53(-/-) pancreatic adenocarcinoma cell growth. PDTC or DSF synergistically inhibited cell proliferation when used in combination with GEM by inducing apoptotic cell death. This effect was associated with an increased mitochondrial O(2)(•-) production and was further enhanced by zinc ions. Basal levels of mitochondrial O(2)(•-) or manganese superoxide dismutase (MnSOD) strictly correlated with the IC(50) for GEM or the percentage of synergism. Thus, the most relevant values of the antiproliferative synergism were obtained in GEM-resistant pancreatic adenocarcinoma cell lines. Interestingly, the GEM-sensitive T3M4 cells transfected with MnSOD expression vector showed mitochondrial O(2)(•-) and IC(50) for GEM similar to those of resistant cell lines. In vivo experiments performed on nude mice xenotransplanted with the GEM-resistant PaCa44 cell line showed that only the combined treatment with GEM and DSF/Zn completely inhibited the growth of the tumoral masses. These results and the consideration that DSF is already used in clinics strongly support the GEM and DSF/Zn combination as a new approach to overcoming pancreatic cancer resistance to standard chemotherapy.

  17. Intensity-Modulated Radiotherapy for Pancreatic Adenocarcinoma

    Abelson, Jonathan A.; Murphy, James D.; Minn, Ann Yuriko; Chung, Melody [Department of Radiation Oncology, Stanford University, Stanford, CA (United States); Fisher, George A.; Ford, James M.; Kunz, Pamela [Department of Medical Oncology, Stanford University, Stanford, CA (United States); Norton, Jeffrey A.; Visser, Brendan C.; Poultsides, George A. [Department of Surgical Oncology, Stanford University, Stanford, CA (United States); Koong, Albert C. [Department of Radiation Oncology, Stanford University, Stanford, CA (United States); Chang, Daniel T., E-mail: [Department of Radiation Oncology, Stanford University, Stanford, CA (United States)


    Purpose: To report the outcomes and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for pancreatic adenocarcinoma. Methods and Materials: Forty-seven patients with pancreatic adenocarcinoma were treated with IMRT between 2003 and 2008. Of these 47 patients, 29 were treated adjuvantly and 18 definitively. All received concurrent 5-fluorouracil chemotherapy. The treatment plans were optimized such that 95% of the planning target volume received the prescription dose. The median delivered dose for the adjuvant and definitive patients was 50.4 and 54.0 Gy, respectively. Results: The median age at diagnosis was 63.9 years. For adjuvant patients, the 1- and 2-year overall survival rate was 79% and 40%, respectively. The 1- and 2-year recurrence-free survival rate was 58% and 17%, respectively. The local-regional control rate at 1 and 2 years was 92% and 80%, respectively. For definitive patients, the 1-year overall survival, recurrence-free survival, and local-regional control rate was 24%, 16%, and 64%, respectively. Four patients developed Grade 3 or greater acute toxicity (9%) and four developed Grade 3 late toxicity (9%). Conclusions: Survival for patients with pancreatic cancer remains poor. A small percentage of adjuvant patients have durable disease control, and with improved therapies, this proportion will increase. Systemic therapy offers the greatest opportunity. The present results have demonstrated that IMRT is well tolerated. Compared with those who received three-dimensional conformal radiotherapy in previously reported prospective clinical trials, patients with pancreatic adenocarcinoma treated with IMRT in our series had improved acute toxicity.

  18. Microglia in the mouse retina alter the structure and function of retinal pigmented epithelial cells: a potential cellular interaction relevant to AMD.

    Wenxin Ma

    Full Text Available BACKGROUND: Age-related macular degeneration (AMD is a leading cause of legal blindness in the elderly in the industrialized word. While the immune system in the retina is likely to be important in AMD pathogenesis, the cell biology underlying the disease is incompletely understood. Clinical and basic science studies have implicated alterations in the retinal pigment epithelium (RPE layer as a locus of early change. Also, retinal microglia, the resident immune cells of the retina, have been observed to translocate from their normal position in the inner retina to accumulate in the subretinal space close to the RPE layer in AMD eyes and in animal models of AMD. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we examined the effects of retinal microglia on RPE cells using 1 an in vitro model where activated retinal microglia are co-cultured with primary RPE cells, and 2 an in vivo mouse model where retinal microglia are transplanted into the subretinal space. We found that retinal microglia induced in RPE cells 1 changes in RPE structure and distribution, 2 increased expression and secretion of pro-inflammatory, chemotactic, and pro-angiogenic molecules, and 3 increased extent of in vivo choroidal neovascularization in the subretinal space. CONCLUSIONS/SIGNIFICANCE: These findings share similarities with important pathological features found in AMD and suggest the relevance of microglia-RPE interactions in AMD pathogenesis. We speculate that the migration of retinal microglia into the subretinal space in early stages of the disease induces significant changes in RPE cells that perpetuate further microglial accumulation, increase inflammation in the outer retina, and fosters an environment conducive for the formation of neovascular changes responsible for much of vision loss in advanced AMD.

  19. Endometrial Adenocarcinoma Presenting in a Premenopausal Patient with Tuberous Sclerosis

    Jaffe, J. S.; Chambers, J. T.


    Background: Endometrial adenocarcinoma is very uncommon in women under 40 years of age. Case: A 39-year-old woman with tuberous sclerosis and severe intellectual disability presented with irregular bleeding unresponsive to oral contraceptive therapy. She was subsequently found to have a deeply invasive endometrial adenocarcinoma. Conclusion:…

  20. Laparoscopic treatment of mucinous urachal adenocarcinoma with mucocele.

    Oberndoerfer, Marine; Bucher, Pascal; Caviezel, Alessandro; Platon, Alexandra; Ott, Vincent; Egger, Jean-François; Morel, Philippe


    We present a case of an asymptomatic 76-year-old woman treated laparoscopically for an urachal mucocele owing to a nonmetastatic urachal mucinous adenocarcinoma. Since laparoscopic en bloc resection of the urachus and partial cystectomy, the patient has been healthy and disease-free for 12 months. Modern surgical treatment of urachal adenocarcinoma is discussed in the light of this case.

  1. Prostate adenocarcinoma with unusual first presentation-A case report

    Fariba Binesh; Shokouh Taghipour-zahir; Saeedeh Zare


    Prostate adenocarcinoma most often metastasis to the bones of spine and pelvis. Metastasis to the supradia-phragmatic lymph nodes as uncommon presentation of this disease has been increasingly reported. Here we reported a 61 years old man with prostatic adenocarcinoma who presented with generalized lymphadenopathy.

  2. Primary Papillary Mucinous Adenocarcinoma of the Ureter Mimicking Genitourinary Tuberculosis

    Hanni Gulwani


    Full Text Available Primary adenocarcinomas of the renal pelvis and ureter are rare and account for less than 1% of all malignancies at this site. We report a case of primary papillary mucinous adenocarcinoma of the ureter that clinically mimicked genitourinary tuberculosis. Early diagnosis is important for the better outcome.

  3. Comparative proteomic and phosphoproteomic profiling of pancreatic adenocarcinoma cells treated with CB1 or CB2 agonists.

    Brandi, Jessica; Dando, Ilaria; Palmieri, Marta; Donadelli, Massimo; Cecconi, Daniela


    The pancreatic adenocarcinoma cell line Panc1 was treated with cannabinoid receptor ligands (arachidonylcyclopropylamide or GW405833) in order to elucidate the molecular mechanism of their anticancer effect. A proteomic approach was used to analyze the protein and phosphoprotein profiles. Western blot and functional data mining were also employed in order to validate results, classify proteins, and explore their potential relationships. We demonstrated that the two cannabinoids act through a widely common mechanism involving up- and down-regulation of proteins related to energetic metabolism and cell growth regulation. Overall, the results reported might contribute to the development of a therapy based on cannabinoids for pancreatic adenocarcinoma.

  4. Expression of C4.4A in precursor lesions of pulmonary adenocarcinoma and squamous cell carcinoma

    Jacobsen, Benedikte; Santoni-Rugiu, Eric; Illemann, Martin


    in precursor lesions of lung squamous cell carcinoma and adenocarcinoma was investigated by stainings with a specific anti-C4.4A antibody. In the transformation from normal bronchial epithelium to squamous cell carcinoma, C4.4A was weakly expressed in basal cell hyperplasia but dramatically increased......The protein C4.4A, a structural homologue of the urokinase-type plasminogen activator receptor, is a potential new biomarker in non-small cell lung cancer, with high levels of expression recently shown to correlate to poor survival of adenocarcinoma patients. In this study, C4.4A immunoreactivity...... finding that C4.4A expression levels do not provide prognostic information on the survival of squamous cell carcinoma patients. In the progression from normal alveolar epithelium to peripheral adenocarcinoma, we observed an unexpected, distinct cytoplasmic staining for C4.4A in a fraction of atypical...

  5. Screening for membrane proteins differentially expressed between the lung adenocarcinoma cell lines with high-and low-metastatic potential using iTRAQ technology%应用iTRAQ技术筛选高转移和低转移肺腺癌细胞中差异表达的膜蛋白

    林河春; 张方琳; 耿沁; 赵方瑜; 孙磊; 孔韩卫; 李静; 姚明


    目的:筛选高转移和低转移肺腺癌细胞中差异表达的膜蛋白,以寻找肺癌的生物学标志物或治疗的潜在靶点.方法:提取具有相同来源、不同转移潜能的肺腺癌SPC-A-1和SPC-A-1 sci细胞的膜蛋白,应用核素标记相对和绝对定量(isobaric tags for relative and absolute quantitation,iTRAQ)技术标记膜蛋白,联合纳升液相色谱和串联质谱(nano liquid chromatography-tandem mass spectrometry,Nano-LC-MS/MS)分离、分析肽段,采用Proteinpilot 4.0软件对蛋白进行鉴定和定量分析,对获得的差异蛋白进行GO (Gene Ontology)分析,应用实时荧光定量PCR和蛋白质印迹法进行验证.结果:样品进行4次Nano LC-MS/MS,鉴定出符合假阳性率<1%的分别有1 413、1 374、1 297和1 351个蛋白,标记率>95%,其中4次都上调的蛋白有27个(膜蛋白20个)、下调的蛋白有32个(膜蛋白25个).GO分析显示,差异蛋白的分子功能主要集中在细胞骨架蛋白结合、同源蛋白结合和酶结合.生物学进程主要集中在代谢进程和细胞定位.SPC-A-1 sci细胞中ITGA3(integrin alpha-3)、MYH9 (myosin,heavy chain 9)、PLEC1 (plectin 1)、HADHA (3-hydroxyacyl-CoA dehydrogenase)、HK1(hexokinase-1)、KTN1 (kinectin 1)、ESYT1 (extended synaptotagmin-like protein 1)、ALDH18A1 (aldehyde dehydrogenase 18 family,member A1)、ATP5A1 (ATP synthase alpha-subunit)、LMNB2 (lamin-B2)、CAV1(caveolin-1)和CK-19 (keratin,type Ⅰ cytoskeletal 19) mRNA的表达水平以及CLTC (clathrin,heavy chain)、HK1、LMNB2和CK-19蛋白的表达水平均高于SPC-A-1细胞,与质谱定量结果一致.结论:iTRAQ联合NanoLC-MS/MS技术能高通量地筛选与转移相关的膜蛋白,为肺腺癌患者转移的诊断和预后提供可能的生物学标志物或治疗靶点.%Objective: To screen for the membrane proteins differentially expressed between the lung adenocarcinoma cell lines with high- and low- metastatic potential, and to explore the potential targets for

  6. Genome-wide characterization of pancreatic adenocarcinoma patients using next generation sequencing.

    Winnie S Liang

    Full Text Available Pancreatic adenocarcinoma (PAC is among the most lethal malignancies. While research has implicated multiple genes in disease pathogenesis, identification of therapeutic leads has been difficult and the majority of currently available therapies provide only marginal benefit. To address this issue, our goal was to genomically characterize individual PAC patients to understand the range of aberrations that are occurring in each tumor. Because our understanding of PAC tumorigenesis is limited, evaluation of separate cases may reveal aberrations, that are less common but may provide relevant information on the disease, or that may represent viable therapeutic targets for the patient. We used next generation sequencing to assess global somatic events across 3 PAC patients to characterize each patient and to identify potential targets. This study is the first to report whole genome sequencing (WGS findings in paired tumor/normal samples collected from 3 separate PAC patients. We generated on average 132 billion mappable bases across all patients using WGS, and identified 142 somatic coding events including point mutations, insertion/deletions, and chromosomal copy number variants. We did not identify any significant somatic translocation events. We also performed RNA sequencing on 2 of these patients' tumors for which tumor RNA was available to evaluate expression changes that may be associated with somatic events, and generated over 100 million mapped reads for each patient. We further performed pathway analysis of all sequencing data to identify processes that may be the most heavily impacted from somatic and expression alterations. As expected, the KRAS signaling pathway was the most heavily impacted pathway (P<0.05, along with tumor-stroma interactions and tumor suppressive pathways. While sequencing of more patients is needed, the high resolution genomic and transcriptomic information we have acquired here provides valuable information on the

  7. Vitamin D Receptor Polymorphisms Are Associated with Reduced Esophageal Vitamin D Receptor Expression and Reduced Esophageal Adenocarcinoma Risk

    Janmaat, Vincent T; Van De Winkel, Anouk; Peppelenbosch, Maikel P; Spaander, Manon C W; Uitterlinden, André G; Pourfarzad, Farzin; Tilanus, Hugo W; Rygiel, Agnieszka M; Moons, Leon M G; Arp, Pascal P; Krishnadath, Kausilia K; Kuipers, Ernst J; Van Der Laan, Luc J W


    Epidemiological studies indicate that vitamin D exerts a protective effect on the development of various solid cancers. However, concerns have been raised regarding the potential deleterious role of high vitamin D levels in the development of esophageal adenocarcinoma (EAC). This study investigated

  8. [Pseudo-mesotheliomatous adenocarcinoma of the lung].

    Aumann, K; Günter, J; Freudenberg, N


    Both pathologists and clinicians are challenged by the diagnosis of a particular variant of the peripheral adenocarcinoma with involvement of the pleura parietalis, the so-called pseudo-mesotheliomatous adenocarcinoma of the lung (PMAC), which is hard to differentiate from epithelioid mesothelioma on imaging and cytology, macroscopically as well as histologically. However, the exact diagnosis is not only crucial for the patient's therapy but also for insurance matters. Immunohistochemical evaluation represents a quick and a relatively cheap tool for which a few antibody panels have been proposed in recent years as being suitable to distinguish between these two entities. One of the positive markers for epithelioid mesothelioma most often suggested seems to be calretinin. We would like to report on a case of PMAC with the special feature of positive calretinin immunohistochemical staining. Using histochemistry and a few additional antibodies we were able to reliably characterize the tumor and provide the patient with appropriate therapy. This article gives a short overview of the possibilities available for distinguishing between these two entities in the context of a case report.

  9. Metastasis of Prostate Adenocarcinoma to the Testis

    Campara, Zoran; Simic, Dejan; Aleksic, Predrag; Spasic, Aleksandar; Milicevic, Snjezana


    Introduction: Prostate carcinoma is the most frequently diagnosed carcinoma in the male population. The most typical places of the metastases are pelvic lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis. The prognostic importance of testicular metastasis of prostate cancer is not yet well-known, due to a very few published cases. According to the known facts, it is certain that a metastasis of the prostate carcinoma into a testis is a sign of an advanced disease. Case report: This work presents a 48-year-old patient, to whom an adenocarcinoma of the prostate has been proven by the pathohistological finding of transrectal biopsy, performed due to the elevated level of prostate-specific antigen (PSA). Nine years after the initial diagnosis, due to a gradual rise of PSA and tumorous enlargement of the left testis, left inguinal orchectomy and right orchectomy were performed. Metastatic dissemination of prostate adenocarcinoma into a testis was determined by a pathohistological analysis of the left testis. Conclusion: The metastasis of the prostate carcinoma into a testis, as a rare localization of the metastatic dissemination, after additionally performed orchectomy along with further oncological therapy, can provide a continuation of a good life quality as well as a control of the disease in a longer time period. PMID:27703299

  10. Epidermal growth factor receptor mutation in adenocarcinoma lung in a North Indian population: Prevalence and relation with different clinical variables

    Kasana, Basharat Ahmad; Dar, Waseem Raja; Aziz, Sheikh Aijaz; Lone, Abdul Rashid; Sofi, Najeeb Ullah; Dar, Imtiyaz Ahmad; Latief, Muzamil; Arshad, Faheem; Hussain, Moomin; Hussain, Mir


    Introduction: Lung cancer is one of the most common causes of cancer deaths worldwide. Adenocarcinoma is taking over squamous cell lung cancer as the predominant histological subtype. Several cytotoxic drugs are available for the treatment of lung cancer, but side effects limit their use. Recently, targeted therapies for cancers have come into clinical practice. Aims and Objectives: To determine the prevalence of epidermal growth factor receptor (EGFR) mutation in adenocarcinoma lung in a North Indian population and its relation with different clinical variables. Materials and Methods: A total of 57 patients who met inclusion criteria were recruited into the study. Relevant history, clinical examination and investigations were done. EGFR mutation was done in all patients. Results: A total of twenty patients tested positive for EGFR mutation. EGFR was more frequently detected in female patients (53.8%), while as only 19.4% of the male patients expressed EGFR mutation, which was statistically very significant (P = 0.007). EGFR mutation was more frequently detected in nonsmokers (52%) as compared to smokers (21.9%) which also was statistically significant (P value of 0.018). EGFR mutation was more common in Stage III and IV adenocarcinomas (48%) as compared to Stage I and II (21.4%) which was statistically significant (P value 0.034). Conclusion: EGFR mutation should be routinely done in all patients of adenocarcinoma lung particularly non-smoker females with Stage III and IV disease. PMID:27688613

  11. Novel binuclear μ-oxo diruthenium complexes combined with ibuprofen and ketoprofen: Interaction with relevant target biomolecules and anti-allergic potential.

    Seuanes, Gabriela Campos; Moreira, Mariete Barbosa; Petta, Tânia; de Moraes Del Lama, Maria Perpétua Freire; de Moraes, Luiz Alberto Beraldo; de Oliveira, Anderson Rodrigo Moraes; Naal, Rose Mary Zumstein Georgetto; Nikolaou, Sofia


    This work presents the synthesis and characterization of two novel binuclear ruthenium compounds of general formula [Ru2O(carb)2(py)6](PF6)2, where py=pyridine and carb are the non-steroidal anti-inflammatory drugs ibuprofen (1) and ketoprofen (2). Both complexes were characterized by ESI-MS/MS spectrometry. The fragmentation patterns, which confirm the proposed structures, are presented. Besides that, compounds 1 and 2 present the charge transfer transitions within 325-330nm; and the intra-core transitions around 585nm, which is the typical spectra profile for [Ru2O] analogues. This suggests the carboxylate bridge has little influence in their electronic structure. The effects of the diruthenium complexes on Ig-E mediated mast cell activation were evaluated by measuring the enzyme β-hexosaminidase released by mast cells stimulated by antigen. The inhibitory potential of the ketoprofen complex against mast cell stimulation suggests its promising application as a therapeutic agent for treating or preventing IgE-mediated allergic diseases. In addition, in vitro metabolism assays had shown that the ibuprofen complex is metabolized by the cytochrome P450 enzymes.

  12. Potential Risks of Money Laundering in Pawn Industry and Relevant Countermeasures%典当业潜在洗钱风险分析和对策建议

    陈捷; 陈霄; 李黎


    Pawn industry has a dual nature of financial and commercial sector. With stringent supervision on anti-money laundering in non-banking financial institutions, how to prevent the risk of money laundering in pawn industry has become concern to the regulatory agencies of anti-money laundering and pawn sector. In the context of the status quo of china's pawn industry, the article analyses potential risks of money laundering in business procedures. It gives suggestions on how to prevent the risks under the framework of FATF anti-money laundering 40 recommendations.%在非银行业金融机构反洗钱监管要求日趋严格的情况下,如何防范典当业的洗钱风险,成为摆在反洗钱监管部门及典当业管理部门面前亟待解决的问题。本文立足于中国典当业的现状,分业务环节对典当业潜在的洗钱风险进行了逐一分析.并在FATF“反洗钱40条建议”的框架下,对如何防范典当业的洗钱风险给出了对策建议。

  13. Mycobacterial Hsp65 potentially cross-reacts with autoantibodies of diabetes sera and also induces (in vitro) cytokine responses relevant to diabetes mellitus.

    Rani, Pittu Sandhya; Babajan, Banaganapalli; Tulsian, Nikhil K; Begum, Mahabubunnisa; Kumar, Ashutosh; Ahmed, Niyaz


    Diabetes mellitus is a multifactorial disease and its incidence is increasing worldwide. Among the two types of diabetes, type-2 accounts for about 90% of all diabetic cases, whereas type-1 or juvenile diabetes is less prevalent and presents with humoral immune responses against some of the autoantigens. We attempted to test whether the sera of type-1 diabetes patients cross-react with mycobacterial heat shock protein 65 (Hsp65) due to postulated epitope homologies between mycobacterial Hsp65 and an important autoantigen of type-1 diabetes, glutamic acid decarboxylase-65 (GAD65). In our study, we used either recombinant mycobacterial Hsp65 protein or synthetic peptides corresponding to some of the potential epitopes of mycobacterial Hsp65 that are shared with GAD65 or human Hsp60, and a control peptide sourced from mycobacterial Hsp65 which is not shared with GAD65, Hsp60 and other autoantigens of type-1 diabetes. The indirect ELISA results indicated that both type-1 diabetes and type-2 diabetes sera cross-react with conserved mycobacterial Hsp65 peptides and recombinant mycobacterial Hsp65 protein but do not do so with the control peptide. Our results suggest that cross-reactivity of mycobacterial Hsp65 with autoantibodies of diabetes sera could be due to the presence of significantly conserved peptides between mycobacterial Hsp65 and human Hsp60 rather than between mycobacterial Hsp65 and GAD65. The treatment of human peripheral blood mononuclear cells (PBMCs) with recombinant mycobacterial Hsp65 protein or the synthetic peptides resulted in a significant increase in the secretion of cytokines such as IL-1β, IL-8, IL-6, TNF-α and IL-10. Taken together, these findings point towards a dual role for mycobacterial Hsp65: in inducing autoimmunity and in inflammation, the two cardinal features of diabetes mellitus.

  14. Defining the potential of aglycone modifications for affinity/selectivity enhancement against medically relevant lectins: synthesis, activity screening, and HSQC-based NMR analysis.

    Rauthu, Subhash R; Shiao, Tze Chieh; André, Sabine; Miller, Michelle C; Madej, Élodie; Mayo, Kevin H; Gabius, Hans-Joachim; Roy, René


    The emerging significance of lectins for pathophysiological processes provides incentive for the design of potent inhibitors. To this end, systematic assessment of contributions to affinity and selectivity by distinct types of synthetic tailoring of glycosides is a salient step, here taken for the aglyconic modifications of two disaccharide core structures. Firstly we report the synthesis of seven N-linked-lactosides and of eight O-linked N-acetyllactosamines, each substituted with a 1,2,3-triazole unit, prepared by copper-catalyzed azide-alkyne cycloaddition (CuAAC). The totally regioselective β-D-(1 → 4) galactosylation of a 6-O-TBDPSi-protected N-acetylglucosamine acceptor provided efficient access to the N-acetyllactosamine precursor. The resulting compounds were then systematically tested for lectin reactivity in two binding assays of increasing biorelevance (inhibition of lectin binding to a surface-presented glycoprotein and to cell surfaces). As well as a plant toxin, we also screened the relative inhibitory potential with adhesion/growth-regulatory galectins (total of eight proteins). This type of modification yielded up to 2.5-fold enhancement for prototype proteins, with further increases for galectins-3 and -4. Moreover, the availability of (15)N-labeled proteins and full assignments enabled (1)H, (15)N HSQC-based measurements for hu- man galectins-1, -3, and -7 against p-nitrophenyl lactopyranoside, a frequently tested standard inhibitor containing an aromatic aglycone. The measurements confirmed the highest affinity against galectin-3 and detected chemical shift differences in its hydrophobic core upon ligand binding, besides common alterations around the canonical contact site for the lactoside residue. What can be accomplished in terms of affinity/selectivity by this type of core extension having been determined, the applied combined strategy should be instrumental for proceeding with defining structure-activity correlations at other bioinspired

  15. Systems genetics of the nuclear factor-κB signal transduction network. I. Detection of several quantitative trait loci potentially relevant to aging.

    Diego, Vincent P; Curran, Joanne E; Charlesworth, Jac; Peralta, Juan M; Voruganti, V Saroja; Cole, Shelley A; Dyer, Thomas D; Johnson, Matthew P; Moses, Eric K; Göring, Harald H H; Williams, Jeff T; Comuzzie, Anthony G; Almasy, Laura; Blangero, John; Williams-Blangero, Sarah


    A theory of aging holds that senescence is caused by a dysregulated nuclear factor kappa B (NF-κB) signal transduction network (STN). We adopted a systems genetics approach in our study of the NF-κB STN. Ingenuity Pathways Analysis (IPA) was used to identify gene/gene product interactions between NF-κB and the genes in our transcriptional profiling array. Principal components factor analysis (PCFA) was performed on a sub-network of 19 genes, including two initiators of the toll-like receptor (TLR) pathway, myeloid differentiation primary response gene (88) (MyD88) and TIR (Toll/interleukin-1 receptor)-domain-containing adapter-inducing interferon-β (TRIF). TLR pathways are either MyD88-dependent or TRIF-dependent. Therefore, we also performed PCFA on a subset excluding the MyD88 transcript, and on another subset excluding two TRIF transcripts. Using linkage analysis we found that each set gave rise to at least one factor with a logarithm of the odds (LOD) score greater than 3, two on chromosome 15 at 15q12 and 15q22.2, and another two on chromosome 17 at 17p13.3 and 17q25.3. We also found several suggestive signals (2potential associations with single nucleotide polymorphisms within the 1-LOD intervals of our linkage signals.

  16. Why relevance theory is relevant for lexicography

    Bothma, Theo; Tarp, Sven


    , socio-cognitive and affective relevance. It then shows, at the hand of examples, why relevance is important from a user perspective in the extra-lexicographical pre- and post-consultation phases and in the intra-lexicographical consultation phase. It defines an additional type of subjective relevance...... that is very important for lexicography as well as for information science, viz. functional relevance. Since all lexicographic work is ultimately aimed at satisfying users’ information needs, the article then discusses why the lexicographer should take note of all these types of relevance when planning a new...... dictionary project, identifying new tasks and responsibilities of the modern lexicographer. The article furthermore discusses how relevance theory impacts on teaching dictionary culture and reference skills. By integrating insights from lexicography and information science, the article contributes to new...

  17. Meat and heme iron intake and esophageal adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition study.

    Jakszyn, Paula; Luján-Barroso, Leila; Agudo, Antonio; Bueno-de-Mesquita, H Bas; Molina, Esther; Sánchez, Ma José; Fonseca-Nunes, Ana; Siersema, Peter D; Matiello, Amalia; Tumino, Rosario; Saieva, Calogero; Pala, Valeria; Vineis, Paolo; Boutron-Ruault, Marie-Christine; Racine, Antoine; Bastide, Nadie; Travis, Ruth C; Khaw, Kay-Tee; Riboli, Elio; Murphy, Neil; Vergnaud, Anne-Claire; Trichopoulou, Antonia; Valanou, Elissavet; Oikonomidou, Edespina; Weiderpass, Elisabete; Skeie, Guri; Johansen, Dorthe; Lindkvist, Björn; Johansson, Mattias; Duarte-Salles, Talita; Freisling, Heinz; Barricarte, Aurelio; Huerta, Jose Ma; Amiano, Pilar; Tjonneland, Anne; Overvad, Kim; Kuehn, Tilman; Grote, Verena; Boeing, Heiner; Peeters, Petra H M; González, Carlos A


    Although recent studies suggest that high intakes of meat and heme iron are risk factors for several types of cancer, studies in relation to esophageal adenocarcinoma (EAC) are scarce. Previous results in the European Prospective Investigation into Cancer and Nutrition (EPIC) based on a relatively small number of cases suggested a positive association between processed meat and EAC. In this study, we investigate the association between intake of different types of meats and heme iron intake and EAC risk in a larger number of cases from EPIC. The study included 481,419 individuals and 137 incident cases of EAC that occurred during an average of 11 years of follow-up. Dietary intake of meat (unprocessed/processed red and white meat) was assessed by validated center-specific questionnaires. Heme iron was calculated as a type-specific percentage of the total iron content in meat. After adjusting for relevant confounders, we observed a statistically significant positive association of EAC risk with heme iron and processed meat intake, with HR: 1.67, 95% CI: 1.05-2.68 and HR: 2.27, 95% CI:1.33-3.89, respectively, for comparison of the highest vs. lowest tertile of intake. Our results suggest a potential association between higher intakes of processed meat and heme iron and risk of EAC.

  18. Identification of serum biomarkers for diagnosing stage I lung adenocarcinoma by MALDI-TOF mass spectrometry

    Xin-ju Li; Da-lin He; Jun-ke Fu; Jing-ren Liang


    Objectire To identify specific biomarkers that could improve early diagnsis of lung adenuearcinoma using matrix-assisted laser desorptian/ionization (MALDI) technology. Methods Serum samples were isolated from 17 patients with stage I lung adenuearcinoma and 17 age- and sex-matched healthy controls, and the serum proteomic profiles were obtained by matrix-assistcd laser desorption ionization time of flight (MALDI-TOF) mass spectrometry. Results Compared with healthy control group, two highly expressed potential biomarkers were identified with the relative molecular weights of 6 631.64 Da and 4 964. 21 Da. The two best novel protein peaks were automatically chosen for the system training and the development of the constructed model. The constructed model was then used to test an independent set of masked serum samples from 15 lung adenocarcinoma patients and 22 healthy individuals. The analysis yielded a sensitivity of 93.3 %, and a specificity of 95.5 %. Conclusion These results suggest that MALDI-TOF-MS ProteinChip technology is a quick, convenient, and high-output analyzing method that is capable of selecting several relatively potential biomarkers from the serum of lung adenocarcinoma patients and may have a clinical value in the future, and will provide clues to identifying new serologic btomarkers of lung adenocarcinoma.

  19. Expression of p53 protein in Barrett’s adenocarcinoma and adenocarcinoma of the gastric cardia and antrum

    Jovanović Ivan


    Full Text Available Background/Aim. Most studies of esophageal and gastric adenocarcinomas have shown a very high rate of p53 gene mutation and/or protein overexpression, but the influence of the tumor site upon the frequency of p53 protein expression has not been evaluated (gastroesophageal junction, Barret's esophagus, and antrum. The aim of our study was to analyze the correlation between the selected clinico-pthological parameters, and p53 protein overexpression in regards to the particular tumor location. Methods. The material comprised 66 surgical specimens; 10 were Barrett’s carcinomas, 25 adenocarcinomas of the gastric cardia (type II adenocarcinoma of the esophagogastric junction - EGJ, and 31 adenocarcinomas of the antrum. Immunostaining for p53 protein was performed on formalin-fixed, paraffin-embedded tissue sections, using the alkaline phosphatase - antialkaline phosphatase (APAAP method. The cases were considered positive for p53 if at least 5% of the tumor cells expressed this protein by immunostaining. Results. There was no significant difference observed between the studied groups in regards to age, sex, Lauren’s classification and tumor differentiation. There was, however, a significant difference observed in the depth of tumor invasion between Barrrett’s adenocarcinoma and adenocarcinoma of the cardia compared with the adenocarcinoma of the antrum. Namely, at the time of surgery, both Barrett’s adenocarcinomas and adenocarcinomas of the cardia, were significantly more advanced comparing with the adenocarcinomas of the antrum. Overexpression of p53 was found in 40% (4/10 of Barrett’s adenocarcinomas, 72% (18/25 of adenocarcinoma of the cardia and 65% (20/31 of adenocarcinoma of the antrum. No significant differences in p53 expression in relation to sex, type (Lauren of tumor, depth of invasion, lymph node involvement, or tumor differentiation were observed in any of the analyzed groups of tumors. Patients with more advanced Barrett

  20. Progressive silencing of p14ARF in oesophageal adenocarcinoma.

    Huang, Yinghui; Peters, Christopher J; Fitzgerald, Rebecca C; Gjerset, Ruth A


    The frequency of oesophageal adenocarcinoma is increasing in Western countries for unknown reasons, and correlates with a corresponding increase in the pre-malignant condition, Barrett's Oesophagus, which raises the risk of adenocarcinoma by some 40- to 125-fold. We have examined how disease progression correlates with changes in expression of the p14ARF (ARF) tumour suppressor, a key regulator of the p53 tumour suppressor pathway that is silenced in some 30% of cancers overall, but for which a role in oesophageal cancer is unclear. We have used quantitative PCR, RT-PCR, methylation-specific PCR and chromatin-immunoprecipitation to examine the regulation and function of ARF in oesophageal adenocarcinoma tissue specimens and cell lines. We find highly significant reductions (Poesophageal epithelium to Barrett's Oesophagus to adenocarcinoma, with 57/76 (75%) adenocarcinomas displaying undetectable levels of ARF expression. Retention of ARF expression in adenocarcinoma is a highly significant indicator of increased survival (Padenocarcinoma cell lines and can be reversed by 5-aza-2'-deoxycytidine. The results suggest that silencing of ARF is involved in the pathogenesis of oesophageal adenocarcinoma and show that either DNA or histone methylation can provide the primary mechanism for ARF gene silencing. Silencing of ARF could provide a useful marker for increased risk of progression and poor prognosis.

  1. The implications of an incidental chronic lymphocytic leukaemia in a resection specimen for colorectal adenocarcinoma

    Alberts Justin C


    Full Text Available Abstract Background Colorectal cancer and B cell chronic lymphocytic leukaemia (CLL have a significant incidence, which are increasing with the aging population. Evidence has been presented in the literature to suggest that the synchronous presentation of colorectal cancer and B cell CLL may be more than simply coincidental for these two common malignancies. We report an unusual case of a presumed B cell CLL diagnosed on the basis of histological analysis of lymph nodes recovered from a resection specimen for rectal adenocarcinoma. We considered aetiological factors which may have linked the synchronous diagnosis of the two malignancies and the potential implications for the natural history of the two malignancies on one another. Case presentation A 70-year-old male underwent low anterior resection with total mesorectal excision for a rectal adenocarcinoma. His co-morbid conditions were chronic obstructive airways disease and ischaemic heart disease. General examination revealed no lymphadenopathy. Full blood count, urea and electrolytes and liver function tests were all within normal limits. As well as confirming a pT3 N1 adenocarcinoma, histological analysis showed lymph nodes with an infiltrate of small lymphoid cells. Immunohistochemical studies showed these cells to be in keeping with B cell CLL. Conclusion Whilst unable to identify any common aetiological factors in the two malignancies in our patient, immunosuppression and genetic abnormalities have been identified as possible bases for an observed epidemiological association between colorectal cancer and haematological malignancies. Examples such as our case of synchronous diagnosis of two malignancies in a patient are likely to increase with the aging population. The potential affects of one malignancy on the natural history of the other warrants further study. In our case, we considered that slow progression of the B cell CLL may increase the risk of recurrent rectal adenocarcinoma.

  2. Differences in miRNA expression in early stage lung adenocarcinomas that did and did not relapse.

    Mick D Edmonds

    Full Text Available Relapse of adenocarcinoma, the most common non-small cell lung cancer (NSCLC, is a major clinical challenge to improving survival. To gain insight into the early molecular events that contribute to lung adenocarcinoma relapse, and taking into consideration potential cell type specificity, we used stringent criteria for sample selection. We measured miRNA expression only from flash frozen stage I lung adenocarcinomas, excluding other NSCLC subtypes. We compared miRNA expression in lung adenocarcinomas that relapsed within two years to those that did not relapse within three years after surgical resection prior to adjuvant therapy. The most significant differences in mRNA expression for recurrent tumors compared to non-recurrent tumors were decreases in miR-106b*, -187, -205, -449b, -774* and increases in miR-151-3p, let-7b, miR-215, -520b, and -512-3p. A unique comparison between adjacent normal lung tissue from relapse and non-relapse groups revealed dramatically different miRNA expression, suggesting dysregulation of miRNA in the environment around the tumor. To assess patient-to-patient variability, miRNA levels in the tumors were normalized to levels in matched adjacent normal lung tissue. This analysis revealed a different set of significantly altered miRNA in tumors that recurred compared to tumors that did not. Together our analyses elucidated miRNA not previously linked to lung adenocarcinoma that likely have important roles in its development and progression. Our results also highlight the differences in miRNA expression in normal lung tissue in adenocarcinomas that do and do not recur. Most notably, our data identified those miRNA that distinguish early stage tumors likely to relapse prior to treatment and miRNA that could be further studied for use as biomarkers for prognosis, patient monitoring, and/or treatment decisions.

  3. MRI findings of a huge cyst adenocarcinoma of the palate

    Choi, Jin Woo [School of Dentistry, Seoul National University, Seoul (Korea, Republic of)


    Cyst adenocarcinoma of the salivary glands is a very rare, slow growing, and low-grade malignant neoplasm. It is characterized by predominantly cystic growth with or without the intraluminal papillary component. However, it lacks of any additional specific histopathologic features that characterize other types of salivary carcinomas showing cystic growth. Therefore, definite diagnosis of the cyst adenocarcinoma is difficult and it is often misdiagnosed. It is conceptually the malignant counterpart of the benign cyst adenoma. We present a cyst adenocarcinoma on the palate of a 49-year-old man with special emphasis on magnetic resonance imaging.

  4. Effect of anthralin on cell viability in human prostate adenocarcinoma.

    Raevskaya, A A; Gorbunova, S L; Savvateeva, M V; Severin, S E; Kirpichnikov, M P


    The study revealed the key role of serine protease hepsin activity in transition of in situ prostate adenocarcinoma into the metastasizing form. Inhibition of hepsin activity suppresses the invasive growth of the tumor. Hepsin is an convenient target for pharmacological agents, so the study of its inhibitory mechanisms is a promising avenue in drug development. Assay of proteolytic activity in various tumor cell lines in vitro showed that this activity in prostate adenocarcinoma cells significantly surpasses proteolytic activity in other examined tumor cell lines. Selective cytotoxic action of anthralin, an inhibitor of hepsin activity, on human adenocarcinoma cells was demonstrated in comparison with other tumor cell lines.

  5. Targeting Pancreatic Ductal Adenocarcinoma Acidic Microenvironment

    Cruz-Monserrate, Zobeida; Roland, Christina L.; Deng, Defeng; Arumugam, Thiruvengadam; Moshnikova, Anna; Andreev, Oleg A.; Reshetnyak, Yana K.; Logsdon, Craig D.


    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA, accounting for ~40,000 deaths annually. The dismal prognosis for PDAC is largely due to its late diagnosis. Currently, the most sensitive diagnosis of PDAC requires invasive procedures, such as endoscopic ultrasonography, which has inherent risks and accuracy that is highly operator dependent. Here we took advantage of a general characteristic of solid tumors, the acidic microenvironment that is generated as a by-product of metabolism, to develop a novel approach of using pH (Low) Insertion Peptides (pHLIPs) for imaging of PDAC. We show that fluorescently labeled pHLIPs can localize and specifically detect PDAC in human xenografts as well as PDAC and PanIN lesions in genetically engineered mouse models. This novel approach may improve detection, differential diagnosis and staging of PDAC.


    Apeksha Kakkar


    Full Text Available Being the 4th leading cause of cancer deaths in the U.S. and with a global increase in incidence, above 80% of pancreatic cancers are locally advanced or metastatic at the time of diagnosis. As surgical resection is the only hope for a cure, the answer is probably in early screening, proper classification and right therapy. The advancing research will likely lead to a better understanding of Pancreatic Ductal Adenocarcinoma (PDAC as well as enhance the techniques for screening, diagnosis, accurate subtyping and enable the use of targeted therapy. Thus, instead of clubbing together various subtypes of PDAC for trials, improving the subcategorization will ensure statistical significance for the academicians, and the clinicians would avoid administration of placebo drug to a vast number of patients.

  7. Orthovoltage intraoperative radiation therapy for pancreatic adenocarcinoma

    Kapp Daniel S


    Full Text Available Abstract Purpose To analyze the outcomes of patients from a single institution treated with surgery and orthovoltage intraoperative radiotherapy (IORT for pancreatic adenocarcinoma. Methods We retrospectively reviewed 23 consecutive patients from 1990-2001 treated with IORT to 23 discrete sites with median and mean follow up of 6.5 and 21 months, respectively. Most tumors were located in the head of the pancreas (83% and sites irradiated included: tumor bed (57%, vessels (26%, both the tumor bed/vessels (13% and other (4%. The majority of patients (83% had IORT at the time of their definitive surgery. Three patients had preoperative chemoradiation (13%. Orthovoltage X-rays (200-250 kVp were employed via individually sized and beveled cone applicators. Additional mean clinical characteristics include: age 64 (range 41-81; tumor size 4 cm (range 1.4-11; and IORT dose 1106 cGy (range 600-1500. Post-operative external beam radiation (EBRT or chemotherapy was given to 65% and 76% of the assessable patients, respectively. Outcomes measured were infield control (IFC, loco-regional control (LRC, distant metastasis free survival (DMFS, overall survival (OS and treatment-related complications. Results Kaplan-Meier (KM 2-year IFC, LRC, DMFS and OS probabilities for the whole group were 83%, 61%, 26%, and 27%, respectively. Our cohort had three grade 3-5 complications associated with treatment (surgery and IORT. Conclusions Orthovoltage IORT following tumor reductive surgery is reasonably well tolerated and seems to confer in-field control in carefully selected patients. However, distant metastases remain the major problem for patients with pancreatic adenocarcinoma.

  8. High-resolution array comparative genomic hybridization of chromosome 8q: evaluation of putative progression markers for gastroesophageal junction adenocarcinomas.

    van Duin, M; van Marion, R; Vissers, K J; Hop, W C J; Dinjens, W N M; Tilanus, H W; Siersema, P D; van Dekken, H


    Amplification of 8q is frequently found in gastroesophageal junction (GEJ) cancer. It is usually detected in high-grade, high-stage GEJ adenocarcinomas. Moreover, it has been implicated in tumor progression in other cancer types. In this study, a detailed genomic analysis of 8q was performed on a series of GEJ adenocarcinomas, including 22 primary adenocarcinomas, 13 cell lines and two xenografts, by array comparative genomic hybridization (aCGH) with a whole chromosome 8q contig array. Of the 37 specimens, 21 originated from the esophagus and 16 were derived from the gastric cardia. Commonly overrepresented regions were identified at distal 8q, i.e. 124-125 Mb (8q24.13), at 127-128 Mb (8q24.21), and at 141-142 Mb (8q24.3). From these regions six genes were selected with putative relevance to cancer: ANXA13, MTSS1, FAM84B (alias NSE2), MYC, C8orf17 (alias MOST-1) and PTK2 (alias FAK). In addition, the gene EXT1 was selected since it was found in a specific amplification in cell line SK-GT-5. Quantitative RT-PCR analysis of these seven genes was subsequently performed on a panel of 24 gastroesophageal samples, including 13 cell lines, two xenografts and nine normal stomach controls. Significant overexpression was found for MYC and EXT1 in GEJ adenocarcinoma cell lines and xenografts compared to normal controls. Expression of the genes MTSS1, FAM84B and C8orf17 was found to be significantly decreased in this set of cell lines and xenografts. We conclude that, firstly, there are other genes than MYC involved in the 8q amplification in GEJ cancer. Secondly, the differential expression of these genes contributes to unravel the biology of GEJ adenocarcinomas.

  9. Genetic polymorphisms at TIMP3 are associated with survival of adenocarcinoma of the gastroesophageal junction.

    Morteza Bashash

    Full Text Available The poor survival of adenocarcinomas of the gastroesophageal junction (GEJ makes them clinically important. Discovery of host genetic factors that affect outcome may guide more individualized treatment. This study tests whether constitutional genetic variants in matrix metalloproteinases (MMP and tissue inhibitors of metalloproteinases (TIMP genes are associated with outcome of GEJ adenocarcinoma. Single nucleotide polymorphisms (SNPs at four TIMP (TIMP1-4 and three MMP genes (MMP2, MMP7 and MMP9 were genotyped in DNA samples from a prospective cohort of patients with primary adenocarcinoma of the GEJ admitted to the British Columbia Cancer Agency. Cox proportional hazards regression, with adjustment for patient, disease and treatment variables, was used to estimate the association of SNPs with survival. Genotypes for 85 samples and 48 SNPs were analyzed. Four SNPs across TIMP3, (rs130274, rs715572, rs1962223 and rs5754312 were associated with survival. Interaction analyses revealed that the survival associations with rs715572 and rs5754312 are specific and significant for 5FU+cisplatin treated patients. Sanger sequencing of the TIMP3 coding and promoter regions revealed an additional SNP, rs9862, also associated with survival. TIMP3 genetic variants are associated with survival and may be potentially useful in optimizing treatment strategies for individual patients.

  10. Hyperplastic-like colon polyps that preceded microsatellite-unstable adenocarcinomas.

    Goldstein, Neal S; Bhanot, Punam; Odish, Eva; Hunter, Susan


    We compared hyperplastic-like polyps that preceded microsatellite-unstable adenocarcinomas to incidental hyperplastic polyps to identify distinguishing morphologic criteria. The study group included 106 hyperplastic-like, nonadenomatous, serrated polyps, most from the ascending colon in 91 patients; the control group included 106 rectosigmoid hyperplastic polyps from 106 patients in whom adenocarcinoma did not develop. Study group polyps had an expanded crypt proliferative zone, a serrated architectural outline that became apparent in the basilar crypt regions, basilar crypt dilation, inverted crypts, and a predominance of dysmaturational crypts (crypts with minimal cell maturation). In contrast, control group polyps had a proliferative zone confined to the basal crypt region, serrated architecture that became apparent in the superficial crypt region, rare to no basilar crypt dilation, and rare or no dysmaturational crypts. Hyperplastic-like polyps that preceded microsatellite-unstable adenocarcinomas had a distinctive constellation of morphologic features related to altered and decreased cell function and control that resulted in dysmaturational crypts. Dysmaturation constitutes a range of morphologic alterations, some of which overlap with incidental-type innocuous hyperplastic polyps. The morphologic features described herein provide initial guidelines to identify this potentially important subset of premalignant serrated-like polyps.

  11. Primary adenocarcinoma of lung: A pictorial review of recent updates

    Gaikwad, Anand, E-mail: [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Gupta, Ashish, E-mail: [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Hare, Sam, E-mail: [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Gomes, Marcio, E-mail: [Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Sekhon, Harman, E-mail: [Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Souza, Carolina, E-mail: [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Inacio, Joao, E-mail: [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Lad, Shilpa, E-mail: [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada); Seely, Jean, E-mail: [Department of Diagnostic Imaging, The Ottawa Hospital, University of Ottawa, Ottawa, ON (Canada)


    Primary adenocarcinoma of lung has replaced squamous cell carcinoma as the commonest histological subtype of lung cancer and the incidence of primary lung adenocarcinoma appears to be rising. Although the main factors behind this ‘epidemic-like’ situation are largely undiscovered, filter cigarettes appear to significantly contribute to this shift in the histopathological spectrum. The new multidisciplinary classification of adenocarcinoma of lung was introduced to address advances in clinical, pathological, radiological and molecular sciences. The purpose of this essay is to discuss various classes of lung adenocarcinoma in the new classification with their classical imaging features on computed tomography and summarise the recent advances in the field of radiology and review radiology recommendations.

  12. Coexistent adenocarcinoma and microcystic adenoma of the pancreas.

    Posniak, H V; Olson, M C; Demos, T C


    A case with coexistent pancreatic adenocarcinoma and microcystic adenoma is presented. These diagnoses were suspected on the basis of their computed tomography (CT) appearances and confirmed with CT-guided fine-needle aspiration.

  13. Ovarian recurrence after radical trachelectomy for adenocarcinoma of the cervix.

    Piketty, Mathilde; Barranger, Emmanuel; Najat, Mourra; François, Paye; Daraï, Emile


    Radical trachelectomy is an effective fertility-sparing treatment for women with early-stage cervical cancer. We describe the first reported ovarian recurrence after radical trachelectomy for stage IB1 adenocarcinoma cervical cancer.

  14. Discovery of new molecular subtypes in oesophageal adenocarcinoma.

    Berg, Daniela; Wolff, Claudia; Langer, Rupert; Schuster, Tibor; Feith, Marcus; Slotta-Huspenina, Julia; Malinowsky, Katharina; Becker, Karl-Friedrich


    A large number of patients suffering from oesophageal adenocarcinomas do not respond to conventional chemotherapy; therefore, it is necessary to identify new predictive biomarkers and patient signatures to improve patient outcomes and therapy selections. We analysed 87 formalin-fixed and paraffin-embedded (FFPE) oesophageal adenocarcinoma tissue samples with a reverse phase protein array (RPPA) to examine the expression of 17 cancer-related signalling molecules. Protein expression levels were analysed by unsupervised hierarchical clustering and correlated with clinicopathological parameters and overall patient survival. Proteomic analyses revealed a new, very promising molecular subtype of oesophageal adenocarcinoma patients characterised by low levels of the HSP27 family proteins and high expression of those of the HER family with positive lymph nodes, distant metastases and short overall survival. After confirmation in other independent studies, our results could be the foundation for the development of a Her2-targeted treatment option for this new patient subgroup of oesophageal adenocarcinoma.

  15. Adenocarcinoma of the Minor Duodenal Papilla: Report of a Case

    Kazuhiro Takami


    Full Text Available An 81-year-old male was found to have a duodenal tumor by screening upper gastrointestinal endoscopy. The tumor was located in the minor duodenal papilla. Pathological examination of the biopsy specimen revealed adenocarcinoma, and endoscopic ultrasound showed an elevated hypoechoic mass in the minor duodenal papilla. The preoperative diagnosis was therefore considered to be either adenocarcinoma of the minor duodenal papilla or duodenal cancer. We performed a subtotal stomach-preserving pancreaticoduodenectomy. Histopathological examination of the resected specimen showed the tumor cells to be primarily located in the submucosa of the minor duodenal papilla, with slight invasion into the pancreatic parenchyma through the accessory pancreatic duct. We therefore diagnosed a primary adenocarcima of the minor duodenal papilla. Adenocarcinoma of the minor duodenal papilla is considered to be a rare disease, but it may be underestimated because of the difficulty in distinguishing advanced adenocarcinoma of the minor duodenal papilla from primary duodenal cancer and cancer of the pancreatic head.

  16. Discovery of new molecular subtypes in oesophageal adenocarcinoma.

    Daniela Berg

    Full Text Available A large number of patients suffering from oesophageal adenocarcinomas do not respond to conventional chemotherapy; therefore, it is necessary to identify new predictive biomarkers and patient signatures to improve patient outcomes and therapy selections. We analysed 87 formalin-fixed and paraffin-embedded (FFPE oesophageal adenocarcinoma tissue samples with a reverse phase protein array (RPPA to examine the expression of 17 cancer-related signalling molecules. Protein expression levels were analysed by unsupervised hierarchical clustering and correlated with clinicopathological parameters and overall patient survival. Proteomic analyses revealed a new, very promising molecular subtype of oesophageal adenocarcinoma patients characterised by low levels of the HSP27 family proteins and high expression of those of the HER family with positive lymph nodes, distant metastases and short overall survival. After confirmation in other independent studies, our results could be the foundation for the development of a Her2-targeted treatment option for this new patient subgroup of oesophageal adenocarcinoma.

  17. A clear cell adenocarcinoma of the gallbladder with hepatoid differentiation: case report and review of literature

    Zhang C


    Full Text Available Chengsheng Zhang,1,2 Wei Zhang,1,2 Dianbin Mu,1 Xuetao Shi,1 Lei Zhao1,2 1Department of Hepatobiliary Surgery, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Science, 2School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China Abstract: An 80-year-old male was referred to our department for a gallbladder mass. He denied any history of alcohol consumption or cholecystitis and smoking. Hepatitis B surface antigen test and antihepatitis C antibody test were found to be negative. Serum carbohydrate antigen 19-9 (CA19-9 and carcinoembryonic antigen were elevated (CA19-9 was 59.92 U/mL and carcinoembryonic antigen was 12.64 ng/mL, whereas alpha-fetoprotein was below the normal limit (2.46 ng/mL. Computed tomography scan revealed a solid mass with measurements of 4.6×5.6×7.1 cm, which nearly filled the whole gallbladder space. Radical cholecystectomy, including segments IV B and V of the liver and lymphadenectomy, was performed. The neoplasm in gallbladder was completely resected, and the patient obtained a negative margin. Histological and immunohistochemical profile suggested a clear cell adenocarcinoma of the gallbladder with hepatoid differentiation. After reviewing the literature, we reported that this case is the first identified case of cell adenocarcinoma of the gallbladder with extensive hepatoid differentiation. However, clinical features of clear cell adenocarcinoma with hepatoid differentiation remain unclear due to the extremely rare incidence. There was no indication of adjuvant chemotherapy and no literature has been reported on the application of chemotherapy. This case showed a promising clinical outcome after curative resection, which indicated that surgical treatment could be potentially considered for suitable patients. Keywords: gallbladder, clear cell adenocarcinoma, hepatoid differentiation 

  18. Pulmonary adenocarcinoma mutation profile in smokers with smoking-related interstitial fibrosis

    Primiani A


    Full Text Available Andrea Primiani,1 Dora Dias-Santagata,1 A John Iafrate,1 Richard L Kradin1,2 1Pathology Service, 2Pulmonary Medicine/Critical Care Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Abstract: Cigarette smoking is an established cause of lung cancer. However, pulmonary fibrosis is also an independent risk factor for the development of lung cancer. Smoking-related interstitial fibrosis (SRIF has recently been reported. We hypothesized that adenocarcinomas in lungs with SRIF might show distinct molecular changes and examined the molecular phenotype of 168 resected lung adenocarcinomas in lungs with and without SRIF. The diagnosis of SRIF was determined by histological examination, based on the presence of alveolar septal thickening, due to pauci-inflamed, hyalinized, “ropy” collagen, in areas of lung greater than 1 cm away from the tumor. Tumors were concomitantly examined genotypically for mutations in genes frequently altered in cancer, including EGFR and KRAS, by SNaPshot and by fluorescence in situ hybridization for possible ALK rearrangements. Fluorescence in situ hybridization for ROS1 rearrangement (n=36 and/or MET amplification (n=31 were performed when no mutation was identified by either SNaPshot or ALK analysis. Sixty-five cases (38.7% showed SRIF, which was distributed in all lobes of the lungs examined. No differences were observed in sex, average age, or smoking history in patients with and without SRIF. There was no difference in either the percent or types of adenocarcinoma genetic mutations in patients with SRIF versus those without. This data suggests that SRIF does not represent an independent risk factor for the development of the major known and targeted mutations seen in pulmonary adenocarcinoma. However, additional research is required to investigate the potential significance of SRIF in the pathogenesis of lung cancer. Keywords: lung, cancer, smoking, SRIF

  19. Prevalence of prostate adenocarcinoma according to race in an university hospital

    Barros Milton S


    Full Text Available OBJECTIVES: To determine the prevalence of prostate cancer and to assess potential associations between race and prostate adenocarcinoma according to age in patients followed in an outpatient service of general urology in an university hospital. MATERIALS AND METHODS: Retrospective study of men aged from 40 to 79 years, followed during the period from 1999 to 2001. Patients were classified according to race in White, Mulatto and Black. Those with abnormal digital rectal examination and/or serum level of prostate specific antigen (PSA > 4.0 ng/ml, underwent a transrectal prostate biopsy. RESULTS: 580 patients with mean age of 60.7 ± 10.0 years were studied, with 116 Whites (20.0%, 276 Mulattos (47.6% and 188 Blacks (32.4%. There was no significant difference regarding the mean age (p = 0.62, serum level of PSA (p = 0.65 and prevalence of prostate adenocarcinoma between Whites, Mulattos and Blacks (p = 0.36. While studying the association between race classified in 2 groups (Whites versus Mulattos and Blacks and prostate adenocarcinoma according to age, no association was found when the total group was assessed, neither among those with age above 60 years old. In the group between 40 and 60 years, even though without statistical significance, the estimate of prevalence ratio was 2.2 (CI 95%: 0.52 to 9.0; p = 0.38. CONCLUSION: Prostate adenocarcinoma was found in 16.6% of the patients aged between 40 and 79 years. We did not find a racial influence in our population.

  20. Identification of Biomarker and Co-Regulatory Motifs in Lung Adenocarcinoma Based on Differential Interactions.

    Ning Zhao

    Full Text Available Changes in intermolecular interactions (differential interactions may influence the progression of cancer. Specific genes and their regulatory networks may be more closely associated with cancer when taking their transcriptional and post-transcriptional levels and dynamic and static interactions into account simultaneously. In this paper, a differential interaction analysis was performed to detect lung adenocarcinoma-related genes. Furthermore, a miRNA-TF (transcription factor synergistic regulation network was constructed to identify three kinds of co-regulated motifs, namely, triplet, crosstalk and joint. Not only were the known cancer-related miRNAs and TFs (let-7, miR-15a, miR-17, TP53, ETS1, and so on were detected in the motifs, but also the miR-15, let-7 and miR-17 families showed a tendency to regulate the triplet, crosstalk and joint motifs, respectively. Moreover, several biological functions (i.e., cell cycle, signaling pathways and hemopoiesis associated with the three motifs were found to be frequently targeted by the drugs for lung adenocarcinoma. Specifically, the two 4-node motifs (crosstalk and joint based on co-expression and interaction had a closer relationship to lung adenocarcinoma, and so further research was performed on them. A 10-gene biomarker (UBC, SRC, SP1, MYC, STAT3, JUN, NR3C1, RB1, GRB2 and MAPK1 was selected from the joint motif, and a survival analysis indicated its significant association with survival. Among the ten genes, JUN, NR3C1 and GRB2 are our newly detected candidate lung adenocarcinoma-related genes. The genes, regulators and regulatory motifs detected in this work will provide potential drug targets and new strategies for individual therapy.

  1. Curative surgical management of isolated adrenal recurrence of oesophageal adenocarcinoma.

    O'Sullivan, K E


    Adrenal metastases of oesophageal adenocarcinoma are rarely detected in the clinical setting, more frequently being found as an incidental postmortem finding in the presence of widespread metastases. With improvements in the sensitivity of radiological diagnostic modalities, the incidence of adrenal tumour detection is on the rise. We report herein a particularly rare case of primary operative management by adrenalectomy for an isolated right-sided adrenal metastasis secondary to oesophageal adenocarcinoma, with a long-term survival.

  2. [Gastric signet ring cell adenocarcinoma: A distinct entity].

    Tabouret, Tessa; Dhooge, Marion; Rouquette, Alexandre; Brezault, Catherine; Beuvon, Frédéric; Chaussade, Stanislas; Coriat, Romain


    Gastric signet ring cell carcinoma (GSRC) is a distinct entity. Their incidence is increasing. The pathologist plays a central role in the identification of this entity. Diagnosis is based on an adenocarcinoma containing a majority of signet ring cells (above 50 %). The prognosis of GSRC is the same as gastric adenocarcinoma while GSRC appeared more aggressive. Signet ring cells present a low sensitivity to chemotherapy. This review aimed to discuss the histological, the prognostic and the therapeutic aspect of this entity.

  3. Sulindac Prevents Esophageal Adenocarcinomas Induced by Gastroduodenal Reflux in Rats

    Kim, Sung Wook; Jang, Tae Jung; Jung, Ki Hoon; Suh, Jung Il


    Purpose It is known that cyclooxygenase (COX)-2 expression is increased in Barrett's esophagus and esophageal adenocarcinomas. We studied COX-2 expression and the effect sulindac has on the genesis of Barrett's esophagus and adenocarcinoma in rats undergoing esophagogastroduodenal anastomosis (EGDA). Materials and Methods Fifty-one rats were divided into a control group (n = 27), a 500 ppm sulindac-treated group (n = 15) and 1000 ppm sulindac-treated group (n = 9). Randomly selected rats were...

  4. Transcriptomic Profiles Differentiate Normal Rectal Epithelium and Adenocarcinoma


    Adenocarcinoma is a histologic diagnosis based on subjective findings. Transcriptional profiles have been used to differentiate normal tissue from disease and could provide a means of identifying malignancy. The goal of this study was to generate and test transcriptomic profiles that differentiate normal from adenocarcinomatous rectum. Comparisons were made between cDNA microarrays derived from normal epithelium and rectal adenocarcinoma. Results were filtered according to standard deviation ...

  5. Multiple urinary bladder masses from metastatic prostate adenocarcinoma

    Richard Choo


    Full Text Available We present an unusual case of metastatic prostate adenocarcinoma that manifested with multiple exophytic intravesical masses, mimicking a multifocal primary bladder tumor. Biopsy with immunohistochemical analysis confirmed metastatic prostate adenocarcinoma. The patient was treated palliatively with external beam radiotherapy to prevent possible symptoms from local tumor progression. This case illustrates that when a patient with known prostate cancer presents with multifocal bladder tumors, the possibility of metastatic prostate cancer should be considered.

  6. Curative surgical management of isolated adrenal recurrence of oesophageal adenocarcinoma.

    O'Sullivan, K E; Moriarty, A R; Larkin, J O; Reynolds, J V


    Adrenal metastases of oesophageal adenocarcinoma are rarely detected in the clinical setting, more frequently being found as an incidental postmortem finding in the presence of widespread metastases. With improvements in the sensitivity of radiological diagnostic modalities, the incidence of adrenal tumour detection is on the rise. We report herein a particularly rare case of primary operative management by adrenalectomy for an isolated right-sided adrenal metastasis secondary to oesophageal adenocarcinoma, with a long-term survival.

  7. A Rare Case of Aggressive Digital Adenocarcinoma of the Lower Extremity, Masquerading as an Ulcerative Lesion that Clinically Favored Benignancy

    Ryan Vazales


    Full Text Available A rare case report of Aggressive Digital Adenocarcinoma (ADPCa is presented complete with a literature review encompassing lesions that pose potential diagnostic challenges. Similarities between basal cell carcinoma (BCC, marjolin’s ulceration/squamous cell carcinoma (MSCC and ADPCa are discussed. This article discusses potential treatment options for ADPCa and the need for early biopsy when faced with any challenging lesion. An algorithmic approach to ADPCa treatment based on the most current research is recommended.

  8. Analysis of Imp3 Expression in Prostate Adenocarcinomas



    Full Text Available Objective: Prostate cancer is the second most common cause of male cancer deaths after lung cancer in developed countries. The prognostic factors currently identified for prostate carcinoma include preoperative serum PSA, TNM staging system, histological grade and surgical margin status and are composed of the clinically most important and useful parameters. However, all the markers studied have not been applied in clinical practice. The oncofetal protein Insulin-Like Growth Factor II has been demonstrated to be associated with aggressive tumor behavior in many organs including urothelial tumors and renal cell carcinoma. Our aim was to investigate the expression status of Insulin-Like Growth Factor II in benign prostate glands, high grade PIN and prostate adenocarcinoma, and to determine the role of Insulin-Like Growth Factor II in pathogenesis of prostate adenocarcinoma.Material and Method: A total of 70 prostate adenocarcinoma cases accompanied by high grade PIN and benign prostate glands were evaluated by immunohistochemistry for the expression of Insulin-Like Growth Factor II.Results: Insulin-Like Growth Factor II expression was not seen in any of the 70 prostate adenocarcinoma and high grade PIN cases and benign prostate glands.Conclusion: Although the number of our cases was limited, our results suggested that Insulin-Like Growth Factor II protein expression was not included in the pathogenesis of the prostate adenocarcinomas and Insulin-Like Growth Factor II expression status cannot be used for diagnosis of prostate adenocarcinomas.

  9. Intramucosal adenocarcinoma of the ileum originated 40 years after ileosigmoidostomy

    Sameshima Shinichi


    Full Text Available Abstract Background Small bowel adenocarcinomas (SBAs are rare carcinomas. They are asymptomatic and usually neither endoscopy nor contrast studies are performed for screening Case presentation A 72-year-old Japanese male had a positive fecal occult blood test at a regular check-up in 2006. He suffered appendicitis and received an ileosigmoidostomy in 1966. A colonoscopy revealed an irregular mucosal lesion with an unclear margin at the ileum side of the anastomosis. A mucosal biopsy specimen showed adenocarcinoma histopathologically. Excision of the anastomosis was performed for this patient. The resected specimen showed a flat mucosal lesion with a slight depression at the ileum adjacent to the anastomosis. Histological examination revealed a well differentiated intramucosal adenocarcinoma (adenocarcinoma in situ. Immunohistological staining demonstrated the overexpression of p53 protein in the adenocarcinoma. Conclusion Adenocarcinoma of the ileum at such an early stage is a very rare event. In this case, there is a possibility that the ileosigmoidostomy resulted in a back flow of colonic stool to the ileum that caused the carcinogenesis of the small intestine.

  10. Adenocarcinoma primário do duodeno



    Full Text Available OBJETIVO: Revisar a literatura especializada a respeito dos adenocarcinomas duodenais primários e comparar os dados com os aspectos observados nesta casuística. MÉTODOS: Seis doentes com esta neoplasia, excluídas as lesões peri-ampulares, foram operados na Área de Estômago e Duodeno do Departamento de Cirurgia da Santa Casa de São Paulo, entre 1991 e 1999. Houve predominância do tumor no sexo masculino e na 6feminine década de vida. Os sinais e sintomas mais freqüentes foram o emagrecimento (83,3% e a obstrução intestinal crônica (66,6%, com média de duração de seis meses. A gastroduodenoscopia fez o diagnóstico, posteriormente confirmado pela histologia. Utilizamos a tomografia computadorizada e a ultra-sonografia para determinar o estádio da doença. Em três pacientes com lesão restrita à parede do órgão, praticou-se a ressecção duodenal segmentar curativa, e nos outros três, a derivação duodenal paliativa, pois o tumor infiltrava órgãos adjacentes. RESULTADOS: O tempo de internação pós-operatória variou de 5 a 9 dias, com média de 7,3 dias. A mortalidade operatória foi 16,6% (um doente. Não indicamos tratamento complementar com quimio ou radioterapia. O acompanhamento ambulatorial vem ocorrendo em períodos que variam de 15 a 20 meses. Os três pacientes submetidos à ressecção cirúrgica curativa estão sem evidências de recidiva até o 15masculine, 16masculine e 18masculine mês de pós-operatório. Houve seguimento de um e três meses nos dois pacientes submetidos a cirurgias paliativas, depois do que se perderam. CONCLUSÃO: O pequeno número de casos relatados não permitiu conclusões mais consistentes a respeito dos adenocarcinomas duodenais.

  11. Adenocarcinoma of the GEJ: gastric or oesophageal cancer?

    Rüschoff, J


    According to WHO (2010) adenocarcinomas of the esophagogastric junction (GEJ) are defined as tumors that cross the most proximal extent of the gastric folds regardless of where the bulk of the tumor lies. In addition, these neoplasms are now classified as esophageal cancers by UICC (2010). Recent studies, however, revealed two types of carcinogenesis in the distal oesophagus and at the GEJ, one of intestinal type (about 80 %) and the other of gastric type (about 20 %). These are characterized by marked differences in morphology, tumor stage at diagnosis, and prognosis. Furthermore, both cancer types show different targetable biomarker expression profiles such as Her2 in the intestinal and EGFR in the non-intestinal pathway indicating new therapy options. Due to the fact that carcinomas of the intestinal pathway were typically associated with Barrett's mucosa which was not the case in the non-intestinal-type tumors, this challenges the paradigm "no goblets no Barrett's". Moreover, even the cancer risk of intestinal-type metaplasia has seriously been questioned by a Danish population-based study where Barrett's mucosa turned out to be only a weak indicator of esophageal and GEJ cancer (1 case in 860 patients years). Thus, two biologically different types of cancer arise at the GEJ-esophageal and gastric type that open distinctive targeted treatment options and also question our current concept about the diagnostics of potential precursor lesions as well as the associated screening and surveillance strategy.

  12. Role of Nampt and Visceral Adiposity in Esophagogastric Junction Adenocarcinoma

    Haijun Li


    Full Text Available Nampt including eNampt and iNampt may contribute to mediating obesity-associated cancers. This study investigated the role of Nampt in esophagogastric junction adenocarcinoma (EGA, a cancer strongly correlated with obesity. Visceral adiposity was defined by waist circumference or VFA. eNampt in sera were measured by enzyme-linked immunosorbent assay. iNampt expression in EGA was determined by PCR, western blot, and immunohistochemistry. Sera eNampt were significantly elevated in these overweight and obese patients, especially for viscerally obese patients, and positively correlated with BMI, waist circumference, VFA, and also primary tumor, regional lymph nodes, and TNM stage (P<0.05. iNampt expression in both the mRNA and protein levels was upregulated in EGAs (P<0.05. iNampt staining was found primarily in the cytoplasm and nuclei and significantly associated with tumor, lymph nodes, and TNM stage and also correlated positively with serum eNampt, BMI, total fat area, VFA, superficial fat area, and waist circumference (P<0.05. iNampt, eNampt, tumor, lymph nodes, and TNM stage correlated to the survival of EGAs, and iNampt expression and TNM stage affected the prognosis independently (P<0.05. This study highlighted the association of eNampt/iNampt with visceral obesity and a potential impact on the biology of EGA.

  13. The HSP90 Inhibitor Ganetespib Radiosensitizes Human Lung Adenocarcinoma Cells

    Gomez-Casal, Roberto; Bhattacharya, Chitralekha [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Medicine, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Epperly, Michael W. [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Radiation Oncology, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Basse, Per H. [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Immunology, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Wang, Hong [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Biostatistics, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Wang, Xinhui [Harvard Medical School, Harvard University, 25 Shattuck Street, Boston, MA 02115 (United States); Proia, David A. [Synta Pharmaceuticals Corp., 45 Hartwell Avenue, Lexington, MA 02421 (United States); Greenberger, Joel S. [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Radiation Oncology, The University of Pittsburgh, Pittsburgh, PA 15213 (United States); Socinski, Mark A.; Levina, Vera, E-mail: [The University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213 (United States); Department of Medicine, The University of Pittsburgh, Pittsburgh, PA 15213 (United States)


    The molecular chaperone HSP90 is involved in stabilization and function of multiple client proteins, many of which represent important oncogenic drivers in NSCLC. Utilization of HSP90 inhibitors as radiosensitizing agents is a promising approach. The antitumor activity of ganetespib, HSP90 inhibitor, was evaluated in human lung adenocarcinoma (AC) cells for its ability to potentiate the effects of IR treatment in both in vitro and in vivo. The cytotoxic effects of ganetespib included; G2/M cell cycle arrest, inhibition of DNA repair, apoptosis induction, and promotion of senescence. All of these antitumor effects were both concentration- and time-dependent. Both pretreatment and post-radiation treatment with ganetespib at low nanomolar concentrations induced radiosensitization in lung AC cells in vitro. Ganetespib may impart radiosensitization through multiple mechanisms: such as down regulation of the PI3K/Akt pathway; diminished DNA repair capacity and promotion of cellular senescence. In vivo, ganetespib reduced growth of T2821 tumor xenografts in mice and sensitized tumors to IR. Tumor irradiation led to dramatic upregulation of β-catenin expression in tumor tissues, an effect that was mitigated in T2821 xenografts when ganetespib was combined with IR treatments. These data highlight the promise of combining ganetespib with IR therapies in the treatment of AC lung tumors.

  14. Ad-IRF-1 Induces Apoptosis in Esophageal Adenocarcinoma

    Gregory A. Watson


    Full Text Available The nuclear transcription factor interferon regulatory factor-1 (IRF-1 is a putative tumor suppressor, but the expression and function of IRF-1 in esophageal adenocarcinoma (EA remain unknown. We hypothesized that IRF-1 expression was reduced or lost in EA and that restoration of IRF-1 would result in the apoptosis of EA cells in vitro and the inhibition of tumor growth in vivo. Three EA cell lines were used to examine IRF-1 expression, IFN-γ responsiveness, and the effects of IRF-1 overexpression using a recombinant adenoviral vector (Ad-IRF-1. All three EA cell lines produced IRF-1 protein following IFN-γ stimulation, although IFN-γ did not induce cell death. In contrast, Ad-IRF-1 infection resulted in high levels of IRF-1 protein and triggered apoptosis in all three EA cell lines. Potential mechanisms for the differential response to IFN-γ versus Ad-IRF-1-such as modulation of c-Met or extracellular regulated kinase signaling, or altered expression of IRF-2, Fas, or survivin-were investigated, but none of these mechanisms can account for this observation. In vivo administration of IRF-1 in a murine model of EA modestly inhibited tumor growth, but did not lead to tumor regression. Strategies aimed at increasing or restoring IRF-1 expression may have therapeutic benefits in EA.

  15. Study of aggressiveness prediction of mammary adenocarcinoma by Raman spectroscopy

    Andrade Bitar, Renata; da Silva Martinho, Herculano; Zambelli Ramalho, Leandra Náira; dos Santos Junior, Arnaldo Rodrigues; Silva Ramalho, Fernando; Raniero, Leandro; Martin, Airton A.


    Although there are many articles focused on in vivo or ex vivo Raman analysis for cancer diagnosis, to the best of our knowledge its potential to predict the aggressiveness of tumor has not been fully explored yet. In this work Raman spectra in the finger print region of ex vivo breast tissues of both healthy mice (normal) and mice with induced mammary gland tumors (abnormal) were measured and associated to matrix metalloproteinase-19 (MMP-19) immunohistochemical exam. It was possible to verify that normal breast, benign lesions, and adenocarcinomas spectra, including the subtypes (cribriform, papillary and solid) could have their aggressiveness diagnosed by vibrational Raman bands. By using MMP- 19 exam it was possible to classify the samples by malignant graduation in accordance to the classification results of Principal Component Analysis (PCA). The spectra NM /MH were classified correctly in 100% of cases; CA/CPA group had 60 % of spectra correctly classified and for PA/AS 54% of the spectra were correctly classified.

  16. The incremental benefit of EUS for identifying unresectable disease among adults with pancreatic adenocarcinoma: A meta-analysis

    James, Paul D.; Zhang, Mei; Belletrutti, Paul J.; Mohamed, Rachid; Ghali, William; Roberts, Derek J.; Martel, Guillaume; Heitman, Steven J.


    Background and study aims It is unclear to what extent EUS influences the surgical management of patients with pancreatic adenocarcinoma. This systematic review sought to determine if EUS evaluation improves the identification of unresectable disease among adults with pancreatic adenocarcinoma. Patients and methods We searched MEDLINE, EMBASE, bibliographies of included articles and conference proceedings for studies reporting original data regarding surgical management and/or survival among patients with pancreatic adenocarcinoma, from inception to January 7th 2017. Our main outcome was the incremental benefit of EUS for the identification of unresectable disease (IBEUS). The pooled IBEUS were calculated using random effects models. Heterogeneity was explored using stratified meta-analysis and meta-regression. Results Among 4,903 citations identified, we included 8 cohort studies (study periods from 1992 to 2007) that examined the identification of unresectable disease (n = 795). Random effects meta-analysis suggested that EUS alone identified unresectable disease in 19% of patients (95% confidence interval [CI], 10–33%). Among those studies that considered portal or mesenteric vein invasion as potentially resectable, EUS alone was able to identify unresectable disease in 14% of patients (95% CI 8–24%) after a CT scan was performed. Limitations The majority of the included studies were retrospective. Conclusions EUS evaluation is associated with increased identification of unresectable disease among adults with pancreatic adenocarcinoma. PMID:28319148

  17. Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1 and 3 in Gastric and Esophageal Adenocarcinoma.

    Charlotta Hedner

    Full Text Available Gastric and esophageal adenocarcinomas are major global cancer burdens. These cancer forms are characterized by a poor prognosis and a modest response to chemo- radio- and targeted treatment. Hence there is an obvious need for further enhanced diagnostic and treatment strategies. The aim of this study was to examine the expression and prognostic impact of human epidermal growth factor receptor 1 (HER1/EGFR and 3 (HER3, as well as the occurrence of EGFR and KRAS mutations in gastric and esophageal adenocarcinoma.Immunohistochemical expression of EGFR and HER3 was analysed in all primary tumours and a subset of lymph node metastases in a consecutive cohort of 174 patients with adenocarcinoma of the stomach, cardia and esophagus. The anti-HER3 antibody used was validated by siRNA-mediated knockdown, immunohistochemistry and quantitative real-time PCR. EGFR and KRAS mutation status was analysed by pyrosequencing tecchnology.High EGFR expression was an independent risk factor for shorter overall survival (OS, whereas high HER3 expression was associated with a borderline significant trend towards a longer OS. KRAS mutations were present in only 4% of the tumours and had no prognostic impact. All tumours were EGFR wild-type. These findings contribute to the ongoing efforts to decide on the potential clinical value of different HERs and druggable mutations in gastric and esophageal adenocarcinomas, and attention is drawn to the need for more standardised investigational methods.

  18. Comprehensive molecular characterization of gastric adenocarcinoma

    Bass, Adam J.; Thorsson, Vesteinn; Shmulevich, Ilya; Reynolds, Sheila M.; Miller, Michael; Bernard, Brady; Hinoue, Toshinori; Laird, Peter W.; Curtis, Christina; Shen, Hui; Weisenberger, Daniel J.; Schultz, Nikolaus; Shen, Ronglai; Weinhold, Nils; Kelsen, David P.; Bowlby, Reanne; Chu, Andy; Kasaian, Katayoon; Mungall, Andrew J.; Robertson, A. Gordon; Sipahimalani, Payal; Cherniack, Andrew; Getz, Gad; Liu, Yingchun; Noble, Michael S.; Pedamallu, Chandra; Sougnez, Carrie; Taylor-Weiner, Amaro; Akbani, Rehan; Lee, Ju-Seog; Liu, Wenbin; Mills, Gordon B.; Yang, Da; Zhang, Wei; Pantazi, Angeliki; Parfenov, Michael; Gulley, Margaret; Piazuelo, M. Blanca; Schneider, Barbara G.; Kim, Jihun; Boussioutas, Alex; Sheth, Margi; Demchok, John A.; Rabkin, Charles S.; Willis, Joseph E.; Ng, Sam; Garman, Katherine; Beer, David G.; Pennathur, Arjun; Raphael, Benjamin J.; Wu, Hsin-Ta; Odze, Robert; Kim, Hark K.; Bowen, Jay; Leraas, Kristen M.; Lichtenberg, Tara M.; Weaver, Stephanie; McLellan, Michael; Wiznerowicz, Maciej; Sakai, Ryo; Getz, Gad; Sougnez, Carrie; Lawrence, Michael S.; Cibulskis, Kristian; Lichtenstein, Lee; Fisher, Sheila; Gabriel, Stacey B.; Lander, Eric S.; Ding, Li; Niu, Beifang; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Brooks, Denise; Butterfield, Yaron S. N.; Carlsen, Rebecca; Chu, Andy; Chu, Justin; Chuah, Eric; Chun, Hye-Jung E.; Clarke, Amanda; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Li, Haiyan A.; Lim, Emilia; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Nip, Ka Ming; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Beroukhim, Rameen; Carter, Scott L.; Cherniack, Andrew D.; Cho, Juok; Cibulskis, Kristian; DiCara, Daniel; Frazer, Scott; Fisher, Sheila; Gabriel, Stacey B.; Gehlenborg, Nils; Heiman, David I.; Jung, Joonil; Kim, Jaegil; Lander, Eric S.; Lawrence, Michael S.; Lichtenstein, Lee; Lin, Pei; Meyerson, Matthew; Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Schumacher, Steven E.; Sougnez, Carrie; Stojanov, Petar; Tabak, Barbara; Taylor-Weiner, Amaro; Voet, Doug; Rosenberg, Mara; Zack, Travis I.; Zhang, Hailei; Zou, Lihua; Protopopov, Alexei; Santoso, Netty; Parfenov, Michael; Lee, Semin; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Pantazi, Angeliki; Xi, Ruibin; Bristow, Christopher A.; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Kim, Sang-Bae; Lee, Ju-Seog; Lu, Yiling; Mills, Gordon; Laird, Peter W.; Hinoue, Toshinori; Weisenberger, Daniel J.; Bootwalla, Moiz S.; Lai, Phillip H.; Shen, Hui; Triche, Timothy; Van Den Berg, David J.; Baylin, Stephen B.; Herman, James G.; Getz, Gad; Chin, Lynda; Liu, Yingchun; Murray, Bradley A.; Noble, Michael S.; Askoy, B. Arman; Ciriello, Giovanni; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Lee, William; Ramirez, Ricardo; Sander, Chris; Schultz, Nikolaus; Senbabaoglu, Yasin; Sinha, Rileen; Sumer, S. Onur; Sun, Yichao; Weinhold, Nils; Thorsson, Vésteinn; Bernard, Brady; Iype, Lisa; Kramer, Roger W.; Kreisberg, Richard; Miller, Michael; Reynolds, Sheila M.; Rovira, Hector; Tasman, Natalie; Shmulevich, Ilya; Ng, Santa Cruz Sam; Haussler, David; Stuart, Josh M.; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Verhaak, Roeland G.W.; Mills, Gordon B.; Leiserson, Mark D. M.; Raphael, Benjamin J.; Wu, Hsin-Ta; Taylor, Barry S.; Black, Aaron D.; Bowen, Jay; Carney, Julie Ann; Gastier-Foster, Julie M.; Helsel, Carmen; Leraas, Kristen M.; Lichtenberg, Tara M.; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Wise, Lisa; Zmuda, Erik; Penny, Robert; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Curely, Erin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Shelton, Troy; Shelton, Candace; Sherman, Mark; Benz, Christopher; Lee, Jae-Hyuk; Fedosenko, Konstantin; Manikhas, Georgy; Potapova, Olga; Voronina, Olga; Belyaev, Smitry; Dolzhansky, Oleg; Rathmell, W. Kimryn; Brzezinski, Jakub; Ibbs, Matthew; Korski, Konstanty; Kycler, Witold; ŁaŸniak, Radoslaw; Leporowska, Ewa; Mackiewicz, Andrzej; Murawa, Dawid; Murawa, Pawel; Spychała, Arkadiusz; Suchorska, Wiktoria M.; Tatka, Honorata; Teresiak, Marek; Wiznerowicz, Maciej; Abdel-Misih, Raafat; Bennett, Joseph; Brown, Jennifer; Iacocca, Mary; Rabeno, Brenda; Kwon, Sun-Young; Penny, Robert; Gardner, Johanna; Kemkes, Ariane; Mallery, David; Morris, Scott; Shelton, Troy; Shelton, Candace; Curley, Erin; Alexopoulou, Iakovina; Engel, Jay; Bartlett, John; Albert, Monique; Park, Do-Youn; Dhir, Rajiv; Luketich, James; Landreneau, Rodney; Janjigian, Yelena Y.; Kelsen, David P.; Cho, Eunjung; Ladanyi, Marc; Tang, Laura; McCall, Shannon J.; Park, Young S.; Cheong, Jae-Ho; Ajani, Jaffer; Camargo, M. Constanza; Alonso, Shelley; Ayala, Brenda; Jensen, Mark A.; Pihl, Todd; Raman, Rohini; Walton, Jessica; Wan, Yunhu; Demchok, John A.; Eley, Greg; Mills Shaw, Kenna R.; Sheth, Margi; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Davidsen, Tanja; Hutter, Carolyn M.; Sofia, Heidi J.; Burton, Robert; Chudamani, Sudha; Liu, Jia


    Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies. PMID:25079317

  19. Novel pancreatic cancer cell lines derived from genetically engineered mouse models of spontaneous pancreatic adenocarcinoma: applications in diagnosis and therapy.

    María P Torres

    Full Text Available Pancreatic cancer (PC remains one of the most lethal human malignancies with poor prognosis. Despite all advances in preclinical research, there have not been significant translation of novel therapies into the clinics. The development of genetically engineered mouse (GEM models that produce spontaneous pancreatic adenocarcinoma (PDAC have increased our understanding of the pathogenesis of the disease. Although these PDAC mouse models are ideal for studying potential therapies and specific genetic mutations, there is a need for developing syngeneic cell lines from these models. In this study, we describe the successful establishment and characterization of three cell lines derived from two (PDAC mouse models. The cell line UN-KC-6141 was derived from a pancreatic tumor of a Kras(G12D;Pdx1-Cre (KC mouse at 50 weeks of age, whereas UN-KPC-960 and UN-KPC-961 cell lines were derived from pancreatic tumors of Kras(G12D;Trp53(R172H;Pdx1-Cre (KPC mice at 17 weeks of age. The cancer mutations of these parent mice carried over to the daughter cell lines (i.e. Kras(G12D mutation was observed in all three cell lines while Trp53 mutation was observed only in KPC cell lines. The cell lines showed typical cobblestone epithelial morphology in culture, and unlike the previously established mouse PDAC cell line Panc02, expressed the ductal marker CK19. Furthermore, these cell lines expressed the epithelial-mesenchymal markers E-cadherin and N-cadherin, and also, Muc1 and Muc4 mucins. In addition, these cell lines were resistant to the chemotherapeutic drug Gemcitabine. Their implantation in vivo produced subcutaneous as well as tumors in the pancreas (orthotopic. The genetic mutations in these cell lines mimic the genetic compendium of human PDAC, which make them valuable models with a high potential of translational relevance for examining diagnostic markers and therapeutic drugs.

  20. Deep learning relevance

    Lioma, Christina; Larsen, Birger; Petersen, Casper


    train a Recurrent Neural Network (RNN) on existing relevant information to that query. We then use the RNN to "deep learn" a single, synthetic, and we assume, relevant document for that query. We design a crowdsourcing experiment to assess how relevant the "deep learned" document is, compared......What if Information Retrieval (IR) systems did not just retrieve relevant information that is stored in their indices, but could also "understand" it and synthesise it into a single document? We present a preliminary study that makes a first step towards answering this question. Given a query, we...... to existing relevant documents. Users are shown a query and four wordclouds (of three existing relevant documents and our deep learned synthetic document). The synthetic document is ranked on average most relevant of all....

  1. High-resolution array comparative genomic hybridization in sporadic and celiac disease-related small bowel adenocarcinomas.

    Diosdado, B.; Buffart, T.E.; Watkins, R.; Carvalho, B.; Ylstra, B.; Tijssen, M.; Bolijn, A.S.; Lewis, F.; Maude, K.; Verbeke, C.; Nagtegaal, I.D.; Grabsch, H.; Mulder, C.J.; Quirke, P.; Howdle, P.; Meijer, G.A.


    PURPOSE: The molecular pathogenesis of small intestinal adenocarcinomas is not well understood. Understanding the molecular characteristics of small bowel adenocarcinoma may lead to more effective patient treatment. EXPERIMENTAL DESIGN: Forty-eight small bowel adenocarcinomas (33 non-celiac disease

  2. The predictive and prognostic values of factors associated with visceral pleural involvement in resected lung adenocarcinomas

    Zhang HB


    Full Text Available Huibiao Zhang,1 Chen Lu,2 Yingjie Lu,1 Bo Yu,2 Fanzhen Lv,1 Zhenghong Zhu1 1Department of Thoracic Surgery, 2Department of Pathology, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China Background: The predictive and prognostic impact of factors associated with visceral pleural invasion (VPI on survival and recurrence in patients with resected lung adenocarcinomas is not clearly defined.Patients and methods: A total of 505 consecutive patients with stage Ia–IIIa lung adenocarcinomas treated with radical resection were included. The predominant growth pattern was classified according to the new classification system for lung adenocarcinoma proposed by the International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society. The correlations of VPI with clinical and pathologic parameters were analyzed.Results: The incidence of VPI was significantly lower in lepidic predominant group (15.5% vs 4.5%, P<0.001 and higher in solid and micropapillary predominant group (28.6% vs 17.6%, P=0.004 and 14.7% vs 4.2%, P<0.001, respectively. VPI correlated with higher risk in regional postoperative recurrence (hazard ratio, 2.341; 95% confidence interval, 1.564–3.504 and distant recurrence (hazard ratio, 2.193; 95% confidence interval, 1.665–2.89 in surgically resected lung adenocarcinomas. However, when growth patterns of adenocarcinoma were lumped into multivariate analysis, VPI was not a significant independent predictive factor for survival (P=0.854 for overall survival [OS] and P=0.575 for disease-free survival [DFS] and recurrence (P=0.38 for regional recurrence and P=0.089 for distant recurrence. Of the 95 patients with stage Ib, those who received adjuvant chemotherapy had longer DFS and OS than the patients who received no chemotherapy after surgery. However, these differences in DFS and OS did not reach statistical significance (P=0.063 for DFS, P=0.85 for OS

  3. Prognostic role of sex steroid receptors in pancreatic adenocarcinoma.

    Georgiadou, Despoina; Sergentanis, Theodoros N; Sakellariou, Stratigoula; Vlachodimitropoulos, Dimitris; Psaltopoulou, Theodora; Lazaris, Andreas C; Gounaris, Antonia; Zografos, George C


    From the available literature, it is unclear what proportion of pancreatic adenocarcinomas express estrogen receptors (ERα, ERβ), progesterone receptors (PR), and androgen receptors (AR), and if any of these markers have prognostic significance. We aimed to assess (1) the expression and (2) the correlation of the aforementioned markers with clinicopathological parameters and prognosis in patients with pancreatic adenocarcinoma. During a five-year period, 60 patients with pancreatic ductal adenocarcinoma underwent surgical resection at a single institution. Immunohistochemical stains of the studied markers were quantified by Image analysis system. ERα expression was positively associated with PR expression. Moreover, ERβ was inversely associated with the presence of metastases, whereas no significant associations implicated AR. As far as the prognostic significance of the studied receptors is concerned, higher ERα expression correlated with poorer survival at the univariate analysis, but the finding dissipated at the multivariate approach. No significant associations with overall survival were noted regarding the other receptors. The role of sex hormone receptors in the survival from pancreatic adenocarcinoma seems rather limited. Further prospective studies assessing those receptors should ideally be designed in order to confirm our results and possibly outline additional correlations between other steroid receptors and features of pancreatic adenocarcinoma.

  4. ATM protein is deficient in over 40% of lung adenocarcinomas.

    Villaruz, Liza C; Jones, Helen; Dacic, Sanja; Abberbock, Shira; Kurland, Brenda F; Stabile, Laura P; Siegfried, Jill M; Conrads, Thomas P; Smith, Neil R; O'Connor, Mark J; Pierce, Andrew J; Bakkenist, Christopher J


    Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year.

  5. Clinicopathologic features of incidental prostatic adenocarcinoma in radical cystoprostatectomy specimens

    Vuruskan Hakan


    Full Text Available Abstract Background The aim of this study is to review all features of incidentally discovered prostate adenocarcinoma in patients undergoing radical cystoprostatectomy for bladder cancer. Methods The medical charts of 300 male patients who underwent radical cystoprostatectomy for bladder cancer between 1997 and 2005 were retrospectively reviewed. The mean age of the patients was 62 (range 51-75 years. Results Prostate adenocarcinoma was present in 60 (20% of 300 specimens. All were acinar adenocarcinoma. Of these, 40 (66.7% were located in peripheral zone, 20 (33.3% had pT2a tumor, 12 (20% had pT2b tumor, 22(36.7% had pT2c and, 6 (10% had pT3a tumor. Gleason score was 6 or less in 48 (80% patients. Surgical margins were negative in 54 (90% patients, and tumor volume was less than 0.5 cc in 23 (38.3% patients. Of the 60 incidentally detected cases of prostate adenocarcinoma 40 (66.7% were considered clinically significant. Conclusion Incidentally detected prostate adenocarcinoma is frequently observed in radical cystoprostatectomy specimens. The majority are clinically significant.

  6. Effects of Glycyrrhizin in a Mouse Model of Lung Adenocarcinoma

    Qing-Ping Deng


    Full Text Available Background: Currently, there is a global attempt to identify potential anti-cancer agents with low toxicity. Previous studies have found that glycyrrhizin exerts anti-cancer action with low toxicity through suppressing thromboxane A2 (TxA2 in lung cancer cell lines. However, these effects have not yet been determined in animal models of lung cancer. Methods: Human lung adenocarcinoma xenografts were established in nude mice by the introduction of A549 cells with stable transfection of the TxA2 receptor (TPα. The animal model was confirmed by the hematoxylin and eosin (H&E method. Tumor-bearing mice were then administered graded concentrations of glycyrrhizin, cisplatin or both. After the treatments, body weights of all animals were recorded, and immunohistochemistry staining of lung tissues and serum biochemistry detection of aspartate amino transferase (AST, alanine amino transferase (ALT, urea and creatinine were carried out. Results: Treatment with glycyrrhizin alone or the combination of cisplatin and glycyrrhizin profoundly reduced expression of thromboxane synthase (TxAS as well as proliferating cell nuclear antigen (PCNA, recovered the body weight, and rescued damage of liver and kidney in tumor-bearing mice. Although it inhibited PCNA expression, cisplatin could not significantly suppress TxAS expression. Because of a positive feedback loop between TPα and TxAS, the effects of glycyrrhizin are possibly attributable to the suppression of the TxA2 pathway. Conclusions: This study provides in vivo evidence to support glycyrrhizin as a potential candidate for developing new regimens to overcome tumor progression and the resistance and toxicity of cisplatin.

  7. Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma

    Leo; Alexandre; Elizabeth; Long; Ian; LP; Beales


    In recent decades there has been a dramatic rise in the incidence of esophageal adenocarcinoma(EAC) in the developed world. Over approximately the same period there has also been an increase in the prevalence of obesity. Obesity, especially visceral obesity, is an important independent risk factor for the development of gastro-esophageal reflux disease, Barrett’s esophagus and EAC. Although the simplest explanation is that this mediated by the mechanical effects of abdominal obesity promoting gastro-esophageal reflux, the epidemiological data suggest that the EAC-promoting effects are independent of reflux. Several, not mutually exclusive, mechanisms have been implicated, which may have different effects at various points along the refluxBarrett’s-cancer pathway. These mechanisms include a reduction in the prevalence of Helicobacter pylori infection enhancing gastric acidity and possibly appetite byincreasing gastric ghrelin secretion, induction of both low-grade systemic inflammation by factors secreted by adipose tissue and the metabolic syndrome with insulin-resistance. Obesity is associated with enhanced secretion of leptin and decreased secretion of adiponectin from adipose tissue and both increased leptin and decreased adiponectin have been shown to be independent risk factors for progression to EAC. Leptin and adiponectin have a set of mutually antagonistic actions on Barrett’s cells which appear to influence the progression of malignant behaviour. At present no drugs are of proven benefit to prevent obesity associated EAC. Roux-en-Y reconstruction is the preferred bariatric surgical option for weight loss in patients with reflux. Statins and aspirin may have chemopreventative effects and are indicated for their circulatory benefits.

  8. Clinicopathologial features of gastric hepatoid adenocarcinoma

    Cheng-Yu Lin


    Full Text Available Background: Gastric hepatoid adenocarcinoma (GHA, a rare type of primary gastric cancer, is characterized by hepatocellular carcinoma-like histology. As details of this disease remain unknown, the aim of this study was to evaluate the clinicopathological features of GHA. Methods: From January 2001 to December 2010, 4563 patients were diagnosed with primary gastric cancer at Chang Gung Memorial Hospital, Linkou Medical Center. Ten (0.22% of these patients were diagnosed with GHA. The clinicopathological characteristics of these patients were collected retrospectively. Results: The median age at diagnosis was 65.5 years, and six patients (60% were male. Seven patients had lymph node metastasis and five had distant metastasis, with the liver as the most common site (four cases. Serum alpha-fetoprotein (AFP levels were elevated in seven of eight patients (median: 359.2 ng/ml; range: 4.3-6535.6 ng/ml. Endoscopically, six tumors were classified as Borrmann's type III cancer with the appearance of fungating mass lesion with a purple, berry-like surface. Of the five patients without distant metastasis, all received curative-intent surgery and four received adjuvant chemotherapy. Four patients with distant metastasis received either palliative operation or chemotherapy, and one patient received neither operation nor chemotherapy due to a poor performance status. The median survival time was 7.2 months (range: 0.7-131.8 months, and the 5-year survival rate was 20%. There was survival benefit in the chemotherapy groups. Conclusions: GHA is a rare subtype of gastric cancer which is prone to lymph node and liver metastasis. Most GHAs appear as Borrmann's type III fungating mass lesion with a purple, berry-like surface. Although the prognosis of advanced stage GHA is poor, chemotherapy might provide some benefit.

  9. Fuzziness and Relevance Theory

    Grace Qiao Zhang


    This paper investigates how the phenomenon of fuzzy language, such as `many' in `Mary has many friends', can be explained by Relevance Theory. It is concluded that fuzzy language use conforms with optimal relevance in that it can achieve the greatest positive effect with the least processing effort. It is the communicators themselves who decide whether or not optimal relevance is achieved, rather than the language form (fuzzy or non-fuzzy) used. People can skillfully adjust the deployment of different language forms or choose appropriate interpretations to suit different situations and communication needs. However, there are two challenges to RT: a. to extend its theory from individual relevance to group relevance; b. to embrace cultural considerations (because when relevance principles and cultural protocols are in conflict, the latter tends to prevail).

  10. Perceptions of document relevance

    Peter eBruza


    Full Text Available This article presents a study of how humans perceive the relevance of documents.Humans are adept at making reasonably robust and quick decisions about what information is relevant to them, despite the ever increasing complexity and volume of their surrounding information environment. The literature on document relevance has identified various dimensions of relevance (e.g., topicality, novelty, etc., however little is understood about how these dimensions may interact.We performed a crowdsourced study of how human subjects judge two relevance dimensions in relation to document snippets retrieved from an internet search engine.The order of the judgement was controlled.For those judgements exhibiting an order effect, a q-test was performed to determine whether the order effects can be explained by a quantum decision model based on incompatible decision perspectives.Some evidence of incompatibility was found which suggests incompatible decision perspectives is appropriate for explaining interacting dimensions of relevance.

  11. Relevance Theory in Translation

    Shao Jun; Jiang Min


    In perspective of relevance theory, translation is regarded as communication. According to relevance theory, communication not only requires encoding, transfer and decoding processes, but also involves inference in addition. As communication, translation decision-making is also based on the human beings' inferential mental faculty. Concentrating on relevance theory, this paper tries to analyze and explain some translation phenomena in two English versions of Cai Gen Tan-My Crude Philosophy of Life.

  12. Medroxyprogesterone in Treating Patients With Endometrioid Adenocarcinoma of the Uterine Corpus


    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Recurrent Uterine Corpus Carcinoma; Stage I Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage III Uterine Corpus Cancer; Stage IV Uterine Corpus Cancer

  13. Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas

    Wu, Kui; Zhang, Xin; Li, Fuqiang


    The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13...

  14. Mesonephric adenocarcinoma of the cervix: Case report and literature review

    A. Dierickx


    Full Text Available A mesonephric adenocarcinoma of the cervix is a very rare tumor deriving from remnants of the mesonephric duct. Differential diagnosis from other cervical carcinomas is difficult and little is known regarding its biological behavior, prognosis, and the optimal management strategy. We present a case of a mesonephric adenocarcinoma of the cervix with a comprehensive review of the existing literature. In this case a 66-year-old woman presented with postmenopausal vaginal bleeding. She was diagnosed with a FIGO stage IIB mesonephric adenocarcinoma of the cervix and treated with neoadjuvant chemoradiotherapy and a Wertheim hysterectomy. The recovery from surgery was uneventful and the patient remains with no evidence of disease with 2 years of follow-up.

  15. Endometrial Adenocarcinoma and Mucocele of the Appendix: An Unusual Coexistence

    Ioannis Kalogiannidis


    Full Text Available Appendiceal mucocele is a rare clinical entity, which is however quite often associated with mucinous ovarian tumor. The coexistence of mucinous cystadenoma of the appendix and endometrial adenocarcinoma has not been reported before. A 49-year-old woman presented to our clinic with postmenopausal bleeding and no other symptom. Endometrial biopsy revealed endometrial adenocarcinoma of endometrioid type (grade I. Preoperative CT scanning revealed an appendiceal mucocele, and a colonoscopy confirmed the diagnosis. The patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and appendectomy. The final histopathological examination showed a mucinous cystadenoma of the appendix and confirmed the diagnosis of endometrioid endometrial adenocarcinoma. The coexistence of appendiceal mucocele and female genital tract pathology is rare. However, gynecologists should keep a high level of suspicion for such possible coexistence. Both the diagnostic approach and the therapeutic management should be multidisciplinary, most importantly with the involvement of general surgeons.

  16. Primary adenocarcinoma of ureter: A rare histopathological variant

    Prekshi Chaudhary


    Full Text Available Primary carcinoma of ureter is an uncommon malignancy. Of which, mostly are transitional cell carcinomas followed by squamous cell carcinomas and adenocarcinomas being the rarest histopathology encountered. We report a case of adenocarcinoma ureter in a middle-aged male along with its clinical scenario. A 62-year-old male, presented with complaints of lower urinary tract symptoms. Computerized tomography urogram showed a soft tissue lesion at the right ureterovesical junction. Cystoscopic biopsy reported villous adenoma. Diethylene triamine pentaacetic acid scan reported nonfunctioning right kidney. He underwent laparoscopic right nephroureterectomy, and histopathology reported adenocarcinoma of the right lower third of ureter, with positive distal and close radial margins. The patient received external beam radiation to the postoperative bed and lymph nodes, and he is disease-free till date.

  17. Current Standards and Novel Treatment Options for Metastatic Pancreatic Adenocarcinoma.

    Weinberg, Benjamin A; Yabar, Cinthya S; Brody, Jonathan R; Pishvaian, Michael J


    Pancreatic cancer is one of the most lethal solid tumors. The prognosis of metastatic pancreatic adenocarcinoma remains dismal, with a median survival of less than 1 year, due in large part to the fact that pancreatic adenocarcinoma is notoriously refractory to chemotherapy. However, there recently have been significant improvements in outcomes for patients with pancreatic adenocarcinoma: ongoing trials have shown promise, and these may lead to still further progress. Here we review the current treatment paradigms for metastatic disease, focusing on ways to ameliorate symptoms and lengthen survival. We then summarize recent advances in our understanding of the molecular and cellular aspects of pancreatic cancer. Finally, we outline new approaches currently under development for the treatment of metastatic disease, arising from our improved understanding of the genetic and nongenetic alterations within pancreatic cancer cells-and of interactions between cancer cells, the tumor microenvironment, and the immune system.

  18. Adenocarcinoma involving the tongue and the epiglottis in a horse.

    Laus, Fulvio; Rossi, Giacomo; Paggi, Emanuele; Bordicchia, Matteo; Fratini, Margherita; Tesei, Beniamino


    Tumors involving the oral cavity of the horse are uncommon. No cases of equine adenocarcinoma on the dorsum of the tongue have been reported in the literature. We report a case of adenocarcinoma located on the dorsum of the posterior one-third of the tongue in a 29-year-old gelding with severe dysphagia. Endoscopy revealed an epiglottis involvement, and histology was consistent with adenocarcinoma arising from minor salivary glands, which was associated with a severe fungal colonization of affected tissues. The goals of this report are to present an uncommon case of dorsum of the tongue-associated neoplasia and to highlight the association with atypical fungal colonization, to review the literature and to discuss possible clinical approach and prognosis.

  19. Mitochondrial genome instability in colorectal adenoma and adenocarcinoma.

    de Araujo, Luiza F; Fonseca, Aline S; Muys, Bruna R; Plaça, Jessica R; Bueno, Rafaela B L; Lorenzi, Julio C C; Santos, Anemari R D; Molfetta, Greice A; Zanette, Dalila L; Souza, Jorge E S; Valente, Valeria; Silva, Wilson A


    Mitochondrial dysfunction is regarded as a hallmark of cancer progression. In the current study, we evaluated mitochondrial genome instability and copy number in colorectal cancer using Next Generation Sequencing approach and qPCR, respectively. The results revealed higher levels of heteroplasmy and depletion of the relative mtDNA copy number in colorectal adenocarcinoma. Adenocarcinoma samples also presented an increased number of mutations in nuclear genes encoding proteins which functions are related with mitochondria fusion, fission and localization. Moreover, we found a set of mitochondrial and nuclear genes, which cooperate in the same mitochondrial function simultaneously mutated in adenocarcinoma. In summary, these results support an important role for mitochondrial function and genomic instability in colorectal tumorigenesis.

  20. Gastric signet-ring adenocarcinoma presenting with breast metastasis

    Anastasios L Boutis; Charalambos Andreadis; Frideriki Patakiouta; Despina Mouratidou


    Breast metastases from gastric cancer are extremely rare. A case report of a 37-year-old female with breast inflammatory invasion and ascites is described. Breast biopsy revealed carcinomatous invasion of the lymphatics from adenocarcinoma cells with signet-ring features.Estrogen (ER) and progesterone receptors (PR) and c-erb-B2 were negative. Upper gastrointestinal endoscopy revealed a prepyloric ulcerative mass. Histopathologic examination of the lesion showed infiltration from a highgrade adenocarcinoma, identical with that of the breast.Immunostaining was positive for cytokeratins CK-7 and CK-20 and CEA and negative for ER and PR. Ascitic fluid cytology was positive for adenocarcinoma cells. Mammography was not diagnostic. Abdominal CT scanning revealed large ovarian masses suggestive of metastases (Krukenberg's tumor). A cisplatin-based regimen was given but no objective response was observed. The patient died six months after initial diagnosis. A review of the literature is performed.

  1. Duodenal adenocarcinoma: Advances in diagnosis and surgical management

    Jordan M Cloyd; Elizabeth George; Brendan C Visser


    Duodenal adenocarcinoma is a rare but aggressive malignancy. Given its rarity, previous studies have traditionally combined duodenal adenocarcinoma(DA) with either other periampullary cancers or small bowel adenocarcinomas, limiting the available data to guide treatment decisions. Nevertheless, management primarily involves complete surgical resection when technically feasible. Surgery may require pancreaticoduodenectomy or segmental duodenal resection; either are acceptable options as long as negative margins are achievable and an adequate lymphadenectomy can be performed. Adjuvant chemotherapy and radiation are important components of multi-modality treatment for patients at high risk of recurrence. Further research would benefit from multiinstitutional trials that do not combine DA with other periampullary or small bowel malignancies. The purpose of this article is to perform a comprehensive review of DA with special focus on the surgical management and principles.

  2. Absorption spectra of adenocarcinoma and squamous cell carcinoma cervical tissues

    Ivashko, Pavlo; Peresunko, Olexander; Zelinska, Natalia; Alonova, Marina


    We studied a methods of assessment of a connective tissue of cervix in terms of specific volume of fibrous component and an optical density of staining of connective tissue fibers in the stroma of squamous cancer and cervix adenocarcinoma. An absorption spectra of blood plasma of the patients suffering from squamous cancer and cervix adenocarcinoma both before the surgery and in postsurgical periods were obtained. Linear dichroism measurements transmittance in polarized light at different orientations of the polarization plane relative to the direction of the dominant orientation in the structure of the sample of biotissues of stroma of squamous cancer and cervix adenocarcinoma were carried. Results of the investigation of the tumor tissues showed that the magnitude of the linear dichroism Δ is insignificant in the researched spectral range λ=280-840 nm and specific regularities in its change observed short-wave ranges.

  3. Gastric adenocarcinoma of fundic gland type: Endoscopicand clinicopathological features


    Gastric adenocarcinoma of fundic gland type (GA-FG)with chief cell differentiation was recently proposed asan extremely rare type of gastric adenocarcinoma. Here,we report 4 cases of GA-FG with chief cell differentiation.Endoscopic features included a submucosal tumor shapeor a flat shape, whitish discolorationand dilated vesselson the surface. The tumors were located in the upper ormiddle third of the stomach. All cases were preoperativelydiagnosed as GA-FG by biopsy, and endoscopic submucosaldissection was performed. Resected specimensrevealed well-differentiated adenocarcinomas resemblingchief cells. Tumor cells were diffusely positive for pepsinogen-Ⅰ,but partially positive for H+/K+-ATPase inscattered locations around the tumor margin. Despitethe presence of minimal invasion of the carcinoma intothe submucosal layer, which was observed in two cases,neither lymphatic nor venous invasion was detected inany of the cases. Finally, all cases showed less aggressiveclinical behavior with low grade malignancy.

  4. Adenocarcinoma in an ano-vaginal fistula in Crohn's disease

    Alfa-Wali, Maryam; Atinga, Angela; Mohsen, Yasser; Anthony, Andrew; Myers, Alistair


    INTRODUCTION Fistulas are a relatively common occurrence in Crohn's disease (CD), and often present early in the disease process. Additionally, patients suffering from either CD or ulcerative colitis are shown to have an increased risk of colorectal malignancies compared with the general population. PRESENTATION OF CASE We present a case of adenocarcinoma in an ano-vaginal fistula in a patient with longstanding CD. DISCUSSION Various pathogenic mechanisms for the development of carcinoma in fistulas have been suggested, but there is no consensus and indeed this risk may be cumulative. In this case report, we also discuss the pathogenesis of mucinous adenocarcinoma in fistulas secondary to CD. CONCLUSION Better detection of adenocarcinoma in patients presenting with persistent non-resolving fistulas in the presence of CD should be undertaken with regular biopsies following examinations under anaesthetic of the anorectum. PMID:23702362

  5. Pancreatic adenocarcinoma in type 2 progressive familial intrahepatic cholestasis

    Green Richard M


    Full Text Available Abstract Background BSEP disease results from mutations in ABCB11, which encodes the bile salt export pump (BSEP. BSEP disease is associated with an increased risk of hepatobiliary cancer. Case Presentation A 36 year old woman with BSEP disease developed pancreatic adenocarcinoma at age 36. She had been treated with a biliary diversion at age 18. A 1.7 × 1.3 cm mass was detected in the pancreas on abdominal CT scan. A 2 cm mass lesion was found at the neck and proximal body of the pancreas. Pathology demonstrated a grade 2-3 adenocarcinoma with invasion into the peripancreatic fat. Conclusions Clinicians should be aware of the possibility of pancreatic adenocarcinoma in patients with BSEP disease.

  6. The Impact on Clinical Practice of Endoscopic Ultrasonography Used for the Diagnosis and Staging of Pancreatic Adenocarcinoma

    Queneau PE


    Full Text Available CONTEXT: Endoscopic ultrasonography is considered a highly accurate procedure for diagnosing small pancreatic tumors and assessing their locoregional extension. OBJECTIVE: To evaluate the impact of endoscopic ultrasonography on the management of pancreatic adenocarcinoma in clinical practice. PATIENTS: Sixty-four consecutive patients (mean age 70.5 plus/minus 11.9 years hospitalized for staging or diagnosis of pancreatic adenocarcinoma were retrospectively (from January 1995 to November 1997 or prospectively studied (from December 1997 to August 1999. SETTING: Group 1 consisted of 52 patients with pancreatic adenocarcinoma which was discovered using computerized tomography scanning and/or ultrasound. Endoscopic ultrasonography was utilized for staging purposes only in patients who were considered to be operable and the tumor to be resectable based on computerized tomography scanning criteria. Group 2 consisted of 12 patients who were diagnosed as having a pancreatic adenocarcinoma using endoscopic ultrasonography whereas computerized tomography scanning and ultrasound was negative. MAIN OUTCOME MEASURES: The impact of endoscopic ultrasonography was analyzed on the basis of the number of patients requiring endoscopic ultrasonography as a staging procedure (Group 1 and by evaluating the performance of endoscopic ultrasonography in determining resectability (Groups 1 and 2 based on the surgical and anatomopathological results. RESULTS: Endoscopic ultrasonography was performed in 20 out of 64 patients (31.3%: 8/52 in Group 1 (15.4% and all 12 patients of Group 2. Endoscopic ultrasonography correctly assessed an absolute contraindication to resection in 11 cases. Resection was confirmed in 8 of the 9 cases selected by endoscopic ultrasonography. The positive predictive value, negative predictive value and overall accuracy of endoscopic ultrasonography for determining resection were 89%, 100%, and 95%, respectively. CONCLUSIONS: The impact of

  7. Making Science Relevant

    Eick, Charles; Deutsch, Bill; Fuller, Jennifer; Scott, Fletcher


    Science teachers are always looking for ways to demonstrate the relevance of science to students. By connecting science learning to important societal issues, teachers can motivate students to both enjoy and engage in relevant science (Bennet, Lubben, and Hogarth 2007). To develop that connection, teachers can help students take an active role in…

  8. Tratamento paliativo do adenocarcinoma gástrico Palliative treatment of gastric adenocarcinoma

    Fernando de Oliveira Souza


    Full Text Available INTRODUÇÃO: Embora decrescendo nos países do chamado primeiro mundo, o adenocarcinoma gástrico mantém-se como terceiro tumor mais frequente no sexo masculino mundialmente. Sua mortalidade é muito elevada, fruto do diagnóstico tardio em lesões muito avançadas, o que frequentemente torna paliativo seu tratamento, motivos pelos quais se justificam estudos no sentido de melhorar estes resultados. MÉTODO: Revisão da literatura através do portal de periódicos da CAPES indicados por busca no sites da Bireme e PubMed. Além disso, foram consultados os sumários do 8º Congresso Internacional de Câncer Gástrico em 2009. Foi apresentada uma sugestão de algoritmo de atendimento destes pacientes. CONCLUSÕES: O surgimento de novas drogas anticancer, mais efetivas, está propiciando novas alternativas para a ressecção gástrica como tratamento paliativo. Novos protocolos estão surgindo mostrando boas perspectivas para melhorar os resultados desta doença.INTRODUCTION: Although decreasing in the well developed countries, gastric adenocarcinoma still represents the third most common cancer in males worldwide. Its mortality is very high because of the lateness of its diagnosis over advanced lesions, which turns palliative its treatment in the majority of the cases. METHOD: Literature review using CAPES, PubMed and Bireme sites as well as the abstracts of the 8 º International Gastric Cancer Congress which was held in Krakow in 2009. CONCLUSIONS: The release of new anticancer drugs against gastric cancer is providing a revival of gastrectomy as an effective palliative treatment of advanced gastric cancer. New protocols are being published, showing better results in the treatment of this disease.

  9. Metastatic Ampullary Adenocarcinoma Presenting as a Hydrocele: A Case Report

    Whitney O Lane


    Full Text Available Context Metastases from ampullary malignancies are common, but spread to the testicle and paratesticular tissue is exceedingly rare with only 2 reported cases in the literature. Case Report We report a case of a 70 year-old male with a history of ampullary adenocarcinoma status post pancreaticoduodenectomy who presented with a symptomatic right-sided hydrocele. Subsequent pathology revealed metastatic ampullary adenocarcinoma. Conclusions Metastasis to the testicle and paratesticular tissue from ampullary malignancies is rare, but must be considered in the evaluation of scrotal masses in patients with a history of ampullary malignancy.

  10. Primary pulmonary adenocarcinoma in a 16-year-old boy

    Måreng, Ane Stillits; Langer, Seppo W; Bodtger, Uffe


    Primary pulmonary adenocarcinoma in children or adolescents is a rare disease, and as such, there are no randomised studies on lung cancer for this age group. Treatment choice is extrapolated from studies in adults (mean age of participants: 60 years). We present the 5-year follow-up of a 16-year......-old boy who presented with metastatic primary pulmonary adenocarcinoma (T3N3M1a) and was treated aggressively, including radiation therapy for local and distant recurrence. He had complete remission, had completed his education, was employed full-time, and suffered only from mild side effects to treatment....

  11. Neurinoma del plexo braquial simulando metastasis de adenocarcinoma de mama

    Gregorio Rodríguez Boto; Angela Moreno-Gutiérrez; Raquel Gutiérrez-González; Ángel Villar-Martín; Luis A. Arraez-Aybar; Javier Serrano Hernando


    Los neurinomas del plexo braquial son tumores infrecuentes que pueden confundirse con otras lesiones de índole tumoral. Se presenta el caso de una mujer de 40 años, tratada previamente de un adenocarcinoma de mama derecha en el pasado, que en el estudio de extensión realizado 5 años después se detectó una lesión localizada en el plexo braquial derecho. La paciente se encontraba asintomática. El diagnóstico radiológico de presunción fue metástasis de adenocarcinoma mamario. Se realizó un abord...

  12. Isolated axillary lymph node metastasis in oesophageal adenocarcinoma.

    Toh, Vi Vien; Shirley, Rebecca; Duffy, John; Starley, Ian Francis


    Oesophageal adenocarcinoma metastatic to the axilla is a rare occurrence. The authors present a case of a woman who developed an axillary metastasis from a completely excised oesophageal adenocarcinoma with no prior evidence of nodal disease. With aggressive local treatment, including multiple local operations and radiotherapy, she remains alive and disease-free 12 years after her diagnosis following surgical resection of her axillary metastasis with adjuvant radiotherapy. This case report suggests that there are occasions when aggressive local treatment of apparently isolated metastases can result in a cure.

  13. File list: His.Lng.05.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

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  14. File list: NoD.Lng.20.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

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    Full Text Available NoD.Lng.05.AllAg.Lung_adenocarcinoma mm9 No description Lung Lung adenocarcinoma ...

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    Full Text Available ALL.Lng.10.AllAg.Lung_adenocarcinoma mm9 All antigens Lung Lung adenocarcinoma SRX2...RX213848 ...

  1. File list: His.Lng.50.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Full Text Available His.Lng.50.AllAg.Lung_adenocarcinoma mm9 Histone Lung Lung adenocarcinoma SRX213854...58,SRX213853,SRX213863,SRX213849,SRX213862 ...

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    Full Text Available ALL.Lng.50.AllAg.Lung_adenocarcinoma mm9 All antigens Lung Lung adenocarcinoma SRX2...RX213862 ...

  4. File list: ALL.Lng.05.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Full Text Available ALL.Lng.05.AllAg.Lung_adenocarcinoma mm9 All antigens Lung Lung adenocarcinoma SRX2...RX213848 ...

  5. File list: NoD.Lng.10.AllAg.Lung_adenocarcinoma [Chip-atlas[Archive

    Full Text Available NoD.Lng.10.AllAg.Lung_adenocarcinoma mm9 No description Lung Lung adenocarcinoma ...

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    Full Text Available NoD.Lng.50.AllAg.Lung_adenocarcinoma mm9 No description Lung Lung adenocarcinoma ...

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    Full Text Available His.Lng.10.AllAg.Lung_adenocarcinoma mm9 Histone Lung Lung adenocarcinoma SRX213850...63,SRX213852,SRX213862,SRX213857,SRX213848 ...

  8. Novel Agents in the Management of Pancreatic Adenocarcinoma: Phase I Studies

    Anastasios T Dimou


    Full Text Available Pancreatic adenocarcinoma has repetitively proved refractory to chemotherapy and biologic compounds with only a few drugs offering limited benefit. A number of novel regimens has been tested in phase I trials and reported recently in the 2011 American Society of Clinical Oncology (ASCO Gastrointestinal Cancers Symposium. Specifically, a novel mitogen-activated protein kinase kinase (MEK inhibitor, a connective tissue growth factor inhibitor, a coagulase factor VIIa inhibitor, as well as adenovirus delivery of herpes simplex virus thymidine synthase gene followed by anti-herpetic treatment have all proven to be safe in pancreatic cancer patients. Phase II trials will provide further evidence whether they can become clinically relevant in the future.

  9. Dermatomyositis as the first manifestation of gallbladder adenocarcinoma: case report and literature overview.

    Jurcic, Petra


    Dermatomyositis (DM) is characterized by pathognomic cutaneous manifestations (heliotrope rash, periorbital edema, Gottron's papules) and proximal muscle weakness. In this paper, I will present the case of a 48-year-old female patient whose dermatomyositis was initially diagnosed as vasculitis. Following the patient's inadequate response to corticosteroid treatment, clinical and radiologic examinations were performed, showing inoperable gallbladder adenocarcinoma. Although initial chemotherapy led to regression, the dermatomyositis developed an independent course with new pathological changes leading to the progression of the disease. I will also present an overview of case reports in English published so far. Gallbladder carcinoma should be added to the list of malignancies with dermatomyositis and has to be excluded by relevant investigation in women.

  10. Clinical response to chemotherapy in oesophageal adenocarcinoma patients is linked to defects in mitochondria.

    Aichler, Michaela; Elsner, Mareike; Ludyga, Natalie; Feuchtinger, Annette; Zangen, Verena; Maier, Stefan K; Balluff, Benjamin; Schöne, Cédrik; Hierber, Ludwig; Braselmann, Herbert; Meding, Stephan; Rauser, Sandra; Zischka, Hans; Aubele, Michaela; Schmitt, Manfred; Feith, Marcus; Hauck, Stefanie M; Ueffing, Marius; Langer, Rupert; Kuster, Bernhard; Zitzelsberger, Horst; Höfler, Heinz; Walch, Axel K


    Chemotherapeutic drugs kill cancer cells, but it is unclear why this happens in responding patients but not in non-responders. Proteomic profiles of patients with oesophageal adenocarcinoma may be helpful in predicting response and selecting more effective treatment strategies. In this study, pretherapeutic oesophageal adenocarcinoma biopsies were analysed for proteomic changes associated with response to chemotherapy by MALDI imaging mass spectrometry. Resulting candidate proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and investigated for functional relevance in vitro. Clinical impact was validated in pretherapeutic biopsies from an independent patient cohort. Studies on the incidence of these defects in other solid tumours were included. We discovered that clinical response to cisplatin correlated with pre-existing defects in the mitochondrial respiratory chain complexes of cancer cells, caused by loss of specific cytochrome c oxidase (COX) subunits. Knockdown of a COX protein altered chemosensitivity in vitro, increasing the propensity of cancer cells to undergo cell death following cisplatin treatment. In an independent validation, patients with reduced COX protein expression prior to treatment exhibited favourable clinical outcomes to chemotherapy, whereas tumours with unchanged COX expression were chemoresistant. In conclusion, previously undiscovered pre-existing defects in mitochondrial respiratory complexes cause cancer cells to become chemosensitive: mitochondrial defects lower the cells' threshold for undergoing cell death in response to cisplatin. By contrast, cancer cells with intact mitochondrial respiratory complexes are chemoresistant and have a high threshold for cisplatin-induced cell death. This connection between mitochondrial respiration and chemosensitivity is relevant to anticancer therapeutics that target the mitochondrial electron transport chain.

  11. Fluorouracil selectively enriches stem-like cells in the lung adenocarcinoma cell line SPC.

    Shi, Mu-mu; Xiong, Yan-lei; Jia, Xin-shan; Li, Xin; Zhang, Li; Li, Xiao-lei; Wang, En-Hua


    Most adult stem cells are in the G0 or quiescent phase of the cell cycle and account for only a small percentage of the cells in the tissue. Thus, isolation of stem cells from tissues for further study represents a major challenge. This study sought to enrich cancer stem cells and explore cancer stem-like cell clones using 5-fluorouracil (5-FU) in the lung adenocarcinoma cell line, SPC. Proliferation inhibition was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, according to which half maximal inhibitory concentration values were calculated. Expression levels of stem cell markers after treatment with 5-FU were examined using immunofluorescence and Western blotting. Additionally, side population (SP) cells were sorted using FACS. Properties of SP cells were evaluated by using Transwell, colony-forming assays, and tumor formation experiments. 5-FU greatly inhibits proliferation, especially of cells in S phase. SP cells possess greater invasive potential, higher clone-forming potential, and greater tumor-forming ability than non-SP cells. Treatment with 5-FU enriches the SP cells with stem cell properties in human lung adenocarcinoma cell lines.

  12. Characterization of spheres derived from canine mammary gland adenocarcinoma cell lines.

    Michishita, Masaki; Akiyoshi, Rui; Yoshimura, Hisashi; Katsumoto, Takuo; Ichikawa, Hitoshi; Ohkusu-Tsukada, Kozo; Nakagawa, Takayuki; Sasaki, Nobuo; Takahashi, Kimimasa


    There is increasing evidence for the presence of cancer stem cells in several solid tumors, and these cancer stem cells have a potential role in tumor initiation, aggression, and recurrence. The stem cell-like properties of spheres derived from canine mammary tumors remain largely elusive. We attempted to induce sphere formation using four cell lines of canine mammary adenocarcinoma, and characterized the spheres derived from a CHMp line in vitro and in vivo. The CHMp-derived spheres showed predominantly CD44+CD24- population, higher expression of stem cell-related genes, such as CD133, Notch3 and MDR, and higher resistance to doxorubicin compared with the CHMp-derived adherent cells. Xenograft transplantations in nude mice demonstrated that only 1 × 10(4)sphere cells were sufficient for tumor formation. Use of the sphere assay on these sphere-derived tumors showed that sphere-forming cells were present in the tumors, and were maintained in serial transplantation. We propose that spheres derived from canine mammary adenocarcinoma cell lines possess a potential characteristic of cancer stem cells. Spheres derived from canine mammary tumors could be a powerful tool with which to investigate novel therapeutic drugs and to elucidate the molecular and cellular mechanisms that underlie tumorigenesis.

  13. Application of Gold Nanorods for Photothermal Therapy in Ex Vivo Human Oesophagogastric Adenocarcinoma.

    Singh, Mohan; Harris-Birtill, David C C; Zhou, Yu; Gallina, Maria E; Cass, Anthony E G; Hanna, George B; Elson, Daniel S


    Gold nanoparticles are chemically fabricated and tuned to strongly absorb near infrared (NIR) light, enabling deep optical penetration and therapy within human tissues, where sufficient heating induces tumour necrosis. In our studies we aim to establish the optimal gold nanorod (GNR) concentration and laser power for inducing hyperthermic effects in tissues and test this photothermal effect on ex vivo human oesophagogastric adenocarcinoma. The ideal GNR concentration and NIR laser power that would elicit sufficient hyperthermia for tumour necrosis was pre-determined on porcine oesophageal tissues. Human ex vivo oesophageal and gastric adenocarcinoma tissues were incubated with GNR solutions and a GNR-free control solution with corresponding healthy tissues for comparison, then irradiated with NIR light for 10 minutes. Temperature rise was found to vary linearly with both the concentration of GNRs and the laser power. Human ex vivo oesophageal and gastric tissues consistently demonstrated a significant temperature rise when incubated in an optimally concentrated GNR solution (3 x 10(10) GNRs/ml) prior to NIR irradiation delivered at an optimal power (2 W/cm2). A mean temperature rise of 27 degrees C was observed in tissues incubated with GNRs, whereas only a modest 2 degrees C rise in tissues not exposed to any GNRs. This study evaluates the photothermal effects of GNRs on oesophagogastric tissue examines their application in the minimally invasive therapeutics of oesophageal and gastric adenocarcinomas. This could potentially be an effective method of clinically inducing irreversible oesophagogastric tumour photodestruction, with minimal collateral damage expected in (healthy) tissues free from GNRs.

  14. Ghrelin relieves cancer cachexia associated with the development of lung adenocarcinoma in mice.

    Tsubouchi, Hironobu; Yanagi, Shigehisa; Miura, Ayako; Matsumoto, Nobuhiro; Kangawa, Kenji; Nakazato, Masamitsu


    Cancer cachexia is a multifactorial, critical illness syndrome characterized by an ongoing loss of skeletal muscle and adipose tissue. The reductions in body weight and skeletal muscle mass are important prognostic indicators for cancer patients that are refractory to current therapies. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is produced in the stomach, stimulates food intake and growth hormone secretion, suppresses inflammation, and prevents muscle catabolism. We investigated the pharmacological potential of ghrelin in the treatment of cancer cachexia by using urethane-treated, bronchioalveolar epithelium-specific Pten-deficient mice that developed lung adenocarcinomas. Ghrelin or phosphate-buffered saline was given to mice daily for four weeks beginning at five months after urethane injection, which corresponded to the time point of lung adenocarcinoma formation. Ghrelin inhibited the inductions of C-reactive protein, tumor necrosis factor-α, interleukin-1β, and interleukin-6, mitigated the reduction of food intake and fat mass, and consequently ameliorated body weight loss in the mouse model of lung adenocarcinoma. We also demonstrated that skeletal muscle mass and muscle contraction force in both fast-twitch muscle and slow-twitch muscle were retained in ghrelin-treated mice in conjunction with an upregulation of local insulin-like growth factor 1/Akt signaling. In addition, ghrelin administration reduced the expressions of phosphorylated-p38 mitogen-activated protein kinase, phosphorylated-nuclear factor-kappa B, Forkhead box protein O1, muscle RING-finger protein-1, and F-Box protein 32 in the lysates of skeletal muscle in the tumor-bearing state. Our results indicate that ghrelin administration exerts a protective effect against cancer cachexia by ameliorating skeletal muscle wasting and regulating systemic inflammation.

  15. Screening for Early Pancreatic Ductal Adenocarcinoma: An Urgent Call! Highlights from the "2009 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 15-17, 2009

    Michael Xiang Lee


    Full Text Available Cancer of the pancreas is the fourth leading cause of cancer mortality in the United States. The annual death rate from the disease almost equals the annual incidence due to the aggressive nature of the cancer as well as to the lack of effective means of screening for it during its early curable stage. Molecular markers and imaging have not proven to be accurate modalities for screening for pancreatic cancer. The diagnosis and management of pancreatic cancer continues to be an overwhelming challenge. The authors discuss the current status of screening for pancreatic cancer and summarize relevant studies presented in the 2009 GI Cancers Symposium: utility of endoscopic ultrasound in screening high risk patients (Abstract #112, diagnostic performance of a highly specific antibody for MUC1 (Abstract #113, use of metabonomics for the early detection of pancreatic adenocarcinoma (Abstract #126, and a report on the potential impact of delay in diagnosis and treatment on pancreatic cancer outcomes at a tertiary care center (Abstract #137.

  16. Isocitrate dehydrogenase-1 is mutated in inflammatory bowel disease-associated intestinal adenocarcinoma with low-grade tubuloglandular histology but not in sporadic intestinal adenocarcinoma.

    Hartman, Douglas J; Binion, David; Regueiro, Miguel; Schraut, Wolfgang; Bahary, Nathan; Sun, Weijing; Nikiforova, Marina; Pai, Reetesh K


    The underlying molecular alterations in chronic idiopathic inflammatory bowel disease-associated intestinal adenocarcinoma remain largely unknown. Somatic IDH mutations are often seen in gliomas and myeloid leukemia but have also been recently reported in a subset of other neoplasms. We analyzed a series of intestinal adenocarcinomas with (n=23) and without (n=39) associated chronic idiopathic inflammatory bowel disease treated at our institution for IDH1 and IDH2 mutations and correlated the clinicopathologic findings with mutation status. Compared with intestinal adenocarcinomas not associated with inflammatory bowel disease, adenocarcinomas associated with inflammatory bowel disease more frequently demonstrated IDH mutations (13% vs. 0%, P=0.047). All IDH mutations were identified in IDH1 and resulted in substitution of arginine by cysteine at position 132 (p.R132C, c.394C>T). IDH1 mutations were frequently (66%) associated with concurrent KRAS mutations (p.G12D, c.35G>A). IDH1-mutated intestinal adenocarcinomas were seen in the setting of both Crohn disease and ulcerative colitis and were located in both the ileum and colon. Compared with IDH1-negative inflammatory bowel disease-associated adenocarcinoma, IDH1-positive adenocarcinomas more frequently demonstrated tubuloglandular histology (100% vs. 25%, P=0.032) and were more frequently associated with precursor lesions exhibiting serrated morphology (66% vs. 6%, P=0.034). IDH1 mutations were also identified in the precursor dysplastic lesions associated with IDH1-positive adenocarcinomas. In conclusion, we demonstrate that IDH1 mutations are occasionally identified in inflammatory bowel disease-associated intestinal adenocarcinoma but not in intestinal adenocarcinoma not associated with inflammatory bowel disease. In addition, IDH1-mutated intestinal adenocarcinoma is associated with a characteristic low-grade tubuloglandular histology and often harbors concurrent KRAS mutations. Identification of patients

  17. Collision tumor of kidney: A case of renal cell carcinoma with metastases of prostatic adenocarcinoma

    Monika Vyas


    Full Text Available Simultaneous occurrence of prostatic adenocarcinoma and renal cell carcinoma is well documented in the literature. However, metastatic prostatic adenocarcinoma in a kidney harboring a renal cell carcinoma (RCC is quite rare. Although renal cell carcinoma is the most common tumor that can harbor metastasis, metastatic prostatic adenocarcinoma in a kidney harboring a RCC is quite rare. There are four cases in the literature showing metastasis of prostatic adenocarcinoma to RCC. However, as per our knowledge, this is the first case of a collision between RCC and metastatic prostatic adenocarcinoma.

  18. Polymorphous low-grade adenocarcinoma of the nasal fossa.

    González-Lagunas, Javier; Alasà-Caparrós, Cristian; Vendrell-Escofet, Gerard; Huguet-Redecilla, Pere; Raspall-Martin, Guillermo


    An unusual case of a T4N2CMx polymorphous low grade adenocarcinoma located in the nasal fossae and extending to the pterygoid area is presented. The primary tumor was excised through a Lefort I maxillotomy and the neck was managed with a supraomohyoid neck dissection. Adjuntive postoperative radiotherapy was also administered to the patient.

  19. Duodenal adenocarcinoma in a 10-year-old boy.

    Mohamed, Zouari; Habib, Bouthour; Rabia, Ben Abdallah; Youssef, Hlel; Riath, Ben Malek; Youssef, Gharbi; Nejib, Kaabar


    Gastrointestinal malignancies are extremely rare in the paediatric population and duodenal cancers represent an even more unusual entity. It represents 0.3-1% of all gastrointestinal tumours. A case report of a 10-year-old boy with duodenal adenocarcinoma is reported and the difficulties of diagnosing and treating this rare tumour are discussed.

  20. Duodenal adenocarcinoma in a 10-year-old boy

    Zouari Mohamed


    Full Text Available Gastrointestinal malignancies are extremely rare in the paediatric population and duodenal cancers represent an even more unusual entity. It represents 0.3-1% of all gastrointestinal tumours. A case report of a 10-year-old boy with duodenal adenocarcinoma is reported and the difficulties of diagnosing and treating this rare tumour are discussed.

  1. Primary appendiceal adenocarcinoma of colonic type with perforating peritonitis.

    Noguch H


    Full Text Available Primary adenocarcinoma of the appendix is rare, especially the colonic type. We report a case of appendiceal adenocarcinoma of colonic type associated with perforating peritonitis after aorto-femoral artery bypass surgery. A 79-year-old woman presented with fever and pain in the right lower abdomen. She had undergone aorto-femoral artery bypass surgery due to arteriosclerosis obliterans 6 months earlier. Abdominal ultrasonography and computed tomography showed a suspected pool of fluid surrounding the artificial vessel and a mass lesion in the upper end of the fluid collection. These findings suggested localized peritonitis due to appendiceal perforation. Emergency laparotomy showed a pool of pus around the artificial vessel and inflamed appendix, which adhered to the surrounding tissue. The mass was excised in combination with an ileocaecal resection, followed by an ileocolic anastomosis. The histological diagnosis was moderately differentiated adenocarcinoma of the appendix, colonic type. The tumour had infiltrated and obstructed the lumen of the orifice of the appendix, which may have caused perforation of the appendix. She was examined at regular periodic follow-ups and no evidence of recurrence or metastasis was noted in the 12-month postoperative period. These findings indicate that, in cases of acute appendicitis, especially with perforation, the possibility of appendiceal adenocarcinoma should be considered.

  2. Primary Adenocarcinoma of Appendix Presenting as Omental Metastasis

    Arun Gupta, Subhash Bhardwaj, Jyotsna Suri


    Full Text Available The adenocarcinoma of appendix is a rare entity The patients present usually with symptoms ofappendicitis, a palpable abdominal mass or rarely as a complication of pseudomyxoma peritonei,We report a case who presented with lump abdomen and ascitis and revealed a tiny infiltrativegrowth at the base of appendix at laparotomy

  3. From Barrett's Esophagus towards Adenocarcinoma: Genetic and Clinical studies

    L.B. Koppert (Linetta)


    textabstractEsophageal adenocarcinoma is a highly aggressive disease from which more than 80% of patients die within 5 years after diagnosis. Worldwide almost 400,000 new patients are diagnosed annually. Herewith esophageal cancer ranks eighth on the list of most common cancers, and sixth on the lis

  4. The distinctive nature of adenocarcinoma of the lung

    Roviello G


    Full Text Available Giandomenico RovielloDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, ItalyAbstract: In recent years, many personalized treatments have been developed for NSCLC (non-small-cell lung cancer patients. Among these, gefitinib, erlotinib, and afatinib are selective epidermal growth factor receptor (EGFR tyrosine kinase inhibitors for patients with EGFR gene mutations, while crizotinib and ceritinib are two new tyrosine kinase inhibitors directed against the echinoderm microtubule-like protein 4-anaplastic lymphoma kinase translocation. The possibility of these new molecules being used to treat patients without adenocarcinoma histology is notably small. For example, EGFR mutations and anaplastic lymphoma kinase fusion gene rearrangement are rare in patients with squamous cell carcinoma (generally <1%. Additionally, the benefit of targeted treatment approaches in patients with small-cell lung cancer histology is limited. All of these findings highlight the distinctive nature of adenocarcinoma of the lung among all lung cancer subtypes. Unfortunately, to date, less than 15% of patients with adenocarcinoma of the lung are ideal candidates for these targeted therapies.Keywords: lung cancer, adenocarcinoma, EGFR, ALK

  5. Sonic hedgehog-Gli1 pathway in colorectal adenocarcinomas

    Yue-Hong Bian; Shu-Hong Huang; Ling Yang; XiaoLi Ma; Jing-Wu Xie; Hong-Wei Zhang


    AIM: To determine the role of Sonic hedgehog (Shh) pathway in colorectal adenocarcinomas through analysis of the expression of Shh pathway-related molecules, Shh, Ptchl, hedgehog-interacting protein (Hip), Gli1, Gli3 and PDGFRα.METHODS: Expression of Shh in 25 colorectal adenocarcinomas was detected by RT-PCR, in situ hybridization and immunohistochemistry. Expression of Ptchl was observed by in situ hybridization and immunohistochemistry. Expression of Hip, Glil, Gli3 and PDGFRa was analyzed by in situ hybridization.RESULTS: Expression of cytokeratin AE1/AE3 was observed in the cytoplasm of colorectal crypts. Members of the Hh signaling pathway were expressed in colorectal epithelium. Shh was expressed in cytoplasm of dysplastic epithelial cells, while expression of Ptchl, Hip and Glil were mainly detected in the malignant crypts of adenocarcinomas. In contrast, PDGFRa was expressed highly in aberrant crypts and moderately in the stroma. Expression of Gli3 could not be detected in colorectal adenocarcinomas.CONCLUSION: These data suggest that Shh-Ptchl-Gli1 signaling pathway may play a role in the progression of colorectal tumor.

  6. Sudden unilateral deafness with endolymphatic sac adenocarcinoma: MRI

    Gaeta, M.; Blandino, A.; Minutoli, F.; Pandolfo, I. [Inst. of Radiological Sciences, Univ. of Messina (Italy)


    A 30-year-old man presented with sudden left deafness and vertigo. CT showed an osteolytic retrolabyrinthine tumour of the left temporal bone. High signal from the tumour and labyrinth was seen on fat-suppressed T 1-weighted images. At surgery, a haemorrhagic papillary-cystic adenocarcinoma of the endolymphatic sac was found. (orig.)

  7. Management of Adenocarcinoma In Situ of Cervix in Pregnancy

    Alireza Abidi


    Full Text Available Adenocarcinoma in situ is one of the premalignant lesions of the cervix and its incidence is believed to be increasing while the pathogenesis of the disease is not clearly understood. Management of Adenocarcinoma in situ (AIS unlike carcinoma in situ (CIS has not been clearly described in the current literature. Here we describe conservative management and serial colposcopy of two pregnant women with adenocarcinoma in situ of the cervix. Both of the cases were diagnosed initially with abnormal Pap smears and were confirmed by colposcopic directed biopsy. None of the patients agreed with any invasive procedure during pregnancy and both of them were followed with serial colposcopy. None of the lesions showed any evidence of progression. All cases underwent cold knife cone biopsies in their postpartum period. Hysterectomy as the final treatment has been done in both cases with no evidence of progression of the disease during pregnancy. We concluded that adenocarcinoma in situ of the cervix during pregnancy could be managed conservatively with definite treatment postponed till after delivery.

  8. Barrett's esophagus and risk of esophageal adenocarcinoma: A retrospective analysis

    Hung-Wei Wang


    Conclusion: Our study found that BE-associated EAC mostly occurred in older men. In the group with BE-associated EAC, the majority of patients were discovered due to alarm symptoms, at the same time as esophageal adenocarcinoma had already developed. Further prospective study is needed to stratify the risk of disease progression in BE patients.

  9. Anal adenocarcinoma complicating chronic Crohn’s disease

    Ioannis Papaconstantinou


    Conclusion: Albeit a rare complication, clinicians should maintain a high degree of vigilance about the possible development of adenocarcinoma in patients with long-standing perianal Crohn’s disease. Thus, these patients should be kept under regular surveillance with examination under anaesthesia and biopsies or curettage of the tracts.

  10. Conjunctival mucinous adenocarcinoma in an ostrich (Struthio camelus)

    Perrin, Kathryn L; Bertelsen, Mads F; Bartholin, Henrik


    . Gross examination revealed a botryoid mass attached to the inferior palpebral conjunctiva and extending onto the palpebral aspect of the nictitating membrane. Euthanasia was selected, and the histological diagnosis of the second mass was a mixed mucinous adenocarcinoma; however, no acid-fast bacteria...

  11. A case report of metastatic adenocarcinoma of the gingiva

    Buddula Aravind


    Full Text Available Localized gingival enlargement is often associated with specific systemic medication, abscess formation, trauma or reactive lesions. Scant literature is available reporting enlargement of gingiva due the metastasis of adenocarcinoma from lung. The case report presents a unique case of an adenocarcinoma in the lung metastasizing to the buccal and lingual interdental papillae of teeth numbering 34 and 35. A 72-year-old female was referred to the Mayo Clinic with a recent diagnosis of metastatic stage IV adenocarcinoma of the left lung presented with an abnormal mass located on the left posterior buccal keratinized tissue adjacent to teeth numbering 34-35. Biopsy of the lesion was performed for CK7, CK20, TTF-1 and p63. The tumor cells were positive for CK7 and TTF-1, and weakly positive for p63 suggesting a diagnosis of adenocarcinoma. The periodontist may be in the unique position to be the first oral health care provider to evaluate any biopsy suspicious intra-oral lesions.


    Chitrawati Bal


    Full Text Available The gastrointestinal tract is the most common site for malakoplakia outside the urinary tract. A variety of conditions co - exists with malakoplakia including inflammatory bowel disease, systemic lupus erythematosus, immunodeficiency and tuberculosis. Rarely, it is associated with colonic ad enocarcinoma or adenomas. We report a case of malakoplakia in association with colonic adenocarcinoma.

  13. Synchronous Adenocarcinoma of the Colon and Rectal Carcinoid

    Vamshidhar Vootla


    Full Text Available Primary colonic adenocarcinoma and synchronous rectal carcinoids are rare tumors. Whenever a synchronous tumor with a nonmetastatic carcinoid component is encountered, its prognosis is determined by the associate malignancy. The discovery of an asymptomatic gastrointestinal carcinoid during the operative treatment of another malignancy will usually only require resection without additional treatment and will have little effect on the prognosis of the individual. This article reports a synchronous rectal carcinoid in a patient with hepatic flexure adenocarcinoma. We present a case of a 46-year-old Hispanic woman with a history of hypothyroidism, uterine fibroids and hypercholesterolemia presenting with a 2-week history of intermittent abdominal pain, mainly in the right upper quadrant. She had no family history of cancers. Physical examination was significant for pallor. Laboratory findings showed microcytic anemia with a hemoglobin of 6.6 g/dl. CT abdomen showed circumferential wall thickening in the ascending colon near the hepatic flexure and pulmonary nodules. Colonoscopy showed hepatic flexure mass and rectal nodule which were biopsied. Pathology showed a moderately differentiated invasive adenocarcinoma of the colon (hepatic flexure mass and a low-grade neuroendocrine neoplasm (carcinoid of rectum. The patient underwent laparoscopic right hemicolectomy and chemotherapy. In patients diagnosed with adenocarcinoma of the colon and rectum, carcinoids could be missed due to their submucosal location, multicentricity and indolent growth pattern. Studies suggest a closer surveillance of the GI tract for noncarcinoid synchronous malignancy when a carcinoid tumor is detected and vice versa.

  14. Synchronous Adenocarcinoma of the Colon and Rectal Carcinoid

    Vootla, Vamshidhar; Ahmed, Rafeeq; Niazi, Masooma; Balar, Bhavna; Nayudu, Suresh


    Primary colonic adenocarcinoma and synchronous rectal carcinoids are rare tumors. Whenever a synchronous tumor with a nonmetastatic carcinoid component is encountered, its prognosis is determined by the associate malignancy. The discovery of an asymptomatic gastrointestinal carcinoid during the operative treatment of another malignancy will usually only require resection without additional treatment and will have little effect on the prognosis of the individual. This article reports a synchronous rectal carcinoid in a patient with hepatic flexure adenocarcinoma. We present a case of a 46-year-old Hispanic woman with a history of hypothyroidism, uterine fibroids and hypercholesterolemia presenting with a 2-week history of intermittent abdominal pain, mainly in the right upper quadrant. She had no family history of cancers. Physical examination was significant for pallor. Laboratory findings showed microcytic anemia with a hemoglobin of 6.6 g/dl. CT abdomen showed circumferential wall thickening in the ascending colon near the hepatic flexure and pulmonary nodules. Colonoscopy showed hepatic flexure mass and rectal nodule which were biopsied. Pathology showed a moderately differentiated invasive adenocarcinoma of the colon (hepatic flexure mass) and a low-grade neuroendocrine neoplasm (carcinoid of rectum). The patient underwent laparoscopic right hemicolectomy and chemotherapy. In patients diagnosed with adenocarcinoma of the colon and rectum, carcinoids could be missed due to their submucosal location, multicentricity and indolent growth pattern. Studies suggest a closer surveillance of the GI tract for noncarcinoid synchronous malignancy when a carcinoid tumor is detected and vice versa. PMID:27920648

  15. Primary Adenocarcinoma in an Oesophageal Gastric Graft – Case Report

    Dranka-Bojarowska Daria


    Full Text Available Primary adenocarcinoma in the esophageal gastric graft is a rare complication diagnosed in patients with long-term survival. Most data concerning the diagnosis and treatment of patients with metachronic cancer in esophageal grafts is derived from Japan and South Korea. The diagnosis of cancer in esophageal gastric grafts in the European countries is rare.

  16. GATA6 expression in Barrett's oesophagus and oesophageal adenocarcinoma

    Pavlov, Kirill; Honing, Judith; Meijer, Coby; Boersma-van Ek, Wytske; Peters, Frans T. M.; van den Berg, Anke; Karrenbeld, Arend; Plukker, John T. M.; Kruyt, Frank A. E.; Kleibeuker, Jan H.


    Background: Barrett's oesophagus can progress towards oesophageal adenocarcinoma through a metaplasia-dysplasia-carcinoma sequence, but the underlying mechanisms are poorly understood. The transcription factor GATA6 is known to be involved in columnar differentiation and proliferation, and GATA6 gen

  17. GATA6 expression in Barrett's oesophagus and oesophageal adenocarcinoma

    Pavlov, Kirill; Honing, Judith; Meijer, Coby; Boersma-van Ek, Wytske; Peters, Frans T.M.; van den Berg, Anke; Karrenbeld, Arend; Plukker, John T.M.; Kruyt, Frank A.E.; Kleibeuker, Jan H.


    BACKGROUND: Barrett's oesophagus can progress towards oesophageal adenocarcinoma through a metaplasia-dysplasia-carcinoma sequence, but the underlying mechanisms are poorly understood. The transcription factor GATA6 is known to be involved in columnar differentiation and proliferation, and GATA6 gen

  18. Prognostic factors in adenocarcinoma of the esophagus or gastroesophageal junction

    S.M. Lagarde; F.W. ten Kate; J.B. Reitsma; O.R.C. Busch; J.J.B. van Lanschot


    The incidence of adenocarcinoma of the esophagus is rising rapidly in Western Europe and North America. It is an aggressive disease with early lymphatic and hematogenous dissemination. TNM cancer staging systems predict survival on the basis of the anatomic extent of the tumor. However, the adequacy

  19. Criticisms of Relevance Theory

    尚静; 孟晔; 焦丽芳


    This paper briefly introduces first the notion of Sperber and Wilson's Relevance Theory. Then, the motivation of S & W putting forward their RT is also mentioned. Secondly, the paper gives some details about the methodology of RT, in which ostensive-inferential communication, context and optimal relevance are highlighted. Thirdly, the paper focuses on the criticisms of RT from different areas of research on human language and communication. Finally, the paper draws a conclusion on the great importance of RT in pragmatics.

  20. Fisetin, a dietary phytochemical, overcomes Erlotinib-resistance of lung adenocarcinoma cells through inhibition of MAPK and AKT pathways.

    Zhang, Liang; Huang, Yi; Zhuo, Wenlei; Zhu, Yi; Zhu, Bo; Chen, Zhengtang


    Erlotinib (Tarceva) is a selective epidermal growth factor receptor tyrosine kinase inhibitor for treatment of non-small cell lung cancer (NSCLC). However, its efficacy is usually reduced by the occurrence of drug resistance. Our recent study showed that a flavonoid found in many plants, Fisetin, might have a potential to reverse the acquired Cisplatin-resistance of lung adenocarcinoma. In the present study, we aimed to test whether Fisetin could have the ability to reverse Erlotinib-resistance of lung cancer cells. Erlotinib-resistant lung adenocarcinoma cells, HCC827-ER, were cultured from the cell line HCC827, and the effects of Fisetin and Erlotinib on the cell viability and apoptosis were evaluated. The possible signaling pathways in this process were also detected. As expected, the results showed that Fisetin effectively increased sensitivity of Erlotinib-resistant lung cancer cells to Erlotinib, possibly by inhibiting aberrant activation of MAPK and AKT signaling pathways resulted from AXL suppression. In conclusion, Fisetin was a potential agent for reversing acquired Erlotinib-resistance of lung adenocarcinoma. Inactivation of AXL, MAPK and AKT pathways might play a partial role in this process.

  1. Ground-glass nodule on thin-section CT: Differentiation among adenocarcinoma in situ, minimally invasive adenocarcinoma and lepidic predominant invasive adenocarcinoma

    Lee, Man Ho; Ryu, Dae Shick; Kim, Do Young; Ahn, Jae Hong; Choi, Soo Jung; Gang, Gil Hyeon; Yoo, Dong Gon; Shin, Dong Rock [Gangneung Asan Hospital, College of Medicine, University of Ulsan, Gangneung (Korea, Republic of)


    To investigate different computed tomography (CT) features among adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and lepidic predominant invasive adenocarcinoma (LPA) that appeared as ground-glass nodules (GGN). We also analyzed different CT findings between Group A (AIS and MIA) and Group B (LPA). We evaluated 19 AIS, 4 MIA, and 9 LPA images that were histologically confirmed and manifested as GGN on thin-section CT scans. CT scans were assessed for lesion characteristics: size, shape, solid portion, internal air density, marginal irregularity and pleural tag. CT findings of Group A and Group B were analyzed using the Kruskal-Wallis test or Fisher's exact test. A significant statistical difference was seen between AIS and LPA for lesion characteristics (p < 0.05). No significant difference was observed between AIS and MIA. Round or polygonal shape with smooth margin was significantly associated with Group A, and complex shape with marginal irregularity was associated with Group B. Group A (AIS and MIA) could be distinguished from Group B (LPA) by smaller lesion size, round or polygonal shape, smaller solid portion and smooth margin.

  2. Frequencies and prognostic role of KRAS and BRAF mutations in patients with localized pancreatic and ampullary adenocarcinomas

    Schultz, Nicolai Aagaard; Roslind, Anne; Christensen, Ib J


    The frequencies and prognostic role of KRAS and BRAF mutations in patients operated on for pancreatic ductal adenocarcinomas (PDACs) and ampullary adenocarcinomas (A-ACs) are scantily studied.......The frequencies and prognostic role of KRAS and BRAF mutations in patients operated on for pancreatic ductal adenocarcinomas (PDACs) and ampullary adenocarcinomas (A-ACs) are scantily studied....

  3. Adenocarcinoma of the paraurethral glands: a case report.

    Massari, Francesco; Ciccarese, Chiara; Modena, Alessandra; Maines, Francesca; Segala, Diego; Luchini, Claudio; Marcolini, Lisa; Cavicchioli, Francesca; Cavalleri, Stefano; Bria, Emilio; Brunelli, Matteo; Martignoni, Guido; Artibani, Walter; Tortora, Giampaolo


    Adenocarcinoma of the paraurethral glands represents a very rare neoplasm of the urinary tract. Due to the rarity of this disease, there is no standard therapeutic approach. We report a case of adenocarcinoma of the paraurethral glands in a 56-year-old woman, presenting with abnormal serous vaginal discharges. The radiologic examination revealed a 5-cm mass around the urethra, which underwent surgical resection. After surgical resection, the histology revealed a moderately differentiated adenocarcinoma, probably arising from the paraurethral glands. One month later, a pelvic recurrent mass was radiologically diagnosed; consequently, an anterior pelvic exenteration with lymph node dissection was performed. Histological examination revealed a moderately differentiated adenocarcinoma, with glandular and micropapillary architecture, with multiple lymph node metastases. The absence of modifications such as urethritis cystic glandularis on the urethral mucosa, as well as the lack of a lesion in situ, associated with the immunohistochemical expression of PAX8 and negativity for GATA3 and S100p, suggested that the adenocarcinoma originated from the paraurethral glands rather than from the urethral mucosa. Post-surgery CT scans revealed no evidence of metastatic disease. The patient received 6 courses of adjuvant chemotherapy with carboplatin and paclitaxel. One year after the pelvic exenteration, because of inguinal lymph node progression, an inguinal lymphadenectomy was performed. Four months later, a TC-PET revealed a multidistrectual lymph node and a lung micronodule disease progression. Invasive micropapillary carcinomas have been characterized as a rare distinctive variant of carcinomas in several anatomic sites and are distinguished by a marked tendency to lymphovascular invasion, justifying the association with high-stage disease and poor prognosis. In the present case, both the poor prognosis connected with micropapillary structure and the lymph node involvement

  4. Mammary adenocarcinoma in a mare Adenocarcinoma mamário em égua

    Marilene de Farias Brito


    Full Text Available A non-lactating 17-year-old grey barren Mangalarga Marchador mare was referred to the Large Animal Veterinary Hospital of the Federal Rural University of Rio de Janeiro (UFRRJ, presenting enlargement of the mammary gland. The owner reported that the animal had a lesion in the mammary gland for at least two years, diagnosed and treated as chronic mastitis. Initially only the right gland was involved, presenting ulceration and exudation on the cutaneous surface. After 20 months, the left gland also became affected. The diagnosis of tubulo-papillary adenocarcinoma was based on the typical microscopic lesions. This work shows the importance of the histopathological examination in the differential diagnosis between the neoplasms and the chronic inflammation in the mammary gland of mares, as well as, to show that the cytological examination cannot detect the tumor, in case the puncture is made in areas of secondary infection.Uma égua tordilha, Mangalarga Marchador, de 17 anos, não-lactante e não-prenhe, foi encaminhada ao Hospital de Grandes Animais da Universidade Federal Rural do Rio de Janeiro, com histórico de mastite crônica há dois anos. No início da lesão, apenas a glândula mamária direita estava muito aumentada, com exsudação sero-hemorrágica e ulcerada. Após 20 meses, a mama esquerda também estava comprometida. A égua foi tratada para mastite crônica, porém o exame histopatológico revelou tratar-se de um adenocarcinoma túbulo-papilar. Este trabalho evidencia a importância do exame histopatológico no diagnóstico diferencial entre neoplasias e inflamação crônica da mama de éguas, uma vez que o exame citopatológico pode não detectar o tumor, quando a punção é feita em áreas de infecção secundária.

  5. The Limits to Relevance

    Averill, M.; Briggle, A.


    Science policy and knowledge production lately have taken a pragmatic turn. Funding agencies increasingly are requiring scientists to explain the relevance of their work to society. This stems in part from mounting critiques of the "linear model" of knowledge production in which scientists operating according to their own interests or disciplinary standards are presumed to automatically produce knowledge that is of relevance outside of their narrow communities. Many contend that funded scientific research should be linked more directly to societal goals, which implies a shift in the kind of research that will be funded. While both authors support the concept of useful science, we question the exact meaning of "relevance" and the wisdom of allowing it to control research agendas. We hope to contribute to the conversation by thinking more critically about the meaning and limits of the term "relevance" and the trade-offs implicit in a narrow utilitarian approach. The paper will consider which interests tend to be privileged by an emphasis on relevance and address issues such as whose goals ought to be pursued and why, and who gets to decide. We will consider how relevance, narrowly construed, may actually limit the ultimate utility of scientific research. The paper also will reflect on the worthiness of research goals themselves and their relationship to a broader view of what it means to be human and to live in society. Just as there is more to being human than the pragmatic demands of daily life, there is more at issue with knowledge production than finding the most efficient ways to satisfy consumer preferences or fix near-term policy problems. We will conclude by calling for a balanced approach to funding research that addresses society's most pressing needs but also supports innovative research with less immediately apparent application.

  6. Gremlin is overexpressed in lung adenocarcinoma and increases cell growth and proliferation in normal lung cells.

    Michael S Mulvihill

    Full Text Available BACKGROUND: Gremlin, a member of the Dan family of BMP antagonists, is a glycosylated extracellular protein. Previously Gremlin has been shown to play a role in dorsal-ventral patterning, in tissue remodeling, and recently in angiogenesis. Evidence has previously been presented showing both over- and under-expression of Gremlin in different tumor tissues. Here, we sought to quantify expression of Gremlin in cancers of the lung and performed in vitro experiments to check whether Gremlin promotes cell growth and proliferation. METHODOLOGY/PRINCIPAL FINDINGS: Expression of Gremlin in 161 matched tumor and normal lung cancer specimens is quantified by quantitative real-time PCR and protein level is measured by immunohistochemistry. GREM1 was transfected into lung fibroblast and epithelial cell lines to assess the impact of overexpression of Gremlin in vitro. RESULTS: Lung adenocarcinoma but not squamous cell carcinoma shows a significant increase in Gremlin expression by mRNA and protein level. Lung fibroblast and epithelial cell lines transfected with GREM1 show significantly increased cell proliferation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that Gremlin acts in an oncogenic manner in lung adenocarcinoma and could hold promise as a new diagnostic marker or potential therapeutic target in lung AD or general thoracic malignancies.

  7. Sleeping Beauty mutagenesis reveals cooperating mutations and pathways in pancreatic adenocarcinoma.

    Mann, Karen M; Ward, Jerrold M; Yew, Christopher Chin Kuan; Kovochich, Anne; Dawson, David W; Black, Michael A; Brett, Benjamin T; Sheetz, Todd E; Dupuy, Adam J; Chang, David K; Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Grimmond, Sean M; Rust, Alistair G; Adams, David J; Jenkins, Nancy A; Copeland, Neal G


    Pancreatic cancer is one of the most deadly cancers affecting the Western world. Because the disease is highly metastatic and difficult to diagnosis until late stages, the 5-y survival rate is around 5%. The identification of molecular cancer drivers is critical for furthering our understanding of the disease and development of improved diagnostic tools and therapeutics. We have conducted a mutagenic screen using Sleeping Beauty (SB) in mice to identify new candidate cancer genes in pancreatic cancer. By combining SB with an oncogenic Kras allele, we observed highly metastatic pancreatic adenocarcinomas. Using two independent statistical methods to identify loci commonly mutated by SB in these tumors, we identified 681 loci that comprise 543 candidate cancer genes (CCGs); 75 of these CCGs, including Mll3 and Ptk2, have known mutations in human pancreatic cancer. We identified point mutations in human pancreatic patient samples for another 11 CCGs, including Acvr2a and Map2k4. Importantly, 10% of the CCGs are involved in chromatin remodeling, including Arid4b, Kdm6a, and Nsd3, and all SB tumors have at least one mutated gene involved in this process; 20 CCGs, including Ctnnd1, Fbxo11, and Vgll4, are also significantly associated with poor patient survival. SB mutagenesis provides a rich resource of mutations in potential cancer drivers for cross-comparative analyses with ongoing sequencing efforts in human pancreatic adenocarcinoma.

  8. Association of tooth loss and oral hygiene with risk of gastric adenocarcinoma.

    Shakeri, Ramin; Malekzadeh, Reza; Etemadi, Arash; Nasrollahzadeh, Dariush; Abedi-Ardekani, Behnoush; Khoshnia, Masoud; Islami, Farhad; Pourshams, Akram; Pawlita, Michael; Boffetta, Paolo; Dawsey, Sanford M; Kamangar, Farin; Abnet, Christian C


    Poor oral health and tooth loss have been proposed as possible risk factors for some chronic diseases, including gastric cancer. However, a small number of studies have tested these associations. We conducted a case-control study in Golestan Province, Iran, that enrolled 309 cases diagnosed with gastric adenocarcinoma (118 noncardia, 161 cardia, and 30 mixed-locations) and 613 sex, age, and neighborhood matched controls. Data on oral health were obtained through physical examination and questionnaire including tooth loss, the number of decayed, missing, and filled teeth, and frequency of tooth brushing. ORs and 95% confidence intervals (95% CI) were obtained using conditional logistic regression models adjusted for potential confounders. Standard one degree-of-freedom linear trend test and a multiple degree-of-freedom global test of the effect of adding oral hygiene variables to the model were also calculated. Our results showed apparent associations between tooth loss and decayed, missing, filled teeth (DMFT) score with risk of gastric cancer, overall and at each anatomic subsite. However, these associations were not monotonic and were strongly confounded by age. The results also showed that subjects who brushed their teeth less than daily were at significantly higher risk for gastric cardia adenocarcinoma ORs (95% CI) of 5.6 (1.6-19.3). We found evidence for an association between oral health and gastric cancer, but the nonmonotonic association, the relatively strong effect of confounder adjustment, and inconsistent results across studies must temper the strength of any conclusions.

  9. Polymorphous Low-Grade Adenocarcinoma of the Tongue Base Treated by Transoral Robotic Surgery

    Jeong Hong Kim


    Full Text Available Polymorphous low-grade adenocarcinoma is a rare malignancy arising from the minor salivary glands in the aerodigestive system, most frequently the hard palate. The treatment of choice is wide surgical resection, and the efficacy of radiotherapy has not been confirmed. A 54-year-old male presenting with a mass at the base of the tongue performed transoral laser microsurgery. The pathologic diagnosis was polymorphous low-grade adenocarcinoma. Complete surgical excision was performed via transoral robotic surgery without a flap reconstruction of the surgical defect. Without complications of bleeding or injury to the hypoglossal nerve, proper surgical margins were obtained, and no recurrence was found after 6 months after surgery. The patient did not complain of dysphagia or aspiration. We conclude that, in surgery for tongue base tumors with unknown malignant potential, transoral robotic surgery can be considered for achieving a definite resection avoiding a mandibulotomy without complications of dysphagia or aspiration after confirmation of malignancy with a frozen biopsy.

  10. Clinicopathologic features and survival of patients with colorectal mucinous, signet-ring cell or non-mucinous adenocarcinoma:experience at an institution in southern China

    SONG Wu; WU Sui-jing; HE Yu-long; CAI Shi-rong; ZHANG Chang-hua; ZHANG Xin-hua; ZHAN Wen-hua


    Background Previous studies have shown conflicting results on the relation between clinicopathologic features and prognosis of patients with colorectal mucinous, signet-ring cell, or non-mucinous adenocarcinoma; only few such studies have been performed in China. This retrospective study analyzed data from our department to investigate clinicopathologic characteristics, prognosis and possible correlations of three histologic types -- colorectal mucinous,signet-ring cell, and non-mucinous adenocarcinoma, to clarity the bases for observed differences which may lead to development of targeted therapies Methods Of 2079 patients diagnosed with colorectal cancer between 1994 and 2007, 144 had mucinous, 25 had signet-ring cell, and 1837 had non-mucinous adenocarcinoma. Their clinicopathologic parameters and survival were analyzed using established statistical methodologies.Results Mucinous and signet-ring cell adenocarcinomas were common in younger patients (P <0.001). Location, size and disease stage differed significantly among the three types. Signet-ring cell tumors were more commonly found in the rectum than mucinous and non-mucinous adenocarcinoma (P <0.001). Mucinous and signet-ring cell tumors presented in a later stage in life more often than non-mucinous adenocarcinoma, with lymph node involvement, serosal infiltration, peritoneal dissemination, and adjacent organ invasion (P <0.01). The rate of radical resection, hepatic metastasis and local recurrence did not differ among types (P >0.05). Compared with patients with non-mucinous adenocarcinoma, patients with mucinous and signet-ring cell tumors who underwent potentially curative resections or stage Ⅱ/Ⅲ disease had poorer long-term overall survival. Survival did not differ by type for patients with either stage Ⅰor Ⅳ disease (P >0.05). Conclusions Mucinous and signet-ring cell adenocarcinoma have unique carcinogenesis and similar biologic behavior.Our study confirms that both histologic types

  11. Ductal adenocarcinoma of the prostate: immunohistochemical findings and clinical significance

    Sha JJ


    Full Text Available Jianjun Sha,1,2 Juanjie Bo,1 Jiahua Pan,1 Lianhua Zhang,1 Hanqing Xuan,1 Wei Chen,1 Dong Li,1 Zhaoliang Wang,1 Dongming Liu,1 Yiran Huang1,2 1Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 2School of Biomedical Engineering, Shanghai Jiaotong University, Shanghai, People's Republic of China Introduction: To investigate the clinical features, diagnosis, treatment, and prognosis of ductal adenocarcinoma of the prostate. Methods: The clinicopathological and immunohistochemical data of seven patients with ductal adenocarcinoma of the prostate were retrospectively analyzed. All patients underwent physical examination, magnetic resonance imaging (MRI, bone scan, cystoscopy, and computed tomography (CT scan. The level of prostate-specific antigen (PSA before and after surgery was assessed. Different prostate cancer markers were used for immunohistochemical staining. Results: The mean age of the seven patients diagnosed with prostatic ductal adenocarcinoma in this study was 76.2 years (range 57–88. Five patients presented with intermittent and painless gross hematuria, one patient with progressive dysuria, and one patient with elevated serum PSA on routine health examination. The level of PSA before surgery ranged from 1.3 to 45.0 ng/mL. Immunohistochemical staining results of the prostatic ductal adenocarcinoma confirmed positivity for PSA, prostatic acid phosphatase, androgen receptor, and alpha-methyacyl co-enzyme A (CoA-reductase markers. Two of the patients underwent bilateral orchiectomy combined with anti-androgen therapy, three underwent transurethral resection of prostate, one received radical prostatectomy, and one received medical castration therapy. The clinical outcomes of all patients were satisfactory, based on follow-up data. The symptoms of hematuria and dysuria were ameliorated well, and the postoperative PSA level decreased below 4.0 ng/mL. Recurrence or metastasis of disease was

  12. Colonic perforation resulting from ingested chicken bone revealing previously undiagnosed colonic adenocarcinoma: report of a case and review of literature.

    McGregor, Douglas H; Liu, Xiaoying; Ulusarac, Ozlem; Ponnuru, Kimberly D; Schnepp, Stephanie L


    An 86 year old male with a four-day history of nonspecific gastrointestinal symptoms was found on colonoscopy to have evidence of sigmoid colon obstruction and possible perforation. Emergent operative exploration revealed diffuse peritonitis, sigmoid perforation, adjacent dense adhesions, and a foreign body protruding through the perforated area. Pathologic examination showed the foreign body to be a sliver of bone consistent with chicken bone and the sigmoid subacute perforation to be associated distally with a circumferential ulcerated obstructing mass, microscopically seen to be transmurally infiltrating adenocarcinoma, signet-ring cell type. There was extensive acute and organizing peritonitis, 100% Escherichia coli was cultured from peritoneal fluid, and the patient died two days postoperatively with sepsis and hypotension. This appears to be the fifth reported case of colonic perforation resulting from foreign body perforation due to previously undiagnosed adenocarcinoma. The four previously reported cases were all deeply invasive adenocarcinoma of sigmoid colon, and the foreign bodies included three chicken/poultry bones and a metallic staple. These five cases are highly unusual examples of a potentially lethal malignant neoplasm being clinically revealed by a usually (but not always) innocuous event, the ingestion of a small foreign body.

  13. Colonic perforation resulting from ingested chicken bone revealing previously undiagnosed colonic adenocarcinoma: report of a case and review of literature

    Ulusarac Ozlem


    Full Text Available Abstract An 86 year old male with a four-day history of nonspecific gastrointestinal symptoms was found on colonoscopy to have evidence of sigmoid colon obstruction and possible perforation. Emergent operative exploration revealed diffuse peritonitis, sigmoid perforation, adjacent dense adhesions, and a foreign body protruding through the perforated area. Pathologic examination showed the foreign body to be a sliver of bone consistent with chicken bone and the sigmoid subacute perforation to be associated distally with a circumferential ulcerated obstructing mass, microscopically seen to be transmurally infiltrating adenocarcinoma, signet-ring cell type. There was extensive acute and organizing peritonitis, 100% Escherichia coli was cultured from peritoneal fluid, and the patient died two days postoperatively with sepsis and hypotension. This appears to be the fifth reported case of colonic perforation resulting from foreign body perforation due to previously undiagnosed adenocarcinoma. The four previously reported cases were all deeply invasive adenocarcinoma of sigmoid colon, and the foreign bodies included three chicken/poultry bones and a metallic staple. These five cases are highly unusual examples of a potentially lethal malignant neoplasm being clinically revealed by a usually (but not always innocuous event, the ingestion of a small foreign body.

  14. High Goblet Cell Count Is Inversely Associated with Ploidy Abnormalities and Risk of Adenocarcinoma in Barrett's Esophagus.

    Amitabh Srivastava

    Full Text Available Goblet cells may represent a potentially successful adaptive response to acid and bile by producing a thick mucous barrier that protects against cancer development in Barrett's esophagus (BE. The aim of this study was to determine the relationship between goblet cells (GC and risk of progression to adenocarcinoma, and DNA content flow cytometric abnormalities, in BE patients.Baseline mucosal biopsies (N=2988 from 213 patients, 32 of whom developed cancer during the follow up period, enrolled in a prospective dynamic cohort of BE patients were scored in a blinded fashion, for the total number (# of GC, mean # of GC/crypt (GC density, # of crypts with ≥ 1 GC, and the proportion of crypts with ≥1 GC, in both dysplastic and non-dysplastic epithelium separately. The relationship between these four GC parameters and DNA content flow cytometric abnormalities and adenocarcinoma outcome was compared, after adjustment for age, gender, and BE segment length.High GC parameters were inversely associated with DNA content flow cytometric abnormalities, such as aneuploidy, ploidy >2.7N, and an elevated 4N fraction > 6%, and with risk of adenocarcinoma. However, a Kaplan-Meier analysis showed that the total # of GC and the total # crypts with ≥1 GC were the only significant GC parameters (p<0.001 and 0.003, respectively.The results of this study show, for the first time, an inverse relationship between high GC counts and flow cytometric abnormalities and risk of adenocarcinoma in BE. Further studies are needed to determine if GC depleted foci within esophageal columnar mucosa are more prone to neoplastic progression or whether loss of GC occurs secondary to underlying genetic abnormalities.

  15. Is Information Still Relevant?

    Ma, Lia


    Introduction: The term "information" in information science does not share the characteristics of those of a nomenclature: it does not bear a generally accepted definition and it does not serve as the bases and assumptions for research studies. As the data deluge has arrived, is the concept of information still relevant for information…

  16. The Relevance of Literature.

    Dunham, L. L.


    The "legacy" of the humanities is discussed in terms of relevance, involvement, and other philosophical considerations. Reasons for studying foreign literature in language classes are developed in the article. Comment is also made on attitudes and ideas culled from the writings of Clifton Fadiman, Jean Paul Sartre, and James Baldwin. (RL)

  17. Relevant Subspace Clustering

    Müller, Emmanuel; Assent, Ira; Günnemann, Stephan;


    Subspace clustering aims at detecting clusters in any subspace projection of a high dimensional space. As the number of possible subspace projections is exponential in the number of dimensions, the result is often tremendously large. Recent approaches fail to reduce results to relevant subspace c...

  18. A rapid in vivo screen for pancreatic ductal adenocarcinoma therapeutics

    Ozhan Ocal


    Full Text Available Pancreatic ductal adenocarcinoma (PDA is the fourth leading cause of cancer-related deaths in the United States, and is projected to be second by 2025. It has the worst survival rate among all major cancers. Two pressing needs for extending life expectancy of affected individuals are the development of new approaches to identify improved therapeutics, addressed herein, and the identification of early markers. PDA advances through a complex series of intercellular and physiological interactions that drive cancer progression in response to organ stress, organ failure, malnutrition, and infiltrating immune and stromal cells. Candidate drugs identified in organ culture or cell-based screens must be validated in preclinical models such as KIC (p48Cre;LSL-KrasG12D;Cdkn2af/f mice, a genetically engineered model of PDA in which large aggressive tumors develop by 4 weeks of age. We report a rapid, systematic and robust in vivo screen for effective drug combinations to treat Kras-dependent PDA. Kras mutations occur early in tumor progression in over 90% of human PDA cases. Protein kinase and G-protein coupled receptor (GPCR signaling activates Kras. Regulators of G-protein signaling (RGS proteins are coincidence detectors that can be induced by multiple inputs to feedback-regulate GPCR signaling. We crossed Rgs16::GFP bacterial artificial chromosome (BAC transgenic mice with KIC mice and show that the Rgs16::GFP transgene is a KrasG12D-dependent marker of all stages of PDA, and increases proportionally to tumor burden in KIC mice. RNA sequencing (RNA-Seq analysis of cultured primary PDA cells reveals characteristics of embryonic progenitors of pancreatic ducts and endocrine cells, and extraordinarily high expression of the receptor tyrosine kinase Axl, an emerging cancer drug target. In proof-of-principle drug screens, we find that weanling KIC mice with PDA treated for 2 weeks with gemcitabine (with or without Abraxane plus inhibitors of Axl signaling

  19. Etiologic factors of gastric cardiac adenocarcinoma among men in Taiwan

    Mei-Ju Chen; Deng-Chyang Wu; Jia-Ming Lin; Ming-Tsang Wu; Fung-Chang Sung


    AIM: To elucidate etiologic associations between Helicobacter pylori ( H pylori), lifestyle, environmental factors and gastric cardiac adenocarcinoma (GCA) among men.METHODS: A hospital-based case-control study was conducted in Taiwan from 2000 to 2009.All cases were newly confirmed as primary GCA.Five controls were selected matching with age, sex, and admission date to each case.Participants were informed of potential risk factors with a structured questionnaire by trained interviewers during hospitalization and provided a blood sample for the determination of H pylori infection.Odds ratio (OR) and 95% confidence interval (95% CI) were used to evaluate risk, and a multivariate conditional logistic regression model was performed.RESULTS: All participants recruited for this study were men, consisting of 41 cases and 205 controls.Results of the univariate analysis showed that significant factors associated with the etiology of GCA included H pylori (OR = 2.69, 95% CI = 1.30-5.53), cigarette smoking (OR = 2.28, 95% CI = 1.05-4.96), working or exercising after meals (OR = 3.26, 95% CI = 1.31-8.11), salted food (OR = 2.51, 95%CI = 1.08-6.11), fresh vegetables (OR = 0.28, 95% CI = 0.09-0.80), fruits (OR = 0.19, 95% CI = 0.04-0.89), and rice as principal food (OR = 0.53, 95% CI = 0.30-0.85).Multivariate conditional logistic regression models indicated that a significantly elevated risk of contracting GCA was associated with working or exercising after meals (OR = 3.18, 95% CI = 1.23-9.36) and H pylori infection (OR = 2.93, 95% CI = 1.42-6.01).In contrast, the consumption of fresh vegetables (OR = 0.22, 95% CI = 0.06-0.83), fruits (OR = 0.28, 95% CI = 0.09-0.79) and rice as principal food (OR = 0.48, 95% CI = 0.24-0.93) remained as significant beneficial factor associated with GCA.CONCLUSION: Working or exercising after meals and H pylori infection increase the risk of GCA, but higher intakes of rice, fresh vegetables and fruits reduce the risk.

  20. Mucinous Bladder Adenocarcinoma: Case Report and Literature Review

    Bruno Mello R. Santos


    Full Text Available Primary mucinous adenocarcinoma is an extremely rare type of bladder cancer, with aggressive behavior and poor response to chemotherapy and radiotherapy. The symptoms are similar to those of other bladder tumors. Surgery is the main treatment and remains the only curative option. There may be a progression from mucinous metaplasia to mucinous adenoma and then mucinous adenocarcinoma. We present the case of a 40-year-old woman with recurrent lower urinary tract infections, submitted to imaging tests, which showed a bladder tumor. After transurethral resection, pathology showed intestinal mucinous carcinoma. Metastatic work-up was negative. New surgical procedure showed metaplasia but no recurrence of the carcinoma. The patient is now using antibiotic prophylaxis and will undergo a cystoscopy every 3 months and computed tomography in one year.

  1. Renal-Adenocarcinoma-Associated Erythrocytosis in a Cat

    Sungjun Noh, Ji-Houn Kang*, Gonhyung Kim, Dongwoo Chang, Byeongwoo Ahn, Ki-Jeong Na and Mhan-Pyo Yang


    Full Text Available A 9-year-old spayed female domestic shorthair cat was referred for erythrocytosis. Even after the correction of dehydration, blood analyses showed that there had been no improvement. An abdominal ultrasonography and computed tomography identified the presence of a mass on the left kidney. Measurement of serum erythropoietin (EPO showed higher concentration than the reference interval. These findings suggested a direct association of the erythrocytosis with excessive EPO production. The cat underwent nephrectomy of the affected (left kidney. Subsequent histopathology was consistent with a diagnosis of renal adenocarcinoma. Following the nephrectomy, serum EPO concentrations decreased gradually, and the erythrocytosis resolved 15 days postoperatively. This case describes the diagnosis and treatment of secondary inappropriate erythrocytosis in a cat with renal adenocarcinoma.

  2. Gastric Adenocarcinoma Presenting with Gastric Outlet Obstruction in a Child

    Abdulrahman Al-Hussaini


    Full Text Available Gastric carcinoma is extremely rare in children representing only 0.05% of all gastrointestinal malignancies. Here, we report the first pediatric case of gastric cancer presenting with gastric outlet obstruction. Upper endoscopy revealed a markedly thickened antral mucosa occluding the pylorus and a clean base ulcer 1.5 cm × 2 cm at the lesser curvature of the stomach. The narrowed antrum and pylorus underwent balloon dilation, and biopsy from the antrum showed evidence of Helicobacter pylori gastritis. The biopsy taken from the edge of the gastric ulcer demonstrated signet-ring-cell type infiltrate consistent with gastric adenocarcinoma. At laparotomy, there were metastases to the liver, head of pancreas, and mesenteric lymph nodes. Therefore, the gastric carcinoma was deemed unresectable. The patient died few months after initiation of chemotherapy due to advanced malignancy. In conclusion, this case report underscores the possibility of gastric adenocarcinoma occurring in children and presenting with gastric outlet obstruction.

  3. Comparison of glycoprotein expression between ovarian and colon adenocarcinomas

    Multhaupt, H A; Arenas-Elliott, C P; Warhol, M J


    OBJECTIVE: Tumor-associated antigens may be expressed as surface glycoproteins. These molecules undergo qualitative and quantitative modifications during cell differentiation and malignant transformation. During malignant transformation, incomplete glycosylation is common, and certain glycosylation...... pathways are preferred. These antigens might help distinguish between ovarian and colonic adenocarcinomas in the primary and metastatic lesions. Different cytokeratins have been proposed as relatively organ-specific antigens. DESIGN: We used monoclonal antibodies against T1, Tn, sialosyl-Tn, B72.3, CA125......, carcinoembryonic antigen, and cytokeratins 7 and 20 to detect tumor-associated glycoproteins and keratin proteins in ovarian and colonic carcinomas. RESULTS: CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 can distinguish between colonic and serous or endometrioid adenocarcinomas of the ovary in both...

  4. Unusual presentation of metastatic adenocarcinoma of the lung

    Blerina Resuli; Roberto Lisi; Daniela Musio; Vincenzo Tombolini


    On September 2013, a 62-year-old man with metastatic adenocarcinoma of the lung complained tenderness and pain of the first terminal phalange of his right hand. The biopsy confirmed metastatic adenocarcinoma of the lung to the finger. A single 8-Gy fraction of palliative radiotherapy was delivered to the patient's right hand. The patient received magnetic resonance-guided focused ultrasound surgery treatment to the phalange because he showed few improvement of clinical symptoms and persistence of moderate pain after radiotherapy. After magnetic resonance-guided focused ultrasound surgery, the clinical symptoms improved significantly. No serious adverse effects were reported and the patient compliance was very high. Our patient showed improvement of clinical symptoms after combined treatment. The patient remains in good health conditions.

  5. Unusual presentation of metastatic adenocarcinoma of the lung

    Blerina Resuli; Roberto Lisi; Daniela Musio; Vincenzo Tombolini


    On September 2013, a 62-year-old man with metastatic adenocarcinoma of the lung complained tenderness and pain of the first terminal phalange of his right hand. The biopsy confirmed metastatic adenocarcinoma of the lung to the finger. A single 8-Gy fraction of palliative radiotherapy was delivered to the patient’s right hand. The patient received magnetic resonance-guided focused ultrasound surgery treatment to the phalange because he showed few improvement of clinical symptoms and persistence of moderate pain after radiotherapy. After magnetic resonance-guided focused ultrasound surgery, the clinical symptoms improved significantly. No serious adverse effects were reported and the patient compliance was very high. Our patient showed improvement of clinical symptoms after combined treatment. The patient remains in good health conditions.

  6. Is tissue CA125 expression in epithelial ovarian adenocarcinoma heterogenic?

    Sparholt, Morten H; Høgdall, Claus K; Nedergaard, Lotte


    To evaluate if heterogeneity of tissue cancer antigen 125 (CA125) expression is present in epithelial serous adenocarcinomas. Furthermore, to investigate whether there is a correlation between levels of CA125 tissue expression, serum level of CA125, stage, and grade. A total of 10 patients...... diagnosed with serous ovarian adenocarcinomas were included. Preoperative blood samples were collected to determine serum CA125 levels. Tumor tissue from primary surgery was collected and processed for immunohistochemical analyses. CA125 was expressed in varying degrees in tumor tissues from all patients....... Mean tissue CA125 expression for each patient ranged from 36% to 98%. Intrapatient variations in tissue expression ranged from 10% to 90% point. No significant correlations between levels of CA125 tissue expression, serum level of CA125, stage, and grade were found. We found that the tissue expression...

  7. Citrobacter koseri Pneumonia As Initial Presentation of Underlying Pulmonary Adenocarcinoma

    Kelly Pennington; Martin Van Zyl; Patricio Escalante


    Citrobacter koseri is a motile, gram-negative rod traditionally known to cause infection in individuals with significant comorbidities and immunocompromised status. While most cases represent nosocomial infections, rarely community-acquired infections have been reported. We present a previously healthy man in his 60s with C. koseri pneumonia who was subsequently found to have underlying pulmonary adenocarcinoma, illustrating the need for further investigation for immunodeficiency and/or intra...

  8. Citrobacter koseri Pneumonia As Initial Presentation of Underlying Pulmonary Adenocarcinoma

    Pennington, Kelly; Van Zyl, Martin; Escalante, Patricio


    Citrobacter koseri is a motile, gram-negative rod traditionally known to cause infection in individuals with significant comorbidities and immunocompromised status. While most cases represent nosocomial infections, rarely community-acquired infections have been reported. We present a previously healthy man in his 60s with C. koseri pneumonia who was subsequently found to have underlying pulmonary adenocarcinoma, illustrating the need for further investigation for immunodeficiency and/or intrapulmonary pathology.

  9. Single cutaneous metastasis of colon adenocarcinoma - Case report*

    Góes, Heliana Freitas de Oliveira; Lima, Caren dos Santos; de Souza, Mariana Boechat; Estrella, Rogério Ribeiro; Faria, Mônica Ali Novaes; Rochael, Mayra Carrijo


    Skin metastases are relatively rare and occur most often when the cancer is already advanced, invading other organs. As to location, they often seem to elect areas located close to the primary tumor, although distant sites, such as the scalp, may be affected with some frequency. We present a case of a 76-year-old woman with colon adenocarcinoma that had a single metastatic lesion on the scalp. PMID:27579752

  10. Hydronephrosis as a complication of adenocarcinoma of the lung.

    Hiraki, Akio; Ueoka, Hiroshi; Gemba, Kenich; Kuyama, Syouich; Kishino, Daizo; Tabata, Masahiro; Kiura, Katsuyuki; Tanimoto, Mitsune; Harada, Mine


    We describe a patient with adenocarcinoma of the lung who developed hydronephrosis secondary to compression by right common iliac lymph node metastases. The most common primary sites of cancers causing ureteral obstruction are the cervix, prostate, bladder and colo-rectum. To date, few reports of ureteral obstruction attributable to lung cancer have been published. Although rare, physicians should be aware that hydronephrosis can complicate the course of patients with non-small cell lung cancer.

  11. Paraneoplastic neurological syndrome as initial presentation of pulmonary adenocarcinoma

    Shahani, Lokesh


    Paraneoplastic neurological syndromes are defined as remote effects of cancer that are not caused by the tumour and its metastasis, or by infection, ischaemia or metabolic disruptions. The author reports a 63-year-old Caucasian woman presenting with slowly progressing cognitive deficits. Initial workup failed to reveal any obvious cause of her cognitive deficits. Retrospective medical data review revealed a pulmonary nodule, which on further evaluation revealed pulmonary adenocarcinoma with m...

  12. Updates on Treatment of Gemcitabine-Refractory Pancreatic Adenocarcinoma

    Nektaria Makrilia


    Full Text Available Gemcitabine monotherapy and gemcitabine-based regimens are the current standard of care for locally advanced or metastatic pancreatic adenocarcinoma. However, there is still great controversy over the role of salvage chemotherapy after failure of gemcitabine. This review is an update on the 2011 American Society of Clinical Oncology (ASCO Annual Meeting regarding the most important developments in the treatment of refractory pancreatic cancer, as they were reported in Abstracts #e14542 and #e14588.

  13. Atypical presentation of colon adenocarcinoma: a case report

    Tumwine Lynnette K


    Full Text Available Abstract Introduction Adenocarcinoma of the colon is the most common histopathological type of colorectal cancer. In Western Europe and the United States, it is the third most common type and accounts for 98% of cancers of the large intestine. In Uganda, as elsewhere in Africa, the majority of patients are elderly (at least 60 years old. However, more recently, it has been observed that younger patients (less than 40 years of age are presenting with the disease. There is also an increase in its incidence and most patients present late, possibly because of the lack of a comprehensive national screening and preventive health-care program. We describe the clinicopathological features of colorectal carcinoma in the case of a young man in Kampala, Uganda. Case presentation A 27-year-old man from Kampala, Uganda, presented with gross abdominal distension, progressive loss of weight, and fever. He was initially screened for tuberculosis, hepatitis, and lymphoma, and human immunodeficiency virus/acquired immunodeficiency syndrome infection. After a battery of tests, a diagnosis of colorectal carcinoma was finally established with hematoxylin and eosin staining of a cell block made from the sediment of a liter of cytospun ascitic fluid, which showed atypical glands floating in abundant extracellular mucin, suggestive of adenocarcinoma. Ancillary tests with alcian blue/periodic acid Schiff and mucicarmine staining revealed that it was a mucinous adenocarcinoma. Immunohistochemistry showed strong positivity with CDX2, confirming that the origin of the tumor was the colon. Conclusions Colorectal carcinoma has been noted to occur with increasing frequency in young adults in Africa. Most patients have mucinous adenocarcinoma, present late, and have rapid disease progression and poor outcome. Therefore, colorectal malignancy should no longer be excluded from consideration only on the basis of a patient's age. A high index of suspicion is important in the

  14. Mucinous adenocarcinoma originating in localized type adenomyomatosis of the gallbladder


    @@ Adenomyomatosis of the gallbladder (GBA) has been defined as an acquired disease characterized by hyperplastic extension of the surface epithelium into, and often beyond, the thickened gallbladder muscular layer (Rokitansky-Aschoff's sinuses, or RA sinuses).1 It is reported as a lesion with no risk of malignant transformation.2 In recent years, however, a few cases of GBA associated with carcinoma have been reported.3-7 We present another case of mucinous adenocarcinoma arising from GBA.

  15. Case Report: Bazex Syndrome Associated With Pulmonary Adenocarcinoma

    Zhao, Jing; Zhang, Xilin; Chen, Zhuo; Wu, Jian-Hua


    Abstract Bazex syndrome, a rare paraneoplastic syndrome characterized by psoriasiform eruptions, palmoplantar keratosis, and symmetric onychodystrophy, is most prevalent with squamous cell carcinomas of the upper aerodigestive tract. Here, we reported an uncommon case of Bazex syndrome about an 83-year-old man with pulmonary adenocarcinoma and osseous metastasis, Physical examination found psoriasiform eruptions on the nose, cheeks, ears, knees, and the dorsa of interphalangeal joints, along ...

  16. Neuroendocrine markers in adenocarcinomas: an investigation of 356 cases

    Gen-You Yao; Ji-Lin Zhou; Mao-De Lai; Xiao-Qing Chen; Pei-Hui Chen


    AIM: To investigate the incidence of neuroendocrine (NE)cells and their hormone products in adenocarcinomas and evaluate their significance in clinical pathology and prognosis.METHODS: By using tissue sectioning and immunocytochemistry, 356 cases of adenocarcinomas were studied to examine the presence of chromorgranin and polypeptide hormones in adenocarcinoma samples from our hospital.RESULTS: The positive rate of NE cells and hormone products was 41.5 % (54/130) and 59.3 % (32/54), respectively in large intestinal adenocarcinoma cases; 39.6 % (38/96) and 36.8 % (14/38), respectively in gastric cancer cases; 38.1%(8/21) and 50.0 % (4/8), respectively in prostatic cancer cases; 21.0 % (17/81) and 17.6 % (3/17), respectively in breasr cancer cases; 17.9 % (5/28) and 60.0 % (3/5),respectively in pancreatic cancer cases. Among carcinomas of large intestine, pancreas and breast, the highly differentiated NE cell numbers were higher than the poorly differentiated NE cell numbers; while the gastric carcinoma cases had more poorly differentiated NE cells than highly differentiated NE cells. The higher detection rate of NE cells and their hormone products, the higher 5-year survival rate among the large intestine cancer cases.CONCLUSION: Close correlation was observed between NE cells and their hormone products with the cancer differentiations. For colorectal carcinomas, there is a close correlation of the presence of NE cells and their hormone products with the tumor staging and prognosis.

  17. Korrek, volledig, relevant

    Bergenholtz, Henning; Gouws, Rufus


    as detrimental to the status of a dictionary as a container of linguistic knowledge. This paper shows that, from a lexicographic perspective, such a distinction is not relevant. What is important is that definitions should contain information that is relevant to and needed by the target users of that specific......In explanatory dictionaries, both general language dictionaries and dictionaries dealing with languages for special purposes, the lexicographic definition is an important item to present the meaning of a given lemma. Due to a strong linguistic bias, resulting from an approach prevalent in the early...... phases of the development of theoretical lexicography, a distinction is often made between encyclopaedic information and semantic information in dictionary definitions, and dictionaries had often been criticized when their definitions were dominated by an encyclopaedic approach. This used to be seen...

  18. Genomic alterations in pancreatic cancer and their relevance to therapy

    Erina; Takai; Shinichi; Yachida


    Pancreatic cancer is a highly lethal cancer type, for which there are few viable therapeutic options. But, with the advance of sequencing technologies for global genomic analysis, the landscape of genomic alterations in pancreatic cancer is becoming increasingly well understood. In this review, we summarize current knowledge of genomic alterations in 12 core signaling pathways or cellular processes in pancreatic ductal adenocarcinoma, which is the most common type of malignancy in the pancreas, including four commonly mutated genes and many other genes that are mutated at low frequencies. We also describe the potential implications of these genomic alterations for development of novel therapeutic approaches in the context of personalized medicine.

  19. Cutaneous metastasis as a first presentation for lung adenocarcinoma

    Yazan Abdeen


    Full Text Available Context: According to the recent World Health Organization reports, lung cancer has become the most common type of malignancy and the leading cause of death from cancer. Lung cancer frequently metastasizes to hilar lymphnodes, brain, adrenal glands, bone, but rarely to skin. Case Report: We report a case of a 72-year-old male with a past medical history of pulmonary fibrosis and no prior history of smoking who presented to the emergency room for progressive dyspnea over three weeks. The patient reported having a rapidly growing scalp lesion as well. A computed tomography (CT scan of the chest showed diffuse fibrotic changes and multiple densities of different diameters; a CT guided biopsy of lung revealed a poorly differentiated adenocarcinoma. Excision of right scalp lesion was performed, and pathology revealed poorly differentiated malignant neoplasm favoring adenocarcinoma. Conclusion: We are presenting a rare case of lung adenocarcinoma presenting with skin metastasis, which was simultaneously diagnosed during the same hospitalization. Although cutaneous metastasis from the lung is rare, it must be ruled out in patients with suspicious skin lesions, smoking history, or lung cancer.

  20. A rare case of thyroid metastasis from pancreatic adenocarcinoma.

    Kelly, Michael E


    CONTEXT: Thyroid metastasis from pancreatic adenocarcinoma is extremely rare, with only two previous cases in the literature. We report a case of pancreatic adenocarcinoma metastasising to the thyroid. We review the incidence, diagnosis, and management of this rare occurrence. CASE REPORT: A 38-year-old man with a synchronous 6-month history of thyroid swelling, presented with epigastric pain and signs of obstructive jaundice. He was investigated by abdominal computerised tomography and endoscopic retrograde cholangiopancreatography. The diagnosis of pancreatic neoplasm was made. His thyroid neoplasm was investigated at another tertiary centre and thought to be a papillary neoplasm. He underwent a pancreaticoduodenectomy and recovered well post-operatively. Eight weeks later he had a total thyroidectomy. Histology confirmed that the thyroid mass was both morphologically and immunophenotypically similar to the pancreatic neoplasm. CONCLUSION: This case demonstrates the importance of a full investigation when a patient with suspected neoplastic history presents with a thyroid nodule. We outline the crucial role that immunohistochemistry plays in detecting and classifying primary and secondary thyroid neoplasms. The detection of a solitary thyroid metastasis from pancreatic adenocarcinoma may indicate a poor prognosis, and it is debatable whether resection of the primary should be undertaken when it presents with a solitary metastasis.

  1. Endoscopic assessment and management of early esophageal adenocarcinoma

    Ghassan; M; Hammoud; Hazem; Hammad; Jamal; A; Ibdah


    Esophageal carcinoma affects more than 450000people worldwide and the incidence is rapidly increasing.In the United States and Europe,esophageal adenocarcinoma has superseded esophageal squamous cell carcinoma in its incidence.Esophageal cancer has a high mortality rates secondary to the late presentation of most patients at advanced stages.Endoscopic screening is recommended for patients with multiple risk factors for cancer in Barrett’s esophagus.These risk factors include chronic gastroesophageal reflux disease,hiatal hernia,advanced age,male sex,white race,cigarette smoking,and obesity.The annual risk of esophageal cancer is approximately 0.25%for patients without dysplasia and 6%for patients with high-grade dysplasia.Twenty percent of all esophageal adenocarcinoma in the United States is early stage with disease confined to the mucosa or submucosa.The significant morbidity and mortality of esophagectomy make endoscopic treatment an attractive option.The American Gastroenterological Association recommends endoscopic eradication therapy for patients with high-grade dysplasia.Endoscopic modalities for treatment of early esophageal adenocarcinoma include endoscopic resection techniques and endoscopic ablative techniques such as radiofrequency ablation,photodynamic therapy and cryoablation.Endoscopic therapy should be precluded to patients with no evidence of lymphovascular invasion.Local tumor recurrence is low after endoscopic therapy and is predicted by poor differentiation of tumor,positive lymph node and submucosal invasion.Surgical resection should be offered to patients with deep submucosal invasion.

  2. Targeting adhesion signaling in KRAS, LKB1 mutant lung adenocarcinoma

    Konen, Jessica; Koo, Junghui; Robinson, Brian S.; Wiles, Walter Guy; Huang, Chunzi; Martin, W. David; Behera, Madhusmita; Smith, Geoffrey H.; Hill, Charles E.; Rossi, Michael R.; Sica, Gabriel L.; Rupji, Manali; Chen, Zhengjia; Kowalski, Jeanne; Kasinski, Andrea L.; Ramalingam, Suresh S.; Khuri, Fadlo R.; Marcus, Adam I.


    Loss of LKB1 activity is prevalent in KRAS mutant lung adenocarcinoma and promotes aggressive and treatment-resistant tumors. Previous studies have shown that LKB1 is a negative regulator of the focal adhesion kinase (FAK), but in vivo studies testing the efficacy of FAK inhibition in LKB1 mutant cancers are lacking. Here, we took a pharmacologic approach to show that FAK inhibition is an effective early-treatment strategy for this high-risk molecular subtype. We established a lenti-Cre–induced Kras and Lkb1 mutant genetically engineered mouse model (KLLenti) that develops 100% lung adenocarcinoma and showed that high spatiotemporal FAK activation occurs in collective invasive cells that are surrounded by high levels of collagen. Modeling invasion in 3D, loss of Lkb1, but not p53, was sufficient to drive collective invasion and collagen alignment that was highly sensitive to FAK inhibition. Treatment of early, stage-matched KLLenti tumors with FAK inhibitor monotherapy resulted in a striking effect on tumor progression, invasion, and tumor-associated collagen. Chronic treatment extended survival and impeded local lymph node spread. Lastly, we identified focally upregulated FAK and collagen-associated collective invasion in KRAS and LKB1 comutated human lung adenocarcinoma patients. Our results suggest that patients with LKB1 mutant tumors should be stratified for early treatment with FAK inhibitors.

  3. Esophageal Adenocarcinoma Developing after Eradication of Helicobacter pylori

    Yasuhiko Abe


    Full Text Available A 75-year-old man underwent endoscopic hemostatic therapy for hemorrhagic gastric ulcer in September 2002. After healing of the gastric ulcer, he underwent Helicobacter pylori eradication therapy in February 2003. In August 2007, an irregular tumor was detected in the lower esophagus at annual checkup for gastric cancer screening using X-ray. Endoscopic examination showed that the lower margin of the tumor almost coincided with the esophagogastric junction and that a short segment of Barrett’s epithelium existed near the tumor. Biopsies of the tumor showed moderately to poorly differentiated adenocarcinoma. Mild reflux esophagitis and minor hiatal hernia was also observed, and the previously treated gastric ulcer was not recurrent. Absence of H. pylori was confirmed by serum antibody and urea breath test. Surgical resection of the lower esophagus and proximal stomach was performed. The tumor invaded into the muscularis propria of the esophageal wall but had no evidence of lymph node metastasis. Based on macroscopic and pathological findings, the tumor was recognized as esophageal adenocarcinoma. Previous endoscopic examination did not detect any apparent signs of tumor in the esophagogastric junction. As far as we know, this is the first report documenting a newly developed esophageal adenocarcinoma after the successful eradication of H. pylori.

  4. Small Undifferentiated Pancreatic Adenocarcinoma which Mimics IPMN at Imaging

    Mirko D’Onofrio


    Full Text Available Context To present the case of an unusual presentation at imaging of a very small solid undifferentiated pancreatic adenocarcinoma which mimics a side-branch intraductal papillary mucinous neoplasm. Case report The patient came to our hospital for a revaluation of a cystic pancreatic lesion. Ultrasound (US and contrast-enhanced ultrasound (CEUS examinations were carried out. A small cystic lesion of about 1.5 cm in diameter was seen in the posterior aspect of the pancreatic uncinate process A very small, solid, vascularized nodule was detected at CEUS within the lesion. Consequently, the patient underwent CT and MRI. MRI confirmed the presence of an intralesional nodule and communication with the main pancreatic duct was demonstrated, suggesting the diagnosis of intraductal papillary mucinous neoplasm with solid intralesional tissue. A pylorus preserving pancreaticoduodenectomy was carried out. An undifferentiated adenocarcinoma having a notable peripheral inflammatory reaction and dilated branch duct was finally diagnosed. Conclusion To our knowledge, we present for the first time, the case of a very small solid undifferentiated pancreatic adenocarcinoma of the uncinate process which mimicked a side-branch intraductal papillary mucinous neoplasm at imaging. The cystic appearance may be an epiphenomenon of a solid lesion and this possibility has to be considered when one encounters incidental cystic lesions at imaging.

  5. Information Needs/Relevance

    Wildemuth, Barbara M.


    A user's interaction with a DL is often initiated as the result of the user experiencing an information need of some kind. Aspects of that experience and how it might affect the user's interactions with the DL are discussed in this module. In addition, users continuously make decisions about and evaluations of the materials retrieved from a DL, relative to their information needs. Relevance judgments, and their relationship to the user's information needs, are discussed in this module. Draft

  6. Synchronous Appearance of Adenocarcinoma and Gastrointestinal Stromal Tumour (GIST) of the Stomach: A Case Report.

    Telugu, Ramesh Babu; Pushparaj, Magesh; Masih, Dipti; Pulimood, Anna


    Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols.

  7. Bortezomib combined with lenalidomide as the first-line treatment for the rare synchronous occurrence of multiple myeloma and pulmonary adenocarcinoma

    Zuo, Wenli; Zhu, Xinghu; Yang, Jingke; Mei, Zhenyang; Deng, Mei; Lin, Quande; Song, Yongping; Yin, Qingsong


    Abstract Background: Simultaneous multiple myeloma (MM) and pulmonary adenocarcinoma is a rare occurrence, and thus, treatment is a challenge. This study reports on 1 such case of MM with concurrent lung cancer, where an accurate diagnosis was made and the patient underwent treatment for both cancers. Case summary: A 68-year-old man presented with 2 months of progressive lower back pain. Visualization with magnetic resonance imaging (MRI) revealed multiple collapsed vertebrae from T12 to S3, as well as an altered signal intensity at the T3 vertebra. The patient was diagnosed with MM upon examination. A chest computed tomography (CT) scan revealed a round mass in the left lower lobe of the lungs, and a CT-guided needle biopsy uncovered a moderately differentiated adenocarcinoma. There were no additional notable findings in the left lung using positron emission tomography computed tomography (PET-CT). Therefore, a diagnosis of MM with pulmonary adenocarcinoma was made. Surgery was performed to excise the lung cancer. Bortezomib was used as first-line induction therapy against both tumors and lenalidomide was used for maintenance. The patient went into complete remission. Using this combined chemotherapy, the patient has survived for over 3 years since a diagnosis was made despite relapsing twice after the first year. Conclusion: This report clearly delineates the diagnosis and treatment of a rare case of synchronous MM and pulmonary adenocarcinoma, as well as depicts a potentially positive outcome for the patient. It also overviews some diagnostic and therapeutic implications for clinicians. PMID:28072730

  8. MicroRNA-330-5p as a Putative Modulator of Neoadjuvant Chemoradiotherapy Sensitivity in Oesophageal Adenocarcinoma.

    Bibby, Becky A S


    Oesophageal adenocarcinoma (OAC) is the sixth most common cause of cancer deaths worldwide, and the 5-year survival rate for patients diagnosed with the disease is approximately 17%. The standard of care for locally advanced disease is neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation therapy (neo-CRT) prior to surgery. Unfortunately, ~60-70% of patients will fail to respond to neo-CRT. Therefore, the identification of biomarkers indicative of patient response to treatment has significant clinical implications in the stratification of patient treatment. Furthermore, understanding the molecular mechanisms underpinning tumour response and resistance to neo-CRT will contribute towards the identification of novel therapeutic targets for enhancing OAC sensitivity to CRT. MicroRNAs (miRNA\\/miR) function to regulate gene and protein expression and play a causal role in cancer development and progression. MiRNAs have also been identified as modulators of key cellular pathways associated with resistance to CRT. Here, to identify miRNAs associated with resistance to CRT, pre-treatment diagnostic biopsy specimens from patients with OAC were analysed using miRNA-profiling arrays. In pre-treatment biopsies miR-330-5p was the most downregulated miRNA in patients who subsequently failed to respond to neo-CRT. The role of miR-330 as a potential modulator of tumour response and sensitivity to CRT in OAC was further investigated in vitro. Through vector-based overexpression the E2F1\\/p-AKT survival pathway, as previously described, was confirmed as a target of miR-330 regulation. However, miR-330-mediated alterations to the E2F1\\/p-AKT pathway were insufficient to significantly alter cellular sensitivity to chemotherapy (cisplatin and 5-flurouracil). In contrast, silencing of miR-330-5p enhanced, albeit subtly, cellular resistance to clinically relevant doses of radiation. This study highlights the need for further investigation into the potential of

  9. MicroRNA-330-5p as a Putative Modulator of Neoadjuvant Chemoradiotherapy Sensitivity in Oesophageal Adenocarcinoma.

    Becky A S Bibby

    Full Text Available Oesophageal adenocarcinoma (OAC is the sixth most common cause of cancer deaths worldwide, and the 5-year survival rate for patients diagnosed with the disease is approximately 17%. The standard of care for locally advanced disease is neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation therapy (neo-CRT prior to surgery. Unfortunately, ~60-70% of patients will fail to respond to neo-CRT. Therefore, the identification of biomarkers indicative of patient response to treatment has significant clinical implications in the stratification of patient treatment. Furthermore, understanding the molecular mechanisms underpinning tumour response and resistance to neo-CRT will contribute towards the identification of novel therapeutic targets for enhancing OAC sensitivity to CRT. MicroRNAs (miRNA/miR function to regulate gene and protein expression and play a causal role in cancer development and progression. MiRNAs have also been identified as modulators of key cellular pathways associated with resistance to CRT. Here, to identify miRNAs associated with resistance to CRT, pre-treatment diagnostic biopsy specimens from patients with OAC were analysed using miRNA-profiling arrays. In pre-treatment biopsies miR-330-5p was the most downregulated miRNA in patients who subsequently failed to respond to neo-CRT. The role of miR-330 as a potential modulator of tumour response and sensitivity to CRT in OAC was further investigated in vitro. Through vector-based overexpression the E2F1/p-AKT survival pathway, as previously described, was confirmed as a target of miR-330 regulation. However, miR-330-mediated alterations to the E2F1/p-AKT pathway were insufficient to significantly alter cellular sensitivity to chemotherapy (cisplatin and 5-flurouracil. In contrast, silencing of miR-330-5p enhanced, albeit subtly, cellular resistance to clinically relevant doses of radiation. This study highlights the need for further investigation into the

  10. MicroRNA-330-5p as a Putative Modulator of Neoadjuvant Chemoradiotherapy Sensitivity in Oesophageal Adenocarcinoma.

    Bibby, Becky A S; Reynolds, John V; Maher, Stephen G


    Oesophageal adenocarcinoma (OAC) is the sixth most common cause of cancer deaths worldwide, and the 5-year survival rate for patients diagnosed with the disease is approximately 17%. The standard of care for locally advanced disease is neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation therapy (neo-CRT) prior to surgery. Unfortunately, ~60-70% of patients will fail to respond to neo-CRT. Therefore, the identification of biomarkers indicative of patient response to treatment has significant clinical implications in the stratification of patient treatment. Furthermore, understanding the molecular mechanisms underpinning tumour response and resistance to neo-CRT will contribute towards the identification of novel therapeutic targets for enhancing OAC sensitivity to CRT. MicroRNAs (miRNA/miR) function to regulate gene and protein expression and play a causal role in cancer development and progression. MiRNAs have also been identified as modulators of key cellular pathways associated with resistance to CRT. Here, to identify miRNAs associated with resistance to CRT, pre-treatment diagnostic biopsy specimens from patients with OAC were analysed using miRNA-profiling arrays. In pre-treatment biopsies miR-330-5p was the most downregulated miRNA in patients who subsequently failed to respond to neo-CRT. The role of miR-330 as a potential modulator of tumour response and sensitivity to CRT in OAC was further investigated in vitro. Through vector-based overexpression the E2F1/p-AKT survival pathway, as previously described, was confirmed as a target of miR-330 regulation. However, miR-330-mediated alterations to the E2F1/p-AKT pathway were insufficient to significantly alter cellular sensitivity to chemotherapy (cisplatin and 5-flurouracil). In contrast, silencing of miR-330-5p enhanced, albeit subtly, cellular resistance to clinically relevant doses of radiation. This study highlights the need for further investigation into the potential of mi

  11. Chylothorax in gastric adenocarcinoma: A case report and systematic review of the English literature


    Background: Chylothorax is a rare complication of gastric adenocarcinoma and data on its identification, prevalence and outcomes are scant. Objectives: To enable identification of gastric carcinoma as a cause of chylothorax. Methods: A case report and a systematic review were conducted of all reported cases of gastric adenocarcinoma with chylothorax as the presenting complaint in the English literature. Results: Chylothorax is a rare presenting complaint of gastric adenocarcinoma. There are o...

  12. Relationship between clinicopathological features and mucin phenotypes of advanced gastric adenocarcinoma

    Fumiaki; Toki; Atsushi; Takahashi; Ryusuke; Aihara; Kyoichi; Ogata; Hiroyuki; Ando; Tetsuro; Ohno; Erito; Mochiki; Hiroyuki; Kuwano


    AIM: To investigate a relationship between the clinicopathological features and mucin phenotypes in advanced gastric adenocarcinoma (AGA). METHODS: Immunohistochemical staining was performed to determine the mucin phenotypes in 38 patients with differentiated adenocarcinomas (DACs), 9 with signet-ring cell carcinomas (SIGs), and 48 with other diffuse-type adenocarcinomas (non-SIGs) of AGA. The mucin phenotypes were classified into 4 types: gastric (G), gastrointestinal (GI), intestinal, and unclassified. RE...

  13. Survival after adjuvant chemoradiotherapy or surgery alone in resectable adenocarcinoma at the gastro-esophageal junction

    Kofoed, Steen Christian; Muhic, A; Jensen, Lene Bæksgaard;


    Longterm survival after curative resection for adenocarcinoma at the gastro-esophageal junction (GEJ) range between 18% and 50%. In the pivotal Intergroup-0116 Phase III trial by Macdonald et all, adjuvant chemoradiotherapy improved both disease-free and overall survival in curatively resected...... patients with mainly gastric adenocarcinoma. We compared survival data for curatively resected patients with adeno-carcinoma solely at the gastro-esophageal junction (GEJ), treated with surgery alone or surgery and adjuvant chemoradio-therapy....

  14. Barrett’s oesophagus and oesophageal adenocarcinoma: time for a new synthesis


    The public health importance of Barrett’s oesophagus lies in its association with oesophageal adenocarcinoma. The incidence of oesophageal adenocarcinoma has risen at an alarming rate over the past four decades in many regions of the Western world and there are indications that the incidence of this disease is on the rise in Asian populations where it has been rare. Much has been learned of host and environmental risk factors that affect the incidence of oesophageal adenocarcinoma and data in...

  15. The feasibility of an exercise intervention in males at risk of oesophageal adenocarcinoma: a randomized controlled trial.

    Brooke M Winzer

    Full Text Available To investigate the feasibility and safety of a 24-week exercise intervention, compared to control, in males with Barrett's oesophagus, and to estimate the effect of the intervention, compared to control, on risk factors associated with oesophageal adenocarcinoma development.A randomized controlled trial of an exercise intervention (60 minutes moderate-intensity aerobic and resistance exercise five days/week over 24 weeks; one supervised and four unsupervised sessions versus attention control (45 minutes stretching five days/week over 24 weeks; one supervised and four unsupervised sessions in inactive, overweight/obese (25.0-34.9 kg/m2 males with Barrett's oesophagus, aged 18-70 years. Primary outcomes were obesity-associated hormones relevant to oesophageal adenocarcinoma risk (circulating concentrations of leptin, adiponectin, interleukin-6, tumour necrosis factor-alpha, C-reactive protein, and insulin resistance [HOMA]. Secondary outcomes included waist circumference, body composition, fitness, strength and gastro-oesophageal reflux symptoms. Outcomes were measured at baseline and 24-weeks. Intervention effects were analysed using generalised linear models, adjusting for baseline value.Recruitment was difficult in this population with a total of 33 participants recruited (target sample size: n = 80; 97% retention at 24-weeks. Adherence to the exercise protocol was moderate. No serious adverse events were reported. A statistically significant intervention effect (exercise minus control was observed for waist circumference (-4.5 [95% CI -7.5, -1.4] cm; p < 0.01. Effects on primary outcomes were not statistically significant.This small, exploratory trial provides important information to inform future trial development including recruitment rates and estimates of effect sizes on outcomes related to oesophageal adenocarcinoma risk. Future trials should investigate a combined dietary and exercise intervention to achieve greater weight loss in this

  16. Presacral Teratocarcinoma Presenting as Anal Fistula and Rectal Adenocarcinoma: A Unique Case Presentation and Literature Review

    S.P. Ho


    Full Text Available Somatic malignancy arising from presacral or retroperitoneal primary teratoma is extremely rare. We report the case of a 37-year-old male patient with adenocarcinoma of respiratory type arising from primary presacral teratoma, but which first presented as anal fistula and rectal adenocarcinoma. The two tumors show the same morphology and immunophenotype (CK7–CK20+CDx2+. Malignant adenocarcinoma transformations from the normal respiratory epithelium are also found. To the best of our knowledge, this is the second case of respiratory type adenocarcinoma arising from primary presacral mature cystic teratoma.

  17. A case with primary signet ring cell adenocarcinoma of the prostate and review of the literature

    Orcun Celik


    Full Text Available Primary signet cell carcinoma of the prostate is a rare histological variant of prostate malignancies. It is commonly originated from the stomach, colon, pancreas, and less commonly in the bladder. Prognosis of the classical type is worse than the adenocarcinoma of the prostate. Primary signet cell adenocarcinoma is diagnosed by eliminating the adenocarcinomas of other organs such as gastrointestinal tract organs. In this case report, we present a case with primary signet cell adenocarcinoma of the prostate who received docetaxel chemotherapy because of short prostate specific antigen doubling time.

  18. Clear cell adenocarcinoma of a female urethra: A case report and review of the literature

    Amel Trabelsi


    Full Text Available Context : Clear cell adenocarcinoma of the urethra is an extremely rare tumour. Its histogenetic derivation remains controversial. Case report : We report a new case of clear cell adenocarcinoma of the proximal urethra in a 56-year-old woman who presented with grossly hematuria. Urethral cystoscopy revealed a tumour protruding from the posterior urethral wall at the bladder neck. Treatment consisted of urethrocystectomy with pelvic lymph node dissection. Histologically, the neoplasm consisted of clear cell adenocarcinoma of the urethra. Conclusion : It appears that female urethral adenocarcinoma has more than one tissue of origin.

  19. Small intestine adenocarcinoma in conjunction with multiple adenomas causing acute colic in a horse.

    Moran, Juan A Muñoz; Lemberger, Karin; Cadoré, Jean-Luc; Lepage, Olivier M


    An 11-year-old Andalusian stallion developed marked signs of colic associated with an acute small intestine obstruction. Exploratory laparotomy revealed a distal jejunum full-thickness wall induration and multiple small adherent intraluminal masses. Fifteen centimeters of jejunum, including the induration, and several intraluminal masses were resected. Histologic examination revealed an adenocarcinoma and multiple polypoid adenomas. The horse was discharged, and no complications were reported 12 months postoperatively. Colic was considered secondary to partial jejunal lumen obstruction by the adenocarcinoma. Adenocarcinoma recurrence or transformation from remaining adenomas into an adenocarcinoma is still a major risk.

  20. Genetic Diversity of Pancreatic Ductal Adenocarcinoma and Opportunities for Precision Medicine.

    Knudsen, Erik S; O'Reilly, Eileen M; Brody, Jonathan R; Witkiewicz, Agnieszka K


    Patients with pancreatic ductal adenocarcinoma (PDA) have a poor prognosis despite new treatments; approximately 7% survive for 5 years. Although there have been advances in systemic, primarily cytotoxic, therapies, it has been a challenge to treat patients with PDA using targeted therapies. Sequence analyses have provided a wealth of information about the genetic features of PDA and have identified potential therapeutic targets. Preclinical and early-phase clinical studies have found specific pathways could be rationally targeted; it might also be possible to take advantage of the genetic diversity of PDAs to develop therapeutic agents. The genetic diversity and instability of PDA cells have long been thought of as obstacles to treatment, but are now considered exploitable features. We review the latest findings in pancreatic cancer genetics and the promise of targeted approaches in PDA therapy.

  1. Layered Double Hydroxide as a Vehicle to Increase Toxicity of Gallate Ions against Adenocarcinoma Cells

    Jenny Arratia-Quijada


    Full Text Available The antineoplasic activity of gallic acid has been reported. This compound induces apoptosis and inhibits the growth of several neoplasic cells. However, this molecule is easily oxidized and degraded in the body. The aim of this work was to intercalate gallate ions into layered double hydroxide (LDH nanoparticles under controlled conditions to reduce oxidation of gallate and to evaluate its toxicity against the A549 adenocarcinoma cell line. An isopropanol medium under nitrogen atmosphere was adequate to intercalate gallate ions with a lesser oxidation degree as detected by electron spin resonance spectroscopy. Concentrations of the hybrid LDH-gallate nanoparticles between 0.39 and 25 µg/mL reduced the cell viability to 67%, while the value reached with the pure gallic acid and LDH was 90% and 78%, respectively, thus proving that the combination of gallate ions with the inorganic nanoparticles increases the toxicity potential within this dose range.

  2. Targeted therapies for pancreatic adenocarcinoma: Where do we stand, how far can we go?

    Dimitra; Grapsa; Muhammad; Wasif; Saif; Konstantinos; Syrigos


    Pancreatic adenocarcinoma(usually referred to aspancreatic cancer) is a highly lethal and aggressive malignancy with a disease-related mortality almost equaling its incidence, and one of the most challenging cancers to treat. The notorious resistance of pancreatic cancer not only to conventional cytotoxic therapies but also to almost all targeted agents developed to date, continues to puzzle the oncological community and represents one of the biggest hurdles to reducing the death toll from this ominous disease. This editorial highlights the most important recent advances in preclinical and clinical research, with regards to targeted therapeutics for pancreatic cancer, outlines current challenges and provides an overview of potential future perspectives in this rapidly evolving field.

  3. BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages

    Rosati, Alessandra; Basile, Anna; D'Auria, Raffaella; d'Avenia, Morena; De Marco, Margot; Falco, Antonia; Festa, Michelina; Guerriero, Luana; Iorio, Vittoria; Parente, Roberto; Pascale, Maria; Marzullo, Liberato; Franco, Renato; Arra, Claudio; Barbieri, Antonio; Rea, Domenica; Menichini, Giulio; Hahne, Michael; Bijlsma, Maarten; Barcaroli, Daniela; Sala, Gianluca; di Mola, Fabio Francesco; di Sebastiano, Pierluigi; Todoric, Jelena; Antonucci, Laura; Corvest, Vincent; Jawhari, Anass; Firpo, Matthew A; Tuveson, David A; Capunzo, Mario; Karin, Michael; De Laurenzi, Vincenzo; Turco, Maria Caterina


    The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of metastasis. Here we report that PDAC cells secrete BAG3, which binds and activates macrophages, inducing their activation and the secretion of PDAC supporting factors. We also identify IFITM-2 as a BAG3 receptor and show that it signals through PI3K and the p38 MAPK pathways. Finally, we show that the use of an anti-BAG3 antibody results in reduced tumour growth and prevents metastasis formation in three different mouse models. In conclusion, we identify a paracrine loop involved in PDAC growth and metastatic spreading, and show that an anti-BAG3 antibody has therapeutic potential. PMID:26522614

  4. Expression of cyclooxygenase-2 in prostate adenocarcinoma and benign prostatic hyperplasia.

    Lee, L M; Pan, C C; Cheng, C J; Chi, C W; Liu, T Y


    Elevated expression of cyclo-oxygenase (COX)-2 has been found in several human cancers, including prostate adenocarcinoma. To evaluate the potential prognostic role of COX-2 in prostate cancer, we assessed the expression of COX-2 in benign prostatic hyperplasia (BPH) and prostate cancer samples employing immunohistochemistry. COX-2 was over-expressed in 15 out of 18 (83%) prostate cancer samples whereas it was detected in only 22% (4 of 18) paired benign tissues. The intensity of immunostaining correlated with the tumor grading. In addition, COX-2 was expressed in 7 of the 22 (32%) BPH samples examined. The significance a COX-2 expression in the BPH samples is not known at present. This data suggest that COX-2 is over-expressed in prostate cancer and COX-2 inhibitors may be useful in combination chemotherapy or chemoprevention for prostate cancer.

  5. Predictive values of H.I.F.-1 alpha, H.I.F.-2 alpha and C.A. 9 expressions by prostate adenocarcinomas treated by exclusive irradiation. Ancillary study of the G.E.T.U.G. 06 protocol; Valeurs predictives des expressions de HIF-1 alpha, HIF-2 alpha et CA 9 par les adenocarcinomes de la prostate traites par irradiation exclusive. Etude ancillaire du protocole GETUG 06

    Simon, J.M.; Mazeron, J.J. [Groupe Hospitalier de la Pitie-Salpetriere, APHP, Service de Radiotherapie, 75 - Paris (France); Comperat, E. [Groupe Hospitalier de la Pitie-Salpetriere, APHP, Lab. d' Anatomie Pathologique, 75 - Paris (France); Beckendorf, V. [Centre Alexis-Vautrin, Dept. de Radiotherapie, 54 - Vandoeuvre-les-Nancy (France); Bey, P. [Institut Curie, 75 - Paris (France); Jaillon, P. [Hopital Saint-Antoine, APHP, Service de Pharmacologie, 75 - Paris (France)


    The adenocarcinomas of the prostate are potentially hypoxic tumors. The strong expression of markers of hypoxia H.I.F.-2 alpha and C.A. 9 are independent predictor factors of biochemical relapse after exclusive radiotherapy. (N.C.)

  6. What is the origin of pancreatic adenocarcinoma?

    Pandey Krishan K


    Full Text Available Abstract The concept of pancreatic cancer origin is controversial. Acinar, ductal or islet cells have been hypothesized as the cell of origin. The pros and cons of each of these hypotheses are discussed. Based on the world literature and recent observations, pancreatic cells seem to have potential for phenotypical transdifferentiation, i.e ductal-islet, ductal-acinar, acinar-ductal, acinar-islet, islet-acinar and islet-ductal cells. Although the possibility is discussed that cancer may arise from either islet, ductal or acinar cells, the circumstances favoring the islet cells as the tumor cell origin include their greater transdifferentiation potency into both pancreatic and extrapancreatic cells, the presence of a variety of carcinogen-metabolizing enzymes, some of which are present exclusively in islet cells and the growth factor-rich environment of islets.

  7. Identification and Characterization of Side Population Cells in Human Lung Adenocarcinoma SPC-A1 Cells

    Yan-liang Zhu; Long-bang Chen; Jing-hua Wang; Xin-yi Xia


    Objective: There has been an increasing interest in recent years in the role of stem cells.With an extensive understanding of their biology,a major role for stem cells in the malignant process has been proposed and the existence of cancer stem cells(CSCs) has been confirmed in hematopoietic malignancies and solid organ malignancies including brain cancer,breast,prostate,colon,and pancreatic cancer.Lung cancer is the leading cause of cancer mortality in most large cities of China.It is possible that lung cancer contains cancer stem cells responsible for its malignancy.The aim of this study is to identify,characterize and enrich the CSC population that drives and maintains lung adenocarcinoma growth and metastasis.Methods: Side population(SP) cell analysis and sorting were applied on human lung adenocarcinoma cell line and an attempt to further enrich them by preliminary serum-free culture before fluorescence activated cell sorting (FACS) was done.Stem cell properties of SP cells were evaluated by their proliferative index,colony-forming efficiency,tumorigenic potential,bi-differentiation capacity and the expression of common stem cell surface markers.Results: Lung cancer cells could grow in a serum-free Medium(SFM) as non-adherent spheres similar to neurospheres or mammospheres.The proportion of SP cells in cell spheres was significantly higher than that in cells grown as monolayers.SP cells had a greater proliferative index,a higher colony-forming efficiency and a greater ability to form tumor in vivo.SP cells were both CCA positive and SP-C positive while non-SP cells were only SP-C positive.Flow cytometric analysis of cell phenotype showed that SP cells expressed CD133 and CD44,the common cell surface markers of cancer stem cells,while non-SP cells only expressed CD44.Conclusion: SP cells existed in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting.SP cells possessed the properties of

  8. Identification and Characterization of Side Population Cells in Human Lung Adenocarcinoma SPC-A1 Cells

    Yan-liang Zhu; Long-bang Chen; Jing-hua Wang; Xin-yi Xia


    Objective:There has been an increasing interest in recent years in the role of stem cells.With an extensive understanding of their biology,a major role for stem cells in the malignant process has been proposed and the existence of cancer stem cells(CSCs)has been confirmed in hematopoietic malignancies and solid organ malignancies including brain cancer,breast,prostate,colon,and pancreatic cancer.Lung cancer is the leading cause of cancer mortality in most large cities of China.It is possible that lung cancer contains cancer stem cells responsible for its malignancy.The aim of this study is to identify,characterize and enrich the CSC population that drives and maintains lung adenocarcinoma growth and metastasis.Methods:Side population(SP)cell analysis and sorting were applied on human lung adenocarcinoma cell line and an attempt to further enrich them by preliminary serum-free culture before fluorescence activated cell sorting(FACS)was done.Stem cell properties of SP cells were evaluated by their proliferative index,colony-forming efficiency,tumorigenic potential,bi-differentiation capacity and the expression of common stem cell surface markers.Results:Lung cancer cells could grow in a serum-free Medium(SFM)as non-adherent spheres similar to neurospheres or mammospheres.The proportion of SP cells in cell spheres was significantly higher than that in cells grown as monolayers.SP cells had a greater proliferative index,a higher colony-forming efficiency and a greater ability to form tumor in vivo.SP cells were both CCA positive and SP-C positive while non-SP cells were only SP-C positive.Flow cytometric analysis of cell phenotype showed that SP cells expressed CD133 and CD44,the common cell surface markers of cancer stem cells,while non-SP cells only expressed CD44.Conclusion:SP cells existed in human lung adenocarcinoma cell lines and they could be further enriched by preliminary serum-free culture before FACS sorting.SP cells possessed the properties of cancer stem

  9. Isolation and biological analysis of tumor stem cells from pancreatic adenocarcinoma

    Peng Huang; Chun-You Wang; Shan-Miao Gou; He-Shui Wu; Tap Liu; Jiang-Xin Xiong


    AIM: To explore the method of isolation and biological analysis of tumor stem cells from pancreatic adenocarcinoma cell line PANC-1.METHODS: The PANC-1 cells were cultured in Dulbecco modified eagle medium F12 (1:1 volume)(DMEM-F12) supplemented with 20% fetal bovine serum (FBS).Subpopulation cells with properties of tumor stem cells were isolated from pancreatic adenocarcinoma cell line PANC-1 according to the cell surface markers CD44 and CD24 by flow cytometry.The proliferative capability of these cells in vitro were estimated by 3-[4,5-dimehyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide (MTT) method.And the tumor growth of different subpopulation cells which were injected into the hypodermisof right and left armpit of nude mice was studied,and expression of CD44 and CD24 of the CD44+CD24+ cell-formed nodules and PANC-1 cells were detected by avidin-biotin-peroxidase complex (ABC) immunohistochemical staining.RESULTS: The 5.1%-17.5% of sorted PANC-1 cells expressed the cell surface marker CD44,57.8% -70.1% expressed CD24,only 2.1%-3.5% of cells were CD44+ CD24+.Compared with CD44-CD24- cells,CD44+CD24+ cells had a lower growth rate in vitro.Implantation of 104 CD44 CD24- cells in nude mice showed no evident tumor growth at wk 12.In contrast,large tumors were found in nude mice implanted with 103 CD44+CD24+ cells at wk 4 (2/8),a 20-fold increase in tumorigenic potential (P<0.05 or P<0.01).There was no obvious histological difference between the cells of the CD44+CD24+ cell-formed nodules and PANC-1 cells.CONCLUSION: CD44 and CD24 may be used as the cell surface markers for isolation of pancreatic cancer stem cells from pancreatic adenocarcinoma cell line PANC-1.Subpopulation cells CD44+CD24+ have properties of tumor stem cells.Because cancer stem cells are thought to be responsible for tumor initiation and its recurrence after an initial response to chemotherapy,it may be a very promising target for new drug development.

  10. Chronobiology: relevance for tuberculosis.

    Santos, Lígia Gabrielle; Pires, Gabriel Natan; Azeredo Bittencourt, Lia Rita; Tufik, Sergio; Andersen, Monica Levy


    Despite the knowledge concerning the pathogenesis of tuberculosis, this disease remains one of the most important causes of mortality worldwide. Several risk factors are well-known, such poverty, HIV infection, and poor nutrition, among others. However, some issues that may influence tuberculosis warrant further investigation. In particular, the chronobiological aspects related to tuberculosis have garnered limited attention. In general, the interface between tuberculosis and chronobiology is manifested in four ways: variations in vitamin D bioavailability, winter conditions, associated infections, and circannual oscillations of lymphocytes activity. Moreover, tuberculosis is related to the following chronobiological factors: seasonality, latitude, photoperiod and radiation. Despite the relevance of these topics, the relationship between them has been weakly reviewed. This review aims to synthesize the studies regarding the association between tuberculosis and chronobiology, as well as urge critical discussion and highlight its applicability to health policies for tuberculosis.

  11. Cerebral metastasis from hepatoid adenocarcinoma of the stomach


    We first report a rare case of metastasis from gastric hepatoid adenocarcinoma (HAC) to cerebral parenchyma, in a 50-year-old Chinese patient. He complained of a one-month history of a paroxysm of headache in the left temple and pars parietalis accompanied with binocular caligation caligo, insensible feeling of limbs and transient anepia. Magnetic resonance (MR) imaging revealed a spherical occupying lesion in the left posterior-temple lobe which was clinically diagnosed as a metastatic tumor. Three years ago, the patient accepted total gastrectomy as he was pathologically diagnosed at gastroscopy having an adenocarcinoma. Eight months after gastrectomy, the occupying lesion in liver was detected by ultrasound and CT, and he accepted transcatheter arterial embolization. Before operation of the brain metastasis, no obvious abnormality was found in liver by ultrasound. Histopathological characteristics of the brain tumor were identical to those of stomach tumor. The growth pattern of both tumors showed solid cell nests. The tumor cells were polygonal, and had abundant eosinophilic cytoplasm and round nuclei with obvious nucleoli. Sinusoid-like blood spaces were located between nodular tumor cells. Immunohistochemistrystained tumor cells were positive for AFP and negative for Hep-Par-1. According to these histopathological findings, both tumors were diagnosed as HAC and metastatic HAC. The patient remained alive 16 mo after tumorectomy of the cerebral metastasis. The differential diagnosis of brain metastasis from metastatic tumors should use a panel of antibodies to avoid confusing with the brain metastasis of hepatocellular carcinoma (HCC). This paper describes this rare case of metastasis from gastric hepatoid adenocarcinoma to cerebral parenchyma, and provides a review of the literature concerning its histopathological and immunohistochemical characteristics.

  12. Role of surgical resection in treatment of pancreatic adenocarcinoma

    Milošević Pavle


    Full Text Available Introduction. Pancreatic adenocarcinoma is the fifth leading cause of death from malignant diseases. The total five-year rate is bellow 5%, but in patients who underwent pancreatic resection, the fiveyear rate may be up to 20%. Surgical resection is still the only therapeutic option that offers the possibility of cure. In recent decades, the perioperative mortality rate has been significantly reduced in the institutions performing a number of these operations per year and has become less than 5%. Postoperative morbidity remains high. Material and Methods. The results of surgical resection in the treatment of pancreatic adenocarcinoma have been analyzed. A retrospective study included the patients operated at the Department for Abdominal, Endocrine and Transplantation surgery, Clinical Center of Vojvodina. Results. In the period from February 1st 1998 to February 1st 2007 a total of 67 patients with pancreatic adenocarcinoma underwent resection. The average age of patients was 58.81±1.42 years. There were 44 (65.7% male and 23 (34.3% female patients. The most common locations of cancer were the head, then the body and the tail of the pancreas and they were found in 57 (85.1% cases, 7 (10,4% cases and 3 (4,47% cases, respectively. The postoperative mortality appeared in 3 (4.47% cases and postoperative morbidity in 21 (31.3% cases. The average survival was 22.89± 3.87 months, the median being 9.0±2.18 months. The five-year survival rate was 13.5%. Conclusion. For patients with pancreatic cancer, surgical resection still remains the only chance of cure. These procedures are performed with acceptable postoperative mortality and morbidity rate. The percentage of cured patients is still unsatisfactorily low.

  13. Hepatic Artery Chemotherapy for Advanced Adenocarcinoma of the Pancreas

    Robert Levin


    Full Text Available Context Seventy patients with adenocarcinoma of the pancreas with liver metastases, received chemotherapy every four weeks and their outcomes are reported in this retrospective series. Objective Advanced adenocarcinoma of the pancreas has a poor prognosis with only 2% 5-year survival reported by SEER (Surveillance, Epidemiology and End Results of the NCI. Chemotherapy given as intra-arterial perfusions is more intense than intravenous chemotherapy. Responses in perfused tumor is expected to be better than that obtained with only intravenous chemotherapy. Design Hepatic artery therapy is given monthly as a 5 hour perfusion of the hepatic artery using DDP and MIC. Also given is monthy Intravenous (IV therapy with four hours of Leucovorin (LV, with an injection of FUDR during the last hour of LV, daily x 5 days. Setting all therapy was given at Midwestern Regional Medical Center. Patients Thirty seven patients had no prior chemotherapy, while 33 patients had progressed after prior IV chemotherapy. Intervention Hepatic artery therapy with IV LV-FUDR was given for up to six months depending upon marrow tolerance and response. At that point, if response was ongoing or improving, therapy was continued monthly with only IV LV-FUDR; all therapy was stopped whenever progressive disease was evident. Results of those without prior chemotherapy, the mean overall survival (OS was 17.3 ± 30.2 months (mean±SD, ranging up to 13 years. Six patients survived more than three years with four are living in continuing complete remission for more than five years. Conclusion This therapy offers the opportunity for long term survival in a subset of patients with metastatic adenocarcinoma of the pancreas who have liver metastases, and some patients can be cured.

  14. Simultaneous large cell neuroendocrine carcinoma and adenocarcinoma of the stomach

    Tadashi Terada; Hirotoshi Maruo


    A large cell neuroendocrine carcinoma (LCNEC) of the stomach is very rare. A 76-year-old Japanese man was admitted to our hospital because of epigastralgia and nausea. Endoscopy revealed 2 large tumors in the stomach. He did not have multiple endocrine neoplasia type Ⅰ or Zollinger-Ellison syndrome. Imaging modali-ties, including computed tomography and magnetic resonance imaging, revealed no other tumors. Gas-trectomy, cholecystectomy, and lymph node dissection were performed. The resected stomach had 2 tumors: one was an antral ulcerated type 3 tumor measuring 5 cm x 5 cm, and the other was a polypoid type 1 tumor measuring 6 cm x 6 cm x 3 cm in the fundus. Micro-scopically, the antral ulcerated tumor was a well differ-entiated adenocarcinoma with deep invasion. The fun-dus polypoid tumor was a LCNEC, being composed of malignant large cells arranged in trabecular and nested patterns. The tumor cells were large and the nuclei were vesicular. Nucleoli were frequently present, and there were many mitotic figures, apoptotic bodies, and necrotic areas. Much lymphovascular permeation was seen. Seven out of 29 dissected lymph nodes showed metastatic foci; 6 were from the LCNEC and 1 from the adenocarcinoma. Many intravascular tumor emboli of LCNEC were seen in the peritoneum around the lymph nodes. Mucins were present in the adenocarcinoma but not in the LCNEC. Immunohistochemically, the LCNEC tumor cells were positive for pancytokeratins, synaptophysin (50% positive), chromogranin A (10% positive), Ki-67 (90% labeled), and platelet-derived growth factor-α (80% positive). They were negative for KIT, p53, CD56, and neuron-specific enolase. The non-cancerous stomach showed a normal number of endocrine cells. The patient is now treated with adju-vant chemotherapy.

  15. Spontaneous necrosis of solid gallbladder adenocarcinoma accompanied with pancreaticobiliary maljunction

    Tomohide Hori; Takashi Wagata; Kenji Takemoto; Takanobu Shigeta; Haruko Takuwa; Koichiro Hata; Shinji Uemoto; Naoki Yokoo


    A 71-year-old Japanese man with acute cholecystitis and an incarcerated gallbladder (GB) stone was admitted. Plain ultrasonography (US) incidentally detected a mass-like lesion in the fundus. Doppler US revealed that this elevated lesion had no blood flow. Computed tomography showed a relatively low-density mass, measuring 5 cm×4 cm in diameter, with no positive enhancement. Magnetic resonance imaging showed a mass in the fundus with a slightly low intensity on T1-weighted images and a slightly high intensity on T2-weighted images. We were agonized in making the qualitative diagnosis of mass-like lesions of the fundus, such as a benign tumor, cancer, or debris. We performed laparoscopic cholecystectomy, because the incarcerated GB stone clearly caused acute cholecystitis. Intra-operative cholangiography clearly revealed pancreaticobiliary maljunction. Amylase levels in the common bile duct and gallbladder were quite high. The elevated lesion in the fundus clearly showed severe necrosis. Although this necrotic nodule included non-viable adenocarcinoma cells, viable cancer cell nests were located in the muscularis propria and subcutaneous layer. Histopathological examination confirmed a solid adenocarcinoma. Thus, we diagnosed it as a gallbladder cancer, based on histopathological analysis of the resected specimen. We therefore undertook radical surgery, including wedge resection of the liver, radical dissection of regional lymph nodes, and resection of the extrahepatic bile duct. Histopathological findings revealed no cancer, hyperplasia or dysplasia in the additionally resected specimens. The patient was finally staged as T2, NO, H0, P0, M(-), stage 11. We present the first case of spontaneous necrosis of solid gallbladder adenocarcinoma, with a review of previous studies.

  16. Therapeutic Endoscopic Ultrasonography: Intratumoral Injection for Pancreatic Adenocarcinoma

    Lawrence A. Shirley


    Full Text Available Pancreatic adenocarcinoma is an aggressive disease that has poor outcomes despite maximal traditional therapies. Thus, treatment of this cancer demands innovative strategies to be used in addition to standing therapies in order to provide new avenues of care. Here, we describe the technique of using endoscopic ultrasound in order to directly inject both novel and conventional therapies into pancreatic tumors. We detail the rationale behind this strategy and the many benefits it provides. We then describe our technique in detail, including our experience injecting the AdV-tk adenoviral vector to create an in situ vaccine effect.


    W.H.Chow; LouisT.C.Chow


    An 88-year-old man presented symptoms and signs of ascending cholangitis and died 20 days after the onset of illness.Postmortem examination revealed a mucinous tumor arising from the head of the pancreas,encasing the common bile duct and invading the liver with multiple hepatic metastasis.The tumor showed a unique and uniform histological appearance,consisting of signet-ring neoplastic cells floating in mucin pools.The rapid clinical course and widespread hepatic metastasis of this patient suggest that this pure,signet-ring variant of mucinous adenocarcinoma of the pancreas might have a poorer prognosis.

  18. Villoglandular papillary adenocarcinoma of the uterine cervix with immunohistochemical characteristics.

    Polat, A; Düsmez, D; Pata, O; Aydin, O; Egilmez, R


    Villoglandular papillary adenocarcinoma of uterine cervix has been recently described and to date fewer than a hundred cases have been reported in the world literature. Here we present a 38-year-old woman who underwent radical hysterectomy combined bilateral pelvic lymphoadenectomy and after 28 months postoperatively no lymph node metastasis and no evidence of recurrent disease ocurred. Immunohistochemically Ki-67 overexpression was detected in the tumour, with no immunoreactivity with p53, estrogen and progesteron receptors and broadly-reactive human papilloma virus including types 6, 11, 16, 18, 31, 33, 42, 51, 52, 56, and 58. In this paper, clinical, macroscopical, microscopical and immunohistochemical characteristics of this tumour are reviewed.

  19. Phenotypic Classification of Well-Differentiated Gastric Adenocarcinoma

    Ying Wu; Zhong-wu Li; Ji-you Li


    Objective: To investigate the genotypes of well-differentiated non-cardiac gastric adenocarcinoma and their clinicopathological significance.Methods: Sixty-four cases of well-differentiated non-cardiac gastric adenocarcinoma were included in this study. The expressions of intestinal phenotypic markers including CDX2, MUC2, Li-cadherin, CD10, Hepatocyte(Hep) and Villin, and gastric phenotypic markers including MUC5AC and pS2 were detected immunohistochemically. Based on the expressions of phenotypic markers, 64 cases can be divided into four phenotypes. Cases only expressing intestinal phenotypic markers were classified as intestinal phenotype; cases only expressing gastric phenotypic markers as gastric phenotype; cases expressing both intestinal and gastric phenotypic markers as gastrointestinal phenotype; and cases expressing neither intestinal nor gastric phenotypic marker as null phenotype. The association of phenotype and clinic-pathological parameters was analyzed. We also detected the expressions of markers related to the development and progression of cancer, including Rb, P53, c-Met, MIF, TGF-β-RII, β-catenin, CD44v6 and E-cadherin.Results: Of 64 cases, 33(51.6%) were intestinal type, 3(4.7%) were gastric type, 25(39.1%) were gastrointestinal type and 3(4.7%) were null type. Fifty-eight cases were either intestinal or gastrointestinal type, which accounted for 90.6% of all the cases. In addition, there was an association between phenotype and biological behaviors (invasion or metastasis). The biological behaviors of intestinal and gastrointestinal type were better than gastric type. Compared with intestinal, gastric and gastrointestinal types, the biological behaviors of null type were the most aggressive. The biological behaviors of gastric carcinoma tended to be better as the number of expression of intestinal markers increased. Expression of markers related to the development and progression of cancer was not significantly correlated with phenotypes

  20. Gastric adenocarcinoma inducing portal hypertension: A rare presentation

    Pradipta Ghosh; Katsumi Miyai; Mario Chojkier


    Advanced gastric cancer usually presents with symptoms due to direct extension into adjacent viscera, distant metastases from lymphatic or hematogenic dissemination and peritoneal seeding. However, portal hypertension as a presentation of metastatic gastric cancer is rare and usually seen in association with other malignancies, e.g. hepatocellular and pancreatic carcinoma. We report a case of signet ring adenocarcinoma of the stomach that presented with esophageal and duodenal varices and bleeding due to portal hypertensive gastropathy. Pagetoid spread of cancer cells likely caused early metastasis and the unusual presentation. We also discussed the pathophysiology of development of portal hypertension in association with malignancies.

  1. Oral malignant acanthosis nigricans associated with endometrial adenocarcinoma

    Han-Wen Chu; Jing-Min Li; Guan-Fu Chen; Jing-Yuan Ma


    We report a 59-year-old patient with malignant acanthosis nigricans associated with metastasis of endometrial carcinoma. The patient presented papillomatosis lesions that appeared to be benign on multiple skins of body folds, particularly on lips. The lesions in lips and axilla had histological characteristic appearances of acanthosis nigricans, while the masses in abdomen and pelvis were metastasis endometrial adenocarcinoma. The article highlights the importance of biopsy and histopathological diagnosis in presumed benign lesions and the role of doctors in screening for body internal tumors.

  2. Uterine adenocarcinoma with abdominal carcinomatosis in a beluga whale.

    Lair, S; De Guise, S; Martineau, D


    A case of uterine adenocarcinoma is reported in a 26-yr-old, free-ranging beluga whale (Delphinapterus leucas) from the St. Lawrence estuary (Quebec, Canada). This neoplasm appeared as a segmental stenotic thickening of the left uterine horn composed of well differentiated, but disorganized and infiltrative, glandular structures surrounded by an extensive scirrhous stroma. Abdominal carcinomatosis was observed on the mesosalpinx and on the serosal aspect of the gastric compartments. This is the first report of a malignancy originating in the uterus of a cetacean.

  3. Adenocarcinoma of the lung presenting with atypical cystic brain lesions

    Costa, Ricardo; Costa, Rubens B; Bacchi, Carlos; Sarinho, Filipe


    Brain metastases occur in up to 10–30% of patients with cancer. Metastatic lesions are usually diagnosed as multiple mass lesions at the junction of the grey and white matter with associated perilesional vasogenic oedema. Cysticercosis is an endemic disease in underdeveloped countries of Africa, Central and South America and is the most common parasitic infection of the central nervous system. The classical radiological finding of neurocysticercosis is cystic lesions showing the scolex in the brain parenchyma. We report a case of metastatic adenocarcinoma of the lung presenting with cystic brain lesions mimicking neurocysticercosis. PMID:24717598

  4. Histopathological spectrum of polymorphous low-grade adenocarcinoma

    Varun Surya


    Full Text Available Polymorphous low-grade adenocarcinomas (PLGA are distinctive salivary gland neoplasms, with an almost exclusive propensity to arise from the minor salivary glands. PLGA frequently manifests as an asymptomatic, slow-growing mass within the oral cavity, which must be separated from adenoid cystic carcinoma and benign mixed tumor for therapeutic and prognostic considerations. We report a case of a 67-year-old male, who presented with a long-standing mass in the palate. This lesion was diagnosed as PLGA based on histopathological findings, which was further confirmed by the immunohistochemical marker.

  5. ANO1 (TMEM16A) in pancreatic ductal adenocarcinoma (PDAC)

    Sauter, Daniel Rafael Peter; Novak, Ivana; Pedersen, Stine Helene Falsig;


    Pancreatic ductal adenocarcinoma (PDAC) has one of the worst survival rates of all cancers. ANO1 (TMEM16A) is a recently identified Ca2+-activated Cl- channel (CaCC) that is upregulated in several tumors. Although ANO1 was subject to extensive studies in the recent years, its pathophysiological f...... intracellular calcium concentration. Functional studies on PDAC behavior showed that surprisingly inhibition of ANO1 did not influence cellular proliferation. On the other hand, we found ANO1 channel to be pivotal in PDAC cell migration as assessed in wound healing experiments....

  6. Transdiaphragmatic adrenalectomy for metastatic cervical adenocarcinoma: a technical case report

    Robert B. Dorman


    Full Text Available We present a 60-year old woman with recurrent cervical adenocarcinoma who presented with metastasis to both lungs and to her right adrenal gland. A thoracotomy was performed for resection of her pulmonary metastasis and then the right adrenal gland was excised through a trans-diaphragmatic approach. The adrenal gland resection was more complex due to involvement of the tumor with the inferior vena cava (IVC which was repaired with a PTFE patch graft. This case demonstrates both an interesting approach to surgical resection of multiple metastases as well as a safe, although more challenging, alternative to partially resect and repair the IVC.

  7. Widespread hematogenous metastases and Trousseau's syndrome in gastric adenocarcinoma

    Santos Vitorino Modesto dos


    Full Text Available A case of widespread hematogenous metastases and Trousseau's syndrome is reported in a 40 year-old white housewife with gastric cancer, presenting subdural hematoma, ecchymoses, epistaxis, stomach and uterine bleeding. After undergoing hematoma drainage, she was unsuccessfully treated with platelets, red blood cells, plasma cryoprecipitate transfusions, and antibiotics. Necropsy disclosed gastric ring-signet adenocarcinoma invading the serous layer, with massive disseminated intravascular coagulation and systemic neoplastic embolism. Multiple old and recent hyaline (rich in fibrin and platelets microthrombi, and tumor emboli were observed in the bone marrow, meninges, liver, lungs, kidneys, lymph nodes, adrenals, thyroid, heart, pancreas, and ovaries (Krukenberg tumor.

  8. Medical image of the week: evolution of low grade adenocarcinoma

    Palacio D


    Full Text Available Ground glass lesions above 5 mm in greatest diameter found on chest computed tomography (CT require initial followed up in 3 months according to the Fleischner Society Guidelines, to exclude a transient inflammatory focus (1. If persistent, surveillance for at least 24 months to confirm stability is recommended. Any change in size or density should warrant further action, ideally surgical consultation, given the suboptimal yield of percutaneous biopsy and risk of inappropriate staging if the whole lesion is not examined. This may result in the inability to recognize the transition from in-situ adenocarcinoma into minimally invasive or invasive lesions, which in turn results in inaccurate staging and prognosis.

  9. "Big IGF-II"-induced hypoglycemia secondary to gastric adenocarcinoma.

    Morbois-Trabut, L; Maillot, F; De Widerspach-Thor, A; Lamisse, F; Couet, C


    Non-islet cell tumor-related hypoglycemia is a rare phenomenon. We report the case of a 63 Year-old man admitted for hemiparesia and a capillary blood glucose of 20 mg/dL. The presence of an immature form of IGF-II that can mimic the effect of insulin, namely "big IGF-II", explained this patient's hypoglycaemia. A moderately differentiated adenocarcinoma of the cardia with metastatic extension to the stomach and the liver was demonstrated. Octreotide failed to control the hypoglycaemia, therefore prednisolone (2 mg/kg per day) and enteral feeding prevented new episodes of severe hypoglycaemia.

  10. A Case of Enzootic Nasal Adenocarcinoma in a Ewe

    Devorah Marks Stowe


    Full Text Available An approximately 2-year-old open Suffolk ewe presented to the North Carolina State University College of Veterinary Medicine Veterinary Health Complex for evaluation of a left nasal mass. An ultrasound-guided aspirate and core biopsies were performed. An epithelial neoplasia with mild mixed inflammation (neutrophils and plasma cells was diagnosed on cytology and confirmed on histopathology. Immunohistochemistry (IHC, reverse transcriptase polymerase chain reaction (RT-PCR, and transmission electron microscopy were also performed. IHC and RT-PCR identified the presence of enzootic nasal tumor virus and confirmed the final diagnosis of enzootic nasal adenocarcinoma.

  11. Superior Vena Cava Thrombosis in a Case of Lung Adenocarcinoma

    Santanu Ghosh


    Full Text Available Superior vena cava syndrome is a common presentation of bronchogenic carcinoma. The mechanism of obstruction is by compression of superior vena cava by the bronchogenic tumor itself or enlarged mediastinal lymph nodes. However obstruction due to intravascular thrombosis is extremely uncommon. Here, we report a rare case of a 65-year-old male smoker who presented with superior vena cava syndrome and bilateral pleural and pericardial effusion with thrombotic occlusion of the superior vena cava in adenocarcinoma of the lung. He was given chemotherapy with carboplatin and gemcitabine with anticoagulant therapy.

  12. Intestinal-type sinonasal adenocarcinoma with bone metastasis: a case report

    Akhavan A.; Binesh F.; Teimoori S.; Soltani H.R.


    Intestinal type adenocarcinoma is a slow growing tumor of sinonasal area, that account for 4% of malignancies of this area. In women it occurs sporadically. This tumor rarely metastasis to other organs. In this article we presented a woman with sinonasal intestinal type adenocarcinoma with optic nerve involvement and multiple bone metastasis.

  13. Detection of KRAS gene mutation and its clinical significance in colorectal adenocarcinoma



    Objective To explore the clinical significance of KRAS mutation detection in colorectal adenocarcinoma. Methods Paraffin-embedded tissue specimens were obtained from 440 patients with colorectal adenocarcinoma. The genomic DNA was extracted. Mutations of exon 2 of KRAS gene were examined by PCR and

  14. Clear-Cell Adenocarcinoma of Vesical Origin: A Case Study of Metastatic Disease Treated with Chemotherapy

    Carolina Pena Álvarez


    Full Text Available Vesical clear cell adenocarcinoma is an uncommon tumour. The description of nearly all published cases focuses on histological issues, providing few clinical particulars and limited followup. The treatment choice is resection. No publications have been found regarding systemic treatments for advanced disease. We present a case of metastatic clear cell adenocarcinoma of the bladder treated with chemotherapy.

  15. A rare case of minimal deviation adenocarcinoma of the uterine cervix in a renal transplant recipient.

    Fanning, D M


    INTRODUCTION: We report the first described case of minimal deviation adenocarcinoma of the uterine cervix in the setting of a female renal cadaveric transplant recipient. MATERIALS AND METHODS: A retrospective review of this clinical case was performed. CONCLUSION: This rare cancer represents only about 1% of all cervical adenocarcinoma.

  16. A rare case of minimal deviation adenocarcinoma of the uterine cervix in a renal transplant recipient.

    Fanning, D M


    INTRODUCTION: We report the first described case of minimal deviation adenocarcinoma of the uterine cervix in the setting of a female renal cadaveric transplant recipient. MATERIALS AND METHODS: A retrospective review of this clinical case was performed. CONCLUSION: This rare cancer represents only about 1% of all cervical adenocarcinoma.

  17. Esophageal adenocarcinoma five years after laparoscopic sleeve gastrectomy. A case report

    Fernando Gabriel Wright


    Conclusion: We present a case of an esophageal adenocarcinoma five years after a laparoscopic sleeve gastrectomy for morbid obesity. There is need to better determine the relationship between sleeve gastrectomy and gastroesophageal reflux disease in order to prevent its related complications, such as esophageal adenocarcinoma.

  18. Perianal mucinous adenocarcinoma associated with chronic anaI fistula: case report

    Park, ChuI Hi; Yang, Dal Mo; Kim, Jee Eun; Choi, Soo Jin [Gil Medical Center, Incheon (Korea, Republic of)


    Perianal mucinous adenocarcinoma is a rare disease. We report here on the CT findings in a case of perianal mucinous adenocarcinoma associated with chronic anal fistula. The CT revealed a low attenuated lesion surrounding the subcutaneous area of chronic anal fistula, anal canal and perirectal area.

  19. Prostate Mucinous Adenocarcinoma with Signet Ring Cells: a Case Report and Literature Review

    Yi Wang; Guang Sun; Jiangang Pan; Jiwu Chang; Shumin Zhang; Tao Li; Binghuang Ren


    @@ Prostate mucinous adenocarcinoma with signet ring cells(MCSRC)is a rare morphologic variant of prostate cancer,with only 12 cases reported to date.[1] Diagnosis of this carcinoma requires that at least 25% of the tumor tissue should consist of an extracellular mucin pool.[2] In this report, we present a case of prostate prostate mucinous adenocarcinoma with signet ring cells.

  20. Brain metastasis as initial presentation of papillary adenocarcinoma of the lung: case report

    Bispo, Irving Gabriel Araujo; Nascimento, Diego Teixeira; Ferreira, Karina Oliveira; Fakhouri, Ricardo; Godinho, Atilano Salvador; Ferrao, Thiago de Oliveira, E-mail: [Universidade Federal de Sergipe (HU-UFS), Aracaju, SE (Brazil). Hospital Universitario


    The authors describe the case of a 33-year-old patient with history of seizures alone without any previous symptom, being diagnosed with brain metastases from primary papillary adenocarcinoma of the lung. Emphasis is given to the diagnostic investigation for brain metastasis and prognostic evaluation of papillary adenocarcinoma of the lung, and a brief literature review on such diseases is performed. (author)

  1. Dietary factors and the risks of oesophageal adenocarcinoma and Barrett's oesophagus.

    Kubo, Ai; Corley, Douglas A; Jensen, Christopher D; Kaur, Rubinder


    Incidence rates for oesophageal adenocarcinoma have increased by over 500% during the past few decades without clear reasons. Gastro-oesophageal reflux disease, obesity and smoking have been identified as risk factors, although the demographic distribution of these risk factors is not consistent with the demographic distribution of oesophageal adenocarcinoma, which is substantially more common among whites and males than any other demographic groups. Numerous epidemiological studies have suggested associations between dietary factors and the risks of oesophageal adenocarcinoma and its precursor, Barrett's oesophagus, though a comprehensive review is lacking. The main aim of the present review is to consider the evidence linking dietary factors with the risks of oesophageal adenocarcinoma, Barrett's oesophagus, and the progression from Barrett's oesophagus to oesophageal adenocarcinoma. The existing epidemiological evidence is strongest for an inverse relationship between intake of vitamin C, β-carotene, fruits and vegetables, particularly raw fruits and vegetables and dark green, leafy and cruciferous vegetables, carbohydrates, fibre and Fe and the risk of oesophageal adenocarcinoma and Barrett's oesophagus. Patients at higher risk for Barrett's oesophagus and oesophageal adenocarcinoma may benefit from increasing their consumption of fruits and vegetables and reducing their intake of red meat and other processed food items. Further research is needed to evaluate the relationship between diet and the progression of Barrett's oesophagus to oesophageal adenocarcinoma. Evidence from cohort studies will help determine whether randomised chemoprevention trials are warranted for the primary prevention of Barrett's oesophagus or its progression to cancer.

  2. Procyanidin induces apoptosis of esophageal adenocarcinoma cells via JNK activation of c-Jun. : Procyanidin induces apoptosis of esophageal adenocarcinoma cells via JNK activation of c-Jun.

    Connor, Carol A; Adriaens, Michiel; Pierini, Roberto; Johnson, Ian T; Belshaw, Nigel J


    Procyanidins are polymeric flavanols found in fruits and vegetables and have shown anticarcinogenic/chemopreventive properties. We previously showed that oligomeric procyanidin extracted from apples induced cell cycle arrest and apoptosis in esophageal adenocarcinoma (OA) cells. To understand the me

  3. Management of primary adenocarcinoma of the female urethra: Report of two cases and review of the literature

    Wang, Xinjun; BAI, PEIMING; SU, HANZHONG; LUO, GUANGCHENG; Zhong, Zhaohui; Zhao, Xiaokun


    Primary adenocarcinoma of the female urethra is rare and only a few retrospective cases have been published. The origin of urethral adenocarcinomas remains unclear. Certain authors have suggested that urethral adenocarcinomas in females originate at the periurethral Skene’s glands. We report one case of urethral adenocarcinoma of the proximal urethra in a 44-year-old female who presented with painless urethral bleeding. Abdominal and pelvic CT scan with contrast and chest radiology were unrem...

  4. Putting oesophageal cancer on the RACK A study of the RACK1 scaffolding protein in oesophageal adenocarcinoma


    Purpose There is a need to identify new therapeutic targets for oesophageal adenocarcinoma. Deoxycholic acid is a component of gastro-oesophageal refluxate and is believed to promote oesophageal adenocarcinoma. RACK1 is an intracellular scaffolding protein whose expression is altered in many cancers. The role of RACK1 in oesophageal adenocarcinoma has not been investigated. The purpose of this study is to examine the expression of RACK1 in oesophageal adenocarcinoma and to a...

  5. MicroRNA-449a enhances radiosensitivity in CL1-0 lung adenocarcinoma cells.

    Yi-Jyun Liu

    Full Text Available Lung cancer is the leading cause of cancer-related mortality worldwide. Radiotherapy is often applied for treating lung cancer, but it often fails because of the relative non-susceptibility of lung cancer cells to radiation. MicroRNAs (miRNAs have been reported to modulate the radiosensitivity of lung cancer cells and have the potential to improve the efficacy of radiotherapy. The purpose of this study was to identify a miRNA that can adjust radiosensitivity in lung adenocarcinoma cells. Two lung adenocarcinoma cell lines (CL1-0 and CL1-5 with different metastatic ability and radiosensitivity were used. In order to understand the regulatory mechanisms of differential radiosensitivity in these isogenic tumor cells, both CL1-0 and CL1-5 were treated with 10 Gy radiation, and were harvested respectively at 0, 1, 4, and 24 h after radiation exposure. The changes in expression of miRNA upon irradiation were examined using Illumina Human microRNA BeadChips. Twenty-six miRNAs were identified as having differential expression post-irradiation in CL1-0 or CL1-5 cells. Among these miRNAs, miR-449a, which was down-regulated in CL1-0 cells at 24 h after irradiation, was chosen for further investigation. Overexpression of miR-449a in CL1-0 cells effectively increased irradiation-induced DNA damage and apoptosis, altered the cell cycle distribution and eventually led to sensitization of CL1-0 to irradiation.

  6. MicroRNA signature characterizes primary tumors that metastasize in an esophageal adenocarcinoma rat model.

    Ali H Zaidi

    Full Text Available To establish a miRNA signature for metastasis in an animal model of esophageal adenocarcinoma (EAC.The incidence of esophageal adenocarcinoma (EAC has dramatically increased and esophageal cancer is now the sixth leading cause of cancer deaths worldwide. Mortality rates remain high among patients with advanced stage disease and esophagectomy is associated with high complication rates. Hence, early identification of potentially metastatic disease would better guide treatment strategies.The modified Levrat's surgery was performed to induce EAC in Sprague-Dawley rats. Primary EAC and distant metastatic sites were confirmed via histology and immunofluorescence. miRNA profiling was performed on primary tumors with or without metastasis. A unique subset of miRNAs expressed in primary tumors and metastases was identified with Ingenuity Pathway Analysis (IPA along with upstream and downstream targets. miRNA-linked gene expression analysis was performed on a secondary cohort of metastasis positive (n=5 and metastasis negative (n=28 primary tumors.The epithelial origin of distant metastasis was established by IF using villin (VIL1 and mucin 5AC (MUC5AC antibodies. miRNome analysis identified four down-regulated miRNAs in metastasis positive primary tumors compared to metastasis negative tumors: miR-92a-3p (p=0.0001, miR-141-3p (p=0.0022, miR-451-1a (p=0.0181 and miR133a-3p (p=0.0304. Six target genes identified in the top scoring networks by IPA were validated as significantly, differentially expressed in metastasis positive primary tumors: Ago2, Akt1, Kras, Bcl2L11, CDKN1B and Zeb2.In vivo metastasis was confirmed in the modified Levrat's model. Analysis of the primary tumor identified a distinctive miRNA signature for primary tumors that metastasized.

  7. Role of anti-stromal polypharmacy in increasing survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma

    Samuel; J; Tingle; John; A; Moir; Steven; A; White


    AIM: To investigate the survival impact of common pharmaceuticals, which target stromal interactions, following a pancreaticoduodenectomy for pancreatic ductal adenocarcinoma. METHODS: Data was collected retrospectively for 164 patients who underwent a pancreaticoduodenectomy for pancreatic ductal adenocarcinoma(PDAC). Survival analysis was performed on patients receiving the following medications: angiotensin-converting enzyme inhibitors(ACEI)/angiotensin Ⅱ receptor blockers(ARB), calcium channel blockers(CCB), aspirin, and statins. Statistical analysis included Kaplan-meier survival estimates and cox multivariate regression; the latter of which allowed for any differences in a range of prognostic indicators between groups. Medications showing a significant survival benefit were investigated in combination with other medications to evaluate synergistic effects.RESULTS: No survival benefit was observed with respect to ACEI/ARB(n = 41), aspirin or statins on individual drug analysis(n = 39). However, the entire CCB group(n = 26) showed a significant survival benefit on multivariate cox regression; hazard ratio(HR) of 0.475(CI = 0.250-0.902, P = 0.023). Further analysis revealed that this was influenced by a group of patients who were taking aspirin in combination with CCB; median survival was significantly higher in the CCB + aspirin group(n = 15) compared with the group taking neither drug(n = 98); 1414 d vs 601 d(P = 0.029, logrank test). Multivariate cox regression revealed neither aspirin nor CCB had a statistically significant impact on survival when given alone, however in combination the survival benefit was significant; HR = 0.332(CI = 0.126-0.870, P = 0.025). None of the other medications showed a survival benefit in any combination.CONCLUSION: Aspirin + CCB in combination appears to increase survival in patients with PDAC, highlighting the potential clinical use of combination therapy to target stromal interactions in pancreatic cancer.

  8. Molecular characterization of the peripheral airway field of cancerization in lung adenocarcinoma.

    Jun-Chieh J Tsay

    Full Text Available Field of cancerization in the airway epithelium has been increasingly examined to understand early pathogenesis of non-small cell lung cancer. However, the extent of field of cancerization throughout the lung airways is unclear. Here we sought to determine the differential gene and microRNA expressions associated with field of cancerization in the peripheral airway epithelial cells of patients with lung adenocarcinoma. We obtained peripheral airway brushings from smoker controls (n=13 and from the lung contralateral to the tumor in cancer patients (n=17. We performed gene and microRNA expression profiling on these peripheral airway epithelial cells using Affymetrix GeneChip and TaqMan Array. Integrated gene and microRNA analysis was performed to identify significant molecular pathways. We identified 26 mRNAs and 5 miRNAs that were significantly (FDR <0.1 up-regulated and 38 mRNAs and 12 miRNAs that were significantly down-regulated in the cancer patients when compared to smoker controls. Functional analysis identified differential transcriptomic expressions related to tumorigenesis. Integration of miRNA-mRNA data into interaction network analysis showed modulation of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK pathway in the contralateral lung field of cancerization. In conclusion, patients with lung adenocarcinoma have tumor related molecules and pathways in histologically normal appearing peripheral airway epithelial cells, a substantial distance from the tumor itself. This finding can potentially provide new biomarkers for early detection of lung cancer and novel therapeutic targets.

  9. Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment

    Gao, Li; Hao, Jian; Niu, Yang-Yang; Tian, Miao; Yang, Xue; Zhu, Cui-Hong; Ding, Xiu-Li; Liu, Xiao-Hui; Zhang, Hao-Ran; Liu, Chang; Qin, Xue-Mei; Wu, Xiong-Zhi


    Abstract Increasing evidence has shown that Chinese Herbal Medicine (CHM) has efficient therapeutic effects for advanced gastric adenocarcinoma, while the therapeutic mechanisms underlying this treatment remain unclear. In this study, the Kaplan–Meier method and Cox regression analysis were used to evaluate the survival benefit of CHM treatment, and correlation analysis was applied to identify the most effective components in the formulas. A network pharmacological approach was developed to decipher the potential therapeutic mechanisms of CHM. CHM treatment was an independent protective factor. The hazard ratio was 0.364 (95% CI 0.245–0.540; P < 0.001). The median survival time was 18 months for patients who received CHM treatment, while for patients without CHM treatment was decreased to 9 months (P < 0.001). Thirteen out of the total 204 herbs were significantly correlated with favorable survival outcomes (P < 0.05), likely representing the most effective components in these formulas. Bioinformatics analyses suggested that the simultaneous manipulation of multiple targets in proliferation pathways (such as epidermal growth factor receptor, fibroblast growth factor receptor 2, human epidermal growth factor receptor 2, proliferating cell nuclear antigen, and insulin like growth factor 2) and the process of cancer metastasis (collagen families, fibronectin 1 and matrix metalloproteinases families) might largely account for the mechanisms of the 13 herbs against gastric adenocarcinoma. A network pharmacology method was introduced to decipher the underlying mechanisms of CHM, which provides a good foundation for herbal research based on clinical data. PMID:27583849

  10. Epithelial-to-mesenchymal transition in a fistula-associated anal adenocarcinoma in a patient with long-standing Crohn's disease.

    Scharl, Michael; Frei, Pascal; Frei, Sandra M; Biedermann, Luc; Weber, Achim; Rogler, Gerhard


    Anal adenocarcinomas arising from perianal fistulae represent a rare complication in Crohn's disease (CD) patients. We have previously demonstrated the involvement of an epithelial-to-mesenchymal transition (EMT) in the pathogenesis of CD-associated fistulae. Although EMT has also been implicated in the development of colorectal and anal carcinoma, the molecular link from fistula to carcinoma is unclear. We present a case of a 48-year-old White woman who developed a mucinous anal adenocarcinoma originating from a perianal, CD-associated fistula 24 years after being diagnosed with CD. To characterize the expression of EMT-associated molecules in fistula and carcinoma tissue, immunohistochemical analysis for Snail1, Slug, β-catenin and E-cadherin was performed. A mucinous anal adenocarcinoma developed on a perianal fistula in a patient with long-standing CD. After neoadjuvant radiochemotherapy, the fistula-associated tumour was resected and the patient is presently in remission. Using immunohistochemical analysis, we detected a remarkable staining of the Slug transcription factor in transitional cells lining the fistula tract. This observation is unique to this 'carcinoma'-fistula: we had previously shown Slug expression in cells surrounding the fistula tract but not in transitional cells. Expression of Snail1, β-catenin and E-cadherin in this case was comparable with our previous findings. We describe a rare case of a CD fistula-associated adenocarcinoma within an area of squamous epithelium of the perianal area and an unusual expression pattern of EMT markers in this fistula. This case seems to underline the relevance of our previous findings demonstrating that EMT plays an important role for fistula pathogenesis and likely carcinogenesis in CD patients.

  11. [A Case of Synchronous Multiple Esophageal Cancers Composed of Squamous Cell Carcinoma and Barrett's Adenocarcinoma].

    Kobayashi, Toshiyuki; Shiozaki, Atsushi; Fujiwara, Hitoshi; Konishi, Hirotaka; Arita, Tomohiro; Kosuga, Toshiyuki; Morimura, Ryo; Murayama, Yasutoshi; Komatsu, Shuhei; Kuriu, Yoshiaki; Ikoma, Hisashi; Nakanishi, Masayoshi; Ichikawa, Daisuke; Okamoto, Kazuma; Otsuji, Eigo


    A 67-year-old man was admitted to our hospital for treatment for multiple superficial esophageal cancers. Screening upper gastrointestinal endoscopy examination revealed a superficial squamous cell carcinoma (SCC) at the middle thoracic esophagus and Barrett's epithelium and a superficial adenocarcinoma at the abdominal esophagus. We performed a subtotal esophagectomy with gastric tube reconstruction via the retrosternal route. Pathological examination revealed a Barrett's adenocarcinoma at the abdominal esophagus. Esophageal cancer is thought to be a multicentric disease, and we sometimes find multiple esophageal cancers. In Japan, most cases of multiple esophageal cancers are composed of SCCs, and the occurrence of multiple esophageal cancers composed of SCC and Barrett's adenocarcinoma is rare. In contrast, the number of the patients with Barrett's esophagus is increasing, and the number of the patients with Barrett's adenocarcinoma also seems to be on the rise. Therefore, it is important be aware of the possibility of multiple esophageal cancers composed of SCC and Barrett's adenocarcinoma while making diagnoses.

  12. Gastroesophageal reflux in relation to adenocarcinomas of the esophagus: a pooled analysis from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON.

    Michael B Cook

    Full Text Available Previous studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA. It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON allowed an in-depth assessment of these issues.Detailed information on heartburn and regurgitation symptoms and covariates were available from five BEACON case-control studies of EA and esophagogastric junction adenocarcinoma (EGJA. We conducted single-study multivariable logistic regressions followed by random-effects meta-analysis. Stratified analyses, meta-regressions, and sensitivity analyses were also conducted.Five studies provided 1,128 EA cases, 1,229 EGJA cases, and 4,057 controls for analysis. All summary estimates indicated positive, significant associations between heartburn/regurgitation symptoms and EA. Increasing heartburn duration was associated with increasing EA risk; odds ratios were 2.80, 3.85, and 6.24 for symptom durations of <10 years, 10 to <20 years, and ≥20 years. Associations with EGJA were slighter weaker, but still statistically significant for those with the highest exposure. Both frequency and duration of heartburn/regurgitation symptoms were independently associated with higher risk. We observed similar strengths of associations when stratified by age, sex, cigarette smoking, and body mass index.This analysis indicates that the association between heartburn/regurgitation symptoms and EA is strong, increases with increased duration and/or frequency, and is consistent across major risk factors. Weaker associations for EGJA suggest that this cancer site has a dissimilar pathogenesis or represents a mixed population of patients.

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