Noninvasive molecular imaging using anti-Trop-2 aptamer for targeted therapy of small cell lung cancer.

Recent advancements in antibody-drug conjugates (ADCs) targeting trophoblast surface cell antigen 2 (Trop-2) have brought important progress in the field of targeted therapy. This progress also holds promise for the treatment of small cell lung cancer (SCLC) as anti-Trop-2 therapy appears to have a safe and effective clinical activity in metastatic SCLC patients. However, effective treatments of anti-Trop-2 ADCs rely on the comprehensive assessment of Trop-2 expression at the tumor sites, SCLC exhibits intratumoral heterogeneity, making the accurate acquisition of histological biopsies a challenge.

Efficacy and safety of neoadjuvant SHR-A1811 with or without pyrotinib in women with locally advanced or early HER2-positive breast cancer: a randomized, open-label, phase 2 trial.

Background: Standard neoadjuvant regimens for HER2-positive breast cancer include trastuzumab and pertuzumab combined with chemotherapy, and the efficacy and safety of third-generation HER2-direted antibody-drug conjugate (ADC) remain to be elucidated.

Patients And Methods: This open-label, randomized, phase 2 study enrolled patients aged 18 years or older with stage II-III Her2-positive breast cancer. Patients were randomly assigned (1:1:1) to receive neoadjuvant treatment either with SHR-A1811 monotherapy, SHR-A1811 with pyrotinib, or nab-paclitaxel combined with carboplatin, trastuzumab, and pertuzumab (PCbHP) for 24 weeks.

Transcription-coupled AID deamination damage depends on ELOF1-associated RNA polymerase II.

In adaptive immunity, transcription-coupled damage (TCD) is introduced into antibody genes by activation-induced cytidine deaminase (AID) to diversify antibody repertoire. However, the coordination between transcription and DNA damage/repair remains elusive. Here, we find that transcription elongation factor 1 (ELOF1) stabilizes paused RNA polymerase II (RNAPII) at transcription barriers, providing a platform for transcription-coupled DNA damage/repair.

PCK1 inhibits cGAS-STING activation by consumption of GTP to promote tumor immune evasion.

Hypoxia induces immunosuppressive phenotypes in tumor cells even in the presence of cytosolic DNA accumulation. The mechanisms by which tumor cells suppress hypoxia-induced cGAS-STING activation for immune evasion remain largely unclear. Here, we demonstrate that hypoxic stimulation induces JNK1/2-mediated S151 phosphorylation of phosphoenolpyruvate carboxykinase 1 (PCK1), a rate-limiting enzyme in gluconeogenesis.

A critical role of N-acetylation of cytidine in mRNA by NAT10 in T cell expansion and antiviral immunity.

Following activation, naive T cells exit quiescence and require global translation for rapid expansion, yet the underlying mechanisms remain unclear. Here, we show that during T cell activation, cells upregulate the expression of N-acetyltransferase 10 (NAT10), an enzyme responsible for N-acetylcytidine (acC) modification of mRNAs. acC-modified Myc mRNAs show higher translation efficiency, enabling rapid synthesis of MYC protein and supporting robust T cell expansion.

Molecular subtyping of stage I lung adenocarcinoma via molecular alterations in pre-invasive lesion progression.

Background: Patients with adenocarcinoma in situ (AIS) and minimally invasive (MIA) lung adenocarcinoma (LUAD) are curable by surgery, whereas 20% stage I patients die within five years after surgery. We hypothesize that poor-prognosis stage I patients may exhibit key molecular characteristics deviating from AIS/MIA. Therefore, we tried to reveal molecularly and prognostically distinct subtypes of stage I LUAD by applying key molecular alterations from AIS/MIA to invasive LUAD progression.

Antigen-presenting cancer associated fibroblasts enhance antitumor immunity and predict immunotherapy response.

Cancer-associated fibroblasts (CAF) play a crucial role in tumor progression and immune regulation. However, the functional heterogeneity of CAFs remains unclear. Here, we identify antigen-presenting CAFs (apCAF), characterized by high MHC II expression, in gastric cancer (GC) tumors and find that apCAFs are preferentially located near tertiary lymphoid structures.

MYC amplification sensitizes TNBC to CHK1 inhibitors.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, for which effective therapy is urgently needed. We demonstrated that MYC overexpression was associated with TNBC subtype and promoted the cell proliferation, invasion and migration in TNBC cells. Moreover, MYC overexpression induced replication stress and DNA damage in TNBC cells.

Evaluative Methodology for HRD Testing: Development of Standard Tools for Consistency Assessment.

Homologous recombination deficiency (HRD) has emerged as a critical prognostic and predictive biomarker in oncology. However, current testing methods, especially those reliant on targeted panels, are plagued by inconsistent results from the same samples. This highlights the urgent need for standardized benchmarks to evaluate HRD assay performance.

Long-term results of locoregionally advanced nasopharyngeal carcinoma treated with cisplatin and 5-fluorouracil induction chemotherapy with or without docetaxel in young and middle aged adults.

Purpose: This study aims to evaluate the efficacy and toxicity of the two induction chemotherapy (IC) regimens (TPF: docetaxel, cisplatin and 5-fluorouracil, and PF: cisplatin and 5-fluorouracil) combined with radiotherapy in young and middle aged patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC).

Methods: A retrospective analysis was conducted on 329 cases with stage III-IVA nasopharyngeal carcinoma from September 2005 to February 2017. Of the 329 cases, 253 cases underwent TPF (docetaxel: 60 mg/m on day 1, cisplatin: 25 mg/m on days 1-3, 5-fluorouracil: 500 mg/m on days 1-5, intravenous 120-h infusion), while 76 cases received the PF regimen (cisplatin: 25 mg/m on days 1-3, 5-fluorouracil: 500 mg/m on days 1-5, intravenous 120-h infusion) every 3 weeks.

Ferroptosis-related genes as prognostic markers for survival and immunotherapy in triple-negative breast cancer: analysis of public databases and a single institution.

Background: Ferroptosis plays a vital role in cancer development and treatment. The relationship between ferroptosis-related genes and breast cancer prognosis, as well as immunotherapy outcomes, remains unknown.

Objectives: To evaluate the prognostic value of ferroptosis-related genes in breast cancer.

Advances of artificial intelligence in clinical application and scientific research of neuro-oncology: Current knowledge and future perspectives.

Brain tumors refer to the abnormal growths that occur within the brain's tissue, comprising both primary neoplasms and metastatic lesions. Timely detection, precise staging, suitable treatment, and standardized management are of significant clinical importance for extending the survival rates of brain tumor patients. Artificial intelligence (AI), a discipline within computer science, is leveraging its robust capacity for information identification and combination to revolutionize traditional paradigms of oncology care, offering substantial potential for precision medicine.

HPLC Analysis of tRNA-Derived Nucleosides.

Transfer RNAs (tRNAs), the essential adapter molecules in protein translation, undergo various post-transcriptional modifications. These modifications play critical roles in regulating tRNA folding, stability, and codon-anticodon interactions, depending on the modified position. Methods for detecting modified nucleosides in tRNAs include isotopic labeling combined with chromatography, antibody-based techniques, mass spectrometry, and high-throughput sequencing.

Endothelial OX40 activation facilitates tumor cell escape from T cell surveillance through S1P/YAP-mediated angiogenesis.

Understanding the complexity of the tumor microenvironment is vital for improving immunotherapy outcomes. Here, we report that the T cell costimulatory molecule OX40 was highly expressed in tumor endothelial cells (ECs) and was negatively associated with the prognosis of patients, which is irrelevant to T cell activation. Analysis of conditional OX40 loss- and gain-of-function transgenic mice showed that OX40 signal in ECs counteracted the antitumor effects produced in T cells by promoting angiogenesis.

Identification of blood-derived exosomal tumor RNA signatures as noninvasive diagnostic biomarkers for multi-cancer: a multi-phase, multi-center study.

Background: Cancer remains a leading global cause of mortality, making early detection crucial for improving survival outcomes. The study aims to develop a machine learning-enabled blood-derived exosomal RNA profiling platform for multi-cancer detection and localization.

Methods: In this multi-phase, multi-center study, we analyzed RNA from exosomes derived from peripheral blood plasma in 818 participants across eight cancer types during the discovery phase.

Characterization of novel mouse esophageal squamous cell carcinoma cell lines and their utility as preclinical models.

Esophageal squamous cell carcinoma (ESCC) has a high incidence, poor treatment response, and high mortality. Subcutaneous transplant tumor models are commonly used to study the immunosuppressive tumor microenvironment and its impact on immunotherapy. In this study, we established two new ESCC mouse cell lines, mEC525M and mEC586F, from 4NQO-induced ESCC mouse models of different sexes.

Uncovering the underlying mechanism of yuanhuacine against colorectal cancer by transcriptomics and experimental investigations.

Background: Colorectal cancer (CRC) holds the third position in terms of incidence and ranks behind lung cancer in terms of mortality worldwide. Yuanhuacine, one of the main active ingredients of genkwa flos, has demonstrated promising application prospects in the field of cancer treatment. However, its underlying mechanism against CRC has not been fully clarified.

An accurate DNA and RNA based targeted sequencing assay for clinical detection of gene fusions in solid tumors.

Gene fusions are one of the most important molecular biomarkers for tumor diagnosis, classification and targeted therapy. How to accurately detect them is a key issue in clinical work. In this study, a custom-designed integration of DNA and RNA-based next generation sequencing (NGS) assay including 16 targeted therapy related genes was developed and validated to identify gene fusions in solid tumors.

TTGA U-Net: Two-stage two-stream graph attention U-Net for hepatic vessel connectivity enhancement.

Accurate segmentation of hepatic vessels is pivotal for guiding preoperative planning in ablation surgery utilizing CT images. While non-contrast CT images often lack observable vessels, we focus on segmenting hepatic vessels within preoperative MR images. However, the vascular structures depicted in MR images are susceptible to noise, leading to challenges in connectivity.

Transcriptome Landscape of Cancer-Associated Fibroblasts in Human PDAC.

Cancer-associated fibroblasts (CAFs) play a crucial role in the progression of pancreatic ductal adenocarcinoma (PDAC). Here, integrated single-cell RNA sequencing analysis is utilized to comprehensively map CAFs in the human PDAC tumor microenvironment (TME). Normal fibroblasts (NFs) and nine distinct CAF subtypes are identified including newly identified CAF subtypes, CDCP1FTL CAFs, transitional CAFs (tCAFs), interferon simulated genes (ISG) myofibroblastic CAFs (myCAFs), and proliferative CAFs (pCAFs).

Pcf11/Spt5 condensates stall RNA polymerase II to facilitate termination and piRNA-guided heterochromatin formation.

The PIWI-interacting RNA (piRNA) pathway plays a crucial role in protecting animal germ cells by repressing transposons. However, the mechanism of piRNA-guided heterochromatin formation and its relationship to transcriptional termination remains elusive. Through RNA interference screening, we discovered Pcf11 and PNUTS as essential for piRNA-guided silencing in Drosophila germ line.

Detection, molecular function and mechanisms of m5C in cancer.

Interest in RNA posttranscriptional modifications, particularly 5-methylcytosine (m5C), has surged in recent years. Studies have shown that m5C plays a key role in cellular processes and is closely linked to tumourigenesis. This growing focus emphasises the importance of understanding the diverse impacts of m5C modifications in both normal cellular functions and cancer development.

A Comprehensive Analysis of FGF/FGFR Signaling Alteration in NSCLC: Implications in Prognosis and Microenvironment.

Fibroblast Growth Factor (FGF) ligands and their receptor have been identified as the potent target in non-small cell lung cancer (NSCLC). However, the clinicopathological and microenvironmental characteristics of FGF/FGFR in NSCLC remain poorly elucidated. Here, we summarize 4656 NSCLCs and analyze clinicopathological features in 478 FGF/FGFR altered cases.

Alcohol accelerates the development of esophageal squamous cell carcinoma through elevated Gram-negative bacteria in peripheral circulation.

Alcohol consumption is intricately linked to the incidence of esophageal squamous cell carcinoma (ESCC). This study comprehensively investigates the role of alcohol-induced microbial alterations in ESCC progression. A retrospective analysis of 328 patients demonstrated that alcohol consumption markedly increases the risk of ESCC and boosts the expression of the proliferation marker Ki67.