Stage IV ovarian clear cell adenocarcinoma treated effectively by chemotherapy with etoposide and cisplatin (EP)

We report a case of stage IV ovarian clear cell adenocarcinoma (OCCA) in a 72-year-old woman who was treated postoperatively with etoposide combined with cisplatin (EP). The patient exhibited bulky intrapelvic and para-aortic lymph nodes with metastases to the cervical lymph nodes. The primary lesion was resected and, postoperatively, she received one course of combination chemotherapy consisting of cyclophosphamide, 500 mg/m²; doxorubicin, 50 mg/m²; and cisplatin, 70mg/m² (CAP), followed by six courses of combination chemotherapy consisting of etoposide, 80mg/m² days 1 through 5 and cisplatin, 70 mg/m² on day 5 every 4 weeks. After five courses of EP, the lymph node metastases had virtually disappeared. The patient is now disease-free 21 months after the initial surgery. These findings suggest that EP may be useful in treating OCCA.     

In vitro and in vivo interaction between cisplatin and topotecan in ovarian carcinoma systems

Topotecan, a camptothecin analogue, is a␣specific inhibitor of topoisomerase I approved for use in the treatment of patients with refractory ovarian carcinoma. The drug's mechanism of action suggests a potential efficacy of drug combinations incorporating DNA-damaging agents. In an attempt better to define a␣rational basis for drug combination we examined the effect of topotecan on the cytotoxicity and antitumor activity of cisplatin in an ovarian carcinoma system growing in vitro and in vivo as a tumor xenograft. The in vitro cell system included a cisplatin-sensitive cell line, IGROV-1, and a cisplatin-resistant subline, IGROV-1/Pt0.5, which is characterized by p53 mutation and loss of normal function of the wild-type gene of the parental cell line. This cell system was chosen since the cell sensitivity to DNA-damaging agents appears to be dependent on p53 gene status. Cytotoxicity was assessed by the growth inhibition assay using different schedules: (a) a 1-h period of cisplatin exposure followed by a 24-h topotecan treatment and (b) a 1-h period of simultaneous exposure to cisplatin and topotecan. In the case of the sequential schedule, an additive interaction was observed in IGROV-1 and IGROV-1/Pt0.5 cells. When the simultaneous schedule was used, a synergistic interaction, more evident for the cisplatin-sensitive cells, was found. On the basis of these observations at a cellular level, the effect of concomitant administration of the two drugs (i.e., the most favorable schedule) was studied in the IGROV-1 tumor xenograft, which is moderately responsive to cisplatin and topotecan. Suboptimal doses of each drug (with a low dose of topotecan, 5.1 mg/kg) achieved an antitumor effect comparable with or superior to that of the optimal dose of a single treatment (tumor weight inhibition, 60%), thus indicating a␣pharmacological advantage of the combination over the single treatment. However, an increase in the topotecan dose (7.1 mg/kg) was associated with an evident increase in the toxicity of the combination, thereby suggesting that the drug interaction was not tumor-specific. Although the molecular basis of the drug interaction is not clear, it is likely that inhibition of topoisomerase I affects the ability of cells to repair cisplatin adducts. Such findings may have pharmacological implications since they suggest the potential clinical interest of topoisomerase I inhibitors in combination with cisplatin. Received: 14 June 1997 / Accepted: 18 September 1997     

LOSS OF HETEROZYGOSITY ON CHROMOSOME 17p13.3 IN OVARIAN CANCER AND CERVICAL CANCER

ＣａｒｃｉｎｏｇｅｎｅｓｉｓｃｏｎｓｉｓｔｓｏｆｍｕｌｔｉｐｌｅｑｕａｌｉｔａｔｉｖｅｌｙｄｉｆｆｅｒｅｎｔｓｔｅｐｓｉｎｗｈｉｃｈａｃｃｕｍｍｕｌａｔｉｏｎｏｆＤＮＡａｌｔｅｒａｔｉｏｎｏｃｕｒｓａｎｄｃｒｉｔｉｃａｌｅｖｅｎｔｓ，ｉｎｖｏｌｖｉ...     

卵巢恶性生殖细胞肿瘤的治疗(附233例临床分析)

目的探讨改进卵巢恶性生殖细胞肿瘤的治疗方法。方法回顾分析我院收治的２３３例卵巢恶性生殖细胞肿瘤。Ｉ期９４例，Ｉ～ＩＶ期４３例，复发转移９６例。单附件或全宫双附件加大网膜阑尾切除分别为７８例和１５１例，活检４例。单纯手术１７例，手术加放疗和化疗６５例，手术加化疗１５１例。结果全组存活１２７例，Ｉ期存活７８例，Ｉ～ＩＶ期１７例，复发转移３２例。总５年生存率为５５．６％。无性细胞肿瘤预后最好，５年生存率为８４．２％，非无性生殖细胞肿瘤为４４．６％，其中ＰＶＢ、ＢＥＰ方案化疗的生存率较高，为６６．０％和７３．３％。结论卵巢恶性生殖细胞肿瘤对化疗敏感，ＰＶＢ、ＢＥＰ是最有效的化疗方案。早期患者可治愈并保留生育功能；晚期先化疗，肿瘤局限后手术，术后巩固化疗可提高存活率     

肿瘤坏死因子、更生霉素和干扰素-γ联合应用对人卵巢癌裸鼠模型的协同作用

目的：研究联合应用肿瘤坏死因子（TNF）、干扰素－γ（IFN－γ）和更生霉素（KSM）对人卵巢癌裸鼠模型的协同作用。方法：将荷瘤裸鼠随机分成4组，分别用生理盐水、KSM、TNF＋IFN－γ、KSM＋TNF＋IFN－γ处理，观察肿瘤生长情况。结果：各组肿瘤相对体积比较，KSM组和KSM＋TNF＋IFN－γ组与对照组比较，差异有显著性（P＜0．05和P＜0．01）；TNF＋IFN－γ组与对照组比较，差异无显著性（P＞0．05），而KSM＋TNF＋IFN－γ组与KSM组比较，差异有显著性（P＜0．05）。结论：KSM与TNF、IFN－γ联合应用有协同抗卵巢癌细胞系3AO的作用，为临床应用提供了理论依据。     

Tissue Inhibitor of Metalloproteinase-1 Concentrations are Attenuated in Peritoneal Fluid and Sera of Women with Endometriosis and Restored in Sera by Gonadotropin-Releasing Hormone Agonist Therapy

Objective: To establish tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations in peritoneal fluid (PF) and sera of women with endometriosis and compare them to disease-free controls.

Design: Prospective randomized study.

Setting: Academic medical center.

Patient(s): Women with laparoscopically documented endometriosis and disease-free women of reproductive age.

Intervention(s): Peritoneal fluid and sera were collected, and some women received gonadotropin-releasing hormone agonist (GnRH-a) therapy for endometriosis.

Main Outcome Measure(s): Peritoneal fluid and sera TIMP-1 concentrations were measured with a specific RIA.

Result(s): The TIMP-1 concentrations were significantly lower in PF and sera of women with endometriosis compared with disease-free women. The GnRH-a therapy restored serum TIMP-1 concentrations.

Conclusion(s): Aberrant expression and localization of TIMP-1 may derange the proteolytic milieu of the peritoneal cavity and contribute to the etiology and underlying physiologic sequelae associated with endometriosis. Measurement of TIMP-1 in serum may aid in diagnosing endometriosis and assist with monitoring treatment efficacy in women with this disease.     

卵巢上皮性癌BRCA1和p53基因表达的临床意义及相互关系研究

目的：探讨BRCA1、p53基因蛋白在卵巢上皮性癌中的表达情况及相互关系。方法：应用S-P免疫组织化学法检测50例卵巢上皮性癌组织中BRCA1和p53蛋白的表达。采用Kaplan—Meier法分析两种蛋白表达情况与患者预后的关系。结果：1)BRCA1蛋白在卵巢癌组织中的阳性表达率仅为30％，明显低于正常卵巢组织(100％)和良性肿瘤组织(90％)(P＜0．01)；BRCA1在低分化癌、有淋巴结转移的卵巢癌组织中表达减少甚至缺失。2)p53蛋白在卵巢癌组织中的表达率为64％，而在正常卵巢及良性肿瘤组织中无表达；其表达仅与病理学分级有关。3)两种基因蛋白表达比较呈显著负相关(P＜0．01)。4)患者生存随访表明，有BRCA1表达的患者平均生存期长于无表达者；而p53对生存时间无影响。结论：BRCA1基因在转录后水平的下调对卵巢上皮性癌的发生发展有重要的作用．同时BRCA1基因与p53基因协同促进肿瘤的演进恶化。     

Adult ovary transfer counteracts the callosal enlargement resulting from prepubertal ovariectomy

The rat corpus callosum (CC) is larger in males than females, and is sensitive to hormone manipulations during development. Previous research found that, in rats, CC sensitivity to testosterone ended by postnatal day 8 (P8). In contrast, more recent findings demonstrated that CC responsivity to ovarian hormones continued at least through P70. The current experiment extends these findings by showing that the female callosum is still sensitive to ovarian hormones as late as P130, well into adulthood.     

会阴腹壁子宫内膜异位症的临床分析

目的:探讨会阴、腹壁子宫内膜异位症(内异症)的诊断和处理.方法:对该院1991～2002年收治的14例会阴、腹壁内异症病例进行回顾性分析.结果:根据临床表现及病理检查,14例均诊断正确.4例会阴内异症均有会阴撕裂或侧切史,10例腹壁切口内异症均有剖宫产史.发病潜伏期,30岁以前多在1年以内,30岁以上多在1年以上.会阴内异症完整切除3例,腹壁内异症完整切除10例,随访1～5年无复发.结论:根据典型的病史和体检,可以对会阴、腹壁内异症做出正确诊断;手术切除为主要治疗方法.