Randomised trial comparing prednimustine with combination chemotherapy in advanced ovarian carcinoma.

A total of 76 patients with advanced epithelial ovarian carcinoma were randomised to receive 6 months of treatment with either a combination of hexamethylmelamine, 5-fluorouracil, cisplatin and prednimustine or prednimustine alone following initial surgery. Pathologically confirmed response rates were 35% for combination chemotherapy and 28% for prednimustine, and the overall survival was identical for the two groups. Seven patients achieved a pathologically defined complete response, one of whom relapsed at 8 months; the others remain disease-free 18-36 months (median, 23 months) after presentation. The extent of initial surgery significantly affected the survival of patients receiving prednimustine but not of those receiving combination chemotherapy. Prednimustine can produce durable responses in advanced ovarian cancer using a schedule that results in negligible toxicity.

Mucinous endometrial carcinoma in a patient with previous ovarian endometrioid adenocarcinoma presenting some 18 years after initial bilateral ovariectomy: a case report.

The association of endometrioid carcinoma of the ovary and primary carcinoma of the endometrium is well recognised. These tumours are often synchronous in occurrence. Oestrogen stimulation is often postulated as a significant factor in the development of the endometrial carcinoma in such cases. We describe the case of a patient who developed a mucinous endometrial carcinoma 18 years after initial bilateral ovariectomy. The aetiology and pathogenesis of the uterine tumour is discussed.

Use of liquid hydrocarbon and amide transfer data to estimate contributions to thermodynamic functions of protein folding from the removal of nonpolar and polar surface from water.

This extension of the liquid hydrocarbon model seeks to quantify the thermodynamic contributions to protein stability from the removal of nonpolar and polar surface from water. Thermodynamic data for the transfer of hydrocarbons and organic amides from water to the pure liquid phase are analyzed to obtain contributions to the thermodynamics of folding from the reduction in water-accessible surface area. Although the removal of nonpolar surface makes the dominant contribution to the standard heat capacity change of folding (delta C0fold), here we show that inclusion of the contribution from removal of polar surface allows a quantitative prediction of delta C0fold within the uncertainty of the calorimetrically determined value. Moreover, analysis of the contribution of polar surface area to the enthalpy of transfer of liquid amides provides a means of estimating the contributions from changes in nonpolar and polar surface area as well as other factors to the enthalpy of folding (delta H0fold). In addition to estimates of delta H0fold, this extension of the liquid hydrocarbon model provides a thermodynamic explanation for the observation [Privalov, P. L., & Khechinashvili, N. N. (1974) J. Mol. Biol. 86, 665-684] that the specific enthalpy of folding (cal g-1) of a number of globular proteins converges to a common value at approximately 383 K. Because amounts of nonpolar and polar surface area buried by these proteins upon folding are found to be linear functions of molar mass, estimates of both delta C0fold and delta H0fold may be obtained given only the molar mass of the protein of interest.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution to the thermodynamics of protein folding from the reduction in water-accessible nonpolar surface area.

Protein folding and the transfer of hydrocarbons from a dilute aqueous solution to the pure liquid phase are thermodynamically similar in that both processes remove nonpolar surface from water and both are accompanied by anomalously large negative heat capacity changes. On the basis of a limited set of published surface areas, we previously proposed that heat capacity changes (delta C degrees p) for the transfer of hydrocarbons from water to the pure liquid phase and for the folding of globular proteins exhibit the same proportionality to the reduction in water-accessible nonpolar surface area (delta Anp) [Spolar, R.S., Ha, J.H., & Record, M.T., Jr. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 8382-8385]. The consequence of this proposal is that the experimental delta C degrees p for protein folding can be used to obtain estimates of delta Anp and of the contribution to the stability of the folded state from removal of a nonpolar surface from water. In this paper, a rigorous molecular surface area algorithm [Richmond, T.J. (1984) J. Mol. Biol. 178, 63-89] is applied to obtain self-consistent values of the water-accessible nonpolar surface areas of the native and completely denatured states of the entire set of globular proteins for which both crystal structures and delta C degrees p of folding have been determined and for the set of liquid and liquefiable hydrocarbons for which delta C degrees p of transfer are known. Both processes (hydrocarbon transfer and protein folding) exhibit the same direct proportionality between delta C degrees p and delta Anp. We conclude that the large negative heat capacity changes observed in protein folding and other self-assembly processes involving proteins provide a quantitative measure of the reduction in the water-accessible nonpolar surface area and of the contribution of the hydrophobic effect to the stability of the native state and to protein assembly.

Grading of cervical dysplasias by frozen section.

Grading of cervical dysplasias at colposcopy by means of rapid frozen section avoids the delay inevitable with paraffin sections. The immediacy of the diagnosis benefits the patient, who can be treated at her first visit. A comparison of grading by frozen sections with paraffin sections has confirmed the safety of the frozen method. Additional advantages are opportunities for optimum orientation and "rescue" of specimens, improved colposcopic training, and the facilitation of special investigations on fresh cervical tissue.

Early stage cervical cancer: psychosocial and sexual outcomes of treatment.

Eighty-three women, mean age 45 years, successfully treated by surgery (S) or radiotherapy (RT) for stage 1b cervical cancer were assessed a mean of 97 weeks post treatment. Forty to 50% reported persistent tiredness, lack of energy and weight gain. Sixty per cent had not resumed their full premorbid functional status. Mean scores for anxiety and depression were higher than general population means and this sample scored higher for psychological distress than published data quoted for disease free cancer patients. These women reported many concerns about cervical cancer, most commonly fear of recurrent disease (91%). More than one-third blamed themselves for the disease. There were no significant differences in functional outcome or psychological status between treatment groups or by age or time since treatment. Psychological distress scores were significantly correlated with physical complaints (P < 0.001) and functional outcomes (P < 0.02). For the 61 women who were sexually active, sexual function post-treatment was rated as significantly poorer than subjectively recalled premorbid sexual function (P < 0.005). RT treated patients were more likely to report pain on intercourse and loss of enjoyment. Psychological as well as physical problems were highly correlated with sexual outcome (P < 0.01) 44% were unable to talk adequately with their partners about their experience. The majority felt they needed more information about cervical cancer, its treatment and how to help themselves rehabilitate. Forty-nine per cent would have liked to have had counselling. Even with the same physical morbidity the functional, emotional and sexual status of these women could be improved by giving more attention to their psychological and sexual concerns.

Cisplatinum and prednimustine, an active regimen for advanced epithelial ovarian cancer.

80 patients with advanced epithelial ovarian carcinoma were treated for 6 months with cisplatinum and prednimustine following initial surgery. Response to treatment was assessed by second-look surgery. The objective response rate was 69% with 38% achieving a complete response for up to 55 months. The toxicity of this regimen was acceptable. Statistically, de-bulking or partial de-bulking had a significant beneficial effect on the likelihood of a complete response. The best survival figures were associated with maximum de-bulking. The combination of cisplatinum and prednimustine is a new and active regimen for operable advanced epithelial ovarian carcinoma.