1.Expression of Cyclooxygenase-2 and its Relationship to p53 Accumulation in Colorectal Cancers.
Sung Chul LIM ; Tae Bum LEE ; Cheol Hee CHOI ; So Yeon RYU ; Kyung Jong KIM ; Young Don MIN
Yonsei Medical Journal 2007;48(3):495-501
PURPOSE: Cyclooxygenase (COX)-2 is an inducible isoform responsive to cytokines, mitogens, and growth factors, and is believed to be an important enzyme related to colorectal cancer (CRC). Existing evidence suggests that COX-2 expression is normally suppressed by wild-type p53 but not mutant p53, suggesting that loss of p53 function may result in the induction of COX-2 expression. The aim of this study was to determine the relationship between COX-2 expression and p53 levels in CRC. MATERIALS AND METHODS: Patients with sporadic colorectal adenocarcinoma (n=161) who underwent curative surgery in Chosun University Hospital were enrolled in this study. Expression of COX-2 and p53 proteins was examined by immunohistochemistry in paraffin-embedded cancer tissue blocks, and the relationship between COX-2 and/or p53 expression with clinicopathologic parameters was analyzed. RESUTLS: Expression of COX- 2 was positive in 47.8% of colorectal cancers, and significantly associated with the depth of tumor invasion (p= 0.042). In contrast, p53 was positive in 50.3% of the cases, and was associated with both age (p=0.025) and the depth of tumor invasion (p=0.014). There was no correlation between COX-2 expression and p53 expression (p=0.118). CONCLUSION: These results suggest that COX-2 expression might play an important role in the progression of colorectal cancer. However, COX-2 expression was not associated with mutational p53. Further studies are needed to clarify the regulatory mechanisms governing COX-2 overexpression in colorectal cancers.
Adenocarcinoma/*metabolism/pathology/surgery
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Aged
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Colorectal Neoplasms/*metabolism/pathology/surgery
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Cyclooxygenase 2/*metabolism
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Female
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Humans
;
Immunohistochemistry
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Male
;
Middle Aged
;
Mutation
;
Tumor Suppressor Protein p53/genetics/*metabolism
2.Pathogenesis and Management of Serrated Polyps: Current Status and Future Directions.
Gut and Liver 2014;8(6):582-589
Hyperplastic or serrated polyps were once believed to have little to no clinical significance. A subset of these polyps are now considered to be precursors to colorectal cancers (CRC) in the serrated pathway that may account for at least 15% of all tumors. The serrated pathway is distinct from the two other CRC pathways and involves an epigenetic hypermethylation mechanism of CpG islands within promoter regions of tumor suppressor genes. This process results in the formation of CpG island methylator phenotype tumors. Serrated polyps are divided into hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The SSA/P and the TSA have the potential for dysplasia and subsequent malignant transformation. The SSA/Ps are more common and are more likely to be flat than TSAs. Their flat morphology may make them difficult to detect and thus explain the variation in detection rates among endoscopists. Challenges for endoscopists also include the difficulty in pathological interpretation as well surveillance of these lesions. Furthermore, serrated polyps may be inadequately resected by endoscopists. Thus, it is not surprising that the serrated pathway has been linked with interval cancers. This review will provide the physician or clinician with the knowledge to manage patients with serrated polyps.
Adaptor Proteins, Signal Transducing/genetics/metabolism
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Adenomatous Polyps/genetics/metabolism/*surgery
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Colonoscopy
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Colorectal Neoplasms/genetics/metabolism/*surgery
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DNA Methylation
;
Humans
;
Intestinal Polyposis/genetics/metabolism/*surgery
;
Intestinal Polyps/genetics/metabolism/*surgery
;
Nuclear Proteins/genetics/metabolism
;
Proto-Oncogene Proteins/genetics/metabolism
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Proto-Oncogene Proteins B-raf/genetics/metabolism
;
ras Proteins/genetics/metabolism
3.Lynch syndrome-related endometrial carcinoma.
Chinese Journal of Pathology 2012;41(7):494-497
Adaptor Proteins, Signal Transducing
;
metabolism
;
Adenocarcinoma, Clear Cell
;
genetics
;
metabolism
;
pathology
;
surgery
;
Adenosine Triphosphatases
;
metabolism
;
Age Factors
;
Carcinoma, Endometrioid
;
genetics
;
metabolism
;
pathology
;
surgery
;
Colorectal Neoplasms, Hereditary Nonpolyposis
;
genetics
;
metabolism
;
pathology
;
surgery
;
Cystadenocarcinoma, Serous
;
genetics
;
metabolism
;
pathology
;
surgery
;
DNA Mismatch Repair
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DNA Repair Enzymes
;
metabolism
;
DNA-Binding Proteins
;
metabolism
;
Endometrial Neoplasms
;
genetics
;
metabolism
;
pathology
;
surgery
;
Female
;
Humans
;
Mismatch Repair Endonuclease PMS2
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MutL Protein Homolog 1
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MutS Homolog 2 Protein
;
metabolism
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Neoplasms, Multiple Primary
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genetics
;
metabolism
;
pathology
;
surgery
;
Nuclear Proteins
;
metabolism
4.Clinicopathologic characteristics, diagnosis, and treatment of 30 patients with hereditary nonpolyposis colorectal cancer.
Heli LIU ; Zhongshu YAN ; Guoqing LIAO ; Hongling YIN ; Xiaoyong XIE
Journal of Central South University(Medical Sciences) 2009;34(8):757-761
OBJECTIVE:
To explore the clinicopathologic and molecular characteristics of hereditary nonpolyposis colorectal cancer (HNPCC), and to improve the level of diagnosis and treatments of HNPCC.
METHODS:
Thirty HNPCC patients (HNPCC group) who were treated in Xiangya Hospital were retrospectively analyzed, and 25 patients with sporadic colorectal cancer in the same duration were randomly chosen as a control group. The onset of age, location of tumor, pathological type, treatment method, and prognosis were compared in the 2 groups. The expression loss rate of mismatch repair gene (MMR) MLH1 and MSH2 in the 2 groups was detected by immunohistochemistry.
RESULTS:
The onset age in the HNPCC group was earlier than that in the control group (P<0.05). The rate of proximal colonic tumor the occurrence of multiple tumors, and the proportion of well differentiated adenocarcinoma in the HNPCC group were all higher than those in the control group (P<0.05). The expression loss rate of MLH1 and MSH2 in the HNPCC group was higher than that in the control group (P<0.05). One third in the HNPCC group received subtotal proctocolectomy. The prognosis of HNPCC patients was comparable with that of patients with sporadic colorectal cancer (P>0.05).
CONCLUSION
HNPCC patients are characterized with early onset associating with multiple tumors. The accuracy of diagnosis can be improved by combining the detection of MMR gene. Optimal surgical treatment and close follow-up may bring good result to HNPCC patients.
Adaptor Proteins, Signal Transducing
;
genetics
;
metabolism
;
Adenocarcinoma
;
diagnosis
;
genetics
;
pathology
;
surgery
;
Aged
;
Case-Control Studies
;
Colorectal Neoplasms, Hereditary Nonpolyposis
;
diagnosis
;
genetics
;
pathology
;
surgery
;
Endometrial Neoplasms
;
pathology
;
Female
;
Humans
;
Male
;
Middle Aged
;
MutL Protein Homolog 1
;
MutS Homolog 2 Protein
;
genetics
;
metabolism
;
Mutation
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Neoplasms, Second Primary
;
pathology
;
Nuclear Proteins
;
genetics
;
metabolism
;
Retrospective Studies
5.Chemotherapy for Colorectal Cancer.
The Korean Journal of Gastroenterology 2009;54(6):355-363
Recent advances in chemotherapy lead to improved survival outcomes in patients with colorectal cancer. The 5-fluorouracil (5-FU) is still one of the important chemotherapeutic agents since 1950s, but the introduction of newer cytotoxic agents, irinotecan and oxaliplatin, or targeted agents, bevacizumab and cetuximab, have changed treatment strategies for these patients. A deliberate choice should be made for adjuvant chemotherapy, because it has became complicated more than ever before. Oxaliplatin plus 5-FU seemed to be superior in terms of disease-free and overall survival than 5-FU alone after curative surgery for colon cancers. However not all of these patients seemed to receive benefit from this intensive adjuvant treatment, and some limitations are present according to the postoperative stage, tumor biology and clinical characteristics. For metastatic disease, there is no doubt that more complicated strategies are present because we have more abundant chemotherapeutic agents available for metastatic setting compared to adjuvant setting. Recently, targeted agents, such as bevacizumab or cetuximab, also took an important place in the treatment of metastatic colorectal cancer, and many efforts are also made to find the biomarkers for predicting treatment responses to these targeted agents. In this review, we intended to sort up the standard strategies of chemotherapy for patients with colorectal cancer according to the latest pivotal publications.
Antibodies, Monoclonal/therapeutic use
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Antineoplastic Agents/therapeutic use
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Chemotherapy, Adjuvant
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Colorectal Neoplasms/*drug therapy/surgery
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Drug Therapy, Combination
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Fluorouracil/therapeutic use
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Humans
;
Organoplatinum Compounds/therapeutic use
;
ras Proteins/genetics/metabolism