Aberrant expression of p21(WAF1/CIP1) and p27(KIP1) in cervical carcinoma

An immuno-histochemical study of p21 and p27 expression in cervical carcinoma was performed in 73 patients. Positive p21 and p27 staining was detected in 35.6 and 11% of tumour tissues, respectively. p21 expression was significantly correlated with advanced disease stage and negative human papilloma virus infection whilst positive p27 staining was not correlated with any clinical and pathological parameters studied. Kaplan-Meier estimation indicated that survival might be related to disease stage, tumour grade and p21 expression. Cox regression analysis confirmed that advanced stage disease and poorly differentiated tumour are independent prognostic factors for cervical carcinoma.     

Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: a phase II study.

PURPOSE: To evaluate the efficacy of carboplatin plus paclitaxel in primarily advanced or recurrent endometrial cancers. PATIENTS AND METHODS: Four distinct patient groups received carboplatin (area under the curve, 5 to 7) plus paclitaxel 175 mg/m(2) for 3 hours at 4-week intervals: group 1 (n = 21), patients with primarily advanced, nonpapillary serous cancers; group 2 (n = 20), the same as group 1 but with papillary serous cancers; group 3 (n = 18), recurrent, nonpapillary serous cancers; and group 4 (n = 4), recurrent, papillary serous cancers. Involved-field irradiation was used in groups 1 and 2 for those with radioencompassable disease. RESULTS: Sixty-three patients were treated. Response rates to chemotherapy in the assessable patients in the four groups were 78% (95% confidence interval [CI], 51% to 100%); 60% (95% CI, 35% to 85%), 56% (95% CI, 34% to 78%), and 50%, respectively. Nineteen patients (90%) in group 1 also were irradiated, and the median failure-free survival time for all 21 patients was 23 months, with a 62% 3-year overall survival rate. Eleven patients (55%) in group 2 were irradiated, and the median failure-free survival time for all 18 patients was 18 months, with a 39% 3-year overall survival rate. The median failure-free interval in the patients in group 3 was 6 months, with a 15-month median overall survival time. Toxicity was manageable, reversible, and predominantly hematologic. Two patients developed neutropenic fever, and three patients, including these two, were hospitalized for complications. CONCLUSION: Carboplatin-paclitaxel is an efficacious, low-toxicity regimen for managing primarily advanced or recurrent endometrial cancers.     

A single Glu(62)-to-Lys(62) mutation in the Mos residues of the R7Delta447Gag-tMos protein causes the mutant virus to induce brain lesions

We previously reported that R7Delta447, a 2954-base-pair (bp) laboratory-generated Moloney murine sarcoma virus, induced subcutaneous tumors in about 14% of infected mice but did not induce brain lesions. We now report that R7Delta447K, a spontaneous mutant of R7Delta447, induced brain lesions as well as subcutaneous tumors in all injected mice. The genomes of the two viruses differ in a single base pair: the deduced Glu(62) of the Mos residue of the R7Delta447 Gag-tMos protein is changed to Lys(62). More R7Delta447 than R7Delta447K focus-forming units were detected in both NIH3T3 and mouse cerebral vascular endothelial (MCVE) cells. However, R7Delta447K transformed NIH3T3 and MCVE cells more acutely than did R7Delta447. A distinctive feature that distinguished the morphologic transformation of R7Delta447- and R7Delta447K-infected MCVE cells is the markedly prolonged spindle-shaped phase exhibited by R7Delta447-infected MCVE cells. In addition, R7Delta447K was more efficient in inducing the phosphorylation of ERK1/2 than R7Delta447 in both MCVE and NIH3T3 cells. Moreover morphologic transformation was inhibited, and levels of phosphorylated ERK1/2 were reduced when R7Delta447- or R7Delta447K-infected NIH3T3 or MCVE cells were grown in the presence of the MEK1/2-specific inhibitor PD98095. Thus, we have identified a key residue in the Gag-tMos protein that profoundly affects activation of the Mos/MEK/ERK pathway, virus and cell replication, morphologic transformation in vitro and pathogenicity in vivo.     

High incidence of somatic mitochondrial DNA mutations in human ovarian carcinomas

To investigate the potential role of somatic mitochondrial DNA (mtDNA) mutations in tumorigenesis, the occurrence of mutations in mtDNA of ovarian carcinomas was studied. We sequenced the D-loop region of mtDNA of 15 primary ovarian carcinomas and their matched normal controls. Somatic mtDNA mutations were detected in 20% (3 of 15) tumor samples carrying single or multiple changes. Complete sequence analysis of the mtDNA genomes of another 10 pairs of primary ovarian carcinomas and control tissues revealed somatic mtDNA mutations in 60% (6 of 10) of tumor samples. Most of these mutations were homoplasmic, and most were T-->C or G-->A transitions, but one represented a differential length within a run of identical C residues. A region of mtDNA sequence including the 16S and 12S rRNA genes, the D-loop and the cytochrome b gene, may represent the zone of preferred mtDNA mutation in ovarian cancer. The high incidence of mtDNA mutations found in ovarian carcinomas and other human cancers suggests that genetic instability of mtDNA might play a significant role in tumorigenesis.     

Heart rate responses and oxygen consumption during Tai Chi Chuan practice.

Tai Chi Chuan (TCC) is a popular Chinese conditioning exercise, however, its exercise intensity remains controversial. The objective of this study was to determine the exercise intensity of Yang TCC by measuring heart rate (HR) responses and oxygen consumption (VO2) during practice. Fifteen men aged 39.9 +/- 9.5 yrs (range 26-56 yrs) participated in this study. Subjects had practiced classical Yang TCC for 5.8 +/- 2.4 years. HR responses and VO2 were measured during practice of TCC by using a K4 telemetry system. Blood lactate was measured before and immediately after TCC practice. Additionally, breath-by-breath measurement of cardiorespiratory function and sequential determination of blood lactate were performed during the incremental exercise of leg cycling. Measurements obtained during the TCC practice and exercise testing were compared to determine the exercise intensity of TCC. While performing TCC, the mean HR of subjects was 140 +/- 10 bpm, and the mean VO2 was 21.4 +/- 1.5 mL x kg(-1) min(-1). Compared with the data of the exercise test, the HR during practice was 58% of the heart rate range. Meanwhile, the VO2 during TCC practice was 55% of the VO2peak. Additionally, the level of blood lactate immediately after TCC practice was 3.8 mM, which reflected the level of lactate during TCC, approximated the onset of blood lactate accumulation (OBLA). The results demonstrate that TCC is an exercise with moderate intensity, and is aerobic in nature.     

Promoting the advancement of minority women faculty in academic medicine: the National Centers of Excellence in Women's Health

Minority physicians provide care in a manner that promotes patient satisfaction and meets the needs of an increasingly diverse U.S. population. In addition, minority medical school faculty bring diverse perspectives to research and teach cross-cultural care. However, men and women of color remain underrepresented among medical school faculty, particularly in the higher ranks. National data show that although the numbers of women in medicine have increased, minority representation remains essentially static. Studying minority women faculty as a group may help to improve our understanding of barriers to diversification. Six National Centers of Excellence in Women's Health used a variety of approaches in addressing the needs of this group. Recommendations for other academic institutions include development of key diversity indicators with national benchmarks, creation of guidelines for mentoring and faculty development programs, and support for career development opportunities.