Search

Objective: Oral cancer examinations seek to clinically identify early oral cancers and discover premalignancies prior to their progression to invasive cancer. Method and materials: A cross-sectional study was conducted between April and August 2017 to explore and quantify the diagnostic approach used by United States (US) general dental practitioners following discovery of an oral lesion suspicious for malignancy/premalignancy. US licensed general dental practitioners who were clinically active members of the US National Dental Practice-Based Research Network were eligible to participate. Data for analysis were obtained via two questionnaires. Results: The majority of participants were males, practiced full-time, had a suburban primary practice, were born during the 1950s, and graduated dental school in the 1980s or 2000s. After identifying an oral lesion suspicious for premalignancy/malignancy, the next action of most general dental practitioner respondents (65.4%) was to refer the patient for consultation/biopsy. Most general dental practitioners (87.2%) referred to an oral and maxillofacial surgeon; 22% of general dental practitioners reported personally biopsying suspicious lesions. There was a relatively weak association between completing an Advanced Education in General Dentistry or General Practice Residency and subsequently personally performing biopsies on patients with oral lesions suspicious for malignancy/premalignancy (OR 1.33, P = .06). Most written referrals took place electronically and often included information, including lesion location (87.0%), lesion sign/symptoms (85.3%), lesion history (83.9%), radiographs (59.3%), medical history (50.6%), dental history (48.8%), and photographs (42.4%). When a referral biopsy was performed, referring clinicians were most frequently informed of the findings via a written report (96.7%, when positive for malignancy/premalignancy, and 95.4% when negative). Conclusion: A snapshot is presented of current actions taken by US general dental practitioners following the discovery of oral abnormalities suspicious for premalignancy/malignancy. [ABSTRACT FROM AUTHOR]

B7-H3, an immunomodulatory protein overexpressed in many cancers, is associated with tumor aggressiveness and poor prognosis, making it a crucial target for imaging to elucidate its role in cancer progression and guide therapeutic interventions. This study employed PET imaging to investigate the in vivo delivery and pharmacokinetics of two anti-B7-H3 antibodies, Ab-1 and Ab-2, in mouse xenograft models with varying B7-H3 expression levels. The antibodies were radiolabeled with [89Zr]Zr and evaluated through PET imaging, biodistribution studies, and in vitro assays to assess binding, tumor uptake, and retention. [89Zr]Zr-Ab-1 demonstrated high initial tumor uptake in B7-H3 positive xenografts but exhibited unexpected decreasing retention over time. This clearance was likely attributed to proteolytic cleavage mediated by matrix metalloproteinases in the tumor and the tumor microenvironment. Conversely, [89Zr]Zr-Ab-2 showed more stable tumor retention but lower overall uptake. Further investigation revealed that Ab-1 had affinity for both 4Ig and 2Ig B7-H3 isoforms, while Ab-2 bound exclusively to the 4Ig isoform. This differential binding to B7-H3 isoforms may explain the observed variations in tumor uptake and retention between the two antibodies. The study provides insights into the complex dynamics of B7-H3 targeted antibodies in vivo, highlighting how antibody characteristics, including isoform-specific binding, and tumor factors influence their behavior. These findings have potential implications for optimizing radiotherapy strategies, suggesting the possibility of tailored approaches based on antibody properties and tumor biology. [Display omitted] • Two 89Zr-antibodies enables non-invasive imaging of B7-H3 expression in tumors. • Preclinical validation shows distinct uptake and pharmacokinetics for each antibody. • MMPs affected tumor accumulation, providing unique opportunities. • Demonstrates high tumor-to-background contrast in PET imaging studies. • PET imaging of B7-H3 supports integration into precision oncology workflows. [ABSTRACT FROM AUTHOR]

Tumor hypoxia is a critical driver of cancer progression, metastasis, and therapy resistance, posing significant challenges in effective cancer treatment. Hypoxia-activable prodrugs offer a promising strategy to target tumors in low-oxygen conditions, but their efficacy is often hindered by intrinsic properties and extrinsic cues. In this study, we developed a dual-prodrug nanoassembly system (CPPA) composed of a hypoxia-triggerable camptothecin (CPT)-based dimeric prodrug (CP) and a lipid-conjugated STAT3 antisense oligonucleotide (ASO) prodrug (PA), aiming to enhance tumor-targeted chemotherapy and overcome the immune evasion within the tumor microenvironment. The CPPA self-assemble into stable nanomicelle capable of co-delivering both agents directly to the tumor site, where the hypoxia-triggered release of CPT induces immunogenic cell death (ICD) while STAT3 inhibition enhances immune response. In murine breast cancer models, CPPA demonstrated superior therapeutic efficacy by improving tumor cell killing, promoting immune cell infiltration, and modulating the immunosuppressive tumor microenvironment. This combination therapy not only reversed drug resistance but also prevented the formation of the pre-metastatic niche, significantly inhibiting tumor progression and metastasis. These findings highlight the potential of CPPA as an effective strategy for enhancing cancer immunotherapy, offering a promising approach to address the complex challenges of tumor hypoxia, immune evasion, and resistance to chemotherapy. A hybrid prodrugs nanoinducer system (CPPA) containing CPT prodrug (CP) and phospholipid conjugated STAT3 ASO (PA) to augment immunogenic chemotherapy in deep hypoxic tumor tissue. [Display omitted] • A hybrid prodrug nanoinducer (CPPA) to enhance immunogenic chemotherapy. • CPPA disrupts STAT3-mediated crosstalk between tumor cells and immune cells. • Dual-action mechanism of CPPA in drug resistance and tumor immune microenvironment. [ABSTRACT FROM AUTHOR]

Heterogeneities among tumor cells significantly contribute towards cancer progression and therapeutic inefficiency. Hence, understanding the nature of cancer through liquid biopsies and isolation of circulating tumor cells (CTCs) has gained considerable interest over the years. Microfluidics has emerged as one of the most popular platforms for performing liquid biopsy applications. Various label-free and labeling techniques using microfluidic platforms have been developed, the majority of which focus on CTC isolation from normal blood cells. However, sorting and profiling of various cell phenotypes present amongst those CTCs is equally important for prognostics and development of personalized therapies. In this review, firstly, we discuss the biophysical and biochemical heterogeneities associated with tumor cells and CTCs which contribute to cancer progression. Moreover, we discuss the recently developed microfluidic platforms for sorting and profiling of tumor cells and CTCs. These techniques are broadly classified into biophysical and biochemical phenotyping methods. Biophysical methods are further classified into mechanical and electrical phenotyping. While biochemical techniques have been categorized into surface antigen expressions, metabolism, and chemotaxis-based phenotyping methods. We also shed light on clinical studies performed with these platforms over the years and conclude with an outlook for the future development in this field. [ABSTRACT FROM AUTHOR]

Ovarian cancer is one of the most prevalent gynaecological malignancies. The rapid development of single-cell RNA sequencing (scRNA-seq) has allowed scientists to use this technique to study ovarian cancer development, heterogeneity, and tumour environment. Although multiple original research articles have reported the use of scRNA-seq in understanding ovarian cancer and how therapy resistance occurs, there is a lack of a comprehensive review that could summarize the findings from multiple studies. Therefore, this review aimed to fill this gap by comparing and summarizing the results from different studies that have used scRNA-seq in understanding ovarian cancer development, heterogeneity, tumour microenvironment, and treatment resistance. This review will begin with an overview of scRNA-seq workflow, followed by a discussion of various applications of scRNA-seq in studying ovarian cancer. Next, the limitations and future directions of scRNA-seq in ovarian cancer research will be presented. [Display omitted] • ScRNA-seq is a powerful tool for studying ovarian tumour development, cancer heterogeneity, tumour microenvironment, and the mechanism of treatment resistance in ovarian cancer. • Over 50 original research articles and at least three trials have used scRNA-seq to understand ovarian cancer progression and to identify potential biomarkers and therapeutic targets in this cancer. • Integrating scRNA-seq with bulk RNA-seq, spatial transcriptomic analysis, and an advanced 3D-mass spectrometry technique can help improve our understanding of how the molecular landscape of ovarian tumour changes dynamically as the disease progresses. [ABSTRACT FROM AUTHOR]

N6-methyladenosine (m6A) modification is the most common epitranscriptomic modification in eukaryotic RNA and has garnered extensive attention in the context of breast cancer research. The m6A modification significantly impacts tumorigenesis and tumor progression by regulating RNA stability, splicing, translation, and degradation. In this review we summarize recent advances in understanding the roles of m6A modification in the mechanisms underlying angiogenesis and vasculogenic mimicry in breast cancer. We review how m6A modification and associated transcripts influence relevant factors by affecting key factors and signaling pathways, highlighting the interactions among m6A "writers," "erasers," and "readers," and their overall impact on tumor angiogenesis and vasculogenic mimicry, as well as potential new therapeutic targets. • M6A modification regulates key factors in breast cancer angiogenesis and vasculogenic mimicry. • Vasculogenic mimicry in breast cancer is influenced by m6A modification. • Targeting m6A regulators offers new avenues for breast cancer treatment. • M6A modification impacts both tumor growth and response to therapy. • Understanding m6A's role opens new paths for personalized breast cancer therapy. [ABSTRACT FROM AUTHOR]

The efficacy of microwave ablation (MWA) and radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) patients with decompensated cirrhosis remains unclear. A total of 315 patients with decompensated cirrhosis and HCC who underwent MWA or RFA were recruited. Recurrence beyond the Milan criteria (RBM), local tumor progression (LTP), overall survival (OS), and complications were evaluated and compared. After propensity score matching, the overall liver-related complication rates were 12.1 % in the current study. The cumulative RBM rates were lower in patients treated with MWA compared to those treated with RFA (21.9 % vs. 23.4 % at 1 year; 42.3 % vs. 66.8 % at 5 years; p = 0.016). In addition, lower cumulative rates of LTP were found in patients treated with MWA compared to those treated with RFA (6.2 % vs. 19.9 % at 1 year; 14.7 % vs. 27.8 % at 3 years; p = 0.032). The OS rates at 1 and 5 years were 89.9 % and 58.9 % in the MWA group, and 80.7 %, and 38.9 % in the RFA group, respectively (p = 0.105). HCC patients with decompensated cirrhosis can undergo MWA or RFA with acceptable mortality, morbidity and liver-rated complications rates. MWA demonstrates superiority over RFA in tumor control. [ABSTRACT FROM AUTHOR]

Background: In the past several decades, cisplatin (DDP), in combination with other drugs, has been used as the mainstay chemotherapy drug for the treatment of gastric cancer (GC). However, the clinical application of DDP is restricted because of its toxic side effects, it is imperative to explore less toxic and more effective treatment strategies. Dihydroartemisinin (DHA) has been shown to exert potent anticancer effects through ferroptosis in multiple malignancies and has shown high efficacy and safety. Methods: Cell viability assay, live/dead staining assay, EDU proliferation assay, MitoTracker assay, BODIPY C11 assay and other cell assays in vitro were employed to observe DHA in combination with DDP inducing ferroptosis in GC. Subsequently, proteomic analysis integrated with database analysis and clinical sample detection were utilized to elucidate the mechanism of DHA inducing ferroptosis in GC both in vitro and in vivo. Results: In this study, we found that DHA combined with DDP can synergistically inhibit the proliferation, invasion and migration of GC cells and induce ferroptosis. Further studies have shown that DHA acts in combination with DDP to induce ferroptosis in GC cells by inhibiting GPX4 in vivo and in vitro. Conclusion: In summary, this study is the first to report that DHA and DDP synergically promote ferroptosis in GC cells, the combination of DDP and DHA is a promising strategy from the perspective of toxicity of DDP, which may be a promising therapeutic approach. [ABSTRACT FROM AUTHOR]

TGF-β is a pivotal cytokine that orchestrates various aspects of cancer progression, including tumor growth, metastasis, and immune evasion. In this review, we present a comprehensive overview of the multifaceted role of transforming growth factor β (TGF-β) in cancer biology, focusing on its intricate interactions with monocytes and macrophages within the tumor microenvironment (TME). We specifically discuss how TGF-β modulates monocyte and macrophage activities, leading to immunosuppression and tumor progression. We conclude with the current translational and clinical efforts targeting TGF-β, recognizing the promising role of this strategy in immunooncology. PLAIN LANGUAGE SUMMARY: Transforming growth factor β (TGF-β), a pivotal cytokine, plays a crucial role in maintaining homeostasis and influencing cancer development by affecting various cell types. In cancer, TGF-β initially suppresses tumor cell growth but later contributes to tumor progression and metastasis, presenting challenges in developing therapeutics targeting this cytokine. Mechanistically, TGF-β impacts diverse cellular processes through canonical Smad and non-Smad pathways, that explains its diverse regulation of different, sometimes opposing, cellular processes. In the context of immunity, exposure to TGF-β renders immune cells immunosuppressive, hindering their ability to fight tumor development. This article explores the effects of TGF-β on monocytes and macrophages, highlighting its role in creating an immunosuppressive tumor microenvironment (TME) required for tumor survival and growth. The article provides an update on recent studies that underscore the potential of TGF-β inhibition in modulating the immune response within the TME, thereby enhancing the effectiveness of cancer immunotherapy. Overall, this review article delves into the multifaceted role of TGF-β in cancer biology, with a specific focus on its interactions with monocytes and macrophages. It underscores the knowledge gaps and the importance of targeting TGF-β signaling in tumor-associated monocytes and macrophages as a promising therapeutic approach in TGF-β secreting tumors. [ABSTRACT FROM AUTHOR]

Mitotic arrest deficient 2 like 1 (MAD2L1) is a component of the mitotic spindle assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate, a process that confirms genomic stability. As several human cancers experience abnormal expression of such components, MAD2L1 has been studied in different human cancers owing to its oncogenic behavior. Here, we employed several omics-related tools to investigate the characteristics of MAD2L1 in a pan-cancer model of analysis, with a focus on its impact on the infiltration of multiple immune components in the tumor microenvironment as a mechanism allowing for tumor progression and poor patient survival. Our analysis revealed that MAD2L1 was significantly upregulated in several human tumors, and this upregulation was further confirmed at the protein level. In addition, a significant hypomethylation status of MAD2L1 was detected in multiple cancers compared with the corresponding controls. The consequences of this upregulation on tumor progression and clinical outcome were further assessed, where tumor stage, grade and metastasis were positively correlated with MAD2L1 overexpression in a panel of tumors. Moving to the immune interaction, our analysis demonstrated that MAD2L1 significantly increased the infiltration of the myeloid-derived suppressor cells (MDSCs) and reduced the infiltration of tumor-attacking natural killer (NK) cells. Furthermore, MAD2L1 expression positively correlated with the expression of exhaustion markers and immunosuppressive chemokines. Owing to its role in tumor progression, we detected MAD2L1 as a target for anticancer therapy, where high-throughput screening (HTS) was performed to identify possible inhibitors that could act as antitumor drugs. Our screening process identified nine FDA-approved drugs with favorable binding energies (>−7 kcal/mol) among the 3180 compounds examined. Meropenem, Glipizide and Dolutegravir were particularly promising candidates, showing distinctive interactions within the active pocket of MAD2L1. Here, we describe the stages and output of our multi-omics analysis with a drug screening assessment. MAD2L1 is significantly upregulated in several human tumors, where tumor stage, grade and metastasis were positively correlated with MAD2L1 overexpression in a panel of tumors. MAD2L1 significantly increased the infiltration of the myeloid-derived suppressor cells (MDSCs) and reduced the infiltration of tumor-attacking natural killer (NK) cells. Furthermore, MAD2L1 expression positively correlated with the expression of exhaustion markers and immunosuppressive chemokines. High-throughput screening identified Meropenem, Glipizide and Dolutegravir as promising candidates, showing distinctive interactions within the active pocket of MAD2L1. [ABSTRACT FROM AUTHOR]

In this review, we explore the potential of cAMP-Phosphodiesterase 4 (PDE4), a key intracellular enzyme, as a therapeutic target for cancer treatment. cAMP-PDEs play a critical role in regulating intracellular levels of cyclic adenosine monophosphate (cAMP), an essential second messenger involved in cell proliferation and metastasis in a tissue-specific manner depending on the PDE isoforms present. Elevated PDE4 expression has been reported in cancers such as breast, cervical, and lung cancer. Specific PDE4 subtypes are recognized for their roles in cancer progression, making PDE4 inhibitors promising candidates for therapeutic intervention. This review examines the role of PDE4 in cancer progression and highlights the therapeutic potential of studied PDE4 inhibitors. [ABSTRACT FROM AUTHOR]

To report toxicity from the multicenter phase III randomized trial of Bladder Adjuvant Radiation Therapy (BART) after radical cystectomy and chemotherapy in high-risk muscle-invasive bladder cancer (MIBC). Patients with nonmetastatic urothelial MIBC with ≥1 high-risk feature after radical cystectomy- pT3-4, pN1-3, nodal yield <10, positive margin, or ≥cT3 downstaged with neoadjuvant chemotherapy- were randomized 1:1 to observation (Obs) or adjuvant radiation therapy (RT) at 4 centers, stratified by pN stage (N0, N+) and chemotherapy (neoadjuvant, adjuvant, none). Stoma-sparing image guided intensity modulated RT 50.4 Gy in 28# was prescribed to the cystectomy bed and pelvic nodes. Acute toxicity (≤3 months of RT/randomization) and late toxicity were assessed per protocol using Common Terminology Criteria for Adverse Event v5.0. Patients progressing within 3 or 6 months of randomization were excluded from acute or late toxicity analysis, respectively. The BART trial enrolled 153 patients (Obs = 76, RT = 77). About half (49%) had pN+. Nearly 90% received chemotherapy (70% neoadjuvant; most commonly gemcitabine plus cisplatin). In the RT arm, 63/77 completed RT per protocol with no toxicity-related RT termination. Of the 134 patients analyzable for acute toxicity, no difference was observed in grade 3 (Obs 4.2% vs RT 1.6%, P =.34). Grade 2 effects were higher with RT (17.5% vs 1.1%, P <.001), mainly diarrhea/enteritis or proctitis. Late toxicity was analyzable for 104 patients (Obs = 57, RT = 47) with a median follow-up of 27 months. Grades 3 to 4 toxicity were about 10% (Obs 10.5% vs RT 8.4%, P =.62), and cumulative late grade 2+ toxicity was similar in both groups (17.5% vs 23.3%, P =.27). In the largest trial of adjuvant RT for high-risk urothelial MIBC, severe acute and late toxicity were low and similar with obervation or radiation therapy. The oncological outcomes are awaited. [ABSTRACT FROM AUTHOR]

Objectives: C–C Motif Chemokine Ligand 5 (CCL5) is known for its role in immune regulation and has been implicated in cancer progression. However, its expression and prognostic significance in pan-cancer require comprehensive evaluation. This study was initiated to decipher the pan-cancer role of CCL5 genes. Methods: In silico analyses involving various online databases and molecular experiments involving CCL5 knockdown experiments in KIRC cell lines evaluated its role in cell proliferation, colony formation, and migration. Results: CCL5 expression was significantly up-regulated in several cancers. High CCL5 expression correlated with poorer overall survival in kidney renal cell carcinoma (KIRC) and esophageal cancer (ESCA) patients. Promoter hypomethylation correlated with elevated CCL5 expression and poorer prognosis. CCL5 mutations were rare; indicating its role in cancer is driven by overexpression rather than genetic alterations. Positive correlations with immune inhibitory and MHC genes suggested CCL5's role in fostering an immunosuppressive tumor microenvironment. High CCL5 expression correlated with increased immune cell infiltration, particularly CD8 T cells and macrophages. CCL5 expression did not significantly influence drug sensitivity. CCL5 knockdown in resulted in reduced proliferation, colony formation, and migration, underscoring its critical role in cancer cell dynamics. Conclusion: Our study highlights the significance of CCL5 in cancer progression and prognosis, particularly in KIRC and ESCA. CCL5's role in modulating the tumor immune microenvironment and its potential as a therapeutic target warrant further investigation. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a primary malignant neoplasm exhibiting a high mortality rate. Taxifolin is a naturally occurring flavonoid compound that exhibits a range of pharmacological properties. The effects of taxifolin on HCC remain largely unexplored. Therefore, the aim of this study was to examine the potential roles of taxifolin in the development and progression of HCC. In this study, CCK-8 assay was utilized to examine the impact of taxifolin on the cell viability. The copper ions level and the activity of mitochondrial respiratory chain were determined by the correspondent kits. The biological properties of HCC cells were evaluated using colony formation, transwell, flow cytometry, and TUNEL assays, respectively. Transcriptome sequencing was carried out either with or without taxifolin treatment. The expression of cuproptosis-related proteins was determined by Western blot. We observed significant decrease of cell viability, Glutathione (GSH), and mitochondrial respiratory chain under the treatment of taxifolin, while an increase of copper ions level. Taxifolin was observed to suppress HCC progression both in vitro and in vivo. The intersection analysis was performed between upregulated genes and cuproptosis-related genes to obtain one intersection gene-SLC31A1. The knockdown of SLC31A1 reversed the tumor-suppressive effects induced by taxifolin. Taxifolin inhibited HCC progression through inducing cuproptosis in an SLC31A1-mediated manner. [ABSTRACT FROM AUTHOR]

Background: Previous studies have identified the long non-coding RNA (lncRNA) Uc001kfo as significantly upregulated in hepatocellular carcinoma (HCC) tissues, particularly in advanced stages, compared to adjacent non-cancerous tissues. This study aims to further explore the molecular mechanisms by which Uc001kfo promotes HCC metastasis, focusing on its regulation of α-SMA expression. Methods: The study investigate the effects of Uc001kfo on proliferation, migration, and invasion in HCC cells using in vitro assays. Additionally, we also explored the molecular mechanism by which Uc001kfo indirectly regulates α-SMA gene transcription through its targeting of Sp1. Finally, we conducted preliminary validation in mice model to assess the potential for Uc001kfo-targeted silencing to inhibit HCC cell invasion and metastasis. Results: The results of the study demonstrate that the Uc001kfo/Sp1/α-SMA pathway plays a role in regulating HCC metastasis. Uc001kfo inhibits the degradation of Sp1 protein, thereby promoting Sp1 binding to the α-SMA promoter and enhancing its transcription. Consequently, silencing Uc001kfo can indirectly suppress α-SMA expression, effectively inhibiting HCC cell proliferation, invasion, and migration in vitro, as well as liver metastasis in mice through the spleen. Conclusion: Uc001kfo plays a critical role in promoting HCC metastasis, making it a potential a promising therapeutic target for inhibiting tumor progression and metastasis in HCC. [ABSTRACT FROM AUTHOR]

Background/Aim: The tumor microenvironment greatly influences cancer occurrence, progression, and treatment resistance, making it a key target alongside cancer cells. In squamous cell carcinoma, the invasive front is crucial for studying invasion mechanisms driven by the surrounding microenvironment and for identifying biomarkers to diagnose and predict invasive cancer. In this study, we aimed to elucidate the regulation of cancer characteristics through the interactions between factors at the invasive tumor front and the surrounding tumor microenvironment. Materials and Methods: The invasive tumor front (ITF) and tumor center (TC) of collective cancer invasion were analyzed using microarray to compare gene expression. A stable cell line with depleted DEFA1 expression was established, and its effect on cancer growth was observed using a mouse tongue xenograft model. Invasive activity was assessed using Transwell assays. Gene profiling of cancer cells and analysis of secreted proteins interacting with U937 monocytic cells during co-culture were conducted using QuantSeq 3' mRNA sequencing and LC-MS/MS analysis. Results: DEFA1 was overexpressed at the ITF of collective cancer invasion. YD10B cells with depleted DEFA1 expression exhibited significantly reduced invasiveness and tumor growth without changes in the cell cycle distribution. Co-culture with U937 cells significantly enhanced the invasiveness of YD10B cells, which was inhibited by anti-DEFA1 treatment. QuantSeq 3' mRNA sequencing and LC-MS/MS analyses confirmed that DEFA1 derived from U937 cells increased the invasiveness of YD10B cells. Recombinant DEFA1 (rDEFA1) significantly enhanced the invasiveness of YD10B cells via the JNK MAPK/NF-B signaling pathway, independent of changes in DEFA1 expression within YD10B cells. Conclusion: DEFA1 is crucial for cancer invasion and growth, and monocyte-derived DEFA1 exacerbates these traits. This study highlights DEFA1's role in promoting invasion at the tumor front, where interactions with the microenvironment are active. [ABSTRACT FROM AUTHOR]

Skin cutaneous melanoma (SKCM) is one of the most lethal cancers translating into 75% of skin cancer-related deaths. Despite the advances in SKCM management and treatment strategies, the overall survival of patients remains unsatisfactory due to the metastatic properties of SKCM as well as the absence of effective prognostic biomarkers. Recent studies have shown that overload copper renders accumulation of mitochondrial proteins and fuels a form of cell death at odds with known death mechanisms and is hinged on mitochondrial respiration, the so-called cuproptosis. However, the exact role of cuproptosis in SKCM development and progression is unknown, and painting a clear picture of its functions in SKCM is fraught with challenges. A more systematic investigation is justified. In this study, we were posed to dissect the clout and latent regulatory mechanisms of cuproptosis-related genes (CRGs) in reining in SKCM progression. Also, we identified three CRGs that stood out were used to construct a prognostic model, which could be employed to predict the prognosis of patients with SKCM. Finally, through pan-cancer analysis, we found that the four cuproptosis key genes play a role in multiple tumors, suggesting that cuproptosis may impact tumor progression at the pan-cancer level. Taken together, these findings may not only contribute to the development of treatment strategies but also provide clues for treatment decision-making. [ABSTRACT FROM AUTHOR]

Gliomas, a heterogeneous group of tumors affecting the brain and spinal cord, present a significant clinical challenge. Ephrin B1 (EFNB1) has been implicated in various malignancies. However, its role in gliomas remained poorly understood. Hence, this study aimed to elucidate the connection between EFNB1 and the progression of glioma. A retrospective RNA-seq analysis was conducted by utilizing the data from glioma patients in the TCGA and CGGA databases. Kaplan–Meier survival analysis and multivariate regression models were employed to evaluate the prognostic significance of EFNB1. RT-PCR was used to quantify EFNB1 expression in glioma tissues and cell lines. Meanwhile, in vitro assays were carried out to assess its functional roles in glioma cells. Our findings demonstrated that EFNB1 expression was significantly elevated in gliomas and other cancers. Moreover, high EFNB1 expression was closely correlated with advanced clinical stages and poor prognosis. Notably, multivariate analysis identified EFNB1 as an independent prognostic factor for overall survival. KEGG pathway analysis suggested that EFNB1 was involved in critical biological processes, including the cell cycle, protein processing in the endoplasmic reticulum, Epstein-Barr virus infection, and Salmonella infection. Furthermore, EFNB1 expression was associated with immune cell infiltration, particularly Th2 cells, macrophages, and plasmacytoid dendritic cells. In glioma cells, EFNB1 expression was markedly increased. Consequently, functional experiments demonstrated that EFNB1 knockdown inhibited glioma cell proliferation, invasion, and migration. These results highlighted EFNB1 as a novel independent prognostic biomarker and suggest its potential role in shaping the immunological microenvironment of gliomas. [ABSTRACT FROM AUTHOR]

Background: Tripartite motif-containing 44 (TRIM44) involves in various tumor development. This study investigated role of TRIM44 in multiple myeloma (MM). Materials and methods: TRIM44 levels in bone marrow tissues and MM cell lines was detected by quantitative reverse transcription PCR (RT-qPCR). Cell viability, migration, and invasion of MM cells were evaluated under the interference of TRIM44 expression. The role of TRIM44 on regulating tumor growth in vivo was also investigated in subcutaneous tumor xenograft models. The protein interact between TRIM44 and Zinc Finger E-Box Binding Homeobox 1 (ZEB1) was also studied according IP followed by western blotting assay. Results: TRIM44 was all highly expressed in collected bone marrow tissues and MM cell lines. Cell viability, migration, and invasion of MM cells with low expression of TRIM44 was significantly inhibited. Over-expression of TRIM44 can down-regulate the ZEB1 ubiquitination to enhance the protein stability. Conclusions: TRIM44 exerts as an oncogenic factor to induce the oncogenesis of MM by stabilizing ZEB1. [ABSTRACT FROM AUTHOR]

Background: Digestive system cancers are among the most common malignancies, exhibiting consistently high incidence and mortality rates, yet effective detection and treatment targets remain limited. Integrin αv (ITGAV, CD51) is a significant member of the integrin family, widely recognized for its role in mediating interactions between cells and the extracellular matrix, as well as intracellular signaling. In recent years, ITGAV has been found to have significantly elevated expression in multiple tumors, such as prostate cancer, breast cancer, and osteosarcoma, and was considered to be a key component in various stages of tumor progression. However, no systematic digestive system cancer analysis has been conducted to explore its function in prognosis, diagnosis, and immunology. Methods: Transcriptome sequencing and clinical data of samples were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), Human Protein Atlas (HPA), cBioPortal, TIMER and TISIDB databases. Bioinformatics methods were employed to investigate the potential oncogenicity of ITGAV, focusing specifically on the analysis of its prognosis, diagnostic value, and immune infiltration level of ITGAV in digestive system cancers. In addition, GO, KEGG, and PPI network analysis revealed the biological functions and related signaling pathways related to ITGAV. Finally, the role of ITGAV in regulating cancer progression was experimentally verified using hepatocellular carcinoma and pancreatic cancer as examples. Results: We found that ITGAV was highly expressed in multiple digestive system cancers. In addition, high expression of ITGAV was closely associated with poor prognosis and showed potential for early diagnosis. Enrichment of pathways related to extracellular matrix organizing processes and tumor migratory movements was identified. In vitro , results showed that the knockdown of ITGAV significantly inhibited the migratory movement ability of hepatocellular carcinoma and pancreatic cancer cells, while its overexpression significantly promoted the migration of the above cells. Finally, immunoassays showed a significant correlation between ITGAV expression and the infiltration level of various immune cells, further clarifying the critical role of ITGAV in the tumor immune microenvironment. Conclusion: Our results elucidated the importance of ITGAV in the prognostic assessment, early diagnosis, and targeted immunotherapy of digestive system cancers, and revealed its multifaceted role in regulating cancer progression. [ABSTRACT FROM AUTHOR]

Background: Circular RNA (circRNA) plays an important regulatory role in the development of human malignancies, but the potential mechanisms of circRNA in non-small cell lung cancer (NSCLC) remain largely unknown. Methods: Microarray analysis was used to test for circRNAs differing in expression between NSCLC tumors and healthy adjacent tissues. Using qRT-PCR, the expression of circZNF707 was determined. Through a number of loss-of-function and gain-of-function investigations, the biological behavior of NSCLC cells was evaluated. Finally, tests using Western blotting, RIP, qRT-PCR, and luciferase reporter gene detection and rescue assays revealed the potential mechanism of circZNF707. Results: Increased expression of circZNF707 was found in NSCLC tissues. Functionally, circZNF707 enhances proliferation, migration, invasion, and glycolysis of NSCLC cells. Mechanistically, circZNF707 can upregulate PFKM by acting as a sponge for miR-668-3p, thus contributing to the progression of NSCLC. Conclusions: Through the circZNF707/miR-668-3p/PFKM axis, upregulation of circZNF707 promotes tumor development. CircZNF707 may provide new insights into the treatment and diagnosis of NSCLC. [ABSTRACT FROM AUTHOR]

Background: How to select muscle-invasive bladder cancer (MIBC) patients who are sensitive to immunotherapy is an unmet medical need. This study aimed to explore the role of immunoproteasome subunits as a novel signature for predicting efficacy of immunotherapy in MIBC. Methods: The expression profile of immunoproteasome subunits of MIBC and normal tissues was evaluated from data of The Cancer Genome Atlas (TCGA) and of the Chongqing University Cancer Hospital (CQUCH) cohort. Survival analysis and response to immunotherapy was further explored and compared between immunoproteasome subunitshigh and immunoproteasome subunitslow MIBC patients in the TCGA, the CQUCH and the IMvigor210 cohort. The association of the expression of immunoproteasome subunits with immune checkpoint molecules and the tumor immune microenvironment was explored by immunohistochemistry staining and bioinformatic analysis in MIBC of these three cohorts. Results: The expression of the immunoproteasome subunits PSMB8, PSMB9 and PSMB10 was significantly upregulated in MIBC. MIBC patients with high expression of immunoproteasome subunits, especially high expression of PSMB9, showed a trend of prolonged overall and progression free survival, which was further significantly improved in response to immunotherapy. Bioinformatics and immunohistochemistry staining revealed a positive correlation of the expression of immunoproteasome subunits with the expression of immune checkpoint molecules, with T cell activation and with T cell-mediated cytotoxicity. Conclusions: Immunoproteasome subunits, in particular PSMB9, are immune microenvironment-related molecules of MIBC and are promising signatures for survival prediction in response to immunotherapy of MIBC. [ABSTRACT FROM AUTHOR]

Macrophage plays an important role in homeostasis and immunity, and dysfunctional macrophage polarization is believed to be associated with the pathogenesis of tissue fibrosis and tumor progression. Colony stimulating factor-1 (CSF-1), a polypeptide chain cytokine, through its receptor (CSF-1R) regulates the differentiation of macrophages. Recently, the promising therapeutic potential of CSF-1/CSF-1R signaling pathway inhibition in cancer treatment is widely used. Furthermore, inhibition of CSF-1/CSF-1R signaling combined with radiotherapy has been extensively studied to reduce immunosuppression and promote abscopal effect. In addition, cumulative evidence demonstrated that M2 phenotype macrophage is dominant in tissue fibrosis and the inhibition of CSF-1/CSF-1R signaling pathway ameliorated pulmonary fibrosis, including radiation-induced lung fibrosis. Herein, we provide a comprehensive review of the CSF-1/CSF-1R signaling pathway in radiotherapy, with a focus on advances in macrophage-targeted strategies in the treatment of cancer and pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

The acidic tumor microenvironment plays a critical role in the malignant transformation of cancer cells. One mechanism underlying this transformation involves epithelial-mesenchymal transition (EMT). This is induced by prolonged exposure to acidic conditions. EMT is an essential process in cancer progression, with Transforming Growth Factor Beta (TGF-β) playing a central role in its induction. However, little was known about the factors regulating TGF-β under acidic conditions. This study aimed to elucidate the mechanism of EMT under acidic conditions and identify novel therapeutic targets to inhibit cancer cell migration and metastasis. Focusing on lung cancer, we explored microRNAs associated with EMT that were differentially expressed under acidic conditions in A549 cells and identified miR-193b-3p as a novel candidate. Under acidic conditions, miR-193b-3p expression decreased around days 3–14. Downregulation of miR-193b-3p promoted increased TGFβ2 expression, resulting in EMT changes in A549 cells. Our study suggests that the interaction between miR-193b-3p, TGFβ2, and the acidic tumor microenvironment promotes cancer EMT change. Understanding these interactions may not only enhance our biological comprehension of cancer, but also pave the way for the development of targeted therapies to inhibit cancer metastasis. [ABSTRACT FROM AUTHOR]

Estrogen receptor-positive breast cancer (ERPBC) accounts for approximately 70% of breast cancers in women worldwide. The therapeutic strategy process for ERPBC is well-established and significantly reduces the mortality rate. The discovery of new therapeutic targets remains essential for ERPBC patients with metastasis or endocrine resistance. This study indicated that USP7 is highly expressed in ERBPC and promotes tumor progression and metastasis. Inhibition of USP7 activity repressed proliferation, induced apoptosis, suppressed migration and invasive activities, and reversed the epithelial-mesenchymal transition of ERPBC. Mass spectrometry analysis indicated that USP7 regulates CDK1 expression, which is highly expressed and correlates with a poor overall survival rate in ERPBC. USP7 directly interacts with CDK1 and regulates its stability. The combined inhibition of USP7 and CDK1 by GNE-6776 and Ro-3306 synergistically represses the malignant process and metastasis of ERPBC. These findings proved that targeting USP7 and CDK1 is a potential strategy for overcoming endocrine resistance in patients with advanced ERPBC. [ABSTRACT FROM AUTHOR]

Background: Tumor metastasis is responsible for approximately 90% of mortality in lung cancer. Understanding the molecular mechanisms of lung cancer metastasis is crucial for developing new treatment strategies. Cellular prion protein (PrPc), encoded by PRNP gene, was previously found to enhance lung cancer invasiveness. However, research on the post-transcriptional regulation of PRNP remains limited. Methods: Dual-luciferase reporter assays identified miRNAs targeting the PRNP 3'-UTR, and RNA immunoprecipitation (RIP) confirmed the interaction between miR-193b-3p and PRNP mRNA. Promoter deletions and chromatin immunoprecipitation (ChIP) assays established c-Jun as a transcriptional repressor of miR-193b-3p. Functional validation of the c-Jun-miR-193b-3p-PrPc axis was conducted using transwell assays, LNA-in situ hybridization, RT-PCR, Western blot, and immunohistochemistry. Subcutaneous mouse xenograft models assessed the anti-tumor effects of miR-193b-3p in vivo. Results: We demonstrated that miR-193b-3p downregulates PrPc expression by directly targeting the 3'-UTR of PRNP. Overexpression of miR-193b-3p significantly suppressed PRNP expression at both mRNA and protein levels, and reduced lung cancer cell migration, invasion and proliferation, which was reversed by PrPc overexpression. Conversely, miR-193b-3p silencing enhanced PRNP expression as well as those oncogenic properties, which were mitigated by PRNP knockdown. Spearman correlation analysis revealed a significant negative association between miR-193b-3p and PrPc expression in lung cancer tissues (p = 0.017), and Kaplan–Meier survival analysis demonstrated that high PrPc (p = 0.039) or low miR-193b-3p (p = 0.027) expression correlated with poorer overall survival. Intra-tumoral injection of the miR-193b-3p mimic in mouse xenograft models significantly reduced tumor volume. In addition, c-Jun was identified as a transcriptional repressor of miR-193b-3p. Functional studies revealed that c-Jun knockdown inhibited lung cancer cell migration, invasion, and proliferation, effects that were reversed by either PrPc overexpression or miR-193b-3p inhibitor treatment. A significant association between PrPc and c-Jun expression in lung cancer tissues (p = 0.004) was observed. High expression of PrPc and/or c-Jun was found to be associated with poor overall survival of patients (p < 0.05). Conclusions: This study is the first to uncover a novel regulatory pathway where c-Jun acts as a transcriptional repressor of miR-193b-3p, leading to PRNP upregulation, which promotes lung cancer migration and invasion. This previously unrecognized c-Jun-miR-193b-3p-PrPc axis also provides valuable insights for the potential development of new therapeutic strategies against lung cancer metastasis through RNA-targeting technology. [ABSTRACT FROM AUTHOR]

Radiotherapy is one of the most effective treatments for malignant tumors. Radioresistance is a major factor that contributes to radiotherapy failure and poor prognosis. Recent studies have elucidated the pivotal role of aberrant N6-methyladenosine (m6A) modification, the predominant internal mRNA modification in eukaryotic cells, influences cancer progression by disrupting gene expression and other critical cellular processes. Furthermore, aberrant m6A methylation provides a substrate for tumor therapy; however, whether it regulates tumor radioresistance remains unclear. Methylated transferase (writer), demethylated transferase (eraser), and methylated recognition protein (reader) are the three essential proteins that regulate m6A modification via different mechanisms in different tumors. This review summarizes the latest research advances in m6A methylation and aims to provide novel perspectives on the advancement of regimens to overcome radioresistance and tumor invasion. [ABSTRACT FROM AUTHOR]

In the present era, noncoding RNAs (ncRNAs) have become a subject of considerable scientific interest, with peptides encoded by ncRNAs representing a particularly promising avenue of investigation. The identification of ncRNA-encoded peptides in human cancers is increasing. These peptides regulate cancer progression through multiple molecular mechanisms. Here, we delineate the patterns of diverse ncRNA-encoded peptides and provide a synopsis of the methodologies employed for the identification of ncRNAs that possess the capacity to encode these peptides. Furthermore, we discuss the impacts of ncRNA-encoded peptides on the biological behavior of cancer cells and the underlying molecular mechanisms. In conclusion, we describe the prospects of ncRNA-encoded peptides in cancer and the challenges that need to be overcome. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the safety, tolerability, and preliminary efficacy of combining laser interstitial thermal therapy (LITT) with early administration of temozolomide (TMZ) in patients with recurrent glioblastoma (rGBM). Ten patients with rGBM were enrolled. Following the LITT procedure, TMZ was administered at a dose of 75 mg/m2/day during the early-TMZ phase for three weeks. After a 7-day interval, TMZ was given according to the standard dosage scheme for 6 cycles. Adverse events and complications encountered were documented. Regular follow-up assessments were conducted to evaluate both patient performance status and tumor progression. All patients demonstrated good tolerance to LITT, with six out of ten achieving an ablation rate above 90%, and only one patient had an ablation rate below 70%. Oral administration of TMZ was well-tolerated by all patients during the early-TMZ phase. Mild headache was the most common adverse event (3/10), and only one severe adverse event occurred. At a 6-month follow-up post-LITT, tumor progression was observed in five patients; noneof the patients reached survival endpoints. This preliminary report substantiates the favorable tolerability of early application of TMZ in combination with LITT. The safety profile was found to be acceptable, and the initial efficacy results were promising. Future studies should explore the potential of LITT combination therapy in greater detail and with larger patient samples. [ABSTRACT FROM AUTHOR]

In this study, the influence of glycoproteomic changes, specifically MUC16, on NK cell-mediated immunotherapy response in ovarian cancer is explored. Analysis of glycoprotein data from the CPTAC database identified significant upregulation of MUC16 in ovarian cancer tissues, associated with tumor invasiveness and immune evasion. Experimental findings showed that MUC16 knockdown increased NK cell cytotoxicity, decreased invasiveness, and boosted NK cell activation, while MUC16 overexpression resulted in the opposite effects. In vivo experiments demonstrated that MUC16 knockdown suppressed tumor growth, enhanced NK cell infiltration, and bolstered NK cell activation, underscoring the potential of MUC16 as a target for novel immunotherapy approaches in ovarian cancer treatment. [ABSTRACT FROM AUTHOR]

Introduction: Lung cancer is a highly prevalent and deadly disease worldwide, causing over 1.2 million deaths each year. Pingxiao Pian (PXP) tablets, a Chinese traditional medicine, have been widely applied in the treatment of lung cancer. However, the mechanism underlying therapeutic effects of PXP tablets remains undisclosed. Methods: A549 human LUAD cell line was utilized for in vitro experiments. Transfection of miR-29b mimic was performed using Lipofectamine 3000. PXP was purchased and dissolved into PBS and drinking water after carefully removing the outer coating. Dual-luciferase reporter assay was conducted to assess the regulatory effect of miR-29b on TGF-β1. The protein levels of epithelial-mesenchymal transition (EMT) markers and activation of TGF-β1 pathway were characterized using immunoblotting analysis. Results: PXP reduced the invasiveness and proliferation of LUAD cells by increasing miR-29b-3p expression in vitro. Overexpression of miR-29b-3p resulted in decreased cell proliferation and invasiveness, while silencing of miR-29b-3p in the A549 cells displayed the opposite effect. Moreover, PXP treatment reversed the increased cell proliferating rate triggered by miR-29b-3p silencing. Additionally, PXP was found to hamper EMT occurrence in A549 cells by regulating miR-29b-3p and reduce expression of N-cad and vimentin. Overexpression of miR-29b-3p blocked the phosphorylation of Smad2/3 and decreased TGF-β1 expression. Luciferase assay results indicated that miR-29b-3p directly regulated TGF-β1 expression. In vivo tumor formation experiments confirmed the tumor-reducing effects of PXP and the role of miR-29b in tumor progression. PXP treatment decreased tumor size and weight via regulating miR-29b-3p. Conclusion: Our study suggests that PXP exerts anti-tumor effects in LUAD through the regulation of miR-29b and the inhibition of EMT via the TGF-β1/Smad2/3 pathway. [ABSTRACT FROM AUTHOR]

Heparin, traditionally known for its anticoagulant properties, has recently been identified as a potential agent in cancer therapy. Its derivatives, including low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH), are being investigated for their multifaceted roles in oncology. This review focuses on the expanding exploration of heparin's anticancer effects and its possible integration into cancer treatment protocols. The primary aim is to consolidate and analyze current research on the anticancer properties of heparin and its derivatives. It seeks to illuminate the mechanisms by which these compounds influence cancer progression, including their impact on angiogenesis, tumor cell proliferation, immune response modulation, and the inhibition of cancer cell migration and invasion. Additionally, the review aims to evaluate the potential of heparin and its derivatives in complementing existing chemotherapy treatments. An extensive literature review was conducted, encompassing in vitro, in vivo, and clinical studies. Sources included a range of scientific databases, employing keywords related to heparin and oncology. The selected studies were critically reviewed to extract relevant data on the efficacy, mechanisms, and potential clinical applications of heparin in cancer therapy. The results reveals that heparin and its derivatives exhibit significant anticancer activity across various research settings; key findings include the inhibition of angiogenesis, reduction in tumor cell proliferation, stimulation of immune responses, and the limitation of cancer cell migration and invasion. The compounds also show promise as adjuncts to conventional chemotherapy, potentially enhancing the efficacy of existing cancer treatments. This review highlights the burgeoning role of heparin and its derivatives in the realm of cancer therapy, marking a shift from their traditional use as anticoagulants. While promising, the research underscores the need for further comprehensive studies to fully understand the mechanisms of action, optimal dosing, potential side effects, and patient selection criteria. The potential integration of heparin into cancer treatment regimens opens new therapeutic possibilities warranting continued investigation in this rapidly evolving field. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer (CRC) is among the most common malignant tumors worldwide, posing a significant threat to human health. Most patients with CRC are refractory to existing treatment regimens, such as immune checkpoint blockades (ICBs), yielding unsatisfactory outcomes. This study aimed to explore the effect and mechanism of a natural product, indole-3-carbinol (I3C), in CRC pathogenesis and immunotherapy. Methods: A series of in vitro experiments, such as the cell counting kit-8 and wound healing assays, were used to assess the proliferative, colony-formating and migratory capacity of human CRC cells after I3C treatment. In vivo experiment, xenograft growth assay was conducted to verify the effect of I3C on CRC. Hematoxylin–eosin (HE) staining was utilized to evaluated the toxic effect of I3C. Immunohistochemical staining was used to detect CD8+ T cell infiltration. Subcutaneous CRC models constructed in immunocompetent mice were used to test the effects of I3C treatment in combination with PD1ab therapy. The Human Protein Atlas (HPA) database, cell transfection, and quantitative real-time polymerase chain reaction (RT-qPCR) experiments were used to explore the mechanism of I3C in CRC. Results: I3C significantly inhibited CRC cell proliferation, colony formation, and migration capacity in vitro and in vivo. The result of HE staining indicated that I3C exert no significant toxic effect on heart, liver and kidney. HPA data analysis and RT-qPCR results demonstrated that PTEN expression was lower in CRC tissues than in normal tissues or cells. Besides, I3C exerted antitumor activity and promoted CD8+ T cell infiltration by upregulating PTEN expression. Consequently, I3C, in conjunction with PD1ab therapy, synergistically enhanced the antitumor effect on CRC in immunocompetent mice. Conclusions: These findings suggested that by upregulating PTEN expression, the natural product I3C strongly prevented tumor progression and exerted no systematic toxicity in the major organs such as heart, kidney and liver. Furthermore, I3C significantly enhanced PD1ab therapeutic effect in CRC, highlighting its role as a candidate preventive or therapeutic compound for CRC therapy, especially in combination with PD1ab therapy. Further clinical trial should be conducted in the future. [ABSTRACT FROM AUTHOR]

Background: Disulfidoptosis is increasingly linked to cancer progression, yet its immunological impacts and prognostic value in lung adenocarcinoma (LUAD) remain poorly understood. This study aims to delineate the predictive significance of disulfidoptosis-related genes (DRGs) in LUAD, their potential as therapeutic targets, and their interaction with the tumor microenvironment. Methods: We analyzed the expression profiles of 23 DRGs and survival data, performing consensus clustering to identify molecular subtypes. Survival analysis and gene set variation analysis (GSVA) were used to explore cluster differences. Key DRGs were selected for Cox and LASSO regression to develop a prognostic model. Tensin4 (TNS4), a key gene in the model, was further evaluated through immunohistochemistry (IHC) in LUAD and normal tissues and gene knockdown experiments in vitro. Results: Two clusters were identified, with 225 differentially expressed genes. A six-gene signature was developed, which classified LUAD patients into high- and low-risk groups, showing significant survival differences. The risk score independently predicted LUAD prognosis and correlated with immunotherapy responses. IHC showed elevated TNS4 levels in LUAD tissues, while in vitro TNS4 knockdown reduced both cell proliferation and migration. Conclusion: This study highlights the role of DRGs in LUAD, with a validated gene signature offering new avenues for targeted therapies, potentially improving LUAD treatment outcomes. [ABSTRACT FROM AUTHOR]

Tumor metastasis is the main cause of therapeutic failure and mortality in cancer patients. The intricate metastastic process is influenced by both the intrinsic properties of tumor cells and extrinsic factors, such as microorganisms. Notably, some microbiota have been discovered to colonize tumor tissues, collectively known as intratumoral microbiota. Intratumoral microbiota can modulate tumor progression through multiple mechanisms, including regulating immune responses, inducing genomic instability and gene mutations, altering metabolic pathways, controlling epigenetic pathways, and disrupting cancer-related signaling pathways. Furthermore, intratumoral microbiota have been shown to directly impact tumor metastasis by regulating cell adhesion, stem cell plasticity and stemness, mechanical stresses and the epithelial-mesenchymal transition. Indirectly, they may affect tumor metastasis by modulating the host immune system and the tumor microenvironment. These recent findings have reshaped our understanding of the relationship between microorganims and the metastatic process. In this review, we comprehensively summarize the existing knowledge on tumor metastasis and elaborate on the properties, origins and carcinogenic mechanisms of intratumoral microbiota. Moreover, we explore the roles of intratumoral microbiota in tumor metastasis and discuss their clinical implications. Ongoing research in this field will establish a solid foundation for novel therapeutic strategies and clinical treatments for various tumors. [ABSTRACT FROM AUTHOR]

Krüppel-like factors (KLFs) regulate various biological processes such as cell proliferation, migration, invasion, and differentiation as gene transcription factors. Signaling pathways which mediated by KLF4 and KLF4 have a sophisticated role in tumors due to multiple factors, including the types or stage of tumors. KLF4 plays a promoter role in tumorigenesis and development, or tumor suppressor as a context-dependent anti- and pro-inflammatory factor. KLF4 over-expression increases CD8+T cell differentiation and enhances the antitumor immunity. This review aims to provide information about the relationship of KLF4 in immunity with tumors and to guide the future study. [ABSTRACT FROM AUTHOR]

Background: Vesical Imaging-Reporting and Data System (VI-RADS) based on multiparametric magnetic resonance imaging (mp-MRI) performed well in diagnosing muscle-invasive bladder cancer (MIBC). However, certain cases may present challenges in determining the final VI-RADS score using only T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) sequences, especially in the absence of dynamic contrast-enhanced (DCE) imaging. This study aims to evaluates whether biparametric MRI (bp-MRI) achieve comparable diagnostic performance to mp-MRI for predicting MIBC and seeks to identify the most suitable bp-MRI criterion by establishing four specific conditions based on T2WI and DWI. Methods: A retrospective analysis was conducted on 447 patients who underwent preoperative mp-MRI. Images were evaluated according to the VI-RADS protocol by three independent readers. In the bp-DWI and bp-DWI Plus criteria, DWI was the primary sequence used for lesion assessment, while T2WI was the primary sequence for bp-T2WI and bp-T2WI Plus criteria. The Plus criteria (bp-DWI Plus and bp-T2WI Plus) assigned a final VI-RADS score of 4 when both T2WI and DWI scores were 3. The gold standard for diagnosis was histopathological evaluation after surgery. Diagnostic performance was evaluated by comparing the area under the curve (AUC), sensitivity, specificity, and inter-reader agreement using Cohen's kappa analysis. Results: Among 447 patients, 304 confirmed as NMIBC and 143 as MIBC. The kappa values were 0.876, 0.873, 0.873, 0.642, and 0.642 for mp-MRI, bp-DWI, bp-DWI Plus, bp-T2WI, and bp-T2WI Plus, respectively, when VI-RADS cutoff > 2. Similarly, when cutoff > 3, the kappa values were 0.848, 0.811, 0.873, 0.811, and 0.873. No significant differences were observed between mp-MRI and bp-DWI (AUC: 0.916 vs. 0.912, p = 0.498), but mp-MRI and bp-DWI had higher AUCs compared to bp-DWI Plus, bp-T2WI, and bp-T2WI Plus. Conclusions: Both mp-MRI and bp-DWI demonstrate excellent performance in predicting MIBC, with bp-DWI being an alternative to mp-MRI. Trial registration: retrospectively. [ABSTRACT FROM AUTHOR]

Desmoplastic infantile ganglioglioma (DIG) is a rare intracranial benign tumor occurring in infants under 2 years of age. It has good biological and behavioral characteristics and occasionally has malignant characteristics, such as multiple intracranial lesions, postoperative progression or recurrence, meningeal diffusion, and metastasis. We present a non-infant with DIG who underwent tumor progression. A 16-year-old girl presented with DIG in the cerebral cistern and underwent subtotal resection. A magnetic resonance imaging (MRI) of the brain 2 years later revealed that the area of abnormal enhancement in the surgical site was approximately the same as before, and follow-up was continued. A reexamination 5 years later showed that the residual extent of the operative area was significantly larger than before and involved the right frontal and temporal lobes, considering the progression of the residual part of the tumor. This case report focuses on the occurrence of DIG and its potential malignant features, as assessed through magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

Background: Dysbindin domain-containing 1 (DBNDD1) is strongly connected with the occurrence and development of malignancies, but the DBNDD1 function and mechanism in invasive breast cancer (IBC) remain poorly understood. Our objective was to ascertain the possible diagnosis and prognostic importance of DBNDD1 in IBC. Method: An analysis was done to ascertain the connection between the DBNDD1 expression level in IBC and clinicopathological features employing the relevant databases, and to evaluate DBNDD1 in the diagnosis and prognosis of IBC. We explored possible cellular mechanisms and biological functions as well as explored DBNDD1-related interacting proteins, analyzed DBNDD1 methylation status, and investigated its correlation with immune cell infiltration. The effect of DBNDD1 on the function of breast cancer (BC) cells was studied in vitro. Result: DBNDD1 mRNA and protein levels exhibited higher expression in IBC, and were significantly correlated with a worse outcome. DBNDD1 hypomethylation status was linked to a negative prognosis. Enrichment analysis revealed that the genes exhibiting a positive correlation with DBNDD1 expression were mostly enriched in pathways linked to DNA synthesis and DNA methylation. Furthermore, the DBNDD1 expression level exhibited a substantial correlation with the immune cell infiltration in tissue. DBNDD1 overexpression emerged to enhance the BC cell's proliferation, invasion and migration as well as suppress the BC cell's apoptosis, as validated by in vitro tests. Conclusion: DBNDD1 upregulation is directly linked to the tumor immune cell infiltration and the unfavorable IBC prognosis. DBNDD1 possesses the capacity to be a biomarker for diagnosing and predicting the outcome of a disease, as well as a possible target for therapeutic interventions in IBC. [ABSTRACT FROM AUTHOR]

SOX2 is one of the members of the SOX transcription factor family, which is believed to be an important transcription factor that plays a role in embryonic development, maintenance of stem cells, cancer progression, and resistance to cancer treatment. There is increasing evidence suggesting that SOX2 is crucial for the initiation, progression, invasion, metastasis, and treatment resistance of prostate cancer, therefore understanding the mechanism of SOX2 in prostate cancer can provide better targets for the treatment of prostate cancer. This article reviews the structural domains, normal physiological functions, and role in prostate cancer progression of SOX2, providing potential targets for prostate cancer treatment. [ABSTRACT FROM AUTHOR]

Background: To assess the efficacy and safety of PD-1 and PD-L1 immune checkpoint inhibitors (ICIs) in managing advanced intrahepatic cholangiocarcinoma (ICC). Methods: A retrospective analysis of treatment data for patients with advanced ICC who received ICIs at the Second Affiliated Hospital of Chongqing Medical University from the inception of the inpatient medical record database until 30 April 2024. The analysis concentrated on the safety and efficacy of the treatment. The primary endpoint was progression-free survival (PFS), while the secondary endpoints included overall survival (OS) and safety. The Kaplan-Meier method was employed to plot survival curves, and differences between groups were assessed using log-rank tests. Results: 96 patients diagnosed with ICC were included, comprising 60 males (62.50%) and 36 females (37.50%). 85 patients exhibited disease progression, 22 patients succumbed, and 38 patients were lost to follow-up finally. Those who initiated immunotherapy promptly following first-line antitumor treatment exhibited a notably prolonged PFS compared to those experiencing tumor progression (5.63 months (95%CI: 3.12~8.14) vs 2.50 months (95%CI: 1.83~3.17), P= 0.002). However, no significant disparity in the PFS with immunotherapy in different lines therapy(P= 0.406) and the OS was observed between the two groups(P= 0.360). 18 patients (18.75%) experienced treatment-emergent adverse events (AEs), with 3 patients encountering AEs of grade ≥3. All patients returned to normal after symptomatic treatment. Conclusions: In patients with advanced ICC, the timely initiation of ICIs as adjuvant therapy following first-line antitumor treatment can result in favorable efficacy and a good safety profile. [ABSTRACT FROM AUTHOR]

Single-cell spatial omics analysis requires consideration of biological functions and mechanisms in a microenvironment. However, microenvironment analysis using bioinformatic methods is limited by the need to detect histological morphology and extend it to the surrounding area. In this study, we developed SpatialKNifeY (SKNY), an image-processing-based toolkit that detects spatial domains that potentially reflect histology and extends these domains to the microenvironment. Using spatial transcriptomic data from breast cancer, we applied the SKNY algorithm to identify tumor spatial domains, followed by clustering of the domains, trajectory estimation, and spatial extension to the tumor microenvironment (TME). The results of the trajectory estimation were consistent with the known mechanisms of cancer progression. We observed tumor vascularization and immunodeficiency at mid- and late-stage progression in TME. Furthermore, we applied the SKNY to integrate and cluster the spatial domains of 14 patients with metastatic colorectal cancer, and the clusters were divided based on the TME characteristics. In conclusion, the SKNY facilitates the determination of the functions and mechanisms in the microenvironment and cataloguing of the features. Author summary: The advent of high-resolution and high-density spatial omics platforms has created a growing need for practical analytical tools in cancer research. While significant efforts have been made to develop unsupervised clustering methods, advancements in downstream analyses have been relatively slower. To address this issue, we developed SpatialKNifeY (SKNY), a versatile toolkit designed to analyze spatial omics data by defining the spatial domains of cancer cells and their microenvironment. SKNY offers a suite of analyses, including clustering and trajectory analysis, with a unique capability to extract spatial domains and their surrounding regions. The tool enables integrated studies of cancer cells alongside their stroma, immune cells, and vascular environment. Using SKNY, we quantified the vascular and immune environments surrounding cancer cells during progression, revealing insights consistent with established cancer pathology and progression models. These results highlight the toolkit's utility and the biological interpretability of its analyses, providing a valuable resource for spatial omics research. [ABSTRACT FROM AUTHOR]

The objective of this study was to explore the potential genetic link between Crohn's disease and breast cancer, with a focus on identifying druggable genes that may have therapeutic relevance. We assessed the causal relationship between these diseases through Mendelian randomization and investigated gene-drug interactions using computational predictions. This study sought to identify common genetic pathways possibly involved in immune responses and cancer progression, providing a foundation for future targeted treatment research. The dataset comprises single nucleotide polymorphisms used as instrumental variables for Crohn's disease, analyzed to explore their possible impact on breast cancer risk. Gene ontology and pathway enrichment analyses were conducted to identify genes shared between the two conditions, supported by protein–protein interaction networks, colocalization analyses, and deep learning-based predictions of gene-drug interactions. The identified hub genes and predicted gene-drug interactions offer preliminary insights into possible therapeutic targets for breast cancer and immune-related conditions. This dataset may be valuable for researchers studying genetic links between autoimmune diseases and cancer and for those interested in the early identification of potential drug targets. [ABSTRACT FROM AUTHOR]

Purpose: Nasopharyngeal carcinoma is a common clinical malignant tumour in the nasopharynx. The secretion of vIL-10 by EB virus can promote the development of nasopharyngeal carcinoma. The purpose of this study was to provide a theoretical basis for potential targets and mechanisms of vIL-10 in nasopharyngeal carcinoma. Methods: A total of 100 ng/mL vIL-10 was applied to the nasopharyngeal carcinoma CNE-2 cell line for 48 h, and then whole transcriptome sequencing analysis was performed to identify potential targets and signalling pathways of vIL-10 in nasopharyngeal carcinoma. The effects of vIL-10 on the proliferation, migration, invasion and apoptosis of human nasopharyngeal carcinoma cells were determined by ELISA, Ki67 immunofluorescence, colony formation, transwell migration/invasion, Hoechst 33,258 staining, flow cytometry and other experiments, and the potential effects of vIL-10 on nasopharyngeal carcinoma cells were verified at the cellular level. Western blotting was performed to measure the changes in key factors of the JAK1-STAT3 signalling pathway in nasopharyngeal carcinoma cells after vIL-10 treatment. Results: The whole transcriptome gene sequencing results showed that vIL-10 could effectively activate the JAK-STAT signalling pathway and upregulate the expression of JAK1 and STAT3. Moreover, vIL-10 inhibited the apoptosis of nasopharyngeal carcinoma cells, enhanced their migration and invasion capabilities, and further promoted the proliferation of nasopharyngeal carcinoma cells. Conclusion: vIL-10 regulates the JAK1-STAT3 signalling pathway, promotes the proliferation of NPC cells, enhances their migration and invasion capabilities, inhibits tumour cell apoptosis, and participates in the progression of nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Cellular aging is a multifactorial and intricately regulated physiological process with profound implications. The interaction between cellular senescence and cancer is complex and multifaceted, senescence can both promote and inhibit tumor progression through various mechanisms. M6A methylation modification regulates the aging process of cells and tissues by modulating senescence-related genes. In this review, we comprehensively discuss the characteristics of cellular senescence, the signaling pathways regulating senescence, the biomarkers of senescence, and the mechanisms of anti-senescence drugs. Notably, this review also delves into the complex interactions between senescence and cancer, emphasizing the dual role of the senescent microenvironment in tumor initiation, progression, and treatment. Finally, we thoroughly explore the function and mechanism of m6A methylation modification in cellular senescence, revealing its critical role in regulating gene expression and maintaining cellular homeostasis. In conclusion, this review provides a comprehensive perspective on the molecular mechanisms and biological significance of cellular senescence and offers new insights for the development of anti-senescence strategies. [ABSTRACT FROM AUTHOR]

Objective: Nonfunctioning macroadenoma is a commonly diagnosed pituitary tumor. Resection is the favored treatment, with radiosurgery often utilized for residual or progressing disease. Long-term outcomes are established in the literature for single-fraction frame-based radiosurgery, but mature outcomes are lacking for fractionated frameless radiosurgery. We report our institution's 5-year efficacy and toxicity results for unfavorable nonfunctioning pituitary macroadenoma patients treated with 5-fraction robotic radiosurgery. Methods: Between 2010 and 2020, patients who completed 5-fraction robotic radiosurgery for the treatment of unfavorable nonfunctioning pituitary macroadenomas were included. A tumor was considered unfavorable if the gross tumor volume (GTV) was larger than 5 cc or if it closely approached a critical structure (optic apparatus, brainstem, or pituitary gland). Local control was calculated using the Kaplan–Meier method. Results: Twenty predominantly female patients (60%), ages 21–77 (median: 53 years), were included in this study. All underwent primary resection at the time of diagnosis. The indication for radiosurgery was tumor progression (n = 14, 70%) or residual tumor after subtotal resection (n = 6, 30%). Eighty-five percent of patients treated with radiosurgery (n = 17) had cavernous sinus involvement. Median GTV was 3.4 cm3 (range: 0.3–20.8 cm3), and 40% of the tumors had suprasellar extension. A mean dose of 28.8 Gy (range: 25–30 Gy) was delivered to a median isodose line of 80% (range: 75%–89%). The median optic chiasm maximum point dose was 21.8 Gy (range: 12.0–25.0 Gy). Acute toxicity was minimal with eight patients (40%) developing short-lived headaches and one patient (5%) developing a brief ipsilateral sixth nerve palsy. There was no late radiation-induced neurologic or optic dysfunction identified in this cohort. At a median follow-up of 5 years, local control was 94%. There was one in-field failure pathologically confirmed following surgery for pituitary hemorrhage and two radiographically confirmed out-of-field failures in patients with larger tumors (>20 cc). Conclusions: The treatment of unfavorable nonfunctioning pituitary macroadenoma with 5-fraction robotic radiosurgery provides excellent local control to date, with acceptable toxicity. However, tumors with GTVs greater than 20 cc may still require conventionally fractionated treatment with a margin to optimize local control. [ABSTRACT FROM AUTHOR]

Disrupting the interaction between tumor-cell surface PD-L1 and T cell membrane PD-1 can elicit durable clinical responses. However, only about 10% of ovarian cancer patients respond to PD-1/PD-L1 blockade. Here, we show that PD-L1 expression in ovarian cancer-patient tumors is predominantly intracellular. Notably, PARP inhibitor treatment highly increased intracellular PD-L1 accumulation in both ovarian cancer-patient tumor samples and cell lines. We investigated whether intracellular PD-L1 might play a critical role in ovarian cancer progression. Mutating the PD-L1 acetylation site in PEO1 and ID8Brca1−/− ovarian cancer cells significantly decreased PD-L1 levels and impaired colony formation, which was accompanied by cell cycle G2/M arrest and apoptosis induction. PEO1 and ID8Brca1−/− tumors with PD-L1 acetylation site mutation also exhibited significantly reduced growth in mice. Furthermore, targeting intracellular PD-L1 with a cell-penetrating antibody effectively decreased ovarian tumor-cell intracellular PD-L1 level and induced tumor-cell growth arrest and apoptosis, as well as enhanced DNA damage and STING activation, both in vitro and in vivo. In conclusion, we have shown the critical role of intracellular PD-L1 in ovarian cancer progression. [ABSTRACT FROM AUTHOR]

Breast cancer is a highly heterogeneous disease; hence, it is crucial to understand its biology and identify new targets for the development of effective treatments. Galectin-1 is known to play an oncogenic role in breast cancer progression. It is known that oncogenic factors can influence cancer progression through interactions with miRNAs. The purpose of this study is to identify the clinical significance and biological role of galectin-1 and miR-22-3p in cancer progression according to the molecular subtype of breast cancer. We analyzed the expression of galectin-1 and miR-22-3p using cancer tissues and the correlation with clinical pathological characteristics. In addition, we investigated the regulation of the cell cycle and EMT processes of cancer progression through the galectin-1/miR-22-3p axis using cell lines of different breast cancer subtypes. miR-22-3p negatively regulates galectin-1 expression and the two molecules have opposite patterns of oncogenic and tumor-suppressive functions, respectively; furthermore, these two molecules are associated with metastasis-free survival. Cell experiments showed that miR-22-3p overexpression and galectin-1 knockdown inhibited the proliferation and invasion of breast cancer cells. Galectin-1 regulates different cancer progression pathways depending on the molecular subtype. In hormone receptor-positive breast cancer cells, galectin-1 knockdown mainly inhibited cell cycle-related substances and induced G0/G1 arrest, whereas in triple-negative breast cancer cells, it suppressed molecules related to the epithelial–mesenchymal transition pathway. In conclusion, the miR-22-3p/galectin-1 axis regulates different cancer metastasis mechanisms depending on the specific molecular subtype of breast cancer, and miR-22-3p/galectin-1 axis modulation may be a novel target for molecular subtype-specific personalized treatment. [ABSTRACT FROM AUTHOR]

Autophagy, a cellular process essential for maintaining homeostasis, plays a fundamental role in recycling damaged components and in adapting to stress. The dysregulation of autophagy is implicated in numerous human diseases, including cancer, where it exhibits a dual role as both a suppressor and a promoter, depending on the context and the stage of tumor development. The significant sex differences observed in autophagic processes are determined by biological factors, such as genetic makeup and sex hormones. Estrogens, through their interaction with specific receptors, modulate autophagy and influence tumor progression, therapy resistance, and the immune response to tumors. In females, the escape from X inactivation and estrogen signaling may be responsible for the advantages, in terms of lower incidence and longer survival, observed in oncology. Women often show better responses to traditional chemotherapy, while men respond better to immunotherapy. The action of sex hormones on the immune system could contribute to these differences. However, women experience more severe adverse reactions to anticancer drugs. The estrogen/autophagy crosstalk—involved in multiple aspects of the tumor, i.e., development, progression and the response to therapy—deserves an in-depth study, as it could highlight sex-specific mechanisms useful for designing innovative and gender-tailored treatments from the perspective of precision medicine. [ABSTRACT FROM AUTHOR]

Expression of BCL-B, an anti-apoptotic BCL-2 family member, is correlated with worse survival in lung adenocarcinomas. Here, we show that BCL-B can mitigate cell death initiation through interaction with the effector protein BOK. We found that this interaction can promote sublethal mitochondrial outer membrane permeabilization (MOMP) and consequently generate apoptosis-flatliners, which represent a source of drug-tolerant persister cells (DTPs). The engagement of endothelial-mesenchymal-transition (EMT) further promotes cancer cell invasiveness in such DTPs. Our results reveal that BCL-B fosters cancer cell aggressiveness by counteracting complete MOMP. [ABSTRACT FROM AUTHOR]