Studies on Reproduction in Rats with Meclofenamate Sodium, a Nonsteroidal Anti-inflammatory Agent

Studies on Reproduction in Rats with Meclofenamate Sodium, aNonsteroidal Anti-inflammatory Agent. PETRERE, J. A., HUMPHREY,R. R., ANDERSON, J. A., FITZGERALD, J. E., AND DE LA IGLESIA,F. A. (1985). Fundam. Appl. Toxicol. 5, 665–671. Reproductionand teratology studies were performed in rats given meclofenamatesodium, a nonsteroidal anti-inflammatory agent. Dosages of 0,3, 6, and 9 mg/kg were administered orally as dietary admixturesin the Fertility and Perinatal-Postnatal studies. In the Teratologystudy, dosages of 10, 12, 15, and 20 mg/kg were administeredby intragastric intubation. In the Male-Fertility study no adverseeffects on fertility or litter and offspring parameters wereobserved in two generations. In the Female-Fertility and Perinatal-Postnatalstudies, maternal toxicity (death associated with intestinalulceration and adhesions) was particularly evident during lactation.Prolonged gestation periods, decreased weanling weights, andincreased weanling mortality were evident at dosages of 6 and9 mg/kg. Increased postimplantation loss occurred at 6 and 9mg/kg in the Term Sacrifice subgroup of the Female-Fertilitystudy. Fertility rates were unaffected and all other litterand offspring parameters of the F₁ and F₂ generations appearednormal. In the Teratology study no adverse effects on embryonicor fetal development were evident at maternally toxic dosagesup to 20 mg/kg. © 1985 Society of Texicology.     

Prognostic and predictive value of changes in tumour cell proliferation in locally advanced breast cancer primarily treated with doxorubicin

We previously reported that high tumour cell proliferation evaluated by Ki-67 expression, high mitotic frequency and high histological grade were associated with resistance to primary doxorubicin monotherapy in locally advanced breast cancer harbouring wild-type (wt) TP53. The aim of our present study was to evaluate the predictive and prognostic impact of proliferation parameters assessed in tumour tissue obtained after chemotherapy, and alterations induced in tumour cell proliferation. While we found a significant reduction in Ki-67 expression and mitotic frequency in tumours with wtTP53 (p=0.001 and p=0.008, respectively), no significant change was recorded in tumours expressing mutant TP53. For histological grade there was no significant change in either group. There was a direct correlation between pre- and post-treatment values for Ki-67 and mitotic frequency in tumours harbouring wtTP53 (p=0.0001 for both), but no correlation in tumours harbouring mutated TP53. High post-treatment Ki-67 expression and mitotic frequency were found to predict doxorubicin resistance only in patients with wtTP53 (p=0.04 and p=0.03, respectively). The prognostic importance of proliferation markers and histological grade was found to be similar whether they were determined in the pre- or post-treatment samples (Ki-67; pre: p=0.02; post: p=0.03; mitotic frequency; p=0.002 and p=0.01, respectively; histological grade; p=0.0001 and p=0.002, respectively). While the reduction in mitotic frequency was associated with improved survival (p=0.03), no significant associations between changes in other parameters and outcome were recorded.     

Early detection of breast cancer based on gene-expression patterns in peripheral blood cells

Introduction

Existing methods to detect breast cancer in asymptomatic patients have limitations, and there is a need to develop more accurate and convenient methods. In this study, we investigated whether early detection of breast cancer is possible by analyzing gene-expression patterns in peripheral blood cells.

Methods

Using macroarrays and nearest-shrunken-centroid method, we analyzed the expression pattern of 1,368 genes in peripheral blood cells of 24 women with breast cancer and 32 women with no signs of this disease. The results were validated using a standard leave-one-out cross-validation approach.

Results

We identified a set of 37 genes that correctly predicted the diagnostic class in at least 82% of the samples. The majority of these genes had a decreased expression in samples from breast cancer patients, and predominantly encoded proteins implicated in ribosome production and translation control. In contrast, the expression of some defense-related genes was increased in samples from breast cancer patients.

Conclusion

The results show that a blood-based gene-expression test can be developed to detect breast cancer early in asymptomatic patients. Additional studies with a large sample size, from women both with and without the disease, are warranted to confirm or refute this finding.     

Molecular pathogenesis and prognostic factors in endometrial carcinoma

Endometrial carcinoma is today among the most common gynecologic malignancies in industrialized countries. In order to improve the treatment and follow-up of these patients, various prognostic factors have been extensively studied. Patient age, stage of disease, histologic type and histologic grade have been shown to influence survival significantly, and the prognostic impact of these traditional clinicopathologic variables is well established. In addition, parity, hormone receptor concentration in the tumor, DNA ploidy and morphometric nuclear grade have all been found to influence prognosis. Information about DNA ploidy has especially been used in the clinical situation to determine individualized treatment. The prognostic significance of markers for tumor cell proliferation, cell cycle regulation (p53, p21 and p16) and angiogenesis is discussed as well as the molecular basis of endometrial carcinoma. In conclusion, several prognostic markers have been identified. It is likely that the information derived from these tumor biomarkers will reduce the need for extensive surgical staging and adjuvant treatment in endometrial carcinoma.     

Glomeruloid microvascular proliferation is associated with p53 expression,germline BRCA1 mutations and an adverse outcome following breast cancer

Glomeruloid microvascular proliferation (GMP) in breast cancer independently adversely affected survival (relative risk 1.9, 95% CI: 1.2-3.0), particularly among women who received adjuvant chemotherapy (10-year survival 27 vs 69%, P=0.0003), and was significantly associated with p53 overexpression and BRCA1 germline mutations. The presence of GMP may influence treatment decisions.     

慢性乙肝患者肝组织纤维化程度与HBV-DNA复制水平的相关性研究

目的:探讨HBV-DNA复制水平与肝纤维化之间的相关性。方法:对210例慢性乙型肝炎患者进行HBV-DNA和肝纤维化血清学标志透明质酸(HA)、层粘蛋白(LN)、III型前胶原(PCIII)、IV型胶原(IV-C)进行定量检测。应用SPSS10.0统计软件对结果数据进行分析处理。结果:随慢性乙肝临床类型的加重,肝纤维化血清学标志逐渐升高(P<0.01),而肝纤维化血清学标志与HBV复制水平呈正相关(P<0.05);结论:HBV复制水平与肝纤维化之间呈正相关。