Bladder cancer is a type of malignant tumor that disrupts normal urinary function in patients, thereby significantly impacting their quality of life. This disease also imposes a heavy economic burden on both patients and public health agencies due to high medical costs. Current common therapies, such as surgical intervention, chemical treatment, and radiotherapy, are associated with serious adverse reactions and risks of metastasis recurrence. Effective attenuation of bladder cancer proliferation and invasion remains a significant challenge. Circular RNAs have shown promise in regulating proliferation and migration of cancer cells, thus making it a potential therapeutic target for bladder cancer treatment and prognosis. This study aims to evaluate the impact of regulating circPTK2 expression on progression of bladder cancer.

Neoadjuvant chemotherapy (NACT) is the standard treatment for patients with locally advanced breast cancer. In recent years, it has also been used for early-stage triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2-positive (HER2+) breast cancers.

KRAS mutations are associated with treatment and prognostic outcomes in colorectal cancer patients.There have been no studies on utilizing the peritumoral images to predict KRAS mutation status in rectal cancer patients. We aim to develop a radiomics model utilizing intratumoral and peritumoral ultrasound images for predicting KRAS mutation status in rectal cancer.

The aim of this retrospective study was to investigate the impact of setup errors on the dosimetry and radiobiology of left-sided breast cancer (BC) patients with different breast sizes undergoing conventionally fractionated volumetric modulated arc therapy (VMAT) radiotherapy.

Cancer immunotherapy predominantly targets CD8 T cells, but recent evidence highlights the importance of CD4 T cells in adoptive cell therapy (ACT). The TAM receptor MerTK regulates immune responses and has been shown to provide costimulatory signals in CD8 T cells. However, its role in CD4 T cells remains poorly understood. Here, we demonstrate that ProS1-MerTK signaling is upregulated in activated CD4 T cells, where it enhances central memory formation, metabolic fitness, and proliferation. Mechanistically, ProS1-MerTK signaling was linked to type 1 immune responses, suggesting a regulatory role in CD4 T cell polarization. Using CRISPR-Cas9-mediated knockout, we found that loss of MerTK reduced CD4 T cell fitness, function, and polarization. Furthermore, when ProS1 was added during the expansion of tumor-infiltrating lymphocytes (TILs) from advanced melanoma biopsies, it showed potential to promote favorable CD4 T cell memory and helper phenotypes, increase stemness, and reduce exhaustion - features associated with improved responses to ACT. These findings establish ProS1-MerTK as a key pathway for modulating CD4 T cell functionality and highlight its therapeutic potential to enhance TIL-based ACT outcomes.

Lenvatinib, as a multi-kinase inhibitor, has been approved as a first-line drug for patients with advanced hepatocellular carcinoma (HCC). Gasdermin E (GSDME)-mediated pyroptosis, a form of programmed cell death, can be induced by chemotherapy drugs or certain kinase inhibitors. However, the role of Lenvatinib in inducing pyroptosis in HCC warrants further investigation. Phase contrast microscopy, LDH assays, and gain- and loss-of-function strategies were used to evaluate Lenvatinib-induced pyroptosis in HCC cells. GSDME palmitoylation was assessed via the acyl-biotin exchange method. In vivo, a subcutaneous HCC xenograft model in nude mice were established to assess the effects of interfering with GSDME on the sensitivity of HCC to Lenvatinib. Lenvatinib induced pyroptosis in HCC cells in a dose- and time-dependent manner. Additionally, Lenvatinib promoted GSDME cleavage, with upregulation of GSDME enhancing pyroptosis and downregulation reducing this effect. The ABE method revealed that GSDME is palmitoylated, and Lenvatinib increased its palmitoylation, promoting plasma membrane localization and enhancing protein stability. Inhibition of GSDME palmitoylation by 2-BP blocked Lenvatinib-induced pyroptosis. In vivo, upregulation of GSDME increased HCC sensitivity to Lenvatinib and inhibited tumor growth. Lenvatinib induces pyroptosis in HCC by promoting the palmitoylation of GSDME, enhancing its localization to the plasma membrane and increasing its protein stability. Interfering with GSDME, both in vitro and in vivo, affects Lenvatinib-induced pyroptosis, thereby altering the therapeutic sensitivity of HCC to Lenvatinib. Targeting GSDME palmitoylation represents a potential therapeutic strategy for HCC, as it enhances Lenvatinib-induced pyroptosis and improves the therapeutic response.

Patients who receive long-term anti-hepatitis B virus (HBV) treatment with nucleos(t)ide analogues (NAs) are still at risk for primary hepatocellular carcinoma (HCC). Aim The purpose of this study was to compare clinical features of HBV-related HCC in NA-treated vs. untreated patients. The records of patients who were diagnosed with HCC for the first time at the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between January 1, 2019 and September 31, 2024 were retrospectively reviewed. Patients with chronic HBV (CHB)-related HCC were grouped into the NA-treated group and untreated group. A total of 562 patients with CHB-related HCC were identified and divided into the NA treatment group (n = 146) and the untreated group (n = 416). Patient age was similar between the groups (50.9 ± 10.1 vs. 52.5 ± 12.1 years, p > 0.05). HBV DNA level, alanine aminotransferase (ALT) level and gamma glutamyl transpeptidase (GGT) level were significantly lower in the NA group (all, p < 0.001). Alpha fetoprotein (AFP) level was significantly higher in the untreated group (p < 0.05). However, the HBeAg positive rate was significantly greater in the NA group (27.4% vs. 17.5%, p < 0.05), and79.5% (116/146) of HCCs occurred in the first 5 years of NA treatment. Blood biochemical indexes and AFP values of patients who develop CHB-related HCC after NA treatment are usually normal. However, the high HBeAg seropositive rate in patients treated with NAs requires attention.

Rapid progression in late-stage is a characteristic of pancreatic cancer (PC), leading to mortality. The critical role of lncRNA A2M-AS1 (long non-coding RNA alpha-2-macroglobulin antisense RNA 1) is involved in cancer progression, but the upstream regulator of A2M-AS1 in the PC progression phenotype remains elusive.

Non-small cell lung cancer (NSCLC) is the third most common type of cancer in Palestine and has the highest mortality rate. Treatment approaches for NSCLC depend on many factors including stage, histology, molecular profile, and patient performance status.

Oral cancer remains a major global health challenge due to its aggressive nature, high recurrence rates, and limited treatment options. Resveratrol (RV), a naturally occurring polyphenol, has demonstrated promising anticancer properties in various malignancies, including oral cancer. This systematic review aimed to evaluate preclinical evidence on RV's therapeutic effects in oral cancer, focusing on its mechanisms of apoptosis induction, metastasis inhibition, autophagy regulation, and immune modulation.

Our understanding of prognostic and predictive factors in the context of nivolumab combined with chemotherapy remains limited. In our multicenter study conducted across 16 centers, data from 153 patients with metastatic gastric adenocarcinoma and a PD-L1 CPS score ≥ 5, who received nivolumab in combination with chemotherapy as first-line treatment, were retrospectively analyzed for the period between 2021 and 2024. The study aimed to investigate the prognostic and predictive significance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), Systemic Immune-Inflammation Index (SII), as well as various clinical parameters. The estimated median progression-free survival (PFS) was 11.06 months while the estimated median overall survival (OS) was 16.03 months. Patients who were initially diagnosed with metastatic disease had a significantly worse prognosis, as was those with lung metastases. Lower NLR, PLR, and SII values were associated with longer PFS and OS in the univariate analysis; however, their statistical significance was not mantained in the multivariate analysis. SII and PD-L1 CPS score were determined as independent predictive factors for nivolumab plus chemotherapy treatment response. Our study is the only one to date that sheds light on prognostic and predictive factors in patients with metastatic gastric or GEJ adenocarcinoma and a PD-L1 CPS score ≥ 5, who received nivolumab in combination with chemotherapy.

Neurofibromatosis type 1 (NF1) is a rare genetic disorder with highly variable phenotypes, ranging from psychosocial challenges and congenital malformations to benign tumors and even aggressive cancers. We hypothesize that this variability stems from additional rare variants in other genes, in addition to NF1 variants. The analysis of 32 NF1 patients revealed that those with solid cancers carried a higher average of cancer driver variants especially in DNA repair genes compared to those without (p < 0.05). An extended validation study using 217 NF1 carriers (71 cancer and 146 controls) from UK biobank confirmed significant enrichment of pathogenic (P), likely pathogenic (LP) and uncertain significant (VUS) variants in DNA repair genes, in NF1 patients with tumors (FDR ≤ 0.05). Furthermore, P/LP variants in other genes are shown in those patients with NF1 ancillary traits such as cognitive impairments, macrocephaly, and connective defects. This study provides novel evidence suggesting that additional genetic variants in other genes may contribute to the phenotypic variability observed in NF1, indicating that rare secondary mutational events could influence specific manifestations, adding complexity to its variable expressivity.

Transcription factors (TFs) are pivotal in tumor initiation and progression, regulating downstream gene expression and modulating cellular processes. In this study, we conducted a comprehensive analysis of TF gene sets to define the molecular subtypes of gliomas. Using nonnegative matrix factorization (NMF), we identified two distinct glioma subtypes characterized by significant differences in survival outcomes and clinical features. Additionally, we identified TF gene sets with differential expression across gliomas of various World Health Organization (WHO) states, followed by protein‒protein interaction (PPI) network analysis. By applying 101 machine learning models, five key genes (EZH2, TWIST1, EGR1, FOSL2, and TCF3) involved in glioma were identified. Among these genes, TCF3 has emerged as a potential key prognostic marker because of its distinct expression patterns and functional relevance. By performing multi-omics and multi-dataset analyses, we explored the aberrant expression of TCF3 across multiple cancers, with robust validation at both the cellular and tissue levels. Furthermore, our analysis revealed a strong association between TCF3 mutation and glioma prognosis, underscoring its potential as a therapeutic target. In summary, this study not only introduces a novel method for the molecular subtyping of glioma but also highlights TCF3 as a promising target for precision medicine. Our findings provide crucial insights into the molecular mechanisms of glioma and offer a foundation for the development of novel therapeutic strategies.

Lung cancer is the most common malignant tumour and the leading cause of cancer-related death. circular RNAs (circRNAs) have important biological functions and are closely related to tumour development. The 5-methylcytosine (m5C) modification can regulate the molecular fate of RNA molecules and thus influence disease development.

Metabolic reprogramming is a hallmark of cancer, with acute myeloid leukemia (AML) being no exception. Mitochondrial function, particularly its role in protecting tumor cells against chemotherapy, is of significant interest in AML chemoresistance. In this study, we identified mitochondrial DNA content (mtDNAc), measured by quantitative PCR, as a simple and precise marker to stratify the metabolic states of AML patients. We show that patients with high mtDNAc are associated with increased mitochondrial metabolism and a higher dependency on oxidative phosphorylation (OXPHOS), often correlating with chemoresistance. Clinically, patients receiving cytarabine and an anthracycline-based regimen (7 + 3 regimen) experienced inferior relapse-free survival and a higher overall rate of leukemia recurrence. Ex vivo experiments using primary AML samples confirmed cytarabine resistance in high mtDNAc patients, which could be overcome by inhibiting mitochondrial complex I. The FDA-approved drug metformin, which targets mitochondrial metabolism, significantly enhanced apoptosis in response to chemotherapy or targeted agents, such as venetoclax, in AML models. However, metformin-treated cells adapted by increasing glycolysis and NAD+ production, a resistance mechanism that could be bypassed by targeting the nicotinamide phosphoribosyltransferase (NAMPT) enzyme. In summary, we demonstrated that mtDNAc is an effective tool for assessing the metabolic state of AML cells. This method can be easily implemented in clinical practice to identify chemoresistant patients and guide personalized treatment strategies, including novel combination therapies for those with a high reliance on mitochondrial metabolism.

Nucleoli are large nuclear sub-compartments where vital processes, such as ribosome assembly, take place. Most nucleolar proteins are essential; thus, their abrogation cannot be achieved through conventional approaches. This technical obstacle has limited our understanding of the biological functions of nucleolar proteins in cell homeostasis and cancer pathogenesis.

The human microbiome consists of the diverse microorganisms with their equally diverse functional abilities that have evolved over millions of years with humans. This microbiome creates a mutually beneficial symbiotic relationship with their host. Through their varied functions, the human gut microbiota is crucial for preserving health and homeostasis. Any imbalance in this microbial population can lead to an array of diseased states, including cancer especially of the gastrointestinal system. The focus of this chapter is to discuss the mechanisms through which the gut microbiome creates a conducive environment for initiation and progression of cancer. In addition, the effect of microbial products such as short chain fatty acids, bile acids and Trimethylamine N-oxide on the formation of gastrointestinal cancer is also discussed. The various experimental methods and new molecular techniques that have facilitated the characterization and study of microorganisms is also discussed. The developments in microbiome research have shed light on the potential role of gut microbiota for novel biomarker discovery and therapeutic interventions in gastrointestinal cancer, like fecal microbiota transplantation. The prospects of these areas for further exploration are discussed.

Our previous research demonstrated that the Wenxia Changfu Formula (WCF), as a neoadjuvant therapy, inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis. Given tumor-associated macrophages (TAMs) in epithelial-mesenchymal transition (EMT), this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer (NSCLC) cells. Utilizing a co-culture model treated with or without WCF, we observed that WCF downregulated cluster of differentiation 163 (CD163) expression in macrophages, reduced CCL18 levels in the conditioned medium, and inhibited the growth, invasion, and EMT of NSCLC cells induced by macrophage co-culture. Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF's effects are mediated through CCL18 and Src signaling. In vivo, WCF inhibited recombinant CCL18 (rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling. These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT via antagonistic modulation of CCL18, providing evidence for its potential development and clinical application in NSCLC patients.

A 47-year-old man presented with a large midline skull base lesion, with panclival erosion leading to a very rare event of CV junction instability causing severe neck pain and movement restriction as the predominant symptom presented. Sub-total excision of the lesion through the endonasal endoscopic transsphenoidal transclival approach followed by occiput-C2-C3 fixation was successfully performed as a one-stage procedure. Although the initial hormonal evaluation showed normal values, serial dilution confirmed very high prolactin levels. Careful evaluation for instability and the importance of the serial dilution method for prolactin levels is emphasized for proper treatment. We present an extremely rare scenario of invasive giant pituitary adenoma and review the pertinent literature.

Ionizing radiation is known to induce brain tumors such as meningiomas and gliomas over a time. Similar tumorogenic effects have been described with chemotherapeutic agents also. However, the literature is sparse regarding this entity. There has been some new understanding derived from the molecular studies regarding the mechanism of such tumorogenesis. To highlight such updates in the current knowledge is the objective. Two patients treated for malignancy in their childhood developed meningiomas in later part of their life. This highlights the possibility of developing meningiomas or other endocrinal tumors following the treatment for malignancy at a younger age. The need for long-term follow-up of these patients is the highlight of the report. Both the meningiomas were successfully removed surgically with favorable clinical outcomes. However, prevalence and risk projection need to be identified to plan the clinical management and long-term follow-up. Though meningiomas are known to be induced by previous radiotherapy, the exact mechanisms are not yet clear. Recent research indicates the genetic abnormalities and molecular abnormalities that can induce or evolve Meningiomas following radiotherapy. These tumors seem to form a distinctly different group molecularly and can be aggressive clinically. Understanding biomolecular pathogenesis is important to manage such patients adequately.