The clinical research about early diagnosis of small cell lung cancer through mad2 de-tection / 中国肿瘤临床

Objective:To explore combined detection of mad2 with anti-nuclear mitotic spindle apparatus antibody(MSA)and anti-centromere antibody(ACA)and their clinical value for the diagnosis of small cell lung cancer(SCLC).Methods:One hundred and twen-ty SCLC patients,110 non-small cell lung cancer(NSCLC)patients,and 115 pulmonary nodule(PN)patients were enrolled in this study. The expression of mad2 was analyzed by qt-PCR.MSA and ACA were detected by indirect immunofluorescence(IIF)staining.Results:mad2 was overexpressed in SCLC and NSCLC samples(P<0.05).There were significant differences between the results obtained for SCLC and NSCLC samples by qt-PCR(P<0.05).AUC in ROC curve for mad2 expression was 0.799 with an intermediate diagnostic value. In the correlative analysis,the odds ratio of MSA and ACA was 6.94 and 5.60,respectively.In the correlation analysis,Kappa value of mad2 with MSA was 0.49,and Kappa value of mad2 with ACA was 0.42.In the parallel analysis,the sensitivity and specificity was 83.31% and 79.34%,respectively,while the Youden Index was 0.62.Moreover,in the serial analysis,the sensitivity and specificity was 65.32% and 93.35%,respectively,and the Youden Index was 0.59.Conclusions:In comparison with the NSCLC and PN samples,mad2 was overexpressed in SCLC samples.Therefore,mad2 ought to play a critical role in the pathology of SCLC.The combined expression of mad2 with MSA and ACA may contribute to enhancing the sensitivity and specificity of detection;this expression may allow early diag-nosis and clinical diagnosis of SLCC and may be a promising treatment for SCLC.

Research progress of mitotic arrest deficient gene abnormalities in tumor / 实用肿瘤学杂志

The spindle assembly checkpoint ( SAC) is an important monitoring mechanism to monitor the connection between centromeres and microtubules and to ensure proper chromosome separation in human .Mitotic arrest defective protein(Mad)family,as an important part of SAC,plays a crucial role in the process of mitosis. Mutations or altered expressions of Mad may lead to abnormal separations of chromosomes and play a partial role in tumorigenesis ,poor prognosis and chemotherapy drug resistance .

Pseudolaric acid B induced apoptosis and mitotic arrest circumventing Fas receptor pathway in MCF-7 cells / 中国药理学通报

Aim To study the mechanisms of Pseudolaric acid B(PAB)-induced MCF-7 cell apoptosis and mitotic arrest.Methods MTT assay was performed to assess the cell growth inhibition,contrast phase microscope was used to observe cellular morphologic alteration,and the change of DNA was detected by fluorescent microscopy.The distribution of cell cycle was determined by flow cytometric analysis of propidium iodide staining,and the protein expression was examined by Western blot analysis.Results PAB inhibited MCF-7 cell growth in a dose-and time-dependent manner.4 ?mol?L-1 PAB induced DNA condensation at 24 h.PAB cleaved PARP in a time-dependent manner.At 36 h,PAB up-regulated the expression of cdc 2 and nuclear cyclin B1.Fas antagonistic antibody UB2 had no effect on apoptosis,but agonistic antibody CH11 enhanced the apoptosis induced by PAB.UB2 exerted no effect on cell cycle arrest,and CH11 had the same action as UB2 except for reducing the mitotic arrest through enhancing apoptotic subdiploid peak.Conclusion PAB inhibited MCF-7 cell growth through mitotic arrest and apoptosis.Apoptosis and mitotic arrest were independent of Fas pathway.

Effect of the Paclitaxel and Radiation on the Large Bowel Mucosa of the Rat / 대한방사선종양학회지

PURPOSE: Paclitaxel is a chemotherapeutic agent with a potent microtubule stabilizing activity that arrests mitosis at G2-M phase of cell cycle which is the most radiosensitive period. Therefore paclitaxel is considered as a cell cycle-specific radiosensitizer. This study investigates the effect of paclitaxel on the radiation response of the normal large bowel mucosa of the rat. MATERIALS AND METHODS: The rats were divided into the three groups i.e., single intraperitoneal infusion of paclitaxel (10 mg/kg), a single fraction of irradiation (8 Gy, x-ray) to the whole abdomen, and a combination of irradiation (8 Gy, x-ray) given 24 hours after paclitaxel infusion. The histological changes as well as kinetics of mitotic arrest and apoptosis were evaluated on the large bowel mucosa at 6 hours, 1 day, 3 days and 5 days after treatment with paclitaxel alone, radiation alone and combination of paclitaxel and radiation. RESULTS: The incidence of the mitotic arrest was not increased by paclitaxel infusion. The apoptosis appeared in 24 hours after paclitaxel infusion, and the histopathologic changes such as vesiculation, atypia and reduction of the goblet cell of the mucosa of the large bowel were demonstrated during the period from 6 hours to 3 days after, and returned to normal in 5 days after paclitaxel infusion. In irradiated group, the apoptosis was increased in 6 and 24 hours after irradiation, and the histopathologic changes of the mucosa were appeared in 24 hours and markedly increased in 3 days and returned to normal in 5 days. In combined group of irradiation and paclitaxel infusion, the apoptosis was appeared in 3 days and the histopathologic changes appeared during the period from 6 hours to 3 days after infusion. On the basis of the incidence of apoptosis and the degree of the histopathologic changes of the large bowel mucosa, there seemed to be additive effect by paclitaxel on radiation rather than sensitizing effect. CONCLUSION: The histopathological changes of large bowel mucosa in combined group compared to radiation alone group suggested an additive effect of paclitaxel on radiation response in the large bowel of rat.

Effect of the Paclitaxel and Radiation on the Gastric Mucosa of the Rat / 대한방사선종양학회지

PURPOSE: Paclitaxel is a chemotherapeutic agent with potent microtubule stabilizing activity that arrests cells in G2-M phase. Because G2 and M are the most radiosensitive phase of the cell cycle, paclitaxel has potential role as a cell-cycle specific radiosensitizer. This study was performed to see the effects of paclitaxel on the radiation-induced damage of gastric mucosa of the rat. MATERIALS AND METHODS: The rats were divided into the three groups i.e., paclitaxel alone group, radiation alone group and, a combination of paclitaxel and radiation in combined group. A single intraperitoneal infusion of paclitaxel (10 mg/kg) was done in paclitaxel alone group. In radiation alone group, a single fraction of irradiation (8 Gy, x-ray) to the whole abdomen and, a combination of a single fraction of irradiation (8 Gy, x-ray) to the whole abdomen was given 24 hrs after paclitaxel infusion in combined group of paclitaxel and radiation. The incidence of mitosis and apoptosis as well as histologic changes of the gastric mucosa were evaluated at 6 hrs, 24 hrs, 3 days and 5 days after treatment. RESULTS: The number of the mitosis was not increased by paclitaxel infusion. The incidence of the apoptosis was similar from 6 hrs to 3 days after paclitaxel infusion and was decreased at 5 days. Paclitaxel induced minimal glandular dilatation and cellular atypia of gastric mucosa at 24 hrs and 3 days. In irradiation group, the incidence of apoptosis was 6.0% in 6 hrs and 1.25% in 24 hrs after irradiation and minimal glandular dilatation and cellular atypia were noted throughout the experimental period. The incidence of apoptosis in the combined group of paclitaxel and irradiation (4.5%) was significantly higher than irradiation alone group (1.25%) at 3 days (p<0.05). CONCLUSION: Paclitaxel had no effect on mitotic arrest in gastric mucosa of the rat. Increased number of apoptosis in combined paclitaxel and irradiation group suggested the additive effects of paclitaxel on irradiation.

Effects of the Paciltaxel and Radiation in the Mucosa of the Small Bowel of Rat / 대한치료방사선과학회지

PURPOSE: Paclitaxel is a chemotherapeutic agent with potent microtublue stablelizing activity that arrests cell cycle in G2-M. Because G2-M is the most radiosensitive phase of the cell cycle. Paclitaxel has potential as a cell cycle- specic radio sensitizer. This study was design to investigate the ablity of paclitaxel to increase the radiotoxicity in normal small bowl mucosa of the rat. METHODS AND MATERIALS: A single intraperitoneal infusion of paciltaxel(10mg/kg). And a single irradiation(8 Gy, x-ray) to the whole abdomen and combination of radiation(8 Gy, x-ray) 24 hours after paclitaxel infusion in the rats were done. The changes of jejunal mucosa. And kinetics of mitotic arrest and apoptosis in the jejunal crypt were defined at 6 hours – 5 days after each treatment histologically. RESULTS: Paclitaxel blocked jejunal crypt cell in mitosis and induced minmal apoptosis. Mitotic arrest by paclitaxel was peaked at 6 hours after infusion and returned to normal by 24 hours. Radiation induced apoptosis and peaked at 6 hours and returned to normal by 24 hours. Combination of paclitaxel and radiation blocked crypt cell in mitosis at 3 days and induced apoptosis slightly at 6 hours and 24 hours and returned to normal by 3 days. The incidence of apopsis in combined group at 6hours was slightly higher than normal control buy significantly lower than radiation alone group. The major changes of jejunal mucosa were nuclear vesicle and atypia which were appered at 6 hours – 3 days and returned to normal by 5 days. The degree of mucosal changes are no different in 3groups except for absence of inflmatory reaction in radiation group. CONCLUSION: Mitotic arrest by paclitaxel was peaked at 6hours and returned to normal by 24 hours and paclitaxel induced minimal apoptosis. Radiation induced apoptosis. Peaked at 6 hours and returned to normal by 24 hours. Radiation induced apoptosis was less in combined group which suggested that paclitaxel have a radioprotective effech when radiation was given 24 hours after paclitaxel infusion.