Alexander Y. Mitrophanov
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View article: IMMU-82. Neuronal modulation of immunity in glioblastoma
IMMU-82. Neuronal modulation of immunity in glioblastoma Open
Recent studies determined that in glioblastoma, tumor cells integrate into neural networks, forming synapses with neurons, enhancing neuronal firing facilitating tumor growth. We sought to understand how neuronal activity alters the functi…
View article: Phase II proof-of-concept study of durvalumab and cediranib with and without olaparib in recurrent ovarian cancer
Phase II proof-of-concept study of durvalumab and cediranib with and without olaparib in recurrent ovarian cancer Open
Platinum-resistant epithelial ovarian cancer (EOC) represents a population with limited therapeutic options. We conducted a proof-of-concept, phase II single-center, multi-arm study of durvalumab plus cediranib (D + C) or durvalumab, cedir…
View article: Markov-Chain Perturbation and Approximation Bounds in Stochastic Biochemical Kinetics
Markov-Chain Perturbation and Approximation Bounds in Stochastic Biochemical Kinetics Open
Markov chain perturbation theory is a rapidly developing subfield of the theory of stochastic processes. This review outlines emerging applications of this theory in the analysis of stochastic models of chemical reactions, with a particula…
View article: The Arsenal of Perturbation Bounds for Finite Continuous-Time Markov Chains: A Perspective
The Arsenal of Perturbation Bounds for Finite Continuous-Time Markov Chains: A Perspective Open
Perturbation bounds are powerful tools for investigating the phenomenon of insensitivity to perturbations, also referred to as stability, for stochastic and deterministic systems. This perspective article presents a focused account of some…
View article: Mismatch repair protein MLH1 suppresses replicative stress in BRCA2-deficient breast tumors
Mismatch repair protein MLH1 suppresses replicative stress in BRCA2-deficient breast tumors Open
Loss of BRCA2 (breast cancer 2) is lethal for normal cells. Yet it remains poorly understood how, in BRCA2 mutation carriers, cells undergoing loss of heterozygosity overcome the lethality and undergo tissue-specific neoplastic transformat…
View article: Saturation genome editing of 11 codons and exon 13 of BRCA2 coupled with chemotherapeutic drug response accurately determines pathogenicity of variants
Saturation genome editing of 11 codons and exon 13 of BRCA2 coupled with chemotherapeutic drug response accurately determines pathogenicity of variants Open
The unknown pathogenicity of a significant number of variants found in cancer-related genes is attributed to limited epidemiological data, resulting in their classification as variant of uncertain significance (VUS). To date, Breast Cancer…
View article: PKM2 dictates the poised chromatin state of <i>PFKFB3</i> promoter to enhance breast cancer progression
PKM2 dictates the poised chromatin state of <i>PFKFB3</i> promoter to enhance breast cancer progression Open
The hypoxic milieu is a critical modulator of aerobic glycolysis, yet the regulatory mechanisms between the key glycolytic enzymes in hypoxic cancer cells are largely unchartered. In particular, the M2 isoform of pyruvate kinase (PKM2), th…
View article: Thrombin Generation in Trauma Patients: How Do we Navigate Through Scylla and Charybdis?
Thrombin Generation in Trauma Patients: How Do we Navigate Through Scylla and Charybdis? Open
Purpose of Review Coagulopathy is a complex pathological condition manifested through the insufficient or excessive tendency to form blood thrombi, which can be caused by trauma and surgery. A promising strategy to mitigate coagulopathy is…
View article: Kinetic model facilitates analysis of fibrin generation and its modulation by clotting factors: implications for hemostasis-enhancing therapies
Kinetic model facilitates analysis of fibrin generation and its modulation by clotting factors: implications for hemostasis-enhancing therapies Open
We developed a computational model that accounts for essential kinetic features of thrombin generation, fibrin formation, and fibrinolysis in diverse in vitro systems. We applied it to characterize strategies to improve hemostasis.
View article: Injury Length and Arteriole Constriction Shape Clot Growth and Blood-Flow Acceleration in a Mouse Model of Thrombosis
Injury Length and Arteriole Constriction Shape Clot Growth and Blood-Flow Acceleration in a Mouse Model of Thrombosis Open
Objective: Quantitative relationships between the extent of injury and thrombus formation in vivo are not well understood. Moreover, it has not been investigated how increased injury severity translates to blood-flow modulation. Here, we i…
View article: Predictive Approach Identifies Molecular Targets and Interventions to Restore Angiogenesis in Wounds With Delayed Healing
Predictive Approach Identifies Molecular Targets and Interventions to Restore Angiogenesis in Wounds With Delayed Healing Open
Impaired angiogenesis is a hallmark of wounds with delayed healing, and currently used therapies to restore angiogenesis have limited efficacy. Here, we employ a computational simulation-based approach to identify influential molecular and…
View article: <scp>LPS</scp>‐stimulated<scp>NF</scp>‐<i>κ</i>B p65 dynamic response marks the initiation of<scp>TNF</scp>expression and transition to<scp>IL</scp>‐10 expression in<scp>RAW</scp>264.7 macrophages
<span>LPS</span>‐stimulated<span>NF</span>‐<i>κ</i>B p65 dynamic response marks the initiation of<span>TNF</span>expression and transition to<span>IL</span>‐10 expression in<span>RAW</span>264.7 macrophages Open
During injury and infection, inflammation is a response by macrophages to effect healing and repair. The kinetics of the responses of proinflammatory TNFα, anti-inflammatory IL-10, and inflammatory master regulator NF-κB elicited by lipopo…
View article: Computational analysis identifies putative prognostic biomarkers of pathological scarring in skin wounds
Computational analysis identifies putative prognostic biomarkers of pathological scarring in skin wounds Open
Our method for predicting putative prognostic wound-outcome biomarkers may serve as an effective means to guide the identification of proteins predictive of pathological scarring.
View article: Impact of Tissue Factor Localization on Blood Clot Structure and Resistance under Venous Shear
Impact of Tissue Factor Localization on Blood Clot Structure and Resistance under Venous Shear Open
The structure and growth of a blood clot depend on the localization of tissue factor (TF), which can trigger clotting during the hemostatic process or promote thrombosis when exposed to blood under pathological conditions. We sought to und…
View article: Wound healing in Mac‐1 deficient mice
Wound healing in Mac‐1 deficient mice Open
Mac‐1 (CD11b/CD18) is a macrophage receptor that plays several critical roles in macrophage recruitment and activation. Because macrophages are essential for proper wound healing, the impact of Mac‐1 deficiency on wound healing is of signi…
View article: Computational identification and analysis of signaling subnetworks with distinct functional roles in the regulation of TNF production
Computational identification and analysis of signaling subnetworks with distinct functional roles in the regulation of TNF production Open
We developed, validated, and analyzed a computational model of the signaling network controlling the production of the essential pro-inflammatory cytokine TNF and its anti-inflammatory counterpart IL-10.