Smart Nanoformulations for Brain Cancer Theranostics: Challenges and Promises.

Despite their low prevalence, brain tumors are among the most lethal cancers. They are extremely difficult to diagnose, monitor and treat. Conventional anti-cancer strategies such as radio- and chemotherapy have largely failed, and to date, the development of even a single effective therapeutic strategy against central nervous system (CNS) tumors has remained elusive. There are several factors responsible for this. Brain cancers are a heterogeneous group of diseases with variable origins, biochemical properties and degrees of invasiveness. High-grade gliomas are amongst the most metastatic and invasive cancers, which is another reason for therapeutic failure in their case. Moreover, crossing the blood brain and the blood brain tumor barriers has been a significant hindrance in the development of efficient CNS therapeutics. Cancer nanomedicine, which encompasses the application of nanotechnology for diagnosis, monitoring and therapy of cancers, is a rapidly evolving field of translational medicine. Nanoformulations, because of their extreme versatility and manipulative potential, are emerging candidates for tumor targeting, penetration and treatment in the brain. Moreover, suitable nanocarriers can be commissioned for theranostics, a combinatorial personalized approach for simultaneous imaging and therapy. This review first details the recent advances in novel bioengineering techniques that provide promising avenues for circumventing the hurdles of delivering the diagnostic/therapeutic agent to the CNS. The authors then describe in detail the tremendous potential of utilizing nanotechnology, particularly nano-theranostics for brain cancer imaging and therapy, and outline the different categories of recently developed next-generation smart nanoformulations that have exceptional potential for making a breakthrough in clinical neuro-oncology therapeutics.

Therapeutic potential and critical analysis of trastuzumab and bevacizumab in combination with different chemotherapeutic agents against metastatic breast/colorectal cancer affecting various endpoints.

Researchers are working day and night across the globe to eradicate or at least lessen the menace of cancer faced by the mankind. The two very frequently occurring cancers faced by the human beings are metastatic breast cancer and metastatic colorectal cancer. The various chemotherapeutic agents like anthracycline, cyclophosphamide, paclitaxel, irinotecan, fluorouracil and leucovorin etc., have been used impressively for long. But the obstinate character of metastatic breast cancer and metastatic colorectal cancer needs more to tackle the threat. So, the scientists found the use of monoclonal antibodies trastuzumab (Herceptin(®)) and bevacizumab (Avastin(®)) for the same. The current study critically investigates the therapeutic potential of trastuzumab and bevacizumab in combination with various chemotherapeutic agents against metastatic breast cancer and metastatic colorectal cancer. To the best of our knowledge, this is the very first critical analysis showing percent wise increase in various positive endpoints like median time to disease progression, median survival, and progression free survival etc. for the treatment of metastatic breast/colorectal cancer using trastuzumab and bevacizumab in combination with different chemotherapeutic agents and provides the rational for the success and failure of the selected monoclonal antibodies.

Association of P2X7 A1513C (rs3751143) gene polymorphism with risk of tuberculosis: evidence from a meta-analysis.

AIM: Many case-control studies have been performed in the past to elucidate the association between the P2X7 receptor 1513 A>C (rs3751143) polymorphism and tuberculosis (TB) risk. However, their data interpretation was difficult due to scattered and inconsistent results that led to limited power. In this study, a quantitative summary assessment has been done through meta-analysis to appraise the association between the 1513 A>C polymorphism and TB susceptibility. METHODOLOGY: Systematic assessment was performed for the published studies related with the association between the P2X7 1513 A>C polymorphism and TB risk retrieved from PubMed (Medline), EMBASE search. A meta-analysis was done using a statistical program to evaluate the said association. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for allele contrast, homozygous, heterozygous, dominant, and recessive genetic models. RESULTS: A total of 2710 controls and 2521 TB cases were included in this meta-analysis. Meta-analysis results showed that C allele carrier status was significantly associated with increased TB risk (C vs. A: p=0.001; OR=1.382, 95% CI=1.248-1.531). Significant risk of TB was associated with the homozygous mutant CC (CC vs. AA: p=0.001; OR=1.676, 95% CI=1.251-2.247) and heterozygous AC (AC vs. AA: p=0.001; OR=1.429, 95% CI=1.260-1.621) comparisons. Similarly, dominant (CC vs. AA+AC: p=0.008; OR=1.481, 95% CI=1.109-1.978) and recessive (CC+AC vs. AA: p=0.001; OR=1.458, 95% CI=1.292-1.645) genetic models also revealed increased risk of developing TB. CONCLUSION: We found that the P2X7 1513 A>C gene polymorphism is significantly associated with increased susceptibility to TB. Also, future well-designed epidemiological studies with stratified case-control and biological characterization may be beneficial to validate these findings.