• Title, Summary, Keyword: Colorectal carcinoma

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MicroRNA-451 Inhibits Growth of Human Colorectal Carcinoma Cells via Downregulation of Pi3k/Akt Pathway

  • Li, Hong-Yan;Zhang, Yan;Cai, Jian-Hui;Bian, Hong-Lei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3631-3634
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    • 2013
  • MicroRNAs (MiRNAs) play important roles in coordinating a variety of cellular processes and abnormal expression has been linked to the occurrence of several cancers. The miRNA miR-451 is downregulated in colorectal carcinoma (CRC) cells, suggested by several research groups including our own. In this study, synthetic miR-451 mimics were transfected into the SW620 human CRC cell line using Lipofectamine 2000 and expression of miR-451 was analyzed by real time PCR, while expression of CAB39, LKB1, AMPK, AKT, PI3K and Bcl2 was analyzed by Western blot, and cell growth was detected by MTT assay. In comparison to the controls, a significant increase in the expression of miR-451 was associated with significantly decreased expression of CAB39, LKB1, AMPK, AKT, PI3K and Bcl2. The capacity of cell proliferation was significantly decreased by miR-451 expression, which also inhibited cell growth. Our study confirmed that miR-451 has a repressive role in CRC cells by inhibiting cell growth through down-regulating the P13K/AKT pathway.

The Aetiological Role of Human Papillomavirus in Colorectal Carcinoma: An Iranian Population- Based Case Control Study

  • Ranjbar, Reza;Saberfar, Esmaiel;Shamsaie, Alireza;Ghasemian, Ehsan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1521-1525
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    • 2014
  • Background: Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide and the association between HPV infection and genital cancers has been well established. This study concerned the possible role of HPV infection in colorectal carcinoma (CRC) in the Iranian population. Materials and Methods: We examined 80 tissues obtained from patients with colorectal cancer consisting of 58 colon cancer samples and 22 rectal cancer samples and 80 tissues from patients with unremarkable pathologic changes as matched controls by sex, study center and anatomical sites. HPV infection and genotypes were detected using nested PCR and sequencing methods, respectively. Results: HPV DNA was detected in 5/80 (6.25%) cases including 1 of 22 (4.54%) patients with rectum cancer and 4 of 58 (6.9%) patients with colon cancer and 1/80 (1.25%) of controls. Furthermore, HPV-18 was detected as the most frequent type and we found no significant correlation between prevalence of HPV infection and anatomical sub- sites. Conclusions: Although a causal relation between human papillomavirus and colorectal cancer was not found through this study, analysis of medical records pointed to a possible role for high- risk types of HPV in increasing the potential of aggressiveness in colorectal cancer. This study shows a particular frequency of HPV genotypes in patients with colorectal cancer in Iran. Since HPV vaccines are limited to a few types of virus, using cohort studies in different geographical zones to screen for patterns of HPV infection in different organs might increase the efficacy and optimization of the current vaccines.

A Case-control Study of the Relationships between Reproductive Factors and Degree of Dysplasia of the Colorectal Adenoma and Cancer (대장 선종 이형성 및 대장암과 임신, 출산, 월경 요인의 관련성에 관한 환자-대조군 연구)

  • Lee, Se-Young;Choi, Kyu-Yong;Kim, Mi-Kyung;Lee, Jin-Hee;Meng, Kwang-Ho;Lee, Won-Chul
    • Journal of Preventive Medicine and Public Health
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    • v.36 no.3
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    • pp.279-288
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    • 2003
  • Objectives : Evidence for an effect of rerroductive factors on colorectal carcinogenesis is not yet consistent. Little research has been conducted to investigate whether reproductive factors were associated with colorectal adenomas that are the precursors of colorecta1 cancer, We evaluated the relationships between reproductive factors and the degree of dysplasia of the colorectal adenoma and cancer as colorectal adenoma-carcinoma sequence. Methods : For this study, 241 adenoma cases with histopathologically confirmed incident colorectal adenoma, 76 cancer cases with colorectal cancer and 1677 controls were collected from Our Lady of Mercy Hospital, The Catholic University of Korea, during 1994-1999. Before colonoscopy, information on demographic characteristics, reproductive factors, life style habits and dietary intake were obtained by interviewed questionnaire. Adjusted OR and 95% CI were estimated by using polytomous logistic regression model, Potential confounders that were selected based on the goodness of fit Statistics and interaction between risk factors were considered in this adjustment. The Wald statistic was calculated to test the heterogeneity of the odds ratios for each case. Results .: Postmenopausal women with natural menopause were found to be positively associated with the risk of mild dysplasia adenoma (multivariate-adjusted OR : 2.59, 95% CI=1.1-0.2). Parity was found to be negatively associated with the risk of colorectal lancer (age-adjusted OR : 0.40, 95% CI=0.2-0.9), but did not significantly decrease the risk of colorectal cancer (multivariate-adjusted OR : 0.95, 95% CI=0.3-2.9). Me associations were seen between a9e at menarche, breast feeding, induced abortion, oral contraceptive use, menopausal types, menopausal age or hormone replacement therapy (HRT and the degree of dysplasia of the colorectal adenoma and cancer. However, none of these associations differed' significantly between the degree of dysplasia of the colorectal adenoma and cancer. Conclusions : These findings suggest that postmenopausal women with natural menopause may experience increased risk of mild dysplasia adenorna among colorectal adenoma-carcinoma sequence.

Expression of Oncogene Product in the Colorectal Carcinoma (결장암 및 직장암에서 암유전자 산물의 발현)

  • Shim, Young-Ran;Jang, Woo-Young;Choi, Kyoung-Chan;Choi, Joon-Hyuk;Choi, Won-Hee;Shim, Min-Chul
    • Yeungnam University Journal of Medicine
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    • v.12 no.2
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    • pp.210-225
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    • 1995
  • The expression of $p62^{c-myc}$ and $p21^{ras}$ can be seen in many solid tumor, but the pattern and incidence of expression were different according to organ, countries, and examiners, thus it is not definitely defined. Total 67 colorectal carcinoma in paraffin sections are analysed by immunohistochemically for evaluation of the $p62^{c-myc}$ and $p21^{ras}$ expression according to the age, sex, chief complaints, location, differentiation, modified Dukes stage, using the specific monoclonal antibodies. The results were summarized as follows : The age of patients ranged from 32 years to 82 years. The mean age was 57.6 years. The expression of $p62^{c-myc}$ and $p21^{ras}$ was not correlated with age. Male was 29 cases(43.3%) and female was 38 cases(56.7%). The male to female ratio was 1:1.31. The expression of $p21^{ras}$ was increased in female(p<0.05). Abdominal pain(43.7%) was the most frequent chief complaint. The most frequent tumor location was rectum(44.8%). The expression of $p62^{c-myc}$ was increased in the rectum(p<0.05). The 65 cases(97.0%) out of 67 cases showed positive reaction of $p62^{c-myc}$ in the nucleus, cytoplasmic membrane, and cytoplasm. The 62 cases(92.5%) out of 67 cases showed positive reaction of $p21^{ras}$ in the cytoplasmic membrane and cytoplasm. The positive rate of $p62^{c-myc}$ and $p21^{ras}$ was 97.0% and 91.4% in well differentiated adenocarcinoma, 100.0% and 95.0% in moderately differentiated adenocarcinoma, 90.0% and 90.0% in poorly differentiated adenocarcinoma, 100.0% and 100.0% in mucinous carcinoma. The positive rate of $p62^{c-myc}$ and $p21^{ras}$ was 94.1% and 88.2% in Dukes stage $B_1$, 96.0% and 96.0% in Dukes stage $B_2$, 100.0% and 100.0% in Dukes stage $C_1$, 100.0% and 88.9% in Dukes stage $C_2$, and 100.0% and 100.0% in Dukes stage D. The expression of $p62^{c-myc}$ in metastatic colorectal carcinoma showed diffuse and strongly positive reaction than primary colorectal carcinoma. The expression of $p21^{ras}$ in primary colorectal carcinoma showed diffuse and strongly positive reaction than metastatic colorectal carcinoma.

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MiR-1297 Regulates the Growth, Migration and Invasion of Colorectal Cancer Cells by Targeting Cyclo-oxygenase-2

  • Chen, Pu;Wang, Bei-Li;Pan, Bai-Shen;Guo, Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9185-9190
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    • 2014
  • Cyclo-oxygenase-2(Cox-2), a key regulator of inflammation-producing prostaglandins, promotes cell proliferation and growth. Therefore, a better understanding of the regulatory mechanisms of Cox-2 could lead to novel targeted cancer therapies. MicroRNAs are strongly implicated in colorectal cancer but their specific roles and functions have yet to be fully elucidated. MiR-1297 plays an important role in lung adenocarcinoma and laryngeal squamous cell carcinoma, but its significance in colorectal cancer (CRC) has yet to be reported. In our present study, we found miR-1297 to be down regulated in both CRC-derived cell lines and clinical CRC samples, when compared with normal tissues. Furthermore, miR-1297 could inhibit human colorectal cancer LOVO and HCT116 cell proliferation, migration, and invasion in vitro and tumorigenesis in vivo by targeting Cox-2. Moreover, miR-1297 directly binds to the 3'-UTR of Cox-2, and the expression level was drastically decreased in LOVO and HCT116 cells following overexpression of miR-1297. Additionally, Cox-2 expression levels are inversely correlated with miR-1297 expression in human colorectal cancer xenograft tissues. These results imply that miR-1297 has the potential to provide a new approach to colorectal cancer therapy by directly inhibiting Cox-2 expression.

Helicobacter pylori Infection and the Risk of Colorectal Adenoma and Adenocarcinoma: an Updated Meta-analysis of Different Testing Methods

  • Chen, Yao-Sheng;Xu, Song-Xin;Ding, Yan-Bing;Huang, Xin-En;Deng, Bin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7613-7619
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    • 2013
  • Background and Aims: Helicobacter pylori infection may be associated with an increased risk of colorectal carcinoma. However, as most studies on this subject were relatively small in size and differed at least partially in their designs, their results remain controversial. In this study, we aimed to carry out a meta-analysis to evaluate the potential association of H. pylori infection with colorectal adenoma and adenocarcinoma risk, covering all of the different testing methods. Methods: We conducted a search in PubMed, Medline, EBSCO, High Wire Press, OVID, and EMBASE covering all published papers up to March 2013. According to the established inclusion criteria, essential data were then extracted from the included studies and further analyzed by a systematic meta-analysis. Odds ratios were employed to evaluate the relationship between H. pylori infection and the risk of colorectal neoplasms. Results: Twenty-two studies were included, and the odds ratio for the association between H. pylori infection and colorectal cancer was 1.49 (95% confidence interval 1.30-1.72). No statistically significant heterogeneity was observed. Publication bias was ruled out. Conclusion: The pooled data suggest H. pylori infection indeed increases the risk of colorectal adenoma and adenocarcinoma.

The Caudal-Related Homeodomain Proteins Upregulate catalase Expression in Drosophila Hindgut and Human Colorectal Carcinoma Cells (초파리 대장조직과 인간 대장암세포주에서의 caudal 단백질에 의한 catalase 발현 조절)

  • Park, Jae-Hong;Park, So-Young;Lee, Dong-Ho;Kim, Young-Shin;Yoo, Mi-Ae
    • Journal of Life Science
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    • v.21 no.2
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    • pp.194-201
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    • 2011
  • Caudal-related homeodomain proteins play critical roles in intestine development and maintenance from Drosophila to humans. The loss or reduction of CDX1 and CDX2 are known to be associated with colon cancers. It has been well known that colorectal carcinogenesis is associated with serious oxidative stress and that catalase is decreased in colon carcinomas. However, the underlying molecular mechanisms remain elusive. Here, we report that Caudal-related homeodomain proteins positively regulate catalase expression in both Drosophila and humans. We found that Drosophila caudal heterozygotes have a decreased catalase expression and increased ROS generation in the hindgut, and that the overexpression of Caudal increases catalase promoter activity and catalase mRNA levels. We also found that CDX1 and CDX2 up-regulate catalase promoter activity and protein levels in HCT116 cells - human colorectal carcinoma cell lines. The level of catalase protein in several colorectal carcinoma cell lines was associated with CDX1 expression. These results suggest that CDX1 and CDX2 may be involved in intestinal homeostasis and tumorigenesis via regulation of catalase expression.

Aldose Reductase Inhibitor Fidarestat as a Promising Drug Targeting Autophagy in Colorectal Carcinoma: a Pilot Study

  • Pandey, Saumya
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4981-4985
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    • 2015
  • Background: Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide. Targeting autophagic cell death is emerging as a novel strategy in cancer chemotherapy. Aldose reductase (AR) catalyzes the rate limiting step of the polyol pathway of glucose metabolism; besides reducing glucose to sorbitol, AR reduces lipid peroxidation-derived aldehydes and their glutathione conjugates. A complex interplay between autophagic cell death and/or survival may in turn govern tumor metastasis. This exploratory study aimed to investigate the potential role of AR inhibition using a novel inhibitor Fidarestat in the regulation of autophagy in CRC cells. Materials and Methods: For glucose depletion (GD), HT-29 and SW480 CRC cells were rinsed with glucose-free RPMI-1640, followed by incubation in GD medium +/- Fidarestat ($10{\mu}M$). Proteins were extracted by a RIPA-method followed by Western blotting ($35-50{\mu}g$ of protein; n=3). Results: Autophagic regulatory markers, primarily, microtubule associated protein light chain (LC) 3, autophagy-related gene (ATG) 5, ATG 7 and Beclin-1 were expressed in CRC cells; glyceraldehyde-3 phosphate dehydrogenase (GAPDH) was used as an internal reference. LC3 II (14 kDa) expression was relatively high compared to LC3A/B I levels in both CRC cell lines, suggesting occurrence of autophagy. Expression of non-autophagic markers, high mobility group box (HMG)-1 and Bcl-2, was comparatively low. Conclusions: GD +/- ARI induced autophagy in HT-29 and SW-480 cells, thereby implicating Fidarestat as a promising therapeutic agent for colorectal cancer; future studies with more potent ARIs are warranted to fully dissect the molecular regulatory networks for autophagy in colorectal carcinoma.

Phase II Study of Pemetrexed as Second or Third Line Combined Chemotherapy in Patients with Colorectal Cancer

  • Wu, Xue-Yan;Huang, Xin-En;You, Shan-Xi;Lu, Yan-Yan;Cao, Jie;Liu, Jin;Xiang, Jin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.2019-2022
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    • 2013
  • Purpose: To investigate the safety and efficacy of pemetrexed combined with chemotherapy as second or third line in patients with stage IV colorectal cancer (CRC). Patients and Methods: This trial was conducted to evaluate the effectiveness and safety of pemetrexed given to patients with recurrent or metastatic colorectal carcinoma who previously received 5-FU-based chemotherapy. All patients were required to have a histological diagnosis of colorectal adenocarcinoma with measurable metastatic disease and prior chemotherapy. Patients received pemetrexed at a dose of 500 $mg/m^2$ by 10 minute infusion on day 1, repeated every 21 days. Doses were modified depending on nadir counts. Combined chemotherapy included Oxaliplatin, Irinotecan and cis-platinum. Results: Thirty patients were enrolled and twenty-nine were evaluable for response. One patient did not have repeat radiological testing to determine response because he went off study after only one cycle of treatment for economic reasons. For 29 evaluable patients, 1 partial response, 6 stable disease and 22 progressive disease were recorded. Response rate was 3.45% (1/29). All responses occurred in patients receiving a starting dose of pemetrexed 500 $mg/m^2$. Median time to progression for all eligible patients was 2.5 months. The most common toxicities experienced were mild to moderate fever, hepatic damage, myelosuppression, nausea, vomiting, constipation, abdominal pain, diarrhea, and skin rash. Conclusion: Pemetrexed at 500 $mg/m^2$ given every three weeks combined with chemotherapy is associated with moderate response and good tolerability in patients with stage IV CRC.

Effective Response of the Peritoneum Microenvironment to Peritoneal and Systemic Metastasis from Colorectal Carcinoma

  • Yu, Min;Niu, Zhi-Min;Wei, Yu-Quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7289-7294
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    • 2013
  • We here document discovery of a new and simple model of tumor seeding involving the mouse peritoneum. Irradiated tumor cells administered by i.p. injection provided effective vaccination against peritoneal carcinomatosis and distal metastasis with colorectal carcinomas. In flow cytometric analysis, CD4+ and CD8+ T lymphocytes, macrophages and myeloid-derived suppressor cells (MDSCs), which are easy to obtain in the peritoneal cavity, were revealed to have significant differences between immunized and non-immunized mice and these contributed to antitumor responses. We also observed that both serum and peritoneal lavage fluid harvested from immunized mice showed the presence of CT26-specific autoantibodies. In addition, increase in level of TGF-${\beta}1$ and IL-10 in serum but a decrease of TGF-${\beta}1$ in peritoneum was found. Taken together, these findings may provide a new vaccine strategy for the prevention of peritoneal and even systemic metastasis of carcinomas through induction of an autoimmune response in the peritoneum.