In-silico studies to analyse the possible interactions of CircPPP1R12A translated peptide with Mst proteins.

The Mammalian sterile 20 kinase (Mst) pathway controls organ development by regulating cell proliferation through apoptosis and has a noncanonical role in cancer. Overexpression of the peptide translated from circular RNA, circPPP1R12A, corelated with the activation of YAP, an oncogene whose expression is triggered upon dysregulation of Mst signalling. The exact mode of molecular interaction(s) leading to inactivation of the Mst pathway by this peptide is hitherto unknown. Mst1 and Mst2 are two prime proteins that require dimerization with their scaffold protein, Sav1 at the early step of Mst signalling. We have investigated the interaction of Mst1/2 proteins with this peptide using molecular docking and molecular dynamics simulation studies. The amino acids involved in binding of the peptide were identified and a comparison between the binding interfaces of Mst1/2 - peptide with Mst1/2 - Sav1 complexes indicated that the binding of the peptide to these Mst proteins may prevent the interactions of these proteins with Sav1. Studying the possible binding modes of Sav1 to the Mst proteins already complexed with the peptide further confirmed that the binding of the peptide may hinder their activation. The in-silico study indicated for the first time the possible molecular mechanism of how the peptide can promote cancer by interfering with the Mst pathway.

Characterizations of a novel peptide encoded by a circular RNA using in-silico analyses.

CircRNAs have gained importance in recent times due to their involvement in gene regulation and also in the prognosis of cancer. Generally, the circRNA directly interact with miRNA or RNA binding proteins to exert their action, but some of them can be translated. These translated peptides often participate in the regulation of cellular processes. The circPPP1R12A translated peptide has been shown to influence the functioning of the Mst pathway. The Mst signaling is noteworthy for its role in the process of development, but it also has a function as a regulator of apoptosis, which is significant for regulation of cancer. Overexpression of this novel peptide deactivates the Mst signaling to induce the expression of the proliferative oncogene, Yap. Its molecular interaction with the molecules in the Mst pathway is hitherto unknown. In this short report we present our findings from in-silico studies the plausible structure of the peptide through bioinformatics and dynamics simulation studies. This is the first such report on the structure of the novel peptide encoded by circPPP1R12A, which could be important to predict in future its molecular interactions to understand its functionality.

SIRT1 inhibition-induced senescence as a strategy to prevent prostate cancer progression.

Emerging evidence suggests an important role for SIRT1, a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase in cancer development, progression and therapeutic resistance; making it a viable therapeutic target. Here, we examined the impact of resveratrol-mediated pharmacological activation of SIRT1 on the progression of HGPIN lesions (using the Pten-/- mouse model) and on prostate tumor development (using an orthotopic model of prostate cancer cells stably silenced for SIRT1). We show that precise SIRT1 modulation could benefit both cancer prevention and treatment. Positive effect of SIRT1 activation can prevent Pten deletion-driven development of HGPIN lesions in mice if resveratrol is administered early (pre-cancer stage) with little to no benefit after the establishment of HGPIN lesions or tumor cell implantation. Mechanistically, our results show that under androgen deprivation conditions, SIRT1 inhibition induces senescence as evidenced by decreased gene signature associated with negative regulators of senescence and increased senescence-associated ß-galactosidase activity. Furthermore, pharmacological inhibition of SIRT1 potentiated growth inhibitory effects of clinical androgen receptor blockade agents and radiation. Taken together, our findings provide an explanation for the discrepancy regarding the role of SIRT1 in prostate tumorigenesis. Our results reveal that the bifurcated roles for SIRT1 may occur in stage and context-dependent fashion by functioning in an antitumor role in prevention of early-stage prostate lesion development while promoting tumor development and disease progression post-lesion development. Clinically, these data highlight the importance of precise SIRT1 modulation to provide benefits for cancer prevention and treatment including sensitization to conventional therapeutic approaches.

Application of coke breeze for removal of colour from coke plant wastewater.

Treatment of coking waste water has always been a challenge because of its complex and toxic nature. Numbers of technologies like biological treatment, advanced oxidation processes, activated carbon treatment etc. are available for removal of color and organic contaminants from wastewater. However, challenges and problems associated with application of biological, advanced oxidation methods for removal of color, chemical oxygen demand (COD), cyanides led to thrust for the development of new promising technologies. In this study, the application of coke breeze for the treatment of wastewater through adsorption has been demonstrated. A pseudo second order reaction kinetics has been observed through batch process adsorption study. Furthermore, adsorption data has found to be best fitted with the Freundlich adsorption isotherm model. Color removal efficiency of 80-90% along with COD removal efficiency of 40-50% was observed within 30 min by 120 g/L dosage of the adsorbent. The removal of phenolic and other organic compounds from coking wastewater has been measured through UV-Vis spectroscopy. The morphological changes of the adsorbent coke breeze have been captured through scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) analysis. However, because of the significant abundance in the steel plant, cost effectiveness and applicability of the post-treated coke breeze in sintered plant as fuel, turn it into a suitable adsorbent despite of having much lower specific surface area compared to commercial activated carbon (AC). Therefore, application of the coke breeze turns it into a very promising material and the technique is sustainable towards the coke quenching effluent treatment.

A375 melanoma cells are sensitized to cisplatin-induced toxicity by a synthetic nitro-flavone derivative 2-(4-Nitrophenyl)-4H-chromen-4-one through inhibition of PARP1.

BACKGROUND: Cisplatin has been extensively used in therapeutics for its broad-spectrum anticancer activity and frequently used for the treatment of solid tumors. However, it presents several side-effects and several cancers develop resistance. Combination therapy of cisplatin with poly (ADP-ribose) polymerase 1 (PARP1) inhibitors has been effective in increasing its efficacy at lower doses. METHODS AND RESULTS: In this work, we have shown that the nitro-flavone derivative, 2-(4-Nitrophenyl)-4H-chromen-4-one (4NCO), can improve the sensitivity of cancer cells to cisplatin through inhibition of PARP1. The effect of 4NCO on cisplatin toxicity was studied through combination therapy in both exponential and density inhibited A375 melanoma cells. Combination index (CI) was determined from isobologram analysis. The mechanism of cell killing was assessed by lactate dehydrogenase (LDH) assay. Temporal nicotinamide adenine dinucleotide (NAD+) assay was done to show the inhibition of PARP1. We also performed in silico molecular modeling studies to know the binding mode of 4NCO to a modeled PARP1-DNA complex containing cisplatin-crosslinked adduct. The results from both in silico and in cellulo studies confirmed that PARP1 inhibition by 4NCO was most effective in sensitizing A375 melanoma cells to cisplatin. Isobologram analysis revealed that 4NCO reduced cell viability both in exponential and density inhibited A375 cells synergistically. The combination led to cell death through apoptosis. CONCLUSION: The synthetic nitro-flavone derivative 4NCO effectively inhibited the important nuclear DNA repair enzyme PARP1 and therefore, could complement the DNA-damaging anticancer drug cisplatin in A375 cells and thus, could act as a potential adjuvant to cisplatin in melanoma therapy.

Evidence for 2-Methoxyestradiol-Mediated Inhibition of Receptor Tyrosine Kinase RON in the Management of Prostate Cancer.

2-Methoxyestradiol (2-ME2) possesses anti-tumorigenic activities in multiple tumor models with acceptable tolerability profile in humans. Incomplete understanding of the mechanism has hindered its development as an anti-tumorigenic compound. We have identified for the first-time macrophage stimulatory protein 1 receptor (MST1R) as a potential target of 2-ME2 in prostate cancer cells. Human tissue validation studies show that MST1R (a.k.a RON) protein levels are significantly elevated in prostate cancer tissues compared to adjacent normal/benign glands. Serum levels of macrophage stimulatory protein (MSP), a ligand for RON, is not only associated with the risk of disease recurrence, but also significantly elevated in samples from African American patients. 2-ME2 treatment inhibited mechanical properties such as adhesion and elasticity that are associated with epithelial mesenchymal transition by downregulating mRNA expression and protein levels of MST1R in prostate cancer cell lines. Intervention with 2-ME2 significantly reduced tumor burden in mice. Notably, global metabolomic profiling studies identified significantly higher circulating levels of bile acids in castrated animals that were decreased with 2-ME2 intervention. In summary, findings presented in this manuscript identified MSP as a potential marker for predicting biochemical recurrence and suggest repurposing 2-ME2 to target RON signaling may be a potential therapeutic modality for prostate cancer.

pH-Responsive Vesicle Formation by PEGylated Cholesterol Derivatives: Physicochemical Characterization, Stability, Encapsulation, and Release Study.

PEGylated vesicles are known to serve as blood-persistent drug-delivery systems (DDSs) with potential applications in intravenous drug administration. pH-responsive PEGylated vesicles are also among the most promising stimuli-responsive carriers for drug delivery and controlled release for cancer chemotherapy. Herein, we report design and synthesis of two novel pH-responsive amphiphiles by coupling a cholesterol (Chol) and poly(ethylene glycol) chain with l-cysteine amino acid through hydrolysable linkages. The objective of this work is to physicochemically characterize the nanoaggregates of the amphiphiles under different experimental conditions. We have demonstrated spontaneous vesicle formation by the amphiphiles in water using various spectroscopic, calorimetric, and microscopic techniques. The size of vesicles was observed to increase on reduction of solution pH and increase in amphiphile concentration. The vesicles were found to be sufficiently stable under physiological conditions and were shown to be able to encapsulate not only hydrophilic dyes in their aqueous core but also hydrophobic guest molecules in the bilayer membrane constituted by the Chol units. These nanosized vesicles exhibit pH-triggered release of encapsulated dye molecules in acidic pH. Thus, these spontaneously formed stable vesicles might hold potential as biocompatible DDSs in cancer chemotherapy.

Anticancer activity of a 1,4-dihydropyridine in DMBA-induced mouse skin tumor model.

Antitumor potential of a 1,4-dihydropyridine derivative (DHP-8) has been successfully studied previously in a number of cancer cell lines including the human melanoma cells, A375. In order to validate its anticancer activity, DMBA induced tumor in Swiss Albino mice was considered for this study. DMBA causes skin carcinoma in murine systems and is an important in vivo model for evaluating the efficacy of any new chemical entity against skin cancer. Topical administration of DHP-8 at the dose rate of 33.3 and 50.0 mg/kg body weight showed a significant reduction in tumor parameters. It also prevented the progression and differentiation of squamous cell carcinoma, as evidenced from histopathological studies. Immunohistochemical analysis for the expression of Ki67 indicated that it also reduced cancer cell proliferation. Additionally, it induced apoptosis in the tumor cells by activation of Caspase3. Our results indicated that DHP-8 efficiently attenuated DMBA induced tumor progression and it could be a potent therapeutic agent for skin cancer treatment.

Contextual role of E2F1 in suppression of melanoma cell motility and invasiveness.

The general transcription factor E2F1 reportedly functions in a protumorigenic manner in several cancer models. We show that the genetic context of cancer cells influence E2F1's role to impede the protumorigenic role. Thirty to fifty percent of melanoma patients carry mutant BRAF with about 90% of mutant BRAF melanomas being V600E mutation. Tissue microarrays from melanoma patients were used to establish an association between E2F1 and BRAFV600E . We show for the first time that low E2F1 levels in BRAFV600E melanomas are associated with lymph node metastasis. Genetic manipulation of E2F1 in BRAFV600E and BRAFwt cells were used to determine its role in malignant melanoma progression by examining effects on migration and invasion. E2F1-mediated negative regulation of myosin light chain kinase (MYLK) increased migration and invasion in BRAFV600E cells by phosphorylating myosin light chain and increased stress fiber formation. We show that E2F1 inhibits extracellular signal-regulated kinase (ERK) activation in BRAFV600E cells and provide evidence for a negative feedback loop between E2F1 and ERK in these cells. This study shows for the first time that E2F1 has a cancer protective role in oncogenic BRAF-activated melanoma cells and that loss of E2F1 can allow disease progression through a novel mechanism of E2F1-mediated MYLK regulation. This study has implications for oncogenic BRAF-activated tumors and resistance to targeted oncogenic BRAF therapy.

Receptor tyrosine kinase recepteur d'origine nantais as predictive marker for aggressive prostate cancer in African Americans.

Published evidence shows a correlation between several molecular markers and prostate cancer (PCa) progression including in African Americans (AAs) who are disproportionately affected. Our early detection efforts led to the identification of elevated levels of antiapoptotic protein, c-FLIP and its upstream regulatory factors such as androgen receptor (AR), recepteur d'origine nantais (RON), a receptor tyrosine kinase in human prostate tumors. The primary objective of this study was to explore whether these markers play a role in racial disparities using immunohistochemistry in prostatectomy samples from a cohort of AA, Hispanic Whites (HWs), and non-Hispanic Whites (NHWs). Bivariable and multivariable logistic regression analyses were used to identify a statistical association between molecular markers, possible correlation with risk factors including race, obesity, prostate-specific antigen (PSA) and disease aggressiveness. Further, changes in the levels and expression of these molecular markers were also evaluated using human PCa cell lines. We found significantly elevated levels of RON ( P = 0.0082), AR ( P = 0.0001), c-FLIP ( P = 0.0071) in AAs compared with HWs or NHWs. Furthermore, a higher proportion of HW and NHWs had a high Gleason score (>6) but not PSA as compared to AAs ( P = 0.032). In summary, our findings suggest that PSA was important in predicting aggressive disease for the cohort overall; however, high levels of RON may play a role in predisposing AA men to develop aggressive disease. Future research is needed using large datasets to confirm these findings and to explore whether all or any of these markers could aid in race-specific stratification of patients for treatment.

Self-Assembly of Unconventional Low-Molecular-Mass Amphiphiles Containing a PEG Chain.

The design and synthesis of biocompatible surfactants are important for a wide range of applications in cosmetics, personal care products, and nanomedicine. This feature article summarizes our studies over the past 8 years on the design, synthesis, surface activity, and self-assembly of a series of unconventional low-molecular-mass amphiphiles containing a poly(ethylene glycol) (PEG) tail or spacer and different ionic or zwitterionic headgroups, including carboxylate, sulfonate, and quaternary ammonium salts. Despite having a so-called polar PEG chain as a tail or spacer, these ionic amphiphiles are found to have a tendency to adsorb at the air/water interface and self-assemble in pH 7.0 buffers at 298 K in the same way that conventional hydrocarbon tail surfactants do. However, they are observed to be relatively less surface-active compared to hydrocarbon tail surfactants. Although these amphiphilic molecules have less surface activity, they do self-assemble in aqueous buffer at 298 K, producing a range of microstructures, including spherical micelles, disclike micelles, and vesicles. In fact, our group is the first to report the self-assembly of PEG-tailed ionic amphiphiles in water at room temperature. Some of these molecules are also found to gel various organic liquids on heat-cool treatment or by ultrasound irradiation. We think that the present article will arouse general interest among researchers working toward the development of new biocompatible amphiphiles and soft materials.

Novel 1,4-dihydropyridine induces apoptosis in human cancer cells through overexpression of Sirtuin1.

1,4-Dihydropyridines (1,4-DHPs) are important as a class of heterocyclic compounds that exhibit wide range of biological actions. Many of its derivatives are already characterized as medicinally important drugs and used worldwide. In this study, we have screened some novel Hantzsch 1,4-DHP compounds using both in silico (QSAR and Pharmacophore) and in vitro (cytotoxic screening). 1,4-DHP showed selective cytotoxicity against five human cancerous cell lines; A375, A549, HeLa, HepG2 and SH-SY5Y but limited effect towards normal skin keratinocyte (HaCaT), lung fibroblast (WL-38) and healthy peripheral blood mononuclear cells. In A375 and HepG2 cells, one of the 1,4-DHP derivative (DHP-8) was found to inhibit cell proliferation, and simultaneously increased the apoptotic population as well as mitochondrial membrane depolarization. Furthermore, the mitochondrial signal was triggered with the activation of cleaved Caspase9, Caspase3 and PARP. The treatment with DHP-8 also increased the expression level of SIRT1, subsequently decreasing the level of pAKTser473 and survivin. Reduced pAKTser473 expression led to decrease the phosphorylated inactive form of GSK3ßser9 and as a result, proteasomal degradation of Mcl-1 occurred in both the cell lines. Here, we suggest that the apoptotic effect of DHP-8 in A375 and HepG2 cells was mediated by AKT and survivin pathways through SIRT1 activation. The involvement of DHP-8 in SIRT1 activation was further verified by co-treatment of nicotinamide with DHP-8 in both A375 and HepG2 cells. Overall, this study emphasizes the possible potential and therapeutic role of DHP-8 in skin and liver cancer.

BRCA1 Interacting Protein COBRA1 Facilitates Adaptation to Castrate-Resistant Growth Conditions.

COBRA1 (co-factor of BRCA1) is one of the four subunits of the negative elongation factor originally identified as a BRCA1-interacting protein. Here, we provide first-time evidence for the oncogenic role of COBRA1 in prostate pathogenesis. COBRA1 is aberrantly expressed in prostate tumors. It positively influences androgen receptor (AR) target gene expression and promoter activity. Depletion of COBRA1 leads to decreased cell viability, proliferation, and anchorage-independent growth in prostate cancer cell lines. Conversely, overexpression of COBRA1 significantly increases cell viability, proliferation, and anchorage-independent growth over the higher basal levels. Remarkably, AR-positive androgen dependent (LNCaP) cells overexpressing COBRA1 survive under androgen-deprivation conditions. Remarkably, treatment of prostate cancer cells with well-studied antitumorigenic agent, 2-methoxyestradiol (2-ME2), caused significant DNA methylation changes in 3255 genes including COBRA1. Furthermore, treatment of prostate cancer cells with 2-ME2 downregulates COBRA1 and inhibition of prostate tumors in TRAMP (transgenic adenocarcinomas of mouse prostate) animals with 2-ME2 was also associated with decreased COBRA1 levels. These observations implicate a novel role for COBRA1 in progression to CRPC and suggest that COBRA1 downregulation has therapeutic potential.

Food-based natural products for cancer management: Is the whole greater than the sum of the parts?

The rise in cancer incidence and mortality in developing countries together with the human and financial cost of current cancer therapy mandates a closer look at alternative ways to overcome this burgeoning global healthcare problem. Epidemiological evidence for the association between cancer and diet and the long latency of most cancer progression have led to active exploration of whole and isolated natural chemicals from different naturally occurring substances in various preclinical and clinical settings. In general the lack of systemic toxicities of most 'whole' and 'isolated' natural compounds, their potential to reduce toxic doses and potential to delay the development of drug-resistance makes them promising candidates for cancer management. This review article examines the suggested molecular mechanisms affected by these substances focusing to a large extent on prostate cancer and deliberates on the disparate results obtained from cell culture, preclinical and clinical studies in an effort to highlight the use of whole extracts and isolated constituents for intervention. As such these studies underscore the importance of factors such as treatment duration, bioavailability, route of administration, selection criteria, standardized formulation and clinical end points in clinical trial design with both entities. Overall lack of parallel comparison studies between the whole natural products and their isolated compounds limits decisive conclusions regarding the superior utility of one over the other. We suggest the critical need for rigorous comparative research to identify which one of the two or both entities from nature would be best qualified to take on the mantle of cancer management.

Combination of Nexrutine and docetaxel suppresses NFκB-mediated activation of c-FLIP.

Lack of effective options following failure to conventional chemotherapeutic agent such as Docetaxel (DX) is a major clinical challenge in the management of prostate cancer. These observations underscore the need for deciphering the underlying mechanism of DX resistance to enable the development of effective therapeutic approaches. We observed up regulation of the anti-apoptotic protein c-FLIP and its up stream regulators including receptor tyrosine kinase RON and transcription factor NFκB (p65) in tumors obtained from metastatic prostate cancer patients. We also observed significant downregulation of these molecules in prostate tumors isolated from patients treated with DX as first line therapy. Further, we identified the over the counter anti-inflammatory agent, Nexrutine (NX) suppresses c-FLIP protein levels, and expression in androgen-independent prostate cancer cells (PC-3). Remarkably, the observed decreased levels of c-FLIP were further reduced in combination with DX. Transient expression assays coupled with electrophoretic mobility shift and DNA affinity protein assay revealed that NX and DX suppresses c-FLIP promoter activity by preventing p65 binding. Notably, NX in combination with DX abolished binding of p65 to the c-FLIP promoter sequence containing NFκB binding sites. Biologically, these alterations resulted in reduced growth of PC-3 cells. Taken together, these observations suggest the utility of RON, p65, and c-FLIP as potential markers to predict response to DX treatment. Furthermore, our results also identified NX as an agent to potentiate the therapeutic response of DX by suppressing activation of c-FLIP and its upstream regulators.

Downregulation of STAT3/NF-κB potentiates gemcitabine activity in pancreatic cancer cells.

There is an unmet need to develop new agents or strategies against therapy resistant pancreatic cancer (PanCA). Recent studies from our laboratory showed that STAT3 negatively regulates NF-κB and that inhibition of this crosstalk using Nexrutine® (Nx) reduces transcriptional activity of COX-2. Inhibition of these molecular interactions impedes pancreatic cancer cell growth as well as reduces fibrosis in a preclinical animal model. Nx is an extract derived from the bark of Phellodendron amurense and has been utilized in traditional Chinese medicine as antidiarrheal, astringent, and anti-inflammatory agent for centuries. We hypothesized that "Nx-mediated inhibition of survival molecules like STAT3 and NF-κB in pancreatic cancer cells will improve the efficacy of the conventional chemotherapeutic agent, gemcitabine (GEM)." Therefore, we explored the utility of Nx, one of its active constituents berberine and its derivatives, to enhance the effects of GEM. Using multiple human pancreatic cancer cells we found that combination treatment with Nx and GEM resulted in significant alterations of proteins in the STAT3/NF-κB signaling axis culminating in growth inhibition in a synergistic manner. Furthermore, GEM resistant cells were more sensitive to Nx treatment than their parental GEM-sensitive cells. Interestingly, although berberine, the Nx active component used, and its derivatives were biologically active in GEM sensitive cells they did not potentiate GEM activity when used in combination. Taken together, these results suggest that the natural extract, Nx, but not its active component, berberine, has the potential to improve GEM sensitivity, perhaps by down regulating STAT3/NF-κB signaling. © 2016 Wiley Periodicals, Inc.

Vesicle-to-Micelle Transition in Aqueous Solutions of l-Cysteine-Derived Carboxylate Surfactants Containing Both Hydrocarbon and Poly(ethylene glycol) Tails.

In our recent reports, we have shown that when a poly(ethylene glycol) (PEG) chain is covalently linked to any ionic group, the resultant molecule behaves like an amphiphile. Depending upon the nature of ionic head groups, they self-assemble to form micelles or vesicles, in which the PEG chain constitutes the micellar core or vesicle bilayer. In this study, we intend to examine what happens when both hydrocarbon (HC) and PEG chains are attached to a carboxylate head group. Therefore, we have synthesized two novel amphiphiles in which a PEG and a HC chain is covalently linked to l-cysteine. The surface activities and the solution behavior of the sodium salts of these amphiphiles were investigated at neutral pH. The amphiphiles self-organize to form large unilamellar vesicles in dilute solutions, which transformed into small micelles at higher concentrations. The HC chains of the molecules have been shown to constitute the bilayer membrane of the vesicles and core of micelles. In acidic pH, the amphiphiles were found to form large disklike micelles. The thermodynamic parameters of self-assembly formation were also measured by isothermal titration calorimetry. The vesicle and micelle formation was found to be spontaneous and thermodynamically favorable. The thermal stability of the micelles at neutral and acidic pH was studied. The addition of cholesterol was observed to increase the physical stability of vesicles.

An Unconventional Zwitterionic Bolaamphiphile Containing PEG as Spacer Chain: Surface Tension and Self-Assembly Behavior.

Monolayer lipid membrane formation based on self-assembly of bolaamphiphiles containing hydrophobic spacer are well-established in the literature, but monolayer vesicle formation by so-called hydrophilic poly(ethylene glycol) (PEG) spacer has not been reported to date. Here, a novel l-cysteine-derived bolaamphiphile with PEG as spacer has been developed and characterized. The interfacial properties and the solution behavior of the amphiphile were investigated in pH 7.0 at 25 °C. The self-assembly properties of the bolaamphiphile in aqueous buffer were investigated by using different techniques, such as surface tensiometry, fluorescence spectroscopy, UV-vis spectroscopy, isothermal titration calorimetry, dynamic light scattering, transmission electron microscopy, and atomic force microscopy. Surprisingly, despite having so-called polar spacer in between two polar head groups, it exhibits formation of microstructures in aqueous buffer as well as in water at 25 °C. The molecule undergoes self-organization leading to the formation of monolayer vesicles with hydrodynamic diameters between 100 and 250 nm in a wide range of concentration. The thermodynamic parameters clearly suggest that the aggregate formation is mainly driven by the hydrophobic effect. The monolayer vesicles were found to form at a very low concentration (≥0.63 mM) and within a wide pH range (2-10). The vesicles exhibit excellent shelf life at physiological temperature.

Effect of radiofrequency radiation in cultured mammalian cells: A review.

The use of mobile phone related technologies will continue to increase in the foreseeable future worldwide. This has drawn attention to the probable interaction of radiofrequency electromagnetic radiation with different biological targets. Studies have been conducted on various organisms to evaluate the alleged ill-effect on health. We have therefore attempted to review those work limited to in vitro cultured cells where irradiation conditions were well controlled. Different investigators have studied varied endpoints like DNA damage, cell cycle arrest, reactive oxygen species (ROS) formation, cellular morphology and viability to weigh the genotoxic effect of such radiation by utilizing different frequencies and dose rates under various irradiation conditions that include continuous or pulsed exposures and also amplitude- or frequency-modulated waves. Cells adapt to change in their intra and extracellular environment from different chemical and physical stimuli through organized alterations in gene or protein expression that result in the induction of stress responses. Many studies have focused on such effects for risk estimations. Though the effects of microwave radiation on cells are often not pronounced, some investigators have therefore combined radiofrequency radiation with other physical or chemical agents to observe whether the effects of such agents were augmented or not. Such reports in cultured cellular systems have also included in this review. The findings from different workers have revealed that, effects were dependent on cell type and the endpoint selection. However, contradictory findings were also observed in same cell types with same assay, in such cases the specific absorption rate (SAR) values were significant.

To be an ally or an adversary in bladder cancer: the NF-κB story has not unfolded.

Signaling and regulation of transcription factor nuclear factor-kappaB (NF-κB) has been an area of extensive research since its first discovery nearly three decades ago. Members of the NF-κB family have been reported to critically mediate a multitude of responses in normal cells. Therefore, it is not surprising that NF-κB function can go awry and result in pathological conditions including cancer. Despite its critical importance, the functional role of NF-κB has not received the same attention in cancers of all tissue types. In the case of cancer of the urinary bladder, which is the second most common urologic cancer, the involvement of NF-κB in the development of superficial or muscle invasive disease and during cancer recurrence is rudimentary at best. Nuclear expression of p65/RelA is seen in bladder cancer patients and has been found to negatively affect survival of patients with superficial and muscle invasive disease. Despite these observations, the exact mechanism of NF-κB upregulation and function remains unknown. Furthermore, the emergence of a tumor suppressive role for NF-κB in recent years suggests that the family may play the role of a double-edged sword in cancer, which remains unexplored in bladder cancer. The challenge now is to delineate the increasing complexity of this pathway in the development and progression of bladder cancer. Here, we review key aspects of the current knowledge of signaling and regulation by the NF-κB family focusing on its controversial role in cancer and highlight the importance of studying NF-κB in bladder cancer in particular.