Alteration of DNA ploidy status and cell proliferation induced by preoperative radiotherapy is a prognostic factor in rectal cancer
Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA. Clinical Cancer Research
(Impact Factor: 8.72).
To identify predictors of prognosis after preoperative radiotherapy, DNA ploidy and cell proliferation were investigated in 116 patients with rectal cancer. For flow cytometry, a nuclear suspension was prepared by pepsin digestion of paraffin samples of biopsies taken before preoperative radiotherapy (15 x 2 Gy) and also of the resected rectal tumors after radiotherapy. The median follow-up period was 6 years. The proportion of tumor necrosis was evaluated in histological sections before and after irradiation. There was a significant decrease (74 to 48%) in aneuploid tumors after radiation. Of 86 patients with aneuploid biopsies, 28 revealed no reduction in the proportion of aneuploid tumor cells [group AN(=/increase)], and 58 showed a reduction (mean 48.9%) or complete elimination of aneuploid tumor cells [group AN(decrease/psi)]. The incidence of local or distal failure was significantly reduced in the group AN(decrease/psi) (7.8%/20%), compared with the group AN (=/increase) (27%/54%) and the group of constant diploid tumors (n = 22; 13.6%/31.8 %; P = 0.034). There was a trend of decreased recurrence rate in diploid tumors with a reduced fraction of cells in S-phase after radiotherapy. Survival was significantly increased in group AN(decrease/psi) (P < 0.0001). In a multivariate regression analysis, variables of independent prognostic significance were increased proportion of necrosis after irradiation and DNA ploidy group and the postoperative tumor stage. These results suggest that alterations in tumor DNA ploidy and cell proliferation induced by preoperative radiotherapy might help to identify patients likely to benefit from preoperative radiation in rectal cancer.
Available from: Dianne Langford
- "Tumour necrosis is caused by a rapid tumor growth without sufficient blood supply, which leads to ischemia and necrosis of the tumour cells. Previous studies by others did demonstrate that necrosis was associated with a poor clinical outcome . In the present study of all patients, we found a positive relationship between PINCH at the invasive margin and necrosis. "
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ABSTRACT: The clinical significance between particularly interesting new cysteine-histidine rich protein (PINCH) expression and radiotherapy (RT) in tumours is not known. In this study, the expression of PINCH and its relationship to RT, clinical, pathological and biological factors were studied in rectal cancer patients.
PINCH expression determined by immunohistochemistry was analysed at the invasive margin and inner tumour area in 137 primary rectal adenocarcinomas (72 cases without RT and 65 cases with RT). PINCH expression in colon fibroblast cell line (CCD-18 Co) was determined by western blot.
In patients without RT, strong PINCH expression at the invasive margin of primary tumours was related to worse survival, compared to patients with weak expression, independent of TNM stage and differentiation (P = 0.03). No survival relationship in patients with RT was observed (P = 0.64). Comparing the non-RT with RT subgroup, there was no difference in PINCH expression in primary tumours (invasive margin (P = 0.68)/inner tumour area (P = 0.49). In patients with RT, strong PINCH expression was related to a higher grade of LVD (lymphatic vessel density) (P = 0.01)
PINCH expression at the invasive margin was an independent prognostic factor in patients without RT. RT does not seem to directly affect the PINCH expression.
Available from: Elsayed I Salim
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ABSTRACT: The present study was designated to evaluate the effect of direct current induced permanent magnetic field (DC-MF) on chemically induced rat colon carcinogenesis. Five experimental groups of male S.D. rats were injected with 1,2-dimethylhydrazine (DMH) subcutaneously, 20 mg/kg b.wt., once a week for four weeks, with exposure to 1 mT DC-MF (12 hours/day) as follows: Before (pre) the carcinogen administration (group 1), simultaneously (group 2), after (post) the carcinogen administration (group 3) and daily from the beginning to the end of the experiment after 12 weeks (group 4). Rats of group 5 served as carcinogen-only treated controls while those of group 6 were non-treated controls. There were no differences in the incidences and multiplicities of colonic aberrant crypt foci (ACF), putative preneoplastic lesions, among all groups except that large foci in group 1 were significantly fewer in numbers than those found in group 5. Proliferating cell nuclear antigen labeling indexes (PCNA-LI) in the colon epithelium were essentially the same in MF-treated and control rats. Histopathological examination showed evident hemorrhage in the pituitary glands of some rats of groups 1-3, and in most rats of group 4. Transmission electron microscopy also revealed ultrastructural changes, but DNA ploidy analysis revealed no carcinogenicity to MF-exposed pituitary glands. Serum levels of AST, ALT, total protein, creatinine, albumin, albumin/globulin ratio and growth hormone levels did not change among the groups. The present study revealed that the action of an artificial MF on rats is not carcinogenic/or cancer-promoting, at least in the present protocol for colon carcinogenesis.
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ABSTRACT: Substantial advances have been made in the adjuvant management of patients with resectable rectal cancer. Increasing interest in patient quality of life has promoted the use of radiation therapy to enhance sphincter-preserving surgical approaches as an alternative to the standard abdominoperineal resection. Because of the suggestion of enhanced sphincter preservation with preoperative therapy and the potential advantage of decreased acute morbidity, randomized trials comparing preoperative and postoperative adjuvant combined modality therapy are ongoing. Recent progress in adjuvant postoperative treatment regimens relates to the integration of systemic therapy to radiation, and redefining the techniques for both modalities. The incorporation of improved radiation planning may reduce treatment-related bowel toxicity. The integration of novel chemotherapeutic agents in the adjuvant therapy of rectal cancer remains an active area of investigation.
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