WorldWideScience

Sample records for human colorectal carcinomas

  1. Telomerase activity and human telomerase reverse transcriptase expression in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jian-Lun Liu; Lian-Ying Ge; Gui-Nian Zhang

    2006-01-01

    AIM: To study the activity of telomerase and the expression of human telomerase reverse transcriptase(hTERT) in colorectal carcinoma and its adjacent tissues,normal mucosa and adenomatoid polyp, and to evaluate their relation with carcinogenesis and progression of colorectal carcinoma.METHODS: Telomerase activity and hTERT expression were determined in 30 samples of colorectal carcinoma and its adjacent tissues, normal mucosa and 20samples of adenomatoid polyp by modified telomeric repeat amplification protocol (TRAP), enzyme-linked immunosorbent assay (ELISA) and immunohistochemical method.RESULTS: Telomerase activity and hTERT expression were 83.33% (25/30) and 76.67% (23/30) respectively in colorectal carcinoma, which were obviously higher than those in paracancerous tissues (13.33%, 16.67%),normal mucosa (3.33%, 3.33%) and adenomatoid polyp(10%, 10%). There was a significant difference between colorectal carcinoma and other tissues (P=0.027). The telomerase activity and hTERT expression were higher in colorectal carcinoma with lymphatic metastasis than in that without lymphatic metastasis (P=0.034). When the histological classification and clinical stage were greater,the telomerase activity and hTERT expression increased,but there was no significant difference between them.In colorectal carcinoma, the telomerase activity was correlated with hTERT expression (positive vs negative expression of telomerase activity and hTERT, P=0.021).CONCLUSION: Telomerase activity is closely correlated with the occurrence, development and metastasis of colorectal carcinoma. Overexpression of hTERT may play a critical role in the regulation of telomerase activity.

  2. 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....

  3. 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.

  4. Human Neutrophil Peptides 1-3 – Early Markers in Development of Colorectal Adenomas and Carcinomas

    Science.gov (United States)

    Mothes, Henning; Melle, Christian; Ernst, Günther; Kaufmann, Roland; von Eggeling, Ferdinand; Settmacher, Utz

    2008-01-01

    Expression of Human Neutrophil Peptides (HNP) 1–3 was recently found to be associated with development of colorectal cancer. Raised defensin-expression in tumours is believed to stem from increased infiltration of neutrophils into tumour environment. To further specify the role of α-defensins in tumourigenesis and progression, HNP1–3 were analyzed in colorectal adenomas and carcinomas of 87 patients and quantified in relation to cancer stage and grading. Using the ProteinChip arrays, HNP1–3 were found upregulated in both colorectal adenomas and carcinomas. By combining the array with Laser capture microscopy we were able to confirm that HNP1–3 are expressed by tumour cells but not by neutrophils or other tumour invading cells. These findings suggest that α-defensins are more likely to contribute to tumour growth than they are to mount an effective host anti-tumour response. However, the amount of HNP-expression was not found to be related to tumour stage, grading, and serological tumour markers. PMID:18957723

  5. Codon 201 Mutation of DCC Gene and Tumor Biologic Behavior in Human Colorectal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To explore the relationship between a point mutation of codon 201 in deleted in colorectal carcinoma ( DCC) gene and the biological behavior of colorectal carcinoma. Methods Tumor tissues and matched adjacent normal colon mucosa collected in 35 patients during surgical resection for colorectal carcinoma were analyzed. Forty normal colon mucosa tissues obtained by biopsy from patients who had neither colorectal tumor nor a family history of colorectal cancer during colonscop ic examination were used as control. Codon 201 mutatian was detected with allele-specific PCR and a restriction enzyme digestion method. The tumors were reviewed as clinical data, tumor location, histology,metastasis, and pathological staging (Dukes classification). Results The frequency of mutation at codon 201 in tumor tissue and corresponding adjacent normal mucosa was 71.4 % and 60 %, respectively, and either of the rates was significantly higher than that of normal control(32.5 % ). The point mutation rate in tumor tissues did not differ from that in the corresponding normal adjacent tissues. Statistic analysis showed that the mutation rate had no relationship to the sex, age of the patients, the histological pattern , differentiation, and invasion depth of the tumors. However, 93. 8 % of the mutation rate in colorectal cancer with lymph node invasion and/or distant metastasis is significantly higher than 52. 6 % of mutant rate in colorectal cancer uithout lymph nodes invasion or metastasis ( P <0. 05). Conclusion The point mutation at codon 201 of DCC gene is an early genetic event in colorectal cancer, and play some role in invasion and metastasis of colorectal carcinoma. It may serve as a useful genetic marker for identifying higher risk patients with colorectal carcinoma.

  6. Codon 201 Mutation of DCC Gene and Tumor Biologic Behavior in Human Colorectal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To explore the relationship between a point mutation of codon 201 in deleted in colorectal carcinoma ( DCC) gene and the biological behavior of colorectal carcinoma. Methods Tumor tissues and matched adjacent normal colon mucosa collected in 35 patients during surgical resection for colorectal carcinoma were analyzed. Forty normal colon mucosa tissues obtained by biopsy from patients who had neither colorectal tumor nor a family history of colorectal cancer during colonscop ic examination were used as control. Codon 201 mutatian was detected with allele-specific PCR and a restriction enzyme digestion method. The tumors were reviewed as clinical data, tumor location, histology,metastasis, and pathological staging (Dukes classification). Results The frequency of mutation at codon 201 in tumor tissue and corresponding adjacent normal mucosa was 71.4 % and 60 %, respectively, and either of the rates was significantly higher than that of normal control(32.5 % ). The point mutation rate in tumor tissues did not differ from that in the corresponding normal adjacent tissues. Statistic analysis showed that the mutation rate had no relationship to the sex, age of the patients, the histological pattern , differentiation, and invasion depth of the tumors. However, 93. 8 % of the mutation rate in colorectal cancer with lymph node invasion and/or distant metastasis is significantly higher than 52. 6 % of mutant rate in colorectal cancer uithout lymph nodes invasion or metastasis ( P <0. 05). Conclusion The point mutation at codon 201 of DCC gene is an early genetic event in colorectal cancer, and play some role in invasion and metastasis of colorectal carcinoma. It may serve as a useful genetic marker for identifying higher risk patients with colorectal carcinoma.

  7. 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.

  8. Inducing effects of hepatocyte growth factor on the expression of vascular endothelial growth factor in human colorectal carcinoma cells through MEK and PI3K signaling pathways

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yu-hua; WEI Wei; XU Hao; WANG Yan-yan; WU Wen-xi

    2007-01-01

    Background Vascular endothelial growth factor plays a key role in human colorectal carcinoma invasion and metastasis. However, the regulation mechanism remains unknown. Recent studies have shown that several cytokines can regulate the expression of vascular endothelial growth factor in tumor cells. In this study, we investigated whether hepatocyte growth factor can regulate the expression of vascular endothelial growth factor in colorectal carcinoma cells.Methods Hepatocyte growth factor and vascular endothelial growth factor in human serum were measured by ELISA.The mRNA level of vascular endothelial growth factor was analyzed by reverse transcription-PCR. Western blot assay was performed to evaluate levels of c-Met and several other proteins involved in the MAPK and PI3K signaling pathways in colorectal carcinoma cells.Results Serum hepatocyte growth factor and vascular endothelial growth factor were significantly increased in colorectal carcinoma subjects. In vitro extraneous hepatocyte growth factor markedly increased protein and mRNA levels of vascular endothelial growth factor in colorectal carcinoma cells. Hepatocyte growth factor induced phosphorylation of c-Met, ERK1/2 and AKT in a dose-dependent manner. Specific inhibitors on MEK and PI3K inhibited the hepatocyte growth factor-induced expression of vascular endothelial growth factor in colorectal carcinoma cells.Conclusion This present study indicates that hepatocyte growth factor upregulates the expression of vascular endothelial growth factor in colorectal carcinoma cells via the MEK/ERK and PI3K/AKT signaling pathways.

  9. Induction of Apoptosis and Cell Cycle Arrest in Human Colorectal Carcinoma by Litchi Seed Extract

    Directory of Open Access Journals (Sweden)

    Chih-Ping Hsu

    2012-01-01

    Full Text Available The Litchi (Litchi chinensis fruit products possess rich amounts of flavanoids and proanthocyanidins. Its pericarp has been shown to inhibit breast and liver cancer cell growth. However, the anticolorectal cancer effect of Litchi seed extract has not yet been reported. In this study, the effects of polyphenol-rich Litchi seed ethanol extract (LCSP on the proliferation, cell cycle, and apoptosis of two colorectal cancer cell lines Colo320DM and SW480 were examined. The results demonstrated that LCSP significantly induced apoptotic cell death in a dose-dependent manner and arrested cell cycle in G2/M in colorectal carcinoma cells. LCSP also suppressed cyclins and elevated the Bax : Bcl-2 ratio and caspase 3 activity. This study provides in vitro evidence that LCSP serves as a potential chemopreventive agent for colorectal cancer.

  10. FBI-1 enhances ETS-1 signaling activity and promotes proliferation of human colorectal carcinoma cells.

    Science.gov (United States)

    Zhu, Min; Li, Mingyang; Zhang, Fan; Feng, Fan; Chen, Weihao; Yang, Yutao; Cui, Jiajun; Zhang, Dong; Linghu, Enqiang

    2014-01-01

    In this study, we investigated a potential regulatory role of FBI-1 in transcription factor activity of ETS-1. The protein interaction was identified between ETS-1 and FBI-1 in lovo cells. The accumulating data showed that FBI-1 promoted the recruitment of ETS-1 to endogenous promoter of its target genes and increase ETS-1 accumulation in the nuclear. Our work also indicated that the FBI-1 enhances ETS-1 transcription factor activity via down-regulating p53-mediated inhibition on ETS-1. Further, FBI-1 plays a role in regulation of colorectal carcinoma cells proliferation. These findings supported that FBI-1 might be a potential molecule target for treating colorectal carcinoma.

  11. FBI-1 enhances ETS-1 signaling activity and promotes proliferation of human colorectal carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Min Zhu

    Full Text Available In this study, we investigated a potential regulatory role of FBI-1 in transcription factor activity of ETS-1. The protein interaction was identified between ETS-1 and FBI-1 in lovo cells. The accumulating data showed that FBI-1 promoted the recruitment of ETS-1 to endogenous promoter of its target genes and increase ETS-1 accumulation in the nuclear. Our work also indicated that the FBI-1 enhances ETS-1 transcription factor activity via down-regulating p53-mediated inhibition on ETS-1. Further, FBI-1 plays a role in regulation of colorectal carcinoma cells proliferation. These findings supported that FBI-1 might be a potential molecule target for treating colorectal carcinoma.

  12. Differential BCCIP gene expression in primary human ovarian cancer, renal cell carcinoma and colorectal cancer tissues.

    Science.gov (United States)

    Liu, Xiaoxia; Cao, Lingling; Ni, Jinsong; Liu, Ning; Zhao, Xiaoming; Wang, Yanfang; Zhu, Lin; Wang, Lingyao; Wang, Jin; Yue, Ying; Cai, Yong; Jin, Jingji

    2013-12-01

    Human BCCIP, a protein which interacts with BRCA2 and CDKN1A (Cip1, p21), has been implicated in many cellular processes including cell cycle regulation, DNA recombination and damage repair, telomere maintenance, embryonic development and genomic stability. BCCIP gene expression, which is an important BRCA2 cofactor in tumor suppression, has been identified in some primary cancers. Thus, we investigated the role of BCCIP expression in a large sample of clinically diagnosed primary ovarian cancer, renal cell carcinoma (RCC) and colorectal cancer (CRC) tissues. Using clinically diagnosed frozen primary cancer tissues, quantitative PCR (qPCR), western blot analysis (WB) and immunohistochemical staining (IHC) approaches were used to detect and measure gene expression. Reduced BCCIP gene expression in ovarian cancer, RCC and CRC tissues occurred in 74, 89 and 75% of tissue samples, respectively. qPCR analysis of mRNA expression in 54 ovarian cancer, 50 RCC and 44 CRC samples revealed significant (>2-fold decreased) BCCIP downregulation in 56, 70 and 46% of tissue samples, respectively. Although BCCIP expression in three different tumor tissues decreased, the relationship between BCCIP expression and clinicopathological features of each cancer was distinct. Compared to normal tissues, BCCIP expression in ovarian cancers was significantly downregulated in serous, endometrioid and mucinous carcinomas. Downregulation of BCCIP expression was strongly associated with clear cell RCC (ccRCC) and Fuhrman tumor grading, but significant differences in BCCIP expression between CRC and matched normal tissues occurred only in male CRC tissues (ptissue with a T4 tumor stage (ptissue samples (phuman ovarian cancer, RCC and CRC tissues, suggesting a role for the gene in the pathogenesis of these cancers.

  13. 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.

  14. Induction of autophagy by dimethyl cardamonin is associated with proliferative arrest in human colorectal carcinoma HCT116 and LOVO cells.

    Science.gov (United States)

    Ko, Hyeonseok; Kim, Young-Joo; Amor, Evangeline C; Lee, Jong Wha; Kim, Han-Cheon; Kim, Hee Ju; Yang, Hyun Ok

    2011-09-01

    Dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone; DMC) is a naturally occurring chalcone, and it is the major compound isolated from the leaves of Syzygium samarangense (Blume) Merr. & L.M. Perry (Myrtaceae). Experiments were conducted to determine the effects of DMC on cell proliferation, cell-cycle distribution, and programmed cell death in cultures of human colorectal carcinoma HCT116 and LOVO cells. Results showed that DMC inhibited HCT116 and LOVO cell proliferation and induced G(2) /M cell cycle arrest, which was associated with the conversion of microtubule associated protein light chain 3 (LC3)-I-LC3-II, an autophagosome marker, and the incorporation of monodansylcadaverine (MDC), a marker for the acidic compartment of autolysosomes or acidic vesicular organelles. The treatment of HCT116 and LOVO cells using a combination of DMC with an autophagy inhibitor, such as 3-methyladenine (3-MA), beclin 1 siRNA, or atg5 siRNA, suppressed the effect of DMC-mediated anti-proliferation. These results imply that DMC can suppress colorectal carcinoma HCT116 and LOVO cell proliferation through a G(2) /M phase cell-cycle delay, and can induce autophagy, the hallmark of Type II programmed cell death (PCD). Taken together, our results suggest that DMC may be an effective chemotherapeutic agent for HCT116 and LOVO colorectal carcinoma cells.

  15. Cannabinoid receptor-independent cytotoxic effects of cannabinoids in human colorectal carcinoma cells: synergism with 5-fluorouracil.

    Science.gov (United States)

    Gustafsson, Sofia B; Lindgren, Theres; Jonsson, Maria; Jacobsson, Stig O P

    2009-03-01

    Cannabinoids (CBs) have been found to exert antiproliferative effects upon a variety of cancer cells, including colorectal carcinoma cells. However, little is known about the signalling mechanisms behind the antitumoural effect in these cells, whether the effects are shared by endogenous lipids related to endocannabinoids, or whether such effects are synergistic with treatment paradigms currently used in the clinic. The aim of this preclinical study was to investigate the effect of synthetic and endogenous CBs and their related fatty acids on the viability of human colorectal carcinoma Caco-2 cells, and to determine whether CB effects are synergistic with those seen with the pyrimidine antagonist 5-fluorouracil (5-FU). The synthetic CB HU 210, the endogenous CB anandamide, the endogenous structural analogue of anandamide, N-arachidonoyl glycine (NAGly), as well as the related polyunsaturated fatty acids arachidonic acid and eicosapentaenoic acid showed antiproliferative and cytotoxic effects in the Caco-2 cells, as measured by using [(3)H]-thymidine incorporation assay, the CyQUANT proliferation assay and calcein-AM fluorescence. HU 210 was the most potent compound examined, followed by anandamide, whereas NAGly showed equal potency and efficacy as the polyunsaturated fatty acids. Furthermore, HU 210 and 5-FU produced synergistic effects in the Caco-2 cells, but not in the human colorectal carcinoma cell lines HCT116 or HT29. The compounds examined produced cytotoxic, rather than antiproliferative effects, by a mechanism not involving CB receptors, since the CB receptor antagonists AM251 and AM630 did not attenuate the effects, nor did pertussis toxin. However, alpha-tocopherol and the nitric oxide synthase inhibitor L-NAME attenuated the CB toxicity, suggesting involvement of oxidative stress. It is concluded that the CB system may provide new targets for the development of drugs to treat colorectal cancer.

  16. [The colorectal carcinoma risk factors].

    Science.gov (United States)

    Sobczak, Andrzej; Wawrzyn-Sobczak, Katarzyna; Sobaniec-Lotowska, Maria

    2005-12-01

    Colorectal carcinoma constitutes the second, as for the rate, death cause due to a malignant disease both in the western countries and in Poland. Despite deep knowledge concerning morphogenesis and spread of colorectal carcinoma as well as vast achievements in surgery, chemo- and radiotherapy, the percentage of 5-year-survivals still reaches 40%. According to most authors there are 4 risk factor categories: epidemiological, intestinal, dietetic, and mixed. It is well-known that colorectal carcinoma, like neoplasms localized in other organs and systems, is a disease, in which genetic mutations of somatic cells are the molecular base/source of the disease. The inner innervation of the colon seems to play an important role in carcinoma pathogenesis and spread. At present, 80% of colorectal carcinomas are diagnosed in the advanced stage, with infiltration exceeding the intestinal wall or spreading to neighboring organs, which gives full clinical symptoms. The prognosis as to survival and disease progression is usually poor. Therefore, the ways of early diagnosis, monitoring, and the knowledge of etiological factors are so important in medical practice.

  17. Inhibition of cell-cycle progression in human colorectal carcinoma Lovo cells by andrographolide.

    Science.gov (United States)

    Shi, Ming-Der; Lin, Hui-Hsuan; Lee, Yi-Che; Chao, Jian-Kang; Lin, Rong-An; Chen, Jing-Hsien

    2008-08-11

    In recent years, attention has been focused on the anti-cancer properties of pure components, an important role in the prevention of disease. Andrographolide (Andro), the major constituent of Andrographis paniculata (Burm. F.) Nees plant, is implicated towards its pharmacological activity. To investigate the mechanism basis for the anti-tumor properties of Andro, Andro was used to examine its effect on cell-cycle progression in human colorectal carcinoma Lovo cells. The data from cell growth experiment showed that Andro exhibited the anti-proliferation effect on Lovo cells in a time- and dose-dependent manner. This event was accompanied the arrest of the cells at the G1-S phase by Andro at the tested concentrations of 0-30 microM. Cellular uptake of Andro and Andro was confirmed by capillary electrophoresis analysis and the intracellular accumulation of Andro (0.61+/-0.07 microM/mg protein) was observed when treatment of Lovo cells with Andro for 12h. In addition, an accumulation of the cells in G1 phase (15% increase for 10 microM of Andro) was observed as well as by the association with a marked decrease in the protein expression of Cyclin A, Cyclin D1, Cdk2 and Cdk4. Andro also inducted the content of Cdk inhibitor p21 and p16, and the phosphorylation of p53. Further immunoprecipitation studies found that, in response to the treatment, the formation of Cyclin D1/Cdk4 and Cyclin A/Cdk2 complexes had declined, preventing the phosphorylation of Rb and the subsequent dissociation of Rb/E2F complex. These results suggested Andro can inhibit Lovo cell growth by G1-S phase arrest, and was exerted by inducing the expression of p53, p21 and p16 that, in turn, repressed the activity of Cyclin D1/Cdk4 and/or Cyclin A/Cdk2, as well as Rb phosphorylation.

  18. Human Neutrophil Peptides 1-3 – Early Markers in Development of Colorectal Adenomas and Carcinomas

    Directory of Open Access Journals (Sweden)

    Henning Mothes

    2008-01-01

    Full Text Available Expression of Human Neutrophil Peptides (HNP 1–3 was recently found to be associated with development of colorectal cancer. Raised defensin-expression in tumours is believed to stem from increased infiltration of neutrophils into tumour environment.

  19. Differential expression proteomics of human colorectal cancer based on a syngeneic cellular model for the progression of adenoma to carcinoma.

    Science.gov (United States)

    Roth, Udo; Razawi, Hanieh; Hommer, Julia; Engelmann, Katja; Schwientek, Tilo; Müller, Stefan; Baldus, Stephan E; Patsos, Georgios; Corfield, Anthony P; Paraskeva, Christos; Hanisch, Franz-Georg

    2010-01-01

    This is the first differential expression proteomics study on a human syngeneic cellular in vitro progression model of the colorectal adenoma-to-carcinoma sequence, the anchorage-dependent non-tumorigenic adenoma derived cell line AA/C1 and the derived anchorage-independent and tumorigenic carcinoma cell line AA/C1/SB10C. The study is based on quantitative 2-DE and is complemented by Western blot validation. Excluding redundancies due to proteolysis and post-translational modified isoforms of over 2000 protein spots, 13 proteins were revealed as regulated with statistical variance being within the 95th confidence level and were identified by peptide mass fingerprinting in MALDI MS. Progression-associated proteins belong to the functional complexes of anaerobic glycolysis/gluconeogenesis, steroid biosynthesis, prostaglandin biosynthesis, the regulation and maintenance of the cytoskeleton, protein biosynthesis and degradation, the regulation of apoptosis or other functions. Partial but significant overlap was revealed with previous proteomics and transcriptomics studies in colorectal carcinoma. Among upregulated proteins we identified 3-HMG-CoA synthase, protein phosphatase 1, prostaglandin E synthase 2, villin 1, annexin A1, triosephosphate isomerase, phosphoserine aminotransferase 1, fumarylacetoacetate hydrolase and pyrroline-5-carboxylate reductase 1 (PYCR1), while glucose-regulated protein 78, cathepsin D, lamin A/C and quinolate phosphoribosyltransferase were downregulated.

  20. Cloning and expression of ornithine decarboxylase gene from human colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hai-Yan Hu; Xiao-Ming Wang; Wei Wang; Xian-Xi Liu; Chun-Ying Jiang; Yan Zhang; Ji-Feng Bian; Yi Lu; Zhao Geng; Shi-Lian Liu; Chuan-Hua Liu

    2003-01-01

    AIM: To construct and express ODC recombinant gene for further exploring its potential use in early diagnosis of colorectal carcinoma.METHODS: Total RNA was extracted from colon cancer tissues and amplified by reverse-transcription PCR with two primers, which span the whole coding region of ODC. The synthesized ODC cDNA was cloned into vector pQE-30 at restriction sites BamH I and Sal I which constituted recombinant expression plasmid pQE30-ODC. The sequence of inserted fragment was confirmed by DNA sequencing,the fusion protein including 6His-tag was facilitated for purification by Ni-NTA chromatographic column.RESULTS: ODC expression vector was constructed and confirmed with restriction enzyme digestion and subsequent DNA sequencing. The DNA sequence matching on NCBI Blast showed 99 % affinity. The vector was transformed into E.coli M15 and expressed. The expressed ODC protein was verified with Western blotting.CONCLUSION: The ODC prokaryote expression vector is constructed and thus greatly facilitates to study the role of ODC in colorectal carcinoma.

  1. Inhibition of invasiveness and expression of epidermal growth factor receptor in human colorectal carcinoma cells induced by retinoic acid

    Institute of Scientific and Technical Information of China (English)

    SUNBAODONG; JINDANSONG

    1995-01-01

    Human amniotic basement membrane (HABM) model and agarose drop explant method were used to investigate the effects of retinoic acid(RA) on the invasive ness and adhesiveness to the basement membrane,and the migration of a highly invasive human colorectal cancer cell line CCL229.Results showed that 5×106 MRA markedly reduced the in vitro invasiveness and adhesiveness to the HABM,and the migration of the CCL229 cells.In addition,to elucidate the relation between expression of epidermal growth factor receptor(EGFR) and the invasiveness of the colorectal carcinoma cells,two well-differentiated,but with different invasiveness colorectal cancer cell lines were compared at mRNA level for expression of EGFR by using EGFR cDNA probe labeled with digoxigenin(DIG). Expression of EGFR was shown to be markedly higher in the highly invassive CCL229 cells than that in the low invasive CX-1 cells.Furthermore,expression of EGFR in RA treated CCL229 cells gradually decreased with time,the level being the lowest on day 6 of the RA treatment.

  2. T-cell factor-4 frameshift mutations occur frequently in human microsatellite instability-high colorectal carcinomas but do not contribute to carcinogenesis.

    Science.gov (United States)

    Ruckert, Stefan; Hiendlmeyer, Elke; Brueckl, Wolfgang M; Oswald, Ursula; Beyser, Kurt; Dietmaier, Wolfgang; Haynl, Angela; Koch, Claudia; Rüschoff, Josef; Brabletz, Thomas; Kirchner, Thomas; Jung, Andreas

    2002-06-01

    Colorectal carcinomas with microsatellite instability accumulate errors in short repetitive DNA repeats, especially mono and dinucleotide repeats. One such error-prone A(9) monorepeat is found in exon 17 of the TCF-4 gene. TCF-4 and beta-catenin form a transcription complex, which is important for both maintenance of normal epithelium and development of colorectal tumors. To elucidate the relevance of frameshift mutations in the TCF-4 in colorectal carcinogenesis, a variety of investigations in human tumors and cell lines was performed. It was found that mutations in the TCF-4 A(9) repeat do not contribute to tumorigenesis and seem to be passenger mutations.

  3. Grape seed extract inhibits in vitro and in vivo growth of human colorectal carcinoma cells.

    Science.gov (United States)

    Kaur, Manjinder; Singh, Rana P; Gu, Mallikarjuna; Agarwal, Rajesh; Agarwal, Chapla

    2006-10-15

    Accumulating evidences suggest the beneficial effects of fruit-and-vegetable consumption in lowering the risk of various cancers, including colorectal cancer. Herein, we investigated the in vitro and in vivo anticancer effects and associated mechanisms of grape seed extract (GSE), a rich source of proanthocyanidins, against colorectal cancer. Effects of GSE were examined on human colorectal cancer HT29 and LoVo cells in culture for proliferation, cell cycle progression, and apoptosis. The in vivo effect of oral GSE was examined on HT29 tumor xenograft growth in athymic nude mice. Xenografts were analyzed by immunohistochemistry for proliferation and apoptosis. The molecular changes associated with the biological effects of GSE were analyzed by Western blot analysis. GSE (25-100 microg/mL) causes a significant dose- and time-dependent inhibition of cell growth with concomitant increase in cell death. GSE induced G1 phase cell cycle arrest along with a marked increase in Cip1/p21 protein level and a decrease in G1 phase-associated cyclins and cyclin-dependent kinases. GSE-induced cell death was apoptotic and accompanied by caspase-3 activation. GSE feeding to mice at 200 mg/kg dose showed time-dependent inhibition of tumor growth without any toxicity and accounted for 44% decrease in tumor volume per mouse after 8 weeks of treatment. GSE inhibited cell proliferation but increased apoptotic cell death in tumors. GSE-treated tumors also showed enhanced Cip1/p21 protein levels and poly(ADP-ribose) polymerase cleavage. GSE may be an effective chemopreventive agent against colorectal cancer, and that growth inhibitory and apoptotic effects of GSE against colorectal cancer could be mediated via an up-regulation of Cip1/p21.

  4. Reduced fructosamine-3-kinase activity and its mRNA in human distal colorectal carcinoma.

    Science.gov (United States)

    Notarnicola, M; Caruso, Maria G; Tutino, V; Guerra, V; Frisullo, S; Altomare, D F; Misciagna, G

    2010-09-01

    Fructosamine-3-Kinase (FN3K) is an enzyme phosphorilating fructoselysine (FL) residues on glycated proteins, resulting in the production of protein-bound FL-3-phosphate. The pathological role of the non-enzymatic modification of proteins by reducing sugars has become increasingly evident in various types of disorders, including the cancer. In this study, our aim was to study FN3K enzyme activity, as well as its mRNA in human colorectal cancer (CRC). Thirty consecutive CRC patients undergoing surgery of the colon were enrolled in the study. FN3K enzymatic activity and gene expression were analyzed using a radiometric assay and quantitative RT-PCR, respectively. FN3K is a functionally active enzyme in human colon tissue, without significant differences between normal mucosa and cancer. The mean level of FN3K mRNA was significantly lower in cancer than in the corresponding normal colorectal mucosa The colorectal tumors located on the left side showed lower levels of both enzymatic activity and mRNA FN3K than tumors located in the right side of colon. This paper is the first studying FN3K enzyme activity in human CRC, showing a significant relationship between enzymatic activity, its mRNA and tumor side.

  5. Lobaplatin suppresses proliferation and induces apoptosis in the human colorectal carcinoma cell Line LOVO in vitro.

    Science.gov (United States)

    Dai, Hong-yu; Liu, Lin; Qin, Shu-kui; He, Xiang-ming; Li, Su-yi

    2011-06-01

    Lobaplatin, as the third-generation platinum antineoplastic agent, showed promising antineoplastic effects in variety of preclinical test tumor models. We investigated the inhibition effect of lobaplatin on the colorectal carcinoma cell line LOVO in vitro, and explored its mechanism of action. The MTT assay was used to determine the inhibitory effect and inhibition ratio of lobaplatin on LOVO at various lobaplatin concentrations (500 μM, 1000 μM, 2000 μM). Apoptosis was detected by terminal deoxynucleotide transferase-mediated dUTP nickend labelling (TUNEL). The cell cycle and apoptotic rate were analyzed by flow cytometry (FCM) and the expression of caspase-3,8,9 in cells was detected by chromometry. The results of MTT assay showed that proliferation of LOVO cells was inhibited by lobaplatin in a concentration-dependent manner. Apoptosis was detected in LOVO cells by TUNEL. The FCM assay indicated that lobaplatin altered the cell cycle and induced apoptosis of the LOVO cells when treated for 24h, the percentages of cells in the S phase transition were increased, whereas the percentages of cells in the G(2) transition were decreased. The expressions of caspase-389 is higher than the control group after LOVO cells were treated by lobaplatin. Lobaplatin can inhibit the proliferation of colorectal carcinoma cell line LOVO by inducing apoptosis in vitro. The mechanism may be related to the "S" cycle arrest in cell cycle distribution and the up-regulated expression of caspase-8 and caspase-9 which up-regulated the expression of caspase-3.

  6. Nuclear factor-κB p65 (RelA) transcription factor is constitutively activated in human colorectal carcinoma tissue

    Institute of Scientific and Technical Information of China (English)

    Liang-Liang Yu; Hong-Gang Yu; Jie-Ping Yu; He-Sheng Luo; Xi-Ming Xu; Jun-Hua Li

    2004-01-01

    AIM: Activation of transcription factor nuclear factor-κB (NF-κB) has been shown to play a role in cell proliferation,apoptosis, cytokine production, and oncogenesis. The purpose of this study was to determine whether NF-κB was constitutively activated in human colorectal tumor tissues and, if so, to determine the role of NF-κB in colorectal tumorigenesis, and furthermore, to determine the association of RelA expression with tumor cell apoptosis and the expression of Bcl-2 and Bcl-xL.METHODS: Paraffin sections of normal epithelial, adenomatous and adenocarcinoma tissues were analysed immunohistochemically for expression of RelA, Bcl-2 and Bcl-xL proteins.Electrophoretic mobility shift assay (EMSA) was used to confirm the increased nuclear translocation of RelA in colorectal tumor tissues. The mRNA expressions of Bcl-2 and Bcl-xL were determined by reverse transcription polymerase chain reaction (RT-PCR) analysis. Apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method.RESULTS: The activity of NF-κB was significantly higher in adenocarcinoma tissue in comparison with that in adenomatous and normal epithelial tissues. The apoptotic index (AI)significantly decreased in the transition from adenoma to adenocarcinoma. Meanwhile, the expressions of Bcl-2 and Bcl-xL protein and their mRNAs were significantly higher in adenocarcinoma tissues than that in adenomatous and normal epithelial tissues.CONCLUSION: NF-κB may inhibit apoptosis via enhancing the expression of the apoptosis genes Bcl-2 and BCl-xL. And the increased expression of RelA/nuclear factor-κB plays an important rote in the pathogenesis of colorectal carcinoma.

  7. MicroRNA-221 inhibits CDKN1C/p57 expression in human colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Kai SUN; Wei WANG; Jun-jie ZENG; Cheng-tang WU; Shang-tong LEI; Guo-xin LI

    2011-01-01

    Aim: To investigate the regulatory effect of microRNA-221 (miR-221) on CDKN1C/p57 expression in colorectal carcinoma (CRC).Methods: Thirty four CRC and adjacent non-tumorous tissue samples were collected individually. Total RNA and protein were isolatedand from these samples and four human CRC-derived cell lines (including HT-29, Lovo, SW-480 and Caco2). MiR-221 expression was examined using real-time RT-PCR. CRC cells were treated with or without anti-p57-siRNA prior to the addition of premiR-221 or anti-miR-221. The mRNA and protein levels of CDKN1C/p57 were examined using semi-quantitative RT-PCR and Western blot, respectively. CRC cell proliferation and apoptosis were assessed using MTT assay and flow cytometry, respectively.The CDKN1C/p57 3'-UTR fragment was amplified using PCR from the genomic DNA of human colon cells and inserted into a luciferase reporter construct. The reporter construct was then transfected into CRC cells together with pre-miR-221 or anti-miR-221, and the luciferase activity in the transfected cells was examined.Results: MiR-221 expression was significantly up-regulated in 90% of CRC samples compared to that in the adjacent non-tumorous tissue, and the expression level was positively correlated to an advanced TNM stage and local invasion. There was no significant difference in CDKN1C/p57 mRNA expression between CRC and corresponding non-tumorous tissues, whereas CDKN1C/p57 protein expression was markedly decreased in the CRC samples. A significant inverse correlation between miR-221 and CDKN1C/p57expression was found in CRC cells. Moreover, a miR-221-specific inhibitor significantly increased CDKN1C/p57 protein expression in CRC cells. Anti-miR-221 markedly inhibited CRC cell proliferation and induced apoptosis. This inhibitory effect was abolished by pretreatment with a nti-p57-siRNA, suggesting that the inhibition was mediated by CDKN1C/p57. A significant increase of the luciferase activity was observed in CRC cells co-transfected with

  8. Calvatia lilacina protein-extract induces apoptosis through glutathione depletion in human colorectal carcinoma cells.

    Science.gov (United States)

    Tsay, Jwu-Guh; Chung, King-Thom; Yeh, Chung-Hung; Chen, Wan-Ling; Chen, Chi-Hung; Lin, Martin Hsiu-Chu; Lu, Fung-Jou; Chiou, Jeng-Fong; Chen, Ching-Hsein

    2009-02-25

    This paper reports that a novel protein extract isolated from Calvatia lilacina (CL) can induce cell death against four types of human colorectal cancer cells. Importantly, CL was shown to be free of apoptotic effects against normal rat liver cells. We have also identified that CL-induced glutathione (GSH) depletion is the major contributor responsible for the apoptotic cell death induction of SW 480 cells, as evidenced by the observation that exogenously added N-acetylcysteine (NAC), or GSH, but not vitamin C, could offer a near complete protection of CL-treated cells against apoptotic cell death. Furthermore, the participation of reactive oxygen species (ROS) evoked a drop in the transmembrane potential (Delta Psi(m)) in the CL-induced apoptotic cell death. This observation can only be deemed as a minor pathway due to the fact that cyclosporine A (CyA) could only partially rescue the CL-treated cells from apoptotic cell death. Likewise, despite the fact that CL could induce the upregulation of Bax, its knockdown via siRNA (48 h) failed to completely mitigate apoptotic cell death, indicating that its role in this apoptotic process was insignificant. To further explore the possible underlying mechanism associated with CL-induced GSH depletion, we proceeded to determine the effect of CL on the cellular gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme responsible for GSH biosynthesis, and demonstrated that indeed gamma-GCS could be repressed by CL. Taken together, we report here for the first time that the anticancer effect of CL on human colorectal cancer cells is mediated through GSH depletion mechanism rather than a ROS-mediated killing process. This functional attribute of CL can thus provide the basis for the strategic design of a treatment of colorectal cancer.

  9. Localization of human BRCA1 and BRCA2 in non-inherited colorectal carcinomas and matched normal mucosas.

    Science.gov (United States)

    Bernard-Gallon, D J; Peffault de Latour, M; Hizel, C; Vissac, C; Cure, H; Pezet, D; Dechelotte, P J; Chipponi, J; Chassagne, J; Bignon, Y J

    2001-01-01

    We characterized the expression of BRCA1 and BRCA2 in 38 sporadic colorectal carcinomas and matched normal mucosas with 9 anti-BRCA1 antibodies and 4 anti-BRCA2 antibodies, raised against several different epitopes, using immunohistochemical technique. We demonstrated an increased BRCA1 and BRCA2 staining in the apical cell pole of epithelial malignant cells and we also revealed a significant increase in BRCA1 and BRCA2 nuclear foci in tumor colorectal specimens in comparison with corresponding normal tissues. These increases in BRCA1 and BRCA2 expression may be explained by the fact that colorectal tissue is subject to very active proliferation and differentiation.

  10. pH-sensitive nanomicelles for controlled and efficient drug delivery to human colorectal carcinoma LoVo cells.

    Directory of Open Access Journals (Sweden)

    Shi-Ting Feng

    Full Text Available BACKGROUND: The triblock copolymers PEG-P(Asp-DIP-P(Lys-Ca (PEALCa of polyethylene glycol (PEG, poly(N-(N',N'-diisopropylaminoethyl aspartamide (P(Asp-DIP, and poly (lysine-cholic acid (P(Lys-Ca were synthesized as a pH-sensitive drug delivery system. In neutral aqueous environment such as physiological environment, PEALCa can self-assemble into stable vesicles with a size around 50-60 nm, avoid uptake by the reticuloendothelial system (RES, and encase the drug in the core. However, the PEALCa micelles disassemble and release drug rapidly in acidic environment that resembles lysosomal compartments. METHODOLOGY/PRINCIPAL FINDINGS: The anticancer drug Paclitaxel (PTX and hydrophilic superparamagnetic iron oxide (SPIO were encapsulated inside the core of the PEALCa micelles and used for potential cancer therapy. Drug release study revealed that PTX in the micelles was released faster at pH 5.0 than at pH 7.4. Cell culture studies showed that the PTX-SPIO-PEALCa micelle was effectively internalized by human colon carcinoma cell line (LoVo cells, and PTX could be embedded inside lysosomal compartments. Moreover, the human colorectal carcinoma (CRC LoVo cells delivery effect was verified in vivo by magnetic resonance imaging (MRI and histology analysis. Consequently effective suppression of CRC LoVo cell growth was evaluated. CONCLUSIONS/SIGNIFICANCE: These results indicated that the PTX-SPION-loaded pH-sensitive micelles were a promising MRI-visible drug release system for colorectal cancer therapy.

  11. Ornithine decarboxylase gene is overexpressed in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hai-Yan Hu; Bing Zhang; Xian-Xi Liu; Chun-Ying Jiang; Yi Lu; Shi-Lian Liu; Ji-Feng Bian; Xiao-Ming Wang; Zhao Geng; Yan Zhang

    2005-01-01

    AIM: To investigate the ornithine decarboxylase (ODC)gene expression in colorectal carcinoma, ODC mRNA was assayed by RT-PCR and ODC protein was detected by a monoclonal antibody against fusion of human colon ODC prepared by hybridoma technology.METHODS: Total RNA was extracted from human colorectal cancer tissues and their normal counterpart tissues. ODC mRNA levels were examined by RT-PCR.ODC genes amplified from RT-PCR were cloned into a prokaryotic vector pQE-30. The expressed proteins were purified by chromatography. Anti-ODC mAb was prepared with classical hybridoma techniques and used to determine the ODC expression in colon cancer tissues by immunohistochemical and Western blotting assay.RESULTS: A cell line, which could steadily secrete antiODC mAb, was selected through subcloning four times.Western blotting reconfirmed the mAb and ELISA showed that its subtype was IgG2a. RT-PCR showed that the ODC mRNA level increased greatly in colon cancer tissues (P<0.01). Immunohistochemical staining showed that colorectal carcinoma cells expressed a significantly higher level of ODC than normal colorectal mucosa (98.6±1.03%vs 5.26±5%, P<0.01).CONCLUSION: ODC gene overexpression is significantly related to human colorectal carcinoma. ODC gene expression may be a marker for the gene diagnosis and therapy of colorectal carcinoma.

  12. FRAGILE HISTIDINE TRIAD GENE EXPRESSION AND ITS CORRALATION WITH MISMATCH REPAIR PROTEIN IN HUMAN SPORADIC COLORECTAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    姚成才; 林从尧

    2004-01-01

    Objective: To investigate the expression of fragile histidine triad (FHIT) gene and its correlation with clinicopathological features and correlation with mismatch repair protein (mainly MLH1 and MSH2) in human sporadic colorectal carcinoma (SCC). Methods:Immunohistochemistry SP method was used to determine the expression of FHIT, MLH1 and MSH2 protein in surgically resected specimens of 84 human SCC. Results:The positive rates of FHIT, MLH1 and MSH2 protein expression were 48.81%, 92.86% and 100% respectively.Loss or reduced expression of FHIT protein was not related with tumors clinicopathological features such as age, gender,tumors site and histological type (P>0.05), but was correlated with tumors invade depth, degree of the differentiation, Ducks' stage and metastasis (P<0.05). There was no relationship between FHIT gene expression and MLH1 protein (r=0.0991, P>0.05) and MSH2 protein (r=0.0000, P=l.00) expression in human SCC. Conclusion:Absent or reduction of FHIT gene expression consists of high proportion and is a frequent event in SCC. FHIT gene is involved in the development and progression of human SCC and may be a candidate tumors suppressor gene. The relationship between alteration of FHIT gene expression and mismatch repair protein (mainly MLH1 and MSH2)deserved further study in human SCC.

  13. Effect of chronic restraint stress on human colorectal carcinoma growth in mice.

    Directory of Open Access Journals (Sweden)

    Qiang Lin

    Full Text Available Stress alters immunological and neuroendocrinological functions. An increasing number of studies indicate that chronic stress can accelerate tumor growth, but its role in colorectal carcinoma (CRC progression is not well understood. The aim of this study is to investigate the effects of chronic restraint stress (CRS on CRC cell growth in nude mice and the possible underlying mechanisms. In this study, we showed that CRS increased the levels of plasma catecholamines including epinephrine (E and norepinephrine (NE, and stimulated the growth of CRC cell-derived tumors in vivo. Treatment with the adrenoceptor (AR antagonists phentolamine (PHE, α-AR antagonist and propranolol (PRO, β-AR antagonist significantly inhibited the CRS-enhanced CRC cell growth in nude mice. In addition, the stress hormones E and NE remarkably enhanced CRC cell proliferation and viability in culture, as well as tumor growth in vivo. These effects were antagonized by the AR antagonists PHE and PRO, indicating that the stress hormone-induced CRC cell proliferation is AR dependent. We also observed that the β-AR antagonists atenolol (ATE, β1- AR antagonist and ICI 118,551 (ICI, β2- AR antagonist inhibited tumor cell proliferation and decreased the stress hormone-induced phosphorylation of extracellular signal-regulated kinases-1/2 (ERK1/2 in vitro and in vivo. The ERK1/2 inhibitor U0126 also blocked the function of the stress hormone, suggesting the involvement of ERK1/2 in the tumor-promoting effect of CRS. We conclude that CRS promotes CRC xenograft tumor growth in nude mice by stimulating CRC cell proliferation through the AR signaling-dependent activation of ERK1/2.

  14. Cysteine peptidase and its inhibitor activity levels and vitamin E concentration in normal human serum and colorectal carcinomas

    Institute of Scientific and Technical Information of China (English)

    Robert Szwed; Zygmunt Grzebieniak; Yousif Saleh; Godwin Bwire Ekonjo; Maciej Siewinski

    2005-01-01

    AIM: Cysteine peptidase (CP) and its inhibitor (CPI) are a matrix protease that may be associated with colorectal carcinoma invasion and progression, and vitamin E is also a stimulator of the immunological system. Our purpose was to determine the correlation between the expression of cysteine peptidases and their endogenous inhibitors,and the level of vitamin E in sera of patients with colorectal cancer in comparison with healthy individuals.METHODS: The levels of cysteine peptidases and their inhibitors were determined in the sera of patients with primary and metastatic colorectal carcinoma and healthy individuals using fluorogenic substrate, and the level of vitamin E was determined by HPLC.RESULTS: The levels of cysteine peptidases and their inhibitors were significantly higher in the metastatic colorectal cancer patients than that in the healthy controls (P<0.05).The activity of CP increased 2.2-fold, CPI 2.8-fold and vitamin E decreased 3.4-fold in sera of patients with metastasis in comparison with controls. The level of vitamin E in healthy individuals was higher, whereas the activity of cysteine peptidases and their inhibitors associated with complexes was lower than that in patients with cancer of the digestive tract.CONCLUSION: These results suggest that the serum levels of CP and their inhibitors could be an indicator of the prognosis for patients with metastatic colorectal cancer. Vitamin E can be administered prophylactically to prevent digestive tract neoplasmas.

  15. Functional differences between two morphologically distinct cell subpopulations within a human colorectal carcinoma cell line

    Directory of Open Access Journals (Sweden)

    Solimene A.C.C.

    2001-01-01

    Full Text Available The LISP-I human colorectal adenocarcinoma cell line was isolated from a hepatic metastasis at the Ludwig Institute, São Paulo, SP, Brazil. The objective of the present study was to isolate morphologically different subpopulations within the LISP-I cell line, and characterize some of their behavioral aspects such as adhesion to and migration towards extracellular matrix components, expression of intercellular adhesion molecules and tumorigenicity in vitro. Once isolated, the subpopulations were submitted to adhesion and migration assays on laminin and fibronectin (crucial proteins to invasion and metastasis, as well as to anchorage-independent growth. Two morphologically different subpopulations were isolated: LISP-A10 and LISP-E11. LISP-A10 presents a differentiated epithelial pattern, and LISP-E11 is fibroblastoid, suggesting a poorly differentiated pattern. LISP-A10 expressed the two intercellular adhesion molecules tested, carcinoembryonic antigen (CEA and desmoglein, while LISP-E11 expressed only low amounts of CEA. On the other hand, adhesion to laminin and fibronectin as well as migration towards these extracellular matrix proteins were higher in LISP-E11, as expected from its poorly differentiated phenotype. Both subpopulations showed anchorage-independent growth on a semi-solid substrate. These results raise the possibility that the heterogeneity found in the LISP-I cell line, which might have contributed to its ability to metastasize, was due to at least two different subpopulations herein identified.

  16. Protective role of p21(Waf1/Cip1) against prostaglandin A2-mediated apoptosis of human colorectal carcinoma cells.

    Science.gov (United States)

    Gorospe, M; Wang, X; Guyton, K Z; Holbrook, N J

    1996-01-01

    Prostaglandin A2 (PGA2) suppresses tumor growth in vivo, is potently antiproliferative in vitro, and is a model drug for the study of the mammalian stress response. Our previous studies using breast carcinoma MCF-7 cells suggested that p21(Waf1/Cip1) induction enabled cells to survive PGA2 exposure. Indeed, the marked sensitivity of human colorectal carcinoma RKO cells to the cytotoxicity of PGA2 is known to be associated with a lack of a PGA2-mediated increase in p21(Waf1/Cip1) expression, inhibition of cyclin-dependent kinase activity, and growth arrest. To determine if cell death following exposure to PGA2 could be prevented by forcing the expression of p21(Waf1/Cip1) in RKO cells, we utilized an adenoviral vector-based expression system. We demonstrate that ectopic expression of p21(Waf1/Cip1) largely rescued RKO cells from PGA2-induced apoptotic cell death, directly implicating p21(Waf1/Cip1) as a determinant of the cellular outcome (survival versus death) following exposure to PGA2. To discern whether p21(Waf1/Cip1)-mediated protection operates through the implementation of cellular growth arrest, other growth-inhibitory treatments were studied for the ability to attenuate PGA2-induced cell death. Neither serum depletion nor suramin (a growth factor receptor antagonist) protected RKO cells against PGA2 cytotoxicity, and neither induced p21(Waf1/Cip1) expression. Mimosine, however, enhanced p21(Waf1/Cip1) expression, completely inhibited RKO cell proliferation, and exerted marked protection against a subsequent PGA2 challenge. Taken together, our results directly demonstrate a protective role for p21(Waf1/Cip1) during PGA2 cellular stress and provide strong evidence that the implementation of cellular growth arrest contributes to this protective influence. PMID:8943319

  17. Anticancer Activity of Marine Sponge Hyrtios sp. Extract in Human Colorectal Carcinoma RKO Cells with Different p53 Status

    Directory of Open Access Journals (Sweden)

    Hyun Kyung Lim

    2014-01-01

    Full Text Available Drug development using marine bioresources is limited even though the ocean occupies about 70% of the earth and contains a large number of biological materials. From the screening test of the marine sponge extracts, we found Hyrtios sp. sponge collected from Chuuk island, Micronesia. In this study, the Hyrtios sp. extract was examined for anticancer activity against human colorectal carcinoma RKO cells that are wildtype for p53 and RKO-E6 that are p53 defective. The Hyrtios sp. extract dose-dependently inhibited viability in both cell lines. Multinucleation as an indication of mitotic catastrophe was also observed. Cytotoxicity tests gave significantly different results for RKO and RKO-E6 cells after 48 h exposure to Hyrtios sp. extract. In RKO cells treated with Hyrtios sp. extract, cell death occurred by induction of p53 and p21 proteins. In p53-defective RKO-E6 cells, Hyrtios sp. extract decreased expression of JNK protein and increased p21 protein. These results indicate that Hyrtios sp. extract induced apoptosis via different pathways depending on p53 status and could be a good natural product for developing new anticancer drugs.

  18. Construction of a metastasis-associated gene subtracted cDNA library of human colorectal carcinoma by suppression subtraction hybridization

    Institute of Scientific and Technical Information of China (English)

    Li Liang; Yan-Qing Ding; Xin Li; Guang-Zhi Yang; Jun Xiao; Li-Chun Lu; Jin-Hua Zhang

    2004-01-01

    AIM: To construct a differentially-expressed gene subtracted cDNA library from two colorectal carcinoma (CRC) cell lines with different metastatic phenotypes by suppression subtractive hybridization.METHODS: Two cell lines of human CRC from the same patient were used. SW620 cell line showing highly metastatic potential was regarded as tester in the forward subtractive hybridization, while SW480 cell line with lowly metastatic potential was treated as tester in the reverse hybridization. Suppression subtractive hybridization (SSH)was employed to obtain cDNA fragments of differentially expressed genes for the metastasis of CRC. These fragments were ligated with T vectors, screened through the bluewhite screening system to establish cDNA library.RESULTS: After the blue-white screening, 235 white clones were picked out from the positive-going hybridization and 232 from the reverse. PCR results showed that 200-700 bp inserts were seen in 98% and 91% clones from the forward and reverse hybridizations, respectively.CONCLUSIONS: A subtractive cDNA library of differentially expressed genes specific for metastasis of CRC can be constructed with SSH and T/A cloning techniques.

  19. 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.

  20. Andrographolide could inhibit human colorectal carcinoma Lovo cells migration and invasion via down-regulation of MMP-7 expression.

    Science.gov (United States)

    Shi, Ming-Der; Lin, Hui-Hsuan; Chiang, Tai-An; Tsai, Li-Yu; Tsai, Shu-Mei; Lee, Yi-Chieh; Chen, Jing-Hsien

    2009-08-14

    Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to possess multiple pharmacological activities. In our previous study, Andro had been shown to have potent anti-cancer activity against human colorectal carcinoma Lovo cells by inhibiting cell-cycle progression. To further investigate the mechanism for the anti-cancer properties of Andro, it was used to examine the effect on migration and invasion of Lovo cells. The results of wound-healing assay and in vitro transwell assay revealed that Andro inhibited dose-dependently the migration and invasion of Lovo cells under non-cytotoxic concentrations. Using zymographic assay and RT-PCR, the results revealed that Andro diminished the activity and the mRNA and protein levels of MMP-7, but not MMP-2 or MMP-9. The down-regulation of MMP-7 appeared to be via the inactivation of activator protein-1 (AP-1) since the treatment with Andro suppressed the nuclear protein level of AP-1, which was accompanied by a decrease in DNA-binding level of the factor. Taken together, these results indicated that Andro reduces the MMP-7-mediated cellular events in Lovo cells, and provided a new mechanism for its anti-cancer activity.

  1. Andrographolide sensitizes the cytotoxicity of human colorectal carcinoma cells toward cisplatin via enhancing apoptosis pathways in vitro and in vivo.

    Science.gov (United States)

    Lin, Hui-Hsuan; Shi, Ming-Der; Tseng, Hsien-Chun; Chen, Jing-Hsien

    2014-05-01

    Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, has been shown to suppress the growth and invasion of human colorectal carcinoma (CRC) Lovo cells, and trigger apoptosis in vitro. The potential of Andro as a chemotherapeutic agent in CRC was evaluated by investigating its cytotoxic effects as a single agent or in coadministration with cisplatin (CDDP). Andro potentiated the cytotoxic effect of CDDP in Lovo cells through apoptosis. The molecular mechanism for these favorable cellular response was further investigated by analyzing the apoptotic profiles, protein levels, and mRNA expression patterns of several key genes after treatments of Andro or/and CDDP. Molecular results indicated that the effect of Andro alone might be mediated via both intrinsic and extrinsic apoptotic pathways in Lovo cells. The addition of Andro to CDDP induced synergistic apoptosis, which could be corroborated to the changes in protein and mRNA levels of Bax and Bcl-2, and the increased Fas/FasL association in these cells, resulting in increased release of cytochrome c, and activation of caspases. Pretreatment of Nok-1 monoclonal antibody, a Fas signaling inhibitor, or Bax inhibitor peptide V5 repressed the Andro-induced cleavage of procaspase and the sensitization to CDDP-induced apoptosis. Finally, the combination therapy of Andro with CDDP was evidenced by its synergistic inhibition on the growth of Lovo cells in xenograft tumor studies. The results indicate that Andro, in combination with chemotherapeutics, is likely to represent a potential therapeutic strategy for CRC.

  2. 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

  3. Quantitative analysis of anti-CEA antibody accumulation in human colorectal carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Bares, R. (Technische Hochschule Aachen (Germany). Dept. of Nuclear Medicine); Fass, J. (Technische Hochschule Aachen (Germany). Dept. of Surgery); Hauptmann, S. (Technische Hochschule Aachen (Germany). Dept. of Pathology); Braun, J. (Technische Hochschule Aachen (Germany). Dept. of Surgery); Grehl, O. (Technische Hochschule Aachen (Germany). Dept. of Nuclear Medicine); Reinartz, R. (Technische Hochschule Aachen (Germany). Dept. of Surgery); Buell, U. (Technische Hochschule Aachen (Germany). Dept. of Nuclear Medicine); Schumpelick, V. (Technische Hochschule Aachen (Germany). Dept. of Surgery); Mittermayer, C. (Technische Hochschule Aachen (Germany). Dept. of Pathology)

    1993-04-01

    In order to obtain quantitative data on intratumoral anitbody accumulation we analyzed resected colorectal adenocarcinomas of 25 patients who had undergone immunoscintigraphy 4-14 days earlier. All had been injected with 0.5-1.0 mg intact anti-CEA antibody (BW 431/26) labelled with 70-80 MBq [sup 131]I. Correlation of tissue radioactivity concentrations with tumor characteristics revealed significantly higher values in necrotic compared to viable as well as in CEA-positive compared to CEA-negative viable tumor tissue indicating action of both specific and unspecific uptake mechanisms. In contrast, diagnostic results of immunoscintigraphy were influenced by tumor size only. 11 of 12 falsenegative findings were obtained in tumors <4 cm in diameter. Since ex-vivo scintigraphy of resected specimens correctly visualized all but one of these lesions, it is concluded that technical limitations of scintigraphy are the main cause of negative results of radioimmunoimaging with [sup 131]I-labelled antibodies. (orig.)

  4. Studies on mechanism of Sialy Lewis-X antigen in liver metastases of human colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xiao Wei Li; Yan Qing Ding; Jun Jie Cai; Shao Qing Yang; Lian Bing An; Dong Fang Qiao

    2001-01-01

    @@INTRODUCTION Sialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells .

  5. Increases in c-Yes expression level and activity promote motility but not proliferation of human colorectal carcinoma cells.

    Science.gov (United States)

    Barraclough, Jane; Hodgkinson, Cassandra; Hogg, Alison; Dive, Caroline; Welman, Arkadiusz

    2007-09-01

    Increases in the levels and/or activity of nonreceptor tyrosine kinases c-Src and c-Yes are often associated with colorectal carcinogenesis. The physiological consequences of increased c-Yes activity during the early and late stages of tumorigenesis, in addition to the degree of redundancy between c-Yes and c-Src in colorectal cancer cells, remain elusive. To study the consequences of increases in c-Yes levels and activity in later stages of colorectal carcinogenesis, we developed human colorectal cancer cell lines in which c-Yes levels and activity can be inducibly increased by a tightly controlled expression of wild-type c-Yes or by constitutively active mutants of c-Yes, c-YesY537F, and c-Yes Delta t6aa. c-Yes induction resulted in increased cell motility but did not promote proliferation either in vitro or in vivo. These results suggest that in later stages of colorectal carcinogenesis, elevations in c-Yes levels/activity may promote cancer spread and metastasis rather than tumor growth.

  6. Antitumour effects on human colorectal carcinomas cells by stable silencing of phospholipase C-gamma 1 with lentivirus-delivered siRNA

    Institute of Scientific and Technical Information of China (English)

    TAN Li; XIAO Bing-xiang; ZENG Wei-sen; LIN Jun; ZOU Zhi-peng; XU Ai-min; LUO Shen-qiu

    2007-01-01

    Background In most colorectal carcinomas, the level of phospholipase C (PLC)-gamma 1 expression is greatly elevated. Increased expression of PLC-gamma 1 may play an important role in colon carcinogenesis, but the mechanism is not well known. The aim of this study was to evaluate the role of PLC-gamma 1 in colon carcinogenesis by using recombinant lentivirus that stably suppressed the PLC-gamma 1 expression in human colorectal carcinoma LoVo cells.Methods Recombinant lentivirus producing PLC-gamma 1 siRNA were prepared. After LoVo cells were transduced by each lentivirus, stably transduced cells were selected by Blasticidin. The protein and mRNA expression of PLC-gamma 1 were examined by Western-blot and reverse transcription-polymerase chain reaction (RT-PCR) analysis, and the effects of the lentivirus on the cell adhesion, migration and apoptosis were analyzed.Results Stable LoVo cell line deficient in PLC-gamma 1, was established. Notably, PLC-gamma 1 was silenced without affecting the levels of other subtypes of PLC so that the role of PLC-gamma 1 in colon carcinogenesis could be examined.Silencing of endogenous PLC-gamma 1 resulted in efficient inhibition of the adhesion and migration of LoVo cells in vitro and a great increase of 5-fluorouracil induced apoptosis (30%-40%) of LoVo cells.Conclusions PLC-gamma 1 may play an important role in metastasis and anti-apoptosis in human colorectal carcinomas.

  7. Changes in subcellular localization of visfatin in human colorectal HCT-116 carcinoma cell line after cytochalasin B treatment

    Directory of Open Access Journals (Sweden)

    R.J. Bułdak

    2014-09-01

    Full Text Available The aim of the study was to assess the expression and subcellular localization of visfatin in HCT-116 colorectal carcinoma cells after cytokinesis failure using Cytochalasin B (CytB and the mechanism of apoptosis of cells after CytB. We observed translocation of visfatin’s antigen in cytB treated colorectal carcinoma HCT-116 cells from cytosol to nucleus. Statistical and morphometric analysis revealed significantly higher area-related numerical density visfatin-bound nano-golds in the nuclei of cytB-treated HCT-116 cells compared to cytosol. Reverse relation to visfatin subcellular localization was observed in un-treated HCT-116 cells. The total amount of visfatin protein and visfatin mRNA level in HCT-116 cells was also decreased after CytB treatment. Additionally, CytB significantly decreased cell survival, increased levels of G2/M fractions, induced bi-nuclei formation as well as increased reactive oxygen species (ROS level in HCT-116 cells. CytB treatment showed cytotoxic effect that stem from oxidative stress and is connected with the changes in the cytoplasmic/nuclear amount of visfatin in HCT-116 cells.

  8. Expression of Wntless in colorectal carcinomas is associated with invasion, metastasis, and poor survival.

    Science.gov (United States)

    Xu, Hanfeng; Jiang, Wen; Zhu, Fang; Zhu, Chuandong; Wei, Juan; Wang, Jiandong

    2016-06-01

    Wntless also known as WLS, GPR177, or Evi, is a key modulator of Wnt protein secretion. Its overexpression is found in certain types of human cancers such as malignant astrocytoma and breast cancers. We hypothesized that this protein may be aberrantly expressed in colorectal carcinoma which also possesses aberrant Wnt signaling. To investigate the association between the expression of Wnt and clinicopathological parameters in colorectal carcinomas, a set of colorectal carcinoma tissue samples was analyzed for the expression of WLS using an anti-GPR177 monoclonal antibody specific for the WLS protein. High expression of WLS protein was observed in most colorectal carcinoma samples compared with nontumor mucosa in the same patients (117/201, 58.2%). High expression of WLS was associated with sex (p = 0.005), age (p = 0.009), depth of invasion (p < 0.001), lymph node metastasis (p = 0.026), and tumor-node-metastasis (TNM) stage (p = 0.003). No significant relationship between the expression of WLS and tumor location, size, and differentiation was found. The survival analyses showed WLS was an independent prognostic marker and that patients whose carcinoma exhibited high expression of WLS had a poorer outcome (p = 0.033). Our results indicate that WLS may play a role in invasion and metastasis of colorectal carcinoma. The WLS protein expression level may be used as a potential prognostic marker in colorectal carcinoma. Furthermore, the WLS gene may provide a novel target for therapy of colorectal carcinoma.

  9. Photodynamic inhibitory effects of three perylenequinones on human colorectal carcinoma cell line and primate embryonic stem cell line

    Institute of Scientific and Technical Information of China (English)

    Lan Ma; Hong Tai; Cong Li; Yu Zhang; Ze-Hua Wang; Wei-Zhi Ji

    2003-01-01

    AIM: To investigate the photodynamic inhibitory effects of Elsinochrome A (EA), Hypocrellin A (HA) and Hypocrellin B (HB) on human colorectal carcinoma Hce-8693 cells and rhesus monkey embryonic stem R366.4 cells, via inducing apoptosis.METHODS: EA, HA and HB were extracted from metabolites of Hypomyces (Fr) Tul.Sp. R366.4 cells or Hce8693 cells were cultured with different concentrations of EA, HA or HB respectively, irradiated and incubated with fresh medium for 2 h. Cell cycle analysis was performed by flow cytometry (FCM). Data were expressed as means ±SD and analysis of variance and Student' t-test for individual comparisons.RESULTS: The photodynamic bioactivity of EA was first reported in this study. After irradiation for 5 min, 6 min, 10 min or 20 min, photoactivated EA at lower concentrations,which were 10-7 Mol/L, 10-6 Mol/L, 10-5 Mol/L respectively,had no cytotoxic effects on R366.4 ES ceils. Whereas, all of the three perylenequinones could induce apoptosis with a dose-dependent manner when Hce-8693 cells were incubated with photoactivated EA, HA and HB respectively. When Hce-8693 cells were incubated with EA at 10-6 Mol/L and irradiated 5 lin, 6 min, 10 min and 20 min respectively,the rates of EA-induced apoptosis were 0, 0, 13.4 % and 40.5 %. While the rates of HA-induced apoptosis were 29.5 %, 32.0 %, 40.2 % and 22.6 %. And the rates of HBinduced apoptosis were 0, 0, 0 and 13.7 % respectively.Meanwhile, after 10-5 Mol/L treatment, the rates of EA-induced apoptosis were 32.7 %, 19.3 %, 26.4 % and 52.7 %, the rates of HA-induced apoptosis were 47.2 %, 39.1%, 45.2% and 56.6 %, and the rates of HB-induced apoptosis were 0, 0, 20.0 % and 13.9 % respectively.CONCLUSION: EA, HA and HB have significant anti-cancer activity. The order of photodynamic inhibitory effects on tumor cells would be approximately HA>EA>HB. The molecular mechanisms of apoptosis may not be induced by reactive oxygen species and are worth further investigation.

  10. Anti-cancer effect of Cordyceps militaris in human colorectal carcinoma RKO cells via cell cycle arrest and mitochondrial apoptosis

    OpenAIRE

    Lee, Hwan Hee; Lee, Seulki; Lee, Kanghyo; Shin, Yu Su; Kang, Hyojeung; Cho, Hyosun

    2015-01-01

    Background Cordyceps militaris has been used as a traditional medicine in Asian countries for a long time. Different types of Cordyceps extract were reported to have various pharmacological activities including an anti-cancer effect. We investigated the inhibitory effect of Cordyceps militaris ethanol extract on a human colorectal cancer-derived cell line, RKO. Methods RKO cells were treated with various concentrations of nucleosides-enriched ethanol extract of Cordyceps militaris for 48 h an...

  11. COLORECTAL-CARCINOMA - AN UPDATE

    NARCIS (Netherlands)

    SINNIGE, HAM; MULDER, NH

    1991-01-01

    During the last decade important advances have occurred in the fields of understanding genesis, molecular biology, detection of "precancerous data", intervention, and metastatic behaviour of colorectal cancer. An important step forward has been made in adjuvant therapy. Better understanding of 5-flu

  12. Relationship between miRNA-338-3p expression and progression and prognosis of human colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Sun Kai; Su Guiyuan; Deng Haijun; Dong Jingqing; Lei Shangtong; Li Guoxin

    2014-01-01

    Background miR-338-3p is a recently discovered miRNA and is involved in cell differentiation.However,few data are yet available on the aberrant expression of miR-338-3p in human colorectal carcinoma (CRC).This work aimed to investigate the relationship between miR-338-3p expression pattern and clinicopathological features of human CRC and the possible regulative mechanisms.Methods The 40 CRC,adjacent nontumorous tissues and 2 human CRC-derived cell lines (SW-480 and SW-620) were collected,respectively,and the total RNA and protein were isolated routinely.The miR-338-3p expression pattern was detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Northern blotting.Smoothened (SMO,possible target of miR-338-3p) mRNA and corresponding protein expression pattern were detected by semiquantitative RT-PCR and Western blotting.miR-338-3p expression patterns were compared between nontumor mucosa and CRC samples,graded by progression-related factors.Disease outcome was calculated by Kaplan-Meier survival analysis to determine whether miR-338-3p was related to disease-free survival (DFS) and overall survival (OS) of patients.Moreover,SMO 3'-UTR fragment was PCR amplified from genome DNA of human colon and inserted into a luciferase reporter plasmid.The luciferase reporter plasmid construct was then transfected into CRC cells together with pre-miR-338-3p or anti-miR-338-3p and the luciferase activity in the transfected cells was detected.Results The expression of miR-338-3p was significantly downregulated in CRCs than those in the adjacent nontumorous tissues,and the value was negatively related to advanced TNM stage and local invasion (P <0.01).Furthermore,miR338-3p value was decreased markedly in SW-620 cell line relative to SW-480 (P <0.01).Low expression of miR-338-3p was associated with unfavorable outcome in DFS but not in OS independent of clinical covariates.Moreover,RT-PCR and Western blotting analysis demonstrated that there was no

  13. The role of cyclooxygenase in n-6 and n-3 polyunsaturated fatty acid mediated effects on cell proliferation, PGE2 synthesis and cytotoxicity in human colorectal carcinoma cell lines

    NARCIS (Netherlands)

    Dommels, Y.E.M.; Haring, M.M.G.; Keestra, N.G.M.; Alink, G.M.; Bladeren, P.J. van; Ommen, B. van

    2003-01-01

    This study was conducted to investigate the role of the enzyme cyclooxygenase (COX) and its prostaglandin product PGE2 in n-6 and n-3 polyunsaturated fatty acid (PUFA)-mediated effects on cellular proliferation of two human colorectal carcinoma cell lines. The long chain PUFAs eicosapentaenoic acid

  14. The role of cyclooxygenase in n-6 and n-3 polyunsaturated fatty acid mediated effects on cell proliferation, PGE2 synthesis and cytotoxicity in human colorectal carcinoma cell lines

    NARCIS (Netherlands)

    Dommels, Y.E.M.; Haring, M.M.G.; Keestra, N.G.M.; Alink, G.M.; Bladeren, P.J. van; Ommen, B. van

    2003-01-01

    This study was conducted to investigate the role of the enzyme cyclooxygenase (COX) and its prostaglandin product PGE2 in n-6 and n-3 polyunsaturated fatty acid (PUFA)-mediated effects on cellular proliferation of two human colorectal carcinoma cell lines. The long chain PUFAs eicosapentaenoic acid

  15. Radioimmunoscintigraphy of colorectal carcinoma using technetium-99m-labeled, totally human monoclonal antibody 88BV59H21-2.

    Science.gov (United States)

    Gulec, S A; Serafini, A N; Moffat, F L; Vargas-Cuba, R D; Sfakianakis, G N; Franceschi, D; Crichton, V Z; Subramanian, R; Klein, J L; De Jager, R L

    1995-12-01

    Radioimmunoscintigraphy (RIS) using human monoclonal antibodies offers the important clinical advantage of repeated imaging over murine monoclonal antibodies by eliminating the cross-species antibody response. This article reports a Phase I-II clinical trial with Tc-99m-labeled, totally human monoclonal antibody 88BV59H21-2 in patients with colorectal carcinoma. The study population consisted of 34 patients with colorectal cancer (20 men and 14 women; age range, 44-81 years). Patients were administered 5-10 mg antibody labeled with 21-41 mCi Tc-99m by the i.v. route and imaged at 3-10 and 16-24 h after infusion using planar and single-photon emission computed tomographic (CT) techniques. Pathological confirmation was obtained in 25 patients who underwent surgery. Human antihuman antibody (HAHA) titers were checked prior to and 1 and 3 months after the infusion. RIS with Tc-99m-labeled 88BV59H21-2 revealed a better detection rate in the abdomen-pelvis region compared with axial CT. The combined use of both modalities increased the sensitivity in both the liver and abdomen-pelvis regions. Ten patients developed mild adverse reactions (chills and fever). No HAHA response was detected in this series. Tc-99m-labeled human monoclonal antibody 88BV59H21-2 RIS shows promise as a useful diagnostic modality in patients with colorectal cancer. RIS alone or in combination with CT is more sensitive than CT in detecting tumor within the abdomen and pelvis. Repeated RIS studies may be possible, due to the lack of a HAHA response.

  16. 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 wa

  17. CLINICOPATHOLOGICAL FEATURES OF RER+ COLORECTAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    XU Ning; DING Yan-Qing; XU LI; Qiu Hong-ming

    1999-01-01

    Objective: Replication errors (RER) is related to initiation and development of colorectal carcinoma (CRC).To investigate the different biological behavior of RER+ and RER- CRC. Methods: Silver staining PCR-single strand conformation polymorphism (PCR-SSCP) and denatured polyacrylamide gel electrophoresis methods were used to detect microsatellite instability (MSI) at 4 loci on chromosome 2, 5, 17 in paraffin-embedded specimens of 60 colorectal carcinoma (CRC) and their paired normal tissue.RER+ was scored if 2 or more loci behaved as gaining extra bands. Results: The results showed that RER+ was found in 19/60 CRC, among which 7 cases had a family history.According to the criteria of Amsterdam, 4 were diagnosed as hereditary nonpolyposis colorectal cancer (HNPCC), and of which 3 cases were RER+. The ratio RER+ in HNPCC (75%) was significantly higher than that among sporadic CRC (28.5%). Most of the RER+ CRC have the feature of poorly differentiated adenocarcinoma (P<0.01), the tendency to involve the right side of the colon (P<0.05), a higher proportion with a family history (P<0.05), Duckes' A and B stage (P<0.05). Conclusion: The results indicated that RER+ is a relatively common molecular event in CRC.There are different clinico-pathological features and behavior between RER+ and RER- CPC.

  18. Diagnostic and therapeutic evaluation of {sup 111}In-vinorelbine-liposomes in a human colorectal carcinoma HT-29/luc-bearing animal model

    Energy Technology Data Exchange (ETDEWEB)

    Chow, T.-H.; Lin, Y.-Y. [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); Hwang, J.-J. [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan (China)], E-mail: jjhwang@ym.edu.tw; Wang, H.-E. [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan (China); Tseng, Y.-L. [Taiwan Liposome Company, Taipei, Taiwan (China); Pang, V.F. [Department of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); Wang, S.-J. [Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Whang-Peng, Jacqueline; Ting Gann [National Health Research Institute, Taipei, Taiwan (China)

    2008-07-15

    Colorectal carcinoma is a highly prevalent and common cause of cancer in Taiwan. There is still no available cure for this malignant disease. To address this issue, we applied the multimodality of molecular imaging to explore the efficacy of diagnostic and therapeutic nanoradiopharmaceuticals in an animal model of human colorectal adenocarcinoma [colorectal cancer (CRC)] that stably expresses luciferase (luc) as a reporter. In this study, an in vivo therapeutic efficacy evaluation of dual-nanoliposome (100 nm in diameter) encaged vinorelbine (VNB) and {sup 111}In-oxine on HT-29/luc mouse xenografts was carried out. HT-29/luc tumor cells were transplanted subcutaneously into male SCID mice. Multimodality of molecular imaging approaches including bioluminescence imaging (BLI), gamma scintigraphy, whole-body autoradiography (WBAR) and in vivo tumor growth tracing, histopathology and biochemistry/hematology analyses were applied on xenografted SCID mice to study the treatments with 6% polyethylene glycol (PEG) of {sup 111}In-NanoX/VNB-liposomes. In vivo tumor growth tracing and BLI showed that tumor volume could be completely inhibited by the combination therapy with {sup 111}In-VNB-liposomes and by chemotherapy with NanoX/VNB-liposomes (i.e., without Indium-111) (P<.01). The nuclear medicine images of gamma scintigraphy and WBAR also revealed the conspicuous inhibition of tumor growth by the combination therapy with {sup 111}In-VNB-liposomes. Animal body weights, histopathology and biochemistry/hematology analyses were used to confirm the safety and feasibility of radiopharmaceuticals. A synergistic therapeutic effect on CRC xenografted SCID mice was proven by combining an Auger electron-emitting radioisotope (Indium-111) with an anticancer drug (VNB). This study further demonstrates the beneficial potential applications of multimodality molecular imaging as part of the diagnostic and therapeutic approaches available for the evaluation of new drugs and other strategic

  19. Obstructive Colitis Proximal to Obstructive Colorectal Carcinoma

    Directory of Open Access Journals (Sweden)

    Hye Kyung Chang

    2009-01-01

    Full Text Available The term “obstructive colitis” refers to ulceroinflammatory lesions occurring in the colon proximal to a completely or partially obstructing lesion. It has been referred to by various terms in the literature. This entity differs from the carcinoma of the colon that complicates true ulcerative colitis where there is involvement distal to the neoplasm as well as proximal to it. Although it has appeared in the literature over several decades, it remains an uncommon and troublesome disease. In Yonsei University Medical Center, for 11 years from January 1996 to December 2006 we encountered seven patients with obstructing colorectal carcinoma complicated by obstructive colitis. Here we report our cases to share our experience and to review the literature to facilitate the recognition and proper management of this rare disease entity.

  20. Significance of carbohydrate antigen 50 expression in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To evaluate the significance of carbohydrate antigen 50(CA50)expression in colorectal carcinoma.Methods Immunohistochemical staining was used to detect CA50 expression in 10 cases of normal colorectal mucosa and 40 cases of cancer mucosa.Results The expression of CA50 increased in normal colorectal mucosa,cancer distant mucosa,cancer adjacent mucosa and cancer mucosa,and there were significant differences among them(P<0.05).The expression of CA50 in colorectal carcinoma was correlated with the deg...

  1. The UVB1 Vitamin D analogue inhibits colorectal carcinoma progression.

    Science.gov (United States)

    Ferronato, María Julia; Alonso, Eliana Noelia; Gandini, Norberto Ariel; Fermento, María Eugenia; Villegas, María Emilia; Quevedo, Mario Alfredo; Arévalo, Julián; López Romero, Alejandro; Rivadulla, Marcos Lois; Gómez, Generosa; Fall, Yagamare; Facchinetti, María Marta; Curino, Alejandro Carlos

    2016-10-01

    Vitamin D has been shown to display a wide variety of antitumour effects, but their therapeutic use is limited by its severe side effects. We have designed and synthesized a Gemini vitamin D analogue of calcitriol (UVB1) which has shown to display antineoplastic effects on different cancer cell lines without causing hypercalcemia. The aim of this work has been to investigate, by employing in silico, in vitro, and in vivo assays, whether UVB1 inhibits human colorectal carcinoma progression. We demonstrated that UVB1 induces apoptotic cell death and retards cellular migration and invasion of HCT116 colorectal carcinoma cells. Moreover, the analogue reduced the tumour volume in vivo, and modulated the expression of Bax, E-cadherin and nuclear β-catenin in tumour animal tissues without producing toxic effects. In silico analysis showed that UVB1 exhibits greater affinity for the ligand binding domain of vitamin D receptor than calcitriol, and that several characteristics in the three-dimensional conformation of VDR may influence the biological effects. These results demonstrate that the Gemini vitamin D analogue affects the growth of the colorectal cancer and suggest that UVB1 is a potential chemotherapeutic agent for treatment of this disease.

  2. 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.

  3. Significance of carbohydrate antigen 50 expression in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zhen-hua Ma; Kang Wang; Wei-hua Shang; Si-guang Li; Mao Zhang

    2009-01-01

    Objective To evaluate the significance of carbohydrate antigen 50 (CA50) expression in colorectal carcinoma. Methods Immunohistochemical staining was used to detect CA50 expression in 10 cases of normal colorectal mucosa and 40 cases of cancer mucosa. Results The expression of CA50 increased in normal colorectal mucosa, cancer distant mucosa, cancer adjacent mucosa and cancer mucosa, and there were significant differences among them (P<0.05). The expression of CA50 in colorectal carcinoma was correlated with the degree of differentiation, Duke's stage and lymphatic metastases (P<0.05). Conclusion The expression of CA50 can be used as a valuable index in evaluating the biological characteristics and prognosis of colorectal carcinoma.

  4. The Cytotoxic Effect of Essential Oil of Syrian Citrus limon Peel on Human Colorectal Carcinoma Cell Line (Lim1863

    Directory of Open Access Journals (Sweden)

    Mohammad Eyad Chatty

    2012-01-01

    Full Text Available Background: Essential oils are the volatile fraction of aromatic and medicinal plants created after extraction by steam or water distillation. Species of the genus Citrus(Rutaceae have been widely used in traditional medicine as volatile oils and are currently the subject of numerous research. Citrus essential oil consists of different terpens that have antitumor activities. This study determines the cytotoxic effect of the essential oils of Citrus limon L. peels on a colorectal cancer cell line (LIM1863.Methods: We harvested four samples from four locations in Syria. Essential oils were prepared by hydrodistillation and analyzed by Gas chromatography-mass spectrometry (GC-MS.Various concentrations ofessential oils (0.5-48 μg/ml were added to cultured cells and incubated for 72 h. Cell viability was evaluated byMTT-basedcytotoxicity assay.Results: We noted 18 components that represented 98.81% of the total oil content. The major components were: limonene (61.8%-73.8%, γ-terpinene (9.4%-10.4%, β-pinene (3.7%-6.9%, O-cymene(1%-2.4%,and citral (0.8%-5.4%.The obtained IC50 value range of Citrus limon essential oils was 5.75-7.92 μg/ml against LIM1863.Conclusion: This study revealed that Syrian Citrus limon essential oil has a cytotoxic effect on the human colorectalcarcinoma cell line LIM1863 when studied in vitro.

  5. Isolation of lignans from Schisandra chinensis with anti-proliferative activity in human colorectal carcinoma: Structure-activity relationships.

    Science.gov (United States)

    Gnabre, John; Unlu, Irem; Chang, Tso-Cheng; Lisseck, Paul; Bourne, Bryan; Scolnik, Ryan; Jacobsen, Neil E; Bates, Robert; Huang, Ru Chih

    2010-10-15

    Separate benzocyclooctadiene lignans were isolated from the berries of Schisandra chinensis in milligram quantities on analytical reverse phase (RP) HPLC by an automated repeat-injection method and shown to have anti-proliferative activity against human colorectal cancer cells. Structures of the compounds were determined by a combination of NMR and mass spectrometry. Stereospecific NMR assignments for gomisin-N and deoxyschisandrin, gave more complete and accurate data than previously reported, based on 600MHz 2D HSQC, DQF-COSY and HMBC data. Comparison of coupling constants and HMBC crosspeak intensities with calculated and X-ray crystal structures confirmed their stereochemistry and conformation. Analysis of structure-activity relationships revealed the importance of key structural determinants. The S-biphenyl configuration of gomisin N, the most active lignan, correlated with increased anti-proliferative activity, while the presence of a hydroxyl group at the C7 position reduced or abolished this activity. Increased activity was also observed when a methylenedioxy group was present between C12 and C13. The percent yield of the most active compounds relative to the starting plant materials was 0.0156% for deoxyschisandrin and 0.0173% for gomisin N. The results of these studies indicate that automated repeat-injection method of analytical HPLC may provide a superior alternative to the standard semi-preparative HPLC techniques for separation of complex mixtures.

  6. CATHEPSIN B EXPRESSION AND ITS RELATIONSHIP WITH MICROVESSEL DENSITY AND BIOLOGICAL BEHAVIOUR OF COLORECTAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    王娅兰; 林晓

    2002-01-01

    Objective: To investigate cathepsin B(CB) expression in colorectal carcinoma and its relationship with microvessel density (MVD) and biological behavior. Methods: CB and MVD were detected by immunohistochemistry in 47 cases of colorectal carcinoma. Results: The expression of CB in mucinous colorectal carcinoma was significantly higher than that in no-mucinous colorectal carcinoma. There was significant difference (P<0.05). The MVD in group with positive CB was stronger than that in group with negative CB. There was also significant difference (P<0.05). Conclusion: The results suggest that CB expression has correlation with MVD, invasion and metastasis in colorectal carcinoma, especially in mucinous colorectal carcinoma.

  7. Tiam1 gene expression and its significance in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Li Liu; De-Hua Wu; Yan-Qing Ding

    2005-01-01

    AIM: To explore the expression of Tiam1 gene in colorectal carcinoma and its correlation with tumor metastasis.METHODS: Expressions of Tiam1 gene in 8 colorectal carcinoma cell lines were detected by reverse transcriptasepolymerase chain reaction. In vitro invasiveness was determined by means of Matrigel invasion assay. The correlation of Tiam1 expression with the invasive ability was also analyzed.RESULTS: Tiam1 gene was highly expressed in LoVo and SW620, which were established from metastatic colorectal carcinomas in comparison with LS174T, SW480, HCT116,LST, HRT-18 and Hee8693, which were established from primary colorectal carcinomas. In vitro cell invasivion demonstrated that LoVo and SW620 had a higher invasive ability than LS174T, SW480, HCT116, LST, HRT-18 and Hee8693. The expression of Tiam1 gene was highly related to the metastatic potential of colorectal carcinoma cells.CONCLUSION: Tiam1 gene may play an important role in invasion and metastasis of colorectal carcinoma and is a metastasis-related gene.

  8. Postprocessing techniques of CT colonography in detection of colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ming-Yue Luo; Hong Shan; Li-Qing Yao; Kang-Rong Zhou; Wen-Wei Liang

    2004-01-01

    AIM: To evaluate the value of postprocessing techniques of CT colonography, including multiplanar reformation (MPR),virtual colonoscopy (VC), shaded surface display (SSD) and Raysum, in detection of colorectal carcinomas.METHODS: Sixty-four patients with colorectal carcinoma underwent volume scanning with spiral CT. MPR, VC, SSD and Raysum images were obtained by using four kinds of postprocessing techniques in workstation. The results were comparatively analyzed according to circumferential extent,lesion length and pathology pattern of colorectal carcinomas.All diagnoses were proved pathologically and surgically.RESULTS: The accuracy of circumferential extent of colorectal carcinoma determined by MPR, VC, SSD and Raysum was 100.0%, 82.8%, 79.7% and 79.7%,respectively. There was a significant statistical difference between MPR and VC. The consistent rate of lesion length was 89.1%, 76.6%, 95.3% and 100.0%, respectively.There was a statistical difference between VC and SSD.The accuracy of discriminating pathology pattern was 81.3%,92.2%, 71.9% and 71.9%, respectively. There was a statistical difference between VC and SSD. MPR could determine accurately the circumference of colorectal carcinoma, Raysum could determine the length of lesion more precisely than SSD, VC was helpful in discriminating pathology patterns.CONCLUSION: MPR, VC, SSD and Raysum have advantage and disadvantage in detection of colorectal carcinoma, use of these methods in combination can disclose the lesion more accurately.

  9. Effects of ghrelin, leptin and melatonin on the levels of reactive oxygen species, antioxidant enzyme activity and viability of the HCT 116 human colorectal carcinoma cell line.

    Science.gov (United States)

    Bułdak, Rafał Jakub; Pilc-Gumuła, Katarzyna; Bułdak, Łukasz; Witkowska, Daria; Kukla, Michał; Polaniak, Renata; Zwirska-Korczala, Krystyna

    2015-08-01

    Obesity is associated with an increased risk of certain types of cancer, including colon cancer. Adipose tissue is an endocrine organ that produces biologically active substances, such as leptin and ghrelin. Recent research has suggested that adipose-derived hormones may be associated with mechanisms linked to tumorigenesis and cancer progression. Furthermore, previous studies have demonstrated that pineal gland-derived melatonin possesses important oncostatic and antioxidant properties. The present study aimed to determine the effects of the adipokines ghrelin and leptin, and the melatonin on intracellular levels of reactive oxygen species (ROS) and the activity of selected antioxidant enzymes, such as superoxide dismutase, catalase (CAT) and glutathione peroxidase. The effects of these compounds were also determined on the viability of HCT 116 human colorectal carcinoma cells in vitro. The pro-oxidant and growth inhibitory effects of melatonin resulted in an accumulation of ROS and decreased antioxidant capacity in melatonin-treated cells. Ghrelin administration alone caused a significant decrease in the levels of ROS, due to an increased activity of CAT in the HCT 116 cells. In addition, the present study observed increased lipid peroxidation following melatonin treatment, and decreased levels of malondialdehyde following ghrelin or leptin treatment. In conclusion, ghrelin, leptin and melatonin have various influences on the antioxidant capacity of HCT 116 cells. Compared with the adipokines, treatment with melatonin increased ROS levels and decreased cellular viability.

  10. Comparison of human gut microbiota in control subjects and patients with colorectal carcinoma in adenoma: Terminal restriction fragment length polymorphism and next-generation sequencing analyses.

    Science.gov (United States)

    Kasai, Chika; Sugimoto, Kazushi; Moritani, Isao; Tanaka, Junichiro; Oya, Yumi; Inoue, Hidekazu; Tameda, Masahiko; Shiraki, Katsuya; Ito, Masaaki; Takei, Yoshiyuki; Takase, Kojiro

    2016-01-01

    Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in Japan. The etiology of CRC has been linked to numerous factors including genetic mutation, diet, life style, inflammation, and recently, the gut microbiota. However, CRC-associated gut microbiota is still largely unexamined. This study used terminal restriction fragment length polymorphism (T-RFLP) and next-generation sequencing (NGS) to analyze and compare gut microbiota of Japanese control subjects and Japanese patients with carcinoma in adenoma. Stool samples were collected from 49 control subjects, 50 patients with colon adenoma, and 9 patients with colorectal cancer (3/9 with invasive cancer and 6/9 with carcinoma in adenoma) immediately before colonoscopy; DNA was extracted from each stool sample. Based on T-RFLP analysis, 12 subjects (six control and six carcinoma in adenoma subjects) were selected; their samples were used for NGS and species-level analysis. T-RFLP analysis showed no significant differences in bacterial population between control, adenoma and cancer groups. However, NGS revealed that i), control and carcinoma in adenoma subjects had different gut microbiota compositions, ii), one bacterial genus (Slackia) was significantly associated with the control group and four bacterial genera (Actinomyces, Atopobium, Fusobacterium, and Haemophilus) were significantly associated with the carcinoma-in-adenoma group, and iii), several bacterial species were significantly associated with each type (control: Eubacterium coprostanoligens; carcinoma in adenoma: Actinomyces odontolyticus, Bacteroides fragiles, Clostridium nexile, Fusobacterium varium, Haemophilus parainfluenzae, Prevotella stercorea, Streptococcus gordonii, and Veillonella dispar). Gut microbial properties differ between control subjects and carcinoma-in-adenoma patients in this Japanese population, suggesting that gut microbiota is related to CRC prevention and development.

  11. Altered expression of MUC2 and MUC5AC in progression of colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To study the expression profiles of MUC2 and MUC5AC in tumorigenesis of colorectal carcinoma and in its different pathologic types.METHODS:Formalin-fixed,paraffin-embedded human colorectal tissue specimens were immunostained with antibodies against MUC2 and MUC5AC.Six samples of normal mucosa(NM),12 samples of hyperplastic polyp(HP),15 samples of tubular adenoma with low-grade dysplasia(LGD),14 samples of tubular adenoma with high-grade dysplasia(HGD),26 samples of conventional colorectal adenocarcinoma...

  12. HLA class I gene expression on human primary tumours and autologous metastases: demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas.

    Science.gov (United States)

    López-Nevot, M. A.; Esteban, F.; Ferrón, A.; Gutiérrez, J.; Oliva, M. R.; Romero, C.; Huelin, C.; Ruiz-Cabello, F.; Garrido, F.

    1989-01-01

    The expression of HLA class I antigens was studied in 99 primary tumour (colorectal, gastric and laryngeal carcinomas) and 57 autologous metastases using immunohistological techniques and monoclonal antibodies against class I monomorphic determinants, HLA-B isotypic determinants and HLA polymorphic determinants. Fourteen per cent of colorectal, 9.6% of gastric and 20% of laryngeal carcinomas completely lacked class I molecules. Selective losses of HLA-B antigens were also detected in 8.8, 3.4 and 5.8% of these tumours respectively. Taking into account complete and selective loss of HLA-B the average alteration in the class I molecules expression totalled 21%. The comparison of class I expression between primary tumours and autologous metastases showed differences in 24% of the patients. These differences consisted mainly in a decrease of class I expression by metastases. Nevertheless, four types of divergence were detected in laryngeal carcinomas, namely: +/-, +/+, -/+, -/-. In addition, a clear correlation between degree of differentiation and class I expression was observed in laryngeal tumours. Finally, when class I gene RFLPs were compared with DNA from 15 tumours and autologous normal mucosa or peripheral lymphocytes, no differences were detected between these samples. Images Figure 1 Figure 2 PMID:2649129

  13. Role of SIRT6 in Metabolic Reprogramming During Colorectal Carcinoma

    Science.gov (United States)

    2015-09-01

    Ac Ac Ac Ac Ac Ac Ac Ac AcAcAc Colonocyte Colorectal cancer cell Lactate TCA TCA ButyrateGlucoseGlucose Glucose Pyruvate Pyruvate HDACs Butyrate HDACs...ISC expansion and the generation of potential tumor-initiating cells. 15. SUBJECT TERMS SIRT6, intestinal tumorigenesis, cancer metabolism...INTRODUCTION Colorectal carcinoma (CRC) is the third leading cause of cancer morbidity and mortality in the United States. Familial Adenomatous

  14. Assessment of spiral CT pneumocolon in preoperative colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Can-Hui Sun; Zi-Ping Li; Quan-Fei Meng; Shen-Ping Yu; Da-Sheng Xu

    2005-01-01

    AIM: To investigate the value of spiral CT pneumocolon in preoperative colorectal carcinoma.METHODS: Spiral CT pneumocolon was performed prior to surgery in 64 patients with colorectal carcinoma. Spiral CT images were compared to specimens from the resected tumor.RESULTS: Spiral CT depicted the tumor in all patients.Comparison of spiral CT and histologic results showed that the sensitivity and specificity were 95.2%, 40.9% in detection of local invasion, and 75.0%, 90.9% in detection of lymph node metastasis. Compared to the Dukes classification,the disease was correctly staged as A in 6 of 18 patients,as B in 18 of 23, as C in 10 of 15, and as D in 7 of 8. Overall,spiral CT correctly staged 64.1% of patients.CONCLUSION: Spiral CT pneumocolon may be useful in the preoperative assessment of patients with colorectal carcinoma as a means for assisting surgical planning.

  15. Expressions of MGMT and Survivin in Colorectal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    QI Xiao-li; WANG Fa-liang; BO Ai-hua; HOU Jin-chao; NIU Shu-lei

    2008-01-01

    Objective:To investigate the expressions of O6-methyguanine-DNA methytransferase(MGMT) and Survivin in colorectal carcinoma and their clinical significance.Methods:Formalin-fixed,paraffin-embedded specimens from polypus and colorectal carcinoma were examined with streptavidin-biotin peroxidase(S-P)immunohistochemical technique for the expressions of MGMT and Survivin.Results:We found that there were significant differences in MGMT and Survivin between polypus and colorectal carcinoma.Expression of MGMT was correlated with ages and lymph node metastasis while Survivin was associated with lymph node metastasis only.Meanwhile,the expression of MGMT was correlated with Survivin (P<0.01,r=0.65).But there was no significant difference between male and female and the different depth of infiltration.Conclusion:It is concluded that the abnormal expressions of MGMT and Survivin were associated with the degree of malignancy of colorectal tumor.They possibly could be useful indexes for the primary screening and prognosis of colorectal carcinoma.ExaminatiOn of them may have an important guiding significance in the chemotherapy strategy.

  16. 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

    2016-06-03

    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

  17. The study on specific umbilical blood Dc vaccine for Beige nude mice loaded human colorectal carcinoma to induce anti-tumor immunity.

    Science.gov (United States)

    Fu, Z-X; Han, J-S; Liu, F; Zhao, Z-L; Li, D-B; Shi, L; Dong, J-T; Zhou, Y; Cai, J-H

    2017-05-01

    This study is to observe the immunosuppression of CD137L transfected umbilical blood Dcs (Dendritic cell) vaccine to tumor development of SCID/ Beige nude mice. Samples of umbilical blood in the childbirth pregnant women were collected by density gradient centrifugation. Umbilical cord blood dendritic cells (Dcs) were transfected by specific CD137L via LipofectamineTM method and cells were harvested. Meanwhile, the peripheral blood of volunteers was collected to isolate Dcs, the Dcs were cultured for 5 days and hatched with SW-1116 cells antigen. The mature Dcs were harvested. The male SCID/Beige nude mice were subcutaneously injected with human SW-1116 cells in axillary to build colorectal carcinoma model as blank control (Blank). The naked peripheral blood Dc vaccine group (cPBMCs), the SW-1116 antigen-specific peripheral blood Dc vaccine group (pDcs) and the CD137L specific umbilical blood Dc vaccine group (tuDcs) were injected 24 h before tumor cells injection, respectively to recur the humanized immune reconstruction. The general life, living habits changes, tumor growing time and tumor size were observed. The nude mice were sacrificed 18 days after tumor formation. The tumor size, mice weight, in vitro tumor weight, liver weight and spleen weight of mice were recorded to evaluate the anti-tumor effect of the specific immune cells. The nude mice in pDcs group showed better general living condition, slower tumor growth, smaller tumor volume and no ulceration, necrosis, and death in nude mice. The tumor formation time in different groups was 4.71 ± 0.18 ds (blank), 7.71 ± 0.29 ds (cPBMCs), 7.86 ± 0.26 ds (pDcs) and 8.14 ± 0.69 ds (tuDcs) respectively. There were significant differences between blank and other three groups (F = 40.96, p human colon cancer in nude mice via increasing the number of immune effector cell in tumor microenvironment.

  18. CCR7和L-选择素在大肠癌组织中的表达及意义%Expression and significance of CCR7 and L-selectin in human colorectal carcinoma tissue

    Institute of Scientific and Technical Information of China (English)

    李坤; 金春亭; 张果; 赵秀芳; 白睿; 刘博

    2012-01-01

    目的 探讨CC趋化因子受体7(CCR7)和黏附分子L-选择素在大肠癌组织中的表达及二者与大肠癌淋巴转移的关系.方法 采用免疫组织化学方法检测63份大肠癌组织(大肠癌组)、44份癌旁正常组织(癌旁组)和31份转移灶组织(转移组)中CCR7和L-选择素的表达.结果 大肠癌组、转移组CCR7、L-选择素阳性率明显高于癌旁组(P<0.01);CCR7与L-选择素表达显著相关(r=0.653,P<0.01);有淋巴结转移者明显高于无转移者,P<0.05.结论 CCR7与L-选择素在大肠癌中的表达与大肠癌的发生和淋巴转移有关,二者可能共同参与了大肠癌发生及淋巴结转移过程;检测二者表达情况有助于判断大肠癌患者的预后.%Objective To investigate the expression of chemokine receptor 7 ( CCR7 ) and adhesion molecule L-selec-tin in human colorectal carcinoma, and analyze their correlation with lymph node metastasis. Methods The expression of CCR7 and L-selectin were tested by immunohistochemical method in 63 cases of colorectal carcinoma specimens ( colorectal carcinoma group) , 44 cases of normal intestinal mucosa adjacent to carcinoma (adjacent group) and 31 cases of metastatic . Tumor tissue (metastasis group). Results The positive rate of CCR7 and L-selectin expression in the colorectal carcinoma group and metastatic tumor tissue were significantly higher than that in adjacent group and metastasis group (P < 0. 01) ; There was significantly positive dependability between expression of CCR7 and L-selectin ( r =0. 653 , P < 0. 01) . The expression in the tissue with lymph node metastasis was significantly higher than that in the tissue without lymph node metastasis (P<0. 05). Conclusions The expression of CCR7 and L-selectin are closely associated with development and metastasis of the colorectal carcinoma. CCR7 and L-selectin maybe participate together in the carcinogenesis and lymph node metastasis of colorectal carcinoma. Detection of the two

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

    DEFF Research Database (Denmark)

    Lorentzen, Anders Blomkild; Mitchelmore, Cathy

    2017-01-01

    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......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...... 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...

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

    Institute of Scientific and Technical Information of China (English)

    Saber A Sakr; Moshira M Abdel-Wahed; Asmaa G Abdou; Eman K El-Adely

    2016-01-01

    Objective:To evaluate the histochemical alterations inDNA 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.

  1. 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.

  2. A cost-effectiveness analysis of colorectal screening of hereditary nonpolyposis colorectal carcinoma gene carriers

    NARCIS (Netherlands)

    Vasen, HFA; van Ballegooijen, M; Buskens, E; Kleibeuker, JK; Taal, BG; Griffioen, G; Nagengast, FM; Menko, FH; Khan, PM

    1998-01-01

    BACKGROUND. It has been estimated that the prevalence of carriers of a mutated mismatch repair (MMR) gene among the general population in Western countries is between 5 and 50 per 10,000. These carriers have a risk of >85% of developing colorectal carcinoma (CRC) and therefore need careful

  3. A cost-effectiveness analysis of colorectal screening of hereditary nonpolyposis colorectal carcinoma gene carriers

    NARCIS (Netherlands)

    Vasen, HFA; van Ballegooijen, M; Buskens, E; Kleibeuker, JK; Taal, BG; Griffioen, G; Nagengast, FM; Menko, FH; Khan, PM

    1998-01-01

    BACKGROUND. It has been estimated that the prevalence of carriers of a mutated mismatch repair (MMR) gene among the general population in Western countries is between 5 and 50 per 10,000. These carriers have a risk of >85% of developing colorectal carcinoma (CRC) and therefore need careful follow-up

  4. Ese-3在结肠癌组织中的表达及意义%Expression and clinical significance of Ese-3 in human colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    聂娜; 宋杨; 杨静; 郑蕾; 冯英明; 苏海川

    2015-01-01

    Objective:To explore the expression of Ese-3 and the relation between Ese-3 expression and clini-cal pathological features in human colorectal cancer. Methods:Using immunohistochemical technique,we detected the expression of Ese-3 in tumor tissue and para-tumor tissue in 76 patients with colorectal cancer. The correlation be-tween Ese-3 expression and clinical pathological features was analyzed. Results:We found that Ese-3 protein was expressed in the nucleus. Ese-3 protein expression in para-tumor tissue was significantly higher than tumor tissue in human colorectal cancer. Expression of Ese-3 was associated with clinical TNM stage and tumor differentiation de-gree(p﹤0. 05). Conclusion:The reduced expression of Ese-3 in tumor tissues may play an important role in the occurrence and development of human colorectal cancer.%目的:探讨上皮转录调控因子-3(epithelium-specific Ets transcription factor-3,Ese-3)在结肠癌组织中的表达及与临床病理特征之间的关系。方法:采用免疫组化SP法检测76例结肠癌组织及癌旁组织标本中Ese-3的表达,分析其表达与患者临床病理特征之间的关系。结果:Ese-3表达于细胞核中。Ese-3蛋白在癌旁正常组织中的表达明显高于相应结肠癌中的表达。在结肠癌组织中Ese-3表达与病理分期( p

  5. Towards the human colorectal cancer microbiome.

    Directory of Open Access Journals (Sweden)

    Julian R Marchesi

    Full Text Available Multiple factors drive the progression from healthy mucosa towards sporadic colorectal carcinomas and accumulating evidence associates intestinal bacteria with disease initiation and progression. Therefore, the aim of this study was to provide a first high-resolution map of colonic dysbiosis that is associated with human colorectal cancer (CRC. To this purpose, the microbiomes colonizing colon tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA sequencing. The results revealed striking differences in microbial colonization patterns between these two sites. Although inter-individual colonization in CRC patients was variable, tumors consistently formed a niche for Coriobacteria and other proposed probiotic bacterial species, while potentially pathogenic Enterobacteria were underrepresented in tumor tissue. As the intestinal microbiota is generally stable during adult life, these findings suggest that CRC-associated physiological and metabolic changes recruit tumor-foraging commensal-like bacteria. These microbes thus have an apparent competitive advantage in the tumor microenvironment and thereby seem to replace pathogenic bacteria that may be implicated in CRC etiology. This first glimpse of the CRC microbiome provides an important step towards full understanding of the dynamic interplay between intestinal microbial ecology and sporadic CRC, which may provide important leads towards novel microbiome-related diagnostic tools and therapeutic interventions.

  6. Clinicopathological significance and prognostic value of LRP16 expression in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To explore the expression of leukemia related protein 16 (LRP16) in colorectal carcinoma, and analyze its correlation with clinicopathologic features and prognosis. METHODS: Immunohistochemistry for LRP16 was performed in 201 cases of colorectal carcinoma and 60 cases of distal normal mucosa. Medical records were reviewed and clinicopathological analysis was performed. RESULTS: LRP16 expression was detected in 117 of 201 cases of the colorectal carcinoma and in 21 cases of 60 distal normal mucosa. The ...

  7. Systemic treatment of advanced colorectal carcinoma.

    NARCIS (Netherlands)

    Laarhoven, H.W.M. van; Punt, C.J.A.

    2004-01-01

    For advanced colorectal cancer (ACC), 5-fluorouracil (5-FU) based chemotherapy has been the standard for some decades. Attempts have been made to improve its results by biochemical modulation and schedule modulation of 5-FU which, in combination with leucovorin (LV), has been regarded as standard ch

  8. MICROSATELLITE ALTERATION AND ITS CHARACTERISTICS IN COLORECTAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To determine the role of microsatellite alterations incarcinogenesis of colorectal carcinoma (CRC). Methods: Alterations of 10 microsatellite loci from 5 different chromosomes were detected in 92 colorectal cancers and their paired normal mucosa by PCR, denatured polyacrylamide gel electrophoresis and silver staining. Associations of microsatellite alterations with clinopathologic parameters were statistically clarified.Results: Alterations of microsatellite were classified into microsatellite instability type I, type II and loss of heterozygosity (LOH). The carcinoma with ≥30% loci microsatellite alterations was defined as replication error(RER) positive tumors. Of 92 cases, 14 were RER+. Microsatellite alterations of P53(1) and D18S363 loci (64.29% ) was most commonly identified in the RER+ tumors. RER+ were more commonly seen in poorly differentiated carcinomas and tended to occur in mucoid carcinomas. The type of microsatellite alterations varied in different histological types of CRC. Conclusions: Microsatellite alteration is a common molecular event in CRC. Different microsatellite loci showed various biologic significance. P53(1) and D18S363 should be essentially detected loci that can show the RER status of tumors.

  9. Difluoro analogue of UCS15A triggers activation of exogenously expressed c-Src in HCT 116 human colorectal carcinoma cells.

    Science.gov (United States)

    Atatreh, Noor; Barraclough, Jane; Welman, Arkadiusz; Cawthorne, Christopher; Bryce, Richard A; Dive, Caroline; Freeman, Sally

    2007-10-01

    UCS 15A, an antibiotic produced by Streptomyces sp., has been reported to specifically disrupt SH3 domain-mediated interactions in eukaryotic cells. Interestingly, in the case of the non-receptor tyrosine kinase Src, UCS15A was effective in suppressing the SH3 domain-mediated intermolecular rather than intramolecular interactions, and thus prevented Src interactions with certain downstream effectors without affecting Src kinase activity. Here the synthesis of a novel difluoro analogue of UCS15A is described. The effects of this compound (8) on Src activity were tested in HCT 116 colorectal carcinoma cells engineered for inducible expression of c-Src. The presence of compound (8) resulted in the increased activity of the induced c-Src implicating that (8) acts as a c-Src activator in vivo. These observations are supported by computer modelling studies which suggest that the aldehyde group of (8) may covalently bind to a lysine residue in the SH2-kinase linker region situated in the proximity of the SH3 domain, which could promote a conformational change resulting in increased Src activity.

  10. Pharmacogenomics of cetuximab in metastatic colorectal carcinoma.

    Science.gov (United States)

    Silvestris, Nicola; Vincenzi, Bruno; Brunetti, Anna Elisabetta; Loupakis, Fotious; Dell'Aquila, Emanuela; Russo, Antonio; Scartozzi, Mario; Giampieri, Riccardo; Cascinu, Stefano; Lorusso, Vito; Tonini, Giuseppe; Falcone, Alfredo; Santini, Daniele

    2014-09-01

    Cetuximab is a chimeric monoclonal antibody that has revolutionized the treatment of metastatic colorectal cancer. Knowledge of the mechanisms that underlie its effectiveness, as well as the primary and secondary resistance mechanisms, have led to important developments in the understanding of cetuximab biology. In light of knowledge gained from recent trials, the efficacy of cetuximab has been clearly demonstrated to depend upon RAS mutational status, moreover cetuximab should only be used in a subset of patients who may benefit. In this article, we critically review clinical and pharmacogenetic issues of cetuximab, focusing on the cost-effectiveness involved with the use of the drug.

  11. TELOMERASE ACTIVITY IN COLORECTAL CARCINOMA AND ITS CORRELATION WITH EXPRESSION OF C-MYC

    Institute of Scientific and Technical Information of China (English)

    LIU Jian-Lun; GE Lian-ying; ZHANG Gui-nian

    2005-01-01

    Objective: To study the role of telomerase activity and c-myc in pathogenesis and progression of colorectal carcinoma,and to investigate the possible regulatory mechanism of telomerase activation. Methods: A modified telomeric repeat amplification protocol (TRAP) and immunohistochemical staining was used to detect telomerase activity and the expression of c-myc in tissue samples from colorectal carcinoma, paracarcinomatousl tissues, normal mucosa, and adenomatoid polyp.Results: The positive rates of telomerase activity and c-myc expression were 83.33% and 80.00% in colorectal carcinoma,13.33% and 23.33% in paracarcinomatousl tissues, 13.33% and 20.00% in normal mucosa, and 10.00% and 45.00% in adenomatoid polyp respectively, they were significantly higher in colorectal carcinoma than in paracarcinomatousl tissues,normal mucosa, and adenomatoid polyp (P<0.05). The rates of telomerase activity and c-myc expression were much higher in colorectal carcinoma with lymph nodes metastases than that without lymph nodes metastases. The expression of c-myc was found being significantly higher in the telomerase positive colorectal carcinoma than in the telomerase negative group(P<0.05). Conclusion: The activation of telomerase and abnormal expression of c-myc might play an important role in the process of carcinogenesis and progression of colorectal carcinoma. The over-expression of c-myc may be related to telomerase activation and up-regulation in colorectal carcinoma.

  12. Relationship of PARG with PARP, VEGF and b-FGF in Colorectal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ling Lin; Jia Li; Ya-lan Wang; Xiao Lin

    2009-01-01

    Objective: To investigate the relationship of poly(ADP-ribose)glycohydrolase(PARG) with poly (ADP-ribose) polymerase(PARP), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor(b-FGF) in colorectal carcinoma(CRC).Methods: Immunohistochemical analysis was used to detect PARG, PARP, VEGF and b-FGF in human colorectal carcinoma. Flow cytometry was used to detect PARG and PARP in murine CT26 cell line. Gallotannin (GLTN) was served as PARG inhibitor. Results: The individual positive rates of PARG, PARP, VEGF and b-FGF were 55.81%(24/43), 97.67%(42/43), 79.07%(34/43) and 81.40%(35/43), respectively, which were significantly higher than those of control group. The positive PARG was correlated to PARP(r=0.3703, P<0.05) and b-FGF (r=0.4838, P<0.05). The positive PARP was correlated to VEGF (r=0.3968, P<0.05) and b-FGF (r=0.5610, P<0.05). Both PARG and PARP were expressed in CT26 cells. The positive staining rates of PARG and PARP in GLTN-treated group were 7.3% and 52.38%, respectively. They were markedly reduced than those of control group (55.41% and 95.28%, P<0.01, n=10000).Conclusion: The data suggest that PARG expression probably plays a role for VEGF and b-FGF expression in colorectal carcinoma.

  13. Ki-67 proliferation index and clinicopathological patterns in colorectal carcinomas

    Directory of Open Access Journals (Sweden)

    Bhagya Lakshmi A

    2015-04-01

    Full Text Available Background : Tumour, Node, Metastasis (TNM staging system provides useful prognostic information in patients with colorectal carcinoma (CRC. An improved prognostication and patient survival may be achieved by employing immunohistochemistry studies with proliferation markers like Ki-67. Materials and methods: We prospectively studied 51 patients with CRC and evaluated the clinicopathological patterns of CRC and the relationship of with the clinicopathological variables Results: Their mean age was 48 (range 17-75 years; majority (64.7% were males. Rectum was the most common subsite affected (45.1%. Histopathologically most of the tumours (86.3% were usual type adenocarcinomas and were of grade 1 morphology (51%. The Ki-67 proliferation index (PI ranged from 8.4% to 84.4%. The mean PI was greater in patients aged less than or equal to 50 years than in those aged above 50 years, in males than females, in rectal cancers than colonic cancers. It was greater in mucinous carcinomas than usual type adenocarcinomas, in grade 3 tumours than lower grade tumours (grades 1 and 2 and in T4 than T3 and T2 tumours. There was a significant positive correlation between the PI values and grade of the tumour. Conclusion: We concluded that Ki-67 proliferation marker may be useful as an additional tool to assess the tumour aggressiveness with respect to certain clinicopathological parameters in colorectal carcinomas.

  14. Autophagy is upregulated during colorectal carcinogenesis, and in DNA microsatellite stable carcinomas.

    Science.gov (United States)

    Sena, Paola; Mariani, Francesco; Mancini, Stefano; Benincasa, Marta; Magnani, Giulia; Pedroni, Monica; Palumbo, Carla; Roncucci, Luca

    2015-12-01

    Cancer cells are exposed to a wide range of stress sources, such as nutrient deprivation and hypoxia, as well as cytotoxic chemotherapy and radiotherapy. Certain forms of stress can also promote survival activating the metabolic autophagy pathway in cancer cells. Autophagy is dramatically increased in cancer cells. In these conditions, it is becoming evident that autophagy protects cells, by providing an alternative energy source and by eliminating dysfunctional organelles or proteins. Its role in tumorigenesis is more controversial and both the presence and the absence of autophagy have been implicated. Autophagy is known to be associated with the poor outcome of patients with various types of cancers, and its effectiveness as a prognostic marker in colorectal cancer was demonstrated by several studies. The inhibition of autophagy may be a potential therapeutic target in colorectal cancer. In vitro experiments have shown that the inhibition of autophagy increases 5-FU-induced apoptosis. There are two trials currently investigating the addition of chloroquine to 5-FU-based chemotherapy and bevacizumab. In the present study, we evaluated the expression of LC3B-II in samples of human colorectal microadenomas (i.e., dysplastic aberrant crypt foci) and carcinomas compared to normal mucosa. Furthermore, the expression pattern of LC3B-II was assessed in carcinomas classified as DNA microsatellite stable (MSS) and unstable (MSI). Thus, immunofluorescence techniques coupled with confocal microscopy and immunoblot experiments were performed. The results clearly showed a significant increase in expression of the autophagic key factor in microadenomas and carcinomas with respect to normal mucosa. In MSS carcinomas, the level of LC3B-II expression was higher than that in the MSI carcinomas.

  15. Localization of colorectal carcinoma by rhenium-188-labeled B72.3 antibody in xenografted mice

    Energy Technology Data Exchange (ETDEWEB)

    Hosono, Masako N. [Osaka City Univ. (Japan). Medical School; Hosono, Makoto; Zamora, P.O.; Guhlke, S.; Haberberger, T.; Bender, H.; Knapp, F.F.R.; Biersack, H.J.

    1998-04-01

    In order to evaluate the feasibility of {sup 188}Re-labeled antibodies for radioimmunotargeting, monoclonal antibody B72.3, recognizing TAG-72, expressed on the surface membranes of colorectal cancer cells, was directly labeled with {sup 188}Re, obtained from a {sup 188}W/{sup 188}Re generator, using stannous tartrate and compared with {sup 125}I-labeled B72.3. As a control, a human IgG was also radiolabeled with {sup 188}Re and {sup 125}I. Prepared antibodies for {sup 188}Re labeling could be stored as kits. Biodistribution was determined in nude mice inoculated with human colorectal carcinoma LoVo. Labeling efficiency and immunoreactivity of {sup 188}Re-B72.3 were 80.3% and 64.7%, respectively. {sup 188}Re-B72.3 localized specifically in the LoVo tumors. Although the absolute tumor accumulation level of {sup 188}Re-B72.3 was lower than {sup 125}I-B72.3, {sup 188}Re-B72.3 demonstrated higher tumor-to-blood contrast than the {sup 125}I-labeled counterpart, 2.04{+-}0.44 vs. 1.05{+-}0.28 at 96 hours, because of fast clearance from the blood. {sup 188}Re-B72.3 seemed efficient for the imaging and therapy of colorectal carcinoma. (author)

  16. 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.

  17. [The biological behavior of colorectal carcinoma in young patients].

    Science.gov (United States)

    Valdovinos Díaz, M A; Guerrero, C; Nava, A A; Jacobo, J; Villalobos, J J

    1991-01-01

    Patients of the Instituto Nacional de la Nutrición Salvador Zubirán under 40 years of age with colorectal carcinoma were compared with similar patients above 40 in a retrospective and longitudinal study. Patterns of presentation, stage at diagnosis, degree of tumor differentiation and survival were analyzed. Abdominal pain, rectal bleeding and weight loss were the most frequent clinical manifestations in both groups. Constipation was more common in the young adults (60.5% vs 34.2%; p less than 0.05). In both groups, rectosigmoid was the most frequent location of the neoplasm. Cecal carcinoma was found in 2.6% of patients under 40 years and in 11.8% (p less than 0.05) in older patients. There was a higher frequency of mucinous tumors in the young patients (26% vs 13%; p = NS). Colon cancer in both groups were in advanced stage at presentation. The survival rate for young adults was 30%, and 21% for the other group (p = NS). The degree of tumor differentiation did not affect survival in both groups. Dukes stage was the only prognostic factor identified. The need for early recognition of colorectal cancer in young adults is emphasized by the greater incidence of advanced disease and poor prognosis.

  18. Clinical, pathologic, and molecular features of early-onset colorectal carcinoma.

    Science.gov (United States)

    Yantiss, Rhonda K; Goodarzi, Mahmoud; Zhou, Xi K; Rennert, Hanna; Pirog, Edyta C; Banner, Barbara F; Chen, Yao-Tseng

    2009-04-01

    The incidence of colorectal carcinoma has increased among patients or =40 years of age served as controls. Cases were evaluated for clinical risk factors of malignancy and pathologic features predictive of outcome. The tumors were immunohistochemically stained for O6-methylguanine methyltransferase, MLH-1, MSH-2, MSH-6, beta-catenin, chemokine (C-X-C motif) receptor 4, epidermal growth factor receptor, TP53, p16, survivin, and alpha-methylacyl-CoA racemase; assessed for microsatellite instability and mutations in beta-catenin, APC, EGFR, PIK3CA, KRAS, and BRAF; evaluated for micro-RNA expression (miR-21, miR-20a, miR-183, miR-192, miR-145, miR-106a, miR-181b, and miR-203); and examined for evidence of human papillomavirus infection. One study patient each had ulcerative colitis and hereditary nonpolyposis colorectal cancer. Ninety-two percent of tumors from young patients occurred in the distal colon (P=0.006), particularly the rectum (58%, P=0.02), and 75% were stage III or IV. Tumors from young patients showed more frequent lymphovascular (81%, P=0.03) and/or venous (48%, P=0.003) invasion, an infiltrative growth pattern (81%, P=0.03), and alpha-methylacyl-CoA racemase expression (83%, P=0.02) compared with controls. Carcinomas in this group showed significantly increased expression of miR-21, miR-20a, miR-145, miR-181b, and miR-203 (P< or =0.005 for all comparisons with controls). These results indicate that early-onset carcinomas commonly show pathologic features associated with aggressive behavior. Posttranslational regulation of mRNA and subsequent protein expression may be particularly important to the development of colorectal carcinomas in young patients.

  19. RNAi抑制人大肠癌LOVO细胞Bmi-1基因的表达%Effects of RNAi on expression of Bmi-1 gene in human colorectal carcinoma LOVO cells

    Institute of Scientific and Technical Information of China (English)

    卢敏; 沙卫红; 王启仪

    2011-01-01

    目的 探讨RNA干扰(RNAi)技术沉默Bmi-1基因表达对人大肠癌细胞株LOVO增殖和侵袭力的影响及机制.方法 将化学法合成的针对Bmi-1 mRNA不同位点设计的3对siRNA序列(siR-NA1~3)和1对带有荧光标记的FAM-siRNA(siRNA4)转染至人大肠癌LOVO细胞,荧光显微镜下观察siRNA的转染效率,QRT-PCR检测Bmi-1 mRNA表达抑制作用,Western Blot检测Bmi-1蛋白表达变化,MTT法检测LOVO细胞体外增殖变化,小室侵袭实验检测LOVO细胞侵袭能力.结果 利用荧光标记的Oligo观察到siRNA转染效率达70%.siRNA1对mRNA表达抑制率最高,从而筛选出沉默效应最强的siRNA序列为siRNA1.siRNA1转染组LOVO细胞Bmi-1蛋白表达,增殖及侵袭力明显低于阴性对照组和空白对照组(P<0.05).结论 化学合成的靶向Bmi-1 siRNA转染人大肠癌LOVO细胞能有效抑制Bmi-1的mRNA和蛋白质表达水平,Bmi-1基因的RNA干扰可有效抑制人大肠癌LOVO细胞的增殖和侵袭能力.%Objective To investigate the mechanism and effect of small interfering RNA (siRNA) on Bmi-1 in the human colorectal carcinoma LOVO cells. Methods Three si RNA sequences targeting Bmi-1 (siRNAI, siRNA2, siRNA3), a fluorescein-labeled double-stranded RNA (dsRNA) oligomer (siRNA4), and the negative control were chemically synthesized. All siRNA sequences were transinfected into LOVO cells. Inverse microscopy was used to observe the efficacy of transinfecion. Bmi-1 mRNA expression and protein expression were detected by real time quantitative PCR (QRT-PCR) and Western blot, respectively. The proliferation and invasion of LOVO cells were detected by MTT and transwell invasion assay, respectively. Results The efficacy of transfection was 70%. The Bmi-1 mRNA expression inhibition rate of siRNAI was the most effective, and therefore was selected to interfere with the expression of Bmi-1 gene. The Bmi-1 protein expression and cell proliferation and invasion were significantly fewer than that in the

  20. Colorectal carcinogenesis: Review of human and experimental animal studies

    Directory of Open Access Journals (Sweden)

    Tanaka Takuji

    2009-01-01

    Full Text Available This review gives a comprehensive overview of cancer development and links it to the current understanding of tumorigenesis and malignant progression in colorectal cancer. The focus is on human and murine colorectal carcinogenesis and the histogenesis of this malignant disorder. A summary of a model of colitis-associated colon tumorigenesis (an AOM/DSS model will also be presented. The earliest phases of colorectal oncogenesis occur in the normal mucosa, with a disorder of cell replication. The large majority of colorectal malignancies develop from an adenomatous polyp (adenoma. These can be defined as well-demarcated masses of epithelial dysplasia, with uncontrolled crypt cell proliferation. When neoplastic cells pass through the muscularis mucosa and infiltrate the submucosa, they are malignant. Carcinomas usually originate from pre-existing adenomas, but this does not imply that all polyps undergo malignant changes and does not exclude de novo oncogenesis. Besides adenomas, there are other types of pre-neoplasia, which include hyperplastic polyps, serrated adenomas, flat adenomas and dysplasia that occurs in the inflamed colon in associated with inflammatory bowel disease. Colorectal neoplasms cover a wide range of pre-malignant and malignant lesions, many of which can easily be removed during endoscopy if they are small. Colorectal neoplasms and/or pre-neoplasms can be prevented by interfering with the various steps of oncogenesis, which begins with uncontrolled epithelial cell replication, continues with the formation of adenomas and eventually evolves into malignancy. The knowledge described herein will help to reduce and prevent this malignancy, which is one of the most frequent neoplasms in some Western and developed countries.

  1. 结直肠癌与人乳头状瘤病毒16型感染的相关性研究%Correlation between type 16 human papillomavirus infection and colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    秦双; 董良鹏; 王雷

    2012-01-01

    OBJECTIVE To investigate the relationship between type 15 human papillomavirus infection and the development of colorectal carcinoma. METHODS A total of 75 colorectal carcinoma patients were enrolled in our hospital from Jul 2007 to Mar 2011, and 50 healthy persons were also enrolled. The colorectal tissues of both groups were analyzed by immunohistochemistry. All patients were divided into the poorly differentiated group (21 cases), the oderately differentiated group (25 cases) and highly differentiated group (29 cases) according to their pathological findings. All patients were also divided into 27 cases in the dukes A stage.31 cases in the dukes stage B and 17 cases in the dukes C+D stage according to dukes stages. The type 16 human papillomavirus infections of the three groups were compared. RESULTS There were 51 colorectal carcinoma patients who were infected with type 16 human papillomavirus with the positive rate of 68. 0% i there were 6 positive healthy cases with the positive rate of 12. 0% , the difference between the two groups was statistically significant (P<0. 05) , the positive rates of the poorly differentiated group, the moderately differentiated group and the highly differentiated group were 66. 7% ,68. 0% and 65. 5%, respectively, as compared with the three groups , the difference was not statistically significant; the positive rates of the stage A, stage B and stage C+D were 55. 6%, 70. 9%, and 82.3%, respectively, the difference among the three groups was statistically significant (P<0. 05 ). CONCLUSION Type 16 human papillomavirus infection is closely related to the colorectal carcinoma as well its clinical stages, but its malignancy is not significantly correlated with human papillomavirus infection.%目的 探讨结直肠癌与人乳头状瘤病毒(HPV)16型感染的相关性.方法 入选2007年6月- 2011年3月在医院住院治疗的结直肠癌患者75例,同时收集50名健康人群资料,采用免疫组化的方法检测病理

  2. The expression of glucose regulated protein—94 in colorectal carcinoma cells treated by sodium butyrate

    Institute of Scientific and Technical Information of China (English)

    WUYIDI; JINDANSONG

    2000-01-01

    The expression of glucose regulated protein 94 (GPR94) during the treatment of human colorectal carcinoma cell lineClone A cells with codium butyrate was studied.Dodium butyrate (SB) can cause functional and morphological effects on Clone A cells including growth arrest at G0/G1 stage and cell differentiation as observed by morphological changes,MTT and flow cytometry assays,as well as reduced Grp94 gene expression as shown by Northern blot and Western blot assays.The possible mechanism of the correlation between Grp94 gene expression and tumor growth inhibition and cell differentiation is briefly discussed.

  3. Comparative ultrastructural study of endoplasmic reticulum in colorectal carcinoma cell lines with different degrees of differentiation

    Institute of Scientific and Technical Information of China (English)

    Shu Feng; Jin Dan Song

    2000-01-01

    The endoplasmic reticulum (ER) consists of a complex system of tubules, lamellae, and flattened vesicles, and has a variety of morphologies in different cells. It is believed to play a central role in the biosynthesis of cholesterol, phospholipids, steroids, prostaglandins, membrane and secretory proteins[1]. Cancer cells have different functions and ultrastmcture from their original cells[2-4]. The studies on ER membrane system of cancer cells are of great significance in understanding their malignant behavior. In the present work, the ultrastructural characteristics of ER in human colorectal carcinoma cell lines with different differentiation degrees were investigated.

  4. The expression of glucose regulated protein-94 in colorectal carcinoma cells treated by sodium butyrate

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The expression of glucose regulated protein 94 (GRP94)during the treatment of human colorectal carcinoma cell lineClone A cells with sodium butyrate was studied. Sodium butyrate (SB) can cause functional and morphological effects on Clone A cells including growth arrest at G0/G1 stage and cell differentiation as observed by morphological changes, MTT and flow cytometry assays, as well as reduced Grp94 gene expression as shown by Northern blot and Western blot assays. The possible mechanism of the correlation between Grp94 gene expression and tumor growth inhibition and cell differentiation is briefly discussed.

  5. Silibinin Suppresses Growth of Human Colorectal Carcinoma SW480 Cells in Culture and Xenograft through Down-regulation of β-Catenin-Dependent Signaling

    Directory of Open Access Journals (Sweden)

    Manjinder Kaur

    2010-05-01

    Full Text Available Mutations in APC/β-catenin resulting in an aberrant activation of Wnt/β-catenin pathway are common in colorectal cancer (CRC, suggesting that targeting the β-catenin pathway with chemopreventive/anticancer agents could be a potential translational approach to control CRC. Using human CRC cell lines harboring mutant (SW480 versus wildtype (HCT116 APC gene and alteration in β-catenin pathway, herein we performed both in vitro and in vivo studies to examine for the first time whether silibinin targets β-catenin pathway in its efficacy against CRC. Silibinin treatment inhibited cell growth, induced cell death, and decreased nuclear and cytoplasmic levels of β-catenin in SW480 but not in HCT116 cells, suggesting its selective effect on the β-catenin pathway and associated biologic responses. Other studies, therefore, were performed only in SW480 cells where silibinin significantly decreased β-catenin-dependent T-cell factor-4 (TCF-4 transcriptional activity and protein expression of β-catenin target genes such as c-Myc and cyclin D1. Silibinin also decreased cyclin-dependent kinase 8 (CDK8, a CRC oncoprotein that positively regulates β-catenin activity, and cyclin C expression. In a SW480 tumor xenograft study, 100- and 200-mg/kg doses of silibinin feeding for 6 weeks inhibited tumor growth by 26% to 46% (P < .001. Analyses of xenografts showed that similar to cell culture findings, silibinin decreases proliferation and expression of β-catenin, cyclin D1, c-Myc, and CDK8 but induces apoptosis in vivo. Together, these findings suggest that silibinin inhibits the growth of SW480 tumors carrying the mutant APC gene by down-regulating CDK8 and β-catenin signaling and, therefore, could be an effective agent against CRC.

  6. The plant alkaloid and anti-leukemia drug homoharringtonine sensitizes resistant human colorectal carcinoma cells to TRAIL-induced apoptosis via multiple mechanisms.

    Science.gov (United States)

    Beranova, Lenka; Pombinho, Antonio R; Spegarova, Jarmila; Koc, Michal; Klanova, Magdalena; Molinsky, Jan; Klener, Pavel; Bartunek, Petr; Andera, Ladislav

    2013-06-01

    TNF-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic ligand from the TNF-alpha family that is under consideration, along with agonistic anti-TRAIL receptor antibodies, as a potential anti-tumor agent. However, most primary human tumors are resistant to monotherapy with TRAIL apoptogens, and thus the potential applicability of TRAIL in anti-tumor therapy ultimately depends on its rational combination with drugs targeting these resistances. In our high-throughput screening for novel agents/drugs that could sensitize TRAIL-resistant colorectal cancer cells to TRAIL-induced apoptosis, we found homoharringtonine (HHT), a cephalotaxus alkaloid and tested anti-leukemia drug, to be a very effective, low nanomolar enhancer of TRAIL-mediated apoptosis/growth suppression of these resistant cells. Co-treatment of TRAIL-resistant RKO or HT-29 cells with HHT and TRAIL led to the effective induction of apoptosis and the complete elimination of the treated cells. HHT suppressed the expression of the anti-apoptotic proteins Mcl-1 and cFLIP and enhanced the TRAIL-triggered activation of JNK and p38 kinases. The shRNA-mediated down-regulation of cFLIP or Mcl-1 in HT-29 or RKO cells variably enhanced their TRAIL-induced apoptosis but it did not markedly sensitize them to TRAIL-mediated growth suppression. However, with the notable exception of RKO/sh cFLIP cells, the downregulation of cFLIP or Mcl-1 significantly lowered the effective concentration of HHT in HHT + TRAIL co-treatment. Combined HHT + TRAIL therapy also led to the strong suppression of HT-29 tumors implanted into immunodeficient mice. Thus, HHT represents a very efficient enhancer of TRAIL-induced apoptosis with potential application in TRAIL-based, anti-cancer combination therapy.

  7. Treatment with capecitabine + bevacizumab following induction treatment with FOLFIRI + bevacizumab in metastatic colorectal carcinoma

    Science.gov (United States)

    Tatlı, Ali Murat; Coşkun, Hasan Şenol; Uysal, Mükremin; Arslan, Deniz; Sezgin Göksu, Sema; Güenay Gündüz, Şeyda; Çakal, Selda; Bozcuk, Hakan Şat; Savaş, Burhan

    2014-01-01

    Bevacizumab is a humanized monoclonal antibody that inhibits vascular endothelial growth factor, and it has been found to increase both progression-free survival and overall survival when it is combined with chemotherapeutic agents in the first-line and subsequent treatment of metastatic colorectal carcinoma. The objective of this study was to show the efficacy of maintenance treatment with capecitabine plus bevacizumab in patients with metastatic colorectal cancer who responded to treatment with FOLFIRI plus bevacizumab. The study included patients with metastatic colorectal cancer who received FOLFIRI plus bevacizumab as a first-line treatment. Patients who had objective response with FOLFIRI plus bevacizumab treatment after an average period of 6 months received a maintenance treatment with capecitabine plus bevacizumab (capecitabine 2 x 1000 mg/m2, 1 - 14 days, every 21 days, bevacizumab 7.5 mg/m2, every 21 days) until disease progression or toxicity. The time to progression on bevacizumab treatment was evaluated. A total of 29 patients (15 male, 14 female) were included. The mean age was 62 years. The mean number of cycles for maintenance treatment with capecitabine plus bevacizumab was 12. The median PFS was 16 ± 3 months, and OS was 42 ± 11 months. PFS and OS were remarkably higher in patients with a complete or near complete response to induction treatment. Fourteen patients (48%) experienced hand-foot syndrome associated with capecitabine plus bevacizumab treatment, without any severe toxicity. Inselected patients with metastatic colorectal carcinoma who had a remarkable objective response to FOLFIRI plus bevacizumab treatment, a maintenance treatment with capecitabine plus bevacizumab following FOLFIRI plus bevacizumab until disease progression may be a suitable, effective and tolerable regimen, which requires further studies. PMID:25232406

  8. Expressing patterns of p16 and CDK4 correlated to prognosis in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Po Zhao; Ying-Chuan Hu; Ian C. Talbot

    2003-01-01

    AIM: To describe the correlation between innunostaining patterns of p16 and CDK4 and prognosis in colorectal carcinoma.METHODS: Paraffin sections of 74 cases of colorectal carcinoma were analysed immunohistochemically for expression of p16 and CDK4 proteins.RESULTS: Most carcinomas showed stronger p16 and CDK4immunostaining in the cytoplasm than the adenomas or the adjacent normal mucosa. Strong immunostaining of p16 was a predictor for better prognosis whereas strong cytoplasmic immunostaining of CDK4 was a predictor for poor prognosis.Both p16 and CDK4 immunostainings were correlated with histological grade or Dukes' stage.CONCLUSION: These results support the experimental evidence that interaction of expression of p16 and CDK4may play an important role in the Rb/p16 pathway, and the expression paterns of CDK4 and p16 may be imperative in the development of colorectal carcinoma, thus becoming a new prognostic marker in colorectal cancer.

  9. Ophthalmoscopy for congenital hypertrophy of the retinal pigment epithelium (CHRPE) in patients with sporadic colorectal carcinoma

    DEFF Research Database (Denmark)

    Hartvigsen, A; Myrhøj, T; Bülow, Steffen

    1995-01-01

    In order to investigate the frequency of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in sporadic colorectal cancer, ophthalmoscopy was carried out in 34 patients with colorectal carcinoma without known familial disposition. CHRPE is one of the most frequent extracolonic...

  10. Ophthalmoscopy for congenital hypertrophy of the retinal pigment epithelium (CHRPE) in patients with sporadic colorectal carcinoma

    DEFF Research Database (Denmark)

    Hartvigsen, A; Myrhøj, T; Bülow, Steffen

    1995-01-01

    In order to investigate the frequency of congenital hypertrophy of the retinal pigment epithelium (CHRPE) in sporadic colorectal cancer, ophthalmoscopy was carried out in 34 patients with colorectal carcinoma without known familial disposition. CHRPE is one of the most frequent extracolonic...

  11. Colorectal carcinomas with KRAS mutation are associated with distinctive morphological and molecular features.

    Science.gov (United States)

    Rosty, Christophe; Young, Joanne P; Walsh, Michael D; Clendenning, Mark; Walters, Rhiannon J; Pearson, Sally; Pavluk, Erika; Nagler, Belinda; Pakenas, David; Jass, Jeremy R; Jenkins, Mark A; Win, Aung Ko; Southey, Melissa C; Parry, Susan; Hopper, John L; Giles, Graham G; Williamson, Elizabeth; English, Dallas R; Buchanan, Daniel D

    2013-06-01

    KRAS-mutated carcinomas comprise 35-40% of all colorectal carcinomas but little is known about their characteristics. The aim of this study was to examine the pathological and molecular features of KRAS-mutated colorectal carcinomas and to compare them with other carcinoma subgroups. KRAS mutation testing was performed in 776 incident tumors from the Melbourne Collaborative Cohort Study. O(6)-methylguanine DNA methyltransferase (MGMT) status was assessed using both immunohistochemistry and MethyLight techniques. Microsatellite instability (MSI) phenotype and BRAF V600E mutation status were derived from earlier studies. Mutation in KRAS codon 12 or codon 13 was present in 28% of colorectal carcinomas. Compared with KRAS wild-type carcinomas, KRAS-mutated carcinomas were more frequently observed in contiguity with a residual polyp (38 vs 21%; Pcarcinomas showed more frequent location in the proximal colon (41 vs 27%; P=0.001), mucinous differentiation (46 vs 25%; Pcarcinomas were distributed in a bimodal pattern along the proximal-distal axis of the colorectum. Compared with male subjects, female subjects were more likely to have KRAS-mutated carcinoma in the transverse colon and descending colon (39 vs 15%; P=0.02). No difference in overall survival was observed in patients according to their tumor KRAS mutation status. In summary, KRAS-mutated carcinomas frequently develop in contiguity with a residual polyp and show molecular features distinct from other colorectal carcinomas, in particular from tumors with neither BRAF nor KRAS mutation.

  12. 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.

  13. KRAS gene mutations are more common in colorectal villous adenomas and in situ carcinomas than in carcinomas

    Science.gov (United States)

    Zauber, Peter; Marotta, Stephen; Sabbath-Solitare, Marlene

    2013-01-01

    We have evaluated the frequency of KRAS gene mutations during the critical transition from villous adenoma to colorectal carcinoma to assess whether the adenomas contain a KRAS mutation more frequently than carcinomas. We analyzed sporadic villous and tubulovillous adenomas, in situ carcinomas, and primary colorectal carcinomas from multiple patients. The cancers were further evaluated for mucinous status and microsatellite instability. Standard PCR molecular techniques were used for KRAS and microsatellite analyses. A KRAS mutation was found in 61.9% of 134 adenomas, 67.8% of 84 in situ carcinomas, and just 31.6% of 171 carcinomas. Our study clearly demonstrates that tubulovillous and villous adenomas, as well as both the benign and malignant parts of in situ carcinomas, are statistically more likely to contain a somatic KRAS gene mutation than colorectal carcinomas. This difference is confined to the non-mucinous and the microsatellite stable tumors. Our data support the possibility that non-mucinous and microsatellite stable carcinomas with wild-type KRAS gene may have had a mutation in the KRAS gene during their earlier stages, with the mutation lost during further growth. PMID:23565319

  14. Resection of the Liver for Colorectal Carcinoma Metastases

    Science.gov (United States)

    Hughes, Kevin S.; Rosenstein, Rebecca B.; Songhorabodi, Sate; Adson, Martin A.; Ilstrup, Duane M.; Fortner, Joseph G.; Maclean, Barbara J.; Foster, James H.; Daly, John M.; Fitzherbert, Diane; Sugarbaker, Paul H.; Iwatsuki, Shunzaboro; Starzl, Thomas; Ramming, Kenneth P.; Longmire, William P.; O’Toole, Kathy; Petrelli, Nicholas J.; Herrera, Lemuel; Cady, Blake; McDermott, William; Nims, Thomas; Enker, Warren E.; Coppa, Gene F.; Blumgart, Leslie H.; Bradpiece, Howard; Urist, Marshall; Aldrete, Joaquin S.; Schlag, Peter; Hohenberger, Peter; Steele, Glenn; Hodgson, W. John; Hardy, Thomas G.; Harbora, Denise; McPherson, T. Alexander; Lim, Christoper; Dillon, Daniel; Happ, Richard; Ripepi, Phillip; Villella, Edward; Smith, William; Rossi, Ricardo L.; Remine, Stephen G.; Oster, Mary; Connolly, David P.; Abrams, Jerome; Al-Jurf, Adel; Hobbs, K.E.F.; Li, Michael K. W.; Howard, Ted; Lee, Emonuel

    2010-01-01

    In this review of a collected series of patients undergoing hepatic resection for colorectal metastases, 100 patients were found to have survived greater than five years from the time of resection. Of these 100 long-term survivors, 71 remain disease-free through the last follow-up, 19 recurred prior to five years, and ten recurred after five years. Patient characteristics that may have contributed to survival were examined. Procedures performed included five trisegmentectomies, 32 lobectomies, 16 left lateral segmentectomies, and 45 wedge resections. The margin of resection was recorded in 27 patients, one of whom had a positive margin, nine of whom had a less than or equal to l-cm margin, and 17 of whom had a greater than 1-cm margin. Eighty-one patients had a solitary metastasis to the liver, 11 patients had two metastases, one patient had three metastases, and four patients had four metastases. Thirty patients had Stage C primary carcinoma, 40 had Stage B primary carcinoma, and one had Stage A primary carcinoma. The disease-free interval from the time of colon resection to the time of liver resection was less than one year in 65 patients, and greater than one year in 34 patients. Three patients had bilobar metastases. Four of the patients had extrahepatic disease resected simultaneously with the liver resection. Though several contraindications to hepatic resection have been proposed in the past, five-year survival has been found in patients with extrahepatic disease resected simultaneously, patients with bilobar metastases, patients with multiple metastases, and patients with positive margins. Five-year disease-free survivors are also present in each of these subsets. It is concluded that five-year survival is possible in the presence of reported contraindications to resection, and therefore that the decision to resect the liver must be individualized. PMID:3366020

  15. EXPRESSION OF DPC4 PROTEIN IN COLORECTAL CARCINOMA IN DIFFERENT STAGES

    Institute of Scientific and Technical Information of China (English)

    唐朝晖; 邹声泉; 郝友华; 杨想平; 陈启奇; 裘法祖

    2003-01-01

    Objective. To determine whether the non-expression of DPC4 protein only occurs late in the devel-opment of colorectal carcinoma. Methods. In this study, we examined the expression of DPC4 protein in formalin-fixed archival specimens from 102 colorectal neoplasm with immunohistochemical analysis. Those specimens were classified into 5 stages: stage Ⅰ (adenoma, 36 cases); stage Ⅱ (intramucosal carcinoma, 8 cases); stage Ⅲ (primary invasive carcinoma without infiltration of the lymph nodes, 11 cases); stage Ⅳ ( primary invasive carcinoma with infiltration of the lymph nodes, 25 cases); and stage Ⅴ ( carcinoma metastasized to distant tissue, 22 cases). Results. The frequency of non-expression of DPC4 proteins were 5.5% (2/36) in stage Ⅰ, 12.5%(1/8) in stage Ⅱ; 9%(1/11) in stage Ⅲ; 36%(9/25) in stage Ⅳ; 32%(7/22) in stage Ⅴ. The frequency of negative expression of DPC4 protein were analyzed by X2 test for stage Ⅱ and Ⅲ versus stage Ⅳ and Ⅴ and there was statistically significant difference (P<0.01). At same time, there was statistically significant difference (P<0.01) for adenoma (stage Ⅰ ) versus carcinoma ( stages Ⅱ~Ⅴ). Conclusions. The frequency of non-expression of DPC4 protein increases as the stage of colorectal carcinoma advances and the non-expression of DPC4 protein is likely to be a late event in the sequential pathogenesis of colorectal carcinoma. The non-expression DPC4 protein in colorectal neoplasm may suggest its malignant characteristic, which will help us to increase the insight on colorectal carcinoma.

  16. Expression of the Intestinal Biomarkers Guanylyl Cyclase C and CDX2 in Poorly Differentiated Colorectal Carcinomas

    Science.gov (United States)

    Winn, Brody; Tavares, Rosemarie; Matoso, Andres; Noble, Lelia; Fanion, Jacqueline; Waldman, Scott A.; Resnick, Murray B.

    2009-01-01

    Guanylyl cyclase C a receptor for bacterial diarrheagenic enterotoxins is expressed selectively by intestinal epithelium and is an endogenous downstream target of CDX2. The expression of Guanylyl cyclase C is preserved throughout the adenoma/carcinoma sequence in the colorectum. Detection of Guanylyl cyclase C expression by RT-PCR is currently being validated as a technique to identify occult lymph node metastases in patients with colorectal cancer and for circulating cells in the blood for postoperative surveillance. Although Guanylyl cyclase C is widely expressed by well differentiated colorectal cancer, its expression in poorly differentiated colorectal cancer has not been evaluated. A tissue microarray was created from 69 archival specimens including 44 poorly differentiated, 15 undifferentiated or medullary and 10 signet ring cell colorectal carcinomas. Matched normal colonic mucosa was used as a positive control. Immunohistochemical staining for Guanylyl cyclase C and CDX2 was evaluated as positive or negative based on at least a 10% extent of staining. Out of the 69 tumor samples 75%, 47%, and 90% of the poorly differentiated, medullary and signet ring cell tumors were positive for Guanylyl cyclase C and 75%, 40% and 90% of these subsets were positive for CDX2 respectively. There was excellent correlation between Guanylyl cyclase C and CDX2 expression on a case per case basis (p<0.0001). There was also a statistically significant difference in the GCC staining pattern between MC and PDC (p=0.05). Immunopositivity for Guanylyl cyclase C was greater than 95% in a separately stained microarray series of well/moderately differentiated colorectal carcinomas. In conclusion, Guanylyl cyclase C expression is lost in a quarter of poorly differentiated and half of undifferentiated colorectal carcinomas. Therefore the utility of Guanylyl cyclase C expression as a diagnostic marker for colorectal carcinoma may be questionable in poorly differentiated colorectal

  17. Tumor angiogenesis and dynamic CT in colorectal carcinoma: Radiologic-pathologic correlation

    Institute of Scientific and Technical Information of China (English)

    Zi-Ping Li; Quan-Fei Meng; Can-Hui Sun; Da-Sheng Xu; Miao Fan; Xu-Feng Yang; Dong-Ying Chen

    2005-01-01

    AIM: To investigate the correlation between microvessel density and spiral CT perfusion imaging in colorectal carcinoma.METHODS: Thirty-seven patients, with histologically proven colorectal carcinoma, underwent water enema spiral CT scan. The largest axial surface of the primary tumor was searched on unenhanced spiral CT images. At this level, the enhanced dynamic scan series was acquired.Time-density curves (TDC) were created from the region of interest drawn over the tumor, target artery by Toshiba Xpress/SX spiral CT with perfusion functional software.Then the perfusion was calculated. Microvessel density(MVD) was evaluated using immunohistochemical staining of surgical specimens with anti-CD34, and then MVD was correlated with perfusion.RESULTS: MVD of colorectal carcinomas was 33.11-173.44,mean 87.28, and perfusion was 15.60-64.80 mL/min/100 g, mean 39.74 mL/min/100 g. MVD and perfusionwere not associated with invasive depth, metastasis and disease stage, and they all decreased with increasing Dukes' stage, but no significant correlation was found between them (r= 0.L8, P = 0.29).CONCLUSION: There is no significant correlation between MVD and perfusion. Neovascularizaton and perfusion are highly presented in early colorectal carcinoma.CT perfusion imaging may be more suited for assessing tumorigenesis in colorectal carcinoma than histological MVD technique.

  18. Clinical features of Bacteroides bacteremia and their association with colorectal carcinoma.

    Science.gov (United States)

    Yoshino, Y; Kitazawa, T; Ikeda, M; Tatsuno, K; Yanagimoto, S; Okugawa, S; Ota, Y; Yotsuyanagi, H

    2012-02-01

    We investigated the clinical features of Bacteroides bacteremia for 5 years to determine the risk factors for mortality and to ascertain whether bacteremia due to Bacteroides spp. is associated with colorectal carcinoma. This study comprised a review of all patients with Bacteroides bacteremia at a teaching hospital in Tokyo from April 2003 to March 2008. We also conducted a case-control study between Bacteroides bacteremia and bacteremia due to other pathogens. During the study period, 25 cases of bacteremia were due to Bacteroides spp. Bacteroides bacteremia was associated with a high mortality rate (24%). Malignancy (76%) was the major comorbidity, followed by a history of surgery (40%). Colorectal carcinoma was the most frequent (n = 8, 32%) of the comorbid malignancies and was recognized as the primary infection site in six cases. Prevalence of colorectal carcinoma as comorbidity was significantly higher in Bacteroides bacteremia than in other bacteremia. In the Bacteroides bacteremia cases of this study, colorectal carcinoma was the major comorbidity and primary infection site. Colorectal carcinoma screening in Bacteroides bacteremia patients is potentially an important diagnostic marker for the early detection of this infection in the future.

  19. [The impact of the consumption of vegetables, fruits, coffee and tea on the development of colorectal carcinoma].

    Science.gov (United States)

    Marciniak, Kuba; Kiedrowski, Mirosław; Gajewska, Danuta; Deptała, Andrzej; Włodarek, Dariusz

    2016-10-19

    The development of colorectal carcinoma is a multistep process of accumulation of mutations and epigenetic changes associated with DNA repair, proliferation, apoptosis, intra- and extracellular signaling, adhesion and other physiological functions of cells and tissues. A long period of development, high colorectal carcinoma-related mortality as well as significant social and economic costs due to this condition are prerequisites for seeking efficient methods of cancer prevention, including nutritional approach. A number of bioactive components of food is extensively tested for antitumor activity, however limited number of reliable studies on humans impedes the formulation of unequivocal nutritional recommendations. Plant products represent a rich source of numerous phytochemicals endowed with anticancer potential due to, first of all, their free radical scavenger activity. The purpose of this paper was to present the relationship between consumption of selected foods reach in numerous bioactive compounds with proven or putative anticancer activity - vegetables, fruits, coffee and tea - and the development of colorectal carcinoma, based on selected studies. A number of controversies related to the anti-tumor potential of the above ingredients was also discussed.

  20. Augmented pentose phosphate pathway plays critical roles in colorectal carcinomas.

    Science.gov (United States)

    Shibuya, Norisuke; Inoue, Ken-ichi; Tanaka, Genki; Akimoto, Kazumi; Kubota, Keiichi

    2015-01-01

    Glycolysis and the pentose phosphate pathway (PPP) are preferentially activated in cancer cells. Accumulating evidence indicated the significance of the altered glucose metabolism in cancer, but the implication for oncotherapy remains unclear. Here we report that the synthesis of glycolytic and PPP enzymes is almost ubiquitously augmented in colorectal carcinoma (CRC) specimens. The mammalian target of rapamycin (mTOR) inhibitor INK128 (300 nM) and phytochemical Avemar (1 mg/ml) inhibited the synthesis of PPP enzymes in CRC cell lines. INK128 (150-600 nM) and resveratrol (75-300 μM) inhibited aerobic glycolysis in the cell lines. INK128 (300 nM) and Avemar (1 mg/ml) decreased the NADPH/NADP(+) ratio as well as the GSH/GSSG ratio in the cell lines. Finally, per os administration of INK128 (0.8 mg/kg) or Avemar (1 g/kg) suppressed tumor growth and delayed tumor formation by transplantable CRC specimens derived from patients. Taken together, pharmacological inhibition of the mTOR-PPP axis is a promising therapeutic strategy against CRCs.

  1. Chemokine expression in hepatocellular carcinoma versus colorectal liver metastases

    Institute of Scientific and Technical Information of China (English)

    Claudia Rubie; Vilma Oliveira Frick; Mathias Wagner; Christina Weber; Bianca Kruse; Katja Kempf; Jochen K(o)nig; Bettina Rau; Martin Schilling

    2006-01-01

    AIM: To evaluate and compare the expression profiles of CXCL12 (SDF-1), CCL19 (MIP-3β), CCL20 (MIP-3α) and CCL21 (6Ckine, Exodus2) and their receptors on RNA and protein levels in hepatocellular carcinoma (HCC) versus colorectal liver metastases (CRLM) and to elucidate their impact on the carcinogenesis and progression of malignant liver diseases.METHODS: Chemokine expression was analyzed by RT-PCR and ELISA in 11 cases of HCC specimens and in 23 cases of CRLM and corresponding adjacent nontumorous liver tissues, respectively. Expressions of their receptors CXCR4, CCR6 and CCR7 were analyzed by RTPCR and Western blot analysis in the same cases of HCC and CRLM.RESULTS: Significant up-regulation for CCL20/CCR6 was detected in both cancer types. Moreover, CCL20demonstrated significant overexpression in CRLM in relation to the HCC tissues. Being significantly upregulated only in CRLM, CXCR4 displayed an aberrant expression pattern with respect to the HCC tissues.CONCLUSION: Correlation of CXCR4 expression with CRLM suggests CXCR4 as a potential predictive factor for CRLM. High level expression of CCL20 and its receptor CCR6 in HCC and CRLM with marked upregulation of CCL20 in CRLM in relation to HCC tissues indicates involvement of the CCL20/CCR6 ligand-receptor pair in the carcinogenesis and progression of hepatic malignancies.

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

    Science.gov (United States)

    Mármol, Inés; Sánchez-de-Diego, Cristina; Pradilla Dieste, Alberto; Cerrada, Elena; Rodriguez Yoldi, María Jesús

    2017-01-01

    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 with

  3. 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

  4. Biliary carcinoembryonic antigen levels in diagnosis of occult hepatic metastases from colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jaques Waisberg; Rog(e)rio T. Palma; Lu(i)s Contim Neto; Lourdes C. Martins; Maur(i)cio S. L. Oliveira; Carlos A. Nagashima; Antonio C. Godoy; Fabio S. Goffi

    2003-01-01

    AIM: To prospectively explore the role of carcinoembryonic antigen (CEA) in gallbladder bile in patients with colorectal carcinoma and the morphological and clinical features of neoplasia and the occurrence of hepatic metastases.METHODS: CEA levels in the gallbladder and peripheral blood were studied in 44 patients with colorectal carcinoma and 10 patients with uncomplicated cholelithiasis. CEA samples were collected from the gallbladder bile and peripheral blood during the operation, immediately before extirpating the colorectal neoplasia or cholecystectomy.Values of up to 5 ng/ml were considered normal for bile and serum CEA.RESULTS: In the 44 patients with colorectal carcinoma who underwent operation with curative intent, the average level of serum CEA was 8.5 ng/ml (range: 0.1 to 111.0 ng/ml) and for bile CEA it was 74.5 ng/ml (range: 0.2 to 571.0ng/ml). In the patients with uncomplicated cholelithiasis who underwent cholecystectomy, the average level of serum CEA was 1.9 ng/ml (range: 1.0 to 3.5 ng/ml) and for bile CEA it was 1.2 ng/ml (range: 0.3 to 2.9 ng/ml).The average duration of follow-up time was 16.5 months (range: 6 to 48 months). Four patients who underwent extirpation of the colorectal carcinoma without evidence of hepatic metastasis and with an average bile CEA value of 213.2 ng/ml presented hepatic metastases between three and seventeen months after removal of the primary colorectal neoplasia. Three of them successfully underwent extirpation of the hepatic lesions.CONCLUSION: High CEA levels in gallbladders of patients undergoing curative operation for colorectal carcinoma may indicate the presence of hepatic metastases. Such patients must be followed up with special attention to the diagnosis of such lesions.

  5. Arginine starvation in colorectal carcinoma cells: Sensing, impact on translation control and cell cycle distribution.

    Science.gov (United States)

    Vynnytska-Myronovska, Bozhena O; Kurlishchuk, Yuliya; Chen, Oleh; Bobak, Yaroslav; Dittfeld, Claudia; Hüther, Melanie; Kunz-Schughart, Leoni A; Stasyk, Oleh V

    2016-02-01

    Tumor cells rely on a continued exogenous nutrient supply in order to maintain a high proliferative activity. Although a strong dependence of some tumor types on exogenous arginine sources has been reported, the mechanisms of arginine sensing by tumor cells and the impact of changes in arginine availability on translation and cell cycle regulation are not fully understood. The results presented herein state that human colorectal carcinoma cells rapidly exhaust the internal arginine sources in the absence of exogenous arginine and repress global translation by activation of the GCN2-mediated pathway and inhibition of mTOR signaling. Tumor suppressor protein p53 activation and G1/G0 cell cycle arrest support cell survival upon prolonged arginine starvation. Cells with the mutant or deleted TP53 fail to stop cell cycle progression at defined cell cycle checkpoints which appears to be associated with reduced recovery after durable metabolic stress triggered by arginine withdrawal.

  6. THE STUDY OF COLORECTAL CARCINOMA ASSOCIATED ANTIGEN LEA IN CLINICAL PATHOLOGICAL DIAGNOSIS

    Institute of Scientific and Technical Information of China (English)

    冯慧; 宋今丹

    2002-01-01

    Objective: To study the expression and the clinical significance of LEA in colorectal carcinoma. Methods: Immunohistochemistry S-P method to detect the expression of LEA and CEA in 140 colorectal cancer specimens and 100 non-cancerous colorectal specimens. Results: The expression of LEA is relative to tumor differentiation degree and exhibits higher selectivity in well-differentiated adeno-carcinoma (P0.05). Compared with CEA, the expression of LEA has lower positive rate in non-cancerous tissue (P<0.05). The positive rate of LEA in adenoma is much higher than surrounding non-cancerous mucosa and normal mucosa. In normal mucosa the positive rate of LEA is obviously lower than that of CEA (P<0.05). The expression of LEA and CEA has similar rule except in normal mucosa. In histological diagnosis of colorectal cancer the sensitivity of LEA is 82.9% and the specificity is 48%, while the sensitivity of CEA is 88.6% and the specificity is 35%. Conclusion: The expression of LEA is related to the differentiation degree of colorectal cancer tissue. LEA can be used as an auxiliary index for early diagnosis and a reference for the judgment of the malignancy degree of colorectal carcinoma, thus may be a new tumor marker with applicable clinic value.

  7. Appendicitis presenting as the first manifestation of colorectal carcinoma: a 13-year retrospective study.

    Science.gov (United States)

    Shine, Rebecca J; Zarifeh, Abigail; Frampton, Chris; Rossaak, Jeremy

    2017-07-21

    Appendicitis in older adults may present as the first sign of underlying colorectal cancer. We aim to determine whether there was a difference in the rate of diagnosis of colorectal carcinoma for patients ≥45 years following a presentation with appendicitis, compared with New Zealand standardised rates. Retrospective study of patients ≥45 years with a confirmed diagnosis of appendicitis from 2003 to 2015 inclusive. The rate of colorectal carcinoma diagnosed during the 36-month follow-up period was calculated and compared to standardised rates, as per the New Zealand cancer registry. Six hundred and twenty-nine patients were included for analysis, 15 had a diagnosis of colorectal cancer in the follow-up period. Patients ≥45 years had a 6.3-fold (CI 3.6-10.2) increased risk of colorectal carcinoma than predicted given the population demographics. Those patients aged between 45-60 years had a 17-fold (95% CI 8-32.2) increased standardised risk ratio. This is the first study of its kind conducted in Australasia. This study found patients ≥45 years who present with appendicitis have significantly increased risk of underlying colorectal cancer. Until further research is conducted the authors recommend clinicians consider colonic investigation for older adults following a diagnosis of appendicitis.

  8. Transcriptional gene expression profiles of HGF/SF-met signaling pathway in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xue-Nong Li; Yan-Qing Ding; Guo-Bing Liu

    2003-01-01

    AIM: To explore the transcriptional gene expression profiles of HGF/SF-met signaling pathway in colorectal carcinoma to understand mechanisms of the signaling pathway at so gene level.METHODS: Total RNA was isolated from human colorectal carcinoma cell line LoVo treated with HGF/SF (80 ng/L)for 48 h. Fluorescent probes were prepared from RNA labeled with cy3-dUTP for the control groups and with cy5-dUTP for the HGF/SF-treated groups through reversetranscription. The probes were mixed and hybridized on the microarray at 60 ℃ for 15-20 h, then the microarray was scanned by laser scanner (GenePix 4000B). The intensity of each spot and ratios of Cy5/Cy3 were analyzed and finally the differentially expressed genes were selected by GenePix Pro 3.0 software. 6 differential expression genes (3 up-regulated genes and 3 down-regulated genes) were selected randomly and analyzed by β-actin semiquantitative RT-PCR.RESULTS: The fluorescent intensities of built-in negative control spots were less than 200, and the fluorescent intensities of positive control spots were more than 5000.Of the 4004 human genes analyzed by microarray, 129 genes (holding 3.22 % of the investigated genes) revealed differential expression in HGF/SF-treated groups compared with the control groups, of which 61 genes were up-regulated (holding 1.52 % of the investigated genes) and 68 genes were down-regulated (holding 1.70 % of the investigated genes), which supplied abundant information about target genes of HGF/SF-met signaling.CONCLUSION: HGF/SF-met signaling may up-regulate oncogenes, signal transduction genes, apoptosis-related genes, metastasis related genes, and down-regulate a number of genes. The complexity of HGF/SF-met signaling to control the gene expression is revealed as a whole by the gene chip technology.

  9. Vitronectin in human breast carcinomas

    DEFF Research Database (Denmark)

    Aaboe, Mads; Offersen, Birgitte Vrou; Christensen, Anni;

    2003-01-01

    We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters and in the subendothe......We have analysed the occurrence of the extracellular glycoprotein vitronectin in carcinomas and normal tissue of human breast. Immunohistochemical analysis of carcinomas revealed a strong vitronectin accumulation in extracellular matrix (ECM) around some cancer cell clusters...... and in the subendothelial area of some blood vessels. In normal tissue, vitronectin had a homogeneous periductal occurrence, with local accumulation much lower than that in the carcinomas. Using a new solid phase radioligand assay, the vitronectin concentrations of extracts of carcinomas and normal breast tissue were...... determined and found to be indistinguishable. Comparison of the vitronectin and the hemoglobin concentrations of the extracts showed that their vitronectin content was not derived from blood contamination. Vitronectin mRNA was undetectable in both carcinomas and normal tissue. We conclude that vitronectin...

  10. Mandibular osteomas in sporadic colorectal carcinoma. A genetic marker

    DEFF Research Database (Denmark)

    Søndergaard, J O; Rasmussen, M S; Videbaek, H;

    1993-01-01

    Pantomography of the mandible was performed in 98 patients with sporadic colorectal adenocarcinoma. Twenty-eight patients (29%) had osteomas versus 5% in a control group (P osteomas are found in most patients with the premalignant dominant syndrome familial adenomatous...... polyposis. Sporadic colorectal cancer examinations of married couples have shown that diet has only a moderate influence on the development of colorectal cancer, whereas pedigree studies indicate a genetic component. On this basis we conclude that mandibular osteomas are probably genetic markers...

  11. 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.

  12. End-to-End Thiocyanato-Bridged Helical Chain Polymer and Dichlorido-Bridged Copper(II) Complexes with a Hydrazone Ligand: Synthesis, Characterisation by Electron Paramagnetic Resonance and Variable-Temperature Magnetic Studies, and Inhibitory Effects on Human Colorectal Carcinoma Cells.

    Science.gov (United States)

    Das, Kuheli; Datta, Amitabha; Sinha, Chittaranjan; Huang, Jui-Hsien; Garribba, Eugenio; Hsiao, Ching-Sheng; Hsu, Chin-Lin

    2012-04-01

    The reactions of the tridentate hydrazone ligand, N'-[1-(pyridin-2-yl)ethylidene]acetohydrazide (HL), obtained by condensation of 2-acetylpyridine with acetic hyadrazide, with copper nitrate trihydrate in the presence of thiocyanate, or with CuCl2 produce two distinct coordination compounds, namely a one-dimensional helical coordination chain of [CuL(NCS)] n (1) units, and a doubly chlorido-bridged dinuclear complex [Cu2L2Cl2] (2) (where L=CH3C(O)=N-N=CCH3C5H4N). Single-crystal X-ray structural determination studies reveal that in complex 1, a deprotonated hydrazone ligand L(-) coordinates a copper(II) ion that is bridged to two neighbouring metal centres by SCN(-) anions, generating a one-dimensional helical coordination chain. In complex 2, two symmetry-related, adjacent copper(II) coordination entities are doubly chlorido-bridged, producing a dicopper entity with a Cu⋅⋅⋅Cu distance of 3.402 (1) Å. The two coordination compounds have been fully characterised by elemental analysis, spectroscopic techniques including IR, UV-vis and electron paramagnetic resonance, and variable-temperature magnetic studies. The biological effects of 1 and 2 on the viability of human colorectal carcinoma cells (COLO-205 and HT-29) were evaluated using an MTT assay, and the results indicate that these complexes induce a decrease in cell-population growth of human colorectal carcinoma cells with apoptosis.

  13. MicroRNA profiles in colorectal carcinomas, adenomas and normal colonic mucosa: variations in miRNA expression and disease progression.

    Science.gov (United States)

    Slattery, Martha L; Herrick, Jennifer S; Pellatt, Daniel F; Stevens, John R; Mullany, Lila E; Wolff, Erica; Hoffman, Michael D; Samowitz, Wade S; Wolff, Roger K

    2016-03-01

    MiRNAs are small, non-protein-coding RNA molecules that regulate gene expression either by post-transcriptionally suppressing mRNA translation or by mRNA degradation. We examine differentially expressed miRNAs in colorectal carcinomas, adenomas and normal colonic mucosa. Data come from population-based studies of colorectal cancer conducted in Utah and the Kaiser Permanente Medical Care Program. A total of 1893 carcinoma/normal-paired samples and 290 adenoma tissue samples were run on the Agilent Human miRNA Microarray V19.0 which contained 2006 miRNAs. We tested for significant differences in miRNA expression between paired carcinoma/adenoma/normal colonic tissue samples. Fewer than 600 miRNAs were expressed in >80% of people for colonic tissue; of these 86.5% were statistically differentially expressed between carcinoma and normal colonic mucosa using a false discovery rate of 0.05. Roughly half of these differentially expressed miRNAs showed a progression in levels of expression from normal to adenoma to carcinoma tissue. Other miRNAs appeared to be altered at the normal to adenoma stage, while others were only altered at the adenoma to carcinoma stage or only at the normal to carcinoma stage. Evaluation of the Agilent platform showed a high degree of repeatability (r = 0.98) and reasonable agreement with the NanoString platform. Our data suggest that miRNAs are highly dysregulated in colorectal tissue among individuals with colorectal cancer; the pattern of disruption varies by miRNA as tissue progresses from normal to adenoma to carcinoma.

  14. Identification and validation of highly frequent CpG island hypermethylation in colorectal adenomas and carcinomas.

    Science.gov (United States)

    Oster, Bodil; Thorsen, Kasper; Lamy, Philippe; Wojdacz, Tomasz K; Hansen, Lise Lotte; Birkenkamp-Demtröder, Karin; Sørensen, Karina D; Laurberg, Søren; Orntoft, Torben F; Andersen, Claus L

    2011-12-15

    In our study, whole-genome methylation arrays were applied to identify novel genes with tumor specific DNA methylation of promoter CpG islands in pre-malignant and malignant colorectal lesions. Using a combination of Illumina HumanMethylation27 beadchips, Methylation-Sensitive High Resolution Melting (MS-HRM) analysis, and Exon arrays (Affymetrix) the DNA methylation pattern of ∼14,000 genes and their transcript levels were investigated in six normal mucosas, six adenomas and 30 MSI and MSS carcinomas. Sixty eight genes with tumor-specific hypermethylation were identified (p mucosas, 12 adenomas, 40 MSS and nine MSI cancer samples. The methylation patterns of 15 selected genes, hypermethylated in adenomas and carcinomas (FLI1, ST6GALNAC5, TWIST1, ADHFE1, JAM2, IRF4, CNRIP1, NRG1 and EYA4), 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 hypermethylation, were identified and validated. Inverse correlation to gene expression was observed for six of the 15 genes with Spearman correlation coefficients ranging from -0.39 to -0.60. For six of these genes the altered methylation patterns had a profound transcriptional association, indicating that methylation of these genes may play a direct regulatory role. The hypermethylation changes often occurred already in adenomas, indicating that they may be used as biomarkers for early detection of CRC.

  15. 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.

  16. Berberine inhibits the growth of human colorectal adenocarcinoma in vitro and in vivo.

    Science.gov (United States)

    Cai, Yuchen; Xia, Qing; Luo, Rongzhen; Huang, Peiyu; Sun, Yueli; Shi, Yanxia; Jiang, Wenqi

    2014-01-01

    Berberine is an alkaloid isolated from the Chinese herbal medicine Huanglian, and has long been used as an antibiotic. Its antineoplastic properties were subsequently discovered in vitro. The purpose of this study was to investigate the effects of berberine on the growth of human colorectal carcinoma cells in vitro and in vivo. The results showed that berberine inhibited human colorectal adenocarcinoma (LoVo) cell growth in a time- and dose-dependent manner. A WST-1 assay showed that the IC50 value after 72 h was 40.79 ± 4.11 μM. Cell cycle analysis of 40 μM berberine-treated LoVo cells by flow cytometry showed accumulation of cells in the G2/M phase. The inhibition of LoVo cell growth by berberine was associated with the suppression of cyclin B1, cdc2, and cdc25c proteins. Berberine at a dose of 50 mg kg(-1) day(-1) showed inhibitory rates of 45.3% in a human colorectal adenocarcinoma xenograft in nude mice. The combination of berberine and 5-fluorouracil (5-FU) had a higher inhibitory rate (59.8%) than the berberine group (36.4%, P = 0.01), but no significant difference was observed between the 5-FU group (43.0%, P = 0.06) and the combination group. These results support the possibility that berberine may be useful as an alternative therapy for colorectal carcinoma.

  17. High occurrence of Fusobacterium nucleatum and Clostridium difficile in the intestinal microbiota of colorectal carcinoma patients

    Directory of Open Access Journals (Sweden)

    Márcia H. Fukugaiti

    2015-01-01

    Full Text Available AbstractColorectal carcinoma is considered the fourth leading cause of cancer deaths worldwide. Several microorganisms have been associated with carcinogenesis, including Enterococcus spp., Helicobacter pylori, enterotoxigenic Bacteroides fragilis, pathogenic E. coli strains and oral Fusobacterium. Here we qualitatively and quantitatively evaluated the presence of oral and intestinal microorganisms in the fecal microbiota of colorectal cancer patients and healthy controls. Seventeen patients (between 49 and 70 years-old visiting the Cancer Institute of the Sao Paulo State were selected, 7 of whom were diagnosed with colorectal carcinoma. Bacterial detection was performed by qRT-PCR. Although all of the tested bacteria were detected in the majority of the fecal samples, quantitative differences between the Cancer Group and healthy controls were detected only for F. nucleatum and C. difficile. The three tested oral microorganisms were frequently observed, suggesting a need for furthers studies into a potential role for these bacteria during colorectal carcinoma pathogenesis. Despite the small number of patients included in this study, we were able to detect significantly more F. nucleatumand C. difficile in the Cancer Group patients compared to healthy controls, suggesting a possible role of these bacteria in colon carcinogenesis. This finding should be considered when screening for colorectal cancer.

  18. Prognostic significance of COX-2 and β-catenin in colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Amani Kazem

    2014-09-01

    Conclusion: Both β-catenin and COX-2 expression may play an important role in the evolution of colon carcinogenesis. Increased expression of both could be used as a marker of tumor progression and poor prognosis. This might be of therapeutic value for allocating patients with colorectal carcinoma to different treatment modalities.

  19. 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...

  20. STUDIES ON THE DETECTION KIT FOR THE COLORECTAL CARCINOMA ASSOCIATED LARGE EXTERNAL ANTIGEN

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the detecting method and diagnostic value of the tumor marker colorectal carcinoma associated large external antigen (LEA) for colorectal carcinoma. Methods: Monoclonal antibody ND-1, which can recognize LEA, was labeled with biotin aminocaproylhydrazide (BACH) and horseradish peroxidase (HRP) respectively. One step sandwich ELISA Kit for detecting LEA in serum was developed by the biotinylated antibody and enzyme conjugation. The validity and reliability of the kit were evaluated by sera selected from clinic. Results: the OD405 of healthy group was 0.056± 0.038, and that of patients was 0.553± 0.441. The difference between the two groups was significant (P<0.01). The cutoff value, which was 0.248, was determined by analysis of ROC. The diagnosis sensitivity, specificity and validity of the kit were 89.29%, 87.5%, 88.54% respectively. The ROC value was 0.95. The intra-CV was less than 5%, and the internal-CV was less than 10%. There was no significant difference between the results obtained by the kit and those obtained by pathological diagnosis (P<0.01). The expression of LEA was associated with the differentiated degree of colorectal carcinoma and had no relation to the Dukes' phase of the disease. Conclusion: LEA is practically useful tumor marker for the diagnosis of colorectal carcinoma. The kit developed can be used for the qualitative diagnosis for the disease.

  1. 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.

  2. [Oral fluoropyrimidines registered for the treatment of metastatic colorectal carcinoma: a possible gain

    NARCIS (Netherlands)

    Croockewit, A.J.; Boer, J.E. de; Loenhout, J.W.A. van; Koopmans † , P.P.

    2002-01-01

    Up until now the standard treatment for metastasized colorectal carcinoma has been fluorouracil (5-FU) in combination with folonic acid in low doses administered intravenously, even after the recent registration of a number of new intravenously administered cytostatics, such as irinotecan and oxalip

  3. Assessing global transitions in human development and colorectal cancer incidence.

    Science.gov (United States)

    Fidler, Miranda M; Bray, Freddie; Vaccarella, Salvatore; Soerjomataram, Isabelle

    2017-06-15

    Colorectal cancer incidence has paralleled increases in human development across most countries. Yet, marked decreases in incidence are now observed in countries that have attained very high human development. Thus, in this study, we explored the relationship between human development and colorectal cancer incidence, and in particular assessed whether national transitions to very high human development are linked to temporal patterns in colorectal cancer incidence. For these analyses, we utilized the Human Development Index (HDI) and annual incidence data from regional and national cancer registries. Truncated (30-74 years) age-standardized incidence rates were calculated. Yearly incidence rate ratios and HDI ratios, before and after transitioning to very high human development, were also estimated. Among the 29 countries investigated, colorectal cancer incidence was observed to decrease after reaching the very high human development threshold for 12 countries; decreases were also observed in a further five countries, but the age-standardized incidence rates remained higher than that observed at the threshold. Such declines or stabilizations are likely due to colorectal cancer screening in some populations, as well as varying levels of exposure to protective factors. In summary, it appears that there is a threshold at which human development predicts a stabilization or decline in colorectal cancer incidence, though this pattern was not observed for all countries assessed. Future cancer planning must consider the increasing colorectal cancer burden expected in countries transitioning towards higher levels of human development, as well as possible declines in incidence among countries reaching the highest development level. © 2017 UICC.

  4. Lynch syndrome-associated colorectal carcinoma: frequent involvement of the left colon and rectum and late-onset presentation supports a universal screening approach.

    Science.gov (United States)

    Hartman, Douglas J; Brand, Randall E; Hu, Huankai; Bahary, Nathan; Dudley, Beth; Chiosea, Simon I; Nikiforova, Marina N; Pai, Reetesh K

    2013-11-01

    The optimal strategy for screening patients with colorectal carcinoma for Lynch syndrome (LS) is a subject of continued debate in the literature with some advocating universal screening while others arguing for selective screening. We evaluated 1292 colorectal carcinomas for DNA mismatch repair protein abnormalities and identified 150 (11.6%) tumors demonstrating high-levels of microsatellite instability (MSI-H). MSI-H colorectal carcinomas were divided into sporadic (112/1292, 8.7%) and LS/probable LS-associated (38/1292, 2.9%) groups based on BRAF V600E mutation, MLH1 promoter hypermethylation, cancer history, and germline mismatch repair gene mutation. All MSI-H colorectal carcinomas were analyzed for grade, location, and tumor histology. The utility of the revised Bethesda guidelines and published predictive pathology models for MSI-H colorectal carcinomas (PREDICT and MSPath) were evaluated. Left-sided MSI-H colorectal carcinomas were more frequently associated with LS compared with right-sided MSI-H colorectal carcinomas (12/21, 57% versus 26/129, 20%, P = .0008). There was no significant difference in histology between sporadic MSI-H and LS/probable LS-associated colorectal carcinomas except for a slightly higher proportion of sporadic MSI-H tumors demonstrating tumor-infiltrating lymphocytes (81% versus 61%, P = .015). Neither pathology predictive model identified all LS-associated colorectal carcinomas (PREDICT: 33/38, 87%; MSPath: 35/38, 92%). 12/117 (10%) MSI-H colorectal carcinomas identified in patients >60 years were LS/probable LS-associated. Our results demonstrate that models of predicting MSI-H fail to identify LS-associated colorectal carcinoma given their reliance on right-sided location. A significant proportion (32%) of LS-associated colorectal carcinoma is identified in patients >60 years. Finally, our results demonstrate similar morphologic features between LS-associated and sporadic MSI-H colorectal carcinomas.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  6. Matrix metalloproteinase-2 and tissue inhibitor of metallo-proteinase-2 in colorectal carcinoma invasion and metastasis

    OpenAIRE

    Li, Bing-hui; zhao,Peng; Liu, Shi-Zheng; Yu, Yue-Ming; Han, Mei; Wen, Jin-kun

    2005-01-01

    AIM: To explore the relationship between matrix metallopr-oteinase-2 (MMP-2) and tissue inhibitor of metallopr-oteinase-2 (TIMP-2) in the development of colorectal carcinoma and to provide a valuable marker for clinical diagnosis.

  7. T-cell response to p53 tumor-associated antigen in patients with colorectal carcinoma.

    Science.gov (United States)

    Bueter, Marco; Gasser, Martin; Schramm, Nicolai; Lebedeva, Tatiana; Tocco, Georges; Gerstlauer, Christiane; Grimm, Martin; Nichiporuk, Ekaterina; Thalheimer, Andreas; Thiede, Arnulf; Meyer, Detlef; Benichou, Gilles; Waaga-Gasser, Ana Maria

    2006-02-01

    Despite the radical surgical resection performed in patients with colorectal carcinoma, there is a high rate of tumor recurrence. Over an observation period of 3 years, 18% of the patients in our collective suffered a tumor relapse with local or distinct metastases after initial R0-resection. Some evidence suggests that this may be due to suppression of anti-tumor responses, a phenomenon that might be attributed to regulatory T cells. The aim of our study was to investigate the tumor-specific immune response depending on the UICC stage of patients with colorectal cancer. The cellular immune responses against defined antigens that are overexpressed in most of the patients with colorectal cancer were characterized. For this purpose, the tumor suppressor gene, p53, was chosen as the tumor-associated antigen that exhibits mutations and overexpression in up to 60% of colorectal carcinoma. We observed that p53 induced both IFN-gamma and IL-10 secretion. The predominance of IL-10 production indicated that regulatory T cells directly participate in modulating the anti-tumor immune response. IL-10 levels in the blood as well as the expression of regulatory T-cell specific genes at the tumor site correlate with the UICC stage of the disease. These results may provide an explanation for the poor prognosis and increased recurrence rate in patients with advanced carcinoma.

  8. Expression of p21WAF1 is related to acetylation of histone H3 in total chromatin in human colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Ying-Xuan Chen; Jing-Yuan Fang; Rong Lu; De-Kai Qiu

    2007-01-01

    AIM: To explore the relationship between acetylation of histone in total chromatin and p21WAF1 expression regulation in human colorectal carcinoma.METHODS: We analyzed the expression of tumor suppressor gene p21WAF1 mRNA by RT-PCR or realtime PCR in 33 samples of colorectal cancerous tissue,corresponding para-cancerous tissue and normal colorectal mucosa, and also examined the level of acetylated histone H3 in total chromatin using Western blotting.RESULTS: The expression level of p21WAF1 mRNA was significantly lower in colorectal cancerous tissue from 33 patients than in para-cancerous tissue and normal colorectal mucosa (2377.95 ± 865.80 vs 3216.58 ±1149.42 and 3541.61 ± 1433.17 respectively, P <0.01). In addition, when p21WAF1 mRNA expression was undectectable or at very low level (50% less than that in adjacent tissue and normal colorectal mucosa) in all tissues, the level of acetylated histone H3 in colorectal cancerous tissue was significantly lower than that in corresponding para-cancerous tissue and normal colorectal mucosa in five of seven (71.43%) cases. The transcriptional level of p21WAF1 in colorectal carcinoma might not be associated with its biological behaviors.CONCLUSION: The down-regulation of p21WAF1 transcription is involved in the tumorigenesis and development of colorectal carcinoma. The down-expression of p21WAF1 mRNA in colorectal carcinoma might be associated with histone hypoacetylation in chromatin but not with biological behaviors.

  9. ZEB1 Promotes invasiveness of colorectal carcinoma cells through the opposing regulation of uPA and PAI-1

    DEFF Research Database (Denmark)

    Sánchez-Tilló, Ester; de Barrios, Oriol; Siles, Laura

    2013-01-01

    a mechanism implicating the histone acetyltransferase p300. In contrast, inhibition of PAI-1 by ZEB1 does not involve transcriptional repression but rather downregulation of mRNA stability. ZEB1-mediated tumor cell migration and invasion depend on its induction of uPA. ZEB1 coexpresses with uPA in cancer...... DESIGN: Through multiple experimental approaches, colorectal carcinoma (CRC) cell lines and samples from human primary CRC and ZEB1 (-/-) mice were used to examine ZEB1-mediated regulation of uPA and PAI-1 at the protein, mRNA, and transcriptional level. RESULTS: ZEB1 regulates uPA and PAI-1 in opposite......PURPOSE: Carcinoma cells enhance their invasive capacity through dedifferentiation and dissolution of intercellular adhesions. A key activator of this process is the ZEB1 transcription factor, which is induced in invading cancer cells by canonical Wnt signaling (β-catenin/TCF4). Tumor invasiveness...

  10. TELOMERASE ACTIVITY IN HUMAN GASTRIC AND COLORECTAL CANCER AND SURROUNDING TISSUES

    Institute of Scientific and Technical Information of China (English)

    CHEN Wen; ZHANG Qiao; WAN De-sen; CUN Ling-yun; WU Cheng-qiu; PAN Zhi-zhong

    1999-01-01

    Objective: To study the telomerase activities in human gastric and colorectal tumors. Methods: The telomerase activity was assayed by the telomeric repeat amplification protocol (TRAP) technique. Forty human tumor samples including 9 colonic, 20 rectal and 11gastric carcinomas and their surrounding tissues were used for the detection. Results: Thirty-six out of 40human tumor samples exhibited telomerase activity regardless of the stages or the differentiation of the tumors. However, only 1 out of 39 tumor surrounding tissues showed telomerase activity. Conclusion: Telomerase may be a good diagnosis biomarker for tumor detection.

  11. SERUM INTERLEUKIN-18 LEVEL AS A PROGNOSTIC MARKER IN PATIENTS WITH COLORECTAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    韩明勇; 于金明; 郑树; 郭其森; 王家林; 彭佳萍; 董奇

    2004-01-01

    Objective: Interleukin-18(IL-18) is a cytokine with many functions. This study was to investigate the serum levels of IL-18 and their clinical significance in patients with colore3ctaql carcinomas. Methods: Peripheral blood samples were obtained from 106 patients with colorectal carcinoma and 60 volunteers. The serum IL-18 levels were determined in each sample with an enzyme-linked immunosorbent assay (ELISA). Results: In patients before 1997, the mean IL-18 level was 338.46 pg/ml; in patients after 1997, the mean IL-18 level was 328.85 pg/ml, there is no evidence of loss of IL-18 immunoreactivity after prolonged storage at -80℃. The mean serum IL-18 level in 106 patients with colorectal carcinoma was significantly higher compared with the 60 healthy volunteers (P0.05). The survival rate of patients with IL-18 levels ≥346 pg/ml (n=47 patients) was significantly worse compared with patients who had IL-18 levels <346 pg/ml(n=57 patients). The 5-year-survival rates were 5.3% and 18.6%, respectively. Multivariate analysis using a Cox proportional hazards model identified the serum IL-18 level as an independent prognostic factor for survival Conclusion: The serum IL-18 level has a significant correlation with survival curve. The serum IL-18 level may represent a significant postoperative prognostic determinant in patients with colorectal carcinoma.

  12. Single nucleotide polymorphisms in the CDH17 gene of colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ren-Yin Chen; Juan-Juan Cao; Juan Chen; Jian-Ping Yang; Xiao-Bo Liu; Guo-Qiang Zhao; Yu-Feng Zhang

    2012-01-01

    AIM:To investigate the relationship between c.343A>G and c.2216A>C polymorphism sites in the CDH17 gene and colorectal carcinoma.METHODS:Ninety-three non-consanguineous colorectal carcinoma patients admitted to the Department of Oncology at the First Affiliated Hospital of Zhengzhou University were included in this study.Ninety-three peripheral venous blood samples,of approximately one milliliter from each patient,were collected between December 2009 and August 2010.The genomic DNA of these peripheral venous blood samples were extTacted and purified using a Fermentas Genomic DNA Purification Kit (Fermentas,CA) according to the manufacturer's protocol.The single nucleotide polymorphisms (SNPs) of the liver-intestine cadherin (CDH17) gene c.343A>G and c.2216A>C were determined by the polymerase chain reaction-single strand conformation polymorphism method (PCR-SSCP) in 93 peripheral venous blood sampies from patients suffering with colorectal carcinoma.Typical samples that showed different migration bands in SSCP were confirmed by sequencing.Directed DNA sequencing was used to check the correctness of the genotype results from the PCR-SSCP method.RESULTS:There was a significant association between the c.2216 A>C SNPs of the CDH17 gene and the tumor-node-metastasis (TNM) grade,as well as with lymph node status,in 93 peripheral venous blood sampies from colorectal carcinoma patients.The genotype frequencies of A/C,A/A,and C/C were 12.90%,33.33% and 53.76%,respectively.There was a significant correlation between lymph node metastasis,TNM grade,and the genotype distribution (P < 0.05).The C/C genotype raised the risk of lymph node metastasis and the TNM grade.There was a significant difference in the TNM grade and lymph node metastasis between the A/A and C/C genotypes (P =0.003 and P =0.013,respectively).Patients with colorectal carcinoma carrying the C allele tended to have a higher risk of lymph node metastasis and have a higher TNM grade

  13. Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    ZHAO Dan-ping; DING Xiao-wen; PENG Jia-ping; ZHENG Yi-xiong; ZHANG Su-zhan

    2005-01-01

    Objective: This study was designed to detect the expression ofbcl-2 and p53 proteins in colorectal carcinomas and to determine their association with the patient survival and stage of the diseases. Methods: Immunohistochemistry method was used to detect the expression ofbcl-2 and p53 proteins in 93 cases of colorectal carcinoma. The stain results were obtained by analyzing the clinic-pathological characteristics of patients. Results: Fifty-seven percent (53/93) of the colorectal carcinomas were bcl-2 protein positive. The positive rate of bcl-2 protein in lymph node involvement cases was lower (15/37) than the cases without node involvement (38/58, P<0.01). The positive rate of p53 protein was 43% (40/93) in colon-rectum carcinomas. No significant correlation was observed between p53 protein expression and clinic-pathological manifestations (P>0.05) but the survival was significantly worse (P=0.0001) in the p53 protein positive cases. Neither bcl-2 nor p53 alone was correlated with stage of the disease. When combined bcl-2/p53 status was analyzed, a group with bcl-2(+) and p53(-) had the best prognosis. This group was significantly associated with earlier Dukes' stages (P=0.1763). In multivariate Cox regression analysis, lymph node involvement and p53 protein expression were two independent factors correlated with survival time. Conclusion: The expression of bcl-2 and p53 represent biological characteristics of colorectal carcinomas. Assessment of both bcl-2 and p53 status may be valuable in predicting the prognosis of patients.

  14. High expression of HLA-E in colorectal carcinoma is associated with a favorable prognosis

    Directory of Open Access Journals (Sweden)

    Monaco Elisa Lo

    2011-10-01

    Full Text Available Abstract Background Human Leukocyte Antigen (HLA-E is a non-classical class I HLA molecule that can be stabilized by ligands donated by other classical (HLA-A, -B, -C and non-classical (HLA-G family members. HLA-E engages a variety of immune receptors expressed by cytotoxic T lymphocytes (CTLs, Natural killer (NK cells and NK-CTLs. In view of the opposing outcomes (activation or inhibition of the different HLA-E receptors, the preferred role (if any of HLA-E expressed in vivo on tumor cells remains to be established. Methods Taking advantage of MEM-E/02, a recently characterized antibody to denatured HLA-E molecules, HLA-E expression was assessed by immunohistochemistry on an archival collection (formalin-fixed paraffin-embedded of 149 colorectal primary carcinoma lesions paired with their morphologically normal mucosae. Lymphoid infiltrates were assessed for the expression of the HLA-E-specific, inhibitory, non-rearranging receptor NKG2A. Results High HLA-E expression did not significantly correlate with the expression of classical HLA-B and HLA-C molecules, but it did correlate with high expression of its preferential ligand donor HLA-A. In addition, it correlated with lymphoid cell infiltrates expressing the inhibitory NKG2A receptor, and was an independent predictor of good prognosis, particularly in a subset of patients whose tumors express HLA-A levels resembling those of their paired normal counterparts (HLA-A. Thus, combination phenotypes (HLA-Elo-int/HLA-AE and HLA-Ehi/HLA-AE of classical and non-classical class I HLA molecules mark two graded levels of good prognosis. Conclusions These results suggest that HLA-E favors activating immune responses to colorectal carcinoma. They also provide evidence in humans that tumor cells entertain extensive negotiation with the immune system until a compromise between recognition and escape is reached. It is implied that this process occurs stepwise, as predicted by the widely accepted

  15. Treatment of metastatic colorectal carcinomas by systemic inhibition of vascular endothelial growth factor signaling in mice

    Institute of Scientific and Technical Information of China (English)

    Volker Schmitz; Miroslaw Kornek; Tobias Hilbert; Christian Dzienisowicz; Esther Raskopf; Christian Rabe; Tilman Sauerbruch; Cheng Qian; Wolfgang H Caselmann

    2005-01-01

    AIM: Tumor angiogenesis has been shown to be promoted by vascular endothelial growth factor (VEGF) via stimulating endothelial cell proliferation, migration, and survival.Blockade of VEGF signaling by different means has been demonstrated to result in reduced tumor growth and suppression of tumor angiogenesis in distinct tumor entities.Here, we tested a recombinant adenovirus, AdsFlt1-3,that encodes an antagonistically acting fragment of the VEGF receptor 1 (Flt-1), for systemic antitumor effects in pre-established subcutaneous CRC tumors in mice.METHODS: Murine colorectal carcinoma cells (CT26) were inoculated subcutaneously into Balb/c mice forin vivo studies. Tumor size and survival were determined. 293cell line was used for propagation of the adenoviral vectors.Human lung cancer line 4549 and human umbilical vein endothelial cells were transfected forin vitro experiments.RESULTS: Infection of tumor cells with AdsFlt1-3 resulted in protein secretion into cell supernatant, demonstrating correct vector function. As expected, the secreted sFlt1-3 protein had no direct effect on CT26 tumor cell proliferation in vitro, but endothelial cell function was inhibited by about 46% as compared to the AdLacZ control in a tube formation assay. When AdsFlt1-3 (5×109 PFU/animal) was applied to tumor bearing mice, we found a tumor inhibition by 72% at d 12 after treatment initiation. In spite of these antitumoral effects, the survival time was not improved.According to reduced intratumoral microvessel density in AdsFlt1-3-treated mice, the antitumor mechanism can be attributed to angiostatic vector effects. We did not detect increased systemic VEGF levels after AdsFlt1-3 treatment and liver toxicity was low as judged by serum alanine aminotransferase determination.CONCLUSION: In this study we confirmed the value of a systemic administration of AdsFlt1-3 to block VEGF signaling as antitumor therapy in an experimental metastatic colorectal carcinoma model in mice.

  16. B7-H1 expression is associated with poor prognosis in colorectal carcinoma and regulates the proliferation and invasion of HCT116 colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Sheng-Jia Shi

    Full Text Available BACKGROUND AND OBJECTIVE: The investigation concerning the B7-H1 expression in colorectal cancer cells is at an early stage. It is unclear whether B7-H1 expression may have diagnostic or prognostic value in colorectal carcinoma. Additionally, how B7-H1 is associated with the clinical features of colorectal carcinoma is not known. In order to investigate the relationship between B7-H1 and colorectal cancer, we analyzed B7-H1 expression and its effect in clinical specimens and HCT116 cells. METHODS: Paraffin-embedded specimens from 143 eligible patients were used to investigate the expression of CD274 by immunohistochemistry. We also examined whether B7-H1 itself may be related to cell proliferation, apoptosis, migration and invasion in colon cancer HCT116 cells. RESULTS: Our results show that B7-H1 was highly expressed in colorectal carcinoma and was significantly associated with cell differentiation status and TNM (Tumor Node Metastasis stage. Patients with positive B7-H1 expression showed a trend of shorter survival time. Using multivariate analysis, we demonstrate that positive B7-H1 expression is an independent predictor of colorectal carcinoma prognosis. Our results indicate that B7-H1 silencing with siRNA inhibits cell proliferation, migration and invasion. Furthermore, cell apoptosis was also increased by B7-H1 inhibition. CONCLUSIONS: Positive B7-H1 expression is an independent predictor for colorectal carcinoma prognosis. Moreover, knockdown of B7-H1 can inhibit cell proliferation, migration and invasion.

  17. 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.

  18. Association of colorectal carcinoma with metabolic diseases; experience with 138 cases from Kelantan, Malaysia.

    Science.gov (United States)

    Othman, Nor Hayati; Zin, Anani Aila Mat

    2008-01-01

    Kelantan in Malaysia has a high prevalence of diabetes and colorectal cancer is also on the rise. This study is to determine the association of metabolic diseases, particularly diabetes type 2 [DM2] and hypertension, with colorectal cancer patients in our population. This retrospective study was conducted on all colorectal carcinomas in Hospital Universiti Sains Malaysia (HUSM) in Kelantan from ythe ears 2001-2006. The data were retrieved from the Registry in Pathology laboratory and the clinical details from the patients' clinical records and analyzed using SSPS Version 12.0, with a value of pKelantan population. In this preliminary study we noted a strong association of metabolic diseases with the stage and site of the cancer. To reduce CRC incidence, the high prevalence of DM2 in Kelantan needs to be addressed.

  19. Effect of DPC4 Gene on Invasion and Metastasis of Colorectal Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    De-Sheng XIAO; Ji-Fang WEN; Jing-He LI; Kuan-Song WANG; Zhong-Liang HU; Jian-Hua ZHOU; Zheng-Hao DENG; Ying LIU

    2006-01-01

    To investigate the effect of DPC4 gene on invasion and metastasis of colorectal carcinoma cells, the expression of DPC4 was detected in sixty-three samples of colorectal tumors and seven cases of colorectal mucosa. The biological behavior of tumors expressing DPC4 was evaluated (including tumor staging, differentiation degree and metastasis), pcDNA3.1-DPC4 plasmid was constructed and transferred into HCT116 cells not expressing DPC4. The cell models (DPC4+-HCT116) steadily expressing DPC4 were obtained. Compared with HCT116 and pcDNA3.1-HCT116 cells, the doubling time of DPC4+-HCT 116 cells was lengthened obviously (P<0.01), the apoptosis rate of DPC4+-HCT116 cells was significantly increased (P<0.01), the cloning efficiency, cell adherency, migration and invasion ability of DPC4+-HCT116 cells were dropped obviously (P<0.01). The number of cancer nodules was decreased significantly in abdominal cavity and liver of the nude mice inoculated with DPC4+-HCT116 cells. The activity of MMP-9 and MMP-2 was detected by gelatin zymography. In comparison with HCT116 and pcDNA3.1-HCT116 cells, the activity of MMP-9 was decreased in DPC4+-HCT116 cells. Therefore, the down-regulation of DPC4 expression may be associated with the carcinogenesis of colorectal carcinoma. DPC4 may inhibit the proliferation of colon cancer cell by restraining growth and inducing apoptosis, and the invasion and metastasis of colorectal carcinoma cells. MMP-9 may be one of the downstream target genes regulated by DPC4.

  20. Quantitative Real-Time Reverse Transcription-PCR Assay for the Expression of Tob mRNA in Human Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    Dian-chao WU

    2010-01-01

    OBJECTIVE Tob is a member of Tob/BTG antiproliferative family. To date, Tob expression in human carcinoma using clinical specimens has not been studied in depth except for lung carcinoma and thyroid carcinoma. This study is the first to investigate the expression levels of Tob gene in human colorectal cancer tissues,and their corresponding para-cancerous tissues. The correlation of expression of the Tob gene with clinicopathological characteristics of colorectal cancer was also analyzed.METHODS Quantitative real time RT-PCR was used to detect the expression of Tob mRNA in 31 colorectal cancers.RESULTS Compared with normal tissues, up-regulation of Tob mRNA was observed in 31 colorectal cancer tissues (P = 0.020).The expression level of Tob at Dukes C + D phase was higher than Dukes A + B phase, and the difference was signifi cant (P < 0.05).However, in this study, it was found that the expression of Tob mRNA was not related with age, gender, and pathological type of colorectal cancer.CONCLUSION The up-regulation of Tob may be closely associated with tumorigenesis of colorectal carcinoma.

  1. Comparative proteomic study of colorectal carcinoma with different clinical stages%不同临床分期大肠癌组织的蛋白质组学比较研究

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective: Colorectal carcinoma clinical stage associated proteins would be found by comparing differential expressed proteins from colorectal carcinoma tissues with different clinical stages. Methods: Total protein from colorectal carcinoma tissues were extracted; differential proteome profiles were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Results: Well-resolved, reproducible 2-DE profiles of human colorectal carcinoma tissues were obtained. Average protein spots were 970±41,980±32,1010±43,1240±34 in stage Ⅰ, stage Ⅱ,stage Ⅲ, stage Ⅳ respectively; Compared to stage Ⅰ, differential expressed protein spots was 52.00 ± 12 in stage Ⅱ, 42.00± 11 in stage Ⅲ, 72.00 ± 15 in stage Ⅳ; Part of differential expressing proteins were analyzed by mass spectrometry and bioinformation, 19 of them were well characterized. Three proteins were overexpressed in stage Ⅰ, stage Ⅲ, stage Ⅳ, and one protein were overexpressed in stage Ⅳ exclusively. Conclusion: Differential expressed proteins exist in clinical stage of colorectal carcinoma, which would be biomarkers for diagnosis and prediction of prognosis.

  2. Evidence for colorectal sarcomatoid carcinoma arising from tubulovillous adenoma

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Sarcomatoid carcinomas of the colorectum are rare tu- mors that display both malignant epithelial and stromal components. Clinically, they are aggressive tumors with early metastasis. Due to their infrequent occurrence, the pathogenesis is poorly understood. We report a case of a 52-year-old woman who presented with a rectal mass and intermittent hematochezia. Superficial biopsies during colonoscopy revealed a tubulovillous adenoma with high-grade dysplasia. Endoscopic ultra- sonography confirmed an invasive nature of the mass, and deeper biopsies revealed the presence of neoplasm with mixed histological components. The surgically- excised specimen demonstrated the presence of poorly differentiated spindle cells underneath the tubulovillous adenoma and an intermediate stage of invasive acleno- carcinoma. Based on the histological appearance and imrnunohistochemical studies, a diagnosis of sarcoma- toid carcinoma was made. Only nine cases of sarcoma- told carcinomas of the colorectum have been reported to date. As a result, the terminology and pathogenesis of sarcomatoid carcinoma remain speculative. To the best of our knowledge, this is the first report of co- existence of sarcomatoid carcinoma and invasive ad-enocarcinoma with tubulovillous adenoma; all stagesrepres ented within the same tumor. This observation supports the "monoclonal theory" of pathogenesis with an adenoma-sarcoma progression with or without an intermediate stage of carcinoma.

  3. Continuous-infusion cisplatin and bolus 5-fluorouracil in colorectal carcinoma.

    Science.gov (United States)

    Posner, M R; Belliveau, J F; Weitberg, A B; Sabbath, K; Wiemann, M C; Cummings, F J; Calabresi, P

    1987-10-01

    Twenty-one evaluable patients with metastatic colorectal carcinoma were treated with a combination of continuous-infusion cisplatin (25 mg/m2/day X 3 days) and bolus 5-fluorouracil (400 mg/m2/day X 3 days). Toxicity was minimal. Seven patients (33%) responded. All responses were observed among the 16 previously untreated patients (44%) and lasted a median of 30 weeks. The results indicate the need for phase III trials of this treatment.

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

    Directory of Open Access Journals (Sweden)

    Tops Carli MJ

    2009-06-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

  5. Expression of Obesity Hormone Leptin in Human Colorectal Cancer

    Institute of Scientific and Technical Information of China (English)

    Jin-chun Cong; Xian-wei Dai; Ming-yang Shen; Jun-jiang Wang; Chun-sheng Chen; Hong Zhang; Lei Qiao

    2009-01-01

    Objective: The obesity hormone, leptin, has been found to participate in the development and proliferation of normal and malignant tissues. The aim of this study was to evaluate the role of leptin in human colorectal cancer.Methods: Serum leptin levels were measured via ABC-ELLSA in 30 colorectal cancers and 24 normal controls. Leptin concentration in colorectal cancer was analyzed in terms of selected clinicopathological features and some oncogenes.Results: The mean concentration of leptin was significantly higher for colorectal cancers(3.54±1.46 ng/ml) than normal controls(2.27±0.99 ng/ml), no gender difference was observed in this study. Leptin expression in poorly differentiated tumors was obviously lower than those in moderately and well differentiated tumors. There were no statistically significant correlations between leptin and the serum CEA and CA199 in colorectal cancers (P>0.05), and between leptin and the expressions of K-RAS, P53, APC, DCC genes in tumor tissues (P>0.05).Conclusion: Leptin is overexpressed in human colorectal cancer, which is related to the differentiation degrees of the tumor. There is no correlation between leptin expression and chages of oncogenes in colorectal cancers.

  6. 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.

  7. 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.

  8. 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.

  9. Proteomic analysis reveals novel proteins associated with progression and differentiation of colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Yi Gan

    2014-01-01

    Full Text Available Aim: The objective of this study is to characterize differential proteomic expression among well-differentiation and poor-differentiation colorectal carcinoma tissues and normal mucous epithelium. Materials and Methods: The study is based on quantitative 2-dimensional gel electrophoresis and analyzed by PDquest. Results: Excluding redundancies due to proteolysis and posttranslational modified isoforms of over 600 protein spots, 11 proteins were revealed as regulated with statistical variance being within the 95 th confidence level and were identified by peptide mass fingerprinting in matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Progression-associated proteins belong to the functional complexes of tumorigenesis, proliferation, differentiation, metabolism, and the regulation of major histocompatibility complex processing and other functions. Partial but significant overlap was revealed with previous proteomics and transcriptomics studies in CRC. Among various differentiation stage of CRC tissues, we identified calreticulin precursor, MHC class I antigen (human leukocyte antigen A , glutathione S-transferase pi1, keratin 8, heat shock protein 27, tubulin beta chain, triosephosphate, fatty acid-binding protein, hemoglobin (deoxy mutant with val b 1 replaced by met (HBB, and zinc finger protein 312 (FEZF2. Conclusions: Their functional networks were analyzed by Ingenuity systems Ingenuity Pathways Analysis and revealed the potential roles as novel biomarkers for progression in various differentiation stages of CRC.

  10. THE EXPRESSION AND CLINICAL SIGNIFICANCE OF P21 (WAF1/CIP1)AND CYCLIN D1 PROTEIN IN COLORECTAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To study the effect of P21 (WAF1/CIP1) and cyclin D1 and their relationship in colorec- tal carcinoma. Methods The expression of P21 and cyclin D1 was studied in 40 colorectal carcinoma and 10 normal tissues using S-P immunohistochemical technique. Results Decreased expression of P12 and overexpression of cyclin D1 were revealed in colorectal carcinoma. Decreased expression of P21 was related to lymph node metastasis. No cor- relation was found between cyclin D1 and clinicopathological parameters. Conclusion Decreased expression of P21 and overexpression of cyclin D1 may be involved in colorectal tumorigenesis,and were associated with poor prognosis. No correlation was found between P21 and cyclin D1 in colorectai carcinoma.

  11. PET and PET/CT imaging for the earliest detection and treatment of colorectal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Carter, Kevin [Michigan State Univ., Pontiac, MI (United States). POH Medical Center; Kotlyarov, Eduard [Michigan State Univ., Pontiac, MI (United States). POH Medical Center; Georgetown Univ. (United States)

    2005-10-15

    Approximately 150,000 new cases of colorectal cancer are diagnosed each year with the life time risk of developing colon caner in developed nations being 4.6% in men and 3.2% in women. Screening patients is essential early detection of colon carcinoma to aid in complete resection. Unfortunately current screening methods carry with them poor patient compliance. PET and PET/CT may be a significant part of this screening solution. The authors reviewed and analyzed the English language articles and case reports identified on Medline during the last 10 years. PET and PET/CT results for colorectal carcinoma were tabulated and presented for the fifth Scientific Meeting of the Brazilian Society of Nuclear Biosciences. Though most studies have been retrospective analysis in using PET for staging for other malignant processes the cases that have identified additional uptake in the colon are important. The accuracy when utilizing PET and PET/CT in this screening method has a sensitivity between 65 and 90% with a specificity of 84 to 90% and a positive predictive value 71 to 78%. Early stages of malignancies and pre-cancerous polyps avidly accumulates F-18 Deoxyfluoro glucose allowing us to conclude that whole body PET and PET/CT is an essential component in the work up, staging or treatment monitoring in colon carcinoma. We have to continue to accumulate data for possible introduction for whole body PET and PET/CT scanning for colon carcinoma and precancerous polyps.(author)

  12. BRAF V600E mutation detection by immunohistochemistry in colorectal carcinoma.

    Science.gov (United States)

    Affolter, Kajsa; Samowitz, Wade; Tripp, Sheryl; Bronner, Mary P

    2013-08-01

    The serine/threonine-protein kinase B-raf (BRAF) is an oncogene mutated in various neoplasms, including 5-15% of colorectal carcinomas. The T1799A point mutation, responsible for a large majority of these alterations, results in an amino acid substitution (V600E) causing the constitutive activation of a protein kinase cascade. BRAF V600E in MLH1 deficient tumors implicates somatic tumor-only methylation of the MLH1 promoter region instead of a germline MLH1 mutation. BRAF V600E also predicts poor prognosis in microsatellite stable colorectal cancers and may be a marker of resistance to anti-EGFR therapy in metastatic disease. Currently, only molecular methods are available for assessing BRAF mutational status. An immunohistochemical approach is evaluated here. Colon cancers from 2008 to 2012 tested by pyrosequencing for BRAF V600E mutation were selected. A total of 31 tumors with (n = 14) and without (n = 17) the BRAF V600E mutation were analyzed by immunohistochemistry using a commercially available antibody specific to the V600E-mutated protein. All 14 colorectal carcinomas with the BRAF V600E mutation demonstrated cytoplasmic positivity in tumor cells with the anti-BRAF antibody. In a minority of cases, staining intensity for the mutated tumor samples was weak (n = 2) or heterogeneous (n = 4); however, the majority of cases showed diffuse, strong cytoplasmic positivity (8 of 14 cases). None of the 17 BRAF wild-type colorectal cancers showed immunoreactivity to the antibody. The overall sensitivity and specificity of the immunohistochemical BRAF V600E assay was 100%. Detection of the BRAF V600E mutation in colorectal cancer by immunohistochemistry is a viable alternative to molecular methods.

  13. Antitumor effects and radiosensitization of cytosine deaminase and thymidine kinase fusion suicide gene on colorectal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    De-Hua Wu; Li Liu; Long-Hua Chen

    2005-01-01

    AIM: To investigate the killing effect and radiosensitization of double suicide gene mediated by adenovirus on colorectal carcinoma cells.METHODS: Colorectal carcinoma cell line SW480 was transfected with adenovirus expression vector containing cytosine deaminase (CD) and thymidine kinase (Tk) fusion gene. The expression of CD-TK fusion gene was detected by reverse transcriptase-polymerase chain reaction. The toxic effect of ganciclovir (GCV) and 5-fiuorocytosine (5FC) on infected cells was determined by MTT assay. The radiosensitization of double suicide gene was evaluated by clonogenic assay.RESULTS: After prodrugs were used, the survival rate of colorectal carcinoma cells was markedly decreased. When GCV and 5-FC were used in combination, the cytotoxicity and bystandereffect were markedly superior to a single prodrug (x2 = 30.371, P<0.01). Both GCV and 5-FC could sensitize colorectal carcinoma cells to the toxic effect of radiation, and greater radiosensitization was achieved when both prodrug were used in combination. CONCLUSION: CD-TK double suicide gene can kill and radiosensitize colorectal carcinoma cells.

  14. Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma

    Directory of Open Access Journals (Sweden)

    Marios Giannakis

    2016-04-01

    Full Text Available Large-scale genomic characterization of tumors from prospective cohort studies may yield new insights into cancer pathogenesis. We performed whole-exome sequencing of 619 incident colorectal cancers (CRCs and integrated the results with tumor immunity, pathology, and survival data. We identified recurrently mutated genes in CRC, such as BCL9L, RBM10, CTCF, and KLF5, that were not previously appreciated in this disease. Furthermore, we investigated the genomic correlates of immune-cell infiltration and found that higher neoantigen load was positively associated with overall lymphocytic infiltration, tumor-infiltrating lymphocytes (TILs, memory T cells, and CRC-specific survival. The association with TILs was evident even within microsatellite-stable tumors. We also found positive selection of mutations in HLA genes and other components of the antigen-processing machinery in TIL-rich tumors. These results may inform immunotherapeutic approaches in CRC. More generally, this study demonstrates a framework for future integrative molecular epidemiology research in colorectal and other malignancies.

  15. Morphological and quantitative analysis of BCL6 expression in human colorectal carcinogenesis.

    Science.gov (United States)

    Sena, Paola; Mariani, Francesco; Benincasa, Marta; De Leon, Maurizio Ponz; Di Gregorio, Carmela; Mancini, Stefano; Cavani, Francesco; Smargiassi, Alberto; Palumbo, Carla; Roncucci, Luca

    2014-01-01

    The aim of the present study was to determine whether BCL6 is expressed during malignant transformation of the large bowel and to assess whether, and to what extent, immunoreactivity is related to the different stages of neoplastic progression. Samples of normal colorectal mucosa (n=22), microadenomas (n=22) and colorectal cancer (n=22), were analyzed by immunohistochemistry, immunofluorescence coupled with confocal microscopy and western blotting. Our results clearly outlined the marked increase occurring in both intensity and density of BCL6 protein expression in the normal mucosa-microadenoma-carcinoma sequence. Immunohistochemistry and immunofluorescence analyses showed that BCL6 is expressed at low levels in normal mucosa and increases in microadenoma and in cancer with statistical significance. These results were confirmed by western blotting data. The increasing expression of BCL6 in human colorectal cancer development suggests the involvement of BCL6 in tumor progression, from the earliest stages of carcinogenesis with significant increase in cancer. The enhanced understanding of the biological role of BCL6, previously shown to exert a key role in lymphomagenesis, may lead to a re-evaluation of this protein and may highlight the importance of performing further studies in order to identify novel therapeutic targets for colorectal cancer.

  16. Assessment of BRAF V600E Status in Colorectal Carcinoma: Tissue-Specific Discordances between Immunohistochemistry and Sequencing.

    Science.gov (United States)

    Estrella, Jeannelyn S; Tetzlaff, Michael T; Bassett, Roland L; Patel, Keyur P; Williams, Michelle D; Curry, Jonathan L; Rashid, Asif; Hamilton, Stanley R; Broaddus, Russell R

    2015-12-01

    Although sequencing provides the gold standard for identifying colorectal carcinoma with BRAF V600E mutation, immunohistochemistry (IHC) with the recently developed mouse monoclonal antibody VE1 for BRAF V600E protein has shown promise as a more widely available and rapid method. However, we identified anecdotal discordance between VE1 IHC and sequencing results and therefore analyzed VE1 staining by two different IHC methods (Leica Bond and Ventana BenchMark) in whole tissue sections from 480 colorectal carcinomas (323 BRAF wild-type, 142 BRAF V600E mutation, and 15 BRAF non-V600E mutation). We also compared the results with melanomas and papillary thyroid carcinomas (PTC). With the Bond method, among 142 BRAF V600E-mutated colorectal carcinomas, 77 (54%) had diffuse VE1 staining and 48 (33%) had heterogeneous staining, but 17 (12%) were negative. Among 323 BRAF wild-type colorectal carcinomas, 196 (61%) were negative, but 127 (39%) had staining, including 7 with diffuse staining. When positivity was defined as staining in ≥ 20% of tumor cells, VE1 IHC had sensitivity of 75% and specificity of 93% for BRAF V600E mutation. With the Ventana method, among 57 BRAF V600E-mutated colorectal carcinomas, 36 (63%) had diffuse VE1 staining, whereas 6 (11%) had no or weak (Ventana VE1 IHC in melanoma and PTC were highly concordant with sequencing results. We conclude that VE1 IHC produces suboptimal results in colorectal carcinoma and should not be used to guide patient management.

  17. 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.

  18. Immunohistochemical analysis of p53 and ras p21 expression in colorectal adenomas and early carcinomas.

    Science.gov (United States)

    Ieda, S; Watatani, M; Yoshida, T; Kuroda, K; Inui, H; Yasutomi, M

    1996-01-01

    To further investigate whether multiple genetic changes are involved in the development of colorectal cancer, we performed an immunohistochemical analysis of p53 and ras p21 protein expression in 139 specimens of colorectal adenoma with varying degrees of dysplasia, 57 specimens of early cancer with an adenomatous component, and 12 specimens of superficial early cancer without any adenomatous component. Positive p53 staining was found in 15% of the adenomas with moderate dysplasia and in 42% of the adenomas with severe dysplasia or intramucosal carcinoma (IMCA). Positive immunostaining of p53 was observed to be significantly correlated with the degree of dysplasia and the depth of invasion, as was the expression of ras p21. However, a closer correlation was observed with the increasing size of the adenomas. Furthermore, p53 staining was positive in 42% of the 12 superficial early cancer specimens, while ras staining was positive in only 1 specimen (8%). These results indicate that p53 gene overexpression may play some biological role in both the adenoma-to-carcinoma sequence and in de novo cancer development, whereas ras p21 expression may not be as involved in de novo cancer development as in the malignant conversion of colorectal adenomas.

  19. 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.

  20. 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 (pbeta-catenin, axin 1 and GSK3β proteins indicated that the destruction complex of beta-catenin was maintained, while in colorectal carcinoma, the increased expression of beta-catenin, GSK3β, axin 1, and ubiquitin proteins indicated that the destruction complex of beta-catenin was disrupted. Avaliar o complexo de destruição da betacatenina no carcinoma colorretal e no adenoma do colo pela expressão das proteínas betacatenina, adenomatous polyposis coli, GSK3β, axina e ubiquitina. Amostras de tecidos de 64 doentes com carcinoma colorretal e de 53 pacientes com adenoma do colo foram analisadas. Blocos de tecidos foram submetidos ao estudo imuno-histoquímico com anticorpos policlonais nos tecidos do carcinoma, mucosa não neoplásica adjacente e adenoma. A imunorreatividade foi avaliada pela porcentagem de positividade de células coradas e pela intensidade do grau de coloração das proteínas no citoplasma e no núcleo das células. Na análise estatística, foram

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

    Directory of Open Access Journals (Sweden)

    David Omoareghan Irabor

    2011-01-01

    Full Text Available 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 Pubmed, 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.

  2. Glasgow Prognostic Score (GPS) can be a useful indicator to determine prognosis of patients with colorectal carcinoma.

    Science.gov (United States)

    Nozoe, Tadahiro; Matono, Rumi; Ijichi, Hideki; Ohga, Takefumi; Ezaki, Takahiro

    2014-01-01

    The Glasgow Prognostic Score (GPS), an inflammation-based score, has been used to predict the biologic behavior of malignant tumors. The aim of the current study was to elucidate a further significance of GPS in colorectal carcinoma. Correlation of GPS and modified GPS (mGPS), which are composed of combined score provided for serum elevation of C-reactive protein and hypoalbuminemia examined before surgical treatment, with clinicopathologic features was investigated in 272 patients with colorectal carcinoma. Survival of GPS 1 patients was significantly worse than that of GPS 0 patients (P= 0.009), and survival of GPS 2 patients was significantly worse than that of GPS 1 patients (P GPS (P GPS and mGPS could classify outcome of patients with a clear stratification, and could be applied as prognostic indicators in colorectal carcinoma.

  3. THE APOPTOSIS OF EXPERIMENTAL COLORECTAL CARCINOMA CELLS INDUCED BY PEPTIDOGLYCAN OF BIFIDOBACTERIUM AND THE EXPRESSION OF APOPTOTIC REGULATING GENES

    Institute of Scientific and Technical Information of China (English)

    WANG Li-sheng; PAN Ling-jia; SHI Li; SUN Yong; ZHANG Ya-li; ZHOU Dian-yuan

    1999-01-01

    Objective: To explore the antitumor mechanisms of whole peptidoglycan of bifidobacterium. Methods: The apoptotic cells and the positive expression of bcl-2 and bax oncoprotein were studied nude mice transplantation tumors of colorectal carcinoma by employing in situ end labeling technique and immunohistochemical staining. Results:The apoptotic cell density, the positive rate and the staining intensity of bax oncoprotein of the transplantation tumor of colorectal carcinoma in the whole peptidoglycan injection group were significantly higher when compared with the tumor control group. The positive rate of bcl-2 oncoprotein in the whole peptidoglycan injection group was obviously lower than that in the tumor control group (P<0.01).Conclusion: Whole peptidoglycan of Bifidobacterium bifidum could induce cell apoptosis of nude mice transplantation tumors of colorectal carcinoma by downregulating the expression of the bcl-2 gene and upregulating the expression of the bax gene.

  4. Thrombocytosis portends adverse prognostic significance in patients with stage II colorectal carcinoma

    DEFF Research Database (Denmark)

    Guo, Tianhua; Krzystanek, Marcin; Szallasi, Zoltan Imre

    2014-01-01

    Thrombocytosis portends adverse prognostic significance in many types of cancers including ovarian and lung carcinoma. In this study, we determined the prevalence and prognostic significance of thrombocytosis (defined as platelet count in excess of 400 K/μl) in patients with colorectal cancer. We...... concluded that thrombocytosis at diagnosis indicates adverse clinical outcome in colorectal cancer patients with stage II or III disease. This observation is especially intriguing in stage II patients because the clinical management of these patients is controversial. If our data are confirmed in larger...... with stage III and IV disease (14.4% of patients). Although the mean platelet count increased with the depth of tumor invasion (pT), its values remained within normal limits in the whole patient cohort. No patient with stage I cancer (n=57) had elevated platelet count at diagnosis. By contrast, five...

  5. Colorectal carcinoma in a patient with prior breast cancer: Is there a causal link?

    Energy Technology Data Exchange (ETDEWEB)

    Scarles, Elaine [Blackpool Victoria Hospital, Blackpool, Lancashire FY3 8NR (United Kingdom); Nightingale, Julie [Department of Radiography, School of Health Care Professions, University of Salford, Salford, Greater Manchester, M6 6PU (United Kingdom)], E-mail: j.nightingale@salford.ac.uk

    2008-02-15

    A 70-year-old female patient with prior breast cancer was diagnosed with colorectal carcinoma six years following the original breast referral. The cancers were both discovered at an early stage enabling potentially curative surgery to be performed, with an associated good long-term prognosis. This article explores a range of cancer risk factors associated with lifestyle, genetics and medication to ascertain whether the two primary cancers were independent oncological events, or whether they were related. Factors such as smoking, alcohol consumption, genetic predisposition and the use of contraceptives and Tamoxifen may increase the relative risk for both cancers. Various studies have offered conflicting data regarding the relative risk for developing the second cancer, but long-term cohort studies will continue to add to the evidence base. It is possible that the outcomes of these studies may have implications for the follow up of breast cancer patients within the colorectal cancer screening service.

  6. Relationship Between β -Catenin Expression and Prognostic Parameters of Colorectal Carcinomas

    Directory of Open Access Journals (Sweden)

    Kemal PEKER

    2013-01-01

    Full Text Available Objective: Colorectal carcinomas are the most frequent tumors of the gastrointestinal tract. β-catenin, which is related to cadherins, is a cytoplasmic protein responsible for intercellular adhesion. It is also an important component in the Wnt signal pathway. Recent studies have shown structural alterations in the APC gene and axin in patients with colorectal carcinoma, along with β-catenin. We aimed to compare β-catenin expression, which is a prognostic factor itself, with other prognostic parameters.Material and Method: A total of 70 patients who had surgical intervention for colorectal malignancies between January 1994 and December 2003 were included in the study. Fift y-nine of the patients (84.3% were male, 11 of the patients (15.7% were female; their ages varied between 24 and 82 (mean 60.3 ±15.2 years. Paraff in blocks were immunohistochemically stained for β-catenin. The number of stained cell nuclei was assessed according to the stage of disease using the TNM classification, histological grade, lymphatic invasion, vascular invasion and tumor's local invasion.Results: When groups constituted according to tumor histologic grade were compared for prognostic parameters in terms of stain density for β-catenin and number of stained cell nuclei, stain density was mild (+ and the number of stained nuclei was smaller in well-diff erentiated groups while stain density was strong (+++ and the number of stained nuclei was higher in poorly diff erentiated groups. There was a relation between β-catenin expression and diff erentiation grade, lymph node metastasis, stage and tumor size but not with vascular invasion.Conclusion: These data indicate that β- catenin, with functions in cell homeostasis and relations with the APC gene, has a substantial role in colorectal carcinogenesis.

  7. [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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

    AIM: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. METHODS: Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were eletrophoresed 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 . RESULTS: 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 (< 30%) by detailed deletion mapping. Significant opposite difference was observed between LOH frequency and tumor diameter on D4S412 and D4S1546 locus (0% vs 16.67%, P = 0.041; 54.55% vs 11.11%, P = 0.034, respectively). On D4S403 locus, LOH was significantly associated with tumor gross pattern (11.11%, 0, 33.33%, P = 0.030). No relationship was detected on other loci compared with clinicopathologial features. CONCLUSION: By deletion mapping, two obvious high frequency LOH regions spanning D4S3013 (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).

  9. Tumor suppress genes screening analysis on 4q in sporadic colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Li-Xin Jiang; Jie Xu; Zhao-Wen Wang; Da-Peng Li; Zhi-Hai Peng; Jian-Jun Gao; Lin He; Hai-Tao Zheng

    2008-01-01

    AIM: To search candidate tumor suppressor genes (TSGs) on chromosome 4Cl through detecting high loss of heterozygosity (LOH) regions in sporadic colorectal carcinoma in Chinese patients.METHODS: Thirteen fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by polymerase chain reaction (PCR).PCR products were eletrophoresed on an ABI 377 DNA sequencer.Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis.Comparison between LOH frequency and clinicopathological factors were performed by X2 test.RESULTS: Data were collected on all informative loci.The average LOH frequency on 4q was 28.56%,The D4S2915 locus showed highest LOH frequency (36.17%).Two obvious deletion regions were detected: one between D4S3000 and D4S2915 locus (4q12-21.1),another flanked by D4S407 and D4S2939 locus (4q25-31.1).None case showed complete deletion of 4q,most cases displayed interstitial deletion pattern solely.Furthermore,compared with clinicopathological features,a significant relationship was observed between LOH frequencies on D4S3018 locus.In tumors larger than 5 cm in diameter,LOH frequency was significantly higher than tumors that were less than 5 cm (56% vs 13.79%,P=0.01).On D4S1534 locus,LOH was significantly associated with liver metastasis (80% vs 17.25%,P=0.012).No relationship was detected on other locus compared with clinicopathologial features.CONCLUSION: By high resolution deletion mapping,two high frequency regions of LOH (4q12-21.1 and 4q25-31.1) were detected,which may contribute to locate TSGs on chromosome 4q involved in carcinogenesis and progression of sporadic colorectal carcinoma.

  10. Evaluation of angiogenesis in colorectal carcinoma with multidetector-row CT multislice perfusion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Feng Shiting, E-mail: fst1977@163.co [Department of Radiology, First Affiliated Hospital of SunYat-sen University, Guangzhou 510080 (China); Sun Canhui, E-mail: canhuisun@sina.co [Department of Radiology, First Affiliated Hospital of SunYat-sen University, Guangzhou 510080 (China); Li Ziping, E-mail: liziping163@tom.co [Department of Radiology, First Affiliated Hospital of SunYat-sen University, Guangzhou 510080 (China); Mak, Henry Ka-Fung, E-mail: makkf@hkucc.hku.h [Department of Diagnostic Radiology, University of Hong Kong, Hong Kong (China); Peng Zhenpeng, E-mail: ppzhen@21cn.co [Department of Radiology, First Affiliated Hospital of SunYat-sen University, Guangzhou 510080 (China); Guo Huanyi, E-mail: guohuanyi@163.co [Department of Radiology, First Affiliated Hospital of SunYat-sen University, Guangzhou 510080 (China); Meng Quanfei, E-mail: mzycoco@gmail.co [Department of Radiology, First Affiliated Hospital of SunYat-sen University, Guangzhou 510080 (China)

    2010-08-15

    To evaluate the correlation between 64 multidetector-row CT (64MDCT) perfusion imaging in colorectal carcinoma and microvessel density (MVD) and vascular endothelial growth factor (VEGF), 64MDCT perfusion imaging was performed in 33 patients with pathologically verified colorectal carcinoma. These images were analyzed with perfusion functional software, and time-density curves (TDC) were created for the region of interest (ROI) encompassing the tumor, the target artery and vein. The individual perfusion maps generated indicated blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability-surface area product (PS). MVD and VEGF were evaluated by immunohistochemical staining with anti-CD34 and anti-VEGF, respectively. Correlations between MVD or VEGF with CT perfusion parameters and clinicopathological factors (Dukes' stages, invasion depth, and lymph node and liver metastasis) were also investigated. MVD in the colorectal carcinoma was 22.61 {+-} 9.01 per x200 field. The scores obtained for VEGF expression were 4.15 {+-} 1.09. VEGF staining was positive in 25 of 29 tumors (86.2%). There was no significant correlation between the presence of MVD, VEGF expression and clinicopathological factors (P > 0.05). There was also no correlation between MVD, VEGF expression, and any dynamic CT parameters (P > 0.05). The BV and MTT were significantly higher in tumors demonstrating serous coat invasion than in those without it (t = -2.63, -2.24, P = 0.0137, 0.0331, respectively). BV was also significantly correlated with tumor size (r = 0.41, P = 0.02). Neither BF nor PS was correlated with clinicopathological factors. In conclusion, 64MDCT perfusion imaging, MVD, and VEGF may reflect angiogenic activity, but no significant correlation among these factors.

  11. Photoacoustic tomography of vascular therapy in a preclinical mouse model of colorectal carcinoma

    Science.gov (United States)

    Johnson, S. P.; Ogunlade, O.; Zhang, E.; Laufer, J.; Rajkumar, V.; Pedley, R. B.; Beard, P.

    2014-03-01

    Vascular therapy in oncology exploits the differences between normal blood vessels and abnormal tumour neoangiogenesis to selectively target cancer. For optimal treatment efficacy, and translation of novel compounds, the response of the tumour vasculature needs to be assessed. Photoacoustic tomography (PAT) is capable of this as it provides highly spatially resolved 3D images of vascular networks in biological tissue to cm depths. In preclinical models of cancer this is sufficient to encompass entire subcutaneous tumours, and can therefore be used to evaluate pharmacological intervention directed at the vasculature. In this study the vascular disrupting agent OXi4503 was used to treat subcutaneous tumour mouse models of two human colorectal carcinoma tumour types (SW1222, LS174T) at a range of concentrations (40mg/kg, 10mg/kg, 1mg/kg and sham dose control). The characteristic destruction of tumour vasculature caused by OXi4503 was observed by PAT and confirmed ex vivo via histology. Differences observed between the two tumour types assessed demonstrate the importance of tumour microenvironment and pathophysiology on response to therapy. Differential response to different doses of OXi4503 was observed, with outward tumour growth only seen once entire tumour viability had been re-established; this demonstrates the potential of PAT to act as a biomarker of response for the translation of novel anti-vascular compounds and also within the clinic. This study shows clearly that PAT can accurately assess the time course of drug action and relapse of pharmacodynamic effect in preclinical models of cancer and the important translational prospects for vascular targeted tumour therapies.

  12. 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.

  13. Combination of cetuximab and PP242 synergistically suppress the progression of wild-type KRAS colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Cheng L

    2015-11-01

    Full Text Available Lei Cheng,1,* Zuguang Xia,2,3,* Xinyu Bian,1 Guangchao Li,4 Jing Hu,1 Ya Cao,5 Qing Wang,1 Xiaoping Qian1 1Comprehensive Cancer Center of Drum-Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, 2Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 4School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, Guangdong, 5Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, People’s Republic of China *These authors contributed equally to this work Abstract: Mammalian target of rapamycin (mTOR has been shown to be overactive in human colorectal cancer, but the first-generation mTOR inhibitor, rapamycin, has failed to show clinical efficacy against colorectal cancer. On the other hand, although the second-generation mTOR inhibitor, PP242, has exerted substantial efficacy, it was revealed that independent inhibition by PP242 was transient, which could lead to positive-feedback loop to EGFR. Using wild-type KRAS colorectal cancer cells as models, we investigate the treatment efficacy of a widely used anti-EGFR monoclonal antibody, cetuximab, and PP242, alone or in combination in vitro and in vivo. Results of cell viability assays confirmed the synergistic inhibitory effect of PP242 and cetuximab on the survival of Caco-2 and HT-29 cells. Moreover, the ability of cancer-cell invasion and proliferation was also significantly inhibited by the combination therapy when compared with cetuximab or PP242 alone. Interestingly, the percentage of CD44-positive cancer cells was substantially decreased by the combination therapy in comparison with PP242 alone through fluorescence-activated cell sorting. The growth of cancer stem-like cell spheres in vitro was

  14. Characterizing metabolic changes in human colorectal cancer.

    Science.gov (United States)

    Williams, Michael D; Zhang, Xing; Park, Jeong-Jin; Siems, William F; Gang, David R; Resar, Linda M S; Reeves, Raymond; Hill, Herbert H

    2015-06-01

    Colorectal cancer (CRC) remains a leading cause of cancer death worldwide, despite the fact that it is a curable disease when diagnosed early. The development of new screening methods to aid in early diagnosis or identify precursor lesions at risk for progressing to CRC will be vital to improving the survival rate of individuals predisposed to CRC. Metabolomics is an advancing area that has recently seen numerous applications to the field of cancer research. Altered metabolism has been studied for many years as a means to understand and characterize cancer. However, further work is required to establish standard procedures and improve our ability to identify distinct metabolomic profiles that can be used to diagnose CRC or predict disease progression. The present study demonstrates the use of direct infusion traveling wave ion mobility mass spectrometry to distinguish metabolic profiles from CRC samples and matched non-neoplastic epithelium as well as metastatic and primary tumors at different stages of disease (T1-T4). By directly infusing our samples, the analysis time was reduced significantly, thus increasing the speed and efficiency of this method compared to traditional metabolomics platforms. Partial least squares discriminant analysis was used to visualize differences between the metabolic profiles of sample types and to identify the specific m/z features that led to this differentiation. Identification of the distinct m/z features was made using the human metabolome database. We discovered alterations in fatty acid biosynthesis and oxidative, glycolytic, and polyamine pathways that distinguish tumors from non-malignant colonic epithelium as well as various stages of CRC. Although further studies are needed, our results indicate that colonic epithelial cells undergo metabolic reprogramming during their evolution to CRC, and the distinct metabolites could serve as diagnostic tools or potential targets in therapy or primary prevention. Graphical Abstract

  15. Expression of Interleukin-11 and Interleukin-11 receptor in human colorectal adenocarcinoma; Immunohistochemical analyses and correlation with clinicopathological factors

    Institute of Scientific and Technical Information of China (English)

    Kazuyuki Yamazumi; Toshiyuki Nakayama; Takafumi Kusaba; Chun Yang Wen; Ayumi Yoshizaki; Yuichi Yakata; Takeshi Nagayasu; Ichiro Sekine

    2006-01-01

    AIM: There is strong evidence that interleukin-11 (IL-11)is involved in the regulation of tumor progression, cellular growth and differentiation. Recently, interleukin-11receptor (IL-11R) has been detected on some cancer cells. In this study, we investigated the expression of IL-11 and IL-11R in colorectal adenocarcinoma.METHODS: To elucidate the involvement of IL-11 and IL-11Rα in human intestinal adenocarcinomas, we examined 115 cases of surgically resected human colonic adenocarcinoma and 11 cases of adenoma by immunohistochemistry and Western blotting.RESULTS: Among 115 cases of adenocarcinoma, 100cases (87.0%) showed positive staining in the cytoplasm of carcinoma cells for the IL-11, and 87 cases (75.6%)were positive for the IL-11Rα. Six cases (54.5%) and four cases (36.4%) of 11 adenomas were positive for IL-11 and IL-11Rα, respectively. The expression of IL-11Rα correlated with the histological differentiation (P =0.033503), the depth of tumor invasion (P= 0.006395),Dukes classification (P= 0.015648) and lymphatic invasion (P=0.003865). However, the expression of IL-11Rα was not correlated with the venous invasion and the presence of lymph node metastasis. The expression of IL-11 was not correlated with any clinicopathological factors. In Western blot analysis, two human colorectal carcinoma cell lines and four tissues of surgically resected human carcinoma expressed both IL-11 and IL-11Rαproteins.CONCLUSION: IL-11 and IL-11Rα are highly expressed in human colorectal adenocarcinoma and the IL-11Rα expression is correlated with clinicopathological factors.These findings suggest that the expression of IL-11Rα is an important factor for the invasion of human colorectal adenocarcinoma.

  16. Potentiation of 5-fluorouracil encapsulated in zeolites as drug delivery systems for in vitro models of colorectal carcinoma.

    Science.gov (United States)

    Vilaça, Natália; Amorim, Ricardo; Machado, Ana F; Parpot, Pier; Pereira, Manuel F R; Sardo, Mariana; Rocha, João; Fonseca, António M; Neves, Isabel C; Baltazar, Fátima

    2013-12-01

    The studies of potentiation of 5-fluorouracil (5-FU), a traditional drug used in the treatment of several cancers, including colorectal (CRC), were carried out with zeolites Faujasite in the sodium form, with different particle sizes (NaY, 700nm and nanoNaY, 150nm) and Linde type L in the potassium form (LTL) with a particle size of 80nm. 5-FU was loaded into zeolites by liquid-phase adsorption. Characterization by spectroscopic techniques (FTIR, (1)H NMR and (13)C and (27)Al solid-state MAS NMR), chemical analysis, thermal analysis (TGA), nitrogen adsorption isotherms and scanning electron microscopy (SEM), demonstrated the successful loading of 5-FU into the zeolite hosts. In vitro drug release studies (PBS buffer pH 7.4, 37°C) revealed the release of 80-90% of 5-FU in the first 10min. To ascertain the drug release kinetics, the release profiles were fitted to zero-order, first-order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas and Weibull kinetic models. The in vitro dissolution from the drug delivery systems (DDS) was explained by the Weibull model. The DDS efficacy was evaluated using two human colorectal carcinoma cell lines, HCT-15 and RKO. Unloaded zeolites presented no toxicity to both cancer cells, while all DDS allowed an important potentiation of the 5-FU effect on the cell viability. Immunofluorescence studies provided evidence for zeolite-cell internalization.

  17. The expression and clinical signiifcance of Galectin­3 and MMP­2, TIMP­2 in human colorectal carcinoma%大肠癌组织中Galectin-3与MMP-2、TIMP-2的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    李英健; 赵恩宏; 苏锐; 侯雷; 刘志满; 申兴斌

    2014-01-01

    ObjectiveTo study the expression of Galectin-3 and MMP-2, TIMP-2 in colorectal carcinoma, and to investigate its in colorectal cancer progression of meaning in the course.MethodTo detect the expression of Galectin-3 and MMP-2,TIMP-2 in 52 cases of colorectal cancer, 20 cases of colorectal adenoma and 20 cases of colorectal normal mucosa tissue through the application of immunohistochemistry. Analyzed the relationship between its expression with the patient’s sex, age, tumor location, tumor differentiation, inifltration and lymph node metastasi.Result ①In colorectal carcinoma, the expression of Galectin-3 and MMP-2 were highest and the expression of TIMP-2 was lowest;②In inifltration over the muscle layer of the colorectal carcinoma and in poorly differentiated colorectal carcinoma and in lymph node metastasis of colorectal cancer tissues, the expression of Galectin-3 and MMP-2 were higher and the expression of TIMP-2 was lower;③The expression of Galectin-3 and MMP-2 were positive correlation and the expression of Galectin-3 and TIMP-2 were negative correlation in colorectal carcinoma.ConclusionThe imbalance expression of Galectin-3, MMP-2 and TIMP-2 is positive corrrelated with the invasion and metastasis of colorectal carcinoma.%目的:研究半乳糖凝集素-3(Galectin-3)与基质金属蛋白酶-2(MMP-2)、组织基质金属蛋白酶抑制剂-2(TIMP-2)在大肠癌中的表达,并探讨其在大肠癌进展过程中的意义。方法应用免疫组化法检测52例大肠癌组织、20例大肠腺瘤和20例大肠正常黏膜组织中Galectin-3与MMP-2、TIMP-2的表达情况。结果①Galectin-3、MMP-2在大肠癌中的阳性表达率最高,而TIMP-2在大肠癌中的阳性表达率最低;②大肠癌组织中,浸润程度深、低分化及有淋巴结转移的Galectin-3、MMP-2的表达明显升高,而TIMP-2的表达则明显降低;③在大肠癌组织中Galectin-3与MMP-2的表达呈正相关,而与TIMP-2的

  18. Identification of differentially expressed circular RNAs in human colorectal cancer.

    Science.gov (United States)

    Zhang, Peili; Zuo, Zhigui; Shang, Wenjing; Wu, Aihua; Bi, Ruichun; Wu, Jianbo; Li, Shaotang; Sun, Xuecheng; Jiang, Lei

    2017-03-01

    Circular RNA, a class of non-coding RNA, is a new group of RNAs and is related to tumorigenesis. Circular RNAs are suggested to be ideal candidate biomarkers with potential diagnostic and therapeutic implications. However, little is known about their expression in human colorectal cancer. In our study, differentially expressed circular RNAs were detected using circular RNA array in paired tumor and adjacent non-tumorous tissues from six colorectal cancer patients. Expression levels of selected circular RNAs (hsa_circRNA_103809 and hsa_circRNA_104700) were measured by real-time polymerase chain reaction in 170 paired colorectal cancer samples for validation. Statistical analyses were conducted to investigate the association between hsa_circRNA_103809 and hsa_circRNA_104700 expression levels and respective patient clinicopathological features. Receiver operating characteristic curve was constructed to evaluate the diagnostic values. Our results indicated that there were 125 downregulated and 76 upregulated circular RNAs in colorectal cancer tissues compared with normal tissues. We also first demonstrated that the expression levels of hsa_circRNA_103809 ( p colorectal cancer than in normal tissues. The expression level of hsa_circRNA_103809 was significantly correlated with lymph node metastasis ( p = 0.021) and tumor-node-metastasis stage ( p = 0.011), and the expression level of hsa_circRNA_104700 was significantly correlated with distal metastasis ( p = 0.036). The area under receiver operating characteristic curves of hsa_circRNA_103809 and hsa_circRNA_104700 were 0.699 ( p colorectal cancer and serve as potential biomarkers for the diagnosis of colorectal cancer.

  19. α-Mangostin Enhances Betulinic Acid Cytotoxicity and Inhibits Cisplatin Cytotoxicity on HCT 116 Colorectal Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Amin Malik Shah Abdul Majid

    2012-03-01

    Full Text Available Despite the progress in colon cancer treatment, relapse is still a major obstacle. Hence, new drugs or drug combinations are required in the battle against colon cancer. α-Mangostin and betulinic acid (BA are cytotoxic compounds that work by inducing the mitochondrial apoptosis pathway, and cisplatin is one of the most potent broad spectrum anti-tumor agents. This study aims to investigate the enhancement of BA cytotoxicity by α-mangostin, and the cytoprotection effect of α-mangostin and BA on cisplatin-induced cytotoxicity on HCT 116 human colorectal carcinoma cells. Cytotoxicity was investigated by the XTT cell proliferation test, and the apoptotic effects were investigated on early and late markers including caspases-3/7, mitochondrial membrane potential, cytoplasmic shrinkage, and chromatin condensation. The effect of α-mangostin on four signalling pathways was also investigated by the luciferase assay. α-Mangostin and BA were more cytotoxic to the colon cancer cells than to the normal colonic cells, and both compounds showed a cytoprotective effect against cisplatin-induced cytotoxicity. On the other hand, α-mangostin enhanced the cytotoxic and apoptotic effects of BA. Combination therapy hits multiple targets, which may improve the overall response to the treatment, and may reduce the likelihood of developing drug resistance by the tumor cells. Therefore, α-mangostin and BA may provide a novel combination for the treatment of colorectal carcinoma. The cytoprotective effect of the compounds against cisplatin-induced cytotoxicity may find applications as chemopreventive agents against carcinogens, irradiation and oxidative stress, or to neutralize cisplatin side effects.

  20. Effect of phytic acid and inositol on the proliferation and apoptosis of cells derived from colorectal carcinoma.

    Science.gov (United States)

    Schröterová, L; Hasková, P; Rudolf, E; Cervinka, M

    2010-03-01

    We characterized the effect of phytic acid (inositol hexaphosphate, IP6) as a potential adjuvant in treatment of colorectal carcinoma and evaluated the optimal concentration and treatment time to produe the maximal therapeutic effect. There is some evidence that myoinositol (Ins) can potentiate anti-cancer effects of IP6. Therefore, we tested both IP6 and Ins individually and in combination on human cell lines HT-29, SW-480 and SW-620 derived from colorectal carcinoma in different stages of malignancy. The effect of tested chemicals on the cells was measured using metabolic activity assay (WST-1), DNA synthesis assay (BrdU), protein synthesis assay (Brilliant Blue) and apoptosis (caspase-3 activity). We tested IP6 and Ins at three concentrations: 0.2, 1 and 5 mM for 24, 48 and 72 h. The concentrations and incubation periods were chosen according to low toxicity of the tested substance that was observed in a long-term clinical study. We found that all employed concentrations of IP6 or IP6/Ins decreased proliferation of the cell lines, with the maximum decrease being observed in HT-29 cells. Metabolic activity of treated cells differed in response to IP6 and IP6/Ins treatment; in HT-29 and SW-620 significant decrease was observed only at the highest concentration, whereas in SW-480 cells metabolic activity was lower at each concentration except 0.2 and 1 mM IP6 or IP6/Ins in 24-h incubation. The results from protein content assay corresponded to the results obtained from WST assay. In addition, we found maximum increase in caspase-3 activity at concentration 5 mM IP6 or IP6/Ins in HT-29 cells and with IP6 at concentration of 0.2 mM or IP6/Ins in SW-480 cells with clear indication of Ins enhancing the proapoptotic effect of IP6 in all the cell lines studied.

  1. Clinical impact of PAI 1 4G/5G gene polymorphism in colorectal carcinoma patients.

    Science.gov (United States)

    Halamkova, J; Kiss, I; Pavlovsky, Z; Tomasek, J; Jarkovsky, J; Cech, Z; Bednarova, D; Tucek, S; Hanakova, L; Moulis, M; Zavrelova, J; Man, M; Benda, P; Robek, O; Kala, Z; Penka, M

    2013-01-01

    Plasminogen activator ihnibitor (PAI 1) belongs to the plasminogen activator system, which is part of the metastatic cascade and significantly contributes to invasive growth and angiogenesis of malignant tumors. Its plasma level is normally low but 4G/4G homozygotes have higher concentrations of PAI 1. This genotype may be associated with worse prognosis and proximal location of colorectal cancer than 5G/5G homozygotes. In our prospective evaluation we examined plasma level PAI 1 (using photometric microplate method ELISA) pre-surgery and, subsequently, 6-8 weeks later, from 80 patients. For the PAI 1 rs1799889 -675 4G/5G polymorphism test the PCR amplification was used.Analysis of collected data was confirmed that significantly higher plasma levels of PAI 1 were found in patients before starting therapy, which decreased (p=0.004) after initiation of treatment. Patients with higher plasma level PAI 1 before (p=0.013) and after therapy (p=0.004) had significantly shorter survival. We found no relationship between polymorphisms of PAI 1 (-675 4G/5G) in relation to stage, survival or tumor location. PAI 1 is useful as a negative marker of prognosis and could be advantageous when planning adjuvant treatment of patients with colorectal carcinoma. Although opinions on the importance of polymorphisms of PAI 1 in relation to the prognosis are not uniform, it does seem that their role in the prognosis of patients with colorectal cancer is not essential.

  2. Consumption of Red/Processed Meat and Colorectal Carcinoma: Possible Mechanisms Underlying the Significant Association.

    Science.gov (United States)

    Hammerling, Ulf; Bergman Laurila, Jonas; Grafström, Roland; Ilbäck, Nils-Gunnar

    2016-01-01

    Epidemiology and experimental studies provide an overwhelming support of the notion that diets high in red or processed meat accompany an elevated risk of developing pre-neoplastic colorectal adenoma and frank colorectal carcinoma (CRC). The underlying mechanisms are disputed; thus several hypotheses have been proposed. A large body of reports converges, however, on haem and nitrosyl haem as major contributors to the CRC development, presumably acting through various mechanisms. Apart from a potentially higher intestinal mutagenic load among consumers on a diet rich in red/processed meat, other mechanisms involving subtle interference with colorectal stem/progenitor cell survival or maturation are likewise at play. From an overarching perspective, suggested candidate mechanisms for red/processed meat-induced CRC appear as three partly overlapping tenets: (i) increased N-nitrosation/oxidative load leading to DNA adducts and lipid peroxidation in the intestinal epithelium, (ii) proliferative stimulation of the epithelium through haem or food-derived metabolites that either act directly or subsequent to conversion, and (iii) higher inflammatory response, which may trigger a wide cascade of pro-malignant processes. In this review, we summarize and discuss major findings of the area in the context of potentially pertinent mechanisms underlying the above-mentioned association between consumption of red/processed meat and increased risk of developing CRC.

  3. Aberrant cytological localization of p16 and CDK4 in colorectal epithelia in the normal adenoma carcinoma sequence

    Institute of Scientific and Technical Information of China (English)

    Po Zhao; Xin Mao; Ian C Talbot

    2006-01-01

    AIM: To study the correlation between the patterns of subcellular expression of p16 and CDK4 in colorectal epithelia in the normal-adenoma-carcinoma sequence.METHODS: Paraffin sections of 43 cases of normal colorectal epithelia and corresponding adenomas as well as carcinomas were analysed immunocytochemically for subcellular expression of p16 and CDK4 proteins.RESULTS: Most carcinomas showed more cytoplasmic overexpression for p16 and CDK4 than the adenomas from which they arised or the adjacent normal mucosa.Most normal or non-neoplastic epithelia showed more p16 and CDK4 expression in the nucleus than their adjacent adenomas and carcinomas. There was a significant difference between the subcellular expression pattern of p16 and CDK4 in normal-adenoma-carcinoma sequence epithelia (P < 0.001). Neither p16 nor CDK4 subcellular patterns correlated with histological grade or Dukes' stage.CONCLUSION: Interaction of expression of p16 and CDK4 plays an important role in the Rb/p16 pathway.Overexpression of p16 and CDK4 in the cytoplasm, as well as loss expression of p16 in the nucleus might be important in the evolution of colorectal carcinoma from adenoma and, of adenoma from normal epithelia.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ng, C.S.; Dixon, A.K. [Department of Radiology, Addenbrooke' s NHS Trust and the University of Cambridge, Cambridge (United Kingdom); Doyle, T.C.; Courtney, H.M.; Bull, R.K.; Freeman, A.H. [Department of Radiology, Addenbrooke' s NHS Trust, Cambridge (United Kingdom); Pinto, E.M.; Prevost, A.T. [Department of Public Health and Primary Care, Institute of Public Health, Cambridge (United Kingdom); Campbell, G.A. [Department of Medicine for the Elderly, Addenbrooke' s NHS Trust, Cambridge (United Kingdom)

    2002-12-01

    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.)

  5. Expression of p27 and Its Clinical Significance in Colorectal Carcinomas

    Institute of Scientific and Technical Information of China (English)

    ZHAOJianguo; WUAiguo; 等

    2002-01-01

    Objective To investigate the significance of p27 expression in colorectal carcinomas(CRCsa).Methods The samples were obtained from 44 cases.P27 expression was detected by immunohistochemisty using the SABC staining method at the three sites:carcinoma tissue,pericarcinoma(1 cm away from CRC)and the incision margin(3 cm away from CRC).Results Expression of p27 was found in 56.82%(25/44)of CRCs,in 88.64%(39/44) of percarcinoma and and in 97.73%(43/44)of the mucosa at the incison margin.P27 expression in CRCs was correlated significantly with Dukes stage(P<0.05), histology grade(P<0.01)and local lymph node involvement(P<0.05),but not with age,gender,and site or size of the CRC.Conclusion The decrease of p27 expression may be involoved in the malignant transformation of colorectal epithelial cells to CRC.Expression of p27 in CRC correlates with some clinicopathological characteristices and may be of prognostic significance.

  6. Decreasing Pin1 suppresses telomerase activity by NF-κB in HCT116 cells colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jianwen Sun; Lijun Fan; Meining Li; Yuehong Zhang; Niuliang Cheng

    2013-01-01

    Objective: The aim of our study was to investigate the effect of Pin1 on the telomerase activity in human colorectal carcinoma HCT116 cells. Methods: Firstly, we transfected plasmid pGenesil-1-Pin1 (p-shRNA) using liposome (Lipofectamine 2000) into colorectal cancer HCT-116 cells to down-regulate the expression of Pin1. To detect the apoptotic rate of HCT116 cells was by cytometry (FCM). The expression of Pin1 and hTERT at RNA levels in human colorectal cancer HCT116 cells were determined by RT-PCR. To evaluate the activity of telomerase was by TRAP-silver staining. The subcellular localization and accumulative level of p-NF-κB/p65 protein at the nuclear was detected by Immunofluorescence and Western blotting. The DNA-binding activity of NF-κB/p65 was detected by electrophoretic mobility shift assay (EMSA). Results: Using liposome into colorectal cancer HCT-116 cells, and down-regulate the expression of Pin1 (0.392 ± 0.072-fold; P = 0.001), and the apoptotic rate was increased (11.40% ± 1.54%; P < 0.05). Compared with transfected p-CON cell group, in transfected p-shRNA cell group, the transcription of hTERT was lower (0.171 ± 0.060-fold; P = 0.001) by quantitative real-time RT-PCR, and the results of TRAP-silver staining analysis suggested that the telomerase activity was significantly declined (0.384 ± 0.015-fold; P < 0.05). Furthermore, it was demonstrated by Immunofluorescence that p-NF-κB/p65 had a nuclear localization, and the level of p-NF-κB/p65 protein at the nuclear was reduced with silencing the expression of Pin1 by Western blotting. Using EMSA, it was suggested that NF-κB/p65 was able to bind to hTERT promoter, and the direct interaction was declined with silencing the expression of Pin1. Conclusion: Taken together, silencing Pin1 may suppress activity of telomerase and the expression of hTERT by inhibiting NF-κB/p65 activity and reducing the combination of NF-κB/p65 and hTERT gene promoter.

  7. Quantitative analysis of gene expression in fixed colorectal carcinoma samples as a method for biomarker validation

    Science.gov (United States)

    OSTASIEWICZ, BEATA; OSTASIEWICZ, PAWEŁ; DUŚ-SZACHNIEWICZ, KAMILA; OSTASIEWICZ, KATARZYNA; ZIÓŁKOWSKI, PIOTR

    2016-01-01

    Biomarkers have been described as the future of oncology. Modern proteomics provide an invaluable tool for the near-whole proteome screening for proteins expressed differently in neoplastic vs. healthy tissues. However, in order to select the most promising biomarkers, an independent method of validation is required. The aim of the current study was to propose a methodology for the validation of biomarkers. Due to material availability the majority of large scale biomarker studies are performed using formalin-fixed paraffin-embedded (FFPE) tissues, therefore these were selected for use in the current study. A total of 10 genes were selected from what have been previously described as the most promising candidate biomarkers, and the expression levels were analyzed with reverse transcription-quantitative polymerase chain reaction (RT-qPCR) using calibrator normalized relative quantification with the efficiency correction. For 6/10 analyzed genes, the results were consistent with the proteomic data; for the remaining four genes, the results were inconclusive. The upregulation of karyopherin α 2 (KPNA2) and chromosome segregation 1-like (CSE1L) in colorectal carcinoma, in addition to downregulation of chloride channel accessory 1 (CLCA1), fatty acid binding protein 1 (FABP1), sodium channel, voltage gated, type VII α subunit (SCN7A) and solute carrier family 26 (anion exchanger), member 3 (SLC26A3) was confirmed. With the combined use of proteomic and genetic tools, it was reported, for the first time to the best of our knowledge, that SCN7A was downregulated in colorectal carcinoma at mRNA and protein levels. It had been previously suggested that the remaining five genes served an important role in colorectal carcinogenesis, however the current study provided strong evidence to support their use as biomarkers. Thus, it was concluded that combination of RT-qPCR with proteomics offers a powerful methodology for biomarker identification, which can be used to analyze

  8. Leptin regulates proliferation and apoptosis of colorectal carcinoma through PI3K/Akt/mTOR signalling pathway

    Indian Academy of Sciences (India)

    Di Wang; Jian Chen; Hui Chen; Zhi Duan; Qimei Xu; Meiyan Wei; Lianghua Wang; Meizuo Zhong

    2012-03-01

    Epidemiological studies have indicated that obesity is associated with colorectal cancer. The obesity hormone leptin is considered as a key mediator for cancer development and progression. The present study aims to investigate regulatory effects of leptin on colorectal carcinoma. The expression of leptin and its receptor Ob-R was examined by immunohistochemistry in 108 Chinese patients with colorectal carcinoma. The results showed that leptin/Ob-R expression was significantly associated with T stage, TNM stage, lymph node metastasis, distant metastasis, differentiation and expression of p-mTOR, p-70S6 kinase, and p-Akt. Furthermore, the effects of leptin on proliferation and apoptosis of HCT-116 colon carcinoma cells were determined. The results showed that leptin could stimulate the proliferation and inhibit the apoptosis of HCT-116 colon cells through the PI3K/Akt/mTOR pathway. Ly294002 (a PI3K inhibitor) and rapamycin (an mTOR inhibitor) could prevent the regulatory effects of leptin on the proliferation and apoptosis of HCT-116 cells via abrogating leptin-mediated PI3K/Akt/mTOR pathway. All these results indicated that leptin could regulate proliferation and apoptosis of colorectal carcinoma through the PI3K/Akt/mTOR signalling pathway.

  9. 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.

  10. Incidence and risk factors for colorectal neoplasia in patients with oral squamous cell carcinoma.

    Science.gov (United States)

    Kishikawa, H; Sato, K; Yamauchi, T; Katakura, A; Shibahara, T; Takano, N; Nishida, J

    2014-11-01

    Colorectal adenoma and cancer are not regarded as being associated with primary oral cancer. The aim of this study was to determine whether screening colonoscopy should be performed for patients with oral cancer in addition to the upper gastrointestinal endoscopic screening that is now routinely performed. Between 2007 and 2013, 162 patients with oral squamous cell carcinoma were enrolled at Tokyo Dental College, Ichikawa General Hospital, and 136 individuals were assigned to colonoscopic surveillance. Advanced neoplasia was defined as an adenoma ≥ 10 mm, adenoma with villous histology or high-grade dysplasia regardless of size and invasive cancer. Associations between advanced neoplasia and clinical factors, including age, sex, body mass index, physical activity, smoking, alcohol consumption and oral cancer site and staging were determined. Advanced neoplasia, including five invasive cancers, was identified in 32 (23.5%) patients. An age- and sex-adjusted multivariate analysis revealed that smoking (Brinkmann index > 400; OR = 3.24, 95% CI = 1.28-8.18), alcohol consumption (lifetime pure ethanol consumption > 600 l; OR = 2.84, 95% CI = 1.18-6.79) and a diagnosis of cancer of the floor of the mouth (OR = 7.97, 95% CI = 2.49-25.46) were independent risk factors for advanced colorectal neoplasia. The prevalence of advanced colorectal neoplasia is unexpectedly high in patients with oral cancer. It should be recognized as a second primary tumour of oral cancer. Screening of oral cancer patients by colonoscopy should be routine practice, particularly among smokers and patients with a high intake of alcohol and cancer of the floor of the mouth. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  11. DNA end binding activity and Ku70/80 heterodimer expression in human colorectal tumor

    Institute of Scientific and Technical Information of China (English)

    Paola Mazzarelli; Carolina Gravina; Marco Caricato; Maria Luana Poeta; Monica Rinaldi; Sergio Valeri; Roberto Coppola; Vito Michele Fazio; Paola Parrella; Davide Seripa; Emanuela Signori; Giuseppe Perrone; Carla Rabitti; Domenico Borzomati; Armando Gabbrielli; Maria Giovanna Matera

    2005-01-01

    AIM: To determine the DNA binding activity and protein levels of the Ku70/80 heterodimer, the functional mediator of the NHEJ activity, in human colorectal carcinogenesis.METHODS: The Ku70/80 DNA-binding activity was determined by electrophoretic mobility shift assays in 20 colon adenoma and 15 colorectal cancer samples as well as matched normal colonic tissues. Nuclear and cytoplasmic protein expression was determined by immunohistochemistry and Western blot analysis.RESULTS: A statistically significant difference was found in both adenomas and carcinomas as compared to matched normal colonic mucosa (P<0.00). However,changes in binding activity were not homogenous with approximately 50% of the tumors showing a clear increase in the binding activity, 30% displaying a modest increase and 15% showing a decrease of the activity.Tumors, with increased DNA-binding activity, also showed a statistically significant increase in Ku70 and Ku86nuclear expression, as determined by Western blot and immunohistochemical analyses (P<0.001). Cytoplasmic protein expression was found in pathological samples,but not in normal tissues either from tumor patients or from healthy subjects.CONCLUSION: Overall, our DNA-binding activity and protein level are consistent with a substantial activation of the NHEJ pathway in colorectal tumors. Since the NHEJ is an error prone mechanism, its abnormal activation can result in chromosomal instability and ultimately lead to tumorigenesis.

  12. Expression of 5-Lipoxygenase in human colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Labile Togba Soumaoro; Satoru Iida; Hiroyuki Uetake; Megumi Ishiguro; Yoko Takagi; Tetsuro Higuchi; Masamichi Yasuno; Masayuki Enomoto; Kenichi Sugihara

    2006-01-01

    AIM: To evaluate the 5-lipoxygenases (Loxs) expression level in human colorectal cancer specimens in order to determine its clinicopathologic significance in human tumorigenesis.METHODS: The relative quantity of 5-Lox mRNA in paired 91 colorectal tumor and adjacent normal mucosa samples was determined by real time quantitative PCR. Additionally, the expression of 5-Lox and cyclooxygenase (Cox)-2 proteins was also examined using immunohistochemical staining methods.RESULTS: There was a marked increase in 5-Lox mRNA levels in the tumor compared with paired normal mucosa samples (P < 0.0001). Sixty six (72.5%) tumors showed high 5-Lox mRNA levels. The positivity rate of 5-Lox and Cox-2 protein expression was 68.7% and 79.1%respectively. There was a significant association between tumoral 5-Lox mRNA level and tumor size (Rho = 0.392,P = 0.0002), depth or vessel invasion.CONCLUSION: These results suggest that 5-Lox is up-regulated in colorectal cancer and that inhibition of its expression might be valuable in the prevention and treatment of colorectal cancer.

  13. Evaluation of 1p Losses in Primary Carcinomas, Local Recurrences and Peripheral Metastases from Colorectal Cancer Patients

    Directory of Open Access Journals (Sweden)

    Lin Thorstensen

    2000-01-01

    Full Text Available Cytogenetic and molecular genetic analyses of colorectal adenomas and carcinomas have shown that loss of the distal part of chromosome arm 1p is common, particularly in tumors of the left colon. Because the importance of 1p loss in colorectal cancer metastases is unknown, we compared the frequency, exact site and extent of ip deletions in primary carcinomas (n=28, local recurrences (n=19 and metastases (n=33 from 67 colorectal cancer patients using 14 markers in an allelic imbalance study. Loss of 1p was found in 50% of the primary carcinomas, 33% of the local recurrences, and 64% of the metastases, revealing a significant difference between the local recurrences and the metastases (P=.04. The smallest region of 1p deletion overlap (SRO defined separately for each group of lesions had the region between markers Di S2647 and D1 S2644, at 1 p35-36, in common. The genes PLA2G2A (1p35.1-36 and TP73 (1p36.3 were shown to lie outside this consistently lost region, suggesting that neither of them are targets for the 1p loss. In the second part of the study, microdissected primary carcinomas and distant metastases from the same colorectal cancer patients (n=18 were analyzed, and the same 1p genotype was found in the majority of patients (12/18, 67%. The finding that primary carcinoma cells with metastatic ability usually contain 1p deletions, and that some cases lacking 1p alterations in the primary tumor acquire such changes during growth of a metastatic lesion, supports the notion that 1p loss may be important both early and late in colorectal carcinogenesis, with the apparent exception of local recurrences.

  14. The expressions of MMP-2,MMP-7,MMP-9 and EMMPRIN in human colorectal carcinoma and its significance%结、直肠癌中MMP-2、MMP-7、MMP-9与EMMPRIN 的表达及意义

    Institute of Scientific and Technical Information of China (English)

    凌林; 胡郁之; 孙礼侠; 刘昌阔; 刘志刚

    2015-01-01

    目的::探讨基质金属蛋白酶( MMP)-2、MMP-7、MMP-9和基质金属蛋白酶诱导因子( EMMPRIN)在结、直肠癌中的表达以及在结、直肠癌发展过程中的作用。方法:采用免疫组织化学法检测100例结、直肠癌组织中MMP-2、MMP-7、MMP-9和EMMPRIN的表达。结果:MMP-2、MMP-7、MMP-9和EMMPRIN在结、直肠癌组织中的表达在结、直肠癌的浸润深度、Dukes分期和有无淋巴结转移间差异均有统计学意义(P<0.01);EMMPRIN分别与MMP-2、MMP-7、MMP-9蛋白在结、直肠癌组织中的表达呈正相关关系(P<0.01)。结论:MMP-2、MMP-7、MMP-9和EMMPRIN在结、直肠癌的演进过程中可能具有一定的协同作用。%Objective:To investigate the expressions of matrix metalloproteinases-2,7 and 9(MMP-2,MMP-7 and MMP-9) and extracellular matrix metalloproteinase inducer ( EMMPRIN ) and their roles in the development process of colorectal carcinoma. Methods:The protein expressions of MMP-2,MMP-7,MMP-9 and EMMPRIN in 100 colorectal carcinoma tissue samples were detected by immunohistochemical method. Results:The differences of the expressions rates of MMP-2, MMP-7, MMP-9 and EMMPRIN in colorectal carcinoma tissue samples with different invasion depth,Dukes stage and lymph node metastasis were statistically significant (P<0. 05). The expressions between EMMPRIN and MMP-2,MMP-7 and MMP-9 in colorectal carcinoma tissue were significant positive correlation,respectively(P<0. 01). Conclusions:The expressions of MMP-2,MMP-7,MMP-9 and EMMPRIN have synergetic effects in the development of colorectal carcinoma.

  15. Colorectal carcinoma in Lagos and Sagamu, Southwest Nigeria: A histopathological review

    Institute of Scientific and Technical Information of China (English)

    Fatimah Blade Abdulkareem; Adekumbiola Aina Fehintola Banjo; Charles Chidozie Anunobi; Emmanuel Kunle Abudu; Nicholas Awodele Awolola; Stephen Olafimihan Elesha; Olorunda Rotirni; Olakanmi Raphael Akinde; Ayoola Oluwole Atoyebi; Adedoyin Adekunle Adesanya; Adetola Olubunmi Daramola

    2008-01-01

    AIM: To study the frequency, gender and age distribution as weld as pathological characteristics of colorectal carcinoma (CRC) in Lagos and Sagamu in SW Nigeria. METHODS: This is a retrospective pathological review of histologically diagnosed CRC from 5 laboratories in and clinical summary were extracted from demographic information. Cases of anal cancer were excluded from this study. RESULTS: There were 420 cases (237 males and 183 females) of CRC. It peaked in the 60-69 year age group (mean: 50.7; SD: 16.2), M:F ratio 1.3:1 and 23% occurred below 40 years. The majority was well to moderately differentiated adenocarcinoma 321 (76.4%), mucinous carcinoma 45 (10.7%) and signet ring carcinoma 5 (1.2%), and more common in patients under 40 years compared to well differentiated tumors. The recto-sigmoid colon was the most common site (58.6%). About 51% and 34% of cases presented at TNM stages Ⅱ and Ⅲ, respectively. CONCLUSION: CRC is the commonest malignant gastrointestinal (GIT) tumor most commonly located in the recto-sigmoid region. The age and sex prevalence and histopathological features concur with reports from other parts of the world. C 2008 The WJG Press. All rights reserved.

  16. 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.

  17. Stromal CEA immunoreactivity is correlated with lymphatic invasion of human esophageal carcinoma.

    Science.gov (United States)

    Kijima, H; Oshiba, G; Kenmochi, T; Kise, Y; Tanaka, H; Chino, O; Shimada, H; Ueyama, Y; Tanaka, M; Makuuchi, H

    2000-04-01

    Carcinoembryonic antigen (CEA) is a good marker of colorectal cancer. Recent studies have demonstrated that CEA may function as a metastatic potentiator by different pathways; i.e. modulation of immune responses, facilitation of intercellular adhesion and cellular migration. However, expression patterns of CEA have not yet been established in human esophageal carcinomas. In this study, we examined CEA expression in human esophageal squamous cell carcinoma and its clinicopathological significance. CEA immunoreactivity was frequently detected in the cancer cells (cytoplasmic type; 81.1%, 43/53) as well as in the cancer stroma (stromal type; 32.1%, 17/53), regardless of the depth of tumor invasion. Lymphatic invasion of cancer cells was frequently found in the stromal CEA-positive esophageal cancer (44.4%, 16/36), compared to stromal CEA-negative cancer (5.9%, 1/17) (pCEA expression plays important roles in lymphatic invasion of human esophageal squamous cell carcinoma.

  18. Correlation of the Serum Level of Carcinoembryonic Antigen and Prolactin with Different Stages of Colorectal Carcinoma According to Dukes' Staging.

    Science.gov (United States)

    Rahman, M R; Sheikh, S H; Lima, I J; Islam, M R; Faisal, M; Islam, M S; Faruk, M O; Jalal, M T

    2016-01-01

    Carcinoembryonic antigen (CEA) is well established tumor marker for colorectal cancers worldwide. Recent studies show that serum prolactin level is also raised in colorectal cancers. The purpose of the study is to evaluate the correlation of serum CEA and Prolactin with Dukes' staging of colorectal carcinomas. Between January 2013 and June 2013, Serum CEA and Serum Prolactin were measured by radioimmunoassay from 103 patients who were histopathologically diagnosed as colorectal carcinomas. Evaluation of the stages of the colorectal cancers was done on the basis of preoperative investigations and postoperative histopathology and correlated with Preoperative Serum CEA and Serum Prolactin. Results were presented as median value, range and percentage. Male to female ratio was 1.4:1 with median age of 42.26 years (range 17-78 years). Most of the patients in this series presented with carcinoma rectum (42%). Most of the patients (52%) were found in Dukes' stage C and 27% and 15% cases were found as Dukes' stage B and Dukes' stage D respectively. Stage of the disease is directly proportionate to percentage of the patient with high serum prolactin except early stage (Dukes' A-50%, Dukes' B-28.6%, Dukes' C-33.3% & Dukes' D-46.7%). Similarly serum CEA level is directly proportionate to tumor stage (Dukes' A-0%, Dukes' B-32%, Dukes' C-40.7% & Dukes' D-74.7%). A preoperative high serum CEA value suggests advanced disease either locally or with distant metastasis. In contrast preoperative high serum prolactin (hyperprolactinaemia) did not suggest advanced disease as it can be elevated even in early stage of disease. Serum CEA and Serum Prolactin both are valuable tumor markers but serum CEA could not be replaced by serum Prolactin. Serum Prolactin may be a helpful marker in earlier stages of the colorectal cancer.

  19. Accuracy of Multi-Slice Spiral Computed Tomography for Preoperative Tumor Node Metastasis (TNM) Staging of Colorectal Carcinoma.

    Science.gov (United States)

    Bai, Rong-Jie; Ren, Shao-Hua; Jiang, Hui-Jie; Li, Jin-Ping; Liu, Xiao-Cheng; Xue, Li-Ming

    2017-07-17

    BACKGROUND With the advances in imaging technologies, multi-slice spiral computed tomography (MSCT) has demonstrated superiority in the diagnosis and staging of colorectal carcinoma. In the current study, preoperative TNM staging of colorectal carcinoma by using MSCT was conducted and compared with the corresponding postoperative pathological examination findings, in order to evaluate the accuracy of preoperative MSCT for TNM staging. MATERIAL AND METHODS Combinations of biphasic or triphasic enhanced-phase MSCT scans were obtained for 76 patients with colorectal carcinoma, and the TNM stage was determined based on imaging reconstruction from various angles and perspectives to display the size, location, and affected range of tumors. The preoperative TNM stage was compared with the postoperative pathological stage, and the consistency between the 2 methods was tested by the k test using SPSS 17.0 software. RESULTS Among the different combinations of enhanced-phase MSCT scanning, triphasic MSCT imaging, comprising the arterial, portal venous, and delayed phases, showed the highest accuracy rates, at 81.6% (62/76), 82.89% (63/76), and 96.1% (73/76) for T, N, and M staging, respectively, with k values of 0.72, 0.65, and 0.56, respectively, indicating consistency with the postoperative pathological staging. CONCLUSIONS Combined MSCT scanning comprising the arterial phase, portal venous phase, and delayed phase showed satisfying consistency with the postoperative pathological analysis results for TNM staging of colorectal carcinoma. Thus, MSCT is an important clinical value for improving the accuracy of TNM staging and for planning the appropriate colorectal cancer treatment.

  20. Colorectal carcinoma evaluated by incremental dynamic CT; Comparison of CT density, histology, and tumor size

    Energy Technology Data Exchange (ETDEWEB)

    Furukawa, Hiroyoshi; Hara, Tsuyoshi; Taniguchi, Tetsushi (Shimizu Kosei Hospital, Shizuoka (Japan))

    1992-06-01

    Evaluation of incremental dynamic CT scan and histologic findings were compared in order to clarify the cause of the differences in colorectal carcinoma as observed on CT after administration of contrast medium. In 48 cases demonstrated on postcontrast dynamic CT scan, the CT density of the tumor was homogeneous (Type 1) in 26 (54.2%) cases and heterogeneous (Type 2) in 22 (45.8%) cases. Well differentiated adenocarcinoma was seen as Type 1 in 11 of 13 (84.6%) cases while moderately differentiated adenocarcinoma was of Type 1 in 15 of 29 (51.7%) cases. Poorly differentiated and mucinous adenocarcinoma were detected as Type 2 in all cases. A comparison of CT types and tumor size showed that as tumor size increased, the number of Type 1 cases decreased while Type 2 cases increased. Histologically, high density areas consisted mainly of well-developed tubular, branching glands of adenocarcinoma, while low density areas were composed of fibrous or mucinous stroma or necrosis. Dynamic CT scans for colorectal cancer are useful not only for preoperative staging but also for tissue characterization. (author).

  1. Clinical significance of vascular endothelial growth factor expression and neovascularization in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Shu Zheng; Ming-Yong Han; Zuo-Xiang Xiao; Jia-Ping Peng; Qi Dong

    2003-01-01

    AIM: To clarify the association of vascular endothelial growth factor (VEGF) and microvascular density (MVD)expression with the angiogenesis and prognosis of colorectal cancer.METHODS: A total of 97 cases of colorectal carcinomas were examined by immunohistochemical staining (SP method), using anti-VEGF and anti-factor CD34+ monoclonal antibodies. RESULTS: VEGF positive staining was obtained in 68 out of 97 cases (70.1%), and observed mainly in the cytoplasm of tumor cells, and also frequently in stromal cells. VEGF expression was more intense in poorly differentiated adenocarcinoma in comparison with others, but there was no significant correlation between VEGF expression and age,sex and stage. A significant correlation was found between the MVD and grades, and there was no significant relationship between the MVD and age, sex, and stage. The MVD in the VEGF positive group (68 cases) was higher than that in the negative group. Upon multivariate analysis, the significant variables were stage, tumor grade and MVD; VEGF expression was not an independent prognostic factor. CONCLUSION: The expression of VEGF has a significant correlation with MVD; MVD expression has prognostic value but VEGF has not in colon cancer.

  2. LBP and CD14 polymorphisms correlate with increased colorectal carcinoma risk in Han Chinese

    Institute of Scientific and Technical Information of China (English)

    Rui Chen; Fu-Kang Luo; Ya-Li Wang; Jin-Liang Tang; You-Sheng Liu

    2011-01-01

    AIM: To explore the associations of polymorphisms of lipopolysaccharide binding protein (LBP), cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR-4), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) with the colorectal carcinoma (CRC) risk in Han Chinese. METHODS: Polymorphisms of LBP (rs1739654, rs2232596, rs2232618), CD14 (rs77083413, rs4914), TLR-4 (rs5030719), IL-6 (rs13306435) and TNF-α (rs35131721) were genotyped in 479 cases of sporadic colorectal carcinoma and 486 healthy controls of Han Chinese in a case-control study. Single-nucleotide polymorphisms (SNPs) between cases and controls were analyzed by unconditional logistic regression. RESULTS: GA and GG genotypes of LBP rs2232596 were associated with a significantly increased risk of CRC [odds ratio (OR) = 1.51, 95% confidence interval (CI) 1.15-1.99, P = 0.003; OR = 2.49, 95% CI 1.16-5.38, P = 0.016, respectively]. A similar association was also observed for the CG genotype of CD14 rs4914 (OR= 1.69, 95% CI 1.20-2.36, P = 0.002). In addition, a combination of polymorphisms in LBP rs2232596 and CD14 rs4914 led to a 3.4-fold increased risk of CRC (OR = 3.44,95% CI 1.94-6.10, P = 0.000).CONCLUSION: This study highlights the LBP rs2232596 and CD14 rs4914 polymorphisms as biomarkers for elevated CRC susceptibility in the Chinese Han population.

  3. Clinical significance of costimulatory molecule B7-H3 expression on CD3+T cells in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    MAO Yong; SUN Jing; WANG Wei-peng; ZHANG Xue-guang; HUA Dong

    2013-01-01

    Background B7-H3 has been widely studied in the context of tumor progression in recent years,and behaves as a tumor cell marker in a variety of tumors including colorectal carcinoma.The mechanism of B7-H3 in tumor progression is complicated and not clear yet.Studies have revealed that B7 family molecules are expressed on infiltrated lymphocytes as well as tumor cells in tumor microenvironment,which indicates that different expression pattern may lead to different clinical outcomes.Methods The expression of B7-H3 was detected in tissues of 98 colorectal carcinoma patients by using immunohistochemistry.Then the expression of B7-H3 on CD3+ T lymphocytes isolated from fresh cancer tissues of 12 colorectal carcinoma patients was analyzed by flow cytometry assay.The relationship between the expression of B7-H3 on CD3+ T lymphocytes and patients' clinical pathological parameters was demonstrated with statistical analysis.Results Patients with more CD3+ T cell infiltration survived much longer than patients with less CD3+ T cell infiltration (P <0.05); B7-H3 was highly expressed by infiltrating CD3+ T lymphocytes in colorectal carcinoma tissues.The expression of B7-H3 was found to be significantly related with lymph node metastasis status (P <0.05),but not with the patient's gender,age,tumor size,differentiation degree,depth of tumor invasion,Dukes' stage,distant metastasis and whether or not mucinous adenocarcinoma was present (P >0.05).Moreover,the survival time of patients with low expression of B7-H3 was obviously longer than those of high B7-H3 expression patients,but the seven-year survival rate showed no difference between the high and low B7-H3 expression patients (P >0.05).Conclusion The negative costimulatory molecule B7-H3 on infiltrating CD3+ T lymphocytes in colorectal carcinoma bears importance in the clinical pathological progress and prognosis of colorectal carcinoma.

  4. Identification of differently expressed genes in human colorectal adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Yao Chen; Yi-Zeng Zhang; Zong-Guang Zhou; Gang Wang; Zeng-Ni Yi

    2006-01-01

    AIM: To investigate the differently expressed genes in human colorectal adenocarcinoma.METHODS: The integrated approach for gene expression profiling that couples suppression subtractive hybridization, high-throughput cDNA array, sequencing,bioinformatics analysis, and reverse transcriptase realtime quantitative polymerase chain reaction (PCR)was carried out. A set of cDNA clones including 1260SSH inserts amplified by PCR was arrayed using robotic printing. The cDNA arrays were hybridized with florescent-labeled probes prepared from RNA of human colorectal adenocarcinoma (HCRAC) and normal colorectal tissues.RESULTS: A total of 86 genes were identified, 16 unknown genes and 70 known genes. The transcription factor Sox9 influencing cell differentiation was downregulated. At the same time, Heat shock protein 10 KDis downregulated and Calmoulin is up-regulated.CONCLUSION: Downregulation of heat shock protein 10 KD lost its inhibition of Ras, and then attenuated the Ras GTPase signaling pathway, increased cell proliferation and inhibited cell apoptosis. Down-regulated transcription factor Sox9 influences cell differentiation and cell-specific gene expression. Down-regulated Sox9 also decreases its binding to calmodulin, accumulates calmodulin as receptor-activated kinase and phosphorylase kinase due to the activation of PhK.

  5. PET and PET/CT imaging for the earliest detection and treatment of colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Kevin Carter

    2005-10-01

    Full Text Available Approximately 150,000 new cases of colorectal cancer are diagnosed each year with the life time risk of developing colon caner in developed nations being 4.6% in men and 3.2% in women. Screening patients is essential early detection of colon carcinoma to aid in complete resection. Unfortunately current screening methods carry with them poor patient compliance. PET and PET/CT may be a significant part of this screening solution. The authors reviewed and analyzed the English language articles and case reports identified on Medline during the last 10 years. PET and PET/CT results for colorectal carcinoma were tabulated and presented for the fifth Scientific Meeting of the Brazilian Society of Nuclear Biosciences. Though most studies have been retrospective analysis in using PET for staging for other malignant processes the cases that have identified additional uptake in the colon are important. The accuracy when utilizing PET and PET/CT in this screening method has a sensitivity between 65 and 90% with a specificity of 84 to 90% and a positive predictive value 71 to 78%. Early stages of malignancies and pre-cancerous polyps avidly accumulates F-18 Deoxyflouro glucose allowing us to conclude that whole body PET and PET/CT is an essential component in the work up, staging or treatment monitoring in colon carcinoma. We have to continue to accumulate data for possible introduction for whole body PET and PET/CT scanning for colon carcinoma and precancerous polyps.Aproximadamente, 150 000 novos casos de câncer coloretal são diagnosticados, anualmente, em países em desenvolvimento. Destes, 4,6% em homens e 3,2% em mulheres. A triagem de pacientes é essencial na detecção precoce do carcinoma de colon para ajudar na completa ressecção. Infelizmente, os métodos de exame atualmente disponíveis contam com uma baixa adesão dos pacientes. Parte significativa da solução desse problema pode estar no uso de PET e PET/CT. Os autores revisaram e

  6. Epigenetic inactivation of SLIT2 in human hepatocellular carcinomas.

    Science.gov (United States)

    Jin, Jie; You, Haiyan; Yu, Bin; Deng, Yun; Tang, Ning; Yao, Genfu; Shu, Huiqun; Yang, Shengli; Qin, Wenxin

    2009-01-30

    Recent findings have shown that SLIT2 appears to function as a novel tumor suppressor gene. In addition, hypermethylation of its promoter region has been detected in various cancers, including breast and lung cancer, colorectal carcinoma, and gliomas. Here, we report for the first time that there is epigenetic silencing of SLIT2 in human hepatocellular carcinoma (HCC). Downregulation of SLIT2 was detected in 6 of 8 (75%) HCC cell lines by quantitative real-time RT-PCR (qRT-PCR), and the downregulation of SLIT2 was generally dependent on the degree of methylation at the promoter region. Furthermore, expression of SLIT2 was restored in relatively low-expressing cell lines after treatment with 5-aza-2-deoxycytidine (5-Aza-dC). Downregulation of SLIT2 expression was also detected in 45 of 54 primary HCC samples (83.3%), and the decrease in expression was significantly correlated with CpG island hypermethylation. This decrease of SLIT2 expression was also associated with lymph node metastasis in HCC. Moreover, overexpression of SLIT2 in SMMC-7721 cells induced by recombinant adenovirus suppressed cell growth, migration, and invasion, These results suggest that epigenetic inactivation of SLIT2 in HCC may be important in the development and progression of HCC. Thus, SLIT2 may be useful as a therapeutic target in the treatment of HCC.

  7. Selumetinib and Cyclosporine in Treating Patients With Advanced Solid Tumors or Advanced or Metastatic Colorectal Cancer

    Science.gov (United States)

    2017-09-04

    Recurrent Colorectal Carcinoma; Solid Neoplasm; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7

  8. STUDY ON NUCLEAR MATRIX PROTEINS FROM HUMAN BREAST CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    HE Qian; ZHANG Shu-qun; CHU Yong-lie; JIA Xiao-li; JIANG Jian-tao

    2009-01-01

    Objective To investigate the marker protein of human breast carcinoma from nuclear matrix proteins (NMPs).Methods NMPs were injected subcutaneously into rabbit to get antiserum, which was used to detect the NMPs specificity for breast carcinoma.Results There was an apparent positive band (100kD) in the NMPs of breast carcinoma, which did not exist in normal breast and other tumors that were detected.Conclusion One or one group of 100kD NMPs were found to be related to human breast carcinoma, which may be involved in the carcinogenesis and development of human breast carcinoma and valuable for breast carcinoma diagnosis.

  9. Template reporting matters--a nationwide study on histopathology reporting on colorectal carcinoma resections.

    Science.gov (United States)

    Haugland, Hans Kristian; Casati, Bettina; Dørum, Liv Marit; Bjugn, Roger

    2011-01-01

    Complete and accurate histopathology reports are fundamental in providing quality cancer care. The Cancer Registry of Norway and the Norwegian Society of Pathology have previously developed a national electronic template for histopathology reporting on colorectal carcinoma resection specimens. The present study was undertaken to investigate (1) whether quality routines in Norwegian pathology laboratories might affect completeness of such histopathology reports and (2) whether the national electronic template improves completeness of histopathology reports compared with other modes of reporting. A questionnaire on quality routines was sent to the 21 pathology laboratories in Norway. All histopathology reports on colorectal cancer submitted to the Cancer Registry for a 3-month period in the autumn of 2007 were then evaluated on the mode of reporting and the presence of 11 key parameters. Of the 20 laboratories that handled resection specimens, 16 had written guidelines on histopathology reporting. Of these, 4 used the national electronic template, 5 used checklists, 3 used locally developed electronic templates, whereas the remaining 4 had neither obligatory checklists nor templates. Of the 650 histopathology reports submitted to the Cancer Registry in the 3-month period, the national template had been used in 170 cases (26.2%), checklists/locally developed templates in 112 cases (17.2%), and free text in 368 cases (56.6%). Quality routines in the pathology laboratories clearly governed reporting practice and the completeness of the histopathology reports. Use of the national electronic template significantly improved (P < .05) the presence of the 11 key parameters compared with reporting by checklists, locally developed electronic templates, or free text.

  10. Thrombocytosis portends adverse prognostic significance in patients with stage II colorectal carcinoma

    Science.gov (United States)

    Guo, Tianhua; Krzystanek, Marcin; Szallasi, Zoltan; Szallasi, Arpad

    2014-01-01

    Thrombocytosis portends adverse prognostic significance in many types of cancers including ovarian and lung carcinoma. In this study, we determined the prevalence and prognostic significance of thrombocytosis (defined as platelet count in excess of 400 × 10 3/μl) in patients with colorectal cancer. We performed a retrospective analysis of 310 consecutive patients diagnosed at our Institution between 2004 and 2013. The patients (48.7% male and 51.3% female) had a mean age of 69.9 years (+/- 12.7 years) at diagnosis. Thrombocytosis was found in a total of 25 patients, with a higher incidence in those with stage III and IV disease (14.4% of patients). Although the mean platelet count increased with the depth of tumor invasion (pT), its values remained within normal limits in the whole patient cohort. No patient with stage I cancer (n=57) had elevated platelet count at diagnosis. By contrast, five of the 78 patients (6.4%) with stage II cancer showed thrombocytosis, and four of these patients showed early recurrence and/or metastatic disease, resulting in shortened survival (they died within one year after surgery). The incidence of thrombocytosis increased to 12.2% and 20.6%, respectively, in patients with stage III and IV disease. The overall survival rate of patients with thrombocytosis was lower than those without thrombocytosis in the stage II and III disease groups, but this difference disappeared in patients with stage IV cancer who did poorly regardless of their platelet count. We concluded that thrombocytosis at diagnosis indicates adverse clinical outcome in colorectal cancer patients with stage II or III disease. This observation is especially intriguing in stage II patients because the clinical management of these patients is controversial. If our data are confirmed in larger studies, stage II colon cancer patients with thrombocytosis may be considered for adjuvant chemotherapy. PMID:25469228

  11. Hepatic resection of metastasis from colorectal carcinoma. Morbidity, mortality, and pattern of recurrence.

    Science.gov (United States)

    Holm, A; Bradley, E; Aldrete, J S

    1989-01-01

    To identify the factors that determine the morbidity and mortality of liver resection of metastases from colorectal carcinoma and the variables that may influence the pattern of recurrence, the survival time and the disease-free rate, a univariate and-multivariate statistical analysis (30 variables using Student's t-test, Fischer's exact test, and chi square test) was performed. Intraoperative blood loss of greater than 3500 ml was found to be a significant risk factor to developing postoperative complications (p less than 0.05 by x2). After a mean follow-up of 25.8 months, 26 of the 35 patients studied (74%) had recurrent disease. In the univariate analysis, the following factors appear to be reliable predictors of early recurrence: poor degree of differentiation of the primary colorectal tumor, the presence of multiple liver metastases, the male gender, and the presence of tumor at the margin of the resected hepatic tissue (p less than 0.05). However, only the latter two factors appeared also to affect the survival time and the disease-free rates at 2 years after hepatic resection of metastases (p less than 0.05). In the multivariate analysis (factors tested simultaneously), presence of an advanced liver metastatic disease (Stage II or III) consistently indicated early recurrence and poor survival (p less than 0.005). The liver was the most common site of recurrence as the sole site of recurrence (54%) or in combination with other sites (88%)--followed by the lungs (31%) and the site of colonic resection (8%). Twenty-nine (83%), 14 (40%), and nine (26%) patients survived without recurrent disease at 1, 2, and 3 or more years, respectively, after hepatic resection of metastases. In six patients (17%), no significant palliation was noted, primarily because of early recurrence (less than 6 months). From this data, resection of hepatic metastases from colorectal cancer appears to offer a realistic therapeutic option to a selected group of patients, but only if the

  12. Short-term Effect of Chemotherapy Concomitant with Multiple Autologous Immunocytes on Patients with Colorectal Carcinoma

    Directory of Open Access Journals (Sweden)

    Junquan Liu

    2013-12-01

    Full Text Available Objective: To compare the differences of cellular immunological functional changes and survival time of chemotherapy concomitant with multiple autologous immunocytes with single chemotherapy on patients with colorectal carcinoma (CRC. Methods: Of the 83 CRC patients, 43 were treated with single chemotherapy (single chemotherapy group while the other 40 were given chemotherapy concomitant with multiple autologous immunocytes (combined chemotherapy group. Blood cell separator was applied to collect autologous peripheral blood mononuclear (PBMC which was used to induce the cultures of peripheral blood CD3AK cell, CIK cell, dendritic cell (DC, γδT cell and NK cell based on routine approaches. Peripheral blood CD3+, CD4+, CD8+, CD19+, CD16+, CD56+, CD4/CD8 and γδT cell ratio as well as the positive expression rates of perforin, granular enzyme B and CD107a in PBMC were determined by flow cytometer. Same chemotherapy (oxaliplatin + CF + 5-FU was intravenously given to both groups, while in combination group, 4, 6, 9, 11 and 10 patients received 3, 6, 7, 10 and > 16 courses of treatment, respectively. Results: Subgroup of immunocytes and absolute value in combined chemotherapy group were evidently higher than in single chemotherapy group, but there was no significant difference in Karnofsky score. In addition, combined chemotherapy group was apparently higher after treatment than treatment before and single chemotherapy group in the results of perforin, granular enzyme B (GranB and CD107a in PBMC. Additionally, 1-, 2- and 5-year survival rates in combined chemotherapy group (in phases Ⅱ , Ⅲ and Ⅳ were 70.0% (28/40, 20.0% (8/40 and 10.0% (4/40, higher than those in single chemotherapy group [23.2% (10/43, 7.0% (3/43 and 4.6% (2/43], respectively, in which the differences in phases Ⅱ and Ⅲ were more significant (P <0.05, but no difference was observed between two groups in 5-year survival rate in patients in phase Ⅳ . Conclusion

  13. Xenotransplanted human prostate carcinoma (DU145) cells develop into carcinomas and cribriform carcinomas: ultrastructural aspects.

    Science.gov (United States)

    Gilloteaux, Jacques; Jamison, James M; Neal, Deborah R; Summers, Jack L; Taper, Henryk S

    2012-10-01

    Androgen-independent, human prostate carcinoma cells (DU145) develop into solid, carcinomatous xenotransplants on the diaphragm of nu/nu mice. Tumors encompass at least two poorly differentiated cell types: a rapidly dividing, eosinophilic cell comprises the main cell population and a few, but large basophilic cells able to invade the peritoneal stroma, the muscular tissue, lymph vessels. Poor cell contacts, intracytoplasmic lumina, and signet cells are noted. Lysosomal activities are reflected by entoses and programmed cell deaths forming cribriform carcinomas. In large tumors, degraded cells may align with others to facilitate formation of blood supply routes. Malignant cells would spread via ascites and through lymphatics.

  14. Micropapillary Pattern at the Invasive Front and Its Association with Unresectable Colorectal Carcinomas

    Directory of Open Access Journals (Sweden)

    Naohiko Akimoto

    2013-01-01

    Full Text Available Unresectable colorectal carcinomas (CRCs as considered incurable even if the primary tumors and the metastatic ones can undergo resection are correlated with poor prognosis. We evaluated the association between micropapillary pattern at the invasive front and unresectable CRCs. Thirty-four out of 264 (12.9% CRC patients with stages III and IV were unresectable cases. The patients with unresectable CRCs had significantly worse survival than those with resectable CRCs (. Micropapillary pattern was evident in 12 (4.5% out of 264 cases. This pattern was observed in 6 of 34 (17.6% unresectable CRCs and in 6 of 230 (2.6% resectable cases (. Unresectable CRCs revealed more frequently deeper invasion (odds ratio (OR, 1.175; 95% confidence interval (CI, 1.113–1.241, lymph node metastasis (OR, 2.356; 95% CI, 1.132–4.905, and presence of micropapillary pattern at the invasive front (OR, 8.000; 95% CI, 2.415–26.504 as compared to resectable cases. By multivariable logistic regression analysis, only micropapillary pattern was shown to be an independent predictor of unresectable CRCs (OR, 9.451; 95% CI, 2.468–36.196; . In conclusion, micropapillary pattern at the invasive front is associated with unresectable CRCs, and detection of it could help identify unresectable CRC cases.

  15. Multispectral Mueller polarimetric imaging detecting residual cancer and cancer regression after neoadjuvant treatment for colorectal carcinomas

    Science.gov (United States)

    Pierangelo, Angelo; Manhas, Sandeep; Benali, Abdelali; Fallet, Clément; Totobenazara, Jean-Laurent; Antonelli, Maria-Rosaria; Novikova, Tatiana; Gayet, Brice; De Martino, Antonello; Validire, Pierre

    2013-04-01

    This work is devoted to a first exploration of Mueller polarimetric imaging for the detection of residual cancer after neoadjuvant treatment for the rectum. Three samples of colorectal carcinomas treated by radiochemotherapy together with one untreated sample are analyzed ex vivo before fixation in formalin by using a multispectral Mueller polarimetric imaging system operated from 500 to 700 nm. The Mueller images, analyzed using the Lu-Chipmann decomposition, show negligible diattenuation and retardation. The nonirradiated rectum exhibits a variation of depolarization with cancer evolution stage. At all wavelengths on irradiated samples, the contrast between the footprint of the initial tumor and surrounding healthy tissue is found to be much smaller for complete tumor regression than when a residual tumor is present, even at volume fractions of the order of 5%. This high sensitivity is attributed to the modification of stromal collagen induced by the cancer. The depolarization contrast between treated cancer and healthy tissue is found to increase monotonously with the volume fraction of residual cancer in the red part of the spectrum. Polarimetric imaging is a promising technique for detecting short-time small residual cancers, which is valuable information for pathological diagnosis and patient management by clinicians.

  16. Total plasma homocysteine and methylenetetrahydrofolate reductase C677T polymorphism in patients with colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Sandra Battistelli; Aurelio Vittoria; Massimo Stefanoni; Camilla Bing; Franco Roviello

    2006-01-01

    AIM: To investigate the behaviour of total plasma homocysteine (tHcy) and its most common genetic determinant defect, the methylenetetrahydrofolate reductase C677T (C677TMTHFR) polymorphism in patients with early stage colorectal carcinoma.METHODS: tHcy was quantified by Abbott IMx immunoassay; screening for C677TMTHFR substitution was performed by PCR and restriction analysis.RESULTS: The frequency of the C/T and T/T genotypes of the C677TMTHFR gene polymorphism did not differ between the groups. The mean tHcy was statistically higher in cancer patients than in control subjects carrying the same C/C or C/T genotype, whereas there was no difference in the T/T homozygous carriers of the two groups. tHcy was significantly higher in the T/T homozygous carriers than in C/C and C/T genotype carriers.CONCLUSION: The statistically significant increase of tHcy observed in C/C and C/T genotype carriers among our cancer patients is related to substrate consumption dependent on the tumor cell proliferation rate, whereas the tHcy increase observed in T/T genotype carriers of both groups probably depends on the enzymatic deficit of the homocysteine conversion to methionine and/or on the folate deficiency.

  17. High expression of GPR116 indicates poor survival outcome and promotes tumor progression in colorectal carcinoma.

    Science.gov (United States)

    Yang, Li; Lin, Xiao-Lu; Liang, Wei; Fu, Seng-Wang; Lin, Wen-Feng; Tian, Xiao-Qing; Gao, Yun-Jie; Chen, Hao-Yan; Dai, Jun; Ge, Zhi-Zheng

    2017-07-18

    Previous studies have found that G-protein-coupled receptor 116 (GPR116) is a regulator of breast cancer metastasis. However, the role of GPR116 in colorectal carcinoma (CRC) carcinogenesis and progression is unknown. In this study, We found GPR116 expression was significantly up-regulated in CRC specimens compared with corresponding non-cancerous tissues. Increased GPR116 expression in CRC was correlated with histological differentiation and distant metastasis. In addition, high expression of GPR116 was significantly associated with poor overall survival of CRC patients, which was also confirmed by GSE14333, GSE17536 and GSE33113 datasets from the Gene Expression Omnibus (GEO). Furthermore, we demonstrated that the ability of proliferation and invasion of CRC cell lines HCT116 and LOVO was markedly reduced after transfected with siRNA-GPR116. Meanwhile, GPR116 may drive EMT in CRC cells through AKT/EKR signaling pathway, resulting in metastasis. Thus, GPR116 may be a novel reliable prognostic indicator and a risk factor in CRC progression.

  18. KRAS, BRAF, and TP53 deep sequencing for colorectal carcinoma patient diagnostics.

    Science.gov (United States)

    Rechsteiner, Markus; von Teichman, Adriana; Rüschoff, Jan H; Fankhauser, Niklaus; Pestalozzi, Bernhard; Schraml, Peter; Weber, Achim; Wild, Peter; Zimmermann, Dieter; Moch, Holger

    2013-05-01

    In colorectal carcinoma, KRAS (alias Ki-ras) and BRAF mutations have emerged as predictors of resistance to anti-epidermal growth factor receptor antibody treatment and worse patient outcome, respectively. In this study, we aimed to establish a high-throughput deep sequencing workflow according to 454 pyrosequencing technology to cope with the increasing demand for sequence information at medical institutions. A cohort of 81 patients with known KRAS mutation status detected by Sanger sequencing was chosen for deep sequencing. The workflow allowed us to analyze seven amplicons (one BRAF, two KRAS, and four TP53 exons) of nine patients in parallel in one deep sequencing run. Target amplification and variant calling showed reproducible results with input DNA derived from FFPE tissue that ranged from 0.4 to 50 ng with the use of different targets and multiplex identifiers. Equimolar pooling of each amplicon in a deep sequencing run was necessary to counterbalance differences in patient tissue quality. Five BRAF and 49 TP53 mutations with functional consequences were detected. The lowest mutation frequency detected in a patient tumor population was 5% in TP53 exon 5. This low-frequency mutation was successfully verified in a second PCR and deep sequencing run. In summary, our workflow allows us to process 315 targets a week and provides the quality, flexibility, and speed needed to be integrated as standard procedure for mutational analysis in diagnostics.

  19. 超声诊断在结肠癌术前分期中的临床应用%Clinical application of ultrasonic probing for preoperative staging of colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    [ Objective]The aim of this study was to assess the value of ultrasonic probe (USP) under colonoscope in the preoperative staging of colorectal carcinoma. [ Methods]75 patients with colorectal carcinomas proven pathologically were given USP (Olympus UM-2R, 12MHz; UM -3R, 20 MHz) under colonoscope before operation. The results were compared with histopathologic findings of resected specimens. [ Results] Colorectal carcinoma appeared as a hypoechoic mass under USP. USP had an overall accuracy rate of 82.7% in the diagnosis of T staging of colorectal carcinoma. In determining lymph node metastasis , the sensitivity and specificity were 53.2% and 61.5%, the positive predictive value and the negative predictive value were 0.87 and 0. 22, respectively. [ Conclusions ] USP is valuable for the staging of colorectal carcinoma and has a high accuracy rate in determining the depth of tumor invasion. The preoperative information obtained by this tool may influence the choice of therapy.

  20. Epidemiological, Clinico-Pathological Profile and Management of Colorectal Carcinoma in a Tertiary Referral Center of Eastern India

    Directory of Open Access Journals (Sweden)

    Shyamal Kumar Halder

    2013-01-01

    Full Text Available Background: The colorectal carcinoma is a common cancer in males and in females and second most common cause of death in Europe and third commonest cause in the United States. Recent Indian study shows that there is a significant increase in incidence of colonic carcinoma but the incidence of rectal carcinoma remains steady. Aims and Objectives: This prospective study was undertaken to assess the clinico-pathological profile and management of colorectal malignancy in a tertiary referral institute of eastern India and to compare the above data with the data from the western world. Material and Methods: The patients admitted with the diagnosis of colorectal carcinoma in IPGME and R (SSKM, a tertiary hospital in eastern India, between January 2006 and December 2010, were included in this study. These patients were prospectively analyzed for age, sex, site of the lesion, clinical presentations, nature of the growth and types of surgery performed. Results: 192 patients were included in this study of which 78 patients were of younger age group (35 years. The mean age of this series was 44.1 years. The male to female ratio of younger and older group was 1.68:1 and 1.85:1 respectively. Reetal bleeding was the commenest symptom irrespective of age and sex. Pain in abdomen (39.7% and intestinal obstruction (21.8% were the predominant presenting features in the patients of younger group whereas weight loss was commonest presenting feature in the patients of older age group. Most common histological type, irrespective of age, was adenocarcinoma (93.8%. Overall, right sided colonic growth was more common in females while rectum was the commonest site of affection in males. The patients of younger age group presented in advanced stage like Duke’s C and Duke’s D. Conclusions: The younger patients are diagnosed with colorectal carcinoma. Cancer of right colon is more common than that of left. The younger patients present more often with abdominal pain and

  1. Human papillomavirus detection in paraffin-embedded colorectal cancer tissues.

    Science.gov (United States)

    Tanzi, Elisabetta; Bianchi, Silvia; Frati, Elena R; Amicizia, Daniela; Martinelli, Marianna; Bragazzi, Nicola L; Brisigotti, Maria Pia; Colzani, Daniela; Fasoli, Ester; Zehender, Gianguglielmo; Panatto, Donatella; Gasparini, Roberto

    2015-01-01

    Human papillomavirus (HPV) has a well-recognized aetiological role in the development of cervical cancer and other anogenital tumours. Recently, an association between colorectal cancer and HPV infection has been suggested, although this is still controversial. This study aimed at detecting and characterizing HPV infection in 57 paired biopsies from colorectal cancers and adjacent intact tissues using a degenerate PCR approach. All amplified fragments were genotyped by means of sequencing. Overall, HPV prevalence was 12.3 %. In particular, 15.8 % of tumour tissues and 8.8 % of non-cancerous tissue samples were HPV DNA-positive. Of these samples, 85.7 % were genotyped successfully, with 41.7 % of sequences identifying four genotypes of the HR (high oncogenic risk) clade Group 1; the remaining 58.3 % of HPV-genotyped specimens had an unclassified β-HPV. Examining additional cases and analysing whole genomes will help to outline the significance of these findings.

  2. Significance and expression of stathmin and endoglin in colorectal carcinoma%微管不稳定蛋白和Endoglin在大肠癌组织中的表达

    Institute of Scientific and Technical Information of China (English)

    高文明; 李双齐; 王静

    2014-01-01

    目的 探讨微管不稳定蛋白(Stathmin)和Endoglin标记的微血管密度计数(MVD)在大肠癌中的表达及其与临床病理学参数之间的关系.方法 收集46例大肠癌患者手术切除的肿瘤组织和癌旁组织,运用免疫组织化学法检测Stathmin和Endoglin标记的MVD在组织中表达水平.结果 Stathmin大肠癌组织的表达率为69.57% (32/46),明显高于癌旁组织表达率[34.78% (16/46)],两者差异有统计学意义(P<0.01),Stathmin表达水平与大肠癌组织学分化程度、浸润深度、TNM分期、淋巴结转移明显相关(P<0.05);Endoglin标记的MVD大肠癌组织的表达强度为(68.27±5.66)个,明显高于癌旁组织的表达强度[(41.51±4.52)个],两者差异有统计学意义(P<0.01);Endoglin标记的MVD表达强度与大肠癌浸润深度、TNM分期、淋巴结转移明显相关(P<0.05).结论 联合检测Stathmin和Endoglin有助于判断大肠癌临床生物学行为.%Objective To analyze the relationship between the expression of Stathmin and endoglin-marked microvessel density (MVD) and clinicopathological features of colorectal carcinoma.Methods Immunohistochemistry was used to detect the expression levels of Stathmin and MVD marked with endoglin in 46 cases of human colorectal carcinoma tissues and non-cancerous adjacent colorectal tissues.Results The expression rate of Stathmin was 69.57% (32/46) in colorectal carcinoma tissues,and 34.78%(16/46) in non-cancerous adjacent colorectal tissues (P <0.01).The expression of Stathmin was related to histologic grade,serosa invasion,TNM stage and lymph node metastasis in colorectal carcinoma (P <0.05).The expression of MVD marked with endoglin was (68.27 ± 5.66) in colorectal carcinoma tissues,and (41.51 ±4.52) in non-cancerous adjacent colorectal tissues (P <0.01).The expression of MVD was related to serosa invasion,TNM stage and lymph node metastasis (P < 0.05).Conclusion The combined detection of Stathmin and endoglin may

  3. Involvement of Krüppel-like factor 6 (KLF6) mutation in the development of nonpolypoid colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To examine Krüppel-like factor 6 (KLF6) mutations in nonpolypoid-type tumors and alterations of K-ras, p53,and B-raf in relation between mutation and morphologic type, particularly nonpolypoid-type colorectal carcinomas.METHODS: Fifty-five early nonpolypoid colorectal carcinomas were analyzed. Loss of heterozygosity (LOH) of KLF6 and p53 was determined by microsatellite assay.Mutations of KLF6, K-ras, and B-raf were examined by polymerase chain reaction-single-strand conformation polymorphism followed by direct sequencing. In LOH-positive and/or mutation-positive tumors, multiple (4-7) samples in each tumor were microdissected and examined for genetic alterations, p53 expression was evaluated by immunohistochemistry.RESULTS: LOH of KLF6 and p53 was found in 14 of 29 (48.3%) and 14 of 31 (45.2%) tumors, respectively. In 10 of the 14 (71.4%) KLF6 LOH-positive tumors and 9 of the 14 (64.3%) p53 LOH-positive tumors, LOH was found in all of the microdissected samples. In 1 of the 10 (10.0%) KLF6 LOH-positive tumors, a single missense mutation was identified. K-ras and B-raf mutations were found in 5 of 55 (9.1%) and 6 of 55 (10.9%) tumors,respectively. However, these mutations were detected only in subsets of microdissected tumor samples.CONCLUSION: These data suggest that KLF6 and p53 mutations are involved in the development of nonpolypoid colorectal carcinoma, whereas K-ras and B-raf mutations are not.

  4. Re-expression of AKAP12 inhibits progression and metastasis potential of colorectal carcinoma in vivo and in vitro.

    Directory of Open Access Journals (Sweden)

    Weiwei Liu

    Full Text Available BACKGROUND: AKAP12/Gravin (A kinase anchor protein 12 is one of the A-kinase scaffold proteins and a potential tumor suppressor gene in human primary cancers. Our recent study demonstrated the highly recurrent loss of AKAP12 in colorectal cancer and AKAP12 reexpression inhibited proliferation and anchorage-independent growth in colorectal cancer cells, implicating AKAP12 in colorectal cancer pathogenesis. METHODS: To evaluate the effect of this gene on the progression and metastasis of colorectal cancer, we examined the impact of overexpressing AKAP12 in the AKAP12-negative human colorectal cancer cell line LoVo, the single clone (LoVo-AKAP12 compared to mock-transfected cells (LoVo-CON. RESULTS: pCMV6-AKAP12-mediated AKAP12 re-expression induced apoptosis (3% to 12.7%, p<0.01, migration (89.6±7.5 cells to 31.0±4.1 cells, p<0.01 and invasion (82.7±5.2 cells to 24.7±3.3 cells, p<0.01 of LoVo cells in vitro compared to control cells. Nude mice injected with LoVo-AKAP12 cells had both significantly reduced tumor volume (p<0.01 and increased apoptosis compared to mice given AKAP12-CON. The quantitative human-specific Alu PCR analysis showed overexpression of AKAP12 suppressed the number of intravasated cells in vivo (p<0.01. CONCLUSION: These results demonstrate that AKAP12 may play an important role in tumor growth suppression and the survival of human colorectal cancer.

  5. 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

  6. The antiproliferative effects of biologically active isomers of conjugated linoleic acid on human colorectal and prostatic cancer cells.

    Science.gov (United States)

    Palombo, John D; Ganguly, Aniruddha; Bistrian, Bruce R; Menard, Michael P

    2002-03-28

    The antiproliferative effects of two commercial preparations of conjugated linoleic acid (CLA) and their constituent isomers, cis-9, trans-11 (c9,t11)-CLA, c9,c11-CLA, and t10,c12-CLA, were determined in vitro using human colorectal (HT-29, MIP-101) and prostate (PC-3) carcinoma cells adapted to serum-free medium. The antiproliferative effects of the preparations were dependent upon the type and concentration of CLA isomer present. The t10,c12-CLA isomer exhibited the greatest potency against colorectal cancer proliferation, and the c9,t11 and t10,c12 isomers were moderately effective against prostate cancer. The t10,c12 isomer induced caspase-dependent apoptosis in MIP-101 and PC-3 cells. The results are the first to demonstrate that physiologic levels of two CLA preparations, their constituent isomers, and the c9,t11-CLA elongation product, c11,t13-conjugated eicosadienoic acid, induce dose-dependent inhibitory effects on cancer proliferation in vitro. Novel CLA preparations may prove effective as chemopreventive supplements for individuals at risk of or diagnosed with colorectal or prostate cancer.

  7. A Big Bang model of human colorectal tumor growth.

    Science.gov (United States)

    Sottoriva, Andrea; Kang, Haeyoun; Ma, Zhicheng; Graham, Trevor A; Salomon, Matthew P; Zhao, Junsong; Marjoram, Paul; Siegmund, Kimberly; Press, Michael F; Shibata, Darryl; Curtis, Christina

    2015-03-01

    What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion producing numerous intermixed subclones that are not subject to stringent selection and where both public (clonal) and most detectable private (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors showed an absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions, as postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations and not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear 'born to be bad', with subclone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH, with important clinical implications.

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

    Directory of Open Access Journals (Sweden)

    Hagen Per

    2006-03-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion Our data suggest an association between smoking and adenoma and CRC development. This association was strongest for cases without APC truncation

  9. Histopathological and genetic differences between polypoid and non-polypoid submucosal colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ichiro Hirata; Fang-Yu Wang; Mitsuyuki Murano; Takuya Inoue; Ken Toshina; Takashi Nishikawa; Kentaro Maemura

    2007-01-01

    AIM: To investigate the histopathological and geneticdifferences between polypoid growth (PG) and nonpolypoid growth (NPG) submucosal invasive colorectal carcinoma (CRC).METHODS: A total of 96 cases of submucosal CRC were divided into two groups according to their growth type;60 cases of PG and 36 cases of NPG. The size, histological degree of dysplasia, depth of submucosal invasion and lymph node metastasis were compared between the two groups. Furthermore, expression of p53 was detected by immunohistochemical staining, and K-ras gene mutation was examined by polymerase chain reaction based single-strand conformation polymorphism (SSCP).RESULTS: The average size of the lesions in the NPG group was significantly smaller than those in the PG group (7.5 mm vs 13.8 mm, P < 0.001). The histological degree of dysplasia tended to be more severe in NPG group, while the incidence of submucosal massive invasion and the lymph node metastasis were both significantly higher in the NPG type than in the PG group (64.3% vs 43.3%, P = 0.004; 43% vs 7%, P =0.008, respectively). In addition, K-ras gene mutations were detected in 67% of lesions in the PG group, but none in the NPG group, while no difference in p53immunohistochemical expression was found between the two groups.CONCLUSION: Compared with PG submucosal CRC,NPG type demonstrates more frequent submucosal massive invasion, more lymph node metastasis and a higher degree dysplasia. Genetically, NPG type shows much less frequent K-ras mutation.

  10. KRAS mutations testing in colorectal carcinoma patients in Italy: from guidelines to external quality assessment.

    Directory of Open Access Journals (Sweden)

    Nicola Normanno

    Full Text Available BACKGROUND: Monoclonal antibodies directed against the epidermal growth factor receptor (EGFR have been approved for the treatment of patients with metastatic colorectal carcinoma (mCRC that do not carry KRAS mutations. Therefore, KRAS testing has become mandatory to chose the most appropriate therapy for these patients. METHODOLOGY/PRINCIPAL FINDINGS: In order to guarantee the possibility for mCRC patients to receive an high quality KRAS testing in every Italian region, the Italian Association of Medical Oncology (AIOM and the Italian Society of Pathology and Cytopathology -Italian division of the International Academy of Pathology (SIAPEC-IAP started a program to improve KRAS testing. AIOM and SIAPEC identified a large panel of Italian medical oncologists, pathologists and molecular biologists that outlined guidelines for KRAS testing in mCRC patients. These guidelines include specific information on the target patient population, the biological material for molecular analysis, the extraction of DNA, and the methods for the mutational analysis that are summarized in this paper. Following the publication of the guidelines, the scientific societies started an external quality assessment scheme for KRAS testing. Five CRC specimens with known KRAS mutation status were sent to the 59 centers that participated to the program. The samples were validated by three referral laboratories. The participating laboratories were allowed to use their own preferred method for DNA extraction and mutational analysis and were asked to report the results within 4 weeks. The limit to pass the quality assessment was set at 100% of true responses. In the first round, only two centers did not pass (3%. The two centers were offered to participate to a second round and both centers failed again to pass. CONCLUSIONS: The results of this first Italian quality assessment for KRAS testing suggest that KRAS mutational analysis is performed with good quality in the majority of

  11. Mitomycin C pharmacokinetics in patients with recurrent or metastatic colorectal carcinoma.

    Science.gov (United States)

    Erlichman, C; Rauth, A M; Battistella, R; Fine, S

    1987-03-01

    The pharmacokinetics of mitomycin C as a single agent have been determined in 25 treatment courses given to 18 patients with recurrent or metastatic colorectal carcinoma using a high performance liquid chromatography (HPLC) assay to analyze plasma and urine samples. The plasma pharmacokinetics conformed to a two-compartment linear model in 21 of 25 courses monitored with a mean t1/2 lambda 1 of 9.8 +/- 1.2 (SEM) min and mean t1/2 lambda z of 64.1 +/- 8.9 (SEM) min. The large variation observed in t1/2 lambda z was not related to dose or treatment, but an interaction of these two factors approached significance (p = 0.057). Renal excretion in the 12 courses in which it was determined averaged only 2.3% of the total administered dose during the first 4 h monitored and no mitomycin C metabolites were detected in plasma or urine by the HPLC technique used. The most common toxicity, thrombocytopenia, did not correlate with t1/2 lambda z or the area under the curve. This may be due to a failure to monitor active metabolites of mitomycin C; other factors besides plasma drug concentrations that mediate toxicity towards marrow elements; or the small number of courses associated with thrombocytopenia (less than 100,000/mm3). Our study indicates that an interaction of drug dose and treatment course may be associated with increasing t1/2 lambda z; the renal clearance contributes a small component of mitomycin C elimination; metabolites of mitomycin C cannot be detected by the present HPLC technique; and routine monitoring of mitomycin C using present methods cannot be recommended for clinical use to predict toxicity.

  12. Cyclooxygenase-2 expression as a predictor of outcome in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jaudah AI-Maghrabi; Abdelbaset Buhrneida; Eman Emam; Kari Syrj(a)nen; Abdulrahman Sibiany; Mohmmad AI-Qahtani; Mahmoud AI-Ahwal

    2012-01-01

    AIM:To correlate cyclooxygenase-2 (COX-2) expression profile with clinical and pathological variables to assess their prognostic/predictive value in colorectal carcinoma (CRC).METHODS:Archival tumor samples were analyzed using immunohistochemistry for COX-2 expression in 94patients with CRC.Patients were diagnosed and treated at the Departments of Surgery and Oncology,King Abdulaziz University Hospital,Saudi Arabia.RESULTS:Fifty-six percent of the tumors showed positive cytoplasmic COX-2 expression,whereas 44% of cases were completely COX-2-negative.There were no significant correlations between COX-2 expression and sex,age,grade or tumor location.However,COX-2 expression revealed a significant correlation with tumor stage (P =0.01) and distant metastasis (P =0.02),and a borderline association with lymph node involvement (P=0.07).Tumors with high COX-2 expression showed a higher recurrence rate than tumors with no expression (P < 0.009).In univariate Kaplan-Meier survival analysis,there was a significant (P =0.026) difference in disease-free survival between COX-2-positive and negative tumors in favor of the latter.COX-2 expression did not significantly predict disease-specific survival,which was much shorter for COX-2-positive tumors.In multivariate (COX) models,COX-2 did not appear among the independent predictors of disease-free survival or disease-specific survival.CONCLUSION:COX-2 expression seems to provide useful prognostic information in CRC,while predicting the patients at high risk for recurrent disease.

  13. Prognostic significance and molecular features of signet-ring cell and mucinous components in colorectal carcinoma.

    Science.gov (United States)

    Inamura, Kentaro; Yamauchi, Mai; Nishihara, Reiko; Kim, Sun A; Mima, Kosuke; Sukawa, Yasutaka; Li, Tingting; Yasunari, Mika; Zhang, Xuehong; Wu, Kana; Meyerhardt, Jeffrey A; Fuchs, Charles S; Harris, Curtis C; Qian, Zhi Rong; Ogino, Shuji

    2015-04-01

    Colorectal carcinoma (CRC) represents a group of histopathologically and molecularly heterogeneous diseases, which may contain signet-ring cell component and/or mucinous component to a varying extent under pathology assessment. However, little is known about the prognostic significance of those components, independent of various tumor molecular features. Utilizing a molecular pathological epidemiology database of 1,336 rectal and colon cancers in the Nurses' Health Study and the Health Professionals Follow-up Study, we examined patient survival according to the proportion of signet-ring cell and mucinous components in CRCs. Cox proportional hazards models were used to compute hazard ratio (HR) for mortality, adjusting for potential confounders including stage, microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Compared to CRC without signet-ring cell component, 1-50 % signet-ring cell component was associated with multivariate CRC-specific mortality HR of 1.40 [95 % confidence interval (CI) 1.02-1.93], and >50 % signet-ring cell component was associated with multivariate CRC-specific mortality HR of 4.53 (95 % CI 2.53-8.12) (P trend 50 % mucinous component (multivariate HR 0.82; 95 % CI 0.54-1.23) was significantly associated with CRC-specific mortality (P trend < 0.57). Even a minor (50 % or less) signet-ring cell component in CRC was associated with higher patient mortality, independent of various tumor molecular and other clinicopathological features. In contrast, mucinous component was not associated with mortality in CRC patients.

  14. Expression of estrogen receptor β in human colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Li-Qun Xie; Jie-Ping Yu; He-Sheng Luo

    2004-01-01

    AIM: To determine the expression of estrogen receptor (ER)β in Chinese colorectal carcinoma (CRC) patients.METHODS: Erβ expression in CRC was investigated by immunohistochemical staining of formalin-fixed, paraffin-embedded tissue sections from 40 CRCs, 10 colonic adenomas,and 10 normal colon mucosa biopsies. The percentage of positive cells was recorded, mRNA expression of Erα and Erβ in 12 CRC tissues and paired normal colon tissues were detected by RT-PCR.RESULTS: Positive ER immunoreactivity was present in part of normal epithelium of biopsy (2/10), adenomas (3/10),and the sections of CRC tissue, most of them were nuclear positive. In CRCs, nuclear Erβ immunoreactivity was detected in over 10% of the cancer cells in 57.5% of the cases and was always associated with cytoplasmic immunoreactivity.There was no statistical significance between Erβ positive and negative groups in regard to depth of invasion and nodal metastases. Of the 12 CRC tissues and paired normal colon tissues, the expression rate of Erα mRNA in CRC tissue and corresponding normal colon tissue was 25% and 16.6%,respectively. Erβ mRNA was expressed in 83.3% CRC tissue and 91.7% paired normal colon tissue, respectively. Therewas no significant difference in Erβ mRNA level between CRC tissues and paired normal colon tissues.CONCLUSION: A large number of CRCs are positive for Erβ, which can also be detected in normal colonic epithelia.There is a different localization of Erβ immunoreactivity among normal colon mucosae, adenomas and CRCs. Erαand Erβ mRNA can be detected both in CRC tissue and in corresponding normal colon tissue. A post-transcriptional mechanism may account for the decrease of Erβ protein expression in CRC tissues.

  15. Colorectal carcinomas with submucosal invasion (pT1): analysis of histopathological and molecular factors predicting lymph node metastasis.

    Science.gov (United States)

    Pai, Reetesh K; Chen, Yuwei; Jakubowski, Maureen A; Shadrach, Bonnie L; Plesec, Thomas P; Pai, Rish K

    2017-01-01

    Submucosally invasive colorectal carcinoma (pT1) has the potential to be cured by local excision. In US surgical intervention is reserved for tumors with high-grade morphology, lymphvascular invasion, and close/positive margin. In other countries, particularly Japan, surgical therapy is also recommended for mucinous tumors, tumors with >1000 μm of submucosal invasion, and those with high tumor budding. These histological features have not been well evaluated in a western cohort of pT1 carcinomas. In a cohort of 116 surgically resected pT1 colorectal carcinomas, high tumor budding (P1000 μm (P=0.04), and high-grade morphology (P=0.04) were significantly associated with lymph node metastasis on univariate analysis. Mucinous differentiation, tumor location, tumor growth pattern, and size of invasive component were not significant. On multivariate analysis, only high tumor budding was associated with lymph node metastasis with an odds ratio of 4.3 (P=0.004). A subset of 48 tumors (22 node-positive and 26 node-negative) was analyzed for mutations in 50 oncogenes and tumor suppressors. No statistically significant molecular alterations in these 50 genes were associated with lymph node status. However, lymphatic invasion was associated with BRAF mutations (P=0.01). Furthermore, high tumor budding was associated with mutations in TP53 (P=0.03) and inversely associated with mutations in the mTOR pathway (PIK3CA and AKT, P=0.02). In conclusion, this study demonstrates the importance of identifying high tumor budding in pT1 carcinomas when considering additional surgical resection. Molecular alterations associated with adverse histological features are identified.

  16. Mycoplasma infections and different human carcinomas

    Institute of Scientific and Technical Information of China (English)

    Su Huang; Ji You Li; Jan Wu; Lin Meng; Cheng Chao Shou

    2001-01-01

    AIM To explore relationships between human carcinomas and mycoplasma infection.METHODS Monoclonal antibody PD4, which specifically recognizes a distinct protein from mycoplasma hyorhinis, was used to detect mycoplasma infection in different paraffinembedded carcinoma tissues with immunohistochemistry. PCR was applied to amplify the mycoplasma DNA from the positive samples for confirming immunohistochemistry.RESULTS Fifty of 90 cases (56%) of gastric carcinoma were positive for mycoplasma hyorhinis. In other gastric diseases, the mycoplasma infection ratio was 28% (18/49) in chronic superficial gastritis, 30% (14/ 46) in gastric ulcer and 37% (18/ 49) in intestinal metaplasia. The difference is significant with gastric cancer (X2=12.06, P<0.05). In colon carcinoma, the mycoplasma infection ratio was 55.1% (32/58), but it was 20.9% (10/49) in adenomarous polyp (X2=13.46, P<0.005).Gastric and colon cancers with high differentiation had a higher mycoplasma infection ratio than those with low differentiation (P< 0.05). Mycoplasma infection in esophageal cancer, lung cancer, breast cancer and glioma was 50.9% (27/53), 52.6% (31/ 59), 39.7%(25/63) and 41% (38/91), respectively. The mycoplasma DNA was successfully amplified with the DNA extracted from the cancer tissues that were positive for mycoplasma infection (detected with antibody PD4).CONCLUSION There was high correlation between mycoplasma infection and different cancers, which suggests the possibility of an association between the two. The mechanism involved in oncogenesis by mycoplasma remains unknown.

  17. 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

  18. Non-steroidal anti-inflammatory drugs and molecular carcinogenesis of colorectal carcinomas

    NARCIS (Netherlands)

    Huls, G; Koornstra, JJ; Kleibeuker, JH

    2003-01-01

    Context Colorectal cancer is the second most common cause of cancer-related mortality in the west. The high incidence and mortality make effective prevention an important public-health and economic issue. Non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit colorectal-carcinogenesis and are am

  19. AXL is an oncotarget in human colorectal cancer

    Science.gov (United States)

    Martinelli, Erika; Troiani, Teresa; Liguori, Giuseppina; Vitagliano, Donata; Napolitano, Stefania; Morgillo, Floriana; Rinaldi, Barbara; Melillo, Rosa Marina; Liotti, Federica; Nappi, Anna; Bianco, Roberto; Berrino, Liberato; Ciuffreda, Loreta Pia; Ciardiello, Davide; Iaffaioli, Vincenzo; Botti, Gerardo; Ferraiolo, Fiorella; Ciardiello, Fortunato

    2015-01-01

    AXL is a tyrosine kinase receptor activated by GAS6 and regulates cancer cell proliferation migration and angiogenesis. We studied AXL as new therapeutic target in colorectal cancer (CRC). Expression and activation of AXL and GAS6 were evaluated in a panel of human CRC cell lines. AXL gene silencing or pharmacologic inhibition with foretinib suppressed proliferation, migration and survival in CRC cells. In an orthotopic colon model of human HCT116 CRC cells overexpressing AXL, foretinib treatment caused significant inhibition of tumour growth and peritoneal metastatic spreading. AXL and GAS6 overexpression by immunohistochemistry (IHC) were found in 76,7% and 73.5%, respectively, of 223 human CRC specimens, correlating with less differentiated histological grading. GAS6 overexpression was associated with nodes involvement and tumour stage. AXL gene was found amplified by Fluorescence in situ hybridization (FISH) in 8/146 cases (5,4%) of CRC samples. Taken together, AXL inhibition could represent a novel therapeutic approach in CRC. PMID:25966280

  20. Influence of the Number of Lymph Nodes Examined on the Prognosis of Patients with Dukes' B and C Colorectal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xinyu Bi; Jianqiang Cai; Jianjun Zhao; Yongfu Shao; Ping Zhao

    2007-01-01

    OBJECTIVE To analyze the influence of the number of lymph nodes examined on the prognosis of Dukes' B and C colorectal cancer patients. METHODS The relationship between the clinicopathologic features of 373 patients with Dukes' B and C colorectal cancer and number of the lymph nodes examined was retrospectively analyzed. The effect of the different number of nodes examined on the prognosis of the patients was appraised RESULTS The overall mean number of retrieved lymph nodes of the 373 patients with Dukes' B and C colorectal cancer was 13.71 ±9.38. The site and size of the tumor as well as the depth of tumor infiltration were the major reasons which influenced the number of lymph nodes retrieved. The mean number of lymph nodes examined in the colon-cancer patients was 17.51 + 12.79, which was significantly more than the 11.09±6.17 (P = 0.000) examined in the rectal-cancer patients. The 5-year survival rate of the patients with Dukes' B large intestinal carcinoma, with fewer lymph nodes retrieved (0 to 10), was only 60.4%, while those with more lymph node retrieved (≥10) had a 5-year survival of 77.5%. So there was a significant difference between the two groups. However the number of lymph nodes examined had no effect on prognosis of the patients with Dukes' C large intestinal carcinoma. Separate analysis of the colon and rectal cancers indicated that to improve the 5-year survival rate, the number of retrieved nodes in cases with rectal cancer should be at least 9, and with colon cancer cases at least 13. CONCLUSION In order to guarantee an accuracy of tumor staging for developing a possible postoperative treatment, at least 9 lymph nodes in rectal cancer patients or 13 in colon cancer patients should be harvested.

  1. Expression and clinical significance of vascular endothelial growth factor-C and nm23-H1 in stage Ⅱ and Ⅲ colorectal carcinomas

    Institute of Scientific and Technical Information of China (English)

    耿倩倩

    2013-01-01

    Objective To discuss the expression and clinical significance of VEGF-C and nm23-H1 in stageⅡandⅢcolorectal carcinomas.Methods SP immunohistochemical staining was employed to determine the expression of vascular endothelial growth factor-C (VEGF-C) and nm23-H1 in the tumor tissues of 110 cases of stageⅡ

  2. Assessment of Nutritional and Inflammatory Status to Determine the Prevalence of Malnutrition in Patients Undergoing Surgery for Colorectal Carcinoma.

    Science.gov (United States)

    Daniele, Antonella; Divella, Rosa; Abbate, Ines; Casamassima, Addolorata; Garrisi, Vito Michele; Savino, Eufemia; Casamassima, Porzia; Ruggieri, Eustachio; DE Luca, Raffaele

    2017-03-01

    Colorectal Cancer is the fourth most frequent cause of cancer death worldwide and its incidence increases from 50 years of age. It is often associated with protein-caloric malnutrition and 20% of cancer deaths occur due to this event. The aim of this study was to assess the prevalence of malnutrition and inflammatory status in 78 patients undergoing surgery for colorectal carcinoma. Nutritional Status was assessed by Mini Nutritional Assessment (MNA). Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured by ELISA, while albumin, C-reactive protein (CRP) and transferrin (TRF) were tested using an immunometric assay. The mean MNA score in colorectal patients was 20.4±8.4, while 23/78 patients (29.4%) were well nourished, 36/78 (46.1%) were at risk of malnutrition and 19/78 (24.3%) were malnourished, reporting in the previous six months from the date of diagnosis a significant weight loss (>10 kg), muscle mass loss and severe reduction of food intake due to loss of appetite and altered taste perception. The serum means of IL-6, TNF-α and CRP, were significantly higher in colorectal patients compared to the control group (pmalnutrition and reported an imbalance between nutritional and inflammatory status. They, therefore, require a nutritional intervention before treatment in order to have a more effective response and improve quality of life. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Role of B7-H4 siRNA in Proliferation, Migration, and Invasion of LOVO Colorectal Carcinoma Cell Line

    Directory of Open Access Journals (Sweden)

    Hai-xia Peng

    2015-01-01

    Full Text Available Objectives. Colorectal cancer is one of the most common malignancies. Recent studies investigated that B7-H4 is highly expressed in various cancers. We aimed at exploring the effect of B7-H4 siRNA on proliferation, invasion, and migration of LOVO cells which expressed B7-H4 notably. Design and Methods. Colon adenocarcinoma dataset was downloaded from The Cancer Genome Atlas. 35 colorectal cancer patients admitted to Shanghai Tongren Hospital were enrolled in this study. Cell proliferation and cell cycle distribution were identified by CCK8 and flow cytometry, respectively. Transwell assay was performed to detect the invasion and migration of LOVO cells. CXCL12/CXCR4 expression and JAK2/STAT3 phosphorylation were determined by real-time PCR and western blot. Results. B7-H4 expressed is elevated in colorectal cancer tissues than in the adjacent normal tissues. B7-H4 siRNA effectively inhibited the proliferation at 24 h and 48 h, arrested cell cycle at G0/G1, and suppressed cell invasion and migration. Gene set enrichment analysis showed that CXCL12/CXCR4 and JAK/STAT were correlative with the B7-H4 expression. Additionally, CXCL12/CXCR4 expression and JAK2/STAT3 phosphorylation were reduced. Conclusions. B7-H4 siRNA can effectively inhibit proliferation, invasion, and migration of LOVO cells by targeting CXCL12/CXCR4 and JAK2/STAT3 signaling, which can serve as a new target for colorectal carcinoma treatment.

  4. Ribosomal protein genes are overexpressed in colorectal cancer: isolation of a cDNA clone encoding the human S3 ribosomal protein.

    Science.gov (United States)

    Pogue-Geile, K; Geiser, J R; Shu, M; Miller, C; Wool, I G; Meisler, A I; Pipas, J M

    1991-08-01

    We have isolated a cDNA clone encoding the human S3 ribosomal protein from a normal human colon cDNA library. The clone was identified as one of many that detected genes whose level of expression was increased in adenocarcinoma of the colon relative to normal colonic mucosa. Increased levels of the S3 transcript were present in the tumors of all eight patients examined. Moreover, the S3 mRNA was also more abundant in 7 of 10 adenomatous polyps, the presumed precursor of carcinoma. Additional studies demonstrated that increased levels of mRNAs encoding several other ribosomal proteins, including S6, S8, S12, L5, and P0, were present in colorectal tumors and polyps. These results suggest that there is increased synthesis of ribosomes in colorectal tumors and that this increase is an early event in colon neoplasia.

  5. LARG at chromosome 11q23 has functional characteristics of a tumor suppressor in human breast and colorectal cancer.

    Science.gov (United States)

    Ong, D C T; Ho, Y M; Rudduck, C; Chin, K; Kuo, W-L; Lie, D K H; Chua, C L M; Tan, P H; Eu, K W; Seow-Choen, F; Wong, C Y; Hong, G S; Gray, J W; Lee, A S G

    2009-11-26

    Deletion of 11q23-q24 is frequent in a diverse variety of malignancies, including breast and colorectal carcinoma, implicating the presence of a tumor suppressor gene at that chromosomal region. We examined a 6-Mb region on 11q23 by high-resolution deletion mapping, using both loss of heterozygosity analysis and customized microarray comparative genomic hybridization. LARG (leukemia-associated Rho guanine-nucleotide exchange factor) (also called ARHGEF12), identified from the analysed region, is frequently underexpressed in breast and colorectal carcinomas with a reduced expression observed in all breast cancer cell lines (n=11), in 12 of 38 (32%) primary breast cancers, 5 of 10 (50%) colorectal cell lines and in 20 of 37 (54%) primary colorectal cancers. Underexpression of the LARG transcript was significantly associated with genomic loss (P=0.00334). Hypermethylation of the LARG promoter was not detected in either breast or colorectal cancer, and treatment of four breast and four colorectal cancer cell lines with 5-aza-2'-deoxycytidine and/or trichostatin A did not result in a reactivation of LARG. Enforced expression of LARG in breast and colorectal cancer cells by stable transfection resulted in reduced cell proliferation and colony formation, as well as in a markedly slower cell migration rate in colorectal cancer cells, providing functional evidence for LARG as a candidate tumor suppressor gene.

  6. Zinc finger protein 278, a potential oncogene in human colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaoqing Tian; Danfeng Sun; Yanjie Zhang; Shuliang Zhao; Hua Xiong; Jingyuan Fang

    2008-01-01

    Zinc finger protein 278 (ZNF278) is a novel Krueppel Cys2-His2-type zinc finger protein that is ubiquitously distributed in human tissues. Whether ZNF278 is related to the development of colorectal cancer is still unclear. The transcriptional level of ZNF278 was studied in colorectal cancer by real-time polymerase chain reaction. The results showed that ZNF278 expression was increased in 53% of colorectal cancer tissues compared to corresponding non-cancerous tissues. The transcriptional down-regulation of ZNF278 was detected in only three (6%) human colorectal cancer tissues compared to corresponding non-cancer tissues. No significant difference was detected in 19 (41%) pairs of samples.However, we failed to find a significant association between the up-regulation of ZNF278 transcription and age, sex, the degree of infiltration, or the tumor size of colorectal cancer.To study the function of ZNF278 in colorectal carcinogenesis,the colon cancer cell line SW1116 was stably transfected with a wild-type ZNF278 plasmid to construct an overexpression system, and was transiently transfected with the small interfering RNA of ZNF278 to construct a ZNF278 knockdown system. Cell proliferation was assessed with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide dye and a cell counter. The results show that ZNF278 promotes cell growth, and its knockdown suppresses cell proliferation. ZNF278 could be a potential proto-oncogene in colorectal cancer.

  7. Human intestinal microbiota: cross-talk with the host and its potential role in colorectal cancer.

    Science.gov (United States)

    Candela, Marco; Guidotti, Marco; Fabbri, Alessia; Brigidi, Patrizia; Franceschi, Claudio; Fiorentini, Carla

    2011-02-01

    In this review, we discuss the multifactorial role of intestinal microbiota in colorectal cancer. The peculiar metabolism of dietary compounds of the individual microbiota complement, its overall immunostimulation and immunomodulatory activity, and eventually the production of toxins that perturb the regulation of cell growth, define the balance of positive and negative risk factors for colorectal cancer development. Moreover, shaping the composition of the human intestinal microbiota, diet has an indirect impact in determining the balance between health and disease. The integration of diet, microbial, and host factors in a system approach is mandatory to determine the overall balance of risk and protective factors for colorectal cancer onset.

  8. Proteomic profiling of a mouse model of acute intestinal Apc deletion leads to identification of potential novel biomarkers of human colorectal cancer (CRC).

    Science.gov (United States)

    Hammoudi, Abeer; Song, Fei; Reed, Karen R; Jenkins, Rosalind E; Meniel, Valerie S; Watson, Alastair J M; Pritchard, D Mark; Clarke, Alan R; Jenkins, John R

    2013-10-25

    Colorectal cancer (CRC) is the fourth most common cause of cancer-related death worldwide. Accurate non-invasive screening for CRC would greatly enhance a population's health. Adenomatous polyposis coli (Apc) gene mutations commonly occur in human colorectal adenomas and carcinomas, leading to Wnt signalling pathway activation. Acute conditional transgenic deletion of Apc in murine intestinal epithelium (AhCre(+)Apc(fl)(/)(fl)) causes phenotypic changes similar to those found during colorectal tumourigenesis. This study comprised a proteomic analysis of murine small intestinal epithelial cells following acute Apc deletion to identify proteins that show altered expression during human colorectal carcinogenesis, thus identifying proteins that may prove clinically useful as blood/serum biomarkers of colorectal neoplasia. Eighty-one proteins showed significantly increased expression following iTRAQ analysis, and validation of nine of these by Ingenuity Pathaway Analysis showed they could be detected in blood or serum. Expression was assessed in AhCre(+)Apc(fl)(/)(fl) small intestinal epithelium by immunohistochemistry, western blot and quantitative real-time PCR; increased nucelolin concentrations were also detected in the serum of AhCre(+)Apc(fl)(/)(fl) and Apc(Min)(/)(+) mice by ELISA. Six proteins; heat shock 60kDa protein 1, Nucleolin, Prohibitin, Cytokeratin 18, Ribosomal protein L6 and DEAD (Asp-Glu-Ala-Asp) box polypeptide 5,were selected for further investigation. Increased expression of 4 of these was confirmed in human CRC by qPCR. In conclusion, several novel candidate biomarkers have been identified from analysis of transgenic mice in which the Apc gene was deleted in the intestinal epithelium that also showed increased expression in human CRC. Some of these warrant further investigation as potential serum-based biomarkers of human CRC.

  9. Differential expression of IGF-1 mRNA isoforms in colorectal carcinoma and normal colon tissue.

    Science.gov (United States)

    Kasprzak, Aldona; Szaflarski, Witold; Szmeja, Jacek; Andrzejewska, Małgorzata; Przybyszewska, Wiesława; Kaczmarek, Elżbieta; Koczorowska, Maria; Kościński, Tomasz; Zabel, Maciej; Drews, Michał

    2013-01-01

    The insulin-like growth factor (IGF)-1 gene consists of 6 exons resulting in the expression of 6 variant forms of mRNA (IA, IB, IC, IIA, IIB and IIC) due to an alternative splicing. The mechanisms of IGF-1 gene splicing and the role of local expression manifested by IGF-1 mRNA variants in colorectal carcinoma (CRC) have not been extensively investigated. Therefore, the aim of our study was to analyse the expression of IGF-1 mRNA isoforms [A, B, C, P1 (class I) and P2 (class II)], as well as the protein expression in CRC and control samples isolated from 28 patients. The expression of Ki-67 was also analysed and clinical data were obtained. For this purpose, we used quantitative real-time PCR (qPCR) and immunocytochemistry. The expression of mRNAs coding for all splicing isoforms of IGF-1 was observed in every tissue sample studied, with a significantly lower expression noted in the CRC as compared to the control samples. The cytoplasmic expression of IGF-1 protein was found in 50% of the CRC and in ~40% of the non-tumor tissues; however, no significant quantitative inter-group differences were observed. The expression of the IGF-1 gene in the 2 groups of tissues was controlled by the P1 and P2 promoters in a similar manner. No significant differences were detected in the expression of the IGF-1 A and B isoforms; however, their expression was significantly higher compared to that of isoform C. No significant differences were observed between the expression of Ki-67 mRNA in the CRC and control tissue even though the expression of the Ki-67 protein was higher in the CRC compared to the control samples. Ki-67 protein expression was associated with the macroscopic and microscopic aspects of CRC. A significant positive correlation was found between the local production of total mRNA and isoform A and the expression of Ki-67 mRNA, although only in the non-tumor tissues. In CRC samples, the local expression of the total IGF-1 mRNA and all splicing isoforms of IGF-1 m

  10. HUMAN DNA QUANTIFICATION IN THE STOOLS OF PATIENTS WITH COLORECTAL CANCER

    Directory of Open Access Journals (Sweden)

    Yolanda TEIXEIRA

    2015-12-01

    Full Text Available Background - Colorectal cancer is one of the main cause of cancer in the world. Colonoscopy is the best screen method, however the compliance is less than 50%. Quantification of human DNA (hDNA in the feces may be a possible screen non-invasive method that is a consequence of the high proliferation and exfoliation of cancer cells. Objective - To quantify the human DNA in the stools of patients with colorectal cancer or polyps. Methods - Fifty patients with CRC, 26 polyps and 53 with normal colonoscopy were included. Total and human DNA were analyzed from the frozen stools. Results - An increased concentration of hDNA in the stools was observed in colorectal cancer patients compared to controls and polyps. Tumors localized in the left side of the colon had higher concentrations of hDNA. There were no difference between polyps and controls. A cut off of 0.87 ng/mL of human DNA was determined for colorectal cancer patients by the ROC curve, with a sensitivity of 66% and a specificity of 86.8%. For polyps the cut off was 0.41, the sensitivity was 41% and the specificity 77.4%. Conclusion - A higher concentration of hDNA had been found in colorectal cancer patients The quantification of hDNA from the stools can be a trial method for the diagnosis of colorectal cancer.

  11. Apoptosis inhibitor 5 (API-5; AAC-11; FIF) is upregulated in human carcinomas in vivo.

    Science.gov (United States)

    Koci, Lenka; Chlebova, Katarina; Hyzdalova, Martina; Hofmanova, Jirina; Jira, Miroslav; Kysela, Petr; Kozubik, Alois; Kala, Zdenek; Krejci, Pavel

    2012-04-01

    Apoptosis inhibitor 5 (API-5) is a 55 kDa nuclear protein with potent anti-apoptotic signaling in tumor cells in vitro. In this study, we analyzed the expression of the API-5 protein in vivo in a broad spectrum of human carcinomas, including those of the colon, lung, liver, kidney, pancreas, stomach and esophagus using tumor tissues obtained during tumor resection. The results showed significant upregulation of API-5 expression in biopsies of lung (23%, n=13) and colorectal tumors (33%, n=27) in comparison with biopsies from the adjacent normal tissue. Colon cancer biopsies were used to study the cell populations with an upregulated level of expression of API-5 more closely. Using a magnetic bead-based selection for the epithelial cell marker EpCAM, we purified epithelial cells from the tumor and control tissues and analyzed these cells for API-5 expression by western immunoblotting. We observed that EpCAM-positive tumor cells expressed API-5 in all three colorectal cancer cases tested, in contrast to the control EpCAM-positive and EpCAM-negative cells isolated from the control or tumor tissues. These data suggest that the expression of the API-5 protein is upregulated in tumor epithelial cells and may serve as a prognostic marker in colorectal cancer.

  12. S100A8 and S100A9 are associated with colorectal carcinoma progression and contribute to colorectal carcinoma cell survival and migration via Wnt/β-catenin pathway.

    Directory of Open Access Journals (Sweden)

    Liang Duan

    Full Text Available BACKGROUND AND OBJECTIVE: S100A8 and S100A9, two members of the S100 protein family, have been reported in association with the tumor cell differentiation and tumor progression. Previous study has showed that their expression in stromal cells of colorectal carcinoma (CRC is associated with tumor size. Here, we investigated the clinical significances of S100A8 and S100A9 in tumor cells of CRC and their underlying molecular mechanisms. METHODS: Expression of S100A8 and S100A9 in colorectal carcinoma and matching distal normal tissues were measured by reverse transcriptase polymerase chain reaction (RT-PCR, immunohistochemistry and western blot. CRC cell lines treated with the recombinant S100A8 and S100A9 proteins were used to analyze the roles and molecular mechanisms of the two proteins in CRC in vitro. RESULTS: S100A8 and S100A9 were elevated in more than 50% of CRC tissues and their expression in tumor cells was associated with differentiation, Dukes stage and lymph node metastasis. The CRC cell lines treatment with recombinant S100A8 and S100A9 proteins promoted the viability and migration of CRC cells. Furthermore, the two recombinant proteins also resulted in the increased levels of β-catenin and its target genes c-myc and MMP7. β-catenin over-expression in CRC cells by Adβ-catenin increased cell viability and migration. β-catenin knock-down by Adsiβ-catenin reduced cell viability and migration. Furthermore, β-catenin knockdown also partially abolished the promotive effects of recombinant S100A8 and S100A9 proteins on the viability and migration of CRC cells. CONCLUSIONS: Our work demonstrated that S100A8 and S100A9 are linked to the CRC progression, and one of the underlying molecular mechanisms is that extracellular S100A8 and S100A9 proteins contribute to colorectal carcinoma cell survival and migration via Wnt/β-catenin pathway.

  13. 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.

  14. Evolution in the treatment of metastatic colorectal carcinoma of the liver

    Institute of Scientific and Technical Information of China (English)

    Charlotte E Ariyan; Ronald R Salem

    2006-01-01

    Metastatic colorectal cancer to the liver is associated with a uniform poor prognosis without treatment. Advances in therapy over the past decades have now allowed surgical resections of the liver to occur with a low morbidity and mortality. Improvements in chemotherapy regimes have paralleled technical improvements and now allow a new group of patients to become eligible for surgical resection. This chapter will review the recent advances in surgical and chemotherapeutic regimes in metastatic colorectal cancer to the liver.

  15. Salinomycin inhibits the growth of colorectal carcinoma by targeting tumor stem cells.

    Science.gov (United States)

    Zhang, Chen; Tian, Yaping; Song, Feiyu; Fu, Changhao; Han, Bo; Wang, Yi

    2015-11-01

    Salinomycin is a monocarboxylic polyether antibiotic that has been reported to induce apoptosis in various types of cancer cells with specificity for cancer stem cells. However, its anticancer effect in colorectal cancer stem cells has never been reported. In the present study, we examined the ability of salinomycin to induce cell death in the colorectal cancer stem cell line CD44+EpCAM+ HCT-116, and we measured its in vivo tumor inhibition capacity. Salinomycin dose-dependently induced cytotoxicity in the CD44+EpCAM+ HCT-116 cells and inhibited colony formation. Salinomycin treatment was shown to induce apoptosis, as evidenced by nuclear fragmentation, an increase in the proportion of acridine orange/ethidium bromide-positive cells and an increase in the percentage of Annexin V-positive cells. Apoptosis was induced in colorectal cancer stem cells in a caspase-dependent manner, as shown by an increase in the levels of cleaved caspase-3, -8 and -9. JC-1 staining further revealed that salinomycin induced colorectal cancer cell apoptosis via the mitochondrial pathway. In addition, salinomycin treatment of xenograft mice inhibited the growth of tumors derived from the CD44+EpCAM+ HCT-116 cells. The present study demonstrated that the antibiotic salinomycin exerts an anti-colorectal cancer effect in vitro and in vivo, suggesting salinomycin as a potential drug for colorectal cancer therapy.

  16. Iatrogenic colorectal Kaposi sarcoma complicating a refractory ulcerative colitis in a human immunodeficiency negative-virus patient.

    Science.gov (United States)

    Hamzaoui, Lamine; Kilani, Houda; Bouassida, Mahdi; Mahmoudi, Moufida; Chalbi, Emna; Siai, Karima; Ezzine, Heykel; Touinsi, Hassen; Azzouz, Mohamed M'saddak; Sassi, Sadok

    2013-01-01

    Kaposi sarcoma is a mesenchymal tumor associated to a human herpes virus-8. It often occurs in human immunodeficiency virus-positive subjects. Colorectal localization is rare. We report the case of a colorectal Kaposi sarcoma complicating a refractory ulcerative colitis treated with surgery after the failure of immunomodulator therapy in a human immunodeficiency virus-negative heterosexual man.

  17. Increased expression of protease-activated receptor 4 and Trefoil factor 2 in human colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Guoyu Yu

    Full Text Available Protease-activated receptor 4 (PAR4, a member of G-protein coupled receptors family, was recently reported to exhibit decreased expression in gastric cancer and esophageal squamous cancer, yet increased expression during the progression of prostate cancer. Trefoil factor 2 (TFF2, a small peptide constitutively expressed in the gastric mucosa, plays a protective role in restitution of gastric mucosa. Altered TFF2 expression was also related to the development of gastrointestinal cancer. TFF2 has been verified to promote cell migration via PAR4, but the roles of PAR4 and TFF2 in the progress of colorectal cancer are still unknown. In this study, the expression level of PAR4 and TFF2 in colorectal cancer tissues was measured using real-time PCR (n = 38, western blotting (n=38 and tissue microarrays (n = 66. The mRNA and protein expression levels of PAR4 and TFF2 were remarkably increased in colorectal cancer compared with matched noncancerous tissues, especially in positive lymph node and poorly differentiated cancers. The colorectal carcinoma cell LoVo showed an increased response to TFF2 as assessed by cell invasion upon PAR4 expression. However, after intervention of PAR4 expression, PAR4 positive colorectal carcinoma cell HT-29 was less responsive to TFF2 in cell invasion. Genomic bisulfite sequencing showed the hypomethylation of PAR4 promoter in colorectal cancer tissues and the hypermethylation in the normal mucosa that suggested the low methylation of promoter was correlated to the increased PAR4 expression. Taken together, the results demonstrated that the up-regulated expression of PAR4 and TFF2 frequently occurs in colorectal cancer tissues, and that overexpression of PAR4 may be resulted from promoter hypomethylation. While TFF2 promotes invasion activity of LoVo cells overexpressing PAR4, and this effect was significantly decreased when PAR4 was knockdowned in HT-29 cells. Our findings will be helpful in further investigations into the

  18. Phorbol myristate acetate and Bryostatin 1 rescue IFN-gamma inducibility of MHC class II molecules in LS1034 colorectal carcinoma cell line

    Directory of Open Access Journals (Sweden)

    Wiseman Charles L

    2003-03-01

    Full Text Available Abstract Background The expression of major histocompatibility complex class II (MHCII antigens in both mouse and human tumors is rare, and these antigens are not easily inducible by IFN-gamma (IFNg. Since MHCII may play an important role in the development of host antitumor immune response, we explored the possibility of restoring MHCII inducibility in several IFNg-resistant tumor cell lines using protein kinase C (PKC agonists phorbol myristate acetate (PMA or Bryostatin. Results Tumor cells were co-cultured with various concentrations of PMA and IFNg for 48 hr. The expression of MHCII antigens and receptors IFNgR1 and IFNgR2 was determined by flow cytometry. We showed that the presence of as little as 0.1 ng/ml of PMA in tissue culture restored the ability of weakly inducible LS1034 colon carcinoma cells to express MHCII in response to IFNg (100 – 10,000 IU/ml in a dose-dependent manner. Likewise, Bryostatin 1, as low as 10 ng/ml produced a 5–6 fold upregulation of MHCII. The effect of PMA was not observed in two other poorly responding cell lines, MSTO-211H mesothelioma and HepG2 hepatocellular carcinoma, and was abrogated by relatively high concentrations of PKC inhibitors staurosporine (100 nM and GF 109203X (1,000 nM. Both surface and intracellular staining of all cell lines with antibodies against IFNgR1 and IFNgR2 failed to detect any increase in IFNg receptor expression following incubation with PMA. Conclusion In this study we showed that IFNg-inducibility of MHCII antigens in weakly inducible LS1034 colorectal carcinoma cell line can be rescued by concomitant incubation with PKC agonists. Bryostatin 1 may be considered for further investigation of IFNg-dependent MHCII induction in resistant tumors in vivo.

  19. Phorbol myristate acetate and Bryostatin 1 rescue IFN-gamma inducibility of MHC class II molecules in LS1034 colorectal carcinoma cell line

    Science.gov (United States)

    Kudinov, Yuri; Wiseman, Charles L; Kharazi, Alexander I

    2003-01-01

    Background The expression of major histocompatibility complex class II (MHCII) antigens in both mouse and human tumors is rare, and these antigens are not easily inducible by IFN-gamma (IFNg). Since MHCII may play an important role in the development of host antitumor immune response, we explored the possibility of restoring MHCII inducibility in several IFNg-resistant tumor cell lines using protein kinase C (PKC) agonists phorbol myristate acetate (PMA) or Bryostatin. Results Tumor cells were co-cultured with various concentrations of PMA and IFNg for 48 hr. The expression of MHCII antigens and receptors IFNgR1 and IFNgR2 was determined by flow cytometry. We showed that the presence of as little as 0.1 ng/ml of PMA in tissue culture restored the ability of weakly inducible LS1034 colon carcinoma cells to express MHCII in response to IFNg (100 – 10,000 IU/ml) in a dose-dependent manner. Likewise, Bryostatin 1, as low as 10 ng/ml produced a 5–6 fold upregulation of MHCII. The effect of PMA was not observed in two other poorly responding cell lines, MSTO-211H mesothelioma and HepG2 hepatocellular carcinoma, and was abrogated by relatively high concentrations of PKC inhibitors staurosporine (100 nM) and GF 109203X (1,000 nM). Both surface and intracellular staining of all cell lines with antibodies against IFNgR1 and IFNgR2 failed to detect any increase in IFNg receptor expression following incubation with PMA. Conclusion In this study we showed that IFNg-inducibility of MHCII antigens in weakly inducible LS1034 colorectal carcinoma cell line can be rescued by concomitant incubation with PKC agonists. Bryostatin 1 may be considered for further investigation of IFNg-dependent MHCII induction in resistant tumors in vivo. PMID:12787470

  20. Chimeric antibody with human constant regions and mouse variable regions directed against carcinoma-associated antigen 17-1A

    Energy Technology Data Exchange (ETDEWEB)

    Sun, L.K.; Curtis, P.; Rakowicz-Szulczynska, E.; Ghrayeb, J.; Chang, N.; Morrison, S.L.; Koprowski, H.

    1987-01-01

    The authors have cloned the genomic DNA fragments encoding the heavy and light chain variable regions of monoclonal antibody 17-1A, and they have inserted them into mammalian expression vectors containing genomic DNA segments encoding human ..gamma..3 and kappa constant regions. The transfer of these expression vectors containing mouse-human chimeric immunoglobulin genes into Sp2/0 mouse myeloma cells resulted in the production of functional IgG that retained the specific binding to the surface antigen 17-1A expressed on colorectal carcinoma cells.

  1. 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

  2. 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

    Directory of Open Access Journals (Sweden)

    Ishikawa Masashi

    2008-07-01

    Full Text Available Abstract Bckground 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. Methods 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. Results 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. Conclusion 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.

  3. 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.

  4. ERβ蛋白和COX-2蛋白在结直肠癌中的表达及临床意义%Expression and significance of estrogen receptor-β and cyclooxygenase-2 in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    殷红专; 梁逸超; 闫兆鹏; 孙威; 尹剑桥; 刘宝林; 苏琪

    2013-01-01

    Objective: To investigate the expressions of estrogen receptor -β(Erβ) and cyclooxygenase -2 ( COX - 2 ) in human colorectal carcinomas and their clinical significance. Methods: The immunohistochemical method was used to detect the expressions of the two proteins in 62 cases of colorectal carcinoma and 13 cases of adenoma, 10 cases of paracancerous tissues. Results: The expressions of the two proteins in 62 cases colorectal carcinoma and 13 cases of adenoma were higher than that in 10 cases of paracancerous tissues (P 0.05). In colorectal carcinoma,the expressions of Erp and COX -2 were not related to sex, degree of differentiation and invasion depth ( P > 0. 05 ) , where as related to the Dukes stages, metastasis of lymphnode (P < 0. 05). Conclusion : The expressions of Erβ and COX - 2 in paracancerous tissues, adenoma and colorectal carcinoma were increased , they are over expressed in colorectal cancer. Erβ and COX - 2 may promote the metastasis and evolution of colorectal cancer.%目的:探讨雌激素受体β(ERβ)和环氧化酶-2(COX-2)在结直肠癌中的表达及其临床意义.方法:采用免疫组化法检测ERβ、COX-2在62例结直肠腺癌组织标本中的表达,以其中大肠腺瘤13例及远癌正常大肠组织10例作对照.结果:ERβ及COX-2在远癌组织中阳性率低于腺瘤性息肉组及腺癌组的表达,其中远癌组织组与腺癌组有统计学差异(P<0.05),腺瘤性息肉组与腺癌组表达率无统计学差异(P>0.05).在结直肠癌病例中ERβ、COX-2表达与结直肠癌患者性别、肿瘤分化程度、肿瘤浸润层次无关(P>0.05),而与Dukes分期、有无转移淋巴结相关.结论:ERβ、COX-2在正常组织、腺瘤性息肉及腺癌中的表达逐步上调,ERβ和COX-2在结直肠癌组织中表达明显升高,可能促进了大肠癌的转移、进展.ERβ、COX-2蛋白在结直肠癌的演进中起着协同作用.

  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. Expression analysis of Stat3 in human lung carcinoma

    Institute of Scientific and Technical Information of China (English)

    WANG Hong; HAN Yi-ping

    2002-01-01

    Objective: To analyze the relationship of Stat3 expression with clinical stages, tissue types, p53and proliferation cell nuclear antigen (PCNA) in human lung carcinoma, and to evaluate the role of Stat3 in the pathogenesis of lung carcinoma. Methods: Immunohistochemical method were used to detected Stat3,p53 and PCNA in different tissues of patients (n= 42) with lung carcinoma who accepted neither radiotherapy nor chemotherapy. Results: The positive rate of Stat3 was 81.0% in lung carcinoma and its expression level was related to the tissue type but not to T, N or the clinical stage. The expression level of Stat3 in non-small cell lung carcinoma (NSCLC) was higher than that in small cell lung carcinoma (SCLC). A positive correlation of the expression of Stat3 with that of p53 and PCNA was identified. Conclusion: The expression level of Stat3 is abnormal in lung carcinoma. Stat3 may be involved in the regulation of p53 gene in lung carcinoma cell, it may accelerate the proliferation of lung carcinoma cells and play an important role in the pathogenesis of lung carcinoma.

  7. 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.

  8. Genetic and Epigenetic Changes of Components Affecting the WNT Pathway in Colorectal Carcinomas Stratified by Microsatellite Instability

    Directory of Open Access Journals (Sweden)

    Lin Thorstensen

    2005-02-01

    Full Text Available An unselected series of 310 colorectal carcinomas, stratified according to microsatellite instability (MSI and DNA ploidy, was examined for mutations and/or promoter hypermethylation of five components of the WNT signaling cascade [APC, CTNNB1 (encoding Rcatenin, AXIN2, TCF4, and WISP3] and three genes indirectly affecting this pathway [CDH1 (encoding β-cadherin, PTEN, and TP53]. APC and TP53 mutations were each present more often in microsatellite-stable (MSS tumors than in those with MSI (P < .001 for both. We confirmed that the aneuploid MSS tumors frequently contained TP53 mutations (P < .001, whereas tumors with APC mutations and/or promoter hypermethylation revealed no associations to ploidy. Mutations in APC upstream of codons 1020 to 1169, encoding the β-catenin binding site, were found in 15/144 mutated tumors and these patients seemed to have poor clinical outcome (P = .096. Frameshift mutations in AXIN2, PTEN, TCF4, and WISP3 were found in 20%, 17%, 46%, and 28% of the MSI tumors, respectively. More than half of the tumors with heterozygote mutations in AXIN2 were concurrently mutated in APC. The present study showed that more than 90% of all samples had alteration in one or more of the genes investigated, adding further evidence to the vital importance of activated WNT signaling in colorectal carcinogenesis.

  9. Fibroblast growth factor receptor 2 IIIc as a therapeutic target for colorectal cancer cells.

    Science.gov (United States)

    Matsuda, Yoko; Hagio, Masahito; Seya, Tomoko; Ishiwata, Toshiyuki

    2012-09-01

    A high percentage of colorectal carcinomas overexpress a lot of growth factors and their receptors, including fibroblast growth factor (FGF) and FGF receptor (FGFR). We previously reported that FGFR2 overexpression was associated with distant metastasis and that FGFR2 inhibition suppressed cell growth, migration, and invasion. The FGFR2 splicing isoform FGFR2IIIb is associated with well-differentiated histologic type, tumor angiogenesis, and adhesion to extracellular matrices. Another isoform, FGFR2IIIc, correlates with the aggressiveness of various types of cancer. In the present study, we examined the expression and roles of FGFR2IIIc in colorectal carcinoma to determine the effectiveness of FGFR2IIIc-targeting therapy. In normal colorectal tissues, FGFR2IIIc expression was weakly detected in superficial colorectal epithelial cells and was not detected in proliferative zone cells. FGFR2IIIc-positive cells were detected by immunohistochemistry in the following lesions, listed in the order of increasing percentage: hyperplastic polyps growth, soft agar colony formation, migration, and invasion, as well as decreased adhesion to extracellular matrices. Furthermore, FGFR2IIIc-transfected colorectal carcinoma cells formed larger tumors in subcutaneous tissues and the cecum of nude mice. Fully human anti-FGFR2IIIc monoclonal antibody inhibited the growth and migration of colorectal carcinoma cells through alterations in cell migration, cell death, and development-related genes. In conclusion, FGFR2IIIc plays an important role in colorectal carcinogenesis and tumor progression. Monoclonal antibody against FGFR2IIIc has promising potential in colorectal carcinoma therapy.

  10. Effect of evodiamine and berberine on miR-429 as an oncogene in human colorectal cancer

    Directory of Open Access Journals (Sweden)

    Liu H

    2016-07-01

    Full Text Available Hong Liu, Chao Huang, Liyun Wu, Bin Wen Institute of Spleen and Stomach, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China Abstract: Loss of epithelial organization and deregulated microRNAs are hallmarks of malignant carcinomas, but the relationship between them has been poorly understood. This study was designed to investigate the changes in the expression of E-cadherin, Par3, and miR-429 during the development of human colorectal cancer (CRC. E-cadherin and Par3 levels were quantitatively detected by immunohistochemistry and Western blotting. An in vitro culture of colorectal tissue was established to analyze the effect of berberine (BER and evodiamine (EVO on the level of miR-429. Our results suggested that E-cadherin and Par3 were remarkably decreased in tumor tissues compared with those in normal tissues, and miR-429 was upregulated in tumor tissues. After treatment of BER and EVO, the level of miR-429 was lower in tumor tissues than in normal tissues. This study investigated the potential relationship between miR-429, E-cadherin, and Par3 in CRC. The data suggested that BER and EVO can be potential therapeutic agents for CRC, as they downregulated the expression level of miR-429. Keywords: microRNAs, tissue culture

  11. FasL EXPRESSION IN HUMAN COLON CARCINOMAS

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective:The Fas and Fas ligand (FasL) play an important role in maintaining immune privilege on malignant tumors. In present study, we investigated the expression of FasL in SW480 and LS174 human colon carcinoma cell lines and twenty primary colon carcinoma specimens. Methods: The expression of FasL in human colon carcinoma cell lines and primary colon carcinomas specimens was detected by immunohistochemistry and Reverse Transcription-PCR (RT-PCR). Results: We found that all of detected human colon carcinoma cell lines and primary colon carcinoma specimens constitutively expressed FasL at the mRNA and protein level. However, the expression of FasL was not found in normal colon epithelial cells. Conclusion: The expression of FasL may occur during malignant transformation from normal colon epithelial cells to colon carcinoma cells. Our results suggest that tumor cells kill cytotoxic T lymphocytes (CTLS) and natural killer (NK) cells by expression of FasL. It may be a new mechanism for tumor cells to escape the host's immune surveillance. The expression of FasL may contribute to the formation of colon carcinomas.

  12. Portuguese propolis disturbs glycolytic metabolism of human colorectal cancer in vitro.

    Science.gov (United States)

    Valença, Isabel; Morais-Santos, Filipa; Miranda-Gonçalves, Vera; Ferreira, Ana Margarida; Almeida-Aguiar, Cristina; Baltazar, Fátima

    2013-07-19

    Propolis is a resin collected by bees from plant buds and exudates, which is further processed through the activity of bee enzymes. Propolis has been shown to possess many biological and pharmacological properties, such as antimicrobial, antioxidant, immunostimulant and antitumor activities. Due to this bioactivity profile, this resin can become an alternative, economic and safe source of natural bioactive compounds.Antitumor action has been reported in vitro and in vivo for propolis extracts or its isolated compounds; however, Portuguese propolis has been little explored. The aim of this work was to evaluate the in vitro antitumor activity of Portuguese propolis on the human colon carcinoma cell line HCT-15, assessing the effect of different fractions (hexane, chloroform and ethanol residual) of a propolis ethanol extract on cell viability, proliferation, metabolism and death. Propolis from Angra do Heroísmo (Azores) was extracted with ethanol and sequentially fractionated in solvents with increasing polarity, n-hexane and chloroform. To assess cell viability, cell proliferation and cell death, Sulforhodamine B, BrDU incorporation assay and Anexin V/Propidium iodide were used, respectively. Glycolytic metabolism was estimated using specific kits. All propolis samples exhibited a cytotoxic effect against tumor cells, in a dose- and time-dependent way. Chloroform fraction, the most enriched in phenolic compounds, appears to be the most active, both in terms of inhibition of viability and cell death. Data also show that this cytotoxicity involves disturbance in tumor cell glycolytic metabolism, seen by a decrease in glucose consumption and lactate production. Our results show that Portuguese propolis from Angra do Heroísmo (Azores) can be a potential therapeutic agent against human colorectal cancer.

  13. Portuguese propolis disturbs glycolytic metabolism of human colorectal cancer in vitro

    Science.gov (United States)

    2013-01-01

    Background Propolis is a resin collected by bees from plant buds and exudates, which is further processed through the activity of bee enzymes. Propolis has been shown to possess many biological and pharmacological properties, such as antimicrobial, antioxidant, immunostimulant and antitumor activities. Due to this bioactivity profile, this resin can become an alternative, economic and safe source of natural bioactive compounds. Antitumor action has been reported in vitro and in vivo for propolis extracts or its isolated compounds; however, Portuguese propolis has been little explored. The aim of this work was to evaluate the in vitro antitumor activity of Portuguese propolis on the human colon carcinoma cell line HCT-15, assessing the effect of different fractions (hexane, chloroform and ethanol residual) of a propolis ethanol extract on cell viability, proliferation, metabolism and death. Methods Propolis from Angra do Heroísmo (Azores) was extracted with ethanol and sequentially fractionated in solvents with increasing polarity, n-hexane and chloroform. To assess cell viability, cell proliferation and cell death, Sulforhodamine B, BrDU incorporation assay and Anexin V/Propidium iodide were used, respectively. Glycolytic metabolism was estimated using specific kits. Results All propolis samples exhibited a cytotoxic effect against tumor cells, in a dose- and time-dependent way. Chloroform fraction, the most enriched in phenolic compounds, appears to be the most active, both in terms of inhibition of viability and cell death. Data also show that this cytotoxicity involves disturbance in tumor cell glycolytic metabolism, seen by a decrease in glucose consumption and lactate production. Conclusion Our results show that Portuguese propolis from Angra do Heroísmo (Azores) can be a potential therapeutic agent against human colorectal cancer. PMID:23870175

  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

    There is emerging evidence of the association between human papillomavirus and a subset of head and neck cancers. However, the role of human papillomavirus as a causal factor is still debated. This review addresses the association between human papillomavirus and oropharyngeal squamous cell...... of well-defined premalignant lesions. However, a causal relationship between human papillomavirus infection and oropharyngeal squamous cell carcinoma seems evident....

  15. High Prevalence of Human Papillomavirus in Colorectal Cancer in Hispanics: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Raul D. Bernabe-Dones

    2016-01-01

    Full Text Available The role of Human Papillomavirus (HPV in colorectal carcinogenesis remains elusive. Based on the high incidence of HPV-associated malignancies among Puerto Rican Hispanics, this study aimed to assess the prevalence of HPV infection and viral integration in colorectal tissues in order to evaluate its putative role in colorectal cancer (CRC. In this case-control study, the prevalence of HPV infection in CRC (cases n = 45 and normal colon mucosa from cancer-free subjects (controls n = 36 was assessed by a nested PCR strategy. HPV-16 genotyping was performed in HPV-positive tissues and the physical status of the HPV-16 genome was determined by E2 detection. HPV was detected in 19 of 45 (42.2% CRC cases (mean age 61.1 ± 10.7 years, 24 males and in 1 of 36 (2.8% controls (mean age 60.9 ± 9.6 years, 24 males with an OR = 25.58 (95% CI 3.21 to 203.49. HPV-16 was detected in 63.2% of the HPV-positive colorectal tumors; genome integration was observed in all HPV-16 positive cases. This is the first report showing the high prevalence of HPV infections in Caribbean Hispanic colorectal tumors. Despite evidence of HPV integration into the host genome, further mechanistic analysis examining HPV oncoprotein expression and the putative role of these oncoproteins in colorectal carcinogenesis is warranted.

  16. Failure of CA19-9 to detect asymptomatic colorectal carcinoma.

    Science.gov (United States)

    Thomas, W M; Robertson, J F; Price, M R; Hardcastle, J D

    1991-06-01

    Serum CA19-9 levels have been measured in 34 patients with asymptomatic colorectal cancer, 39 age and sex matched subjects with healthy colons (as assessed at full colonoscopy) and 55 patients known to have liver metastases from primary colorectal cancers. In subjects with asymptomatic cancer the median CA19-9 was 12.75 U ml-1 (0.0-280.7 U ml-1), in the healthy controls the median CA19-9 was 12.80 U ml-1 (0.0-88.9 U ml-1) and in those with liver metastases was 62.5 U ml-1 (4.8-458.0 U ml-1). Levels were significantly higher in patients with metastatic disease than in patients with asymptomatic tumours or the healthy controls, however there was no significant difference between the asymptomatic group and the controls. Using an upper limit of normal of 37 U ml-1, the sensitivity of CA19-9 was 60.3% for the detection of colorectal cancer with liver metastases but only 17.6% for asymptomatic cancer. Serum CA19-9 estimation is of no value as a means of screening for asymptomatic colorectal cancer.

  17. 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 hi...

  18. Genes Involved in Human Ribosome Biogenesis areTranscriptionally Upregulated in Colorectal Cancer

    DEFF Research Database (Denmark)

    Mansilla, Francisco; Lamy, Philippe; Ørntoft, Torben Falck

    2009-01-01

    Microarray gene expression profiling comprising 168 colorectal adenocarcinomas and 10 normal mucosas showed that over 79% of the genes involved in human ribosome biogenesis are significantly upregulated (log2>0.5, p<10-3) when compared to normal mucosa. Overexpression was independent of microsate......Microarray gene expression profiling comprising 168 colorectal adenocarcinomas and 10 normal mucosas showed that over 79% of the genes involved in human ribosome biogenesis are significantly upregulated (log2>0.5, p... of rRNA processing genes points towards a coordinated process enabling the overproduction of matured ribosomal structures....

  19. Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases

    Institute of Scientific and Technical Information of China (English)

    Johannes H(a)nsler; Thadd(a)us Till Wissniowski; Detlef Schuppan; Astrid Witte; Thomas Bernatik; Eckhart Georg Hahn; Deike Strobel

    2006-01-01

    AIM: To assess if a specific cytotoxic T cell response can be induced in patients with malignant liver tumors treated with radio-frequency ablation (RFA).METHODS: Six Patients with liver metastases of colorectal cancer and 6 with hepatocellular carcinoma (HCC)underwent RFA. Blood was sampled before, 4 and 8 wk after RFA. Test antigens were autologous liver and tumor lysate obtained from each patient by biopsy. Peripheral T cell activation was assessed by an interferon gamma (IFNγ) secretion assay and flow cytometry. T cells were double-stained for CD4/CD8 and IFNγ to detect cytotoxic T cells. The ratio of IFNγ positive and IFNγ negative T cells was determined as the stimulation index (SI). To assess cytolytic activity, T cells were co-incubated with human CaCo colorectal cancer and HepG2 HCC cells and release of cytosolic adenylate kinase was measured by a luciferase assay.RESULTS: Before RFA SI was 0.021 (±0.006) for CD4+and 0.022 (±0.004) for CD8+T cells against nonmalignant liver tissue and 0.018 (±0.005) for CD4+ and 0.021(±0.004) for CD8+ cells against autologous tumor tissue.Four weeks after RFA SI against tumor tissue increased to 0.109 (±0.005) for CD4+ and 0.11 (±0.012) for CD8+T cells against HCC, and to 0.115 (±0.031) for CD4+ and 0.15 (±0.02) for CD8+ cells for colorectal metastases (P <0.0001). No increased SI was observed with nonmalignant tumor tissue at all time points. Before RFA cytolytic activity against the respective cancer cells was low with 2.62 (±0.37) relative luminescence units (RLU), but rose more than 100 fold 4 and 8 wk after RFA. Spontaneous release was <2% of maximum release in all experiments.CONCLUSION: Patients with primary and secondary tumors of the liver show a significant tumor-specific cytotoxic T-cell stimulation with a dramatically increased tumor specific cytolytic activity of CD8+ T cells after RFA.

  20. Hierarchical investigating the predictive value of p53, COX2, EGFR, nm23 in the post-operative patients with colorectal carcinoma

    Science.gov (United States)

    Zhang, Dachuan; Shao, Yingjie; Zheng, Xiao; Li, Xiaodong; Xiong, Yuqi; Wu, Changping; Jiang, Jingting

    2017-01-01

    The aim of this study was to evaluate the correlations between p53, COX2, EGFR, nm23 expression and the progression free survival (PFS) of post-operative patients with colorectal carcinoma. Immunohistochemistry was used to detect the expression of p53, COX2, EGFR and nm23 in 459 specimens from colorectal carcinoma patients. Kaplan-Meier estimates, Cox proportional hazard regression analyses and hierarchical analyses were performed on the collected data. Kaplan-Meier estimates analysis suggested that EGFR expression was as a negative predictor, the median PFS of patients with EGFR high expression was 21.73 months, and the median PFS of patients with low EGFR expression was 57.83 months (χ2=20.880, P<0.001); nm23 expression was positive predictive factor for the prognosis of patients with colorectal carcinoma, the median PFS of patients with high nm23 expression was 37.77 months, and the median PFS was 21.47 months in the patients with low nm23 expression (χ2=7.364, P=0.007). Cox regression analysis revealed that comparing with the patients with low expression of EGFR, the patients with high EGFR expression were at higher risk of tumor progression (HR=1.667, P=0.004); Comparing with the patients with high nm23 expression, the patients with nm23 low expression had a higher risk of tumor progression (HR=0.412, P<0.001); and the risk of tumor progression was higher in the patients with high EGFR expression and low nm23 expression (HR=0.245, P<0.001). Hierarchical analysis showed that EGFR expression mainly correlates with the PFS of TNM stage I-II colorectal cancer patients, the median PFS was 33.53 months in the TNM stage I-II colorectal cancer patients with high EGFR expression patients; The median PFS of the TNM stage I-II colorectal cancer patients with low EGFR expression was 70.43 months (χ2=9.530, P=0.002); The median PFS was 19.2 months in the TNM stage III-IV colorectal cancer patients with high expression EGFR, the PFS of the TNM stage III-IV colorectal

  1. Mast cells and human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Fabio Grizzi; Barbara Franceschini; Maurizio Chiriva-Internati; Young Liu; Paul L. Hermonat; Nicola Dioguardi

    2003-01-01

    AIM: To investigate the density of mast cells (MCs) in human hepatocellular carcinoma (HCC), and to determine whether the MCs density has any correlations with histopathological grading, staging or some baseline patient characteristics.METHODS: Tissue sections of 22 primary HCCs were histochemically stained with toluidine blue, in order to be able to quantify the MCs in and around the neoplasm using a computer-assisted image analysis system. HCC was staged and graded by two independent pathologists. To identify the sinusoidal capillarisation of each specimen 3μm thick sections were histochemically stained with sirius red, and semi-quantitatively evaluated by two independent observers. The data were statistically analysed using Spearman′s correlation and Student′s t-test when appropriate.RESULTS: MCs density did not correlate with the age or sex of the patients, the serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, or the stage or grade of the HCC. No significant differences were found between the MCs density of the patients with and without hepatitis C virus infection, but they were significantly higher in the specimens showing marked sinusoidal capillarisation.CONCLUSION: The lack of any significant correlation between MCs density and the stage or grade of the neoplastic lesions suggests that there is no causal relationship between MCs recruitment and HCC. However, as capillarisation proceeds concurrently with arterial blood supply during hepatocarcinogenesis, MCs may be considered of primary importance in the transition from sinusoidal to capillary-type endothelial cells and the HCC growth.

  2. Expression of p16 in Human Colorectal Cancer and its Clinical Signiifcance

    Institute of Scientific and Technical Information of China (English)

    HE Qian-qian

    2015-01-01

    Objective: To explore the expression of p16 in human colorectal cancer and its clinical signiifcance. Methods: Neoplastic tissues and autologous non-neoplastic tissues were taken from 30 patients with colorectal cancer immediately after the operation. The expression of p16 in these tissues was detected using immunohistochemistry, and then was conifrmed with HT-29 cell line by Western-blot assay. Results: The positive rate of p16 expression in neoplastic tissues was 23.3%, signiifcantly lower than that in non-neoplastic tissues (P<0.01). p16 expression was closely associated with Dukes’ staging (P<0.01), lymph node metastasis(P<0.05) and histological differentiation degrees (P<0.05). And western-blot assay showed that the p16 expression in HT-29 cells was consistent with that of human colorectal cancer. Conclusion:Abnormal expression of p16 may play an important role in the occurrence and progression of colorectal cancer, and hence, it would be associated with the prognosis of colorectal cancer.

  3. Intraarterial chemotherapy in the treatment of liver metastases secondary to colorectal carcinoma; Quimioterapia intraarterial en metastasis hepaticas secundarias a carcinoma colorrectal

    Energy Technology Data Exchange (ETDEWEB)

    Urtasun, F.; Tejedor, M.; Valerdi, J. J.; Barberena, J. [Hospital de Navarra. Pamplona (Spain)

    1999-07-01

    To asses survival and the radiologic response of colorectal liver metastases treated by intraarterial chemotherapy. We used intraarterial chemotherapy to treat 75 patients cytologically diagnosed as having non resectable liver metastases derived from colorectal carcinoma. Computed tomography (CT) of abdomen and pelvis was performed to rule out the presence of disease at other sites. Treatment consisted of continuous perfusion of 5-fluorouracil at a dose of 100 mg/day for 5 days, followed by chemo embolization with an emulsion of lipiodol and 5-fluorouracil (600 mg). The cycles were repeated every 4 weeks and the response was assessed by CT performed prior to administration of the third cycle and 30 days after the sixth. The toxicity was acceptable. One month after the second cycle, 10 patients presented disease progression, 4 showed substantial clinical deterioration and 3 had developed arterial dissection; the treatment was discontinued in all these patients. Fifty-eight patients completed the 6 cycles. In one, the lesions disappeared completely, 51 showed and evident reduction in their size and there were no changes in the remaining 6. the survival rate at one year was 71%, falling to 27% at two years, with a medium survival of 17 months. Survival was greater in those patients whose stage had been Dukes'B prior to treatment (p<0.01) and in those who had shown a radiologic response to treatment (p<0.05). Hepatic intraarterial chemotherapy is associated with low toxicity and a high rate of response, making it the indicated approach in selected patients. The mode of administration should be improved. (Author) 26 refs.

  4. Immunohistochemical and Western blot analysis of two protein tyrosine phosphatase receptors, R and Z1, in colorectal carcinoma, colon adenoma and normal colon tissues.

    Science.gov (United States)

    Woźniak, Marta; Gamian, Elżbieta; Łaczmańska, Izabela; Sąsiadek, Maria M; Duś-Szachniewicz, Kamila; Ziółkowski, Piotr

    2014-05-01

    Two classes of proteins, namely tyrosine kinases (PTK) and phosphatases (PTP), play an important role in cell proliferation and differentiation, thus leading to an acceleration or inhibition of tumour growth. The role of the above proteins in colorectal carcinoma (CRC) growth is a well-known event. In this study we carried out immunohistochemical and Western blot analysis of colorectal carcinoma, adenoma and normal colon tissue in relation to two protein tyrosine phosphatase receptors, R and Z1. Twenty-five cases of CRC were analyzed and the results were compared with similar data obtained in non-malignant tissues. High expression of both PTP receptors was observed in all examined cases of CRC, adenoma and normal colon tissue in this study. These results are not in line with recently published data, showing that genetic coding for PTPRR and PTPRZ1 were hypermethylated in CRC's. We presume that the protein tyrosine phosphatase overexpression in colorectal carcinoma is not enough to protect from the progression of disease.

  5. 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.

  6. The TPM3-NTRK1 rearrangement is a recurring event in colorectal carcinoma and is associated with tumor sensitivity to TRKA kinase inhibition.

    Science.gov (United States)

    Ardini, Elena; Bosotti, Roberta; Borgia, Andrea Lombardi; De Ponti, Cristina; Somaschini, Alessio; Cammarota, Rosaria; Amboldi, Nadia; Raddrizzani, Laura; Milani, Andrea; Magnaghi, Paola; Ballinari, Dario; Casero, Daniele; Gasparri, Fabio; Banfi, Patrizia; Avanzi, Nilla; Saccardo, Maria B; Alzani, Rachele; Bandiera, Tiziano; Felder, Eduard; Donati, Daniele; Pesenti, Enrico; Sartore-Bianchi, Andrea; Gambacorta, Marcello; Pierotti, Marco A; Siena, Salvatore; Veronese, Silvio; Galvani, Arturo; Isacchi, Antonella

    2014-12-01

    The NTRK1 gene encodes Tropomyosin-related kinase A (TRKA), the high-affinity Nerve Growth Factor Receptor. NTRK1 was originally isolated from a colorectal carcinoma (CRC) sample as component of a somatic rearrangement (TPM3-NTRK1) resulting in expression of the oncogenic chimeric protein TPM3-TRKA, but there has been no subsequent report regarding the relevance of this oncogene in CRC. The KM12 human CRC cell line expresses the chimeric TPM3-TRKA protein and is hypersensitive to TRKA kinase inhibition. We report the detailed characterization of the TPM3-NTRK1 genomic rearrangement in KM12 cells and through a cellular screening approach, the identification of NMS-P626, a novel highly potent and selective TRKA inhibitor. NMS-P626 suppressed TPM3-TRKA phosphorylation and downstream signaling in KM12 cells and showed remarkable antitumor activity in mice bearing KM12 tumors. Finally, using quantitative reverse transcriptase PCR and immunohistochemistry (IHC) we identified the TPM3-NTRK1 rearrangement in a CRC clinical sample, therefore suggesting that this chromosomal translocation is indeed a low frequency recurring event in CRC and that such patients might benefit from therapy with TRKA kinase inhibitors.

  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. MR imaging of colorectal carcinomas using an MR endoscopic coil; An in vitro study

    Energy Technology Data Exchange (ETDEWEB)

    Murano, Akihiko; Kido, Choichiro; Sasaki, Fumio; Nakamura, Tsuneya; Kobayashi, Semi; Katoh, Tomoyuki; Hirai, Takashi (Aichi Cancer Center, Nagoya (Japan). Hospital)

    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).

  9. The Use of PET-CT in the Assessment of Patients with Colorectal Carcinoma.

    Science.gov (United States)

    O'Connor, Owen J; McDermott, Shanaugh; Slattery, James; Sahani, Dushyant; Blake, Michael A

    2011-01-01

    Colorectal cancer is the third most commonly diagnosed cancer, accounting for 53,219 deaths in 2007 and an estimated 146,970 new cases in the USA during 2009. The combination of FDG PET and CT has proven to be of great benefit for the assessment of colorectal cancer. This is most evident in the detection of occult metastases, particularly intra- or extrahepatic sites of disease, that would preclude a curative procedure or in the detection of local recurrence. FDG PET is generally not used for the diagnosis of colorectal cancer although there are circumstances where PET-CT may make the initial diagnosis, particularly with its more widespread use. In addition, precancerous adenomatous polyps can also be detected incidentally on whole-body images performed for other indications; sensitivity increases with increasing polyp size. False-negative FDG PET findings have been reported with mucinous adenocarcinoma, and false-positive findings have been reported due to inflammatory conditions such as diverticulitis, colitis, and postoperative scarring. Therefore, detailed evaluation of the CT component of a PET/CT exam, including assessment of the entire colon, is essential.

  10. The Use of PET-CT in the Assessment of Patients with Colorectal Carcinoma

    Directory of Open Access Journals (Sweden)

    Owen J. O'Connor

    2011-01-01

    Full Text Available Colorectal cancer is the third most commonly diagnosed cancer, accounting for 53,219 deaths in 2007 and an estimated 146,970 new cases in the USA during 2009. The combination of FDG PET and CT has proven to be of great benefit for the assessment of colorectal cancer. This is most evident in the detection of occult metastases, particularly intra- or extrahepatic sites of disease, that would preclude a curative procedure or in the detection of local recurrence. FDG PET is generally not used for the diagnosis of colorectal cancer although there are circumstances where PET-CT may make the initial diagnosis, particularly with its more widespread use. In addition, precancerous adenomatous polyps can also be detected incidentally on whole-body images performed for other indications; sensitivity increases with increasing polyp size. False-negative FDG PET findings have been reported with mucinous adenocarcinoma, and false-positive findings have been reported due to inflammatory conditions such as diverticulitis, colitis, and postoperative scarring. Therefore, detailed evaluation of the CT component of a PET/CT exam, including assessment of the entire colon, is essential.

  11. Identification of a characteristic vascular belt zone in human colorectal cancer

    Science.gov (United States)

    Zöllner, Frank Gerrit; Schad, Lothar R.; Sinn, Hans-Peter; Marx, Alexander; Gaiser, Timo; Weis, Cleo-Aron

    2017-01-01

    Blood vessels in cancer Intra-tumoral blood vessels are of supreme importance for tumor growth, metastasis and therapy. Yet, little is known about spatial distribution patterns of these vessels. Most experimental or theoretical tumor models implicitly assume that blood vessels are equally abundant in different parts of the tumor, which has far-reaching implications for chemotherapy and tumor metabolism. In contrast, based on histological observations, we hypothesized that blood vessels follow specific spatial distribution patterns in colorectal cancer tissue. We developed and applied a novel computational approach to identify spatial patterns of angiogenesis in histological whole-slide images of human colorectal cancer. A characteristic spatial pattern of blood vessels in colorectal cancer In 33 of 34 (97%) colorectal cancer primary tumors blood vessels were significantly aggregated in a sharply limited belt-like zone at the interface of tumor tissue to the intestinal lumen. In contrast, in 11 of 11 (100%) colorectal cancer liver metastases, a similar hypervascularized zone could be found at the boundary to surrounding liver tissue. Also, in an independent validation cohort, we found this vascular belt zone: 22 of 23 (96%) samples of primary tumors and 15 of 16 (94%) samples of liver metastases exhibited the above-mentioned spatial distribution. Summary and implications We report consistent spatial patterns of tumor vascularization that may have far-reaching implications for models of drug distribution, tumor metabolism and tumor growth: luminal hypervascularization in colorectal cancer primary tumors is a previously overlooked feature of cancer tissue. In colorectal cancer liver metastases, we describe a corresponding pattern at the invasive margin. These findings add another puzzle piece to the complex concept of tumor heterogeneity. PMID:28253263

  12. Human papillomavirus-related carcinomas of the sinonasal tract.

    Science.gov (United States)

    Bishop, Justin A; Guo, Theresa W; Smith, David F; Wang, Hao; Ogawa, Takenori; Pai, Sara I; Westra, William H

    2013-02-01

    High-risk human papillomavirus (HPV) is an established cause of head and neck carcinomas arising in the oropharynx. The presence of HPV has also been reported in some carcinomas arising in the sinonasal tract, but little is known about their overall incidence or their clinicopathologic profile. The surgical pathology archives of The Johns Hopkins Hospital were searched for all carcinomas arising in the sinonasal tract from 1995 to 2011, and tissue microarrays were constructed. p16 immunohistochemical analysis and DNA in situ hybridization for high-risk types of HPV were performed. Demographic and clinical outcome data were extracted from patient medical records. Of 161 sinonasal carcinomas, 34 (21%) were positive for high-risk HPV DNA, including type 16 (82%), type 31/33 (12%), and type 18 (6%). HPV-positive carcinomas consisted of 28 squamous cell carcinomas and variants (15 nonkeratinizing or partially keratinizing, 4 papillary, 5 adenosquamous, 4 basaloid), 1 small cell carcinoma, 1 sinonasal undifferentiated carcinoma, and 4 carcinomas that were difficult to classify but exhibited adenoid cystic carcinoma-like features. Immunohistochemistry for p16 was positive in 59/161 (37%) cases, and p16 expression strongly correlated with the presence of HPV DNA: 33 of 34 (97%) HPV-positive tumors exhibited high p16 expression, whereas only 26 of 127 (20%) HPV-negative tumors were p16 positive (Pcarcinomas occurred in 19 men and 15 women ranging in age from 33 to 87 years (mean, 54 y). A trend toward improved survival was observed in the HPV-positive group (hazard ratio=0.58, 95% confidence interval [0.26, 1.28]). The presence of high-risk HPV in 21% of sinonasal carcinomas confirms HPV as an important oncologic agent of carcinomas arising in the sinonasal tract. Although nonkeratinizing squamous cell carcinoma is the most common histologic type, there is a wide morphologic spectrum of HPV-related disease that includes a variant that resembles adenoid cystic carcinoma. The

  13. Analysis of mitochondrial ND1 gene in human colorectal cancer

    Directory of Open Access Journals (Sweden)

    Mansoureh Akouchekian

    2011-01-01

    Conclusions: Results showed that a high frequency of somatic alterations of mtDNA occurs during the carcinogenesis and/or the progression of colorectal cancer. Based on the mtDNA mutation pattern observed in this study and other pre-viously studies it is believed that looking for somatic mutations in mtDNA would be one of the diagnostic values in early detection of cancer.

  14. Prognostic significance of TRAIL death receptors in Middle Eastern colorectal carcinomas and their correlation to oncogenic KRAS alterations

    Directory of Open Access Journals (Sweden)

    Hussain Azhar R

    2010-07-01

    Full Text Available Abstract Background Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL is a member of the tumour necrosis factor cytokine family that induces apoptosis upon binding to its death domain containing receptors, TRAIL receptor 1 (DR4 and TRAIL receptor 2 (DR5. Expression of TRAIL receptors is higher in colorectal carcinoma (CRC as compared to normal colorectal mucosa and targeted therapy with TRAIL leads to preferential killing of tumor cells sparing normal cells. Methods We investigated the expression of TRAIL and its receptors in a tissue microarray cohort of 448 Middle Eastern CRC. We also studied the correlation between TRAIL receptors and various clinico-pathological features including key molecular alterations and overall survival. Results CRC subset with TRAIL-R1 expression was associated with a less aggressive phenotype characterized by early stage (p = 0.0251 and a histology subtype of adenocarcinomas (p = 0.0355. Similarly CRC subset with TRAIL-R2 expression was associated with a well-differentiated tumors (p KIP1 and KRAS4A isoforms was significantly higher in CRC subset with TRAIL-R1 and TRAIL-R2 expression; TRAIL-R1 expression was also associated with cleaved caspase-3(p = 0.0011. Interestingly, TRAIL-R2 expression was associated with a microsatellite stable (MS--S/L phenotype (p = 0.0003 and with absence of KRAS mutations (p = 0.0481. Conclusion TRAIL-R1 expression was an independent prognostic marker for better survival in all CRC samples and even in the CRC group that received adjuvant therapy. The biological effects of TRAIL in CRC models, its enhancement of chemosensitivity towards standard chemotherapeutic agents and the effect of endogenous TRAIL receptor levels on survival make TRAIL an extremely attractive therapeutic target.

  15. Study on image feature extraction and classification for human colorectal cancer using optical coherence tomography

    Science.gov (United States)

    Huang, Shu-Wei; Yang, Shan-Yi; Huang, Wei-Cheng; Chiu, Han-Mo; Lu, Chih-Wei

    2011-06-01

    Most of the colorectal cancer has grown from the adenomatous polyp. Adenomatous lesions have a well-documented relationship to colorectal cancer in previous studies. Thus, to detect the morphological changes between polyp and tumor can allow early diagnosis of colorectal cancer and simultaneous removal of lesions. OCT (Optical coherence tomography) has been several advantages including high resolution and non-invasive cross-sectional image in vivo. In this study, we investigated the relationship between the B-scan OCT image features and histology of malignant human colorectal tissues, also en-face OCT image and the endoscopic image pattern. The in-vitro experiments were performed by a swept-source optical coherence tomography (SS-OCT) system; the swept source has a center wavelength at 1310 nm and 160nm in wavelength scanning range which produced 6 um axial resolution. In the study, the en-face images were reconstructed by integrating the axial values in 3D OCT images. The reconstructed en-face images show the same roundish or gyrus-like pattern with endoscopy images. The pattern of en-face images relate to the stages of colon cancer. Endoscopic OCT technique would provide three-dimensional imaging and rapidly reconstruct en-face images which can increase the speed of colon cancer diagnosis. Our results indicate a great potential for early detection of colorectal adenomas by using the OCT imaging.

  16. Detection and location of Helicobacter pylori in human gastric carcinomas

    Institute of Scientific and Technical Information of China (English)

    Yun-Lian Tang; Run-Liang Gan; Bi-Hua Dong; Ri-Chen Jiang; Rong-Jun Tang

    2005-01-01

    AIM: To define the infection status of Helicobacter pylori in 109 patients with gastric cancers and Hpylorilocalization in gastric carcinoma tissues in South China.METHODS: The incidence of Hpyloriinfection in gastric carcinomas was estimated by polymerase chain reaction (PCR), simultaneously; both morphological features and the localization of H pylori in gastric carcinomas were demonstrated by Warthin-Starry (WS) staining. The relationships between Hpylori infection and the clinicalpathologic factors of gastric carcinomas were analyzed by software SPSS10.0.RESULTS: Hpyloriwas found in 42 (39.03%) and 58(53.21%) cases of 109 patients with gastric carcinomas by PCRand WS, respectively. H pyloriinfection rate detected in gastric carcinomas by WS was higher than that by PCR (x2 = 9.735,P<0.005<0.01). WS stain showed that H pylori existed in the gastric antrum mucus, mucosal gland of normal tissues adjacent to gastric carcinomas and the gland, mucus pool of cancer tissues. The positive rate of H pyloriin normal tissues adjacent to carcinomas was higher than that in cancer tissues (x2 = 15.750, P<0.005<0.01). No significant differences in age, sex, site,histological types and lymph node metastasis were found between H pylorFpositive gastric carcinomas and H pylorinegative cases by both methods, but there were statistically significant differences of H pylori positive rate between early and advanced stage of gastric carcinomas (x2=4.548or 5.922, P = 0.033 or 0.015<0.05).CONCLUSION: These results suggested that H pylori infection might play a certain role in the early stage of carcinogenesis of human gastric mucosa epithelia.

  17. Staging of colorectal carcinoma by spiral CT with water enema : correlation with pathologic staging using new AJCC classification

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyoung Jung; Lee, Dong Ho; Ko, Young Tae [Kyunghee Univ. Hospital, Seoul (Korea, Republic of)

    1999-05-01

    In cases of colorectal cancer, to correlate the spiral CT staging with water enema with the pathologic staging according to the new AJCC classification. Ninety four patients with pathologically proven carcinoma of the colon who had undergone spiral CT with water enema were evaluated. CT scans were obtained after enema involving about 600-1,200mL of water. Scanning was performed from the diaphragmatic dome to the symphysis pubis using 10mm collimation thickness, 12mm table feed, and 10mm reconstruction interval. The TNM stage, as seen on spiral CT, was determined without reference to the pathologic results. Staging was performed according to the new AJCC cancer staging manual(1997). The pathologic T-stage was T1 in four cases(4.3%), T2 in 11(11.7%), T3 in 72(76.6%), and T4 in seven(7.4%). The pathologic N-stage was N0 in 57 cases(60.6%), N1 in 25 cases(26.6%), and N2 in 12(12.8%). The pathologic M-stage was M0 in 90 cases(95.7%) and M1 in four(4.3%). The detection rate of colon cancer using spiral CT with water enema was 97.9%. At the T-stage, pathologic correlation was good in 68.1% of cases(64/94). Nine patients(9.6%) were overstaged and 21(22.3%) were understaged. At the N-stage, pathologic correlation was good in 54.3% of cases(51/94), with 27 patients(28.7%) overstaged and sixteen(17.0%) understaged. At the M-stage, pathologic correlation was good in 95.7% of cases(90/94). Four patients(4.3%) were overstaged. The accuracy of staging of colorectal carcinoma by spiral hydro-CT was 68.1% at the T-stage, 54.3% at the N-stage, and 95.7% at the M-stage. As seen on spiral CT with water enema, the T-stage tended to wards understaging and the N-stage towards overstaging.

  18. Somatic Deletions of the PolyA Tract in the 3′ Untranslated Region of Epidermal Growth Factor Receptor Are Common in Microsatellite Instability–High Endometrial and Colorectal Carcinomas

    Science.gov (United States)

    Ma, Deqin; Chen, Zhao; Nero, Christopher; Patel, Keyur P.; Daoud, Emad M.; Cheng, Hanyin; Djordjevic, Bojana; Broaddus, Russell R.; Medeiros, L. Jeffrey; Rashid, Asif; Luthra, Rajyalakshmi

    2013-01-01

    Context Epidermal growth factor receptor (EGFR) is overexpressed in up to 80% of colorectal and endometrial carcinomas. Deletions of the polyA tract in the 3′ untranslated region (3′ UTR) have been reported in microsatellite instability–high (MSI-H) colonic carcinomas, but their impacts on EGFR expression and downstream pathways are unclear. This phenomenon has not been reported in other MSI-H tumors. Objective To assess the 3′ UTR polyA tract of EGFR in both endometrial and colorectal carcinomas and the mutational status of EGFR downstream pathways. Design Ninety-eight colorectal carcinomas and 47 endometrial carcinomas were included. EGFR 3′ UTR polyA status was detected by capillary electrophoresis and Sanger sequencing. EGFR gene expression, EGFR copy numbers, and KRAS and BRAF mutation status were analyzed accordingly. Results The 3′ UTR polyA tract was deleted in 18 of 23 (78%) MSI-H versus 0 of 24 microsatellite-stable endometrial carcinomas (P polyA deletions versus those with wild-type polyA tract. Amplification of the EGFR gene was not observed. Deletions in polyA tract do not seem to affect the frequency of KRAS and BRAF mutations. Conclusions Deletions of EGFR 3′ UTR polyA are frequent in endometrial and colorectal carcinomas, are confined almost exclusively to MSI-H tumors, and do not affect KRAS and BRAF mutations. PMID:22540299

  19. Somatic deletions of the polyA tract in the 3' untranslated region of epidermal growth factor receptor are common in microsatellite instability-high endometrial and colorectal carcinomas.

    Science.gov (United States)

    Deqin, Ma; Chen, Zhao; Nero, Christopher; Patel, Keyur P; Daoud, Emad M; Cheng, Hanyin; Djordjevic, Bojana; Broaddus, Russell R; Medeiros, L Jeffrey; Rashid, Asif; Luthra, Rajyalakshmi

    2012-05-01

    Epidermal growth factor receptor (EGFR) is overexpressed in up to 80% of colorectal and endometrial carcinomas. Deletions of the polyA tract in the 3' untranslated region (3' UTR) have been reported in microsatellite instability-high (MSI-H) colonic carcinomas, but their impacts on EGFR expression and downstream pathways are unclear. This phenomenon has not been reported in other MSI-H tumors. To assess the 3' UTR polyA tract of EGFR in both endometrial and colorectal carcinomas and the mutational status of EGFR downstream pathways. Ninety-eight colorectal carcinomas and 47 endometrial carcinomas were included. EGFR 3' UTR polyA status was detected by capillary electrophoresis and Sanger sequencing. EGFR gene expression, EGFR copy numbers, and KRAS and BRAF mutation status were analyzed accordingly. The 3' UTR polyA tract was deleted in 18 of 23 (78%) MSI-H versus 0 of 24 microsatellite-stable endometrial carcinomas (P polyA deletions versus those with wild-type polyA tract. Amplification of the EGFR gene was not observed. Deletions in polyA tract do not seem to affect the frequency of KRAS and BRAF mutations. Deletions of EGFR 3' UTR polyA are frequent in endometrial and colorectal carcinomas, are confined almost exclusively to MSI-H tumors, and do not affect KRAS and BRAF mutations.

  20. Polymorphisms of the XRCC1, XRCC3 and XPD genes and risk of colorectal adenoma and carcinoma, in a Norwegian cohort: a case control study

    Directory of Open Access Journals (Sweden)

    Aase Steinar

    2006-03-01

    Full Text Available Abstract Background Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of developing cancer. For colorectal cancer the importance of mutations in mismatch repair genes has been extensively documented. Less is known about other DNA repair pathways in colorectal carcinogenesis. In this study we have focused on the XRCC1, XRCC3 and XPD genes, involved in base excision repair, homologous recombinational repair and nucleotide excision repair, respectively. Methods We used a case-control study design (157 carcinomas, 983 adenomas and 399 controls to test the association between five polymorphisms in these DNA repair genes (XRCC1 Arg194Trp, Arg280His, Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln, and risk of colorectal adenomas and carcinomas in a Norwegian cohort. Odds ratio (OR and 95% confidence interval (95% CI were estimated by binary logistic regression model adjusting for age, gender, cigarette smoking and alcohol consumption. Results The XRCC1 280His allele was associated with an increased risk of adenomas (OR 2.30, 95% CI 1.19–4.46. The XRCC1 399Gln allele was associated with a reduction of risk of high-risk adenomas (OR 0.62, 95% CI 0.41–0.96. Carriers of the variant XPD 751Gln allele had an increased risk of low-risk adenomas (OR 1.40, 95% CI 1.03–1.89, while no association was found with risk of carcinomas. Conclusion Our results suggest an increased risk for advanced colorectal neoplasia in individuals with the XRCC1 Arg280His polymorphism and a reduced risk associated with the XRCC1 Arg399Gln polymorphism. Interestingly, individuals with the XPD Lys751Gln polymorphism had an increased risk of low-risk adenomas. This may suggest a role in regression of adenomas.

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

    DEFF Research Database (Denmark)

    Bak, Martin

    1996-01-01

    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...... 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...

  2. 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

    .005). Identified hypermethylated sites were validated in an independent sample set of eight normal mucosas, 12 adenomas, 40 MSS and nine MSI cancer samples. The methylation patterns of 15 selected genes, hypermethylated in adenomas and carcinomas (FLI1, ST6GALNAC5, TWIST1, ADHFE1, JAM2, IRF4, CNRIP1, NRG1, and EYA...

  3. 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.

  4. Nuclear β-catenin expression as a prognostic factor in advanced colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Adam Elzagheid; Abdelbaset Buhmeida; Eija Korkeila; Yrj(o) Collan; Karl Syrj(a)nen; Seppo Pyrh(o)nen

    2008-01-01

    AIM: To investigate the changing pattern of β-catenin expression and its prognostic value in advanced colorectal cancer (CRC).METHODS.Archival tumor samples were analyzed for β-catenin using immunohistochemisry (IHC) in 95 patients with advanced CRC.RESULTS: Membranous β-catenin expression was found in the normal colorectal epithelium.Almost 100% of CRCcases showed membranous and cytoplasmic expression,and 55 (58%) cases showed nuclear expression.In univariate (Kaplan-Meier)survival analysis,only the nuclear index (NI) was a significant predictor of disease free survival (DFS) (P=0.023; n = 35),with a NI above the median associated with longer DFS (34.2 mo) than those with a NI below the median (15.5 mo) (P = 0.045,ANOVA).The other indices were not significant predictors of DFS,and none of the three tested indices (for membranous,cytoplasmic,or nuclear expression) predicted diseasespecific survival (DSS).However,when dichotomized as positive or negative nuclear expression,the former was a significant predictor of more favorable DFS (P =0.041) and DSS (P = 0.046).CONCLUSION: Nuclear β-catenin expression provides additional information in predicting patient outcome in advanced CRC.

  5. Coordinate up-regulation of low-density lipoprotein receptor and cyclo-oxygenase-2 gene expression in human colorectal cells and in colorectal adenocarcinoma biopsies

    Science.gov (United States)

    Lum, D. F.; McQuaid, K. R.; Gilbertson, V. L.; Hughes-Fulford, M.

    1999-01-01

    Many colorectal cancers have high levels of cyclo-oxygenase 2 (COX-2), an enzyme that metabolizes the essential fatty acids into prostaglandins. Since the low-density lipoprotein receptor (LDLr) is involved in the uptake of essential fatty acids, we studied the effect of LDL on growth and gene regulation in colorectal cancer cells. DiFi cells grown in lipoprotein-deficient sera (LPDS) grew more slowly than cells with LDL. LDLr antibody caused significant inhibition of tumor cell growth but did not affect controls. In addition, LDL uptake did not change in the presence of excess LDL, suggesting that ldlr mRNA lacks normal feedback regulation in some colorectal cancers. Analysis of the ldlr mRNA showed that excess LDL in the medium did not cause down-regulation of the message even after 24 hr. The second portion of the study examined the mRNA expression of ldlr and its co-regulation with cox-2 in normal and tumor specimens from patients with colorectal adenocarcinomas. The ratio of tumor:paired normal mucosa of mRNA expression of ldlr and of cox-2 was measured in specimens taken during colonoscopy. ldlr and cox-2 transcripts were apparent in 11 of 11 carcinomas. There was significant coordinate up-regulation both of ldlr and of cox-2 in 6 of 11 (55%) tumors compared with normal colonic mucosa. There was no up-regulation of cox-2 without concomitant up-regulation of ldlr. These data suggest that the LDLr is abnormally regulated in some colorectal tumors and may play a role in the up-regulation of cox-2. Copyright 1999 Wiley-Liss, Inc.

  6. Effect of kaempferol on lipid peroxidation and antioxidant status in 1,2-dimethyl hydrazine induced colorectal carcinoma in rats.

    Science.gov (United States)

    Nirmala, Parthasarathy; Ramanathan, Manickam

    2011-03-01

    Colorectal cancer, a common cause of cancer related deaths in both sexes in western population is often due to persistent oxidative stress leading to DNA damage. Antioxidants scavenge free radicals and inhibit neoplastic process. Kaempferol, a flavonol widely distributed in tea, broccoli, grape fruit, brussels sprouts and apple, is claimed to have chemopreventive action in colon cancer. The aim of our study was to evaluate the effect of kaempferol on tissue lipid peroxidation and antioxidant status in 1,2-dimethyl hydrazine induced colorectal cancer in male Wistar rats and to compare its efficacy with irinotecan. Experimental colon cancer induced by 1,2-dimethyl hydrazine in rats mimic human colon cancer and therefore is an ideal model for chemoprevention studies. The rats were divided into six groups. Group 1 served as control. Group 2 received 1,2-dimethyl hydrazine (20 mg/kg body weight) subcutaneously once a week for four weeks. Group 3 received irinotecan (100 mg/kg body weight) intravenously once a week for four weeks with 1,2-dimethyl hydrazine. Groups 4 to 6 were given a daily oral dose of 50, 100, 200 mg/kg body weight of kaempferol with 1,2-dimethyl hydrazine. The total study period was 16 weeks. Kaempferol supplementation lowered 1,2-dimethyl hydrazine induced erythrocyte lysate and liver thiobarbituric acid reactive substances level and rejuvenated anti oxidant enzymes catalase, super oxide dismutase and glutathione peroxidase. The recovery of enzyme status was maximum at the dose of 200 mg/kg body weight and was comparable to irinotecan. Our study reveals that kaempferol could be safely used as a chemopreventive agent in colorectal cancer.

  7. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) overexpression in human colorectal cancer.

    Science.gov (United States)

    Mansilla, Francisco; da Costa, Kerry-Ann; Wang, Shuli; Kruhøffer, Mogens; Lewin, Tal M; Orntoft, Torben F; Coleman, Rosalind A; Birkenkamp-Demtröder, Karin

    2009-01-01

    The alteration of the choline metabolite profile is a well-established characteristic of cancer cells. In colorectal cancer (CRC), phosphatidylcholine is the most prominent phospholipid. In the present study, we report that lysophosphatidylcholine acyltransferase 1 (LPCAT1; NM_024830.3), the enzyme that converts lysophosphatidylcholine into phosphatidylcholine, was highly overexpressed in colorectal adenocarcinomas when compared to normal mucosas. Our microarray transcription profiling study showed a significant (p mucosas. Immunohistochemical analysis of colon tumors with a polyclonal antibody to LPCAT1 confirmed the upregulation of the LPCAT1 protein. Overexpression of LPCAT1 in COS7 cells localized the protein to the endoplasmic reticulum and the mitochondria and increased LPCAT1 specific activity 38-fold. In cultured cells, overexpressed LPCAT1 enhanced the incorporation of [(14)C]palmitate into phosphatidylcholine. COS7 cells transfected with LPCAT1 showed no growth rate alteration, in contrast to the colon cancer cell line SW480, which significantly (p < 10(-5)) increased its growth rate by 17%. We conclude that LPCAT1 may contribute to total choline metabolite accumulation via phosphatidylcholine remodeling, thereby altering the CRC lipid profile, a characteristic of malignancy.

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

    Science.gov (United States)

    Tang, Ren-Yi; Wang, Zun; Chen, Hong-Qi; Zhu, Si-Bo

    2017-01-01

    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.

  9. Human voltage-gated proton channel hv1: a new potential biomarker for diagnosis and prognosis of colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Yifan Wang

    Full Text Available Solid tumors exist in a hypoxic microenvironment, and possess high-glycolytic metabolites. To avoid the acidosis, tumor cells must exhibit a dynamic cytosolic pH regulation mechanism(s. The voltage-gated proton channel Hv1 mediates NADPH oxidase function by compensating cellular loss of electrons with protons. Here, we showed for the first time, that Hv1 expression is increased in colorectal tumor tissues and cell lines, associated with poor prognosis. Immunohistochemistry showed that Hv1 is strongly expressed in adenocarcinomas but not or lowly expressed in normal colorectal or hyperplastic polyps. Hv1 expression in colorectal cancer is significantly associated with the tumor size, tumor classification, lymph node status, clinical stage and p53 status. High Hv1 expression is associated significantly with shorter overall and recurrence-free survival. Furthermore, real-time RT-PCR and immunocytochemistry showed that Hv1 is highly expressed in colorectal cancer cell lines, SW620, HT29, LS174T and Colo205, but not in SW480. Inhibitions of Hv1 expression and activity in the highly metastatic SW620 cells by small interfering RNA (siRNA and Zn(2+ respectively, markedly decrease the cell invasion and migration, restraint proton extrusion and the intracellular pH recovery. Our results suggest that Hv1 may be used as a potential biomarker for diagnosis and prognosis of colorectal carcinoma, and a potential target for anticancer drugs in colorectal cancer therapy.

  10. Colorectal carcinomas in Uyo City, Southern geopolitical zone of Nigeria: a review of clinicopathological characteristics and literature

    Directory of Open Access Journals (Sweden)

    Emmanuel K. Abudu

    2016-06-01

    Full Text Available Colorectal carcinomas (CRC were initially thought to be rare in Africa including Nigeria, but recent studies have shown a reverse trend in our environment. This study is aimed to identify the clinical and pathological characteristics of CRC diagnosed between July 2006 and June 2015 in the University of Uyo Teaching Hospital, and a Private Specialist Laboratory, Uyo, Akwa Ibom State, Nigeria. All histological diagnosed cases of CRC seen in the two laboratories (University teaching and a private facility in Uyo, Akwa-Ibom state, Nigeria during the study period were retrieved noting their bio-data, pathological and clinical variables. A total of 45 patients of age range 26-80 years with a mean of 55.9 years (SD 3.9 and a male to female ratio of 1.4:1 were seen. The two most common age groups affected in CRCs were 61-70 years (28.9% and 51-60 years (24.4% respectively. Majority of CRC patients were older than 40 years (86.7% with identifiable predisposing factors being tubulo-villous adenoma (4 cases, 8.8%, villous adenoma (2 cases 4.4%, polyposis syndromes (2 cases, 4.4% and schistosomiasis (1 case, 2.2%. Features of large intestinal obstruction were the most common presenting symptom of CRC (53.3%. Rectal bleeding, alteration in bowel habit and fecal incontinence were other symptoms, accounting for 33.3%, 8.9% and 4.4% of cases respectively. Left-sided CRCs were commoner (68.9% with the majority appearing as annular-constricting type macroscopically (60.0%. Recto-sigmoid region was the preponderant site involved in CRC (29 cases, 64.5%. Adenocarcinoma (84.4% was the most frequent histological subtype. Mucinous carcinoma, signet ring carcinoma and carcinoid tumor were other histologic subtypes seen in 8.9, 4.4 and 2.2% of cases respectively. The 22.0% of CRC patients presented at advanced stages of the disease. It can be concluded that majority of CRC patients were older than 40 years (86.7% with features of intestinal obstruction (53.3% and

  11. Loss of fragile histidine triad protein in human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Po Zhao; Xin Song; Yuan-Yuan Nin; Ya-Li Lu; Xiang-Hong Li

    2003-01-01

    AIM: To investigate the expression of fragile histidine triad (FHIT) gene protein, Fhit, which is recently thought to be a candidate tumor suppressor. Abnormal expression of fragile histidine triad has been found in a variety of human cancers,but little is known about its expression in human hepatocellular carcinogenesis and evolution.METHODS: Sections of 83 primary human hepatocellular carcionoma with corresponding para-neoplastic liver tissue and 10 normal liver tissue were evaluated immunohistochemically for Fhit protein expression.RESULTS: All normal liver tissue and para-neoplastic liver tissue showed a strong expression of Fhit, whereas 50 of 83(65.0 %) carcinomas showed a marked loss or absence of Fhit expression. The differences of Fhit expression between carcinoma and normal or para-neoplastic liver tissue werehighly significant (P=0.000). The proportion of carcinomas with reduced Fhit expression showed an increasing trend (a) with decreasing differentiation or higher histological grade (P=0.219); (b) in tumors with higher clinical stage Ⅲ and ⅣV (91.3 %, P=0.000), compared with tumors with lower stage Ⅰ and Ⅱ (27.6 %); and (c) in cancers with bigger tumor size (>50 mm) (75.0 %, P=0.017), compared withsmaller tumor size (≤ 50 mm). CONCLUSION: FHIT inactivation seems to be both an earlyand a later event, associated with carcinogenesis andprogression to more aggressive hepatocellular carcinomas.Thus, evaluation of Fhit expression by immunohistochemistryin hepatocellular carcinoma may provide important diagnosticand prognostic information in clinical application.

  12. Prognostic impact of matched preoperative plasma and serum VEGF in patients with primary colorectal carcinoma

    DEFF Research Database (Denmark)

    Werther, K; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2002-01-01

    . The present study analyzed the prognostic value of matched preoperative serum and plasma vascular endothelial growth factor concentrations in patients with colorectal cancer. To establish the reference range among healthy people, vascular endothelial growth factor was analyzed in 50 matched EDTA......)) and healthy blood donors (220 pg ml(-1)). The preoperative vascular endothelial growth factor concentrations were dichotomized by the 95th percentile of the healthy blood donors (plasma=112 pg ml(-1), serum=533 pg ml(-1)). In univariate survival analyses, both high plasma vascular endothelial growth factor...... (>112 pg ml(-1)) and high serum vascular endothelial growth factor (>533 pg ml(-1)) predicted a reduced survival. In multivariate survival analyses, high serum vascular endothelial growth factor (>533 pg ml(-1)) independently predicted a reduced survival (HR=1.65, P=0.015), while high plasma vascular...

  13. Clinical features and mismatch repair gene mutation screening in Chinese patients with hereditary nonpolyposis colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Shan-Run Liu; Bo Zhao; Zhen-Jun Wang; Yuan-Lian Wan; Yan-Ting Huang

    2004-01-01

    AIM: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly- inherited cancer-susceptibility syndrome that confers an increased risk for colorectal cancer and a variety of other tumors at a young age. It has been associated with germline mutations in five mismatch repair (MMR) genes (hMSH2, hMLH1, hPMS1, hPMS2, and hMSH6/GTBP). The great majority of germline mutations were found in hMSH2 and hMLH1. The purpose of this study was to analyze the clinical features of Chinese HNPCC patients and to screen hMSH2 and hMLH1 gene mutations. METHODS: Twenty-eight independent Chinese families were collected, of which 15 met Amsterdam criteria I and 13 met the Japanese clinical diagnosis criteria. The data were recorded including sex, site of colorectal cancer (CRC),age of diagnosis, history of synchronous and/or metachronous CRC, instance of extracolonic cancers, and histopathology of tumors. Peripheral blood samples were collected from all pedigrees after formal written consents were signed. PCR and denaturing high-performance liquid chromatography (DHPLC) were used to screen the coding regions of hMSH2 and hMLH1 genes. The samples showing abnormal DHPLC profiles were sequenced by a 377 DNA sequencer.RESULTS: One hundred and seventy malignant neoplasms were found in one hundred and twenty-six patients (multiple cancer in twenty-three), including one hundred and twentyseven CRCs, fifteen gastric, seven endometrial, and five esophageal cancers. Seventy-seven point eight percent of the patients had CRCs, sharing the features of early occurrence (average age of onset, 45.9 years) and of the right-sided predominance reported in the literature. In Chinese HNPCC patients, gastric cancer occurred more frequently, accounting for 11.9% of all cancers patients and ranking second in the spectrum of HNPCC predisposing cancers. Synchronous CRCs occurred less frequently, only accounting for 3.1% of the total CRCs. Twenty percent of the colorectal patients had

  14. 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...

  15. Implication of late diagnosis for survival of patients with colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Zdravković Darko

    2009-01-01

    Full Text Available Background/Aim. Colorectal cancer (CRC is one of the most frequent diseases and early diagnosis has a potential role to improve survival. The aim of this study was to analyze influence of delay in diagnosis on survival in patients with colorectal cancer. Methods. A total of 119 patients with pathohystological diagnosis of CRC were included in the study. They were operated at our Department for Surgery from 2000 to 2002. They were divided into two groups according to the duration of symptoms: early operated patients - EOP (symptoms were presented for 3 months and late operated patients - LOP (duration of symptoms was more than 3 months. Follow-up period was 5 year. Results. Weight loss, intermittent abdominal pain and anorexia were more frequent in LOP (p < 0.01. Young age, blood in stool, and tumor localized in rectum were dominant characteristics in EOP (p < 0.05. Overall delay in diagnosis was 2.19 ± 0.79 months in EOP and 11.37 ± 5.68 months in LOP. There was highly statistically significant difference between these two groups (p < 0.01. Overall survival was 44.75%. Five years survival was 65.9% in the group of EOP and 26.5% in the group of LOP (χ2 = 28.16, p < 0.01 Weight loss was dominant characteristics in the patients who did not survive five years (χ2 = 14.26, p < 0.01. A period of 2 months in delay in diagnosis is 'cut-off' value in prediction of death (sensitivity of 75.5% and specificity of 90.3%. Conclusion. A delay in diagnosis and stage of the disease are highly significant factors of patients with CRC survival. In everyday medical practice higher importance should be put on weight loss, intermittent abdominal pain, change in bowel habits, as well as on syderopenic anaemia.

  16. Three Dimensional Culture of Human Renal Cell Carcinoma Organoids.

    Directory of Open Access Journals (Sweden)

    Cynthia A Batchelder

    Full Text Available Renal cell carcinomas arise from the nephron but are heterogeneous in disease biology, clinical behavior, prognosis, and response to systemic therapy. Development of patient-specific in vitro models that efficiently and faithfully reproduce the in vivo phenotype may provide a means to develop personalized therapies for this diverse carcinoma. Studies to maintain and model tumor phenotypes in vitro were conducted with emerging three-dimensional culture techniques and natural scaffolding materials. Human renal cell carcinomas were individually characterized by histology, immunohistochemistry, and quantitative PCR to establish the characteristics of each tumor. Isolated cells were cultured on renal extracellular matrix and compared to a novel polysaccharide scaffold to assess cell-scaffold interactions, development of organoids, and maintenance of gene expression signatures over time in culture. Renal cell carcinomas cultured on renal extracellular matrix repopulated tubules or vessel lumens in renal pyramids and medullary rays, but cells were not observed in glomeruli or outer cortical regions of the scaffold. In the polysaccharide scaffold, renal cell carcinomas formed aggregates that were loosely attached to the scaffold or free-floating within the matrix. Molecular analysis of cell-scaffold constructs including immunohistochemistry and quantitative PCR demonstrated that individual tumor phenotypes could be sustained for up to 21 days in culture on both scaffolds, and in comparison to outcomes in two-dimensional monolayer cultures. The use of three-dimensional scaffolds to engineer a personalized in vitro renal cell carcinoma model provides opportunities to advance understanding of this disease.

  17. Human Blood Autoantibodies in the Detection of Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Ola H Negm

    Full Text Available Colorectal cancer (CRC is the second most common malignancy in the western world. Early detection and diagnosis of all cancer types is vital to improved prognosis by enabling early treatment when tumours should be both resectable and curable. Sera from 3 different cohorts; 42 sera (21 CRC and 21 matched controls from New York, USA, 200 sera from Pittsburgh, USA (100 CRC and 100 controls and 20 sera from Dundee, UK (10 CRC and 10 controls were tested against a panel of multiple tumour-associated antigens (TAAs using an optimised multiplex microarray system. TAA specific IgG responses were interpolated against the internal IgG standard curve for each sample. Individual TAA specific responses were examined in each cohort to determine cutoffs for a robust initial scoring method to establish sensitivity and specificity. Sensitivity and specificity of combinations of TAAs provided good discrimination between cancer-positive and normal serum. The overall sensitivity and specificity of the sample sets tested against a panel of 32 TAAs were 61.1% and 80.9% respectively for 6 antigens; p53, AFP, K RAS, Annexin, RAF1 and NY-CO16. Furthermore, the observed sensitivity in Pittsburgh sample set in different clinical stages of CRC; stage I (n = 19, stage II (n = 40, stage III (n = 34 and stage IV (n = 6 was similar (73.6%, 75.0%, 73.5% and 83.3%, respectively, with similar levels of sensitivity for right and left sided CRC. We identified an antigen panel of sufficient sensitivity and specificity for early detection of CRC, based upon serum profiling of autoantibody response using a robust multiplex antigen microarray technology. This opens the possibility of a blood test for screening and detection of early colorectal cancer. However this panel will require further validation studies before they can be proposed for clinical practice.

  18. Genotoxicity of Cytolethal Distending Toxin (CDT on isogenic human colorectal cell lines: potential promoting effects for colorectal carcinogenesis

    Directory of Open Access Journals (Sweden)

    Vanessa eGraillot

    2016-03-01

    Full Text Available The composition of the human microbiota influences tumorigenesis, notably in colorectal cancer (CRC. Pathogenic Escherichia coli possesses a variety of virulent factors, among them the Cytolethal Distending Toxin (CDT. CDT displays dual DNase and phosphatase activities and induces DNA double strand breaks, cell cycle arrest and apoptosis in a broad range of mammalian cells. As CDT could promote malignant transformation, we investigated the cellular outcomes induced by acute and chronic exposures to E. coli CDT in normal human colon epithelial cells (HCECs. Moreover, we conducted a comparative study between isogenic derivatives cell lines of the normal HCECs in order to mimic the mutation of three major genes found in CRC genetic models: APC, KRAS and TP53. Our results demonstrate that APC and p53 deficient cells showed impaired DNA damage response after CDT exposure, whereas HCECs expressing oncogenic KRASV12 were more resistant to CDT. Compared to normal HCECs, the precancerous derivatives exhibit hallmarks of malignant transformation after a chronic exposure to CDT. HCECs defective in APC and p53 showed enhanced anchorage independent growth and genetic instability, assessed by the micronucleus formation assay. In contrast, the ability to grow independently of anchorage was not impacted by CDT chronic exposure in KRASV12 HCECs, but micronucleus formation is dramatically increased. Thus CDT does not initiate CRC by itself, but may have promoting effects in premalignant HCECs, involving different mechanisms in function of the genetic alterations associated to CRC.

  19. Comparing the DNA hypermethylome with gene mutations in human colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Kornel E Schuebel

    2007-09-01

    Full Text Available We have developed a transcriptome-wide approach to identify genes affected by promoter CpG island DNA hypermethylation and transcriptional silencing in colorectal cancer. By screening cell lines and validating tumor-specific hypermethylation in a panel of primary human colorectal cancer samples, we estimate that nearly 5% or more of all known genes may be promoter methylated in an individual tumor. When directly compared to gene mutations, we find larger numbers of genes hypermethylated in individual tumors, and a higher frequency of hypermethylation within individual genes harboring either genetic or epigenetic changes. Thus, to enumerate the full spectrum of alterations in the human cancer genome, and to facilitate the most efficacious grouping of tumors to identify cancer biomarkers and tailor therapeutic approaches, both genetic and epigenetic screens should be undertaken.

  20. The role and prognostic significance of p53 mutation in colorectal carcinomas

    Institute of Scientific and Technical Information of China (English)

    Chen Yang Ji; DR Smith; HS Goh

    2000-01-01

    AIM To study the prognostic significance of the p53 cDNA mutation and mutant p53 protein in colorectaladenocarcinomas.METHODS p53 cDNA mutaiton was detected with RT-PCR-SSCP, and mutant p53 protein overexpressionwas detected by PAb 240 monoclonal antibody in 100 cases of colorectal adenocarcinomas. The follow-upsurvey of all patients were done within the five years after operation, and comparing with p53 cDNAmutation and mutant p53 protein overexpression for the prognostic significance of colorectaladenocarcinomas. The data is treated with SPSS computer program, Kaplan-Meier Survival Plots werecalculated and analyzed by Log-rank analysis.RESULTS Fifty-one cases of p53 eDNA mutations (51%) were found with RT-PCR-SSCP and 76 cases ofmutant p53 protein overexpression (76%) found with PAb 240 monoclonal antibody immunohistochemistrystaining in 100 cases of colorectal adenocarcinomas. There are no relationship with Dukes stage in thestatistics in p53 eDNA mutation (mutation: Dukes A 9%, B 10%, C 20%, D 12%; No mutation: A 13%, B12%, C 12%, D 12%) and mutant p53 protein overexpression (positive: Dukes A 17%, B 6%, C 27%, D16%; negative: A 5%, B 6%, C 5%, D 8%) (P<0.05). Moreover, the data show p53 cDNA mutation isassociated with mutant p53 protein overexpression (both positive 49%, single positive 29%, both negative22%) (P<0.01), p53 eDNA mutation can provide prognostic information (p53 eDNA mutation positive:alive 35, dead 16; negative: alive 42, dead 7) (P<0.05), and mutant p53 protein overexpression isambiguous and does not assess prognosis (p53 protein overexpression positive: alive 58, dead 18; negative:alive 19, dead 5) (P = 0.72) with Kaplan-Meier Survival Plots and Log-rank analysis.CONCLUSION p53 eDNA mutation is associated with mutant p53 protein overexpression (p53 eDNAmutation and mutant p53 protein overexpression both positive 49%, single positive 29%, both negative 22%)(P<0.01) and p53 eDNA mutation can provide poor prognostic information, and is the

  1. The Relationship Between the Stromal Mast Cell Number, Microvessel Density, C-erbB-2 Staining and Survival and Prognostic Factors in Colorectal Carcinoma

    Directory of Open Access Journals (Sweden)

    Bahar ELEZOĞLU

    2012-05-01

    Full Text Available Objective: Colorectal adenocarcinomas take second place among the causes of death from carcinoma, and account for 98% of colorectal carcinomas. There is a need to determine new prognostic factors because of high frequency and significance.Material and Method: 204 colorectal carcinomas diagnosed between 01.01.2005 - 31.12.2008 at Uludağ University Medical Faculty Pathology Department were studied for Factor VIII and c-erbB-2 immunohistochemically and with toluidine blue stain histochemically. Association of mast cell number, microvessel density, and c-erbB-2 staining pattern with survival and known prognostic factors was evaluated.Results: Follow-up period was 4-60 months. A total of 111 cases were alive, and 65 had died. The mean number of mast cells was 8.00 (1-21 and the mean density of microvessels was 10.00 (2-21. Five-year survival rate of the mast cell group was 48.3% for values under 10 and 57.9% for values of 10 and higher. Five-year survival rate was 58.2% in the group with a microvessel density of 10 and above and 45.9% for values under 10. Five-year survival rate was 53.9% for the group with c-erbB-2 cytoplasmic staining and 48.2% for the group with membranous staining.Conclusion: The grade increased with the number of mast cells, while survival decreased with an increase in the number of mast cells. The ratio of c-erbB-2 staining increased as the grade and stage increased. There was an association between mast cell number and microvessel density. We found no relationship between prognosis and c-erbB-2, mast cell number, and microvessel density.

  2. Endoscopic diagnosis of invasion depth for early colorectal carcinomas: a prospective comparative study of narrow-band imaging, acetic acid, and crystal violet.

    Science.gov (United States)

    Zhang, Jing-Jing; Gu, Li-Yang; Chen, Xiao-Yu; Gao, Yun-Jie; Ge, Zhi-Zheng; Li, Xiao-Bo

    2015-02-01

    Several studies have validated the effectiveness of narrow-band imaging (NBI) in estimating invasion depth of early colorectal cancers. However, comparative diagnostic accuracy between NBI and chromoendoscopy remains unclear. Other than crystal violet, use of acetic acid as a new staining method to diagnose deep submucosal invasive (SM-d) carcinomas has not been extensively evaluated. We aimed to assess the diagnostic accuracy and interobserver agreement of NBI, acetic acid enhancement, and crystal violet staining in predicting invasion depth of early colorectal cancers. A total of 112 early colorectal cancers were prospectively observed by NBI, acetic acid, and crystal violet staining in sequence by 1 expert colonoscopist. All endoscopic images of each technique were stored and reassessed. Finally, 294 images of 98 lesions were selected for evaluation by 3 less experienced endoscopists. The accuracy of NBI, acetic acid, and crystal violet for real-time diagnosis was 85.7%, 86.6%, and 92.9%, respectively. For image evaluation by novices, NBI achieved the highest accuracy of 80.6%, compared with that of 72.4% by acetic acid, and 75.8% by crystal violet. The kappa values of NBI, acetic acid, and crystal violet among the 3 trainees were 0.74 (95% CI 0.65-0.83), 0.68 (95% CI 0.59-0.77), and 0.70 (95% CI 0.61-0.79), respectively. For diagnosis of SM-d carcinoma, NBI was slightly inferior to crystal violet staining, when performed by the expert endoscopist. However, NBI yielded higher accuracy than crystal violet staining, in terms of less experienced endoscopists. Acetic acid enhancement with pit pattern analysis was capable of predicting SM-d carcinoma, comparable to the traditional crystal violet staining.

  3. c-Jun-mediated β-1,3-N-acetylglucosaminyltransferase 8 expression: A novel mechanism regulating the invasion and metastasis of colorectal carcinoma cells.

    Science.gov (United States)

    Liu, Chunliang; Qiu, Hao; Yu, Meiyun; Wang, Zerong; Yuan, Yaqin; Jiang, Zhi; Shao, Xuejun; Hua, Dong; Liu, Min; Wu, Shiliang

    2017-09-01

    β-1,3-N-Acetylglucosaminyltransferase 8 (β3GnT8) is a key enzyme that catalyzes the formation of polylactosamine glycan structures by transferring GlcNAc to tetra-antennary β1-6-branched N-glycans, and it has been reported to participate in tumor invasion and metastasis by regulating the expression of matrix metalloproteinases (MMPs), cluster of differentiation 147 (CD147) and polylactosamine. By contrast, the role of transcription factor c-Jun in cell cycle progression has been well established. c-Jun has an important role in tumor cell invasion and metastasis. However, the precise molecular mechanisms by which c-Jun regulates these processes in colorectal carcinoma cells are not fully elucidated. In the present study, c-Jun had a significant effect on the invasive and migratory abilities of SW480 and LoVo cells. Additionally, overexpression of c-Jun was able to increase the expression of β3GnT8, MMPs, CD147 and polylactosamine. Similarly, knockdown of c-Jun was able to decrease the expression of β3GnT8, MMPs, CD147 and polylactosamine. These results suggest that c-Jun is able to regulate colorectal carcinoma cell invasion and metastasis via β3GnT8. A chromatin immunoprecipitation assay indicated that c-Jun is able to bind directly to the promoter regions of β3GnT8 in SW480 and LoVo cells. This leads to transcriptional activation of β3GnT8, which in turn regulates the expression of tumor invasion and metastasis-associated genes. The results of the present study demonstrate a novel mechanism underlying colorectal carcinoma cell invasion and metastasis, where β3GnT8 is transcriptionally activated via c-Jun binding to its promoter.

  4. Aberrant expressions of c-KIT and DOG-1 in mucinous and nonmucinous colorectal carcinomas and relation to clinicopathologic features and prognosis.

    Science.gov (United States)

    Foda, Abd Al-Rahman Mohammad; Mohamed, Mie Ali

    2015-10-01

    c-KIT and DOG-1 are 2 highly expressed proteins in gastrointestinal stromal tumors. Few studies had investigated c-KIT, but not DOG-1, expression in colorectal carcinoma (CRC). This study aims to investigate expressions of c-KIT and DOG-1 in colorectal mucinous carcinoma and nonmucinous carcinoma using manual tissue microarray technique. In this work, we studied tumor tissue specimens from 150 patients with colorectal mucinous (MA) and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique, and immunohistochemistry for c-KIT and DOG-1 was done. We found that aberrant c-KIT expression was detected in 12 cases (8%); 6 cases (4%) showed strong expression. Aberrant DOG-1 expression was detected in 15 cases (10%); among them, only 4 cases (2.7%) showed strong expression. Nonmucinous adenocarcinoma showed a significantly high expression of c-KIT, but not DOG-1, than MA. Aberrant c-KIT and DOG-1 expressions were significantly unrelated but were associated with excessive microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. In conclusion, aberrant c-KIT and DOG-1 expressions in CRC are rare events, either in NMA or MA. Nonmucinous adenocarcinoma showed a significantly higher expression of c-KIT, but not DOG-1, than MA. The expressions of both in CRC are significantly unrelated but are associated with microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. So, c-KIT and DOG-1 immunostaining is not a cost-effective method of identifying patients with CRC who may benefit from treatment with tyrosine kinase inhibitors. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Quantitative proteomics of extracellular vesicles derived from human primary and metastatic colorectal cancer cells

    OpenAIRE

    Gho, Yong Song; Choi, Dong-Sic; Choi, Do-Young; Hong, Bok Sil; Jang, Su Chul; Kim, Dae-Kyum; Lee, Jaewook; Kim, Yoon-Keun; Kim, Kwang Pyo

    2012-01-01

    Cancer cells actively release extracellular vesicles (EVs), including exosomes and microvesicles, into surrounding tissues. These EVs play pleiotropic roles in cancer progression and metastasis, including invasion, angiogenesis, and immune modulation. However, the proteomic differences between primary and metastatic cancer cell-derived EVs remain unclear. Here, we conducted comparative proteomic analysis between EVs derived from human primary colorectal cancer cells (SW480) and their metastat...

  6. Expression of retinoic acid receptors in human endometrial carcinoma.

    Science.gov (United States)

    Tanabe, Kojiro; Utsunomiya, Hiroki; Tamura, Mitsutoshi; Niikura, Hitoshi; Takano, Tadao; Yoshinaga, Kohsuke; Nagase, Satoru; Suzuki, Takashi; Ito, Kiyoshi; Matsumoto, Mitsuyo; Hayashi, Shin-ichi; Yaegashi, Nobuo

    2008-02-01

    The retinoids (vitamin A and its biologically active derivatives) are essential for the health and survival of the individual. Several studies have reported a strong rationale for the use of retinoids in cancer treatment and chemoprevention. It has been discovered that expression of retinoic acid receptor (RAR) beta is frequently silenced in epithelial carcinogenesis, which has led to the hypothesis that RAR beta could act as a tumor suppressor. However, the status of RAR beta in human endometrial carcinoma has not been examined. In the present study, we initially studied the effects of retinoic acid on cell proliferation and the expression of RAR alpha, RAR beta, and RAR gamma using AM580 (a RAR-specific agonist) in the Ishikawa endometrial cancer cell line. We also examined the expression of RAR in human eutopic endometrium (30 cases), endometrial hyperplasia (28 cases), and endometrial carcinoma (103 cases) using immunohistochemistry. Finally, we correlated these findings with the clinicopathological parameters. In vitro, cell growth was inhibited and RAR beta and RAR gamma mRNA was significantly induced by AM580, compared with vehicle controls, whereas RAR alpha mRNA was significantly attenuated by AM580, compared with vehicle. RAR beta was detected predominantly in endometrial hyperplasia, compared with endometrial carcinoma. No statistically significant correlation was obtained between the expression of any other RAR subtypes and clinicopathological parameters in human endometrial carcinoma. The results of our study demonstrate that AM580 inhibits cell growth and induces RAR beta mRNA expression in the Ishikawa cell line, and the expression level of RAR beta in endometrial carcinoma is significantly lower than that in endometrial hyperplasia. AM580 might therefore be considered as a potential treatment for endometrial carcinoma.

  7. [Familial colorectal and breast carcinoma--genetic counseling and presymptomatic diagnosis].

    Science.gov (United States)

    Müller, H; Scott, R J

    1995-12-01

    Several types of hereditary cancer can be prevented from progressing to advanced stages by regular surveillance of the person at risk and hence by the early treatment of a developing neoplasia. Genetic counselling of such patients and their relatives is therefore an important task whose value often remains unrecognized. This is especially true for the common forms of hereditary cancer such as breast and colorectal cancer, which aggregate in up to 5% of all patients according to the rules of autosomal-dominant inheritance. Preventive measures are particularly promising in the case of familial cancer because persons at risk are motivated to seek medical help. Genetic counselling is a multifaceted process and involves more than an accurate diagnosis and risk estimate. The counseled patient expects and deserves an open and reasonable answer to his questions about the implications of his/her cancer predisposition or his family history. Accurate diagnosis of the underlying susceptibility is the cornerstone of genetic counselling because most cancers seem to have multiple causes. Different genes located on different chromosomes can independently give rise to the same malignancy. Besides heterogeneity, presymptomatic testing for inherited susceptibilities to cancer raises many issues including therapy, access, intense anxiety, and discrimination.

  8. Parenchymal-sparing liver surgery in patients with colorectal carcinoma liver metastases

    Institute of Scientific and Technical Information of China (English)

    Fernando A Alvarez; Rodrigo Sanchez Claria; Sebastian Oggero; Eduardo de Santiba?es

    2016-01-01

    Liver resection is the treatment of choice for patients with colorectal liver metastases(CLM).However,major resections are often required to achieve R0 resection,which are associated with substantial rates of morbidity and mortality.Maximizing the amount of residual liver gained increasing significance in modern liver surgery due to the high incidence of chemotherapyassociated parenchymal injury.This fact,along with the progressive expansion of resectability criteria,has led to the development of a surgical philosophy known as "parenchymal-sparing liver surgery"(PSLS).This philosophy includes a variety of resection strategies,either performed alone or in combination with ablative therapies.A profound knowledge of liver anatomy and expert intraoperative ultrasound skills are required to perform PSLS appropriately and safely.There is a clear trend toward PSLS in hepatobiliary centers worldwide as current evidence indicates that tumor biology is the most important predictor of intrahepatic recurrence and survival,rather than the extent of a negative resection margin.Tumor removal avoiding the unnecessary sacrifice of functional parenchyma has been associated with less surgical stress,fewer postoperative complications,uncompromised cancer-related outcomes and higher feasibility of future resections.The increasing evidence supporting PSLS prompts its consideration as the gold-standard surgical approach for CLM.

  9. Visfatin is involved in promotion of colorectal carcinoma malignancy through an inducing EMT mechanism.

    Science.gov (United States)

    Yang, Jing; Zhang, Kun; Song, Haixing; Wu, Mingbo; Li, Jingyi; Yong, Ziyi; Jiang, Sheng; Kuang, Xi; Zhang, Tao

    2016-05-31

    Increasing evidences suggested visfatin, a newly discovered obesity-induced adipocytokine, is involved in promotion of cancer malignancy and correlated with worse clinical prognosis. While its effects and mechanisms on progression of colorectal cancer (CRC) remain unclear. Our clinical data show that visfatin protein is over expressed, positive associated with lymph node metastasis, high-grade tumor, and poor prognosis in 87 CRC patients. The levels of plasma visfatin are significantly upregulated in Stage IV colon cancer. Visfatin can significantly promote the in vitro migration and invasion of CRC cells via induction epithelial mesenchymal transition (EMT). It can increase the expression and nuclear translocation of Snail, a key transcription factor in regulating EMT. While silencing of Snail attenuates visfatin induced EMT. Further studies reveal visfatin can inhibit the association of Snail with GSK-3β and subsequently suppress ubiquitylation of Snail. In addition, visfatin can increase the expression and nuclear translocation of β-catenin, elevate its binding with Snail promoter, and then increase the transcription of Snail. While inhibitor of PI3K/Akt, LY294002, abolishes visfatin induced up regulation of Snail, Vimentin (Vim), β-catenin, and phosphorylated GSK-3β. In summary, our data suggest that increased expression of visfatin are associated with a more aggressive phenotype of CRC patients. It can trigger the EMT of CRC cells via Akt/GSK-3β/β-catenin signals.

  10. Somatic mutations of APC gene in carcinomas from hereditary non-polyposis colorectal cancer patients

    Institute of Scientific and Technical Information of China (English)

    Jian Huang; Shu Zheng; Shen-Hang Jin; Su-Zhan Zhang

    2004-01-01

    AIM: To investigate the mutational features of adenomatous polyposis coii (APC) gene and its possible arising mechanism in hereditary non-polyposis colorectal cancers (HNPCC).METHODS: PCR-based In Vitro Synthesized Protein Test (IVSP) assay and sequencing analysis were used to confirm somatic mutations of whole APC gene in 19 HNPCC cases. RESULTS: Eleven cases with 13 mutations were determined to harbor APC mutations. The prevalence of APC mutation was 58%(11/19). The mutations consisted of 9 frameshift and 4 nonsense ones, indicating that there were more frameshift mutations (69%). The frameshift mutations allexhibited deletion or insertion of 1-2 bp and most of them (7/9) happened at simple nucleotide repeat sequences, particularly within (A)n tracts (5/9). All point mutations presented C-to-T transitions at CpG sites. CONCLUSION: Mutations of APC gene were detected in more than half of HNPCC, indicating that its mutation was a common molecular event and might play an important role in the tumorigenesis of HNPCC. Locations of frameshift mutations at simple nucleotide repeat sequences and point mutations at CpG sites suggested that many mutations probably derived from endogenous processes including mismatch repair (MMR) deficiency. Defective MMR might affect the nature of APC mutations in HNPCC and likely occur earlier than APC mutational inactivation in some patients.

  11. Determination of boron concentration in blood and tissue samples from patients with liver metastases of colorectal carcinoma using Prompt Gamma Ray Activation Analysis (PGAA)

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, T., E-mail: schmito@uni-mainz.d [Institute for Nuclear Chemistry, University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany); Appelman, K., E-mail: k.appelman@hetnet.n [Institute for Energy, Joint Research Centre of the European Commission, Petten (Netherlands); Kudejova, P., E-mail: petra.kudejova@frm2.tum.d [Forschungs-Neutronenquelle Heinz Maier-Leibnitz (FRM II), Technische Universitaet Muenchen, D-85748 Garching (Germany); Schuetz, C., E-mail: schuetc@uni-mainz.d [Institute for Nuclear Chemistry, University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany); Kratz, J.V., E-mail: jvkratz@uni-mainz.d [Institute for Nuclear Chemistry, University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany); Moss, R., E-mail: raymond.moss@ec.europa.e [Institute for Energy, Joint Research Centre of the European Commission, Petten (Netherlands); Otto, G., E-mail: gerd.otto@unimedizin-mainz.d [Department of Hepatobiliary, Pancreatic and Transplantation Surgery, University of Mainz, Langenbeckstr. 1, D-55131 Mainz (Germany); Hampel, G., E-mail: gabriele.hampel@uni-mainz.d [Institute for Nuclear Chemistry, University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz (Germany)

    2011-07-15

    As part of the studies on Boron Neutron Capture Therapy at the University of Mainz, Germany, a clinical trial has been started in which, four patients suffering from liver metastases of colorectal carcinoma have been enrolled. Specimens of blood and healthy tissue samples taken from the patients were measured at the PGAA facilities at the HFR in Petten, The Netherlands, and at the FRM II in Munich, Germany. From the measured boron concentrations, pharmacokinetic curves and blood-to-tissue concentration ratios were produced.

  12. SOX7 is involved in aspirin-mediated growth inhibition of human colorectal cancer cells

    Institute of Scientific and Technical Information of China (English)

    Xin Zhou; Shu-Yan Huang; Jing-Xin Feng; Yan-Yan Gao; Li Zhao; Jun Lu; Bai-Qu Huang; Yu Zhang

    2011-01-01

    AIM: To confirm the role of sex-determining region Y-box 7 (Sox7) in aspirin-mediated growth inhibition of COX-independent human colorectal cancer cells.METHODS: The cell survival percentage was examined by MTT (Moto-nuclear cell direc cytotoxicity) assay.SOX7 expression was assessed by using reverse transcription-polymerase chain reaction and Western blotting. SB203580 was used to inhibit the p38MAPK signal pathway. SOX7 promoter activity was detected by Luciferase reporter assay.RESULTS: SOX7 was upregulated by aspirin and was involved in aspirin-mediated growth inhibition of SW480 human colorectal cancer cells. The p38MAPK pathway played a role in aspirin-induced SOX7 expression, during which the AP1 transcription factors c-Jun and c-Fos upregulated SOX7 promoter activities.RESULTS: SOX7 is upregulated by aspirin and is involved in aspirin-mediated growth inhibition of human colorectal cancer SW480 cells.

  13. A CpG island hypermethylation profile of primary colorectal carcinomas and colon cancer cell lines

    Directory of Open Access Journals (Sweden)

    Rognum Torleiv O

    2004-10-01

    Full Text Available Abstract Background Tumor cell lines are commonly used as experimental tools in cancer research, but their relevance for the in vivo situation is debated. In a series of 11 microsatellite stable (MSS and 9 microsatellite unstable (MSI colon cancer cell lines and primary colon carcinomas (25 MSS and 28 MSI with known ploidy stem line and APC, KRAS, and TP53 mutation status, we analyzed the promoter methylation of the following genes: hMLH1, MGMT, p16INK4a (CDKN2A α-transcript, p14ARF (CDKN2A β-transcript, APC, and E-cadherin (CDH1. We compared the DNA methylation profiles of the cell lines with those of the primary tumors. Finally, we examined if the epigenetic changes were associated with known genetic markers and/or clinicopathological variables. Results The cell lines and primary tumors generally showed similar overall distribution and frequencies of gene methylation. Among the cell lines, 15%, 50%, 75%, 65%, 20% and 15% showed promoter methylation for hMLH1, MGMT, p16INK4a, p14ARF, APC, and E-cadherin, respectively, whereas 21%, 40%, 32%, 38%, 32%, and 40% of the primary tumors were methylated for the same genes. hMLH1 and p14ARF were significantly more often methylated in MSI than in MSS primary tumors, whereas the remaining four genes showed similar methylation frequencies in the two groups. Methylation of p14ARF, which indirectly inactivates TP53, was seen more frequently in tumors with normal TP53 than in mutated samples, but the difference was not statistically significant. Methylation of p14ARF and p16INK4a was often present in the same primary tumors, but association to diploidy, MSI, right-sided location and female gender was only significant for p14ARF. E-cadherin was methylated in 14/34 tumors with altered APC further stimulating WNT signaling. Conclusions The present study shows that colon cancer cell lines are in general relevant in vitro models, comparable with the in vivo situation, as the cell lines display many of the same

  14. The predictive and prognostic value of the Glasgow Prognostic Score in metastatic colorectal carcinoma patients receiving bevacizumab.

    Science.gov (United States)

    Maillet, Marianne; Dréanic, Johann; Dhooge, Marion; Mir, Olivier; Brezault, Catherine; Goldwasser, François; Chaussade, Stanislas; Coriat, Romain

    2014-11-01

    The Glasgow Prognostic Score (GPS), based on C-reactive protein and albumin levels, has shown its prognostic value in metastatic colorectal carcinoma (mCRC) patients receiving conventional cytotoxic therapy. Bevacizumab, a monoclonal antibody to vascular epidermal growth factor, improves the overall survival in mCRC. The aim of the present study was to assess the prognostic value of GPS in mCRC patients receiving antivascular epidermal growth factor therapy. From August 2005 to August 2012, consecutive patients with mCRC who received chemotherapy plus bevacizumab were eligible for the present analysis. The clinical stage, C-reactive protein, albumin and the Eastern Cooperative Oncology Group performance status were recorded at the time of initiation of bevacizumab. Patients received 5-fluorouracil-based chemotherapy plus bevacizumab in accordance with the digestive oncology multidisciplinary staff proposal and in line with the French recommendations for the treatment of mCRC. Eighty patients were eligible (colon n = 59, rectum n = 21), with a median follow-up of 14 months (range 1-58 months). Chemotherapy given with bevacizumab and 5-fluorouracil was oxaliplatin (n = 41, 51%) or irinotecan (n = 27, 34%). At baseline, 56, 31 and 13% of patients had a GPS of 0 (n = 45), 1 (n = 25) and 2 (n = 10), respectively. The median progression-free survival in these groups was 10.1, 6.5 and 5.6 months (P = 0.16), respectively. The median overall survival was 20.1, 11.4 and 6.5 months, respectively (P = 0.004). Our study confirmed the prognostic value of GPS in mCRC patients receiving chemotherapy plus bevacizumab. Given the poor survival observed in patients with an GPS of 2, studies dedicated to these patients could identify optimal treatment modalities.

  15. 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.

  16. Genetic association of deleted in colorectal carcinoma variants with breast cancer risk: A case-control study.

    Science.gov (United States)

    Liu, Xinghan; Wang, Xijing; Fu, Sidney W; Wang, Meng; Kang, Huafeng; Guan, Haitao; Zhang, Shuqun; Ma, Xiaobin; Lin, Shuai; Liu, Kang; Feng, Yanjing; Dai, Cong; Dai, Zhijun

    2016-05-31

    Deleted in colorectal carcinoma (DCC), a netrin-1 dependence receptor, is correlated with cell progression, migration, and adhesion. Evidence indicated that DCC was frequently down-regulated in many cancers. However, the association of DCC with breast cancer remains uncertain. We conducted a case-control study to investigate the impact of three DCC gene variants (rs2229080, rs7504990, and rs4078288) on breast cancer susceptibility in Chinese women. This study included 560 breast cancer patients and 583 age-matched healthy controls from Northwest China. The three gene variants were genotyped via Sequenom MassARRAY. Odds ratios (ORs) and 95% confidence intervals (CIs) were utilized to evaluate the associations. We found that individuals with the rs2229080 C/G, C/C, and C/G-CC genotypes had a higher breast cancer risk, and the minor allele C was associated with increased breast cancer risk in an allele model. We observed a significantly decreased breast cancer risk with the rs7504990 C/T, T/T, and C/T-T/T genotypes, and the minor allele T was protective against breast cancer in an allele model. In addition, rs2229080 was associated with the axillary lymph node (LN) metastasis status. An age-stratified analysis revealed an association between rs2229080 and reduced breast cancer risk among older patients (≥ 49 years). Furthermore, the haplotype analysis showed that the Crs2229080Crs7504990Ars4078288 haplotype was associated with a decreased breast cancer risk. However, the results indicated a lack of association between rs4078288 and breast cancer risk. These findings affirmed that rs2229080 and rs7504990 polymorphisms in DCC might be related with breast cancer susceptibility in Chinese women.

  17. Molecular spectrum of KRAS, BRAF, and PIK3CA gene mutation: determination of frequency, distribution pattern in Indian colorectal carcinoma.

    Science.gov (United States)

    Bisht, Swati; Ahmad, Firoz; Sawaimoon, Satyakam; Bhatia, Simi; Das, Bibhu Ranjan

    2014-09-01

    Molecular evaluation of KRAS, BRAF, and PIK3CA mutation has become an important part in colorectal carcinoma evaluation, and their alterations may determine the therapeutic response to anti-EGFR therapy. The current study demonstrates the evaluation of KRAS, BRAF, and PIK3CA mutation using direct sequencing in 204 samples. The frequency of KRAS, BRAF, and PIK3CA mutations was 23.5, 9.8, and 5.9 %, respectively. Five different substitution mutations at KRAS codon 12 (G12S, G12D, G12A, G12V, and G12C) and one substitution type at codon 13 (G13D) were observed. KRAS mutations were significantly higher in patients who were >50 years, and were associated with moderate/poorly differentiated tumors and adenocarcinomas. All mutations in BRAF gene were of V600E type, which were frequent in patients who were ≤ 50 years. Unlike KRAS mutations, BRAF mutations were more frequent in well-differentiated tumors and right-sided tumors. PIK3CA-E545K was the most recurrent mutation while other mutations detected were T544I, Q546R, H1047R, G1049S, and D1056N. No significant association of PIK3CA mutation with age, tumor differentiation, location, and other parameters was noted. No concomitant mutation of KRAS and BRAF mutations was observed, while, interestingly, five cases showed concurrent mutation of KRAS and PIK3CA mutations. In conclusion, to our knowledge, this is the first study to evaluate the PIK3CA mutation in Indian CRC patients. The frequency of KRAS, BRAF, and PIK3CA was similar to worldwide reports. Furthermore, identification of molecular markers has unique strengths, and can provide insights into the pathogenic process and help optimize personalized prevention and therapy.

  18. Expression of epidermal growth factor receptors in human endometrial carcinoma

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, Anette Lynge; Ottesen, B

    1993-01-01

    Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous...... hyperplasia. EGF-R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent....../inactive endometria and seven of 13 (54%) endometria with adenomatous hyperplasia were EGF-R positive, with an immunostaining pattern rather similar to that of the carcinomas....

  19. Expression of cyclooxygenase-2 in human esophageal squamous cell carcinomas

    Institute of Scientific and Technical Information of China (English)

    Jian-Gang Jiang; Dao-Wen Wang; Jiang-Bo Tang; Chun-Lian Chen; Bao-Xing Liu; Xiang-Ning Fu; Zhi-Hui Zhu; Wei Qu; Katherine Cianflone; Michael P. Waalkes

    2004-01-01

    AIM: To determine whether cyclooxygenase-2 (COX-2) was expressed in human esophageal squamous cell carcinoma.METHODS: Quantitative reverse transcription-polymerase chain reaction (RT-PCR), western blotting, immunohistochemistry and immunofluorescence were used to assess the expression level of COX-2 in esophageal tissue.RESULTS: COX-2 mRNA levels were increased by >80-fold in esophageal squamous cell carcinoma when compared to adjacent noncancerous tissue. COX-2 protein was present in 21 of 30 cases of esophageal squamous cell carcinoma tissues, but was undetectable in noncancerous tissue. Immunohistochemistry was performed to directly show expression of COX-2 in tumor tissue.CONCLUSION: These results suggest that COX-2 may be an important factor for esophageal cancer and inhibition of COX-2 may be helpful for prevention and possibly treatment of this cancer.

  20. The colorectal carcinoma prognosis factors: Significance of diagnosis delay Factores pronósticos en carcinoma colorrectal: Importancia de la demora diagnóstica

    Directory of Open Access Journals (Sweden)

    E. Gómez-Domínguez

    2006-05-01

    Full Text Available Introduction: detection of early-stage colorectal carcinoma (CRC -( Dukes' A or B- provides better survival rates in these patients. Thus, the effectiveness of screening programs in asymptomatic patients or of early diagnosis in symptomatic individuals has been postulated. The aim of this study was to establish whether a delay in diagnosis or other factors are related to CRC stage. Patients and methods: a retrospective study was performed on 96 patients with CRC. Age at diagnosis, gender distribution, intestinal disorders, diagnosis delay, primary sign and -regarding CRC- localization, stage (Dukes' and grade of differentiation (well differentiated; non-well differentiated; poorly differentiated were recorded. Results: diagnosis delay was 185 ± 190 days. Patients delay in obtaining a diagnosis was 119 ± 158 days. In 40% of patients CRC was diagnosed at an early stage (Dukes' A or B, and in 13% CRC was poorly differentiated. The only factor with an independent effect on Dukes' stage was tumor differentiation (p: 0.0012. Distal location was associated with less advanced tumors without statistical significance (p: 0.156. Conclusion: based on the presented data, a greater effort regarding screening programs for healthy people seems warranted, as improved survival has been demonstrated when diagnosis delay is reduced, particularly in patients with the highest mean delay.Introducción: el diagnóstico precoz del cáncer colorrectal (estadios A y B de Dukes consigue mejorar las tasas de supervivencia de estos pacientes. Con este objetivo se ha propuesto como estrategia acelerar el diagnóstico de enfermos sintomáticos o realizar cribados en enfermos asintomáticos. El objetivo de este trabajo es identificar los factores que influyen en la extensión tumoral del carcinoma colorrectal, especialmente la demora en el diagnóstico. Material y métodos: estudio prospectivo de una serie de 99 pacientes diagnosticados de carcinoma colorrectal en los que se

  1. Complementary analysis of microsatellite tumor profile and mismatch repair defects in colorectal carcinomas

    Institute of Scientific and Technical Information of China (English)

    Alfredo Blanes; Salvador J Diaz-Cano

    2006-01-01

    Microsatellite instability (MSI) is a prognostic factor and a marker of deficient mismatch repair (MMR) in colorectal adenocarcinomas (CRC). However, a proper application of this marker requires understanding the following: (1)The MSI concept: The PCR approach must amplify the correct locus and accurately identify the microsatellite pattern in the patient's normal tissue. MSI is demonstrated when the length of DNA sequences in a tumor differs from that of nontumor tissue. Any anomalous expansion or reduction of tandem repeats results in extra-bands normally located in the expected size range (100 bp,above or below the expected product), differ from the germline pattern by some multiple of the repeating unit,and must show appropriate stutter. (2) MSI mechanisms:MMR gene inactivation (by either mutation or protein down-regulation as frequently present in deep CRC compartments) leads to mutation accumulation in a cell with every cellular division, resulting in malignant transformation. These mechanisms can express tumor progression and result in a decreased prevalence of aneuploid cells and loss of the physiologic cell kinetic correlations in the deep CRC compartments. MSI molecular mechanisms are not necessarily independent from chromosomal instability and may coexist in a given CRC. (3) Because of intratumoural heterogeneity, at least two samples from each CRC should be screened, preferably from the superficial (tumor cells above the muscularis propria) and deep (tumor cells infiltrating the muscularis propria) CRC compartments to cover the topographic tumor heterogeneity. (4) Pathologists play a critical role in identifying microsatellite-unstable CRC, such as occur in young patients with synchronous or metachronous tumors or with tumors showing classic histologic features. In these cases, MSI testing and/or MMR immunohistochemistry are advisable, along with gene sequencing and genetic counseling if appropriate. MSI is an excellent functional and prognostically

  2. The frequency and spectrum of K-ras mutations among Iraqi patients with sporadic colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    N A Al-Allawi

    2012-01-01

    Full Text Available Background: The epidemiology of colorectal cancers (CRC is well known to differ in different geographical regions. K-ras mutations have been implicated in CRC carcinogenesis and they were extensively studied in developed countries; however, such studies are scarce from developing countries, like Iraq. Aim: To determine the frequency and spectrum of K-ras mutations among CRC Iraqi patients, and their clinico-pathological associations, if any. Materials and Methods: Fifty consecutive surgically resected sporadic CRC were evaluated. The evaluation included screening for ten K-ras mutations in codon 12 and 13 by mutant enriched polymerase chain reaction followed by reverse hybridization to oligospecific probes. Results: Out of the 50 enrolled patients, 24 (48% had K-ras mutations. A total of 29 mutations were identified in the tumors of the latter 24 patients (20/24 tumors had single mutations, 3/24 had double mutations and 1/24 had triple mutations. The most frequently encountered mutations were the G>T transversions and G>A transitions (41.4% each. Codon 12 mutations constituted 89.7%, while codon 13 the remaining 10.3%. The most frequent mutation was GGT>GTT (Gly>Val of codon 12 documented in 31%. No significant clinico-pathological correlations with K-ras mutational status were identified. Conclusion : The K-ras mutations are frequently encountered among Iraqi sporadic CRC patients, with relative higher frequencies of G>T transversions and Gly>Val codon 12 substitutions than encountered in their counterparts in developed countries. The latter is most likely to be related to differences in local carcinogens exposure, an aspect which requires further scrutiny.

  3. Endoscopic mucosal resection in colorectal lesion: a safe and effective procedure even in lesions larger than 2 cm and in carcinomas

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Oliveira dos Santos

    2011-12-01

    Full Text Available CONTEXT: Endoscopic mucosal resection is a minimally invasive technique used in the treatment of colorectal neoplasms, including early carcinomas of different size and morphology. OBJECTIVES: To evaluate procedure safety, efficacy, outcomes, and recurrence rate in endoscopic mucosal resection of colorectal lesions. METHODS: A total of 172 lesions in 156 patients were analyzed between May 2003 and May 2009. All lesions showed pit pattern suggestive of neoplasia (Kudo types III-V at high-magnification chromocolonoscopy with indigo carmine. The lesions were evaluated for macroscopic classification, size, location, and histopathology. Lesions 20 mm or smaller were resected en bloc and lesions larger than 20 mm were removed using the piecemeal technique. Complications and recurrence were analyzed. Patients were followed up for 18 months. RESULTS: There were 83 (48.2% superficial lesions, 57 (33.1% depressed lesions, 44 (25.6% laterally spreading tumors, and 45 (26.2% protruding lesions. Mean lesion size was 11.5 mm ± 9.6 mm (2 mm-60 mm. Patients' mean age was 61.6 ± 12.5 years (34-93 years. Regarding lesion site, 24 (14.0% lesions were located in the rectum, 68 (39.5% in the left colon, and 80 (46.5% in the right colon (transverse, ascending, and cecum. There were 167 (97.1% neoplasms: 142 (82.5% adenomatous lesions, 24 (14.0% intramucosal carcinomas, and 1 (0.6% invasive carcinoma. En bloc resection was performed in 158 (91.9% cases and piecemeal resection in 14 (8.1%. Bleeding occurred in 5 (2.9% cases. Recurrence was observed in 4.1% (5/122 of cases and was associated with lesions larger than 20 mm (P<0.01, piecemeal resection (P<0.01, advanced neoplasm (P = 0.01, and carcinoma compared to adenoma (P = 0.04. CONCLUSIONS: Endoscopic mucosal resection of colorectal lesions is a safe and effective procedure, with low complication and local recurrence rates. Recurrence is associated with lesions larger than 20 mm and carcinomas.

  4. Expression of PPARγ and PTEN in human colorectal cancer: An immunohistochemical study using tissue microarray methodology.

    Science.gov (United States)

    Lin, Mao Song; Huang, Jun Xing; Chen, Wei Chang; Zhang, Bao Feng; Fang, Jing; Zhou, Qiong; Hu, Ying; Gao, Heng Jun

    2011-11-01

    Although aberrations of peroxisome proliferator-activated receptor γ (PPARγ) and phosphatase and tensin homolog (PTEN) expression have been identified in several other cancer types, certain previous studies have revealed that PPARγ is abundant in normal and malignant tissue in the colon. The question of whether aberrant PTEN is involved in the initial stage or is a later event during colorectal carcinogenesis remains controversial. Relatively few studies have focused on the correlation of expression of PPARγ and PTEN in various tissues. In the present study, paraffin-embedded blocks from 139 patients with CRC, 18 adenomatous polyps and 50 paired paracancerous benign mucosas were selected and analysed in 4 tissue microarray (TMA) blocks comprising 104, 72, 130 and 54 cores, respectively. Expression of PPARγ and PTEN was examined using immunohistochemical staining on TMAs. There were no significant differences in the expression of PPARγ (P=0.055) and PTEN (P=0.100) between the colorectal cancers, adenomas and paracancerous mucosas. However, correlations of PPARγ expression with clinical stage (P=0.004) and PTEN expression with histological grade (P=0.006) and distant metastasis (P=0.015) were demonstrated in the CRC specimens. Although the differences in PPARγ and PTEN protein expression in human colorectal cancer may not be considered as early diagnostic markers, our results indicate that CRCs with a low expression or deletion of PTEN may progress towards invasion and even metastasis; thus, PTEN may have potential as a prognostic marker in human CRC.

  5. Anticancer effects of oligomeric proanthocyanidins on human colorectal cancer cell line, SNU-C4

    Institute of Scientific and Technical Information of China (English)

    Youn-Jung Kim; Hae-Jeong Park; Seo-Hyun Yoon; Mi-Ja Kim; Kang-Hyun Leem; Joo-Ho Chung; Hye-Kyung Kim

    2005-01-01

    AIM: Oligomeric proanthocyanidins (OPC), natural polyphenolic compounds found in plants, are known to have antioxidant and anti-cancer effects. We investigated whether the anti-cancer effects of the OPC are induced by apoptosis on human colorectal cancer cell line, SNU-C4.METHODS: Colorectal cancer cell line, SNU-C4 was cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum. The cytotoxic effect of OPC was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylt-etrazolium bromide (MTT) assay. To find out the apoptotic cell death, 4, 6-diamidino-2-phenylindole (DAPI) staining,terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, reverse transcriptionpolymerase chain reaction (RT-PCR), and caspase-3 enzyme assay were performed.RESULTS: In this study, cytotoxic effect of OPC on SNUC4 cells appeared in a dose-dependent manner. OPC treatment (100 μg/mL) revealed typical morphological apoptotic features. Additionally OPC treatment (100 μg/mL)increased level of BAX and CASPASE-3, and decreased level of BCL-2 mRNA expression. Caspase-3 enzyme activity was also significantly increased by treatment of OPC (100 μg/mL) compared with control.CONCLUSION: These data indicate that OPC caused cell death by apoptosis through caspase pathways on human colorectal cancer cell line, SNU-C4.

  6. A comparison of flow cytometry and immunohistochemistry in human colorectal cancers

    DEFF Research Database (Denmark)

    Diederichsen, Axel Cosmus Pyndt; Hansen, T P; Nielsen, O

    1998-01-01

    In human colorectal cancer it has been reported that some tumours lack the HLA-ABC antigens. This has been interpreted as reflecting tumour escape from the immune system. Earlier data have been obtained by immunohistochemistry. In this study, we compared the expression of HLA-ABC, HLA-DR, CD80 (B7-1......) and CD54 (ICAM-1) in 20 tumours using both a conventional immunohistochemistry two-layer technique and multiparameter flow cytometry, gating on an epithelial cell marker. Colorectal cancer tissue used in flow cytometry was dissociated with collagenase, deoxyribonuclease and hyaluronidase. The intensity...... was superior to immunohistochemistry in 33 out of 80 cases, and showed that tumours described as HLA-ABC negative by immunohistochemistry were in fact weakly positive for HLA-ABC. We conclude that flow cytometry and immunohistochemistry are complementary, and that flow cytometry is superior...

  7. Induction of Human Squamous Cell-Type Carcinomas by Arsenic

    Directory of Open Access Journals (Sweden)

    Victor D. Martinez

    2011-01-01

    Full Text Available Arsenic is a potent human carcinogen. Around one hundred million people worldwide have potentially been exposed to this metalloid at concentrations considered unsafe. Exposure occurs generally through drinking water from natural geological sources, making it difficult to control this contamination. Arsenic biotransformation is suspected to have a role in arsenic-related health effects ranging from acute toxicities to development of malignancies associated with chronic exposure. It has been demonstrated that arsenic exhibits preference for induction of squamous cell carcinomas in the human, especially skin and lung cancer. Interestingly, keratins emerge as a relevant factor in this arsenic-related squamous cell-type preference. Additionally, both genomic and epigenomic alterations have been associated with arsenic-driven neoplastic process. Some of these aberrations, as well as changes in other factors such as keratins, could explain the association between arsenic and squamous cell carcinomas in humans.

  8. 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

    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.

  9. Microbiota disbiosis is associated with colorectal cancer

    OpenAIRE

    Gao, Zhiguang; Guo, Bomin; Gao, Renyuan; Zhu, Qingchao; Qin, Huanlong

    2015-01-01

    The dysbiosis of the human intestinal microbiota is linked to sporadic colorectal carcinoma (CRC). The present study was designed to investigate the gut microbiota distribution features in CRC patients. We performed pyrosequencing based analysis of the 16S rRNA gene V3 region to investigate microbiota of the cancerous tissue and adjacent non-cancerous normal tissue in proximal and distal CRC samples. The results revealed that the microbial structures of the CRC patients and healthy individual...

  10. Change in anatomic distribution and incidence of colorectal carcinoma over a period of 15 years - Clinical considerations

    NARCIS (Netherlands)

    Mensink, PBF; Kolkman, JJ; van Baarlen, J; Kleibeuker, JH

    2002-01-01

    PURPOSE: Colorectal cancer is the second most common cancer in the Netherlands. Its incidence rates are among the highest in Europe. In the past decades, a right-sided shift of the subsite location of colorectal cancer has been reported. These changes in anatomic distribution might have clinical

  11. Analysis of Snail-1, E-Cadherin and Claudin-1 Expression in Colorectal Adenomas and Carcinomas

    Directory of Open Access Journals (Sweden)

    Kamil Belej

    2012-02-01

    Full Text Available We report the expression of Snail-1, E-cadherin and claudin-1 by indirect immunohistochemistry in colonic neoplasia. Snail-1 is a zinc finger transcription factor expressed in cells that already have undergone almost complete epithelial-mesenchymal transition (EMT and have already evaded from the tumor. The main mechanism by which Snail induces EMT is downregulation of E-cadherin, of which expression was shown to be frequently downregulated in many different types of tumors, where it accompanies the invasiveness and metastatic behavior of malignant cells. Moreover, Snail-1 may downregulate the expression of claudin-1, a cell-cell adhesion protein which plays a likely role in progression and dissemination during tumorigenesis. Snail-1 was expressed in both carcinoma and adenoma cells with histologically normal epithelium in the mucosa, adjacent to the tumors, without significant differences, and predominant strong intensity of staining. Statistically significant differences were revealed between normal and tumorous epithelium (p = 0.003 at the subcellular level, where the shift of the protein to the cytoplasm with combined cytoplasmic/nuclear or pure cytoplasmic expression was observed. E-cadherin expression was present in 100% of cases of both adenocarcinomas and adenomas, with prevailing strong membranous immunoreactivity and no differences between protein expression in tumors and normal mucosa. Predominating strong positivity of claudin-1 was detected in tumor cells of adenocarcinomas and adenomas. Marked differences were seen in protein localization, where membranous staining, typical for nontumorous epithelium, changed to combined membranous/cytoplasmic expression in adenocarcinomas (p = 0.0001 and adenomas (0.0002, in which cytoplasmic shift was associated with a higher degree of dysplasia. Furthermore, membranous/cytoplasmic localization was more frequent in the carcinoma group (87% in comparison with adenomas (51% (p = 0.0001. We conclude

  12. TNM and Modified Dukes staging along with the demographic characteristics of patients with colorectal carcinoma.

    Science.gov (United States)

    Akkoca, Ayşe Neslin; Yanık, Serdar; Ozdemir, Zeynep Tuğba; Cihan, Fatma Gökşin; Sayar, Süleyman; Cincin, Tarık Gandi; Cam, Akın; Ozer, Cahit

    2014-01-01

    Colon adenocarcinoma, is the most common cancer in gastrointesinal system (GIS). The whole world is an important cause of morbidity and mortality. TNM and modified Dukes classification which has great importance in the diagnosis and treatment of Colorectal cancer (CRC). TNM and Modified Dukes classification results of histopathological examination and the demographic characteristics of patients and their relation were investigated. Lower gastrointestinal operation results of 85 patients were examined accepted to clinical Pathology between January 1997-November 2013. Colon cancer had been diagnosed at 85 patients with pathology materials and staging was done according to the TNM and Modified Duke classification. The demographic characteristics of patients, differentiation grade, lymph node involvement, serous involvement were evaluated retrospectively. In this study 37 patients (43.52%) were men and 48 (56.47%) were women. Ages of patients were between 19 and 87 with a mean age of 57.31 ± 15.31. Lymph node, differentiation, serosa involvement, Modified Dukes and TNM classification was assessed according to sex and age. TNM classification by sex was not statistically significant (p > 0.05). There was no statistically significant relationship between age and differentiation (p = 0.085). Value of differentiation increased towards from 1 to 3 inversely proportional to age. So young patients defined as well-differentiated at the conclusion. Negative relationship was evaluated between age and TNM Class variables. As a result, the relationship between age and TNM was not significant (p > 0.05). However, with increasing age the degree of staging was also found to increase. TNM classification was associated with the differentiation and it was significant (p = 0.043). Colon cancer, when contracted at an early stage, it is suitable for surgery and curative treatment can be done with minimal morbidity and mortality. However, some of the patients have advanced disease at

  13. Epidemiology and clinical findings of colorectal carcinoma in two tertiary care hospitals in Benghazi, Libya.

    Science.gov (United States)

    Elzouki, Abdel-Naser; Habel, Salah; Alsoaeiti, Saeid; Abosedra, Adam; Khan, Fahmi

    2014-10-01

    The aim is to determine the pattern of patients with colorectal cancer (CRC) seen in two tertiary hospitals in Benghazi, Libya. The cohort includes all patients of CRC who were presented between January 2007 and December 2009 to the Oncology Department, Aljomhoria Hospital and 7(th) October Hospital, Benghazi. Patient's age, gender, clinical presentation, location of cancer involvement, and histopathologic diagnosis were reviewed. Tumor staging was carried out according to Astler Coller modification of Duke's system, dividing it into stage A to C depending upon the extent of local involvement and regional node spread. Stage D was added to account for distant metastasis in accordance with Turnbull modification. A total of 152 patients with CRC were included, 84 males (55%) and 68 females (45%) with a male to female ratio of 1.2:1.0. The mean age was 57.4 ± 12.92 years (range 21-87 years). 18 (11.8%) patients were below 40 years of age. The most common presenting symptoms were rectal bleeding and abdominal pain and were together present in 71% of the patients. The majority (67.8%) of tumors arise from rectum and sigmoid colon. More than one-third of the patients had poorly differentiated adenocarcinoma. Sixty patients (39.5%) presented in stage D, whereas 30.9% (47/152) and 29.6% (45/152) of patients were in stage B and stage C, respectively. None of the patients had stage A at presentation. The radiological evaluation showed presence of liver metastasis in 14 patients (9.2%) and pulmonary metastasis in two patients (1.3%). Anemia was found in 56 patients (36.8%). It was more common in females (P = 0.01) and in the right sided tumors (66.7%) than left sided tumors (29.5%) (P = 0.001). The majority of CRC patients in Benghazi were diagnosed in locally advanced or metastatic stage. In order to achieve early detection of CRC, a comprehensive cancer education program and screening of high risk population for CRC should be considered in this part of Libya.

  14. KRAS discordance between primary and metastatic tumor in patients with metastatic colorectal carcinoma.

    Science.gov (United States)

    Siyar Ekinci, Ahmet; Demirci, Umut; Cakmak Oksuzoglu, Berna; Ozturk, Ayse; Esbah, Onur; Ozatli, Tahsin; Celik, Burcin; Budakoglu, Burcin; Turker, Ibrahim; Bal, Oznur; Turan, Nedim

    2015-01-01

    Adding targeted therapies to chemotherapy in metastatic colorectal cancer (CRC) improves response rates and survival. KRAS is a predictive indicator for anti-epidermal growth factor receptor (EGFR) treatments. The most important reasons for KRAS discordance are intratumoral heterogeneity and incorrect mutation analysis. Evaluating the status of KRAS in primary and metastatic lesions becomes even more crucial to ensure efficient usage of anti-EGFR treatments. Patients with metastatic CRC, whose primary disease and liver and/or lung metastases were operated, were retrospectively evaluated, and KRAS assessment was performed on 31 patients who were suitable for DNA analysis. Pyrosequencing with polymerase chain reaction (PCR) was used for KRAS analysis. The median age of 31 patients diagnosed with rectal cancer (N=13) and colon cancer (N=18) was 63 years (range 33-73). Metastasectomy locations included the liver (N=27), lung (N=3), and both lung and liver (N=1). KRAS discordance was detected in 22% (7/31) of the patients. While 3 patients with detected discordance had mutated KRAS in the primary material, wild type KRAS was detected in their liver or lung lesions. On the other hand, while 4 patients had wild type KRAS in the primary material, mutated KRAS was determined in their liver or lung lesions. The McNemar test revealed no significant discordance between primary and metastatic disease (p=1.00). No progression free survival (PFS) difference was detected between patients with determined discordance and patients with undetermined discordance (10.6 vs 14.7 months, p=0.719). This is the first study to evaluate KRAS discordance between primary and metastasis in CRC patients, who underwent metastasectomy, together with survival data. In the literature and recent studies with large patient numbers in which modern KRAS tests were used, the KRAS discordance rate varies between 3-12%. In our study, a higher KRAS discordance (22%) was detected, and no survival difference

  15. Differential antitumor effects of vitamin D analogues on colorectal carcinoma in culture.

    Science.gov (United States)

    Wierzbicka, J M; Binek, A; Ahrends, T; Nowacka, J D; Szydłowska, A; Turczyk, Ł; Wąsiewicz, T; Wierzbicki, P M; Sądej, R; Tuckey, R C; Slominski, A T; Chybicki, J; Adrych, K; Kmieć, Z; Żmijewski, M A

    2015-09-01

    Colorectal cancer (CRC) is an emerging global problem with the rapid increase in its incidence being associated with an unhealthy lifestyle. Epidemiological studies have shown that decreased levels of vitamin D3 significantly increases the risk of CRC. Furthermore, negative effects of vitamin D3 deficiency can be compensated by appropriate supplementation. Vitamin D3 was shown to inhibit growth and induce differentiation of cancer cells, however, excessive vitamin D3 intake leads to hypercalcemia. Thus, development of efficient vitamin D3 analogues with limited impact on calcium homeostasis is an important scientific and clinically relevant task. The aims of the present study were to compare the antiproliferative potential of classic vitamin D3 metabolites (1α,25(OH)2D3 and 25(OH)D3) with selected low calcemic analogues (calcipotriol and 20(OH)D3) on CRC cell lines and to investigate the expression of vitamin D-related genes in CRC cell lines and clinical samples. Vitamin D3 analogues exerted anti-proliferative effects on all CRC cell lines tested. Calcipotriol proved to be as potent as 1α,25(OH)2D3 and had more efficacy than 20-hydroxyvitamin D3. In addition, the analogs tested effectively inhibited the formation of colonies in Matrigel. The expression of genes involved in 1α,25(OH)2D3 signaling and metabolism varied in cell lines analysed, which explains in part their different sensitivities to the various analogues. In CRC biopsies, there was decreased VDR expression in tumor samples in comparison to the surgical margin and healthy colon samples (p<0.01). The present study indicates that vitamin D3 analogues which have low calcemic activity, such as calcipotriol or 20(OH)D3, are very promising candidates for CRC therapy. Moreover, expression profiling of vitamin D-related genes is likely to be a powerful tool in the planning of anticancer therapy. Decreased levels of VDR and increased CYP24A1 expression in clinical samples underline the importance of

  16. Oncogenic K-Ras Signals through Epidermal Growth Factor Receptor and Wild-Type H-Ras to Promote Radiation Survival in Pancreatic and Colorectal Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Keith A. Cengel

    2007-04-01

    Full Text Available Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor o was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFRactivated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers.

  17. Oncogenic K-Ras Signals through Epidermal Growth Factor Receptor and Wild-Type H-Ras to Promote Radiation Survival in Pancreatic and Colorectal Carcinoma Cells1

    Science.gov (United States)

    Cengel, Keith A.; Voong, K. Rahn; Chandrasekaran, Sanjay; Maggiorella, Laurence; Brunner, Thomas B.; Stanbridge, Eric; Kao, Gary D.; McKenna, W. Gillies; Bernhard, Eric J.

    2007-01-01

    Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI) radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR) led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor α was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFR-activated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers. PMID:17460778

  18. Oncogenic K-Ras signals through epidermal growth factor receptor and wild-type H-Ras to promote radiation survival in pancreatic and colorectal carcinoma cells.

    Science.gov (United States)

    Cengel, Keith A; Voong, K Rahn; Chandrasekaran, Sanjay; Maggiorella, Laurence; Brunner, Thomas B; Stanbridge, Eric; Kao, Gary D; McKenna, W Gillies; Bernhard, Eric J

    2007-04-01

    Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI) radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras. In these experiments, inhibiting the expression of oncogenic K-Ras, wild-type H-Ras, or epidermal growth factor receptor (EGFR) led to similar levels of radiosensitization as treatment with the FTI tipifarnib. Treatment with the EGFR inhibitor gefitinib led to similar levels of radiosensitization, and the combinations of tipifarnib or gefitinib plus inhibition of K-Ras, H-Ras, or EGFR expression did not provide additional radiosensitization compared with tipifarnib or gefitinib alone. Finally, supplementing culture medium with the EGFR ligand transforming growth factor alpha was able to reverse the radiosensitizing effect of inhibiting K-ras expression. Taken together, these findings suggest that EGFR-activated H-Ras signaling is initiated by oncogenic K-Ras to promote radiation survival in pancreatic and colorectal cancers.

  19. Occurrence of BK Virus and Human Papilloma Virus in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Adrian Jarzyński

    2017-09-01

    Developing colorectal cancer can show no symptoms, even for many years. This is why it is so important to become familiar with as many etiological factors as possible. The development of many human neoplasms is often initiated by exposure to infectious agents – such as bacterial or viral infections. Similar to the human papillomavirus, the BK virus was detected in clinical specimens. It seems that HPV and BKV infections can contribute to the neoplastic process, which requires detailed studies on a larger group of patients.

  20. Carcinoma-associated fibroblasts affect sensitivity to oxaliplatin and 5FU in colorectal cancer cells.

    Science.gov (United States)

    Gonçalves-Ribeiro, Samuel; Díaz-Maroto, Natalia Guillen; Berdiel-Acer, Mireia; Soriano, Antonio; Guardiola, Jordi; Martínez-Villacampa, Mercedes; Salazar, Ramon; Capellà, Gabriel; Villanueva, Alberto; Martínez-Balibrea, Eva; Molleví, David G

    2016-09-13

    The importance of tumor microenvironment (TME) as a relevant contributor to cancer progression and its role in the development of de novo resistance to targeted therapies has become increasingly apparent. However, the mechanisms of microenvironment-mediated drug resistance for nonspecific conventional chemotherapeutic agents, such as platinum compounds or antimetabolites, are still unclear.Here we describe a mechanism induced by soluble factors released by carcinoma-associated fibroblasts (CAFs) that induce the translocation of AKT, Survivin and P38 to the nucleus of tumor cells. These changes are guided to ensure DNA repair and the correct entrance and exit from mitosis in the presence of chemotherapy. We used conditioned media (CM) from normal-colonic fibroblasts and paired CAFs to assess dose response curves of oxaliplatin and 5-fluorouracil, separately or combined, compared with standard culture medium. We also evaluated a colony-forming assay and cell death to demonstrate the protective role of CAF-CM. Immunofluorescence confirmed the translocation of AKT, P38 and Survivin to the nucleus induced by CAF-soluble factors. We also have shown that STAT3 or P38 inhibition provides a promising strategy for overcoming microenvironment-mediated resistance. Conversely, pharmacologic AKT inhibition induces an antagonistic effect that relieves a cMET and STAT3-mediated compensatory feedback that might explain the failure of AKT inhibitors in the clinic so far.

  1. Diagnosis of Desmoplastic Reaction by Immunohistochemical Analysis, in Biopsy Specimens of Early Colorectal Carcinomas, Is Efficacious in Estimating the Depth of Invasion

    Directory of Open Access Journals (Sweden)

    Hiroyuki Mitomi

    2013-06-01

    Full Text Available The aim of our study was to evaluate the diagnosis of desmoplastic reaction (DR by immunostaining for α-smooth muscle actin (αSMA and desmin, for predicting the depth of submucosal invasion in biopsy specimens of early colorectal carcinomas (CRCs. Thirty-eight cases of non-pedunculated early CRCs were included in this study. Positive for DR was defined as αSMA-positive and desmin-negative stroma in the CRC. The depth of submucosal invasion was measured in endoscopically or surgically resected specimens and the lesions were subsequently divided into two groups: Group A (carcinoma in situ/intramucosal carcinoma and submucosal invasive carcinoma with a depth <1000 μm and Group B (submucosal invasion with a depth ≥1000 μm. Twenty-one cases were DR-positive and 17 were DR-negative. No statistical significance was found between the DR with regard to tumor size, location and histological type. All DR-positive cases belonged to Group B whereas 14 (82.4% DR-negative lesions belonged to Group A (p < 0.001. The sensitivity, specificity, positive and negative predictive values and accuracy of DR positivity for diagnosis of Group B were 87.5%, 100%, 100%, 82.4% and 92.1%, respectively. Conclusively, detection of DR in biopsy specimens with ancillary immunohistochemistry (αSMA/desmin would help in preoperative diagnosis for the depth of submucosal invasion of early CRC.

  2. Analysis of the mRNA Expression of Chemotherapy-Related Genes in Colorectal Carcinoma Using the Danenberg Tumor Profile Method

    Directory of Open Access Journals (Sweden)

    Shin Sasaki

    2013-01-01

    Full Text Available The establishment of individualized chemotherapy for colorectal carcinoma based on the expression of genes involved in chemotherapeutic sensitivity or prognosis is necessary. To achieve this, the expression profiles of genes within tumors and their relationship to clinicopathological factors must be elucidated. Here, we selected 10 genes (TS, DPD, TP, FPGS, GGH, DHFR, ERCC1, TOPO-1, VEGF, and EGFR, examined differences in their mRNA expression between the upper and lower thirds of tumors by laser-captured microdissection and real-time RT-PCR (the Danenberg tumor profile, and analyzed the relationships between their expression profiles and clinicopathological factors. Interestingly, the mRNA expression of DPD, TP, and VEGF was significantly higher in the lower third than in the upper third of tumors (P=0.044, 0.023, and 0.013, resp.. Furthermore, increased ERCC1 mRNA expression in the lower third of tumors correlated with recurrence (P=0.049, and VEGF mRNA expression was significantly higher in cases with recurrence than in cases without recurrence, both in the upper and lower thirds of tumors (P=0.018 and 0.036, resp.. These results implied that heterogeneity in DPD, TP, and VEGF expression may exist in colorectal carcinoma and that ERCC-1 and VEGF may be markers predicting recurrence after curative operation.

  3. 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.

  4. Comparative Proteome Analysis of Human Lung Squamous Carcinoma Tissue

    Institute of Scientific and Technical Information of China (English)

    LI Cui; TANG Can'e; DUAN Chaojun; YI Hong; XIAO Zhiqiang; CHEN Zhuchu

    2006-01-01

    Objective: To establish the two-dimensional electrophoresis profiles with high resolution and reproducibility from human lung squamous carcinoma tissue and paired normal tumor-adjacent bronchial epithelial tissue, and to identify differential expression tumor-associated proteins by using proteome analysis. Methods: Comparative proteome analysis with 20 human lung squamous carcinoma tissues and the paired normal bronchial epithelial tissues adjacent to tumors was carried out. The total proteins of human lung squamous carcinoma tissue and paired normal tumor-adjacent bronchial epithelial tissue were separated by means of immobilized pH gradient-based two-dimensional gel electrophoresis (2-DE) and silver staining. The differential expression proteins were analyzed and then identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Results: (1) Well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained. For tumor tissue, average spots of 3 gels were 1567±46, and 1436±54 spots were matched with an average matching rate of 91.6%. For control, average spots of 3 gels were 1349±58, and 1228±35 spots were matched with an average matching rate of 91.03%. The average position deviation of matched spots was 0.924±0.128 mm in IEF direction, and 1.022±0.205 mm in SDS-PAGE direction; (2)A total of 1178±56 spots were matched between the electrophoretic maps of 20 human lung squamous carcinoma tissues and paired normal tumor-adjacent bronchial epithelial tissues. Seventy-six differentially expressed proteins were screened; (3) Sixty-eight differential proteins were identified by PMF, some proteins were the products of oncogenes, and others involved in the regulation of cell cycle and signal transduction;(4) In order to validate the reliability of the identified results, the expression of 3 proteins mdm2, c-jun and EGFR, which was correlated with lung

  5. Synchronous colorectal cancer: Clinical, pathological and molecular implications

    OpenAIRE

    Lam, Alfred King-yin; Chan, Sally Sze-Yan; Leung, Melissa

    2014-01-01

    Synchronous colorectal carcinoma refers to more than one primary colorectal carcinoma detected in a single patient at initial presentation. A literature review has shown that the prevalence of the disease is approximately 3.5% of all colorectal carcinomas. This disease has a male to female ratio of 1.8:1. The mean age at presentation of patients with synchronous colorectal cancer is in the early half of the seventh decade. Patients with inflammatory bowel diseases (ulcerative colitis and Croh...

  6. Selective assembly of laminin variants by human carcinoma cells

    DEFF Research Database (Denmark)

    Wewer, U M; Wayner, E A; Hoffstrom, B G

    1994-01-01

    basement membranes, the pattern of production of various laminin subunits remains to be explored. EXPERIMENTAL DESIGN: The expression of laminin was examined in several human carcinoma cells using a panel of specific cDNA probes as well as polyclonal and chain specific monoclonal antibodies......BACKGROUND: The laminins are heterotrimeric basement membrane glycoproteins. Eight subunits that can be assembled into laminins have been characterized and are known as: A, B1, B2, S, M, K, B2t, B1k laminin chains. Although many neoplastic cells secrete laminins and some of them even assemble....... For this purpose a human laminin S chain 2 kb cDNA was isolated and characterized and used together with existing probes for laminin chains. RESULTS: All carcinoma cell lines had a high level of expression of three light chains (B1, S and B2) mRNA. In contrast, the heavy chains of laminin, A and M, were expressed...

  7. Review of colorectal cancer and its metastases in rodent models: comparative aspects with those in humans

    DEFF Research Database (Denmark)

    Kobaek-Larsen, M; Thorup, I; Diederichsen, Axel Cosmus Pyndt;

    2000-01-01

    that human trials become more directed, with greater chances of success. The orthotopic transplantation of colon cancer cells into the cecum of syngeneic animals or intraportal inoculation appears to resemble the human metastatic disease most closely, providing a model for study of the treatment......BACKGROUND AND PURPOSE: Colorectal cancer (CRC) remains one of the most common cancer forms developing in industrialized countries, and its incidence appears to be rising. Studies of human population groups provide insufficient information about carcinogenesis, pathogenesis, and treatment of CRC...... models approximate many of the characteristics of human colonic carcinogenesis and metastasis. So far few comparative evaluations of the various animal models of CRC have been made. CONCLUSION: Animal studies cannot replace human clinical trials, but they can be used as a pre-screening tool, so...

  8. Polymorphic expression of UDP-glucuronosyltransferase UGTlA gene in human colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Min Wang

    Full Text Available BACKGROUND: Polymorphism of genes encoding drug-metabolizing enzymes is known to play an important role in increased susceptibility of colorectal cancer. UGT1A gene locus has been suggested to define tissue-specific glucuronidation activity. Reduced capacity of glucuronidation is correlated with the development of colorectal cancer. Therefore, we sought to explore polymorphism of UGTlA gene in human colorectal cancer. METHODS: Cancerous and healthy tissues were obtained from selectedpatients. Blood samples were collected and UGTlA mRNA transcriptions were analyzed. Genomic DNA was prepared and UGTlA8 exon-1 sequences were amplified, visualized and purified. The extracted DNA was subcloned and sequenced. Two-tailed Fisher's exact test, Odds ratios (ORs, confidence interval (CIs and Logistics Regression Analysis were used for statistical analysis. RESULTS: UGTlA mRNA expression was reduced in cancerous tissues compared with healthy tissues from the same patient . The UGTlA mRNA expression of healthy tissue in study patients was lower than control . The mRNA expression of cancerous tissue was down-regulated in UGTlAl, 1A3, 1A4, lA6, 1A9 and up-regulated in UGTlA8 and UGTlAl0 UGT1A5 and UGT1A7 were not expressed in colonic tissue of either group. The allele frequency of WT UGTlA8*1 was higher (p = 0.000, frequency of UGTlA8*3 was lowered in control group (p = 0.000. The expression of homozygous UGTlA8*1 was higher in control group (p = 0.000. Higher frequency of both heterozygous UGTlA8*1/*3 and UGTlA8*2/*3 were found in study group (p = 0.000; p = 0.000. The occurrence of colorectal cancer was mainly related to the presence of polymorphic UGTlA8*3 alleles (p = 0.000. CONCLUSION: Regulation of human UGT1A genes is tissue-specific. Individual variation in polymorphic expressions of UGTlA gene locus was noted in all types of colonic tissue tested, whereas hepatic tissue expression was uniform. The high incidence of UGTlA8

  9. Expression of NDRG2 is down-regulated in high-risk adenomas and colorectal carcinoma

    DEFF Research Database (Denmark)

    Lorentzen, Anders; Vogel, Lotte K.; Lewinsky, Rikke H;

    2007-01-01

    BACKGROUND: It has recently been shown that NDRG2 mRNA is down-regulated or undetectable in several human cancers and cancer cell-lines. Although the function of NDRG2 is unknown, high NDRG2 expression correlates with improved prognosis in high-grade gliomas. The aim of this study has been to exa...

  10. Clinical and Metabolic Parameters in Non-Small Cell Lung Carcinoma and Colorectal Cancer Patients with and without KRAS Mutations

    Directory of Open Access Journals (Sweden)

    Ahmet Yilmaz

    2014-08-01

    Full Text Available Lung cancer (LC and colorectal cancer (CRC are the first and second deadliest types of cancer worldwide. EGFR-based therapy has been used in the treatment of these cancers with variable success. Presence of mutations in the KRAS driver oncogene, possibly induced by environmental factors such as carcinogens in diet and cigarette smoke, may confer worse prognosis and resistance to treatment for reasons not fully understood. Data on possible associations between KRAS mutational status and clinical and metabolic parameters, which may help in clinical management, as well as in identifying risk factors for developing these cancers, are limited in the current literature. We sequenced the KRAS gene and investigated the associations of variations in 108 patients with non-small cell lung carcinoma (NSCLC, the most common form of LC, and in 116 patients with CRC. All of the mutations originated from the guanosine nucleotide and over half of all transversions in NSCLC and CRC were c.34 G>T and c.35 G>T, respectively. c.35 G>A was the most frequent type of transition in both cancers. Excluding smoking, the clinical and metabolic parameters in patients carrying mutant and wild type KRAS were similar except that the CRC patients with transversion mutations were 8.6 years younger than those carrying the transitions (P < 0.01. Dyslipidemia, hypertension, family cancer history, and age of diagnosis older than 60 years were more frequent in NSCLC than CRC (P ≤ 0.04. These results suggest that most of the clinical and metabolic parameters investigated in this study are probably not associated with the more aggressive phenotype and differences in response to EGFR-based treatment previously reported in patients with KRAS mutations. However, the increased rates of abnormal metabolic parameters in patients with NSCLC in comparison to CRC indicate that these parameters may be more important in the management of NSCLC. CRC patients carrying transition mutations are

  11. Mecp2-mediated Epigenetic Silencing of miR-137 Contributes to Colorectal Adenoma-Carcinoma Sequence and Tumor Progression via Relieving the Suppression of c-Met

    Science.gov (United States)

    Chen, Tao; Cai, Shi-Lun; Li, Jian; Qi, Zhi-Peng; Li, Xu-Quan; Ye, Le-Chi; Xie, Xiao-Feng; Hou, Ying-Yong; Yao, Li-Qing; Xu, Mei-Dong; Zhou, Ping-Hong; Xu, Jian-Min; Zhong, Yun-Shi

    2017-01-01

    The molecular mechanisms underlying colorectal cancer (CRC) development remain elusive. In this study, we examined the miRNA and mRNA expressions in the adenoma-carcinoma sequence (ACS), a critical neoplastic progression in CRC development. We found that miR-137 was down-regulated in all adenoma and carcinoma tissues. Low miR-137 levels were correlated negatively with tumor progression and metastasis. Then we identified the inhibition effect of the miR-137 in CRC development, both in CRC cell lines and mouse models. MiR-137 was shown to control CRC cell proliferation, colony formation, migration and invasion and to control tumor growth and metastasis. We further confirmed the negative association between miR-137 and c-Met expression and thus validated this important oncogene as the target of miR-137 in CRC. In addition, we found a DNA methyl-CpG-binding protein, Mecp2, was up-regulated in ACS tissues via mRNA sequencing. Further experiment showed that miR-137 expression in CRC was subjected to epigenetic regulation mediated by Mecp2. We also confirmed c-Met expression can be up-regulated by silencing of miR-137 and suppressed by coexpression of Mecp2 and miR-137. These findings highlight the critical role of miR-137-c-Met nexus in CRC development and reveal Mecp2-regulated epigenetic silence causes the downregulation of miR-137 in colorectal adenoma and carcinoma. PMID:28291253

  12. Heterogenous MSH6 loss is a result of microsatellite instability within MSH6 and occurs in sporadic and hereditary colorectal and endometrial carcinomas.

    Science.gov (United States)

    Graham, Rondell P; Kerr, Sarah E; Butz, Malinda L; Thibodeau, Stephen N; Halling, Kevin C; Smyrk, Thomas C; Dina, Michelle A; Waugh, Victoria M; Rumilla, Kandelaria M

    2015-10-01

    Mismatch-repair (MMR) immunohistochemistry is used to detect tumor MMR deficiency associated with high-level microsatellite instability (MSI). Rare tumors show heterogenous loss of mutS homolog 6 (MSH6) with immunohistochemistry, defined by areas of retained staining and separate areas of complete loss of staining. To investigate the clinical interpretation of this phenomenon, we identified 22 cases of heterogenous MSH6 loss interpreted at Mayo Clinic from January 2001 through December 2012 and reviewed histologic features, MSH6 and other MMR immunohistochemistry, and accompanying MSI testing results (n=20). Heterogenous MSH6 loss was seen in colorectal carcinoma (n=18), endometrial carcinoma (n=3), and sebaceous neoplasm (n=1). In the 18 colorectal carcinoma cases, it accompanied complete loss of mutL homolog 1 (MLH1) or PMS2, or both. Heterogenous MSH6 loss was characterized by MSI and MSH6 C8 tract instability in treatment-naive cases and showed mucinous or signet-ring zones in one quarter of cases. Two cases status post neoadjuvant chemoradiation showed heterogenous MSH6 loss but were microsatellite and C8 tract stable. C8 tracts were unstable in 2 of 4 MSH6-associated Lynch syndrome (LS) tumors, but all 4 showed complete MSH6 loss on immunohistochemistry. Further, 12 such MSH6-associated LS cases showed complete MSH6 loss. In conclusion, heterogenous MSH6 loss is uncommon, usually caused by instability in MSH6 exon 5 polycytosine tract, and not associated with germline MSH6 mutation. Although heterogenous MSH6 loss provides evidence against germline MSH6 mutation, patients whose tumors exhibit this immunolabeling pattern may have LS due to a defect in a different MMR gene.

  13. Role of colonic microbiota in colorectal carcinogenesis: a systematic review

    Directory of Open Access Journals (Sweden)

    Marta Borges-Canha

    2015-11-01

    Full Text Available Background and aim: The human colonic mucosa is populated by a wide range of microorganisms, usually in a symbiotic relation with the host. Sometimes this balance is lost and a state of dysbiosis arises, exposing the colon to different metabolic and inflammatory stimuli (according to the microbiota's changing profile. Recent findings lead to hypothesize that this unbalance may create a subclinical pro-inflammatory state that increases DNA mutations and, therefore, colorectal carcinogenesis. In this article we aim to systematically review the scientific evidence regarding colonic microbiota and its role in colorectal carcinogenesis. Methods: Systematic review of PubMed searching results for original articles studying microbiota and colorectal cancer until November 2014. Results: Thirty-one original articles studied the role of colon microbiota in colorectal carcinoma including both human and animal studies. Different and heterogeneous methods were used and different bacteria were considered. Nevertheless, some bacteria are consistently augmented (such as Fusobacteria, Alistipes, Porphyromonadaceae, Coriobacteridae, Staphylococcaceae, Akkermansia spp. and Methanobacteriales, while other are constantly diminished in colorectal cancer (such as Bifidobacterium, Lactobacillus, Ruminococcus, Faecalibacterium spp., Roseburia, and Treponema. Moreover, bacteria metabolites amino acids are increased and butyrate is decreased throughout colonic carcinogenesis. Conclusion: Conclusive evidence shows that colorectal carcinogenesis is associated with microbial dysbiosis. This information may be used to create new prophylactic, diagnostic and therapeutic strategies for colorectal cancer.

  14. SCF/C-Kit/JNK/AP-1 Signaling Pathway Promotes Claudin-3 Expression in Colonic Epithelium and Colorectal Carcinoma.

    Science.gov (United States)

    Wang, Yaxi; Sun, Tingyi; Sun, Haimei; Yang, Shu; Li, Dandan; Zhou, Deshan

    2017-04-06

    Claudin-3 is a major protein of tight junctions (TJs) in the intestinal epithelium and is critical for maintaining cell-cell adhesion, barrier function, and epithelium polarity. Recent studies have shown high claudin-3 levels in several solid tumors, but the regulation mechanism of claudin-3 expression remains poorly understood. In the present study, colorectal cancer (CRC) tissues, HT-29 and DLD-1 CRC cell lines, CRC murine model (C57BL/6 mice) and c-kit loss-of-function mutant mice were used. We demonstrated that elevated claudin-3 levels were positively correlated with highly expressed c-kit in CRC tissues based upon analysis of protein expression. In vitro, claudin-3 expression was clearly increased in CRC cells by overexpressed c-kit or stimulated by exogenous recombinant human stem cell factor (rhSCF), while significantly decreased by the treatment with c-kit or c-Jun N-terminal kinase (JNK) inhibitors. Chromatin immunoprecipitation (ChIP) and luciferase reporter assay showed that SCF/c-kit signaling significantly promoted activator protein-1 (AP-1) binding with CLDN-3 promoter and enhanced its transcription activity. Furthermore, decreased expression of claudin-3 was obtained in the colonic epithelium from the c-Kit loss-of-function mutant mice. In conclusion, SCF/c-kit-JNK/AP-1 signaling pathway significantly promoted claudin-3 expression in colonic epithelium and CRC, which could contribute to epithelial barrier function maintenance and to CRC development.

  15. Primary study of leptin and human hepatocellular carcinoma in vitro

    Institute of Scientific and Technical Information of China (English)

    Jing Zhou; Wei Lei; Lei Shen; He-Sheng Luo; Zhi-Xiang Shen

    2008-01-01

    AIM: To investigate the expression level and effects of leptin in human hepatocellular carcinoma cells in vitro and to explore the correlation between them.METHODS: Human hepatocellular carcinoma cell line HepG2 was cultured in vitro, and (the expression level)mRNA of leptin and leptin receptors in HepG2 were assessed using reverse transcription polymerase chain reaction (RT-PCR). Effects of different concentrations of leptin (50 ng/mL, 100 ng/mL, 200 ng/mL) on HepG2 were detected with colorimetric assay by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) after incubation periods of 24 h, 48 h,and 72 h. Flow cytometry was performed to assess cell cycle progression of different concentrations of leptin as stated above after each 24 h incubation period.RESULTS: mRNA of leptin and leptin receptors (including short and long isoforms) were expressed in HepG2.The 72 h incubation of leptin at different concentrations (50 ng/mL, 100 ng/mL, 200 ng/mL) promoted proliferation of HepG2 in a concentration- and timedependent manner. The experimental group shows significant statistical differences when compared to the controlled group which contained 0 ng/mL of leptin. As the concentration of leptin increases, significant fewer cells were detected in G0-G1 phase and more cells in S and G2-M phases.CONCLUSION: Leptin and leptin receptor are simultaneously expressed in human hepatocellular carcinoma cell line HepG2. Addition of leptin (O ng/mL200 ng/mL) in 72 h periods indicated there is a concentration- and time-dependent correlation in the stimulation of HepG2 cell proliferation. The effect of proliferation by leptin is due to promotion of DNA synthesis and enhancement of mitotic activity. The relationship between leptin and human hepatocellular carcinoma cells might indicate that adipokine could be associated with the progression of human hepatocellular carcinoma.

  16. 1135 Available at: http://ijph.tums.ac.ir Acceptance of Cancer in Patients Diagnosed with Lung, Breast, Colorectal and Prostate Carcinoma

    Directory of Open Access Journals (Sweden)

    Urszula RELIGIONI

    2015-10-01

    Full Text Available Background: The ability to accept illness is a major issue in the life of a person with cancer. Acceptance of disease is simultaneously conducted at two levels: the emotional and cognitive-behavioral one. It is consequential to cancer af-fecting numerous aspects of patient's life, i.e. the physical, mental, social and the spiritual area. The aim of the study was to verify the influence of socioeconomic factors on acceptance of illness in patients suffering from breast, lung, colorectal and prostate carcinoma.Methods: The study included 902 patients treated on an outpatient basis at the Center of Oncology, the Maria Skłodowska-Curie Institute in Warsaw, in the year 2013. The Paper and Pencil Interview (PAPI technique was ap-plied. The questionnaire comprised basic demographic questions (socioeconomic factors and Acceptance of Illness Scale (AIS test estimating the level of disease acceptance in patients.Results: Prostate carcinoma patients scored highest (30, 39, whereas lung carcinoma patients scored lowest (23, 17 concerning illness acceptance according to the AIS scale. In all cases, linear dependence between the net income-per-household-member and the AIS score could be observed. Another diversification factor in the case of prostate carci-noma patients was the level of education. Yet one more dependence could be observed between the level of illness acceptance and chemotherapy over the course of past twelve months.Conclusion: The degree of disease acceptance is subject to a type of carcinoma. Patient income is an economic factor significantly affecting the acceptance of illness score.

  17. Roscovitine synergizes with conventional chemo-therapeutic drugs to induce efficient apoptosis of human colorectal cancer cells

    Institute of Scientific and Technical Information of China (English)

    Mohamed Salah I Abaza; Abdul-Majeed A Bahman; Rajaa J Al-Attiyah

    2008-01-01

    AIM:To examine the ability of cyclin-dependent kinase inhibitor(CDKI)roscovitine(Rosco)to enhance the antitumor effects of conventional chemotherapeutic agents acting by different mechanisms against human colorectal cancer.METHODS:Human colorectal cancer cells were treated,individually and in combination,with Rosco,taxol,5-Fluorouracil(S-FU),doxorubicine or vinblastine.The antiproliferative effects and the type of interaction of Rosco with tested chemotherapeutic drugs were determined.Cell cycle alterations were investigated by fluorescence-activated cell sorter FACS analysis.Apoptosis was determined by DNA fragmentation assay.RESULTS:Rosco inhibited the proliferation of tumor cells in a time- and dose-dependent manner.The efficacies of all tested chemotherapeutic drugs were markedly enhanced 3.0-8.42×103 and 130-5.28×103 fold in combination with 5 and 10 μg/mL Rosco,re-spectively.The combinatiou of Rosco and chemotherapeutic drugs inhibited the growth of human colorectal cancer cells in an additive or synergistic fashion,and in a time and dose dependent manner.Rosco induced apoptosis and synergized with tested chemotherapeutic drugs to induce efficient apoptosis in human colorectal cancer cells.Sequential,inverted sequential and simultaneous treatment of cancer cells with combinations of chemotherapeutic drugs and Rosco arrested the growth of human colorectal cancer cells at various phases of the cell cycle as follows:Taxol/Rosco(G2/M-and S-phases),5-FU/Rosco(S-phase),Dox/Rosco(S-phase)and Vinb/Rosco(G2/M-and S-phases).CONCLUSION:Since the efficacy of many anticancer drugs depends on their ability to induce apoptotic cell death,modulation of this parameter by Cell cycle inhibitors may provide a novel chemo-preventive and chemothempeutic strategy for human colorectal cancer.(C)2008 The WJG Press.All rights reserved.

  18. Hypoxia-targeted triple suicide gene therapy radiosensitizes human colorectal cancer cells

    Science.gov (United States)

    HSIAO, HUNG TSUNG; XING, LIGANG; DENG, XUELONG; SUN, XIAORONG; LING, C. CLIFTON; LI, GLORIA C.

    2014-01-01

    The hypoxic microenvironment, an important feature of human solid tumors but absent in normal tissue, may provide an opportunity for cancer-specific gene therapy. The purpose of the present study was to investigate whether hypoxia-driven triple suicide gene TK/CD/UPRT expression enhances cytotoxicity to ganciclovir (GCV) and 5-fluorocytosine (5-FC), and sensitizes human colorectal cancer to radiation in vitro and in vivo. Stable transfectant of human colorectal HCT8 cells was established which expressed hypoxia-inducible vectors (HRE-TK/eGFP and HRE-CD/UPRT/mDsRed). Hypoxia-induced expression/function of TK, CD and UPRT was verified by western blot analysis, flow cytometry, fluorescent microscopy and cytotoxicity assay of GCV and 5-FC. Significant radiosensitization effects were detected after 5-FC and GCV treatments under hypoxic conditions. In the tumor xenografts, the distribution of TK/eGFP and CD/UPRT/mDsRed expression visualized with fluorescence microscopy was co-localized with the hypoxia marker pimonidazole positive staining cells. Furthermore, administration of 5-FC and GCV in mice in combination with local irradiation resulted in tumor regression, as compared with prodrug or radiation treatments alone. Our data suggest that the hypoxia-inducible TK/GCV+CDUPRT/5-FC triple suicide gene therapy may have the ability to specifically target hypoxic cancer cells and significantly improve the tumor control in combination with radiotherapy. PMID:24912473

  19. Microarray profile of human kidney from diabetes, renal cell carcinoma and renal cell carcinoma with diabetes

    OpenAIRE

    Kosti, Adam; Harry Chen, Hung-I; Mohan, Sumathy; Liang, Sitai; Chen, Yidong; Habib, Samy L.

    2015-01-01

    Recent study from our laboratory showed that patients with diabetes are at a higher risk of developing kidney cancer. In the current study, we have screened whole human DNA genome from healthy control, patients with diabetes or renal cell carcinoma (RCC) or RCC+diabetes. We found that 883 genes gain/163 genes loss of copy number in RCC+diabetes group, 669 genes gain/307 genes loss in RCC group and 458 genes gain/38 genes loss of copy number in diabetes group, after removing gain/loss genes ob...

  20. Plasma membrane proteomics of human embryonic stem cells and human embryonal carcinoma cells.

    NARCIS (Netherlands)

    Dormeyer, W.; van Hoof, D.; Braam, S.R.; Heck, A.J.R.; Mummery, C.L.; Krijgsveld, J.

    2008-01-01

    Human embryonic stem cells (hESCs) are of immense interest in regenerative medicine as they can self-renew indefinitely and can give rise to any adult cell type. Human embryonal carcinoma cells (hECCs) are the malignant counterparts of hESCs found in testis tumors. hESCs that have acquired chromosom

  1. 大肠癌ET-1表达及其与肿瘤细胞增殖和微血管形成的关系%RELATION BETWEEN ET-1 EXPRESSION IN COLORECTAL CARCINOMA AND PCNA INDEX AND ANGIOGENESIS OF TUMOR

    Institute of Scientific and Technical Information of China (English)

    栗华

    2001-01-01

    Objective:To study the effect of endothelin-1 (ET-1) on the pathogenesis of colorectal carcinoma. Methods: Immunohistochemical analysis using antibodies against ET-1, FⅦRAg and proliferating cell nuclear antigen(PCNA) were carried out on the archival specimens of 41 human colorectal carcinoma and 20 adenomas. The relationship between ET-1 expression and PCNA index or microvascular density(MVD)in the colorectal carcinoma was analyzed. Results:ET-1 was stained mainly in the cytoplasm of tumor cells and weakly in vascular endothelial cells and fiberblast. The intensity of ET-1 in vascular endithelial cells with the tumor of ET-1 positive expression was significantly higher than the tumor of ET-1 negative expression. The rate of ET-1 positive expression in the colorectal carcinomas was significantly higher than the adenomas( P < 0. 001 ). Expression of ET-1 in colorectal carcinomas diretly correlated with PCNA index and MVD(P < 0. 001, respective). PCNA index correlated with MVD(P < 0. 001). Conclusion:ET-1 may acts in the growth of human colorectal carcinomas through promoting angiogenesis of tumor.%目的:研究ET-1在大肠腺癌中的表达及其与肿瘤细胞增殖和微血管形成的关系,探讨ET-l在大肠癌发生中的作用机制。方法:应用免疫组化SABC法检测41例大肠腺癌及20例大肠腺瘤组织中ET-1表达、PCNA标记指数(PCNALI)及肿瘤微血管密度(MVD),分析ET-1表达与PCNALI以及MVD的关系。结果:ET-1主要分布于大肠腺癌细胞胞浆,ET-1阳性表达肿瘤组织基质中血管内皮细胞也有增强表达,而癌旁组织及阴性表达的肿瘤组织基质中血管内皮细胞仅有较弱表达。腺癌的ET-1表达率及强度显著高于腺瘤(P<0.001)。等级相关分析表明,ET-1表达与PCNALI及MVD均密切相关(P<0.001),PCNALI与MvD亦呈正相关(P<0.001)。结论:ET-1可能通过促进大肠癌微血管形成来影响肿瘤恶性生长。

  2. Inhibitory effects of xanthohumol from hops (Humulus lupulus L.) on human hepatocellular carcinoma cell lines.

    Science.gov (United States)

    Ho, Yi-Chien; Liu, Chi-Hsien; Chen, Chien-Nan; Duan, Kow-Jen; Lin, Ming-Tse

    2008-11-01

    Xanthohumol is one of the main flavonoids in hop extracts and in beer. Very few investigations of xanthohumol have studied hepatocellular carcinoma. In this study, the inhibitory effects of xanthohumol on human hepatocellular carcinoma cell lines were investigated. The IC(50) values of xanthohumol for two hepatocellular carcinoma cell lines and one normal hepatocyte cell line were 108, 166 and 211 microm, respectively. Normal murine hepatocyte cell line had more resistance to xanthohumol than hepatocellular carcinoma cell lines. Besides, the inhibitory effects of xanthohumol on human hepatocellular carcinoma cell lines were attributed to apoptosis as indicated in the results of flow cytometry, fluorescent nuclear staining and electrophoresis of oligonucleosomal DNA fragments. Hop xanthohumol was more efficient in the growth inhibition of hepatocellular carcinoma cell lines than the flavonoids silibinin and naringin from thistle and citrus. It was shown for the first time that xanthohumol from hops effectively inhibits proliferation of human hepatocellular carcinoma cells in vitro.

  3. Chromosomal Instability, Aneuploidy, and Gene Mutations in Human Sporadic Colorectal Adenomas

    Directory of Open Access Journals (Sweden)

    Walter Giaretti

    2004-01-01

    Full Text Available Whether in vivo specific gene mutations lead to chromosomal instability (CIN and aneuploidy or viceversa is so far not proven. We hypothesized that aneuploidy among human sporadic colorectal adenomas and KRAS2 and APC mutations were not independent. Additionally, we investigated if 1p34–36 deletions by dual target FISH were associated with aneuploidy. Among 116 adenomas, 29 were DNA aneuploid by flow cytometry (25% and 29 were KRAS2 mutated (25%. KRAS2 mutations were associated with aneuploidy (P=0.02. However, while G–C and G–T transversions were strongly associated with DNA aneuploidy (P=0.007, G–A transitions were not. Within a second series of 61 adenomas, we found, instead, that APC mutational status and aneuploidy by flow cytometry were not associated. However, a statistically significant association was found with specific APC mutations, i.e., occurring in the mutation cluster region (MCR, codons 1200–1500 or downstream (P=0.016. Finally, the correlation of 1p34–36 deletions with flow cytometric and FISH detected aneuploidy was also significant (P=0.01. Specific KRAS2 and APC mutations and loss of genes in the 1p34–36 region appear associated with aneuploidy suggesting that these events are not independent and may cooperate in inducing human sporadic colorectal adenomas. A cause effect relationship between gene mutations and aneuploidy remains, however, to be demonstrated.

  4. Overlapping expression of microRNAs in human embryonic colon and colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    MicroRNAs (miRNAs) are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, to date no evidence has linked miRNA expression in embryonic and tumor tissues. We assessed the expression of mature miRNAs in human embryonic colon tissue, and in colorectal cancer and paired normal colon tissue. Overlapping miRNA expression was detected between embryonic colonic mucosa and colorectal cancer. We have found that the miR-17-92 cluster and its target, E2F1, exhibit a similar pattern of expression in human colon development and colonic carcinogenesis, regulating cell proliferation in both cases. In situ hybridization confirmed the high level of expression of miR-17-5p in the crypt progenitor compartment. We conclude that miRNA pathways play a major role in both embryonic development and neoplastic transformation of the colonic epithelium.

  5. P21活化激酶1蛋白在大肠癌及大肠腺瘤异型增生中的表达及意义%P21-activated kinase 1 protein expression and its significance in colorectal carcinoma and colorectal dysplastic adenoma

    Institute of Scientific and Technical Information of China (English)

    谭卫民; 罗时敏; 葛轶群; 庄思敏; 罗建威

    2008-01-01

    Objective To investigate the role of p21-activated kinase 1 (PAK1) in colorectal mucosal carcinogenesis and the relationship between PAK1 expression and biological behavior of colorectal carcinoma. Method PAK1 was detected with immunohistochemical method in 10 normal colorectal mucosas,40 colorectal villous or tubular adenomas and 60 colorectal carcinomas. Results The positive rate for PAK1 was 10.0% in normal colorectal mucesas,and 25.0%, 33.3% and 33.3% in slight, moderate and severe dys-plastic adenomas, respectively, 65.0% was found in colorectul carcinomas. The positive rate for PAK1 in col-orectal carcinomas was higher than that in normal colorectal mucosas(P<0.01), colorectal villous or tubular adenomas(P<0.01), slight dysplastic adenomas(P<0.01) and moderate dysplastic adenomas (P<0.05).The positive rate for PAK1 of poor differentiated colorectal carcinomas was higher than that of high differentiated ones (P<0.05), and the positive rate for PAK1 of patients with lymph node metastasis was higher than that of patients without lymph node metastasis (P<0.05). In clinical stages, the positive rate for PAK1 in Dukes C and D stages patients was higher than that in Dukes A stage patients, respectively (P<0.05). Conclusion PAK1 maybe play some role in the process of carcinogenesis of colorectal mucesa, and be used as an useful marker for assessment of the biological behavior and prognosis of colorectal carcinoma.%目的 探讨p21活化激酶1(PAK1)蛋白与大肠癌发生及生物学行为的关系.方法 采用免疫组化染色法对10例正常大肠黏膜、40例大肠绒毛状或管状腺瘤及60例大肠癌组织进行标记分析.结果 PAK1蛋白在正常大肠黏膜中的阳性率为10.0%,在大肠腺瘤伴轻、中、重度异型增生中的阳性率分别为25.0%、33.3%和33.3%,在大肠癌中的阳性率为65.0%.大肠癌PAK1蛋白阳性率高于正常大肠黏膜(P<0.01)及大肠绒毛状或管状腺瘤(P<0.01),且高于伴轻度异型增生腺瘤(P<0

  6. Comparison of seven cell lines derived from human gastric carcinomas.

    Science.gov (United States)

    Motoyama, T; Hojo, H; Watanabe, H

    1986-01-01

    In an attempt to elucidate various histological features of gastric cancers, seven human gastric adenocarcinomas were studied in vitro and in nude mice. Growth pattern of each cultured cell line in vitro corresponded well to the histological type of parent tumor. The cell lines, MKN7, MKN74, and MKN28 derived from differentiated carcinomas showed morphological characteristics of intestinal differentiation in cell polarity and microvilli with core-filaments in vitro as well as in nude mice. However, they gradually diminished the characteristics in course of time. The cell lines, MKN 45 and OKAJIMA, derived from undifferentiated carcinomas, had natures of not only ordinary gastric mucosa but also intestinal metaplastic mucosa. They seem to have multipotentiality for differentiation, and preserved well the natures for long periods of culture. The KWS-I cell line composed of undifferentiated cells in vitro displayed the potential for differentiation in nude mice. However, the differentiation of KATO-III cells derived from a signet-ring cell carcinoma was suppressed in nude mice. The common abnormality of chromosome was not found, and the growth rate in vitro was not dependent on the histological type of parent tumor.

  7. Regorafenib: A novel tyrosine kinase inhibitor: A brief review of its therapeutic potential in the treatment of metastatic colorectal carcinoma and advanced gastrointestinal stromal tumors

    Directory of Open Access Journals (Sweden)

    P Thangaraju

    2015-01-01

    Full Text Available Regorafenib is a novel oral multitargeted tyrosine kinase inhibitor having both antitumor and anti-angiogenic activities. Regorafenib was recently approved by US Food and Drug Administration in February 25, 2013 in the treatment for patients with advanced gastrointestinal stromal tumor and for the treatment of patients with metastatic colorectal carcinoma after disease progression or intolerance to imatinib mesylate and sunitinib therapy. Oral regorafenib demonstrates a high level of efficacy with acceptable tolerability with the 160 mg daily for 3 weeks followed by 1 week off schedule; a continuous schedule could be of interest. Hypertension, mucositis, hand foot skin reaction, diarrhea and asthenia are the most common side-effects. Regardless of these encouraging results, studies investigating, adjuvant and neoadjuvant settings are awaited, as well as trials using regorafenib in combination with chemotherapy or other targeted therapies. Clinical trials investigating regorafenib in other tumor types are ongoing.

  8. A randomized feasibility study evaluating the effect of radiotherapy alone or combined with 5-fluorouracil in the treatment of locally recurrent or inoperable colorectal carcinoma

    DEFF Research Database (Denmark)

    Overgaard, M; Bertelsen, K; Dalmark, M

    1993-01-01

    The effect of radiotherapy alone or given simultaneously with 5-FU in the treatment of locally recurrent or inoperable colorectal carcinoma was investigated in a randomized feasibility trial. Twenty-nine patients were randomized to radiotherapy alone (50 Gy/5 weeks + 10-20 Gy boost), and 30...... patients to the same radiotherapy with weekly 5-FU (600 mg/m2) given before treatment every Monday during the first 5 weeks. The two groups were comparable with regard to age, sex, previous treatment, symptoms, tumour size and performance status. Treatment compliance to radiotherapy was the same in both...... to be the only parameters having prognostic influence on survival. Addition of 5-FU did neither influence the objective or symptomatic response, nor the development of distant metastases. However, addition of the drug resulted in an apparent increase in the frequency of severe acute radiation complications (33...

  9. Salvia fruticosa, Salvia officinalis, and rosmarinic acid induce apoptosis and inhibit proliferation of human colorectal cell lines: the role in MAPK/ERK pathway.

    Science.gov (United States)

    Xavier, Cristina P R; Lima, Cristovao F; Fernandes-Ferreira, Manuel; Pereira-Wilson, Cristina

    2009-01-01

    Epidemiological studies have shown that nutrition is a key factor in modulating sporadic colorectal carcinoma (CRC) risk. Aromatic plants of the genus Salvia (sage) have been attributed many medicinal properties, which include anticancer activity. In the present study, the antiproliferative and proapoptotic effects of water extracts of Salvia fruticosa (SF) and Salvia officinalis (SO) and of their main phenolic compound rosmarinic acid (RA) were evaluated in two human colon carcinoma-derived cell lines, HCT15 and CO115, which have different mutations in the MAPK/ERK and PI3K/Akt signalling pathways. These pathways are commonly altered in CRC, leading to increased proliferation and inhibition of apoptosis. Our results show that SF, SO, and RA induce apoptosis in both cell lines, whereas cell proliferation was inhibited by the two sage extracts only in HCT15. SO, SF, and RA inhibited ERK phosphorylation in HCT15 and had no effects on Akt phosphorylation in CO115 cells. The activity of sage extracts seems to be due, at least in part, to the inhibition of MAPK/ERK pathway.

  10. Current preventive treatment for recurrence after curative hepatectomy for liver metastases of colorectal carcinoma: A literature review of randomized control trials

    Institute of Scientific and Technical Information of China (English)

    Peng Wang; Zhen Chen; Wen-Xia Huang; Lu-Ming Liu

    2005-01-01

    To review the preventive approaches for recurrence after curative resection of hepatic metastases from coloreclal carcinoma, we have summarized all available publications reporting randomized control trials (RCTs) covered in PubMed. The treatment approaches presented above include adjuvant intrahepatic arterial infusion chemotherapy,systemic chemotherapy, neoadjuvant chemotherapy, and immunotherapy. Although no standard treatment has been established, several approaches present promising results, which are both effective and tolerable in posthepatectomy patients. Intrahepatic arterial infusion chemotherapy should be regarded as effective and tolerable and it increases overall survival (OS) and diseasefree survival (DFS) of patients, while 5-fluorouracil-based systemic chemotherapy has not shown any significant survival benefit. Fortunately chemotherapy combined with hepatic arterial infusion and intravenous infusion has shown OS and DFS benefit in many researches. Few neoadjuvant RCT studies have been conduced to evaluate its effect on prolonging survivals although many retrospective studies and case reports are published in which unresectable colorectal liver metastases are downstaged and made resectable with neoadjuvant chemotherapy.Liver resection supplemented with immunotherapy is associated with optimal results; however, it is also questioned by others. In conclusion, several adjuvant approaches have been studied for their efficacy on recurrence after hepatectomy for liver metastases from colorectal cancer (CRC), but multi-centric RCT is still needed for further evaluation on their efficacy and systemic or local toxicities. In addition, new adjuvant treatment should be investigated to provide more effective and tolerable methods for the patients with resectable hepatic metastases from CRC.

  11. Quantitative proteome profiling of lymph node-positive vs. -negative colorectal carcinomas pinpoints MX1 as a marker for lymph node metastasis.

    Science.gov (United States)

    Croner, Roland S; Stürzl, Michael; Rau, Tilman T; Metodieva, Gergana; Geppert, Carol I; Naschberger, Elisabeth; Lausen, Berthold; Metodiev, Metodi V

    2014-12-15

    We used high-resolution mass spectrometry to measure the abundance of more than 9,000 proteins in 19 individually dissected colorectal tumors representing lymph node metastatic (n = 10) and nonmetastatic (n = 9) phenotypes. Statistical analysis identified MX1 and several other proteins as overexpressed in lymph node-positive tumors. MX1, IGF1-R and IRF2BP1 showed significantly different expression in immunohistochemical validation (Wilcoxon test p = 0.007 for IGF1-R, p = 0.04 for IRF2BP1 and p = 0.02 for MX1 at the invasion front) in the validation cohort. Knockout of MX1 by siRNA in cell cultures and wound healing assays provided additional evidence for the involvement of this protein in tumor invasion. The collection of identified and quantified proteins to our knowledge is the largest tumor proteome dataset available at the present. The identified proteins can give insights into the mechanisms of lymphatic metastasis in colorectal carcinoma and may act as prognostic markers and therapeutic targets after further prospective validation.

  12. Human FK506 binding protein 65 is associated with colorectal cancer

    DEFF Research Database (Denmark)

    Olesen, Sanne Harder; Christensen, Lise Lotte; Sørensen, Flemming Brandt;

    2005-01-01

    this gene hFKBP10 together with its encoded protein hFKBP65 as a novel marker associated with colorectal cancer. Analysis of 31 colorectal adenocarcinomas and 14 normal colorectal mucosa by RealTime PCR for hFKBP10 showed a significant up-regulation in tumors, when compared with normal mucosa...

  13. High ABCC2 and Low ABCG2 Gene Expression Are Early Events in the Colorectal Adenoma-Carcinoma Sequence

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Vogel, Lotte K.; Kopp, Tine Iskov

    2015-01-01

    Development of colorectal cancer (CRC) may result from a dysfunctional interplay between diet, gut microbes and the immune system. The ABC transport proteins ABCB1 (P-glycoprotein, Multidrug resistance protein 1, MDR1), ABCC2 (MRP2) and ABCG2 (BCRP) are involved in transport of various compounds...... across the epithelial barrier. Low mRNA level of ABCB1 has previously been identified as an early event in colorectal carcinogenesis (Andersen et al., PLoS One. 2013 Aug 19; 8(8): e72119). ABCC2 and ABCG2 mRNA levels were assessed in intestinal tissue from 122 CRC cases, 106 adenoma cases (12 with severe...... in carcinogenesis suggesting that these ABC transporters are involved in the early steps of carcinogenesis as previously reported for ABCB1. These results suggest that dysfunctional transport across the epithelial barrier may contribute to colorectal carcinogenesis....

  14. High-sensitivity epidermal growth factor receptor immunostaining for colorectal carcinomas, compared with EGFR PharmDx™: a study of diagnostic accuracy.

    Science.gov (United States)

    Shiogama, Kazuya; Wongsiri, Trai; Mizutani, Yasuyoshi; Inada, Ken-ichi; Tsutsumi, Yutaka

    2013-01-01

    Immunostaining for epidermal growth factor receptor (EGFR) is important in the contemporary therapeutic strategy of colorectal carcinomas. We tried to increase detection sensitivity, and compared the high-sensitivity EGFR immunostaining with a worldwide standard, EGFR PharmDx™ (Dako). In order to pursue high-sensitivity EGFR detection, deparaffinized sections were pressure-cooked in 1 mM EDTA solution, pH 8.0. Two mouse monoclonal antibodies against EGFR, clone EGFR2.5 and DAK-H1-WT, and six kinds of secondary detection reagents, including biotin-free catalyzed signal amplification (CSA II), Simple Stain MAX-PO, PolyVue, Novolink, EnVision™ FLEX+, and MACH3, were evaluated to compare the results with those with EGFR PharmDx™, employing a combination of 2-18-C9 as the primary monoclonal antibody and EnVision™ as the secondary reagent. Furthermore, we replaced EnVision™ in the EGFR PharmDx™ kit with CSAII. EGFR detection sensitivity was higher with DAK-H1-WT than with EGFR2.5, and among the secondary reagents, the strongest signals were observed with Novolink. All 30 colorectal carcinomas showed distinct expression of EGFR with our high-sensitivity EGFR immunostaining, while only 16 (53%) gave focal positivity with EGFR PharmDx™. When EnVision™ in EGFR PharmDx™ was replaced by CSA II, strong signals were seen in all cases, and the expression pattern was comparable with our sequence. Non-neoplastic crypt epithelial cells often showed weakly signal with the standard EGFR PharmDx™, but consistently revealed strong membrane staining in the two high-sensitivity sequences. EGFR PharmDx™ frequently gave false negativity. Importantly, EGFR was consistently and sensitively detected when the secondary polymer in the EGFR PharmDx™ kit was simply replaced by CSA II.

  15. Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and specific method for detecting BRAF V600E mutations in colorectal carcinoma.

    Science.gov (United States)

    Rössle, Matthias; Sigg, Michèle; Rüschoff, Jan H; Wild, Peter J; Moch, Holger; Weber, Achim; Rechsteiner, Markus P

    2013-11-01

    The activating BRAF (V600) mutation is a well-established negative prognostic biomarker in metastatic colorectal carcinoma (CRC). A recently developed monoclonal mouse antibody (clone VE1) has been shown to detect reliably BRAF (V600E) mutated protein by immunohistochemistry (IHC). In this study, we aimed to compare the detection of BRAF (V600E) mutations by IHC, Sanger sequencing (SaS), and ultra-deep sequencing (UDS) in CRC. VE1-IHC was established in a cohort of 68 KRAS wild-type CRCs. The VE1-IHC was only positive in the three patients with a known BRAF (V600E) mutation as assessed by SaS and UDS. The test cohort consisted of 265 non-selected, consecutive CRC samples. Thirty-nine out of 265 cases (14.7%) were positive by VE1-IHC. SaS of 20 randomly selected IHC negative tumors showed BRAF wild-type (20/20). Twenty-four IHC-positive cases were confirmed by SaS (24/39; 61.5%) and 15 IHC-positive cases (15/39; 38.5%) showed a BRAF wild-type by SaS. UDS detected a BRAF (V600E) mutation in 13 of these 15 discordant cases. In one tumor, the mutation frequency was below our threshold for UDS positivity, while in another case, UDS could not be performed due to low DNA amount. Statistical analysis showed sensitivities of 100% and 63% and specificities of 95 and 100% for VE1-IHC and SaS, respectively, compared to combined results of SaS and UDS. Our data suggests that there is high concordance between UDS and IHC using the anti-BRAF(V600E) (VE1) antibody. Thus, VE1 immunohistochemistry is a highly sensitive and specific method in detecting BRAF (V600E) mutations in colorectal carcinoma.

  16. Classification of human carcinoma cells using multispectral imagery

    Science.gov (United States)

    Ćinar, Umut; Y. Ćetin, Yasemin; Ćetin-Atalay, Rengul; Ćetin, Enis

    2016-03-01

    In this paper, we present a technique for automatically classifying human carcinoma cell images using textural features. An image dataset containing microscopy biopsy images from different patients for 14 distinct cancer cell line type is studied. The images are captured using a RGB camera attached to an inverted microscopy device. Texture based Gabor features are extracted from multispectral input images. SVM classifier is used to generate a descriptive model for the purpose of cell line classification. The experimental results depict satisfactory performance, and the proposed method is versatile for various microscopy magnification options.

  17. Expression Status of UBE2Q2 in Colorectal Primary Tumors and Cell Lines

    Directory of Open Access Journals (Sweden)

    Sayed Mohammad Shafiee

    2014-03-01

    Full Text Available Background: Activation of the ubiquitin-proteasome pathway in various malignancies, including colorectal cancer, is established. This pathway mediates the degradation of damaged proteins and regulates growth and stress response. The novel human gene, UBE2Q2, with a putative ubiquitin-conjugating enzyme activity, is reported to be overexpressed in some malignancies. We sought to investigate the expression levels of the UBE2Q2 gene in colorectal cell lines as well as in cancerous and normal tissues from patients with colorectal cancer. Methods: Levels of UBE2Q2 mRNA in cell lines were assessed by Real-Time PCR. Western blotting was employed to investigate the levels of the UBE2Q2 protein in 8 colorectal cell lines and 43 colorectal tumor samples. Results: Expression of UBE2Q2 was observed at the level of both mRNA and protein in colorectal cell lines, HT29/219, LS180, SW742, Caco2, HTC116, SW48, SW480, and SW1116. Increased levels of UBE2Q2 immunoreactivity was observed in the 65.11% (28 out of 43 of the colorectal carcinoma tissues when compared with their corresponding normal tissues. Difference between the mean intensities of UBE2Q2 bands from cancerous and normal tissues was statistically significant at P<0.001 (paired t test. Conclusion: We showed the expression pattern of the novel human gene, UBE2Q2, in 8 colorectal cell lines. Overexpression of UBE2Q2 in the majority of the colorectal carcinoma samples denotes that it may have implications for the pathogenesis of colorectal cancer.

  18. Interaction between the cytostatic effects of quercetin and 5-fluorouracil in two human colorectal cancer cell lines

    NARCIS (Netherlands)

    Boersma, H H; Woerdenbag, H J; Bauer, Joseph; Scheithauer, W; Kampinga, H H; Konings, A W

    1994-01-01

    Therapy with 5-fluorouracil (5-FU) as a single agent has only limited success in palliative treatment of cancer of the large bowel. In the current study, the effect of quercetin on the action of 5-FU in the human colorectal cancer cell lines COLO 320 DM and COLO 205 was evaluated using the MTT and

  19. Interaction between the cytostatic effects of quercetin and 5-fluorouracil in two human colorectal cancer cell lines

    NARCIS (Netherlands)

    Boersma, H H; Woerdenbag, H J; Bauer, Joseph; Scheithauer, W; Kampinga, H H; Konings, A W

    1994-01-01

    Therapy with 5-fluorouracil (5-FU) as a single agent has only limited success in palliative treatment of cancer of the large bowel. In the current study, the effect of quercetin on the action of 5-FU in the human colorectal cancer cell lines COLO 320 DM and COLO 205 was evaluated using the MTT and c

  20. 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

    Directory of Open Access Journals (Sweden)

    C. Valls Bautista

    2009-03-01

    Full Text Available 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 colorectal cancer and/or polyps. In 6 of these patients fresh samples of tumor tissue, polyps, and normal mucosa were obtained; in the 8 remaining cases, we collected only polyps and normal mucosa. We used the fluorescent-telomeric repeat amplification protocol assay (TRAP-F to determine telomerase activity and telomere length using Southern-blot testing. Results: telomerase activity was detected in 86% of polyps and 50% of associated normal mucosa. Mean telomerase activity in polyp tissue was 5.85; in the normal mucosa it was 0.58 TPG. Mean telomere length was 6.78 Kbp and 7.78, respectively. Polyps in patients without synchronous cancer had a telomerase activity that was significantly higher (9.4 than in those with cancer (1.1. Conclusions: telomerase activity increases in the colorectal adenoma-carcinoma sequence, concurrently with a decrease in telomere length. The presence of synchronous cancer modifies telomerase activity in polyps.Objetivo: el papel de la actividad de la telomerasa y la longitud del telómero en la secuencia adenoma-carcinoma de la carcinogénesis colónica no ha sido bien establecido. El objetivo fue determinar el comportamiento de la actividad de la telomerasa y la longitud del telómero en pacientes con pólipos adenomatosos asociados o no a cáncer colorrectal y conocer el papel de la inestabilidad telomérica en la secuencia adenoma-carcinoma. Pacientes y métodos: se estudiaron 14 pacientes intervenidos de cáncer colorrectal y

  1. Expression of ATP7B in human gastric cardiac carcinomas in comparison with distal gastric carcinomas

    Institute of Scientific and Technical Information of China (English)

    Da-Long Wu; Hui-Xing Yi; Feng-Ying Sui; Xiao-Hong Jiang; Xiao-Ming Jiang; Ying-Ying Zhao

    2006-01-01

    AIM: To analyze expression of ATP7B in gastric cardiac adenocarcinomas, its clinicopathologic significance, in comparison with distal gastric adenocarcinomas.METHODS: Immunohistochemical avidin-biotin peroxidase complex method was applied to detect the expression of ATP7B in 49 cases of cardiac carcinomas,the corresponding adjacent non-neoplastic epithelium and 55 cases of distal gastric carcinomas.RESULTS: The proportion of ATP7B positive samples in gastric cardiac carcinomas (51.0%, 25 of 49) was significantly higher than that in the corresponding adjacent non-neoplastic epithelium (22.4%, 11 of 49)(P = 0.003). ATP7B expression in poorly differentiated gastric cardiac carcinomas was significantly higher than that in well/moderately differentiated gastric cardiac carcinomas (P = 0.030). ATP7B expression in gastric cardiac carcinomas was independent of age, tumor size, nodal stage and metastasis status. ATP7B protein was detected in 30.9% (17/55 cases) of distal gastric carcinomas, markedly lower than that in gastric cardiac carcinomas (P = 0.037).CONCLUSION: ATP7B protein is frequently overexpressed in gastric cardiac carcinomas, and correlated with the differentiation of cardiac carcinoma. ATP7B expression in gastric cardiac carcinomas is significantly higher than that in distal gastric carcinomas, which might partially explain the difference of chemotherapy response and prognosis between these two gastric carcinomas.

  2. In Vitro Anticancer Activity of Phlorofucofuroeckol A via Upregulation of Activating Transcription Factor 3 against Human Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Hyun Ji Eo

    2016-03-01

    Full Text Available Phlorofucofuroeckol A (PFF-A, one of the phlorotannins found in brown algae, has been reported to exert anti-cancer property. However, the molecular mechanism for the anti-cancer effect of PFF-A has not been known. Activating transcription factor 3 (ATF3 has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which PFF-A stimulates ATF3 expression and apoptosis in human colorectal cancer cells. PFF-A decreased cell viability through apoptosis of human colorectal cancer cells. PFF-A increased ATF3 expression through regulating transcriptional activity. The responsible cis-element for ATF3 transcriptional activation by PFF-A was cAMP response element binding protein (CREB, located between positions −147 and −85 of the ATF3 promoter. Inhibition of p38, c-Jun N-terminal kinases (JNK, glycogen synthase kinase (GSK 3β, and IκB kinase (IKK-α blocked PFF-A-mediated ATF3 expression. ATF3 knockdown by ATF3 siRNA attenuated the cleavage of poly (ADP-ribose polymerase (PARP by PFF-A, while ATF3 overexpression increased PFF-A-mediated cleaved PARP. These results suggest that PFF-A may exert anti-cancer property through inducing apoptosis via the ATF3-mediated pathway in human colorectal cancer cells.

  3. Expression and significance of PTEN and PCNA in human laryngeal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    李长青; 文莲姬; 金春顺; 崔树勋

    2004-01-01

    Objective: To elucidate the expression and significance of PTEN and PCNA in human laryngeal squamous cell carcinoma. Methods: Immunochemical method was used to study 60 cases of laryngeal carcinoma, 20 cases of normal laryngeal tissues which were closely adjacent to carcinoma and 10 cases of normal laryngeal tissues. Results: It was showed that PTEN gene was expressed in 85 % laryngeal carcinoma tissues. The percentage of lymph node metastasis of laryngeal carcinoma which were negative or positive of PTEN protein was 77.8 % and 33.3 % respectively, and the difference was significance ( P < 0.05). Conclusion: Expression of PTEN in laryngeal carcinoma was different from that of normal laryngeal tissues. It may play a role but not important in the tumorigenesis and development of laryngeal carcinoma.

  4. Flow cytometric investigation of immune-response-related surface molecules on human colorectal cancers

    DEFF Research Database (Denmark)

    Diederichsen, Axel Cosmus Pyndt; Stenholm, A C; Kronborg, O;

    1998-01-01

    Our purpose was to clarify whether human colorectal cancer cells are equipped to present tumour-associated-antigens to the immune system, and whether this ability correlates with lymphoid infiltration, the Dukes' stage and Jass classification. Enzymatically dissociated tumour cells from 70...... molecules, but not the class II, was correlated with lymphoid infiltration and the Jass classification. Expression of these surface molecules was not correlated with the Dukes' stage. The tumour cells were generally equipped to present antigens to the effector arm of the immune system since HLA class I...... is expressed, but the tumour cells were not optimal in stimulating an immune response, since HLA class II and CD58 were only marginally expressed and CD80 and CD54 were absent....

  5. Expression of proliferating cell nuclear antigen and CD44 variant exon 6 in primary tumors and corresponding lymph node metastases of colorectal carcinoma with Dukes'stage C or D

    Institute of Scientific and Technical Information of China (English)

    Ji-Cheng Zhang; Zuo-Ren Wang; Yan-Juan Cheng; Ding-Zhong Yang; Jing-Sen Shi; Ai-Lin Liang; Ning-Na Liu; Xiao-Min Wang

    2003-01-01

    AIM: To study changes in characteristics of colorectal carcinoma during the metastatic process and to investigate the correlation between cell proliferation activity and metastatic ability of patients with Dukes′ stage C or D.METHODS: Formalin fixed and paraffin embedded materials of primary tumors and corresponding lymph node metastases resected from 56 patients with Dukes′ stage C or D of colorectal carcinoma were stained immunohistochemically with proliferating cell nuclear antigen (PCNA) and CD44variant exon 6 (CD44v6).RESULTS: Thirty-one of 56 patients (55.4 %) expressed PCNA in the primary sites and 36 of 56 patients (64.3 %)expressed PCNA in the metastatic lymph nodes. A significant relation in PCNA expression was observed between the primary site and the metastatic lymph node (0.010<P<0.025).Forty-one of 56 patients (73.2 %) expressed CD44v6 in the primary site and 39 of 56 patients (69.6 %) expressed CD44v6 in the metastatic lymph node. There was also an significant relationship of CD44v6 between the primary site and the metastatic lymph node (0.005<P<0.010). No difference was observed between expression of CD44v6 and PCNA in the primary site (0.250<P<0.500).CONCLUSION: This study partially demonstrates that tumor cells in metastatic lymph node of colorectal carcinoma still possess cell proliferation activity and metastatic ability of tumor cells in primary site. There may be no association between cell proliferation activity and metastatic ability in colorectal carcinoma.

  6. Clone-specific expression, transcriptional regulation, and action of interleukin-6 in human colon carcinoma cells

    Directory of Open Access Journals (Sweden)

    Fabjani Gerhild

    2008-01-01

    Full Text Available Abstract Background Many cancer cells produce interleukin-6 (IL-6, a cytokine that plays a role in growth stimulation, metastasis, and angiogenesis of secondary tumours in a variety of malignancies, including colorectal cancer. Effectiveness of IL-6 in this respect may depend on the quantity of basal and inducible IL-6 expressed as the tumour progresses through stages of malignancy. We therefore have evaluated the effect of IL-6 modulators, i.e. IL-1β, prostaglandin E2, 17β-estradiol, and 1,25-dihydroxyvitamin D3, on expression and synthesis of the cytokine at different stages of tumour progression. Methods We utilized cultures of the human colon carcinoma cell clones Caco-2/AQ, COGA-1A and COGA-13, all of which expressed differentiation and proliferation markers typical of distinct stages of tumour progression. IL-6 mRNA and protein levels were assayed by RT-PCR and ELISA, respectively. DNA sequencing was utilized to detect polymorphisms in the IL-6 gene promoter. Results IL-6 mRNA and protein concentrations were low in well and moderately differentiated Caco-2/AQ and COGA-1A cells, but were high in poorly differentiated COGA-13 cells. Addition of IL-1β (5 ng/ml to a COGA-13 culture raised IL-6 production approximately thousandfold via a prostaglandin-independent mechanism. Addition of 17β-estradiol (10-7 M reduced basal IL-6 production by one-third, but IL-1β-inducible IL-6 was unaffected. Search for polymorphisms in the IL-6 promoter revealed the presence of a single haplotype, i.e., -597A/-572G/-174C, in COGA-13 cells, which is associated with a high degree of transcriptional activity of the IL-6 gene. IL-6 blocked differentiation only in Caco-2/AQ cells and stimulated mitosis through up-regulation of c-myc proto-oncogene expression. These effects were inhibited by 10-8 M 1,25-dihydroxyvitamin D3. Conclusion In human colon carcinoma cells derived from well and moderately differentiated tumours, IL-6 expression is low and only marginally

  7. INTERACTIONS BETWEEN THE HUMAN GASTRIC CARCINOMA CELL AND THE HUMAN VASCULAR ENDOTHELIAL CELL

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective To definite the interactions between the human gastric carcinoma cell and the human vascular endothelial cell during the establishment and maintenance of the tumor vascular system and the tumor hematogenous metastasis.Methods We prepared the conditioned mediums of each cell so as to study the effect of the conditioned medium on itself or others by MTT colorimetry. The comprehensive effect of interactions between two cells was determined by stratified transfilter co-culture or direct contact co-culture.Results The conditioned medium of human gastric carcinoma cell can stimulate the proliferation of the human vascular endothelial cell, but the CM of HVEC can inhibit the growth of HGCC. Both kinds of cells can inhibit the growth of itself. The ultimate comprehensive effect of the interactions between two kinds of cells was increase of total cell numbers.Conclusion There exist the complicated interactions between the human gastric carcinoma cell and the human vascular endothelial cell during the tumor angiogenesis and the tumor hematogenous metastasis. The ultimate comprehensive effect of the interactions is increase of total cells numbers and tumor volume.

  8. β-2 microglobulin is unsuitable as an internal reference gene for the analysis of gene expression in human colorectal cancer.

    Science.gov (United States)

    Nihon-Yanagi, Yasuhiro; Terai, Kensuke; Murano, Takeyoshi; Kawai, Takayuki; Kimura, Shinya; Okazumi, Shinichi

    2013-03-01

    It is well-known that gene expression levels should be normalized to a carefully selected and appropriately stable internal control gene. However, numerous studies have demonstrated that the expression of housekeeping (HK) genes, typically used as internal control genes varies considerably. A number of studies have shown that β-2 microglobulin (B2M), an HK gene, frequently used as an internal reference gene, is expressed at low levels in colorectal cancer tissue, when assessed using real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Due to the fact that the expression levels of various HK genes vary depending on the tissue type or experimental conditions, it has been suggested that several control genes should be analyzed in parallel for certain tissues. In the present study, mRNA expression levels of toll-like receptors 2 (TLR2) and 4 (TLR4) in sporadic human colorectal cancerous and non-cancerous tissues were analyzed relative to three HK genes, β-glucuronidase (GUS), β-actin (BA) and B2M, using a commercially available tool. Relative expression levels were quantified using the three genes individually and together, and TLR2 as well as TLR4 expression was compared in cancerous and non-cancerous colorectal tissue specimens. Consistent data were obtained in most cases when GUS and BA were used as internal control genes. When B2M was used as the internal control gene, TLR2 and TLR4 expression was demonstrated to be higher in cancerous compared to non-cancerous colorectal tissues. These results were consistent with previous observations of low-level B2M expression in cancerous colorectal tissue and suggest that B2M may be inappropriate as an internal control gene for gene expression studies of colorectal cancer.

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

    Directory of Open Access Journals (Sweden)

    M. Alcántara Torres

    2005-01-01

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

  10. Clonal karyotypic abnormalities in colorectal adenomas: clues to the early genetic events in the adenoma-carcinoma sequence

    DEFF Research Database (Denmark)

    Bomme, L; Bardi, G; Pandis, N

    1994-01-01

    Cytogenetic analysis of short-term cultures from colorectal adenomas revealed acquired clonal chromosome aberrations in 14 of 17 tumors. In 4 adenomas, only numerical changes were found, whereas 10 had structural rearrangements. Trisomy 7 was found as the sole change in one of the tumors and toge......Cytogenetic analysis of short-term cultures from colorectal adenomas revealed acquired clonal chromosome aberrations in 14 of 17 tumors. In 4 adenomas, only numerical changes were found, whereas 10 had structural rearrangements. Trisomy 7 was found as the sole change in one of the tumors...... and together with other numerical changes in another. A +7 was also present in one case with structural aberrations. Other recurrent numerical aberrations were -14 and -18, both found in 2 adenomas with structural karyotypic changes; in addition, one chromosome 14 was lost in one of the tumors with only...

  11. Application of open-access databases to determine functional connectivity between resveratrol-binding protein QR2 and colorectal carcinoma.

    Science.gov (United States)

    Doonan, Barbara B; Schaafsma, Evelien; Pinto, John T; Wu, Joseph M; Hsieh, Tze-Chen

    2017-08-01

    Colorectal cancer (CRC) is a major cause of cancer-associated deaths worldwide. Recently, oral administration of resveratrol (trans-3,5,4'-trihydroxystilbene) has been reported to significantly reduce tumor proliferation in colorectal cancer patients, however, with little specific information on functional connections. The pathogenesis and development of colorectal cancer is a multistep process that can be categorized using three phenotypic pathways, respectively, chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator (CIMP). Targets of resveratrol, including a high-affinity binding protein, quinone reductase 2 (QR2), have been identified with little information on disease association. We hypothesize that the relationship between resveratrol and different CRC etiologies might be gleaned using publicly available databases. A web-based microarray gene expression data-mining platform, Oncomine, was selected and used to determine whether QR2 may serve as a mechanistic and functional biotarget within the various CRC etiologies. We found that QR2 messenger RNA (mRNA) is overexpressed in CRC characterized by CIN, particularly in cells showing a positive KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation, as well as by the MSI but not the CIMP phenotype. Mining of Oncomine revealed an excellent correlation between QR2 mRNA expression and certain CRC etiologies. Two resveratrol-associated genes, adenomatous polyposis coli (APC) and TP53, found in CRC were further mined, using cBio portal and Colorectal Cancer Atlas which predicted a mechanistic link to exist between resveratrol→QR2/TP53→CIN. Multiple web-based data mining can provide valuable insights which may lead to hypotheses serving to guide clinical trials and design of therapies for enhanced disease prognosis and patient survival. This approach resembles a BioGPS, a capability for mining web-based databases that can elucidate the potential links between compounds to

  12. Influence of the oncolytic parvovirus H-1, CTLA-4 antibody tremelimumab and cytostatic drugs on the human immune system in a human in vitro model of colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Heinrich B

    2013-08-01

    viability of the colon carcinoma cell line. There was no maturation of iDCs after coculture with SW480; instead, H-1PV-infected or drug pretreated SW480 induced maturation. Cytokine production was higher for H-1PV-infected cells but was not significantly enhanced by tremelimumab treatment alone or in combination. Addition of tremelimumab did not interfere with the maturation process as measured by markers of maturation as well as by determination of cytokine levels.Conclusion: By enhancing both cell death and immunogenicity of tumors, H-1PV is of special interest for tumor-directed therapy. These features make it a promising candidate for clinical application in human colorectal cancer. As tremelimumab does not significantly interfere with this process, an interesting therapeutic combination of active enhancement of tumor immunogenicity and independent masking of the CTLA-4 silencing process on tumor cells is highlighted.Keywords: dendritic cells, SW480

  13. Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry.

    Science.gov (United States)

    Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

    2015-01-01

    To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student'st test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

  14. Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Marolla, Ana Paula Cleto [Universidade Federal de São Paulo, São Paulo, SP (Brazil); Waisberg, Jaques [Hospital do Servidor Público Estadual, São Paulo, SP (Brazil); Faculdade de Medicina do ABC, Santo André, SP (Brazil); Saba, Gabriela Tognini [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Waisberg, Daniel Reis [Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP (Brazil); Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva [Faculdade de Medicina do ABC, Santo André, SP (Brazil)

    2015-07-01

    To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student’s t test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

  15. Establishment of highly tumorigenic human colorectal cancer cell line (CR4 with properties of putative cancer stem cells.

    Directory of Open Access Journals (Sweden)

    Rebecca A Rowehl

    Full Text Available BACKGROUND: Colorectal cancer (CRC has the third highest mortality rates among the US population. According to the most recent concept of carcinogenesis, human tumors are organized hierarchically, and the top of it is occupied by malignant stem cells (cancer stem cells, CSCs, or cancer-initiating cells, CICs, which possess unlimited self-renewal and tumor-initiating capacities and high resistance to conventional therapies. To reflect the complexity and diversity of human tumors and to provide clinically and physiologically relevant cancer models, large banks of characterized patient-derived low-passage cell lines, and especially CIC-enriched cell lines, are urgently needed. PRINCIPAL FINDINGS: Here we report the establishment of a novel CIC-enriched, highly tumorigenic and clonogenic colon cancer cell line, CR4, derived from liver metastasis. This stable cell line was established by combining 3D culturing and 2D culturing in stem cell media, subcloning of cells with particular morphology, co-culture with carcinoma associated fibroblasts (CAFs and serial transplantation to NOD/SCID mice. Using RNA-Seq complete transcriptome profiling of the tumorigenic fraction of the CR4 cells in comparison to the bulk tumor cells, we have identified about 360 differentially expressed transcripts, many of which represent stemness, pluripotency and resistance to treatment. Majority of the established CR4 cells express common markers of stemness, including CD133, CD44, CD166, EpCAM, CD24 and Lgr5. Using immunocytochemical, FACS and western blot analyses, we have shown that a significant ratio of the CR4 cells express key markers of pluripotency markers, including Sox-2, Oct3/4 and c-Myc. Constitutive overactivation of ABC transporters and NF-kB and absence of tumor suppressors p53 and p21 may partially explain exceptional drug resistance of the CR4 cells. CONCLUSIONS: The highly tumorigenic and clonogenic CIC-enriched CR4 cell line may provide an important new

  16. Cytoplasmic sequestration of the tumor suppressor p53 by a heat shock protein 70 family member, mortalin, in human colorectal adenocarcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Gestl, Erin E., E-mail: egestl@wcupa.edu [Department of Biology, West Chester University, 750 S Church Street, West Chester, PA 19383 (United States); Anne Boettger, S., E-mail: aboettger@wcupa.edu [Department of Biology, West Chester University, 750 S Church Street, West Chester, PA 19383 (United States)

    2012-06-29

    gene expression levels compared to cell lines without p53 sequestration. Our data reveal the characteristic cytoplasmic sequestration of p53 by the heat shock protein mortalin in human colorectal adenocarcinoma cell lines, as is the case for other cancers, such as glioblastomas and hepatocellular carcinomas.

  17. Human Papillomavirus in Oral Leukoplakia, Verrucous Carcinoma, Squamous Cell Carcinoma, and Normal Mucous Membrane

    Directory of Open Access Journals (Sweden)

    Nasrollah Saghravanian

    2015-11-01

    Full Text Available Objectives: Squamous cell carcinoma (SCC is the most common oral malignancy, and verrucous carcinoma (VC is a less invasive type of SCC. Leukoplakia (LP is the most frequent premalignant lesion in the oral cavity. The human papillomavirus (HPV has been recognized as one of the etiologic factors of these conditions. The association of anogenital and cervical cancers with HPV particularly its high-risk subtypes (HPV HR has been demonstrated. The purpose of our study was to investigate the hypothetical association between HPV and the mentioned oral cavity lesions.  Methods: One hundred and seventy-three samples (114 SCCs, 21 VCs, 20 LPs and 18 normal mucosa samples (as a control group were retrieved from the Department of Oral and Maxillofacial Pathology of Mashhad Dental School, Iran. The association of HPV genotypes in LP, VC, and SCC was compared to normal oral mucosa using the polymerase chain reaction.  Results: The results showed the absence of HPV in normal mucosa and LP lesions. In three samples of VC (14.3%, we observed the presence of HPV HR (types 16 and 18. All VCs were present in the mandibular ridge of females aged over 65 years old. No statistically significant correlation between HPV and VC was observed (p=0.230. Additionally, 15 (13.1% SCCs showed HPV positivity, but this was not significant (p=0.830. The prevalence of SCC was higher on the tongue with the dominant presence of less carcinogenic species of HPV (types 6 and 11. A statistically significant association was not observed between HPV and SCC or VC in the oral cavity.  Conclusions: More studies are necessary to better understand the relationship between HPV and malignant/premalignant oral cavity lesions.

  18. EXPRESSION OF FLIP IN HUMAN COLON CARCINOMAS:A NEW MECHANISM OF IMMUNE EVASION

    Institute of Scientific and Technical Information of China (English)

    XING Bao-cai; S. Wimmenauer; EH. Farthmann

    2005-01-01

    Objective: It has been proposed that Fas ligand (FasL) may play an important role in immune escape of tumors and FLIP is an important mediator of Fas/FasL pathway. In this study, the expression of FLIP was determined in human colon carcinoma cell lines and tissue to investigate the new mechanism of immune evasion of human colon carcinomas. Methods:RT-PCR and immunohistochemistry (IHC) were performed to investigate the expression of FLIP in human colon carcinoma cell lines SW480, LS174 and twenty human primary colon carcinoma specimens. Results: It was shown that SW480 cells,LS174 cells and primary colon carcinoma specimen constitutively expressed FLIP at the mRNA and protein level. The expression of FLIP was not found in the epithelial cells of normal colon mucosa. Conclusion: FLIP was expressed in human primary colon carcinoma specimens but not in the normal counterpart. It suggested that the expression of FLIP may occur during the malignant transformation from normal colon epithelial cells to colon carcinoma cells. Tumor cells might obtain the ability to resist the Fas-mediated apoptosis by expressing FLIP. The expression of FLIP might contribute to the formation of colon carcinomas.

  19. Thrombocytosis portends adverse prognostic significance in patients with stage II colorectal carcinoma [v2; ref status: indexed, http://f1000r.es/4k6

    Directory of Open Access Journals (Sweden)

    Tianhua Guo

    2014-10-01

    Full Text Available Thrombocytosis portends adverse prognostic significance in many types of cancers including ovarian and lung carcinoma. In this study, we determined the prevalence and prognostic significance of thrombocytosis (defined as platelet count in excess of 400 × 103/μl in patients with colorectal cancer. We performed a retrospective analysis of 310 consecutive patients diagnosed at our Institution between 2004 and 2013. The patients (48.7% male and 51.3% female had a mean age of 69.9 years (+/- 12.7 years at diagnosis. Thrombocytosis was found in a total of 25 patients, with a higher incidence in those with stage III and IV disease (14.4% of patients. Although the mean platelet count increased with the depth of tumor invasion (pT, its values remained within normal limits in the whole patient cohort. No patient with stage I cancer (n=57 had elevated platelet count at diagnosis. By contrast, five of the 78 patients (6.4% with stage II cancer showed thrombocytosis, and four of these patients showed early recurrence and/or metastatic disease, resulting in shortened survival (they died within one year after surgery. The incidence of thrombocytosis increased to 12.2% and 20.6%, respectively, in patients with stage III and IV disease. The overall survival rate of patients with thrombocytosis was lower than those without thrombocytosis in the stage II and III disease groups, but this difference disappeared in patients with stage IV cancer who did poorly regardless of their platelet count. We concluded that thrombocytosis at diagnosis indicates adverse clinical outcome in colorectal cancer patients with stage II or III disease. This observation is especially intriguing in stage II patients because the clinical management of these patients is controversial. If our data are confirmed in larger studies, stage II colon cancer patients with thrombocytosis may be considered for adjuvant chemotherapy.

  20. A prospective randomized study of irinotecan (CPT-11), leucovorin (LV) and 5-fluorouracil (5FU) versus leucovorin and 5-fluorouracil in patients with advanced colorectal carcinoma.

    Science.gov (United States)

    Gennatas, C; Papaxoinis, G; Michalaki, V; Mouratidou, D; Andreadis, C; Tsavaris, N; Pafiti, A

    2006-10-01

    The purpose of this study was to compare the activity and toxicity of an irinotecan (CPT-11), leucovorin (LV) and 5-fluorouracil (5FU) combination with a standard regimen of 5FU and LV, in patients with advanced colorectal carcinoma. One hundred and sixty patients were randomized; 80 patients (group A) received LV 20 mg/m(2) bolus i.v. and 5FU 425 mg/m(2) bolus i.v. on days 1-5, every 28 days; 80 patients (group B) received CPT-11 80 mg/m(2) (30-90 min i.v. infusion), followed by LV 20 mg/m(2) bolus i.v. and 5FU 425 mg/m(2) bolus i.v. on days 1, 8, 15, 22, 29, and 36, every 8 weeks. The overall response rate was 30% and 47.5% in groups A and B respectively. Progression-free survival was significantly higher in the triple-drug combination arm (median 7.5 vs. 4.5 months; p= 0. 0335). However, overall survival did not differ significantly between the two arms (15 months vs. 14 months for the groups B and A respectively; p=0.3531). The main grade 3 adverse events were diarrhea (19%, in group A vs. 35% in group B; p=0.032) and mucositis (2% vs. 14%; p=0.017). The regimen containing irinotecan showed activity in advanced colorectal cancer. The overall safety data confirm this combination as a well-tolerated treatment.