Increased angiogenic factor secretion by decidual natural killer cells from pregnancies with high uterine artery resistance alters trophoblast function.

STUDY QUESTION Are the concentrations of factors secreted by decidual natural killer (dNK) cells from pregnancies at high risk of poor spiral artery remodelling different to those secreted from pregnancies at low risk? SUMMARY ANSWER Expression levels of PLGF, sIL-2R, endostatin and angiogenin were significantly increased by dNK cells from high-risk pregnancies, and angiogenin and endostatin were found to alter trophoblast function. WHAT IS KNOWN ALREADY During early pregnancy, maternal uterine spiral arteries are remodelled from small diameter, low-flow, high-resistance vessels into larger diameter, higher flow vessels, with low-resistance. This change is essential for the developing fetus to obtain sufficient oxygen and nutrients. dNK cells have been implicated in this process. STUDY DESIGN, SIZE, DURATION dNK cells were isolated from first trimester terminations of pregnancies (obtained with local ethical approval) screened for normal- or high-resistance index, indicative of cases least (21%) likely to have developed pre-eclampsia had the pregnancy not been terminated (n = 18 each group). Secreted factors and the effects of these on the trophoblast cell line, SGHPL-4, were assessed in vitro. PARTICIPANTS/MATERIALS, SETTING, METHODS A multiplex assay was used to assess dNK cell-secreted factors. SGHPL-4 cell functions were assessed using time-lapse microscopy, 3D invasion assays, endothelial-like tube formation ability and western blot analysis. MAIN RESULTS AND THE ROLE OF CHANCE The expression levels of PLGF (P < 0.01), sIL-2R (P < 0.01), endostatin (P < 0.05) and angiogenin (P < 0.05) were significantly increased by dNK cells from high-risk pregnancies. Endostatin significantly decreased SGHPL-4 invasion (P < 0.05), SGHPL-4 tube formation (P < 0.05) and SGHPL-4 Aktser473 phosphorylation (P < 0.05). Angiogenin significantly decreased SGHPL-4 invasion (P < 0.05), but increased SGHPL-4 tube formation (P < 0.01) and decreased SGHPL-4 Aktser473 phosphorylation (P < 0.05). LIMITATIONS, REASONS FOR CAUTION The culture of dNK cells and protein concentrations in vitro may not fully represent the in vivo situation. Although SGHPL-4 cells are extravillous trophoblast derived, further studies would be needed to confirm the roles of angiogenin and endostatin in vivo. WIDER IMPLICATIONS OF THE FINDINGS The altered expression of secreted factors of dNK cells may contribute to pregnancy disorders associated with poor spiral artery remodelling. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Wellcome Trust (project reference 091550). R.F. was a recipient of a PhD studentship from the Division of Biomedical Sciences, St. George's, University of London. The authors have no conflict of interests

Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group

Our objective was to determine whether oral etoposide and cisplatin combination (EoP) is superior to paclitaxel in the treatment of advanced breast cancer (ABC) patients pretreated with anthracyclines. From December 1997 to August 2003, 201 patients were randomised, 100 to EoP and 101 to paclitaxel arms. Four patients in each arm were ineligible. The doses of etoposide and cisplatin were 50 mg p.o. twice a day for 7 days and 70 mg m−2 intravenously (i.v.) on day 1, respectively, and it was 175 mg m−2 on day 1 for paclitaxel. Both treatments were repeated every 3 weeks. A median of four cycles of study treatment was given in both arms. The response rate obtained in the EoP arm was significantly higher (36.3 vs 22.2%; P=0.038). Median response duration was longer for the EoP arm (7 vs 4 months) (P=0.132). Also, time to progression was significantly in favour of the EoP arm (5.5 vs 3.9 months; P=0.003). Median overall survival was again significantly longer in the EoP arm (14 vs 9.5 months; P=0.039). Toxicity profile of both groups was similar. Two patients in each arm were lost due to febrile neutropenia. The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines

Carboplatin, vinblastine and mitomycin-C in the treatment of non-small cell bronchogenic carcinoma

Thirty patients with advanced non-small cell lung carcinoma were treated with carboplatin, vinblastine and mitomycin-C. Objective tumor regression was noted in 6 patients. Toxicity of this combination was moderate

Leukocytosis associated with and localized bladder cancer: Resolution with radiation therapy

Malignant tumors are occasionally associated with significant leukocytosis,(1) which is attributed to production of colony-stimulating factors.(2,3) Bladder carcinoma is rarely associated with paraneoplastic leukocytosis, which is noted in the presence of metastatic disease and has been shown to result from autonomous production of granulocyte colony-stimulating factor by the tumor.(4,5) We report a case of localized transitional cell carcinoma of the bladder with severe leukocytosis, which resolved with radiation treatment of the tumor

Immunocytochemical detection of P-glycoprotein in the management of malignant effusions

P-glycoprotein (P-gp), a cell membrane protein, has been found in multidrug-resistant cancer cells. A total of 104 smears from patients with breast-cancer associated pleural effusions and ovarian-cancer-related peritoneal effusions were studied for P-gp with the antibody C-219 and the avidin-biotin-immunoperoxidase method. Samples were taken before and 3 and 7 days after intracavitary bleomycin therapy and reaccumulation of effusion was assessed at 30 days. Smears that were P-gp-negative by the 7th day were associated with a good 30-day response to bleomycin in the majority of cases, while P-gp-positive smears were associated with a significant reaccumulation of fluid at 30 days. P-gp status is a valuable prognostic indicator of response to intracavitary bleomycin treatment in effusions from breast or ovarian cancer

Late relapse of nonseminomatous germ cell tumor of the testis: Successful treatment with salvage chemotherapy alone

Late relapses of nonseminomatous germ cell tumors of the testicle are unusual. In such cases, chemotherapy is reported to have only modest success and surgery may be the preferred treatment modality. We report a patient who experienced relapse 11 years after the initial diagnosis of advanced testicular cancer and who achieved a sustained complete remission with salvage chemotherapy alone. (C) 1997, Elsevier Science Inc