Selective MCL-1 inhibitor ABBV-467 is efficacious in tumor models but is associated with cardiac troponin increases in patients.

Background: MCL-1 is a prosurvival B-cell lymphoma 2 family protein that plays a critical role in tumor maintenance and survival and can act as a resistance factor to multiple anticancer therapies. Herein, we describe the generation and characterization of the highly potent and selective MCL-1 inhibitor ABBV-467 and present findings from a first-in-human trial that included patients with relapsed/refractory multiple myeloma (NCT04178902).

Methods: Binding of ABBV-467 to human MCL-1 was assessed in multiple cell lines.

HIV/AIDS-related lymphoma: perspective from a regional cancer center in India.

Background: India has the third largest population of people living with HIV/AIDS (PLHA). Lymphoma is the second most common malignancy among PLHA. However, data are lacking regarding HIV/AIDS-related lymphoma (ARL) in India.

Colorectal cancer presenting as bone metastasis.

Introduction: Bone metastasis is a rare site of metastasis, seen in only 3.7-11% of clinical cases. Isolated bone involvement has been reported very rarely in literature.

Lenalidomide in relapsed refractory non-Hodgkin's lymphoma: An Indian perspective.

Background: Lenalidomide an immunomodulatory agent has shown activity in relapsed/refractory lymphoma. This study was conducted to evaluate its efficacy and optimal dose in Indian patients with relapsed/refractory lymphoma who were unable or unwilling to undergo autologous hematopoietic stem cell transplant.

Materials And Methods: Patients received oral lenalidomide at 20 mg on days 1-21 every 28 days until disease progression or unacceptable toxicity.

Locally advanced oral cavity squamous cell carcinoma: Barriers related to effective treatment.

Background: Oral cavity cancer is a significant health problem in India. Majority of patients present with locally advanced disease requiring multimodality treatment. Compliance to recommended treatment is an important factor affecting outcome.

Presynaptic BK channel localization is dependent on the hierarchical organization of alpha-catulin and dystrobrevin and fine-tuned by CaV2 calcium channels.

Background: Large conductance, calcium-activated BK channels regulate many important physiological processes, including smooth muscle excitation, hormone release and synaptic transmission. The biological roles of these channels hinge on their unique ability to respond synergistically to both voltage and cytosolic calcium elevations. Because calcium influx is meticulously regulated both spatially and temporally, the localization of BK channels near calcium channels is critical for their proper function.

Anaplastic large cell lymphoma: a single institution experience from India.

Background: Systemic anaplastic large cell lymphoma (ALCL) accounts for 2-8% of non-Hodgkin's lymphoma in adults and 10-15% in children. While there is ample data in the world literature about the clinical features and outcome of this disease, prognosis in Indian patients is largely unknown.

Objective: To study the clinical, pathologic profile and outcome ALCL.

Chronic myeloid leukemia in children and adolescents: results of treatment with imatinib mesylate.

Chronic myeloid leukemia (CML) is a rare disease in children, accounting for 2-3% of leukemias in this age group. Few studies have reported on efficacy of imatinib in childhood CML. The purpose of this retrospective study was to determine the efficacy of imatinib in children.

Interaction of α-catulin with dystrobrevin contributes to integrity of dystrophin complex in muscle.

The dystrophin complex is a multimolecular membrane-associated protein complex whose defects underlie many forms of muscular dystrophy. The dystrophin complex is postulated to function as a structural element that stabilizes the cell membrane by linking the contractile apparatus to the extracellular matrix. A better understanding of how this complex is organized and localized will improve our knowledge of the pathogenic mechanisms of diseases that involve the dystrophin complex.

Glutathione is essential for early embryogenesis--analysis of a glutathione synthetase knockout mouse.

Glutathione (GSH) is present in all mammalian tissues and plays a crucial role in many cellular processes. The second and final step in the synthesis involves the formation of GSH from gamma-glutamylcysteine (γ-GC) and glycine and is catalyzed by glutathione synthetase (GS). GS deficiency is a rare autosomal recessive disorder, and is present in patients with a range of phenotypes, from mild hemolytic anemia and metabolic acidosis to severe neurologic disorders or even death in infancy.

N-acetylcysteine amide (NACA) prevents retinal degeneration by up-regulating reduced glutathione production and reversing lipid peroxidation.

Oxidative stress plays a critical role in accelerating retinal pigment epithelial dysfunction and death in degenerative retinal diseases, including age-related macular degeneration. Given the key role of oxidative stress-induced retinal pigment epithelial cell death and secondary photoreceptor loss in the pathogenesis of age-related macular degeneration, we hypothesized that a novel thiol antioxidant, N-acetylcysteine amide (NACA), might ameliorate cellular damage and subsequent loss of vision. Treatment of human retinal pigment epithelial cells with NACA protected against oxidative stress-induced cellular injury and death.

Sub-chronic lead exposure alters kidney proteome profiles.

The current study examined the impact of sub-chronic lead (Pb)-exposure upon global protein profile in rodent kidney (blood Pb levels ~50 μg/dL; 5 weeks oral Pb-acetate exposure). Utilizing 2D SDS-PAGE for kidney protein separation, greater than 500 protein spots were analyzed by densitometry following background noise removal, spot alignment, and intensity filtering. Approximately 100 protein spots were identified by ESI-MS/MS with mitochondrial, chaperone, antioxidant, and Pb-binding proteins included.

An alpha-catulin homologue controls neuromuscular function through localization of the dystrophin complex and BK channels in Caenorhabditis elegans.

The large conductance, voltage- and calcium-dependent potassium (BK) channel serves as a major negative feedback regulator of calcium-mediated physiological processes and has been implicated in muscle dysfunction and neurological disorders. In addition to membrane depolarization, activation of the BK channel requires a rise in cytosolic calcium. Localization of the BK channel near calcium channels is therefore critical for its function.

Determination of glutathione disulfide levels in biological samples using thiol-disulfide exchanging agent, dithiothreitol.

A reverse-phase HPLC method incorporating dithiothreitol (DTT) reduction for quantitative determination of oxidized glutathione (GSSG) in biological samples is described here. This method is based on our previous enzymatic reduction technique that uses N-1-(pyrenyl) maleimide (NPM) as a derivatizing agent. In our earlier method, glutathione disulfide (GSSG) was measured by first reducing it to GSH with glutathione reductase (GR) in the presence of NADPH.

Effects of N-acetylcysteine amide (NACA), a thiol antioxidant on radiation-induced cytotoxicity in Chinese hamster ovary cells.

Ionizing radiation is known to cause tissue damage in biological systems, mainly due to its ability to produce reactive oxygen species (ROS) in cells. Many thiol antioxidants have been used previously as radioprotectors, but their application has been limited by their toxicity. In this investigation, we have explored the possible radioprotective effects of a newly synthesized thiol antioxidant, N-acetylcysteine amide (NACA), in comparison with N-acetylcysteine (NAC), a commonly used antioxidant.

Antioxidant and free radical scavenging properties of N-acetylcysteine amide (NACA) and comparison with N-acetylcysteine (NAC).

The antioxidant potential of N-acetylcysteine amide (NACA), also known as AD4, was assessed by employing different in vitro assays. These included reducing power, free radical scavenging capacities, peroxidation inhibiting activity through linoleic acid emulsion system and metal chelating capacity, as compared to NAC and three widely used antioxidants, alpha-tocopherol, ascorbic acid and butylated hydroxytoluene (BHT). Of the antioxidant properties that were investigated, NACA was shown to possess higher 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging ability and reducing power than NAC, at all the concentrations, whereas the scavenging ability of H(2)O(2) differed with concentration.