咪唑衍生物孵化法与年养二次天蚕

采用人为越冬法和利用咪唑衍生物处理的人工孵化法,使天蚕在一年中孵化二次。但在寒冷地区可利用的栎属落叶饲料树生长期短,这就必须要有缩短卵期经过的技术。为此,探讨了采用比人为越冬法卵期经过更短的咪唑类衍生物孵化法、稚蚕期人工饲料育、壮蚕期室外放养的年养二次天蚕的技术。

PHASE Ⅱ STUDY OF GEMCITABINE COMBINED WITH PLATINUM CHEMOTHERAPY FOR RECURRENT EPITHELIAL OVARIAN CANCER

Objective To evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer. Methods Phase Ⅱ study of gemcitabine combined with platinum chemotherapy was carried out in 22 patients with recurrent epithelial ovarian cancer. Median age of patients was 50. 5 years old. Seven patients were platinum-sensitive and 15 patients were platinum-resistant or -refractory. All patients received gemcitabine combined with carboplatin or oxa/iplatin chemotherapy. Patients＇ response rate （RR） and toxicity of gemcitabine combined with platinum chemotherapy were evaluated. Results A total of 98 gemcitabine-based chemotherapy cycles were performed. Total RR was 36. 4%, RR of platinum-sensitive patients was 4/7 and platinum-resistant and -refractory patients was 4/15. The estimated median survival time was 10.0 months （95% CI. 7.0-13.0） after initiation of gemcitabine combined with platinum chemotherapy. There was no significant difference in survival time between platinum-resistant/refractory group and platinum-sensitive group （P = 0. 061 ）. Side effects of gemcitabine combined with platinum chemotherapy were observed in 81.8% of patients. Grade Ⅱ/Ⅲ anemia （54. 5% ） and grade Ⅲ/Ⅳ neutropenia （54. 5% ） were most common toxicities. Ten （45.5%） patients had to delay their chemotherapy cycles or reduce the dose of chemotherapeutic drugs because of the severe side effects. Fourteen （63.6%） patients received granulocyte colony-stimulating factor to relieve neutropenia, and 8 （ 36. 4% ） patients received component blood transfusion to treat anemia or thrombocytopenia. There was no treatment-associated death. Conclusion Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.

Application value of ATP based bioluminescence tumor chemo-sensitivity assay in the chemotherapy for ascites caused by recurrent ovarian cancer

Objective: To investigate the clinical value and application of ATP based bioluminescence tumor chemo-sensitivity assay (ATP-TCA) in the chemotherapy for ascites caused by recurrent ovarian cancer. Methods: More than 10 kinds of chemotherapeutic drugs or combinations were applied and 35 ascites specimens from recurrent ovarian cancer were analyzed by ATP-TCA. Sensitivity of chemotherapeutic drugs was assessed. After 2-4 chemotherapeutic cycles, clinical outcomes were analyzed, which were compared with those of 40 cases by empirical regimens. Results: 32 of 35 specimens were evaluated with an overall evaluation rate of 91%. The assay results suggested that chemo-naive patients responded to chemotherapeutic drugs with individualized profiles. The sensitivity rates of GEM, EPI, OXA, DDP, CBP, ADM, VP-16, CTX, NVB, 5-FU, PTX and TXT were 40%, 30%, 33%, 29%, 33%, 38%, 25%, 33%, 38%, 33%, 25% and 20%, respectively. While the sensitivity rates of combinations GEM + EPI, GEM + CBP, GEM + DDP, NVB + DDP, CTX + ADM + DDP, CTX + ADM, DDP + VP-16, OXA + 5-FU, VP-16 + IFO, PTX + DDP, TXT + CBP, VCR + CTX + MTX, DDP + CPT-11, OXA + CPT-11, and DTIC + CTX were 47%, 50%, 36%, 44%, 30%, 33%, 27%, 33%, 40%, 27%, 23%, 14%, 28%, 30% and 17%, respectively. In vitro results correlated well with clinical outcomes. Objective response rate (RR) in chemo-sensitivity-guided group was of significance compared with that in empirical-regimen-guided group. Conclusion: ATP-TCA is a choice for the screening of chemotherapeutic drugs against ascites caused by recurrent ovarian cancer with excellent sensitivity and reliability. ATP-TCA assay results correlate well with clinical outcomes, suggesting its clinical value in the management of difficult-to-manage therapeutic situations such as ascites in recurrent ovarian cancer.

THE RELATIONSHIP BETWEEN mdrl GENE EXPRESSION AND DRUG-RESISTANCE IN OVARIAN CARCINOMA

Objective.To investigate the relationship between mdrl gene expression and multidrug-resistance in o- varian carcinoma. Design. We established tumor-bearing mice model of ovarian carcinoma,compared the anticancer drug sensitivity of OC/mdr-cell and OC/mdr+ cell in vitro, investigated the effect of cyclosporin A on reversing the multidrug resistance both in vitro and in the tumor-bearing mice model,detected the mdrl gene expre- sion in human ovarian carcinoma specimens. Main outcome measures. Anticancer drug sensitivity of both OC/mdr-cell and OC/mdr+ cell is mea- sured by the methods of MTT assays. mdrl gene expression is detected by the methods of RT-PCR. Results. Using MTT assay,OC/mdr+ cell is 4. 1 - 15. 5 times more resistant to VP-16,VCR,DNR, and DOX than OC/mdr-cell in vitro.2 μg/ml cyclosporine A(CsA)reduced the resistance of OC/mdr+ cell to DOX,from 0. 324±0. 072μg/ml to 0. 088±0. 024μg/ml. To OC/mdr－cell,CsA did not significantly in－ crease its sensitivity to DOX．Tumor-bearing mice with positive mdrl gene expression showed non-respon- siveness to DOX chemotherapy. When combined with intraperitoneal injection of CsA, the growth rate of tumor cells decreased significantly (P<0. 01 ). Only 4 of 23(17. 39% )tumors from patients who had not received chemotherapy exhibited positive mdrl gene expreession, while 6 of 9 (66. 67%)treated patients showed positive mdrl gene expression (Fisher exact test: P<0. 05 ). After cytoreductive surgery and chemotherapy, 14 of 19 untreated patients with negative mdrl gene expression had partial or complete re- sponse, while in patients with positive mdrl gene expression, 8 of 10 showed poor prognosis(Fisher exact test: P<0. 05 ). Conclusion. The expression of mdrl gene is associated with previous chemotherapy. CsA can reverse the resistance of mdr+ cells to indr-associated drs both in vitro and in vivo’ For the patients with ovarian carcinoma., the percentage of nonresponsiveness to the chemotherapy was found to be significantly higher among patients with positive mdrl gene expression than those with negative mdrl gene expression. mdrl gene expression can be detected to predict the clinical prognosis of patients with ovarian carcinoma.

Platinum-resistant ovarian cancer: Prematurely stopped phase Ⅱ Austrian AGO chemotherapy studies

AIM： To report the results of two phase Ⅱ studies of chemotherapy in patients with platinum-resistant and platinum-refractory ovarian cancer and discuss the cur-rent status of systemic therapy in this disease.METHODS： Two subsequent Austrian Arbeitsgemein-schaft für Gynkologische Onkologie （AGO） phase Ⅱ studies have been carried out. Patients either had platinum-refractory or platinum-resistant disease, i.e., disease progression during first line platinum-based therapy or recurrence within 6 mo following the last platinum-containing chemotherapy, respectively. In the first study, 6 cycles of irinotecan at 55 mg/m2 and docetaxel 25 mg/m2 were both administered on days 1, 8 and 15 of a 4 wk cycle. In the second phase Ⅱ study, either non-pegylated （PEG） liposomal doxorubi-cin （L-DXR） 60 mg/m2 monotherapy on day 1 and PEG filgrastim on day 2 （arm A） or L-DXR at 50 mg/m2 and gemcitabine （GEM） at 650 mg/m2 on day 1 and GEM on day 8 （arm B） were administered every 4 wk. Patients in arm B received prophylactic filgrastim 5 μg/kg per day from days 3 to 6 and from days 9 to 12, respec-tively. RESULTS： Response rates in studies were 14% and 17%, respectively. The progression-free survival was less than 3 mo. Diarrhea was most prevalent in patients treated with irinotecan ＋ docetaxel, while stomatitis/mucositis occurred in a quarter of patients treated with L-DXR ＋/- GEM ＋ granulocyte colony stimulating factor, respectively. Following treatment with the latter regi-men, a total of 11 serious adverse events were record-ed among the 12 patients included. The rate of remis-sions of the regimens used in these two Austrian AGOstudies was low and their toxicity significant. Due to their low therapeutic index, neither of these regimens can be recommended in this heavily pretreated patient population with platinum-resistant ovarian cancer ex-hibiting a high tumor-associated symptom burden. CONCLUSION： The two reported phase Ⅱ studies of the Austrian AGO in platinum-resistant disease had to be terminated prematurely due to a low therapeutic index. Treatment of this disease remains a clinical di-lemma. Bevacizumab seems to be active at this late-stage disease but may be associated with significant bowel toxicity.

Dock180 expression in epithelial ovarian tumors

t Objective： The aim of our study was to investigate the expression of guanine nucleotide exchange factor Dock180 in ovarian tumor, and its significance in the initiation and progression of ovarian cancer. Methods： Immunohistochemical staining with SP method was conducted to identify the expression of Dock180 protein in epithelial ovarian tumor in 68 cases. Results： Dock180 present with higher expression in ovarian cancer, as compared with than that in low malignant tumor and benign ovarian tumor （P 〈 0,01）, In ovarian cancer, Dock180 expression was increased with the increased FIGO stage and grade. Conclusion： Dock180 overexpression may play an important role in the development and progression of ovarian cancer and it could be used as a new measurement of malignant biological behavior of ovarian cancer.