卵巢癌干细胞及卵巢癌治疗

卵巢癌干细胞在卵巢癌发生、化疗耐药和复发过程中起重要作用。传统治疗对减小肿瘤体积有效,但是治疗后留下的卵巢癌干细胞成为卵巢癌复发和难治的根源。兼顾卵巢癌干细胞和普通肿瘤细胞的治疗策略才能真正有效治疗卵巢癌。对卵巢癌干细胞生物学特性和调控机制的了解是研究卵巢癌干细胞靶向治疗的基础。     

The integration of docetaxel into first-line chemotherapy for ovarian cancer

Abstract. Kaye SB. The integration of docetaxel into first-line chemotherapy for ovarian cancer.
Docetaxel is being explored as an alternative to paclitaxel in the treatment of ovarian cancer for several reasons: a) evidence of superiority in preclinical models; b) at least comparable activity in platinum-refractory patients (28% response rate in four pooled Phase II trials), together with activity (23% response rate) in paclitaxel-refractory patients; c) indirect evidence of superiority in breast cancer; d) easier administration, ie, 1 h q3 week schedule vs. 3 or 24 h infusions; and e) potentially superior toxicity profile, particularly regarding neurotoxicity.
The Scottish Gynaecological Cancer Trials Group (SGCTG) has performed successive first-line feasibility trials of docetaxel in combination with cisplatin (100 patients) and carboplatin (141 patients). For docetaxel/carboplatin, a regimen of 75 mg/m² and AUC 5 proved optimal. Over 90% of patients completed six cycles, q3 weekly, and toxicity was very acceptable; a low level of neurotoxicity (5%) was particularly noteworthy, since levels of over 30% are regularly reported for paclitaxel-carboplatin. Activity comparable to paclitaxel-carboplatin (median progression free survival of 16 months) therefore justified a randomized comparison between the two regimens (with paclitaxel 175 mg/m² in 3 h and carboplatin AUC 5). This has now been completed, with 1077 patients (FIGO stage IC-IV disease) randomized, from 83 centers in 10 countries. Accrual was accomplished in 17 months (October 1998 to May 2000). A toxicity analysis has been completed, since the last patient finished treatment in October 2000. Treatment was delivered as prescribed (6 cycles) in a similar number of patients (79–84%). Significant differences in toxicity were seen, and this analysis together with response data is scheduled for presentation at the May 2001 ASCO meeting.     

Identification of genes associated with ovarian cancer metastasis using microarray expression analysis

Although the transition from early- to advanced-stage ovarian cancer is a critical determinant of survival, little is known about the molecular underpinnings of ovarian metastasis. We hypothesize that microarray analysis of global gene expression patterns in primary ovarian cancer and metastatic omental implants can identify genes that underlie the metastatic process in epithelial ovarian cancer. We utilized Affymetrix U95Av2 microarrays to characterize the molecular alterations that underlie omental metastasis from 47 epithelial ovarian cancer samples collected from multiple sites in 20 patients undergoing primary surgical cytoreduction for advanced-stage (IIIC/IV) serous ovarian cancer. Fifty-six genes demonstrated differential expression between ovarian and omental samples (P < 0.01), and twenty of these 56 differentially expressed genes have previously been implicated in metastasis, cell motility, or cytoskeletal function. Ten of the 56 genes are involved in p53 gene pathways. A Bayesian statistical tree analysis was used to identify a 27-gene expression pattern that could accurately predict the site of tumor (ovary versus omentum). This predictive model was evaluated using an external data set. Nine of the 27 predictive genes have previously been shown to be involved in oncogenesis and/or metastasis, and 10/27 genes have been implicated in p53 pathways. Microarray findings were validated by real-time quantitative PCR. We conclude that gene expression patterns that distinguish omental metastasis from primary epithelial ovarian cancer can be identified and that many of the genes have functions that are biologically consistent with a role in oncogenesis, metastasis, and p53 gene networks.     

Identification of risk factors for requiring transfusion during front-line chemotherapy for ovarian cancer

OBJECTIVE: Anemia requiring red blood cell (RBC) transfusion is common in ovarian cancer (OC) patients receiving post-debulking surgery chemotherapy. Erythropoietin use has been shown to decrease transfusion requirements in patients receiving chemotherapy. We sought to identify pretreatment risk factors that could identify patients at increased risk for requiring RBC transfusion during first-line treatment for ovarian cancer. METHODS: One hundred seventy-five consecutive patients who received chemotherapy with either carboplatin-paclitaxel or cisplatin-paclitaxel following debulking surgery for epithelial OC from 1993 to 1996 were identified. No patient received erythropoietin. Patient characteristics recorded included: age, stage, prechemotherapy hemoglobin, nadir hemoglobin, number of cycles and doses of chemotherapy received. The outcome was requiring RBC transfusion. Independent predictors of requiring RBC transfusion were identified using multivariate analyses. RESULTS: Median age of the cohort was 62 years (range, 28-86). Seventy-one and four-tenths percent had FIGO stage III/IV disease. Median prechemotherapy hemoglobin was 11 g/dL (range, 7.1-15.4); median nadir hemoglobin was 9.3 g/dL (range, 6.6-11.1). One hundred nineteen (66%) patients received cisplatin-paclitaxel, and 61 (34%) received carboplatin-paclitaxel. Of 175 patients, 31 (18%, 95% CI = 12-23%) required RBC transfusion. Independent risk factors for RBC transfusion were prechemotherapy hemoglobin <10 g/dL (P < 0.01, odds ratio = 3.78, 95% CI = 1.52-9.44) and carboplatin-paclitaxel versus cisplatin-paclitaxel treatment (P = 0.01, odds ratio = 3.14, 95% CI = 1.27-7.76). Of 175 patients, 40 (22.8%) had a prechemotherapy hemoglobin <10 g/dL. Fifty percent of patients with prechemotherapy hemoglobin <10 g/dL who received carboplatin-paclitaxel required RBC transfusion, compared with 7.7% of patients with hemoglobin >10 g/dL who received cisplatin-paclitaxel. CONCLUSION: Ovarian cancer patients frequently require RBC transfusion during postdebulking platinum-paclitaxel chemotherapy. Patients with prechemotherapy hemoglobin <10 g/dL and those receiving carboplatin-paclitaxel are at increased risk of requiring RBC transfusion. Early initiation of erythropoietin use in such patients may reduce transfusion needs.     

Screening for familial ovarian cancer—management and outcome of women with moderate to high risk of developing ovarian cancer

Abstract.   Rieck GC, Lim K, Rogers MT, France E, Gray JR, Amso N, Evans AS, Howells RH, & Fiander AN. Screening for familial ovarian cancer—management and outcome of women with moderate to high risk of developing ovarian cancer. Int J Gynecol Cancer 2006; 16(Suppl. 1): 86–91.
Five percent to ten percent of ovarian cancers are hereditary. Individual genetic risk of developing ovarian malignancy is discussed in women. Currently, prophylactic surgery is advised to women with a moderate to high risk of developing ovarian cancer. Workload and outcome of the multidisciplinary familial ovarian screening clinic in South Wales were assessed. This was an observational study of 145 women registered with the Familial Ovarian Screening Clinic between January 1998 and December 2003. The data were retrieved from the medical notes. Yearly follow-ups were investigated with a transvaginal scan and CA125 level. Post-surgery women were followed up with yearly CA125 estimations: 46.9% fell into moderate-risk and 50.3% into high-risk category. The median age was 42 (SD 10.4), 71.7% were pre menopausal, and 10.3% had a personal history of breast cancer and 1.4% colon cancer. Whereas 36.5% opted for surgery, the remaining women (but two) opted for annual follow-up. Histology of the women who had surgery showed three cases of malignancies (fallopian tube carcinoma, atypical ovarian epithelial cells, and metastatic breast cancer). Seven women developed breast cancer during the observation period. The follow-up period is too short to come to a final conclusion as to the benefits of yearly screening in this group of women. In our series, a significant number of patients developed malignancies, despite prophylactic surgery.     

Characterization of differentially expressed genes in ovarian cancer by cDNA microarrays

The molecular events leading to the development and progression of ovarian carcinoma are not completely understood. We performed a large-scale survey for the identification of differentially expressed genes between ovarian carcinoma and normal ovarian tissue by using cDNA microarray analysis. We utilized 512 member human novel putative oncogene and tumor suppressor gene cDNA microarrays to study the differences in gene expression between ovarian carcinoma and normal ovarian tissues. Some differentially expressed genes have been further confirmed by immunohistochemical analysis. A total of 39 differentially expressed genes were identified, of which 16 and 23 were specifically expressed in ovarian cancer and normal ovarian tissue, respectively. The comparison of average signal of differentially expressed genes exhibited at least a twofold difference in expression. The differentially expressed genes may be related to the carcinogenesis and progression of the malignant growth. The use of cDNA microarrays allows simultaneous monitor of the expression of many genes, thereby it speeds up the identification of differentially expressed genes. It is essential for further exploration of the mechanisms of the disease.     

乳腺癌术后再发卵巢癌的预防与诊治

乳腺癌是女性最常见的恶性肿瘤,如有未婚未育史、家族遗传史、三阴性乳腺癌、术后口服选择性雌激素拮抗剂及BRCA1/BRCA2基因突变者,应特别警惕乳腺癌术后再发卵巢癌的可能。通过基因检测、临床筛查及降风险输卵管卵巢切除术(risk-reducing salpingo-oophorectomy,RRSO)的方法,可以有效预防乳腺癌术后再发卵巢癌。而对于乳腺癌术后已经发现卵巢癌者,应尽早接受治疗。乳腺癌与卵巢癌的发病间隔≥5年的患者所占比例最高,提示获得长期生存的乳腺癌患者也要警惕卵巢癌的发生。     

Principles and practice of intraperitoneal chemotherapy for ovarian cancer

Intraperitoneal (IP) chemotherapy has been studied for years to improve the survival of patients with ovarian cancer. Recently, the result of Gynecologic Oncology Group 172 trial comparing IP versus intravenous administration of cisplatin-based chemotherapy was published, demonstrating the improvement of survival benefit in favor of the IP arm. This trial is the third trial that showed a survival benefit on IP chemotherapy. The National Cancer Institute (NCI) and Gynecologic Oncology Group have done a meta-analysis on the results of these three US trials and other phase III trials of IP versus intravenous chemotherapy, and significant improvement of survival was shown with IP therapy. Based on this meta-analysis, NCI has released a clinical announcement encouraging the gynecological oncology community to consider IP chemotherapy as the standard treatment for optimally debulked advanced ovarian cancer patients. However, there still are controversial issues regarding the use of IP chemotherapy. It is important to understand how IP chemotherapy works to solve those issues in the future. In this review article, we discuss the principles and clinical aspects of IP chemotherapy and also discuss the current problems and future perspectives in IP chemotherapy.     

Survival in ovarian cancer in Wales: prior to introduction of all Wales guidelines

The objective of the study was to review referral practice, overall management, and survival in women with suspected ovarian cancer in Wales. This study was done prior to introduction of cancer management guidelines in the region. A confidential study questionnaire was sent to 20 participating hospitals. Data on 287 consecutive women with suspected ovarian cancer were collected, of which 250 women underwent primary laparotomy. Information was obtained on referral pattern, preoperative investigations, place of primary surgery, specialty of the primary surgeon, surgical parameters recorded at the time of operation, a final overall stage, adjuvant treatment, and survival outcome. There was a wide variation in referral practice and management of ovarian cancer in Wales. Stage of the disease, attempt at optimal debulking, residual disease, management by a cancer centre multidisciplinary team, and platinum-based chemotherapy were associated with improved overall survival and progression-free survival. More women were alive if managed in the cancer centre at 1 and 3 year after diagnosis (P = 0.022). This study has highlighted the acute issue of the standards of clinical care in the area of ovarian cancer management and will emphasize the implementation of better care pathways for ovarian cancers.     

Dermatomyositis following the diagnosis of ovarian cancer

We present a case history of a woman who developed dermatomyositis following the diagnosis of stage IV ovarian cancer. Dermatomyositis is a rare paraneoplastic syndrome that usually precedes the diagnosis of ovarian cancer by several months or years. Ours is the fifth reported case of dermatomyositis after an established diagnosis of ovarian cancer in the literature.     

Early ovarian cancer: Is there a role for systematic pelvic and para-aortic lymphadenectomy?

Baiocchi G, Raspagliesi F, Grosso G, Fontanelli R, Cobellis L, di Re E, di Re F. Early ovarian cancer: Is there a role for systematic pelvis and para-aortic lymphadenectomy? Int J Gynecol Cancer 1998; 8 : 103–108.
In order to focus on the incidence and the clinical significance of lymphatic spread in patients with cancer apparently confined to the ovaries, we present our 20 year experience in a large series of patients with early ovarian cancer who had systematic pelvic and para-aortic lymphadenectomy. A retrospective study of 280 consecutive patients is presented. Systematic pelvic and para-aortic lymphadenectomy was performed in 205 cases (73.2%). Selective sampling and node biopsy were performed in 30 (10.7%) and 7 (2.5%), respectively. Node metastases were found in 32/242 patients (13.2%). The incidence of metastatic nodes was significantly higher in patients with serous adenocarcinomas and/or poorly-differentiated tumors. When few nodes were involved (1–3) lymphatic spread was most ipsilateral to the tumor. Even though the retrospective nature of the study has to be considered, univariate analysis revealed statistically significant differences in 5-year survival based on FIGO stage, histology, grade of differentiation, and node status. By contrast, using multivariate analysis, none of these risk factors was an independent variable for predicting long-term survival. However, node status closely approached the statistically significant level ( P = 0.06). Only prospective and randomized studies can clarify the role of lymphadenectomy in early ovarian cancer. However, while awaiting these results, this surgical procedure should be a part of a research protocol.     

卵巢癌过度化疗因素分析

化疗是卵巢癌主要的辅助治疗手段。然而,卵巢癌的化疗在临床上仍存在治疗不当,特别是过度治疗的问题。文章旨在对卵巢癌治疗中引起过度化疗的原因作一分析探讨。     

卵巢癌术后化疗卵巢功能保护相关问题

化疗期间的卵巢功能保护是卵巢癌患者保留生育功能手术后急需解决的问题。文章对促性腺激素释放激素激动剂、细胞保护剂、中医药等方面的保护措施的研究进行总结分析。     

上皮性卵巢癌的一线化疗

化疗是上皮性卵巢癌主要的辅助治疗手段,铂类为基础的联合化疗是上皮性卵巢癌的一线化疗方案,但在药物组成、剂量强度、给药方式、腹腔化疗、新辅助化疗及维持和巩固治疗方面仍值得进一步探索。     

Testing for ovarian cancer

Ovarian cancer is responsible for more deaths per annum than cervical and endometrial cancer combined. Patients are often diagnosed at a late stage because of the non-specific symptoms of this disease. It can be difficult to differentiate between benign and malignant ovarian pathology, and a malignancy risk index has been developed to guide clinicians. The accuracy of CA125 and ultrasound scans as screening tests is being assessed in randomised controlled trials and proteomic technology shows promise for the early detection of cancers. At present, without accurate screening and early diagnostic techniques, high-risk patients often chose to have prophylactic surgery.