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Sample records for colorectal carcinoma cell

  1. Expression and interaction of different catenins in colorectal carcinoma cells

    Czech Academy of Sciences Publication Activity Database

    Kučerová, Dana; Šloncová, Eva; Tuháčková, Zdena; Vojtěchová, Martina; Sovová, Vlasta

    2001-01-01

    Roč. 8, č. 6 (2001), s. 695-698 ISSN 1107-3756 R&D Projects: GA ČR GA301/00/0269; GA ČR GV312/96/K204 Institutional research plan: CEZ:AV0Z5052915 Keywords : colorectal carcinoma cells * beta-catenin * p120 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.689, year: 2001

  2. Radiosensitization of colorectal carcinoma cell lines by histone deacetylase inhibition

    International Nuclear Information System (INIS)

    Flatmark, Kjersti; Nome, Ragnhild V; Folkvord, Sigurd; Bratland, Åse; Rasmussen, Heidi; Ellefsen, Mali Strand; Fodstad, Øystein; Ree, Anne Hansen

    2006-01-01

    The tumor response to preoperative radiotherapy of locally advanced rectal cancer varies greatly, warranting the use of experimental models to assay the efficacy of molecular targeting agents in rectal cancer radiosensitization. Histone deacetylase (HDAC) inhibitors, agents that cause hyperacetylation of histone proteins and thereby remodeling of chromatin structure, may override cell cycle checkpoint responses to DNA damage and amplify radiation-induced tumor cell death. Human colorectal carcinoma cell lines were exposed to ionizing radiation and HDAC inhibitors, and cell cycle profiles and regulatory factors, as well as clonogenicity, were analyzed. In addition to G 2 /M phase arrest following irradiation, the cell lines displayed cell cycle responses typical for either intact or defective p53 function (the presence or absence, respectively, of radiation-induced expression of the cell cycle inhibitor p21 and subsequent accumulation of G 1 phase cells). In contrast, histone acetylation was associated with complete depletion of the G 1 population of cells with functional p53 but accumulation of both G 1 and G 2 /M populations of cells with defective p53. The cellular phenotypes upon HDAC inhibition were consistent with the observed repression of Polo-like kinase-1, a regulatory G 2 /M phase kinase. Following pre-treatment with HDAC inhibitors currently undergoing clinical investigation, the inhibitory effect of ionizing radiation on clonogenicity was significantly amplified. In these experimental models, HDAC inhibition sensitized the tumor cells to ionizing radiation, which is in accordance with the concept of increased probability of tumor cell death when chromatin structure is modified

  3. Metachronous colorectal carcinoma

    DEFF Research Database (Denmark)

    Bülow, Steffen; Svendsen, L B; Mellemgaard, A

    1990-01-01

    During the period 1943-67, 903 Danish patients aged less than 40 years had colorectal carcinoma. The patients were followed up for up to 41 years and during this period 44 of 501 (9 per cent) operated on for cure developed a metachronous colorectal carcinoma. The cumulative risk of a metachronous...... colorectal carcinoma was 30 per cent after up to 41 years of observation. The occurrence of a metachronous colorectal carcinoma was evenly distributed in the observation period. The cumulative survival rate after operation for a metachronous colorectal carcinoma was 41 per cent after 20 years of observation....... We propose a lifelong follow-up programme after resection of colorectal carcinoma for cure in this age group, including annual Hemoccult test and colonoscopy at 3-year intervals....

  4. New structural analogues of curcumin exhibit potent growth suppressive activity in human colorectal carcinoma cells

    International Nuclear Information System (INIS)

    Cen, Ling; Hutzen, Brian; Ball, Sarah; DeAngelis, Stephanie; Chen, Chun-Liang; Fuchs, James R; Li, Chenglong; Li, Pui-Kai; Lin, Jiayuh

    2009-01-01

    Colorectal carcinoma is one of the major causes of morbidity and mortality in the Western World. Novel therapeutic approaches are needed for colorectal carcinoma. Curcumin, the active component and yellow pigment of turmeric, has been reported to have several anti-cancer activities including anti-proliferation, anti-invasion, and anti-angiogenesis. Clinical trials have suggested that curcumin may serve as a potential preventive or therapeutic agent for colorectal cancer. We compared the inhibitory effects of curcumin and novel structural analogues, GO-Y030, FLLL-11, and FLLL-12, in three independent human colorectal cancer cell lines, SW480, HT-29, and HCT116. MTT cell viability assay was used to examine the cell viability/proliferation and western blots were used to determine the level of PARP cleavages. Half-Maximal inhibitory concentrations (IC 50 ) were calculated using Sigma Plot 9.0 software. Curcumin inhibited cell viability in all three of the human colorectal cancer cell lines studied with IC 50 values ranging between 10.26 μM and 13.31 μM. GO-Y030, FLLL-11, and FLLL-12 were more potent than curcumin in the inhibition of cell viability in these three human colorectal cancer cell lines with IC 50 values ranging between 0.51 μM and 4.48 μM. In addition, FLLL-11 and FLLL-12 exhibit low toxicity to WI-38 normal human lung fibroblasts with an IC-50 value greater than 1,000 μM. GO-Y030, FLLL-11, and FLLL-12 are also more potent than curcumin in the induction of apoptosis, as evidenced by cleaved PARP and cleaved caspase-3 in all three human colorectal cancer cell lines studied. The results indicate that the three curcumin analogues studied exhibit more potent inhibitory activity than curcumin in human colorectal cancer cells. Thus, they may have translational potential as chemopreventive or therapeutic agents for colorectal carcinoma

  5. Somatic mosaicism of androgen receptor CAG repeats in colorectal carcinoma epithelial cells from men.

    Science.gov (United States)

    Di Fabio, Francesco; Alvarado, Carlos; Gologan, Adrian; Youssef, Emad; Voda, Linda; Mitmaker, Elliot; Beitel, Lenore K; Gordon, Philip H; Trifiro, Mark

    2009-06-01

    The X-linked human androgen receptor gene (AR) contains an exonic polymorphic trinucleotide CAG. The length of this encoded CAG tract inversely affects AR transcriptional activity. Colorectal carcinoma is known to express the androgen receptor, but data on somatic CAG repeat lengths variations in malignant and normal epithelial cells are still sporadic. Using laser capture microdissection (LCM), epithelial cells from colorectal carcinoma and normal-appearing mucosa were collected from the fresh tissue of eight consecutive male patients undergoing surgery (mean age, 70 y; range, 54-82). DNA isolated from each LCM sample underwent subsequent PCR and DNA sequencing to precisely determine AR CAG repeat lengths and the presence of microsatellite instability (MSI). Different AR CAG repeat lengths were observed in colorectal carcinoma (ranging from 0 to 36 CAG repeats), mainly in the form of multiple shorter repeat lengths. This genetic heterogeneity (somatic mosaicism) was also found in normal-appearing colorectal mucosa. Half of the carcinoma cases examined tended to have a higher number of AR CAG repeat lengths with a wider range of repeat size variation compared to normal mucosa. MSI carcinomas tended to have longer median AR CAG repeat lengths (n = 17) compared to microsatellite stable carcinomas (n = 14), although the difference was not significant (P = 0.31, Mann-Whitney test). Multiple unique somatic mutations of the AR CAG repeats occur in colorectal mucosa and in carcinoma, predominantly resulting in shorter alleles. Colorectal epithelial cells carrying AR alleles with shorter CAG repeat lengths may be more androgen-sensitive and therefore have a growth advantage.

  6. The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death

    International Nuclear Information System (INIS)

    Lyu, Qing; Tou, Fangfang; Su, Hong; Wu, Xiaoyong; Chen, Xinyi; Zheng, Zhi

    2015-01-01

    Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules. In this study, we revealed that peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with peiminine resulted in significant cell death. In summary, our discoveries demonstrated that peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death. - Highlights: • Peiminine induces autophagy and upregulates autophagic flux. • Peiminine represses colorectal carcinoma tumor growth. • Peiminine induces autophagic cell death. • Peiminine represses mTOR phosphorylation by influencing PI3K/Akt and AMPK pathway

  7. The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death

    Energy Technology Data Exchange (ETDEWEB)

    Lyu, Qing [School of Life Sciences, Tsinghua University, Beijing, 100084 (China); Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 518055 (China); Tou, Fangfang [Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029 (China); Su, Hong; Wu, Xiaoyong [First Affiliated Hospital, Guiyang College of Traditional Chinese Medicine, Guiyang, 550002 (China); Chen, Xinyi [Department of Hematology and Oncology, Beijing University of Chinese Medicine, Beijing, 100029 (China); Zheng, Zhi, E-mail: zheng_sheva@hotmail.com [Jiangxi Provincial Key Lab of Oncology Translation Medicine, Jiangxi Cancer Hospital, Nanchang, 330029 (China)

    2015-06-19

    Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules. In this study, we revealed that peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with peiminine resulted in significant cell death. In summary, our discoveries demonstrated that peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death. - Highlights: • Peiminine induces autophagy and upregulates autophagic flux. • Peiminine represses colorectal carcinoma tumor growth. • Peiminine induces autophagic cell death. • Peiminine represses mTOR phosphorylation by influencing PI3K/Akt and AMPK pathway.

  8. Astrocyte Elevated Gene-1 Mediates Glycolysis and Tumorigenesis in Colorectal Carcinoma Cells via AMPK Signaling

    Directory of Open Access Journals (Sweden)

    Hong-tao Song

    2014-01-01

    Full Text Available To investigate the role of AEG-1 in glycolysis and tumorigenesis, we construct myc-AEG-1 expression vector and demonstrate a novel mechanism that AEG-1 may increase the activity of AMPK by Thr172 phosphorylation. The higher expression levels of AEG-1 in colorectal carcinoma cells were found but showed significant difference in different cell lines. To study the role of AEG-1 in colorectal cells, myc-AEG-1 vector was constructed and transfected into NCM460 colonic epithelial cells. We observed consistent increasing of glucose consumption and lactate production, typical features of anaerobic glycolysis, suggesting that AEG-1 may promote anaerobic glycolysis. Moreover, we noted that AMPK phosphorylation at Thr172 as well as pPFK2 (Ser466 was increased in NCM460 cells overexpressing AEG-1. Compound C may block AMPK and PFK2 phosphorylation in both control and AEG-1-overexpressed cells and decrease the glucose consumption and lactate production. The present findings indicated that reduced AEG-1 protein levels by RNAi may decrease the glucose consumption and lactate production in HCT116 colorectal carcinoma cells. The present identified AEG-1/AMPK/PFK2 glycolysis cascade may be essential to cell proliferation and tumor growth. The present results may provide us with a mechanistic insight into novel targets controlled by AEG-1, and the components in the AEG-1/AMPK/PFK2 glycolysis process may be targeted for the clinical treatment of cancer.

  9. Thymol Elicits HCT-116 Colorectal Carcinoma Cell Death Through Induction of Oxidative Stress.

    Science.gov (United States)

    Chauhan, Anil Kumar; Bahuguna, Ashutosh; Paul, Souren; Kang, Sun Chul

    2018-02-07

    Colon cancer is one of the most deadly and common carcinomas occurring worldwide and there have been many attempts to treat this cancer. The present work was designed in order to evaluate thymol as a potent drug against colon cancer. Cytotoxicity of thymol at different concentrations was evaluated against a human colon carcinoma cell line (HCT-116 cells). Fluorescent staining was carried out to evaluate the level of ROS as well as mitochondrial and DNA fragmentation and immunoblot analysis were performed to confirm apoptosis and mitoptosis. Results of the study demonstrated that thymol efficiently created an oxidative stress environment inside HCT-116 cells, a colorectal carcinoma cell line, through induction of ROS production along with intense damage to DNA and mitochondria, as observed through Hoechst and rhodamine 123 staining, respectively. Moreover, expression of PARP-1, p-JNK, cytochrome-C and caspase-3 proteins was up-regulated, suggesting HCT-116 cells underwent mitoptotic cell death. Therefore, thymol could be used as a potent drug against colon cancer due to its lower toxicity and prevalence in natural medicinal plants. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Overexpression of xeroderma pigmentosum group C decreases the chemotherapeutic sensitivity of colorectal carcinoma cells to cisplatin.

    Science.gov (United States)

    Zhang, Yi; Cao, Jia; Meng, Yanni; Qu, Chunying; Shen, Feng; Xu, Leiming

    2018-05-01

    Xeroderma pigmentosum group C (XPC) is a DNA-damage-recognition gene active at the early stage of DNA repair. XPC also participates in regulation of cell-cycle checkpoint and DNA-damage-induced apoptosis. In the present study, the expression levels of genes involved in nucleotide excision repair (NER) were assessed in human colorectal cancer (CRC) tissue. This analysis revealed that expression of XPC mRNA significantly increased in colorectal carcinoma tissues compared with matched normal controls. Expression of XPC gradually increased along with the degree of progression of CRC. In vitro , an XTT assay demonstrated that small interfering RNA (siRNA) targeting XPC significantly increased the sensitivity of CRC SW480 cells to cisplatin, whereas cells transfected with a XPC-overexpression plasmid became more resistant to cisplatin. Furthermore, flow cytometry revealed that the proportion of apoptotic cells significantly increased in XPC-knockdown cells upon cisplatin treatment. However, the overexpression XPC significantly increased the resistance of cells to cisplatin. In vivo , tumor growth was significantly reduced in tumor-bearing mice when the XPC gene was knocked down. Upregulation of the expression of pro-apoptotic Bcl-associated X and downregulation of the anti-apoptotic B-cell lymphoma 2 proteins was observed in the implanted tumor tissue. In conclusion, XPC serves a key role in chemotherapeutic sensitivity of CRC to cisplatin, meaning that it may be a potential target for chemotherapy of CRC.

  11. Metastatic paediatric colorectal carcinoma.

    LENUS (Irish Health Repository)

    Woods, R

    2012-03-01

    A 16-year-old girl presented to our unit with crampy abdominal pain, change in bowel habit, a subjective impression of weight loss and a single episode of haematochezia. She was found to have a rectosigmoid adenocarcinoma and proceeded to laparoscopic anterior resection, whereupon peritoneal metastases were discovered. She received chemotherapy and is alive and well ten month later with no radiological evidence of disease. Colorectal carcinoma is rare in the paediatric population but is increasing in incidence. Early diagnosis is critical to enable optimal outcomes.

  12. CXCL12 chemokine expression and secretion regulates colorectal carcinoma cell anoikis through Bim-mediated intrinsic apoptosis.

    Directory of Open Access Journals (Sweden)

    Luke J Drury

    Full Text Available BACKGROUND: Resistance to anoikis, apoptosis triggered by a loss of cellular adhesion to the underlying extracellular matrix, is a hallmark of metastatic cancer. Previously we have shown re-establishment of CXCL12 expression in colorectal carcinoma cells inhibits metastasis by enhancing anoikis sensitivity. The objective of these studies was to define the signaling mechanisms regulating CXCL12-mediated anoikis. METHODOLOGY/PRINCIPAL FINDINGS: Adhesion, examined by crystal violet staining, immunofluorescence microscopy, and immunoblot analysis indicated decreased focal adhesion signaling corresponding with loss of adhesion in cells constitutively simulated by CXCL12. Loss of adhesion was inhibited by pertussis toxin treatment, indicating CXCL12 regulating anoikis through G(αi-protein coupled receptors. Non-adherent HCT116 and HT29 colorectal carcinoma cells expressing CXCL12 exhibited enhanced anoikis sensitivity by propidium iodide staining, caspase activity assays, and immunoblot compared to GFP control cells. CXCL12 producing carcinomas cultured on poly-HEMA displayed heightened Bim and loss of Mcl-1 and Bcl-2 preceding cytochrome c release, and caspase-9 activation. RNAi knockdown of Bim reversed anoikis sensitivity of CXCL12-expressing cells and fostered increased soft-agar foci formation and hepatic tumors in an orthotopic mouse model of metastasis. CONCLUSIONS/SIGNIFICANCE: These data indicate CXCL12 provides a barrier to metastasis by increasing anoikis via activation of a Bim-mediated intrinsic apoptotic pathway. These results underscore the importance of retaining CXCL12 expression to sensitize colorectal carcinomas to anoikis and minimize tumor progression.

  13. Colorectal signet-ring cell carcinoma: benefit from adjuvant chemotherapy but a poor prognostic factor.

    Science.gov (United States)

    Hugen, Niek; Verhoeven, Rob H; Lemmens, Valery E; van Aart, Carola J; Elferink, Marloes A; Radema, Sandra A; Nagtegaal, Iris D; de Wilt, Johannes H

    2015-01-15

    Colorectal signet-ring cell carcinoma (SRCC) has been associated with poor survival compared with mucinous adenocarcinoma (MC) and the more common adenocarcinoma (AC). Efficacy of adjuvant chemotherapy in SRCC has never been assessed. This study analyzes the prognostic impact of SRCC and determines whether colonic SRCC patients benefit from adjuvant chemotherapy equally compared with MC and AC patients. Data on 196,757 colorectal cancer (CRC) patients in the period 1989-2010 was included in this Dutch nationwide population-based study. Five-year relative survival estimates were calculated and multivariate relative survival analyses using a multiple regression model of relative excess risk (RER) were performed. SRCC was found in 1,972 (1.0%) patients. SRCC patients presented more frequently with stage III or IV disease than AC patients (75.2% vs. 43.6%, p chemotherapy (RER 1.10, 95% CI 0.81-1.51), suggesting a comparable benefit from adjuvant chemotherapy in AC and SRCC. In conclusion, the prognostic impact of SRCC is dismal in both colon and rectal cancer patients, but adjuvant chemotherapy is associated with improved survival in AC, MC, and SRCC patients. © 2014 UICC.

  14. Colorectal carcinoma with dome-like phenotype: an under-recognised subset of colorectal carcinoma?

    DEFF Research Database (Denmark)

    Asmussen, L; Pachler, J; Holck, S

    2008-01-01

    The term dome carcinoma has been applied to a variant of colorectal carcinoma, thought to derive from M-cells of the gut-associated lymphoid tissue. Its distinguishing morphological features include a non-polypoid plaque-like lesion composed of closely apposed cystically dilated glands lined...

  15. Colorectal signet ring cell carcinoma: Influence of EGFR, E-cadherin and MMP-13 expression on clinicopathological features and prognosis.

    Science.gov (United States)

    Foda, Abd Al-Rahman Mohammad; Aziz, Azza Abdel; Mohamed, Mie Ali

    2018-02-01

    Signet ring cell carcinoma (SRCC) is unique rare subtype of mucin-producing colorectal adenocarcinoma characterized by presence of signet ring cells, in >50% of the tumor tissue. This study aims to investigate expression of EGFR, E-cadherin and MMP-13 expression on clinicopathological features of signet ring cell type and its prognostic effect using manual tissue microarray technique. In this work, we studied tumor tissue specimens from 150 patients with colorectal cancer cases among which 19 cases of SRCC. High density manual tissue microarrays were constructed using modified mechanical pencil tips technique and immunohistochemistry for EGFR, E-cadherin and MMP-13 expression was done. We found that SRCC was significantly associated with younger age and more frequency of LN metastasis than all other groups. SRCC was also significantly associated with annular gross picture, more depth of invasion, advanced stage, more lymphovascular emboli, more perineural invasion and less arousal from an overlying adenoma. In conclusion, colorectal SRCC has distinctive clinicopathological and histological features with different unique mechanisms of carcinogenesis and more aggressive biologic behavior than other colorectal carcinoma subtypes. Negative/low expressions of EGFR and E-cadherin and MMP-13 were found in SRCC with no effect on the prognosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. The peiminine stimulating autophagy in human colorectal carcinoma cells via AMPK pathway by SQSTM1

    Directory of Open Access Journals (Sweden)

    Zheng Zhi

    2016-01-01

    Full Text Available Autophagy is a conserved catabolic process, which functions in maintenance of cellular homeostasis in eukaryotic cells. The self-eating process engulfs cellular long-lived proteins and organelles with double-membrane vesicles, and forms a so-called autophagosome. Degradation of contents via fusion with lysosome provides recycled building blocks for synthesis of new molecules during stress, e.g. starvation. Peiminine is a steroidal alkaloid extracted from Fritillaria thunbergii which is widely used in Traditional Chinese Medicine. Previously, peiminine has been identified to induce autophagy in human colorectal carcinoma cells. In this study, we further investigated whether peiminine could induce autophagic cell death via activating autophagy-related signaling pathway AMPK-mTOR-ULK by promoting SQSTM1(P62. Xenograft tumor growth in vivo suggested that both peiminine and starvation inhibit the growth of tumor size and weight, which was prominently enhanced when peiminine and starvation combined. The therapeutical effect of peiminine in cancer treatment is to be expected.

  17. B-cell lymphoma 2 is associated with advanced tumor grade and clinical stage, and reduced overall survival in young Chinese patients with colorectal carcinoma.

    Science.gov (United States)

    Wang, Jiasheng; He, Gan; Yang, Qiang; Bai, Lian; Jian, Bin; Li, Qugang; Li, Zhongfu

    2018-06-01

    The development of biomarkers that accurately and reliably detect colorectal cancer is a promising approach for colorectal cancer screening. Therefore, the objective of the present study was to evaluate the protein expression of α-methylacyl-CoA racemase (P504S/AMACR), tumor protein p53 (p53), B-cell lymphoma 2 (Bcl-2) and Ki-67/mindbomb E3 ubiquitin protein ligase 1 (MIB-1) in a population of Chinese patients with colorectal carcinoma. Colorectal tumors with matched normal tissue margins were collected from 148 surgical patients, and the demographic and clinical characteristics were collected. Immunohistochemical staining and western blot analysis of P504S/AMACR, p53, Bcl-2 and Ki-67/MIB-1 were conducted. Statistical analyses were used to compare protein expression in the colorectal tumors and matched normal tissue margins and to identify any associations between them and various clinicopathological parameters. Survival analyses were performed using the Kaplan-Meier method. In the present study, immunohistochemistry and western blot analysis revealed significantly higher expression of all four proteins in colorectal tumors compared with matched normal tissue margins (Pcolorectal carcinoma [relative risk (95% CI), 0.703 (0.552-0.895); P55 years) and reduced overall survival (Pcolorectal carcinoma. In conclusion, low expression of Bcl-2 is significantly correlated with advanced pathological grade and TNM stage and is a prognostic indicator of reduced overall survival in young Chinese patients with colorectal carcinoma.

  18. Construction of a plasmid coding for green fluorescent protein tagged cathepsin L and data on expression in colorectal carcinoma cells

    Directory of Open Access Journals (Sweden)

    Tripti Tamhane

    2015-12-01

    Full Text Available The endo-lysosomal cysteine cathepsin L has recently been shown to have moonlighting activities in that its unexpected nuclear localization in colorectal carcinoma cells is involved in cell cycle progression (Tamhane et al., 2015 [1]. Here, we show data on the construction and sequence of a plasmid coding for human cathepsin L tagged with an enhanced green fluorescent protein (phCL-EGFP in which the fluorescent protein is covalently attached to the C-terminus of the protease. The plasmid was used for transfection of HCT116 colorectal carcinoma cells, while data from non-transfected and pEGFP-N1-transfected cells is also shown. Immunoblotting data of lysates from non-transfected controls and HCT116 cells transfected with pEGFP-N1 and phCL-EGFP, showed stable expression of cathepsin L-enhanced green fluorescent protein chimeras, while endogenous cathepsin L protein amounts exceed those of hCL-EGFP chimeras. An effect of phCL-EGFP expression on proliferation and metabolic states of HCT116 cells at 24 h post-transfection was observed.

  19. Down-regulation of UDP-glucose dehydrogenase affects glycosaminoglycans synthesis and motility in HCT-8 colorectal carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tsung-Pao; Pan, Yun-Ru; Fu, Chien-Yu; Chang, Hwan-You, E-mail: hychang@life.nthu.edu.tw

    2010-10-15

    UDP-glucose dehydrogenase (UGDH) catalyzes oxidation of UDP-glucose to yield UDP-glucuronic acid, a precursor of hyaluronic acid (HA) and other glycosaminoglycans (GAGs) in extracellular matrix. Although association of extracellular matrix with cell proliferation and migration has been well documented, the importance of UGDH in these behaviors is not clear. Using UGDH-specific small interference RNA to treat HCT-8 colorectal carcinoma cells, a decrease in both mRNA and protein levels of UGDH, as well as the cellular UDP-glucuronic acid and GAG production was observed. Treatment of HCT-8 cells with either UGDH-specific siRNA or HA synthesis inhibitor 4-methylumbelliferone effectively delayed cell aggregation into multicellular spheroids and impaired cell motility in both three-dimensional collagen gel and transwell migration assays. The reduction in cell aggregation and migration rates could be restored by addition of exogenous HA. These results indicate that UGDH can regulate cell motility through the production of GAG. The enzyme may be a potential target for therapeutic intervention of colorectal cancers.

  20. Focus on periodontal disease and colorectal carcinoma.

    Science.gov (United States)

    Lauritano, D; Sbordone, L; Nardone, M; Iapichino, A; Scapoli, L; Carinci, F

    2017-01-01

    Diagnosis of focal disease, the theory that the human oral microbial (HOM) could affect the onset and development of systemic diseases, was very popular in the past, but the lack of scientific evidence has led to the abandonment of this idea. Interestingly, increasing evidence over the past 3 or so decades suggests that HOM can indeed serve as a reservoir for systemic dissemination of pathogenic bacteria and their toxins in distant body sites, favouring the developments of malignant tumours. Malignant tumours are complex communities of oncogenically transformed cells with aberrant genomes, associated non-neoplastic cells including immune and stromal cells, and sometimes HOM, including bacteria and viruses. Recent data suggest that HOM and periodontal disease play an active role in the pathogenesis of colorectal cancer, in fact HOM has been found within the colorectal cancer microenvironment, and the composition of the HOM was different from that of adjacent non-neoplastic tissue. An association of fusobacterium nucleatum with the colonic mucosa of colorectal cancer has been proven. Several questions thus arise. Is periodontal disease a risk factor for colorectal carcinoma? Given the connectivity of the digestive tract, could fusubacterium nucleatum or other HOM be involved in additional gastrointestinal disorders? Furthermore, based on the "mobility" of Fusubacterium nucleatum and the omnipresence of cadherins, could this organism be involved in cancers beyond the gastrointestinal tract? Answers to these questions will shed new lights on the role of the HOM in onset of diseases.

  1. [Adenovirus-mediated delivery of nm23-H1 gene inhibits growth of colorectal carcinoma cell line Lovo].

    Science.gov (United States)

    Wang, Qi; He, Xueling; Liu, Yan; Yin, Hailin

    2010-12-01

    This experimental study sought to find out the inhibitory effects of Ad-GFP-nm23-H1 on proliferation and metastasis of human colorectal carcinoma cell line Lovo, and, further, to gain an insight into some theoretical and methodical basis for instituting nm23-H1 gene therapy of cancers. MTT assay and Transwell chamber were used to detect the rates of proliferation and invasion as well as the adhesion of Lovo cells in vitro. The results demonstrated that the proliferation inhibition rates of Lovo cells treated with Ad-GFP-nm23-H1 of 10(10) PFU/ml, 10(9) PFU/ml and 10(8) PFU/ml were 84.9% +/- 1.51%, 48.5% +/- 7.23% and 22.5% +/- 5.47%, that the adherence inhibition rates of Lovo cells treated with Ad-GFP-nm23-H1 of 10(10) PFU/ml, 10(9) PFU/ml and 10(8) PFU/ml were 70.3% +/- 2.40%, 60.1% +/- 5.68% and 18.5% +/- 3.61%, and that the invasiveness inhibition rates of Lovo cells treated with Ad-GFP-nm23-H1 of 10(10) PFU/ml, 10(9) PFU/ml and 10(8) PFU/ml were 83.2% +/- 5.71%, 52.2% +/- 6.94% and 28.1% +/- 8.21%. These data suggested that Ad-GFP-nm23-H1 exerted significant inhibitory effects on the proliferation and metastasis of human colorectal carcinoma cell line Lovo in a dose-dependent way.

  2. Vascular endothelial growth factor receptor-1 mediates migration of human colorectal carcinoma cells by activation of Src family kinases

    Science.gov (United States)

    Lesslie, D P; Summy, J M; Parikh, N U; Fan, F; Trevino, J G; Sawyer, T K; Metcalf, C A; Shakespeare, W C; Hicklin, D J; Ellis, L M; Gallick, G E

    2006-01-01

    Vascular endothelial growth factor (VEGF) is the predominant pro-angiogenic cytokine in human malignancy, and its expression correlates with disease recurrence and poor outcomes in patients with colorectal cancer. Recently, expression of vascular endothelial growth factor receptors (VEGFRs) has been observed on tumours of epithelial origin, including those arising in the colon, but the molecular mechanisms governing potential VEGF-driven biologic functioning in these tumours are not well characterised. In this report, we investigated the role of Src family kinases (SFKs) in VEGF-mediated signalling in human colorectal carcinoma (CRC) cell lines. Vascular endothelial growth factor specifically activated SFKs in HT29 and KM12L4 CRC cell lines. Further, VEGF stimulation resulted in enhanced cellular migration, which was effectively blocked by pharmacologic inhibition of VEGFR-1 or Src kinase. Correspondingly, migration studies using siRNA clones with reduced Src expression confirmed the requirement for Src in VEGF-induced migration in these cells. Furthermore, VEGF treatment enhanced VEGFR-1/SFK complex formation and increased tyrosine phosphorylation of focal adhesion kinase, p130 cas and paxillin. Finally, we demonstrate that VEGF-induced migration is not due, at least in part, to VEGF acting as a mitogen. These results suggest that VEGFR-1 promotes migration of tumour cells through a Src-dependent pathway linked to activation of focal adhesion components that regulate this process. PMID:16685275

  3. The influence of survivin shRNA on the cell cycle and the invasion of SW480 cells of colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Yu Jin

    2008-07-01

    Full Text Available Abstract Background The objective was to understand the influence of Survivin plasmid with short hairpin RNA (shRNA on the cell cycle, invasion, and the silencing effect of Survivin gene in the SW480 cell of colorectal carcinoma. Methods A eukaryotic expression vector, PGCH1/Survivin shRNA, a segment sequence of Survivin as target, was created and transfected into colorectal carcinoma cell line SW480 by the non-lipid method. The influence on the Survivin protein was analyzed by Western blotting, while the cell cycle, cell apoptosis were analyzed by flow cytometry, and invasion of the cell was analyzed by Transwell's chamber method. Results After the transfection of PGCH1/Survivin shRNA, the expression of Survivin protein in SW480 cells was dramatically decreased by 60.68%, in which the cells were stopped at G2/M phase, even though no apoptosis was detected. The number of transmembranous cells of the experimental group, negative control group, and blank control group were 14.46 ± 2.11, 25.12 ± 8.37, and 25.86 ± 7.45, respectively (P 0.05. Conclusion Survivin shRNA could significantly reduce the expression of Survivin protein and invasion of SW480 cells. Changes in cell cycle were observed, but no apoptosis was induced.

  4. BVES regulates EMT in human corneal and colon cancer cells and is silenced via promoter methylation in human colorectal carcinoma.

    Science.gov (United States)

    Williams, Christopher S; Zhang, Baolin; Smith, J Joshua; Jayagopal, Ashwath; Barrett, Caitlyn W; Pino, Christopher; Russ, Patricia; Presley, Sai H; Peng, DunFa; Rosenblatt, Daniel O; Haselton, Frederick R; Yang, Jin-Long; Washington, M Kay; Chen, Xi; Eschrich, Steven; Yeatman, Timothy J; El-Rifai, Wael; Beauchamp, R Daniel; Chang, Min S

    2011-10-01

    The acquisition of a mesenchymal phenotype is a critical step in the metastatic progression of epithelial carcinomas. Adherens junctions (AJs) are required for suppressing this epithelial-mesenchymal transition (EMT) but less is known about the role of tight junctions (TJs) in this process. Here, we investigated the functions of blood vessel epicardial substance (BVES, also known as POPDC1 and POP1), an integral membrane protein that regulates TJ formation. BVES was found to be underexpressed in all stages of human colorectal carcinoma (CRC) and in adenomatous polyps, indicating its suppression occurs early in transformation. Similarly, the majority of CRC cell lines tested exhibited decreased BVES expression and promoter DNA hypermethylation, a modification associated with transcriptional silencing. Treatment with a DNA-demethylating agent restored BVES expression in CRC cell lines, indicating that methylation represses BVES expression. Reexpression of BVES in CRC cell lines promoted an epithelial phenotype, featuring decreased proliferation, migration, invasion, and anchorage-independent growth; impaired growth of an orthotopic xenograft; and blocked metastasis. Conversely, interfering with BVES function by expressing a dominant-negative mutant in human corneal epithelial cells induced mesenchymal features. These biological outcomes were associated with changes in AJ and TJ composition and related signaling. Therefore, BVES prevents EMT, and its epigenetic silencing may be an important step in promoting EMT programs during colon carcinogenesis.

  5. Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells.

    Science.gov (United States)

    Mármol, Inés; Virumbrales-Muñoz, María; Quero, Javier; Sánchez-de-Diego, Cristina; Fernández, Luis; Ochoa, Ignacio; Cerrada, Elena; Yoldi, Mª Jesús Rodríguez

    2017-11-01

    Given the rise of apoptosis-resistant tumors, there exist a growing interest in developing new drugs capable of inducing different types of cell death to reduce colorectal cancer-related death rates. As apoptosis and necroptosis do not share cellular machinery, necroptosis induction may have a great therapeutic potential on those apoptosis-resistant cancers, despite the inflammatory effects associated with it. We have synthesized an alkynyl gold(I) complex [Au(CC-2-NC 5 H 4 )(PTA)] whose anticancer effect was tested on the colorectal adenocarcinoma Caco-2 cell line. With regard to its mechanism of action, this gold complex enters the mitochondria and disrupts its normal function, leading to an increase in ROS production, which triggers necroptosis. Necroptosis induction has been found dependent of TNF-α (Tumor necrosisfactor α) and TNFR1(Tumor necrosisfactor receptor 1) binding, RIP1(Receptor-Interacting Protein 1) activation and NF-κB (Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells) signaling. Moreover, the antitumor potential of [Au(CC-2-NC 5 H 4 )(PTA)] has also been confirmed on the 3D cancer model spheroid. Overall, the obtained data show firstly that gold complexes might have the ability of inducing necroptosis, and secondarily that our compound [Au(CC-2-NC 5 H 4 )(PTA)] is an interesting alternative to current chemotherapy drugs in cases of apoptosis resistance. Copyright © 2017. Published by Elsevier Inc.

  6. Expression of DIAPH1 is up-regulated in colorectal cancer and its down-regulation strongly reduces the metastatic capacity of colon carcinoma cells.

    Science.gov (United States)

    Lin, Yuan-Na; Izbicki, Jakob R; König, Alexandra; Habermann, Jens K; Blechner, Christine; Lange, Tobias; Schumacher, Udo; Windhorst, Sabine

    2014-04-01

    In most cases, metastatic colorectal cancer is not curable, thus new approaches are necessary to identify novel targets for colorectal cancer therapy. Actin-binding-proteins (ABPs) directly regulate motility of metastasising tumor cells, and for cortactin an association with colon cancer metastasis has been already shown. However, as its depletion only incompletely inhibits metastasis, additional, more suitable cellular targets have to be identified. Here we analyzed expression of the ABPs, DIAPH1, VASP, N-WASP, and fascin in comparison with cortactin and found that, besides cortactin, DIAPH1 was expressed with the highest frequency (63%) in colorectal cancer. As well as cortactin, DIAPH1 was not detectable in normal colon tissue and expression of both proteins was positively correlated with metastasis of colorectal cancer. To analyse the mechanistic role of DIAPH1 for metastasis of colon carcinoma cells in comparison with cortactin, expression of the proteins was stably down-regulated in the human colon carcinoma cell lines HT-29, HROC-24 and HCT-116. Analysis of metastasis of colon carcinoma cells in SCID mice revealed that depletion of DIAPH1 reduced metastasis 60-fold and depletion of cortactin 16-fold as compared with control cells. Most likely the stronger effect of DIAPH1 depletion on colon cancer metastasis is due to the fact that in vitro knock down of DIAPH1 impaired all steps of metastasis; adhesion, invasion and migration while down-regulation of cortactin only reduced adhesion and invasion. This very strong reducing effect of DIAPH1 depletion on colon carcinoma cell metastasis makes the protein a promising therapeutic target for individualized colorectal cancer therapy. © 2013 UICC.

  7. The different radiation response and radiation-induced bystander effects in colorectal carcinoma cells differing in p53 status.

    Science.gov (United States)

    Widel, Maria; Lalik, Anna; Krzywon, Aleksandra; Poleszczuk, Jan; Fujarewicz, Krzysztof; Rzeszowska-Wolny, Joanna

    2015-08-01

    Radiation-induced bystander effect, appearing as different biological changes in cells that are not directly exposed to ionizing radiation but are under the influence of molecular signals secreted by irradiated neighbors, have recently attracted considerable interest due to their possible implication for radiotherapy. However, various cells present diverse radiosensitivity and bystander responses that depend, inter alia, on genetic status including TP53, the gene controlling the cell cycle, DNA repair and apoptosis. Here we compared the ionizing radiation and bystander responses of human colorectal carcinoma HCT116 cells with wild type or knockout TP53 using a transwell co-culture system. The viability of exposed to X-rays (0-8 Gy) and bystander cells of both lines showed a roughly comparable decline with increasing dose. The frequency of micronuclei was also comparable at lower doses but at higher increased considerably, especially in bystander TP53-/- cells. Moreover, the TP53-/- cells showed a significantly elevated frequency of apoptosis, while TP53+/+ counterparts expressed high level of senescence. The cross-matched experiments where irradiated cells of one line were co-cultured with non-irradiated cells of opposite line show that both cell lines were also able to induce bystander effects in their counterparts, however different endpoints revealed with different strength. Potential mediators of bystander effects, IL-6 and IL-8, were also generated differently in both lines. The knockout cells secreted IL-6 at lower doses whereas wild type cells only at higher doses. Secretion of IL-8 by TP53-/- control cells was many times lower than that by TP53+/+ but increased significantly after irradiation. Transcription of the NFκBIA was induced in irradiated TP53+/+ mainly, but in bystanders a higher level was observed in TP53-/- cells, suggesting that TP53 is required for induction of NFκB pathway after irradiation but another mechanism of activation must operate in

  8. Interdependence of DNA mismatch repair proteins MLH1 and MSH2 in apoptosis in human colorectal carcinoma cell lines.

    Science.gov (United States)

    Hassen, Samar; Ali, Akhtar A; Kilaparty, Surya P; Al-Anbaky, Qudes A; Majeed, Waqar; Boman, Bruce M; Fields, Jeremy Z; Ali, Nawab

    2016-01-01

    indicator of apoptosis, showed that MLH1 translocation only occurred in MMR proficient (SW480) cells upon induction of apoptosis further suggested a MSH2 dependent role of MLH1 in apoptosis. These data suggest a role of MLH1 in mediation of apoptosis in a MSH2-dependent manner. Taken together, our data supported an interdependence of mismatch repair proteins, particularly MLH1 and MSH2, in the mediation of apoptosis in human colorectal carcinoma cell lines.

  9. Histochemical alterations in colorectal carcinoma and adenoma in Egyptian patients

    Directory of Open Access Journals (Sweden)

    Saber A Sakr

    2016-01-01

    Full Text Available Objective: To evaluate the histochemical alterations in DNA and total carbohydrates, in colorectal cancer cells. Methods: This study was carried out on 48 colorectal carcinoma and 10 adenoma specimens. Hematoxylin and Eosin staining was carried out for histopathological examination to confirm the diagnosis and to evaluate the histopathological characteristics of tumor. Histologic grade and pathologic stage was assessed according to TNM staging system. Staging was also assessed according to original Dukes’ staging system. DNA was demonstrated by Feulgen method and carbohydrates were demonstrated by periodic acid Schiff’s reaction. Results: Adenoma cases showed that the cells lining the glands of the polyp have more crowded, irregular and darker nuclei (hyperchromatic, anisonucleosis, abnormal mitotic figures with prominent nucleoli and variability in the size and shape of nuclei. Colorectal carcinoma cases showed a condensation and reduction in the size of a cell nucleus associated with hyperchromatosis, pyknotic nuclei, abnormal mitotic figures, anisonucleosis, irregular nuclear membrane and inequality in the size of the nuclei (Pleomorphosis. There was a statistical significant differences between adenoma and carcinoma regarding number of mitotic cells (P = 0.03 that was in favour of malignant group. Adenoma and colorectal carcinoma cases showed periodic acid Schiff’s reactivity with different degree. Conclusions: These histochemical alterations can be so characteristic of a given tumor type and stage that they are used in cancer diagnosis and might also be related to the altered functional properties of cancer cells.

  10. The different radiation response and radiation-induced bystander effects in colorectal carcinoma cells differing in p53 status

    Energy Technology Data Exchange (ETDEWEB)

    Widel, Maria, E-mail: maria.widel@polsl.pl [Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice (Poland); Lalik, Anna; Krzywon, Aleksandra [Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice (Poland); Poleszczuk, Jan [College of Inter-faculty Individual Studies in Mathematics and Natural Sciences, University of Warsaw, 93 Zwirki i Wigury Street, 02-089 Warsaw (Poland); Department of Integrated Mathematical Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida (United States); Fujarewicz, Krzysztof; Rzeszowska-Wolny, Joanna [Biosystems Group, Institute of Automatic Control, Silesian University of Technology, 16 Akademicka Street, 44-100 Gliwice (Poland)

    2015-08-15

    Highlights: • We tested radiation response and bystander effect on HCT116p53+/+ and p53−/− cells. • The p53+/+ cells developed premature senescence in exposed and bystander neighbors. • Directly exposed and bystander p53−/− cells died profoundly through apoptosis. • Interleukins 6 and 8 were differently generated by both cell lines. • NFκB path was activated mainly in p53+/+ hit cells, in p53 −/− in bystanders only. - Abstract: Radiation-induced bystander effect, appearing as different biological changes in cells that are not directly exposed to ionizing radiation but are under the influence of molecular signals secreted by irradiated neighbors, have recently attracted considerable interest due to their possible implication for radiotherapy. However, various cells present diverse radiosensitivity and bystander responses that depend, inter alia, on genetic status including TP53, the gene controlling the cell cycle, DNA repair and apoptosis. Here we compared the ionizing radiation and bystander responses of human colorectal carcinoma HCT116 cells with wild type or knockout TP53 using a transwell co-culture system. The viability of exposed to X-rays (0–8 Gy) and bystander cells of both lines showed a roughly comparable decline with increasing dose. The frequency of micronuclei was also comparable at lower doses but at higher increased considerably, especially in bystander TP53-/- cells. Moreover, the TP53-/- cells showed a significantly elevated frequency of apoptosis, while TP53+/+ counterparts expressed high level of senescence. The cross-matched experiments where irradiated cells of one line were co-cultured with non-irradiated cells of opposite line show that both cell lines were also able to induce bystander effects in their counterparts, however different endpoints revealed with different strength. Potential mediators of bystander effects, IL-6 and IL-8, were also generated differently in both lines. The knockout cells secreted IL-6 at

  11. The different radiation response and radiation-induced bystander effects in colorectal carcinoma cells differing in p53 status

    International Nuclear Information System (INIS)

    Widel, Maria; Lalik, Anna; Krzywon, Aleksandra; Poleszczuk, Jan; Fujarewicz, Krzysztof; Rzeszowska-Wolny, Joanna

    2015-01-01

    Highlights: • We tested radiation response and bystander effect on HCT116p53+/+ and p53−/− cells. • The p53+/+ cells developed premature senescence in exposed and bystander neighbors. • Directly exposed and bystander p53−/− cells died profoundly through apoptosis. • Interleukins 6 and 8 were differently generated by both cell lines. • NFκB path was activated mainly in p53+/+ hit cells, in p53 −/− in bystanders only. - Abstract: Radiation-induced bystander effect, appearing as different biological changes in cells that are not directly exposed to ionizing radiation but are under the influence of molecular signals secreted by irradiated neighbors, have recently attracted considerable interest due to their possible implication for radiotherapy. However, various cells present diverse radiosensitivity and bystander responses that depend, inter alia, on genetic status including TP53, the gene controlling the cell cycle, DNA repair and apoptosis. Here we compared the ionizing radiation and bystander responses of human colorectal carcinoma HCT116 cells with wild type or knockout TP53 using a transwell co-culture system. The viability of exposed to X-rays (0–8 Gy) and bystander cells of both lines showed a roughly comparable decline with increasing dose. The frequency of micronuclei was also comparable at lower doses but at higher increased considerably, especially in bystander TP53-/- cells. Moreover, the TP53-/- cells showed a significantly elevated frequency of apoptosis, while TP53+/+ counterparts expressed high level of senescence. The cross-matched experiments where irradiated cells of one line were co-cultured with non-irradiated cells of opposite line show that both cell lines were also able to induce bystander effects in their counterparts, however different endpoints revealed with different strength. Potential mediators of bystander effects, IL-6 and IL-8, were also generated differently in both lines. The knockout cells secreted IL-6 at

  12. Activation of IRE1α-XBP1 pathway induces cell proliferation and invasion in colorectal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Chun [Department of Coloproctology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 (China); Jin, Zhao [Department of Coloproctology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou 325000 (China); Chen, Nian-zhao [Department of Medicine, The Chinese Medicine Hospital of Wenzhou, Wenzhou 325000 (China); Lu, Min; Liu, Chang-bao; Hu, Wan-Le [Department of Coloproctology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 (China); Zheng, Chen-guo, E-mail: zhengchenguo80@163.com [Department of Coloproctology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 (China)

    2016-01-29

    Cell proliferation and tumor metastasis are considered as the main reasons for death in colorectal carcinoma (CRC). IRE1α-XBP1 pathway is the most conserved UPR pathways, which are activated during ER stress caused by the accumulation of unfolded or misfolded protein in the lumen of ER. Here, we demonstrated the critical role of IRE1α-XBP1 pathway and underlying molecular mechanism in cell proliferation and tumor metastasis in CRC. By the use of tissue microarray analysis of samples from 119 patients with CRC, IRE1α was determined to be an independent predictor of overall survival as higher expression of IRE1α in CRC patients showed lower survival rates (p = 0.0041). RNA interference and ectopic expression of IRE1α were applied to determine the molecular effects of IRE1α in CRC cells. The silencing of IRE1α inhibited the proliferation and blocked the invasion of CRC cells in vitro, while ectopic expression of IRE1α in turn promoted cell proliferation and invasion. IRE1α-XBP1 pathway regulated the mitosis of CRC cells through the directly binding of XBP1s to Cyclin D1 promoter to activate Cyclin D1 expression. Our results reveal that IRE1α-XBP1 pathway plays an important role in tumor progression and epithelial-to-mesenchymal transition (EMT), and IRE1α could be employed as a novel prognostic marker and a promising therapeutic target for CRC. - Highlights: • IRE1 was determined to be an independent predictor of overall survival in CRC patient. • IRE1-XBP1 pathway promoted CRC cell proliferation through regulating Cyclin D1 expression. • IRE1-XBP1 pathway played important role in EMT of CRC cells.

  13. Activation of IRE1α-XBP1 pathway induces cell proliferation and invasion in colorectal carcinoma

    International Nuclear Information System (INIS)

    Jin, Chun; Jin, Zhao; Chen, Nian-zhao; Lu, Min; Liu, Chang-bao; Hu, Wan-Le; Zheng, Chen-guo

    2016-01-01

    Cell proliferation and tumor metastasis are considered as the main reasons for death in colorectal carcinoma (CRC). IRE1α-XBP1 pathway is the most conserved UPR pathways, which are activated during ER stress caused by the accumulation of unfolded or misfolded protein in the lumen of ER. Here, we demonstrated the critical role of IRE1α-XBP1 pathway and underlying molecular mechanism in cell proliferation and tumor metastasis in CRC. By the use of tissue microarray analysis of samples from 119 patients with CRC, IRE1α was determined to be an independent predictor of overall survival as higher expression of IRE1α in CRC patients showed lower survival rates (p = 0.0041). RNA interference and ectopic expression of IRE1α were applied to determine the molecular effects of IRE1α in CRC cells. The silencing of IRE1α inhibited the proliferation and blocked the invasion of CRC cells in vitro, while ectopic expression of IRE1α in turn promoted cell proliferation and invasion. IRE1α-XBP1 pathway regulated the mitosis of CRC cells through the directly binding of XBP1s to Cyclin D1 promoter to activate Cyclin D1 expression. Our results reveal that IRE1α-XBP1 pathway plays an important role in tumor progression and epithelial-to-mesenchymal transition (EMT), and IRE1α could be employed as a novel prognostic marker and a promising therapeutic target for CRC. - Highlights: • IRE1 was determined to be an independent predictor of overall survival in CRC patient. • IRE1-XBP1 pathway promoted CRC cell proliferation through regulating Cyclin D1 expression. • IRE1-XBP1 pathway played important role in EMT of CRC cells.

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

    International Nuclear Information System (INIS)

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

    2002-01-01

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

  15. Squamous Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Squamous cell carcinoma Overview Squamous cell carcinoma: This man's skin ... a squamous cell carcinoma on his face. Squamous cell carcinoma: Overview Squamous cell carcinoma (SCC) is a ...

  16. Three-dimensional growth as multicellular spheroid activates the proangiogenic phenotype of colorectal carcinoma cells via LFA-1-dependent VEGF: implications on hepatic micrometastasis

    Directory of Open Access Journals (Sweden)

    Muruzabal Francisco J

    2008-10-01

    Full Text Available Abstract Background The recruitment of vascular stromal and endothelial cells is an early event occurring during cancer cell growth at premetastatic niches, but how the microenvironment created by the initial three-dimensional (3D growth of cancer cells affects their angiogenesis-stimulating potential is unclear. Methods The proangiogenic profile of CT26 murine colorectal carcinoma cells was studied in seven-day cultured 3D-spheroids of Results Spheroid-derived CT26 cells increased vascular endothelial growth factor (VEGF secretion by 70%, which in turn increased the in vitro migration of primary cultured hepatic sinusoidal endothelium (HSE cells by 2-fold. More importantly, spheroid-derived CT26 cells increased lymphocyte function associated antigen (LFA-1-expressing cell fraction by 3-fold; and soluble intercellular adhesion molecule (ICAM-1, given to spheroid-cultured CT26 cells, further increased VEGF secretion by 90%, via cyclooxygenase (COX-2-dependent mechanism. Consistent with these findings, CT26 cancer cells significantly increased LFA-1 expression in non-hypoxic avascular micrometastases at their earliest inception within hepatic lobules in vivo; and angiogenesis also markedly increased in both subcutaneous tumors and hepatic metastases produced by spheroid-derived CT26 cells. Conclusion 3D-growth per se enriched the proangiogenic phenotype of cancer cells growing as multicellular spheroids or as subclinical hepatic micrometastases. The contribution of integrin LFA-1 to VEGF secretion via COX-2 was a micro environmental-related mechanism leading to the pro-angiogenic activation of soluble ICAM-1-activated colorectal carcinoma cells. This mechanism may represent a new target for specific therapeutic strategies designed to block colorectal cancer cell growth at a subclinical micrometastatic stage within the liver.

  17. Temporal morphologic changes in human colorectal carcinomas following xenografting.

    Science.gov (United States)

    Barkla, D H; Tutton, P J

    1983-03-01

    The temporal morphologic changes of human colorectal carcinomas following xenografting into immunosuppressed mice were investigated by the use of light and transmission electron microscopy. The results show that colorectal carcinomas undergo a series of morphologic changes during the initial 30-day period following transplantation. During the initial 1-5-day period the majority of tumor cells die, and during the following 5-10-day period the necrotic debris created during the 1-5-day period is removed by host-supplied inflammatory cells. Only small groups of peripherally placed tumor cells survived at the end of the first 10 days. During the 10-20-day period the tumor cell populations of xenografts were reestablished by a morphologically heterogeneous population of tumor cells, and during the 20-30 day period consolidation of this process continued and some xenografts showed macroscopic evidence of growth. The authors hypothesize that human colorectal carcinomas, like the antecedent epithelium, contain subpopulations of undifferentiated cells that give rise to populations of more-differentiated cells.

  18. Basal Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

  19. Merkel Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Merkel cell carcinoma Overview Merkel cell carcinoma: This rare skin ... hard patch (1) or firm bump (2). Merkel cell carcinoma: Overview What is Merkel cell carcinoma? Merkel ...

  20. Identification of proteins of human colorectal carcinoma cell line SW480 by two-dimensional electrophoresis and MALDI-TOF mass spectrometry

    Institute of Scientific and Technical Information of China (English)

    Ying-Tao Zhang; Yi-Ping Geng; Le Zhou; Bao-Chang Lai; Lv-Sheng Si; Yi-Li Wang

    2005-01-01

    AIM: To conduct the proteomic analysis of human colorectal carcinoma cell line, SW480 by using two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption /ionization-time of flight mass spectrometry (MALDITOFMS).METHODS: The total proteins of human colorectal carcinoma cell line, SW480 were separated with 2-DE by using immobilized pH gradient strips and visualized by staining with silver nitrate. The gel images were acquired by scanner and 2-DE analysis software, Image Master 2D Elite. Nineteen distinct protein spots were excised from gel randomly and digested in gel by TPCK-trypsin. Mass analysis ofthe tryptic digest peptides mixture was performed by using MALDI-TOF MS. Peptide mass fingerprints (PMFs) obtained by the MALDI-TOF analysis were used to search NCBI,SWISS-PROT and MSDB databases by using Mascot software.RESULTS: PMF maps of all spots were obtained by MALDI-TOF MS and thirteen proteins were preliminarily identified.CONCLUSION: The methods of analysis and identification of protein spots of tumor cells in 2-DE gel with silver staining by MALDI-TOF MS derived PMF have been established.Protein expression profile of SW480 has been obtained.It is demonstrated that a combination of proteomics and cell culture is a useful approach to comprehend the process of colon carcinogenesis.

  1. Intake of dietary folate vitamers and risk of colorectal carcinoma

    NARCIS (Netherlands)

    Konings, E.J.M.; Goldbohm, R.A.; Brants, H.A.M.; Saris, W.H.M.; Brandt, P.A. van den

    2002-01-01

    BACKGROUND. Several studies have reported inverse associations between folate intake and colorectal carcinoma risk. Few were prospective studies and none evaluated the association between the intake of individual folate vitamers and colorectal carcinoma risk. METHODS. The aim of the current study

  2. NM23 protein expression in colorectal carcinoma using TMA (tissue microarray: association with metastases and survival

    Directory of Open Access Journals (Sweden)

    Levindo Alves de Oliveira

    2010-12-01

    Full Text Available CONTEXT: NM23, a metastasis suppressor gene, may be associated with prognosis in patients with colorectal carcinoma. OBJECTIVE: To analyze NM23 expression and its association with the presence of lymph node and liver metastases and survival in patients operated on for colorectal carcinoma. METHODS: One hundred thirty patients operated on for colorectal carcinoma were investigated. Tissue microarray blocks containing neoplastic tissue and tumor-adjacent non-neoplastic mucosa were obtained and analyzed by immunohistochemical staining using a monoclonal anti-NM23 antibody. Immunohistochemical expression was assessed using a semiquantitative scoring method, counting the percentage of stained cells. The results were compared regarding morphological and histological characteristics of the colorectal carcinoma, presence of lymph node and liver metastases, tumor staging, and patient survival. Statistical analysis was performed using the Mann-Whitney test, the Kruskal-Wallis test and Fisher's exact test. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. RESULTS: NM23 expression was higher in colorectal carcinoma tissue than in adjacent non-neoplastic mucosa (P<0.0001. NM23 protein expression did not correlate with degree of cell differentiation (P = 0.57, vascular invasion (P = 0.85, lymphatic invasion (P = 0.41, perineural infiltration (P = 0.46, staging (P = 0.19, lymph node metastases (P = 0.08, or liver metastases (P = 0.59. Disease-free survival showed significant association (P = 0.01 with the intensity of NM23 protein immunohistochemical expression in colorectal carcinoma tissue, whereas overall survival showed no association with NM23 protein expression (P = 0.13. CONCLUSIONS: NM23 protein expression was higher in neoplastic colorectal carcinoma tissue than in adjacent non-neoplastic mucosa, showing no correlation with morphological aspects, presence of lymph node or liver metastases, colorectal carcinoma

  3. Vaccination with melanoma lysate-pulsed dendritic cells, of patients with advanced colorectal carcinoma: report from a phase I study

    DEFF Research Database (Denmark)

    Burgdorf, S K; Fischer, A; Claesson, M H

    2006-01-01

    Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma...... contained 3-5 x 10(6) DCs. Five of the six patients received all five vaccines. The treatment was well tolerated in all patients without any observed vaccine-correlated adverse effects. Treatment with this DC-based cancer vaccine proved safe and non-toxic.......Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma...... and selected melanoma cell line enriched in expression of MAGE-A antigens and deficient in expression of melanoma differentiation antigens: tyrosinase, MART-1 and gp100. Vaccinations were administered intradermally on the proximal thigh with a total of five given vaccines at 2 weeks intervals. Each vaccine...

  4. Molecular Diagnostics in Colorectal Carcinoma: Advances and Applications for 2018.

    Science.gov (United States)

    Bhalla, Amarpreet; Zulfiqar, Muhammad; Bluth, Martin H

    2018-06-01

    The molecular pathogenesis and classification of colorectal carcinoma are based on the traditional adenomaecarcinoma sequence, serrated polyp pathway, and microsatellite instability (MSI). The genetic basis for hereditary nonpolyposis colorectal cancer is the detection of mutations in the MLH1, MSH2, MSH6, PMS2, and EPCAM genes. Genetic testing for Lynch syndrome includes MSI testing, methylator phenotype testing, BRAF mutation testing, and molecular testing for germline mutations in MMR genes. Molecular makers with predictive and prognostic implications include quantitative multigene reverse transcriptase polymerase chain reaction assay and KRAS and BRAF mutation analysis. Mismatch repair-deficient tumors have higher rates of programmed death-ligand 1 expression. Cell-free DNA analysis in fluids are proving beneficial for diagnosis and prognosis in these disease states towards effective patient management. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Beclin 1 Expression is Closely Linked to Colorectal Carcinogenesis and Distant Metastasis of Colorectal Carcinoma

    Directory of Open Access Journals (Sweden)

    Mei-Ying Zhang

    2014-08-01

    Full Text Available Beclin 1 participates in development, autophagy, differentiation, anti- apoptosis, neurodegeneration, tumorigenesis and cancer progression. The roles of Beclin 1 in colorectal carcinogenesis and its subsequent progression are still unclear. Here, the mRNA and protein expression of Beclin 1 were determined in colorectal carcinoma and matched mucosa by Reverse transcriptase-polymerase chain reaction and Western blot. Immunohistochemistry and in situ hybridization (ISH were performed on tissue microarryer with colorectal carcinoma, adenoma and mucosa. The expression of Beclin 1 mRNA and protein was found to be higher in colorectal carcinoma than matched mucosa by real-time PCR and Western blot (p < 0.05. According to the ISH data, Beclin 1 expression was lower in colorectal non-neoplastic mucosa (NNM than adenoma and carcinoma (p < 0.05. Immunohistochemically, primary carcinoma showed stronger Beclin 1 expression than NNM and metastatic carcinoma in the liver (p < 0.05. Beclin 1 protein expression was negatively related to liver and distant metastasis (p < 0.05, but not correlated with age, sex, depth of invasion, lymphatic or venous invasion, lymph node metastasis, tumor-node-metastasis (TNM staging, differentiation or serum carcinoembryonic antigen (CEA concentration (p > 0.05. Survival analysis indicated that Beclin 1 expression was not linked to favorable prognosis of the patients with colorectal carcinoma (p > 0.05. Cox’s model indicated that depth of invasion and distant metastasis were independent prognostic factors for colorectal carcinomas (p < 0.05. It was suggested that Beclin 1 expression is closely linked to colorectal carcinogenesis and distant metastasis of colorectal carcinoma.

  6. miR-297 modulates multidrug resistance in human colorectal carcinoma by down-regulating MRP-2.

    Science.gov (United States)

    Xu, Ke; Liang, Xin; Shen, Ke; Cui, Daling; Zheng, Yuanhong; Xu, Jianhua; Fan, Zhongze; Qiu, Yanyan; Li, Qi; Ni, Lei; Liu, Jianwen

    2012-09-01

    Colorectal carcinoma is a frequent cause of cancer-related death in men and women. miRNAs (microRNAs) are endogenous small non-coding RNAs that regulate gene expression negatively at the post-transcriptional level. In the present study we investigated the possible role of microRNAs in the development of MDR (multidrug resistance) in colorectal carcinoma cells. We analysed miRNA expression levels between MDR colorectal carcinoma cell line HCT116/L-OHP cells and their parent cell line HCT116 using a miRNA microarray. miR-297 showed lower expression in HCT116/L-OHP cells compared with its parental cells. MRP-2 (MDR-associated protein 2) is an important MDR protein in platinum-drug-resistance cells and is a predicted target of miR-297. Additionally miR-297 was down-regulated in a panel of human colorectal carcinoma tissues and negatively correlated with expression levels of MRP-2. Furthermore, we found that ectopic expression of miR-297 in MDR colorectal carcinoma cells reduced MRP-2 protein level and sensitized these cells to anti-cancer drugs in vitro and in vivo. Taken together, our findings suggest that miR-297 could play a role in the development of MDR in colorectal carcinoma cells, at least in part by modulation of MRP-2.

  7. Studies on recurrence of colorectal carcinoma

    International Nuclear Information System (INIS)

    Kobayashi, Masayuki; Nosaki, Tadaharu; Murai, Tomoya; Ooshita, Ikuo; Kobayashi, Suzuo

    1989-01-01

    Recurrence patterns of colorectal carcinoma were studied in 402 patients followed up for 5 years or more after surgery. Recurrence was observed in 23% for colon cancer and 38% for rectal canccer. The most frequent site of recurrence or relapse in cases of colon cancer was the liver, followed by multiple organs and a local region; and in the case of rectal cancer, it was multiple organs, followed by a local region, the liver, lung, and bone. The rate of recurrence or relapse tended to be higher in patients with lymph node metastases or more advanced clinical stage. Liver relapse was seen in 13% for colon cancer and 12% for rectal cancer, occurring within 48 months after surgery. Since CT can detect liver relapse within 24 months, abdominal CT and chest plain roentgenography should be performed in the first 6 months, 12 months, and 24 months after surgery. (Namekawa, K)

  8. Cellular effects of the microtubule-targeting agent peloruside A in hypoxia-conditioned colorectal carcinoma cells.

    Science.gov (United States)

    Řehulka, Jiří; Annadurai, Narendran; Frydrych, Ivo; Znojek, Pawel; Džubák, Petr; Northcote, Peter; Miller, John H; Hajdúch, Marián; Das, Viswanath

    2017-07-01

    Hypoxia is a prominent feature of solid tumors, dramatically remodeling microtubule structures and cellular pathways and contributing to paclitaxel resistance. Peloruside A (PLA), a microtubule-targeting agent, has shown promising anti-tumor effects in preclinical studies. Although it has a similar mode of action to paclitaxel, it binds to a distinct site on β-tubulin that differs from the classical taxane site. In this study, we examined the unexplored effects of PLA in hypoxia-conditioned colorectal HCT116 cancer cells. Cytotoxicity of PLA was determined by cell proliferation assay. The effects of a pre-exposure to hypoxia on PLA-induced cell cycle alterations and apoptosis were examined by flow cytometry, time-lapse imaging, and western blot analysis of selected markers. The hypoxia effect on stabilization of microtubules by PLA was monitored by an intracellular tubulin polymerization assay. Our findings show that the cytotoxicity of PLA is not altered in hypoxia-conditioned cells compared to paclitaxel and vincristine. Furthermore, hypoxia does not alter PLA-induced microtubule stabilization nor the multinucleation of cells. PLA causes cyclin B1 and G2/M accumulation followed by apoptosis. The cellular and molecular effects of PLA have been determined in normoxic conditions, but there are no reports of PLA effects in hypoxic cells. Our findings reveal that hypoxia preconditioning does not alter the sensitivity of HCT116 to PLA. These data report on the cellular and molecular effects of PLA in hypoxia-conditioned cells for the first time, and will encourage further exploration of PLA as a promising anti-tumor agent. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Oral Rigosertib for Squamous Cell Carcinoma

    Science.gov (United States)

    2017-06-22

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  10. Establishment, characterization and chemosensitivity of three mismatch repair deficient cell lines from sporadic and inherited colorectal carcinomas.

    Directory of Open Access Journals (Sweden)

    Claudia Maletzki

    Full Text Available BACKGROUND: Colorectal cancer (CRC represents a morphologic and molecular heterogenic disease. This heterogeneity substantially impairs drug effectiveness and prognosis. The subtype of mismatch repair deficient (MMR-D CRCs, accounting for about 15% of all cases, shows particular differential responses up to resistance towards currently approved cytostatic drugs. Pre-clinical in vitro models representing molecular features of MMR-D tumors are thus mandatory for identifying biomarkers that finally help to predict responses towards new cytostatic drugs. Here, we describe the successful establishment and characterization of three patient-derived MMR-D cell lines (HROC24, HROC87, and HROC113 along with their corresponding xenografts. METHODOLOGY: MMR-D cell lines (HROC24, HROC87, and HROC113 were established from a total of ten clinicopathological well-defined MMR-D cases (120 CRC cases in total. Cells were comprehensively characterized by phenotype, morphology, growth kinetics, invasiveness, and molecular profile. Additionally, response to clinically relevant chemotherapeutics was examined in vitro and in vivo. PRINCIPAL FINDINGS: Two MMR-D lines showing CIMP-H derived from sporadic CRC (HROC24: K-ras(wt, B-raf(mut, HROC87: K-ras(wt, B-raf(mut, whereas the HROC113 cell line (K-ras(mut, B-raf(wt was HNPCC-associated. A diploid DNA-status could be verified by flow cytometry and SNP Array analysis. All cell lines were characterized as epithelial (EpCAM(+ tumor cells, showing surface tumor marker expression (CEACAM(+. MHC-class II was inducible by Interferon-γ stimulation. Growth kinetics as well as invasive potential was quite heterogeneous between individual lines. Besides, MMR-D cell lines exhibited distinct responsiveness towards chemotherapeutics, even when comparing in vitro and in vivo sensitivity. CONCLUSIONS: These newly established and well-characterized, low-passage MMR-D cell lines provide a useful tool for future investigations on the

  11. Colorectal carcinoma: preoperative staging with water enema spiral CT

    International Nuclear Information System (INIS)

    Guan Sheng; Gao Jianbo; Li Yintai; Chen Xuejun; Yang Xuehua; Yang Xiaopeng; Cheng Jingliang

    2001-01-01

    Objective: To determine the value and limitation of water enema spiral CT (WESCT) in staging of colorectal carcinoma. Methods: Forty-eight patients with histologically proven rectum or colon carcinoma were included in this study. All of them were examined by SCT, and the preoperative staging of TNM and Duke were used based on the findings of SCT. The results of WESCT were compared with those of surgical and pathological examination in all cases. Results: All lesions in the 47 cases were demonstrated clearly by WESCT and the sensitivity was 97.9%; 39 cases of 48 patients were correctly staged with TNM and 42 cases with Duke, the accuracy was 81.3% and 87.5% respectively, which were higher than the overall 50 % accuracy reported by references; (3) The accuracy of WESCT was 89.6% (43/48) in T stage and 81.3% (39/48) in N stage. Three cases in M stage were all diagnosed correctly; Conclusion: WESCT scan is a better method of depicting the colorectal carcinoma. It allows for accurate depiction and staging of colorectal carcinoma, especially detecting the invasion of adjacent tissues and distant metastasis. It is the best imaging method for staging the colorectal carcinoma . However the value of WESCT for early T staging in colorectal carcinoma and minute metastasis of lymph nodes or liver is limited

  12. Wogonin induced G1 cell cycle arrest by regulating Wnt/β-catenin signaling pathway and inactivating CDK8 in human colorectal cancer carcinoma cells

    International Nuclear Information System (INIS)

    He, Licheng; Lu, Na; Dai, Qinsheng; Zhao, Yue; Zhao, Li; Wang, Hu; Li, Zhiyu; You, Qidong; Guo, Qinglong

    2013-01-01

    Highlights: • Wogonin inhibited HCT116 cells growth and arrested at G1 phase of the cell cycle. • Wogonin down-regulated the canonical Wnt/β-catenin signaling pathway. • Wogonin interfered in the combination of β-catenin and TCF/Lef. • Wogonin limited the kinase activity of CDK8. - Abstract: Wogonin, a naturally occurring mono-flavonoid, has been reported to have tumor therapeutic potential and good selectivity both in vitro and in vivo. Herein, we investigated the anti-proliferation effects and associated mechanisms of wogonin in human colorectal cancer in vitro. The flow-cytometric analysis showed that wogonin induced a G1 phase cell cycle arrest in HCT116 cells in a concentration- and time-dependent manner. Meanwhile, the cell cycle-related proteins, such as cyclin A, E, D1, and CDK2, 4 were down-regulated in wogonin-induced G1 cell cycle arrest. Furthermore, we showed that the anti-proliferation and G1 arrest effect of wogonin on HCT116 cells was associated with deregulation of Wnt/β-catenin signaling pathway. Wogonin-treated cells showed decreased intracellular levels of Wnt proteins, and activated degradation complex to phosphorylated and targeted β-catenin for proteasomal degradation. Wogonin inhibited β-catenin-mediated transcription by interfering in the transcriptional activity of TCF/Lef, and repressing the kinase activity of CDK8 which has been considered as an oncogene involving in the development of colorectal cancers. Moreover, CDK8 siRNA-transfected HCT116 cells showed similar results to wogonin treated cells. Thus, our data suggested that wogonin induced anti-proliferation and G1 arrest via Wnt/β-catenin signaling pathway and it can be developed as a therapeutic agent against human colorectal cancer

  13. NDRG2 gene copy number is not altered in colorectal carcinoma

    DEFF Research Database (Denmark)

    Lorentzen, Anders Blomkild; Mitchelmore, Cathy

    2017-01-01

    AIM To investigate if the down-regulation of N-myc Downstream Regulated Gene 2 (NDRG2) expression in colorectal carcinoma (CRC) is due to loss of the NDRG2 allele(s). METHODS The following were investigated in the human colorectal cancer cell lines DLD-1, LoVo and SW-480: NDRG2 mRNA expression...... levels using quantitative reverse transcription-polymerase chain reaction (qRT-PCR); interaction of the MYC gene-regulatory protein with the NDRG2 promoter using chromatin immunoprecipitation; and NDRG2 promoter methylation using bisulfite sequencing. Furthermore, we performed qPCR to analyse the copy...... numbers of NDRG2 and MYC genes in the above three cell lines, 8 normal colorectal tissue samples and 40 CRC tissue samples. RESULTS As expected, NDRG2 mRNA levels were low in the three colorectal cancer cell lines, compared to normal colon. Endogenous MYC protein interacted with the NDRG2 core promoter...

  14. Comprehensive and Holistic Analysis of HT-29 Colorectal Cancer Cells and Tumor-Bearing Nude Mouse Model: Interactions Among Fractions Derived From the Chinese Medicine Formula Tian Xian Liquid in Effects on Human Colorectal Carcinoma.

    Science.gov (United States)

    Leigh, Annballaw Bridget; Cheung, Ho Pan; Lin, Li-Zhu; Ng, Tzi Bun; Lao, Lixing; Zhang, Yanbo; Zhang, Zhang-Jin; Tong, Yao; Sze, Stephen Cho Wing

    2017-09-01

    The Chinese medicine formula Tian Xian Liquid (TXL) has been used clinically for cancer therapy in China for more than 25 years. However, the comprehensive and holistic effects of its bioactive fractions for various antitumor therapeutic effects have not been unraveled. This is the first study to scientifically elucidate the holistic effect of Chinese medicine formula for treating colon cancer, hence allowing a better understanding of the essence of Chinese medicine formula, through the comparison of the actions of TXL and its functional constituent fractions, including ethyl acetate (EA), butanol (BU), and aqueous (WA) fractions. Tissue-specific proliferative/antiproliferative effects of these fractions on human colorectal carcinoma HT-29 cells and splenocytes were studied by using the MTT assay. Their modulations on the expression of markers of antiproliferation, antimetastasis, reversion of multidrug resistance in treated HT-29 cells were examined with real-time polymerase chain reaction and Western blot analysis, and their modulations in a xenografted nude mouse model were examined by Western blot analysis. Results revealed that EA fraction slightly inhibited the proliferation of HT-29 cells, but tissue-specifically exerted the most potent antiproliferative effect on splenocytes. On the contrary, only TXL and BU fraction tissue-specifically contributed to the proliferation of splenocytes, but inhibited the proliferation of HT-29 cells. WA fraction exerted the most potent antiproliferative effect on HT-29 cells and also the strongest inhibitory action on tumor size in the nude mouse model in our previous study. In the HT-29 model, TXL and WA fraction exerted the most pronounced effect on upregulation of p21 mRNA and protein; TXL, and EA and WA fractions exerted the effect on downregulation of G1 phase cell cycle protein, cyclin D1 mRNA and protein; EA and BU fractions exerted the most prominent anti-invasive effect on anti-invasion via downregulation of MMP-1 m

  15. Gut microbiome development along the colorectal adenoma-carcinoma sequence.

    Science.gov (United States)

    Feng, Qiang; Liang, Suisha; Jia, Huijue; Stadlmayr, Andreas; Tang, Longqing; Lan, Zhou; Zhang, Dongya; Xia, Huihua; Xu, Xiaoying; Jie, Zhuye; Su, Lili; Li, Xiaoping; Li, Xin; Li, Junhua; Xiao, Liang; Huber-Schönauer, Ursula; Niederseer, David; Xu, Xun; Al-Aama, Jumana Yousuf; Yang, Huanming; Wang, Jian; Kristiansen, Karsten; Arumugam, Manimozhiyan; Tilg, Herbert; Datz, Christian; Wang, Jun

    2015-03-11

    Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly involved in colorectal carcinogenesis. The identity and functional capacity of the adenoma- or carcinoma-related gut microbe(s), however, have not been surveyed in a comprehensive manner. Here we perform a metagenome-wide association study (MGWAS) on stools from advanced adenoma and carcinoma patients and from healthy subjects, revealing microbial genes, strains and functions enriched in each group. An analysis of potential risk factors indicates that high intake of red meat relative to fruits and vegetables appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest that faecal microbiome-based strategies may be useful for early diagnosis and treatment of colorectal adenoma or carcinoma.

  16. Diets That Promote Colon Inflammation Associate With Risk of Colorectal Carcinomas That Contain Fusobacterium nucleatum.

    Science.gov (United States)

    Liu, Li; Tabung, Fred K; Zhang, Xuehong; Nowak, Jonathan A; Qian, Zhi Rong; Hamada, Tsuyoshi; Nevo, Daniel; Bullman, Susan; Mima, Kosuke; Kosumi, Keisuke; da Silva, Annacarolina; Song, Mingyang; Cao, Yin; Twombly, Tyler S; Shi, Yan; Liu, Hongli; Gu, Mancang; Koh, Hideo; Li, Wanwan; Du, Chunxia; Chen, Yang; Li, Chenxi; Li, Wenbin; Mehta, Raaj S; Wu, Kana; Wang, Molin; Kostic, Aleksander D; Giannakis, Marios; Garrett, Wendy S; Hutthenhower, Curtis; Chan, Andrew T; Fuchs, Charles S; Nishihara, Reiko; Ogino, Shuji; Giovannucci, Edward L

    2018-04-24

    Specific nutritional components are likely to induce intestinal inflammation, which is characterized by increased levels of interleukin 6 (IL6), C-reactive protein (CRP), and TNF receptor superfamily member 1B (TNFRSF1B) in the circulation and promotes colorectal carcinogenesis. The inflammatory effects of a diet can be estimated based on empirical dietary inflammatory pattern (EDIP) score, calculated based on intake of 18 foods associated with plasma levels of IL6, CRP, and TNFRSF1B. An inflammatory environment in the colon (based on increased levels of IL6, CRP, and TNFRSF1B in peripheral blood) contributes to impairment of the mucosal barrier and altered immune cell responses, affecting the composition of the intestinal microbiota. Colonization by Fusobacterium nucleatum has been associated with presence and features of colorectal adenocarcinoma. We investigated the association between diets that promote inflammation (based on EDIP score) and colorectal cancer subtypes classified by level of F nucleatum in the tumor microenvironment. We calculated EDIP scores based on answers to questionnaires collected from participants in the Nurses' Health Study (through June 1, 2012) and the Health Professionals Follow-up Study (through January 31, 2012). Participants in both cohorts reported diagnoses of rectal or colon cancer in biennial questionnaires; deaths from unreported colorectal cancer cases were identified through the National Death Index and next of kin. Colorectal tumor tissues were collected from hospitals where the patients underwent tumor resection and F nucleatum DNA was quantified by a PCR assay. We used multivariable duplication-method Cox proportional hazard regression to assess the associations of EDIP scores with risks of colorectal cancer subclassified by F nucleatum status. During 28 years of follow up of 124,433 participants, we documented 951 incident cases of colorectal carcinoma with tissue F nucleatum data. Higher EDIP scores associated with

  17. Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma

    International Nuclear Information System (INIS)

    Saelen, Marie Grøn; Ree, Anne Hansen; Kristian, Alexandr; Fleten, Karianne Giller; Furre, Torbjørn; Hektoen, Helga Helseth; Flatmark, Kjersti

    2012-01-01

    The histone deacetylase inhibitor vorinostat is a candidate radiosensitizer in locally advanced rectal cancer (LARC). Radiosensitivity is critically influenced by hypoxia; hence, it is important to evaluate the efficacy of potential radiosensitizers under variable tissue oxygenation. Since fluoropyrimidine-based chemoradiotherapy (CRT) is the only clinically validated regimen in LARC, efficacy in combination with this established regimen should be assessed in preclinical models before a candidate drug enters clinical trials. Radiosensitization by vorinostat under hypoxia was studied in four colorectal carcinoma cell lines and in one colorectal carcinoma xenograft model by analysis of clonogenic survival and tumor growth delay, respectively. Radiosensitizing effects of vorinostat in combination with capecitabine were assessed by evaluation of tumor growth delay in two colorectal carcinoma xenografts models. Under hypoxia, radiosensitization by vorinostat was demonstrated in vitro in terms of decreased clonogenicity and in vivo as inhibition of tumor growth. Adding vorinostat to capecitabine-based CRT increased radiosensitivity of xenografts in terms of inhibited tumor growth. Vorinostat sensitized colorectal carcinoma cells to radiation under hypoxia in vitro and in vivo and improved therapeutic efficacy in combination with capecitabine-based CRT in vivo. The results encourage implementation of vorinostat into CRT in LARC trials

  18. Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma.

    Science.gov (United States)

    Saelen, Marie Grøn; Ree, Anne Hansen; Kristian, Alexandr; Fleten, Karianne Giller; Furre, Torbjørn; Hektoen, Helga Helseth; Flatmark, Kjersti

    2012-09-27

    The histone deacetylase inhibitor vorinostat is a candidate radiosensitizer in locally advanced rectal cancer (LARC). Radiosensitivity is critically influenced by hypoxia; hence, it is important to evaluate the efficacy of potential radiosensitizers under variable tissue oxygenation. Since fluoropyrimidine-based chemoradiotherapy (CRT) is the only clinically validated regimen in LARC, efficacy in combination with this established regimen should be assessed in preclinical models before a candidate drug enters clinical trials. Radiosensitization by vorinostat under hypoxia was studied in four colorectal carcinoma cell lines and in one colorectal carcinoma xenograft model by analysis of clonogenic survival and tumor growth delay, respectively. Radiosensitizing effects of vorinostat in combination with capecitabine were assessed by evaluation of tumor growth delay in two colorectal carcinoma xenografts models. Under hypoxia, radiosensitization by vorinostat was demonstrated in vitro in terms of decreased clonogenicity and in vivo as inhibition of tumor growth. Adding vorinostat to capecitabine-based CRT increased radiosensitivity of xenografts in terms of inhibited tumor growth. Vorinostat sensitized colorectal carcinoma cells to radiation under hypoxia in vitro and in vivo and improved therapeutic efficacy in combination with capecitabine-based CRT in vivo. The results encourage implementation of vorinostat into CRT in LARC trials.

  19. Radiosensitization by the histone deacetylase inhibitor vorinostat under hypoxia and with capecitabine in experimental colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Saelen Marie

    2012-09-01

    Full Text Available Abstract Background The histone deacetylase inhibitor vorinostat is a candidate radiosensitizer in locally advanced rectal cancer (LARC. Radiosensitivity is critically influenced by hypoxia; hence, it is important to evaluate the efficacy of potential radiosensitizers under variable tissue oxygenation. Since fluoropyrimidine-based chemoradiotherapy (CRT is the only clinically validated regimen in LARC, efficacy in combination with this established regimen should be assessed in preclinical models before a candidate drug enters clinical trials. Methods Radiosensitization by vorinostat under hypoxia was studied in four colorectal carcinoma cell lines and in one colorectal carcinoma xenograft model by analysis of clonogenic survival and tumor growth delay, respectively. Radiosensitizing effects of vorinostat in combination with capecitabine were assessed by evaluation of tumor growth delay in two colorectal carcinoma xenografts models. Results Under hypoxia, radiosensitization by vorinostat was demonstrated in vitro in terms of decreased clonogenicity and in vivo as inhibition of tumor growth. Adding vorinostat to capecitabine-based CRT increased radiosensitivity of xenografts in terms of inhibited tumor growth. Conclusions Vorinostat sensitized colorectal carcinoma cells to radiation under hypoxia in vitro and in vivo and improved therapeutic efficacy in combination with capecitabine-based CRT in vivo. The results encourage implementation of vorinostat into CRT in LARC trials.

  20. Basal cell carcinoma of the skin with areas of squamous cell carcinoma: a basosquamous cell carcinoma?

    OpenAIRE

    de Faria, J

    1985-01-01

    The diagnosis of basosquamous cell carcinoma is controversial. A review of cases of basal cell carcinoma showed 23 cases that had conspicuous areas of squamous cell carcinoma. This was distinguished from squamous differentiation and keratotic basal cell carcinoma by a comparative study of 40 cases of compact lobular and 40 cases of keratotic basal cell carcinoma. Areas of intermediate tumour differentiation between basal cell and squamous cell carcinoma were found. Basal cell carcinomas with ...

  1. Obatoclax, a Pan-BCL-2 Inhibitor, Targets Cyclin D1 for Degradation to Induce Antiproliferation in Human Colorectal Carcinoma Cells.

    Science.gov (United States)

    Or, Chi-Hung R; Chang, Yachu; Lin, Wei-Cheng; Lee, Wee-Chyan; Su, Hong-Lin; Cheung, Muk-Wing; Huang, Chang-Po; Ho, Cheesang; Chang, Chia-Che

    2016-12-27

    Colorectal cancer is the third most common cancer worldwide. Aberrant overexpression of antiapoptotic BCL-2 (B-cell lymphoma 2) family proteins is closely linked to tumorigenesis and poor prognosis in colorectal cancer. Obatoclax is an inhibitor targeting all antiapoptotic BCL-2 proteins. A previous study has described the antiproliferative action of obatoclax in one human colorectal cancer cell line without elucidating the underlying mechanisms. We herein reported that, in a panel of human colorectal cancer cell lines, obatoclax inhibits cell proliferation, suppresses clonogenicity, and induces G₁-phase cell cycle arrest, along with cyclin D1 downregulation. Notably, ectopic cyclin D1 overexpression abrogated clonogenicity suppression but also G₁-phase arrest elicited by obatoclax. Mechanistically, pre-treatment with the proteasome inhibitor MG-132 restored cyclin D1 levels in all obatoclax-treated cell lines. Cycloheximide chase analyses further revealed an evident reduction in the half-life of cyclin D1 protein by obatoclax, confirming that obatoclax downregulates cyclin D1 through induction of cyclin D1 proteasomal degradation. Lastly, threonine 286 phosphorylation of cyclin D1, which is essential for initiating cyclin D1 proteasomal degradation, was induced by obatoclax in one cell line but not others. Collectively, we reveal a novel anticancer mechanism of obatoclax by validating that obatoclax targets cyclin D1 for proteasomal degradation to downregulate cyclin D1 for inducing antiproliferation.

  2. Matrix metalloproteinase-13 expression in the progression of colorectal adenoma to carcinoma : Matrix metalloproteinase-13 expression in the colorectal adenoma and carcinoma.

    Science.gov (United States)

    Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza

    2014-06-01

    Most colorectal carcinomas (CRCs) are considered to arise from conventional adenoma based on the concept of the adenoma-carcinoma sequence. Matrix metalloproteinases (MMPs) are known to be overexpressed as normal mucosa progresses to adenomas and carcinomas. There has been little previous investigation about MMP-13 expression in adenoma-carcinoma sequence. In this study, we aimed to investigate the immunohistochemical expression of MMP-13 in colorectal adenoma and CRC specimens using tissue microarray (TMA) technique. A total of 40 cases of CRC associated with adenoma were collected from files of the Pathology laboratory at Mansoura Gastroenterology Center between January 2007 and January 2012. Sections from TMA blocks were prepared and stained for MMP-13. Immunoreactivity to MMP-13 staining was localized to the cytoplasm of mildly, moderately, and severely dysplatic cells of adenomas and CRC tumor cells that were either homogenous or heterogeneous. There was no significant difference in MMP-13 expression between adenomas and CRCs either non-mucinous or mucinous. Adenomas with high MMP-13 expression were significantly associated with moderate to marked degree of inflammatory cellular infiltrate and presence of familial adenomatous polyps. In conclusion, MMP-13 may be a potential biological marker of early tumorigenesis in the adenoma-carcinoma sequence.

  3. Clinical value of the preoperative neutrophil-to-lymphocyte ratio and red blood cell distribution width in patients with colorectal carcinoma.

    Science.gov (United States)

    Han, Fuyan; Shang, Xuming; Wan, Furong; Liu, Zhanfeng; Tian, Wenjun; Wang, Dan; Liu, Yiqing; Wang, Yong; Zhang, Bingchang; Ju, Ying

    2018-03-01

    The aim of the present study was to investigate the clinical value of the preoperative neutrophil-to-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) in the peripheral blood of colorectal carcinoma (CRC) patients. Clinical data obtained from 240 patients with CRC undergoing radical surgical resection in Shandong Provincial Hospital Affiliated to Shandong University (Jinan, Shandong, China) between January 2011 and April 2015 were retrospectively analyzed. Data were also collected from 110 patients with colon polyps and 48 healthy volunteers to serve as controls for comparative analysis. The clinicopathological characteristics of the patients in the low and high NLR and RDW groups were compared. The NLR and RDW values were compared prior to and following surgery. Kaplan-Meier analyses and Cox regression modeling were performed to predict overall survival (OS) and disease-free survival (DFS). The NLR and RDW levels in the CRC patients were markedly higher than those in the colon polyp patients and the healthy controls. The optimum NLR and RDW cutoff points for CRC were 2.06 and 13.45%, respectively. Significant differences were detected in tumor location, diameter, degree of differentiation, tumor depth, carcinoembryonic antigen and carbohydrate antigen 199 when comparing the high and low NLR groups (P0.05). CRC patients with an increased RDW had significantly worse OS and DFS rates, particularly those with metastatic CRC (P<0.05). Patients with a high NLR exhibited a reduced DFS time in CRC (P=0.053), although this difference was not significant, and a significantly worse DFS time in metastatic CRC (P=0.047). In conclusion, it is convenient to use preoperative NLR and RDW to predict prognosis following surgery for patients with CRC.

  4. Morphology of colorectal carcinoma among Nigerians: A 30-year ...

    African Journals Online (AJOL)

    Conclusion: Colorectal carcinoma is no longer a rare disease in Nigeria. The surge in the incidence reported in the last 5 years in this center calls for a pragmatic action in its control, with emphasize on colonoscopic screening for those with family history, and possibly making digital rectal examination a mandatory aspect of ...

  5. Management of Liver Metastasis from Colo-Rectal Carcinoma with ...

    African Journals Online (AJOL)

    Background: Worldwide, colo-rectal carcinoma is the second most common cancer with liver metastases as its major cause of mortality.This malignant condition is now seen more frequently in our environment typically at a late stage with distant metastasis especially to the liver. This study aims at highlighting the current use ...

  6. Molecular profile of 5-fluorouracil pathway genes in colorectal carcinoma

    Czech Academy of Sciences Publication Activity Database

    Kunická, T.; Procházka, Pavel; Krus, I.; Bendová, Petra; Protivová, M.; Susová, S.; Hlaváč, V.; Liška, V.; Novák, P.; Schneiderová, M.; Pitule, P.; Bruha, J.; Vyčítal, O.; Vodička, Pavel; Souček, P.

    2017-01-01

    Roč. 16, oct (2017), s. 795 ISSN 1471-2407 R&D Projects: GA MZd(CZ) NT14329; GA ČR(CZ) GAP304/12/1585 Institutional support: RVO:68378041 Keywords : colorectal carcinoma * 5-fluorouracil * methylation Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 3.288, year: 2016

  7. Gene expression profiles of primary colorectal carcinomas, liver metastases, and carcinomatoses

    Directory of Open Access Journals (Sweden)

    Myklebost Ola

    2007-01-01

    Full Text Available Abstract Background Despite the fact that metastases are the leading cause of colorectal cancer deaths, little is known about the underlying molecular changes in these advanced disease stages. Few have studied the overall gene expression levels in metastases from colorectal carcinomas, and so far, none has investigated the peritoneal carcinomatoses by use of DNA microarrays. Therefore, the aim of the present study is to investigate and compare the gene expression patterns of primary carcinomas (n = 18, liver metastases (n = 4, and carcinomatoses (n = 4, relative to normal samples from the large bowel. Results Transcriptome profiles of colorectal cancer metastases independent of tumor site, as well as separate profiles associated with primary carcinomas, liver metastases, or peritoneal carcinomatoses, were assessed by use of Bayesian statistics. Gains of chromosome arm 5p are common in peritoneal carcinomatoses and several candidate genes (including PTGER4, SKP2, and ZNF622 mapping to this region were overexpressed in the tumors. Expression signatures stratified on TP53 mutation status were identified across all tumors regardless of stage. Furthermore, the gene expression levels for the in vivo tumors were compared with an in vitro model consisting of cell lines representing all three tumor stages established from one patient. Conclusion By statistical analysis of gene expression data from primary colorectal carcinomas, liver metastases, and carcinomatoses, we are able to identify genetic patterns associated with the different stages of tumorigenesis.

  8. Mutational analysis of FLASH and PTPN13 genes in colorectal carcinomas.

    Science.gov (United States)

    Jeong, Eun Goo; Lee, Sung Hak; Yoo, Nam Jin; Lee, Sug Hyung

    2008-01-01

    The Fas-Fas ligand system is considered a major pathway for induction of apoptosis in cells and tissues. FLASH was identified as a pro-apoptotic protein that transmits apoptosis signal during Fas-mediated apoptosis. PTPN13 interacts with Fas and functions as both suppressor and inducer of Fas-mediated apoptosis. There are polyadenine tracts in both FLASH (A8 and A9 in exon 8) and PTPN13 (A8 in exon 7) genes that could be frameshift mutation targets in colorectal carcinomas. Because genes encoding proteins in Fas-mediated apoptosis frequently harbor somatic mutations in cancers, we explored the possibility as to whether mutations of FLASH and PTPN13 are a feature of colorectal carcinomas. We analysed human FLASH in exon 8 and PTPN13 in exon 7 for the detection of somatic mutations in 103 colorectal carcinomas by a polymerase chain reaction (PCR)- based single-strand conformation polymorphism (SSCP). We detected two mutations in FLASH gene, but none in PTPN13 gene. However, the two mutations were not frameshift (deletion or insertion) mutations in the polyadenine tracts of FLASH. The two mutations consisted of a deletion mutation (c.3734-3737delAGAA) and a missense mutation (c.3703A>C). These data indicate that frameshift mutation in the polyadenine tracts in both FLASH and PTPN13 genes is rare in colorectal carcinomas. Also, the data suggest that both FLASH and PTPN13 mutations in the polyadenine tracts may not have a crucial role in the pathogenesis of colorectal carcinomas.

  9. In vivo Expansion of Naïve CD4+CD25high FOXP3+ Regulatory T Cells in Patients with Colorectal Carcinoma after IL-2 Administration

    Science.gov (United States)

    Beyer, Marc; Schumak, Beatrix; Weihrauch, Martin R.; Andres, Bettina; Giese, Thomas; Endl, Elmar; Knolle, Percy A.; Classen, Sabine; Limmer, Andreas; Schultze, Joachim L.

    2012-01-01

    Regulatory T cells (Treg cells) are increased in context of malignancies and their expansion can be correlated with higher disease burden and decreased survival. Initially, interleukin 2 (IL-2) has been used as T-cell growth factor in clinical vaccination trials. In murine models, however, a role of IL-2 in development, differentiation, homeostasis, and function of Treg cells was established. In IL-2 treated cancer patients a further Treg-cell expansion was described, yet, the mechanism of expansion is still elusive. Here we report that functional Treg cells of a naïve phenotype - as determined by CCR7 and CD45RA expression - are significantly expanded in colorectal cancer patients. Treatment of 15 UICC stage IV colorectal cancer patients with IL-2 in a phase I/II peptide vaccination trial further enlarges the already increased naïve Treg-cell pool. Higher frequencies of T-cell receptor excision circles in naïve Treg cells indicate IL-2 dependent thymic generation of naïve Treg cells as a mechanism leading to increased frequencies of Treg cells post IL-2 treatment in cancer patients. This finding could be confirmed in naïve murine Treg cells after IL-2 administration. These results point to a more complex regulation of Treg cells in context of IL-2 administration. Future strategies therefore might aim at combining IL-2 therapy with novel strategies to circumvent expansion and differentiation of naïve Treg cells. PMID:22276195

  10. Gut microbiome development along the colorectal adenoma-carcinoma sequence

    DEFF Research Database (Denmark)

    Feng, Qiang; Liang, Suisha; Jia, Huijue

    2015-01-01

    factors indicates that high intake of red meat relative to fruits and vegetables appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest that faecal microbiome-based strategies may be useful for early diagnosis and treatment......Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly involved in colorectal carcinogenesis. The identity and functional capacity of the adenoma- or carcinoma-related gut microbe...

  11. Metastatic Renal Cell Carcinoma to the Pancreas: A Review.

    Science.gov (United States)

    Cheng, Shaun Kian Hong; Chuah, Khoon Leong

    2016-06-01

    The pancreas is an unusual site for tumor metastasis, accounting for only 2% to 5% of all malignancies affecting the pancreas. The more common metastases affecting the pancreas include renal cell carcinomas, melanomas, colorectal carcinomas, breast carcinomas, and sarcomas. Although pancreatic involvement by nonrenal malignancies indicates widespread systemic disease, metastatic renal cell carcinoma to the pancreas often represents an isolated event and is thus amenable to surgical resection, which is associated with long-term survival. As such, it is important to accurately diagnose pancreatic involvement by metastatic renal cell carcinoma on histology, especially given that renal cell carcinoma metastasis may manifest more than a decade after its initial presentation and diagnosis. In this review, we discuss the clinicopathologic findings of isolated renal cell carcinoma metastases of the pancreas, with special emphasis on separating metastatic renal cell carcinoma and its various differential diagnoses in the pancreas.

  12. Effect of New Water-Soluble Dendritic Phthalocyanines on Human Colorectal and Liver Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Ebru YABAŞ

    2017-08-01

    Full Text Available Human hepatocellular carcinoma (HepG2 cells and colorectal adenocarcinoma (DLD-1 cells were treated with the synthesized water soluble phthalocyanine derivatives to understand the effect of the compounds both on colorectal and liver cancer cells. The compounds inhibited cell proliferation and displayed cytotoxic effect on these cancer cell lines however; the effect of the compounds on healthy control fibroblast cell line was comparatively lower. The compounds can be employed for cancer treatment as anticancer agents.

  13. Gastric and Colorectal Metastases of Lobural Breast Carcinoma: A Case Report

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    David Buka

    2016-04-01

    Full Text Available Background: Occurrence of gastric metastasis as the first symptom of breast carcinoma with a long period of latency before presentation of the primary breast carcinoma is rare. Case Report: A patient with gastric metastasis as the first symptom of lobular breast carcinoma, treated by neoadjuvant preoperative chemoradiotherapy and total gastrectomy, with complete local control. Fourteen months after presentation of the gastric metastasis a primary lobular breast carcinoma was discovered, treated by radiotherapy, chemotherapy and hormonal treatment with complete local response. Twenty-three months after diagnosis of breast cancer multiple colorectal metastases from the breast cancer occurred, which were treated by chemotherapy and hormonal treatment. Eighty-six months after diagnosis of gastric metastasis the patient died due to progression of cancer. Conclusions: Metastases to gastrointestinal or gynaecological tracts are more likely in invasive lobular carcinoma than invasive ductal cancer. The pathologist should determine whether or not they check estrogen and progesterone receptor status not simply by signet ring cell morphology but also by consideration of clinic-pathological correlation of the patient, such as the presence of a past history of breast cancer, or the colorectal localization of poorly differentiated carcinoma, which may occur less frequently than in the stomach.

  14. Evolution and pathology of colorectal carcinoma

    International Nuclear Information System (INIS)

    Hermanek, P.

    1986-01-01

    Numerous clinical, epidemiological, histological and experimental observations favour the adenoma-carcinoma sequence. Metastases occur only after invasion of the submucosa. The elevated rate of synchronous lesions (carcinomas and adenomas) is emphasized. In the rule, lymphatic spread precedes distant metastasis. Typing and grading should be performed according to the rules of WHO. The present UICC staging system will be replaced by a new 4th edition 1987. Early carcinoma (limited to the submucosa) has an excellent prognosis and may be treated by limited procedures (polypectomy, local excision) in the most cases. The modern concept of histology- and stage-adapted cancer therapy requires the pre-, intra- and postoperative cooperation with the pathologist. (Author)

  15. Clinical evaluation of preoperative arterial infusion chemotherapy and surgical operation for colorectal carcinoma

    International Nuclear Information System (INIS)

    Yuan Jianhua; Zhao Zhongsheng; Deng Gaoli; Hu Tingyang; Yu Wenqiang; Chen Fanghong; Luo Zuyan; Ru Guoqing; Dong Quanjin; Tu Shiliang

    2003-01-01

    Objective: To investigate the clinical values of preoperative arterial infusion chemotherapy and surgical operation for colorectal carcinoma. Methods: 66 patients with colorectal carcinoma were subjected to percutaneous femoral artery catheterization by Seldinger's technique with infusion of anti-cancer drugs. The resection was performed 5-30 days after the arterial infusion (mean 12 days). In 50 surgical specimens of the 66 cases, histological findings were evaluated including the density and distribution of the apoptosis cells under the observation by DNA nick end labelling technique. Of which 22 specimens before arterial infusion chemotherapy (got from biopsy of preoperation) and 25 normal mucosa (got from normal surgical specimens) were used as controls. Results: The total histological response rate was 100% with grade I in 20 cases, grade II in 21 cases, grade III in 9 cases. The densities of the apoptosis cells were 31.47 ± 5.58 before arterial infusion chemotherapy, 76.69 ± 17.12 after arterial infusion chemotherapy and 8.01 ± 3.39 in normal mucosa. The density of the apoptosis cells after arterial infusion chemotherapy was significantly higher than that before arterial infusion chemotherapy (P 2 =4.696, P>0.30). There were no significant differences in the apoptosis of adenocarcinoma during different pathological stages (F=0.001376, P>0.05). Conclusions: Peroperative transcatheter arterial infusion chemotherapy resulting in apoptosis of adenocarcinoma, can raise the radical operation rate, and prolong survival rate for colorectal carcinoma patients

  16. Chromogenic in situ hybridization to detect EGFR gene copy number in cell blocks from fine-needle aspirates of non small cell lung carcinomas and lung metastases from colo-rectal cancer

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    Terrenato Irene

    2010-09-01

    Full Text Available Abstract Background Several studies demonstrated that epidermal growth factor receptor (EGFR gene copy number (GCN correlates to the response to tyrosine kinase inhibitors in non small cell lung cancer (NSCLC and to anti-EGFR monoclonal antibodies (MoAbs in metastatic colorectal cancer (CRC. In the presence of lung nodules, cytology is often the only possible diagnostic approach. Chromogenic in situ hybridization (CISH is an alternative technique to fluorescence in situ hybridization (FISH, but its feasibility in detecting EGFR GCN in cell blocks from fine-needle aspiration cytology (FNAC of lung nodules has not yet been established. Methods We evaluated the feasibility of CISH on 33 FNAC from 20 primary NSCLC (5 squamous carcinomas, 8 large cell carcinomas and 7 adenocarcinomas and 13 lung metastases from CRC. Results Of the 33 FNAC analyzed by CISH, 27 (82% presented a balanced increase in EGFR gene and chromosome 7 number: 10 cases (30% showed a low polysomy, 15 (45% a high polysomy and 2 (6% NSCLC were amplified. No significant differences between NSCLC and CRC lung metastases were found in relation to disomic or polysomic status. In addition, no correlation between EGFR GCN and EGFR immunohistochemical overexpression was found. Furthermore, we compared CISH results with those obtained by FISH on the same samples and we found 97% overall agreement between the two assays (k = 0.78, p Conclusions Our study shows that CISH is a valid method to detect EGFR GCN in cell blocks from FNAC of primary NSCLC or metastatic CRC to the lung.

  17. Perspectives on the treatment of colorectal carcinoma

    OpenAIRE

    Zhao, Ren; Li, Jing

    2010-01-01

    Colorectal cancer includes cancerous growths in the colon, rectum and appendix. With 655000 deaths worldwide per year, it is the third most common form of cancer and the second leading cause of cancer-related death in the Western world. Advances in imaging, genetics, molecular diagnostics, surgical techniques and chemotherapy are now making significant gains in our ability to prevent, diagnose, and treat this serious disease. This article reviews some of these recent successes and shares a vi...

  18. Comparative study of colorectal carcinoma examination with four postprocessing of CT colonography

    Energy Technology Data Exchange (ETDEWEB)

    Mingyue, Luo; Kangrong, Zhou [The 3rd Affilated Hospital Sun Yat-sen Univ. of Medical Sciences, Guangzhou (China). Dept. of Radiology

    2001-10-01

    Objective: To study the clinical value of colorectal carcinoma examination by comparison of different postprocessing techniques such as multiplanar reformation (MPR), CT virtual colonoscopy (CTVC), shaded surface display (SSD) and Raysum. Methods: 64 patients with colorectal carcinomas underwent volume scanning using spiral CT. MPR, CTVC, SSD and Raysum images were obtained by using 4 different software in workstation. All cases were proved by surgical or CC biotic histology. The results were compared and analyzed according to the circumferential extension, length and pathologic patterns of colorectal carcinoma with MPR, CTVC, SSD and Raysum. Results: The correction rate of determination the circumferential extension of colorectal carcinoma with MPR, CTVC, SSD and Raysum were 100.0%, 82.8%, 79.7% and 79.7%, respectively. There was significant statistical difference between MPR and CTVC; The accuracy of judging the length of carcinoma were 89.1%, 76.6%, 95.3% and 100.0%, respectively. There was statistical difference between CTVC and SSD; The accuracy of showing carcinoma pathologic patterns were 81.3%, 92.2%, 71.9% and 71.0%, respectively. There was statistical difference between CTVC and SSD, too. MPR could correctly determine the circumferential extension of colorectal carcinoma. In determination the length of carcinoma, Raysum was more accurate than SSD. CTVC could be more helpful in showing carcinoma pathologic patterns. Conclusion: There were advantages and disadvantages in colorectal carcinoma examination with MPR, CTVC, SSD and Raysum, and the combination could display colorectal carcinoma more completely and comprehensively.

  19. Comparative study of colorectal carcinoma examination with four postprocessing of CT colonography

    International Nuclear Information System (INIS)

    Luo Mingyue; Zhou Kangrong

    2001-01-01

    Objective: To study the clinical value of colorectal carcinoma examination by comparison of different postprocessing techniques such as multiplanar reformation (MPR), CT virtual colonoscopy (CTVC), shaded surface display (SSD) and Raysum. Methods: 64 patients with colorectal carcinomas underwent volume scanning using spiral CT. MPR, CTVC, SSD and Raysum images were obtained by using 4 different software in workstation. All cases were proved by surgical or CC biotic histology. The results were compared and analyzed according to the circumferential extension, length and pathologic patterns of colorectal carcinoma with MPR, CTVC, SSD and Raysum. Results: The correction rate of determination the circumferential extension of colorectal carcinoma with MPR, CTVC, SSD and Raysum were 100.0%, 82.8%, 79.7% and 79.7%, respectively. There was significant statistical difference between MPR and CTVC; The accuracy of judging the length of carcinoma were 89.1%, 76.6%, 95.3% and 100.0%, respectively. There was statistical difference between CTVC and SSD; The accuracy of showing carcinoma pathologic patterns were 81.3%, 92.2%, 71.9% and 71.0%, respectively. There was statistical difference between CTVC and SSD, too. MPR could correctly determine the circumferential extension of colorectal carcinoma. In determination the length of carcinoma, Raysum was more accurate than SSD. CTVC could be more helpful in showing carcinoma pathologic patterns. Conclusion: There were advantages and disadvantages in colorectal carcinoma examination with MPR, CTVC, SSD and Raysum, and the combination could display colorectal carcinoma more completely and comprehensively

  20. In vivo expansion of naïve CD4+ CD25(high FOXP3+ regulatory T cells in patients with colorectal carcinoma after IL-2 administration.

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    Marc Beyer

    Full Text Available Regulatory T cells (T(reg cells are increased in context of malignancies and their expansion can be correlated with higher disease burden and decreased survival. Initially, interleukin 2 (IL-2 has been used as T-cell growth factor in clinical vaccination trials. In murine models, however, a role of IL-2 in development, differentiation, homeostasis, and function of T(reg cells was established. In IL-2 treated cancer patients a further T(reg-cell expansion was described, yet, the mechanism of expansion is still elusive. Here we report that functional T(reg cells of a naïve phenotype--as determined by CCR7 and CD45RA expression--are significantly expanded in colorectal cancer patients. Treatment of 15 UICC stage IV colorectal cancer patients with IL-2 in a phase I/II peptide vaccination trial further enlarges the already increased naïve T(reg-cell pool. Higher frequencies of T-cell receptor excision circles in naïve T(reg cells indicate IL-2 dependent thymic generation of naïve T(reg cells as a mechanism leading to increased frequencies of T(reg cells post IL-2 treatment in cancer patients. This finding could be confirmed in naïve murine T(reg cells after IL-2 administration. These results point to a more complex regulation of T(reg cells in context of IL-2 administration. Future strategies therefore might aim at combining IL-2 therapy with novel strategies to circumvent expansion and differentiation of naïve T(reg cells.

  1. Regulatory activity based risk model identifies survival of stage II and III colorectal carcinoma.

    Science.gov (United States)

    Liu, Gang; Dong, Chuanpeng; Wang, Xing; Hou, Guojun; Zheng, Yu; Xu, Huilin; Zhan, Xiaohui; Liu, Lei

    2017-11-17

    Clinical and pathological indicators are inadequate for prognosis of stage II and III colorectal carcinoma (CRC). In this study, we utilized the activity of regulatory factors, univariate Cox regression and random forest for variable selection and developed a multivariate Cox model to predict the overall survival of Stage II/III colorectal carcinoma in GSE39582 datasets (469 samples). Patients in low-risk group showed a significant longer overall survival and recurrence-free survival time than those in high-risk group. This finding was further validated in five other independent datasets (GSE14333, GSE17536, GSE17537, GSE33113, and GSE37892). Besides, associations between clinicopathological information and risk score were analyzed. A nomogram including risk score was plotted to facilitate the utilization of risk score. The risk score model is also demonstrated to be effective on predicting both overall and recurrence-free survival of chemotherapy received patients. After performing Gene Set Enrichment Analysis (GSEA) between high and low risk groups, we found that several cell-cell interaction KEGG pathways were identified. Funnel plot results showed that there was no publication bias in these datasets. In summary, by utilizing the regulatory activity in stage II and III colorectal carcinoma, the risk score successfully predicts the survival of 1021 stage II/III CRC patients in six independent datasets.

  2. Nevoid basal cell carcinoma syndrome

    Science.gov (United States)

    NBCC syndrome; Gorlin-Goltz syndrome; Basal cell nevus syndrome; BCNS; Basal cell cancer - nevoid basal cell carcinoma syndrome ... Nevoid basal cell carcinoma nevus syndrome is a rare genetic ... syndrome is known as PTCH ("patched"). The gene is passed down ...

  3. The association of TP53 mutations with the resistance of colorectal carcinoma to the insulin-like growth factor-1 receptor inhibitor picropodophyllin

    International Nuclear Information System (INIS)

    Wang, Quan; Wei, Feng; Lv, Guoyue; Li, Chunsheng; Liu, Tongjun; Hadjipanayis, Costas G; Zhang, Guikai; Hao, Chunhai; Bellail, Anita C

    2013-01-01

    There is growing evidence indicating the insulin-like growth factor 1 receptor (IGF-1R) plays a critical role in the progression of human colorectal carcinomas. IGF-1R is an attractive drug target for the treatment of colon cancer. Picropodophyllin (PPP), of the cyclolignan family, has recently been identified as an IGF-1R inhibitor. The aim of this study is to determine the therapeutic response and mechanism after colorectal carcinoma treatment with PPP. Seven colorectal carcinoma cell lines were treated with PPP. Following treatment, cells were analyzed for growth by a cell viability assay, sub-G1 apoptosis by flow cytometry, caspase cleavage and activation of AKT and extracellular signal-regulated kinase (ERK) by western blot analysis. To examine the in vivo therapeutic efficacy of PPP, mice implanted with human colorectal carcinoma xenografts underwent PPP treatment. PPP treatment blocked the phosphorylation of IGF-1R, AKT and ERK and inhibited the growth of TP53 wild-type but not mutated colorectal carcinoma cell lines. The treatment of PPP also induced apoptosis in TP53 wild-type cells as evident by the presence of sub-G1 cells and the cleavage of caspase-9, caspase-3, DNA fragmentation factor-45 (DFF45), poly (ADP-ribose) polymerase (PARP), and X-linked inhibitor of apoptosis protein (XIAP). The loss of BAD phosphorylation in the PPP-treated TP53 wild type cells further suggested that the treatment induced apoptosis through the BAD-mediated mitochondrial pathway. In contrast, PPP treatment failed to induce the phosphorylation of AKT and ERK and caspase cleavage in TP53 mutated colorectal carcinoma cell lines. Finally, PPP treatment suppressed the growth of xenografts derived from TP53 wild type but not mutated colorectal carcinoma cells. We report the association of TP53 mutations with the resistance of treatment of colorectal carcinoma cells in culture and in a xenograft mouse model with the IGF-1R inhibitor PPP. TP53 mutations often occur in colorectal

  4. Giant basal cell carcinoma Carcinoma basocelular gigante

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    Nilton Nasser

    2012-06-01

    Full Text Available The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no signs of dissemination or local recurrence have been detected after follow up of five years.O carcinoma basocelular é o tipo mais comum de câncer de pele, mas o carcinoma basocelular gigante vegetante não atinge 0,5% de todos os tipos de carcinomas basocelulares. O Carcinoma Basocelular Gigante, definido como lesão maior que 5 cm no maior diâmetro, é uma forma rara de carcinoma basocelular e comumente ocorre no tronco. Este paciente apresenta um Carcinoma Basocelular Gigante com 180cm² no ombro direito e foi negligente em procurar tratamento. Foi realizado tratamento cirúrgico e nenhum sinal de disseminação ou recorrência local foi detectada após 5 anos.

  5. Colorectal cancer stem cells.

    Science.gov (United States)

    Salama, Paul; Platell, Cameron

    2009-10-01

    Somatic stem cells reside at the base of the crypts throughout the colonic mucosa. These cells are essential for the normal regeneration of the colonic epithelium. The stem cells reside within a special 'niche' comprised of intestinal sub-epithelial myofibroblasts that tightly control their function. It has been postulated that mutations within these adult colonic stem cells may induce neoplastic changes. Such cells can then dissociate from the epithelium and travel into the mesenchyme and thus form invasive cancers. This theory is based on the observation that within a colon cancer, less than 1% of the neoplastic cells have the ability to regenerate the tumour. It is this group of cells that exhibits characteristics of colonic stem cells. Although anti-neoplastic agents can induce remissions by inhibiting cell division, the stem cells appear to be remarkably resistant to both standard chemotherapy and radiotherapy. These stem cells may therefore persist after treatment and form the nucleus for cancer recurrence. Hence, future treatment modalities should focus specifically on controlling the cancer stem cells. In this review, we discuss the biology of normal and malignant colonic stem cells.

  6. Imaging of colorectal carcinoma with radiolabeled antibodies.

    Science.gov (United States)

    Goldenberg, D M; Goldenberg, H; Sharkey, R M; Lee, R E; Higgenbotham-Ford, E; Horowitz, J A; Hall, T C; Pinsky, C M; Hansen, H J

    1989-10-01

    Colorectal cancer has been the tumor type most frequently studied with radiolabeled antibodies. Among the various antibodies, a majority of patients with colorectal cancer have received xenogeneic polyclonal or monoclonal antibodies against carcino-embryonic antigen. This review summarizes the current status of colorectal cancer imaging with radiolabeled antibodies, ie, radioimmunodetection (RAID), and examines the published studies involving carcinoembryonic antigen (CEA) antibodies and 17-1A, 19-9, and B72.3, and other monoclonal antibodies. In order to better address the issue of the current and future clinical usefulness of this emerging technology, particular attention is given to the protocols, methods, and results of the published studies. Despite differences in study parameters, antibodies and forms, labels, administration routes and doses, and scanning instruments and methods, it has been found that (1) almost no adverse reactions have been evident; (2) antibody fragments are preferred over whole immunoglobulin G reagents because they achieve higher tumor-to-background ratios earlier, thus reducing or precluding the need for dual-isotope subtraction methods or long delays before imaging; (3) use of antibody fragments, including the monovalent Fab' form, permits imaging with short-lived radionuclides of excellent photon properties, such as 123I and 99mTc; (4) circulating antigens against which the imaging antibody is directed can complex with the injected antibody, but such complexes have not prevented successful RAID; (5) patients with high serum titers of the appropriate antigen target usually have higher rates of positive RAID; (6) patients who are seronegative for the tumor antigen being studied can have positive RAID findings, which can represent the detection of occult lesions; (7) single photon emission computed tomography appears to provide better image resolution than planar scanning; (8) regardless of the sensitivity reported in any particular

  7. Diagnostic of colorectal carcinoma. An update

    International Nuclear Information System (INIS)

    Schneider, A.R.J.; Caspary, W.F.

    2003-01-01

    Colorectal cancer (CRC) is one of the most frequent tumors in western countries.More than 50% of all CRC are diagnosed at an advanced stage which precludes curative treatment. For this reason, early detection of CRC is mandatory to improve longterm outcome. Fecal occult blood testing (FOBT) once per year and subsequent colonoscopy (if the FOBT is positive) provides up to 30% decrease in mortality from CRC. Due to the fact that current data indicate a 60% reduction in CRC-associated mortality, colonoscopy has recently been approved for CRC screening by german public health insurance companies. Yet efforts in screening largely depend on patient compliance, particularly in view of cost-effectiveness. Introduction of new imaging techniques (CT-/MRI-colonography) may increase general acceptance, but clinical benefit and costs still remain to be determined in larger studies. (orig.) [de

  8. Four jointed box 1 promotes angiogenesis and is associated with poor patient survival in colorectal carcinoma.

    Directory of Open Access Journals (Sweden)

    Nicole T Al-Greene

    Full Text Available Angiogenesis, the recruitment and re-configuration of pre-existing vasculature, is essential for tumor growth and metastasis. Increased tumor vascularization often correlates with poor patient outcomes in a broad spectrum of carcinomas. We identified four jointed box 1 (FJX1 as a candidate regulator of tumor angiogenesis in colorectal cancer. FJX1 mRNA and protein are upregulated in human colorectal tumor epithelium as compared with normal epithelium and colorectal adenomas, and high expression of FJX1 is associated with poor patient prognosis. FJX1 mRNA expression in colorectal cancer tissues is significantly correlated with changes in known angiogenesis genes. Augmented expression of FJX1 in colon cancer cells promotes growth of xenografts in athymic mice and is associated with increased tumor cell proliferation and vascularization. Furthermore, FJX1 null mice develop significantly fewer colonic polyps than wild-type littermates after combined dextran sodium sulfate (DSS and azoxymethane (AOM treatment. In vitro, conditioned media from FJX1 expressing cells promoted endothelial cell capillary tube formation in a HIF1-α dependent manner. Taken together our results support the conclusion that FJX1 is a novel regulator of tumor progression, due in part, to its effect on tumor vascularization.

  9. Radiolabelled monoclonal antibodies: magic bullets for colorectal carcinoma

    International Nuclear Information System (INIS)

    Slade, Linda

    1997-01-01

    Radiolabelled monoclonal antibodies (MoAbs) have been heralded as highly specific detection agents for many types of tumours. However, because of the many problems that have been associated with the use of these agents, their development and successes did not meet expectations. This paper discusses the use of radiolabelled MoAbs in the diagnosis and staging of colorectal cancer, the type of antibodies and radionuclides investigated over the past thirty years, and the advantages and disadvantages of each. An attempt is made to define the role of radioimmunoscintigraphy (RIS) in the investigation and management of patients with colorectal cancer. It appears that this technique can improve tumour detection, especially when used in conjunction with other imaging modalities. High sensitivities and specificities have been found using radio-labelled MoAbs for investigation of colorectal carcinoma. However, the author estimates there are a number of areas that require further research and improvement before naming radiolabelled MoAbs as 'magic bullets' for colorectal cancer. 8 refs., 3 tabs

  10. Apoptosis and histological response of preoperative intraarterial chemotherapy infusion for colorectal carcinoma

    International Nuclear Information System (INIS)

    Yuan Jianhua; Hu Tingyang; Yu Wenqiang; Chen Fanghong; Luo Zuyan; Mao Yinmin; Zhao Zhongsheng; Ru Guoqing; Deng Gaoli; Dong Quanjin; Tu Shiliang

    2003-01-01

    Objective: To investigate apoptosis and histological response of preoperative intraarterial chemotherapy infusion for colorectal carcinoma. Methods: Fifty patients with colorectal carcinoma were treated by intraarterial infusion of anti-cancer drugs. Surgical resection of the tumor was performed 5-30 days after the intraarterial infusion (mean 12 days). The histological response was evaluated. The density and distribution of the apoptosis cells were observed by DNA nick end labelling technique. 22 biopsy specimens before the intraarterial chemotherapy and 25 normal mucosa (obtained from surgery specimen) were used as controls. Results: The total histological response rate was 100% with grade I in 20 cases, grade II in 21 cases, and grade III in 9 cases. The density of the apoptosis cells was 31.47±5.58 before and 76.69±17.12 after the intraarterial chemotherapy infusion, and 8.01±3.39 in normal mucosa, respectively. The density of the apoptosis cells after the intraarterial chemotherapy was significantly higher than that before the intraarterial chemotherapy (t=13.701, P 2 =4.696, P>0.30). The apoptosis of adenocarcinoma was significantly different with different histological response (F=7.73, P 0.05) and for adenocarcinoma with different pathological stages (F=0.001376, P>0.05). Conclusion: As an effective and safe procedure, preoperative transcatheter intraarterial chemotherapy infusion achieves a significant histological response and apoptosis in colorectal adenocarcinoma

  11. Molecular Events in Primary and Metastatic Colorectal Carcinoma: A Review

    Directory of Open Access Journals (Sweden)

    Rani Kanthan

    2012-01-01

    Full Text Available Colorectal cancer (CRC is a heterogeneous disease, developing through a multipathway sequence of events guided by clonal selections. Pathways included in the development of CRC may be broadly categorized into (a genomic instability, including chromosomal instability (CIN, microsatellite instability (MSI, and CpG island methylator phenotype (CIMP, (b genomic mutations including suppression of tumour suppressor genes and activation of tumour oncogenes, (c microRNA, and (d epigenetic changes. As cancer becomes more advanced, invasion and metastases are facilitated through the epithelial-mesenchymal transition (EMT, with additional genetic alterations. Despite ongoing identification of genetic and epigenetic markers and the understanding of alternative pathways involved in the development and progression of this disease, CRC remains the second highest cause of malignancy-related mortality in Canada. The molecular events that underlie the tumorigenesis of primary and metastatic colorectal carcinoma are detailed in this manuscript.

  12. Novel mouse model recapitulates genome and transcriptome alterations in human colorectal carcinomas.

    Science.gov (United States)

    McNeil, Nicole E; Padilla-Nash, Hesed M; Buishand, Floryne O; Hue, Yue; Ried, Thomas

    2017-03-01

    Human colorectal carcinomas are defined by a nonrandom distribution of genomic imbalances that are characteristic for this disease. Often, these imbalances affect entire chromosomes. Understanding the role of these aneuploidies for carcinogenesis is of utmost importance. Currently, established transgenic mice do not recapitulate the pathognonomic genome aberration profile of human colorectal carcinomas. We have developed a novel model based on the spontaneous transformation of murine colon epithelial cells. During this process, cells progress through stages of pre-immortalization, immortalization and, finally, transformation, and result in tumors when injected into immunocompromised mice. We analyzed our model for genome and transcriptome alterations using ArrayCGH, spectral karyotyping (SKY), and array based gene expression profiling. ArrayCGH revealed a recurrent pattern of genomic imbalances. These results were confirmed by SKY. Comparing these imbalances with orthologous maps of human chromosomes revealed a remarkable overlap. We observed focal deletions of the tumor suppressor genes Trp53 and Cdkn2a/p16. High-level focal genomic amplification included the locus harboring the oncogene Mdm2, which was confirmed by FISH in the form of double minute chromosomes. Array-based global gene expression revealed distinct differences between the sequential steps of spontaneous transformation. Gene expression changes showed significant similarities with human colorectal carcinomas. Pathways most prominently affected included genes involved in chromosomal instability and in epithelial to mesenchymal transition. Our novel mouse model therefore recapitulates the most prominent genome and transcriptome alterations in human colorectal cancer, and might serve as a valuable tool for understanding the dynamic process of tumorigenesis, and for preclinical drug testing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Postoperative adjuvant therapy of colorectal carcinoma

    International Nuclear Information System (INIS)

    Scheithauer, W.

    1989-01-01

    Evaluating the results of controlled clinical trials, an attempt has been made to summarize the current status of adjuvant therapy in colorectal cancer. Several different adjuvant treatment approaches including immunotherapy, postoperative fibrinolysis, anticoagulation, pre- and postoperative radiotherapy when used as a single modality, have not resulted in any long-term survival benefit. Rather in contrast to previous experiences, recent prospective randomized trials have provided evidence for the efficacy of chemotherapy in the adjuvant treatment of colon and rectal cancer. Whereas its definitive role in the former disease remains somewhat controversial, for rectal cancer, it seems clear that combined modality therapy including polychemotherapy with or without radiation prolongs the disease-free interval, lowers the local recurrence rate, and may improve survival compared to surgery alone. Questions which remain to be answered by future clinical trials are related to the optimal duration and sequence of combined modality, to the role of different radiation sensitizers, and in both colon and rectal cancer, to the choice of the most effective systemtic chemotherapeutic drugs. (orig./MG) [de

  14. Bilateral papillary renal cell carcinoma

    International Nuclear Information System (INIS)

    Gossios, K.; Vazakas, P.; Argyropoulou, M.; Stefanaki, S.; Stavropoulos, N.E.

    2001-01-01

    Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. We report the clinical and imaging findings of a case with multifocal and bilateral renal cell carcinoma which are nonspecific. (orig.)

  15. Stages of Merkel Cell Carcinoma

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Merkel Cell Carcinoma Treatment (PDQ®)–Patient Version General Information About Merkel Cell Carcinoma Go to Health Professional Version Key ...

  16. Gingival squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Amit Walvekar

    2017-01-01

    Full Text Available Oral squamous cell carcinoma (OSCC is the most common epithelial malignancy affecting the oral cavity. The most common sites for the development are lateral surface of tongue and floor of mouth; the least common sites are soft palate, gingiva, and buccal mucosa. Gingival squamous cell carcinoma can mimic a multitude of oral lesions and enlargements, especially those of inflammatory origin. In addition, predisposing and presenting factors are different from those of other OSCCs. Careful examination as well as routine biopsy are crucial for accurate diagnosis.

  17. Transcriptome analysis of paired primary colorectal carcinoma and liver metastases reveals fusion transcripts and similar gene expression profiles in primary carcinoma and liver metastases

    International Nuclear Information System (INIS)

    Lee, Ja-Rang; Kwon, Chae Hwa; Choi, Yuri; Park, Hye Ji; Kim, Hyun Sung; Jo, Hong-Jae; Oh, Nahmgun; Park, Do Youn

    2016-01-01

    Despite the clinical significance of liver metastases, the difference between molecular and cellular changes in primary colorectal cancers (CRC) and matched liver metastases is poorly understood. In order to compare gene expression patterns and identify fusion genes in these two types of tumors, we performed high-throughput transcriptome sequencing of five sets of quadruple-matched tissues (primary CRC, liver metastases, normal colon, and liver). The gene expression patterns in normal colon and liver were successfully distinguished from those in CRCs; however, RNA sequencing revealed that the gene expression between primary CRCs and their matched liver metastases is highly similar. We identified 1895 genes that were differentially expressed in the primary carcinoma and liver metastases, than that in the normal colon tissues. A major proportion of the transcripts, identified by gene expression profiling as significantly enriched in the primary carcinoma and metastases, belonged to gene ontology categories involved in the cell cycle, mitosis, and cell division. Furthermore, we identified gene fusion events in primary carcinoma and metastases, and the fusion transcripts were experimentally confirmed. Among these, a chimeric transcript resulting from the fusion of RNF43 and SUPT4H1 was found to occur frequently in primary colorectal carcinoma. In addition, knockdown of the expression of this RNF43-SUPT4H1 chimeric transcript was found to have a growth-inhibitory effect in colorectal cancer cells. The present study reports a high concordance of gene expression in the primary carcinoma and liver metastases, and reveals potential new targets, such as fusion genes, against primary and metastatic colorectal carcinoma. The online version of this article (doi:10.1186/s12885-016-2596-3) contains supplementary material, which is available to authorized users

  18. Cryopreservation of human colorectal carcinomas prior to xenografting

    International Nuclear Information System (INIS)

    Linnebacher, Michael; Maletzki, Claudia; Ostwald, Christiane; Klier, Ulrike; Krohn, Mathias; Klar, Ernst; Prall, Friedrich

    2010-01-01

    Molecular heterogeneity of colorectal carcinoma (CRC) is well recognized, forming the rationale for molecular tests required before administration of some of the novel targeted therapies that now are rapidly entering the clinics. For clinical research at least, but possibly even for future individualized tumor treatment on a routine basis, propagation of patients' CRC tissue may be highly desirable for detailed molecular, biochemical or functional analyses. However, complex logistics requiring close liaison between surgery, pathology, laboratory researchers and animal care facilities are a major drawback in this. We here describe and evaluate a very simple cryopreservation procedure for colorectal carcinoma tissue prior to xenografting that will considerably reduce this logistic complexity. Fourty-eight CRC collected ad hoc were xenografted subcutaneously into immunodeficient mice either fresh from surgery (N = 23) or after cryopreservation (N = 31; up to 643 days). Take rates after cryopreservation were satisfactory (71%) though somewhat lower than with tumor tissues fresh from surgery (74%), but this difference was not statistically significant. Re-transplantation of cryopreserved established xenografts (N = 11) was always successful. Of note, in this series, all of the major molecular types of CRC were xenografted successfully, even after cryopreservation. Our procedure facilitates collection, long-time storage and propagation of clinical CRC specimens (even from different centres) for (pre)clinical studies of novel therapies or for basic research

  19. The destruction complex of beta-catenin in colorectal carcinoma and colonic adenoma.

    Science.gov (United States)

    Bourroul, Guilherme Muniz; Fragoso, Hélio José; Gomes, José Walter Feitosa; Bourroul, Vivian Sati Oba; Oshima, Celina Tizuko Fujiyama; Gomes, Thiago Simão; Saba, Gabriela Tognini; Palma, Rogério Tadeu; Waisberg, Jaques

    2016-01-01

    To evaluate the destruction complex of beta-catenin by the expression of the proteins beta-catetenin, adenomatous polyposis coli, GSK3β, axin and ubiquitin in colorectal carcinoma and colonic adenoma. Tissue samples from 64 patients with colorectal carcinoma and 53 patients with colonic adenoma were analyzed. Tissue microarray blocks and slides were prepared and subjected to immunohistochemistry with polyclonal antibodies in carcinoma, adjacent non-neoplastic mucosa, and adenoma tissues. The immunoreactivity was evaluated by the percentage of positive stained cells and by the intensity assessed through of the stained grade of proteins in the cytoplasm and nucleus of cells. In the statistical analysis, the Spearman correlation coefficient, Student's t, χ2, Mann-Whitney, and McNemar tests, and univariate logistic regression analysis were used. In colorectal carcinoma, the expressions of beta-catenin and adenomatous polyposis coli proteins were significantly higher than in colonic adenomas (pcitoplasma e no núcleo das células. Na análise estatística, foram utilizados o coeficiente de correlação de Spearman, os testes t de Student, χ2, Mann-Whitney e de McNemar, e a análise de regressão logística univariada. No carcinoma colorretal, as expressões da betacatenina e da adenomatous polyposis coli foram significativamente maiores do que em adenomas do colo (p<0,001 e p<0,0001, respectivamente). A imunorreatividade das proteínas GSK3β, axina 1 e ubiquitina foi significativamente maior (p=0,03, p=0,039 e p=0,03, respectivamente) no carcinoma colorretal do que no adenoma e na mucosa não neoplásica adjacente. A coloração imuno-histoquímica dessas proteínas não apresentou diferenças significantes em relação às características clinicopatológicas do câncer colorretal e do adenoma. Em adenomas, as menores expressões de betacatenina, axina 1 e GSK3β indicaram que o complexo de destruição da betacatenina estava conservado, enquanto que, no carcinoma

  20. Intraosseous acinic cell carcinoma

    African Journals Online (AJOL)

    2011-12-17

    Dec 17, 2011 ... Salivary gland tumors are also known to develop within jaw bones, arising within the jaw as a ... Treatment of acinic cell carcinoma in most cases is surgical. High recurrence rates ... Panoramic radiograph [Figure 3] showed a ...

  1. DMBT1 expression and glycosylation during the adenoma-carcinoma sequence in colorectal cancer

    DEFF Research Database (Denmark)

    Robbe, C; Paraskeva, C; Mollenhauer, J

    2005-01-01

    , location and its mode of secretion during malignant transformation in colorectal cancer. Using human colorectal PC/AA cell lines and tissue sections from individual patients, we have examined the expression of DMBT1 and its glycosylation in the adenoma-carcinoma sequence leading to the adenocarcinoma......The gene DMBT1 (deleted in malignant brain tumour-1) has been proposed to play a role in brain and epithelial cancer, but shows unusual features for a classical tumour-suppressor gene. On the one hand, DMBT1 has been linked to mucosal protection, whereas, on the other, it potentially plays a role...... in epithelial differentiation. Thus its function in a particular tissue is of mechanistic importance for its role in cancer. Because the former function requires secretion to the lumen and the latter function may depend on its presence in the extracellular matrix, we decided to investigate DMBT1 expression...

  2. Evaluating hepatocellular carcinoma cell lines for tumour samples using within-sample relative expression orderings of genes.

    Science.gov (United States)

    Ao, Lu; Guo, You; Song, Xuekun; Guan, Qingzhou; Zheng, Weicheng; Zhang, Jiahui; Huang, Haiyan; Zou, Yi; Guo, Zheng; Wang, Xianlong

    2017-11-01

    Concerns are raised about the representativeness of cell lines for tumours due to the culture environment and misidentification. Liver is a major metastatic destination of many cancers, which might further confuse the origin of hepatocellular carcinoma cell lines. Therefore, it is of crucial importance to understand how well they can represent hepatocellular carcinoma. The HCC-specific gene pairs with highly stable relative expression orderings in more than 99% of hepatocellular carcinoma but with reversed relative expression orderings in at least 99% of one of the six types of cancer, colorectal carcinoma, breast carcinoma, non-small-cell lung cancer, gastric carcinoma, pancreatic carcinoma and ovarian carcinoma, were identified. With the simple majority rule, the HCC-specific relative expression orderings from comparisons with colorectal carcinoma and breast carcinoma could exactly discriminate primary hepatocellular carcinoma samples from both primary colorectal carcinoma and breast carcinoma samples. Especially, they correctly classified more than 90% of liver metastatic samples from colorectal carcinoma and breast carcinoma to their original tumours. Finally, using these HCC-specific relative expression orderings from comparisons with six cancer types, we identified eight of 24 hepatocellular carcinoma cell lines in the Cancer Cell Line Encyclopedia (Huh-7, Huh-1, HepG2, Hep3B, JHH-5, JHH-7, C3A and Alexander cells) that are highly representative of hepatocellular carcinoma. Evaluated with a REOs-based prognostic signature for hepatocellular carcinoma, all these eight cell lines showed the same metastatic properties of the high-risk metastatic hepatocellular carcinoma tissues. Caution should be taken for using hepatocellular carcinoma cell lines. Our results should be helpful to select proper hepatocellular carcinoma cell lines for biological experiments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Clinicopathological analysis of prognostic factors in colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Aura Jurescu

    2016-12-01

    Full Text Available BACKGROUND Prediction of prognosis is vital for therapy options in patients with colorectal carcinoma (CRC. We aimed to identify some prognostic factors that could ensure a more adequate prediction of CRC patients’ outcome. MATERIALS AND METHODS We performed a study on a group of 253 CRC patients in the County Hospital ofTimișoara. The following variable parameters: age, gender, histological type, depth of tumor invasion (pT, histological grade (G, lymph node metastasis (LNM, lympho-vascular invasion (LVI were analyzed using Fisher’s exact test. RESULTS The incidence of CRC increased with age. Gender distribution was evidenced as follows: 159 (63% were male patients and 94 (37% were female patients. 234 (92% cases were conventional adenocarcinomas (ADK nM, 19 (8% were mucinous adenocarcinomas (ADK M. 1% of cases were pT1 stage, 9% pT2, 58% pT3 and 32% pT4 stage. 5% of the tumors were G1, 95% G2, G3, G4. In pT1&pT2 stages only 4% presented LVI, while in pT3&pT4 LVI was significantly higher, 42% of the examined cases. Only two cases from pT1&pT2 tumors showed LNM vs. 55% (127 cases of pT3&pT4 stages. CONCLUSIONS Tumor stage remains the most important prognostic predictor of clinical outcome for these patients. Pathologic assessment of various clinicopathological factors plays n essential role in patient management. Graphical abstract: Infiltrative aspects of colorectal carcinoma REFERENCES 1. Corman ML. Carcinoma of the Colon. In: Corman ML, editors. Colon and Rectal Surgery. 5-th edition. Philadelphia: Lippincott Williams nad Wilkins. 2005. p. 767-920. 2. Bresalier R. Malignant neoplasms of the large intestine. In: Feldman M, Friedman LS, Sleisenger MH (Editors. Gastrointestinal and Liver Disease (Pathology, Diagnosis, Management. Philadelphia, London,New York: Saunders. 2002. p. 2215-2263. 3. Schneider N, Langner C. Prognostic stratification of colorectal cancer patients: current perspectives. Cancer Management and Research. 2014;6:291- 300.

  4. Scrotal metastases from colorectal carcinoma: a case report.

    LENUS (Irish Health Repository)

    McWeeney, Doireann M

    2012-01-31

    ABSTRACT: A 72-year-old man presented with a two month history of rectal bleeding. Colonoscopy demonstrated synchronous lesions at 3 cm and 40 cm with histological analysis confirming synchronous adenocarcinomata. He developed bilobar hepatic metastases while undergoing neoadjuvant chemoradiotherapy. Treatment was complicated by Fournier\\'s gangrene of the right hemiscrotum which required surgical debridement. Eight months later he re-presented with an ulcerating lesion on the right hemiscrotum. An en-bloc resection of the ulcerating scrotal lesion and underlying testis was performed. Immunohistological analysis revealed metastatic adenocarcinoma of large bowel origin. Colorectal metastasis to the urogenital tract is rare and here we report a case of rectal carcinoma metastasizing to scrotal skin.

  5. Metallic stent placement for the management of acute colorectal obstruction caused by colorectal carcinomas: its effect on scheduled surgery

    International Nuclear Information System (INIS)

    Cao Yan; Liu Bingyan; Mao Aiwu; Yin Xiang; Gao Zhongdu

    2011-01-01

    Objective: To prospectively evaluate the safety and clinical efficacy of a newly designed self-expandable metallic stent (SEMS) placement in the treatment of patients with acute malignant colorectal obstruction due to colorectal carcinomas. Methods: During the period from April 2001 to October 2007, a total of 52 patients with acute malignant colorectal obstruction were treated with stent placement by using a new designed SEMS, which was employed as a preoperative transit means. All the patients were followed up and the relevant data, including technical success rate, clinical efficacy, complications and overall survival rate, were documented. The results were analyzed. Results: Stent placement was successfully carried out in all patients except for two patients who showed complete colorectal obstruction. No procedure-related complications occurred. Technical success rate was 96% (50/52). Two days after the treatment, the relief rate of colorectal obstruction was 98% (49/50). Postoperative complications included stent migration (n=4), anal pain (n=2) and stool impaction (n=1). The stool impaction seen in one patient was successfully removed away with endoscopic manipulation two days after stent placement. An elective one-stage surgical procedure was performed in all 50 patients who successfully received a SEMS placement within a mean interval of (8±2) days (ranged 4-11 days) after stent placement. Mean follow-up time was (36±12) months with a range of (3-70) months. All patients remained alive at the time of this report. Conclusion: The newly designed SEMS placement used as a preoperative transit means is a safe and effective intervention for colonic decompression in patients with acute malignant colorectal obstruction due to colorectal carcinomas. It can reliably ensure most of patients with colorectal carcinomas to successfully accomplish an elective surgery. (authors)

  6. Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas

    International Nuclear Information System (INIS)

    Nielsen, Maartje; Hes, Frederik J; Morreau, Hans; Miranda, Noel FCC de; Puijenbroek, Marjo van; Jordanova, Ekaterina S; Middeldorp, Anneke; Wezel, Tom van; Eijk, Ronald van; Tops, Carli MJ; Vasen, Hans FA

    2009-01-01

    MUTYH-associated polyposis (MAP) is a recessively inherited disorder which predisposes biallelic carriers for a high risk of polyposis and colorectal carcinoma (CRC). Since about one third of the biallelic MAP patients in population based CRC series has no adenomas, this study aimed to identify specific clinicopathological characteristics of MAP CRCs and compare these with reported data on sporadic and Lynch CRCs. From 44 MAP patients who developed ≥ 1 CRCs, 42 of 58 tumours were analyzed histologically and 35 immunohistochemically for p53 and beta-catenin. Cell densities of CD3, CD8, CD57, and granzyme B positive lymphocytes were determined. KRAS2, the mutation cluster region (MCR) of APC, p53, and SMAD4 were analyzed for somatic mutations. MAP CRCs frequently localized to the proximal colon (69%, 40/58), were mucinous in 21% (9/42), and had a conspicuous Crohn's like infiltrate reaction in 33% (13/40); all of these parameters occurred at a higher rate than reported for sporadic CRCs. Tumour infiltrating lymphocytes (TILs) were also highly prevalent in MAP CRCs. Somatic APC MCR mutations occurred in 14% (5/36) while 64% (23/36) had KRAS2 mutations (22/23 c.34G>T). G>T tranversions were found in p53 and SMAD4, although the relative frequency compared to other mutations was low. MAP CRCs show some similarities to micro-satellite unstable cancers, with a preferential proximal location, a high rate of mucinous histotype and increased presence of TILs. These features should direct the practicing pathologist towards a MAP aetiology of CRC as an alternative for a mismatch repair deficient cause. High frequent G>T transversions in APC and KRAS2 (mutated in early tumour development) but not in P53 and SMAD4 (implicated in tumour progression) might indicate a predominant MUTYH effect in early carcinogenesis

  7. Pathophysiological mechanisms of death resistance in colorectal carcinoma.

    Science.gov (United States)

    Huang, Ching-Ying; Yu, Linda Chia-Hui

    2015-11-07

    Colon cancers develop adaptive mechanisms to survive under extreme conditions and display hallmarks of unlimited proliferation and resistance to cell death. The deregulation of cell death is a key factor that contributes to chemoresistance in tumors. In a physiological context, balance between cell proliferation and death, and protection against cell damage are fundamental processes for maintaining gut epithelial homeostasis. The mechanisms underlying anti-death cytoprotection and tumor resistance often bear common pathways, and although distinguishing them would be a challenge, it would also provide an opportunity to develop advanced anti-cancer therapeutics. This review will outline cell death pathways (i.e., apoptosis, necrosis, and necroptosis), and discuss cytoprotective strategies in normal intestinal epithelium and death resistance mechanisms of colon tumor. In colorectal cancers, the intracellular mechanisms of death resistance include the direct alteration of apoptotic and necroptotic machinery and the upstream events modulating death effectors such as tumor suppressor gene inactivation and pro-survival signaling pathways. The autocrine, paracrine and exogenous factors within a tumor microenvironment can also instigate resistance against apoptotic and necroptotic cell death in colon cancers through changes in receptor signaling or transporter uptake. The roles of cyclooxygenase-2/prostaglandin E2, growth factors, glucose, and bacterial lipopolysaccharides in colorectal cancer will be highlighted. Targeting anti-death pathways in the colon cancer tissue might be a promising approach outside of anti-proliferation and anti-angiogenesis strategies for developing novel drugs to treat refractory tumors.

  8. Production and characterisation of a new monoclonal antibody to colorectal carcinoma

    International Nuclear Information System (INIS)

    Teh, Jinghee; Thompson, C.H.; McKenzie, F.C.

    1990-01-01

    In the process of producing MoAb to colorectal carcinomas a new antigenic determinant expressed by the tumour and normal cells was found. As will be shown, the importance of this antigenic determinant was in its distribution on normal and non-malignant mucinous colonic epithelial cells when compared with malignant colonic tumour and premalignant colonic lesions. MoAb5Cl does not detect carcino-embrionic antigens (CEA), human milk fat globules (HMFG), human lymphocyte antigens (HLA) or ABO blood group antigens. The combination of its presence in mucin secreting cells and its broad molecular weight bands suggest that the antigen detected is a mucin. 22 refs., 7 tabs., 7 figs

  9. Penis squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Leonor Hernández Piñero

    2015-09-01

    Full Text Available Cancer has become a first order health problem worldwide, despite the great diagnostic and therapeutic programs achieved during the last years. This is a clinical case of an 81- year-old patient with personal and social history of promiscuous and unprotected sexual behavior that shows a vegetative lesion in his gland and numerous inguinal adenopathies. Biopsy confirms the diagnosis of squamous cell carcinoma infiltrating the penis, which is a relatively rare pathology which is generally diagnosed belatedly. Partial amputation of the penis was considered to be performed, but there was no consent on behalf of his family. The patient’s general condition was getting worse until he died.

  10. Self-renewal molecular mechanisms of colorectal cancer stem cells

    OpenAIRE

    Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang

    2016-01-01

    Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth facto...

  11. Correlation of pathologic features with CpG island methylator phenotype (CIMP) by quantitative DNA methylation analysis in colorectal carcinoma.

    Science.gov (United States)

    Ogino, Shuji; Odze, Robert D; Kawasaki, Takako; Brahmandam, Mohan; Kirkner, Gregory J; Laird, Peter W; Loda, Massimo; Fuchs, Charles S

    2006-09-01

    Extensive gene promoter methylation in colorectal carcinoma has been termed the CpG island methylator phenotype (CIMP). Previous studies on CIMP used primarily methylation-specific polymerase chain reaction (PCR), which, unfortunately, may detect low levels of methylation that has little or no biological significance. Utilizing quantitative real-time PCR (MethyLight), we measured DNA methylation in a panel of 5 CIMP-specific gene promoters (CACNA1G, CDKN2A (p16), CRABP1, MLH1, and NEUROG1) in 459 colorectal carcinomas obtained from 2 large prospective cohort studies. CIMP was defined as tumors that showed methylation in >or=4/5 promoters. CIMP was significantly associated with the presence of mucinous or signet ring cell morphology, marked Crohn's-like lymphoid reaction, tumor infiltrating lymphocytes, marked peritumoral lymphocytic reaction, tumor necrosis, tumor cell sheeting, and poor differentiation. All these features have previously been associated with microsatellite instability (MSI). Therefore, we divided the 459 colorectal carcinomas into 6 subtypes, namely, MSI-high (MSI-H)/CIMP, MSI-H/non-CIMP, MSI-low (MSI-L)/CIMP, MSI-L/non-CIMP, microsatellite stable/CIMP, and micro satellite sstable/non-CIMP. Compared with MSI-H/non-CIMP, MSI-H/CIMP was associated with marked tumor infiltrating lymphocytes, tumor necrosis, sheeting, and poor differentiation (all PCIMP, MSI-L/CIMP was associated with tumors that had CIMP. Both MSI and CIMP appear to play a role in the pathogenesis of specific morphologic patterns of colorectal carcinoma.

  12. Underexpression of mineralocorticoid receptor in colorectal carcinomas and association with VEGFR-2 overexpression.

    Science.gov (United States)

    Di Fabio, Francesco; Alvarado, Carlos; Majdan, Agnieszka; Gologan, Adrian; Voda, Linda; Mitmaker, Elliot; Beitel, Lenore K; Gordon, Philip H; Trifiro, Mark

    2007-11-01

    The human mineralocorticoid receptor (MR) is a steroid receptor widely expressed in colorectal mucosa. A significant role for the MR in the reduction of vascular endothelial growth factor receptor-2 (VEGFR-2) mRNA levels has been demonstrated in vitro. To evaluate a potential contribution of MR to colorectal carcinoma progression, we analyzed the expression of MR in relation to VEGFR-2. Fresh human colorectal cancer tissue and adjacent normal mucosa were harvested from 48 consecutive patients. MR and VEGFR-2 mRNA expression levels were determined by real-time reverse transcriptase-polymerase chain reaction and correlated with clinicopathological parameters. A decline of MR expression was observed in all carcinomas compared to normal mucosa. Expression of MR was a median of 11-fold lower in carcinoma compared to the normal mucosa, irrespective of the location, size, stage, and differentiation. MR was a median of 20-fold underexpressed in carcinomas with VEGFR-2 overexpression vs only 9-fold in carcinomas with VEGFR-2 underexpression (p = 0.035, Mann-Whitney test). These findings support the hypothesis that reduction of MR expression may be one of the early events involved in colorectal carcinoma progression. The inverse association between MR and VEGFR-2 expression in carcinoma suggests a potential tumor-suppressive function for MR.

  13. High expression of testes-specific protease 50 is associated with poor prognosis in colorectal carcinoma.

    Directory of Open Access Journals (Sweden)

    Lei Zheng

    Full Text Available BACKGROUND: Testes-specific protease 50 (TSP50 is normally expressed in testes and abnormally expressed in breast cancer, but whether TSP50 is expressed in colorectal carcinoma (CRC and its clinical significance is unclear. We aimed to detect TSP50 expression in CRC, correlate it with clinicopathological factors, and assess its potential diagnostic and prognostic value. METHODOLOGY/PRINCIPAL FINDINGS: TSP50 mRNAs and proteins were detected in 7 CRC cell lines and 8 CRC specimens via RT-PCR and Western blot analysis. Immunohistochemical analysis of TSP50, p53 and carcinoembryonic antigen (CEA with tissue microarrays composed of 95 CRCs, 20 colorectal adenomas and 20 normal colorectal tissues were carried out and correlated with clinicopathological characteristics and disease-specific survival for CRC patients. There was no significant correlation between the expression levels of TSP50 and p53 (P = 0.751 or CEA (P = 0.663. Abundant expression of TSP50 protein was found in CRCs (68.4% while it was poorly expressed in colorectal adenomas and normal tissues (P<0.0001. Thus, CRCs can be distinguished from them with high specificity (92.5% and positive predictive value (PPV, 95.6%. The survival of CRC patients with high TSP50 expression was significantly shorter than that of the patients with low TSP50 expression (P = 0.010, specifically in patients who had early-stage tumors (stage I and II; P = 0.004. Multivariate Cox regression analysis indicated that high TSP50 expression was a statistically significant independent risk factor (hazard ratio  = 2.205, 95% CI = 1.214-4.004, P = 0.009. CONCLUSION: Our data demonstrate that TSP50 is a potential effective indicator of poor survival for CRC patients, especially for those with early-stage tumors.

  14. Squamous cell carcinoma - invasive (image)

    Science.gov (United States)

    This irregular red nodule is an invasive squamous cell carcinoma (a form of skin cancer). Initial appearance, shown here, may be very similar to a noncancerous growth called a keratoacanthoma. Squamous cell cancers ...

  15. Immunohistochemistry expression of TCF4 protein on carcinoma, adenoma and non neoplastic colorectal mucosa

    Directory of Open Access Journals (Sweden)

    Leonardo Huber Tauil

    2014-01-01

    Full Text Available Purpose: To detect and quantify the immunoreactivity of TCF4 protein in colorectal carci- noma, colorectal adenoma and non-neoplasic colorectal epithelium. Methods: We studied 129 individuals: 40 with colorectal cancer, 52 with colorectal ad- enoma and 37 with non-neoplastic colorectal epithelium. The colorectal adenoma and carcinoma samples were obtained from patients who underwent surgical procedures, and colonoscopies and samples of non-neoplastic colorectal epithelium were taken from patients who died from cardiovascular diseases, without diseases of the large intestine. Samples of different tissues were included in paraffin blocks, and the immunohistochem- ical expression of protein TCF4 was analyzed using the technique of tissue microarray (TMA with polyclonal antibody TCF4. The immunoreactivity was analyzed and classified as positive and negative. Results: The immunohistochemical expression of TCF4 protein was significantly higher (p < 0.01 in colorectal carcinoma than in the non-neoplastic colorectal epithelium and adenoma. There was no difference (p = 0.76 between TCF4 protein immunohistochemical expression in colorectal adenoma and non-neoplastic colorectal tissue. Conclusions: TCF4 protein showed a more intense expression in colorectal carcinoma than in non-neoplastic colorectal epithelium and adenoma, indicating that this protein is in- volved in colorectal carcinogenesis. Resumo: Objetivos: Detectar e quantificar a imunoexpressão da proteína TCF4 no carcinoma e no adenoma colorretal e no epitélio colorretal não neoplásico. Método: Foram estudados 129 indivíduos: 40 com carcinoma colorretal, 52 com adenoma colorretal e 37 com epitélio colorretal não neoplásico. Os tecidos de adenoma e carcinoma colorretais foram representados por amostras da lesão retirada de doentes submetidos a procedimentos cirúrgicos e colonoscópicos, e as amostras de epitélio colorretal não neo- plásico foram retiradas de doentes falecidos por

  16. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Inés Mármol

    2017-01-01

    Full Text Available Colorectal cancer (CRC is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%–5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism. Some of the bacteria responsible for this multiphase process include Fusobacterium spp, Bacteroides fragilis and enteropathogenic Escherichia coli. CRC is caused by mutations that target oncogenes, tumour suppressor genes and genes related to DNA repair mechanisms. Depending on the origin of the mutation, colorectal carcinomas can be classified as sporadic (70%; inherited (5% and familial (25%. The pathogenic mechanisms leading to this situation can be included in three types, namely chromosomal instability (CIN, microsatellite instability (MSI and CpG island methylator phenotype (CIMP. Within these types of CRC, common mutations, chromosomal changes and translocations have been reported to affect important pathways (WNT, MAPK/PI3K, TGF-β, TP53, and mutations; in particular, genes such as c-MYC, KRAS, BRAF, PIK3CA, PTEN, SMAD2 and SMAD4 can be used as predictive markers for patient outcome. In addition to gene mutations, alterations in ncRNAs, such as lncRNA or miRNA, can also contribute to different steps of the carcinogenesis process and have a predictive value when used as biomarkers. In consequence, different panels of genes and mRNA are being developed to improve prognosis and treatment selection. The choice of first-line treatment in CRC follows a multimodal approach based on tumour-related characteristics and usually comprises surgical resection followed by chemotherapy combined

  17. Cutaneous Squamous Cell Carcinoma.

    Science.gov (United States)

    Parekh, Vishwas; Seykora, John T

    2017-09-01

    Cutaneous squamous cell carcinoma (cSCC) is a malignant neoplasm of the skin characterized by an aberrant proliferation of keratinocytes. Cutaneous SCC is the second most common malignancy globally, and usually arises in the chronically sun-damaged skin of elderly white individuals. From a pathologist's perspective, it is important to differentiate cSCC from the benign and reactive squamoproliferative lesions and identify the high-risk features associated with aggressive tumor behavior. In this article, we provide an up-to-date overview of cSCC along with its precursor lesions and important histologic variants, with a particular emphasis on the histopathologic features and molecular pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. MLH1-deficient Colorectal Carcinoma With Wild-type BRAF and MLH1 Promoter Hypermethylation Harbor KRAS Mutations and Arise From Conventional Adenomas.

    Science.gov (United States)

    Farchoukh, Lama; Kuan, Shih-Fan; Dudley, Beth; Brand, Randall; Nikiforova, Marina; Pai, Reetesh K

    2016-10-01

    Between 10% and 15% of colorectal carcinomas demonstrate sporadic DNA mismatch-repair protein deficiency as a result of MLH1 promoter methylation and are thought to arise from sessile serrated adenomas, termed the serrated neoplasia pathway. Although the presence of the BRAF V600E mutation is indicative of a sporadic cancer, up to 30% to 50% of colorectal carcinomas with MLH1 promoter hypermethylation will lack a BRAF mutation. We report the clinicopathologic and molecular features of MLH1-deficient colorectal carcinoma with wild-type BRAF and MLH1 promoter hypermethylation (referred to as MLH1-hypermethylated BRAF wild-type colorectal carcinoma, n=36) in comparison with MLH1-deficient BRAF-mutated colorectal carcinoma (n=113) and Lynch syndrome-associated colorectal carcinoma (n=36). KRAS mutations were identified in 31% of MLH1-hypermethylated BRAF wild-type colorectal carcinomas compared with 0% of MLH1-deficient BRAF-mutated colorectal carcinomas and 37% of Lynch syndrome-associated colorectal carcinomas. When a precursor polyp was identified, MLH1-hypermethylated BRAF wild-type colorectal carcinomas arose from precursor polyps resembling conventional tubular/tubulovillous adenomas in contrast to MLH1-deficient BRAF-mutated colorectal carcinomas, which arose from precursor sessile serrated adenomas (PMLH1-hypermethylated BRAF wild-type colorectal carcinoma and MLH1-deficient BRAF-mutated colorectal carcinoma had a predilection for the right colon compared with Lynch syndrome-associated colorectal carcinoma (86% vs. 92% vs. 49%, P0.05). In conclusion, our results indicate that MLH1-hypermethylated BRAF wild-type colorectal carcinomas can harbor KRAS mutations and arise from precursor polyps resembling conventional tubular/tubulovillous adenomas.

  19. Radiation-induced apoptosis and cell cycle checkpoints in human colorectal tumour cell lines

    International Nuclear Information System (INIS)

    Playle, L.C.

    2001-03-01

    The p53 tumour suppressor gene is mutated in 75% of colorectal carcinomas and is critical for DNA damage-induced G1 cell cycle arrest. Data presented in this thesis demonstrate that after treatment with Ionizing Radiation (IR), colorectal tumour cell lines with mutant p53 are unable to arrest at G1 and undergo cell cycle arrest at G2. The staurosporine derivative, UCN-01, was shown to abrogate the IR-induced G2 checkpoint in colorectal tumour cell lines. Furthermore, in some cell lines, abrogation of the G2 checkpoint was associated with radiosensitisation. Data presented in this study demonstrate that 2 out of 5 cell lines with mutant p53 were sensitised to IR by UCN-01. In order to determine whether radiosensitisation correlated with lack of functional p53, transfected derivatives of an adenoma-derived cell line were studied, in which endogenous wild type p53 was disrupted by expression of a dominant negative p53 mutant protein (and with a vector control). In both these cell lines UCN-01 abrogated the G2 arrest however this was not associated with radiosensitisation, indicating that radiosensitisation is a cell type-specific phenomenon. Although 2 colorectal carcinoma cell lines, with mutant p53, were sensitised to IR by UCN-01, the mechanisms of p53-independent IR-induced apoptosis in the colon are essentially unknown. The mitogen-activated protein kinase (MAPK) pathways (that is the JNK, p38 and ERK pathways) have been implicated in apoptosis in a range of cell systems and in IR-induced apoptosis in some cell types. Data presented in this study show that, although the MAPKs can be activated by the known activator anisomycin, there is no evidence of a role for MAPKs in IR-induced apoptosis in colorectal tumour cell lines, regardless of p53 status. In summary, some colorectal tumour cell lines with mutant p53 can be sensitised to IR-induced cell death by G2 checkpoint abrogation and this may be an important treatment strategy, however mechanisms of IR-induced p53

  20. Body mass index and risk of colorectal carcinoma subtypes classified by tumor differentiation status.

    Science.gov (United States)

    Hanyuda, Akiko; Cao, Yin; Hamada, Tsuyoshi; Nowak, Jonathan A; Qian, Zhi Rong; Masugi, Yohei; da Silva, Annacarolina; Liu, Li; Kosumi, Keisuke; Soong, Thing Rinda; Jhun, Iny; Wu, Kana; Zhang, Xuehong; Song, Mingyang; Meyerhardt, Jeffrey A; Chan, Andrew T; Fuchs, Charles S; Giovannucci, Edward L; Ogino, Shuji; Nishihara, Reiko

    2017-05-01

    Previous studies suggest that abnormal energy balance status may dysregulate intestinal epithelial homeostasis and promote colorectal carcinogenesis, yet little is known about how host energy balance and obesity influence enterocyte differentiation during carcinogenesis. We hypothesized that the association between high body mass index (BMI) and colorectal carcinoma incidence might differ according to tumor histopathologic differentiation status. Using databases of the Nurses' Health Study and Health Professionals Follow-up Study, and duplication-method Cox proportional hazards models, we prospectively examined an association between BMI and the incidence of colorectal carcinoma subtypes classified by differentiation features. 120,813 participants were followed for 26 or 32 years and 1528 rectal and colon cancer cases with available tumor pathological data were documented. The association between BMI and colorectal cancer risk significantly differed depending on the presence or absence of poorly-differentiated foci (P heterogeneity  = 0.006). Higher BMI was associated with a higher risk of colorectal carcinoma without poorly-differentiated foci (≥30.0 vs. 18.5-22.4 kg/m 2 : multivariable-adjusted hazard ratio, 1.87; 95% confidence interval, 1.49-2.34; P trend   0.03, with the adjusted α of 0.01). High BMI was associated with risk of colorectal cancer subtype containing no poorly-differentiated focus. Our findings suggest that carcinogenic influence of excess energy balance might be stronger for tumors that retain better intestinal differentiation throughout the tumor areas.

  1. Evaluation of MR diffusion-weighted imaging in differentiating endometriosis infiltrating the bowel from colorectal carcinoma

    International Nuclear Information System (INIS)

    Busard, M.P.H.; Pieters-van den Bos, I.C.; Mijatovic, V.; Van Kuijk, C.; Bleeker, M.C.G.; Waesberghe, J.H.T.M. van

    2012-01-01

    Objective: Endometriosis infiltrating the bowel may be difficult to differentiate from colorectal carcinoma in cases that present with non-specific clinical and imaging features. The aim of this study is to assess the value of MR diffusion-weighted imaging (DWI) in differentiating endometriosis infiltrating the bowel from colorectal carcinoma. Methods: In 66 patients, MR DWI was added to the standard imaging protocol in patients visiting our outdoor MR clinic for the analysis of suspected or known deep infiltrating endometriosis (DIE). In patients diagnosed with DIE infiltrating the bowel on MR imaging, high b-value diffusion-weighted images were qualitatively assessed by two readers in consensus and compared to high b-value diffusion weighted images in 15 patients evaluated for colorectal carcinoma. In addition, ADC values of lesions were calculated, using b-values of 50, 400 and 800 s/mm 2 . Results: A total of 15 patients were diagnosed with DIE infiltrating the bowel on MR imaging. Endometriosis infiltrating the bowel showed low signal intensity on high b-value diffusion-weighted images in all patients, whereas colorectal carcinoma showed high signal intensity on high b-value diffusion-weighted images in all patients. Mean ADC value in endometriosis infiltrating the bowel (0.80 ± 0.06 × 10 −3 mm 2 /s) was significantly lower compared to mean ADC value in colorectal carcinoma (0.86 ± 0.06 × 10 −3 mm 2 /s), but with considerable overlap between ADC values. Conclusion: Only qualitative assessment of MR DWI may be valuable to facilitate differentiation between endometriosis infiltrating the bowel and colorectal carcinoma.

  2. CEA monitoring of palliative treatment for colorectal carcinoma.

    Science.gov (United States)

    Herrera, M A; Chu, T M; Holyoke, E D; Mittelman, A

    1977-01-01

    Palliative treatment was applied to 131 cases of unresectable or palliatively resected colorectal carcinoma being monitored with serial CEA determinations. There were 84 instances of disease progression with 67 (80%) of them showing an increase in CEA above pretreatment levels or maintaining high levels, and 17 (20%) showing a fall when compared to pretreatment values or maintaining low initial values. There was a clear-cut regression of the disease in only 9 instances. In all 9, the CEA clearly dropped or maintained low valles throughout the period of regression. No patient in regression had a rise or maintained an elevated CEA level. These changes in CEA followed closely the clinical response of our patient to the use of a particular agent, although for the Nitrosourea compounds there may be a tendency to lower the CEA regardless of the patient's tumor response to the drug. This could be due to the fact that the Nitrosoureas produce a diffuse block of cellular activity, both at the nucleous and cytoplasm; while other compounds act as alkylating agents or by inhibition of enzymes involved in the metabolism of nucleic acids (i.e., 5-FU inhibiting thymidylate synthetase). In general, longer survival was found in those patients who had initially lower levels of CEA as compared to those with high initial levels. The patients with a favorable CEA response to the treatment (falling CEA or maintained low value), even in many who did not show a clinical response had a longer survival than the group with rising or stable high levels. The main value in CEA monitoring of patients resides in its correlation with the amount of disease present and then its ability to detect progression of tumor mass which is not clinically measurable. PMID:64132

  3. Radiosensitization by SAHA in Experimental Colorectal Carcinoma Models-In Vivo Effects and Relevance of Histone Acetylation Status

    International Nuclear Information System (INIS)

    Folkvord, Sigurd; Ree, Anne Hansen; Furre, Torbjorn; Halvorsen, Thomas; Flatmark, Kjersti

    2009-01-01

    Purpose: Histone deacetylase inhibitors are being evaluated as antitumor agents in ongoing clinical trials, and promising preclinical results, combined with favorable toxicity profiles, have rendered the drugs as interesting candidates for combination with other treatment modalities, such as radiotherapy. The aim of the present study was to evaluate the radiosensitizing properties of suberoylanilide hydroxamic acid (SAHA) and the possible requirement of histone hyperacetylation at radiation exposure. Methods and materials: Radiosensitization by SAHA was assessed in a colorectal carcinoma cell line and in two colorectal xenograft models by analysis of clonogenic survival and tumor growth delay, respectively. Histone acetylation status at radiation exposure was evaluated by Western blot. Results: In vitro, radiosensitization was demonstrated when cells were preincubated with SAHA, and, in the xenografts, tumor growth was delayed when the mice were treated with fractionated radiation combined with daily SAHA injections compared with radiation alone. Surprisingly, the SAHA-dependent growth delay was still present when radiation was delivered at restored baseline acetylation levels compared with maximal histone hyperacetylation. Conclusion: SAHA was an effective radiosensitizer in experimental colorectal carcinoma models, suggesting that histone deacetylase inhibition might constitute a valuable supplement to current multimodal treatment strategies in rectal cancer. The presence of histone hyperacetylation at radiation was not required to obtain an increased radiation response, questioning the validity of using histone hyperacetylation as a molecular marker for radiosensitivity.

  4. Renal cell carcinoma in childhood

    International Nuclear Information System (INIS)

    Zanier, J.F.C.; Ramos, C.O.P.; Pereira, A.A.

    1990-01-01

    The authors present five cases of renal cell carcinoma in children, describing its aspects on excretory urography, ultra-sonography and computerized tomography. The clinical, pathological and radiological features are compared with those of the literature. (author)

  5. Advanced colorectal adenoma related gene expression signature may predict prognostic for colorectal cancer patients with adenoma-carcinoma sequence.

    Science.gov (United States)

    Li, Bing; Shi, Xiao-Yu; Liao, Dai-Xiang; Cao, Bang-Rong; Luo, Cheng-Hua; Cheng, Shu-Jun

    2015-01-01

    There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinformatics software, and we analyzed the relationship between gene expression profiles of adenoma-adenocarcinoma sequence and clinical prognosis of colorectal cancer. The mRNA expressions of adenoma-carcinoma sequence were significantly different between high-grade intraepithelial neoplasia group and adenocarcinoma group. The biological process of gene ontology function enrichment analysis on differentially expressed genes between high-grade intraepithelial neoplasia group and adenocarcinoma group showed that genes enriched in the extracellular structure organization, skeletal system development, biological adhesion and itself regulated growth regulation, with the P value after FDR correction of less than 0.05. In addition, IPR-related protein mainly focused on the insulin-like growth factor binding proteins. The variable trends of gene expression profiles for adenoma-carcinoma sequence were mainly concentrated in high-grade intraepithelial neoplasia and adenocarcinoma. The differentially expressed genes are significantly correlated between high-grade intraepithelial neoplasia group and adenocarcinoma group. Bioinformatics analysis is an effective way to study the gene expression profiles in the adenoma-carcinoma sequence, and may provide an effective tool to involve colorectal cancer research strategy into colorectal adenoma or advanced adenoma.

  6. miR-330 regulates the proliferation of colorectal cancer cells by targeting Cdc42

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuefeng [The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Zhu, Xiaolan; Xu, Wenlin [The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Wang, Dongqing [The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China); Yan, Jinchuan, E-mail: jiangdalyf2009@126.com [The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001 (China)

    2013-02-15

    Highlights: ► miR-330 was inversely correlated with Cdc42 in colorectal cancer cells. ► Elevated miR-330 suppressed cell proliferation in vivo and in vitro. ► Elevated miR-330 mimicked the effect of Cdc42 knockdown. ► Restoration of Cdc42 could partially attenuate the effects of miR-330. -- Abstract: MicroRNAs are small non-coding RNA molecules that play important roles in the multistep process of colorectal carcinoma (CRC) development. However, the miRNA–mRNA regulatory network is far from being fully understood. The objective of this study was to investigate the expression and the biological roles of miR-330 in colorectal cancer cells. Cdc42, one of the best characterized members of the Rho GTPase family, was found to be up-regulated in several types of human tumors including CRC and has been implicated in cancer initiation and progression. In the present study, we identified miR-330, as a potential regulator of Cdc42, was found to be inversely correlated with Cdc42 expression in colorectal cancer cell lines. Ectopic expression of miR-330 down-regulated Cdc42 expression at both protein and mRNA level, mimicked the effect of Cdc42 knockdown in inhibiting proliferation, inducing G1 cell cycle arrest and apoptosis of the colorectal cancer cells, whereas restoration of Cdc42 could partially attenuate the effects of miR-330. In addition, elevated expression of miR-330 could suppress the immediate downstream effectors of Cdc42 and inhibit the growth of colorectal cancer cells in vivo. To sum up, our results establish a role of miR-330 in negatively regulating Cdc42 expression and colorectal cancer cell proliferation. They suggest that manipulating the expression level of Cdc42 by miR-330 has the potential to influence colorectal cancer progression.

  7. miR-330 regulates the proliferation of colorectal cancer cells by targeting Cdc42

    International Nuclear Information System (INIS)

    Li, Yuefeng; Zhu, Xiaolan; Xu, Wenlin; Wang, Dongqing; Yan, Jinchuan

    2013-01-01

    Highlights: ► miR-330 was inversely correlated with Cdc42 in colorectal cancer cells. ► Elevated miR-330 suppressed cell proliferation in vivo and in vitro. ► Elevated miR-330 mimicked the effect of Cdc42 knockdown. ► Restoration of Cdc42 could partially attenuate the effects of miR-330. -- Abstract: MicroRNAs are small non-coding RNA molecules that play important roles in the multistep process of colorectal carcinoma (CRC) development. However, the miRNA–mRNA regulatory network is far from being fully understood. The objective of this study was to investigate the expression and the biological roles of miR-330 in colorectal cancer cells. Cdc42, one of the best characterized members of the Rho GTPase family, was found to be up-regulated in several types of human tumors including CRC and has been implicated in cancer initiation and progression. In the present study, we identified miR-330, as a potential regulator of Cdc42, was found to be inversely correlated with Cdc42 expression in colorectal cancer cell lines. Ectopic expression of miR-330 down-regulated Cdc42 expression at both protein and mRNA level, mimicked the effect of Cdc42 knockdown in inhibiting proliferation, inducing G1 cell cycle arrest and apoptosis of the colorectal cancer cells, whereas restoration of Cdc42 could partially attenuate the effects of miR-330. In addition, elevated expression of miR-330 could suppress the immediate downstream effectors of Cdc42 and inhibit the growth of colorectal cancer cells in vivo. To sum up, our results establish a role of miR-330 in negatively regulating Cdc42 expression and colorectal cancer cell proliferation. They suggest that manipulating the expression level of Cdc42 by miR-330 has the potential to influence colorectal cancer progression

  8. Independent Induction of Caspase-8 and cFLIP Expression during Colorectal Carcinogenesis in Sporadic and HNPCC Adenomas and Carcinomas

    Directory of Open Access Journals (Sweden)

    D. M. Heijink

    2007-01-01

    Full Text Available Background: TNF-Related Apoptosis Inducing Ligand (TRAIL is a promising agent for the induction of apoptosis in neoplastic tissues. Important determinants of TRAIL sensitivity are two intracellular proteins of the TRAIL pathway, caspase-8 and its anti-apoptotic competitor cellular Flice-Like Inhibitory Protein (cFLIP. Methods: The aim of this study was to investigate basic expression of caspase-8 and cFLIP in normal colorectal epithelium (n = 20, colorectal adenomas (n = 66 and colorectal carcinomas (n = 44 using immunohistochemistry performed on both sporadic and Hereditary Non-Polyposis Colorectal Cancer (HNPCC or Lynch syndrome-associated adenomas and carcinomas. Results: Expression of both caspase-8 and cFLIP was similar in cases with sporadic and hereditary origin. Expression of caspase-8 in colorectal adenomas and carcinomas was increased when compared to normal colon tissue (P = 0.02. Nuclear, paranuclear as well as cytoplasmic localizations of caspase-8 were detected. Immunohistochemistry revealed an upregulation of cFLIP in colorectal carcinomas in comparison to normal epithelium and colorectal adenomas (P < 0.001. A large variation in the caspase-8/cFLIP ratio was observed between the individual adenomas and carcinomas. Conclusion: Caspase-8 and cFLIP are upregulated during colorectal carcinogenesis. Upregulation of caspase-8 and/or downregulation of cFLIP may be interesting approaches to maximize TRAIL sensitivity in colorectal neoplasms.

  9. Synchronous thyroid carcinoma and squamous cell carcinoma. A case report

    International Nuclear Information System (INIS)

    Lee, Jae Seo

    2006-01-01

    Thyroid carcinoma occurring as a second primary associated with head and neck squamous cell carcinoma (SCC) is unusual. This report presents a synchronous thyroid carcinoma and squamous cell carcinoma in the anterior palate region of a 41-year-old man. The clinical, radiologic, and histologic features are described. At 10-month follow-up after operation, no evidence of recurrence ana metastasis was present

  10. Anti-CEA monoclonal antibody in the diagnosis of colorectal, lung and ovarian carcinoma

    International Nuclear Information System (INIS)

    Jiang, N.; Lu, B.; Lu, X.; Sha, X.; Yue, D.

    2000-01-01

    This study evaluated the diagnostic value of radioimmnoimaging (RII) with 99 Tc labeled monoclonal antibody C50, raised originally against carcinoembryonic antigen (anti-CEA) in various tumors. 152 pathologically confirmed patients with a tumor were imaged prior to surgery with an anti-CEA monoclonal antibody labeled with 99 Tc. There were 115 patients with ovarian carcinoma, 26 patients with colorectal carcinoma and 11 patients with lung carcinoma. Images were acquired at 3-6 h post injection and were analyzed by the double blind method. Images of patients with ovarian cancer were compared with B-ultrasound images. Immunohistochemical staining was performed on all cases of colorectal cancer. All RII images demonstrated excellent contrast, clear lesions, and no serious toxic or other side reactions occurred. Transient chills and fever were observed in 3 cases. This study showed a sensitivity=88.2%, specificity=83.2%, and an accuracy=4.0%. The smallest lesion size detected was 2 x 2 cm. The total combined lesion detection rate for primary, metastatic, and recurrence lesions was 84.4%. We conclude that 99 Tc labeled anti-CEA MoAb C50 can be used in the diagnosis of colorectal carcinoma, ovarian carcinoma, and lung carcinoma

  11. Genetic testing for colorectal carcinoma susceptibility: focus group responses of individuals with colorectal carcinoma and first-degree relatives.

    Science.gov (United States)

    Kinney, A Y; DeVellis, B M; Skrzynia, C; Millikan, R

    2001-01-01

    Colorectal carcinoma (CRC) may be the most frequent form of hereditary cancer. Genetic counseling and testing for heritable CRC is a promising approach for reducing the high incidence and mortality rates associated with the disease. Patients with CRC or those with at least one family member with the disease are the most likely persons to request or be offered genetic testing in the clinical or research setting. Currently, however, little is known about the behavioral, psychosocial, ethical, legal, and economic outcomes of CRC genetic counseling and testing. Eight focus group interviews, four for CRC patients (n = 28) and four for first-degree relatives (n = 33), were conducted to obtain insights into attitudes, beliefs, and informational needs about genetic testing for hereditary CRC. Focus group interviews revealed a general lack of knowledge about cancer genetics and genetic testing; worry about confidentiality issues; strong concern for family members, particularly children; and a need for primary care providers to be informed about these issues. Major perceived advantages of genetic testing included improving health-related decisions, guiding physicians in making recommendations for surveillance, and informing relatives about risk potential. Disadvantages included potential discrimination, adverse psychologic effects, and financial costs associated with testing. As knowledge and media coverage of genetics continue to expand, it becomes increasingly important to continue efforts on behalf of, and in partnership with, those individuals most affected by genetic testing for hereditary cancer syndromes. These findings provide data needed to develop and implement informational, educational, counseling, and research-oriented programs that are sensitive to individuals' concerns and preferences. Copyright 2001 American Cancer Society.

  12. Correlation between spiral CT features of pericolic infiltration and tumor angiogenesis in colorectal carcinoma

    International Nuclear Information System (INIS)

    Zhang Ruiping; Li Jianding

    2007-01-01

    Objective: To investigate the correlation of spiral CT (SCT) features with pathology, microvessel density (MVD), expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2( MMP-2) in colorectal carcinoma. Methods: Forty patients with colorectal carcinoma confirmed by operation were examined by SCT. The resected tumor specimens were immunohistochemically stained for the expression of VEGF, MMP-2 and the calculation of MVD. Results: The accuracy of SCT in depicting the pericolic and wall infiltration was 92.5%. The metastasis rates of colorectal cancer with pericolic infiltration and wall infiltration were 75.0% and 33.3%, respectively, the differences were statistically significant between the two groups (P<0.05). The differences of CT enhancement value, MVD, expressions of VEGF and MMP-2 between the two groups were statistically significant (P<0.05). The enhancement degree of CT had a positive correlation with MVD (P<0.05). Conclusion: SCT is accurate for depicting pericolic and wall infiltration, pericolic infiltration in colorectal carcinoma indicates the tendency of metastasis. The enhancement degree of CT might be used to quantitatively evaluate the tumor angiogenesis, expressions of VEGF and MMP-2 and MVD are closely correlated with the infiltration of colorectal cancer. (authors)

  13. Colorectal carcinomas from Middle East: Molecular and tissue microarray analysis of genomic instability pathways

    International Nuclear Information System (INIS)

    Bavi, P.P.; Abubaker, Jehad A.; Jehan, Zeenath D.; Al-Jomah, Naif A.; Siraj, Abdul K.; Al-Harbi, Sayer R.; Atizado, Valerie L.; Uddin, S.; Al-Kuraya, Khawla S.; Abduljabbar, Alaa S.; Al-Homoud, Samar J.; Ashari, Luai H.; Al-Sanea, Nasser A.; Al-Dayel, Fouad H.

    2008-01-01

    Objective was to evaluate the overall incidence of microsatellite instability (MSI), hereditary non polyposis colorectal cancer and tumor suppressor gene (TP53) mutations in Saudi colorectal carcinomas. We studied the MSI pathway in Saudi colorectal cancers (CRC) from 179 unselected patients using 2 methods: MSI by polymerase chain reaction and immunohistochemistry detection of mutL homologs 1 and mutS homologs 2 proteins. The TP53 mutations were studied by sequencing exons 5, 6, 7 and 8. Of the 150 colorectal carcinomas analyzed for MSI, 16% of the tumors showed high level instability (MSI-H), 19.3% had low level instability (MSI-L) and the remaining 64% tumors were stable. Survival of the MSI-H group was better as compared to the MSI-L or microsatellite stable group (p=0.0217). In the MSI-H group, 48% were familial MSI tumors which could be attributable to the high incidence of consanguinity in the Saudi population. The TP53 mutations were found in 24% of the cases studied. A high production of familial MSI cases and a lower incidence of TP53 mutations are some of the hallmarks of the Saudi colorectal carcinomas which need to be explored further. (author)

  14. An evaluation of nuclear factor kappa B expression in colorectal carcinoma: An analysis of 50 cases

    Directory of Open Access Journals (Sweden)

    Nikhil Moorchung

    2014-01-01

    Conclusions: It is likely that NFkB is an important factor in the pathogenesis of CRC. Further studies including therapeutic intervention using strategies which prevent activation of NFkB in colorectal carcinoma patients will tell if we could alter the course of the disease favorably.

  15. Cytogenetic comparisons of synchronous carcinomas and polyps in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Bardi, G; Parada, L A; Bomme, L

    1997-01-01

    Thirty tumorous lesions from seven patients with colorectal cancer were short-term cultured and cytogenetically analysed: 16 non-adenomatous polyps, six adenomas, seven carcinomas, including one in polyp, and one lymph node metastasis. Clonal chromosome aberrations were found in 20 samples in 100...

  16. Bergenin suppresses the growth of colorectal cancer cells by ...

    African Journals Online (AJOL)

    Purpose: To investigate anticancer effects of bergenin on human colorectal cancer cell lines. Methods: Human colorectal adenocarcinoma cell line HCT116 was treated with various concentrations of bergenin for 24 and 48 h. Cell viability, apoptosis, cell cycle arrest and reactive oxygen species (ROS) level were analyzed ...

  17. Appendiceal goblet cell carcinoids and adenocarcinomas ex-goblet cell carcinoid are genetically distinct from primary colorectal-type adenocarcinoma of the appendix

    DEFF Research Database (Denmark)

    Jesinghaus, Moritz; Konukiewitz, Björn; Foersch, Sebastian

    2018-01-01

    The appendix gives rise to goblet cell carcinoids, which represent special carcinomas with distinct biological and histological features. Their genetic background and molecular relationship to colorectal adenocarcinoma is largely unknown. We therefore performed a next-generation sequencing analysis...... a morphomolecular entity, histologically and genetically distinct from appendiceal colorectal-type adenocarcinomas and its colorectal counterparts. Altered Wnt-signaling associated genes, apart from APC, may act as potential drivers of these neoplasms. The absence of KRAS/NRAS mutations might render some....../adenocarcinoma ex-goblet cell carcinoid (n=2, respectively). Mutations in colorectal cancer-related genes (eg, TP53, KRAS, APC) were rare to absent in both, goblet cell carcinoids and adenocarcinomas ex-goblet cell carcinoid, but frequent in primary colorectal-type adenocarcinomas of the appendix. Additional large...

  18. Detection of recurrent colorectal carcinoma with 18F-FDG positron emission tomography (PET)

    International Nuclear Information System (INIS)

    Scott, A.M.; Berlangieri, S.U.; Zalcberg, J.; Fox, R.; Cebon, J.; McLeish, A.; Thomas, D.; Chan, G.; Tochon-Danguy, H.; Egan, G.F.; McKay, W.J.

    1998-01-01

    Full text: The appropriate surgical management of recurrent colorectal carcinoma is dependent on the accurate detection of possible primary site recurrence and distant spread of disease. The aim of this study was therefore to evaluate the clinical accuracy of 18 F-FDG PET in detecting recurrent colorectal carcinoma. Over a 12-month period we have performed 21 studies in 17 patients (12 M: 5 F, age range 52-73 y) with known or suspected recurrent colorectal carcinoma. All patients underwent PET imaging of the abdomen and pelvis, or whole body imaging, with a whole body PET scanner (Siemens 951/R) following injection of 400 MBq of 18 F-FDG. All PET studies were interpreted with full knowledge of CT findings, and results were compared to subsequent surgical findings, biopsy or follow-up by conventional imaging methods (e.g. CT scan). Of the 21 studies performed, 18 (86%) had abnormal sites of 18 F-FDG uptake; all sites were subsequently confirmed as recurrent colorectal carcinoma. PET identified a total of 30 sites of disease in the pelvis (n = 4), abdomen (n =10), liver (n = 6), thorax (n = 9) and abdominal surgical scar (n 1), and was false negative in one lung lesion. CT scan correctly identified 14 sites as recurrent tumour; 9/12 patients (pts) with equivocal changes on CT scan had recurrent disease identified by PET. In 10 pts with elevated serum CEA but negative or equivocal CT scans, PET correctly identified 8 pts with proven recurrent disease. Previously unsuspected disease was found at six sites by PET. Lesions as small as 1.2 cm proven at surgery were identified with PET. In conclusion, this study shows 18 F-FDG PET to be a promising method for accurate detection of recurrent colorectal carcinoma

  19. 3-D visualization and quantitation of microvessels in transparent human colorectal carcinoma [corrected].

    Directory of Open Access Journals (Sweden)

    Yuan-An Liu

    Full Text Available Microscopic analysis of tumor vasculature plays an important role in understanding the progression and malignancy of colorectal carcinoma. However, due to the geometry of blood vessels and their connections, standard microtome-based histology is limited in providing the spatial information of the vascular network with a 3-dimensional (3-D continuum. To facilitate 3-D tissue analysis, we prepared transparent human colorectal biopsies by optical clearing for in-depth confocal microscopy with CD34 immunohistochemistry. Full-depth colons were obtained from colectomies performed for colorectal carcinoma. Specimens were prepared away from (control and at the tumor site. Taking advantage of the transparent specimens, we acquired anatomic information up to 200 μm in depth for qualitative and quantitative analyses of the vasculature. Examples are given to illustrate: (1 the association between the tumor microstructure and vasculature in space, including the perivascular cuffs of tumor outgrowth, and (2 the difference between the 2-D and 3-D quantitation of microvessels. We also demonstrate that the optically cleared mucosa can be retrieved after 3-D microscopy to perform the standard microtome-based histology (H&E staining and immunohistochemistry for systematic integration of the two tissue imaging methods. Overall, we established a new tumor histological approach to integrate 3-D imaging, illustration, and quantitation of human colonic microvessels in normal and cancerous specimens. This approach has significant promise to work with the standard histology to better characterize the tumor microenvironment in colorectal carcinoma.

  20. Potential targets for lung squamous cell carcinoma

    Science.gov (United States)

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  1. General Information about Merkel Cell Carcinoma

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Merkel Cell Carcinoma Treatment (PDQ®)–Patient Version General Information About Merkel Cell Carcinoma Go to Health Professional Version Key ...

  2. Molecular Mechanism of Enhanced Anticancer Effect of Nanoparticle Formulated LY2835219 via p16-CDK4/6-pRb Pathway in Colorectal Carcinoma Cell Line

    Directory of Open Access Journals (Sweden)

    Xu Tang

    2016-01-01

    Full Text Available LY2835219 is a dual inhibitor to CDK4 and CDK6. This study was to prepare LY2835219-loaded chitosan nanoparticles (CNP/LY and LY2835219-loaded hyaluronic acid-conjugated chitosan nanoparticles (HACNP/LY and revealed their anticancer effect and influence on p16-CDK4/6-pRb pathway against colon cell line. The nanoparticle sizes of CNP/LY and HACNP/LY were approximately 195±39.6 nm and 217±31.1 nm, respectively. The zeta potentials of CNP/LY and HACNP/LY were 37.3±1.5 mV and 30.3±2.2 mV, respectively. And the preparation process showed considerable drug encapsulation efficiency and loading efficiency. LY2835219, CNP/LY, and HACNP/LY inhibited HT29 cell proliferation with 0.68, 0.54, and 0.30 μM of IC50, respectively. G1 phase was arrested by LY2835219 and its formulations. Furthermore, inhibition of CDK4/6 by LY2835219 formulations induced CDK4, CDK6, cyclin D1, and pRb decrease and p16 increase at both protein and mRNA levels. Overall, nanoparticle formulated LY2835219 could enhance the cytotoxicity and cell cycle arrest, and HACNP/LY strengthened the trend furtherly compared to CNP/LY. It is the first time to demonstrate the anticancer effect and mechanism against HT29 by LY2835219 and its nanoparticles. The drug and its nanoparticle formulations delay the cell growth and arrest cell cycle through p16-CDK4/6-pRb pathway, while the nanoparticle formulated LY2835219 could strengthen the process.

  3. Primary orbital squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ana L. Campos Arbulú

    2017-02-01

    Full Text Available Primary orbital squamous cell carcinoma is a rare entity. There is little published literature. We report a case of primary squamous cell carcinoma of the orbital soft tissues. Surgical resection offered the best treatment for the patient. Complete resection of the lesion was achieved. The patient received adjuvant radiotherapy due to the proximity of the lesion to the surgical margins. Surgical treatment is feasible and should be considered as part of the surgeon's arsenal. However, therapeutic decisions must be made on a case-by-case basis

  4. Carcinoma-specific Ulex europaeus agglutinin-I binding glycoproteins of human colorectal carcinoma and its relation to carcinoembryonic antigen.

    Science.gov (United States)

    Matsushita, Y; Yonezawa, S; Nakamura, T; Shimizu, S; Ozawa, M; Muramatsu, T; Sato, E

    1985-08-01

    Glycoproteins binding to Ulex europaeus agglutinin-I (UEA-I) lectin, which recognizes the terminal alpha-L-fucose residue, were analyzed in 18 cases of human colorectal carcinoma by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by the Western blotting method. In the distal large bowel (descending and sigmoid colon and rectum), high-molecular-weight glycoproteins binding to UEA-I existed in carcinoma tissue but not in normal mucosa. In the proximal large bowel (ascending and transverse colon), high-molecular-weight glycoproteins binding to UEA-I were found both in normal mucosa and in carcinoma tissue, whereas those from the carcinoma tissue had an apparently lower molecular weight as compared to the weight of those from the normal mucosa. Thus there is a biochemical difference in UEA-I binding glycoproteins between the normal mucosa and the carcinoma tissue, although in our previous histochemical study no difference was observed in UEA-I binding glycoproteins of the proximal large bowel between the carcinoma tissue and the normal mucosa. Furthermore, carcinoembryonic antigen from the carcinoma tissue was found to have the same electrophoretical mobility as the UEA-I binding glycoproteins.

  5. Herbal medicine Guan Chang Fu Fang enhances 5-fluorouracil cytotoxicity and affects drug-associated genes in human colorectal carcinoma cells.

    Science.gov (United States)

    Yu, Chen; Liu, Shen-Lin; Qi, Ming-Hao; Zou, Xi; Wu, Jian; Zhang, Jing

    2015-02-01

    Guan Chang Fu Fang (GCFF) is a natural compound, which is extracted from three medicinal plants, Agrimonia pilosa Ledeb ., Patrinia scabiosaefolia and Solanum nigrum L . GCFF has demonstrated clinical efficacy in the treatment of colon cancer. At present, 5-fluorouracil (5-FU) is the primary active chemotherapeutic agent used for treating colon cancer. Using median-effect and apoptosis analyses, fluorescence microscopy and western blotting, the present study analyzed the association between GCFF and 5-FU in the human colon adenocarcinoma LoVo cell line. The effect of GCFF on the expression of chemotherapeutic agent-associated genes was also investigated. The results of the synergistic analysis revealed that GCFF exhibited a significant effect upon 5-FU-associated cytotoxicity within the LoVo cell line. This effect was observed over a broad dose-inhibition range (5-95%), but was particularly significant in the lower concentrations. The flow cytometry results revealed that low doses of GCFF or 5-FU induced S-phase arrest, as did a low-dose combination of the two drugs. After 48 h, GCFF significantly suppressed the expression levels of the chemotherapeutic agent resistance-associated genes within the colon cancer cells. The western blot analysis revealed that the combined effects of 5-FU and GCFF were due to a regulation of the B-cell lymphoma-2 family of proteins. The findings of the present study suggested that GCFF, when combined with 5-FU, has the potential to be a novel, chemotherapeutic compound for the treatment of colon cancer.

  6. Oncogenic K-Ras Activates p38 to Maintain Colorectal Cancer Cell Proliferation during MEK Inhibition

    Directory of Open Access Journals (Sweden)

    Winan J. van Houdt

    2010-01-01

    Full Text Available Background: Colon carcinomas frequently contain activating mutations in the K-ras proto-oncogene. K-ras itself is a poor drug target and drug development efforts have mostly focused on components of the classical Ras-activated MEK/ERK pathway. Here we have studied whether endogenous oncogenic K-ras affects the dependency of colorectal tumor cells on MEK/ERK signaling.

  7. Sensitivity of single and double contrast barium enema in the detection of colorectal carcinoma

    International Nuclear Information System (INIS)

    Myllylae, V.; Paeivansalo, M.; Laitinen, S.; Oulu Univ.

    1984-01-01

    The preoperative barium enema of the 188 colorectal carcinoma patients operated at the Oulu University Central Hospital (Finland) during 1977-1982 were examined retrospectively. Altogether 112 single contrast studies and 87 double contrast studies had been made on these patients. The single contrast barium enemas had resulted in a correct diagnosis of colorectal carcinoma in 93 cases (sensitivity 83%). The correct diagnosis in the double contrast studies numbered 71 (sensitivity 82%). Most of the overlooked carcinomas were located in the caecum, in the sigmoid or the rectum. Most of the errors made in the single contrast studies were due to detection errors and poor evacuation. The most common failures in double contrast enemas were detection errors and nonvisualisation of the sigmoid. The authors recommend use of the double contrast technique and suggest that the two methods of barium enema be used to complement each other. A false negative diagnosis delayed the operation of the colorectal carcinoma patients by 2.2 months (median). (orig.) [de

  8. Basal cell carcinoma-treatment with cryosurgery

    Directory of Open Access Journals (Sweden)

    Kaur S

    2003-03-01

    Full Text Available Basal cell carcinoma is a common cutaneous malignancy, frequently occurring over the face in elderly individuals. Various therapeutic modalities are available to treat these tumors. We describe three patients with basal cell carcinoma successfully treated with cryosurgery and discuss the indications and the use of this treatment modality for basal cell carcinomas.

  9. Selective in vivo radiosensitization by 5-fluorocytosine of human colorectal carcinoma cells transduced with the E. coli cytosine deaminase (CD) gene

    International Nuclear Information System (INIS)

    Gabel, M.; Kim, J.H.; Kolozsvary, A.; Khil, M.; Freytag, S.

    1998-01-01

    Purpose: The E. coli cytosine deaminase (CD) gene encodes an enzyme capable of converting the nontoxic prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU), a known radiosensitizer. Having previously shown that combined CD suicide gene therapy and radiation (RT) results in pronounced radiosensitization in vitro, we progressed to in vivo studies of combined therapy. Methods and Materials: WiDr human colon cancer cells were transduced in vitro with the CD gene and cells expressing CD were selected for use as xenografts in a nude mouse model. After administration of 5-FC, tumors received 10-30 Gy local field radiation (RT) and tumor growth delay was compared to control animals receiving either 5-FU, 5-FC, or RT alone. Results: Maximal growth delay was seen in mice treated with 5-FC for 6 consecutive days prior to RT. Combined treatment with 15 Gy radiation resulted in a dose-modifying factor (DMF) of 1.50, and a greater DMF was observed with higher doses of radiation. There was no appreciable toxicity using this new approach. In contrast, a similar treatment of combined 5-FU and radiation resulted in considerable toxicity and no appreciable radiosensitization. Conclusion: The present results show that combined suicide gene therapy and RT results in pronounced antitumor effect without any notable toxicity. This indicates that the CD gene may be useful in the development of novel treatment strategies combining radiation and gene therapy in the treatment of locally advanced cancers

  10. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review

    DEFF Research Database (Denmark)

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda Plovmand

    2016-01-01

    Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis.......Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis....

  11. Pharmacokinetic study of radiolabeled anti-colorectal carcinoma monoclonal antibodies in tumor-bearing nude mice

    Energy Technology Data Exchange (ETDEWEB)

    Douillard, J.Y.; Chatal, J.F.; Curtet, C.; Kremer, M.; Saccavini, J.C.; Peuvrel, P.; Koprowski, H.

    1985-09-01

    Monoclonal antibodies (MoAbs) 17-1A and 19-9, which specifically bind human colorectal carcinoma (CRC) cells, were tested for their usefulness in localizing colorectal tumors in nude mice. One of the /sup 131/I-labeled MoAbs and an irrelevant /sup 125/I-labeled immunoglobulin of the same isotype were injected into nude mice simultaneously bearing a human CRC and a human melanoma. The percentage of the injected dose of antibody per gram of tissue, the CRC/tissue ratios of antibody distribution, and the localization indicees were calculated at various time intervals (2 h to 10 days). For both MoAbs, labeling to a specific activity of 10 ..mu..Ci/..mu..g by the iodogen method gave optimum immunoreactivity. The accumulation of MoAb 17-1A in CRC reached its maximum at 5 days and remained at this level for up to 9 days postinjection. For MoAb 19-9, which detects a circulating antigen shed by the tumor into the serum, the accumulation in the CRC was maximum at 24 h, and decreased thereafter. The CRC/organ ratios and localization indices for-both MoAbs increased with time in the CRC tissue, but remained low and unchanged in the melanoma and normal tissue. Using F(ab')/sub 2/ antibody fragments, faster kinetics with earlier maximum accumulation, higher tumor/organ ratios, and better localization indices were achieved than with intact MoAbs. The data obtained was useful in defining parameters which must be considered before radiolabeled MoAbs are used in cancer patients for diagnostic purposes.

  12. Vaccination with apoptosis colorectal cancer cell pulsed autologous ...

    African Journals Online (AJOL)

    To investigate vaccination with apoptosis colorectal cancer (CRC) cell pulsed autologous dendritic cells (DCs) in advanced CRC, 14 patients with advanced colorectal cancer (CRC) were enrolled and treated with DCs vaccine to assess toxicity, tolerability, immune and clinical responses to the vaccine. No severe toxicity ...

  13. Spontaneous regression of metastatic Merkel cell carcinoma.

    LENUS (Irish Health Repository)

    Hassan, S J

    2010-01-01

    Merkel cell carcinoma is a rare aggressive neuroendocrine carcinoma of the skin predominantly affecting elderly Caucasians. It has a high rate of local recurrence and regional lymph node metastases. It is associated with a poor prognosis. Complete spontaneous regression of Merkel cell carcinoma has been reported but is a poorly understood phenomenon. Here we present a case of complete spontaneous regression of metastatic Merkel cell carcinoma demonstrating a markedly different pattern of events from those previously published.

  14. Self-renewal molecular mechanisms of colorectal cancer stem cells.

    Science.gov (United States)

    Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang

    2017-01-01

    Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) and Hedgehog-Gli (HH-GLI), specific roles mediated by cell surface markers and micro-environmental factors are involved in the regulation of self-renewal. The elucidation of the molecular mechanisms behind self-renewal may lead to the development of novel targeted interventions for the treatment of colorectal cancer.

  15. Multiple gastrointestinal metastases of Merkel cell carcinoma.

    Science.gov (United States)

    Poškus, Eligijus; Platkevičius, Gediminas; Simanskaitė, Vilma; Rimkevičiūtė, Ernesta; Petrulionis, Marius; Strupas, Kestutis

    2016-01-01

    Merkel cell carcinoma is an aggressive skin malignancy. Primary Merkel cell carcinomas are treated by wide radical excision with or without adjuvant radiotherapy, while benefits of adjuvant chemotherapy remain doubtful. There are only several cases of gastrointestinal metastases of Merkel cell carcinoma reported so far. We report a case of recurrent Merkel cell carcinoma with metastases to the stomach and the small intestines after wide excision of primary Merkel cell carcinoma. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  16. Metastatic renal cell carcinoma management

    Directory of Open Access Journals (Sweden)

    Flavio L. Heldwein

    2009-06-01

    Full Text Available PURPOSE: To assess the current treatment of metastatic renal cell carcinoma, focusing on medical treatment options. MATERIAL AND METHODS: The most important recent publications have been selected after a literature search employing PubMed using the search terms: advanced and metastatic renal cell carcinoma, anti-angiogenesis drugs and systemic therapy; also significant meeting abstracts were consulted. RESULTS: Progress in understanding the molecular basis of renal cell carcinoma, especially related to genetics and angiogenesis, has been achieved mainly through of the study of von Hippel-Lindau disease. A great variety of active agents have been developed and tested in metastatic renal cell carcinoma (mRCC patients. New specific molecular therapies in metastatic disease are discussed. Sunitinib, Sorafenib and Bevacizumab increase the progression-free survival when compared to therapy with cytokines. Temsirolimus increases overall survival in high-risk patients. Growth factors and regulatory enzymes, such as carbonic anhydrase IX may be targets for future therapies. CONCLUSIONS: A broader knowledge of clear cell carcinoma molecular biology has permitted the beginning of a new era in mRCC therapy. Benefits of these novel agents in terms of progression-free and overall survival have been observed in patients with mRCC, and, in many cases, have become the standard of care. Sunitinib is now considered the new reference first-line treatment for mRCC. Despite all the progress in recent years, complete responses are still very rare. Currently, many important issues regarding the use of these agents in the management of metastatic renal cancer still need to be properly addressed.

  17. Malnutrition In Patients With Colorectal Carcinoma (Oncologist's Point Of View)

    International Nuclear Information System (INIS)

    Zanova, M.

    2008-01-01

    Colorectal cancer is a worldwide health, social and economic problem. The incidence of malnutrition in patients with colorectal cancer is stated as 54 - 60 %. Primary cachexia is caused by hormonal, metabolic and energetic abnormalities; secondary cachexia is a consequence of functional and anatomic damage to digestive apparatus resulting from a tumor itself or its treatment. Colorectal carcinoma treatment is a complex process involving surgery, radiotherapy and cytostatic treatment. Each treatment modality also brings desirable and undesirable effects and influences patient's nutritional status. Malnutrition worsens patient's overall chances of successful treatment; therefore nutritional support aims to increase his/her anti-infection and antitumor immunity by means of mineral and water industry adjustment as well as by energetic stabilization. (author)

  18. Meat, vegetables and genetic polymorphisms and the risk of colorectal carcinomas and adenomas

    International Nuclear Information System (INIS)

    Skjelbred, Camilla F; Sæbø, Mona; Hjartåker, Anette; Grotmol, Tom; Hansteen, Inger-Lise; Tveit, Kjell M; Hoff, Geir; Kure, Elin H

    2007-01-01

    The risk of sporadic colorectal cancer (CRC) is mainly associated with lifestyle factors, particularly dietary factors. Diets high in red meat and fat and low in fruit and vegetables are associated with an increased risk of CRC. The dietary effects may be modulated by genetic polymorphisms in biotransformation genes. In this study we aimed to evaluate the role of dietary factors in combination with genetic factors in the different stages of colorectal carcinogenesis in a Norwegian population. We used a case-control study design (234 carcinomas, 229 high-risk adenomas, 762 low-risk adenomas and 400 controls) to test the association between dietary factors (meat versus fruit, berries and vegetables) genetic polymorphisms in biotransformation genes (GSTM1, GSTT1, GSTP1 Ile 105 Val, EPHX1 Tyr 113 His and EPHX1 His 139 Arg), and risk of colorectal carcinomas and adenomas. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by binary logistic regression. A higher ratio of total meat to total fruit, berry and vegetable intake was positively associated with both high and low-risk adenomas, with approximately twice the higher risk in the 2 nd quartile compared to the lowest quartile. For the high-risk adenomas this positive association was more obvious for the common allele (Tyr allele) of the EPHX1 codon 113 polymorphism. An association was also observed for the EPHX1 codon 113 polymorphism in the low-risk adenomas, although not as obvious. Although, the majority of the comparison groups are not significant, our results suggest an increased risk of colorectal adenomas in individuals for some of the higher ratios of total meat to total fruit, berry and vegetable intake. In addition the study supports the notion that the biotransformation enzymes GSTM1, GSTP1 and EPHX1 may modify the effect of dietary factors on the risk of developing colorectal carcinoma and adenoma

  19. ADAMTS9 is Silenced by Epigenetic Disruption in Colorectal Cancer and Inhibits Cell Growth and Metastasis by Regulating Akt/p53 Signaling

    Directory of Open Access Journals (Sweden)

    Ling Chen

    2017-11-01

    Full Text Available Background/Aims: ADAMTS (disintegrin-like and metalloproteinase with thrombospondin motifs proteins are extracellular zinc metalloproteinases that play an important role in extracellular matrix assembly and degradation, connective tissue structuring, angiogenesis, and cell migration. Multiple studies suggest that ADAMTS proteins (e.g. ADAMTS9 can act as tumor suppressors. In gastric, esophageal, and nasopharyngeal carcinomas ADAMTS9 is frequently down-regulated by promoter methylation. Whether ADAMTS9 can function as a tumor suppressor gene (TSG in colorectal cancer is still unclear. Methods: We performed immunohistochemistry, RT-PCR, and qRT-PCR, to examine the expression of ADAMTS9 in colorectal cancer cell lines and primary colorectal cancer tissues. Methylation-specific PCR was also carried out to investigate the promoter methylation status of ADAMTS9. We also explored the functions of ADAMTS9 in colorectal cancer cell lines through in vitro experiments. Results: ADAMTS9 expression was down-requlated or silenced in 83.3% (5/6 of colorectal cancer cell lines, and frequently repressed in 65.6% (21/32 of colorectal cancer tissues. Down-regulation of ADAMTS9 was partially due to promoter methylation. Exogenous expression of ADAMTS9 in colorectal cancer cell lines inhibited cell proliferation and migration through the regulation of cell cycle and apoptosis. In addition, ADAMTS9 prevented the activation of Akt, and its downstream targets in colorectal cancer cell lines. Conclusion: Our findings suggest ADAMTS9 is a TSG in colorectal cancer.

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

    International Nuclear Information System (INIS)

    Stoinova, V.; Nedevska, M.

    2006-01-01

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

  1. Identifying and quantifying the stromal fibrosis in muscularis propria of colorectal carcinoma by multiphoton microscopy

    Science.gov (United States)

    Chen, Sijia; Yang, Yinghong; Jiang, Weizhong; Feng, Changyin; Chen, Zhifen; Zhuo, Shuangmu; Zhu, Xiaoqin; Guan, Guoxian; Chen, Jianxin

    2014-10-01

    The examination of stromal fibrosis within colorectal cancer is overlooked, not only because the routine pathological examinations seem to focus more on tumour staging and precise surgical margins, but also because of the lack of efficient diagnostic methods. Multiphoton microscopy (MPM) can be used to study the muscularis stroma of normal and colorectal carcinoma tissue at the molecular level. In this work, we attempt to show the feasibility of MPM for discerning the microstructure of the normal human rectal muscle layer and fibrosis colorectal carcinoma tissue practicably. Three types of muscularis propria stromal fibrosis beneath the colorectal cancer infiltration were first observed through the MPM imaging system by providing intercellular microstructural details in fresh, unstained tissue samples. Our approach also presents the capability of quantifying the extent of stromal fibrosis from both amount and orientation of collagen, which may further characterize the severity of fibrosis. By comparing with the pathology analysis, these results show that the MPM has potential advantages in becoming a histological tool for detecting the stromal fibrosis and collecting prognosis evidence, which may guide subsequent therapy procedures for patients into good prognosis.

  2. Colorectal Carcinomas With Isolated Loss of PMS2 Staining by Immunohistochemistry.

    Science.gov (United States)

    Alpert, Lindsay; Pai, Reetesh K; Srivastava, Amitabh; McKinnon, Wendy; Wilcox, Rebecca; Yantiss, Rhonda K; Arcega, Ramir; Wang, Hanlin L; Robert, Marie E; Liu, Xiuli; Pai, Rish K; Zhao, Lei; Westerhoff, Maria; Hampel, Heather; Kupfer, Sonia; Setia, Namrata; Xiao, Shu-Yuan; Hart, John; Frankel, Wendy L

    2018-04-01

    - Isolated loss of PMS2 staining is an uncommon immunophenotype in colorectal carcinomas, accounting for approximately 4% of tumors with microsatellite instability. Limited information regarding these tumors is available in the literature. - To compare the clinicopathologic features of colorectal carcinomas with isolated PMS2 loss by immunohistochemistry to those with other forms of mismatch repair deficiency. - Ninety-three colorectal carcinomas with isolated PMS2 loss by immunohistochemistry and 193 with other forms of mismatch repair deficiency were identified. Forty (43%) of the isolated PMS2 loss cases and 35 control cases (18%) had a known germline mutation or a clinical diagnosis of Lynch syndrome. - Overall, isolated PMS2-loss tumors occurred in significantly younger patients ( P PMS2-loss group also exhibited increased odds of disease-specific death (odds ratio [OR], 3.09; 95% CI, 1.41-6.85; P = .007). When the analysis was restricted to germline mutation/Lynch syndrome cases and controls, no significant differences were detected for age, sex, tumor location, tumor grade, histologic features, or distant metastases, although a trend toward increased odds of disease-specific death in the isolated PMS2-loss group was evident (OR, 3.87; 95% CI, 0.89-27.04; P = .10). - Unusual clinicopathologic features observed in colorectal carcinomas with isolated PMS2 loss are likely related to the high proportion of cases caused by germline mutations. Isolated PMS2-loss tumors may demonstrate more aggressive behavior than other tumors with microsatellite instability, but larger studies are needed to investigate that possibility further.

  3. Primary enteric-type adenocarcinomas of the urinary bladder are histogenetically analogous to colorectal carcinomas: Immunohistochemical evaluation of 109 cases

    Directory of Open Access Journals (Sweden)

    Saad S. Eissa

    2010-04-01

    In conclusion, primary non-urachal enteric-type adenocarcinoma of the urinary bladder is morphologically and immunophenotypically similar – if not identical – to colonic adenocarcinoma. The frequent association of enteric carcinomas of the urinary bladder with intestinal metaplasia and/or colonic-type adenomas with dysplasia suggests possible carcinogenetic pathways similar to that observed in colorectal carcinomas.

  4. MR imaging of colorectal carcinomas using an MR endoscopic coil

    International Nuclear Information System (INIS)

    Murano, Akihiko; Kido, Choichiro; Sasaki, Fumio; Nakamura, Tsuneya; Kobayashi, Semi; Katoh, Tomoyuki; Hirai, Takashi

    1994-01-01

    Diagnosis of the depth of wall invasion by rectal carcinoma using MR endoscopy was performed in ten resected specimens, including five rectal carcinomas, three colon carcinomas, two normal gastric wall. In addition, the gastric wall of a pig was examined. MR imaging was done with a 1.5-T Signa Advantage (GE Medical System) system, with the surface coil of the MR endoscope acting as the receiver coil. Five layers could be distinguished in the bowel wall: mucosa, submucosa and muscularis propria divided into circular muscle, longitudinal muscle and intervening connective tissue. Tumors had almost the same signal intensity as muscle. The MR images of colon carcinomas, rectal carcinomas, and extrinsically metastatic involvement of the sigmoid colon by rectal carcinoma all correlated well with the pathological findings. The normal structure of the gastric wall was similar to that of the colon. 3D-fast Spoiled Grass (SPGR) sequence has a fairly short scanning time. Thus, the possibility of precise clinical diagnosis by this method was suggested. (author)

  5. Up-regulation of GTPBP4 in colorectal carcinoma is responsible for tumor metastasis

    International Nuclear Information System (INIS)

    Yu, Haitao; Jin, Sufeng; Zhang, Na; Xu, Qi

    2016-01-01

    GTP binding protein 4(GTPBP4), a member of GTP-binding protein family, was previously characterized as a tumor suppressor that regulates and requires merlin to suppress cell proliferation. However, the role of GTPBP4 in the metastasis of colorectal carcinoma (CRC) remains unelucidated. Here, we observed that GTPBP4 was detected at higher levels in CRC metastatic tissues than that in the primary tumor tissues. Notably, up-regulation of GTPBP4 was closely correlated with tumor metastasis in CRCs. Kaplan-Meier and multivariate Cox regression analysis indicated GTPBP4 as an independent prognostic factor for CRC patients (hazard ratio = 2.693, 95% confident interval: 1.193–6.083, p = 0.017). Functional studies established that knockdown of GTPBP4 impeded, whereas ectopic expression of GTPBP4 enhanced cell motility and tumor metastasis in CRC cells. Interestingly, mechanistic investigations suggested that GTPBP4 may disorganize actin cytoskeleton through repressing RhoA signaling. Taken together, our research uncovered that GTPBP4 promotes CRC metastasis by disrupting actin cytoskeleton, which is mediated by the reduced RhoA activity. Strategies targeting GTPBP4 will be promising for CRC patients with metastases. - Highlights: • Up-regulation of GTPBP4 is detected in CRC metastatic tissues and closely correlated with tumor metastasis. • Increase of GTPBP4 is closely associated with poor prognosis. • GTPBP4 promotes cell motility and tumor metastasis in CRC cells. • GTPBP4 induces filamentous actin rearrangement specifically by repressing the activity of RhoA. • GTPBP4 may be a novel therapeutic target for CRC patients with metastasis.

  6. Are there tumor suppressor genes on chromosome 4p in sporadic colorectal carcinoma?

    Science.gov (United States)

    Zheng, Hai-Tao; Jiang, Li-Xin; Lv, Zhong-Chuan; Li, Da-Peng; Zhou, Chong-Zhi; Gao, Jian-Jun; He, Lin; Peng, Zhi-Hai

    2008-01-07

    To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients. Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by c2 test. Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).

  7. Radioimmunoscintigraphy with 99mTc-labelled anti-CEA monoclonal antibodies in colorectal carcinoma patients

    International Nuclear Information System (INIS)

    Sergieva, S.; Baychev, G.; Tzingilev, D.; Delijski, T.; Kirova, G.; Kirilova, B.; Nenovska, M.

    1998-01-01

    Sixteen patients (2 female and 14 male, aged 42-75) were given intravenous injections with 99m Tc (555-740 MBq)-labelled anti-CEA MAb (CEA-Scan, Mallinckrodt Medical and M-CEATEC, Sorin Biomedica). Five of them were with duly established or established or suspected primary colorectal carcinoma, and eleven were studied postoperatively after recording an increase CEA levels in serum. The patients were scanned within 4-24 h of infusion using planar and tomographic imaging in rotation gamma-camera DIACAM (Siemens). At all 16 patients 27 true positive results were obtained: in 7 primary colorectal carcinomas, 5 locally recurrent tumors, 7 liver metastases, 6 lymphogeneous lesions and two - in the ureteral region. True negative results were established at three patients, false positive - in one patient with chronic inflammation, and false negative results - in 3 cases with liver metastases foci < 8 mm. Having 90 % sensitivity, 75 % specificity and 82.3 % accuracy, radioimmunoscintigraphy is a highly informative and sensitive imaging method for diagnosing and following up of primary, recurrent and metastatic foci in colorectal carcinoma patients. (author)

  8. Squamous Cell Carcinoma In Situ Overlying Merkel Cell Carcinoma.

    Science.gov (United States)

    McGowan, Maria A; Helm, Matthew F; Tarbox, Michelle B

    2016-11-01

    Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neoplasm that has exhibited an exponential increase in incidence in the past 3 decades. Combined MCC and cutaneous squamous cell carcinoma (SCC/MCC) is an uncommon variant of MCC that exhibits worse prognosis than pure MCC. To describe the clinical presentation, dermoscopy, and histology of an unusual subtype of combined SCC/MCC. A 73-year-old white woman presented with an ulcerated and violaceous 10-mm plaque on her right jawline that had been present for 2 to 3 months. On dermoscopy, the lesion was predominantly milky pink to red with peripheral crusting and large-caliber polymorphous vessels. Histology revealed SCC in situ above and adjacent to MCC. The tumor was excised with clear margins, and sentinel lymph node scintography was negative for nodal involvement. © The Author(s) 2016.

  9. Meeting An Unmet Need in Metastatic Colorectal Carcinoma with Regorafenib

    Directory of Open Access Journals (Sweden)

    Barbara Melosky

    2016-01-01

    Full Text Available Colorectal cancer is a global issue, affecting men and women equally. Over the last 25 years, advances in therapy and multidisciplinary care have led to improvements in survival for those with colorectal cancer. Despite these advances, more therapeutic options are needed for those being treated for this disease.Regorafenib is an oral drug that is a new therapeutic option for our patients. The CORRECT and CONCUR trials demonstrate the efficacy of regorafenib in the last line setting. This article summarizes some of the regorafenib clinical trial data and discusses the strategies to help manage the side effects of this drug including patient education, dose reductions and interruptions, and monitoring hypertension and liver function.

  10. Immunohistochemical expression of the epidermal growth factor receptor (EGFR in colorectal carcinoma: relation with clinicopathological parameters

    Directory of Open Access Journals (Sweden)

    Maurício Andrade Azevedo

    2011-09-01

    Full Text Available Introduction: The study of tissue immunostaining of the epidermal growth factor receptor (EGFR may contribute with the understanding of its role in the prognosis of colorectal carcinoma. Objective: To analyze the immunohistochemical expression of EGFR in colorectal carcinoma tissues and transitional tumor-mucosa and mucosa adjacent to neoplasia, and its relation with cancer. Method: The study was conducted with 40 patients with colorectal carcinoma who had surgery with curative intent in order to analyze the immunoexpression of EGFR with anti-EGFR. We used parametric and nonparametric tests. Results: The immunohistochemical expression of EGFR in tumor samples showed a significant difference as to the level of immunostaining in tissue specimens of transitional tumor-mucosa (p=0.01 and the level of immunoreactivity in tissues of the adjacent mucosa (p=0, 04. The immunoexpression of EGFR showed no significant relation with the size of the tumor, angiolymphatic invasion, neural invasion, cellular differentiation, level of carcinoma infiltration in the intestinal wall, lymph node metastases and liver metastases. Conclusions: The EGFR showed a more intense expression in the mucosa of colorectal carcinoma than in the transitional epithelium and adjacent non-neoplastic mucosa. The immunoexpression of EGFR did not correlate with pathological parameters of colorectal carcinoma and liver metastases.Introdução: O estudo da imunoexpressão tecidual do receptor do fator de crescimento epitelial (EGFR pode contribuir para o entendimento de seu papel no prognóstico do carcinoma colorretal. Objetivo: Analisar a expressão imuno-histoquímica do EGFR no carcinoma colorretal e nos tecidos da transição tumor-mucosa e da mucosa adjacente à neoplasia, e avaliar a relação com os aspectos anatomopatológicos da neoplasia. Método: Em 40 doentes com carcinoma colorretal operados com intenção curativa, estudou-se a imunoexpressão do EGFR com anticorpo anti

  11. Combination Effect of Nimotuzumab with Radiation in Colorectal Cancer Cells

    International Nuclear Information System (INIS)

    Shin, Hye Kyung; Kim, Mi Sook; Jeong, Jae Hoon

    2010-01-01

    To investigate the radiosensitizing effect of the selective epidermal growth factor receptor (EGFR) inhibitor nimotuzumab in human colorectal cancer cell lines. Four human colorectal cancer cell lines, HCT-8, LoVo, WiDr, and HCT-116 were treated with nimotuzumab and/or radiation. The effects on cell proliferation, viability, and cell cycle progression were measured by MTT, clonogenic survival assay, flow cytometry, and Western blot. An immunoblot analysis revealed that EGFR phosphorylation was inhibited by nimotuzumab in colorectal cancer cell lines. Under these experimental conditions, pre-treatment with nimotuzumab increased radiosensitivity of colorectal cancer cell lines, except for cell line HCT-116. However, cell proliferation or cell cycle progression was not affected by the addition of nimotuzumab, irrespective of irradiation. Nimotuzumab enhanced the radiosensitivity of colorectal cancer cells in vitro by inhibiting EGFR-mediated cell survival signaling. This study provided a rationale for the clinical application of the selective EGFR inhibitor, nimotuzumab in combination with radiation in colorectal cancer cells.

  12. Update on Merkel Cell Carcinoma.

    Science.gov (United States)

    Harms, Paul W

    2017-09-01

    Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine malignancy. Merkel cell polyomavirus, a tumorigenic DNA virus, is present in most MCC tumors, with implications for tumor biology, diagnosis, and management. Merkel cell polyomavirus-negative tumors have a high burden of UV-signature mutations, similar to melanoma. The histopathologic diagnosis of MCC requires immunohistochemistry to exclude morphologically similar entities. Therapies for advanced disease are currently lacking. Here, the features of MCC are reviewed, including recent molecular discoveries with implications for improved therapy for advanced disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Clinicopathological Characteristics and Prognosis of Colorectal Cancer in Chinese Adolescent Patients

    Directory of Open Access Journals (Sweden)

    Feng Du

    2015-01-01

    Conclusions: Colorectal cancer in Chinese adolescents was very rare. The chinese adolecents with colorectal cancer were frequently diagnosed in the right colon, as Stage III/IV disease with signet ring cell carcinoma. The prognosis was relatively poor.

  14. Merkel cell carcinoma in an immunosuppressed patient.

    Science.gov (United States)

    Góes, Heliana Freitas de Oliveira; Lima, Caren Dos Santos; Issa, Maria Cláudia de Almeida; Luz, Flávio Barbosa; Pantaleão, Luciana; Paixão, José Gabriel Miranda da

    2017-01-01

    Merkel cell carcinoma is an uncommon neuroendocrine carcinoma with a rising incidence and an aggressive behavior. It predominantly occurs in older patients, with onset occurring at a mean age of 75-80 years. Recognized risk factors are ultraviolet sunlight exposure, immunosuppression, and, more recently, Merkel cell polyomavirus. We report a case of Merkel cell carcinoma in a young HIV positive patient with Merkel Cell polyomavirus detected in the tumor.

  15. A STAT3-decoy oligonucleotide induces cell death in a human colorectal carcinoma cell line by blocking nuclear transfer of STAT3 and STAT3-bound NF-κB

    Directory of Open Access Journals (Sweden)

    Le Coquil Stéphanie

    2011-04-01

    Full Text Available Abstract Background The transcription factor STAT3 (signal transducer and activator of transcription 3 is frequently activated in tumor cells. Activated STAT3 forms homodimers, or heterodimers with other TFs such as NF-κB, which becomes activated. Cytoplasmic STAT3 dimers are activated by tyrosine phosphorylation; they interact with importins via a nuclear localization signal (NLS one of which is located within the DNA-binding domain formed by the dimer. In the nucleus, STAT3 regulates target gene expression by binding a consensus sequence within the promoter. STAT3-specific decoy oligonucleotides (STAT3-decoy ODN that contain this consensus sequence inhibit the transcriptional activity of STAT3, leading to cell death; however, their mechanism of action is unclear. Results The mechanism of action of a STAT3-decoy ODN was analyzed in the colon carcinoma cell line SW 480. These cells' dependence on activated STAT3 was verified by showing that cell death is induced by STAT3-specific siRNAs or Stattic. STAT3-decoy ODN was shown to bind activated STAT3 within the cytoplasm, and to prevent its translocation to the nucleus, as well as that of STAT3-associated NF-κB, but it did not prevent the nuclear transfer of STAT3 with mutations in its DNA-binding domain. The complex formed by STAT3 and the STAT3-decoy ODN did not associate with importin, while STAT3 alone was found to co-immunoprecipitate with importin. Leptomycin B and vanadate both trap STAT3 in the nucleus. They were found here to oppose the cytoplasmic trapping of STAT3 by the STAT3-decoy ODN. Control decoys consisting of either a mutated STAT3-decoy ODN or a NF-κB-specific decoy ODN had no effect on STAT3 nuclear translocation. Finally, blockage of STAT3 nuclear transfer correlated with the induction of SW 480 cell death. Conclusions The inhibition of STAT3 by a STAT3-decoy ODN, leading to cell death, involves the entrapment of activated STAT3 dimers in the cytoplasm. A mechanism is

  16. Small cell glioblastoma or small cell carcinoma

    DEFF Research Database (Denmark)

    Hilbrandt, Christine; Sathyadas, Sathya; Dahlrot, Rikke H

    2013-01-01

    was admitted to the hospital with left-sided loss of motor function. A MRI revealed a 6 cm tumor in the right temporoparietal area. The histology was consistent with both glioblastoma multiforme (GBM) and small cell lung carcinoma (SCLC) but IHC was suggestive of a SCLC metastasis. PET-CT revealed...

  17. Pattern of distant lymph node metastasis in colorectal carcinoma and its correlation with distant organ metastasis: CT evaluation

    International Nuclear Information System (INIS)

    Cha, Sang Hoon; Park, Cheol Min; Cha, In Ho; Chung, Kyoo Byung; Suh, Won Hyuck

    1995-01-01

    To evaluate the pattern of distant lymph node metastasis in colorectal carcinoma and its correlation with distant organ metastasis. We retrospectively reviewed abdominal CT scans of 46 patients with pathologically proven colorectal carcinoma. The incidence of distant lymphadenopathy in colorectal carcinoma was 30.4%(14/46). The most commonly involved distant lymph node was the left paraortic lymph node below the renal hilum(9/25). The most common type of distant lymphadenopathy was solitary type(7/14) and all of these lymphadenopathies were noted in the left paraortic lymph node below the renal hilum. Six cases of left sided colorectal carcinoma showed left paraortic lymphadenopathy with solitary type. The incidence of distant organ metastasis was 17.4%(8/46) and markedly increased if distant lymphadenopathy was multiple and confluent, or confluent type(5/7). The incidence of distant lymphadenopathy in colorectal carcinoma was not high and the most common lymphadenopathy was the left paraortic lymph node with solitary type below the renal hilum. The possibility of distant organ metastasis was high if distant lymphadenopathy was multiple and confluent, or confluent type

  18. PIK3CA activating mutation in colorectal carcinoma: associations with molecular features and survival.

    Directory of Open Access Journals (Sweden)

    Christophe Rosty

    Full Text Available Mutations in PIK3CA are present in 10 to 15% of colorectal carcinomas. We aimed to examine how PIK3CA mutations relate to other molecular alterations in colorectal carcinoma, to pathologic phenotype and survival. PIK3CA mutation testing was carried out using direct sequencing on 757 incident tumors from the Melbourne Collaborative Cohort Study. The status of O-6-methylguanine-DNA methyltransferase (MGMT was assessed using both immunohistochemistry and methyLight techniques. Microsatellite instability, CpG island phenotype (CIMP, KRAS and BRAF V600E mutation status, and pathology review features were derived from previous reports. PIK3CA mutation was observed in 105 of 757 (14% of carcinomas, characterized by location in the proximal colon (54% vs. 34%; P<0.001 and an increased frequency of KRAS mutation (48% vs. 25%; P<0.001. High-levels of CIMP were more frequently found in PIK3CA-mutated tumors compared with PIK3CA wild-type tumors (22% vs. 11%; P = 0.004. There was no difference in the prevalence of BRAF V600E mutation between these two tumor groups. PIK3CA-mutated tumors were associated with loss of MGMT expression (35% vs. 20%; P = 0.001 and the presence of tumor mucinous differentiation (54% vs. 32%; P<0.001. In patients with wild-type BRAF tumors, PIK3CA mutation was associated with poor survival (HR 1.51 95% CI 1.04-2.19, P = 0.03. In summary, PIK3CA-mutated colorectal carcinomas are more likely to develop in the proximal colon, to demonstrate high levels of CIMP, KRAS mutation and loss of MGMT expression. PIK3CA mutation also contributes to significantly decreased survival for patients with wild-type BRAF tumors.

  19. Differential expression of matrix metalloproteinase-13 in mucinous and nonmucinous colorectal carcinomas.

    Science.gov (United States)

    Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira K; Abdel-Aziz, Azza

    2013-08-01

    Colorectal carcinoma (CRC) is a major health problem all over the world. Mucinous CRCs are known to have a peculiar behavior and genetic derangements. This study aimed to investigate matrix metalloproteinase (MMP)-13 expression in mucinous and nonmucinous CRCs. We studied tumor tissue specimens from 150 patients with mucinous and nonmucinous CRC who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using MMP-13. Statistical analysis was performed for clinical and pathological data of all studied cases together with MMP-13 expression in mucinous and nonmucinous groups. Mucinous carcinoma was significantly associated with young age, more depth of invasion, lymph node metastasis, and less peritumoral and intratumoral neutrophils. Nonmucinous carcinomas showed higher MMP-13 expression compared with mucinous carcinomas. Despite the negative or low expression of MMP-13, mucinous carcinomas had more depth of invasion and more frequency of lymph node metastasis than did nonmucinous carcinomas. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Nevoid basal cell carcinoma syndrome

    Directory of Open Access Journals (Sweden)

    Kannan Karthiga

    2006-01-01

    Full Text Available Binkley and Johnson first reported this syndrome in 1951. But it was in 1960, Gorlin-Goltz established the association of basal cell epithelioma, jaw cyst and bifid ribs, a combination which is now frequently known as Gorlin-Goltz syndrome as well as Nevoid Basal Cell Carcinoma Syndrome (NBCCS. NBCCS is inherited as an autosomal dominant trait with high penetrance and variable expressivity. NBCCS is characterized by variety of cutaneous, dental, osseous, opthalmic, neurologic and sexual abnormalities. One such case of Gorlin-Goltz syndrome is reported here with good illustrations.

  1. Activated human primary NK cells efficiently kill colorectal cancer cells in 3D spheroid cultures irrespectively of the level of PD-L1 expression.

    Science.gov (United States)

    Lanuza, Pilar M; Vigueras, Alan; Olivan, Sara; Prats, Anne C; Costas, Santiago; Llamazares, Guillermo; Sanchez-Martinez, Diego; Ayuso, José María; Fernandez, Luis; Ochoa, Ignacio; Pardo, Julián

    2018-01-01

    Haploidentical Natural Killer (NK) cells have been shown as an effective and safe alternative for the treatment of haematological malignancies with poor prognosis for which traditional therapies are ineffective. In contrast to haematological cancer cells, that mainly grow as single suspension cells, solid carcinomas are characterised by a tridimensional (3D) architecture that provide specific surviving advantages and resistance against chemo- and radiotherapy. However, little is known about the impact of 3D growth on solid cancer immunotherapy especially adoptive NK cell transfer. We have recently developed a protocol to activate ex vivo human primary NK cells using B lymphoblastic cell lines, which generates NK cells able to overcome chemoresistance in haematological cancer cells. Here we have analysed the activity of these allogeneic NK cells against colorectal (CRC) human cell lines growing in 3D spheroid culture and correlated with the expression of some of the main ligands regulating NK cell activity. Our results indicate that activated NK cells efficiently kill colorectal tumour cell spheroids in both 2D and 3D cultures. Notably, although 3D CRC cell cultures favoured the expression of the inhibitory immune checkpoint PD-L1, it did not correlate with increased resistance to NK cells. Finally, we have analysed in detail the infiltration of NK cells in 3D spheroids by microscopy and found that at low NK cell density, cell death is not observed although NK cells are able to infiltrate into the spheroid. In contrast, higher densities promote tumoural cell death before infiltration can be detected. These findings show that highly dense activated human primary NK cells efficiently kill colorectal carcinoma cells growing in 3D cultures independently of PD-L1 expression and suggest that the use of allogeneic activated NK cells could be beneficial for the treatment of colorectal carcinoma.

  2. Photodynamic therapy for basal cell carcinoma.

    Science.gov (United States)

    Fargnoli, Maria Concetta; Peris, Ketty

    2015-11-01

    Topical photodynamic therapy is an effective and safe noninvasive treatment for low-risk basal cell carcinoma, with the advantage of an excellent cosmetic outcome. Efficacy of photodynamic therapy in basal cell carcinoma is supported by substantial research and clinical trials. In this article, we review the procedure, indications and clinical evidences for the use of photodynamic therapy in the treatment of basal cell carcinoma.

  3. Imaging of primary and metastatic colorectal carcinoma with monoclonal antibody 791T/36 and the therapeutic potential of antibody-drug conjugates

    International Nuclear Information System (INIS)

    Pimm, M.V.; Armitage, N.C.; Ballantyne, K.; Baldwin, R.W.; Perkins, A.C.; Durrant, L.G.; Garnett, M.C.; Hardcastle, J.D.

    1987-01-01

    Monoclonal antibody 791T/36, prepared against a tumor-associated 72,000 dalton glycoprotein, reacted with cells from primary and metastatic colorectal carcinomas. I-131 or In-111-labelled antibody localized in xenografts of colorectal carcinomas established from in vitro clonogenic populations. Clinically, with I-131-labelled antibody, 8/11 colonic tumors imaged positively. Imaging was negative in four patients with benign colon disease. 5/11 rectal tumors were positively imaged, but excreted I-131 in the bladder obscured tumors in several studies. In-111-labelled antibody gave superior images and positively imaged primary and metastatic sites in 13/14 patients. Prospectively in the detection of recurrent disease, I-131 or In-111-antibody detected 29/33 separate sites in 24 patients. Seven negative patients remain disease free. There were 3 false positives; overall sensitivity was 88%, with 70% specificity. Specific localization of radiolabel was confirmed immunochemically and by counting radioactivity in resected specimens. Antibody conjugates with methotrexate, vindesine and daunomycin retained drug activity and antibody function, including xenograft localization and conjugates were therapeutically effective against xenografts. 791T/36 antibody has potential for immunodetection of primary and recurrent colorectal carcinoma and for targeting of therapeutic agents

  4. Distinct patterns of ALDH1A1 expression predict metastasis and poor outcome of colorectal carcinoma

    Science.gov (United States)

    Xu, Sen-Lin; Zeng, Dong-Zu; Dong, Wei-Guo; Ding, Yan-Qing; Rao, Jun; Duan, Jiang-Jie; Liu, Qing; Yang, Jing; Zhan, Na; Liu, Ying; Hu, Qi-Ping; Zhang, Xia; Cui, You-Hong; Kung, Hsiang-Fu; Yu, Shi-Cang; Bian, Xiu-Wu

    2014-01-01

    Purpose: Aldehyde dehydrogenase 1A1 (ALDH1A1) has been proposed as a candidate biomarker for colorectal carcinoma (CRC). However, the heterogeneity of its expression makes it difficult to predict the outcome of CRC. The aim of this study was to evaluate the diagnostic and prognostic value of this molecule in CRC. Methods and Results: In this study, we examined ALDH1A1 expression by immunohistochemistry including 406 cases of primary CRC with corresponding adjacent mucosa, with confirmation of real-time PCR and Western blotting. We found that the expression patterns of ALDH1A1 were heterogeneous in the CRC and corresponding adjacent tissues. We defined the ratio of ALDH1A1 level in adjacent mucosa to that in tumor tissues as RA/C and found that the capabilities of tumor invasion and metastasis in the tumors with RA/C < 1 were significantly higher than those with RA/C ≥ 1. Follow-up data showed the worse prognoses in the CRC patients with RA/C < 1. For understanding the underlying mechanism, the localization of β-catenin was detected in the CRC tissues with different patterns of ALDH1A1 expression from 221 patients and β-catenin was found preferentially expressed in cell nuclei of the tumors with RA/C < 1 and ALDH1A1high expression of HT29 cell line, indicating that nuclear translocation of β-catenin might contribute to the increased potentials of invasion and metastasis. Conclusion: Our results indicate that RA/C is a novel biomarker to reflect the distinct expression patterns of ALDH1A1 for predicting metastasis and prognosis of CRC. PMID:25031716

  5. [Colorectal Carcinoma with Suspected Lynch Syndrome: A Multidisciplinary Algorithm].

    Science.gov (United States)

    Schneider, R; Schneider, C; Büttner, R; Reinacher-Schick, A; Tannapfel, A; Fürst, A; Rüschoff, J; Jakobeit, C; Royer-Pokora, B; Möslein, G

    2015-12-01

    Lynch syndrome is the most frequent hereditary cancer syndrome, accounting for approximately 3-5 % of all colorectal cancers. In addition, it is the most frequent predisposing hereditary cause of endometrial cancer and is also associated with gastric cancer, ovarian cancer, cancer of the urinary tract as well as several other cancers. In clinical practise Lynch syndrome is frequently not detected and many clinicians admit uncertainties regarding diagnostic procedures. Also, counselling of patients is considered difficult regarding therapeutic - especially prophylactic surgical and chemopreventive options and recommendations. Based on a review of available literature we discuss optimized strategies for improved detection of suspected Lynch syndrome patients. The aim of this review is to establish a clinical algorithm of how to proceed on a diagnostic level and to discuss surgical options at the time of a colorectal cancer. In order to identify patients with Lynch syndrome, family history should be ascertained and evaluated in regards to fulfilment of the Amsterdam-II- and/or the revised Bethesda criteria. Subsequently immunohistochemical staining for the mismatch-repair-genes, BRAF testing for MLH1 loss of expression, as well as testing for microsatellite instability in some, followed by genetic counselling and mutation analysis when indicated, is recommended. Pathological identification of suspected Lynch syndrome is readily feasible and straightforward. However, the need of performing these analyses in the tumor biopsy at the time of (gastroenterological) diagnosis of CRC neoplasia is essential, in order to offer patients the option of a prophylactically extended surgery and - as recommended in the German S3 guidelines - to discuss the option of a merely prophylactical hysterectomy and oophorectomy (if postmenopausal) in women. Close cooperation between gastroenterologists, pathologists and surgeons is warranted, so that patients may benefit from options of

  6. Colorectal Carcinoma: Why Is There a Lower Incidence in Nigerians When Compared to Caucasians?

    International Nuclear Information System (INIS)

    Irabor, D. O.

    2011-01-01

    Carcinoma of the colon and rectum is the 2nd commonest cancer in the United States; the leading cancer being lung cancer. It has been estimated that 130,200 new cases of colorectal cancer will be diagnosed annually while 56,300 sufferers will die from the disease (Murphy et al., 2000). In developing countries especially West Africa, the rate has not yet reached such magnitude. This suggests that there may be factors either anthropomorphic or environmental which may be responsible for this. The paper acknowledges the reduced incidence of colorectal cancer in native West Africans living in Africa and endeavours to highlight the various factors that produce this observation in medical literature. A diligent search through available literature on the aetiology, epidemiology and comparative anthropology of colorectal cancer was done. Internet search using Pub med, British library online and Google scholar was also utilized. The rarity of adenomatous polyposis syndromes in the native West African contributes to the reduced incidence of colorectal cancer. Cancer prevention and cancer-protective factors are deemed to lie in the starchy, high-fiber, spicy, peppery foodstuff low in animal protein which many West African nations consume.

  7. Pulmonary squamous cell carcinoma following head and neck squamous cell carcinoma: Metastasis or second primary?

    NARCIS (Netherlands)

    Geurts, Tom W.; Nederlof, Petra M.; van den Brekel, Michiel W. M.; van't Veer, Laura J.; de Jong, Daphne; Hart, August A. M.; van Zandwijk, Nico; Klomp, Houke; Balm, Alfons J. M.; van Velthuysen, Marie-Louise F.

    2005-01-01

    Purpose: To distinguish a metastasis from a second primary tumor in patients with a history of head and neck squamous cell carcinoma and subsequent pulmonary squamous cell carcinoma. Experimental Design: For 44 patients with a primary squamous cell carcinoma of the head and neck followed by a

  8. Breast Cancer with Synchronous Renal Cell Carcinoma: A Rare Presentation.

    Science.gov (United States)

    Arjunan, Ravi; Kumar, Durgesh; Kumar, K V Veerendra; Premlatha, C S

    2016-10-01

    Primary cancer arising from multiple organs is a well known fact. Synchronous tumours have been most commonly associated with kidney cancer. Bladder, prostate, colorectal and lung cancer are the most common synchronous primaries with Renal Cell Carcinoma (RCC) identified till date. We found metachronous tumours of breast with RCC in literature search which included both metastatic tumours as well second primaries. Overall, 25 cases of metastatic breast tumours and eight cases of second primary in previously treated RCC have been reported in the literature. Here, we are reporting a case of synchronous presentation of carcinoma breast with RCC which is very rare because most of the multiple malignancies reported in the literature are metastatic tumours or metachronous breast malignancy with RCC.

  9. In vitro biologic efficacy of sunitinib drug-eluting beads on human colorectal and hepatocellular carcinoma-A pilot study.

    Directory of Open Access Journals (Sweden)

    Steven Lahti

    Full Text Available Sunitinib drug eluting beads (DEB are a novel anti-angiogenic bead preparation for use in transarterial chemoembolization. However, systematic studies of sunitinib DEB's effect on cancer cells have not been reported. Herein, we assess their direct biologic efficacy against carcinoma cell lines and correlate cell viability with drug release in vitro.Sunitinib-HCl (10mg/mL in Milli-Q water was mixed with LC Bead® 300-500μm (Biocompatibles UK Ltd.. Loading and release were assessed by measurement of drug UV absorbance using UV-visible spectrophotometer. Viability of human colorectal cancer (CRC, HCT116 and HT29 and hepatocellular carcinoma (HCC, HepG2 cells upon exposure to sunitinib DEB was measured using a bioluminescent assay. Drug concentration during exposure was quantified using HPLC.When added to cultured HepG2 cells, sunitinib DEB rapidly inhibited viability with a significant decrease observed within 1 hour of incubation. Viability of HCT116 and HT29 cells decreased relatively slower, with significant reductions observed after 8 and 24 hours, respectively. After 24 hours there was nearly complete inhibition of all three cell lines. There was no difference in viability observed between cells treated with 5 μl, 10 μL, or 20 μL of sunitinib DEB. HPLC analysis of the cell culture supernatant demonstrated saturation of the cell medium within approximately 4 hours for each amount added, with sunitinib achieving a final concentration of 17.61 μM (SE ±1.01.Sunitinib can be efficiently loaded to and released from LC beads, and the resulting sunitinib DEB demonstrate strong in vitro inhibition of human CRC and HCC cells.

  10. Genetics Home Reference: head and neck squamous cell carcinoma

    Science.gov (United States)

    ... and neck squamous cell carcinoma Head and neck squamous cell carcinoma Printable PDF Open All Close All Enable Javascript ... Consumer Version: Overview of Mouth, Nose, and Throat Cancers Orphanet: Squamous cell carcinoma of head and neck University of Michigan ...

  11. Histopathological report of colorectal carcinoma resections: A 5-year audit in Lagos.

    Science.gov (United States)

    Badmos, Kabir Bolarinwa; Rotimi, Olorunda; Lawal, Abdulrazzaq Oluwagbemiga; Osinowo, Adedapo O; Habeebu, Mohammed Y; Abdulkareem, Fatimah Biade

    2018-01-01

    Complete and accurate pathology reporting of colorectal carcinoma (CRC) resection specimen is critical to clinical management of individual patients. The study aims to audit colorectal cancer histopathology reporting in Lagos between 2011 and 2015 before the adoption of the Society for Gastroenterology and Hepatology in Nigeria pro forma in 2016. All resected CRC cases were identified from the Histopathology record of our Department and that of a private Laboratory in Lagos over a 5-year from 2011 to 2015. The dataset as contained in the pro forma was extracted from the reports and analysed using SPSS version 16 software. A total of 92 colorectal resections were received during the 5-year period consisting of 90 colonic and 2 rectal tumours. Data inclusiveness on tumour differentiation, extent of primary tumour, total lymph node and lymph node involvement were 96.7%, 91.3%, 83.7% and 92.4%, respectively. Tumour perforation, level of venous involvement and distant metastasis were reported in 73.9%, 21.7% and 96.7% respectively. The circumferential resection margin (CRM) in the 2 rectal tumours had 100% inclusiveness. Tumour node metastasis staging was complete in 87% of cases while Dukes staging was documented in 8.7% of the reports. None of the data items was 100% complete except the CRM for rectal carcinoma. Free text reporting results in incomplete data resulting in improper staging, especially the lymph node status. This highlights the need for pro forma reporting to ensure and maintain consistent reporting of important parameters required for proper staging and management of patients with colorectal cancer.

  12. Expression of heparanase in basal cell carcinoma and squamous cell carcinoma.

    Science.gov (United States)

    Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado, Carlos D'Apparecida Santos

    2016-01-01

    Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment.

  13. Urinary bladder carcinoma with divergent differentiation featuring small cell carcinoma, sarcomatoid carcinoma, and liposarcomatous component.

    Science.gov (United States)

    Yasui, Mariko; Morikawa, Teppei; Nakagawa, Tohru; Miyakawa, Jimpei; Maeda, Daichi; Homma, Yukio; Fukayama, Masashi

    2016-09-01

    Both small cell carcinoma and sarcomatoid carcinoma of the urinary bladder are highly aggressive tumors, and a concurrence of these tumors is extremely rare. We report a case of urinary bladder cancer with small cell carcinoma as a predominant component, accompanied by sarcomatoid carcinoma and conventional urothelial carcinoma (UC). Although the small cell carcinoma component had resolved on receiving chemoradiotherapy, rapid growth of the residual tumor led to a fatal outcome. A 47-year-old man presented with occasional bladder irritation and had a 2-year history of asymptomatic hematuria. Cystoscopy revealed a huge mass in the urinary bladder, and transurethral resection was performed. Microscopically, small cell carcinoma was detected as the major tumor component. Spindle-shaped sarcomatoid cells were also observed that were intermingled with small cell carcinoma and conventional UC. In addition, a sheet-like growth of the lipoblast-like neoplastic cells was observed focally. Initially, by providing chemoradiotherapy, we achieved a marked tumor regression; however, the tumor rapidly regrew after the completion of chemoradiotherapy, and the patient underwent radical cystectomy. Only conventional UC and sarcomatoid carcinoma were identified in the cystectomy specimen. The patient died of the disease 4 months after cystectomy. Urinary bladder cancer may include a combination of multiple aggressive histologies as in the present case. Because the variation in the tumor components may affect the efficacy of therapy, a correct diagnosis of every tumor component is necessary. Copyright © 2016 Elsevier GmbH. All rights reserved.

  14. Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression

    International Nuclear Information System (INIS)

    Fang, Zhengyu; Wan, Jun; Yao, Wantong; Xiong, Yi; Li, Jiana; Liu, Li; Shi, Lei; Zhang, Wei; Zhang, Chao; Nie, Liping

    2011-01-01

    Earlier studies have reported the production of histamine in colorectal cancers (CRCs). The effect of histamine is largely determined locally by the histamine receptor expression pattern. Recent evidence suggests that the expression level of histamine receptor H4 (HRH4) is abnormal in colorectal cancer tissues. However, the role of HRH4 in CRC progression and its clinical relevance is not well understood. The aim of this study is to evaluate the clinical and molecular phenotypes of colorectal tumors with abnormal HRH4 expression. Immunoblotting, real-time PCR, immunofluorescence and immunohistochemistry assays were adopted to examine HRH4 expression in case-matched CRC samples (n = 107) and adjacent normal tissues (ANTs). To assess the functions of HRH4 in CRC cells, we established stable HRH4-transfected colorectal cells and examined cell proliferation, colony formation, cell cycle and apoptosis in these cells. The protein levels of HRH4 were reduced in most of the human CRC samples regardless of grade or Dukes classification. mRNA levels of HRH4 were also reduced in both early-stage and advanced CRC samples. In vitro studies showed that HRH4 over-expression caused growth arrest and induced expression of cell cycle proteins in CRC cells upon exposure to histamine through a cAMP -dependent pathway. Furthermore, HRH4 stimulation promoted the 5-Fu-induced cell apoptosis in HRH4-positive colorectal cells. The results from the current study supported previous findings of HRH4 abnormalities in CRCs. Expression levels of HRH4 could influence the histamine-mediated growth regulation in CRC cells. These findings suggested a potential role of abnormal HRH4 expression in the progression of CRCs and provided some new clues for the application of HRH4-specific agonist or antagonist in the molecular therapy of CRCs

  15. Attenuated expression of HRH4 in colorectal carcinomas: a potential influence on tumor growth and progression

    Directory of Open Access Journals (Sweden)

    Zhang Wei

    2011-05-01

    Full Text Available Abstract Background Earlier studies have reported the production of histamine in colorectal cancers (CRCs. The effect of histamine is largely determined locally by the histamine receptor expression pattern. Recent evidence suggests that the expression level of histamine receptor H4 (HRH4 is abnormal in colorectal cancer tissues. However, the role of HRH4 in CRC progression and its clinical relevance is not well understood. The aim of this study is to evaluate the clinical and molecular phenotypes of colorectal tumors with abnormal HRH4 expression. Methods Immunoblotting, real-time PCR, immunofluorescence and immunohistochemistry assays were adopted to examine HRH4 expression in case-matched CRC samples (n = 107 and adjacent normal tissues (ANTs. To assess the functions of HRH4 in CRC cells, we established stable HRH4-transfected colorectal cells and examined cell proliferation, colony formation, cell cycle and apoptosis in these cells. Results The protein levels of HRH4 were reduced in most of the human CRC samples regardless of grade or Dukes classification. mRNA levels of HRH4 were also reduced in both early-stage and advanced CRC samples. In vitro studies showed that HRH4 over-expression caused growth arrest and induced expression of cell cycle proteins in CRC cells upon exposure to histamine through a cAMP -dependent pathway. Furthermore, HRH4 stimulation promoted the 5-Fu-induced cell apoptosis in HRH4-positive colorectal cells. Conclusion The results from the current study supported previous findings of HRH4 abnormalities in CRCs. Expression levels of HRH4 could influence the histamine-mediated growth regulation in CRC cells. These findings suggested a potential role of abnormal HRH4 expression in the progression of CRCs and provided some new clues for the application of HRH4-specific agonist or antagonist in the molecular therapy of CRCs.

  16. Determinants of survival after liver resection for metastatic colorectal carcinoma.

    Science.gov (United States)

    Parau, Angela; Todor, Nicolae; Vlad, Liviu

    2015-01-01

    Prognostic factors for survival after liver resection for metastatic colorectal cancer identified up to date are quite inconsistent with a great inter-study variability. In this study we aimed to identify predictors of outcome in our patient population. A series of 70 consecutive patients from the oncological hepatobiliary database, who had undergone curative hepatic surgical resection for hepatic metastases of colorectal origin, operated between 2006 and 2011, were identified. At 44.6 months (range 13.7-73), 30 of 70 patients (42.85%) were alive. Patient demographics, primary tumor and liver tumor factors, operative factors, pathologic findings, recurrence patterns, disease-free survival (DFS), overall survival (OS) and cancer-specific survival (CSS) were analyzed. Clinicopathologic variables were tested using univariate and multivariate analyses. The 3-year CSS after first hepatic resection was 54%. Median CSS survival after first hepatic resection was 40.2 months. Median CSS after second hepatic resection was 24.2 months. The 3-year DFS after first hepatic resection was 14%. Median disease free survival after first hepatic resection was 18 months. The 3-year DFS after second hepatic resection was 27% and median DFS after second hepatic resection 12 months. The 30-day mortality and morbidity rate after first hepatic resection was 5.71% and 12.78%, respectively. In univariate analysis CSS was significantly reduced for the following factors: age >53 years, advanced T stage of primary tumor, moderately- poorly differentiated tumor, positive and narrow resection margin, preoperative CEA level >30 ng/ml, DFS <18 months. Perioperative chemotherapy related to metastasectomy showed a trend in improving CSS (p=0.07). Perioperative chemotherapy improved DFS in a statistically significant way (p=0.03). Perioperative chemotherapy and achievement of resection margins beyond 1 mm were the major determinants of both CSS and DFS after first liver resection in multivariate

  17. Clinical implementation of KRAS testing in metastatic colorectal carcinoma: the pathologist's perspective.

    Science.gov (United States)

    Ross, Jeffrey S

    2012-10-01

    Mutation status of the KRAS gene identifies a distinct disease subtype of metastatic colorectal carcinoma that does not respond to antibody therapeutics targeting the epidermal growth factor receptor. This is currently the only validated marker in metastatic colorectal carcinoma with a clear implication in treatment selection. KRAS testing is widely accepted in clinical practice to guide metastatic colorectal carcinoma therapeutic decisions, and there are many commercially available platforms to perform the test. To evaluate the critical role of pathologists in the full implementation of KRAS testing by optimizing tumor tissue collection and fixation procedures and by choosing testing technologies and reliable Clinical Laboratory Improvement Amendments of 1988-certified laboratories to perform the tests. Prospective clinical trials, retrospective studies, and quality assessment and survey reports were identified in the following databases: PubMed, American Society of Clinical Oncology Proceedings (American Society of Clinical Oncology Annual Meeting and Gastrointestinal Cancer Symposium) and European Society for Medical Oncology Proceedings (Annals of Oncology European Society for Medical Oncology Congress and Annals of Oncology World Congress on Gastrointestinal Cancers). More bona fide standards are needed to address the variety of available test methods, which have different performance characteristics including speed, sensitivity to detect rare mutations, and technical requirements. Refined standards addressing timing of KRAS testing, laboratory performance and accuracy, quality assurance and control, proper tissue collection, and appropriate result reporting would also be greatly beneficial. Pathologists should be aware that the amount of information they need to manage will increase, because future trends and technological advances will enhance the predictive power of diagnostic tests or the scope of the biomarker panels tested routinely across tumor types.

  18. Clinicopathological comparison of colorectal and endometrial carcinomas in patients with Lynch-like syndrome versus patients with Lynch syndrome.

    Science.gov (United States)

    Mas-Moya, Jenny; Dudley, Beth; Brand, Randall E; Thull, Darcy; Bahary, Nathan; Nikiforova, Marina N; Pai, Reetesh K

    2015-11-01

    Screening for DNA mismatch repair (MMR) deficiency in colorectal and endometrial carcinomas identifies patients at risk for Lynch syndrome. Some patients with MMR-deficient tumors have no evidence of a germline mutation and have been described as having Lynch-like syndrome. We compared the clinicopathological features of colorectal and endometrial carcinomas in patients with Lynch-like syndrome and Lynch syndrome. Universal screening identified 356 (10.6%) of 3352 patients with colorectal carcinoma and 72 (33%) of 215 patients with endometrial carcinoma with deficient DNA MMR. Sixty-six patients underwent germline mutation analysis with 45 patients (68%) having evidence of a germline MMR gene mutation confirming Lynch syndrome and 21 patients (32%) having Lynch-like syndrome with no evidence of a germline mutation. Most patients with Lynch-like syndrome had carcinoma involving the right colon compared to patients with Lynch syndrome (93% versus 45%; P Lynch syndrome confirmed by germline mutation analysis. Synchronous or metachronous Lynch syndrome-associated carcinoma was more frequently identified in patients with Lynch syndrome compared to Lynch-like syndrome (38% versus 7%; P = .04). There were no significant differences in clinicopathological variables between patients with Lynch-like syndrome and Lynch syndrome with endometrial carcinoma. In summary, 32% of patients with MMR deficiency concerning Lynch syndrome will have Lynch-like syndrome. Our results demonstrate that patients with Lynch-like syndrome are more likely to have right-sided colorectal carcinoma, less likely to have synchronous or metachronous Lynch syndrome-associated carcinoma, and less likely to demonstrate isolated loss of MSH6 expression within their tumor. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Colorectal carcinoma in a ten-year-old girl: A case report

    Directory of Open Access Journals (Sweden)

    Sarbani Chattopadhyay

    2012-01-01

    Full Text Available Colorectal carcinoma is very rare in childhood. In this case report, we depict a ten-year-old girl who presented with features of intestinal obstruction which turned out to be due to poorly differentiated mucin secreting adenocarcinoma of descending colon. Only increased awareness of this malignancy in this age-group and a high index of suspicion can help when a child complains of persistent pain of abdomen, altered bowel habits or rectal bleeding, and may provide diagnosis at an earlier stage, thereby improving the prognosis.

  20. Neglected basal cell carcinoma on scalp

    Directory of Open Access Journals (Sweden)

    Sudip Sarkar

    2016-01-01

    Full Text Available Giant basal cell carcinoma (BCC is a very rare entity. Usually, they occur due to the negligence of the patient. Local or distant metastasis is present in most cases. Here, we present a case of giant BCC that clinically resembled squamous cell carcinoma and demonstrated no metastasis at presentation.

  1. Combination therapies in oral squamous cell carcinomas

    International Nuclear Information System (INIS)

    Krishnamurthi, S.; Shanta, V.

    1982-01-01

    The clinical trials are reported involving combined radiotherapy and chemotherapy in oral squamous cell carcinomas. Bleomycin was the only drug that potentiated radiation response in buccal squamous cell carcinomas. The response of the primary tumors was consistent, predictable and reproducible. The following drugs or chemicals were used: synkavit, methotrexate, metronidazole, bleomycin, pepleomycin, and hyperbaric oxygen. The results and their comparison is given in tables

  2. Scalp squamous cell carcinoma in xeroderma pigmentosum.

    Science.gov (United States)

    Awan, Basim A; Alzanbagi, Hanadi; Samargandi, Osama A; Ammar, Hossam

    2014-02-01

    Xeroderma pigmentosum is a rare autosomal-recessive disorder that appears in early childhood. Squamous cell carcinoma is not uncommon in patients with xeroderma pigmentosum and mostly involving the face, head, neck, and scalp. However, squamous cell carcinoma of the scalp may exhibit an aggressive course. Here, we present a huge squamous cell carcinoma of the scalp in a three-years-old child with xeroderma pigmentosum. In addition, we illustrate the challenges of a child with xeroderma pigmentosum who grows up in a sunny environment where the possibility of early onset of squamous cell carcinoma is extremely high in any suspected skin lesion. In xeroderma pigmentosum patients, squamous cell carcinoma of the scalp can present early and tends to be unusually aggressive. In sunny areas, proper education to the patient and their parents about ultra-violet light protection and early recognition of any suspicious lesion could be life-saving.

  3. Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells

    Directory of Open Access Journals (Sweden)

    Claudia Schlimper

    2012-01-01

    Full Text Available Adoptive therapy of malignant diseases with cytokine-induced killer (CIK cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR with an antibody-defined specificity for carcinoembryonic antigen (CEA. CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions.

  4. Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-16-1-0260 TITLE: Lung Squamous Cell Carcinoma Stem Cells as Immunotherapy Targets PRINCIPAL INVESTIGATOR: Carla Kim... Cell Carcinoma Stem Cells as Immunotherapy Targets 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0260 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...SUPPLEMENTARY NOTES 14. ABSTRACT Lung squamous cell carcinoma (SCC) is the second most common type of lung cancer, and immunotherapy is a promising new

  5. The impact of bone marrow micrometastases on metastatic disease-free survival in patients with colorectal carcinoma.

    LENUS (Irish Health Repository)

    O'Connor, O J

    2012-02-03

    AIMS: The biological relevance of bone marrow micrometastases (BMM) in colorectal cancer remains unknown. Here, we investigate their nature by examining the impact of the presence of BMM on metastatic disease-free survival in a cohort of patients with this disease. METHODS: Sixty-three consecutive patients undergoing surgery for colorectal cancer of any stage were studied after approval of the study protocol by the local ethics committee and with full individual informed consent. All had bilateral iliac crest bone marrow aspirates prior to operation. Aspirates were then examined for the presence of aberrant cytokeratin-18-positive cells by a blinded observer using both flow cytometric and APAAP immunohistochemical techniques. RESULTS: Mean follow-up after surgery was 4.6 years (range 1.9-6.9) for those without hepatic metastases at diagnosis. Seven of 34 patients with Dukes\\' stage A or B developed metastatic disease after a mean interval of 4.7 years (range 3.8-6.8). However, only 2 of these patients demonstrated BMM at the time of surgery. Nine of 15 patients with Dukes\\' C carcinoma at the time of surgery subsequently developed metastases after a mean interval of 4.4 years (range 1.9-6.9). Again, only two of these patients had BMM detectable initially. In only three of the 14 patients known to have metastases at the time of operation (i.e. Dukes\\'\\'D\\' disease) were BMM found. CONCLUSION: The presence of BMM as detected by this methodology was not predictive of tumour recurrence or metastasis. This study does not support the consideration of adjuvant therapy based on the presence of BMM at a single pre-operative time point in patients with colorectal cancer.

  6. Thrombotic microangiopathy purpura in a patient with metastatic colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Tea Nizič-Kos

    2015-09-01

    Full Text Available  AbstractBackground: Thrombotic microangiopathy (TMA is a rare syndrome that leads to excessive formation of blood clots, microthrombosis and is accompanied by non-autoimune haemolytic anemia and thrombocytopenia. Only few cases describing TMA caused by cancer are being reported in the literature.Patient: A 42-year old male patient with metastatic carcinoma of sigma and several accompanying diagnoses (pulmonary embolism, deep vein thrombosis, cerebrovascular insult had later developed clinical and laboratory signs of TMA. TMA was unresponsive to plasmapheresis, which was discontinued and first cycle of chemotherapy was applied. The patient died soon after. The autopsy did not provide any additional information about the disease, there were no signs of malignant bone marrow infiltration.Conclusion: The diagnosis of secondary TMA remains a diagnostic and therapeutic challenge. It appears as a rare complication in patients with cancer. Treatment is difficult because the cause of TMA (malignancy is hard to remove. Patients with cancer do not respond to plasmapheresis, which often delays the application of chemotherapy, the only effective treatment for TMA. Consequently this condition has poor prognosis.

  7. Clinicopathologic and Molecular Features of Colorectal Adenocarcinoma with Signet-Ring Cell Component.

    Directory of Open Access Journals (Sweden)

    Qing Wei

    Full Text Available We performed a retrospective study to assess the clinicopathological characters, molecular alterations and multigene mutation profiles in colorectal cancer patients with signet-ring cell component.Between November 2008 and January 2015, 61 consecutive primary colorectal carcinomas with signet-ring cell component were available for pathological confirmation. RAS/BRAF status was performed by direct sequencing. 14 genes associated with hereditary cancer syndromes were analyzed by targeted gene sequencing.A slight male predominance was detected in these patients (59.0%. Colorectal carcinomas with signet-ring cell component were well distributed along the large intestine. A frequently higher TNM stage at the time of diagnosis was observed, compared with the conventional adenocarcinoma. Family history of malignant tumor was remarkable with 49.2% in 61 cases. The median OS time of stage IV patients in our study was 14 months. RAS mutations were detected in 22.2% (12/54 cases with KRAS mutations in 16.7% (9/54 cases and Nras mutations in 5.4%(3/54 cases. BRAF V600E mutation was detected in 3.7% (2/54 cases. As an exploration, we analyzed 14 genes by targeted gene sequencing. These genes were selected based on their biological role in association with hereditary cancer syndromes. 79.6% cases carried at least one pathogenic mutation. Finally, the patients were classified by the percentage of signet-ring cell. 39 (63.9% cases were composed of ≥50% signet-ring cells; 22 (36.1% cases were composed of <50% signet-ring cells. We compared clinical parameters, molecular and genetic alterations between the two groups and found no significant differences.Colorectal adenocarcinoma with signet-ring cell component is characterized by advanced stage at diagnosis with remarkable family history of malignant tumor. It is likely a negative prognostic factor and tends to affect male patients with low rates of RAS /BRAF mutation. Colorectal patients with any component of

  8. Vaccination with apoptosis colorectal cancer cell pulsed autologous ...

    African Journals Online (AJOL)

    user

    2011-02-18

    Feb 18, 2011 ... with DCs vaccine to assess toxicity, tolerability, immune and clinical responses to the vaccine. No ... Key words: Dendritic cells, immunotherapy, colorectal cancer. .... color analyses of DCs, cells were labeled simultaneously with ..... promote CD8+ Tc1 cell survival, memory response, tumor localization and ...

  9. Concerted down-regulation of immune-system related genes predicts metastasis in colorectal carcinoma

    International Nuclear Information System (INIS)

    Fehlker, Marion; Huska, Matthew R; Jöns, Thomas; Andrade-Navarro, Miguel A; Kemmner, Wolfgang

    2014-01-01

    This study aimed at the identification of prognostic gene expression markers in early primary colorectal carcinomas without metastasis at the time point of surgery by analyzing genome-wide gene expression profiles using oligonucleotide microarrays. Cryo-conserved tumor specimens from 45 patients with early colorectal cancers were examined, with the majority of them being UICC stage II or earlier and with a follow-up time of 41–115 months. Gene expression profiling was performed using Whole Human Genome 4x44K Oligonucleotide Microarrays. Validation of microarray data was performed on five of the genes in a smaller cohort. Using a novel algorithm based on the recursive application of support vector machines (SVMs), we selected a signature of 44 probes that discriminated between patients developing later metastasis and patients with a good prognosis. Interestingly, almost half of the genes was related to the patients’ immune response and showed reduced expression in the metastatic cases. Whereas up to now gene signatures containing genes with various biological functions have been described for prediction of metastasis in CRC, in this study metastasis could be well predicted by a set of gene expression markers consisting exclusively of genes related to the MHC class II complex involved in immune response. Thus, our data emphasize that the proper function of a comprehensive network of immune response genes is of vital importance for the survival of colorectal cancer patients

  10. Over-expression of GAPDH in human colorectal carcinoma as a preferred target of 3-bromopyruvate propyl ester.

    Science.gov (United States)

    Tang, Zhenjie; Yuan, Shuqiang; Hu, Yumin; Zhang, Hui; Wu, Wenjing; Zeng, Zhaolei; Yang, Jing; Yun, Jingping; Xu, Ruihua; Huang, Peng

    2012-02-01

    It has long been observed that many cancer cells exhibit increased aerobic glycolysis and rely more on this pathway to generate ATP and metabolic intermediates for cell proliferation. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a key enzyme in glycolysis and has been known as a housekeeping molecule. In the present study, we found that GAPDH expression was significantly up-regulated in human colorectal carcinoma tissues compared to the adjacent normal tissues, and also increased in colon cancer cell lines compared to the non-tumor colon mucosa cells in culture. The expression of GAPDH was further elevated in the liver metastatic tissues compared to the original colon cancer tissue of the same patients, suggesting that high expression of GAPDH might play an important role in colon cancer development and metastasis. Importantly, we found that 3-bromopyruvate propyl ester (3-BrOP) preferentially inhibited GAPDH and exhibited potent activity in inducing colon cancer cell death by causing severe depletion of ATP. 3-BrOP at low concentrations (1-10 μM) inhibited GAPDH and a much higher concentration (300 μM) was required to inhibit hexokinase-2. The cytotoxic effect of 3-BrOP was associated with its inhibition of GAPDH, and colon cancer cells with loss of p53 were more sensitive to this compound. Our study suggests that GAPDH may be a potential target for colon cancer therapy.

  11. Results of CT in the diagnosis of recurrence of colorectal carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Majewski, A.; Haubitz, B.; Laprell, H.

    1983-06-01

    Postoperative CT was performed in 179 colo-rectal carcinoma patients who had undergone abdominoperineal extirpation (n = 71), resection and rectosigmoid anastomosis (n = 37), hemicolectomy (n = 32), resection of sigma (n = 31), and others (n = 8). Normal CT-findings were found in 25% only, in more than 75% of all cases pathological CT-findings were seen. CT detected loxal recurrence in 87 patients. Based on CT findings local recurrent colo-rectal carcinoma was classified as Stage 0, or intraluminal mass, in 2 patients (2%). Stage 1, or extraluminal mass without invasion of adjacent organs, was found in 38 (44%) patients; Stage 2a, tumor mass with direct invasions of adjacent organs but not the pelvic side walls could be demonstrated in 13 (15%) of the cases; Stage 2b, for extension of mass to pelvic side walls, and Stage 3, or distant metastatic disease, was found in 14 (16%) and 20 (23%) patients. CT was negative in 2 patients with local recurrence (beside Stage 0), an incorrect diagnosis of recurrence due postoperative scarring was found in 4 patients. CT detected exclusive also metastatic disease of the liver in 23 patients and intraabdominal lymph node involvement in 8 patients.

  12. Evaluation of CT in identifying colorectal carcinoma in the frail and disabled patient

    International Nuclear Information System (INIS)

    Ng, C.S.; Dixon, A.K.; Doyle, T.C.; Courtney, H.M.; Bull, R.K.; Freeman, A.H.; Pinto, E.M.; Prevost, A.T.; Campbell, G.A.

    2002-01-01

    Frail and physically or mentally disabled patients frequently have difficulty in tolerating formal colonic investigations. The aims of this study were to evaluate the accuracy of minimal-preparation CT in identifying colorectal carcinoma in this population and to determine the clinical indications and radiological signs with the highest yield for tumour. The CT technique involved helical acquisition (10-mm collimation, 1.5 pitch) following 2 days of preparation with oral contrast medium only. The outcome of 4 years of experience was retrospectively reviewed. The gold standards were pathological and cancer registration records, together with colonoscopy and barium enema when undertaken, with a minimum of 15 months follow-up. One thousand seventy-seven CT studies in 1031 patients (median age 80 years) were evaluated. CT correctly identified 83 of the 98 colorectal carcinomas in this group but missed 15 cases; sensitivity and specificity (with 95% confidence interval) 85% (78-92%) and 91% (90-93%), respectively. Multivariate analysis identified: (a) a palpable abdominal mass and anaemia to be the strongest clinical indications, particularly in combination (p<0.0025); and (b) lesion width and blurring of the serosal margin of lesions to be associated with tumours (p<0.0001). Computed tomography has a valuable role in the investigation of frail and otherwise disabled patients with symptoms suspicious for a colonic neoplasm. Although interpretation can be difficult, the technique is able to exclude malignancy with good accuracy. (orig.)

  13. Colorectal cancer cells suppress CD4+ T cells immunity through canonical Wnt signaling.

    Science.gov (United States)

    Sun, Xuan; Liu, Suoning; Wang, Daguang; Zhang, Yang; Li, Wei; Guo, Yuchen; Zhang, Hua; Suo, Jian

    2017-02-28

    Understanding how colorectal cancer escapes from immunosurveillance and immune attack is important for developing novel immunotherapies for colorectal cancer. In this study we evaluated the role of canonical Wnt signaling in the regulation of T cell function in a mouse colorectal cancer model. We found that colorectal cancer cells expressed abundant Wnt ligands, and intratumoral T cells expressed various Frizzled proteins. Meanwhile, both active β-catenin and total β-catenin were elevated in intratumoral T cells. In vitro study indicated that colorectal cancer cells suppressed IFN-γ expression and increased IL-17a expression in activated CD4+ T cells. However, the cytotoxic activity of CD8+ T cells was not altered by colorectal cancer cells. To further evaluate the importance of Wnt signaling for CD4+ T cell-mediated cancer immunity, β-catenin expression was enforced in CD4+ T cells using lentiviral transduction. In an adoptive transfer model, enforced expression of β-catenin in intratumoral CD4+ T cells increased IL-17a expression, enhanced proliferation and inhibited apoptosis of colorectal cancer cells. Taken together, our study disclosed a new mechanism by which colorectal cancer impairs T cell immunity.

  14. Analysis of APC allelic imbalance/loss of heterozygosity and APC protein expression in cutaneous squamous cell carcinomas.

    LENUS (Irish Health Repository)

    Gray, Sarah E

    2011-05-01

    The adenomatous polyposis coli (APC) gene is a tumor suppressor gene which is mutated in the hereditary disease, familial adenomatous polyposis (FAP). Somatic mutations of the APC gene have also been identified in the majority of sporadic colorectal carcinomas, and mutation of the APC gene appears to be an early step in the initiation of colon cancer. Loss of heterozygosity (LOH) of APC has been described in a variety of other cancer types, including renal cell carcinoma, gastric cancer, non-small cell lung cancer, endometrial cancer and oral squamous cell carcinomas (SCC).

  15. MLH1-Silenced and Non-Silenced Subgroups of Hypermutated Colorectal Carcinomas Have Distinct Mutational Landscapes

    Science.gov (United States)

    Donehower, Lawrence A.; Creighton, Chad J.; Schultz, Nikolaus; Shinbrot, Eve; Chang, Kyle; Gunaratne, Preethi H.; Muzny, Donna; Sander, Chris; Hamilton, Stanley R.; Gibbs, Richard A.; Wheeler, David

    2014-01-01

    Approximately 15% of colorectal carcinomas (CRC) exhibit a hypermutated genotype accompanied by high levels of microsatellite instability (MSI-H) and defects in DNA mismatch repair. These tumors, unlike the majority of colorectal carcinomas, are often diploid, exhibit frequent epigenetic silencing of the MLH1 DNA mismatch repair gene, and have a better clinical prognosis. As an adjunct study to The Cancer Genome Atlas consortium that recently analyzed 224 colorectal cancers by whole exome sequencing, we compared the 35 CRC (15.6%) with a hypermutated genotype to those with a non-hypermutated genotype. We found that 22 (63%) of hypermutated CRC exhibited transcriptional silencing of the MLH1 gene, a high frequency of BRAF V600E gene mutations and infrequent APC and KRAS mutations, a mutational pattern significantly different from their non-hypermutated counterparts. However, the remaining 13 (37%) hypermutated CRC lacked MLH1 silencing, contained tumors with the highest mutation rates (“ultramutated” CRC), and exhibited higher incidences of APC and KRAS mutations, but infrequent BRAF mutations. These patterns were confirmed in an independent validation set of 250 exome-sequenced CRC. Analysis of mRNA and microRNA expression signatures revealed that hypermutated CRC with MLH1 silencing had greatly reduced levels of WNT signaling and increased BRAF signaling relative non-hypermutated CRC. Our findings suggest that hypermutated CRC include one subgroup with fundamentally different pathways to malignancy than the majority of CRC. Examination of MLH1 expression status and frequencies of APC, KRAS, and BRAF mutation in CRC may provide a useful diagnostic tool that could supplement the standard microsatellite instability assays and influence therapeutic decisions. PMID:22899370

  16. Double-modulation of 5-Fluorouracil by methotrexate and leucovorin in advanced colorectal-carcinoma.

    Science.gov (United States)

    Leone, B; Romero, A; Rabinovich, M; Vallejo, C; Bianco, A; Perez, J; Rodriguez, R; Cuevas, M; Machiavelli, M; Paris, A; Lacava, J

    1993-11-01

    A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and leucovorin (LV) as first line chemotherapy in advanced colorectal carcinoma. Between January 1990, and April 1992, 42 patients with metastatic or advanced recurrent (inoperable) colorectal cancer were entered into the study. Therapy consisted of a sequential combination of MTX, LV and 5-FU. MTX was administered at a dose of 150 mg/m2 over 20 minutes I.V. infusion at hour (h) 0, followed 19 h later by LV 50 mg/m2 over 2 h infusion. 5-FU 900 mg/m2 was given by I.V. push injection at h 20. Starting 24 h after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 h for six doses. Treatment was repeated every 15 days until progressive disease, severe toxicity, or death. Four patients were considered not evaluable for response. Objective regression (OR) was observed in 14 of 38 patients (37%, 95% confidence interval 23-53%). Two patients (5%) obtained complete response (CR) and 12 (32%) partial response (PR). Median time to treatment failure was 6 months (range 1-21). Median survival for the whole group of patients was 13 months (range 1-27). Toxicity was within acceptable limits but one therapy-related death due to severe leukopenia and sepsis was observed. Double modulation of 5-FU with MTX and low dose of LV is an active regimen against advanced colorectal carcinoma and represents a promising strategy that should be further explored.

  17. Role of SIRT6 in Metabolic Reprogramming During Colorectal Carcinoma

    Science.gov (United States)

    2015-09-01

    One of the main targets for LKB1 is AMP - activated protein kinase (AMPK), a key enzyme that regulates cellular energy homeostasis [128]. LKB1...EC. Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondria. Biochemistry 2010;49:304–11. [55] Rahman M, Nirala NK, Singh A...Juhnn YS. Cyclic AMP signaling reduces sirtuin 6 expression in non-small cell lung cancer cells by promoting ubiquitin-proteasomal degradation via

  18. Merkel cell carcinoma: is this a true carcinoma?

    Science.gov (United States)

    Jankowski, Marek; Kopinski, Piotr; Schwartz, Robert; Czajkowski, Rafal

    2014-11-01

    Recent years have brought an enhanced understanding of Merkel cell carcinoma (MCC) biology, especially with regard to the Merkel cell polyoma virus as a causative agent. Differences between Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative MCC in morphology; gene expression, miRNA profiles and prognosis have been reported. Origin of MCC is controversial. Presence of neurosecretory granules has suggested that these carcinomas originate from one of the neurocrest derivatives, most probably Merkel cells; the name Merkel cell carcinoma is now widely accepted. Expression of PGP 9.5, chromogranin A and several neuropeptides, initially regarded as specific markers for neural and neuroendocrine cells, has recently been shown in a subset of lymphomas. MCC commonly expresses terminal deoxynucleotidyl transferase and PAX5. Their co-expression under physiologic circumstances is restricted to pro/pre-B cells and pre-B cells. These findings lead to the hypothesis by zur Hausen et al. that MCC originates from early B cells. This review was intended to critically appraise zur Hausen's hypothesis and discuss the possibility that MCC is a heterogenous entity with distinct subtypes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Effect of β,β-Dimethylacrylshikonin on Inhibition of Human Colorectal Cancer Cell Growth in Vitro and in Vivo

    OpenAIRE

    Fan, Yingying; Jin, Shaoju; He, Jun; Shao, Zhenjun; Yan, Jiao; Feng, Ting; Li, Hong

    2012-01-01

    In traditional Chinese medicine, shikonin and its derivatives, has been used in East Asia for several years for the prevention and treatment of several diseases, including cancer. We previously identified that β,β-dimethylacrylshikonin (DA) could inhibit hepatocellular carcinoma growth. In the present study, we investigated the inhibitory effects of DA on human colorectal cancer (CRC) cell line HCT-116 in vitro and in vivo. A viability assay showed th...

  20. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

    Science.gov (United States)

    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

    2016-06-01

    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

  1. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    OpenAIRE

    Barkla, D. H.; Whitehead, R. H.; Foster, H.; Tutton, P. J.

    1988-01-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting f...

  2. Leptin regulates proliferation and apoptosis of colorectal carcinoma ...

    Indian Academy of Sciences (India)

    ways, including Ras/Raf/mitogen-activated protein kinase http://www.ias.ac.in/ ... After blocking with 3% skim milk, the sections were incubated with primary ..... Liu Z, Uesaka T, Watanabe H and Kato N 2001 High fat diet enhances colonic cell ...

  3. Neglected Giant Scalp Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Anne Kristine Larsen, MD

    2014-03-01

    Full Text Available Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence 1 year postoperatively.

  4. Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face.

    Science.gov (United States)

    Feller, L; Khammissa, R A G; Kramer, B; Altini, M; Lemmer, J

    2016-02-05

    Ultraviolet light (UV) is an important risk factor for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin. These cancers most commonly affect persons with fair skin and blue eyes who sunburn rather than suntan. However, each of these cancers appears to be associated with a different pattern of UV exposure and to be mediated by different intracellular molecular pathways.Some melanocortin 1 receptor (MC1R) gene variants play a direct role in the pathogenesis of cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma apart from their role in determining a cancer-prone pigmentory phenotype (fair skin, red hair, blue eyes) through their interactions with other genes regulating immuno-inflammatory responses, DNA repair or apoptosis.In this short review we focus on the aetiological role of UV in cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin, and on some associated biopathological events.

  5. Role of SIRT6 in Metabolic Reprogramming During Colorectal Carcinoma

    Science.gov (United States)

    2014-09-01

    pathway. To test this possibility, we analyzed the activation of oncogenic signaling pathways in SIRT6-deficient cells. Because deregulation of most...that SIRT6 sits at a critical metabolic node, modulating both glycolytic metabolism and ribosome biosynthesis (Figure 7L). SIRT6 deficiency deregulates ...C. Metabolic reprogramming: driving tumorigenesis from the origin In 1966, at the meeting of Nobel-Laureates at Lindau, Germany , Otto Warburg

  6. Association Between Inflammatory Diet Pattern and Risk of Colorectal Carcinoma Subtypes Classified by Immune Responses to Tumor.

    Science.gov (United States)

    Liu, Li; Nishihara, Reiko; Qian, Zhi Rong; Tabung, Fred K; Nevo, Daniel; Zhang, Xuehong; Song, Mingyang; Cao, Yin; Mima, Kosuke; Masugi, Yohei; Shi, Yan; da Silva, Annacarolina; Twombly, Tyler; Gu, Mancang; Li, Wanwan; Hamada, Tsuyoshi; Kosumi, Keisuke; Inamura, Kentaro; Nowak, Jonathan A; Drew, David A; Lochhead, Paul; Nosho, Katsuhiko; Wu, Kana; Wang, Molin; Garrett, Wendy S; Chan, Andrew T; Fuchs, Charles S; Giovannucci, Edward L; Ogino, Shuji

    2017-12-01

    Dietary patterns affect systemic and local intestinal inflammation, which have been linked to colorectal carcinogenesis. Chronic inflammation can interfere with the adaptive immune response. We investigated whether the association of a diet that promotes intestinal inflammation with risk of colorectal carcinoma was stronger for tumors with lower lymphocytic reactions than tumors with higher lymphocytic reactions. We collected data from the molecular pathological epidemiology databases of 2 prospective cohort studies: the Nurses' Health Study (since 1976) and the Health Professionals Follow-Up Study (since 1986). We used duplication-method time-varying Cox proportional cause-specific hazards regression to assess the association of empirical dietary inflammatory pattern (EDIP) score (derived from food frequency questionnaire data) with colorectal carcinoma subtype. Foods that contribute to high EDIP scores include red and processed meats, refined grains, carbonated beverages, and some vegetables; foods that contribute to low EDIP scores include beer, wine, coffee, tea, yellow and leafy vegetables, and fruit juice. Colorectal tissue samples were analyzed histologically for patterns of lymphocytic reactions (Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, and tumor-infiltrating lymphocytes). During follow-up of 124,433 participants, we documented 1311 incident colon and rectal cancer cases with available tissue data. The association between the EDIP and colorectal cancer risk was significant (P trend  = .02), and varied with degree of peritumoral lymphocytic reaction (P heterogeneity colorectal cancer with an absent or low peritumoral lymphocytic reaction (highest vs lowest EDIP score quintile hazard ratio, 2.60; 95% confidence interval, 1.60-4.23; P trend .80). In 2 prospective cohort studies, we associated inflammatory diets with a higher risk of colorectal cancer subtype that contains little or no peritumoral

  7. Stromal Expression of Hypoxia Regulated Proteins Is an Adverse Prognostic Factor in Colorectal Carcinomas

    Directory of Open Access Journals (Sweden)

    Arjen H. G. Cleven

    2007-01-01

    Full Text Available Background: Hypoxia modifies the phenotype of tumors in a way that promotes tumor aggressiveness and resistance towards chemotherapy and radiotherapy. However, the expression and influence of hypoxia-regulated proteins on tumor biology are not well characterized in colorectal tumors. We studied the role of protein expression of hypoxia-inducible factor (HIF-1α, HIF-2α, carbonic anhydrase 9 (CA9 and glucose transporter 1 (GLUT1 in patients with colorectal adenocarcinomas. Methods: Expression of HIF-1α, HIF-2α, CA9 and GLUT1 was quantified by immunohistochemistry in 133 colorectal adenocarcinomas. The expression of hypoxia markers was correlated with clinicopathological variables and overall patient survival. Results: Expression of these hypoxia markers was detected in the epithelial compartment of the tumor cells as well as in tumor-associated stromal cells. Although tumor cells frequently showed expression of one or more of the investigated hypoxia markers, no correlation among these markers or with clinical response was found. However, within the tumor stroma, positive correlations between the hypoxia markers HIF-2α, CA9 and GLUT1 were observed. Furthermore expression of HIF-2α and CA9 in tumor-associated stroma were both associated with a significantly reduced overall survival. In the Cox proportional hazard model, stromal HIF-2α expression was an independent prognostic factor for survival. Conclusion: These observations show, that expression of hypoxia regulated proteins in tumor-associated stromal cells, as opposed to their expression in epithelial tumor cells, is associated with poor outcome in colorectal cancer. This study suggests that tumor hypoxia may influence tumor-associated stromal cells in a way that ultimately contributes to patient prognosis.

  8. 18F FDG PET/CT for staging of colorectal carcinoma - literature review and case report

    International Nuclear Information System (INIS)

    Ilcheva, M.; Hadzhiyska, V.; Petrov, T.; Mladenov, K.; Malla, V.; Zlatareva, D.; Nedevska, M.; Neychev, V.

    2017-01-01

    Colorectal cancer is the third most common cancer worldwide. The role of PET/CT in initial diagnosis of primary colorectal cancer is limited. PET is used for restaging of colorectal carcinoma or for evaluating the hepatic and pulmonary metastasis. On the other hand, MRI is used for T- and N- staging and also in the evaluation of liver metastasis. The aim of the study is to demonstrate the capabilities of the imaging modalities (PET/CT and MRI) as well as to show the importance of collaborative work of the units to determine the correct therapeutic decision. In this case, we present a 63 years old patient with rectal carcinoma. Confirmation of the disease was proven using colonoscopy and biopsy. Then we perform FDG-PET/CT on a GE Discovery 16T according to a standard protocol, using diuretic stimulation and oral contrast intake, followed by 3Tesla MRI of the abdomen and pelvis with intravenous contrast. PET/CT: data on metabolic active tumor formation in the recto-sigmoid region, liver dissemination and lesion near the navel as well as the presence of two metabolically active peritoneal lesions of small size. MRI: Rectal tumor data with a suspected infiltration of the wall of the ileum and bladder as well as dissemination in the liver and abdominal wall. Additionally, there was a thrombosis of the left branch of the portal vein. By applying both methods it is possible to accurately stage the disease and choose the most appropriate therapeutic behavior. Our impressions of the application of the two imaging methods PET/CT and MRI matches the science publications that each one has a specific application, capabilities and advantages. For example, PET/CT provide sufficient functional and morphological information for the initial staging and also for the peritoneal lesions, which are identified as non-specific and non-definite in MRI. On the other hand, after MRI we receive detailed information for the anatomic and topographic characteristic of the major tumor formation

  9. A pathway-centric survey of somatic mutations in Chinese patients with colorectal carcinomas.

    Directory of Open Access Journals (Sweden)

    Chao Ling

    Full Text Available Previous genetic studies on colorectal carcinomas (CRC have identified multiple somatic mutations in four candidate pathways (TGF-β, Wnt, P53 and RTK-RAS pathways on populations of European ancestry. However, it is under-studied whether other populations harbor different sets of hot-spot somatic mutations in these pathways and other oncogenes. In this study, to evaluate the mutational spectrum of novel somatic mutations, we assessed 41 pairs of tumor-stroma tissues from Chinese patients with CRC, including 29 colon carcinomas and 12 rectal carcinomas. We designed Illumina Custom Amplicon panel to target 43 genes, including genes in the four candidate pathways, as well as several known oncogenes for other cancers. Candidate mutations were validated by Sanger sequencing, and we further used SIFT and PolyPhen-2 to assess potentially functional mutations. We discovered 3 new somatic mutations in gene APC, TCF7L2, and PIK3CA that had never been reported in the COSMIC or NCI-60 databases. Additionally, we confirmed 6 known somatic mutations in gene SMAD4, APC, FBXW7, BRAF and PTEN in Chinese CRC patients. While most were previously reported in CRC, one mutation in PTEN was reported only in malignant endometrium cancer. Our study confirmed the existence of known somatic mutations in the four candidate pathways for CRC in Chinese patients. We also discovered a number of novel somatic mutations in these pathways, which may have implications for the pathogenesis of CRC.

  10. Cetuximab & Nivolumab in Patients With Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

    Science.gov (United States)

    2018-04-10

    Squamous Cell Carcinoma of the Oropharynx; Squamous Cell Carcinoma of the Larynx; Squamous Cell Carcinoma of the Oral Cavity; Squamous Cell Carcinoma of the Hypopharynx; Squamous Cell Carcinoma of the Paranasal Sinus; Head and Neck Squamous Cell Carcinoma; Squamous Cell Cancer; Head and Neck Carcinoma

  11. Treatment Options by Stage (Merkel Cell Carcinoma)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... common for Merkel cell carcinoma to recur. Treatment Option Overview Key Points There are different types of ...

  12. Treatment Option Overview (Merkel Cell Carcinoma)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... common for Merkel cell carcinoma to recur. Treatment Option Overview Key Points There are different types of ...

  13. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    Directory of Open Access Journals (Sweden)

    Yeliz Bilir

    2014-01-01

    Full Text Available Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts, the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  14. Merkel Cell Carcinoma Therapeutic Update.

    Science.gov (United States)

    Cassler, Nicole M; Merrill, Dean; Bichakjian, Christopher K; Brownell, Isaac

    2016-07-01

    Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Early-stage disease can be cured with surgical resection and radiotherapy (RT). Sentinel lymph node biopsy (SLNB) is an important staging tool, as a microscopic MCC is frequently identified. Adjuvant RT to the primary excision site and regional lymph node bed may improve locoregional control. However, newer studies confirm that patients with biopsy-negative sentinel lymph nodes may not benefit from regional RT. Advanced MCC currently lacks a highly effective treatment as responses to chemotherapy are not durable. Recent work suggests that immunotherapy targeting the programmed cell death receptor 1/programmed cell death ligand 1 (PD-1/PD-L1) checkpoint holds great promise in treating advanced MCC and may provide durable responses in a portion of patients. At the same time, high-throughput sequencing studies have demonstrated significant differences in the mutational profiles of tumors with and without the Merkel cell polyomavirus (MCV). An important secondary endpoint in the ongoing immunotherapy trials for MCC will be determining if there is a response difference between the virus-positive MCC tumors that typically lack a large mutational burden and the virus-negative tumors that have a large number of somatic mutations and predicted tumor neoantigens. Interestingly, sequencing studies have failed to identify a highly recurrent activated driver pathway in the majority of MCC tumors. This may explain why targeted therapies can demonstrate exceptional responses in case reports but fail when treating all comers with MCC. Ultimately, a precision medicine approach may be more appropriate for treating MCC, where identified driver mutations are used to direct targeted therapies. At a minimum, stratifying patients in future clinical trials based on tumor viral status should be considered as virus-negative tumors are more likely to harbor activating driver mutations.

  15. MicroRNA let-7, T cells, and patient survival in colorectal cancer

    Science.gov (United States)

    Dou, Ruoxu; Nishihara, Reiko; Cao, Yin; Hamada, Tsuyoshi; Mima, Kosuke; Masuda, Atsuhiro; Masugi, Yohei; Shi, Yan; Gu, Mancang; Li, Wanwan; da Silva, Annacarolina; Nosho, Katsuhiko; Zhang, Xuehong; Meyerhardt, Jeffrey A.; Giovannucci, Edward L.; Chan, Andrew T.; Fuchs, Charles S.; Qian, Zhi Rong; Ogino, Shuji

    2016-01-01

    Experimental evidence suggests that the let-7 family of noncoding RNAs suppresses adaptive immune responses, contributing to immune evasion by the tumor. We hypothesized that the amount of let-7a and let-7b expression in colorectal carcinoma might be associated with limited T-lymphocyte infiltrates in the tumor microenvironment and worse clinical outcome. Utilizing the molecular pathological epidemiology resources of 795 rectal and colon cancers in two U.S.-nationwide prospective cohort studies, we measured tumor-associated let-7a and let-7b expression levels by quantitative reverse-transcription PCR, and CD3+, CD8+, CD45RO (PTPRC)+, and FOXP3+ cell densities by tumor tissue microarray immunohistochemistry and computer-assisted image analysis. Logistic regression analysis and Cox proportional hazards regression were used to assess associations of let-7a (and let-7b) expression (quartile predictor variables) with T-cell densities (binary outcome variables) and mortality, respectively, controlling for tumor molecular features, including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Compared with cases in the lowest quartile of let-7a expression, those in the highest quartile were associated with lower densities of CD3+ [multivariate odds ratio (OR), 0.40; 95% confidence interval (CI), 0.23 to 0.67; Ptrend = 0.003] and CD45RO+ cells (multivariate OR, 0.31; 95% CI, 0.17 to 0.58; Ptrend = 0.0004), and higher colorectal cancer-specific mortality (multivariate hazard ratio, 1.82; 95% CI, 1.42 to 3.13; Ptrend = 0.001). In contrast, let-7b expression was not significantly associated with T-cell density or colorectal cancer prognosis. Our data support the role of let-7a in suppressing antitumor immunity in colorectal cancer, and suggest let-7a as a potential target of immunotherapy. PMID:27737877

  16. Merkel cell polyomavirus and Merkel cell carcinoma.

    Science.gov (United States)

    DeCaprio, James A

    2017-10-19

    Merkel cell polyomavirus (MCPyV) causes the highly aggressive and relatively rare skin cancer known as Merkel cell carcinoma (MCC). MCPyV also causes a lifelong yet relatively innocuous infection and is one of 14 distinct human polyomaviruses species. Although polyomaviruses typically do not cause illness in healthy individuals, several can cause catastrophic diseases in immunocompromised hosts. MCPyV is the only polyomavirus clearly associated with human cancer. How MCPyV causes MCC and what oncogenic events must transpire to enable this virus to cause MCC is the focus of this essay.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Author(s).

  17. Eyelid Squamous Cell Carcinoma in a Dog

    Directory of Open Access Journals (Sweden)

    Chang-hyun Song1§, Sae-kwang Ku2§, Hwan-soo Jang3, Eun-young Kye, Sung-ho Yun, Kwang-ho Jang and Young-sam Kwon*

    2012-06-01

    Full Text Available A 10-year-old, female, Yorkshire Terrier was presented with a left lower eyelid mass. No other abnormality was detected on affected eye in a general eye examination. The mass was surgically removed and histologically diagnosed as a squamous cell carcinoma. The advancement flap used in this case may be an appropriate therapeutic choice for eyelid squamous cell carcinoma in dogs.

  18. The value of radiotherapy in colorectal and anal carcinomas, judged on the basis of radiation results obtained in Wuerzburg between 1977 and 1985

    International Nuclear Information System (INIS)

    Aydin, H.

    1987-01-01

    Investigations were carried out into the effectiveness of radiotherapy in colorectal and anal carcinomas as well as metastases formed by those tumours. The relevance of changes in CT findings and CEA values is discussed in detail. (MBC) [de

  19. Tissue detection of natural killer cells in colorectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Patsouris Efstratios S

    2004-09-01

    Full Text Available Abstract Background Natural killer (NK cells represent a first line of defence against a developing cancer; however, their exact role in colorectal cancer remains undetermined. The aim of the present study was to evaluate the expression of CD16 and CD57 [immunohistochemical markers of natural NK cells] in colorectal adenocarcinoma. Methods Presence of NK cells was investigated in 82 colorectal adenocarcinomas. Immunohistochemical analysis was performed, using 2 monoclonal antibodies (anti-Fc Gamma Receptor II, CD16 and an equivalent to Leu-7, specific for CD-57. The number of immunopositive cells (% was evaluated by image analysis. The cases were characterized according to: patient gender and age, tumor location, size, grade, bowel wall invasion, lymph node metastases and Dukes' stage. Results NK cells were detected in 79/82 cases at the primary tumor site, 27/33 metastatic lymph nodes and 3/4 hepatic metastases; they were detected in levels similar to those reported in the literature, but their presence was not correlated to the clinical or pathological characteristics of the series, except for a negative association with the patients' age (p = 0.031. Conclusions Our data do not support an association of NK cell tissue presence with clinical or pathological variables of colorectal adenocarcinoma, except for a negative association with the patients' age; this might possibly be attributed to decreased adhesion molecule expression in older ages.

  20. Squamous cell carcinoma arising in an odontogenic cyst

    International Nuclear Information System (INIS)

    Yu, Jae Jung; Hwang, Eui Hwan; Lee, Sang Rae; Choi, Jeong Hee

    2003-01-01

    Squamous cell carcinoma arising in an odontogenic cyst is uncommon. The diagnosis of carcinoma arising in a cyst requires that there must be an area of microscopic transition from the benign epithelial cyst lining to the invasive squamous cell carcinoma. We report a histopathologically proven case of squamous cell carcinoma arising in a residual mandibular cyst in a 54-year-old woman.

  1. Characteristics and prognostic factors of colorectal mucinous adenocarcinoma with signet ring cells

    Directory of Open Access Journals (Sweden)

    Kong XQ

    2017-11-01

    Full Text Available Xiangquan Kong,* Xueqing Zhang,* Yunxia Huang, Lirui Tang, Qingqin Peng, Jinluan Li Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China *These authors contributed equally to this work. Background: Colorectal signet ring cell (SRC carcinoma occurs rarely with a poor prognosis. The present study assessed the prognostic factors and predictive value of SRC ratio in colorectal mucinous adenocarcinoma (MAC with SRCs (MAC-SRC.Patients and methods: A total of 95 consecutive colorectal MAC-SRC patients, confirmed pathologically from February 1987 to December 2015, were analyzed retrospectively in our institute. Clinical characteristics, pathological grade, TNM staging, and SRC ratio were assessed to identify the prognostic factors related to progression-free survival (PFS and overall survival (OS. SPSS 22.0 was used for statistical analyses.Results: The median follow-up time was 29.7 months (range 0.8–165. Meanwhile, 5-year PFS and OS rates were 25.6% (95% confidence interval [CI] 16.192–35.008% and 40.5% (95% CI 29.524–51.476%, respectively. Among the 81 patients who underwent surgery, 78 (96.3% were diagnosed as stage T3 or T4; 74 (91.4% showed lymph node involvement, and 27 (29.3% presented distant metastasis. Metastases of the peritoneal cavity and ovaries were observed commonly in colorectal MAC-SRC. In the multivariate Cox regression model, SRC ratio ≥35%, absence of preoperative radiotherapy, and distant metastasis were independent predictors of PFS. Furthermore, SRC ratio ≥35%, absence of preoperative chemotherapy (pre-CT, and distant metastasis were independent risk factors for poor prognosis.Conclusion: A long-term follow-up of colorectal MAC-SRC reveals that it is a rare subtype of colorectal MAC with a dismal prognosis. Furthermore, SRC ratio, pre-CT, and M stage seem to affect OS independently. Keywords: colorectal mucinous adenocarcinoma

  2. Antibody-based screening for hereditary nonpolyposis colorectal carcinoma compared with microsatellite analysis and sequencing

    DEFF Research Database (Denmark)

    Christensen, Mariann; Katballe, Niels; Wikman, Friedrik

    2002-01-01

    BACKGROUND: Germline mutations in the DNA mismatch repair genes, MSH2, MLH1, and others are associated with hereditary nonpolyposis colorectal cancer (HNPCC). Due to the high costs of sequencing, cheaper screening methods are needed to identify HNPCC cases. Ideally, these methods should have a high...... carcinoma of whom 11 met the Amsterdam criteria and 31 were suspected to belong to HNPCC families. Thirty-five patients were examined by microsatellite analysis, 40 by immunohistochemical staining, and in 31 patients both the MLH1 and MSH2 genes were sequenced. RESULTS: Ninety-two percent of patients...... the three methods was found in 74 % of the tumors. CONCLUSIONS: The authors suggest that immunohistochemistry should be used in combination with microsatellite analysis to prescreen suspected HNPCC patients for the selection of cases where sequencing of the MLH1 and MSH2 mismatch repair genes is indicated....

  3. Gingival squamous cell carcinoma: A diagnostic impediment

    Directory of Open Access Journals (Sweden)

    Rekha Rani Koduganti

    2012-01-01

    Full Text Available Oral squamous cell carcinomas represent 3% of cancers in men and 2% of cancers in women. More than 90% of oral cancer occurs in people older than 45 years Lesions of gingiva account for approximately 10% of the oral squamous cell carcinomas and may present clinically as an area of ulceration, exophytic mass, or red/white speckled patches. The proximity to the underlying periosteum may invite early bone invasion. Carcinoma of gingiva constitutes an extremely important group of neoplasms as the lesion frequently mimics the reactive and inflammatory conditions affecting the periodontium, delaying the diagnosis and making the prognosis of the patient poorer. A rare case of gingival squamous cell carcinoma has been reported here, in a 40 Year old male patient. Careful recording of the case history and results of clinical examination, radiographic, and laboratory investigations, along with a critical review of similar conditions led to the diagnosis, and treatment was initiated.

  4. Neoexpression of a functional primary cilium in colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Blanche Sénicourt

    2016-05-01

    Full Text Available The Hedgehog (HH signaling pathway is involved in the maintenance of numerous cell types both during development and in the adult. Often deregulated in cancers, its involvement in colorectal cancer has come into view during the last few years, although its role remains poorly defined. In most tissues, the HH pathway is highly connected to the primary cilium (PC, an organelle that recruits functional components and regulates the HH pathway. However, normal epithelial cells of the colon display an inactive HH pathway and lack a PC. In this study, we report the presence of the PC in adenocarcinoma cells of primary colorectal tumors at all stages. Using human colorectal cancer cell lines we found a clear correlation between the presence of the PC and the expression of the final HH effector, GLI1, and provide evidence of a functional link between the two by demonstrating the recruitment of the SMO receptor to the membrane of the primary cilium. We conclude that the primary cilium directly participates in the HH pathway in colorectal cancer cells.

  5. Radiation exposure and familial aggregation of cancers as risk factors for colorectal cancer after radioiodine treatment for thyroid carcinoma

    International Nuclear Information System (INIS)

    Rubino, Carole; Adjadj, Elisabeth; Doyon, Francoise; Shamsaldin, Akhtar; Abbas, Tahaa Moncef; Caillou, Bernard; Colonna, Marc; Cecarreli, Claudia; Schvartz, Claire; Bardet, Stephane; Langlois, Christiane B.Sc.; Ricard, Marcel; Schlumberger, Martin; Vathaire, Florent de

    2005-01-01

    Purpose: In thyroid cancer patients, radioiodine treatment has been shown to be associated with an increased risk of colon carcinoma. The aim of this study in thyroid cancer patients was to evaluate the role of familial factors in the risk of colorectal cancer and their potential interaction with radioiodine exposure. Methods and Materials: We performed a case-control study on 15 colorectal cancer patients and 76 matched control subjects, nested in a cohort of 3708 thyroid cancer patients treated between 1933 and 1998. For each patient, the radiation dose delivered to the colon by radioiodine was estimated by use of standard tables. In those who received external radiation therapy, the average radiation doses delivered to the colon and rectum were estimated by use of DOS E g software. A complete familial history was obtained by face-to-face interviews, and a familial index was defined to evaluate the degree of familial aggregation. Results: The risk of colorectal cancer increased with familial aggregation of colorectal cancer (p = 0.02). After adjustment for the radiation dose delivered to the colon and rectum, the risk of colorectal cancer was 2.8-fold higher (95% CI, 1.0-8.0) for patients with at least one relative affected by colorectal cancer than for patients without such a family history (p = 0.05). The radiation dose delivered to the colon and rectum by 131 I and external radiation therapy was associated with an increase of risk near the significance threshold (p = 0.1). No significant interaction was found between radiation dose and having an affected relative (p = 0.9). Conclusions: The role of familial background in the risk of colorectal cancer following a differentiated thyroid carcinoma appears to increase with the radiation dose delivered to the colon and rectum. However, the study population was small and no interaction was found between these two factors

  6. Histone Deacetylase Inhibitors Activate Tristetraprolin Expression through Induction of Early Growth Response Protein 1 (EGR1 in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Cyril Sobolewski

    2015-08-01

    Full Text Available The RNA-binding protein tristetraprolin (TTP promotes rapid decay of mRNAs bearing 3' UTR AU-rich elements (ARE. In many cancer types, loss of TTP expression is observed allowing for stabilization of ARE-mRNAs and their pathologic overexpression. Here we demonstrate that histone deacetylase (HDAC inhibitors (Trichostatin A, SAHA and sodium butyrate promote TTP expression in colorectal cancer cells (HCA-7, HCT-116, Moser and SW480 cells and cervix carcinoma cells (HeLa. We found that HDAC inhibitors-induced TTP expression, promote the decay of COX-2 mRNA, and inhibit cancer cell proliferation. HDAC inhibitors were found to promote TTP transcription through activation of the transcription factor Early Growth Response protein 1 (EGR1. Altogether, our findings indicate that loss of TTP in tumors occurs through silencing of EGR1 and suggests a therapeutic approach to rescue TTP expression in colorectal cancer.

  7. Synchronous lung tumours in a patient with metachronous colorectal carcinoma and a germline MSH2 mutation.

    LENUS (Irish Health Repository)

    Canney, A

    2012-02-01

    Mutations of DNA mismatch repair genes are characterised by microsatellite instability and are implicated in carcinogenesis. This mutation susceptible phenotype has been extensively studied in patients with hereditary non-polyposis colon carcinoma, but little is known of the contribution of such mutations in other tumour types, particularly non-small-cell lung carcinoma. This report describes the occurrence of two synchronous lung tumours, one mimicking a metastatic colon carcinoma, in a male patient with a history of metachronous colonic carcinoma. Immunohistochemistry supported a pulmonary origin for both lesions. Mismatch repair protein immunohistochemistry showed loss of MSH2 and MSH6 expression in both colonic tumours and in one lung tumour showing enteric differentiation. Subsequent mutational analysis demonstrated a deleterious germline mutation of the MSH2 mismatch repair gene. The significance of these findings and the practical diagnostic difficulties encountered in this case are discussed.

  8. Colorectal carcinoma metastases: Detection with In-111-labeled monoclonal antibody CCR 086

    International Nuclear Information System (INIS)

    Abdel-Nabi, H.H.; Levine, G.; Lamki, L.M.; Murray, J.L.; Tauxe, W.N.; Shah, A.N.; Patt, Y.Z.; Doerr, R.J.; Klein, H.A.; Gona, J.

    1990-01-01

    A phase I/II clinical trial with indium-111-labeled antimucin murine monoclonal antibody (MoAb) CCR 086 was conducted. Seventeen patients with histologically proved colorectal carcinoma and known metastatic disease underwent external scintigraphy after administration of 5.5 mCi (203.5 MBq) of In-111 CCR 086 at doses of 5 and 20 mg. Of 25 known lesions, 17 were detected (sensitivity, 68%). The smallest detected lesion in the lung was 1 cm and in the liver was 1.5 cm. The serum half-life of In-111-labeled CCR 086 MoAb was approximately 64 hours. The formation of human antimouse antibody (HAMA) was detected in the serum of four of five patients who received 20 mg of MoAb. No HAMAs were detected in four patients receiving 5 mg of MoAb. No side effects were encountered. Because of effective detection of liver and lung metastases with lower doses (5-20 mg) of CCR 086 conjugated with In-111, further investigations are warranted to assess clinical and therapeutic potentials of CCR 086 in the management of colorectal cancer

  9. Absence of prognostic value of nuclear shape factor analysis in colorectal carcinoma: relevance of interobserver and intraobserver variability.

    Science.gov (United States)

    Di Fabio, Francesco; Shrier, Ian; Bégin, Louis R; Gordon, Philip H

    2008-12-01

    Several retrospective studies, including our previous investigation, have shown a prognostic value of nuclear shape factor in colorectal carcinomas. This prospective study was designed to assess the reliability of nuclear shape factor determined by nuclear morphometry and to confirm its prognostic value. Ninety-eight patients who underwent colorectal carcinoma resection were prospectively enrolled. Measurement of nuclear shape factor was performed by using a computer-based image analysis system. Nuclear shape factor was defined as the degree of circularity of the nucleus (1.0 for a perfect circle and values by American Joint Committee on Cancer stage were: 0.73 (0.07) in Stage I, 0.74 (0.06) in Stage II, and 0.75 (0.05) in Stage III carcinomas (P = 0.78, ANOVA). The intraobserver agreement was poor for observer A (r = 0.28) and practically nonexistent for observer B (r = -0.004, Pearson correlation). The intraclass coefficient for interobserver agreement was practically nonexistent. No significant association between nuclear shape factor and ten-year survival was found. Our prospective results, as opposed to our previous retrospective results, suggest that the reliability for nuclear shape factor morphometric analysis is very poor. We failed to confirm a prognostic value for nuclear shape factor in colorectal carcinoma.

  10. Immunosuppressive Environment in Basal Cell Carcinoma

    DEFF Research Database (Denmark)

    Omland, Silje Haukali; Nielsen, Patricia S; Gjerdrum, Lise M R

    2016-01-01

    Interaction between tumour survival tactics and anti-tumour immune response is a major determinant for cancer growth. Regulatory T cells (T-regs) contribute to tumour immune escape, but their role in basal cell carcinoma (BCC) is not understood. The fraction of T-regs among T cells was analysed b...

  11. Importance of circulating tumor cells in newly diagnosed colorectal cancer

    NARCIS (Netherlands)

    van Dalum, Guus; Stam, Gerrit-Jan; Scholten, Loes F.A.; Mastboom, Walter J.B.; Vermes, I.; Tibbe, Arjan G.J.; De Groot, Marco R.; Terstappen, Leonardus Wendelinus Mathias Marie

    2015-01-01

    Presence of circulating tumor cells (CTC) is associated with poor prognosis in patients with metastatic colorectal cancer (CRC). The present study was conducted to determine if the presence of CTC prior to surgery and during follow‑up in patients with newly diagnosed non-metastatic CRC can identify

  12. Metastatic giant basal cell carcinoma: a case report.

    Science.gov (United States)

    Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M'rabti, Hind; Errihani, Hassan

    2016-01-01

    Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy.

  13. Aberrant Apoptotic Response of Colorectal Cancer Cells to Novel Nucleoside Analogues.

    Directory of Open Access Journals (Sweden)

    Leonie Harmse

    Full Text Available Despite the increased understanding of colorectal cancer and the introduction of targeted drug therapy, the metastatic phase of the disease remains refractory to treatment. Since the deregulation of normal apoptosis contributes to the pathogenesis of colorectal cancer, novel nucleoside analogues were synthesized here and evaluated for their ability to induce apoptosis and cause cell death in two colorectal adeno-carcinoma cell lines, Caco-2 and HT-29. Three novel nucleoside analogues assessed here showed cytotoxic activity, as measured by the MTT assay against both cell lines: the IC50 values ranged between 3 and 37 μM, with Caco-2 cells being more sensitive than HT-29 cells. Compared to camptothecin, the positive control, the nucleoside analogues were significantly less toxic to normal unstimulated leukocytes (p>0.05. Moreover, the nucleosides were able to induce apoptosis as measured by an increase in caspase 8 and caspase 3 activity above that of the control. This was additionally supported by data derived from Annexin V-FITC assays. Despite marginal changes to the mitochondrial membrane potential, all three nucleosides caused a significant increase in cytosolic cytochrome c (p>0.05, with a corresponding decrease in mitochondrial cytochrome c. Morphological analysis of both cell lines showed the rapid appearance of vacuoles following exposure to two of the nucleosides, while a third caused cellular detachment, delayed cytoplasmic vacuolisation and nuclear abnormalities. Preliminary investigations, using the autophagic indicator monodansylcadaverine and chloroquine as positive control, showed that two of the nucleosides induced the formation of autophagic vacuoles. In summary, the novel nucleoside analogues showed selective cytotoxicity towards both cancer cell lines and are effective initiators of an unusual apoptotic response, demonstrating their potential to serve as structural scaffolds for more potent analogues.

  14. Aberrant Apoptotic Response of Colorectal Cancer Cells to Novel Nucleoside Analogues.

    Science.gov (United States)

    Harmse, Leonie; Dahan-Farkas, Nurit; Panayides, Jenny-Lee; van Otterlo, Willem; Penny, Clement

    2015-01-01

    Despite the increased understanding of colorectal cancer and the introduction of targeted drug therapy, the metastatic phase of the disease remains refractory to treatment. Since the deregulation of normal apoptosis contributes to the pathogenesis of colorectal cancer, novel nucleoside analogues were synthesized here and evaluated for their ability to induce apoptosis and cause cell death in two colorectal adeno-carcinoma cell lines, Caco-2 and HT-29. Three novel nucleoside analogues assessed here showed cytotoxic activity, as measured by the MTT assay against both cell lines: the IC50 values ranged between 3 and 37 μM, with Caco-2 cells being more sensitive than HT-29 cells. Compared to camptothecin, the positive control, the nucleoside analogues were significantly less toxic to normal unstimulated leukocytes (p>0.05). Moreover, the nucleosides were able to induce apoptosis as measured by an increase in caspase 8 and caspase 3 activity above that of the control. This was additionally supported by data derived from Annexin V-FITC assays. Despite marginal changes to the mitochondrial membrane potential, all three nucleosides caused a significant increase in cytosolic cytochrome c (p>0.05), with a corresponding decrease in mitochondrial cytochrome c. Morphological analysis of both cell lines showed the rapid appearance of vacuoles following exposure to two of the nucleosides, while a third caused cellular detachment, delayed cytoplasmic vacuolisation and nuclear abnormalities. Preliminary investigations, using the autophagic indicator monodansylcadaverine and chloroquine as positive control, showed that two of the nucleosides induced the formation of autophagic vacuoles. In summary, the novel nucleoside analogues showed selective cytotoxicity towards both cancer cell lines and are effective initiators of an unusual apoptotic response, demonstrating their potential to serve as structural scaffolds for more potent analogues.

  15. Silencing of RhoA and RhoC expression by RNA interference suppresses human colorectal carcinoma growth in vivo

    Directory of Open Access Journals (Sweden)

    Wang Haibo

    2010-09-01

    Full Text Available Abstract Background RhoA and RhoC have been proved to be over-expressed in many solid cancers, including colorectal cancer. The reduction of RhoA and RhoC expression by RNA interference (RNAi resulted growth inhibition of cancer cells. The present study was to evaluate the effect of silencing of RhoA and RhoC expression by RNAi on growth of human colorectal carcinoma (CRC in tumor-bearing nude mice in vivo. Methods To establish HCT116 cell transplantable model, the nude mice were subcutaneously inoculated with 1.0 × 107 HCT116 cells and kept growing till the tumor xenografts reached 5-7 mm in diameter. Then the mice were randomly assigned to three groups(seven mice in each group: (1 normal saline(NS group, (2replication-defective recombinant adenovirus carrying the negative control shRNA (Ad-HK group and (3replication-defective recombinant adenovirus carrying the 4-tandem linked RhoA and RhoC shRNAs (Ad-RhoA-RhoC group. Ad-HK (4 × 108 pfu, 30 ul/mouse, Ad-RhoA-RhoC (4 × 108 pfu, 30 ul/mouse or PBS (30 ul/mouse was injected intratumorally four times once every other day. The weight and volumes of tumor xenografts were recorded. The levels of RhoA and RhoC mRNA transcripts and proteins in tumor xenografts were detected by reverse quantitative transcription polymerase chain reaction (QRT-PCR and immunohistochemical staining respectively. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL assay was used to detect the death of cells. Results The xenografts in mice could be seen at 5th day from the implantation of HCT116 cells and all had reached 5-7 mm in size at 9th day. After injection intratumorally, the growth speed of tumor xenografts in Ad-RhoA-RhoC group was significantly delayed compared with those in NS and Ad-HK group(P RhoA and RhoC reduced more in Ad-RhoA-RhoC group than those in NS and Ad-HK group. The relative RhoA and RhoC mRNA transcripts were decreased to 48% and 43% respectively (P RhoA and Rho

  16. Metastatic renal cell carcinoma in the nasopharynx.

    Science.gov (United States)

    Atar, Yavuz; Topaloglu, Ilhan; Ozcan, Deniz

    2013-01-01

    Metastatic renal cell carcinoma of the nasopharynx, nasal cavity, and paranasal sinuses can be misdiagnosed as primary malignant or benign diseases. A 33-year-old male attended our outpatient clinic complaining of difficulty breathing through the nose, bloody nasal discharge, postnasal drop, snoring, and discharge of phlegm. Endoscopic nasopharyngeal examination showed a vascularized nasopharyngeal mass. Under general anesthesia, multiple punch biopsies were taken from the nasopharynx. Pathologically, the tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. After the initial pathological examination, the pathologist requested more information about the patient's clinical status. A careful history revealed that the patient had undergone left a nephrectomy for a kidney mass diagnosed as renal cell carcinoma 3 years earlier. Subsequently, nasopharyngeal metastatic renal cell carcinoma was diagnosed by immunohistochemical staining with CD10 and vimentin. Radiotherapy was recommended for treatment.

  17. Metastatic renal cell carcinoma in the nasopharynx

    Directory of Open Access Journals (Sweden)

    Yavuz Atar

    2013-01-01

    Full Text Available Metastatic renal cell carcinoma of the nasopharynx, nasal cavity, and paranasal sinuses can be misdiagnosed as primary malignant or benign diseases. A 33-year-old male attended our outpatient clinic complaining of difficulty breathing through the nose, bloody nasal discharge, postnasal drop, snoring, and discharge of phlegm. Endoscopic nasopharyngeal examination showed a vascularized nasopharyngeal mass. Under general anesthesia, multiple punch biopsies were taken from the nasopharynx. Pathologically, the tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. After the initial pathological examination, the pathologist requested more information about the patient′s clinical status. A careful history revealed that the patient had undergone left a nephrectomy for a kidney mass diagnosed as renal cell carcinoma 3 years earlier. Subsequently, nasopharyngeal metastatic renal cell carcinoma was diagnosed by immunohistochemical staining with CD10 and vimentin. Radiotherapy was recommended for treatment.

  18. Small cell type neuroendocrine carcinoma colliding with squamous cell carcinoma at esophagus

    Science.gov (United States)

    Yang, Luoluo; Sun, Xun; Zou, Yabin; Meng, Xiangwei

    2014-01-01

    Collision tumor is an extremely rare tumor which defined as the concrescence of two distinct primaries neoplasms. We report here a case of collision tumor at lower third esophagus composed of small cell type neuroendocrine carcinoma (NEC), which is an very rare, highly aggressive and poorly prognostic carcinoma and squamous cell carcinoma (SqCC). In our case, pathologically, the small cell carcinoma display the characteristic of small, round, ovoid or spindle-shaped tumor cells with scant cytoplasm, which colliding with a moderately differentiated squamous cell carcinoma. Immunohistochemical staining demonstrated positive activities for CD56, synaptophysin, 34βE12, CK 5/6, ki-67 (70%-80%), but negative for CD99, chromogranin A, and TTF-1. Accurate diagnosis was made base on these findings. PMID:24817981

  19. Cold atmospheric plasma treatment inhibits growth in colorectal cancer cells.

    Science.gov (United States)

    Schneider, Christin; Arndt, Stephanie; Zimmermann, Julia L; Li, Yangfang; Karrer, Sigrid; Bosserhoff, Anja-Katrin

    2018-06-01

    Plasma oncology is a relatively new field of research. Recent developments have indicated that cold atmospheric plasma (CAP) technology is an interesting new therapeutic approach to cancer treatment. In this study, p53 wildtype (LoVo) and human p53 mutated (HT29 and SW480) colorectal cancer cells were treated with the miniFlatPlaSter - a device particularly developed for the treatment of tumor cells - that uses the Surface Micro Discharge (SMD) technology for plasma production in air. The present study analyzed the effects of plasma on colorectal cancer cells in vitro and on normal colon tissue ex vivo. Plasma treatment had strong effects on colon cancer cells, such as inhibition of cell proliferation, induction of cell death, and modulation of p21 expression. In contrast, CAP treatment of murine colon tissue ex vivo for up to 2 min did not show any toxic effect on normal colon cells compared to H2O2 positive control. In summary, these results suggest that the miniFlatPlaSter plasma device is able to kill colorectal cancer cells independent of their p53 mutation status. Thus, this device presents a promising new approach in colon cancer therapy.

  20. Influence of inhibitors of serotonin uptake on intestinal epithelium and colorectal carcinomas.

    OpenAIRE

    Tutton, P. J.; Barkla, D. H.

    1982-01-01

    Previous studies have shown that in certain tissues, including colonic carcinomas, cell proliferation may be promoted by serotonin, and indirect evidence suggests that the effects of this amine on colonic tumours involves a cellular-uptake mechanism. In the present study, two specific inhibitors of serotonin uptake, Citalopram and Fluoxetine, are examined for their effects on cell proliferation and tumour growth. Each of the agents was found to suppress cell division in dimethylhydrazine-indu...

  1. Suppressor of cytokine signaling 1 modulates invasion and metastatic potential of colorectal cancer cells.

    Science.gov (United States)

    David, Muriel; Naudin, Cécile; Letourneur, Martine; Polrot, Mélanie; Renoir, Jack-Michel; Lazar, Vladimir; Dessen, Philippe; Roche, Serge; Bertoglio, Jacques; Pierre, Josiane

    2014-07-01

    Suppressor of cytokine signaling (SOCS) 1 is an inducible negative regulator of cytokine signaling but its role in human cancer is not completely established. Here we report that, while SOCS1 is expressed in normal colonic epithelium and colon adenocarcinomas, its level decreases during progression of colon adenocarcinomas, the lowest level being found in the most aggressive stage and least differentiated carcinomas. Forced expression of SOCS1 in metastatic colorectal SW620 cells reverses many characteristics of Epithelial-Mesenchymal Transition (EMT), as highlighted by the disappearance of the transcription factor ZEB1 and the mesenchymal form of p120ctn and the re-expression of E-cadherin. Furthermore, miRNA profiling indicated that SOCS1 also up-regulates the expression of the mir-200 family of miRNAs, which can promote the mesenchymal-epithelial transition and reduce tumor cell migration. Accordingly, overexpression of SOCS1 induced cell morphology changes and dramatically reduced tumor cell invasion in vitro. When injected in nude mice, SOCS1-expressing SW620 cells induced metastases in a smaller number of animals than parental SW620 cells, and did not generate any adrenal gland or bone metastasis. Overall, our results suggest that SOCS1 controls metastatic progression of colorectal tumors by preventing the mesenchymal-epithelial transition (MET), including E-cadherin expression. This pathway may be associated with survival to colorectal cancer by reducing the capacity of generating metastases. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  2. Clinicopathological characteristics of head and neck Merkel cell carcinomas.

    Science.gov (United States)

    Knopf, Andreas; Bas, Murat; Hofauer, Benedikt; Mansour, Naglaa; Stark, Thomas

    2017-01-01

    There are still controversies about the therapeutic strategies and subsequent outcome in head and neck Merkel cell carcinoma. Clinicopathological data of 23 Merkel cell carcinomas, 93 cutaneous head and neck squamous cell carcinomas (HNSCCs), 126 malignant melanomas, and 91 primary parotid gland carcinomas were comprehensively analyzed. Merkel cell carcinomas were cytokeratin 20 (CK20)/neuron-specific enolase (NSE)/chromogranin A (CgA)/synaptophysin (Syn)/thyroid transcription factor-1 (TTF-1)/MIB1 immunostained. All Merkel cell carcinomas underwent wide local excision. Parotidectomy/neck dissection was performed in 40%/33% cutaneous Merkel cell carcinoma and 100%/100% in parotid gland Merkel cell carcinoma. Five-year recurrence-free interval (RFI)/overall survival (OS) was significantly higher in malignant melanoma (81/80%) than in cutaneous Merkel cell carcinoma/HNSCC. Interestingly, 5-year RFI/OS was significantly higher in Merkel cell carcinoma (61%/79%) than in HNSCC (33%/65%; p Merkel cell carcinoma and parotid gland carcinomas, nor in the immunohistochemical profile. Five-year RFI/OS was significantly better in cutaneous Merkel cell carcinoma when compared with TNM classification matched HNSCC. Five-year RFI/OS was comparable in parotid gland Merkel cell carcinoma and other primary parotid gland malignancies. © 2016 Wiley Periodicals, Inc. Head Neck 39: 92-97, 2017. © 2016 Wiley Periodicals, Inc.

  3. Malnutrition In Patients With Colorectal Carcinoma (Oncologist's Point Of View); Problematika malnutricie u pacientov s kolorektalnym karcinomom (z pohladu onkologa)

    Energy Technology Data Exchange (ETDEWEB)

    Zanova, M. [Oddelenie radiacnej a klinickej onkologie UVN SNP, Ruzomberok (Slovakia)

    2008-07-01

    Colorectal cancer is a worldwide health, social and economic problem. The incidence of malnutrition in patients with colorectal cancer is stated as 54 - 60 %. Primary cachexia is caused by hormonal, metabolic and energetic abnormalities; secondary cachexia is a consequence of functional and anatomic damage to digestive apparatus resulting from a tumor itself or its treatment. Colorectal carcinoma treatment is a complex process involving surgery, radiotherapy and cytostatic treatment. Each treatment modality also brings desirable and undesirable effects and influences patient's nutritional status. Malnutrition worsens patient's overall chances of successful treatment; therefore nutritional support aims to increase his/her anti-infection and antitumor immunity by means of mineral and water industry adjustment as well as by energetic stabilization. (author)

  4. A data management approach to quality assurance using colorectal carcinoma reports from two institutions as a model.

    Science.gov (United States)

    Sorge, John P; Harmon, C Reid; Sherman, Susan M; Baillie, E Eugene

    2005-07-01

    We used data management software to compare pathology report data concerning regional lymph node sampling for colorectal carcinoma from 2 institutions using different dissection methods. Data were retrieved from 2 disparate anatomic pathology information systems for all cases of colorectal carcinoma in 2003 involving the ascending and descending colon. Initial sorting of the data included overall lymph node recovery to assess differences between the dissection methods at the 2 institutions. Additional segregation of the data was used to challenge the application's capability of accurately addressing the complexity of the process. This software approach can be used to evaluate data from disparate computer systems, and we demonstrate how an automated function can enable institutions to compare internal pathologic assessment processes and the results of those comparisons. The use of this process has future implications for pathology quality assurance in other areas.

  5. Tumor-derived circulating endothelial cell clusters in colorectal cancer.

    KAUST Repository

    Cima, Igor; Kong, Say Li; Sengupta, Debarka; Tan, Iain B; Phyo, Wai Min; Lee, Daniel; Hu, Min; Iliescu, Ciprian; Alexander, Irina; Goh, Wei Lin; Rahmani, Mehran; Suhaimi, Nur-Afidah Mohamed; Vo, Jess H; Tai, Joyce A; Tan, Joanna H; Chua, Clarinda; Ten, Rachel; Lim, Wan Jun; Chew, Min Hoe; Hauser, Charlotte; van Dam, Rob M; Lim, Wei-Yen; Prabhakar, Shyam; Lim, Bing; Koh, Poh Koon; Robson, Paul; Ying, Jackie Y; Hillmer, Axel M; Tan, Min-Han

    2016-01-01

    Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor-derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naïve as well as pathological early-stage (≤IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be used as a means of noninvasive screening for colorectal cancer. In contrast to CTCs, tumor-derived endothelial cell clusters may also provide important information about the underlying tumor vasculature at the time of diagnosis, during treatment, and throughout the course of the disease.

  6. Tumor-derived circulating endothelial cell clusters in colorectal cancer.

    KAUST Repository

    Cima, Igor

    2016-06-29

    Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor-derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naïve as well as pathological early-stage (≤IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be used as a means of noninvasive screening for colorectal cancer. In contrast to CTCs, tumor-derived endothelial cell clusters may also provide important information about the underlying tumor vasculature at the time of diagnosis, during treatment, and throughout the course of the disease.

  7. Cytotoxic Activity of Selected Iranian Traditional Medicinal Plants on Colon, Colorectal and Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Leila Mohammad Taghizadeh Kashani

    2014-11-01

    Full Text Available Background: Many natural products from plants have been recognized to exert anticancer activity. In this study, ethanolic extracts of selected medicinal herbs from Iranian flora including Alyssum homolocarpum Fisch. (from seeds, Urtica dioica L. (from aerial parts, Cichorium intybus L. (from roots and Solanum nigrum L. (from fruits, were evaluated for their cytotoxic effect on different cell lines.Methods: Cytotoxic effect of these extracts was studied on three different cancer cell lines; colon carcinoma (HT-29, colorectal adenocarcinoma (Caco-2 and breast ductal carcinoma (T47D. In addition, Swiss mouse embryo fibroblasts (NIH 3T3 were used as normal nonmalignant cells. MTT assay (3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide was utilized for calculating the cytotoxicity of extracts on cell lines.Results: Results showed the potent cytotoxic activity of U. dioica ethanolic extract against T47D cell line with IC50 value of 46.14±4.55 µg/ml. Other extracts showed poor activity with IC50>100 µg/ml.Conclusions: Cytotoxic activity recorded in the present study revealed high potential antiproliferative activity of U. dioica ethanolic extract against T47D cell line. The real IC50 values of this extract may be considerably lower than the IC50 measured in our study if its pharmacological active compounds become pure. The results emphasize the importance of studies on U. dioica ethanolic extract to characterize potential components as cytotoxic natural medicines.

  8. Sub-lethal irradiation of human colorectal tumor cells imparts enhanced and sustained susceptibility to multiple death receptor signaling pathways.

    Directory of Open Access Journals (Sweden)

    Victoria Ifeadi

    Full Text Available BACKGROUND: Death receptors (DR of the TNF family function as anti-tumor immune effector molecules. Tumor cells, however, often exhibit DR-signaling resistance. Previous studies indicate that radiation can modify gene expression within tumor cells and increase tumor cell sensitivity to immune attack. The aim of this study is to investigate the synergistic effect of sub-lethal doses of ionizing radiation in sensitizing colorectal carcinoma cells to death receptor-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The ability of radiation to modulate the expression of multiple death receptors (Fas/CD95, TRAILR1/DR4, TRAILR2/DR5, TNF-R1 and LTβR was examined in colorectal tumor cells. The functional significance of sub-lethal doses of radiation in enhancing tumor cell susceptibility to DR-induced apoptosis was determined by in vitro functional sensitivity assays. The longevity of these changes and the underlying molecular mechanism of irradiation in sensitizing diverse colorectal carcinoma cells to death receptor-mediated apoptosis were also examined. We found that radiation increased surface expression of Fas, DR4 and DR5 but not LTβR or TNF-R1 in these cells. Increased expression of DRs was observed 2 days post-irradiation and remained elevated 7-days post irradiation. Sub-lethal tumor cell irradiation alone exhibited minimal cell death, but effectively sensitized three of three colorectal carcinoma cells to both TRAIL and Fas-induced apoptosis, but not LTβR-induced death. Furthermore, radiation-enhanced Fas and TRAIL-induced cell death lasted as long as 5-days post-irradiation. Specific analysis of intracellular sensitizers to apoptosis indicated that while radiation did reduce Bcl-X(L and c-FLIP protein expression, this reduction did not correlate with the radiation-enhanced sensitivity to Fas and/or TRAIL mediated apoptosis among the three cell types. CONCLUSIONS/SIGNIFICANCE: Irradiation of tumor cells can overcome Fas and TRAIL

  9. Jolkinolide B induces apoptosis of colorectal carcinoma through ROS-ER stress-Ca2+-mitochondria dependent pathway.

    Science.gov (United States)

    Zhang, Jing; Wang, Yang; Zhou, Ye; He, Qing-Yu

    2017-10-31

    Colorectal carcinoma (CRC) remains one of the leading causes of death in cancer-related diseases. In this study, we aimed to investigate the anticancer effect of Jolkinolide B (JB), a bioactive diterpenoid component isolated from the dried roots of Euphorbia fischeriana Steud, on CRC cells and its underlying mechanisms. We found that JB suppressed the cell viability and colony formation of CRC cells, HT29 and SW620. Annexin V/PI assay revealed that JB induced apoptosis in CRC cells, which was further confirmed by the increased expression of cleaved-caspase3 and cleaved-PARP. iTRAQ-based quantitative proteomics was performed to identify JB-regulated proteins in CRC cells. Gene Ontology (GO) analysis revealed that these JB-regulated proteins were mainly involved in ER stress response, which was evidenced by the expression of ER stress marker proteins, HSP90, Bip and PDI. Moreover, we found that JB provoked the generation of reactive oxygen species (ROS), and that inhibition of the ROS generation with N-acetyl L-cysteine could reverse the JB-induced apoptosis. Confocal microscopy and flow cytometry showed that JB treatment enhanced intracellular and mitochondrial Ca 2+ level and JC-1 assay revealed a loss of mitochondrial membrane potential in CRC after JB treatment. The mitochondrial Ca 2+ uptake and depolarization can be blocked by Ruthenium Red (RuRed), an inhibitor of mitochondrial Ca 2+ uniporter. Taken together, we demonstrated that JB exerts its anticancer effect by ER stress-Ca 2+ -mitochondria signaling, suggesting the promising chemotherapeutic potential of JB for the treatment of CRC.

  10. Transcatheter hepatic arterial thermo-chemotherapy and thermo-lipiodol embolization for the treatment of hepatic metastases from colorectal carcinoma

    International Nuclear Information System (INIS)

    Wang Xuan; Chen Xiaofei

    2009-01-01

    Objective: To evaluate the clinical efficacy of transcatheter hepatic arterial thermo-chemotherapy and thermo-lipiodol embolization in the treatment of hepatic metastases from colorectal carcinoma. Methods: Sixty-eight cases with hepatic metastases from colorectal carcinoma were equally and randomly divided into two groups. The patients in study group were treated with transcatheter hepatic arterial thermo-chemotherapy and thermo-lipiodol embolization, while the patients in control group were treated with conventional (normal temperature) transcatheter hepatic arterial chemotherapy lipiodol embolization. Results: The effective rate of study group and control group was 65%(22/34) and 32%(11/34) respectively, the difference between two groups was statistically significant (P<0.05). No significant difference in the postoperative changes of hepatic function tests was found between the two groups. The survival rate at 6,12,18 and 24 months after the treatment was 100%, 82%, 44% and 18% respectively in study group, while it was 91%, 47%, 15% and 6% respectively in control group. Conclusion: Transcatheter hepatic arterial thermo-chemotherapy and thermo-lipiodol embolization is an effective and safe treatment for the hepatic metastases from colorectal carcinoma and has no obvious damage to the hepatic function. (authors)

  11. Metastatic Squamous Cell Carcinoma of the Stomach.

    Science.gov (United States)

    Hamzaoui, Lamine; Bouassida, Mahdi; Kilani, Houda; Medhioub, Mouna; Chelbi, Emna

    2015-11-01

    Primary squamous cell carcinoma of the stomach is very rare. Its pathogenesis is unclear and the treatment strategy is controversial. We report an agressive primary squamous cell carcinoma of the stomach with liver and lung metastases in a 55-year-old man. The patient presented with a 1-month history of abdominal pain, vomiting and weight loss. Abdominal ultrasound revealed multiple liver metastases. Endoscopic examination showed two tumour masses on the fundus of the stomach. Biopsy of the lesions revealed squamous cell carcinoma of the stomach. Chest x-ray showed multiple large pulmonary nodules highly suggestive of pulmonary metastases. The patient died ten days after he was admitted because of progression of the tumour and before any therapeutic decision.

  12. Identification of Prognostic Biomarkers for Progression of Invasive Squamous Cell Carcinoma

    Science.gov (United States)

    2017-10-09

    Carcinoma, Squamous Cell; Carcinoma, Squamous; Squamous Cell Carcinoma; Lung Neoplasms; Cancer of Lung; Cancer of the Lung; Lung Cancer; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms

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

    Directory of Open Access Journals (Sweden)

    Ren-Yi Tang

    2017-01-01

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

  14. Development of radioimmunoconjugate for diagnosis and management of head-and-neck subclinical cancer and colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Raquel Benedetto

    2018-04-01

    Full Text Available ABSTRACT Scientific innovations in diagnostic methods are important drivers of cancer control and prevention. Noninvasive imaging of the epidermal growth factor receptor (EGFR in head-and-neck squamous, cell carcinoma and colorectal cancer could be valuable to select patients for EGFR-targeted therapy, as well as to monitor the efficacy and occurrence of resistance to immunotherapy. In order to develop the first Brazilian radioimmunoconjugate for diagnosis, Cetuximab has been conjugated to p-SCN-Bn-DTPA chelator and radiolabeled with Indium-111. The conjugation methodology was optimized using different mAb:DTPA molar ratios, time was then reduced for immunoconjugate preparation, besides the protein recovery’ percentage increased after purification (m = 83.8 ± 0.91 %. The stability of Cetuximab-DTPA at - 20 oC was evaluated for six months, and its integrity was greater than 90% (m =93.9 ± 1.5%, N = 24. The radioimmunoconjugate with specific activity of 185 MBq/mg showed radiochemical purity above 95% (m=96.8 ± 1.31 %, N = 15. We conclude that the radioimmunoconjugate 111In-DTPA-cetuximab is stable and may be applied to the diagnosis of EGFR-positive tumors.

  15. Merkel Cell Carcinoma Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Merkel cell carcinoma treatment options include surgery, radiation therapy, and chemotherapy. Get detailed information about the diagnosis and treatment of newly diagnosed and recurrent Merkel cell carcinoma in this summary for clinicians.

  16. Disruption of a -35kb enhancer impairs CTCF binding and MLH1 expression in colorectal cells.

    Science.gov (United States)

    Liu, Qing; Thoms, Julie A; Nunez, Andrea C; Huang, Yizhou; Knezevic, Kathy; Packham, Deborah; Poulos, Rebecca C; Williams, Rachel; Beck, Dominik; Hawkins, Nicholas J; Ward, Robyn L; Wong, Jason W H; Hesson, Luke B; Sloane, Mathew A; Pimanda, John

    2018-06-13

    MLH1 is a major tumour suppressor gene involved in the pathogenesis of Lynch syndrome and various sporadic cancers. Despite their potential pathogenic importance, genomic regions capable of regulating MLH1 expression over long distances have yet to be identified. Here we use chromosome conformation capture (3C) to screen a 650-kb region flanking the MLH1 locus to identify interactions between the MLH1 promoter and distal regions in MLH1 expressing and non-expressing cells. Putative enhancers were functionally validated using luciferase reporter assays, chromatin immunoprecipitation and CRISPR-Cas9 mediated deletion of endogenous regions. To evaluate whether germline variants in the enhancer might contribute to impaired MLH1 expression in patients with suspected Lynch syndrome, we also screened germline DNA from a cohort of 74 patients with no known coding mutations or epimutations at the MLH1 promoter. A 1.8kb DNA fragment, 35kb upstream of the MLH1 transcription start site enhances MLH1 gene expression in colorectal cells. The enhancer was bound by CTCF and CRISPR-Cas9 mediated deletion of a core binding region impairs endogenous MLH1 expression. 5.4% of suspected Lynch syndrome patients have a rare single nucleotide variant (G>A; rs143969848; 2.5% in gnomAD European, non-Finnish) within a highly conserved CTCF binding motif, which disrupts enhancer activity in SW620 colorectal carcinoma cells. A CTCF bound region within the MLH1 -35 enhancer regulates MLH1 expression in colorectal cells and is worthy of scrutiny in future genetic screening strategies for suspected Lynch syndrome associated with loss of MLH1 expression. Copyright ©2018, American Association for Cancer Research.

  17. Renal cell carcinoma presenting as mandibular metastasis

    Directory of Open Access Journals (Sweden)

    Hassan Ahmadnia

    2013-01-01

    Full Text Available Renal clear cell carcinoma (RCC has different manifestations, including uncommon metastasis and paraneoplastic syndromes. Here we report a rare case of RCC presenting as metastasis to the mandible. A 57-year-old patient with mandibular swelling was referred to the dentist. After necessary evaluations, an incisional biopsy of mandible showed metastatic RCC. The patient was referred to the urologist. The patient underwent right radical nephrectomy. Pathological examination showed clear renal cell carcinoma. Every abnormal bone lesion in the oral cavity should be evaluated carefully and the possibility of a malignant lesion should always be considered.

  18. Basal Cell Carcinoma Arising in a Tattooed Eyebrow

    Science.gov (United States)

    Lee, Jong-Sun; Park, Jin; Kim, Seong-Min; Kim, Han-Uk

    2009-01-01

    Malignant skin tumors, including squamous cell carcinoma and malignant melanoma, have occurred in tattoos. Seven documented cases of basal cell carcinoma associated with tattoos have also been reported in the medical literature. We encountered a patient with basal cell carcinoma in a tattooed eyebrow. We report on this case as the eighth reported case of a patient with basal cell carcinoma arising in a tattooed area. PMID:20523804

  19. Methylenetetrahydrofolate reductase gene polymorphisms and the risk of colorectal carcinoma in a sample of Egyptian individuals.

    Science.gov (United States)

    El Awady, Mostafa K; Karim, Amr M; Hanna, Laila S; El Husseiny, Lamia A; El Sahar, Medhat; Menem, Hanan A Abdel; Meguid, Nagwa A

    2009-01-01

    The study was planned as a pilot study to investigate two common polymorphisms in the MTHFR gene c.677C > T and c.1298A > C and their association with enhanced risk of colorectal cancer (CRC) in a sample of Egyptian individuals. Venous blood samples were withdrawn from 35 cases of CRC and 68 healthy controls. Specimens from colonic and rectal carcinoma tissues in addition to cancer free tissues were obtained from all cases. Frequencies of MTHFR677T and 1298C alleles were significantly higher among cases of CRC tumor tissues (50% and 56%, respectively) than germ line alleles in CRC patients (33% and 41%, respectively) and healthy controls (21% and 35%, respectively). Frequencies of heterozygous and homoyzgous polymorphisms of MTHFR at positions 677 and 1298 in carcinoma tissues were always the highest. At position 677, TT and CT genotype frequencies were 17% and 66% with an odds ratio {OR} of 11 [95% confidence interval {CI} 2.39-50.59] and OR 8.34 [95%CI 2.97-23.92], respectively, in carcinoma tissues. While in the germ line of patients the genotype frequencies of 677TT and CT were 6% and 54% with OR 1.57 [95%CI 0.26-9.51] and 2.99 [95%CI 1.25-7.12], respectively, compared to controls (6% and 29%, respectively). The combined genotype MTHFR 1298CC + AC frequencies were 86% with OR 3.71 [95%CI 1.28-10.78] in carcinoma tissues, 69% with OR 1.35 [95%CI 0.57-3.21] in germ line of patients and 62% in controls. The combined genotype 677CT plus any of the following genotypes 1298AA, AC or CC enhanced risk of CRC, when comparing germ line DNA polymorphism of patients versus peripheral blood DNA of control subjects with OR 4.5 [95%CI 0.94-21.56], OR 3.12 [95%CI 0.79-12.36] and OR 18 [95%CI 1.56-207.5], respectively, suggesting strong genetic predisposition of certain Egyptian population to CRC. These results suggested that at least one C to T polymorphism at 677MTHFR gene is required to significantly increase the risk for CRC development. Further large scale studies are

  20. Asymptomatic renal cell carcinoma incidentally detected by abdominal CT

    International Nuclear Information System (INIS)

    Yoneda, Fumio; Miyake, Noriaki; Tsujimura, Haruhiro; Nakajima, Mikio; Akiyama, Hajime

    1987-01-01

    Four cases of renal cell carcinoma that were incidentally detected by abdominal CT are reported. Abdominal CT was performed during gastro-intestinal examination in two patients and for suspected liver disease in the other two. No patient had symptoms of renal cell carcinoma, or hematuria. In all cases, the histopathological diagnosis was renal cell carcinoma of a low stage. (author)

  1. Histologic Mimics of Basal Cell Carcinoma.

    Science.gov (United States)

    Stanoszek, Lauren M; Wang, Grace Y; Harms, Paul W

    2017-11-01

    - Basal cell carcinoma (BCC) is the most common human malignant neoplasm and is a frequently encountered diagnosis in dermatopathology. Although BCC may be locally destructive, it rarely metastasizes. Many diagnostic entities display morphologic and immunophenotypic overlap with BCC, including nonneoplastic processes, such as follicular induction over dermatofibroma; benign follicular tumors, such as trichoblastoma, trichoepithelioma, or basaloid follicular hamartoma; and malignant tumors, such as sebaceous carcinoma or Merkel cell carcinoma. Thus, misdiagnosis has significant potential to result in overtreatment or undertreatment. - To review key features distinguishing BCC from histologic mimics, including current evidence regarding immunohistochemical markers useful for that distinction. - Review of pertinent literature on BCC immunohistochemistry and differential diagnosis. - In most cases, BCC can be reliably diagnosed by histopathologic features. Immunohistochemistry may provide useful ancillary data in certain cases. Awareness of potential mimics is critical to avoid misdiagnosis and resulting inappropriate management.

  2. Clinical presentation of renal cell carcinoma

    International Nuclear Information System (INIS)

    Rehman, R.A.; Ashraf, S.; Jamil, N.

    2015-01-01

    Most common malignant tumour of the kidney is Renal Cell Carcinoma (RCC) and is known for its unpredictable clinical behaviour. Aetiology and risk factors are not completely understood. Extensive workup is being done in the understanding of the disease, especially to diagnose early and to treat promptly. The objective of this study was to determine the clinical presentation and pathological pattern of RCC. Methods: After approval from ethical committee a retrospective review of records was conducted extending from January 2012 to January 2014 to identify clinical characteristics of renal cell carcinomas. The study included all renal cancer patients presented to Sheikh Zayed Hospital Lahore with in this specified period. The data was retrieved regarding, history, physical examination and necessary investigations such as ultrasonography of abdomen and pelvis and CT scan of abdomen and pelvis. Results: There were total of 50 cases. The male to female ratio was 3:2. Mean age of patients were 52.38 (18-93) years old. Most common clinical presentation was gross haematuria(66%).The mean tumour size was 8.34 (3-24) cm. Tumour histology were clear cell (84%), papillary transitional cell carcinoma (12%) and oncosytoma contributed 4%. Conclusion: We observed that large number of the patients with RCC presented with haematuria and most of them were male. Common pathological type was clear cell carcinoma. (author)

  3. Usefulness of analytical CEA doubling time and half-life time for overlooked synchronous metastases in colorectal carcinoma.

    Science.gov (United States)

    Ito, Katsuki; Hibi, Kenji; Ando, Hideyuki; Hidemura, Kazuhiko; Yamazaki, Taiji; Akiyama, Seiji; Nakao, Akimasa

    2002-02-01

    Measurement of carcinoembryonic antigen (CEA) has been widely applied to detect recurrence, especially of colorectal carcinoma. The validity however, is still controversial. We investigated serial changes in CEA values to calculate whether the CEA doubling time and half-life time could predict metastatic progression or prognosis in colorectal carcinoma. Pre- and post-operative serial serum CEA contents were determined in 22 cases of colorectal cancer with or without metastasis. CEA values were determined by enzyme immunoassay (EIA). Patients were assigned depending upon survival time (within vs. more than 18 months after primary resection) for assessment of CEA doubling time. From the gradient of the semi-logarithmic CEA graph, the preoperative doubling time was calculated and the postoperative half-life time was estimated according to the diagnosis of metastases within 2 years after primary resection [metastasis (+) or (-)]. In spite of the effect of curative re-operation of metastatic lesions or of postoperative adjuvant chemotherapy, the CEA doubling time of the groups showed a relation with prognosis (p = 0.045, Student's t-test) when the patients were divided into >18 and time. The CEA half-life time of the groups without overlooked metastases was statistically longer than those with (mean +/- SD 8.01 +/- 2.07 and 4.33 +/- 1.11, respectively, p Clearance (k) showed a significant difference between the groups (p time appeared to be a less independent prognostic factor, whereas prolongation of the CEA half-life time might potentially suggest the existence of overlooked synchronous metastases from colorectal carcinoma.

  4. VMP1 related autophagy and apoptosis in colorectal cancer cells: VMP1 regulates cell death

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Qinyi [Department of Ultrasonograph, Changshu No. 2 People’s Hospital, Changshu (China); Zhou, Hao; Chen, Yan [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou (China); Shen, Chenglong [Department of General Surgery, Changshu No. 2 People’s Hospital, Changshu (China); He, Songbing; Zhao, Hua; Wang, Liang [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou (China); Wan, Daiwei, E-mail: 372710369@qq.com [Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou (China); Gu, Wen, E-mail: 505339704@qq.com [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou (China)

    2014-01-17

    Highlights: •This research confirmed VMP1 as a regulator of autophagy in colorectal cancer cell lines. •We proved the pro-survival role of VMP1-mediated autophagy in colorectal cancer cell lines. •We found the interaction between VMP1 and BECLIN1 also existing in colorectal cancer cell lines. -- Abstract: Vacuole membrane protein 1 (VMP1) is an autophagy-related protein and identified as a key regulator of autophagy in recent years. In pancreatic cell lines, VMP1-dependent autophagy has been linked to positive regulation of apoptosis. However, there are no published reports on the role of VMP1 in autophagy and apoptosis in colorectal cancers. Therefore, to address this gap of knowledge, we decided to interrogate regulation of autophagy and apoptosis by VMP1. We have studied the induction of autophagy by starvation and rapamycin treatment in colorectal cell lines using electron microscopy, immunofluorescence, and immunoblotting. We found that starvation-induced autophagy correlated with an increase in VMP1 expression, that VMP1 interacted with BECLIN1, and that siRNA mediated down-regulation of VMP1-reduced autophagy. Next, we examined the relationship between VMP1-dependent autophagy and apoptosis and found that VMP1 down-regulation sensitizes cells to apoptosis and that agents that induce apoptosis down-regulate VMP1. In conclusion, similar to its reported role in other cell types, VMP1 is an important regulator of autophagy in colorectal cell lines. However, in contrast to its role in pancreatic cell lines, in colorectal cancer cells, VMP1-dependent autophagy appears to be pro-survival rather than pro-cell death.

  5. Optical coherence tomography of basal cell carcinoma

    DEFF Research Database (Denmark)

    Yücel, D.; Themstrup, L.; Manfredi, Maddalena

    2016-01-01

    Background: Basal cell carcinoma (BCC) is the most prevalent malignancy in Caucasians. Optical coherence tomography (OCT) is a non-invasive optical imaging technology using the principle of interferometry. OCT has shown a great potential in diagnosing, monitoring, and follow-up of BCC. So far most...

  6. Neglected giant scalp Basal cell carcinoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; El-Charnoubi, Waseem-Asim Ghulam; Gehl, Julie

    2014-01-01

    control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence...

  7. Basal Cell Carcinoma: 10 Years of Experience

    International Nuclear Information System (INIS)

    Cigna, E.; Tarallo, M.; Maruccia, M.; Sorvillo, V.; Pollastrini, A.; Scuderi, N.

    2011-01-01

    Introduction. Basal cell carcinoma (BCC) is a locally invasive malignant epidermal tumour. Incidence is increasing by 10% per year; incidence of metastases is minimal, but relapses are frequent (40%-50%). The complete excision of the BCC allows reduction of relapse. Materials and Methods. The study cohort consists of 1123 patients underwent surgery for basal cell carcinoma between 1999 and 2009. Patient and tumor characteristics recorded are: age; gender; localization (head and neck, trunk, and upper and lower extremities), tumor size, excisional margins adopted, and relapses. Results. The study considered a group of 1123 patients affected by basal cell carcinoma. Relapses occurred in 30 cases (2,67%), 27 out of 30 relapses occurred in noble areas, where peripheral margin was <3mm. Incompletely excised basal cell carcinoma occurred in 21 patients (1,87%) and were treated with an additional excision. Discussion. Although guidelines indicate 3mm peripheral margin of excision in BCC <2cm, in our experience, a margin of less than 5mm results in a high risk of incomplete excisions

  8. Granuloma Inguinale Simulating Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    M Z Mani

    1981-01-01

    Full Text Available A case of extensive granuloma inguinale simulating squamous cell carcinoma is described. There was past history of urethritis leading to a urethral fistula. The ulcer healed almost completely within 19 days of receiving streptomycin injections. The patient had associated scabies and presumably also had latent syphillis (His VDRL was reactive in 1:8 dilution. The patient belonged to Madhya Pradesh.

  9. Basal cell carcinoma on the left cheek

    International Nuclear Information System (INIS)

    Jancar, B.

    2007-01-01

    A 91-year-old female patient was treated with irradiation for histologically confirmed basal cell carcinoma on the left cheek. The tumour, measuring 3 x 3 cm, with the depth of 2 cm, was extending up to the lower lid of the left eye. (author)

  10. Merkel cell carcinoma of the abdominal wall

    International Nuclear Information System (INIS)

    Dunlop, P.; Sapp, H.; Walsh, N.M.G.; Logan, P.M.

    1998-01-01

    Merkel cell carcinoma is a rare highly malignant tumour. There have been previous descriptions of the CT appearances of this tumour, but to our knowledge this is the first MRI description. MRI may be a more sensitive method of initial evaluation of the local extension of the primary tumour. (orig.)

  11. Vulvar basal cell carcinoma, a rare location

    Directory of Open Access Journals (Sweden)

    Cornelia Nitipir

    2018-05-01

    Full Text Available Basal Cell Carcinoma is the most common human malignant neoplasm. Vulvar basal cell carcinoma is rare, accounting for less than 5% of all vulvar neoplasms. Vulvar basal cell carcinomas are usually diagnosed late because they are often asymptomatic and tend to grow at slow rates. They are usually diagnosed late because they are often asymptomatic. However, these tumours may appear in areas which are normally covered with ultraviolet light. We present the case of a 60 years old woman diagnosed with invasive breast cancer for which she underwent surgery followed by chemotherapy and radiotherapy. The patient presented to our department with an ulcerated vulvar lesion. On inspection, the tumour measured 3/2 cm and was located on the left labium majus. The biopsy confirmed the diagnosis of vulvar basal cell carcinoma and a wide local excision was performed with no relapse at one year. In conclusion, early detection of BCC’s is critical to allow complete surgical cure so any abnormality on the vulva should be biopsied. A wide safety margin of 1cm should be achieved when resecting the tumour and the physician should keep in mind that the BCC’s of the vulva has a high recurrence rate. Previous chemotherapy is not associated with this type of non-melanoma skin cancer.

  12. Cardiac Metastasis in Renal Cell Carcinoma

    African Journals Online (AJOL)

    abp

    2015-10-21

    Oct 21, 2015 ... Metastatic disease of the heart is over twenty times more common than primary heart tumors [1]. They are among the least known and highly debated issues in oncology, and few systematic studies are devoted to this topic. Cardiac involvement in renal cell carcinoma (RCC) commonly arises from direct ...

  13. Squamous cell carcinoma in bladder extrophy

    OpenAIRE

    Cabral-Ribeiro, J; Silva, C; Sousa, L; Pérez García, D; Ribeiro dos Santos, A

    2005-01-01

    Bladder extrophy is a rare congenital malformation that nowadays is surgically corrected in neonatal period. We present a case report of a 71-year-old male with a verrucous squamous cell carcinoma arising in a classical uncorrected form of bladder extrophy.

  14. Presumed choroidal metastasis of Merkel cell carcinoma

    International Nuclear Information System (INIS)

    Small, K.W.; Rosenwasser, G.O.; Alexander, E. III; Rossitch, G.; Dutton, J.J.

    1990-01-01

    Merkel cell carcinoma is a rare skin tumor of neural crest origin and is part of the amine precursor uptake and decarboxylase system. It typically occurs on the face of elderly people. Distant metastasis is almost uniformly fatal. Choroidal metastasis, to our knowledge, has not been described. We report a patient with Merkel cell carcinoma who had a synchronous solid choroidal tumor and a biopsy-proven brain metastasis. Our 56-year-old patient presented with a rapidly growing, violaceous preauricular skin tumor. Computed tomography of the head disclosed incidental brain and choroidal tumors. Light and electron microscopy of biopsy specimens of both the skin and the brain lesions showed Merkel cell carcinoma. Ophthalmoscopy, fluorescein angiography, and A and B echography revealed a solid choroidal mass. The brain and skin tumors responded well to irradiation. A radioactive episcleral plaque was applied subsequently to the choroidal tumor. All tumors regressed, and the patient was doing well 28 months later. To our knowledge this is the first case of presumed choroidal metastasis of Merkel cell carcinoma

  15. Merkel cells carcinoma of the aged patient

    International Nuclear Information System (INIS)

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

    2009-01-01

    The carcinoma at Merkel cells is a rare and aggressive skin cancer, principally of the aged adult. The surgery is the fundamental treatment. The interest of the adjuvant radiotherapy is discussed for the aged patient. In the limits of this retrospective analysis, the postoperative radiotherapy appeared to bring a similar benefit as for younger patients. (N.C.)

  16. CT differentiation of renal tumor invading parenchyma and pelvis: renal cell carcinoma vs transitional cell carcinoma

    International Nuclear Information System (INIS)

    Lee, Chang Hee; Cho, Seong Beum; Park, Cheol Min; Cha, In Ho; Chung, Kyoo Byung

    1994-01-01

    The differentiation between renal cell carcinoma(RCC) and transitional cell carcinoma(TCC) is important due to the different methods of treatment and prognosis. But occasionally it is difficult to draw a distinction between the two diseases when renal parenchyma and renal collecting systems are invaded simultaneously. We reviewed CT scans of 37 cases of renal cell carcinoma and 12 cases of transitional cell carcinoma which showed involvement of renal parenchyma and renal sinus fat on CT. Retrospective analysis was performed by 3 abdominal radiologists. Check points were renal contour bulging or reinform shape, location of mass center, intact parenchyma overlying the tumor, cystic change, calcification, LN metastasis, vessel invasion, and perirenal extention. There were renal contour bulging due to the tumor mass in 33 out of 37 cases of renal cell carcinoma, where a and nine of 12 cases of transitional cell carcinoma maintained the reinform appearance. This is significant statiscal difference between the two(P<0.005). Center of all TCCs were located in the renal sinus, and 24 out of 35 cases of RCC were located in the cortex(P<0.005). Thirty-six out of 37 cases of RCC lost the overlying parenchyma, where as 4 out of 9 cases of well enhanced TCC had intact overlying parenchyma(P<0.005) RCC showed uptic change within the tumor mags in 31 cases which was significanity higher than the 4 cases in TCC(P<0.05). CT findings of renal cell carcinoma are contour bulging, peripheral location, obliteration of parenchyma, and cystic change. Findings of transitional cell carcinoma are reinform appearance, central location within the kidney, intact overlying parenchyma, and rare cystic change

  17. Influence of inhibitors of serotonin uptake on intestinal epithelium and colorectal carcinomas.

    Science.gov (United States)

    Tutton, P J; Barkla, D H

    1982-08-01

    Previous studies have shown that in certain tissues, including colonic carcinomas, cell proliferation may be promoted by serotonin, and indirect evidence suggests that the effects of this amine on colonic tumours involves a cellular-uptake mechanism. In the present study, two specific inhibitors of serotonin uptake, Citalopram and Fluoxetine, are examined for their effects on cell proliferation and tumour growth. Each of the agents was found to suppress cell division in dimethylhydrazine-induced colonic tumours in rats, and to retard the growth of 2 out of 3 lines of human colonic tumours propagated as xenografts in immune-deprived mice.

  18. Psychologic distress after disclosure of genetic test results regarding hereditary nonpolyposis colorectal carcinoma.

    Science.gov (United States)

    Murakami, Yoshie; Okamura, Hitoshi; Sugano, Kokichi; Yoshida, Teruhiko; Kazuma, Keiko; Akechi, Tatsuo; Uchitomi, Yosuke

    2004-07-15

    To the authors' knowledge, there have been few studies of the psychologic distress after disclosure of genetic test results for hereditary nonpolyposis colorectal carcinoma (HNPCC). The objectives of this study were to identify the prevalence rates and predictors of psychologic distress and to evaluate the feelings of guilt after disclosure of the test results in Japanese probands and unaffected relatives. Probands and unaffected relatives were interviewed immediately after the first genetic counseling session for HNPCC and again 1 month after disclosure of the genetic test results. The prevalence of major and minor depression, acute stress disorder (ASD), posttraumatic stress disorder (PTSD), and posttraumatic stress symptoms (PTSS) were assessed using the Structured Clinical Interview based on the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition revised (DSM-III-R) or the DSM-IV; feelings of guilt were investigated using a numeric scale and a semistructured interview. Among 47 participants who completed the baseline interview, 42 participants (89%) completed the 1-month follow-up interview. Although none of the participants met the criteria for major depression, ASD, or PTSD at the follow-up interview, 3 of 42 participants (7%) met the criteria for minor depression and 2 participants (5%) had PTSS. The only predictor of psychologic distress found was the presence of a history of major or minor depression (odds ratio, 19.41; 95% confidence interval, 1.42-264.95; P depression and PTSS. Copyright 2004 American Cancer Society.

  19. Linc-POU3F3 is overexpressed in hepatocellular carcinoma and regulates cell proliferation, migration and invasion.

    Science.gov (United States)

    Li, Yichun; Li, Yannan; Wang, Dan; Meng, Qingdong

    2018-06-12

    Linc-POU3F3 showed an up-regulated tendency and functioned as tumor promoter in glioma, esophageal cancer and colorectal cancer. There was no report about the expression pattern and clinical value of linc-POU3F3 in hepatocellular carcinoma. Thus, the purpose of our study is to explore the clinical significance and biological role of linc-POU3F3 in hepatocellular carcinoma. Our results suggested that levels of linc-POU3F3 were dramatically increased in hepatocellular carcinoma tissues and cell lines compared with paired normal hepatic tissues and normal hepatic cell line, respectively. Levels of linc-POU3F3 were positively correlated with clinical stage, tumor size, vascular invasion and metastasis. Moreover, high-expression of linc-POU3F3 was an independent prognostic factor for hepatocellular carcinoma patients. The gain- and loss-of-function experiments showed that linc-POU3F3 expression significantly promoted tumor cell proliferation, migration and invasion. In addition, linc-POU3F3 expression was negatively correlated with POU3F3 mRNA and protein expressions in hepatocellular carcinoma tissues, and negatively regulated POU3F3 mRNA and protein expressions in hepatocellular carcinoma cells. In conclusion, our study supports the first evidence that linc-POU3F3 plays an oncogenic role in hepatocellular carcinoma, and represents a potential therapeutic strategy for hepatocellular carcinoma patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  20. Squamous cell carcinoma of the breast: a case report

    Directory of Open Access Journals (Sweden)

    Hofstee Mans

    2008-12-01

    Full Text Available Abstract Background Squamous cells are normally not found inside the breast, so a primary squamous cell carcinoma of the breast is an exceptional phenomenon. There is a possible explanation for these findings. Case presentation A 72-year-old woman presented with a breast abnormality suspected for breast carcinoma. After the operation the pathological examination revealed a primary squamous cell carcinoma of the breast. Conclusion The presentation of squamous cell carcinoma could be similar to that of an adenocarcinoma. However, a squamous cell carcinoma of the breast could also develop from a complicated breast cyst or abscess. Therefore, pathological examination of these apparent benign abnormalities is mandatory.

  1. Paeoniflorin inhibits cell growth and induces cell cycle arrest through inhibition of FoxM1 in colorectal cancer cells.

    Science.gov (United States)

    Yue, Meng; Li, Shiquan; Yan, Guoqiang; Li, Chenyao; Kang, Zhenhua

    2018-01-01

    Paeoniflorin (PF) exhibits tumor suppressive functions in a variety of human cancers. However, the function of PF and molecular mechanism in colorectal cancer are elusive. In the present study, we investigated whether PF could exert its antiproliferative activity, anti-migration, and anti-invasive function in colorectal cancer cells. We found that PF inhibited cell growth and induced apoptosis and blocked cell cycle progression in the G0/G1 phase in colorectal cancer cells. Moreover, we found that PF suppressed cell migration and invasion in colorectal cancer cells. FoxM1 has been reported to play an important oncogenic role in human cancers. We also determine whether PF inhibited the expression of FoxM1, leading to its anti-cancer activity. We found that PF treatment in colorectal cancer cells resulted in down-regulation of FoxM1. The rescue experiments showed that overexpression of FoxM1 abrogated the tumor suppressive function induced by PF treatment. Notably, depletion of FoxM1 promoted the anti-tumor activity of PF in colorectal cancer cells. Therefore, inhibition of FoxM1 could participate in the anti-tumor activity of PF in colorectal cancer cells.

  2. Cutaneous metastasis of bilateral renal cell carcinoma.

    Science.gov (United States)

    Abbasi, Fariba; Alizadeh, Mansur; Noroozinia, Farahnaz; Moradi, Amin

    2013-01-01

    Renal cell carcinoma (RCC) is a malignant lethal tumour with high potential of metastasis. However, metastasis from RCC to the skin is much less common. It is virtually a sign of poor prognosis. We represent a 42 years old man with bilateral RCC of clear cell type followed by metastasis to the scalp one month later. In this case the relatively young age of the patient, bilaterality of RCC and occurance of skin metastasis in the absence of recurrent kidney tumour are interesting.

  3. Response rates of hepatocellular carcinoma and hepatic colorectal cancer metastases to drug eluting bead regional liver therapy

    Institute of Scientific and Technical Information of China (English)

    Glenn W. Stambo; Deborah Cragan

    2017-01-01

    Aim: The purpose of this study was to evaluate and compare how hepatocellular carcinoma (HCC) and colorectal metastases respond to LC Bead chemoembolization using doxorubicin and irinotecan. Methods: The authors report their experience with doxorubicin and irinotecan eluting beads to treat 13 patients with primary HCC and 25 patients with colorectal metastases over a 1-year period at a single community based oncology practice. Within the colorectal cancer group they compared irinotecan eluting beads to doxorubicin eluting beads. Results:Nine of the 11 (81.8%) doxorubicin treated HCC patients had either complete response or partial response. All of the HCC lesions showed reduction in size and tumor enhancement and 10/11 (91%) HCC patients were alive at 24 months post treatment. Fisher's exact test revealed that among the 22 with colorectal metastases for whom follow-up data were available, those 11 who were treated with doxorubicin were significantly more likely to demonstrate complete or partial response compared to the 11 in the irinotecan treated group (P < 0.001). Conclusion:Overall, HCC and colon metastasis patients clearly demonstrated the effectiveness of drug eluting beads with 91% of the HCC patients alive 24 months after treatment.

  4. MSI-Testing in Hereditary Non-Polyposis Colorectal Carcinoma (HNPCC

    Directory of Open Access Journals (Sweden)

    Annegret Müller

    2004-01-01

    Full Text Available Genomic instability at simple repeated sequences, termed microsatellite instability (MSI, plays an important role in the analysis of sporadic and hereditary colon cancers. In hereditary non-polyposis colorectal cancer syndrome (HNPCC more than 90% of cases show MSI, whereas only 10–15% of sporadic colorectal cancers do so. Thus, microsatellite analysis is commonly used as the first diagnostic screening test for HNPCC. In 1997, an international collaborative workshop sponsored by the National Cancer Institute (NCI proposed a set of guidelines for MSI-testing to improve reliability and reproducibility of the analysis as well to allow comparisons between different studies and different laboratories. In this review we assess the value of current protocols forMSI-testing and discuss some diagnostic pitfalls. Our findings support continued use of the MSI marker panel recommended in 1997. Additionally, MSI-testing should be improved by use of microdissection, which helps to identify additional patients with MSI due to enrichment of tumor cells and therefore increased sensitivity. In our view, immunohistochemical staining for mismatch repair protein expression is not a substitute for MSI-analysis but complements MSI screening and helps direct further testing. In summary, MSI-analysis is a highly sensitive and reliable screening method for HNPCC, that requires a well-equipped laboratory as well as an experienced pathologist. Integration of family history and histo-pathological features is also critical.

  5. Physcion induces mitochondria-driven apoptosis in colorectal cancer cells via downregulating EMMPRIN.

    Science.gov (United States)

    Chen, Xuehong; Gao, Hui; Han, Yantao; Ye, Junli; Xie, Jing; Wang, Chunbo

    2015-10-05

    Physcion, an anthraquinone derivative widely isolated and characterized from both terrestrial and marine sources, has anti-tumor effects on a variety of carcinoma cells, mainly through inhibition of cell proliferation, apoptosis induction and cell cycle arrest. However, little is known about the mechanisms underlying its role in tumor progression. In the present study, we investigated the molecular mechanisms involved in physcion-induced apoptosis in human colorectal cancer (CRC) lines HCT116. Our results showed that physcion inhibited tumor cell viability in a dose- and time-dependent manner, and induced cell apoptosis via intrinsic mitochondrial pathway. Our results also revealed that physcion treatment significantly inhibited extracelluar matrix metalloproteinase inducer (EMMPRIN) expression in HCT116 cells in a dose-dependent manner and overexpression of EMMPRIN protein markedly reduced physcion-induced cell apoptosis. Furthermore, our results strongly indicated the modulating effect of physcion on EMMPRIN is correlated with AMP-activated protein kinase (AMPK)/Hypoxia-inducible factor 1α (HIF-1α) signaling pathway. Our data provide the first experimental evidence that physcion induces mitochondrial apoptosis in CRC cells by downregulating of EMMPRIN via AMPK/HIF-1α signaling pathway and suggest a new mechanism to explain its anti-tumor effects. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Diagnostic accuracy and cost-effectiveness of FDG-PET in recurrent colorectal carcinoma. An analysis based on the results of questionnaire

    International Nuclear Information System (INIS)

    Ito, Kengo; Kato, Takashi; Inagaki, Hiroshi

    2000-01-01

    This study was done by the PET working group under Japan Radioisotope Association. The usefulness of [ 18 F]fluorodeoxyglucose (FDG)-PET in detecting local recurrence of colorectal carcinoma was investigated retrospectively, by the results of questionnaire. Six institutions participated in this study. One hundred and four cases were analyzed to calculate the diagnostic accuracy. The accuracy of FDG-PET in detecting local recurrence of colorectal carcinoma was 96.2%, with two false positive and two false negative cases. We also evaluated the cost-effectiveness of FDG-PET in staging recurrent colorectal carcinoma based on the results of questionnaire. FDG-PET reduced unnecessary radical surgery by 50% in comparison with that in the conventional protocol without PET, and the net savings were about 6.6 billion yen per year in Japan. (author)

  7. Effects of polymorphisms in ERCC1, ASE-1 and RAI on the risk of colorectal carcinomas and adenomas: a case control study

    International Nuclear Information System (INIS)

    Skjelbred, Camilla F; Sæbø, Mona; Nexø, Bjørn A; Wallin, Håkan; Hansteen, Inger-Lise; Vogel, Ulla; Kure, Elin H

    2006-01-01

    The risk of sporadic colorectal cancer is mainly associated with lifestyle factors and may be modulated by several genetic factors of low penetrance. Genetic variants represented by single nucleotide polymorphisms in genes encoding key players in the adenoma carcinoma sequence may contribute to variation in susceptibility to colorectal cancer. In this study, we aimed to evaluate whether the recently identified haplotype encompassing genes of DNA repair and apoptosis, is associated with increased risk of colorectal adenomas and carcinomas. We used a case-control study design (156 carcinomas, 981 adenomas and 399 controls) to test the association between polymorphisms in the chromosomal region 19q13.2-3, encompassing the genes ERCC1, ASE-1 and RAI, and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR) and 95% confidence interval (CI) were estimated by binary logistic regression model adjusting for age and gender. The ASE-1 polymorphism was associated with an increased risk of adenomas, OR of 1.39 (95% CI 1.06–1.81), which upon stratification was apparent among women only, OR of 1.66 (95% CI 1.15–2.39). The RAI polymorphism showed a trend towards risk reduction for both adenomas (OR of 0.70, 95% CI 0.49–1.01) and carcinomas (OR of 0.49, 95% CI 0.21–1.13) among women, although not significant. Women who were homozygous carriers of the high risk haplotype had an increased risk of colorectal cancer, OR of 2.19 (95% CI 0.95–5.04) compared to all non-carriers although the estimate was not statistically significant. We found no evidence that the studied polymorphisms were associated with risk of adenomas or colorectal cancer among men, but we found weak indications that the chromosomal region may influence risk of colorectal cancer and adenoma development in women

  8. IL-15 Overcomes Hepatocellular Carcinoma-Induced NK Cell Dysfunction

    Directory of Open Access Journals (Sweden)

    Nicholas J. W. Easom

    2018-05-01

    Full Text Available NK cells have potent antitumor capacity. They are enriched in the human liver, with a large subset specialized for tissue-residence. The potential for liver-resident versus liver-infiltrating NK cells to populate, and exert antitumor functions in, human liver tumors has not been studied. We examined liver-resident and liver-infiltrating NK cells directly ex vivo from human hepatocellular carcinomas (HCCs and liver colorectal (CRC metastases, compared with matched uninvolved liver tissue. We found that NK cells were highly prevalent in both HCC and liver CRC metastases, although at lower frequencies than unaffected liver. Up to 79% of intratumoral NK cells had the CXCR6+CD69+ liver-resident phenotype. Direct ex vivo staining showed that liver-resident NK cells had increased NKG2D expression compared to their non-resident counterparts, but both subsets had NKG2D downregulation within liver tumors compared to uninvolved liver. Proliferation of intratumoral NK cells (identified by Ki67 was selectively impaired in those with the most marked NKG2D downregulation. Human liver tumor NK cells were functionally impaired, with reduced capacity for cytotoxicity and production of cytokines, even when compared to the hypo-functional tissue-resident NK cells in unaffected liver. Coculture of human liver NK cells with the human hepatoma cell line PLC/PRF/5, or with autologous HCC, recapitulated the defects observed in NK cells extracted from tumors, with downmodulation of NKG2D, cytokine production, and target cell cytotoxicity. Transwells and conditioned media confirmed a requirement for cell contact with PLC/PRF/5 to impose NK cell inhibition. IL-15 was able to recover antitumor functionality in NK cells inhibited by in vitro exposure to HCC cell lines or extracted directly from HCC. In summary, our data suggest that the impaired antitumor function of local NK cells reflects a combination of the tolerogenic features inherent to liver-resident NK cells

  9. Reevaluation and reclassification of resected lung carcinomas originally diagnosed as squamous cell carcinoma using immunohistochemical analysis

    Science.gov (United States)

    Kadota, Kyuichi; Nitadori, Jun-ichi; Rekhtman, Natasha; Jones, David R.; Adusumilli, Prasad S.; Travis, William D.

    2015-01-01

    Currently, non-small cell lung carcinomas are primarily classified by light microscopy. However, recent studies have shown that poorly-differentiated tumors are more accurately classified by immunohistochemistry. In this study, we investigated the use of immunohistochemical analysis in reclassifying lung carcinomas that were originally diagnosed as squamous cell carcinoma. Tumor slides and blocks were available for histologic evaluation, and tissue microarrays were constructed from 480 patients with resected lung carcinomas originally diagnosed as squamous cell carcinoma between 1999 and 2009. Immunohistochemistry for p40, p63, thyroid transcription factor-1 (TTF-1; clone SPT24 and 8G7G3/1), Napsin A, Chromogranin A, Synaptophysin, and CD56 were performed. Staining intensity (weak, moderate, or strong) and distribution (focal or diffuse) were also recorded. Of all, 449 (93.5%) patients were confirmed as having squamous cell carcinomas; the cases were mostly diffusely positive for p40 and negative for TTF-1 (8G7G3/1). Twenty cases (4.2%) were reclassified as adenocarcinoma since they were positive for TTF-1 (8G7G3/1 or SPT24) with either no or focal p40 expression, and all of them were poorly-differentiated with squamoid morphology. In addition, 1 case was reclassified as adenosquamous carcinoma, 4 cases as large cell carcinoma, 4 cases as large cell neuroendocrine carcinoma, and 2 cases as small cell carcinoma. In poorly-differentiated non-small cell lung carcinomas, an accurate distinction between squamous cell carcinoma and adenocarcinoma cannot be reliably determined by morphology alone and requires immunohistochemical analysis, even in resected specimens. Our findings suggest that TTF-1 8G7G3/1 may be better suited as the primary antibody in differentiating adenocarcinoma from squamous cell carcinoma. PMID:25871623

  10. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    Science.gov (United States)

    Barkla, D H; Whitehead, R H; Foster, H; Tutton, P J

    1988-09-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting from the apical surface. The microvilli are attached by a core of long microfilaments passing deep into the apical cytoplasm. Between the microvilli are parallel arrays of vesicles (caveoli) containing flocculent material. Two different but not mutually exclusive explanations for the presence of tuft cells are proposed. The first explanation is that tuft cells came from the resected tumour and have survived by mitotic division during subsequent passages. The second explanation suggests that tuft cells are the progeny of undifferentiated tumour cells. Descriptions of tuft cells in colon carcinomas are uncommon and possible reasons for this are presented. The morphology of tuft cells is consistent with that of a highly differentiated cell specialised for absorption, and these new models provide an opportunity to further investigate the structure and function of tuft cells.

  11. Late pancreatic metastasis of renal cell carcinoma with absence of FDG-uptake in PET-CT

    Directory of Open Access Journals (Sweden)

    Elif Karadeli

    2016-03-01

    Full Text Available The primary tumors, which raise isolated pancreas metastases are frequently of renal origin, where colorectal cancer, melanoma, breast and lung cancers and sarcoma are the following causes of metastatic pancreas cancer . In this article, we present a case of pancreas-metastatic renal cell carcinoma with its radiological features, which did not exert anF-18 FDG-uptake in the whole-body positron emission tomography (PET. [Cukurova Med J 2016; 41(0.100: 92-94

  12. Nodular intra-abdominal panniculitis: an accompaniment of colorectal carcinoma and diverticular disease

    DEFF Research Database (Denmark)

    Bak, Martin

    1996-01-01

    should not be regarded as a specific nosological entity but merely a result of injury to the fat cells. Intra-abdominal panniculitis is seen more often as a secondary local phenomenon than as a primary condition, and in both cases it is associated with considerable differential diagnostic problems......Intra-abdominal panniculitis is a tumour-like inflammatory condition of adipose tissue. The aetiology and pathogenesis of the disease is unknown, but a number of associated diseases have been recorded. It has been customary to deal with only primary cases in the literature. This study...... was undertaken in order to describe the entire spectrum of the disease including primary as well as secondary cases. Eleven patients are reported, nine of which had an associated colorectal disease in direct continuity with areas of intra-abdominal panniculitis. It is concluded that intra-abdominal panniculitis...

  13. Advanced colorectal adenoma related gene expression signature may predict prognostic for colorectal cancer patients with adenoma-carcinoma sequence

    OpenAIRE

    Li, Bing; Shi, Xiao-Yu; Liao, Dai-Xiang; Cao, Bang-Rong; Luo, Cheng-Hua; Cheng, Shu-Jun

    2015-01-01

    Background: There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. Methods: All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinform...

  14. Immunisation of colorectal cancer patients with autologous tumour cells

    DEFF Research Database (Denmark)

    Diederichsen, Alice; Stenholm, Anna Catharina Olsen; Kronborg, O

    1998-01-01

    Patients with colorectal cancer were entered into a clinical phase I trial of immunotherapy with an autologous tumour cell/bacillus Calmette-Guerin (BCG) vaccine. We attempted to describe the possible effects and side effects of the immunisation, and further to investigate whether expression...... of immune-response-related surface molecules on the tumour cells in the vaccine correlated with survival. The first and second vaccine comprised of 107 irradiated tumour cells mixed with BCG, the third of irradiated tumour cells only. Thirty-nine patients were considered, but only 6 patients fulfilled...... the criteria for inclusion. No serious side effects were observed. With three years of observation time, two patients are healthy, while the rest have had recurrence, and two of them have died. In all vaccines, all tumour cells expressed HLA class I, some expressed HLA class II and none expressed CD80...

  15. NSAIDs and Cell Proliferation in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Raj Ettarh

    2010-06-01

    Full Text Available Colon cancer is common worldwide and accounts for significant morbidity and mortality in patients. Fortunately, epidemiological studies have demonstrated that continuous therapy with NSAIDs offers real promise of chemoprevention and adjunct therapy for colon cancer patients. Tumour growth is the result of complex regulation that determines the balance between cell proliferation and cell death. How NSAIDs affect this balance is important for understanding and improving treatment strategies and drug effectiveness. NSAIDs inhibit proliferation and impair the growth of colon cancer cell lines when tested in culture in vitro and many NSAIDs also prevent tumorigenesis and reduce tumour growth in animal models and in patients, but the relationship to inhibition of tumour cell proliferation is less convincing, principally due to gaps in the available data. High concentrations of NSAIDs are required in vitro to achieve cancer cell inhibition and growth retardation at varying time-points following treatment. However, the results from studies with colon cancer cell xenografts are promising and, together with better comparative data on anti-proliferative NSAID concentrations and doses (for in vitro and in vivo administration, could provide more information to improve our understanding of the relationships between these agents, dose and dosing regimen, and cellular environment.

  16. RENAL MALIGNANT NEOPLASMS: RENAL CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Elisangela Giachini

    2017-06-01

    Full Text Available The aim of this study is to evaluate the incidence and prevalence of malignant kidney tumors, to contribute to identifying factors which the diagnosis of renal cell carcinomas. Through this study, we understand that kidney disease over the years had higher incidence rates, especially in adults in the sixth decade of life. The renal cell carcinoma (RCC is the third most common malignancy of the genitourinary tract, affecting 2% to 3% of the population. There are numerous ways of diagnosis; however, the most important are ultrasonography, magnetic resonance imaging and computed tomography. In general most of the patients affected by the CCR, have a good prognosis when diagnosed early and subjected to an effective treatment. This study conducted a literature review about the CCR, through this it was possible to understand the development needs of the imaging methods used for precise diagnosis and classification of RCC through the TNM system.

  17. Association between cigarette smoking, APC mutations and the risk of developing sporadic colorectal adenomas and carcinomas

    International Nuclear Information System (INIS)

    Sæbø, Mona; Skjelbred, Camilla F; Breistein, Rebecca; Lothe, Inger Marie B; Hagen, Per Chr; Bock, Gunter; Hansteen, Inger-Lise; Kure, Elin H

    2006-01-01

    The association between colorectal cancer (CRC) and smoking has not been consistent. Incomplete smoking history and association to a specific subset of CRC tumors have been proposed as explanations. The adenomatous polyposis coli (APC) gene has been reported to have a 'gatekeeper' function in the colonic mucosa. To evaluate the hypothesis that cigarette smoking is associated with adenoma and carcinoma development and further to investigate whether this association is due to mutations in the APC gene, we used a study population consisting of 133 cases (45 adenomas and 88 carcinomas) and 334 controls. All tumors were sequenced in the mutation cluster region (MCR) of the APC gene. Cases and controls were drawn from a homogeneous cohort of Norwegian origin. The mutational spectra of the APC gene revealed no difference in frequencies of mutations in cases based on ever and never smoking status. An overall case-control association was detected for adenomas and 'ever smoking' OR = 1.73 (95% CI 0.83–3.58). For CRC cases several smoking parameters for dose and duration were used. We detected an association for all smoking parameters and 'duration of smoking > 30 years', yielded a statistically significant OR = 2.86 (1.06–7.7). When cases were divided based on APC truncation mutation status, an association was detected in adenomas without APC mutation in relation to 'ever smoking', with an OR = 3.97 (1.26–12.51). For CRC cases without APC mutation 'duration of smoking > 30 years', yielded a statistically significant OR = 4.06 (1.20–13.7). The smoking parameter 'starting smoking ≥ 40 years ago' was only associated with CRC cases with APC mutations, OR = 2.0 (0.34–11.95). A case-case comparison revealed similar findings for this parameter, OR = 2.24 (0.73–6.86). Our data suggest an association between smoking and adenoma and CRC development. This association was strongest for cases without APC truncation

  18. Neuroendocrine Differentiation in Sporadic CRC and Hereditary Nonpolyosis Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    M. H. Sun

    2004-01-01

    Full Text Available Extent neuroendocrine differentiation can be encountered in many human neoplasm derived from different organs and systems using immunohistochemistry and ultrastructural techniques. The tumor cells' behaviors resemble those of neurons and neuroendocrine cells. The presence of neuroendocrine differentiation reputedly appears to be associated with a poorer prognosis than the adenocarcinoma counterparts in sporadic human neoplasm. In this review the neuroendocrine carcinoma and the adenocarcinoma with neuroendocrine differentiation of colon and rectum both in sporadic colorectal carcinoma and the hereditary nonpolyposis colorectal cancer, the relationship of neuroendocrine differentiation and some possible molecular pathways in tumorogenesis of colorectal cancer will be discussed. Possible treatment strategy will also be addressed.

  19. Squamous cell carcinoma in situ after irradiation

    International Nuclear Information System (INIS)

    Kambara, Takeshi; Nishiyama, Takafumi; Yamada, Rie; Nagatani, Tetsuo; Nakajima, Hiroshi; Sugiyama, Asami

    1997-01-01

    We report two cases with Squamous Cell Carcinoma (SCC) in situ caused by irradiation to hand eczemas, resistant to any topical therapies. Both of our cases clinically show palmer sclerosis and flexor restriction of the fingers, compatible to chronic radiation dermatitis. Although SCC arising in chronic radiation dermatitis is usually developed ten to twenty years after irradiation, in our cases SCC were found more than forty years after irradiation. (author)

  20. Linear Basal Cell Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Yuko Ichinokawa

    2011-07-01

    Full Text Available Basal cell carcinoma (BCC presents with diverse clinical features, and several morphologic and histologic variants of BCC have been reported [Sexton et al.: J Am Acad Dermatol 1990;23:1118–1126]. Linear BCC was first described as a new clinical subtype in 1985 by Lewis [Int J Dematol 1985;24:124–125]. Here, we present a case of linear BCC that we recently encountered in an elderly Japanese patient, and review other cases reported in Japan.

  1. Avelumab Impresses in Merkel Cell Carcinoma.

    Science.gov (United States)

    2017-06-01

    The PD-L1 inhibitor avelumab-approved by the FDA in March for the treatment of Merkel cell carcinoma-demonstrated a high number of durable responses in an international, open-label, prospective phase II study. The results of the study, which supported the FDA's decision, were presented in April at the American Association for Cancer Research (AACR) Annual Meeting 2017. ©2017 American Association for Cancer Research.

  2. Papillary renal cell carcinoma in allograft kidney

    International Nuclear Information System (INIS)

    Roy, Catherine; El Ghali, Sofiane; Buy, Xavier; Gangi, Afshin; Lindner, Veronique

    2005-01-01

    Papillary renal cell carcinoma is a subgroup of malignant renal epithelial neoplasms. Its occurrence in allograft transplanted kidney has not been debated in the literature. We report two pathologically proven cases and discuss the clinical hypothesis for such neoplasms and the aspect on MR images. The paramagnetic effect of the iron associated with an absence of signal coming from calcifications is a plausible explanation for this unusual hypointense appearance on T2-weighted sequence. (orig.)

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Swetha Gudiseva

    2017-03-01

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

  5. HSP60, a protein downregulated by IGFBP7 in colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Lin Jie

    2010-04-01

    Full Text Available Abstract Background In our previous study, it was well defined that IGFBP7 was an important tumor suppressor gene in colorectal cancer (CRC. We aimed to uncover the downstream molecules responsible for IGFBP7's behaviour in this study. Methods Differentially expressed protein profiles between PcDNA3.1(IGFBP7-transfected RKO cells and the empty vector transfected controls were generated by two-dimensional gel electrophoresis (2-DE and mass spectrometry (MS identification. The selected differentially expressed protein induced by IGFBP7 was confirmed by western blot and ELISA. The biological behaviour of the protein was explored by cell growth assay and colony formation assay. Results Six unique proteins were found differentially expressed in PcDNA3.1(IGFBP7-transfected RKO cells, including albumin (ALB, 60 kDa heat shock protein(HSP60, Actin cytoplasmic 1 or 2, pyruvate kinase muscle 2(PKM2, beta subunit of phenylalanyl-tRNA synthetase(FARSB and hypothetical protein. The downregulation of HSP60 by IGFBP7 was confirmed by western blot and ELISA. Recombinant human HSP60 protein could increase the proliferation rate and the colony formation ability of PcDNA3.1(IGFBP7-RKO cells. Conclusion HSP60 was an important downstream molecule of IGFBP7. The downregulation of HSP60 induced by IGFBP7 may be, at least in part, responsible for IGFBP7's tumor suppressive biological behaviour in CRC.

  6. Large Cell Neuroendocrine Carcinoma of the Rectum Presenting with Extensive Metastatic Disease

    Directory of Open Access Journals (Sweden)

    Vinay Minocha

    2014-01-01

    Full Text Available Introduction. Rectal large cell neuroendocrine carcinoma (LCNEC is a poorly differentiated neoplasm that is very rare and belongs within the poorest prognostic subgroup among primary colorectal neoplasms. Here, we describe a case of LCNEC of the rectum, which highlights the aggressive clinical course and poor prognosis associated with this disease. Case Presentation. We report a case of a 63-year-old male who presented to our hospital with a one-month history of lower abdominal pain, constipation, and weight loss. A computed tomography (CT scan of the chest, abdomen, and pelvis revealed a rectal mass as well as metastatic disease of the liver and lung. Flexible sigmoidoscopy revealed a fungating, ulcerated and partially obstructing rectal mass located 6 cm from the anal verge. This mass was biopsied and pathological examination of the resected specimen revealed features consistent with a large cell neuroendocrine carcinoma. Conclusion. Rectal large cell neuroendocrine carcinomas are rare and have a significantly worse prognosis than adenocarcinomas. At diagnosis, a higher stage and metastatic disease are likely to be found. It is important to differentiate large cell, poorly differentiated neuroendocrine carcinomas from adenocarcinomas of the colon and rectum pathologically because patients may benefit from alternative cytotoxic chemotherapeutic regimens.

  7. CT features of nonfunctioning islet cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Eelkema, E.A.; Stephens, D.H.; Ward, E.M.; Sheedy, P.F. II

    1984-11-01

    To determine the computed tomographic (CT) characteristics of nonfunctioning islet cell carcinoma of the pancreas, the CT scans of 27 patients with that disease were reviewed. The pancreatic tumor was identified as a mass in 26 patients (96%) Of the 25 tumors evaluated with contrast enhancement, 20 became partially diffusely hyperdense relative to nearby normal pancreatic tissue. Hepatic metastases were identified in 15 patients (56%), regional lymphadenopathy in 10 (37%), atrophy of the gland proximal to the tumor in six (22%), dilatation of the biliary ducts in five (19%), and dilatation of the pancreatic duct in four (15%). The CT appearances of the nonfunctioning islet cell tumors were compared with those of 100 ordinary (ductal) pancreatic adenocarcinomas. Although the two types of tumors were sometimes indistinguishable, features found to be more characteristic of islet cell carcinoma included a pancreatic mass of unusually large size, calcification within the tumor, and contrast enhancement of either the primary tumor or hepatic metastases. Involvement of the celiac axis or proximal superior mesenteric artery was limited to ductal carcinoma.

  8. Intradural squamous cell carcinoma in the sacrum

    Directory of Open Access Journals (Sweden)

    Fujisawa Kozo

    2009-02-01

    Full Text Available Abstract Background Leptomeningeal carcinomatosis occurs in patients with cancer at the rate of approximately 5%; it develops particularly in patients with breast cancer, lung cancer, melanoma, leukemia, or malignant lymphoma. We describe a rare case of leptomeningeal carcinomatosis in which spinal intradural squamous cell carcinoma with no lesions in the cerebral meninges and leptomeninx, was the primary lesion. Methods A 64-year-old man complained of sacral pain. Although the patient was treated with analgesics, epidural block and nerve root block, sacral pain persisted. Since acute urinary retention occurred, he was operated on. The patient was diagnosed as having an intradural squamous cell carcinoma of unknown origin. Results Since the patient presented with a slightly decreased level of consciousness 2 months after surgery, he was subjected to MRI scanning of the brain and spinal cord, which revealed disseminated lesions in the medulla oblongata. The patient died of pneumonia and sepsis caused by methicillin-resistant Staphylococcus aureus 5 months after surgery. Conclusion We report the first case of a patient with intradural squamous cell carcinoma with unknown origin that developed independently in the sacrum.

  9. Clinical Implications of Intestinal Stem Cell Markers in Colorectal Cancer

    DEFF Research Database (Denmark)

    Espersen, Maiken Lise Marcker; Olsen, Jesper; Linnemann, Dorte

    2015-01-01

    Colorectal cancer (CRC) still has one of the highest incidence and mortality rate among cancers. Therefore, improved differential diagnostics and personalized treatment are still needed. Several intestinal stem cell markers have been found to be associated with CRC and might have a prognostic...... and predictive significance in CRC patients. This review provides an overview of the intestinal stem cell markers leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), B cell–specific Moloney murine leukemia virus insertion site 1 (BMI1), Musashi1 (MSI1), and sex-determining region y-box 9 (SOX9......) and their implications in human CRC. The exact roles of the intestinal stem cell markers in CRC development and progression remain unclear; however, high expression of these stem cell markers have a potential prognostic significance and might be implicated in chemotherapy resistance...

  10. Cabozantinib (advanced renal cell carcinoma)

    Science.gov (United States)

    ... cancer cells.Cabozantinib is also available as a capsule (Cometriq) to treat a certain type of thyroid ... vomiting material that is bloody or looks like coffee grounds menstrual bleeding that is heavier than usual ...

  11. Mutational analysis of circulating tumor cells from colorectal cancer patients and correlation with primary tumor tissue.

    Directory of Open Access Journals (Sweden)

    Anna Lyberopoulou

    Full Text Available Circulating tumor cells (CTCs provide a non-invasive accessible source of tumor material from patients with cancer. The cellular heterogeneity within CTC populations is of great clinical importance regarding the increasing number of adjuvant treatment options for patients with metastatic carcinomas, in order to eliminate residual disease. Moreover, the molecular profiling of these rare cells might lead to insight on disease progression and therapeutic strategies than simple CTCs counting. In the present study we investigated the feasibility to detect KRAS, BRAF, CD133 and Plastin3 (PLS3 mutations in an enriched CTCs cell suspension from patients with colorectal cancer, with the hypothesis that these genes` mutations are of great importance regarding the generation of CTCs subpopulations. Subsequently, we compared CTCs mutational status with that of the corresponding primary tumor, in order to access the possibility of tumor cells characterization without biopsy. CTCs were detected and isolated from blood drawn from 52 colorectal cancer (CRC patients using a quantum-dot-labelled magnetic immunoassay method. Mutations were detected by PCR-RFLP or allele-specific PCR and confirmed by direct sequencing. In 52 patients, discordance between primary tumor and CTCs was 5.77% for KRAS, 3.85% for BRAF, 11.54% for CD133 rs3130, 7.69% for CD133 rs2286455 and 11.54% for PLS3 rs6643869 mutations. Our results support that DNA mutational analysis of CTCs may enable non-invasive, specific biomarker diagnostics and expand the scope of personalized medicine for cancer patients.

  12. Anogenital squamous cell carcinoma in neglected patient.

    Science.gov (United States)

    Svecova, D; Havrankova, M; Weismanova, E; Babal, P

    2012-01-01

    Skin squamous cell carcinomas (SCCs) are arguably the second most common carcinoma of the skin and are responsible for the majority of non-melanoma skin cancer deaths. Gynecologist treated a Caucasian 56-years old female patient for genital wart with podophyllotoxin cream. She did not achieve complete response and therefore she has interrupted the therapy and the collaboration with the gynecologist. At the time of evaluation the lesion had a size of man's palm in anogenital region and showed characteristic features of neoplasm. The regional lymph nodes have produced infiltrated painful bubo. PCR analysis for HPV proved negative. Histopathology revealed well-differentiated squamous cell keratinizing carcinoma from the tumor as well as from the regional lymph node packet. Staging computed tomography scans proved negative and pelvis scans disclosed regional lymphadenopathy underlying the tumor. Palliative radiation therapy (by linear accelerator) was administered for the oversized tumor to the total TD 50.0Gy. The patient died 6 months after diagnostic assessment from cardio-respiratory failure. Staging computed tomography before her death did not disclose distinct metastases in her inner organs. Well-differentiated squamous cell keratinizing carcinoma could be growing endophytically affecting the underlying adipose tissue and musculature, with spreading into the regional lymph nodes. The rate of metastases into inner organs seems to vary according to the aggressiveness and metastatic behavior of each SCC. The case report calls for attention to the importance of collaboration among various specialists assisting in the diagnosis and management of skin neoplasm (Fig. 5, Ref. 12). Full Text in PDF www.elis.sk.

  13. Systems-wide RNAi analysis of CASP8AP2/FLASH shows transcriptional deregulation of the replication-dependent histone genes and extensive effects on the transcriptome of colorectal cancer cells

    OpenAIRE

    Hummon Amanda B; Pitt Jason J; Camps Jordi; Emons Georg; Skube Susan B; Huppi Konrad; Jones Tamara L; Beissbarth Tim; Kramer Frank; Grade Marian; Difilippantonio Michael J; Ried Thomas; Caplen Natasha J

    2012-01-01

    Abstract Background Colorectal carcinomas (CRC) carry massive genetic and transcriptional alterations that influence multiple cellular pathways. The study of proteins whose loss-of-function (LOF) alters the growth of CRC cells can be used to further understand the cellular processes cancer cells depend upon for survival. Results A small-scale RNAi screen of ~400 genes conducted in SW480 CRC cells identified several candidate genes as required for the viability of CRC cells, most prominently C...

  14. The radiosensitizing effect of doranidazole on human colorectal cancer cells exposed to high doses of irradiation

    International Nuclear Information System (INIS)

    Zhang, Li; Gong, Aimin; Ji, Jun; Wu, Yuanyuan; Zhu, Xiaoyu; Lv, Suqing; Lv, Hongzhu; Sun, Xizhuo

    2007-01-01

    This paper investigates the effects of a new radiosensitizer, doranidazole, and enhancing irradiation on colorectal cancer cells. The radiosensitizing effect of doranidazole was determined using colony formation and propidium iodide (PI) assays to measure cell growth inhibition and the cell killing effect of human colorectal cancer cell lines exposed to high doses of γ-ray irradiation under hypoxic conditions in vitro. Fluorescence staining and cell migration assays were also used to assess the radiosensitizing effect. Cell proliferation evaluated by clonogenic survival curves was significantly inhibited by 5 mmol/L doranidazole, particularly at doses ranging from 10 to 30 Gy of irradiation. The radiosensitizing effect of doranidazole on colorectal cancer cells occurs in a time- and dose-dependent manner. Doranidazole also inhibited the mobility of cell invasion and migration. Doranidazole can enhance the killing effect and the cell growth inhibition of colorectal cancer after high-dose irradiation in a time and dose-dependent manner

  15. Squamous cell carcinoma of the anal canal.

    LENUS (Irish Health Repository)

    Martin, F T

    2012-01-31

    Squamous cell carcinoma ofthe anal canal represents 1.5% of all malignancies affectingthe gastrointestinal tract. Over the past 20 years dramatic changes have been seen in both the epidemiological distribution of the disease and in the therapeutic modalities utilised to manage it. CLINICAL MANAGEMENT: Historically abdominoperineal resection had been the treatment of choice with local resection reserved for early stage disease. Work by Nigro et al. has revolutionised how we currently manage carcinoma of the anal canal, demonstrating combined modality chemoradiotherapy as an appropriate alternative to surgical resection with the benefit of preserving sphincter function. Surgery is then reserved for recurrent disease with salvage abdominoperineal resection. This article reviews current literature and highlights the changing therapeutic modalities with selected clinical cases

  16. Squamous cell carcinoma of the oral cavity

    International Nuclear Information System (INIS)

    Lindeloev, B.; Kirkegaard, J.; Hansen, H.S.; Copenhagen Univ. Hospital

    1990-01-01

    Three hundred and four patients with squamous cell carcinomas of the oral cavity were treated at the Finsen Institute in cooperation with the ENT-surgical departments between 1978 and 1982. The primary treatment consisted of radiotherapy alone in 74%, surgery alone in 4%, and a combination of radiotherapy and surgery in 15% of the patients. 2% received other treatment (cryotherapy), 5% did not complete the planned radiotherapy, and 1% were not treated at all. Of 203 patients with tumour remnant or first recurrence, 45% were operated, 2% received radiotherapy, and 2% combined treatment. This treatment strategy made 38% of the patients free of disease in the follow-up period (3 1/2 to 8 years) or until the patients died from other causes. Fifty-nine percent of the patients died from their oral carcinomas. Tumour size (T), lymph node status (N), and tumour stage were as expected important prognostic factors. (orig.)

  17. Radioimmunodetection of metastases of colorectal carcinoma by external scintigraphy after administration of 131I-antibody to carcinoembryonic antigen

    International Nuclear Information System (INIS)

    Jones, B.E.; Begent, R.H.J.; Jewkes, R.F.; Vernon, P.; Searle, F.; Keep, P.A.; Green, A.J.; Bagshawe, K.D.

    1982-01-01

    Patients suspected of having metastases of colorectal carcinoma but without palpable tumour deposits were given an intravenous injection of affinity purified goat antibody to carcinoembryonic antigen (CEA) which had been labelled with 131 I by the chloramine T method. 24 Hours later images of antibody distribution were obtained with a large field gamma camera. Computer substraction of background radioactivity was performed using the image obtained after injection of sup(99m)Technetium labelled albumen and free sup(99m)TcO 4 . 23 Scans were carried out in 16 patients and 22 scan images showed residual uptake in specific areas which were considered positive for tumour. Evidence of metastasis was found at these sites in 10 patients, at surgery in 6, by computerised tomography in 3 and by ultrasound in 1. Probable false positive results were obtained in 3 scans. Metastases are still suspected in 4 patients although localisation has not been confirmed. Radioimmunodetection appears to have potential as a method for detecting metastases of colorectal carcinoma. (Author)

  18. Epidermal Growth Factor Receptor and K-RAS status in two cohorts of squamous cell carcinomas

    International Nuclear Information System (INIS)

    Van Damme, Nancy; Pauwels, Patrick; Peeters, Marc; Deron, Philippe; Van Roy, Nadine; Demetter, Pieter; Bols, Alain; Dorpe, Jo Van; Baert, Filip; Van Laethem, Jean-Luc; Speleman, Franki

    2010-01-01

    With the availability of effective anti-EGFR therapies for various solid malignancies, such as non-cell small lung cancer, colorectal cancer and squamous cell carcinoma of the head and neck, the knowledge of EGFR and K-RAS status becomes clinically important. The aim of this study was to analyse EGFR expression, EGFR gene copy number and EGFR and K-RAS mutations in two cohorts of squamous cell carcinomas, specifically anal canal and tonsil carcinomas. Formalin fixed, paraffin-embedded tissues from anal and tonsil carcinoma were used. EGFR protein expression and EGFR gene copy number were analysed by means of immunohistochemistry and fluorescence in situ hybridisation. The somatic status of the EGFR gene was investigated by PCR using primers specific for exons 18 through 21. For the K-RAS gene, PCR was performed using exon 2 specific primers. EGFR immunoreactivity was present in 36/43 (83.7%) of anal canal and in 20/24 (83.3%) of tonsil squamous cell carcinomas. EGFR amplification was absent in anal canal tumours (0/23), but could be identified in 4 of 24 tonsil tumours. From 38 anal canal specimens, 26 specimens were successfully analysed for exon 18, 30 for exon 19, 34 for exon 20 and 30 for exon 21. No EGFR mutations were found in the investigated samples. Thirty samples were sequenced for K-RAS exon 2 and no mutation was identified. From 24 tonsil specimens, 22 were successfully analysed for exon 18 and all 24 specimens for exon 19, 20 and 21. No EGFR mutations were found. Twenty-two samples were sequenced for K-RAS exon 2 and one mutation c.53C > A was identified. EGFR mutations were absent from squamous cell carcinoma of the anus and tonsils, but EGFR protein expression was detected in the majority of the cases. EGFR amplification was seen in tonsil but not in anal canal carcinomas. In our investigated panel, only one mutation in the K-RAS gene of a tonsil squamous cell carcinoma was identified. This indicates that EGFR and K-RAS mutation analysis is not

  19. Epidermal Growth Factor Receptor and K-RAS status in two cohorts of squamous cell carcinomas

    Directory of Open Access Journals (Sweden)

    Van Laethem Jean-Luc

    2010-05-01

    Full Text Available Abstract Background With the availability of effective anti-EGFR therapies for various solid malignancies, such as non-cell small lung cancer, colorectal cancer and squamous cell carcinoma of the head and neck, the knowledge of EGFR and K-RAS status becomes clinically important. The aim of this study was to analyse EGFR expression, EGFR gene copy number and EGFR and K-RAS mutations in two cohorts of squamous cell carcinomas, specifically anal canal and tonsil carcinomas. Methods Formalin fixed, paraffin-embedded tissues from anal and tonsil carcinoma were used. EGFR protein expression and EGFR gene copy number were analysed by means of immunohistochemistry and fluorescence in situ hybridisation. The somatic status of the EGFR gene was investigated by PCR using primers specific for exons 18 through 21. For the K-RAS gene, PCR was performed using exon 2 specific primers. Results EGFR immunoreactivity was present in 36/43 (83.7% of anal canal and in 20/24 (83.3% of tonsil squamous cell carcinomas. EGFR amplification was absent in anal canal tumours (0/23, but could be identified in 4 of 24 tonsil tumours. From 38 anal canal specimens, 26 specimens were successfully analysed for exon 18, 30 for exon 19, 34 for exon 20 and 30 for exon 21. No EGFR mutations were found in the investigated samples. Thirty samples were sequenced for K-RAS exon 2 and no mutation was identified. From 24 tonsil specimens, 22 were successfully analysed for exon 18 and all 24 specimens for exon 19, 20 and 21. No EGFR mutations were found. Twenty-two samples were sequenced for K-RAS exon 2 and one mutation c.53C > A was identified. Conclusion EGFR mutations were absent from squamous cell carcinoma of the anus and tonsils, but EGFR protein expression was detected in the majority of the cases. EGFR amplification was seen in tonsil but not in anal canal carcinomas. In our investigated panel, only one mutation in the K-RAS gene of a tonsil squamous cell carcinoma was identified

  20. Activin pathway enhances colorectal cancer stem cell self-renew and tumor progression.

    Science.gov (United States)

    Liu, Rui; Wang, Jun-Hua; Xu, Chengxiong; Sun, Bo; Kang, Sa-Ouk

    2016-10-28

    Activin belongs to transforming growth factor (TGF)-β super family of growth and differentiation factors and activin pathway participated in broad range of cell process. Studies elaborated activin pathway maintain pluripotency in human stem cells and suggest that the function of activin/nodal signaling in self-renew would be conserved across embryonic and adult stem cells. In this study, we tried to determine the effect of activin signaling pathway in regulation of cancer stem cells as a potential target for cancer therapy in clinical trials. A population of colorectal cancer cells was selected by the treatment of activin A. This population of cell possessed stem cell character with sphere formation ability. We demonstrated activin pathway enhanced the colorectal cancer stem cells self-renew and contribute to colorectal cancer progression in vivo. Targeting activin pathway potentially provide effective strategy for colorectal cancer therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Colorectal carcinoma: Ex vivo evaluation using 3-T high-spatial-resolution quantitative T2 mapping and its correlation with histopathologic findings.

    Science.gov (United States)

    Yamada, Ichiro; Yoshino, Norio; Hikishima, Keigo; Miyasaka, Naoyuki; Yamauchi, Shinichi; Uetake, Hiroyuki; Yasuno, Masamichi; Saida, Yukihisa; Tateishi, Ukihide; Kobayashi, Daisuke; Eishi, Yoshinobu

    2017-05-01

    In this study, we aimed to evaluate the feasibility of determining the mural invasion depths of colorectal carcinomas using high-spatial-resolution (HSR) quantitative T2 mapping on a 3-T magnetic resonance (MR) scanner. Twenty colorectal specimens containing adenocarcinomas were imaged on a 3-T MR system equipped with a 4-channel phased-array surface coil. HSR quantitative T2 maps were acquired using a spin-echo sequence with a repetition time/echo time of 7650/22.6-361.6ms (16 echoes), 87×43.5-mm field of view, 2-mm section thickness, 448×224 matrix, and average of 1. HSR fast-spin-echo T2-weighted images were also acquired. Differences between the T2 values (ms) of the tumor tissue, colorectal wall layers, and fibrosis were measured, and the MR images and histopathologic findings were compared. In all specimens (20/20, 100%), the HSR quantitative T2 maps clearly depicted an 8-layer normal colorectal wall in which the T2 values of each layer differed from those of the adjacent layer(s) (PT2 maps and histopathologic data yielded the same findings regarding the tumor invasion depth. Our results indicate that 3-T HSR quantitative T2 mapping is useful for distinguishing colorectal wall layers and differentiating tumor and fibrotic tissues. Accordingly, this technique could be used to determine mural invasion by colorectal carcinomas with a high level of accuracy. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Telomerase activity and telomere length in the colorectal polyp-carcinoma sequence Actividad de la telomerasa y longitud del telómero en la secuencia pólipo-carcinoma colorrectal

    OpenAIRE

    C. Valls Bautista; C. Piñol Felis; J. M. Reñe Espinet; J. Buenestado García; J. Viñas Salas

    2009-01-01

    Objective: the role of telomerase activity and telomere length in the adenoma-carcinoma sequence of colon carcinogenesis has not been well established. The objective of this study was to determine telomerase activity and telomere length patterns in patients with adenomatous polyps either associated or not with colorectal cancer, as well as the role of telomeric instability in the adenoma-carcinoma sequence. Patients and methods: we included in the study 14 patients who underwent surgery for c...

  3. Radioimmunoassay for tumor antigen of human cervical squamous cell carcinoma

    International Nuclear Information System (INIS)

    Kato, H.; Torigoe, T.

    1977-01-01

    A heterologous antiserum for human cervical squamous cell carcinoma was prepared and specificity determined by Ouchterlony immunodiffusion and immunofluorescence studies. With this antiserum, a tumor antigen was purified from human cervical squamous cell carcinoma tissue. The specificities of the antigen and the antiserum were then re-examined by a radioimmunoassay method using 125 I-labeled purified antigen. Although normal cervical tissue extract showed a moderate cross-reactivity in the radioimmunoassay, the circulating antigen activity could not be detected in normal women or in several patients with other carcinomas, whereas 27 of 35 patients with cervical squamous cell carcinoma showed detectable serum antigen activity. All patients with advanced stages of cervical squamous cell carcinoma showed detectable antigen levels. These results indicate that there is a quantitative abnormality, at least, of this tumor antigen in patients with cervical squamous cell carcinoma and that the radioimmunoassay for the antigen is a potentially useful tool in clinical care

  4. Tumor growth pattern and thymidine phosphorylase expression are related with the risk of hematogenous metastasis in patients with Astler Coller B1/B2 colorectal carcinoma.

    NARCIS (Netherlands)

    Halteren, H.K. van; Peters, H.F.M.; Krieken, J.H.J.M. van; Coebergh, J.W.W.; Roumen, R.M.H.; Worp, E. van der; Wagener, D.J.T.; Vreugdenhil, G.R.

    2001-01-01

    BACKGROUND: The benefit of adjuvant chemotherapy appears to be limited for patients with Astler Coller B1/B2 colorectal carcinoma but may be better in a subgroup of patients with a high recurrence risk. In the current case-control analysis, the authors evaluated whether patients with a high risk of

  5. Hepatic vascular isolation and perfusion for patients with progressive unresectable liver metastases from colorectal carcinoma refractory to previous systemic and regional chemotherapy

    Czech Academy of Sciences Publication Activity Database

    Alexander, HR.; Libutti, S. K.; Barlett, D. L.; Pingpank, J. F.; Kranda, Karel; Helsabeck, C.; Beresnev, T.

    2002-01-01

    Roč. 95, č. 4 (2002), s. 730-736 ISSN 0008-543X R&D Projects: GA AV ČR KSK4055109 Keywords : colorectal carcinoma * liver metastases * regional chemotherapy Subject RIV: FD - Oncology ; Hematology Impact factor: 1.000, year: 2002

  6. Photodynamic Therapy With HPPH in Treating Patients With Squamous Cell Carcinoma of the Oral Cavity

    Science.gov (United States)

    2016-04-19

    Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Oral Cavity

  7. Immunotherapy and immunoescape in colorectal cancer

    Science.gov (United States)

    Mazzolini, Guillermo; Murillo, Oihana; Atorrasagasti, Catalina; Dubrot, Juan; Tirapu, Iñigo; Rizzo, Miguel; Arina, Ainhoa; Alfaro, Carlos; Azpilicueta, Arantza; Berasain, Carmen; Perez-Gracia, José L; Gonzalez, Alvaro; Melero, Ignacio

    2007-01-01

    Immunotherapy encompasses a variety of interventions and techniques with the common goal of eliciting tumor cell destructive immune responses. Colorectal carcinoma often presents as metastatic disease that impedes curative surgery. Novel strategies such as active immunization with dendritic cells (DCs), gene transfer of cytokines into tumor cells or administration of immunostimulatory monoclonal antibodies (such as anti-CD137 or anti-CTLA-4) have been assessed in preclinical studies and are at an early clinical development stage. Importantly, there is accumulating evidence that chemotherapy and immunotherapy can be combined in the treatment of some cases with colorectal cancer, with synergistic potentiation as a result of antigens cross-presented by dendritic cells and/or elimination of competitor or suppressive T lymphocyte populations (regulatory T-cells). However, genetic and epigenetic unstable carcinoma cells frequently evolve mechanisms of immunoevasion that are the result of either loss of antigen presentation, or an active expression of immunosuppressive substances. Some of these actively immunosuppressive mechanisms are inducible by cytokines that signify the arrival of an effector immune response. For example, induction of 2, 3 indoleamine dioxygenase (IDO) by IFNγ in colorectal carcinoma cells. Combinational and balanced strategies fostering antigen presentation, T-cell costimulation and interference with immune regulatory mechanisms will probably take the stage in translational research in the treatment of colorectal carcinoma. PMID:17990348

  8. Transitional cell carcinoma express vitamin D receptors

    DEFF Research Database (Denmark)

    Hermann, G G; Andersen, C B

    1997-01-01

    Recently, vitamin D analogues have shown antineoplastic effect in several diseases. Vitamin D analogues exert its effect by interacting with the vitamin D receptor (VDR). Studies of VDR in transitional cell carcinoma (TCC) have not been reported. The purpose of the present study was therefore.......05). Similarly, also tumor grade appeared to be related to the number of cells expressing the receptor. Normal urothlium also expressed VDR but only with low intensity. Our study shows that TCC cells possess the VDR receptor which may make them capable to respond to stimulation with vitamin D, but functional...... studies of vitamin D's effect on TCC cells in vitro are necessary before the efficacy of treatment with vitamin D analogues in TCC can be evaluated in patients....

  9. Carcinoma basocelular em localizações incomuns Basal cell carcinoma in unusual locations

    Directory of Open Access Journals (Sweden)

    Ane Beatriz Mautari Niwa

    2006-10-01

    Full Text Available Os autores apresentam cinco pacientes que desenvolveram carcinomas basocelulares em locais incomuns de ocorrência desse tumor. O objetivo é relatar a raridade topográfica da neoplasia cutânea e discutir o conceito de localização incomum para o carcinoma basocelular.The authors present five patients who develop basal cell carcinomas in sites this tumor rarely occurs. The aim is to report the rare location of this frequent cutaneous malignancy and to briefly discuss the concept of unusual location of basal cell carcinoma.

  10. Colorectal adenoma stem-like cell populations: associations with adenoma characteristics and metachronous colorectal neoplasia.

    Science.gov (United States)

    Bartley, Angela N; Parikh, Nila; Hsu, Chiu-Hsieh; Roe, Denise J; Buckmeier, Julie A; Corley, Lynda; Phipps, Ron A; Gallick, Gary; Lance, Peter; Thompson, Patricia A; Hamilton, Stanley R

    2013-11-01

    Cancer stem cells have tumor-initiation and tumor-maintenance capabilities. Stem-like cells are present in colorectal adenomas, but their relationship to adenoma pathology and patient characteristics, including metachronous development of an additional adenoma ("recurrence"), has not been studied extensively. We evaluated the expression of aldehyde dehydrogenase isoform 1A1 (ALDH1A1), a putative stem cell marker, in baseline adenomas from the placebo arm of chemoprevention trial participants with colonoscopic follow-up. An exploratory set of 20 baseline adenomas was analyzed by ALDH1A1 immunohistochemistry with morphometry, and a replication set of 89 adenomas from 76 high-risk participants was evaluated by computerized image analysis. ALDH1A1-labeling indices (ALI) were similar across patient characteristics and in advanced and nonadvanced adenomas. There was a trend toward higher ALIs in adenomas occurring in the right than left colon (P = 0.09). ALIs of synchronous adenomas were correlated (intraclass correlation coefficient 0.67). Participants in both sample sets who developed a metachronous adenoma had significantly higher ALIs in their baseline adenoma than participants who remained adenoma free. In the replication set, the adjusted odds for metachronous adenoma increased 1.46 for each 10% increase in ALIs (P = 0.03). A best-fit algorithm-based cutoff point of 22.4% had specificity of 75.0% and positive predictive value of 70.0% for metachronous adenoma development. A larger population of ALDH1A1-expressing cells in an adenoma is associated with a higher risk for metachronous adenoma, independent of adenoma size or histopathology. If confirmed, ALDH1A1 has potential as a novel biomarker in risk assessment and as a potential stem cell target for chemoprevention. ©2013 AACR

  11. Gut microbiota modulate T cell trafficking into human colorectal cancer.

    Science.gov (United States)

    Cremonesi, Eleonora; Governa, Valeria; Garzon, Jesus Francisco Glaus; Mele, Valentina; Amicarella, Francesca; Muraro, Manuele Giuseppe; Trella, Emanuele; Galati-Fournier, Virginie; Oertli, Daniel; Däster, Silvio Raffael; Droeser, Raoul A; Weixler, Benjamin; Bolli, Martin; Rosso, Raffaele; Nitsche, Ulrich; Khanna, Nina; Egli, Adrian; Keck, Simone; Slotta-Huspenina, Julia; Terracciano, Luigi M; Zajac, Paul; Spagnoli, Giulio Cesare; Eppenberger-Castori, Serenella; Janssen, Klaus-Peter; Borsig, Lubor; Iezzi, Giandomenica

    2018-02-06

    Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers. Expression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues. Chemokine receptor expression on TILs was evaluated by flow cytometry on cell suspensions from digested tissues. Chemokine production by CRC cells was evaluated in vitro and in vivo, on generation of intraperitoneal or intracecal tumour xenografts in immune-deficient mice. T cell trafficking was assessed on adoptive transfer of human TILs into tumour-bearing mice. Gut flora composition was analysed by 16SrRNA sequencing. CRC infiltration by distinct T cell subsets was associated with defined chemokine gene signatures, including CCL5, CXCL9 and CXCL10 for cytotoxic T lymphocytes and T-helper (Th)1 cells; CCL17, CCL22 and CXCL12 for Th1 and regulatory T cells; CXCL13 for follicular Th cells; and CCL20 and CCL17 for interleukin (IL)-17-producing Th cells. These chemokines were expressed by tumour cells on exposure to gut bacteria in vitro and in vivo. Their expression was significantly higher in intracecal than in intraperitoneal xenografts and was dramatically reduced by antibiotic treatment of tumour-bearing mice. In clinical samples, abundance of defined bacteria correlated with high chemokine expression, enhanced T cell infiltration and improved survival. Gut microbiota stimulate chemokine production by CRC cells, thus favouring recruitment of beneficial T cells into tumour tissues. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  12. Iodine-131-labelled CDR grafted monoclonal antibody huA33 metastatic colorectal carcinoma: A case study

    International Nuclear Information System (INIS)

    Thomas, D.L.; Lee, F.T.; Scott, A.M.

    1997-01-01

    Full text: A 58-year-old woman was diagnosed with metastatic colorectal carcinoma two years after initial surgery for sigmoid carcinoma. As part of the staging work-up she was initially referred for a 18 F-FDG PET scan at the PET Centre. FDG PET scans of the abdomen and pelvis demonstrated multiple hepatic lesions, but there was no evidence of disease outside the liver. On the basis of extensive hepatic disease, the patient was scheduled for a laparotomy for insertion of an hepatic artery catheter for chemotherapy. In view of her clinical presentation, the patient was eligible for a Phase 1 trial with 131 l-labelled huA33, and agreed to participate. HuA33 is a humanised CDR-grafted recombinant monoclonal antibody directed against an antigen found on >95 per cent of all colorectal carcinomas, and on small bowel and colonic mucosa. The phase 1 trial is a protein dose escalation study designed to examine the biodistribution, pharmacokinetics, dosimetry and safety profile of huA33, and sequential gamma camera images of the whole body were obtained daily until seven days post infusion. SPECT images were obtained on day 6. Excellent localisation of 131 l-huA33 was seen in hepatic lesions. Calculation of whole body retention and tumour uptake was performed, and pharmacokinetic analysis also undertaken. Biopsies of tumour obtained at surgery were used to quantitate tumour uptake and cellular trafficking of 131 l-huA33. On the basis of this phase 1 study, future therapeutic trials of 131 I-huA33 are planned

  13. Basaloid squamous cell carcinoma of the esophagus.

    Science.gov (United States)

    Chen, Shao-Bin; Weng, Hong-Rui; Wang, Geng; Yang, Jie-Sheng; Yang, Wei-Ping; Li, Hua; Liu, Di-Tian; Chen, Yu-Ping

    2012-07-01

    Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare carcinoma with distinct characteristics. No standard treatment has been established. This retrospective study was designed to investigate the clinical and pathological characteristics, diagnosis, treatment, and prognosis of esophageal BSCC. Clinical data were retrospectively analyzed from 26 patients with pathologically confirmed esophageal BSCC who underwent transthoracic esophagectomy with lymphadenectomy between January 1995 and June 2010 at the Cancer Hospital of Shantou University Medical College. Clinicopathologic data between BSCC patients and different histologic grades of esophageal squamous cell carcinoma (ESCC) patients were statistically compared by means of the χ(2) test or Fisher's exact test. The Kaplan-Meier and log-rank methods were used to estimate and compare survival rates. Microscopically, BSCC was characterized by a nesting, lobular, or trabecular arrangement of small crowded cells with scant cytoplasm. None of the histologic specimens taken at preoperative esophagoscopy were diagnosed as BSCC. The median survival time (MST) of the 26 patients was 29.0 months (95% confidence interval, 9.0-49.0), and the 1-, 3-, and 5-year overall survival rates were 73.1, 42.7, and 36.6%, respectively. The MST for BSCC patients was significantly lower than that of well-differentiated SCC patients (P = 0.024), but there were no significant differences between the MST for BSCC patients and that of moderately or poorly differentiated SCC patients (P > 0.05). BSCC of the esophagus is a rare but distinctive disease and is prone to be misdiagnosed by endoscopic biopsy. The prognosis is poorer than well-differentiated SCC, but similar to moderately or poorly differentiated SCC.

  14. The association between human papillomavirus and oropharyngeal squamous cell Carcinoma

    DEFF Research Database (Denmark)

    Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe

    2016-01-01

    carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils...... incidence in human papillomavirus positive oropharyngeal squamous cell carcinoma is associated with sexual behaviour. These associations have been repeatedly observed and are in accordance with our current knowledge. The time relation between cause and effect remains the main challenge, due to the lack...... of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident....

  15. Nonsurgical Treatment Options for Basal Cell Carcinoma

    International Nuclear Information System (INIS)

    Lien, M. H.; Sondak, V. K.; Sondak, V. K.

    2011-01-01

    Basal cell carcinoma (BCC) remains the most common form of non melanoma skin cancer (NMSC) in Caucasians, with perhaps as many as 2 million new cases expected to occur in the United States in 2010. Many treatment options, including surgical interventions and nonsurgical alternatives, have been utilized to treat BCC. In this paper, two non-surgical options, imiquimod therapy and photodynamic therapy (PDT), will be discussed. Both modalities have demonstrated acceptable disease control rates, cosmetically superior outcomes, and short-term cost-effectiveness. Further studies evaluating long-term cure rates and long-term cost effectiveness of imiquimod therapy and PDT are needed.

  16. Fanconi anemia and vaginal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Jesus Paula Carvalho

    2012-01-01

    Full Text Available Fanconi Anemia (FA is an autosomal recessive disease characterized by chromosome instability, cellular hypersensitivity to DNA cross-linking agents, and increased predisposition to malignancies. We describe here a 28 year-old female with FA and vaginal squamous cell carcinoma treated by radiation therapy alone. The patient developed arm phlebitis, pulmonary fungal infection, and severe rectal bleeding, followed by hypocalcaemia, hypokalemia, vaginal bacterial and fungal infection, with subsequent leg and arm phlebitis, perineal abscess, and sepsis. The patient died 12 weeks later.

  17. Unilateral Renal Cell Carcinoma in a Dog

    Directory of Open Access Journals (Sweden)

    J. Y. Chung

    2014-01-01

    Full Text Available A 4-year-old, neutered male, American Cocker Spaniel weighing 8.3 kg was presented with a 1-month history of weight-loss, anorexia, intermittent vomiting and bloody-diarrhea. Abnormal blood tests results, a large mass on the kidney field in radiographic views and ultrasonography were presented. Nephroureterectomy was tried, but a large mass in the kidney and metastasis to the spleen caused to decline the surgery and treatment. The dog was euthanized, and necropsy and histological review revealed the renal cell carcinoma.

  18. Basal cell carcinoma after radiation therapy

    International Nuclear Information System (INIS)

    Shimbo, Keisuke; Terashi, Hiroto; Ishida, Yasuhisa; Tahara, Shinya; Osaki, Takeo; Nomura, Tadashi; Ejiri, Hirotaka

    2008-01-01

    We reported two cases of basal cell carcinoma (BCC) that developed after radiation therapy. A 50-year-old woman, who had received an unknown amount of radiation therapy for the treatment of intracranial germinoma at the age of 22, presented with several tumors around the radiation ulcer. All tumors showed BCC. A 33-year-old woman, who had received an unknown amount of radiation therapy on the head for the treatment of leukemia at the age of 2, presented with a black nodule within the area of irradiation. The tumor showed BCC. We discuss the occurrence of BCC after radiation therapy. (author)

  19. Postoperative radiotherapy for merkel cell carcinoma

    International Nuclear Information System (INIS)

    Inoue, Kazuya; Asakawa, Isao; Katayama, Emiko; Kajitani, Chikae; Tamamoto, Tetsuro; Hasegawa, Masatoshi; Fukumoto, Takaya; Asada, Hideo

    2014-01-01

    Seven patients with Merkel cell carcinoma (MCC) who visited our department of radiation oncology from February 2005 to July 2011 received postoperative radiotherapy (50-60 Gy). All patients were alive without recurrence (median follow-up period: 47.6 (14.7-88.4) months). All of them had grade 2 dermatitis, and one grade 2 oral mucositis and three grade 2 lymphedema were observed. No adverse event grade 3 (CTCAE v4.0) or over was observed. In our hospital, clinical results of postoperative radiotherapy for MCC were fairly good, and adverse events were acceptable during the follow-up period. (author)

  20. Large cell neuroendocrine carcinoma of the ampulla of Vater.

    LENUS (Irish Health Repository)

    Beggs, Rachel E

    2012-09-01

    Large cell neuroendocrine carcinomas of the ampulla of Vater are rare and confer a very poor prognosis despite aggressive therapy. There are few case reports of large cell neuroendocrine carcinomas of the ampulla of Vater in the literature and to date no studies have been done to establish optimal management. We describe a pooled case series from published reports of neuroendocrine carcinomas of the ampulla of Vater including a case which presented to our institution.

  1. Hürthle cell carcinoma: current perspectives

    Directory of Open Access Journals (Sweden)

    Ahmadi S

    2016-11-01

    Full Text Available Sara Ahmadi,1 Michael Stang,2 Xiaoyin “Sara” Jiang,3 Julie Ann Sosa2,4,5 1Division of Endocrinology, Department of Medicine, 2Section of Endocrine Surgery, Department of Surgery, 3Department of Pathology, Duke University Medical Center, 4Duke Cancer Institute, 5Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA Abstract: Hürthle cell carcinoma (HCC can present either as a minimally invasive or as a widely invasive tumor. HCC generally has a more aggressive clinical behavior compared with the other differentiated thyroid cancers, and it is associated with a higher rate of distant metastases. Minimally invasive HCC demonstrates much less aggressive behavior; lesions <4 cm can be treated with thyroid lobectomy alone, and without radioactive iodine (RAI. HCC has been observed to be less iodine-avid compared with other differentiated thyroid cancers; however, recent data have demonstrated improved survival with RAI use in patients with HCC >2 cm and those with nodal and distant metastases. Patients with localized iodine-resistant disease who are not candidates for a wait-and-watch approach can be treated with localized therapies. Systemic therapy is reserved for patients with progressive, widely metastatic HCC. Keywords: thyroid cancer, thyroid nodule, follicular cell carcinoma, Hurthle cell lesion, minimally invasive HCC

  2. Merkel cell polyomavirus infection and Merkel cell carcinoma.

    Science.gov (United States)

    Liu, Wei; MacDonald, Margo; You, Jianxin

    2016-10-01

    Merkel cell polyomavirus is the only polyomavirus discovered to date that is associated with a human cancer. MCPyV infection is highly prevalent in the general population. Nearly all healthy adults asymptomatically shed MCPyV from their skin. However, in elderly and immunosuppressed individuals, the infection can lead to a lethal form of skin cancer, Merkel cell carcinoma. In the last few years, new findings have established links between MCPyV infection, host immune response, and Merkel cell carcinoma development. This review discusses these recent discoveries on how MCPyV interacts with host cells to achieve persistent infection and, in the immunocompromised population, contributes to MCC development. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse

    NARCIS (Netherlands)

    Merlos-Suarez, A.; Barriga, F.M.; Jung, P.; Iglesias, M.; Cespedes, M.V.; Rossell, D.; Sevillano, M.; Hernando-Momblona, X.; da Silva-Diz, V.; Munoz, P.; Clevers, H.; Sancho, E.; Mangues, R.; Batlle, E.

    2011-01-01

    A frequent complication in colorectal cancer (CRC) is regeneration of the tumor after therapy. Here, we report that a gene signature specific for adult intestinal stem cells (ISCs) predicts disease relapse in CRC patients. ISCs are marked by high expression of the EphB2 receptor, which becomes

  4. Primary Squamous Cell Carcinoma of Stomach: A Rare Entity ...

    African Journals Online (AJOL)

    Schmidt C, Schmid A, Lüttges JE, Kremer B, Henne-Bruns D. Primary squamous cell carcinoma of the stomach. Report of a case and review of literature. Hepatogastroenterology 2001;48:1033-6. 5. Muto M, Hasebe T, Muro K, Boku N, Ohtsu A, Fujii T, et al. Primary squamous cell carcinoma of the stomach: A case report with ...

  5. Amyloid in basal cell carcinoma and seborrheic keratosis

    DEFF Research Database (Denmark)

    Olsen, K E; Westermark, Per

    1994-01-01

    The frequency of amyloid substance was studied in two different types of skin tumours: basal cell carcinoma and seborrheic keratosis. In 9 out of 49 cases of seborrheic keratosis amyloid substance was found. In the basal cell carcinomas, 194 out of 260 cases showed amyloid deposits, a rate...

  6. Squamous cell carcinoma of the conjunctiva in Ilorin, Nigeria ...

    African Journals Online (AJOL)

    The aim was to determine the incidence of conjunctival squamous cell carcinoma at UITH over an 11 – year period. Nineteen patients (11males and 8 females) had histological confirmation of conjunctival squamous cell carcinoma out of 21 conjunctival specimens, representing 22.9% of all orbito-ocular tumours reviewed ...

  7. induced acute cytotoxicity in human cervical epithelial carcinoma cells

    African Journals Online (AJOL)

    Molecular basis of arsenite (As +3 )-induced acute cytotoxicity in human cervical epithelial carcinoma cells. ... Libyan Journal of Medicine ... Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and ...

  8. Colorectal cancer: genetic abnormalities, tumor progression, tumor heterogeneity, clonal evolution and tumor-initiating cells.

    Science.gov (United States)

    Testa, Ugo; Pelosi, Elvira; Castelli, Germana

    2018-04-13

    Colon cancer is the third most common cancer worldwide. Most colorectal cancer occurrences are sporadic, not related to genetic predisposition or family history; however, 20-30% of patients with colorectal cancer have a family history of colorectal cancer and 5% of these tumors arise in the setting of a Mendelian inheritance syndrome. In many patients, the development of a colorectal cancer is preceded by a benign neoplastic lesion: either an adenomatous polyp or a serrated polyp. Studies carried out in the last years have characterized the main molecular alterations occurring in colorectal cancers, showing that the tumor of each patient displays from two to eight driver mutations. The ensemble of molecular studies, including gene expression studies, has led to two proposed classifications of colorectal cancers, with the identification of four/five non-overlapping groups. The homeostasis of the rapidly renewing intestinal epithelium is ensured by few stem cells present at the level of the base of intestinal crypts. Various experimental evidence suggests that colorectal cancers may derive from the malignant transformation of intestinal stem cells or of intestinal cells that acquire stem cell properties following malignant transformation. Colon cancer stem cells seem to be involved in tumor chemoresistance, radioresistance and relapse.

  9. Lgr5 Methylation in Cancer Stem Cell Differentiation and Prognosis-Prediction in Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Shasha Su

    Full Text Available Leucine-rich-repeat-containing G-protein-coupled receptor 5 (lgr5 is a candidate marker for colorectal cancer stem cells (CSC. In the current study, we investigated the methylation status within thelgr5 promoter and evaluated its relationship with CSC differentiation, prognosis for colorectal cancer, and its clinicopathological features.The methylation status within Lgr5 promoter was detected with a methylation-specific PCR in six colorectal cancer cell lines as well as 169 primary colorectal tumor tissues. Differentiation of CSC was examined with immunofluorescence and immunocytochemistry. Down-regulation of lgr5 was achieved with gene-specific siRNA. The associations between lgr5 methylation and the clinicopathological features as well as survival of patients were analyzed with statistical methods.The lgr5 promoter was methylated to different degrees for the six colorectal cell lines examined, with complete methylation observed in HCT116 cells in which the lgr5 expression was partially recovered following DAC treatment. The stem-cell sphere formation from HCT116 cells was accompanied by increasing methylation within the lgr5 promoter and decreasing expression of lgr5. Knocking down lgr5 by siRNA also led to stem-cell spheres formation. Among primary colorectal tumors, 40% (67/169 were positive for lgr5 methylation, while none of the normal colon tissues were positive for lgr5 methylation. Furthermore, lgr5 methylation significantly associated with higher tumor grade, and negative distant metastasis (p < 0.05, as well as better prognosis (p = 0.001 in patients with colorectal cancer.Our data suggests that lgr5 methylation, through the regulation of lgr5 expression and colorectal CSC differentiation, may constitute a novel prognostic marker for colorectal cancer patients.

  10. Primary peritoneal clear cell carcinoma versus ovarian carcinoma versus malignant transformation of endometriosis: a vexing issue.

    Science.gov (United States)

    Insabato, Luigi; Natella, Valentina; Somma, Anna; Persico, Marcello; Camera, Luigi; Losito, Nunzia Simona; Masone, Stefania

    2015-05-01

    Peritoneum is a site for both primary and secondary tumors. Primary peritoneal tumors are fairly rare. The most common primary tumors of the peritoneum are malignant mesothelioma and serous papillary adenocarcinoma. Clear cell carcinoma of the peritoneum is extremely rare and often misdiagnosed as mesothelioma, serous carcinoma, or metastatic adenocarcinoma, so it represents a diagnostic challenge for both clinicians and pathologists. Up to date, to the best of our knowledge, only 11 cases of primary peritoneal clear cell carcinoma have been reported in the English literature. Distinguishing this tumor of the peritoneum versus ovarian carcinoma can be problematic. Herein, we report a rare case of primary peritoneal clear cell carcinoma occurring in a 49-year-old woman, along with a review of the literature. © The Author(s) 2015.

  11. Rising incidence of Merkel cell carcinoma

    DEFF Research Database (Denmark)

    Lyhne, Dorte; Lock-Andersen, Jørgen; Dahlstrøm, Karin

    2011-01-01

    Abstract Merkel cell carcinoma (MCC) is a rare, aggressive, skin cancer of obscure histogenesis, the incidence of which is rising. There is no consensus on the optimal treatment. Our aim was to evaluate the staging, investigation, treatment, and follow-up of MCC in eastern Denmark, and to investi......Abstract Merkel cell carcinoma (MCC) is a rare, aggressive, skin cancer of obscure histogenesis, the incidence of which is rising. There is no consensus on the optimal treatment. Our aim was to evaluate the staging, investigation, treatment, and follow-up of MCC in eastern Denmark......, and to investigate the incidence. We suggest guidelines for treatment. First we reviewed the medical records of 51 patients diagnosed with MCC from 1995 until 2006 in eastern Denmark. The nation-wide incidence of MCC was extracted from the Danish Cancer Registry for the calculations for the period 1986-2003. We...... reviwed published papers about MCC based on a MEDLINE search. Fourteen of the 51 patients developed recurrence, and 37 (73%) died during the study period. Mean follow-up was 13 months (range 1-122). A total of 153 patients were identified in the Danish Cancer Registry, and showed that incidence rates had...

  12. Treatment of early glottic squamous cell carcinoma

    International Nuclear Information System (INIS)

    Rikimaru, Fumihide; Matsuo, Mioko; Higaki, Yuichiro; Tomita, Kichinobu

    2011-01-01

    We treat early glottic squamous cell carcinoma with chemoradiation and evaluate the effects of the chemoradiation at the dose of 30-40 Gy as an intermediate evaluation. To investigate the need for this intermediate evaluation, we retrospectively analyzed 97 patients, 92 men and 5 women aged 36 to 86 years, with glottic squamous cell carcinoma at stage I and II treated at our institution from January 2000 to May 2007. The three-year survival rate was 98% in all cases, 100% in T1a, 93% in T1b and 94% in T2. The three-year preservation rate of the larynx was 92% in all cases, 98% in T1a, 93% in T1b and 83% in T2. In the intermediate evaluation, complete response was 78% in T1a, 85% in T1b and 53% in T2. In cases of larynx preservation, the recurrence rate of the primary site was significantly higher in cases without complete response in the intermediate evaluation than in cases with complete response (p<0.05). It seemed that the not complete response case in the intermediate evaluation paid attention to a primary tumor recurrence in particular and needed careful follow-up. (author)

  13. Downregulation of MDM2 expression by RNAi inhibits LoVo human colorectal adenocarcinoma cells growth and the treatment of LoVo cells with mdm2siRNA3 enhances the sensitivity to cisplatin

    International Nuclear Information System (INIS)

    Yu Yan; Sun Ping; Sun Lichun; Liu Guoyi; Chen Guohua; Shang Lihua; Wu Hongbo; Hu Jing; Li Yue; Mao Yinling; Sui Guangjie; Sun Xiwen

    2006-01-01

    To investigate the biological effect of mdm2 in human colorectal adenocarcinoma LoVo cells, three mdm2siRNA constructions were recombinated and transient transfected into human colorectal adenocarcinoma LoVo cells with low differentiation character in vitro. The results showed that mdm2siRNA3 reduced mRNA level of mdm2 and protein level of mdm2, leading to proliferation inhibition on LoVo cells, and reduced tumor growth in nude mice. It was found that depletion of MDM2 in this pattern promoted apoptosis of LoVo cells and Cisplatin (DDP) treated in the mdm2siRNA3 transfected cell population would result in a substantial decrease by MTT colorimetry. Decreasing the MDM2 protein level in LoVo cells by RNAi could significantly inhibit tumor growth both in vitro and in vivo, which indicated that mdm2 gene played a definite role in the development and aggressiveness of human colon carcinoma. It also could be a therapeutic target in colorectal carcinoma. The synergistic activation of RNAi and cell toxicity agents indicated that the combination of chemotherapy and gene therapy will be a promising approach in the future

  14. Airway Basal Cell Heterogeneity and Lung Squamous Cell Carcinoma.

    Science.gov (United States)

    Hynds, Robert E; Janes, Sam M

    2017-09-01

    Basal cells are stem/progenitor cells that maintain airway homeostasis, enact repair following epithelial injury, and are a candidate cell-of-origin for lung squamous cell carcinoma. Heterogeneity of basal cells is recognized in terms of gene expression and differentiation capacity. In this Issue, Pagano and colleagues isolate a subset of immortalized basal cells that are characterized by high motility, suggesting that they might also be heterogeneous in their biophysical properties. Motility-selected cells displayed an increased ability to colonize the lung in vivo The possible implications of these findings are discussed in terms of basal cell heterogeneity, epithelial cell migration, and modeling of metastasis that occurs early in cancer evolution. Cancer Prev Res; 10(9); 491-3. ©2017 AACR See related article by Pagano et al., p. 514 . ©2017 American Association for Cancer Research.

  15. Which Are the Cells of Origin in Merkel Cell Carcinoma

    International Nuclear Information System (INIS)

    Tilling, T.; Moll, I.

    2012-01-01

    Merkel cell carcinoma (MCC), a highly aggressive skin tumour with increasing incidence, is associated with the newly discovered Merkel cell polyoma virus (MCPyV). Studies on MCC and MCPyV as well as other risk factors have significantly increased our knowledge of MCC pathogenesis, but the cells of origin, which could be important targets in future therapies, are still unknown. Merkel cells (MCs), the neuroendocrine cells of the skin, were believed to be at the origin of MCC due to their phenotypic similarities. However, for several reasons, for example, heterogeneous differentiation of MCCs and post mitotic character of MCs, it is not very likely that MCC develops from differentiated MCs. Skin stem cells, probably from the epidermal lineage, are more likely to be cells of origin in MCC. Future studies will have to address these questions more directly in order to identify the physiological cells which are transformed to MCC cells.

  16. Genetic dissimilarity between primary colorectal carcinomas and their lymph node metastases: ploidy, p53, bcl-2, and c-myc expression--a pilot study.

    Science.gov (United States)

    Zalata, Khaled Refaat; Elshal, Mohamed Farouk; Foda, Abd AlRahman Mohammad; Shoma, Ashraf

    2015-08-01

    The current paradigm of metastasis proposes that rare cells within primary tumors acquire metastatic capability via sequential mutations, suggesting that metastases are genetically dissimilar from their primary tumors. This study investigated the changes in the level of expression of a well-defined panel of cell proliferation, differentiation, and apoptosis markers between the primary colorectal cancer (CRC) and the corresponding synchronous lymph node (LN) metastasis from the same patients. DNA flow cytometry and immunostaining of p53, bcl-2, and c-myc were carried out on 36 cases of CRC radical resection specimens with their corresponding LN metastases. There was very low probability that the histological patterns of primary tumors and LN metastases are independent (p < 0.001). Metastatic tumors were significantly more diffusely positive for p53 than the primary tumors (p < 0.001). Conversely, primary tumors were significantly more diffusely positive for c-myc than metastatic tumors (p = 0.011). No significant difference was found between the LNs and the primary tumors in bcl-2 positivity (p = 0.538) and DNA aneuploidy (p = 0.35), with a tendency towards negative bcl-2 and less aneuploidy in LN metastases than primary tumors. In conclusion, LN metastatic colorectal carcinomas have a tendency of being less differentiated, with a higher incidence of diffuse p53 staining, lower incidence of bcl-2 staining, and less aneuploidy in comparison to their primary counterparts suggesting a more aggressive biological behavior, which could indicate the necessity for more aggressive adjuvant therapy.

  17. Cancer stem cells in colorectal cancer: a review.

    Science.gov (United States)

    Munro, Matthew J; Wickremesekera, Susrutha K; Peng, Lifeng; Tan, Swee T; Itinteang, Tinte

    2018-02-01

    Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men. Adenocarcinoma accounts for 90% of CRC cases. There has been accumulating evidence in support of the cancer stem cell (CSC) concept of cancer which proposes that CSCs are central in the initiation of cancer. CSCs have been the focus of study in a range of cancers, including CRC. This has led to the identification and understanding of genes involved in the induction and maintenance of pluripotency of stem cells, and markers for CSCs, including those investigated specifically in CRC. Knowledge of the expression pattern of CSCs in CRC has been increasing in recent years, revealing a heterogeneous population of cells within CRC ranging from pluripotent to differentiated cells, with overlapping and sometimes unique combinations of markers. This review summarises current literature on the understanding of CSCs in CRC, including evidence of the presence of CSC subpopulations, and the stem cell markers currently used to identify and localise these CSC subpopulations. Future research into this field may lead to improved methods for early detection of CRC, novel therapy and monitoring of treatment for CRC and other cancer types. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Squamous cell carcinoma following radiation therapy for the infiltrative thymoma

    International Nuclear Information System (INIS)

    Ozawa, Shinji; Kitao, Takeshi

    1992-01-01

    This report represents one case of infiltrative thymoma followed by squamous cell carcinoma of the lungs. A 69-year-old man suffered from infiltrative thymoma which reduced by the radiation therapy. Seven years later its replase and the onset of squamous cell carcinoma were found simultaneously. Infiltrative thymoma metastasized not only to the mediastinum but also to the liver and bronchus. Squamous cell carcinoma developed in the right upper lobe. In spite of chemotherapy against them, the patient died. There are many cases in which infiltrative thymoma is accompanied by squamous cell carcinoma of the lung simultaneously; however, secondary onset of squamous cell carcinoma after the radiation therapy of infiltrative thymoma is rare. Secondary carcinogenesis of this case was considered to be closely related with immunological abnormalities caused by thymoma, effects of radiation, smoking and so on. (author)

  19. Dendritic cells recognize tumor-specific glycosylation of carcinoembryonic antigen on colorectal cancer cells through dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin

    NARCIS (Netherlands)

    van Gisbergen, Klaas P. J. M.; Aarnoudse, Corlien A.; Meijer, Gerrit A.; Geijtenbeek, Teunis B. H.; van Kooyk, Yvette

    2005-01-01

    Dendritic cells play a pivotal role in the induction of antitumor immune responses. Immature dendritic cells are located intratumorally within colorectal cancer and intimately interact with tumor cells, whereas mature dendritic cells are present peripheral to the tumor. The majority of colorectal

  20. CT staging of renal cell carcinoma

    International Nuclear Information System (INIS)

    Spina, Juan C.; Garcia, Adriana T.; Rogondino, Jose; Spina, Juan C. h; Vidales, Valeria; Troiani, Guillermo; Iotti, Alejandro; Venditti, Julio

    2002-01-01

    Objective: To assess the usefulness of computerized tomography (CT) in the characterization of renal masses, in order to stage them, determine their prognosis and their appropriate clinical and/or surgical management. Material and Methods: Between 1988 and 2001, we selected 63 patients with renal tumors that had been examined by pathology. Patient's ages ranged from 16 to 88 years (25 women, 38 men). The studies were performed with a sequential helical CT, using 5 mm thickness sections every 5mm evaluating the cortico medullar and nephrographic phases. Renal tumors were characterized and staged without any knowledge about the pathological findings; subsequently the tomographic characteristics were compared to such findings. The following characteristics were evaluated: 1) mixed solid-cystic nature; 2) size; 3) borders; 4) enhancement; 5) necrosis; 6) hemorrhage; 7) central scar; 8) presence of fat; 9) collecting system; 10) capsular invasion; 11) perirenal fat invasion; 12) vessels; 13) Gerota's fascia; 14) lymph nodes; and 15) local and/or distant metastases. Results: Of the 63 tumors, 2 were complicated cysts; of the 61 remaining tumors, 10 were angiomyolipomas, 1 was a renal lymphoma, 1 was a focal xantogranulomatose pyelonephritis, 1 was a metanephric adenoma, 3 papillary renal cell carcinoma (RCC), 4 transitional cell tumors, 4 oncocytomas, 37 clear cell renal carcinoma. The CT could correctly characterize the 2 cystic tumors as such, as well as the 9 angiomyolipomas and the 4 transitional cell tumors. The 48 other tumors (1 angiomyolipoma, 1 lymphoma, 1 focal xantogranulomatose pyelonephritis, 1 metanephric adenoma, 3 papillary RCC, 4 oncocytomas, and 37 cell renal carcinomas) remaining were characterized as renal adenocarcinomas and CT staged. Conclusion: CT is a useful method to characterize renal masses since it determines their solid-cystic or fatty structure; aiding in many cases to define a surgical treatment. For the CT staging of renal tumors, the

  1. Clinical implications of thymidylate synthetase, dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase activity levels in colorectal carcinoma following radical resection and administration of adjuvant 5-FU chemotherapy

    International Nuclear Information System (INIS)

    Ishikawa, Masashi; Miyauchi, Takayuki; Kashiwagi, Yutaka

    2008-01-01

    A number of studies have investigated whether the activity levels of enzymes involved in 5-fluorouracil (5-FU) metabolism are prognostic factors for survival in patients with colorectal carcinoma. Most reports have examined thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) in unresectable or metastatic cases, therefore it is unclear whether the activity of these enzymes is of prognostic value in colorectal cancer patients treated with radical resection and adjuvant chemotherapy with 5-FU. This study examined fresh frozen specimens of colorectal carcinoma from 40 patients who had undergone curative operation and were orally administered adjuvant tegafur/uracil (UFT) chemotherapy. TS, DPD and orotate phosphoribosyl transferase (OPRT) activities were assayed in cancer tissue and adjacent normal tissue and their association with clinicopathological variables was investigated. In addition, the relationships between TS, DPD and OPRT activities and patient survival were examined to determine whether any of these enzymes could be useful prognostic factors. While there was no clear relationship between pathological findings and TS or DPD activity, OPRT activity was significantly lower in tumors with lymph node metastasis than in tumors lacking lymph node metastasis. Postoperative survival was significantly better in the groups with low TS activity and/or high OPRT activity. TS and OPRT activity levels in tumor tissue may be important prognostic factors for survival in Dukes' B and C colorectal carcinoma with radical resection and adjuvant chemotherapy with UFT

  2. Synchronous presentation of nasopharyngeal and renal cell carcinomas

    Directory of Open Access Journals (Sweden)

    Cem Boruban

    2006-06-01

    Full Text Available We report a rare case of synchronous presentation of nasopharyngeal and renal cell carcinomas in a-50-year old male patient with long standing smoking history. The patient was initially presented with a diagnosis of nasopharyngeal carcinoma. During staging process, the abdominal computed tomography detected a right renal solid mass, 6.5 cm in diameter, originating from posterior portion of the right renal cortex. Right radical nephrectomy was performed and pathological examination revealed renal cell carcinoma. Smoking was thought to be a risk factor for both cancers. Systemic evaluation of kidney should not be discarded in patients diagnosed with nasopharyngeal carcinoma living in western countries with a smoking history.

  3. Merkel cell carcinoma: A rare presentation

    Directory of Open Access Journals (Sweden)

    Prosanta Kumar Bhattacharjee

    2014-01-01

    Full Text Available A 33-year-old man presented with a lump at the right side of chest wall of 4 months duration which started bleeding suddenly from an ulcer at its center. Examination revealed a globular ulcerated mass 2 cm in diameter, on the anterior axillary fold, with adherent clot at its center. No regional lymphadenopathy was noted. Wide local excision with 2 cm margin was done. Biopsy report revealed malignant small round-cell tumor. Immunohistochemistry showed it to be cytokeratin-20-positive and S100-negative, suggesting the diagnosis of Merkel cell carcinoma. The patient did not receive any other adjuvant therapy. He is being followed-up for the last 4 years and has shown no features of recurrence so far.

  4. Frequency and phenotypic spectrum of germline mutations in POLE and seven other polymerase genes in 266 patients with colorectal adenomas and carcinomas.

    Science.gov (United States)

    Spier, Isabel; Holzapfel, Stefanie; Altmüller, Janine; Zhao, Bixiao; Horpaopan, Sukanya; Vogt, Stefanie; Chen, Sophia; Morak, Monika; Raeder, Susanne; Kayser, Katrin; Stienen, Dietlinde; Adam, Ronja; Nürnberg, Peter; Plotz, Guido; Holinski-Feder, Elke; Lifton, Richard P; Thiele, Holger; Hoffmann, Per; Steinke, Verena; Aretz, Stefan

    2015-07-15

    In a number of families with colorectal adenomatous polyposis or suspected Lynch syndrome/HNPCC, no germline alteration in the APC, MUTYH, or mismatch repair (MMR) genes are found. Missense mutations in the polymerase genes POLE and POLD1 have recently been identified as rare cause of multiple colorectal adenomas and carcinomas, a condition termed polymerase proofreading-associated polyposis (PPAP). The aim of the present study was to evaluate the clinical relevance and phenotypic spectrum of polymerase germline mutations. Therefore, targeted sequencing of the polymerase genes POLD1, POLD2, POLD3, POLD4, POLE, POLE2, POLE3 and POLE4 was performed in 266 unrelated patients with polyposis or fulfilled Amsterdam criteria. The POLE mutation c.1270C>G;p.Leu424Val was detected in four unrelated patients. The mutation was present in 1.5% (4/266) of all patients, 4% (3/77) of all familial cases and 7% (2/30) of familial polyposis cases. The colorectal phenotype in 14 affected individuals ranged from typical adenomatous polyposis to a HNPCC phenotype, with high intrafamilial variability. Multiple colorectal carcinomas and duodenal adenomas were common, and one case of duodenal carcinoma was reported. Additionally, various extraintestinal lesions were evident. Nine further putative pathogenic variants were identified. The most promising was c.1306C>T;p.Pro436Ser in POLE. In conclusion, a PPAP was identified in a substantial number of polyposis and familial colorectal cancer patients. Screening for polymerase proofreading mutations should therefore be considered, particularly in unexplained familial cases. The present study broadens the phenotypic spectrum of PPAP to duodenal adenomas and carcinomas, and identified novel, potentially pathogenic variants in four polymerase genes. © 2014 UICC.

  5. Expression of core clock genes in colorectal tumour cells compared with normal mucosa

    DEFF Research Database (Denmark)

    Fonnes, S; Donatsky, A M; Gögenur, I

    2015-01-01

    AIM: Experimental studies have shown that some circadian core clock genes may act as tumour suppressors and have an important role in the response to oncological treatment. This study investigated the evidence regarding modified expression of core clock genes in colorectal cancer and its...... expression of colorectal cancer cells compared with healthy mucosa cells from specimens analysed by real-time or quantitative real-time polymer chain reaction. The expression of the core clock genes Period, Cryptochrome, Bmal1 and Clock in colorectal tumours were compared with healthy mucosa and correlated...... with clinicopathological features and survival. RESULTS: Seventy-four articles were identified and 11 studies were included. Overall, gene expression of Period was significantly decreased in colorectal cancer cells compared with healthy mucosa cells. This tendency was also seen in the gene expression of Clock. Other core...

  6. Experimental study on the expression of CD44 and CD54 in liver metastasis of colorectal carcinoma

    International Nuclear Information System (INIS)

    Ma Chen; Mao Dabeng; Wang Chengzhong; Guo Yu

    2004-01-01

    Objective: To study the significance of CD44 and CD54 expression in animal models with liver metastasis of colorectal cancer and try to find a stable biological marker for the early diagnosis of liver metastasis of colorectal cancer. Methods: Fourth two nude mice of 4-6 wks were adopted in the study. Thirty-six were used to establish animal models with liver metastasis of colorectal cancer, the rest 6 mice were used as the controls. 36 mice of the experimental group were divided into 6 subgroups, each containing 6 mice, in which low grade colorectal adenocarcinoma cells were injected in the subcapsule of the spleen. On the day 10th, 15th, 20th, 25th, 30th day and at the time of the brink of death, animas in each subgroup were sacrificed by eyeball removal and blood letting. Serum CD44, CD54 and CEA levels of the nude mice were measured by ELISA and the sizes and number of liver metastatic loci were observed and noted. the 6 mice for control were raised in the same cages and were killed on the 30th day, and were compared with that in the experimental group. Results: Through the measurement at different phrases, authors found with the development progression and metastasis of cancer, CD44 and CD54 levels in the animal serum tend to increase gradually and were correlated positively with the growth time, size, and extent metastasis of the cancer. Conclusion: CD44 and CD54 may be early tumor markers for liver metastasis of colorectal cancer

  7. Foreign Body Granulomas Simulating Recurrent Tumors in Patients Following Colorectal Surgery for Carcinoma: a Report of Two Cases

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Baek, Moo Joon; Cho, Hyun Deuk [Cheonan Hospital, Soonchunhyang University, Cheonan (Korea, Republic of)

    2009-06-15

    We report here two cases of foreign body granulomas that arose from the pelvic wall and liver, respectively, and simulated recurrent colorectal carcinomas in patients with a history of surgery. On contrast-enhanced CT and MR images, a pelvic wall mass appeared as a well-enhancing mass that had invaded the distal ureter, resulting in the development of hydronephrosis. In addition, a liver mass had a hypointense rim that corresponded to the fibrous wall on a T2-weighted MR image, and showed persistent peripheral enhancement that corresponded to the granulation tissues and fibrous wall on dynamic MR images. These lesions also displayed very intense homogeneous FDG uptake on PET/CT.

  8. Hyperplastic polyps of the colon and rectum - reclassification, BRAF and KRAS status in index polyps and subsequent colorectal carcinoma

    DEFF Research Database (Denmark)

    Janjua, Huma Gul Rehana; Høgdall, Estrid; Linnemann, Dorte

    2015-01-01

    (THP), sessile serrated lesions (SSL), and other lesions. All patients were confirmed in the Danish National Pathology Database for the occurrence of metachronous polyps/adenomas, colorectal cancer (CRC), and other gastrointestinal malignancies. Molecular pathology of the CRC were characterized...... and correlated with the index lesion. In total, 591 HP biopsy specimens were obtained from 480 patients. The lesions were reclassified as: 358 THP, 109 SSL, 35 TA, 81 unspecified non-neoplastic lesions, four traditional serrated adenoma, and 4 SSL with cytological dysplasia. Seven patients developed CRC...... in the follow-up period (1 patient had SSL, 4 had THP, and 2 had unspecified non-neoplastic lesions). Ten patients developed other gastrointestinal malignancies. The patient with SSL as index lesions who developed CRC harbored V600E BRAF mutation in both index lesion and the carcinoma. Sixteen percent...

  9. Prevalence of adenomas and hyperplastic polyps in mismatch repair mutation carriers among CAPP2 participants: report by the colorectal adenoma/carcinoma prevention programme 2

    DEFF Research Database (Denmark)

    Liljegren, Annelie; Barker, Gail; Elliott, Faye

    2008-01-01

    PURPOSE: To determine the prevalence of adenomatous and hyperplastic polyps in a large cohort of individuals with a germline mutation in a mismatch repair (MMR) gene, the major genetic determinant of hereditary nonpolyposis colorectal cancer (HNPCC). These prevalences have been estimated previously...... in smaller studies, and the results have been found to be variable. PATIENTS AND METHODS: Colorectal Adenoma/Carcinoma Prevention Programme 2 trial is a chemoprevention trial in people classified as having HNPCC. The 695 patients with a proven germline MMR mutation and documented screening history before...

  10. Multiple squamous cell carcinomas within the head and neck region

    International Nuclear Information System (INIS)

    Sato, Katsuro; Hanazawa, Hideyuki; Sato, Yuichiro; Takahashi, Sugata

    2004-01-01

    Clinical features of multiple squamous cell carcinoma (SCC) cases within the head and neck that were treated in our department during the recent 10 years are discussed. Multiple SCCs arose in 6.6% of the cases with primary SCC; 67% of the cases had two carcinomas, and 33% had more than three carcinomas. The most common site of the multiple SCCs was the oral cavity (54%). The most frequent interval between treatment of previous carcinoma and diagnosis of subsequent carcinoma was simultaneous, but more than 5 years' interval was observed in 36% of the patients. The most common initial treatment of the carcinoma was irradiation, but the ratio of surgery increased for subsequent carcinomas. Prognosis of the patients with more than three carcinomas was not worse than that of patients with two carcinomas. Therefore, early diagnosis of the subsequent carcinomas based on careful long-term observation in the head and neck is necessary for follow-up of the patients with SCC of the head and neck. Treatment strategies considering the treatment of subsequent carcinomas are needed for the patients with primary head and neck SCC. (author)

  11. Effects of polymorphisms in ERCC1, ASE-1 and RAI on the risk of colorectal carcinomas and adenomas: a case control study

    Directory of Open Access Journals (Sweden)

    Wallin Håkan

    2006-07-01

    Full Text Available Abstract Background The risk of sporadic colorectal cancer is mainly associated with lifestyle factors and may be modulated by several genetic factors of low penetrance. Genetic variants represented by single nucleotide polymorphisms in genes encoding key players in the adenoma carcinoma sequence may contribute to variation in susceptibility to colorectal cancer. In this study, we aimed to evaluate whether the recently identified haplotype encompassing genes of DNA repair and apoptosis, is associated with increased risk of colorectal adenomas and carcinomas. Methods We used a case-control study design (156 carcinomas, 981 adenomas and 399 controls to test the association between polymorphisms in the chromosomal region 19q13.2-3, encompassing the genes ERCC1, ASE-1 and RAI, and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR and 95% confidence interval (CI were estimated by binary logistic regression model adjusting for age and gender. Results The ASE-1 polymorphism was associated with an increased risk of adenomas, OR of 1.39 (95% CI 1.06–1.81, which upon stratification was apparent among women only, OR of 1.66 (95% CI 1.15–2.39. The RAI polymorphism showed a trend towards risk reduction for both adenomas (OR of 0.70, 95% CI 0.49–1.01 and carcinomas (OR of 0.49, 95% CI 0.21–1.13 among women, although not significant. Women who were homozygous carriers of the high risk haplotype had an increased risk of colorectal cancer, OR of 2.19 (95% CI 0.95–5.04 compared to all non-carriers although the estimate was not statistically significant. Conclusion We found no evidence that the studied polymorphisms were associated with risk of adenomas or colorectal cancer among men, but we found weak indications that the chromosomal region may influence risk of colorectal cancer and adenoma development in women.

  12. Inflammatory Cell Distribution in Primary Merkel Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wheat, Rachel [School of Cancer Sciences and CR UK Centre for Cancer Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT (United Kingdom); Roberts, Claudia [School of Cancer Sciences and CR UK Centre for Cancer Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT (United Kingdom); University Hospitals Birmingham NHS Foundation Trust, New Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB (United Kingdom); Waterboer, Tim [Infection and Cancer Program, DKFZ (German Cancer Research Centre), 69120 Heidelberg (Germany); Steele, Jane [Human Biomaterials Resource Centre, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT (United Kingdom); Marsden, Jerry [University Hospitals Birmingham NHS Foundation Trust, New Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB (United Kingdom); Steven, Neil M., E-mail: n.m.steven@bham.ac.uk [School of Cancer Sciences and CR UK Centre for Cancer Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT (United Kingdom); University Hospitals Birmingham NHS Foundation Trust, New Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB (United Kingdom); Blackbourn, David J., E-mail: n.m.steven@bham.ac.uk [Department of Microbial and Cellular Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH (United Kingdom)

    2014-05-06

    Merkel cell carcinoma (MCC) is an aggressive poorly differentiated neuroendocrine cutaneous carcinoma associated with older age, immunodeficiency and Merkel cell polyomavirus (MCPyV) integrated within malignant cells. The presence of intra-tumoural CD8+ lymphocytes reportedly predicts better MCC-specific survival. In this study, the distribution of inflammatory cells and properties of CD8+ T lymphocytes within 20 primary MCC specimens were characterised using immunohistochemistry and multicolour immunofluorescent staining coupled to confocal microscopy. CD8+ cells and CD68+ macrophages were identified in 19/20 primary MCC. CD20+ B cells were present in 5/10, CD4+ cells in 10/10 and FoxP3+ cells in 7/10 specimens. Only two specimens had almost no inflammatory cells. Within specimens, inflammatory cells followed the same patchy distribution, focused at the edge of sheets and nodules and, in some cases, more intense in trabecular areas. CD8+ cells were outside vessels on the edge of tumour. Those few within malignant sheets typically lined up in fine septa not contacting MCC cells expressing MCPyV large T antigen. The homeostatic chemokine CXCL12 was expressed outside malignant nodules whereas its receptor CXCR4 was identified within tumour but not on CD8+ cells. CD8+ cells lacked CXCR3 and granzyme B expression irrespective of location within stroma versus malignant nodules or of the intensity of the intra-tumoural infiltrate. In summary, diverse inflammatory cells were organised around the margin of malignant deposits suggesting response to aberrant signaling, but were unable to penetrate the tumour microenvironment itself to enable an immune response against malignant cells or their polyomavirus.

  13. Inflammatory Cell Distribution in Primary Merkel Cell Carcinoma

    International Nuclear Information System (INIS)

    Wheat, Rachel; Roberts, Claudia; Waterboer, Tim; Steele, Jane; Marsden, Jerry; Steven, Neil M.; Blackbourn, David J.

    2014-01-01

    Merkel cell carcinoma (MCC) is an aggressive poorly differentiated neuroendocrine cutaneous carcinoma associated with older age, immunodeficiency and Merkel cell polyomavirus (MCPyV) integrated within malignant cells. The presence of intra-tumoural CD8+ lymphocytes reportedly predicts better MCC-specific survival. In this study, the distribution of inflammatory cells and properties of CD8+ T lymphocytes within 20 primary MCC specimens were characterised using immunohistochemistry and multicolour immunofluorescent staining coupled to confocal microscopy. CD8+ cells and CD68+ macrophages were identified in 19/20 primary MCC. CD20+ B cells were present in 5/10, CD4+ cells in 10/10 and FoxP3+ cells in 7/10 specimens. Only two specimens had almost no inflammatory cells. Within specimens, inflammatory cells followed the same patchy distribution, focused at the edge of sheets and nodules and, in some cases, more intense in trabecular areas. CD8+ cells were outside vessels on the edge of tumour. Those few within malignant sheets typically lined up in fine septa not contacting MCC cells expressing MCPyV large T antigen. The homeostatic chemokine CXCL12 was expressed outside malignant nodules whereas its receptor CXCR4 was identified within tumour but not on CD8+ cells. CD8+ cells lacked CXCR3 and granzyme B expression irrespective of location within stroma versus malignant nodules or of the intensity of the intra-tumoural infiltrate. In summary, diverse inflammatory cells were organised around the margin of malignant deposits suggesting response to aberrant signaling, but were unable to penetrate the tumour microenvironment itself to enable an immune response against malignant cells or their polyomavirus

  14. Primary Small Cell Carcinoma of the Upper Urinary Tract

    Directory of Open Access Journals (Sweden)

    Victor Ka-Siong Kho

    2010-03-01

    Full Text Available We report a case of primary extrapulmonary small cell carcinoma of the distal ureter, with a synchronous small cell carcinoma of the ipsilateral renal pelvis. These tumors, rarely reported in the urinary tract, are locally aggressive and have a poor prognosis. A 77-year-old male bedridden patient presented with fever and chills with left side-flank pain for 3 days. Following a diagnosis of ureteral urothelial carcinoma, hand-assisted laparoscopic nephroureterectomy with bladder cuff excision was carried out. Adjuvant chemotherapy was given after pathologic report of primary small cell carcinoma of the distal ureter and a synchronous small cell carcinoma of the ipsilateral renal pelvis. After 3 cycles of combination chemotherapy, the patient died 4 months postoperatively due to sepsis.

  15. A rare case of choroid plexus carcinoma that led to the diagnosis of Lynch syndrome (hereditary nonpolyposis colorectal cancer).

    Science.gov (United States)

    Zhu, Viola W; Hinduja, Sanjay; Knezevich, Stevan R; Silveira, William R; DeLozier, Celia D

    2017-07-01

    Lynch syndrome (hereditary nonpolyposis colorectal cancer) is an autosomal dominant disorder characterized by a significant risk of colorectal and endometrial cancers. A variety of other epithelial cancers may be associated with this syndrome. Brian tumors are infrequent, but have been reported in series. Here, we report a case of a 34-year-old Caucasian woman with WHO grade III choroid plexus carcinoma (CPC). Comprehensive genomic profiling of the patient's resected brain tumor revealed mutations in six genes: PTEN, VHL, MSH6, NOTCH1, RB1, and TP53. Family history is significant for endometrial cancer in her mother and sister as well as colon cancer in her maternal grandfather suggestive of Lynch syndrome. Site-specific mutational analysis showed the MSH6 mutation (p.R482*) in peripheral lymphocytes. Subsequently we performed immunohistochemical staining of the tumor tissue which demonstrated widespread loss of MSH6 with intact MSH2, MLH1, and PMS2. The diagnosis of Lynch syndrome due to a mutation in MSH6 was therefore established. Our patient elected to have adjuvant radiation to the surgical bed only followed by prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy and is doing very well. To our knowledge, this is the first case report of CPC in an adult patient with a germline MSH6 mutation. We believe our data have provided molecular evidence to suggest that CPC could potentially be part of the Lynch syndrome spectrum. Published by Elsevier B.V.

  16. Collision tumor of Small Cell Carcinoma and Squamous Cell Carcinoma of maxillary sinus

    Directory of Open Access Journals (Sweden)

    Irfan Sugianto

    2016-06-01

    Full Text Available Two kinds of different malignant tumors occurring within the same organ is defined as collision tumor. Small Cell Carcinoma (SmCC is high-grade derived from neuroendocrine cell tumors, occurance in the head and neck is rare. Squamous Cell Carcinoma (SCC is the most common malignancies encountered in head and neck area, but the occuranceof collision tumor is very rare. This report describe a 82 year-old woman patient with a SmCC and SCC that occurred in the maxillary sinus. CT was performed including with enhancement, MRI examination was T1WI, STIR and contrast enhancement. We also conducted analysis of Dynamic Contrast Enhancement (DCE. Histopathologic examination revealed small cell carcinoma. A distant metastasis was not detected. After patient received chemoradiotherapy (CCRT, most of  tumorwas reduced although a part of the tumor was remained. Pathological examination of surgery tumor specimen revealed that specimen consisted of SCC and SmCC was disappeared, and six months after surgery, the patient suffered tumor recurrence and multiple metastasis to the organs in the abdomen. This time we have to report that the experience one cases that are considered collision cancer of SmCC and SCC that occurred in the maxillary sinus.

  17. Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma.

    Science.gov (United States)

    Cohen, Philip R

    2017-03-22

    Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that

  18. A case report of renal cell carcinoma in a dog

    Directory of Open Access Journals (Sweden)

    A.-S. Paşca

    2013-10-01

    Full Text Available Mix renal carcinoma was noticed during the necropsic examination of a 14 year old mix breed female. Tumours were bilateral and metastasis was noticed in the spleen and myocard. Histological examination evidenced morphological aspects characteristic to the mixt renal carcinoma. Histological aspects described in this individual characterize renal cell carcinoma, also known as renal adenocarcinoma, hypernephroma or, in older literature, Grawitz tumour.

  19. Squamous cell carcinoma of penis in patient with incipient neurosyphilis

    Directory of Open Access Journals (Sweden)

    D. V. Zaslavsky

    2016-01-01

    Full Text Available Squamous cell carcinoma of the skin (SSCC is one of the most common malignant skin tumors. Syphilis is a sexually transmitted disease caused by Treponema pallidum, with human beings as the only host. The combination of syphilis and squamous cell carcinoma of the skin is not uncommon, particularly if the lesions are located on different parts of the body. However, simultaneous development of the chancre and squamous cell carcinoma of the glans penis seems exceptional. Considering rarity of the manifestation observed we feel the rare case of combined syphilis and squamous cell skin cancer is of interest.

  20. Merkel Cell Carcinoma Metastatic to Pleural Fluid: A Case Report

    Directory of Open Access Journals (Sweden)

    Ye-Young Rhee

    2018-05-01

    Full Text Available Merkel cell carcinoma (MCC is a rare aggressive neuroendocrine carcinoma of the skin that shows locoregional or distant metastasis. Metastasis of MCC to body cavity effusion is extremely rare; only three cases have been reported so far. Metastatic MCC in effusion cytology shows small blue round cells with fine stippled chromatin like other small blue round cell tumors such as small cell lung carcinoma or lymphoma. The diagnosis of metastatic MCC can grant patients good chances at recently advanced therapeutic options. Here, we present a case of metastatic MCC to pleural effusion with characteristic single file-like pattern.

  1. Merkel Cell Carcinoma Metastatic to Pleural Fluid: A Case Report.

    Science.gov (United States)

    Rhee, Ye-Young; Kim, Soo Hee; Kim, Eun Kyung; Kim, Se Hoon

    2018-05-01

    Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine carcinoma of the skin that shows locoregional or distant metastasis. Metastasis of MCC to body cavity effusion is extremely rare; only three cases have been reported so far. Metastatic MCC in effusion cytology shows small blue round cells with fine stippled chromatin like other small blue round cell tumors such as small cell lung carcinoma or lymphoma. The diagnosis of metastatic MCC can grant patients good chances at recently advanced therapeutic options. Here, we present a case of metastatic MCC to pleural effusion with characteristic single file-like pattern.

  2. Rare Case of Duodenal Metastasis From Pulmonary Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Zain Memon DO

    2017-10-01

    Full Text Available Pulmonary squamous cell carcinoma is the second most common non–small cell malignancy of the lung. It commonly metastasizes to the adrenal glands, bone, liver, brain, and kidneys. Most occurrences of metastatic squamous cell carcinoma involving the gastrointestinal tract originate from primary lung tumors. Metastasis to the duodenum, however, is exceedingly rare, with very few cases of stomach or duodenal involvement described in the literature. We report the case of a patient with stage IV pulmonary squamous cell carcinoma metastasizing to the duodenum with an uncommon presentation to add to the paucity of literature available regarding this rare finding.

  3. Highly efficient elimination of colorectal tumor-initiating cells by an EpCAM/CD3-bispecific antibody engaging human T cells.

    Directory of Open Access Journals (Sweden)

    Ines Herrmann

    2010-10-01

    Full Text Available With their resistance to genotoxic and anti-proliferative drugs and potential to grow tumors and metastases from very few cells, cancer stem or tumor-initiating cells (TICs are a severe limitation for the treatment of cancer by conventional therapies. Here, we explored whether human T cells that are redirected via an EpCAM/CD3-bispecific antibody called MT110 can lyse colorectal TICs and prevent tumor growth from TICs. MT110 recognizes EpCAM, a cell adhesion molecule expressed on TICs from diverse human carcinoma, which was recently shown to promote tumor growth through engagement of elements of the wnt pathway. MT110 was highly potent in mediating complete redirected lysis of KRAS-, PI3 kinase- and BRAF-mutated colorectal TICs, as demonstrated in a soft agar assay. In immunodeficient mice, MT110 prevented growth of tumors from a 5,000-fold excess of a minimally tumorigenic TIC dose. T cells engaged by MT110 may provide a potent therapeutic means to eradicate TICs and bulk tumor cells derived thereof.

  4. Ileocecal Adenocarcinoma and Ureteral Transitional Cell Carcinoma with Multiple Sebaceous Tumors and Keratoacanthomas in a Case of Muir-Torre Syndrome

    Directory of Open Access Journals (Sweden)

    Michael C. Lynch

    2010-01-01

    Full Text Available Cutaneous neoplasms including sebaceous tumors, keratoacanthomas, and basal cell carcinomas with sebaceous differentiation can be markers of internal malignancy associated with the Muir-Torre Syndrome (MTS. We report a 56-year-old man with a diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC and ureteral transitional cell carcinoma who subsequently developed two sebaceous gland neoplasms and several keratoacanthomas, leading to the diagnosis of MTS. Our case highlights the clinical advantages of immunohistochemistry (IHC in identifying mutations in the mismatch repair (MMR genes responsible for both HNPCC and MTS. The importance of continued clinical suspicion in the dermatological assessment of patients with sebaceous neoplasms is emphasized.

  5. Oncolytic vaccinia therapy of squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Yu Yong A

    2009-07-01

    Full Text Available Abstract Background Novel therapies are necessary to improve outcomes for patients with squamous cell carcinomas (SCC of the head and neck. Historically, vaccinia virus was administered widely to humans as a vaccine and led to the eradication of smallpox. We examined the therapeutic effects of an attenuated, replication-competent vaccinia virus (GLV-1h68 as an oncolytic agent against a panel of six human head and neck SCC cell lines. Results All six cell lines supported viral transgene expression (β-galactosidase, green fluorescent protein, and luciferase as early as 6 hours after viral exposure. Efficient transgene expression and viral replication (>150-fold titer increase over 72 hrs were observed in four of the cell lines. At a multiplicity of infection (MOI of 1, GLV-1h68 was highly cytotoxic to the four cell lines, resulting in ≥ 90% cytotoxicity over 6 days, and the remaining two cell lines exhibited >45% cytotoxicity. Even at a very low MOI of 0.01, three cell lines still demonstrated >60% cell death over 6 days. A single injection of GLV-1h68 (5 × 106 pfu intratumorally into MSKQLL2 xenografts in mice exhibited localized intratumoral luciferase activity peaking at days 2–4, with gradual resolution over 10 days and no evidence of spread to normal organs. Treated animals exhibited near-complete tumor regression over a 24-day period without any observed toxicity, while control animals demonstrated rapid tumor progression. Conclusion These results demonstrate significant oncolytic efficacy by an attenuated vaccinia virus for infecting and lysing head and neck SCC both in vitro and in vivo, and support its continued investigation in future clinical trials.

  6. Origin of clear cell carcinoma: nature or nurture?

    Science.gov (United States)

    Kolin, David L; Dinulescu, Daniela M; Crum, Christopher P

    2018-02-01

    A rare but serious complication of endometriosis is the development of carcinoma, and clear cell and endometrioid carcinomas of the ovary are the two most common malignancies which arise from endometriosis. They are distinct diseases, characterized by unique morphologies, immunohistochemical profiles, and responses to treatment. However, both arise in endometriosis and can share common mutations. The overlapping mutational profiles of clear cell and endometrioid carcinomas suggest that their varied histologies may be due to a different cell of origin which gives rise to each type of cancer. Cochrane and colleagues address this question in a recent article in this journal. They show that a marker of ovarian clear cell carcinoma, cystathionine gamma lyase, is expressed in ciliated cells. Similarly, they show that markers of secretory cells (estrogen receptor and methylenetetrahydrofolate dehydrogenase 1) are expressed in ovarian endometrioid carcinoma. Taken together, they suggest that endometrioid and clear cell carcinomas arise from cells related to secretory and ciliated cells, respectively. We discuss Cochrane et al's work in the context of other efforts to determine the cell of origin of gynecological malignancies, with an emphasis on recent developments and challenges unique to the area. These limitations complicate our interpretation of tumor differentiation; does it reflect nature imposed by a specific cell of origin or nurture, by either mutation(s) or environment? Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  7. Efficacy of the MEK Inhibitor Cobimetinib and its Potential Application to Colorectal Cancer Cells.

    Science.gov (United States)

    Gong, Shu; Xu, Dongsheng; Zhu, Jialin; Zou, Fangdong; Peng, Rui

    2018-05-22

    Mutations in the Ras/Raf/MEK/ERK pathway are detected in 50% of colorectal cancer cases and play a crucial role in cancer development and progression. Cobimetinib is a MEK inhibitor approved for the treatment of advanced melanoma and inhibits the cell viability of other types of cancer cells. HCT116 colorectal cancer cells were treated with cobimetinib, and MTT assay, colony formation assay, and flow cytometry were used to evaluate cell viability, cell cycle, and apoptosis, respectively. The expression of genes associated with the cell cycle and apoptosis were evaluated by quantitative real-time PCR and western blotting. To explore use of cobimetinib in colorectal cancer treatment and further understand its mechanisms, RNA-seq technology was used to identify differentially expressed genes (DEGs) between cobimetinib-treated and untreated HCT116 cells. Furthermore, we compared these DEGs with Gene Expression Omnibus data from colorectal cancer tissues and normal colonic epithelial tissues. We found that cobimetinib not only inhibited cell proliferation but also induced G1 phase arrest and apoptosis in HCT116 colorectal cancer cells, suggesting that cobimetinib may useful in colorectal cancer therapy. After cobimetinib treatment, 3,495 DEGs were obtained, including 2,089 upregulated genes and 1,406 downregulated genes, and most of these DEGs were enriched in the cell cycle, DNA replication, and DNA damage repair pathways. Our results revealed that some genes with high expression in colorectal cancer tissues were downregulated by cobimetinib in HCT116 cells, including CCND1, E2F1, CDC25C, CCNE2, MYC, and PCNA. These genes have vital roles in DNA replication and the cell cycle. Furthermore, genes with low expression in colorectal cancer tissues were upregulated by cobimetinib, including PRKCA, PI3K, RTK, and PKC. Based on our results, the PKC and PI3K pathways were activated after cobimetinib treatment, and inhibition of these two pathways can increase the cytotoxicity

  8. Identification and validation of highly frequent CpG island hypermethylation in colorectal adenomas and carcinomas

    DEFF Research Database (Denmark)

    Øster, Bodil; Thorsen, Kasper; Lamy, Philippe

    2011-01-01

    ), in carcinomas only (ABHD9, AOX1 and RERG), or in MSI but not MSS carcinomas (RAMP2, DSC3 and MLH1) were validated using MS-HRM. Four of these genes (MLH1, AOX1, EYA4 and TWIST1) had previously been reported to be hypermethylated in CRC. Eleven genes, not previously known to be affected by CRC specific...

  9. Perineural Infiltration of Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma Without Clinical Features

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Charles, E-mail: Charles_Lin@health.qld.gov.au [Cancer Care Services, Royal Brisbane and Women' s Hospital, Brisbane, Queensland (Australia); Tripcony, Lee; Keller, Jacqui [Cancer Care Services, Royal Brisbane and Women' s Hospital, Brisbane, Queensland (Australia); Poulsen, Michael [Mater Hospital, Brisbane, Queensland (Australia); Martin, Jarad [St. Andrews Hospital, Toowoomba, Queensland (Australia); Jackson, James; Dickie, Graeme [Cancer Care Services, Royal Brisbane and Women' s Hospital, Brisbane, Queensland (Australia)

    2012-01-01

    Purpose: To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy. Methods and Materials: Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis. Results: Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors. Conclusions: Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.

  10. Merkel Cell Carcinoma: An Update and Immunotherapy

    Directory of Open Access Journals (Sweden)

    Hiroshi Uchi

    2018-03-01

    Full Text Available Merkel cell carcinoma (MCC is a rare but aggressive skin cancer with frequent metastasis and death. MCC has a mortality rate of 30%, making it more lethal than malignant melanoma, and incidence of MCC has increased almost fourfold over the past 20 years in the USA. MCC has long been considered to be an immunogenic cancer because it occurs more frequently in immunosuppressed patients from organ transplant and HIV infection than in those with immunocompetent. Chronic UV light exposure and clonal integration of Merkel cell polyomavirus (MCPyV are two major causative factors of MCC. Approximately 80% of MCC are associated with MCPyV, and T cells specific for MCPyV oncoproteins are present in the blood and tumors of patients. Several studies have shown that a subset of MCCs express PD-1 on tumor-infiltrating lymphocytes and express PD-L1 on tumor cells, which suggests an endogenous tumor-reactive immune response that might be unleashed by anti-PD-1 or anti-PD-L1 drugs.

  11. Optimization of a Pretargeted Strategy for the PET Imaging of Colorectal Carcinoma via the Modulation of Radioligand Pharmacokinetics.

    Science.gov (United States)

    Zeglis, Brian M; Brand, Christian; Abdel-Atti, Dalya; Carnazza, Kathryn E; Cook, Brendon E; Carlin, Sean; Reiner, Thomas; Lewis, Jason S

    2015-10-05

    Pretargeted PET imaging has emerged as an effective strategy for merging the exquisite selectivity of antibody-based targeting vectors with the rapid pharmacokinetics of radiolabeled small molecules. We previously reported the development of a strategy for the pretargeted PET imaging of colorectal cancer based on the bioorthogonal inverse electron demand Diels-Alder reaction between a tetrazine-bearing radioligand and a transcyclooctene-modified huA33 immunoconjugate. Although this method effectively delineated tumor tissue, its clinical potential was limited by the somewhat sluggish clearance of the radioligand through the gastrointestinal tract. Herein, we report the development and in vivo validation of a pretargeted strategy for the PET imaging of colorectal carcinoma with dramatically improved pharmacokinetics. Two novel tetrazine constructs, Tz-PEG7-NOTA and Tz-SarAr, were synthesized, characterized, and radiolabeled with (64)Cu in high yield (>90%) and radiochemical purity (>99%). PET imaging and biodistribution experiments in healthy mice revealed that although (64)Cu-Tz-PEG7-NOTA is cleared via both the gastrointestinal and urinary tracts, (64)Cu-Tz-SarAr is rapidly excreted by the renal system alone. On this basis, (64)Cu-Tz-SarAr was selected for further in vivo evaluation. To this end, mice bearing A33 antigen-expressing SW1222 human colorectal carcinoma xenografts were administered huA33-TCO, and the immunoconjugate was given 24 h to accumulate at the tumor and clear from the blood, after which (64)Cu-Tz-SarAr was administered via intravenous tail vein injection. PET imaging and biodistribution experiments revealed specific uptake of the radiotracer in the tumor at early time points (5.6 ± 0.7 %ID/g at 1 h p.i.), high tumor-to-background activity ratios, and rapid elimination of unclicked radioligand. Importantly, experiments with longer antibody accumulation intervals (48 and 120 h) yielded slight decreases in tumoral uptake but also concomitant

  12. Subungual squamous cell carcinoma: A case study

    Energy Technology Data Exchange (ETDEWEB)

    Neill, Cory J., E-mail: coryjneill@gmail.com

    2017-07-01

    The purpose of this case study is to describe a dosimetric delivery of radiation to a superficial disease process involving the skin and bone of the distal finger. A 76-year-old male patient presented with a subungual squamous cell carcinoma (SCC) of the left distal index finger with bony involvement. The patient refused conventional surgical treatment but agreed to external beam radiation therapy (EBRT). There is a gap in the current literature describing how to successfully immobilize fingers and which EBRT modality is dosimetrically advantageous in treating them. The construction of a simple immobilization method with the patient in a reproducible position is described. The use of photons and electrons were compared ultimately showing photons to be dosimetrically advantageous. Long-term efficacy of the treatment was not evaluated because of patient noncompliance.

  13. Sequential Therapy in Metastatic Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Bradford R Hirsch

    2016-04-01

    Full Text Available The treatment of metastatic renal cell carcinoma (mRCC has changed dramatically in the past decade. As the number of available agents, and related volume of research, has grown, it is increasingly complex to know how to optimally treat patients. The authors are practicing medical oncologists at the US Oncology Network, the largest community-based network of oncology providers in the country, and represent the leadership of the Network's Genitourinary Research Committee. We outline our thought process in approaching sequential therapy of mRCC and the use of real-world data to inform our approach. We also highlight the evolving literature that will impact practicing oncologists in the near future.

  14. Imaging in Patients with Merkel Cell Carcinoma

    International Nuclear Information System (INIS)

    Enzenhofer, E.; Ubl, P.; Czerny, C.; Erovic, B. M.

    2013-01-01

    Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine tumor of the skin with a mortality rate of approximately 25% (Peloschek et al., 2010). Accurate assessment of nodal involvement in patients with MCC predicts significantly overall outcome (Smith et al., 2012 and Ortin-Perez et al., 2007). Due to the rarity of this highly aggressive disease, only a few imaging reports on MCC were published, and subsequently still to date no accepted imaging algorithm for MCC is available. For primary staging of MCC, general recommendations have included ultrasonography, chest X-ray CT, and MRI, but recent articles show that the use of sentinel node and FDG-PET/PET-CT is gaining more and more importance

  15. Merkel cell carcinoma with seborrheic keratosis: A unique association.

    Science.gov (United States)

    Anand, Murthy S; Krishnamurthy, Shantha; Ravindranath, Suvarna; Ranganathan, Jyothi

    2018-01-01

    Merkel cell carcinoma (MCC) is a rare, clinically aggressive neuroendocrine carcinoma of the skin; MCC is 40 times less common as compared to melanoma. The most frequently reported sites have been the head and neck, extremities, and trunk. Potential mimics include malignant melanoma, lymphoma, or metastatic small cell (neuroendocrine) carcinomas. Histopathology of MCC resembles small cell carcinoma both morphologically and on IHC. The possible cell of origin was proposed as the Merkel cell, which functions as a mechanoreceptor. It has a high chance of local recurrence, regional and distant spread. In recent times, Merkel cell polyomavirus has been implicated as the causative agent for this tumor. The same agent has a reported etiologic association with other skin lesions, including seborrheic keratosis.

  16. Watermelon stomach, hemorrhagic pericarditis, small cell carcinoma of the lung and synchronous squamous cell carcinoma of the tongue base

    Directory of Open Access Journals (Sweden)

    A. Murinello

    2010-07-01

    Full Text Available Based on a case of gastric antral vascular ectasia (watermelon stomach that was associated with hemorrhagic pericarditis, small cell lung carcinoma with mediastinal lymph node metastases and a synchronous squamous cell carcinoma of the base of the tongue, the authors made a review of the clinical, endoscopic and histopathological aspects of this type of gastropathy, and its association with other diseases, and of the results of its endoscopic therapy. The causes of hemorrhagic pericarditis are considered, emphasizing the necessity to know if the effusion has a malignant etiology. To the best of our knowledge the association of watermelon stomach to small cell lung carcinoma and squamous cell carcinoma of the base of the tongue has not yet been described. Extensive metastases to mediastal lymph nodes are common to small cell lung carcinoma. Resumo: Baseados num caso de gastropatia antral com ectasia vascular (estômago em melancia associado a pericardite hemorrágica e a um carcinoma de pequenas células do pulmão com metástases ganglionares ao longo do mediastino e a um carcinoma pavimentocelular síncrono da base da língua, os autores fazem uma revisão dos aspectos clínicos, endoscópicos e histopatológicos deste tipo de gastropatia, da sua associação a outras doenças e das possibilidades terapêuticas actuais por via endoscópica. Referem-se igualmente as causas mais frequentes de pericardite hemorrágica, salientando-se a necessidade de esclarecer se o derrame é ou não de origem neoplásica. Não está referida na literatura a associação deste tipo de gastropatia ao carcinoma de pequenas células do pulmão nem ao carcinoma pavimento-celular da base da língua. A invasão extensa dos gânglios mediastínicos pelo carcinoma de pequenas células do pulmão é ocorrência frequente. Key-words: Gastric antral vascular ectasia, watermelon stomach, small cell lung carcinoma, oat cell lung carcinoma, squamous cell carcinoma of the base

  17. Targeting cancer stem cells in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    He AR

    2014-12-01

    Full Text Available Aiwu Ruth He,1 Daniel C Smith,1 Lopa Mishra2 1Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 2Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The poor outcome of patients with hepatocellular carcinoma (HCC is attributed to recurrence of the disease after curative treatment and the resistance of HCC cells to conventional chemotherapy, which may be explained partly by the function of liver cancer stem cells (CSCs. Liver CSCs have emerged as an important therapeutic target against HCC. Numerous surface markers for liver CSCs have been identified, and include CD133, CD90, CD44, CD13, and epithelial cell adhesion molecules. These surface markers serve not only as tools for identifying and isolating liver CSCs but also as therapeutic targets for eradicating these cells. In studies of animal models and large-scale genomic analyses of human HCC samples, many signaling pathways observed in normal stem cells have been found to be altered in liver CSCs, which accounts for the stemness and aggressive behavior of these cells. Antibodies and small molecule inhibitors targeting the signaling pathways have been evaluated at different levels of preclinical and clinical development. Another strategy is to promote the differentiation of liver CSCs to less aggressive HCC that is sensitive to conventional chemotherapy. Disruption of the tumor niche essential for liver CSC homeostasis has become a novel strategy in cancer treatment. To overcome the challenges in developing treatment for liver CSCs, more research into the genetic makeup of patient tumors that respond to treatment may lead to more effective therapy. Standardization of HCC CSC tumor markers would be helpful for measuring the CSC response to these agents. Herein, we review the current strategies for developing treatment to eradicate liver CSCs and to improve the outcome for patients with

  18. Ultrastructural proof of polyomavirus in Merkel cell carcinoma tumour cells and its absence in small cell carcinoma of the lung.

    Directory of Open Access Journals (Sweden)

    Charlotte T A H Wetzels

    Full Text Available BACKGROUND: A new virus called the Merkel Cell Polyomavirus (MCPyV has recently been found in Merkel Cell Carcinoma (MCC. MCC is a rare aggressive small cell neuroendocrine carcinoma primarily derived from the skin, morphologically indistinguishable from small cell lung carcinoma (SCLC. So far the actual presence of the virus in MCC tumour cells on a morphological level has not been demonstrated, and the presence of MCPyV in other small cell neuroendocrine carcinomas has not been studied yet. METHODOLOGY/PRINCIPAL FINDINGS: We investigated MCC tissue samples from five patients and SCLCs from ten patients for the presence of MCPyV-DNA by PCR and sequencing. Electron microscopy was used to search ultrastructurally for morphological presence of the virus in MCPyV-DNA positive samples. MCPyV was detected in two out of five primary MCCs. In one MCC patient MCPyV-DNA was detected in the primary tumour as well as in the metastasis, strongly suggesting integration of MCPyV in the cellular DNA of the tumour in this patient. In the primary MCC of another patient viral particles in tumour cell nuclei and cytoplasm were identified by electron microscopy, indicating active viral replication in the tumour cells. In none of the SCLCs MCPyV-DNA was detected. CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest that MCPyV is an oncogenic polyomavirus in humans, and is potentially causally related to the development of MCC but not to the morphological similar SCLC.

  19. Transcriptomic dissection of tongue squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Schwartz Joel L

    2008-02-01

    Full Text Available Abstract Background The head and neck/oral squamous cell carcinoma (HNOSCC is a diverse group of cancers, which develop from many different anatomic sites and are associated with different risk factors and genetic characteristics. The oral tongue squamous cell carcinoma (OTSCC is one of the most common types of HNOSCC. It is significantly more aggressive than other forms of HNOSCC, in terms of local invasion and spread. In this study, we aim to identify specific transcriptomic signatures that associated with OTSCC. Results Genome-wide transcriptomic profiles were obtained for 53 primary OTSCCs and 22 matching normal tissues. Genes that exhibit statistically significant differences in expression between OTSCCs and normal were identified. These include up-regulated genes (MMP1, MMP10, MMP3, MMP12, PTHLH, INHBA, LAMC2, IL8, KRT17, COL1A2, IFI6, ISG15, PLAU, GREM1, MMP9, IFI44, CXCL1, and down-regulated genes (KRT4, MAL, CRNN, SCEL, CRISP3, SPINK5, CLCA4, ADH1B, P11, TGM3, RHCG, PPP1R3C, CEACAM7, HPGD, CFD, ABCA8, CLU, CYP3A5. The expressional difference of IL8 and MMP9 were further validated by real-time quantitative RT-PCR and immunohistochemistry. The Gene Ontology analysis suggested a number of altered biological processes in OTSCCs, including enhancements in phosphate transport, collagen catabolism, I-kappaB kinase/NF-kappaB signaling cascade, extracellular matrix organization and biogenesis, chemotaxis, as well as suppressions of superoxide release, hydrogen peroxide metabolism, cellular response to hydrogen peroxide, keratinization, and keratinocyte differentiation in OTSCCs. Conclusion In summary, our study provided a transcriptomic signature for OTSCC that may lead to a diagnosis or screen tool and provide the foundation for further functional validation of these specific candidate genes for OTSCC.

  20. Detection of Secondary Liver Tumors in Patients with Colorectal Carcinoma by Using Tumor Markers

    Czech Academy of Sciences Publication Activity Database

    Holubec jr., L.; Topolčan, O.; Třeška, V.; Holubec sen., L.; Pecen, Ladislav; Pikner, R.; Finek, J.; Visokai, V.; Lipská, L.

    2002-01-01

    Roč. 17, č. 3 (2002), s. 134-135 ISSN 0886-3849. [International Conference on Human Tumor Markers /19./. 25.08.2002-29.08.2002, Velje] Institutional research plan: AV0Z1030915 Keywords : tumor markers * colorectal CA Subject RIV: BA - General Mathematics

  1. Checking the Course of Colorectal Carcinoma Follow up Using Mathematical Classification of Tumor Marker Profiles

    Czech Academy of Sciences Publication Activity Database

    Holubec jr., L.; Botterlich, N.; Topolčan, O.; Finek, J.; Pikner, R.; Pecen, Ladislav; Holubec, L.

    2002-01-01

    Roč. 23, Suppl.1 (2002), s. 57 ISSN 1010-4283. [Meeting of the International Society for Oncodevelopmental Biology and Medicine /30./. 08.09.2002-12.09.2002, Boston] R&D Projects: GA MŠk ME 438 Institutional research plan: AV0Z1030915 Keywords : tumor markers * colorectal CA * mathematical classification Subject RIV: BA - General Mathematics

  2. Benefit of FOLFOX to unresectable liver metastases secondary from colorectal carcinoma in an oncologic emergency.

    Science.gov (United States)

    Sugimoto, Maki; Yasuda, Hideki; Koda, Keiji; Yamazaki, Masato; Tezuka, Tohru; Takenoue, Tomohiro; Kosugi, Chihiro; Higuchi, Ryota; Yamamoto, Shiho; Watayo, Yoshihisa; Yagawa, Yohsuke; Suzuki, Masato

    2007-09-01

    Liver metastasis is an important prognostic factor in colorectal cancer. The efficacy of resection of metastatic lesions in liver metastasis of colorectal cancer is also widely recognized. However, studies on treatment methods of unresectable cases have not been sufficient and obtaining complete remission (CR) for liver metastasis is rare with chemotherapy. Selection of reliable chemotherapy for unresectable liver metastasis is an urgent necessity. The usefulness of oxaliplatin, 5-flurouracil and leucovorin combination therapy (FOLFOX) has recently been reported, but CR of liver metastasis is rare. The current status and new therapeutic significance of FOLFOX therapy are discussed based on the literature of colorectal cancer chemotherapy to date, and the clinical experience in which we obtained CR for liver metastasis is reported. The patient had stage IV rectal cancer, perforative peritonitis, pelvic abscess and simultaneous multiple liver metastasis. The patient underwent an emergency operation using the Hartmann's procedure. Liver metastasis is considered to be a prognostic factor and FOLFOX was selected as the postoperative chemotherapy, CR of the liver metastasis was obtained. FOLFOX was suggested to have new clinical significance in oncologic emergencies against unresectable liver metastasis in colorectal cancer and should serve as adjuvant chemotherapy that will contribute to improvement of treatment results.

  3. Physical and Nutritional Prehabilitation in Older Patients With Colorectal Carcinoma : A Systematic Review

    NARCIS (Netherlands)

    Looijaard, Stéphanie M L M; Slee-Valentijn, Monique S; Otten, René H J; Maier, Andrea B

    2017-01-01

    BACKGROUND AND PURPOSE: Sarcopenia and malnourishment are highly prevalent in older patients with colorectal cancer (CRC), who form a growing group of patients at risk of adverse outcome after surgery. Intervention on physical function and/or nutritional status may decrease the risk of postoperative

  4. Immunoscreening of the extracellular proteome of colorectal cancer cells

    International Nuclear Information System (INIS)

    Klein-Scory, Susanne; Schwarte-Waldhoff, Irmgard; Kübler, Salwa; Diehl, Hanna; Eilert-Micus, Christina; Reinacher-Schick, Anke; Stühler, Kai; Warscheid, Bettina; Meyer, Helmut E; Schmiegel, Wolff

    2010-01-01

    The release of proteins from tumors can trigger an immune response in cancer patients involving T lymphocytes and B lymphocytes, which results in the generation of antibodies to tumor-derived proteins. Many studies aim to use humoral immune responses, namely autoantibody profiles, directly, as clinical biomarkers. Alternatively, the antibody immune response as an amplification system for tumor associated alterations may be used to indicate putative protein biomarkers with high sensitivity. Aiming at the latter approach we here have implemented an autoantibody profiling strategy which particularly focuses on proteins released by tumor cells in vitro: the so-called secretome. For immunoscreening, the extracellular proteome of five colorectal cancer cell lines was resolved on 2D gels, immobilized on PVDF membranes and used for serological screening with individual sera from 21 colorectal cancer patients and 24 healthy controls. All of the signals from each blot were assigned to a master map, and autoantigen candidates were defined based of the pattern of immunoreactivities. The corresponding proteins were isolated from preparative gels, identified by MALDI-MS and/or by nano-HPLC/ESI-MS/MS and exemplarily confirmed by duplex Western blotting combining the human serum samples with antibodies directed against the protein(s) of interest. From 281 secretome proteins stained with autoantibodies in total we first defined the 'background patterns' of frequently immunoreactive extracellular proteins in healthy and diseased people. An assignment of these proteins, among them many nominally intracellular proteins, to the subset of exosomal proteins within the secretomes revealed a large overlap. On this basis we defined and consequently confirmed novel biomarker candidates such as the extreme C-terminus of the extracellular matrix protein agrin within the set of cancer-enriched immunorectivities. Our findings suggest, first, that autoantibody responses may be due, in

  5. Five cases of squamous cell carcinoma induced by irradiation

    International Nuclear Information System (INIS)

    Omoto, Kayo; Tani, Tasaburo; Nagata, Hiroyuki; Kohda, Mamoru; Ueki, Hiroaki

    1985-01-01

    Five cases of squamous cell carcinoma (skin) induced by irradiation are reported. Three cases had been given radiotherapy for benign skin disorders, tinea pedis, lichen Vidal, and dermatitis papillaris capillitis. The other two cases were medical doctors who had developed carcinoma as the result of advanced radiodermatitis. (author)

  6. Humeral Metastasis in a case of Squamous Cell Carcinoma - a ...

    African Journals Online (AJOL)

    A rare case of squamous cell carcinoma with metastasis to distal acral skeleton – humerus within two months of diagnosis of the primary is being reported. The metastasis to the bones from carcinoma cervix is uncommon especially in the distal appendicular skeleton. A 47 years female came with spontaneous fracture of ...

  7. Percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma under C-arm cone beam CT guidance.

    Science.gov (United States)

    Amouyal, G; Pernot, S; Déan, C; Cholley, B; Scotté, F; Sapoval, M; Pellerin, O

    2017-11-01

    The aim of this study was to assess the feasibility, safety and efficacy of percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma using C-arm cone beam computed tomography (CBCT) guidance. This single-center prospective observational study was performed from August 2013 to August 2016, and included consecutive patients referred for radiofrequency ablation of lung metastases from colorectal cancer. Radiofrequency ablation procedures were performed under C-arm CBCT guidance. Feasibility was assessed by probe accuracy placement, time to accurate placement and number of C-arm CBCT acquisitions to reach the target lesion. Safety was assessed by the report of adverse event graded using the common terminology criteria for adverse events (CTCAE-V4.0). Efficacy was assessed by metastases response rate using RECIST 1.1 and 18 FDG-PET-CT tumor uptake at 6months. Fifty-four consecutive patients (32 men, 22 women) with a mean age of 63±8 (SD) years (range: 51-81years) with a total of 56 lung metastasis from colorectal metastases were treated in a single session. The mean tumor diameter was 25.6±4.5 (SD)mm (range: 17-31mm). Median time to insert the needle into the target lesion was 10min (range: 5-25min). Median number of needles repositioning and C-arm CBCT acquisition per patient was 1 (range: 0-3) and 4 (range: 3-6) respectively. The accuracy for radiofrequency ablation probe placement was 2±0.2 (SD)mm (range: 0-9mm). Pneumothorax requiring chest tube placement occurred in one patient (CTCAE-V4.0 grade 3). At 6months, all patients were alive with tumor response rate of -27% and had no significant activity on the 18 FDG-PET CT follow-up. Percutaneous radiofrequency ablation of lung metastases from colorectal cancer under C-arm CBCT guidance is feasible and safe, with immediate and short-term results similar to those obtained using conventional CT guidance. Copyright © 2017 Éditions françaises de radiologie. Published by Elsevier Masson SAS

  8. MiRNA-21 Expression Decreases from Primary Tumors to Liver Metastases in Colorectal Carcinoma.

    Directory of Open Access Journals (Sweden)

    Fabian Feiersinger

    Full Text Available Metastasis is the major cause of death in colorectal cancer patients. Expression of certain miRNAs in the primary tumors has been shown to be associated with progression of colorectal cancer and the initiation of metastasis. In this study, we compared miRNA expression in primary colorectal cancer and corresponding liver metastases in order to get an idea of the oncogenic importance of the miRNAs in established metastases.We analyzed the expression of miRNA-21, miRNA-31 and miRNA-373 in corresponding formalin-fixed paraffin-embedded (FFPE tissue samples of primary colorectal cancer, liver metastasis and healthy tissues of 29 patients by quantitative real-time PCR.All three miRNAs were significantly up-regulated in the primary tumor tissues as compared to healthy colon mucosa of the respective patients (p < 0.01. MiRNA-21 and miRNA-31 were also higher expressed in liver metastases as compared to healthy liver tissues (p < 0.01. No significant difference of expression of miRNA-31 and miRNA-373 was observed between primary tumors and metastases. Of note, miRNA-21 expression was significantly reduced in liver metastases as compared to the primary colorectal tumors (p < 0.01.In the context of previous studies demonstrating increased miRNA-21 expression in metastatic primary tumors, our findings raise the question whether miRNA-21 might be involved in the initiation but not in the perpetuation and growth of metastases.

  9. Squamous cell carcinoma of temporal bone: four case reports

    International Nuclear Information System (INIS)

    Lee, Jun Ha; Sung, Ki Joon; Sim, Young; Shim, Sue Yoen; Yoon, Byoung Moon

    2000-01-01

    We report the CT findings of four cases of squamous cell carcinoma, paying special attention to the epicenter of the lesion and the pattern of bony destruction. All four patients had a past history of chronic otitis media. Squamous cell carcinoma affected mainly the hypotympanum and inferior wall of the external auditory canal. and in all cases revealed an irregular pattern of bony destruction. Irregular destruction of the tegmen tympani occurred in two cases. In cases of squamous cell carcinoma, CT findings suggesting involvement of the promontory are usually noted. (author)

  10. Squamous cell carcinoma of temporal bone: four case reports

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jun Ha; Sung, Ki Joon; Sim, Young; Shim, Sue Yoen; Yoon, Byoung Moon [Wonju College of Medicine, Yonsei University, Wonju (Korea, Republic of)

    2000-04-01

    We report the CT findings of four cases of squamous cell carcinoma, paying special attention to the epicenter of the lesion and the pattern of bony destruction. All four patients had a past history of chronic otitis media. Squamous cell carcinoma affected mainly the hypotympanum and inferior wall of the external auditory canal. and in all cases revealed an irregular pattern of bony destruction. Irregular destruction of the tegmen tympani occurred in two cases. In cases of squamous cell carcinoma, CT findings suggesting involvement of the promontory are usually noted. (author)

  11. Merkel Cell Carcinoma: Interdisciplinary Management of a Rare Disease

    International Nuclear Information System (INIS)

    Schneider, S.; Thurnher, D.; Erovic, B. M.

    2013-01-01

    The goal of this paper is to review contemporary multidisciplinary treatment with reference to Milkier cell carcinoma. Management of this rare but highly aggressive skin cancer is a complex undertaking that necessitates an understanding of its etiology, epidemiology, clinical presentation, and the coordinated work of several clinical specializations. Recent Findings. The contemporary literature employs a multidisciplinary approach to achieve the best patient's treatment. Conclusion. This paper presents an algorithm for contemporary management for the rare and aggressive Merkel cell carcinoma. Multidisciplinary approach in a tumor center provides high-quality care for patients with Merkel cell carcinoma.

  12. treatment of Merkel cell carcinoma: a report of four cases

    International Nuclear Information System (INIS)

    Song Yongwen; Liu Xinfan; Wang Xiaozhen; Li Yexiong

    2002-01-01

    Objective: To study the clinical characteristics and progress so as to establish a better therapeutic principle for Merkel cell carcinoma. Methods: Manifestations and results of 4 Merkel cell carcinoma patients treated, with review of relevant papers is presented. Results: Among these 4 patients, local recurrence developed in 2, regional lymphatic metastasis in 3 and distant metastasis in 2. One of them died of the disease. Conclusions: High risks of local recurrence and regional/distant metastasis feature Merkel cell carcinoma. We recommend postoperative radiotherapy for stage I disease and radiotherapy combined with chemotherapy for resected stage II and stage III disease

  13. The neuroendocrine (Merkel cell) carcinoma of head and neck

    International Nuclear Information System (INIS)

    Weidauer, H.; Altmannsberger, H.M.

    1987-01-01

    The neuroendocrine carcinoma of the skin has its histogenetic origin in Merkel cells and a preference in head and neck area in the seventh decade of life. The definitive diagnosis can be made with a combination of electron microscopy and immunohistochemistry. Merkel cell carcinoma is a primary cutaneous neoplasma and is rarely found on the lips or gingiva. Operation and radiation are the therapy of choice. The value of an additional antineoplastic chemotherapy in the treatment of Merkel cell carcinoma is still controversial. Although long survival times had been described in literature the occurrence of local relapses and metastases demands for frequent controls. (orig.) [de

  14. Merkel Cell Carcinoma: Interdisciplinary Management of a Rare Disease

    Directory of Open Access Journals (Sweden)

    Sven Schneider

    2013-01-01

    Full Text Available Background. The goal of this paper is to review contemporary multidisciplinary treatment with reference to Merkel cell carcinoma. Management of this rare but highly aggressive skin cancer is a complex undertaking that necessitates an understanding of its etiology, epidemiology, clinical presentation, and the coordinated work of several clinical specializations. Recent Findings. The contemporary literature employs a multidisciplinary approach to achieve the best patient's treatment. Conclusion. This paper presents an algorithm for contemporary management for the rare and aggressive Merkel cell carcinoma. Multidisciplinary approach in a tumor center provides high-quality care for patients with Merkel cell carcinoma.

  15. Osteopontin-enhanced hepatic metastasis of colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Jianjin Huang

    Full Text Available Liver metastasis is a major cause of mortality from colorectal cancer (CRC. However, mechanisms underlying this process are largely unknown. Osteopontin (OPN is a secreted phosphorylated glycoprotein that is involved in tumor migration and metastasis. The role of OPN in cancer is currently unclear. In this study, OPN mRNA was examined in tissues from CRC, adjacent normal mucosa, and liver metastatic lesions using quantitative real-time PCR analysis. The protein expression of OPN and its receptors (integrin αv and CD44 v6 was detected by using an immunohistochemical (IHC method. The role of OPN in liver metastasis was studied in established colon cancer Colo-205 and SW-480 cell lines transfected with sense- or antisense-OPN eukaryotic expression plasmids by flow cytometry and cell adhesion assay. Fluorescence redistribution after photobleaching (FRAP was used to study gap functional intercellular communication (GJIC among OPN-transfected cells. It was found that OPN was highly expressed in metastatic hepatic lesions from CRC compared to primary CRC tissue and adjacent normal mucosa. The expression of OPN mRNA in tumor tissues was significantly related with the CRC stages. OPN expression was also detected in normal hepatocytes surrounding CRC metastatic lesions. Two known receptors of OPN, integrin αv and CD44v6 proteins, were strongly expressed in hepatocytes from normal liver. CRC cells with forced OPN expression exhibited increased heterotypic adhesion with endothelial cells and weakened intercellular communication. OPN plays a significant role in CRC metastasis to liver through interaction with its receptors in hepatocytes, decreased homotypic adhesion, and enhanced heterotypic adhesion.

  16. Identification of Human Cutaneous Basal Cell Carcinoma Cancer Stem Cells.

    Science.gov (United States)

    Morgan, Huw; Olivero, Carlotta; Patel, Girish K

    2018-04-20

    The cancer stem cell model states that a subset of tumor cells, called "cancer stem cells," can initiate and propagate tumor growth through self-renewal, high proliferative capacity, and their ability to recreate tumor heterogeneity. In basal cell carcinoma (BCC), we have shown that tumor cells that express the cell surface protein CD200 fulfill the cancer stem cell hypothesis. CD200+ CD45- BCC cells represent 0.05-3.96% of all BCC cells and reside in small clusters at the tumor periphery. Using a novel, reproducible in vivo xenograft growth assay, we determined that tumor-initiating cell (TIC) frequencies are approximately 1 per 1.5 million unsorted BCC cells. The CD200+ CD45- BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200+ CD45- cells, representing ~1500-fold enrichment. The methods used to identify and purify CD200+ CD45- BCC cells, as well as characterize gene expression, are described herein.

  17. Squamous Cell Carcinoma of the Hilar Bile Duct

    Directory of Open Access Journals (Sweden)

    Ippei Yamana

    2011-08-01

    Full Text Available We herein report a rare case of squamous cell carcinoma of the hilar bile duct. A 66-year-old Japanese male patient was admitted to our hospital because of appetite loss and jaundice. Abdominal computed tomography revealed an enhanced mass measuring 10 × 30 mm in the hilar bile duct region. After undergoing biliary drainage, the patient underwent extended right hepatic lobectomy with regional lymph nodes dissection. The tumor had invaded the right portal vein. Therefore, we also performed resection and reconstruction of the portal vein. Histopathologically, the carcinoma cells exhibited a solid structure with differentiation to squamous cell carcinoma with keratinization and intercellular bridges. Immunohistochemical staining of the tumor cells revealed positive cytokeratin staining and negative CAM 5.2 staining. Based on these findings, a definitive diagnosis of well-differentiated squamous cell carcinoma of the hilar bile duct was made.

  18. Radiation sensitivity of Merkel cell carcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Leonard, J.H.; Ramsay, J.R.; Birrell, G.W. [Queensland Institute of Medical Research (Australia)] [and others

    1995-07-30

    Merkel cell carcinoma (MCC), being a small cell carcinoma, would be expected to be sensitive to radiation. Clinical analysis of patients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. Some of the MCC lines grew as suspension cultures and could not be single cell cloned; therefore, it was not possible to use clonogenic survival for all cell lines. A tetrazolium based (MTT) assay was used for these lines, to estimate cell growth after {gamma} irradiation. Control experiments were conducted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate that the two assays were comparable under the conditions used. We have examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas, Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for their sensitivity to {gamma} irradiation using both clonogenic cell survival and MTT assays. The results show that the tumor cell lines have a range of sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results under the conditions used. Both assays gave a range of SF2 values for the MCC cell lines, suggesting that these cancers would give a heterogeneous response in vivo. The results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop resistance during clonogenic evolution. 25 refs., 3 figs., 1 tab.

  19. Radiation sensitivity of Merkell cell carcinoma cell lines

    International Nuclear Information System (INIS)

    Leonard, J. Helen; Ramsay, Jonathan R.; Kearsley, John H.; Birrell, Geoff W.

    1995-01-01

    Purpose: Merkel cell carcinoma (MCC), being a small cell carcinoma, would be expected to be sensitive to radiation. Clinical analysis of patients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. Methods and Materials: Some of the MCC lines grew as suspension cultures and could not be single cell cloned; therefore, it was not possible to use clonogenic survival for all cell lines. A tetrazolium based (MTT) assay was used for these lines, to estimate cell growth after γ irradiation. Control experiments were conducted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate that the two assays were comparable under the conditions used. Results: We have examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas, Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for their sensitivity to γ irradiation using both clonogenic cell survival and MTT assays. The results show that the tumor cell lines have a range of sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results under the conditions used. Conclusion: Both assays gave a range of SF2 values for the MCC cell lines, suggesting that these cancers would give a heterogeneous response in vivo. The results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop resistance during clonogenic evolution

  20. The CEA−/lo colorectal cancer cell population harbors cancer stem cells and metastatic cells

    Science.gov (United States)

    Zhang, Bo; Mu, Lei; Huang, Kaiyu; Zhao, Hui; Ma, Chensen; Li, Xiaolan; Tao, Deding; Gong, Jianping; Qin, Jichao

    2016-01-01

    Serum carcinoembryonic antigen (CEA) is the most commonly used tumor marker in a variety of cancers including colorectal cancer (CRC) for tumor diagnosis and monitoring. Recent studies have shown that colonic crypt cells expressing little or no CEA may enrich for stem cells. Numerous studies have clearly shown that there exist CRC patients with normal serum CEA levels during tumor progression or even tumor relapse, although CEA itself is considered to promote metastasis and block cell differentiation. These seemingly contradictory observations prompted us to investigate, herein, the biological properties as well as tumorigenic and metastatic capacity of CRC cells that express high (CEA+) versus low CEA (CEA−/lo) levels of CEA. Our findings show that the abundance of CEA−/lo cells correlate with poor differentiation and poor prognosis, and moreover, CEA−/lo cells form more spheres in vitro, generate more tumors and exhibit a higher potential in developing liver and lung metastases than corresponding CEA+ cells. Applying RNAi-mediated approach, we found that IGF1R mediated tumorigenic and capacity of CEA−/lo cells but did not mediate those of CEA+ cells. Notably, our data demonstrated that CEA molecule was capable of protecting CEA−/lo cells from anoikis, implying that CEA+ cells, although themselves possessing less tumorigenic and metastatic capacity, may promote metastasis of CEA−/lo cells via secreting CEA molecule. Our observations suggest that, besides targeting CEA molecule, CEA−/lo cells may represent a critical source of tumor progression and metastasis, and should therefore be the target of future therapies. PMID:27813496

  1. CTGF enhances resistance to 5-FU-mediating cell apoptosis through FAK/MEK/ERK signal pathway in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Yang K

    2016-11-01

    Full Text Available Kai Yang, Kai Gao, Gui Hu, Yanguang Wen, Changwei Lin, Xiaorong Li Department of General Surgery, The Third Affiliated Hospital of Central South University, Central South University, Changsha, Hunan, People’s Republic of China Abstract: Colorectal cancer (CRC is one of the most commonly diagnosed cancers among both males and females; the chemotherapy drug 5-fluorouracil (5-FU is one of a doctors’ first lines of defense against CRC. However, therapeutic failures are common because of the emergence of drug resistance. Connective tissue growth factor (CTGF is a secreted protein that binds to integrins, and regulates the invasiveness and metastasis of certain carcinoma cells. Here, we found that CTGF was upregulated in drug-resistant phenotype of human CRC cells. Overexpression of CTGF enhanced the resistance to 5-FU-induced cell apoptosis. Moreover, downregulating the expression of CTGF promoted the curative effect of chemotherapy and blocked the cell cycle in the G1 phase. We also found that CTGF facilitated resistance to 5-FU-induced apoptosis by increasing the expression of B-cell lymphoma-extra large (Bcl-xL and survivin. Then we pharmacologically blocked MEK/ERK signal pathway and assessed 5-FU response by MTT assays. Our current results indicate that the expression of phosphorylated forms of MEK/ERK increased in high CTGF expression cells and MEK inhibited increases in 5-FU-mediated apoptosis of resistant CRC cells. Therefore, our data suggest that MEK/ERK signaling contributes to 5-FU resistance through upstream of CTGF, and supports CRC cell growth. Comprehending the molecular mechanism underlying 5-FU resistance may ultimately aid the fight against CRC. Keywords: connective tissue growth factor, 5-fluorouracil, mitogen-activated protein kinase/extracellular regulated protein kinases, phosphatidyl inositol 3-kinase/serine/threonine kinase Akt, colorectal cancer

  2. Renal cell carcinoma: evolving approaches to advanced non-clear cell carcinoma

    Directory of Open Access Journals (Sweden)

    Daniel Y.C. Heng

    2011-12-01

    Full Text Available The treatment of metastatic renal cell carcinoma (RCC has changed dramatically with the introduction of targeted therapies including sunitinib, sorafenib, and temsirolimus. Because patients with conventional clear cell histology account for 75- 80% of all patients with RCC, there has been little accumulated evidence on the treatment of patients with non-clear cell histologies. Most clinical trials have excluded them from enrolment, except for randomized studies investigating temsirolimus. Many retrospective studies on the use of all three of these targeted therapies in patients with non-clear cell histology have demonstrated response rates ranging from 3.7%–16%. Although response rates may not be as high compared to patients with clear cell histologies, targeted therapy does provide a clinically meaningful response.

  3. Tissue Specific Promoters in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    A. R. Rama

    2015-01-01

    Full Text Available Colorectal carcinoma is the third most prevalent cancer in the world. In the most advanced stages, the use of chemotherapy induces a poor response and is usually accompanied by other tissue damage. Significant progress based on suicide gene therapy has demonstrated that it may potentiate the classical cytotoxic effects in colorectal cancer. The inconvenience still rests with the targeting and the specificity efficiency. The main target of gene therapy is to achieve an effective vehicle to hand over therapeutic genes safely into specific cells. One possibility is the use of tumor-specific promoters overexpressed in cancers. They could induce a specific expression of therapeutic genes in a given tumor, increasing their localized activity. Several promoters have been assayed into direct suicide genes to cancer cells. This review discusses the current status of specific tumor-promoters and their great potential in colorectal carcinoma treatment.

  4. Mapping the HLA ligandome of Colorectal Cancer Reveals an Imprint of Malignant Cell Transformation.

    Science.gov (United States)

    Löffler, Markus W; Kowalewski, Daniel J; Backert, Linus; Bernhardt, Jörg; Adam, Patrick; Schuster, Heiko; Dengler, Florian; Backes, Daniel; Kopp, Hans-Georg; Beckert, Stefan; Wagner, Silvia; Königsrainer, Ingmar; Kohlbacher, Oliver; Kanz, Lothar; Königsrainer, Alfred; Rammensee, Hans-Georg; Stevanovic, Stefan; Haen, Sebastian P

    2018-05-22

    Immune cell infiltrates have proven highly relevant for colorectal carcinoma (CRC) prognosis, making CRC a promising candidate for immunotherapy. Since tumors interact with the immune system via HLA-presented peptide ligands, exact knowledge of the peptidome constitution is fundamental for understanding this relationship. Here we comprehensively describe the naturally presented HLA-ligandome of CRC and corresponding non-malignant colon (NMC) tissue. Mass spectrometry identified 35,367 and 28,132 HLA-class I ligands on CRC and NMC, attributable to 7,684 and 6,312 distinct source proteins, respectively. Cancer-exclusive peptides were assessed on source protein level using Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein analysis through evolutionary relationships (PANTHER), revealing pathognomonic CRC-associated pathways including Wnt, TGF-β, PI3K, p53, and RTK-RAS. Relative quantitation of peptide presentation on paired CRC and NMC tissue further identified source proteins from cancer- and infection-associated pathways to be over-represented merely within the CRC ligandome. From the pool of tumor-exclusive peptides, a selected HLA-ligand subset was assessed for immunogenicity, with the majority exhibiting an existing T cell repertoire. Overall, these data show that the HLA-ligandome reflects cancer-associated pathways implicated in CRC oncogenesis, suggesting that alterations in tumor cell metabolism could result in cancer-specific, albeit not mutation-derived tumor-antigens. Hence, a defined pool of unique tumor peptides, attributable to complex cellular alterations that are exclusive to malignant cells might comprise promising candidates for immunotherapeutic applications. Copyright ©2018, American Association for Cancer Research.

  5. Clinicopathological evaluation of radiation induced basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Meibodi Naser

    2008-01-01

    Full Text Available Background: Development of skin neoplasms is one of the most important chronic complications of radiation therapy. Basal cell carcinoma (BCC is the most frequent carcinoma occurring at the region of the body to which radiotherapy was delivered. Aim: The aim of this study was to evaluate clinical and histological aspects of basal cell carcinoma in patients with a history of radiotherapy. Materials and Methods: Medical records and microscopic slides of 80 patients with basal cell carcinoma who had received radiotherapy (1996-2006 were reviewed in pathology department of Imam Reza hospital of Mashhad, Iran. Collected data were analyzed statistically using descriptive test. Results: 60 men and 20 women were included, majority of them in their sixties. Plaque was the most common clinical pattern of basal cell carcinoma. Fifty one percent of the patients had pigmented and 42.5% had multiple lesions. Scalp was the most common site of involvement. Histologically, macronodular and pigmented carcinoma were the most predominant forms of basal cell carcinoma. Discussion: Majority of patients had scalp involvement and multiple lesions. Nodular and pigmented forms were the most common histological findings. We suggest the need for close supervision in patients with a history of radio therapy in the past.

  6. Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Jin; Van Wie, Peter G.; Fai, Leonard Yenwong; Kim, Donghern [Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536 (United States); Wang, Lei; Poyil, Pratheeshkumar [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Luo, Jia [Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536 (United States); Zhang, Zhuo, E-mail: Zhuo.Zhang@uky.edu [Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536 (United States)

    2016-11-15

    Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin-inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells. The results show that knockdown of NEDD9 inhibited cell migration, invasion, and metastasis and that overexpression of NEDD9 promoted cell migration and invasion of DLD1 cells and SW4890 cells. Apigenin treatment attenuated NEDD9 expression at protein level, resulting in reduced phosphorylations of FAK, Src, and Akt, leading to inhibition on cell migration, invasion, and metastasis of both DLD1 and SW480 cells. The present study has demonstrated that apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt cascade in colorectal cancer cells. NEDD9 may function as a biomarker for evaluation of cancer aggressiveness and for selection of therapeutic drugs against cancer progression. - Highlights: • Apigenin inhibits migration, invasion, and metastasis of colorectal cancer cells. • Apigenin downregulates NEDD9. • Apigenin decreases phosphorylations of FAK, Src, and Akt. • Apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt.

  7. Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells

    International Nuclear Information System (INIS)

    Dai, Jin; Van Wie, Peter G.; Fai, Leonard Yenwong; Kim, Donghern; Wang, Lei; Poyil, Pratheeshkumar; Luo, Jia; Zhang, Zhuo

    2016-01-01

    Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin-inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells. The results show that knockdown of NEDD9 inhibited cell migration, invasion, and metastasis and that overexpression of NEDD9 promoted cell migration and invasion of DLD1 cells and SW4890 cells. Apigenin treatment attenuated NEDD9 expression at protein level, resulting in reduced phosphorylations of FAK, Src, and Akt, leading to inhibition on cell migration, invasion, and metastasis of both DLD1 and SW480 cells. The present study has demonstrated that apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt cascade in colorectal cancer cells. NEDD9 may function as a biomarker for evaluation of cancer aggressiveness and for selection of therapeutic drugs against cancer progression. - Highlights: • Apigenin inhibits migration, invasion, and metastasis of colorectal cancer cells. • Apigenin downregulates NEDD9. • Apigenin decreases phosphorylations of FAK, Src, and Akt. • Apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt.

  8. Hsa-miR-875-5p exerts tumor suppressor function through down-regulation of EGFR in colorectal carcinoma (CRC).

    Science.gov (United States)

    Zhang, Tiening; Cai, Xun; Li, Qi; Xue, Peng; Chen, Zhixiao; Dong, Xiao; Xue, Ying

    2016-07-05

    Hsa-miRNA-875-5p (miR-875-5p) has recently been discovered to have anticancer efficacy in different organs. However, the role of miR-875-5p on colorectal carcinoma (CRC) is still ambiguous. In this study, we investigated the role of miR-875-5p on the development of CRC. The results indicated that miR-875-5p was significantly down-regulated in primary tumor tissues and very low levels were found in CRC cell lines. Ectopic expression of miR-875-5p in CRC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4 and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-875-5p induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-875-5p inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene EGFR was revealed to be a putative target of miR-875-5p, which was inversely correlated with miR-875-5p expression in CRC. Taken together, our results demonstrated that miR-875-5p played a pivotal role on CRC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic EGFR.

  9. Nevoid basal cell carcinoma syndrome (Gorlin syndrome

    Directory of Open Access Journals (Sweden)

    Lo Muzio Lorenzo

    2008-11-01

    Full Text Available Abstract Nevoid basal cell carcinoma syndrome (NBCCS, also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs, odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies. Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling. Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome. Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser

  10. Genomic instability in human actinic keratosis and squamous cell carcinoma

    Science.gov (United States)

    Cabral, Luciana Sanches; Neto, Cyro Festa; Sanches, José A; Ruiz, Itamar R G

    2011-01-01

    OBJECTIVE: To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION: Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS: Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS: MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70% actinic keratoses, 76% squamous cell carcinoma-I, and 90% squamous cell carcinoma-II, to 100% squamous cell carcinoma-III. DISCUSSION: The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses. CONCLUSION: The overall alterations that were observed in the repetitive DNA of actinic keratoses and

  11. High-level mRNA quantification of proliferation marker pKi-67 is correlated with favorable prognosis in colorectal carcinoma.

    Science.gov (United States)

    Ihmann, Thomas; Liu, Jian; Schwabe, Wolfgang; Häusler, Peter; Behnke, Detlev; Bruch, Hans-Peter; Broll, Rainer; Windhövel, Ute; Duchrow, Michael

    2004-12-01

    The present study retrospectively examines the expression of pKi-67 mRNA and protein in colorectal carcinoma and their correlation to the outcome of patients. Immunohistochemistry and quantitative RT-PCR were used to analyze the expression of pKi-67 in 43 archival specimens of patients with curatively resected primary colorectal carcinoma, who were not treated with neo-adjuvant therapy. We determined a median pKi-67 (MIB-1) labeling index of 31.3% (range 10.3-66.4%), and a mean mRNA level of 0.1769 (DeltaC(T): range 0.01-0.69); indices and levels did not correlate. High pKi-67 mRNA DeltaC(T) values were associated with a significantly favorable prognosis, while pKi-67 labeling indices were not correlated to prognostic outcome. A multivariate analysis of clinical and biological factors indicated that tumor stage (UICC) and pKi-67 mRNA expression level were independent prognostic factors. Quantitatively determined pKi-67 mRNA can be a good and new prognostic indicator for primary resected colorectal carcinoma.

  12. Treatment of early glassy cell carcinoma of uterine cervix

    International Nuclear Information System (INIS)

    Kim, Ok Bae; Kim, Jin Hee; Choi, Tae Jin

    2006-01-01

    The purpose of this study was to investigate the clinical findings, treatment, and outcome of patients with glassy cell carcinoma of cervix. We reviewed all cases of glassy cell carcinoma of the uterine cervix confirmed and treated at the Dongsan Medical Center, Keimyung University, between January 1993 and December 2005. There were 7 cases with histopathologically confirmed gassy cell carcinoma. A tumor was diagnosed as glassy cell carcinoma if over 50% of the tumor cell type displayed glassy cell features. Six patients with stage IB had radical hysterectomy and bilateral pelvic node dissection, and 2 of them received adjuvant external pelvic irradiation with concurrent chemotherapy. Remaining one patient with stage IIA had curative concurrent chemoradiotherapy with external pelvic irradiation and brachytherapy. There were 7 patients diagnosed as glassy cell carcinoma among the 3,745 (0.2%) patients of carcinoma of uterine cervix. The mean age of 7 patients was 44 years with range of 35 to 53 years of age. The most frequent symptom was vaginal bleeding (86%). By the punch biopsy undertaken before treatment of 7 cases, 2 only cases could diagnose as glassy cell carcinoma of uterine cervix, but remaining of them confirmed by surgical pathological examination. The mean follow up duration was 73 months with range of 13 to 150 months. All 7 patients were alive without disease after treatment. Glassy cell carcinoma of the uterine cervix is a distinct clinicopathologic entity that demonstrates an aggressive biologic behavior. However for early-stage disease, we may have more favorable clinical outcome with radical surgery followed by chemoradiotherapy

  13. Facial skin follllicular hyperkeratosis of patients with basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    M. V. Zhuchkov

    2016-01-01

    Full Text Available This article provides a clinical observation of paraneoplastic syndrome of a patient with basal cell carcinoma of skin. Authors present clinical features of the described for the first time, paraneoplastic retentional follicular hyperkeratosis of facial area.

  14. Leukemoid reaction associated with transitional cell carcinoma: A ...

    African Journals Online (AJOL)

    Leukemoid reaction associated with transitional cell carcinoma: A case report ... Nigerian Journal of Clinical Practice ... At 3 months later, patient was admitted to our 21 22 hospital with the complaints of the left leg edema, diagnosed as pelvic

  15. Squamous cell carcinoma arising in mature cystic teratoma of ovary

    Directory of Open Access Journals (Sweden)

    Ranu Patni

    2014-01-01

    Full Text Available Squamous cell carcinoma of the ovary is a rare condition and usually arises in mature cystic teratoma (MCT or dermoid cyst of the ovary. The reported incidence of malignant transformation in MCT is approximately 2%. A case of squamous cell carcinoma arising in a dermoid cyst of the ovary presenting at an early stage is presented here. A 53-year-old postmenopausal lady, presented with the complaint of pain in right lower abdomen since one month and a large complex abdomino-pelvic mass on examination and investigations. Final histopathology was reported as squamous cell carcinoma of left ovary arising from dermoid cyst and a benign dermoid cyst in the right ovary. The patient was assigned to squamous cell carcinoma of the ovary arising in a mature cystic teratoma, surgical stage Ic2. In view of the poor prognosis, adjuvant chemotherapy was started.

  16. Ovarian Small Cell Carcinoma Hypercalcemic Type: A Case Report

    LENUS (Irish Health Repository)

    Rahma, M B.

    2016-09-01

    A 31-year-old female was diagnosed with small cell carcinoma of the ovary hypercalcaemic type (OSCCHT) post left oophorectomy. This is a rare aggressive ovarian tumour of which less than 300 cases were reported.

  17. A case of renal cell carcinoma and angiomyolipoma in an ...

    African Journals Online (AJOL)

    Abstract. We describe a case of renal cell carcinoma in the right kidney together with an angiomyolipoma in the left kidney, encountered in an adolescent girl at Potchefstroom Provincial Hospital, North West Province, South Africa.

  18. Merkel Cell Carcinoma in Immunosuppressed Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Janice E. [Mayo Clinic College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (United States); Brewer, Jerry D., E-mail: brewer.jerry@mayo.edu [Department of Dermatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (United States)

    2014-06-27

    Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy. The infectivity of Merkel cell polyomavirus (MCPyV), an apparent agent in MCC development, may be exacerbated with impaired immune responses. This paper reviews relevant data regarding the role of immunosuppression in the development of MCC and describes modes of immunodeficient states. Because of the inherently low incidence rate of MCC, several case studies and series are also briefly mentioned to provide a more comprehensive summary of MCC in the setting of immunosuppression. We describe immunosuppressed patients who have experienced excessive UV radiation, organ transplantation, human immunodeficiency virus infection/AIDS, autoimmune diseases, and lymphoproliferative disorders. Iatrogenic forms of immunosuppression are also highlighted. Studies that quantify risks consistently report that individuals with a history of solid organ transplantation, autoimmune diseases, AIDS, and/or lymphoproliferative diseases have a significantly elevated risk of developing MCC. Overall, immunocompromised patients also appear to have an early onset and more aggressive course of MCC, with poorer outcomes. Recommendations for multidisciplinary approaches are proposed to effectively prevent and manage MCC in these patients.

  19. Wnt Signaling in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Qi Xu

    2016-06-01

    Full Text Available Renal cell carcinoma (RCC accounts for 90% of all kidney cancers. Due to poor diagnosis, high resistance to the systemic therapies and the fact that most RCC cases occur sporadically, current research switched its focus on studying the molecular mechanisms underlying RCC. The aim is the discovery of new effective and less toxic anti-cancer drugs and novel diagnostic markers. Besides the PI3K/Akt/mTOR, HGF/Met and VHL/hypoxia cellular signaling pathways, the involvement of the Wnt/β-catenin pathway in RCC is commonly studied. Wnt signaling and its targeted genes are known to actively participate in different biological processes during embryonic development and renal cancer. Recently, studies have shown that targeting this pathway by alternating/inhibiting its intracellular signal transduction can reduce cancer cells viability and inhibit their growth. The targets and drugs identified show promising potential to serve as novel RCC therapeutics and prognostic markers. This review aims to summarize the current status quo regarding recent research on RCC focusing on the involvement of the Wnt/β-catenin pathway and how its understanding could facilitate the identification of potential therapeutic targets, new drugs and diagnostic biomarkers.

  20. Merkel Cell Carcinoma in Immunosuppressed Patients

    International Nuclear Information System (INIS)

    Ma, Janice E.; Brewer, Jerry D.

    2014-01-01

    Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous malignancy. The infectivity of Merkel cell polyomavirus (MCPyV), an apparent agent in MCC development, may be exacerbated with impaired immune responses. This paper reviews relevant data regarding the role of immunosuppression in the development of MCC and describes modes of immunodeficient states. Because of the inherently low incidence rate of MCC, several case studies and series are also briefly mentioned to provide a more comprehensive summary of MCC in the setting of immunosuppression. We describe immunosuppressed patients who have experienced excessive UV radiation, organ transplantation, human immunodeficiency virus infection/AIDS, autoimmune diseases, and lymphoproliferative disorders. Iatrogenic forms of immunosuppression are also highlighted. Studies that quantify risks consistently report that individuals with a history of solid organ transplantation, autoimmune diseases, AIDS, and/or lymphoproliferative diseases have a significantly elevated risk of developing MCC. Overall, immunocompromised patients also appear to have an early onset and more aggressive course of MCC, with poorer outcomes. Recommendations for multidisciplinary approaches are proposed to effectively prevent and manage MCC in these patients

  1. Mutational Analysis of Merkel Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Erstad, Derek J. [Department of Surgery, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114 (United States); Cusack, James C. Jr., E-mail: jcusack@mgh.harvard.edu [Division of Surgical Oncology, Harvard Medical School, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114 (United States)

    2014-10-17

    Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy that is associated with a poor prognosis. The pathogenesis of MCC is not well understood, and despite a recent plethora of mutational analyses, we have yet to find a set of signature mutations implicated in the majority of cases. Mutations, including TP53, Retinoblastoma and PIK3CA, have been documented in subsets of patients. Other mechanisms are also likely at play, including infection with the Merkel cell polyomavirus in a subset of patients, dysregulated immune surveillance, epigenetic alterations, aberrant protein expression, posttranslational modifications and microRNAs. In this review, we summarize what is known about MCC genetic mutations and chromosomal abnormalities, and their clinical significance. We also examine aberrant protein function and microRNA expression, and discuss the therapeutic and prognostic implications of these findings. Multiple clinical trials designed to selectively target overexpressed oncogenes in MCC are currently underway, though most are still in early phases. As we accumulate more molecular data on MCC, we will be better able to understand its pathogenic mechanisms, develop libraries of targeted therapies, and define molecular prognostic signatures to enhance our clinicopathologic knowledge.

  2. Mutational Analysis of Merkel Cell Carcinoma

    International Nuclear Information System (INIS)

    Erstad, Derek J.; Cusack, James C. Jr.

    2014-01-01

    Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy that is associated with a poor prognosis. The pathogenesis of MCC is not well understood, and despite a recent plethora of mutational analyses, we have yet to find a set of signature mutations implicated in the majority of cases. Mutations, including TP53, Retinoblastoma and PIK3CA, have been documented in subsets of patients. Other mechanisms are also likely at play, including infection with the Merkel cell polyomavirus in a subset of patients, dysregulated immune surveillance, epigenetic alterations, aberrant protein expression, posttranslational modifications and microRNAs. In this review, we summarize what is known about MCC genetic mutations and chromosomal abnormalities, and their clinical significance. We also examine aberrant protein function and microRNA expression, and discuss the therapeutic and prognostic implications of these findings. Multiple clinical trials designed to selectively target overexpressed oncogenes in MCC are currently underway, though most are still in early phases. As we accumulate more molecular data on MCC, we will be better able to understand its pathogenic mechanisms, develop libraries of targeted therapies, and define molecular prognostic signatures to enhance our clinicopathologic knowledge

  3. Microbiome and Colorectal Carcinoma Insights From Germ-Free and Conventional Animal Models

    Czech Academy of Sciences Publication Activity Database

    Tlaskalová-Hogenová, Helena; Vannucci, Luca; Klimešová, Klára; Štěpánková, Renata; Křižan, Jiří; Kverka, Miloslav

    2014-01-01

    Roč. 30, č. 3 (2014), s. 217-224 ISSN 1528-9117 R&D Projects: GA ČR(CZ) GAP304/11/1252; GA ČR GAP303/12/0535; GA AV ČR IAA500200917; GA MŠk(CZ) EE2.3.30.0003 Institutional support: RVO:61388971 Keywords : Microbiota * microbiome * colorectal cancer Subject RIV: EC - Immunology Impact factor: 4.237, year: 2014

  4. 3D cell cultures of human head and neck squamous cell carcinoma cells are radiosensitized by the focal adhesion kinase inhibitor TAE226

    International Nuclear Information System (INIS)

    Hehlgans, Stephanie; Lange, Inga; Eke, Iris; Cordes, Nils

    2009-01-01

    Background and purpose: Focal adhesion kinase (FAK), a main player in integrin signaling and survival, is frequently overexpressed in human cancers and therefore postulated as potential target in cancer therapy. The aim of this study was to evaluate the radiosensitizing potential of the FAK inhibitor TAE226 in three-dimensional (3D) tumor cell cultures. Materials and methods: Head and neck squamous cell carcinoma (HNSCC) cells (FaDu, UT-SCC15, UT-SCC45), lung cancer cells (A549), colorectal carcinoma cells (DLD-1, HCT-116) and pancreatic tumor cells (MiaPaCa2, Panc1) were treated with different concentrations of TAE226 (0-1 μm; 1 or 24 h) without or in combination with irradiation (0-6 Gy, X-ray, single dose). Subsequently, 3D clonogenic survival assays (laminin-rich extracellular matrix) and Western blotting (expression/phosphorylation, e.g. FAK, Akt, ERK1/2) were performed. Results: All investigated 3D cell cultures showed a dose-dependent reduction in clonogenic survival by TAE226. Intriguingly, TAE226 only significantly radiosensitized 3D HNSCC cell cultures accompanied by a pronounced dephosphorylation of FAK, Akt and ERK1/2. Conclusions: Our data demonstrate TAE226 as potent FAK inhibitor that enhances the cellular radiosensitivity particularly of HNSCC cells grown in a 3D cell culture model. Future in vitro and in vivo investigations will clarify, to which extent this approach might be clinically relevant for radiotherapy of HNSCC.

  5. Histological, Immunohistological, and Clinical Features of Merkel Cell Carcinoma in Correlation to Merkel Cell Polyomavirus Status

    Directory of Open Access Journals (Sweden)

    T. Jaeger

    2012-01-01

    Full Text Available Merkel cell carcinoma is a rare, but highly malignant tumor of the skin with high rates of metastasis and poor survival. Its incidence rate rises and is currently about 0.6/100000/year. Clinical differential diagnoses include basal cell carcinoma, cyst, amelanotic melanoma, lymphoma and atypical fibroxanthoma. In this review article clinical, histopathological and immunhistochemical features of Merkel cell carcinoma are reported. In addition, the role of Merkel cell polyomavirus is discussed.

  6. Characterization of Aes nuclear foci in colorectal cancer cells

    Science.gov (United States)

    Itatani, Yoshiro; Sonoshita, Masahiro; Kakizaki, Fumihiko; Okawa, Katsuya; Stifani, Stefano; Itoh, Hideaki; Sakai, Yoshiharu; Taketo, M. Mark

    2016-01-01

    Amino-terminal enhancer of split (Aes) is a member of Groucho/Transducin-like enhancer (TLE) family. Aes is a recently found metastasis suppressor of colorectal cancer (CRC) that inhibits Notch signalling, and forms nuclear foci together with TLE1. Although some Notch-associated proteins are known to form subnuclear bodies, little is known regarding the dynamics or functions of these structures. Here, we show that Aes nuclear foci in CRC observed under an electron microscope are in a rather amorphous structure, lacking surrounding membrane. Investigation of their behaviour during the cell cycle by time-lapse cinematography showed that Aes nuclear foci dissolve during mitosis and reassemble after completion of cytokinesis. We have also found that heat shock cognate 70 (HSC70) is an essential component of Aes foci. Pharmacological inhibition of the HSC70 ATPase activity with VER155008 reduces Aes focus formation. These results provide insight into the understanding of Aes-mediated inhibition of Notch signalling. PMID:26229111

  7. Par3L enhances colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway

    International Nuclear Information System (INIS)

    Li, Taiyuan; Liu, Dongning; Lei, Xiong; Jiang, Qunguang

    2017-01-01

    Partitioning defective 3-like protein (Par3L) is a recently identified cell polarity protein that plays an important role in mammary stem cell maintenance. Previously, we showed that high expression of Par3L is associated with poor survival in malignant colorectal cancer (CRC), but the underlying mechanism remained unknown. To this end, we established a Par3L knockout colorectal cancer cell line using the CRISPR/Cas system. Interestingly, reduced proliferation, enhanced cell death and caspase-3 activation were observed in Par3L knockout (KO) cells as compared with wildtype (WT) cells. Consistent with previous studies, we showed that Par3L interacts with a tumor suppressor protein liver kinase B1 (Lkb1). Moreover, Par3L depletion resulted in abnormal activation of Lkb1/AMPK signaling cascade. Knockdown of Lkb1 in these cells could significantly reduce AMPK activity and partially rescue cell death caused by Par3L knockdown. Furthermore, we showed that Par3L KO cells were more sensitive to chemotherapies and irradiation. Together, these results suggest that Par3L is essential for colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway, and is a putative therapeutic target for CRC. - Highlights: • Par3L knockout using the CRISPR/Cas system induces apoptosis in colorectal cancer cells. • Par3L interacts with Lkb1 and regulates the activity of AMPK signaling cascade. • Par3L knockout cells are more sensitive to treatment of different chemotherapy drugs and irradiation.

  8. Clear cell carcinoma of the uterine corpus following irradiation therapy for squamous cell carcinoma of the cervix

    International Nuclear Information System (INIS)

    Iwaoki, Yasuhisa; Katsube, Yasuhiro; Nanba, Koji.

    1992-01-01

    A case of clear cell carcinoma of the endometrium following squamous cell carcinoma of the cervix is reported. The patient had had a previous cervical biopsy which revealed squamous cell carcinoma (large cell non-keratinizing type), classified clinically as a stage IIb lesion. She was treated with external pelvic irradiation delivering an estimated tumor dose of approximately 7,000 rads and intracavital radium application delivering 4,995 mg.hr.radiation when she was 51 years old. She complained of post-menopausal bleeding at age 66 and was diagnosed by endometrial cytology as having clear cell carcinoma of the endometrium. Total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy were performed. The clinical stage of the endometrial cancer was Ib. She is alive after 2 years with no evidence of disease. Endometrial cytology revealed several adenocarcinoma cells in small clusters. The shape of the nuclei was somewhat irregular, the chromatin pattern was fine granular, and single or multiple nucleoli were seen. The diameter of these nuclei ranged from 10 to 30 μm. The cytoplasm was pale green or vacuolated. The volume of the cytoplasm varied from scanty to abundant. These findings suggested clear cell carcinoma. Histopathologically, an irregular shaped polypoid tumor, 3 x 1.5 cm in size, was located on the lower anterior wall of the uterine corpus. The tumor was a clear cell carcinoma showing a solid and papillary pattern. A hobnail pattern was not observed. The cytoplasm was clear and abundant, and PAS-positive granules digestible by diastase were seen. These 2 cancers had different pathological features and their immunohistochemical reactivities for CEA and keratin were also different. The patient was regarded as having a rare heterochronous double cancer consisting of squamous cell carcinoma of the cervix and clear cell carcinoma of the endometrium. (author)

  9. Clear cell carcinoma of the uterine corpus following irradiation therapy for squamous cell carcinoma of the cervix; A case report

    Energy Technology Data Exchange (ETDEWEB)

    Iwaoki, Yasuhisa; Katsube, Yasuhiro (Kure Kyosai Hospital, Hiroshima (Japan)); Nanba, Koji

    1992-01-01

    A case of clear cell carcinoma of the endometrium following squamous cell carcinoma of the cervix is reported. The patient had had a previous cervical biopsy which revealed squamous cell carcinoma (large cell non-keratinizing type), classified clinically as a stage IIb lesion. She was treated with external pelvic irradiation delivering an estimated tumor dose of approximately 7,000 rads and intracavital radium application delivering 4,995 mg.hr.radiation when she was 51 years old. She complained of post-menopausal bleeding at age 66 and was diagnosed by endometrial cytology as having clear cell carcinoma of the endometrium. Total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy were performed. The clinical stage of the endometrial cancer was Ib. She is alive after 2 years with no evidence of disease. Endometrial cytology revealed several adenocarcinoma cells in small clusters. The shape of the nuclei was somewhat irregular, the chromatin pattern was fine granular, and single or multiple nucleoli were seen. The diameter of these nuclei ranged from 10 to 30 {mu}m. The cytoplasm was pale green or vacuolated. The volume of the cytoplasm varied from scanty to abundant. These findings suggested clear cell carcinoma. Histopathologically, an irregular shaped polypoid tumor, 3 x 1.5 cm in size, was located on the lower anterior wall of the uterine corpus. The tumor was a clear cell carcinoma showing a solid and papillary pattern. A hobnail pattern was not observed. The cytoplasm was clear and abundant, and PAS-positive granules digestible by diastase were seen. These 2 cancers had different pathological features and their immunohistochemical reactivities for CEA and keratin were also different. The patient was regarded as having a rare heterochronous double cancer consisting of squamous cell carcinoma of the cervix and clear cell carcinoma of the endometrium. (author).

  10. Breast carcinoma with osteoclast-like giant cells

    DEFF Research Database (Denmark)

    Gjerdrum, L M; Lauridsen, M C; Sørensen, Flemming Brandt

    2001-01-01

    Primary carcinoma with osteoclast-like giant cells is a very rare tumour of the female breast. The clinical course, histological, immunohistochemical and ultrastructural features of 61 cases of invasive duct carcinoma with osteoclast-like multinucleated giant cells (OMGCs) are reviewed and a new...... in the literature have shown that 86% of patients with these tumours are still alive after 5 years. Histologically, these tumours are invasive ductal carcinomas with OMGCs next to the neoplastic glands and within their lumen. Signs of recent and past haemorrhage are ubiquitously present in the highly vascularized...

  11. Nevoid basal cell carcinoma syndrome; Naevoid Basalzellkarzinom-Syndrom

    Energy Technology Data Exchange (ETDEWEB)

    Grgic, A.; Heinrich, M.; Heckmann, M.; Kramann, B. [Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany). Abt. fuer Diagnostische und Interventionelle Radiologie; Aliani, S. [Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany). Klinik fuer Kinder- und Jugendmedizin; Dill-Mueller, D. [Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany). Hautklinik und Poliklinik; Uder, M. [Erlange-Nuernberg Univ. (Germany). Inst. fuer Diagnostische Radiologie

    2005-07-01

    Nevoid Basal Cell Carcinoma Syndrome (NBCCS) is an autosomal-dominant disorder characterized by multiple basal cell carcinomas, jaw cysts, palmar/plantar pits, calcification of the falx cerebri, and spine and rib anomalies. The combination of clinical, imaging, and histological findings is helpful in identifying NBCCS patients. Imaging plays a crucial role in evaluation of these patients. We present a wide variety of clinical and radiological findings characteristic of this disease. (orig.)

  12. Spindle-cell carcinoma of esophagus: a case report

    International Nuclear Information System (INIS)

    Kim, Ji Chang; Lee, Jae Mun; Jung, Seung Eun; Lee, Kyo Young; Hahn, Seong Tai; Kim, Man Deuk

    2001-01-01

    Spindle-cell carcinoma of the esophagus is a rare malignant tumor composed of both carcinomatous and sarcomatous elements, and has generated many terminology problems. It is characterized by a bulky polypoid intraluminal mass with a lobulated surface located in the middle third of the esophagus. Local expansion of this organ is observed. The lesion may be pedunculated but despite its bulk, causes little obstruction. We report the imaging findings of a case of spindle-cell carcinoma arising in the upper esophagus

  13. Staghorn calculi and xanthogranulomatous pyelonephritis associated with transitional cell carcinoma

    Directory of Open Access Journals (Sweden)

    Chao-Wei Tseng

    2015-03-01

    Full Text Available Untreated staghorn calculi can cause xanthogranulomatous pyelonephritis (XGP, diminished renal function, and renal malignancy. Squamous cell carcinoma (SCC of the upper urinary tract is associated with kidney stones and chronic infection, but their association with transitional cell carcinoma (TCC has not been proven and has rarely been reported in literature. We present a rare case of staghorn calculi and XGP associated with TCC.

  14. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

    Science.gov (United States)

    Linehan, W Marston; Spellman, Paul T; Ricketts, Christopher J; Creighton, Chad J; Fei, Suzanne S; Davis, Caleb; Wheeler, David A; Murray, Bradley A; Schmidt, Laura; Vocke, Cathy D; Peto, Myron; Al Mamun, Abu Amar M; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W Kimryn; Brooks, Angela N; Hoadley, Katherine A; Robertson, A Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J; Bootwalla, Moiz; Baylin, Stephen B; Laird, Peter W; Cherniack, Andrew D; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Leiserson, Mark D M; Raphael, Benjamin J; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K; Czerniak, Bogdan; Godwin, Andrew K; Hakimi, A Ari; Ho, Thai H; Hsieh, James; Ittmann, Michael; Kim, William Y; Krishnan, Bhavani; Merino, Maria J; Mills Shaw, Kenna R; Reuter, Victor E; Reznik, Ed; Shelley, Carl S; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D; Penny, Robert J; Shelton, Candace; Shelton, W Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T; Bowen, Jay; Gastier-Foster, Julie M; Gerken, Mark; Leraas, Kristen M; Lichtenberg, Tara M; Ramirez, Nilsa C; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A; Felau, Ina; Hutter, Carolyn M; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C; Zhang, Jiashan; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S N; Carlsen, Rebecca; Carter, Scott L; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, Harsha V; Drummond, Jennifer A; Gabriel, Stacey B; Gibbs, Richard A; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D Neil; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven J M; Jones, Corbin D; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A; Moore, Richard A; Morton, Donna; Mose, Lisle E; Mungall, Andrew J; Muzny, Donna; Parker, Joel S; Perou, Charles M; Roach, Jeffrey; Schein, Jacqueline E; Schumacher, Steven E; Shi, Yan; Simons, Janae V; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L; Boice, Lori; Bollag, Roni J; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L; Slaton, Joel; Stanton, Melissa; Thompson, R Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M; Winemiller, Cynthia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-14

    Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

  15. Breast Metastasis from Renal Cell Carcinoma: A Case Report

    International Nuclear Information System (INIS)

    Kim, Seon Jeong; Kim, Ji Young; Jeong, Myeong Ja; Kim, Jae Hyung; Kim, Soung Hee; Kim, Soo Hyun; Jun, Woo Sun; Kim, Hyun Jung; Han, Se Hwan

    2010-01-01

    Metastatic breast cancer from renal cell carcinoma is extremely rare and has non-specific findings that include a well circumscribed lesion without calcification on mammography and a well circumscribed hypoechoic lesion without posterior acoustic shadowing on sonography. We report a case of metastatic breast cancer from renal cell carcinoma and describe the radiologic findings in a 63-year-old woman who has no history of primary neoplasm

  16. Breast Metastasis from Renal Cell Carcinoma: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seon Jeong; Kim, Ji Young; Jeong, Myeong Ja; Kim, Jae Hyung; Kim, Soung Hee; Kim, Soo Hyun; Jun, Woo Sun; Kim, Hyun Jung; Han, Se Hwan [Sanggye Paik Hospital, Seoul (Korea, Republic of)

    2010-01-15

    Metastatic breast cancer from renal cell carcinoma is extremely rare and has non-specific findings that include a well circumscribed lesion without calcification on mammography and a well circumscribed hypoechoic lesion without posterior acoustic shadowing on sonography. We report a case of metastatic breast cancer from renal cell carcinoma and describe the radiologic findings in a 63-year-old woman who has no history of primary neoplasm.

  17. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    Science.gov (United States)

    Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-01

    Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

  18. Corneal squamous cell carcinoma in a Border Collie.

    Science.gov (United States)

    Busse, Claudia; Sansom, Jane; Dubielzig, R R; Hayes, Alison

    2008-01-01

    A 6-year-old, female, spayed Border Collie was presented to the Unit of Comparative Ophthalmology at the Animal Health Trust with a 6-month history of a progressive nonpainful opacity of the left cornea. A keratectomy was performed and the tissue submitted for histopathology. The diagnosis was squamous cell carcinoma. There has been no recurrence of the neoplasm to date (5 months). Canine corneal squamous cell carcinoma (SCC) has not been reported previously in the UK.

  19. Secondary mutation in a coding mononucleotide tract in MSH6 causes loss of immunoexpression of MSH6 in colorectal carcinomas with MLH1/PMS2 deficiency.