Transcriptional profiling reveals -associated genes induced inflammatory cell infiltration and chemoresistance in gastric cancer.

Background: infection is closely associated with the tumor microenvironment (TME) in gastric cancer (GC), yet its underlying mechanism is elusive. Hence, it is imperative to explore the microenvironment and drug resistance arising from to enhance therapeutic strategies for GC.

Methods: Employing transcriptional bioinformatics, we computed a -associated prognostic index (HPI) using datasets from TCGA and GSE62254 containing ACSM5 and HSPB2 gene expression.

Cleavage of CAD by caspase-3 determines the cancer cell fate during chemotherapy.

Metabolic heterogeneity resulting from the intra-tumoral heterogeneity mediates massive adverse outcomes of tumor therapy, including chemotherapeutic resistance, but the mechanisms inside remain largely unknown. Here, we find that the de novo pyrimidine synthesis pathway determines the chemosensitivity. Chemotherapeutic drugs promote the degradation of cytosolic Carbamoyl-phosphate synthetase II, Aspartate transcarbamylase, and Dihydroorotase (CAD), an enzyme that is rate-limiting for pyrimidine synthesis, leading to apoptosis.

Venetoclax confers synthetic lethality to chidamide in preclinical models with transformed follicular lymphoma.

Transformed follicular lymphoma (t-FL) is an aggressive and heterogeneous hematological malignancy with limited treatment success; the development of novel therapeutic approaches is urgently needed for patients with t-FL. Here, we conducted high-throughput screening (HTS) and in vitro experiments using t-FL cell lines and primary samples to assess the synergistic effects of the histone deacetylase inhibitor chidamide and the BCL-2 inhibitor venetoclax. In vivo efficacy was further tested in xenograft models.

Ritanserin suppresses acute myeloid leukemia by inhibiting DGKα to downregulate phospholipase D and the Jak-Stat/MAPK pathway.

Refractory or relapsed (R/R) AML is the most challenging form of AML to treat. Due to frequent genetic mutations, therapy alternatives are limited. Here, we identified the role of ritanserin and its target DGKα in AML.

High-Throughput Drug Screen for Potential Combinations With Venetoclax Guides the Treatment of Transformed Follicular Lymphoma.

Transformed follicular lymphoma (t-FL) is an aggressive malignancy that is refractory and rapidly progressing with poor prognosis. There is currently no effective treatment. High-throughput screening (HTS) platforms are used to profile the sensitivity or toxicity of hundreds of drug molecules, and this approach is applied to identify potential effective treatments for t-FL.

Preclinical Studies of Chiauranib Show It Inhibits Transformed Follicular Lymphoma through the VEGFR2/ERK/STAT3 Signaling Pathway.

Transformed follicular lymphoma (t-FL), for which there is no efficient treatment strategy, has a rapid progression, treatment resistance, and poor prognosis, which are the main reasons for FL treatment failure. In this study, we identified a promising therapeutic approach with chiauranib, a novel orally developed multitarget inhibitor targeting VEGFR/Aurora B/CSF-1R. We first determined the cytotoxicity of chiauranib in t-FL cell lines through CCK-8, EdU staining, flow cytometry, and transwell assays.

Stratification and therapeutic potential of ELL in cytogenetic normal acute myeloid leukemia.

Optimizing prognostic stratification of patients with cytogenetic normal acute myeloid leukemia (CN-AML), a highly heterogeneous subgroup in AML, appears to be important to improve its treatment and clinical outcome. Here, we report a potential role of ELL, a gene associated with leukemogenesis in AML, in prognostic stratification of CN-AML patients. By analyzing public available databases, we found that ELL was highly expressed in AML patients compared with healthy donors.

Orelabrutinib and venetoclax synergistically induce cell death in double-hit lymphoma by interfering with the crosstalk between the PI3K/AKT and p38/MAPK signaling.

Purpose: Double-hit lymphoma (DHL) is a rare and aggressive mature B-cell malignancy with concurrent MYC and BCL2 rearrangements. When DHL becomes relapsed or refractory, it becomes resistant to the majority of therapeutic approaches and has subpar clinical results. Therefore, innovative therapeutics for this particular patient population are urgently needed.

Therapeutic inhibition of PPARα-HIF1α-PGK1 signaling targets leukemia stem and progenitor cells in acute myeloid leukemia.

Treatment of acute myeloid leukemia (AML) with chemotherapeutic agents fails to eliminate leukemia stem cells (LSC)，and thus patients remain at high risk for relapse. Therefore, the identification of agents that target LSC is an important consideration for the development of new therapies. Enhanced glycolysis in LSC contributes to the aggressiveness of AML, which is difficult to be targeted.

Preclinical Evaluation of the HDAC Inhibitor Chidamide in Transformed Follicular Lymphoma.

The key factors leading to transformed follicular lymphoma (t-FL) include the aberrations of epigenetic modifiers as early and driving events, especially mutations in the gene encoding for histone acetyltransferase. Therefore, reversal of this phenomenon by histone deacetylase (HDAC) inhibitors is essential for the development of new treatment strategies in t-FL. Several t-FL cell lines were treated with various doses of chidamide and subjected to cell proliferation, apoptosis and cell cycle analyses with CCK-8 assay, Annexin V/PI assay and flow cytometry, respectively.

Therapeutic Interaction of Apatinib and Chidamide in T-Cell Acute Lymphoblastic Leukemia through Interference with Mitochondria Associated Biogenesis and Intrinsic Apoptosis.

T-cell acute lymphoblastic leukemia (T-ALL) shows poor clinical outcome and has limited therapeutic options, indicating that new treatment approaches for this disease are urgently required. Our previous study demonstrated that apatinib, an orally selective VEGFR-2 antagonist, is highly effective in T-ALL. Additionally, chidamide, a histone deacetylase inhibitor, has proven to be cytotoxic against T-ALL in preclinical and clinical settings.

3D printed two-in-one on-capillary detector: Combining contactless conductometric and photometric detection for capillary electrophoresis.

In this work, for the first time, a 3D printed two-in-one on-capillary detector, combining contactless conductometric detection (CD) and photometric detection (PD), is fabricated for capillary electrophoresis (CE). The CD Faraday shield (FS) is printed using electrically conductive composite polylactic acid (PLA) to minimize the stray capacitance. Non-conductive PLA is also used to print the insulator of FS to prevent the electrical conduction with two stainless steel electrodes.