Publications by authors named "Vasan N"

Colorectal cancer (CRC) remains a leading cause of cancer death due to metastatic spread. LIN28B is overexpressed in 30% of CRCs and promotes metastasis, yet its mechanisms remain unclear. In this study, we genetically modified CRC cell lines to overexpress LIN28B, resulting in enhanced PI3K/AKT pathway activation and liver metastasis in mice.

View Article and Find Full Text PDF

Introduction Effective postoperative analgesia following lower segment cesarean section (LSCS) is crucial for promoting surgical recovery and fostering maternal-neonatal bonding. This study aimed to compare the efficacy of two IV dexamethasone doses (8 mg and 4 mg) in managing postoperative pain in LSCS patients. The objective was to assess whether the 4 mg dose provides comparable pain relief to the 8 mg dose, with the goal of identifying the optimal dosage for effective pain management with minimal side effects.

View Article and Find Full Text PDF

Introduction: Approximately 20% of patients living with colorectal cancer (CRC) have activating mutations in their tumors in the PIK3CA oncogene. Two or more activating mutations (multi-hit) for the PIK3CA allele increase PI3K⍺ signaling compared to single-point mutations, resulting in exceptional response to PI3K⍺ inhibition. We aimed to identify the prevalence of PIK3CA multi-hit mutations in metastatic CRC to identify patients who may benefit from PI3K inhibitors.

View Article and Find Full Text PDF

Background: Tumors harboring two or more PIK3CA short variant (SV) ("multi-hit") mutations have been linked to improved outcomes with anti-PIK3CA-targeted therapies in breast cancer. The landscape and clinical implications of multi-hit PIK3CA alterations in clinically advanced prostate cancer (CAPC) remains elusive.

Objective: To evaluate the genomic landscape of single-hit and multi-hit PIK3CA genomic alterations in CAPC.

View Article and Find Full Text PDF

Purpose: Medication nonadherence is common among patients with breast cancer (BC) and increases BC mortality and complications from comorbidities. There is growing interest in mobile health interventions such as smartphone applications (apps) to promote adherence.

Methods: Use of Medisafe, a medication reminder and tracking app, was tested over 12 weeks among patients on BC treatment and at least one oral medication.

View Article and Find Full Text PDF

In their recent paper published in Nature, Luo et al. investigate the cancer-cell-intrinsic roles of the PI3Kγ complex in leukemia. Their findings pinpoint PI3Kγ inhibition as a possible novel treatment avenue for a subset of acute leukemias.

View Article and Find Full Text PDF

Single-nucleotide variants (SNVs) in key T cell genes can drive clinical pathologies and could be repurposed to improve cellular cancer immunotherapies. Here, we perform massively parallel base-editing screens to generate thousands of variants at gene loci annotated with known or potential clinical relevance. We discover a broad landscape of putative gain-of-function (GOF) and loss-of-function (LOF) mutations, including in PIK3CD and the gene encoding its regulatory subunit, PIK3R1, LCK, SOS1, AKT1 and RHOA.

View Article and Find Full Text PDF

Phosphorylation of proteins on tyrosine (Tyr) residues evolved in metazoan organisms as a mechanism of coordinating tissue growth. Multicellular eukaryotes typically have more than 50 distinct protein Tyr kinases that catalyse the phosphorylation of thousands of Tyr residues throughout the proteome. How a given Tyr kinase can phosphorylate a specific subset of proteins at unique Tyr sites is only partially understood.

View Article and Find Full Text PDF

Objective: This study aimed to solve the debate over the role and extent of neck dissection to treat any occult nodal metastasis in patients undergoing salvage laryngectomy for recurrent and/or residual squamous cell carcinoma of larynx.

Methods: This was a retrospective study over a time frame of 6 years (2016-2022) of 74 patients who underwent bilateral neck dissection and salvage laryngectomy for recurrent or persistent disease with N0 neck. We calculated the incidence of occult nodal metastasis in ipsilateral and contralateral neck.

View Article and Find Full Text PDF

Base editing enables generation of single nucleotide variants, but large-scale screening in primary human T cells is limited due to low editing efficiency, among other challenges . Here, we developed a high-throughput approach for high-efficiency and massively parallel adenine and cytosine base-editor screening in primary human T cells. We performed multiple large-scale screens editing 102 genes with central functions in T cells and full-length tiling mutagenesis of selected genes, and read out variant effects on hallmarks of T cell anti-tumor immunity, including activation, proliferation, and cytokine production.

View Article and Find Full Text PDF

The climate crisis is upon us, already exacting a health cost, with likely acceleration over our lifetimes. Our existing medical curricula do not adequately prepare medical students to deal with climate health nor to be leaders in the public health sphere. Current faculty have themselves not often been exposed to climate health training nor often to leadership training.

View Article and Find Full Text PDF

Goiter with substernal extension is common, with a reported incidence of up to 20% in patients undergoing thyroidectomy. It has been shown that the vast majority of substernal goiters can be removed through a cervical incision. However, if this is not possible, a sternotomy is usually required, which could add significant morbidity to an otherwise routine operation.

View Article and Find Full Text PDF

The phosphoinositide 3-kinase p110α is an essential mediator of insulin signaling and glucose homeostasis. We interrogated the human serine, threonine, and tyrosine kinome to search for novel regulators of p110α and found that the Hippo kinases phosphorylate p110α at T1061, which inhibits its activity. This inhibitory state corresponds to a conformational change of a membrane-binding domain on p110α, which impairs its ability to engage membranes.

View Article and Find Full Text PDF

This is the first peer-reviewed report of an allosteric, mutant-selective PI3Kα inhibitor, STX-478, that reduces PIK3CA-mutant tumor growth in mice. However, in contrast to the FDA-approved PI3Kα isoform-selective inhibitor alpelisib, STX-478 does not induce hyperglycemia or other metabolic dysfunctions. See related article by Buckbinder et al.

View Article and Find Full Text PDF

The medical humanities, an umbrella term for the fields of ethics, social science, and fine arts, are increasingly recognized as an important component of medical education. Since the Flexner report, the primacy of science and evidence-based medicine has replaced subjectivity and nuance. While this has been critical for standardization of care and patient safety, an exclusive emphasis on science in undergraduate medical education can devalue more humanistic pursuits.

View Article and Find Full Text PDF

The cell-autonomous balance of immune-inhibitory and -stimulatory signals is a critical process in cancer immune evasion. Using patient-derived co-cultures, humanized mouse models, and single-cell RNA-sequencing of patient melanomas biopsied before and on immune checkpoint blockade, we find that intact cancer cell-intrinsic expression of CD58 and ligation to CD2 is required for anti-tumor immunity and is predictive of treatment response. Defects in this axis promote immune evasion through diminished T cell activation, impaired intratumoral T cell infiltration and proliferation, and concurrently increased PD-L1 protein stabilization.

View Article and Find Full Text PDF

We present a case of an adult with concurrent severe aortic coarctation, bilateral carotid artery stenosis, and anomalous right subclavian artery, posing the interventional dilemma of accepting potential cerebral hyperperfusion syndrome vs hypoperfusion ischemic injury. Transcatheter stenting of the aortic coarctation was successfully performed without any neurological deficits. ().

View Article and Find Full Text PDF
Article Synopsis
  • Protein phosphorylation is a major biological process, with over 90,000 phosphorylation sites identified and linked to various human diseases.
  • Researchers analyzed the substrate specificity of 303 Ser/Thr kinases in humans, revealing a diverse range of preferences and the role of negative selectivity in their activity.
  • The findings provide insights into cellular signaling pathways, identify kinases responsible for phosphorylation events, and enhance our understanding of biological processes affected by various stimuli.
View Article and Find Full Text PDF

Purpose: To comprehensively characterize tissue-specific and molecular subclasses of multiple PIK3CA (multi-PIK3CA) mutations and assess their impact on potential therapeutic outcomes.

Experimental Design: We profiled a pan-cancer cohort comprised of 352,392 samples across 66 tumor types using a targeted hybrid capture-based next-generation sequencing panel covering at least 324 cancer-related genes. Molecularly defined subgroups, allelic configuration, clonality, and mutational signatures were identified and tested for association with PI3K inhibitor therapeutic response.

View Article and Find Full Text PDF

Partial anomalous pulmonary venous return (PAPVR) is a rare congenital cardiovascular condition in which some of the pulmonary veins drain into the systemic circulation. We report on the cadaveric dissection of a 71-year-old Caucasian male donor who died of chronic obstructive pulmonary disease with hypertension. We noted a faint incisional scar on the thorax extending from the parasternal region at the 4th intercostal level to the midaxillary line.

View Article and Find Full Text PDF

Mucoepidermoid carcinoma (MEC) and sclerosing MEC with eosinophilia (SMECE) are rare primary thyroid carcinomas. In this study, we aimed to present our multicenter series of MEC and SMECE and integrated our data with published literature to further investigate the clinicopathological characteristics and prognoses of these tumors. We found 2 MECs and 4 SMECEs in our multicenter archives.

View Article and Find Full Text PDF

Unlabelled: Although many digital mental health interventions are available, clinicians do not routinely use them in clinical practice. In this pilot survey, we review the factors that supported the rapid transition to televisits during the COVID-19 pandemic, and we explore the barriers that continue to prevent clinicians from using other digital mental health interventions, such as mindfulness applications, mood trackers, and digital therapy programs. We conducted a pilot survey of mental health clinicians in different practice environments in the USA.

View Article and Find Full Text PDF

Numerous agents targeting various phosphatidylinositol 3-kinase (PI3K) pathway components, including PI3K, AKT and mTOR, have been tested in oncology clinical trials, resulting in regulatory approvals for the treatment of selected patients with breast cancer, certain other solid tumours or particular haematological malignancies. However, given the prominence of PI3K signalling in cancer and the crucial role of this pathway in linking cancer growth with metabolism, these clinical results could arguably be improved upon. In this Review, we discuss past and present efforts to overcome the somewhat limited clinical efficacy of PI3Kα pathway inhibitors, including optimization of inhibitor specificity, patient selection and biomarkers across cancer types, with a focus on breast cancer, as well as identification and abrogation of signalling-related and metabolic mechanisms of resistance, and interventions to improve management of prohibitive adverse events.

View Article and Find Full Text PDF

Robotic assistance technologies are being incorporated into minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) to minimize radiation exposure to the patient and operating staff. However, they introduce new issues including increased operating time and difficult incorporation into surgical workflow. This study, conducted with 42 patients under the care of one neurosurgeon in Sydney, Australia, investigates the operating time increase with three different robotic modalities, and the learning curves they pose to the surgeon.

View Article and Find Full Text PDF

De novo metastatic breast cancer (dnMBC) represents a minority of MBC cases, and as such, its genomics are poorly understood. Characterizing the genomics of dnMBC represents an opportunity to delineate metastatic drivers in the absence of treatment selection. In this review, we first summarize the literature of the genomics of MBC which showed that MBCs have greater mutational burden than early stage, treatment naïve breast cancers.

View Article and Find Full Text PDF