Current clinical trials and patent update on lung cancer: a retrospective review.

Several clinical trials using different interventions are currently being sponsored to combat lung cancer at its different stages. The purpose of this study was to provide a portfolio of those trials. All active, open and recruiting clinical trials registered at ClinicalTrials.gov up to March 2018 were included. Information related to 6092 registered lung cancer trials was downloaded. Phase II trials were in the majority, comprising nearly 48.7% of total clinical trials with industry the major sponsor (41.3%) followed by NIH (12.3%). Multicenter studies were the norm accounting for 47.9% and the main study location was the USA (50.9%). Common interventions were radiation (26%), surgery (22%) and EGFR inhibitors (17%). Patent information includes major patent filing office and sponsors. The data analysis provides a comprehensive description of lung cancer trials.

Curcumin in combination with anti-cancer drugs: A nanomedicine review.

A huge surge of research is being conducted on combination therapy with anticancer compounds formulated in the form of nanoparticles (NPs). Numerous advantages like dose minimalization and synergism, reversal of multi drug resistance (MDRs), enhanced efficacy have emerged with nanoencapsulation of chemotherapeutic agents with chemo-sensitizing agent like curcumin. Within last couple of years various nano-sized formulations have been designed and tested both in vitro with cell lines for different types of cancers and in vivo with cancer types and drug resistance models. Despite the combinatorial models being advanced, translation to human trials has not been as smooth as one would have hoped, with as few as twenty ongoing clinical trials with curcumin combination, with less than 1/10th being nano-particulate formulations. Mass production of nano-formulation based on their physico-chemical and pharmacokinetics deficits poses as major hurdle up the ladder. Combination of these nano-sized dosage with poorly bioavailable drugs, unspecific target binding ability and naturally unstable curcumin further complicates the formulation aspects. Emphasis is now therefore being laid on altering natural forms of curcumin and usage of formulations like prodrug or coating of curcumin to overcome stability issues and focus more on enhancing the pharmaceutical and therapeutic ability of the nano-composites. Current studies and futuristic outlook in this direction are discussed in the review, which can serve as the basis for upcoming research which could boost commercial translational of improved nano-sized curcumin combination chemotherapy.

RodentSQL: a software suite for colony management of animal protocols.

AIM: Animal experiments tend to generate large-scale data. Some existing tools like Microsoft Excel and colony management cloud-based tools are either cumbersome or expensive. There is a need for an inexpensive and uncomplicated colony management software with specific individual database solutions. METHODS: We have developed a database application named RodentSQL to meet most of the requirements of such animal colony management programs. RESULTS: We present a user-friendly secure system for managing records of phenotype, genotype and metadata for comprehensive data analysis and mining. RodentSQL can be altered based upon user needs. We have successfully tested its usage in beta users for managing data of hamsters and mice. CONCLUSION: A central facility can share and benefit from this colony management system. RodentSQL can increase workflow efficiency and data security leading to significant cost savings and enhanced scientific results. RodentSQL is offered to the scientific community as an open source software.

Effects of 5-Hydroxymethylcytosine Epigenetic Modification on the Stability and Molecular Recognition of VEGF i-Motif and G-Quadruplex Structures.

Promoters often contain asymmetric G- and C-rich strands, in which the cytosines are prone to epigenetic modification via methylation (5-mC) and 5-hydroxymethylation (5-hmC). These sequences can also form four-stranded G-quadruplex (G4) or i-motif (iM) secondary structures. Although the requisite sequences for epigenetic modulation and iM/G4 formation are similar and can overlap, they are unlikely to coexist. Despite 5-hmC being an oxidization product of 5-mC, the two modified bases cluster at distinct loci. This study focuses on the intersection of G4/iM formation and 5-hmC modification using the vascular endothelial growth factor (VEGF) gene promoter's CpG sites and examines whether incorporation of 5-hmC into iM/G4 structures had any physicochemical effect on formation, stability, or recognition by nucleolin or the cationic porphyrin, TMPyP4. No marked changes were found in the formation or stability of iM and G4 structures; however, changes in recognition by nucleolin or TMPyP4 occurred with 5-hmC modification wherein protein and compound binding to 5-hmC modified G4s was notably reduced. G4/iM structures in the VEGF promoter are promising therapeutic targets for antiangiogenic therapy, and this work contributes to a comprehensive understanding of their governing principles related to potential transcriptional control and targeting.

Identification and characterization of a new G-quadruplex forming region within the kRAS promoter as a transcriptional regulator.

kRAS is one of the most prevalent oncogenic aberrations. It is either upregulated or mutationally activated in a multitude of cancers, including pancreatic, lung, and colon cancers. While a significant effort has been made to develop drugs that target kRAS, their clinical activity has been disappointing due to a variety of mechanistic hurdles. The presented works describe a novel mechanism and molecular target to downregulate kRAS expression--a previously undescribed G-quadruplex (G4) secondary structure within the proximal promoter acting as a transcriptional silencer. There are three distinct guanine-rich regions within the core kRAS promoter, including a previously examined region (G4near). Of these regions, the most distal region does not form an inducible and stable structure, whereas the two more proximal regions (termed near and mid) do form strong G4s. G4near is predominantly a tri-stacked structure with a discontinuous guanine run incorporated; G4mid consists of seven distinct runs of continuous guanines and forms numerous competing isoforms, including a stable three-tetrad stacked mixed parallel and antiparallel loop structures with longer loops of up to 10 nucleotides. Comprehensive analysis of the regulation of transcription by higher order structures has revealed that the guanine-rich region in the middle of the core promoter, termed G4mid, is a stronger repressor of promoter activity than G4near. Using the extensive guanine-rich region of the kRAS core promoter, and particularly the G4mid structure, as the primary target, future drug discovery programs will have potential to develop a potent, specifically targeted small molecule to be used in the treatment of pancreatic, ovarian, lung, and colon cancers.