The mechanisms involved in renal cell carcinoma (RCC) development and progression remain unclear, and new biomarkers for early detection, follow-up of the disease and prognosis are needed in routine practice to improve the diagnostic and/or prognostic accuracy. There is increasing evidence that microRNAs (miRNAs) are involved in cancer development and progression. The up-regulation of miR-221/222 has been described in several human cancers, and during RCC development, this up-regulation can modulate the metastatic process. Our purpose was to investigate the circulating expression levels of miR-221/222 as potential biomarkers for RCC detection and their influence in patients' overall survival. The circulating miR-221/222 was studied by relative quantification in 77 plasma samples. A follow-up study was undertaken to evaluate the overall survival. We observed that RCC patients presented higher circulating expression levels of miR-221 and miR-222 than healthy individuals (2(-ΔΔCt) = 2.8, P = 0.028; 2(-ΔΔCt) = 2.2, P = 0.044, respectively). The RCC patients with metastasis at diagnosis also presented higher circulating expression levels of miR-221 than patients with no metastasis (2(-ΔΔCt) = 10.9, P = 0.001). We also observed a significantly lower overall survival in patients with higher expression levels of miR-221 (48 vs 116 months, respectively; P = 0.024). Furthermore, multivariate Cox regression analysis using the tumour, nodes and metastasis stage (TNM stage); Fuhrman nuclear grade and age (≥60 years) as covariants demonstrated a higher risk of specific death by cancer in patients who presented higher expression levels of miR-221 (hazard ratio (HR) = 10.7, 95% confidence interval 1.33-85.65, P = 0.026). The concordance (c) index showed that the definition of profiles that contain information regarding tumour characteristics associated with circulating miR-221 expression information presents an increased capacity to predict the risk of death by RCC (c index model 1, 0.800 vs model 2, 0.961). Our results, which identified the plasma miR-221/222 at variable levels during RCC development, suggest that these miRNAs may have a potential as noninvasive biomarkers of RCC development.

Interleukin-6 (IL-6) is a pleiotropic cytokine involved in prostate regulation and in prostate cancer (PC) development/progression. IL-6 acts as a paracrine and autocrine growth stimulator in benign and tumor prostate cells. The levels of IL-6 and respective receptors are increased during prostate carcinogenesis and tumor progression. Several studies reported that increased serum and plasma IL-6 and soluble interleukin-6 receptor levels are associated with aggressiveness of the disease and are associated with a poor prognosis in PC patients. In PC treatment, patients diagnosed with advanced stages are frequently submitted to hormonal castration, although most patients will eventually fail this therapy and die from recurrent castration-resistant prostate cancer (CRPC). Therefore, it is important to understand the mechanisms involved in CRPC. Several pathways have been proposed to be involved in CRPC development, and their understanding will improve the way to more effective therapies. In fact, the prostate is known to be dependent, not exclusively, on androgens, but also on growth factors and cytokines. The signaling pathway mediated by IL-6 may be an alternative pathway in the CRPC phenotype acquisition and cancer progression, under androgen deprivation conditions. The principal goal of this review is to evaluate the role of IL-6 pathway signaling in human PC development and progression and discuss the interaction of this pathway with the androgen recepto pathway. Furthermore, we intend to evaluate the inclusion of IL-6 and its receptor levels as a putative new class of tumor biomarkers.The IL-6/IL-6R signaling pathway may be included as a putative molecular marker for aggressiveness in PC and it may be able to maintain tumor growth through the AR pathway under androgen-deprivation conditions. The importance of the IL-6/IL-6R pathway in regulation of PC cells makes it a good candidate for targeted therapy.

No abstract

-765C carrier status should be considered as another susceptibility marker for gastric adenocarcinoma development in patients with atrophy or intestinal metaplasia.

Human papillomavirus (HPV) infection is necessary but not a sufficient cause for the development of invasive cervical cancer (ICC). Epithelial tissues, target for HPV, are exposed to reactive oxygen species (ROS) associated with tumor initiation and progression. The NADPH oxidase (NOX) and catalase (CAT) are involved in hydrogen peroxide (H2O2) production and inactivation, respectively. P22phox is the NOX subunit encoded by the CYBA gene that has a functional polymorphism (C-242T). This protein is involved in the regulation of electron transfer to oxygen. CAT is a hemic enzyme that plays a role in regulating H2O2 concentration, with a functional polymorphism (C-262T) in its gene. We evaluated CYBA C-242T and CAT C262T genetic polymorphisms and their interaction in 132 women with ICC. We found that CYBA C-242T and CAT C262T genotype frequencies were significantly different between ICC and controls (χ (2) test, p = 0.017 and p = 0.009, respectively). Women with the C/T CYBA-242 genotype had a lower risk for ICC development (odds ratio (OR) = 0.515, 95% confidence interval (CI) 0.291-0.914, p = 0.023) whereas T/T CAT-262 genotype carriers present an increased risk for ICC (OR = 3.034, 95% CI 1.462-6.298, p = 0.003). Women with C/C genotype for CYBA and T/T genotype for CAT had an increased risk to develop ICC comparing with the interaction of the other possible genotypes of both genes (OR = 3.952, 95% CI 1.075-14.521, p = 0.032). The CYBA C-242T and CAT C-262T genetic polymorphisms and their epistatic interactions can be associated with ICC through mechanisms related with the role of ROS in cell proliferation and apoptosis.

PurposeCervical 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.MethodsA 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.ResultsThe 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).ConclusionHIV/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.

Cancer is a major public health problem, but despite the several treatment approaches available, patients develop resistance in short time periods, making overcoming resistance or finding more efficient treatments an imperative challenge. Silver nanoparticles (AgNPs) have been described as an alternative option due to their physicochemical properties. The scope of this review was to systematize the available scientific information concerning these characteristics in AgNPs synthesized according to green chemistry’s recommendations as well as their cytotoxicity in different cancer models. This is the first paper analyzing, correlating, and summarizing AgNPs’ main parameters that modulate their cellular effect, including size, shape, capping, and surface plasmon resonance profile, dose range, and exposure time. It highlights the strong dependence of AgNPs’ cytotoxic effects on their characteristics and tumor model, making evident the strong need of standardization and full characterization. AgNPs’ application in oncology research is a new, open, and promising field and needs additional studies.

Lung cancer was found to be the most commonly diagnosed cancer, as well as the primary cause of cancer-related mortality for males worldwide and the second leading cause of cancer-related deaths for women. Cytokines are fundamental for several biological processes-associated malignant tumors. The IL-6 is a cytokine involved in the regulation of cellular functions including processes associated with cancer, such as proliferation, apoptosis, angiogenesis, and differentiation. Furthermore, IL-6 is a potent pleiotropic inflammatory cytokine that is considered a key growth-promoting and antiapoptotic factor. The polymorphism-174G/C SNP is a G to C transition in the -174 position of the promoter region of the IL-6 gene. The aim of our study was to evaluate the influence of -174G/C polymorphism in clinical outcome of non-small cell cancer (NSCLC) patients. DNA was extracted from peripheral blood of 424 patients diagnosed with cytologically or histologically NSCLC. The characterization of IL-6 -174G/C genotypes was performed by PCR-RFLP (NlaIII). IL-6 polymorphism's genotypes were divided according to functional activity, so the G carriers (CG/GG) is the high-producer IL-6, and CC genotype is the low-producer IL-6. Regarding survival, we verify that patients with genotypes carrying the G allele (CG/GG) had a statistically significant diminished survival when compared with patients with CC genotype (62.79 and 42.31 months, respectively; P = 0.032). In the promoter region of the IL-6 gene, polymorphic variants were located and may be responsible for alterations in transcription that consequently affect serum levels of the cytokine. With our study, we demonstrated that genetic variant (-174G/G and G/C) can be responsible for changes in prognosis of NSCLC patients.