Background/Aims: The microenvironment produces important factors that are crucial to prostate cancer (PCa) progression. However, the extent to which the cancer cells stimulate periprostatic adipose tissue (PPAT) to produce these proteins is largely unknown. Our purpose was to determine whether PCa cell-derived factors influence PPAT metabolic activity. Methods: Primary cultures of human PPAT samples from PCa patients (adipose tissue organotypic explants and primary stromal vascular fraction, SVF) were stimulated with conditioned medium (CM) collected from prostate carcinoma (PC3) cells. Cultures without CM were used as control. We used multiplex analysis and ELISA for protein quantification, qPCR to determine mitochondrial DNA (mtDNA) copy number and zymography for matrix metalloproteinase activity, in order to evaluate the response of adipose tissue explants and SVFs to PC3 CM. Results: Stimulation of PPAT explants with PCa PC3 CM induced adipokines associated with cancer progression (osteopontin, tumoral necrosis factor alpha and interleukin-6) and reduced the expression of the protective adipokine adiponectin. Notably, osteopontin protein expression was 13-fold upregulated. Matrix metalloproteinase 9 activity and mitochondrial DNA copy number were higher after stimulation with cancer CM. Stromovascular cells from PPAT in culture were not influenced by tumor-derived factors. Conclusion: The modulation of adipokine expression by tumor CM indicates the pervasive extent to which tumor cells command PPAT to produce factors favorable to their aggressiveness.
Penile cancer is an uncommon malignancy that occurs most frequently in developing countries. Two pathways for penile carcinogenesis are currently recognized: one driven by human papillomavirus (HPV) infection and another HPV-independent route, associated with chronic inflammation. Progress on the clinical management of this disease has been slow, partly due to the lack of preclinical models for translational research. However, exciting recent developments are changing this landscape, with new in vitro and in vivo models becoming available. These include mouse models for HPV+ and HPV− penile cancer and multiple cell lines representing HPV− lesions. The present review addresses these new advances, summarizing available models, comparing their characteristics and potential uses and discussing areas that require further improvement. Recent breakthroughs achieved using these models are also discussed, particularly those developments pertaining to HPV-driven cancer. Two key aspects that still require improvement are the establishment of cell lines that can represent HPV+ penile carcinomas and the development of mouse models to study metastatic disease. Overall, the growing array of in vitro and in vivo models for penile cancer provides new and useful tools for researchers in the field and is expected to accelerate pre-clinical research on this disease.
This inter-individual variation is found only in humans and aroused about 100,000 years ago in Southeast Asia.The great majority of other mammals have only one band corresponding to the human Hp1-1, except the sheep, deer and cows (Ruminantia), which have only slow bands corresponding to Hp2-2 (Bowman BH and Kurosky A 1982, Wicher KB andFries 2007).The appearance of Hp2 can represent an important evolutionary genetic contribution for interpopulational diversity in human pathology (ER Giblett 1968, Maeda et al 1984, Wicher KB and Fries 2007).This allele is predominant in the human population (about 80% in some Acute Phase Proteins 56
Cervical cancer is the leading cause of cancer-related morbidity and mortality in women in Tanzania. Any impact of the HIV/AIDS epidemic on cervical precancerous lesions and invasive cervical cancer has a significant implication, as for any public health concern, especially in an area such as the Morogoro region in Tanzania, which has one of the highest rates of cervical cancer in the world.A comparative retrospective study was performed of 536 women screened for cervical cancer by visual inspection methods at the Morogoro Regional Referral Hospital over a period of 3 years; the women were grouped according to their HIV status. The odds ratios (OR) with 95% CIs were estimated using χ2 test and multivariate analysis. The test statistics were evaluated with a significance level of P < .05.The prevalence of precancerous lesions was 71.8% in HIV-positive women and 27.3% in HIV-seronegative women. Furthermore, the prevalence of extensive or large precancerous lesions was 40.5% in HIV-positive women and 13.5% in HIV-seronegative women. The prevalence of invasive cervical cancer was 8% in HIV-seronegative women and 11% in HIV-positive women. The risk factors for the cervical lesions were HIV-positive status (OR, 6.8; 95% CI, 4.2 to 11.2; P < .001) and being older than 30 years of age (OR, 11.99; 95% CI, 6.86 to 21.21; P < .001).HIV/AIDS has a highly statistically significant association with (P < .001) and a great influence on the development of cervical precancerous lesions in HIV-positive women; however, its direct involvement in the progression to invasive cervical cancer, especially in this era of highly active antiretroviral therapy, is questionable.
Major depressive disorder (MDD) is a highly prevalent disorder, which has been associated with an abnormal response of the hypothalamus-pituitary-adrenal (HPA) axis. Reports have argued that an abnormal HPA axis response can be due to an altered P-Glycoprotein (P-GP) function. This argument suggests that genetic polymorphisms in ABCB1 may have an effect on the HPA axis activity; however, it is still not clear if this influences the risk of MDD. Our study aims to evaluate the effect of ABCB1 C1236T, G2677TA and C3435T genetic polymorphisms on MDD risk in a subset of Portuguese patients. DNA samples from 80 MDD patients and 160 control subjects were genotyped using TaqMan SNP Genotyping assays. A significant protection for MDD males carrying the T allele was observed (C1236T: odds ratio (OR)=0.360, 95% confidence interval [CI]: [0.140-0.950], p=0.022; C3435T: OR=0.306, 95% CI: [0.096-0.980], p=0.042; and G2677TA: OR=0.300, 95% CI: [0.100-0.870], p=0.013). Male Portuguese individuals carrying the 1236T/2677T/3435T haplotype had nearly 70% less risk of developing MDD (OR=0.313, 95% CI: [0.118-0.832], p=0.016, FDR p=0.032). No significant differences were observed regarding the overall subjects. Our results suggest that genetic variability of the ABCB1 is associated with MDD development in male Portuguese patients. To the best of our knowledge, this is the first report in Caucasian samples to analyze the effect of these ABCB1 genetic polymorphisms on MDD risk.
Desmoplastic ameloblastoma (DA) is a tumor characterized by unique clinical, radiological, and histopathologic features, mostly an abundance of densely collagenous stroma with small nests and islands of odontogenic epithelium. Due to its aggressive, highly invasive nature, there is a tendency to treat DA with bone resection. This article reports and discusses an uncommon case of mandibular DA, focusing on the importance of early, effective treatment.