Significance of PSCA as a novel prognostic marker and therapeutic target for cancer

Abstract One of the contributing factors in the diagnosis and treatment of most cancers is the identification of their surface antigens. Cancer tissues or cells have their specific antigens. Some antigens that are present in many cancers elicit different functions. One of these antigens is the prostate stem cell antigen (PSCA) antigen, which was first identified in the prostate. PSCA is a cell surface protein that has different functions in different tissues. It can play an inhibitory role in cell proliferation as well as a tumor-inducing role. PSCA has several genetic variants involved in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship with clinical features can provide more information on diagnosis and treatment of patients with cancers. Most studies on the PSCA have focused on prostate cancer. While it is also expressed in other cancers, little attention has been paid to its role as a valuable diagnostic, prognostic, and therapeutic tool in other cancers. PSCA has several genetic variants that seem to play a significant role in cancer susceptibility in some tissues, so identifying the characteristics of this antigen and its relationship and variants with clinical features can be beneficial in concomitant cancer therapy and diagnosis, as theranostic tools. In this study, we will review the alteration of the PSCA expression and its polymorphisms and evaluate its clinical and theranostics significance in various cancers

Evaluation of anti-tumor potential of lactobacillus acidophilus atcc4356 culture supernatants in mcf-7 breast cancer

Background: The anti-cancer activity of some lactic acid bacterial strains is well documented in several kinds of literatures. Lactobacillus strains have received considerable attention as a beneficial microbiota. The aim of this study is to evaluate the effects of anti-tumor activities of L. acidophilus ATCC4356 culture supernatants on the MCF-7 human breast cancer cells. Materials and Methods: The anti-cancer effects of 24h and 48h culture supernatants at various concentrations (1.25, 2.5, 5, 10 and 20 µg/ml) were determined by various in vitro and in vivo assays including MTT, tumor volume measurement as well as99mTc-MIBI biodistribution in MCF-7 tumor bearing nude mice and histopathology test. For evaluation of the related mechanism of action, quantitative PCR was conducted. Results: The 48h culture supernatants at 10 and 20 µg/ml exhibited significant in vitro inhibition of MCF-7 cell proliferation. However, this inhibition was not observed for HUVEC human endothelial normal cells. Q-PCR indicated that treatment by the supernatant led to a significant downregulation of VEGFR (~ 0.009 fold) and Bcl-2 (~ 0.5 fold) and upregulation of p53 (~ 1.3 fold). In vivo study using MCF-7 xenograft mouse models demonstrated a reduction in tumor weight and volume by both 24h and 48h supernatants (2 mg/kg) after 15 days. According to the99mTc-MIBI biodistribution result, treatment of MCF-7 bearing nude mice with both 24h and 48h supernatant (2mg/kg) led to a significant decrease in tumor uptake compared with the control group. Conclusion: These results suggest that the culture supernatants of L. acidophilus ATCC4356 at suitable concentrations can be considered as a good alternative nutraceutical with promising therapeutic indexes for breast cancer

Inhibition of leptin gene expression and secretion by silibinin: possible role of estrogen receptors

Leptin plays the role of mitogenic factor in the breast carcinogenesis. Therefore, it could be considered as a target for breast cancer therapy. Leptin gene expression could be modulated by activation of estrogen receptors. Silibinin is an herbal compound with anti-cancer activity on prostate and colorectal cancers. Based on the fact that targeting of leptin can be considered as a novel strategy for breast cancer therapy, the aim of this study was the investigation of potentiality of silibinin for inhibition of leptin gene expression and secretion, and its link with expression of estrogen receptors. Cytotoxic effect of silibinin on T47D breast cancer cells was investigated by MTT assay test after 24, 48 and 72\ua0h treatments with different concentrations of silibinin. The levels of leptin, estrogen receptor α and estrogen receptor β genes expression was measured by reverse-transcription real-time PCR. The amount of secreted leptin in the culture medium was determined by ELISA. Data were statistically analyzed by one-way ANOVA test. Silibinin inhibits growth of T47D cells in a time and dose dependent manner. There was significant difference between control and treated cells in the levels of leptin, estrogen receptor β expression levels and the quantity of secreted leptin was decreased in the treated cells in comparison to control cells. In conclusion, silibinin inhibits the expression and the secretion of leptin and in the future it might probably be a drug candidate for breast cancer therapy through leptin targeting

Multifunctional nanostructures : Intelligent design to overcome biological barriers

Over the past three decades, nanoscience has offered a unique solution for reducing the systemic toxicity of chemotherapy drugs and for increasing drug therapeutic efficiency. However, the poor accumulation and phar-macokinetics of nanoparticles are some of the key reasons for their slow translation into the clinic. The is inti-mately linked to the non-biological nature of nanoparticles and the aberrant features of solid cancer, which together significantly compromise nanoparticle delivery. New findings on the unique properties of tumors and their interactions with nanoparticles and the human body suggest that, contrary to what was long-believed, tumor features may be more mirage than miracle, as the enhanced permeability and retention based efficacy is estimated to be as low as 1%. In this review, we highlight the current barriers and available solutions to pave the way for approved nanoformulations. Furthermore, we aim to discuss the main solutions to solve inefficient drug delivery with the use of nanobioengineering of nanocarriers and the tumor environment. Finally, we will discuss the suggested strategies to overcome two or more biological barriers with one nanocarrier. The variety of design formats, applications and implications of each of these methods will also be evaluated.Peer reviewe