Publications by authors named "Anil Pahuja"

Background: Measurable residual disease (MRD) assessed by multiparametric flow cytometry (MFC) has gained importance in clinical decision-making for acute myeloid leukemia (AML) patients. However, complying with the recent In Vitro Diagnostic Regulations (IVDR) in Europe and Food and Drug Administration (FDA) guidance in the United States requires rigorous validation prior to their use in investigational clinical trials and diagnostics. Validating AML MRD-MFC assays poses challenges due to the unique underlying disease biology and paucity of patient specimens.

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Purpose: Neoadjuvant immunotherapy may improve the clinical outcome of regionally advanced operable melanoma and allows for rapid clinical and pathologic assessment of response. We examined neoadjuvant pembrolizumab and high-dose IFNα-2b (HDI) therapy in patients with resectable advanced melanoma.

Patients And Methods: Patients with resectable stage III/IV melanoma were treated with concurrent pembrolizumab 200 mg i.

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Neoadjuvant therapy with ipilimumab in combination with high dose IFNα was evaluated in patients with locally/regionally advanced melanoma in a previously reported clinical trial [NCT01608594]. In this study, peripheral immune cell profiling was performed in order to investigate the underlying mechanisms of tumor immune susceptibility and resistance. Peripheral blood mononuclear cells (PBMCs) from treated patients (N = 28) were collected at baseline and then at 6-weeks, 3-months and 12-months.

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Article Synopsis
  • *The rise in CAR T clinical trials is driven by regulatory support and patient acceptance, highlighting the growing interest in these therapies.
  • *Flow cytometry is essential in analyzing CAR T cells throughout their development, but there are specific challenges in creating and validating methods to track these cells effectively during both manufacturing and clinical use.*
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Exceptional clinical responses produced by the first chimeric antigen receptor T [CAR-T] cell therapies, and their entry into commercial markets prompted a logarithmic increase in the number of next generation CAR-T clinical trials. As a result, there is a growing interest in understanding the analytical approaches utilized for reliable monitoring of these "living" drugs, and the challenges encountered during their clinical development. Multiparametric flow cytometry (MFC) assays have played a crucial role in understanding the phenotype and function of first approved CAR-T therapies.

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Background: Missed accessory spleen (AcS) can cause recurrence of hematologic disease after splenectomy. The objective of the study was to determine whether detection of AcS is more accurate with preoperative computed tomography (CT) scan or with exploration during laparoscopic splenectomy.

Methods: A retrospective chart review was performed for 75 adult patients who underwent laparoscopic splenectomy for various hematologic disorders from 1999 to 2009.

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Background: Bariatric surgery is currently the most effective treatment for morbid obesity. It provides not only substantial weight loss, but also resolution of obesity-related comorbidities. Laparoscopic sleeve gastrectomy (LSG) has rapidly been gaining in popularity.

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Tregs play an important role in controlling immune responses, particularly autoimmunity. In NOD mouse model, an excellent model for autoimmune diabetes, transfer of Tregs was shown to prevent diabetes, whereas depletion of Tregs in vivo enhanced disease progression, suggesting that Treg dysfunction contributes to the pathogenesis of diabetes. However, the mechanisms leading to Treg dysfunction and their role in diabetes progression has remained unclear.

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Background: The major obstacle faced by patients with type 1 diabetes who undergo islet transplantation is a gradual decline in insulin independence. This decline may reflect alloimmune rejection, autoimmune recurrence and toxicity of drugs such as rapamycin to islet beta cells. Thus, there is a pressing need to refine immunosuppressive protocols in order to reduce toxicity to islet grafts and yet prevent rejection.

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Background: Central pancreatectomy has a unique application for lesions in the neck of the pancreas. It preserves the distal pancreas and its endocrine functions. It also preserves the spleen.

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Introduction: Higher-throughput chemotaxis assays have had limited use in chemokine receptor pharmacology studies mainly because of the unavailability of optimal assay formats in addition to an incompatibility of chemotactic cell backgrounds with other pharmacological assays. Here, we developed a high-throughput 96-well chemotaxis assay for leukocytic cell lines and identified the human U937 monocytic line as an excellent cell background for both chemotaxis and the high-throughput calcium mobilization Fluorescent Imaging Plate Reader (FLIPR) assay.

Methods: Optimal chemotactic conditions were developed using the Neuroprobe MBA96 nondisposable and the Millipore MultiScreen-MIC disposable apparatuses with responses to CXC chemokine receptor (CXCR)-4 endogenously expressed on the human H9 T lymphoma line, and confirmed with Jurkat T cell and U937 monocytic cell lines.

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The CXC chemokine receptor 3 (CXCR3) is predominantly expressed on T helper type 1 (Th1) cells that are involved in inflammatory diseases. The three CXCR3 ligands CXCL9, CXCL10, and CXCL11 are produced at sites of inflammation and elicit migration of pathological Th1 cells. Here, we are the first to characterize the pharmacological potencies and specificity of a CXCR3 antagonist, N-1R-[3-(4-ethoxy-phenyl)-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl]-ethyl-N-pyridin-3-ylmethyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-acetamide (NBI-74330), from the T487 small molecule series.

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Following the discovery of the very high binding affinity of 4-anilinopyrimidines against corticotropin-releasing factor receptor-1 (CRF(1)) (e.g., 1, K(i) = 2 nM), a new series of triazoles bearing different groups has been synthesized and evaluated.

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The binding pocket of family A GPCRs that bind small biogenic amines is well characterized. In this study we identify residues on CC chemokine receptor 7 (CCR-7) that are involved in agonist-mediated receptor activation but not in high affinity ligand binding. The mutations also affect the ability of the ligands to induce chemotaxis.

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Previous corticotropin releasing factor 1 (CRF1) receptor characterization has been performed using radiolabeled agonists, which bind predominantly the receptor-G-protein complex. The pharmacological profile of other receptor states, and their abundance, remain poorly characterized. Here we investigated the affinity states of the CRF1 receptor heterologously expressed in Ltk- cells and endogenously expressed in rat cerebellum.

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The nonobese diabetic (NOD) mouse is a good model for human type 1 diabetes, which is characterized by autoreactive T-cell-mediated destruction of insulin-producing islet beta-cells of the pancreas. The 9-23 amino acid region of the insulin B-chain [B((9-23))] is an immunodominant T-cell target antigen in the NOD mouse that plays a critical role in the disease process. By testing a series of B((9-23)) peptide analogs with single or double alanine substitutions, we identified a set of altered peptide ligands (APLs) capable of inhibiting B((9-23))-induced proliferative responses of NOD pathogenic T-cell clones.

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Synopsis of recent research by authors named "Anil Pahuja"

  • - Anil Pahuja's recent research focuses on improving diagnostic processes and treatment outcomes in cancer, particularly through the validation of immunotherapy techniques and flow cytometric methods for acute myeloid leukemia (AML) and melanoma patients
  • - His studies emphasize the importance of measurable residual disease (MRD) assessment and monitoring CAR T-cell therapies, leveraging multiparametric flow cytometry for better patient management in clinical trials
  • - Pahuja also investigates the immune cellular responses associated with various cancer therapies, such as immunotherapy in melanoma, highlighting the role of tumor immune profiles in predicting treatment efficacy and toxicity

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