Publications by authors named "Ali Vaziri-Gohar"

Article Synopsis
  • * Reducing NR4A2 levels through RNA interference (RNAi) leads to decreased cell growth, invasion, and movement, indicating its role in cancer progression.
  • * Targeting NR4A2 and its associated genes, like HuR, with specific inhibitors shows promise for new treatment strategies against PDAC by significantly inhibiting tumor growth in experimental models.
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Pancreatic cancer is the third leading cause of cancer death in the United States, and while conventional chemotherapy remains the standard treatment, responses are poor. Safe and alternative therapeutic strategies are urgently needed . A ketogenic diet has been shown to have anti-tumor effects across diverse cancer types but will unlikely have a significant effect alone.

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Article Synopsis
  • Pancreatic ductal adenocarcinoma (PDAC) has a low 5-year survival rate of 13%, and most patients develop resistance to chemotherapy.
  • Researchers discovered that overexpression of isocitrate dehydrogenase 1 (IDH1) in PDAC cells helps them survive chemotherapy by aiding mitochondrial function and managing oxidative stress.
  • Inhibiting IDH1 with the drug ivosidenib alongside standard chemotherapy not only boosts treatment effectiveness in lab studies but is also being tested in clinical trials for potential application in patient care.
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Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, as chemotherapy remains the best available systemic treatment. However, the discovery of safe and available adjuncts to enhance chemotherapeutic efficacy can still improve survival outcomes.

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~90% metastatic pancreatic ductal adenocarcinoma (mPDAC) occurs in the liver, and the 5-year survival rate for patients with mPDAC is only at 3%. The liver has a unique endothelial cell (EC)-rich microenvironment, and preclinical studies showed that ECs promote cancer cell survival pathways by secreting soluble factors in a paracrine fashion in other types of cancer. However, the effects of liver ECs on mPDAC have not been elucidated.

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Metabolites of tryptophan degradation are known to alter mood. Their effects have only been superficially examined in the context of pancreatic cancer. Herein, we study the role of indoleamine 2,3-dioxygenase 1 (IDO1), an enzyme important in the conversion of tryptophan to kynurenine, in a murine model of pancreatic cancer-associated depression.

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Background: Alternative treatment strategies in melanoma beyond immunotherapy and mutation-targeted therapy are urgently needed. Wild-type isocitrate dehydrogenase 1 (wtIDH1) has recently been implicated as a metabolic dependency in cancer. The enzyme protects cancer cells under metabolic stress, including nutrient limited conditions in the tumor microenvironment.

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Nutrient-deprived conditions in the tumor microenvironment (TME) restrain cancer cell viability due to increased free radicals and reduced energy production. In pancreatic cancer cells a cytosolic metabolic enzyme, wild-type isocitrate dehydrogenase 1 (wtIDH1), enables adaptation to these conditions. Under nutrient starvation, wtIDH1 oxidizes isocitrate to generate α-ketoglutarate (αKG) for anaplerosis and NADPH to support antioxidant defense.

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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis and chemotherapy with gemcitabine has limited effects and is associated with development of drug resistance. Treatment of Panc1 and MiaPaca2 pancreatic cancer cells with gemcitabine induced expression of the orphan nuclear receptor 4A2 (NURR1) and analysis of the cancer genome atlas indicated the NURR1 is overexpressed in pancreatic tumors and is a negative prognostic factor for patient survival. Results of NURR1 knockdown or treatment with the NURR1 antagonist 1,1-bis(3΄-indolyl)-1-(p-chlorophenyl)methane (C-DIM 12) demonstrated that NURR1 was pro-oncogenic in pancreatic cancer cells and regulated cancer cell and tumor growth and survival.

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Objective: To determine the frequency of depression or anxiety preceding a diagnosis of pancreatic cancer (PC). Further, to examine the association of PC-associated depression or anxiety with treatment compliance and survival.

Methods: 856 patients with PC from a single institution were identified using International Classification of Diseases (ICD) codes.

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Unlabelled: We previously identified that human epidermal growth factor receptor 3 (HER3, also known as ERBB3) is a key mediator in liver endothelial cell (EC) promoting colorectal cancer growth and chemoresistance, and suggested HER3-targeted therapy as a strategy for treating patients with metastatic colorectal cancer in the liver. Meanwhile, KRAS mutations occur in 40%-50% of metastatic colorectal cancer and render colorectal cancer resistant to therapies targeting the other HER family protein epidermal growth factor receptor (EGFR). It is necessary to elucidate the roles of KRAS mutation status in HER3-mediated cell survival and colorectal cancer response to HER3 inhibition.

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Isocitrate dehydrogenase 1 (IDH1) has been investigated as a promising therapeutic target in select cancers with a mutated version of the enzyme (mtIDH1). With only one phase III trial published to date and two indications approved for routine clinical use by the FDA, we reviewed the entire clinical trial portfolio to broadly understand mtIDH1 inhibitor activity in patients. We queried PubMed.

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Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer with a long-term survival rate under 10%. Available cytotoxic chemotherapies have significant side effects, and only marginal therapeutic efficacy. FDA approved drugs currently used against PDA target DNA metabolism and DNA integrity.

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Article Synopsis
  • * The regulatory protein HuR stabilizes both mutant and wild-type IDH1 mRNAs in IDH1-mutant tumors, and its suppression negatively impacts cancer cell growth and survival under stress conditions.
  • * Targeting the HuR-IDH1 regulatory relationship could enhance the effectiveness of therapies aimed at IDH1-mutant cancers, indicating that fully inhibiting this survival axis is crucial for improving treatment outcomes.
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Cancer aggressiveness may result from the selective pressure of a harsh nutrient-deprived microenvironment. Here we illustrate how such conditions promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Glucose or glutamine withdrawal resulted in a 5- to 10-fold protective effect with chemotherapy treatment.

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Tamoxifen is a common adjuvant treatment for estrogen receptor (ER)α-positive patients with breast cancer; however, acquired resistance abrogates the efficacy of this therapeutic approach. We recently demonstrated that G protein-coupled estrogen receptor 1 (GPER1) mediates tamoxifen action in breast cancer cells by inducing insulin-like growth factor-binding protein-1 (IGFBP-1) to inhibit IGF-1-dependent signaling. To determine whether dysregulation of IGFBP-1 induction is associated with tamoxifen resistance, IGFBP-1 transcription was measured in tamoxifen-resistant MCF-7 cells (TamR) after tamoxifen (Tam) treatment.

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Tamoxifen, a selective estrogen receptor modulator, is a commonly prescribed adjuvant therapy for estrogen receptor-α (ERα)-positive breast cancer patients. To determine if extracellular factors contribute to the modulation of IGF-1 signaling after tamoxifen treatment, MCF-7 cells were treated with IGF-1 in conditioned medium (CM) obtained from 4-OHT-treated MCF-7 cells and the accumulation of phospho-Akt (S473) was measured. CM inhibited IGF-1-dependent cell signaling and suggesting the involvement of extracellular factors (ie.

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Intracellular protein transport and localization to subcellular regions are processes necessary for normal protein function. Fluorescent proteins can be fused to proteins of interest to track movement and determine localization within a cell. Currently, fluorescence microscopy combined with image processing is most often used to study protein movement and subcellular localization.

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Synopsis of recent research by authors named "Ali Vaziri-Gohar"

  • - Ali Vaziri-Gohar's recent research primarily focuses on the mechanisms underlying pancreatic ductal adenocarcinoma (PDAC), exploring potential therapeutic targets and strategies to enhance treatment efficacy in a context marked by high chemotherapy resistance.
  • - Key findings include the discovery of the NR4A2-HuR axis as a pivotal driver of PDAC growth, identification of IDH1 as a promising target to improve chemotherapy response, and the potential of metabolic interventions, such as ketogenic diets and nutrient manipulation, to sensitize pancreatic cancer cells to conventional treatments.
  • - Vaziri-Gohar's work emphasizes the role of the tumor microenvironment, particularly the liver's endothelial cells, and the impact of metabolic pathways on cancer progression, underscoring the complexity of PDAC and the need for innovative therapeutic approaches.

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