The development of priority cervical cancer trials: a Gynecologic Cancer InterGroup report.

Since the late 1990s, when a spate of US studies reported the benefit of chemoradiation for cervical cancer, there has been a dearth of clinical trials in cervical cancer. This requires to be addressed with urgency because this disease is responsible for a quarter of a million deaths globally each year, mostly in developing countries, but therapeutic advances are required in all health care settings. The Gynecologic Cancer InterGroup (GCIG) is a worldwide collaborative of leading national groups that develops and promotes multinational trials in gynecologic cancer. In recognition of the pressing need for action, the GCIG convened an international meeting with expert representations from most of the GCIG groups and selected large centers in low- and middle-income countries. The focus was to identify consensus on several concepts for clinical trials, which would be developed and promoted by the GCIG and launched with major international participation. The first half of the meeting was devoted to a resume of the current state of the knowledge and identifying the gaps most needing new evidence. The second half of the meeting was concerned with achieving consensus on the way forward. There were 2 principal outcomes. The first was a proposal to establish, under the umbrella of GCIG, a cervical cancer trials network of centers from countries currently outside GCIG (Eastern Europe, India, Thailand, Southern Africa, and South and Central America), which could increase international participation in trials, conducted within the principles of good clinical practice. The second was to identify the priorities for clinical trials. These included additional systemic therapy before or after chemoradiation; less radical surgery for small, early-stage tumors; the use of fewer fractions to improve cost-effectiveness of treatment in centers with limited resources; and chemotherapy to improve resectability of bulky tumors.

The PDZ protein Tip-1 is a gain of function target of the HPV16 E6 oncoprotein.

Previous work has indicated that the PDZ domain Tax interacting protein 1 (Tip-1) is a target of the HTLV1 Tax protein and is a potential RhoA effector. We have used the yeast two-hybrid system to show that Tip-1 also interacts with the HPV16 E6 protein. This interaction was confirmed by co-immunoprecipitation from E6 expressing C33A cervical carcinoma cells (C33A-E6) which showed that Tip-1 was not degraded by interaction with the HPV16 E6 oncoprotein. During routine passage we observed that C33A-E6 had a less compact morphology and were less adherent than control vector transfected cells C33A-V cells - a known effect of GTP-RhoA. Comparison of C33A-E6 to C33A-V demonstrated that E6 expressing cells had higher levels of phosphorylated myosin light chains (MLC) and increased cell motility, which was inhibited by antisense silencing of Tip-1 expression and by the RhoA kinase (ROCK) inhibitor Y27632. Both C33A-E6 and C33A-V cells were shown to express GTP activated RhoA. Since ROCKs can be activated by GTP RhoA these data indicate that E6 may increase cell motility by augmenting GTP RhoA mediated activation of ROCKs and that this is dependent on the expression of the Tip-1 protein.

Transvaginal biopsy in the diagnosis of ovarian cancer.

Laparotomy and debulking surgery followed by chemotherapy have been the treatment of choice in late stage ovarian carcinoma. Developments in the chemotherapeutic management of ovarian cancer have resulted in a change in opinion as to the optimal management of this disease. Many patients are now receiving initial chemotherapy and trials are in place to compare up front and adjuvant surgery. Tissue diagnosis is required prior to commencing chemotherapy. This article describes one method for accurately obtaining a tumour biopsy. A retrospective case note review of 14 women with a provisional diagnosis of ovarian carcinoma who underwent transvaginal biopsy of their pelvic disease is described. Only 7/12 cases with a positive biopsy had a definite diagnosis of ovarian cancer. The procedure was found to be safe and well tolerated.