Induction chemotherapy for breast carcinoma: predictive markers and relation with outcome

Induction chemotherapy provides an excellent model for evaluation of potential predictive factors. We studied expression of SBR grade, estrogen (ER) and progesterone (PR) receptors, HER2, Ki67 and P53 on core biopsies before and after chemotherapy in a series of 115 patients, who received anthracycline-based induction chemotherapy for primary breast cancer. HER2 overexpression independently predicted response to neoadjuvant anthracycline-based chemotherapy. Patients with HER2-positive status are 4.54 times more likely to have a pathological complete response than those with negative status (p<0.005). HER2, ER and PR status were stable during treatment. P53 and Ki67 significantly increased after treatment (p<0.005 and p<0.0005). SBR grade, proliferation markers, ER evaluated before and after treatment predicted disease-free survival (DFS) in univariate analysis.     

Oridonin induces growth inhibition and apoptosis of a variety of human cancer cells

PC-SPES is an eight herbal mixture that was shown to have activity against prostate cancer. Recently, we purified oridonin from Rabdosia rubescens, one component of PC-SPES, by high performance liquid chromatography (HPLC). The ability of oridonin to inhibit the proliferation of cancer cells was examined by MTT assay. Oridonin effectively inhibited the proliferation of a wide variety of cancer cells including those from prostate (LNCaP, DU145, PC3), breast (MCF-7, MDA-MB231), non-small cell lung (NSCL) (NCI-H520, NCI-H460, NCI-H1299) cancers, acute promyelocytic leukemia (NB4), and glioblastoma multiforme (U118, U138) with ED50s ranging from 1.8 to 7.5 micro g/ml. TUNEL assay and cell cycle analysis showed that oridonin induced apoptosis and G0/G1 cell cycle arrest in LNCaP prostate cancer cells. In addition, expression of p21waf1 was induced in LNCaP and NCI-H520 cells in a p53-dependent manner. Interestingly, when p53 was suppressed by over-expression of E6 from human papilloma virus type 16 (HPV-16), these cells lost their sensitivity to oridonin-induced growth inhibition and apoptosis. Taken together, oridonin inhibited the proliferation of cancer cells via apoptosis and cell cycle arrest with p53 playing a central role in several cancer types which express the wild-type p53 gene. Oridonin may be a novel, adjunctive therapy for a large variety of malignancies and probably represents one of the major, active components of PC-SPES.     

Health-seeking behaviour and rural/urban variation in Kazakhstan

This paper seeks to analyse the findings of an extensive household survey, uncovering interesting evidence of variation in health-seeking behaviour across rural and urban areas due, it is suggested, to differences in real costs, quality of care, and perceptions of the value of health and health care. It is shown that, ceteris paribus, urban households in Kazakhstan are more likely to consult, to be admitted to hospital, to report illness, and will spend relatively more on health care.The data suggest the need for further qualitative study into the factors underlying these patterns leading to strategies to increase the quality, acceptability and affordability of rural health services. This is important given the decline in health indicators such as life expectancy in Kazakhstan and the increased burden on households of funding health care in a time of economic insecurity and deterioration of public services.     

Scientific controversy and asbestos: making disease invisible

Despite irrefutable evidence that asbestos causes asbestosis, lung cancer, and mesothelioma, asbestos mining, milling, and manufacturing continue. The authors discuss three scientific debates over the roles of fiber types, viruses, and genetics in the development of mesothelioma. While these controversies might appear internal to science and unconnected to policies of the global asbestos industry, they argue that scientific debates, whether or not fostered by industry, play a central role in shaping conceptualization of the problem of asbestos-related disease. In South Africa, India, and elsewhere, these controversies help to make the disease experience of asbestos-exposed workers and people in asbestos-contaminated communities invisible, allowing the asbestos industry to escape accountability for its practices.     

Factors related to the uptake of breast cancer screening (mammography and breast ultrasound): a retrospective survey on a sample of resident women, 50-70 years aged, from Abruzzo region

Within the context of a large breast cancer screening program we conducted a retrospective survey to identify the personal, socioeconomic and behavioural characteristics associated with previous use of mammograms (Ma) and breast ultrasound examination (US). Contact was made with a sample of more than 10,000 resident women who were asked to complete three questionnaires. Achieving an answer rate of 86%, we collected data from 9,087 women, 50-70 years aged, coming from Abruzzo, a central Italian region. 61% of the participants performed Ma, while US was performed by 34%, and 67% of women attended at least one of those examinations. Multiple logistic regression results indicated that older age, low level of education, not performing diets and breast self examination were significant predictors of a lower use of both examinations. Women that were married, mothers, on menopause, with a family history of cancer, uterine fibroma, past users of oral contraceptives were more likely to having performed Ma, but not US. Age at menarche, BMI and smoking were found not to be significant in predicting attendance for both screening examinations, with the exception of ex-smokers for US. Our findings represent an important contribution to the development of the needed tailored interventions to increase breast screening participation.     

Cryptococosis and HIV/AIDS: a review of 21 cases reported in the Tropical Diseases Centre, Ho Chi Minh City (Vietnam)

Cryptococcus neoformans affections during HIV-infection are frequent and serious. The aim of this study was to analyse the epidemiological, clinical, biological and therapeutic characteristics of cryptococcal meningitis in HIV-positive patients, admitted into the Center for Tropical Diseases Ho Chi Minh City (Vietnam), during a 5-month period (May-September 2001). Twenty-one patients (20 men and one woman) were included (identification of C. neoformans from the cerebrospinal fluid). The mean age was 28 years. The majority of patients had been living in Ho Chi Minh City (48%). The use of drugs and unprotected sexual relations were the principal risk factors of HIV-infection. The paucity and the confusion of clinical signs and symptoms, along with a high frequency of meningitis have been analysed. Clinical presentation features included: headache (95%), emaciation (90%), oro-pharyngeal candidiasis (90%), stiff neck (80%), nausea/vomiting (70%), fever (67%), coughing (38%), diarrhoea (33%), skin lesions (5%), convulsion (5%), photophobia (5%), and hemiparesis (5%). The severity of the prognosis was mainly linked to the delay before hospitalization, to the possible association with other opportunistic infections, and to the availability of appropriate treatment.     

Delphinidin,an active compound of red wine,inhibits endothelial cell apoptosis via nitric oxide pathway and regulation of calcium homeostasis

1. Epidemiological studies have suggested that moderate consumption of natural dietary polyphenolic compounds might reduce the risk of cardiovascular disease and also protect against cancer. The present study investigates the effects of delphinidin, an anthocyanin present in red wine, on bovine aortic endothelial cells apoptosis. 2. Based on flow cytometry, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis and detection of mitochondrial cytochrome c release, we show that delphinidin (10(-2) g l(-1)) alone had no effect either on necrosis or on apoptosis, but it significantly reduced apoptosis elicited by actinomycin D (1 micro g ml(-1), 24 h) and 7beta-hydroxycholesterol (10 micro g ml(-1), 18 h). 3. The protective effect of delphinidin was abolished by inhibitors of nitric oxide-synthase (NOS) (L-NA, 100 micro M and SMT, 100 micro M), guanylyl cyclase (ODQ, 100 micro M) and MAP kinase (PD98059, 30 micro M). 4. Western blot analysis and protein detection by confocal microscopy demonstrate that the antiapoptotic effect of delphinidin was associated with an increased endothelial NOS expression mediated by a MAP kinase pathway. 5. Finally, delphinidin alone had no effect on cytosolic-free calcium ([Ca(2+)](i)), but normalized the changes in [Ca(2+)](i) produced by actinomycin D towards the control values, suggesting that the antiapoptotic effect of delphinidin is associated with the maintenance of [Ca(2+)](i) in the physiological range. 6. All of the observed effects of delphinidin may preserve endothelium integrity, the alteration of which lead to pathologies including cardiovascular diseases, such as atherosclerosis, and is often associated with cancers. In conclusion, the protective effect of delphinidin against endothelial cell apoptosis contributes to understand the potential benefits of a consumption rich in polyphenols.     

Women's substance use and experiences of intimate partner violence: a longitudinal investigation among a community sample

Although cross-sectional studies reveal an association between women's substance use and experiencing physical violence from one's intimate partner, the temporal ordering of these variables is not clearly established. The current study involved longitudinal examination of the association of women's substance use with subsequent experiences of intimate partner violence as well as the association between women's experiences of intimate partner violence and their subsequent substance use. Women ages 18-30 who were in heterosexual relationships (n=724) were recruited through random digit dialing in the Buffalo, NY, area. Within ongoing relationships, women's use of hard drugs was associated with increased odds of experiencing intimate partner violence over the next 12 months. Both marijuana and hard drug use were associated with increased likelihood of experiencing violence in new relationships. Women's heavy episodic drinking did not predict subsequent experiences of partner violence in ongoing or new relationships. Experiences of intimate partner violence had a significant effect on subsequent relationship satisfaction, which was modestly associated with subsequent heavy episodic drinking but not with subsequent drug use.     

Intradermal Injection of Transforming Growth Factor-β1 Gene Enhances Wound Healing in Genetically Diabetic Mice

Purpose. To evaluate the biologic effect of direct cutaneous TGF-1 gene delivery on impaired wound healing models using genetically diabetic mice. Methods. Diabetic mice (C57BKS.Cg-m +/+ Leprdb female mice) with 1 cm × 1 cm excisional wounds were intradermally injected with 60 g of plasmid DNA encoding TGF-1 gene. The wound closure was measured up to 14 days postwounding. At days 7 and 14 postwounding, sections of skin were taken for hematoxylin and eosin and Masson's trichome staining to examine the morphology and collagen deposition. The cell proliferation and TGF-1 gene expression were studied using immunohistochemical stainings for 5-bromo-2-deoxy-uridine and for TGF-1. Results. A higher cell proliferation rate and a denser and more organized new extracellular matrix were observed in the treated wound site. Complete wound closure was detected as early as 7 days for TGF-1-treated group in comparison with 11-14 days for the untreated, control plasmid DNA- and PBS-treated groups. Conclusion. A single intradermal injection of TGF-1 plasmid DNA was sufficient to enhance wound healing. This approach represents a new strategy that may be applied to the treatment of excisional wounds in human diabetic patients.