Mechanisms of Resistance to Oncogenic KRAS Inhibition in Pancreatic Cancer

Mechanisms of Resistance to Carcinogenic KRAS Inhibition in Pancreatic Cancer Background Pancreatic Ductal Adenocarcinoma (PDAC) is a highly lethal disease. Most patients are diagnosed at an advanced stage and typically die within 12 months, primarily due to limited treatment options and poor response to standard chemotherapy. KRAS is the most crit...

Targeting Acute Myeloid Leukemia Stem Cells Through Perturbation of Mitochondrial Calcium

Targeting Acute Myeloid Leukemia Stem Cells Through Perturbation of Mitochondrial Calcium

This is an academic paper report on the study of acute myeloid leukemia (AML) stem cells. The study found that venetoclax treatment targeting the BCL-2 protein induces different mitochondrial calcium signaling changes in drug-sensitive and drug-resistant AML stem cells, thereby affecting their oxidative phosphorylation metabolism and survival. The ...

Mechanisms of Response and Tolerance to Active RAS Inhibition in KRAS-Mutant NSCLC

Response and Resistance Mechanisms of RAS Inhibitors in KRAS-Mutant NSCLC Research Background With the clinical development of RAS inhibitors, the treatment of KRAS-mutant Non-Small Cell Lung Cancer (NSCLC) faces a new turning point. However, in clinical practice, patients show poor long-term responses to RAS inhibitors, influencing clinical effica...

Activating Point Mutations in the MET Kinase Domain Represent a Unique Molecular Subset of Lung Cancer and Other Malignancies Targetable with MET Inhibitors

This study reveals a new targetable cancer subtype characterized by activating point mutations in the MET tyrosine kinase domain (TKD). Researchers identified MET TKD activating mutations in approximately 0.5% of patients across a genomic data set of over 600,000 cancer cases, encompassing various tumor types, with the highest prevalence in renal c...

Iron-(Fe3+)-Dependent Reactivation of Telomerase Drives Colorectal Cancers

Iron-(Fe3+)-Dependent Reactivation of Telomerase Drives Colorectal Cancers

Iron (Ferric Ion, Fe3+)-Dependent Telomerase Reactivation Drives Colorectal Cancer Development I. Research Background Colorectal Cancer (CRC) is the third most common cancer globally, involving both genetic and non-genetic factors in its pathogenesis. Existing research shows a significant association between high iron content, hereditary iron overl...

Spatially Segregated Macrophage Populations Predict Distinct Outcomes in Colon Cancer

Spatially Segregated Macrophage Populations Predict Distinct Outcomes in Colon Cancer

Spatially Isolated Macrophage Populations Predict Different Outcomes in Colon Cancer Introduction Macrophages are sentinel immune cells in tissues, performing a variety of functions including pathogen defense, antigen presentation, phagocytosis of dead cells, and the secretion of signals that drive tissue repair. In tumors, macrophage infiltration ...

CRISPRi-based Circuits to Control Gene Expression in Plants

CRISPRi-based Circuits to Control Gene Expression in Plants

Academic Background In the field of plant biotechnology, traditional gene manipulation methods focus on producing the desired phenotypes and cellular activities through continuous transgene expression. However, strong continuous promoters may lead to gene silencing, metabolic burdens, or other adverse effects on yield, preventing the full realizati...

Generation of Allogeneic CAR-NKT Cells from Hematopoietic Stem and Progenitor Cells Using a Clinically Guided Culture Method

Generation of Clinically Applicable CAR-NKT Cells Research Background Chimeric Antigen Receptor (CAR) T cell therapy has been approved by the Food and Drug Administration (FDA) for the treatment of B-cell malignancies and multiple myeloma. However, the use of autologous CAR-T cell products presents challenges such as high costs, long manufacturing ...

Mapping Medically Relevant RNA Isoform Diversity in the Aged Human Frontal Cortex with Deep Long-Read RNA-Seq

Academic Background RNA isoforms play a critical role in gene expression regulation. On average, human protein-coding genes contain over eight RNA isoforms, leading to nearly four distinct protein-coding sequences. Traditional short-read sequencing technologies, due to their limitations in read length, cannot accurately assemble and quantify RNA is...

Trans-Nuclease Activity of Cas9 Activated by DNA or RNA Target Binding

In this study, we demonstrated that another type of Type II CRISPR-Cas system—the II type Cas9 system—also possesses “trans-cleavage” activity. This activity is guided by crRNA and tracrRNA and is activated via the binding of DNA or RNA targets. By combining the trans-cleavage activity of the Cas9 effector nuclease with nucleic acid amplification t...