Immunohistochemical expressions of p16 and p53 proteins in cervical intraepithelial neoplasia and in benign cervical tissue.

PURPOSE OF INVESTIGATION: To evaluate the immunohistochemical expressions of p16 and p53 in cervical intraepithelial neoplasia (CIN) and do a comparison with non-neoplastic cervical lesions. METHODS: Sixty cases diagnosed as CIN after histopathological examination and 25 controls diagnosed as chronic cervicitis were included in the study. Immunohistochemical expressions for p16 and p53 were evaluated and compared in all cases. The cases in the study were defined according to the Bethesda system. Of these, 31.8% (n = 27) had a low-grade squamous intraepithelial lesion (LGSIL), and 38.8% (n = 33) had a high-grade squamous intraepithelial lesion (HGSIL). RESULTS: There was a statistically significant difference between chronic cervicitis and CIN in terms of p53 and p16 expression levels (p = 0.001). On the other hand, the level of p16 expression was statistically different between LGSIL and HGSIL (p = 0.001), while there was no significant difference in terms of p53 expression. Among the HGSIL cases (n = 33), 91% had p16 expression, while 66.7% (n = 27) of the LGSIL patients had no p16 expression. In the chronic cervicitis group, 84% (n = 21) did not reveal any p16 expression, while 96% (n = 24) did not reveal any p53 expression. Various levels of p53 expressions were detected in 59.2% (n = 16) of CIN1 cases, 69.3% (n = 9) of CIN2 cases, and 90% (n = 18) of CIN3 cases. CONCLUSION: While p16 is useful in detecting high-grade cervical lesions, p53 is not a good biomarker for distinguishing high-grade lesions from low grade ones.

Pegylated liposomal doxorubicin in heavily pretreated epithelial ovarian cancer patients.

PURPOSE: While most patients with ovarian cancer respond to first-line treatment, 50-75% of these patients will eventually relapse. Pegylated liposomal doxorubicin (PLD) is an active agent indicated for the treatment of patients with disease that is refractory to both paclitaxel- and platinum-based regimens, but skin toxicity remains the dose-limiting toxicity of the drug. The primary objective of this retrospective study was to evaluate the activity and safety of this agent in patients with heavily pretreated ovarian cancer. PATIENTS AND METHODS: Patients with platinum-refractory/ resistant, paclitaxel-pretreated epithelial ovarian carcinoma were treated with PLD 50 mg/m2 in 4-week courses until disease progression or unacceptable toxicity. All patients had progressive disease (PD) before starting PLD. Primary endpoints were response rate, progression free survival (PFS) and toxicity and secondary endpoints duration of response (DOS) and overall survival (OS). RESULTS: Seventeen heavily pretreated patients (median number of previous chemotherapy regimens 3, range 1-5) with taxane- and platinum-refractory disease were analysed. No complete response (CR) was achieved, while 3 (17%) partial responses (PR) and 2 (11%) cases with stable disease (SD) were observed. The median PFS was 15 weeks (range 10-21) and median OS 32 weeks (range 16-47). Palmar plantar erythrodysesthesia (PPE) occurred in 4 (23%) patients and was of grade 4 in 1 (6%) patient. Stomatitis occurred in 3 (17%) patients and was grade 3 in 1 (6%) patient. Grade 3-4 neutropenia occurred in only 2 (12%) patients. No febrile neutropenia was encountered. CONCLUSION: Pegylated liposomal doxorubicin is an active and tolerable agent in heavily pretreated epithelial ovarian cancer patients.

In vitro effects of ritodrine, magnesium sulfate and their combination on spontaneous contractions of myometrial strips of pregnant rat uteri.

OBJECTIVE: To investigate in vitro effects of ritodrine, magnesium sulfate and their combination on spontaneous contractions of myometrial strips obtained from pregnant rat uteri. METHOD: A total of 13 pregnant Sprague Dawley rats with weights between 180-200 g were used in this study. Three strips from each rat were kept in an organ bath containing 20 ml Krebs-Henseleit solution (pH: 7.4 and 37 degrees C). 10(-8) 10(-6) and 10(-4) M concentrations of ritodrine, magnesium sulfate and the combination was applied over myometrial strips in Groups I (n: 10), II (n: 10) and III (n: 8), respectively. Amplitude and frequency of spontaneous myometrial contractions, which were recorded at the beginning of each experiment, were considered as reference values. Amplitude and frequency changes in spontaneous myometrial contractions were calculated at approximately ten-minute intervals right after the application of drugs as the percentage of difference at the first reference response. RESULTS: Magnesium sulfate application did not lead to any significant difference on the amplitude and frequency of contractions at any of its concentrations. 10 and 10(-4) M concentrations of ritodrine caused a significant decrease in the amplitude of contractions. It was also found that ritodrine significantly decreased the frequency values at all concentrations. A significant decrease in amplitude was observed at 10(-8) and 10(-6) M concentrations in the combination group. No significant decrease in frequency values was found at any concentration in the combination group. CONCLUSION: The tocolytic effect of ritodrine is superior to that of magnesium sulfate.

Mammographic density changes during different postmenopausal hormone replacement therapies.

OBJECTIVE: To determine the degree of change in mammographic breast densities during different types of postmenopausal hormone replacement therapies. DESIGN: A retrospective study. SETTING: Ege University Hospital. PATIENT(S): The mammographies of 216 women on various postmenopausal hormone replacement therapies were evaluated. INTERVENTION(S): Estrogen alone (n = 76) or estrogen in cyclic (n = 44) or continuous (n = 61) combination with progestin or tibolone-only (n = 35) replacement therapies were used. Mammographic density was quantified according to the Wolfe classification in patients with different hormone replacement regimens. MAIN OUTCOME MEASURE(S): Mammographic density changes were interpreted. RESULT(S): An increase in mammographic density was much more common among women receiving continuous combination hormone replacement therapy 31.1% (19 of 61) than among those receiving estrogen-only 3.9% (3 of 76) treatment. There were no significant mammographic breast density changes among women receiving cyclic continuous combination hormone replacement therapy or tibolone-only treatment. The increase in density was apparent already at first visit after the start of hormone replacement therapy. In continuous combined postmenopausal hormone replacement therapy with norethisterone acetate, the increase in mammographic density was 34.1% (15 of 44), followed by medroxyprogesterone acetate 23.5% (4 of 17). CONCLUSION(S): Our findings show that mammographic breast density changes related to postmenopausal hormone replacement therapy are dependent on the selected hormone regimen. The continuous administration of the progestin component of the combined-hormone replacement therapy seems to effect the breast density most.