Publications by authors named "Kunal Chaudhary"

Lung cancer is the leading cause of cancer deaths in the United States and worldwide. While influenza illness is known to be particularly dangerous for frail and elderly patients, the relationship between influenza illness and outcomes in patients with cancer remains largely unknown. The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with non-small cell lung cancer (NSCLC) diagnosed between 2009 and 2015.

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Ferroptosis is mediated by lipid peroxidation of phospholipids containing polyunsaturated fatty acyl moieties. Glutathione, the key cellular antioxidant capable of inhibiting lipid peroxidation via the activity of the enzyme glutathione peroxidase 4 (GPX-4), is generated directly from the sulfur-containing amino acid cysteine, and indirectly from methionine via the transsulfuration pathway. Herein we show that cysteine and methionine deprivation (CMD) can synergize with the GPX4 inhibitor RSL3 to increase ferroptotic cell death and lipid peroxidation in both murine and human glioma cell lines and in ex vivo organotypic slice cultures.

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Article Synopsis
  • Estrogen receptor-positive breast tumors often respond to endocrine therapy but can develop resistance due to genetic changes, particularly in the estrogen receptor alpha (ESR1).
  • A study found that the incidence of new (de novo) ESR1 mutations in treatment-naïve primary breast tumors is much lower compared to metastatic tumors and previously treated tumors, suggesting these mutations are not common at the initial stage.
  • The findings indicate that pathogenic ESR1 mutations typically relate to acquired resistance rather than an intrinsic resistance mechanism, implying universal testing of primary breast cancer for ESR1 mutations may not be necessary.
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Lung cancer has been the most common cancer worldwide for several decades. The outcomes of patients with locally advanced lung cancer remain dismal, and only a minority of patients survive more than 5 years. However, tumor therapeutic resistance mechanisms are poorly studied.

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Background: Treatment paradigms for large cell neuroendocrine carcinoma (LCNEC) of the lung are based largely upon small retrospective studies and smaller prospective trials. It is unclear if these tumors behave like non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). Data are lacking with regard to the role of radiotherapy (RT).

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Background: Lymphedema is a frequent complication after surgical treatments of cancer involving lymph node resection. However, research of lymphedema treatments, such as vascularized lymph node transfer, is limited by the absence of an adequate lymphedema animal model. The purpose of this study was to determine if we could create sustainable lower limb lymphedema in the rat with a combination of inguinal lymphadenectomy, circumferential skin and subcutaneous tissue excision, and radiotherapy.

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Objective: Investigate the temporal effects of focused ultrasound (FUS)-induced blood-brain barrier (BBB) opening in post-radiotherapy mouse brains.

Methods And Materials: C57B6 mice without tumors were used to simulate the scenario after gross total resection (GTR) of brain tumor. Radiation dose of 6 Gy x 5 was delivered to one-hemisphere of the mouse brain.

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Radiotherapy is commonly used to treat a variety of solid human tumors, including localized prostate cancer. However, treatment failure often ensues due to tumor intrinsic or acquired radioresistance. Here we find that the MEK5/ERK5 signaling pathway is associated with resistance to genotoxic stress in aggressive prostate cancer cells.

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Although radiation is widely used to treat cancers, resistance mechanisms often develop and involve activation of DNA repair and inhibition of apoptosis. Therefore, compounds that sensitize cancer cells to radiation via alternative cell death pathways are valuable. We report here that ferroptosis, a form of nonapoptotic cell death driven by lipid peroxidation, is partly responsible for radiation-induced cancer cell death.

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Introduction: Large-cell neuroendocrine carcinoma (LCNEC) accounts for approximately 3% of lung malignancies. There are limited data on the epidemiology and best treatment practices for this malignancy. This study aimed to be the largest cohort with the most up-to-date analysis of the epidemiology of LCNEC.

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Introduction: Locally advanced non-small cell lung cancer (NSCLC) is highly resistant to chemoradiotherapy, and many cancer patients experience chronic stress. Studies that suggest stimulation of β-adrenergic receptors (β-AR) promotes tumor invasion and therapy resistance. We investigated whether β-AR inhibition with beta-blockers acts as a chemotherapy and radiation sensitizer in vitro and in patients treated with chemoradiation for locally advanced NSCLC.

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In the proper context, radiotherapy can promote antitumor immunity. It is unknown if elective nodal irradiation (ENI), a strategy that irradiates tumor-associated draining lymph nodes (DLN), affects adaptive immune responses and combinatorial efficacy of radiotherapy with immune checkpoint blockade (ICB). We developed a preclinical model to compare stereotactic radiotherapy (Tumor RT) with or without ENI to examine immunologic differences between radiotherapy techniques that spare or irradiate the DLN.

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Purpose: To implement Velocity-based image fusion and adaptive deformable registration to enable treatment planning for preclinical murine models of fractionated stereotactic radiosurgery (fSRS) using the small animal radiation research platform (SARRP).

Methods And Materials: C57BL6 mice underwent 3 unique cone beam computed tomography (CBCT) scans: 2 in the prone position and a third supine. A single T1-weighted post-contrast magnetic resonance imaging (MRI) series of a murine metastatic brain tumor model was selected for MRI-to-CBCT registration and gross tumor volume (GTV) identification.

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Hypertension and proteinuria in pregnant women are most commonly signs of preeclampsia which develops after 20 weeks of gestation. There are rare incidences of uncontrolled hypertension and nephrotic range proteinuria even in the first trimester of pregnancy which can be indicators of severe underlying fetal and placental abnormalities rather than preeclampsia. A G2P0 30-year-old Caucasian woman was admitted to University Hospital for the incidental finding of severe hypertension and proteinuria during her regular prenatal checkup at 14 weeks.

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Background: Lupus nephritis (LN) is a common complication in many patients with systemic lupus erythematosus, although renal-limited lupus nephritis has been reported as well. Early diagnosis of lupus nephritis is critical as early detection and effective treatment can improve renal outcomes in such patients.

Objective: The treatment of lupus nephritis is largely determined based on the histological class present on the renal biopsy specimen.

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The global incidence and prevalence of diabetes continues to expand due primarily to the influences of obesity and the contribution of obesity to the progression of type 2 diabetes mellitus. The rising prevalence of type 2 diabetes has driven an increase in rates of CKD in the past 3 decades in the United States. In turn, so have the rates for complications related to type 2 diabetes including CKD, eg, diabetic kidney disease (DKD).

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Purpose: To establish a novel preclinical model for stereotactic radiosurgery (SRS) with combined mouselike phantom quality assurance in the setting of brain metastases.

Methods And Materials: C57B6 mice underwent intracranial injection of B16-F10 melanoma cells. T1-weighted postcontrast magnetic resonance imaging (MRI) was performed on day 11 after injection.

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Nutritional deficiencies are very common among the patient on chronic hemodialysis. But they can be easily overlooked or misdiagnosed. Deficiencies of trace elements and phosphorous is rare among this patient population but if neglected can lead to catastrophic effects.

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Peritoneal dialysis (PD) is an excellent treatment option for the patients with end-stage renal disease, having been shown to yield improved patient satisfaction and economic benefit. Many surgeons and physicians believe that patients with prior abdominal surgeries or other abdominal complications are not viable candidates for PD and that prevalent PD patients needing abdominal surgery should be switched to hemodialysis. The purpose of the present review is to address those misconceptions.

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Obstructive sleep apnea (OSA), hypertension, and chronic kidney disease (CKD) are different entities and are generally managed individually most of the time. However, CKD, OSA, and hypertension share many common risk factors and it is not uncommon to see this complex triad together. In fact, they share similar pathophysiology and have been interlinked with each other.

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Despite greater blood pressure reactivity to acute cardiovascular stressors and a higher prevalence of hypertension in type 2 diabetes (T2D) patients, limited information is available regarding arterial baroreflex (ABR) control in T2D. We hypothesized that ABR control of muscle sympathetic nerve activity (MSNA) and heart rate (HR) are attenuated in T2D patients. Seventeen T2D patients (50 ± 2 yr; 31 ± 1 kg/m), 9 weight-matched controls (WM-CON, 46 ± 2 yr; 32 ± 2 kg/m) and 10 lean controls (Lean-CON, 49 ± 3 yr; 23 ± 1 kg/m), underwent bolus infusions of sodium nitroprusside (100 μg) followed 60 s later by phenylephrine (150 μg) and weighted linear regression performed.

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The mineralocorticoid aldosterone is a key hormone in the regulation of plasma volume and blood pressure in man. Excessive levels of this mineralocorticoid have been shown to mediate metabolic disorders and end-organ damage more than what can be attributed to its effects on blood pressure alone. Inappropriate excess levels of aldosterone contribute significantly to the cardiorenal metabolic syndrome and target organ injury that include atherosclerosis, myocardial hypertrophy, fibrosis, heart failure, and kidney disease.

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