Types Of Cancer Research Articles

Therapeutic indications for antibody-drug conjugates estimated from HER2 and p53 expressions in endometrial carcinoma

ObjectiveWhile human epidermal growth factor receptor 2 (HER2) is upregulated in endometrial carcinoma—especially in the p53 aberrant type— conventional anti-HER2 therapy is not typically used for this cancer type. Recently, HER2-targeted antibody-drug conjugates have shown antitumor effects against HER2 low-expressing cancers. Therefore, we analyzed the clinicopathological characteristics of HER2-positive endometrial carcinomas including those with low expression, as well as the prognostic significance of p53 and HER2 co-expression. MethodsImmunohistochemistry for HER2 and p53 was performed in 530 patients with endometrial carcinoma; 124 cases (23%) were HER2-positive. ResultsOf the HER2-positive cases, >50% were 1+. A high prevalence of HER2 expression was observed in serous (64%), clear-cell (73%), and mixed (64%) carcinomas. Notably, 19% of endometrioid carcinomas were HER2-positive. HER2 positivity was significantly associated with age ≥60 years, high-grade histological subtype, deep myometrium invasion, stage III/IV, recurrence, and death. Univariate analysis showed that HER2-positive cases had reduced progression-free survival (PFS) (p = 0.007) and overall survival (OS) (p = 0.012). However, after adjusting for stage, HER2 positivity was not associated with survival. In the early stage, co-expression of HER2-positive and p53 aberrant types was associated with shorter PFS (p < 0.001) and OS (p < 0.001) compared with at least one negative result. Multivariate analysis of PFS showed HER2 and p53 co-expression (hazard ratio, 1.891; 95% confidence interval, 1.183–5.971, p = 0.008) as an independent prognostic factor. ConclusionsThis study presents detailed clinicopathological characteristics and the prognostic impact of HER2-positivity in endometrial carcinomas. HER2-targeted antibody-drug conjugate therapy may be broadly applicable to endometrial carcinoma.

Cancer and the Microbiome of the Human Body.

Cancer remains a public health concern worldwide, with its incidence increasing worldwide and expected to continue growing during the next decades. The microbiome has emerged as a central factor in human health and disease, demonstrating an intricate relationship between the microbiome and cancer. Although some microbiomes present within local tissues have been shown to restrict cancer development, mainly by interacting with cancer cells or the host immune system, some microorganisms are harmful to human health and risk factors for cancer development. This review summarizes the recent evidence concerning the microbiome and some of the most common cancer types (i.e., lung, head and neck, breast, gastric, colorectal, prostate, and cervix cancers), providing a general overview of future clinical approaches and perspectives.

Impact of Social Needs and Identity Experiences on the Burden of Illness in Patients with Multiple Myeloma: A Mixed-Methods Study.

Multiple myeloma (MM) is a common hematologic malignancy, but due to its incurable nature, patients experience many relapses in their lifetime and hence face unique challenges. This mixed-methods study consisting of an online survey and subsequent focus groups aimed to understand how social and identity experiences affected the diagnostic, treatment, and care journey for patients with MM. Twenty-three adult patients with MM participated in this study. The survey participants identified common determinants negatively impacting their health, including mental health concerns (experienced by 90.5% of respondents), worries about food shortage (42.9%), and transportation concerns (28.6%). Focus group participants described high physical and mental health burdens associated with MM. Frequent monitoring, fear of a relapse, and unpredictable side effects contributed to high anxiety. Participants indicated that MM differed from other types of cancer and chronic health conditions in many ways, particularly how and where the diagnosis was made, disease progression and relapse, treatments and side effects, and financial concerns. Most participants (65.0%) reported ≥1 social need that negatively impacted health outcomes including lack of knowledge about MM, financial instability, and lack of insurance, transportation, and social support. The findings reveal that patients with MM continually experience patient-specific mental and physical health burdens indicating high unmet needs throughout the disease journey.

Leveraging PARP-1/2 to Target Distant Metastasis.

Poly (ADP-Ribose) Polymerase (PARP) inhibitors have changed the outcomes and therapeutic strategy for several cancer types. As a targeted therapeutic mainly for patients with BRCA1/2 mutations, PARP inhibitors have commonly been exploited for their capacity to prevent DNA repair. In this review, we discuss the multifaceted roles of PARP-1 and PARP-2 beyond DNA repair, including the impact of PARP-1 on chemokine signalling, immune modulation, and transcriptional regulation of gene expression, particularly in the contexts of angiogenesis and epithelial-to-mesenchymal transition (EMT). We evaluate the pre-clinical role of PARP inhibitors, either as single-agent or combination therapies, to block the metastatic process. Efficacy of PARP inhibitors was demonstrated via DNA repair-dependent and independent mechanisms, including DNA damage, cell migration, invasion, initial colonization at the metastatic site, osteoclastogenesis, and micrometastasis formation. Finally, we summarize the recent clinical advancements of PARP inhibitors in the prevention and progression of distant metastases, with a particular focus on specific metastatic sites and PARP-1 selective inhibitors. Overall, PARP inhibitors have demonstrated great potential in inhibiting the metastatic process, pointing the way for greater use in early cancer settings.

Diagnostic Performance of Preoperative Calcitonin and Procalcitonin Tests for Differential Diagnosis of Medullary Thyroid Cancer.

Medullary thyroid cancer (MTC) shows a relatively poor prognosis among thyroid cancers. Though calcitonin has been used as a diagnostic marker for MTC, it has disadvantages including poor sample stability and discrepancies among results by assay. This study aimed to compare the usefulness of preoperative calcitonin and procalcitonin (PCT) in the diagnosis of MTC. Serum calcitonin and PCT levels were measured before thyroidectomy from MTC (n = 23) and other types of thyroid cancers in patients (n = 1308). Diagnostic performances of calcitonin and PCT for discerning MTC were estimated. In a multivariate analysis, preoperative calcitonin level was independently associated with the diagnosis of MTC, whereas PCT was not. Calcitonin and PCT, respectively, exhibited area under the curve values of 0.997 and 0.979 for the diagnosis of MTC, without significant differences. For calcitonin, the sensitivity, specificity, and positive and negative predictive values were 0.957, 0.992, 0.688, and 0.999, respectively, at a cut-off of 7.2 pg/mL. The corresponding values for PCT were 0.913, 0.995, 0.778, and 0.998 at a cut-off of 0.19 ng/mL. Preoperative calcitonin and PCT showed similar diagnostic utility for MTC. Depending on the patient's clinical status and laboratory environment, these tests can be used as complementary methods for detecting MTC.

Aloe and coconut extracts mediated CuInS2 nanoparticles induce apoptosis in non-small lung cancer cells (A549)

The most prevalent type of cancer found in the world is lung cancer. Furthermore, chemotherapeutic intervention for lung carcinomas is frequently associated with severe off-target effects. As a result, there is a worldwide push to investigate alternative medicines with superior tolerance profiles, such as natural compounds, to substitute routinely used chemotherapeutics. The purpose of this study is to examine the anticancer potential of aloe (S1) and coconut (S2) extract-mediated CuInS2 (CIS) nanoparticles against non-small cell lung carcinoma (A549) cells. S1 and S2 both efficiently showed a dose-proportionate cytotoxic effect on A549 cells, while causing negligible toxic effects on normal healthy lung cells (WI-38), indicating their safety against healthy cells. Reduced cell viability was validated by acridine orange and ethidium bromide double staining, demonstrating that apoptosis was induced in A549 cells treated with both nanoparticles. In addition, the mitochondrial membrane potential was reduced by both nanoparticles, leading to an increase in ROS generation. Both nanoparticles increased caspase-3, caspase-9, and caspase-8 levels in A549 cells. To summarize, both nanoparticles induced apoptotic cell damage in A549 cells by targeting mitochondria, causing increased ROS production, activating the caspase cascade, and inducing apoptosis. Aloe (S1) and coconut (S2) extract-mediated CIS nanoparticles may represent viable therapeutic options for lung cancer management.

Inhibition of MSH6 augments the antineoplastic efficacy of cisplatin in non-small cell lung cancer as autophagy modulator

The altered response to chemotherapeutic agents predominantly stems from heightened single-point mutations within coding regions and dysregulated expression levels of genes implicated in drug resistance mechanisms. The identification of biomarkers based on mutation profiles and expression levels is pivotal for elucidating the underlying mechanisms of altered drug responses and for refining combinatorial therapeutic strategies in the field of oncology. Utilizing comprehensive bioinformatic analyses, we investigated the impact of eight mismatch repair (MMR) genes on overall survival across 23 cancer types, encompassing more than 7500 tumors, by integrating their mutation profiles. Among these genes, MSH6 emerged as the most predictive biomarker, characterized by a pronounced mutation frequency and elevated expression levels, which correlated with poorer patient survival outcomes.The wet lab experiments disclosed the impact of MSH6 in mediating altered drug responses. Cytotoxic assays conducted revealed that the depletion of MSH6 in H460 non-small lung cancer cells augmented the efficacy of cisplatin, carboplatin, and gemcitabine. Pathway analyses further delineated the involvement of MSH6 as a modulator, influencing the delicate equilibrium between the pro-survival and pro-death functions of autophagy.Our study elucidates the intricate interplay between MSH6, autophagy, and cisplatin efficacy, highlighting MSH6 as a potential therapeutic target to overcome cisplatin resistance. By revealing the modulation of autophagy pathways by MSH6 inhibition, our findings offer insights into novel approaches for enhancing the efficacy of cisplatin-based cancer therapy through targeted interventions.

Cannabidiol Enhances the Anticancer Activity of Etoposide on Prostate Cancer Cells.

Introduction: Cannabis sativa extract has been used as an herbal medicine since ancient times. It is one of the most researched extracts, especially among supportive treatments against cancer. Prostate cancer is one of the most frequently diagnosed cancer types in men worldwide and an estimated 288,300 new cases were diagnosed in 2023. Today, many advanced therapeutic approaches are used for prostate cancer, such as immunotherapy and chemotherapy, but acquired drug resistance, long-term drug usage and differentiation of cancer cells mostly restricted the efficiency of therapies. Therefore, it is thought that the use of natural products to overcome these limitations and improve the effectiveness of existing therapies may offer promising approaches. The present study focused on the investigation of the possible enhancer role of cannabidiol (CBD), which is a potent ingredient compound of Cannabis, on the chemotherapeutic agent etoposide in prostate cancer cells. Methods: Herein, we tested the potentiator role of CBD on etoposide in prostate cancer cells by testing the cytotoxic effect, morphological alterations, apoptotic effects, autophagy, unfolded protein response (UPR) signaling, endoplasmic reticulum-associated degradation mechanism (ERAD), angiogenic and androgenic factors, and epithelial-mesenchymal transition (EMT). In addition, we examined the combined treatment of CBD and etoposide on colonial growth, migrative, invasive capability, 3D tumor formation, and cellular senescence. Results: Our findings demonstrated that cotreatment of etoposide with CBD importantly suppressed autophagic flux and induced ERAD and UPR signaling in LNCaP cells. Also, CBD strongly enhanced the etoposide-mediated suppression of androgenic signaling, angiogenic factor VEGF-A, protooncogene c-Myc, EMT, and also induced apoptosis through activation caspase-3 and PARP-1. Moreover, coadministration markedly decreased tumorigenic properties, such as proliferative capacity, colonial growth, migration, and 3D tumor formation and also induced senescence. Altogether, our data revealed that CBD has a potent enhancer effect on etoposide-associated anticancer activities. Conclusion: The present study suggests that the use of CBD as a supportive therapy in existing chemotherapeutic approaches may be a promising option, but this effectiveness needs to be investigated on a large scale.

METTL3 and IGF2BP1-mediated m6A modification of ZHX2 promotes tumor property of renal cell carcinoma.

Renal cell carcinoma (RCC) is a common type of kidney cancer with limited treatment options and a high mortality rate. Therefore, it is essential to understand the role and mechanism of key genes in RCC development and progression. This study aimed to analyze the role of zinc fingers and homeoboxes 2 (ZHX2) in RCC and the underlying mechanism. RNA expression was analyzed by quantitative real-time polymerase chain reaction, while protein expression was analyzed by western blotting assay and immunohistochemistry assay. Cell viability was evaluated using CCK-8 assay, and cell proliferation was assessed by EdU assay. The rate of cell apoptosis was quantified by flow cytometry. Transwell assays were conducted to analyze cell migration and invasion. The sphere formation assay was performed to assess the formation of microspheres. Additionally, m6A RNA immunoprecipitation assay and RNA immunoprecipitation assay were utilized to investigate the relationship between ZHX2 and two proteins, methyltransferase like 3 (METTL3) and insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1). The stability of ZHX2 mRNA was analyzed through the Actinomycin D assay. Furthermore, a xenograft mouse model assay was conducted to analyze the effect of ZHX2 overexpression and METTL3 silencing on RCC cell tumor properties in vivo. ZHX2 expression was upregulated in both RCC tissues and cells when compared with healthy renal tissues and human renal cortex proximal convoluted tubule epithelial cells. Depletion of ZHX2 inhibited RCC cell proliferation, migration, invasion and spheroid-forming capacity but promoted cell apoptosis. Moreover, it was found that METTL3 mediated m6A methylation of ZHX2 and IGF2BP1 also stabilized ZHX2 through m6A methylation modification. Furthermore, ZHX2 overexpression showed a potential for attenuating the effects induced by METTL3 silencing and counteracted the inhibitory effect of METTL3 depletion on tumor formation in vivo. METTL3 and IGF2BP1-mediated m6A modification of ZHX2 promoted RCC progression. The finding suggests that ZHX2 may serve as a potential therapeutic target in RCC, providing valuable insights for future clinical interventions.

Eurycomanone inhibits osteosarcoma growth and metastasis by suppressing GRP78 expression

Ethnopharmacological relevanceOsteosarcoma (OS) is characterized by rapid growth and frequent pulmonary metastasis. Eurycoma longifolia Jack, a flowering plant primarily found in Southeast Asian countries, is commonly used in traditional herbal medicine. Its root extract is mainly used for against cancer, malaria, parasites and other conditions. The active compound in its root extract, eurycomanone (EUR), has been proven to inhibit lung and liver cancer proliferation. Aim of the studyOur research aimed to investigate the inhibitory effect and underlying molecular mechanism of EUR on OS growth and metastasis. Materials and methodsIn vitro experiments: western blotting (WB) screened 41 compounds that inhibited GRP78 expression and evaluated the protein levels of GRP78, PARP, cleaved-PARP, MMP2, and MMP9. Cell proliferation was evaluated using CCK-8, EdU, colony formation assay, and cell apoptosis was assessed by flow cytometry. Transwell, wound healing, and tube formation assays were performed to determine the effect of EUR on tumor invasion, migration, and angiogenesis, respectively. Quantitative real-time polymerase chain (qRT-PCR) and dual-luciferase activity assays detected GRP78 mRNA stability and transcription levels post-EUR and thapsigargin treatment. RNA-Seq identified signaling pathways inhibited by EUR. In vivo experiments: effects of EUR in mice were evaluated by H&E staining to detect lung metastasis and potential toxic effects in tissues. Immunohistochemical (IHC) staining detected the expression of Ki-67, CD31, and cleaved caspase-3 in tumors. ResultsGRP78 is highly expressed in OS and correlated with poor prognosis. In vitro, eurycomanone (EUR) significantly downregulated GRP78 expression, inhibited cell proliferation, migration, invasion, tube formation, and induced apoptosis. Moreover, it enhanced trichostatin A (TSA) sensitivity and exhibited inhibitory effects on other cancer types. Mechanistically, EUR decreased GRP78 mRNA stability and transcription. In vivo, EUR inhibited proliferation and invasion in tibial and PDX models. ConclusionsOur study demonstrated that EUR inhibits the growth and metastasis of OS by reducing GRP78 mRNA stability and inhibiting its transcription, which offers a novel approach for clinical treatment of OS.

Prognostic Nomogram Predicting Survival and Propensity Score Matching with Demographics and Comparative Analysis of Prostate Small Cell and Large Cell Neuroendocrine Carcinoma.

Background: This retrospective study aims to examine the patient demographics, survival rates, and treatment methods for small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC) of prostate origin while also identifying the main differences between common types of prostate cancer with comparative analysis for survival. Methods: Our analysis utilized the Surveillance, Epidemiology, and End Results database (SEER), and data was collected from 2000-2020. Cox proportional hazards and chi-squared analysis were used for statistical analysis. Results: A total of 718 cases of prostate small and large neuroendocrine carcinoma were identified. The median age was 71.5 years, and the median follow-up was 11.0 years (95% confidence interval (95% CI) = 9.2-12.8). Most patients were over the age of 80 years (33.8%) and Caucasian (74.4%). The overall 5-year survival was 8.0% (95% CI = 6.8-9.2). The 5-year OS for Caucasians was 7.3% (95% C.I. 6.0-8.3). For Black Americans, the 5-year OS was 11.9% (95% C.I. 7.3-16.5). For Hispanics, the 5-year OS was 12.2% (95% C.I. 7.7-16.7). The 5-year cause-specific survival (CSS) was 16.2% (95% CI = 14.3-18.1). For treatment modality, the five-year survival for each were as follows: chemotherapy, 3.5% (95% CI = 2.1-4.9); surgery, 18.2% (95% CI = 13.6-22.8); multimodality therapy (surgery and chemotherapy), 4.8% (95% CI = 1.7-7.9); and combination (chemoradiation with surgery), 5.0% (95% CI = 1.0-9.0). The prognostic nomogram created to predict patient survivability matched the findings from the statistical analysis with a statistical difference found in race, income, housing, stage, and nodal status. The nomogram also indicated a slight increase in mortality with tumors of greater size. This analysis showed a slight increase in mortality for patients of Asian race. In addition, there was a significant increase in death for patients with stage 3 tumors, as well as patients who underwent surgery and radiation. Furthermore, we performed propensity score matching for survival differences, and no survival difference was found between SCNEC and LCNEC. Conclusions: Asian patients, larger tumor size, and distant disease were associated with worse long-term clinical outcomes. By leveraging insights from registry-based studies, clinicians can better strategize treatment options, improving patient outcomes in this challenging oncology arena.

Construction of CeRNA Regulatory Network Based on WGCNA to Reveal Potential Prognostic Biomarkers for AML Cancer

Background: Acute myeloid leukemia (AML) is a type of blood cancer with diverse genetic pathogenesis. The identification of potential molecular biomarkers could improve the AML diagnosis and targeted therapy. Recently, competing endogenous RNAs (ceRNAs) became an active area in cancer research to determine molecular mechanisms underlying tumor development. Objectives: The aim of the present study was to investigate the key molecular biomarkers that are closely related to AML through bioinformatics analysis. Methods: In this research, the RNA-seq data of 151 AML patients and 151 corresponding health samples were retrieved from The Cancer Genome Atlas (TCGA) database and GTEx Portal (genotype-tissue expression), respectively. After that we screened the differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs by “limma” package in R to construct the co-expression network ceRNA (miRNA-lncRNA-mRNA) with weighted gene co-expression network analysis (WGCNA) package in R and Cytoscape (version 3.7.2) software, respectively. Then the relevant modules were identified and functional enrichment analysis was used to uncover the modules that are biologically related to AML cancer. Results: Based on our bioinformatics studies, we constructed a significant module which contain 333 genes. Among them, five up-regulated miRNAs with the highest GS (gene significant), include hsa-miR-374B, hsa-miR-553, hsa-miR-3679, hsa-miR-548L, hsa-miR-597 and five down-regulated miRNAs with the lowest GS including hsa-miR-3934, hsa-miR-4746, hsa-miR-466, hsa-miR-6722, hsa-miR-4490. For protein-coding genes (PCGs), the top-five up-regulated PCGs with the highest GS were AMIGO3, H2AC17, SPACA5, GPR21, and OR13C3. The top-five down-regulated PCGs with the lowest GS were XBP1, TOMM6, TREX1, TNFRSF6B, and BOLA2. Among the lncRNAs, the five up-regulated lncRNAs with the highest level of GS were GREP1, ZBTB20-AS2, LINC01596, LINC00345, and RMRP. The five down-regulated lncRNAs with the lowest GS were LINC01609, LINC01707, LINC02270, LINC02309, and LINC02243. These lncRNAs can serve as potential biomarkers to distinguish between AML and normal samples. Conclusions: Finally, considering the role of ceRNA network in various biological processes, examining the role of ceRNAs in AML may provide a deeper insight into molecular mechanisms underlying the pathogenesis of cancer. This understanding may propose potential biomarkers for diagnosis and therapeutic interventions.

Health harms that discourage alcohol consumption: A randomized experiment of warning messages

BackgroundHealth warnings about alcohol consumption could inform consumers and discourage alcohol consumption, but little is known about what topics these warnings should address. We sought to identify promising topics for alcohol warnings. MethodsIn January 2024, we recruited a convenience sample of 2,522 US adults ages ≥ 21 years. In an online within-subjects experiment, participants viewed messages about 6 topics (5 warning topics selected from a pool of 16 topics [e.g., liver disease, liver cancer] and 1 control topic [i.e., recycling or reselling products]) shown in random order. For each topic, participants viewed and rated 2 statements about that topic on perceived message effectiveness (primary outcome) and reactance (secondary outcome). ResultsThe 16 warning topics elicited higher perceived message effectiveness than the control topic (ps < 0.001). Among the warning topics, liver disease, most cancer types, dementia or mental decline, and hypertension elicited the highest perceived message effectiveness, while breast cancer, sleep, and drinking guidelines elicited the lowest. Fourteen of the 16 warning topics (all except for fetal harms and impaired driving) elicited more reactance than the control topic (ps < 0.001). Warning topics that elicited high perceived message effectiveness generally elicited high reactance, except for messages about liver disease and liver cancer, which elicited high perceived message effectiveness but only moderate reactance. DiscussionWarning messages about a variety of topics hold promise for discouraging alcohol consumption. Messages about liver disease, most cancer types, dementia or mental decline, and hypertension are perceived as especially effective; however, none of these topics are included in the current US alcohol warning.

Elucidating the pan-oncologic landscape of S100A9: prognostic and therapeutic corollaries from an integrative bioinformatics and Mendelian randomization analysis.

The calcium-binding protein S100A9 has emerged as a pivotal biomolecular actor in oncology, implicated in numerous malignancies. This comprehensive bioinformatics study transcends traditional boundaries, investigating the prognostic and therapeutic potential of S100A9 across diverse neoplastic entities. Leveraging a wide array of bioinformatics tools and publicly available cancer genomics databases, such as TCGA, we systematically examined the S100A9 gene. Our approach included differential expression analysis, mutational burden assessment, protein interaction networks, and survival analysis. This robust computational framework provided a high-resolution view of S100A9's role in cancer biology. The study meticulously explored S100A9's oncogenic facets, incorporating comprehensive analyses of its relationship with prognosis, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, and immune cell infiltration across various tumor types. This study presents a panoramic view of S100A9 expression across a spectrum of human cancers, revealing a heterogeneous expression landscape. Elevated S100A9 expression was detected in malignancies such as BLCA (Bladder Urothelial Carcinoma), CESC (Cervical squamous cell carcinoma and endocervical adenocarcinoma), COAD (Colon adenocarcinoma), ESCA (Esophageal carcinoma), and GBM (Glioblastoma multiforme), while reduced expression was noted in BRCA (Breast invasive carcinoma), HNSC (Head and Neck squamous cell carcinoma), and KICH (Kidney Chromophobe). This disparate expression pattern suggests that S100A9's role in cancer biology is multifaceted and context-dependent. Prognostically, S100A9 expression correlates variably with patient outcomes across different cancer types. Furthermore, its expression is intricately associated with TMB and MSI in nine cancer types. Detailed examination of six selected tumors-BRCA, CESC, KIRC (Kidney renal clear cell carcinoma), LUSC (Lung squamous cell carcinoma), SKCM (Skin Cutaneous Melanoma); STAD (Stomach adenocarcinoma)-revealed a negative correlation of S100A9 expression with the infiltration of most immune cells, but a positive correlation with neutrophils, M1 macrophages, and activated NK cells, highlighting the complex interplay between S100A9 and the tumor immune environment. This bioinformatics synthesis posits S100A9 as a significant player in cancer progression, offering valuable prognostic insights. The data underscore the utility of S100A9 as a prognostic biomarker and its potential as a therapeutic target. The therapeutic implications are profound, suggesting that modulation of S100A9 activity could significantly impact cancer management strategies.

Beyond breast cancer: role of selective estrogen receptor modulators in reducing systemic malignancies: evidence from population-based data

Background Raloxifene and bazedoxifene are selective estrogen receptor modulators (SERMs) used to prevent and treat osteoporosis in postmenopausal women. Raloxifene is also known for its preventive effect against invasive breast cancer; however, its effect on other cancer types is unclear. This study investigated the incidence of various cancers in osteoporosis patients receiving SERM therapy to determine its association with the risk of developing specific cancer types. Methods This retrospective cohort study examined the association between SERM use and the incidence of cervical, endometrial, ovarian, and colorectal cancers in postmenopausal women using data from the Korean National Health Insurance Service. Propensity score matching ensured group comparability by analyzing 95,513 participants. Cox proportional hazard models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the cancer risk associated with SERM therapy, differentiating between the effects of raloxifene and bazedoxifene. Results SERM therapy was associated with a reduced risk of cervical (adjusted HR = 0.47, 95% CI = 0.31–0.71), ovarian (adjusted HR = 0.61, 95% CI = 0.42–0.88), and colorectal cancer (adjusted HR = 0.49, 95% CI = 0.42–0.57). No significant risk reduction was observed for endometrial cancer (adjusted HR = 1.05, 95% CI = 0.70–1.59). A comparison between raloxifene and bazedoxifene revealed no significant differences in their cancer prevention effects. Conclusion SERM therapy administration is associated with a decreased incidence of cervical, ovarian, and colorectal cancers. Notably, the effects of raloxifene and bazedoxifene were consistent. Further investigations are crucial to elucidate the mechanisms underlying these observations and their clinical implications.

ETS1 drives EGF-induced glycolytic shift and metastasis of epithelial ovarian cancer cells

Epithelial ovarian cancer (EOC), a leading cause of gynecological cancer-related morbidity and mortality and the most common type of ovarian cancer (OC), is widely characterized by alterations in the Epidermal Growth Factor (EGF) signaling pathways. The phenomenon of metastasis is largely held accountable for the majority of EOC-associated deaths. Existing literature reports substantiate evidence on the indispensable role of metabolic reprogramming, particularly the phenomenon of the ‘Warburg effect’ or aerobic glycolysis in priming the cancer cells towards Epithelial to Mesenchymal transition (EMT), subsequently facilitating EMT. Considering the diverse roles of growth factor signaling across different stages of oncogenesis, our prime emphasis was laid on unraveling mechanistic details of EGF-induced ‘Warburg effect’ and resultant metastasis in EOC cells. Our study puts forth Ets1, an established oncoprotein and key player in OC progression, as the prime metabolic sensor to EGF-induced cues from the tumor microenvironment (TME). EGF treatment has been found to induce Ets1 expression in OC cells predominantly through the Extracellular Signal-Regulated Kinase1/2 (ERK1/2) pathway activation. This subsequently results in pronounced glycolysis, characterized by an enhanced lactate production through transcriptional up-regulation of key determinant genes of the central carbon metabolism namely, hexokinase 2 (HK2) and monocarboxylate transporter 4 (MCT4). Furthermore, this study reports an unforeseen combinatorial blockage of HK2 and MCT4 as an effective approach to mitigate cellular metastasis in OC. Collectively, our work proposes a novel mechanistic insight into EGF-induced glycolytic bias in OC cells and also sheds light on an effective therapeutic intervention approach exploiting these insights.

Exploring the Association between Health-Related Physical Fitness and Quality of Life in Patients with Cancer: A Cross-Sectional Study.

Whereas an exercise intervention effectively improves patients' quality of life, little information is available about the contribution of each physical fitness component. This study aims to explore the association between physical fitness components and the quality-of-life domain in patients with cancer. Between September 2021 and August 2023, 160 patients with mixed cancer types visiting the Oncology Unit were selected on a consecutive basis according to selection criteria. They underwent a comprehensive baseline assessment including the six-minute walking test, the handgrip strength test, the isometric leg press test, the back scratch, sit and reach tests, their waist-hip ratio, and their body mass index. The European Organization for Research and Treatment of Cancer Quality of Life and Core Questionnaire was used to measure the quality of life. The sample size was based on the use of regression models to study associations between clinical characteristics and fitness outcomes. All of the analyses were performed using the SPSS v.25 statistical package. Patients had a mean age of 58 years, 68% were female, 42% were affected by breast cancer, and all were receiving anticancer treatments. Higher functional capacity was associated with better global health status (p < 0.0001) and physical (p < 0.0001), role (p < 0.0001), emotional (p = 0.026), and social function (p = 0.016) and inversely linked with fatigue (p = 0.001). Lower-limb flexibility was significantly associated with all of the domains except for role and social functions. The waist-hip ratio was inversely associated with physical function (p < 0.0001) and positively related to fatigue (p = 0.037). Exercise programs aiming to improve the quality of life in cancer should be addressed to optimize these fitness components.

CT Derived Measurement of Body Composition: Observations from a Comparative Analysis of Patients with Colorectal and Lung Cancer

Background CT-derived measures of body composition have been shown to have prognostic value in patients with cancer. However, few studies have compared these observations across tumor types and stages of disease. The aim of the present study was to compare body composition measures between two types of cancers, i.e. colorectal cancer (CRC), which is less inflammatory and patients maintain body composition over a longitudinal study period, whereas lung cancer (LC) is proinflammatory and patients lose more fat and muscle mass using a standard methodology. Methods Clinicopathological characteristics, including those pertaining to nutritional risk/status and systemic inflammation in patients with colorectal cancer (CRC, n = 1047) and lung cancer (LC, n = 662), were compared. The CT image at L3 was used to assess body composition. Comparison of these cohorts was carried out using the chi-square test. Binary logistic regression analysis was performed to assess the impact of clinico-pathological variables on body composition, and scatter plots were used to examine the relationship between body mass index (BMI) and CT-derived measures of body composition. Results According to CT-derived body composition, high subcutaneous (SFI) and visceral fat index (VFI) were common (>70%) in both CRC and LC. Also, low skeletal muscle index (SMI) and density (SMD) were approximately 40–50% and 60–70% in both CRC and LC. Compared with CRC, patients with LC had a higher American Society of Anaesthesia (ASA) (P < 0.001), Malnutrition Universal Screening Tool (MUST) (P < 0.001), modified frailty index (mFI) (P < 0.001), modified Glasgow Prognostic Score (mGPS) (P < 0.001), and neutrophil lymphocyte ratio (NLR) (P < 0.001) scores. On binary logistic regression analysis, MUST, mFI, and NLR were predictors of subcutaneous adiposity (P < 0.05); type of cancer, MUST, and mFI were predictors of visceral obesity (P < 0.001); age, type of cancer, MUST, and mGPS were predictors of low SMI (P < 0.001); and age, type of cancer, mFI, and mGPS were predictors of low SMD (P < 0.05). There was a similar relationship between BMI and other measures of CT-derived body composition across two types of cancers. Conclusion Obesity and low skeletal muscle mass were common in both CRC and LC cohorts despite large differences in comorbidity, nutritional risk, systemic inflammation, and survival, even when normalized for TNM stage. These observations would support the hypothesis that, although prognostic, CT derived body composition analysis primarily reflects patient constitution rather than the effect of tumor stage in patients with cancer. The systemic inflammatory response, as evidenced by mGPS, can be considered as an important therapeutic target and loss of muscle mass in patients with advanced cancer is related to the systemic inflammatory response.

Sumo-regulatory SENP2 controls the homeostatic squamous mitosis-differentiation checkpoint.

Squamous or epidermoid cancer arises in stratified epithelia but also is frequent in the non-epidermoid epithelium of the lung by unclear mechanisms. A poorly studied mitotic checkpoint drives epithelial cells bearing irreparable genetic damage into epidermoid differentiation. We performed an RNA-sequencing gene search to target unknown regulators of this response and selected the SUMO regulatory protein SENP2. Alterations of SENP2 expression have been associated with some types of cancer. We found the protein to be strongly localised to mitotic spindles of freshly isolated human epidermal cells. Primary cells rapidly differentiated after silencing SENP2 with specific shRNAs. Loss of SENP2 produced in synchronised epithelial cells delays in mitotic entry and exit and defects in chromosomal alignment. The results altogether strongly argue for an essential role of SENP2 in the mitotic spindle and hence in controlling differentiation. In addition, the expression of SENP2 displayed an inverse correlation with the immuno-checkpoint biomarker PD-L1 in a pilot collection of aggressive lung carcinomas. Consistently, metastatic head and neck cancer cells that do not respond to the mitosis-differentiation checkpoint were resistant to depletion of SENP2. Our results identify SENP2 as a novel regulator of the epithelial mitosis-differentiation checkpoint and a potential biomarker in epithelial cancer.

TMEM17 Promotes Tumor Progression in Glioblastoma by Activating the PI3K/AKT Pathway.

Glioblastoma (GBM) is a highly aggressive and fast-growing brain tumor, characterized by rapid progression, a very poor prognosis, and a high likelihood of recurrence. Thus, effective new therapeutic targets are urgently needed. Transmembrane proteins (TMEMs) have pro-cancer effects on multiple cancer types, but the mechanisms underlying the effects of TMEM17, particularly its role in GBM, remain unclear. We conducted bioinformatics analyses and immunohistochemistry to evaluate the role of TMEM17 in a variety of cancer types. Functional assays were conducted included the Cell Counting Kit-8 assay, annexin V-FITC/PI double staining, 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, wound healing assay, transwell invasion assay, and dual luciferase assay. We found that TMEM17 is associated with a poor prognosis in GBM. Prognostic analyses confirmed that high TMEM17 expression predicted poorer survival, establishing its significance as an independent prognostic factor. Functional assays demonstrated that silencing TMEM17 in GBM cell lines inhibited proliferation and invasion, and induced apoptosis, underscoring its role in tumor aggressiveness. From a mechanistic perspective, we discovered that the Ying Yang 1 (YY1) transcription factor can bind to the promoter of TMEM17, regulating its upregulation. Regarding downstream mechanisms, knocking down TMEM17 inhibited the phosphoinositide 3-kinase/AKT pathway. These findings suggest that TMEM17 plays a significant role in GBM and may be a potential therapeutic target for this cancer. These data prove that TMEM17 plays a key role in the regulation of GBM and has great potential as a clinical therapeutic target for GBM.