Biology subjects

Ilyas, S.

Publications and source records attributed to Ilyas, S..

6 recordsLinked to original sources

bioRxiv2026

Therapy-induced senescent-like cancer cells drive macrophage-mediated immunosuppression in cholangiocarcinoma

Cholangiocarcinoma (CCA) is a lethal biliary cancer in which chemoresistance is nearly universal, and its tumor immune microenvironment is dominated by immunosuppressive tumor-associated macrophages (TAMs) that exclude cytotoxic CD8+ T cells. How tumor cells sustain this immunosuppressive state during chemotherapy is undefined. Here we demonstrate that therapy-induced senescent-like (Sen-L) cancer cells accumulate after gemcitabine/cisplatin in human and murine CCA, are predominantly cancer cells, and predict shorter survival. Genetic elimination of Sen-L cancer cells reduces tumor burden, lowers TAM abundance, and restores intratumoral CD8+ T cells, establishing them as causal drivers. Growth differentiation factor 15 (GDF-15) is the dominant Sen-L-secreted factor and reprograms macrophages to suppress CD8+ T cells through the non-canonical receptor TGFBR2 and STAT6, and p16-restricted Gdf15 silencing phenocopies Sen-L elimination. Combined with chemotherapy, Sen-L elimination improves survival beyond chemotherapy alone. These findings establish Sen-L cancer cells and their GDF-15 output as causal, targetable drivers of macrophage-mediated immune evasion in CCA. SIGNIFICANCE STATEMENTTherapy-induced senescent-like cancer cells, not stromal cells, are the dominant senescent-like and immunosuppressive population in cholangiocarcinoma, and their elimination restores antitumor immunity. GDF-15 is their dominant secreted effector and engages a non-canonical macrophage receptor, TGFBR2, identifying a cancer-cell-to-macrophage axis and a Sen-L-elimination strategy to restore chemosensitivity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=170 SRC="FIGDIR/small/734341v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@7d3fd8org.highwire.dtl.DTLVardef@ea9efborg.highwire.dtl.DTLVardef@16ba16borg.highwire.dtl.DTLVardef@132b821_HPS_FORMAT_FIGEXP M_FIG Graphical abstract. Senescent-like CCA cells promote tumor immunosuppression through TAMs polarization by GDF-15 C_FIG

Cancer Biology↗

bioRxiv2025

Reduced CSF1R expression in myeloid cells has limited impact on chronic lymphocytic leukemia progression

Targeting the colony-stimulating factor 1 receptor (CSF1R) to remove tumor-associated macrophages is being explored as cancer therapy. This strategy may be relevant for chronic lymphocytic leukemia (CLL), which strongly depends on support from myeloid cells. However, it is unclear how CSF1R expression affects the CLL microenvironment and leukemic progression. To examine this question, we created CLL mice with Csf1r haploinsufficiency to investigate changes in myeloid cells, Csf1r expression, and leukemia progression. Reducing Csf1r expression on circulating monocytes did not change the overall numbers of monocytes or macrophages in blood and lymphoid tissues. Mice with lower Csf1r levels had less leukemia during early disease, but this effect faded with disease progression, and their overall survival was similar to controls. Furthermore, reduced Csf1r expression on macrophages did not affect the survival or migration of patient-derived CLL cells. In summary, our results show that while the CSF1R pathway is important for maintaining the myeloid cells that support CLL, simply reducing CSF1R expression has only a limited effect on disease progression. Attempts to target the CSF1R for leukemic therapy might benefit from a stronger depletion of macrophages or the combination with other agents.

cancer biology↗

bioRxiv2024

Clinical and Molecular Characterization of Glioma Patients: miR-21 Expression as a Prognostic Biomarker in Tissue and Serum

BackgroundGlioma remains challenging due to high recurrence rates and resistance to treatment. Diagnosis and follow-up in resource-constrained regions often leads to significant patient attrition. Serum microRNA (miRNA) expression profiles, which have been shown to correlate with tissue expression profiles, are detectable in peripheral blood samples, providing a promising avenue for non-invasive and repeatable liquid biopsies. miR-21 shows promise in many populations; however, there is a dearth of data from our region. MethodologyWe collected 90 tumor tissues, 42 pre- and post-operative serum samples from glioma patients, and included 10 normal tissue adjacent to the tumor (NATs) along with serum samples from 8 healthy individuals and analyzed for miR-21 expression through RT-qPCR. Shapiro Wilk test was applied to calculate data distribution, ANOVA, Fishers exact, and Wilcox test, along with pairwise Students t-test, were applied to determine the differences in gene expression. The expression level of miR-21 was assessed for correlation with Kaplan-Meier survival curves and different molecular markers (IDH, Ki-67, ATRX and p53). The quantitative hazard ratio was determined using Cox regression analysis. ResultsmiR-21 expression in tissue increased with the mean log fold expression 0.101 (median fold = 2.35) in grade 2, 1.00 (median fold = 7.49) in grade 3 and 1.53 (median fold = 26.0) in grade 4 for glioma patients. The expression level showed significant difference between control tissue and grade 4 patients along with significant inter-comparison between grade 1 and grade 4, as well as grade 2 and grade 4.A significant elevated expression of miR-21 has been noticed in patients above 50 years of age. Similarly, in serum samples a significant decline in miR-21 expression was observed in post-operative samples as compared to pre-operative samples mean log fold in grade 2 is 1.30 (11.6-fold), grade 3 is 1.08 (15.3-fold) and grade 4 is 0.749 (13.2-fold). Furthermore, there was positive correlation of miR-21 expression with tumor volume. IDH-wildtype and high Ki-67 expression in gliomas showed significant upregulation of miR-21 compared to IDH-mutant and low Ki-67 respectively. Patients with low miR-21 expression had significantly longer overall survival (OS) than patients with high miR-21 expression. Quantitative hazard analysis indicates that patients in the high expression group have a 3.4 times higher risk of mortality (95% CI: 1.6-7.1), in comparison to patients in the low expression group with AUC of 0.742 (all p <0.05). ConclusionThis study demonstrates the potential of microRNA 21 as a serum biomarker for early, cost-effective diagnosis of glioma. Furthermore, it may inform the development of targeted treatment strategies for various glioma grades, particularly in our population.

molecular biology↗

bioRxiv2020

Protein Plasticity and its Role in Cellular Functions

The contribution of redox active properties of cysteines in intrinsically disordered regions (IDRs) of proteins is not very well acknowledged. Despite of providing structural stability and rigidity, intrinsically disordered cysteines are exceptional redox sensors and the redox status of the protein defines its structure. Experimental evidence suggests that the conformational heterogeneity of cysteines in intrinsically disordered proteins (IDPs) is related to numerous functions including regulation, structural changes and fuzzy complex formation. The unusual plasticity of IDPs make them suitable candidate to interact with many clients under specific conditions. Binding capabilities, dimerization and folding or unfolding nature of IDPs upon interaction with multiple clients assign distinct conformational changes associated with disulfide formation. Here we are going to focus on redox activity of IDPs, their dramatic roles that are not only restricted to cellular redox homeostasis and signaling pathways but also provide antioxidant, anti-apoptotic, binding and interactive power.

molecular biology↗

bioRxiv2020

Smartphone-based Sickle Cell Disease Detection and Monitoring for Point-of-Care Settings

Sickle cell disease (SCD) is a worldwide hematological disorder causing painful episodes, anemia, organ damage, stroke, and even deaths. It is more common in sub-Saharan Africa and other resource-limited countries. Conventional laboratory-based diagnostic methods for SCD are time-consuming, complex, and cannot be performed at point-of-care (POC) and home settings. Optical microscope-based classification and counting demands a significant amount of time, extensive setup, and cost along with the skilled human labor to distinguish the normal red blood cells (RBCs) from sickled cells. There is an unmet need to develop a POC and home-based test to diagnose and monitor SCD and reduce mortality in resource-limited settings. An early-stage and timely diagnosis of SCD can help in the effective management of the disease. In this article, we utilized a smartphone-based image acquisition method for capturing RBC images from the SCD patients in normoxia and hypoxia conditions. A computer algorithm is developed to differentiate RBCs from the patients blood before and after cell sickling. Using the developed smartphone-based technique, we obtained similar percentage of sickle cells in blood samples as analyzed by conventional method (standard microscope). The developed method of testing demonstrates the potential utility of the smartphone-based test for reducing the overall cost of screening and management for SCD, thus increasing the practicality of smartphone-based screening technique for SCD in low-resource settings. Our setup does not require any special storage requirements and is particularly useful in assessing the severity of the SCD. This is the characteristic advantage of our technique as compared to other hemoglobin-based POC diagnostic techniques.

bioengineering↗

bioRxiv2019

Expressing of Cytochrome-c, ADAM 17, Wnt-5a, and Hedgehog gene during the tissue regeneration of digit tip mice (Mus musculus) var Swiss Webster post amputation

The tissue regeneration of digit tip mice needs some proteins that play a role in overcoming the inflammatory state. The functional protein plays a role in the continuous growth of specific cells, continuous migration, functional differentiation, and tissue morphogenesis. All of the cells need energy related to cell respiration. Naturally expressing mRNA of ADAM 17, Wnt-5a, Hedgehog (HH), and Cytochrome-c (Cyt-c) reliably produced the accordance with their respective roles in each specific phase of tissue regeneration until the whole tissues formed again. The ADAM 17 gen expressed in the inflammatory phase, it positively related its essential role to the inflammatory process. Cyt-c gene expression naturally occurs throughout the tissue regeneration because of its key role in the cellular respiration. Expressed Wnt-5a gene mRNA in the granulation phase, the specific HH gene expressed after the blastema phase. Both expressed genes positively correlate with the continual growth of the digit tip mice by the specific Spearman test (p <0.05) because of their active role of cell proliferation, cell differentiation, extensive migration, and morphogenesis.

developmental biology↗