• Title, Summary, Keyword: Colorectal carcinoma

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Cordycepin inhibits lipopolysaccharide-induced cell migration and invasion in human colorectal carcinoma HCT-116 cells through down-regulation of prostaglandin E2 receptor EP4

  • Jeong, Jin-Woo;Park, Cheol;Cha, Hee-Jae;Hong, Su Hyun;Park, Shin-Hyung;Kim, Gi-Young;Kim, Woo Jean;Kim, Cheol Hong;Song, Kyoung Seob;Choi, Yung Hyun
    • BMB Reports
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    • v.51 no.10
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    • pp.532-537
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    • 2018
  • Prostaglandin $E_2$ ($PGE_2$), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because $PGE_2$ functions by signaling through $PGE_2$ receptors (EPs), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting EPs. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibiting the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinase (MMP)-9 as well as the down-regulation of COX-2 expression and $PGE_2$ production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the EP4 antagonist AH23848 prevented LPS-induced MMP-9 expression and cell invasion in HCT116 cells. However, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

Carcinoma of the Colon and Rectum : Sonographic Findings and usefulness (Cases Review) (결직장암의 초음파검사 소견 및 유용성(증례 중심으로))

  • Jung, Hong-Ryang;Kim, Myeong-Soo;Sim, Hyun-Sun
    • Journal of radiological science and technology
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    • v.26 no.2
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    • pp.43-47
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    • 2003
  • Colorectal cancer produce focal mass or segmental thickening which can be detected with sonography. The purpose of this study was to describe sonographic findings of colorectal cancer. we reviewed sonograms of 51 patients with colorectal cancer in whom sonography was performed before colon study. In 51 patients who had more common coloretal cancer 27cases(53%) had 40 to 50 years of age(60%). Sonographic findings included segmental thickening 42cases, or irregular mass 9 cases. With careful examination, these findings can be detectable, and therefore bowel should be carefully examination in patients with sign and symptoms suggesting carcinoma of the colon and rectum.

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Analysis of Hereditary Nonpolyposis Colorectal Cancer in Malay Cohorts using Immunohistochemical Screening

  • Juhari, Wan Khairunnisa Wan;Rahman, Wan Faiziah Wan Abdul;Sidek, Ahmad Shanwani Mohd;Hassan, Muhammad Radzi Abu;Noordin, Khairul Bariah Ahmad Amin;Zakaria, Andee Dzulkarnaen;Macrae, Finlay;Zilfalil, Bin Alwi
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3767-3771
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    • 2015
  • Background: Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1, MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malay cohort by immunohistochemistry. Materials and Methods: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2. Results: Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively. Conclusions: Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.

Histopathological Features of Colorectal Cancer in Al-Madinah Region of Saudi Arabia: 8 Years Experience

  • Albasri, Abdulkader;Yosef, Hala;Hussainy, Akbar Shah;Sultan, Saud Ahmad;Alhujaily, Ahmed
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3133-3137
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    • 2014
  • Background: To determine the histopathological pattern of colorectal cancer (CRC) among Saudi patients with a view to determine various epidemiological and histopathological features of the disease. Materials and Methods: We retrospectively collected and analyzed the demographic and histopathological data of all the patients with CRC diagnosed at King Fahad Hospital, Madinah, Saudi Arabia over a period of 8 years from January 2006 to December 2013. Results: Of 324 cases of CRC reviewed, 200 cases (61.7%) were males while 124 cases (38.3%) were females giving a male to female ratio of 1.6: 1. Age of the patients ranged from 20 to 100 years with a mean age 57.9 years. The rectosigmoid region was the most frequent anatomical site (13.6%) involved and adenocarcinoma (88.6%) was the most common histopathological type. The majority of adenocarcinomas (87.3%) were moderately differentiated. A total of 47.8% of patients were in stage B and 43.5% of patients were in stage C of the Aster-Coller classification. Most patients (75.7%) presented with large size tumors. Lymphovascular invasion and lymph node metastasis were recorded in 67.9% and 43.6% of cases, respectively. Conclusions: Colorectal cancer is common in our environment and the majority of patients present late with an advanced stage. Screening programs regarding CRC should be enhanced to improve the outcome of the patients.

MicroRNAs in Colorectal Cancer: from Diagnosis to Targeted Therapy

  • Orang, Ayla Valinezhad;Barzegari, Abolfazl
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.6989-6999
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    • 2014
  • Colorectal cancer (CRC) is one of the major healthcare problems worldwide and its processes of genesis include a sequence of molecular pathways from adenoma to carcinoma. The discovery of microRNAs, a subset of regulatory non-coding RNAs, has added new insights into CRC diagnosis and management. Together with several causes of colorectal neoplasia, aberrant expression of oncomiRs (oncogenic and tumor suppressor miRNAs) in cancer cells was found to be indirectly result in up- or down-regulation of targeted mRNAs specific to tumor promoter or inhibitor genes. The study of miRNAs as CRC biomarkers utilizes expression profiling methods from traditional tissue samples along with newly introduced non-invasive samples of faeces and body fluids. In addition, miRNAs could be employed to predict chemo- and radio-therapy responses and be manipulated in order to alleviate CRC characteristics. The scope of this article is to provide a comprehensive review of scientific literature describing aberrantly expressed miRNAs, and consequently dysregulation of targeted mRNAs along with the potential role of miRNAs in CRC diagnosis and prognosis, as well as to summarize the recent findings on miRNA-based manipulation methods with the aim of advancing in anti-CRC therapies.

Effects of Parafibromin Expression on the Phenotypes and Relevant Mechanisms in the DLD-1 Colon Carcinoma Cell Line

  • Zhao, Shuang;Sun, Hong-Zhi;Zhu, Shi-Tu;Lu, Hang;Niu, Zhe-Feng;Guo, Wen-Feng;Takano, Yasuo;Zheng, Hua-Chuan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4249-4254
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    • 2013
  • Background: Parafibromin is a protein encoded by the HRPT2 (hyperparathyroidism 2) oncosuppressor gene and its down-regulated expression is involved in pathogenesis of parathyroid, breast, gastric and colorectal carcinomas. This study aimed to clarify the effects of parafibromin expression on the phenotypes and relevant mechanisms of DLD-1 colon carcinoma cells. Methods: DLD-1 cells transfected with a parafibromin-expressing plasmid were subjected to examination of phenotype, including proliferation, differentiation, apoptosis, migration and invasion. Phenotype-related proteins were measured by Western blot. Parafibromin and ki-67 expression was detected by immunohistochemistry on tissue microarrays. Results: The transfectants showed higher proliferation by CCK-8, better differentiation by electron microscopy and ALP activity and more apoptotic resistance to cisplatin by DNA fragmentation than controls. There was no difference in early apoptosis by annexin V, capase-3 activity, migration and invasion between DLD-1 cells and their transfectants. Ectopic parafibromin expression resulted in down-regulated expression of smad4, MEKK, GRP94, GRP78, $GSK3{\beta}$-ser9, and Caspase-9. However, no difference was detectable in caspase-12 and -8 expression. A positive relationship was noted between parafibromin and ki-67 expression in colorectal carcinoma. Conclusions: Parafibromin overexpression could promote cell proliferation, apoptotic resistance, and differentiation of DLD-1 cells.

Loss of p15INK4b Expression in Colorectal Cancer is Linked to Ethnic Origin

  • Abdel-Rahman, Wael Mohamed;Nieminen, Taina Tuulikki;Shoman, Soheir;Eissa, Saad;Peltomaki, Paivi
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2083-2087
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    • 2014
  • Colorectal cancers remain to be a common cause of cancer-related death. Early-onset cases as well as those of various ethnic origins have aggressive clinical features, the basis of which requires further exploration. The aim of this work was to examine the expression patterns of $p15^{INK4b}$ and SMAD4 in colorectal carcinoma of different ethnic origins. Fifty-five sporadic colorectal carcinoma of Egyptian origin, 25 of which were early onset, and 54 cancers of Finnish origin were immunohistochemically stained with antibodies against $p15^{INK4b}$ and SMAD4 proteins. Data were compared to the methylation status of the $p15^{INK4b}$ gene promotor. $p15^{INK4b}$ was totally lost or deficient (lost in ${\geq}50%$ of tumor cell) in 47/55 (85%) tumors of Egyptian origin as compared to 6/50 (12%) tumors of Finnish origin (p=7e-15). In the Egyptian cases with $p15^{INK4b}$ loss and available $p15^{INK4b}$ promotor methylation status, 89% of cases which lost $p15^{INK4b}$ expression were associated with $p15^{INK4b}$ gene promotor hypermethylation. SMAD4 was lost or deficient in 25/54 (46%) tumors of Egyptian origin and 28/48 (58%) tumors of Finnish origin. 22/54 (41%) Egyptian tumors showed combined loss/deficiency of both $p15^{INK4b}$ and SMAD4, while $p15^{INK4b}$ was selectively lost/deficient with positive SMAD4 expression in 24/54 (44%) tumors. Loss of $p15^{INK4b}$ was associated with older age at presentation (>50 years) in the Egyptian tumors (p=0.04). These data show for the first time that $p15^{INK4b}$ loss of expression marks a subset of colorectal cancers and ethnic origin may play a role in this selection. In a substantial number of cases, the loss was independent of SMAD4 but rather associated with $p15^{INK4b}$ gene promotor hypermethylation and old age which could be related to different environmental exposures.