76 research outputs found
Abstract 5818: Disrupting the Aurora kinase A interactome in pediatric cancer
No full textAbstract
Neuroblastoma is the most common extra-cranial solid tumor of childhood. Amplification of the MYCN proto-oncogene occurs in 50% of the high-risk neuroblastoma and indicates an aggressive and lethal form of the disease. As a transcription factor with no apparent small-molecule surfaces, direct inhibition of MYCN has proven challenging. Proteolytic cleavage of MYCN is regulated in part by an activity-independent scaffold function of Aurora Kinase A (AURKA). The dynamic expression and activation of AURKA allows for precise cell cycle regulation of several substrates identified by protein-protein interaction studies that are also viable anti-cancer targets, such as the aforementioned MYCN oncoprotein. Utilizing co-immunopreciptation, flow cytometry, and other pertinent cell biology techniques, we aim to delineate a novel mechanism of targeting the AURKA interactome by conformation disruption of AURKA. We have recently described a neoteric class of confirmation disrupting “amphosteric” inhibitors of AURKA (CD-AURKAi) that orthosterically inhibit the ATP-binding pocket to dramatically disrupt the active conformation of AURKA to dissociate and degrade MYCN, a critical oncogenic driver of the pediatric cancer neuroblastoma. In addition to MYCN, our preliminary results show CD532 will also dissociate other oncogenic proteins that interact with AURKA. We hypothesize that conformation disruption of AURKA and subsequent blockade of an array of protein-protein interactions will delineate the roles of AURKA, MYC, and MYCN in the cell cycle and expand the clinical applications for CD-AURKAi in cancer to include non-MYCN driven diseases.
Citation Format: Sucheta Mukherjee, Carolyn Tu, Clay Gustafson. Disrupting the Aurora kinase A interactome in pediatric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5818. doi:10.1158/1538-7445.AM2017-5818</jats:p
A study evaluating the effect of mifepristone (RU-486) for the treatment of leiomyomata uteri
No full textMorphotectonics and resultant features in Kaliani River Basin (Assam)
Get PDFThe surficial structure and impressions upon the crust due to endogenetic and exogenetic mechanisms are witnessed all around us. These landforms have evolved as a result of plate movements, subsidence, upliftment and various erosional processes. This concept can be collectively referred to as morphotectonics of any region and can be used as a key to understand its genesis as well as present physical state. Morphotectonics refers to forms and shapes that have evolved in the past or in recent times as a result of past or recent tectonic activity. The most vivid evidences of past tectonic activity can be assessed through drainage lines, in any area which are guided and controlled by physical structures over which they flow.</jats:p
Morphotectonics and resultant features in Kaliani River Basin (Assam) / Ação Morfotectonica e Paisagens Resultantes na Bacia Hidrográfica de Kaliani (Assam)
Get PDFThe surficial structure and impressions upon the crust due to endogenetic and exogenetic mechanisms are witnessed all around us. These landforms have evolved as a result of plate movements, subsidence, upliftment and various erosional processes. This concept can be collectively referred to as morphotectonics of any region and can be used as a key to understand its genesis as well as present physical state. Morphotectonics refers to forms and shapes that have evolved in the past or in recent times as a result of past or recent tectonic activity. The most vivid evidences of past tectonic activity can be assessed through drainage lines, in any area which are guided and controlled by physical structures over which they fl o
Morphotectonics and resultant features in Kaliani River Basin (Assam) / Ação Morfotectonica e Paisagens Resultantes na Bacia Hidrográfica de Kaliani (Assam)
Get PDFThe surfi cial structure and impressions upon the crust due to endogenetic and exogenetic mechanisms
are witnessed all around us. These landforms have evolved as a result of plate movements, subsidence,
upliftment and various erosional processes. This concept can be collectively referred to as morphotectonics
of any region and can be used as a key to understand its genesis as well as present physical state.
Morphotectonics refers to forms and shapes that have evolved in the past or in recent times as a result of
past or recent tectonic activity. The most vivid evidences of past tectonic activity can be assessed through
drainage lines, in any area which are guided and controlled by physical structures over which they fl o
How cyanobacterial signalling system behaves in different media component with time? - a Genomics and Transcriptomics approach
No full textStimuli-responsive release-active dressing: A promising solution for eradicating biofilm-mediated wound infections
No full textBiofilm-mediated wound infections pose a significant challenge due to the limitations of conventional antibiotics, which often exhibit narrow-spectrum activity, fail to eliminate recurrent bacterial contamination, and are unable to penetrate the biofilm matrix. While the search for alternatives has explored the use of metal nanoparticles and synthetic biocides, these solutions often suffer from unintended toxicity to surrounding tissues and lack controlled administration and release. In this study, we engineered a pH-responsive release-active dressing film based on carboxymethyl cellulose, incorporating a synthetic antibacterial molecule (SAM-17). The dressing film exhibited optimal mechanical stability for easy application and demonstrated excellent fluid absorption properties, allowing for prolonged moisturization at the site of injury. The film exhibited pH-dependent release of cargo, with 78% release within 24 h at acidic pH, enabling targeted antibacterial drug delivery within the wound microenvironment. Furthermore, the release-active film effectively eliminated repeated challenges of bacterial contamination. Remarkably, the film demonstrated a minimal toxicity profile in both in vitro and in vivo models. The film eliminated preformed bacterial biofilms, achieving a reduction of 2.5 log against methicillin-resistant Staphylococcus aureus (MRSA) and 4.1 log against vancomycin-resistant S. aureus (VRSA). In a biofilm-mediated MRSA wound infection model, this release-active film eradicated the biofilm-embedded bacteria by over 99%, resulting in accelerated wound healing. These findings highlight the potential of this film as an effective candidate for tackling biofilm-associated wound infections
Multifunctional suture coating for combating surgical site infections and mitigating associated complications
No full textDespite advancements in preventive measures and hospital protocols, surgical site infections (SSIs) remain a significant concern following surgeries. Sutures, commonly used for wound closure, can serve as a platform for microbial adherence and contamination, leading to extensive debridement and recurrent antibiotic therapy. The emergence of drug resistance and the formation of biofilms on sutures have further complicated the management of SSIs. Drug-eluting sutures incorporating biocides like triclosan have limitations due to uncontrolled release and associated toxicity. Therefore, there is a need for alternative approaches to impart antimicrobial properties to sutures. In this study, we present a one-step covalent cross-linking method to coat surgical sutures with an antimicrobial small molecule, quaternary benzophenone-based antimicrobial (QSM). Additionally, the sutures are dip-coated with ibuprofen, a nonsteroidal anti-inflammatory drug with analgesic properties. The coated sutures maintained their morphological and tensile properties after in vivo implantation. The antimicrobial coating demonstrated efficacy against a broad-spectrum pathogens, including drug-resistant bacteria and fungi. The optimized formulation retained its biodegradability in vivo. Furthermore, the coated sutures exhibited ∼3 log reduction in methicillin-resistant Staphylococcus aureus (MRSA) burden in a subcutaneous implantation mouse model. Overall, this multifunctional coating provides antimicrobial properties to surgical sutures while preserving their mechanical integrity and biodegradability. These coated sutures have the potential to address the challenge of SSIs and contribute to improved surgical outcomes
Clinico- Pathological profiling of Emergency Adolescent Gynecological Problems: A Six Months Retrospective Study
Get PDFBackground: India is one of the fastest growing countries and is home for more than 243 million adolescents. Adolescent gynecological problem needs careful and important attention as it has immense implication on future reproductive and personal health of women.Objective(s): To study the profile of adolescent girls, seeking in patient treatment for emergency gynecological problems.Method(s): A total of 294 adolescent girls admitted for inpatient treatment for their emergency gynecological problems. Meticulous history taking, examination and investigations were done.Results: 294 adolescent girls attended emergency for in- patient treatment in the study period (July 2014 – December 2014). Patients with pregnancy related complications [230, (78%)] outnumbered the patients having gynecological problems [64 (22%)]. Among pregnancy related complications, incomplete abortion [104, 35%] was the single most common cause for hospital admission, seeking inpatient treatment whereas among gynecological causes, menorrhagia [18, 6%] was most common cause.Conclusion: Adolescent gynecology needs increased awareness and greater attention in order to protect and promote the health of teenagers with the help of specialized adolescent clinic. Measures should be taken to prevent teenage pregnancy and unwanted pregnancy
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