Value of serum P53 antibody as a tumor marker surveillance of colorectal cancer within follow-up after curative resection / 中华胃肠外科杂志

P53 gene mutations and the abnormal P53 protein can introduce the production to P53 antibody. A large number of studies showed that serum levels of P53 antibody had the correlation with the prognosis of patients with different cancers, the lymph node invasion and metastasis of colorectal cancer, and its recurrence after the curative resection. And it is possible for its application in predicting the early recurrence and metastasis in colorectal cancer after the curative resection.However, there are still a lot of work needed to be done before its use in the clinical settings.

HIWI expression profile in cancer cells and its prognostic value for patients with colorectal cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>HIWI is a member of PIWI gene family and its expression is found in various tumors, indicating that it may play a pivotal role in tumor development. This study was designated to examine HIWI protein expression profile in several cancer cell lines and its prognostic value for patients with colorectal cancer.</p><p><b>METHODS</b>Totally 270 patients who underwent surgical resection of primary colorectal cancer between January 1999 and December 2002 with a median follow-up time of 33 months were registered in the study. Formalin-fixed and paraffin-embedded specimens from these patients and 236 matched adjacent non-cancerous normal colorectal tissues were collected. Anti-HIWI monoclonal antibodies were generated and used for evaluating HIWI protein expression. χ(2) tests were conducted to determine the association between HIWI expression and the other variables. Survival curves were estimated using the Kaplan-Meier method and compared by the log-rank test. Multivariate analysis was performed by using the Cox regression model.</p><p><b>RESULTS</b>By generating antibodies specific for HIWI, we examined HIWI protein expression in several cancer cell lines and demonstrated positive expression of HIWI in 69 out of 270 (25.6%) colorectal cancer tissues; 15 of 236 (6.4%) matched adjacent non-cancerous tissues were also positive for HIWI. Patients with positive HIWI expression in adjacent non-cancerous tissue had statistically lower overall survival (OS) and disease free survival (DFS) compared with negative patients (OS: 10.4% vs. 55.5%, P = 0.009; DFS: 10.4% vs. 55.1%, P = 0.015). For early stage group (stages I and II), patients with positive HIWI expression had significantly lower OS and DFS (OS: 57.4% vs. 79.5%, P = 0.014; DFS: 56.7% vs. 80.5%, P = 0.010). In lymph node negative group, patients with positive HIWI expression had statistically lower OS and DFS (OS: 53.0% vs. 73.5%, P = 0.037; DFS: 52.2% vs. 74.6%, P = 0.025). Multivariate analysis revealed that HIWI over-expression was a significant prognostic factor for OS (95%CI: 1.132 - 2.479, P = 0.010).</p><p><b>CONCLUSION</b>HIWI could be a potential prognostic biomarker for the patients with colorectal cancer, especially for those at early stages or without lymph node metastasis.</p>

Application of biotherapy in recurrent or metastatic gastric cancer / 中华胃肠外科杂志

Post-operative recurrence and metastasis remain the leading causes of death for patients with gastric cancer. The major determinants of recurrence and metastasis are the biological characteristics of cancer cells and the immunological status of the patients. In recent years, due to the target-specificity, biotherapy has yielded efficacious responses in diverse clinical applications for cancer treatment, partially for the treatment of recurrence and metastasis of gastric cancer. However, because of the high diversities in clinical manifestations, patients' condition, and tumor's characteristics, there is no ideal strategy of biotherapy established for the prevention and treatment of recurrence and metastasis in gastric cancer. Therefore, a lot of work need to be done in basic research and clinical trial to make the biotherapy effective in treatment of gastric cancer recurrence.

Effect of trastuzumab on tumor cell lines shedding high or low level of HER-2 ECD / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To examine the effect of trastuzumab on cell proliferation, colony formation and changes of HER-2 proteins in human breast cancer cell line SKBR3 and human ovarian cancer cell line SKOV3 cells which overexpress p185 HER-2 but shed high or low HER-2 extracellular domain (ECD) levels.</p><p><b>METHODS</b>SKBR3 cells and SKOV3 cells were treated with or without trastuzumab. Cell number and the rate of colony formation were calculated. Western blot analysis was used to detect p185 HER-2, HER-2 ECD and phospho-HER-2. Two-site ELISA assay was used for the detection of HER-2 ECD.</p><p><b>RESULTS</b>Trastuzumab inhibited cell proliferation, colony formation, and decreased or eliminated the levels of two uncharacterized phospho-proteins (molar weight about 90 000 and 40 000) in SKBR3 cells shedding high level of HER-2 ECD expression. These responses were not observed in SKOV3 cells shedding low level of HER-2 ECD expression. But total p185, phospho-p185 and phospho-p95 proteins did not appear to change in SKBR3 and SKOV3 cells after treatment with trastuzumab. Trastuzumab reacts not only with proteolytic cleavage HER-2 ECD containing HER-2 ECD I , II , III and IV subdomains of p185 HER-2 extracellular domain, but also with the secreted autoinhibitor p68/ECD III a specifying 340 residues, identical to subdomains I and II from the extracellular domain of p185 HER-2, followed by a unique C-terminal sequence of 79 aa encoded by intron 8, which suggested that there may be a trastuzumab binding site on p68/ECD III a protein. Comparing with HER-2 ECD levels of the same number of SKBR3 cells, there was no significant decrease of HER-2 ECD shedding level after treatment with or without trastuzumab for 4 days in serum-free medium.</p><p><b>CONCLUSION</b>Antitumor effects of trastuzumab may be related to the two uncharacterized phospho-p90 and/or phospho-p40 proteins. There is probably a trastuzumab epitope on p68/ECD III a. The decrease of HER-2 ECD levels may be positively correlated with the number of SKBR3 cells.</p>