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Uterine sarcoma is a very aggressive and highly lethal disease. Even after a comprehensive staging surgery or en block cytoreduction surgery followed by multimodality therapy (often chemotherapy and/or radiation therapy), many patients relapse or present with distant metastases, and finally die of diseases. The worst outcome of uterine sarcomas is partly because of their rarity, unknown etiology, and highly divergent genetic aberration. Uterine sarcomas are often classified into four distinct subtypes, including uterine leiomyosarcoma, low-grade uterine endometrial stromal sarcoma, high-grade uterine endometrial stromal sarcoma, and undifferentiated uterine sarcoma. Currently, evidence from tumor biology found that these tumors showed alternation and/or mutation of genomes and the intracellular signal pathway. In addition, some preclinical studies showed promising results for targeting receptor tyrosine kinase signaling, phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, various kinds of growth factor pathways, Wnt/beta-catenin signaling pathway, transforming growth factor β/bone morphogenetic protein signal pathway, aurora kinase A, MDM2 proto-oncogene, histone deacetylases, sex hormone receptors, certain types of oncoproteins, and/or loss of tumor suppressor genes. The current review is attempted to summarize the recurrent advance of targeted therapy for uterine sarcomas.

High-level expression of vascular endothelial growth factor (VEGF)-C is associated with chemoresistance and adverse prognosis in acute myeloid leukemia (AML). Our previous study has found that VEGF-C induces cyclooxygenase-2 (COX-2) expression in AML cell lines and significant correlation of VEGF-C and COX-2 in bone marrow specimens. COX-2 has been reported to mediate the proliferation and drug resistance in several solid tumors. Herein, we demonstrated that the VEGF-C-induced proliferation of AML cells is effectively abolished by the depletion or inhibition of COX-2. The expression of endothelin-1 (ET-1) rapidly increased following treatment with VEGF-C. We found that ET-1 was also involved in the VEGF-C-mediated proliferation of AML cells, and that recombinant ET-1 induced COX-2 mRNA and protein expressions in AML cells. Treatment with the endothelin receptor A (ETRA) antagonist, BQ 123, or ET-1 shRNAs inhibited VEGF-C-induced COX-2 expression. Flow cytometry and immunoblotting revealed that VEGF-C induces S phase accumulation through the inhibition of p27 and the upregulation of cyclin E and cyclin-dependent kinase-2 expressions. The cell-cycle-related effects of VEGF-C were reversed by the depletion of COX-2 or ET-1. The depletion of COX-2 or ET-1 also suppressed VEGF-C-induced increases in the bcl-2/bax ratio and chemoresistance against etoposide and cytosine arabinoside in AML cells. We also demonstrated VEGF-C/ET-1/COX-2 axis-mediated chemoresistance in an AML xenograft mouse model. Our findings suggest that VEGF-C induces COX-2-mediated resistance to chemotherapy through the induction of ET-1 expression. Acting as a key regulator in the VEGF-C/COX-2 axis, ET-1 represents a potential target for ameliorating resistance to chemotherapy in AML patients.

Objective To evaluate the effectiveness and toxicity of distearoylphosphatidylcholine pegylated liposomal doxorubicin (DPLD) combined with carboplatin for the treatment of platinum-sensitive, paclitaxel-pretreated, recurrent, epithelial ovarian cancer. Methods A phase II study of carboplatin/DPLD treatment for platinum-sensitive, paclitaxel-pretreated, recurrent, epithelial ovarian cancer was initiated in July 2002. As of March 2008, a total of 32 patients were enrolled. Results Of the 32 patients, one achieved a complete response; 19 (59%) achieved a partial response. The overall objective response rate was 62% (95% confidence interval [CI], 45%–80%). The median progression-free survival and overall survival for all 32 patients was 9.1 months (95% CI, 6.4–10.4 months) and 27.9 months (95% CI, 13.9–38.6 months), respectively. Toxicity was tolerable. The most common grade 3 or 4 toxicities were anemia (n=3) and nausea/vomiting (n=3). Grade 3/4 leukopenia (n=2), grade 3/4 thrombocytopenia (n=2) and grade 4 hepatitis (n=1) occurred in five patients. Conclusion Carboplatin/DPLD appears to be an effective regimen with low toxicity for treatment of patients with platinum-sensitive, paclitaxel-pretreated, recurrent, epithelial ovarian cancer.

Objectives. To evaluate the efficacy and safety of a distearoylphosphatidylcholine pegylated liposomal doxorubicin, Lipo-Dox®, in platinum-resistant or refractory epithelial ovarian cancer. Methods. A multicenter phase II trial enrolled women with platinum-resistant or refractory epithelial ovarian carcinoma and naive to anthracycline. Eligible patients had either measurable tumor(s) or elevated serum CA 125 titer. Lipodox was initiated with a dose of 45 mg/m2 at a 4-week interval with subsequent escalation or reduction. A total of six cycles were scheduled. Results. 29 patients, 20 with platinum-resistant and 9 with platinum refractory tumors, were enrolled. Lipo-Dox was given for an average of 4.6 cycles per patient with a total of 134 cycles. Among the 26 evaluable patients, one achieved CR, 5 PR and 9 SD. The overall response rate was 23.1% (95% CI, 6.8%–39.3%) with a median response duration of 11.6 weeks. 5 of the 6 responses were in patients with resistant disease. The median progression-free duration in the SD patients was 25.7 weeks. With a median follow-up of 13.8 months, the median progression-free and median overall survivals in the 26 patients were 5.4 months and 13.8 months, respectively. Hand–foot skin reaction occurred in 4.5% and skin pigmentation in 11.2% of all treatment cycles, all were Grade 1/2. Nausea and vomiting occurred in 14.2%, while anemia, leukopenia and thrombocytopenia occurred in 20.9%, 32.8% and 9% of cycle, respectively, and were mostly Grade 1 or 2. Conclusion. Lipo-Dox, the third liposome encapsulated doxorubicin, at 45 mg/m2 every 4 weeks, is effective against recurrent, platinum-resistant epithelial ovarian cancers.

Summary Objective Pelvic tuberculosis is rare, but is problematic for differential diagnosis. In this communication, we report a case series of pelvic tuberculosis clinically presenting as ovarian malignancy. Case Series Over the past 10 years in our hospital, six cases of pelvic tuberculosis were seen. Five were thought to be ovarian malignancies, presenting either with ascites, an elevation of serum CA-125, or an adnexal tumor. Four patients underwent exploratory laparotomy and one received only peritoneoscopic biopsy. Extensive peritoneal seedings and omental thickening were discovered in all cases. Caseating granuloma on histopathologic examination was found in all of the patients. Four out of five patients received a complete course of combined anti-tuberculous treatment. All remain free of disease. Conclusion Pelvic tuberculosis should be taken into account, especially in premenopausal women who manifest with massive ascites and adnexal tumors. Tumor markers such as CA-125 give limited information for the differential diagnosis of pelvic tuberculosis and ovarian carcinoma. We suggest exploratory laparotomy and intraoperative frozen pathology for the diagnosis of pelvic tuberculosis. New insight needs to be applied to tuberculosis.

Interleukin-6 (IL-6), a central proinflammatory cytokine, has been implicated in cervical cancer, though its role remains elusive. This study was an attempt to elucidate the role of IL-6 in the pathogenesis of cervical cancer, with particular emphasis on tumor angiogenesis.Cytosolic IL-6, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) levels were determined via enzyme immunoassay in 60 FIGO stage IB-IIA cervical cancer patients. Immunohistochemical staining in tissue sections was performed to analyze the distributions of IL-6 and IL-6 receptors. Meanwhile, human papillomavirus (HPV) DNA was detected by polymerase chain reaction-based survey. In vitro studies of two cervical cancer cell lines, C33A and SiHa, for the interaction between IL-6 and VEGF were also performed.Consistently higher expression of IL-6 and VEGF was evident in cancerous tissues than in adjacent noncancer tissues in early-stage cervical cancer patients (P0.01). After recombinant human IL-6 was added, VEGF was induced in a time- and dose-dependent manner in cervical cancer cell line C33A. Correspondingly, interrupting the IL-6 autocrine machinery with either anti-IL-6 or anti-IL-6 receptor antibody markedly reduced the expression of VEGF at the transcriptional level in SiHa cells. Significantly higher levels of IL-6 in cancer tissues were observed in patients older than 45 (P0.01), patients with tumors2 cm (P0.01), patients with oncogenic HPV-16 or -18 infections (P0.01), and patients with squamous cell carcinoma (P = 0.02). Patients with a deeper stromal invasion, vaginal invasion, lymphovascular emboli, or lymph node metastasis appeared to have higher intratumoral IL-6 levels, although the differences were statistically insignificant.Substantially high microenvironmental IL-6 levels promote tumor angiogenesis and the development of cervical cancer. Thus, inhibition of the biological activity of IL-6 may be potentially beneficial.