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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]

Bladder cancer (BC) is an epidemiological urologic malignancy that continues to increase each year. Early diagnosis and prognosis monitoring is always significant in clinical practice, especially in distinguishing non-muscle-invasive bladder cancer (NMIBC) from muscle-invasive bladder cancer (MIBC), due to the various depths of tumor invasion related to different therapeutic schedules and recurrence rates. Common diagnostic approaches are too invasive or generally inefficient in accuracy and specificity. In this work, a totally non-invasive and cost-effective method is established by investigating urine samples using surface-enhanced Raman spectroscopy (SERS) and multivariate statistical analysis. The comparison of urine SERS spectra shows the intensities of characteristic peaks for DNA/RNA, hypoxanthine, albumin, D-(+)-galactosamine, fatty acids, and some amino acids are distinguishable in BC occurrence and invasion progression. A PLS-LDA-based two-step binary classification scheme is performed on urine SERS spectra and the diagnostic accuracies were 97.7% and 96.3% for healthy individuals versus BC patients and NMIBC versus MIBC patients, respectively. Moreover, the impact of urine SERS spectral lengths in reaching high-precision recognition of BC is investigated. The results show that the Raman peaks at 803, 893, 1139, 1375, and 1466 cm−1 play an essential role in correctly categorizing healthy control, NMIBC, and MIBC patients, and SERS spectra ranges from 400 to 1600 cm−1 are enough for this identification task. These findings provide a sensitive, label-free, rapid, and totally non-invasive way for assessment of invasion depth of BC to its early diagnosis and prognosis monitoring, as well as valuable insights for selecting reasonable spectral range to enhance the measurement efficiency especially in large-scale sample datasets. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) poses a significant threat to human health. Resistance to sorafenib in the chemotherapy of HCC is a common and significant issue that profoundly impacts clinical treatment. While several members of the transmembrane (TMEM) protein family have been implicated in the occurrence and progression of HCC, the association between TMEM39b and HCC remains unexplored. This study revealed a significant overexpression of TMEM39b in HCC, which correlated with a poor prognosis. Subsequent investigation revealed that RAS-selective lethal 3 (RSL3) induced pronounced ferroptosis in HCC, and knocking down the expression of TMEM39b significantly decreased its severity. Similarly, following the induction of ferroptosis in HCC by sorafenib, knocking down the expression of TMEM39b also decreased the severity of ferroptosis, enhancing HCC tolerance to sorafenib. In conclusion, we propose that TMEM39b promotes tumor progression and resistance to sorafenib by inhibiting ferroptosis in HCC. [ABSTRACT FROM AUTHOR]

Purpose: Primary breast cancer in children and adolescents is extremely uncommon and presents with different characteristics from those found in adult women. We aimed to conduct a population‐based cohort study to predict overall survival (OS) in pediatric patients with breast cancer. Methods: Demographic and clinicopathological data on pediatric breast cancer patients were obtained from the Surveillance, Epidemiology, and End Results database (2000–2019). The survival rates were measured using the Kaplan–Meier method. Univariate survival analysis used the log‐rank test, while multivariate analysis used Cox proportional hazards regression to identify factors influencing OS. Furthermore, we created a nomogram to predict OS in pediatric patients. Results: A total of 115 pediatric patients were analyzed, with a median age at diagnosis of 18 years (range: 2–19 years). In terms of tumor grade, 27 (23.4%) patients had well or moderately differentiated tumors and 32 (27.8%) had poorly or undifferentiated tumors. The predominant histological type was phyllodes tumor, accounting for 36.5%, followed by infiltrating duct carcinoma at 31.3%, and other types at 32.2%. The SEER and M stages were substantial independent indicators of OS. A nomogram was created to predict OS in pediatric breast cancer patients. Conclusions: Our findings confirmed that the SEER stage and M stage were the most critical predictors of OS in pediatric patients with breast cancer. By focusing on this rare demographic, our study fills an important gap in the literature, as there are few comprehensive studies available that explore a prognosis in pediatric breast cancer. [ABSTRACT FROM AUTHOR]

Recently tetraspanin CD151 has been identified as an important biological target involved in metastatic processes which include cell adhesion, tumor progression processes, and so forth in different types of cancers, such as breast cancer and glioblastoma. This in Silico study considered 1603 compounds from the Food and Drug Administration database, after performing an ADMET analysis; we selected 853 ligands, which were used for docking analysis. The most promising ligands were selected from docking studies, based on two criteria: (a) showed lowest affinity to the CD151 protein and (b) they interact with the QRD motif, located in the second extracellular loop. Furthermore, we investigate the stability of the protein‐ligand complexes through MD simulations as well as free energy MM‐PBSA calculations. From these results, loperamide and glipizide were identified as the best evaluated drugs. We suggest an in vitro analysis is needed to confirm our in silico prediction studies. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Accurate diagnostic staging of upper tract urothelial cancer (UTUC) is challenging. Endoscopic staging is limited by its ability to provide adequate sampling of deeper layers of the ureter and renal pelvis. Further ability to accurately predict invasive disease would aid in better selecting the appropriate treatment for patients. We aimed to analyze the ability of preoperative cross-sectional radiologic findings to predict pathologic outcomes, including tumor grade, muscle-invasive disease, and presence of lymphovascular invasion (LVI). METHODS: All patients diagnosed with localized UTUC (cN0M0) who underwent nephroureterectomy between February 2012 and December 2018 in Manitoba, Canada, were identified. Preoperative radiologic characteristics, including the presence and severity of hydronephrosis, as well as tumor location, were recorded. Patients’ and pathologic characteristics were also recorded. Logistic regression analysis was used to assess the association between radiologic variables and pathologic outcomes at radical surgery. RESULTS: A total of 112 pathology reports of patients with UTUC were obtained. The median age was 70 years (range 50–87), and 58.8% of patients were men. On univariate analysis, ureteric location on computed tomography (odds ratio [OR] 2.240, 95% confidence interval [CI] 1.049–4.783, p=0.037) and presence of hydronephrosis (OR 2.455, 95% CI 1.094–5.506, p=0.0029) were each independently associated with locally invasive disease (>pT2). No radiologic variables were found to be predictors of adverse pathology on multivariable analysis. Only the presence of hydronephrosis was associated with high-grade disease on univariate analysis (OR 2.533, 95% CI 1.083–5.931, p=0.032). CONCLUSIONS: Our findings suggest a limited role for cross-sectional imaging in predicting the presence of high-grade disease, LVI, or locally advanced disease in UTUC. [ABSTRACT FROM AUTHOR]

Aim: This study investigated the impact of coronavirus disease 2019 (COVID‐19) on the clinical characteristics and interregional movement of patients with uterine cervical cancer. Methods: This study included 1189 patients who underwent treatment for cervical cancer, including cervical intraepithelial neoplasm and adenocarcinoma in situ, at our hospital in Tokyo, Japan, in 2017–2018 and in 2021, before and after the pandemic, respectively. The patients' clinical information was compared during both periods. The clinical stage was unified using the International Federation of Gynecology and Obstetrics (FIGO) 2008 staging. Results: The number of patients treated for cervical cancer was 355, 420, and 414 in 2017, 2018, and 2021, respectively. The percentage of invasive carcinomas significantly increased from 158 (44.5%) and 196 (46.7%) to 219 (52.9%) (p = 0.049). In all periods, no significant differences were observed in median age, histological type, and treatment. The proportions of FIGO Stage IA1 were significantly elevated from 3.9% and 3.8% to 11.4% (p < 0.001). The percentage of patients from prefectures other than Tokyo significantly increased from 34.9% to 40.8% (p = 0.049). Furthermore, the proportion of patients with invasive carcinoma in private clinics increased from 28.0% to 37.9% (p = 0.014). Conclusions: The number of patients with invasive carcinoma and the percentage of patients with invasive carcinoma referred from private clinics increased, indicating that the COVID‐19 pandemic influenced patients to delay consultations. Furthermore, the surge in patients from other prefectures indicates that medical resources were more limited in rural areas, another impact of COVID‐19. [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of death worldwide. Glioblastoma (GBM) is a major challenge in oncology due to its highly invasive nature and limited treatment options. GBM's aggressive migration beyond tumor margins and rapid tumor growth hinders success in patient treatment. Localized therapeutic delivery, such as the use of transition metals like copper, is highlighted as a novel therapeutic agent for many potential biomedical applications. Herein, it is aimed to study the effects of Cu release on the proliferation and invasiveness of cancer cells. To this end, novel copper‐based nanostructures with different release patterns are designed. Using a complex 3D cell culture model to mimic the tumor microenvironment, it is shown that different patterns of copper ion release have a strong impact on GBM progression and invasiveness. The findings highlight the importance of optimizing localized copper release patterns to tailor different tumor treatment strategies. They also show the potential and suitability of 3D microchips as instruments to study the behavior of tumor spheroids. In spite of their limitations, these 3D microdevices enable a controlled and close monitoring of the influence of environmental factors (such as the presence of Cu ions) on the proliferation and invasiveness of the cells, with a better approach to reality compared to 2D models and with a more controlled environment, compared to an in vivo model. [ABSTRACT FROM AUTHOR]

In submucosal invasive adenocarcinoma of the esophagogastric junction (pT1b-SM AEG), the extent of tumor submucosal (SM) invasion is measured using the vertical depth of SM invasion with the muscularis mucosa. This study aimed to investigate whether tumor thickness and depth of invasion without accounting for muscularis mucosa were superior to the vertical depth of SM invasion as metastasis predictors. We enrolled patients with pT1b-SM AEG who underwent endoscopic resection or surgical resection (SR) at our institution between January 2011 and September 2019 and were followed up for ≥2 years. The relationship between metastasis and clinicopathological factors was examined. Metastasis was defined as pathologically confirmed lymph node metastasis in the surgical specimen or recurrence during follow-up. This study included 57 patients (44 men; median age, 72 years). Endoscopic resection and SR were performed in 16 and 41 patients, respectively. Nine patients were diagnosed with metastasis: five who underwent SR showed pathologically confirmed lymph node metastasis in the surgical specimens, and four experienced recurrences during a median follow-up of 48 months. Univariate analyses showed that tumor thickness was significantly associated with metastasis (P  = 0.021), and the vertical depth of SM invasion (P  = 0.48) and depth of invasion (P  = 0.38) were not. Furthermore, in multivariate analysis, tumor thickness ≥2800 μm (odds ratio, 38.70; P  = 0.013) was a significant predictor for metastasis. Tumor thickness may be a more convenient and useful predictor of metastasis in patients with pT1b-SM AEG than the vertical depth of SM invasion. [ABSTRACT FROM AUTHOR]

Mitochondrial respiration and metabolism play a pivotal role in facilitating the migratory and invasive capacities of cancer cells. In this study, we aimed to explore the potential influence of glycoprotein SPARC on mitochondrial respiration and its subsequent influence on the migration and invasion of hepatocellular carcinoma (HCC) cells. Lentivirus-mediated shRNA delivery was employed to deplete SPARC in HCC cell lines. The mitochondria localization of SPARC was validated using cellular fractionation followed by Western blot analysis, as well as immunofluorescence staining and Proteinase K protection assay. Co-immunoprecipitation was employed to investigate the interaction between SPARC and GPD2. Seahorse XF Cell Mito Stress Test was conducted to assess the mitochondrial respiration and functionality of HCC cells. Our study identifies an active pool of SPARC within the mitochondria of HCC cells, with the mitochondrial subset proving crucial for the regulation of migration and invasion. The mitochondrial SPARC interacts with GPD2, influencing its expression levels and subsequently modulating GPD2-mediated mitochondrial respiration. This regulatory mechanism orchestrates the migratory and invasive phenotypes of HCC cells. Notably, SPARC and GPD2 exhibit upregulated expression in HCC tissues compared to normal liver tissues. High expression levels of both SPARC and GPD2 in HCC patients are associated with a poorer prognosis. Our study unveils a novel role for SPARC in governing HCC cell migration and invasion through regulating GPD2-mediated mitochondrial respiration. These findings underscore the importance of mitochondrial processes in cancer progression and propose the SPARC/GPD2 axis as a promising target for HCC interventions. [ABSTRACT FROM AUTHOR]

Recent research has shown that Doublecortin-like kinase 1 (DCLK1) is overexpressed in different types of cancer. It has recently been described as a cancer stem cells (CSCs) marker, is associated with carcinogenesis, and positively correlates with infiltration of multiple immune cell types in some cancers. However, studies focused on assessing DCLK1 expression in HCC are limited, and the role of DCLK1 in HCC tumor immunity remains to be determined. In this study, we used a modified model of the resistant hepatocyte (MRHM) to evaluate DCLK1 expression in HCC. Furthermore, DCLK1 expression in HCC was analyzed using TIMER 2.0, UALCAN, GEPIA, GEO, and HPA web-based tools. Correlations between DCLK1 expression and clinicopathological factors in patients were analyzed using the UALCAN web-based tool. Finally, correlations between DCLK1 and immune infiltrates were investigated using the TIMER 2.0 and TISIDB web-based tools. The results showed that DCLK1 is significantly overexpressed during progression of the HCC carcinogenic process in the MRHM. DCLK1 is overexpressed in HCC according to multiple publics web-based tools, and its overexpression is associated with cancer stage. Furthermore, DCLK1 expression was correlated with infiltration levels of multiple immune cells, immunomodulatory factors, immunoinhibitors, MHC molecules, chemokines, receptors, and immune cell-specific markers. These results suggest that DCLK1 is a potential prognostic biomarker that determines cancer progression and correlates with immune cell infiltration in HCC. [ABSTRACT FROM AUTHOR]

Context.--Acquisition of genetic aberrations during cervical carcinogenesis in individual patients is poorly documented. Objective.--To provide a comparative analysis of high-grade squamous intraepithelial lesions (n = 7) and pT1a squamous cancers (n = 1) and their recurrences, subsequent widely invasive cancers, and metastases developed during 1-24 years. Design.--Archival tissues of 8 patients were analyzed immunohistochemically for reserve-cell origin, human papillomavirus genotypes, mutations in 50 cancer genes, and chromosomal copy number variations. Results.--Intraepithelial lesions arose either from cytokeratin 17- or 7-expressing reserve cells. All preinvasive and invasive tumors carried human papillomavirus high-risk genotypes and lacked somatic mutations. Chromosomal copy number variations were identified in all intraepithelial lesions and invasive cancers. Four of 8 high-grade intraepithelial lesions progressed to invasive cancer after incomplete treatment, and 4 of 8 invasive cancers arose de novo after in sano resection. Four of 8 cancers carried mutations with high mutational frequency (PIK3CA E545K [n = 2]; PIK3CA and SMAD1 [n = 1]; HRAS, RB1, and EGFR [n = 1]), as did their corresponding regional metastases. One nonmetastasized cancer had a subclonal PIK3CA mutation, and an initially nonmutated, low-stage cancer developed ovarian metastases with PIK3CA amplification. One patient had neither mutations nor metastases. The patient with treated PIK3CA E545K-mutated pT1a cancer developed a subsequent nonmutated intraepithelial lesion that progressed to invasive cancer with a subclonal PIK3-CA-H1047R mutation. Cancer-related deaths in 4 of 8 (50%) patients occurred independent of mutational status or metastatic disease. Conclusions.--Recurrences arose after persistent or de novo human papillomavirus infection of residual reserve cells or squamous metaplasia. Activating driver mutations were identified in invasive cancers only. High mutational load correlated with metastases, which in turn represented clonal disease. [ABSTRACT FROM AUTHOR]

The intricate cooperation between cancer cells and nontumor stromal cells within melanoma microenvironment (MME) enables tumor progression and metastasis. We previously demonstrated that the interplay between tumor-associated macrophages (TAMs) and melanoma cells can be disrupted by using long-circulating liposomes (LCLs) encapsulating prednisolone phosphate (PLP) (LCL-PLP) that inhibited tumor angiogenesis coordinated by TAMs. In this study, our goal was to improve LCL specificity for protumor macrophages (M2-like (i.e., TAMs) macrophages) and to induce a more precise accumulation at tumor site by loading PLP into IL-13-conjugated liposomes (IL-13-LCL-PLP), since IL-13 receptor is overexpressed in this type of macrophages. The IL-13-LCL-PLP liposomal formulation was obtained by covalent attachment of thiolated IL-13 to maleimide-functionalized LCL-PLP. C57BL/6 mice bearing B16.F10 s.c melanoma tumors were used to investigate the antitumor action of LCL-PLP and IL-13-LCL-PLP. Our results showed that IL-13-LCL-PLP formulation remained stable in biological fluids after 24h and it was preferentially taken up by M2 polarized macrophages. IL-13-LCL-PLP induced strong tumor growth inhibition compared to nonfunctionalized LCL-PLP at the same dose, by altering TAMs-mediated angiogenesis and oxidative stress, limiting resistance to apoptosis and invasive features in MME. These findings suggest IL-13-LCL-PLP might become a promising delivery platform for chemotherapeutic agents in melanoma. [ABSTRACT FROM AUTHOR]

Background: Improving quality of life (QOL) in advanced and metastatic cancer is a priority with increasing survivorship. This systematic review synthesizes psychosocial and behavioral interventions incorporating culture with the goal of examining their benefit for understudied and medically underserved populations with advanced and metastatic cancer. Method: Reports were systematically screened for (1) a focus on advanced and metastatic cancer survivors, (2) psychosocial or behavioral intervention intended to improve QOL, (3) evidence of incorporating the culture(s) of understudied/underserved populations, and (4) availability in English. Bias was evaluated using the JBI Critical Appraisal Checklist and the Methodological index for non‐randomized studies. Qualitative synthesis and quantitative meta-analyses were completed. Results: Eighty-six reports containing 5981 participants' data were examined. Qualitative synthesis of 23 studies identified four overarching themes relevant for incorporating culture in interventions. Meta-analysis of 19 RCTs and 4 quasi-experimental studies containing considerable heterogeneity indicated greater improvements in QOL (g = 0.84), eudaimonic well-being (g = 0.53), distress (g = −0.49), and anxiety (g = −0.37) for main intervention conditions compared to controls. Meta-analysis of 10 single-arm trials containing minimal to moderate heterogeneity found benefit for anxiety (g = −0.54), physical symptoms (g = −0.39), and depression (g = −0.38). Conclusion: Psychosocial and behavioral interventions with cultural incorporation appear beneficial for improving QOL-related outcomes in advanced and metastatic cancer. Studies incorporating culture in psychosocial or behavioral interventions offer noteworthy insight and suggestions for future efforts such as attending to deep cultural structure. [ABSTRACT FROM AUTHOR]

Nucleosomes, as key players in epigenetic regulation, interact with various chromatin factors and enzymes. Recently, a variety of studies have highlighted the significant roles that histone mutations play in the progression of various cancers. Cancer-associated mutations can disrupt nucleosome stability, dynamics and interactions, leading to profound effects on higher-order chromatin structure and epigenetic processes. In this review, we summarize the latest research that provides a comprehensive analysis of how histone mutations in cancers influence nucleosome dynamics, stability and interactions by altering their physicochemical properties. Moreover, we briefly explore the molecular mechanisms by which these mutations disrupt higher-order chromatin organization and epigenetic landscape. Cancer-associated histone mutations significantly affect nucleosome stability and interactions, leading to profound effects on chromatin structure and epigenetic processes. This review summarizes the latest research that gives a comprehensive analysis of impact of histone mutations on nucleosome. We also discuss the molecular mechanisms of how these mutations disrupt higher-order chromatin organization and epigenetic landscape. [ABSTRACT FROM AUTHOR]

• Integrin α11β1 locates in fibrillar adhesions in fibroblast, but not α2β1. • Integrin α11β1 translocation into fibrillar adhesions is tensin-1 dependent. • α5β1 and α11β1 integrins are in same fibrillar adhesions but do not overlap. • Integrin α11β1 contributes to cell surface-associated collagen I assembly. Solid epithelial cancers with significant desmoplasia are characterized by an excessive deposition of collagen-based matrix, which often supports tumor progression. However, the mechanism of how collagen receptors mediate collagen fibrillogenesis still remains mostly unclear. We show that the collagen-binding integrin α11β1 can co-localize with tensin-1 and deposited collagen I in human pancreatic ductal adenocarcinoma (PDAC) stroma. In addition to the canonical fibrillar adhesion integrin α5β1 expressed by human PDAC cancer-associated fibroblasts (CAFs), tensin-1-positive fibrillar adhesions contained α11β1 but lacked α1β1 and α2β1. CAFs lacking α5β1 expression displayed mechanoregulated and tensin-1 dependent α11β1 fibrillar adhesions, suggesting independent roles of the two integrins with regards to fibrillar adhesions-based de novo fibrillogenesis. Further, we demonstrate that cell surface-associated collagen I assembly necessitated α11β1, but not α5β1 expression. In summary, α11β1 integrin is a novel component of fibrillar adhesions, which is strategically positioned to mediate de novo collagen fibrillogenesis at the cell surface under pro-fibrotic conditions. [ABSTRACT FROM AUTHOR]

• mCAFs shaped the COL18high COL5high collagen landscape in OSCC. • OSCC-derived EVs educate fibroblasts to COL18+ COL5+ mCAFs. • OSCC-derived EVs promote tumor invasion and COL18high COL5high matrix deposition. • TGF-β1 in EVs educate mCAFs via TGF-β1/Smad3 signaling pathway. • TGF-β1 in EVs promotes tumor progression and COL18high COL5high matrix deposition. Cancer-associated myofibroblasts (mCAFs) represent a significant component of the tumor microenvironment due to their contributions to extracellular matrix (ECM) remodeling. The pro-tumor mechanisms of extracellular vesicles (EVs) by regulating mCAFs and related collagens remain poorly understood in oral squamous cell carcinoma (OSCC). In this study, through analysis of single-cell sequencing data and immunofluorescence staining, we confirmed the increased presence of mCAFs and enrichment of specific collagen types in OSCC tissues. Furthermore, we demonstrated that OSCC-derived EVs promote the transformation of fibroblasts into mCAFs, leading to tumor invasion. Proteomic analysis identified the presence of TGF-β1 in EVs and revealed its role in inducing mCAFs via the TGF-β1/SMAD signaling pathway. Experiments in vivo confirmed that EVs, particularly those carrying TGF-β1, trigger COL18high COL5high matrix deposition, thereby forming the pro-tumor ECM in OSCC. In summary, our investigation unveils the significant involvement of OSCC-derived EVs in orchestrating the differentiation of fibroblasts into mCAFs and modulating specific collagen types within the ECM. Therefore, this study provides a theoretical basis for targeting the EV-mediated TGF-β1 signaling pathway as a potential therapeutic strategy for OSCC. [ABSTRACT FROM AUTHOR]

Introduction: Total resection of cystic craniopharyngiomas is challenging, especially for some large cystic tumors, because it is often associated with high recurrence and morbidity rates. Minimally invasive cyst decompression and continuous drainage are appropriate to manage clinical symptoms. We reviewed our experience of the past 11 years to determine the long-term effects of neuroendoscopic surgery (NES) combined with Ommaya reservoir (OR) for the treatment of cystic craniopharyngiomas. Methods: We retrospectively analyzed the data of 15 adult patients with cystic craniopharyngiomas at a single institution with the primary goal to evaluate the treatment mode with initial adequate decompression of the cyst under visualization and continuous drainage. The study endpoints were functional outcome, cyst volume changes, and tumor progression. Results: The median follow up was 77 (20–136) months. Clinical symptoms, e.g. increased intracranial pressure and visual impairment, could be rapidly improved after NES. The postoperative reduction in cyst volume (p < 0.001) and improvement in Karnofsky performance status (p < 0.001) were significant, and long-term tumor control was achieved in 10 patients (67%). Aspiration from the OR after progression of the tumor's cystic portion remains a major option, with only few patients requiring repeat NES procedures. No patient developed acute or severe clinical symptoms during follow up. Conclusions: NES could decompress the craniopharyngioma cyst under visualization and enable faster clinical-symptom improvement. The minimally invasive NES combined with OR allowed long-term symptom control in most patients without surgery-related injury. This palliative treatment strategy could be an alternative modality for cystic craniopharyngioma treatment. [ABSTRACT FROM AUTHOR]

PURPOSE: Alterations in DNA damage response (DDR) genes, including ERCC2 , have been correlated with response to neoadjuvant cisplatin-based chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC). The SWOG 1314 (S1314) trial enrolled patients with MIBC who received one of two NAC regimens followed by radical cystectomy. We examined the prevalence of DDR alterations in NAC responders versus nonresponders and correlated DDR alteration status with response. METHODS: Pretreatment tumor specimens from 179 evaluable patients underwent next-generation sequencing (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets assay). Associations were determined between any or only deleterious alterations within nine predefined DDR genes, or any alterations in ERCC2 , and progression-free survival (PFS) and overall survival using Cox regression, and, in a subset of evaluable patients, pathologic response (complete response, pT0, or downstaging to

PURPOSE: The lack of personalized management of bladder cancer (BlCa) results in patients' lifelong post-treatment monitoring with invasive interventions, underlying the urgent need for tailored and minimally invasive health care services. On the basis of our previous findings on miR-143/145 cluster methylation in bladder tumors, we evaluated its clinical significance in pretreatment cell-free DNA (cfDNA) of patients with BlCa. MATERIALS AND METHODS: Methylation analysis was performed in our screening cohort (120 patients with BlCa; 20 age-matched healthy donors) by bisulfite-based pyrosequencing. Tumor recurrence/progression for patients with non–muscle-invasive bladder cancer, and progression and mortality for patients with muscle-invasive bladder cancer (MIBC) were used as clinical end point events in survival analysis. Bootstrap analysis was applied for internal validation of Cox regression models and decision curve analysis for assessment of clinical benefit on disease prognosis. RESULTS: Decreased methylation of MIR145 core promoter in pretreatment cfDNA was associated with short-term disease progression (multivariate Cox: hazard ratio [HR], 2.027 [95% CI, 1.157 to 3.551]; P =.010) and poor overall survival (multivariate Cox: HR, 2.098 [95% CI, 1.154 to 3.817]; P =.009) of patients with MIBC after radical cystectomy (RC). Multivariate models incorporating MIR145 promoter methylation in cfDNA with tumor stage clearly ameliorated patients' risk stratification, highlighting superior clinical benefit in MIBC prognostication. CONCLUSION: Reduced pretreatment cfDNA methylation of MIR145 core promoter was markedly correlated with increased risk for short-term progression and worse survival of patients with MIBC after RC and adjuvant therapy, supporting modern personalized and minimally invasive prognosis. Methylation profiling of MIR145 core promoter in pretreatment cfDNA could serve as a minimally invasive and independent predictor of MIBC treatment outcome and emerge as a promising marker for blood-based test in BlCa. Cell-free DNA methylation profile of MIR145 promoter as a blood-based test for MIBC treatment outcome. [ABSTRACT FROM AUTHOR]

PURPOSE: Patients with residual invasive bladder cancer after neoadjuvant chemotherapy (NAC) and radical cystectomy have a poor prognosis. Data on adjuvant therapy for these patients are conflicting. We sought to evaluate the natural history and genomic landscape of chemotherapy-resistant bladder cancer to inform patient management and clinical trials. METHODS: Data were collected on patients with clinically localized muscle-invasive urothelial bladder cancer treated with NAC and cystectomy at our institution between May 15, 2001, and August 15, 2019, and completed four cycles of gemcitabine and cisplatin NAC, excluding those treated with adjuvant therapies. Survival was estimated using the Kaplan-Meier method, and multivariable Cox proportional hazards models were used to identify predictors of recurrence-free survival (RFS). Genomic alterations were identified in targeted exome sequencing (Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets) data from post-NAC specimens from a subset of patients. RESULTS: Lymphovascular invasion (LVI) was the strongest predictor of RFS (hazard ratio, 2.15 [95% CI, 1.37 to 3.39]) on multivariable analysis. Patients with ypT2N0 disease without LVI had a significantly prolonged RFS compared with those with LVI (70% RFS at 5 years). Lymph node yield did not affect RFS. Among patients with sequencing data (n = 101), chemotherapy-resistant tumors had fewer alterations in DNA damage response genes compared with tumors from a publicly available chemotherapy-naïve cohort (15% v 29%; P =.021). Alterations in CDKN2A/B were associated with shorter RFS. PIK3CA alterations were associated with LVI. Potentially actionable alterations were identified in more than 75% of tumors. CONCLUSION: Although chemotherapy-resistant bladder cancer generally portends a poor prognosis, patients with organ-confined disease without LVI may be candidates for close observation without adjuvant therapy. The genomic landscape of chemotherapy-resistant tumors is similar to chemotherapy-naïve tumors. Therapeutic opportunities exist for targeted therapies as adjuvant treatment in chemotherapy-resistant disease. [ABSTRACT FROM AUTHOR]

PURPOSE: Sarcomas are a complex group of highly aggressive and metastatic tumors with over 100 distinct subtypes. Because of their diversity and rarity, it is challenging to generate multisarcoma signatures that are predictive of patient outcomes. MATERIALS AND METHODS: Here, we identify a DNA methylation signature for progression and metastasis of numerous sarcoma subtypes using multiple epigenetic and genomic patient data sets. Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are highly metastatic sarcomas with frequent loss of the histone methyltransferase, PRC2. Loss of PRC2 is associated with MPNST metastasis and plays a critical noncanonical role in DNA methylation. RESULTS: We found that over 900 5′—C—phosphate—G—3′ (CpGs) were hypermethylated in MPNSTs with PRC2 loss. Furthermore, we identified eight differentially methylated CpGs in the IL17D / RD family that correlate with the progression and metastasis of MPNSTs in two independent patient data sets. Similar trends were identified in other sarcoma subtypes, including osteosarcoma, rhabdomyosarcoma, and synovial sarcoma. Analysis of scRNAseq data sets determined that IL17D / RD expression occurs in both the tumor cells and the surrounding stromal populations. CONCLUSION: These results might have broad implications for the clinical management and surveillance of sarcoma. [ABSTRACT FROM AUTHOR]

Summary: The adipose tissue is a complex organ that can play endocrine, metabolic, and immune regulatory roles in cancer. In particular, adipocytes provide metabolic substrates for cancer cell proliferation and produce signaling molecules that can stimulate cell adhesion, migration, invasion, angiogenesis, and inflammation. Cancer cells, in turn, can reprogram adipocytes towards a more inflammatory state, resulting in a vicious cycle that fuels tumor growth and evolution. These mechanisms are enhanced in obesity, which is associated with the risk of developing certain tumors. Diet, an exogenous source of lipids with pro‐ or anti‐inflammatory functions, has also been connected to cancer risk. This review analyzes how adipocytes and lipids are involved in tumor development and progression, focusing on the relationship between obesity and cancer. In addition, we discuss how diets with varying lipid intakes can affect the disease outcomes. Finally, we introduce novel metabolism‐targeted treatments and adipocyte‐based therapies in oncology. [ABSTRACT FROM AUTHOR]

The article presents the case study of a 13-year-old boy diagnosed with metastatic embryonal rhabdomyosarcoma (RMS) of the prostate after presenting with urinary symptoms. Topics include the symptoms and initial findings, such as weakened urine stream, urinary frequency, and hematuria; the types and risk factors of RMS; and the age-related incidence pattern of RMS, which peaks in early childhood and adolescence.

Objective(s): Breast neoplasm is a malignancy that can have a poor prognosis. The PI3K/AKT signaling pathway is frequently activated in various tumor types, including breast cancer, leading to alterations in the tumor microenvironment and radioresistance. Selective inhibition of PI3Kca (p110a) has been considered an alternative approach to overcome radioresistance, owing to concerns surrounding the excessive side effects of pan-PI3K inhibitors tested in clinical trials. This investigation aimed to evaluate the efficacy of co-administering PI3Kca knocking out with radiation therapy in mitigating radioresistance and suppressing tumor growth in the MDA-MB-231 cell line. Materials and Methods: The present investigation utilized the CRISPR/Cas9 technique to induce a knockout of the PI3Kca gene. Subsequently, after 24 hr of transfection, gene expression, cell proliferation, apoptosis rate, and angiogenesis were assessed. Results: We demonstrated that knocking out PI3Kca, in combination with radiation, increased apoptosis, reduced the expression of PI3Kca and AKT1 genes, and decreased cell proliferation. The CAM assay analysis has demonstrated that knocking out the PI3Kca gene and radiotherapy substantially reduced the total vessel network length and the number of junctions. Conclusion: The findings of our investigation indicate that the integration of radiation therapy with PI3Kca yielded enhanced radiosensitivity, leading to a marked retardation of tumor progression and an increased survival rate. [ABSTRACT FROM AUTHOR]

Background: Since differentiating malignant ascites from benign ascites has always been a clinical difficult, recognition of novel biomarkers in malignant ascites of hepatocellular carcinoma (HCC) patients could be helpful for establishing a diagnosis for HCC patients with ascitic fluids. Methods: Thirty-five HCC patients with malignant ascites and chronic liver diseases patients with benign ascites were enrolled. Serum and ascites specimens were collected to determine TAN subpopulations and NETs concentration. Then, the correlation between ascitic NETs levels and clinical features were analyzed, and ROC curves were generated to evaluate the diagnostic value of NETs. For in vitro study, fresh neutrophils were employed to explore the underlying mechanism of TAN polarization and NETs formation using RNAseq analysis. Results: Significantly increased pro-tumor PD-L1+ TANs and higher lactate levels were measured in HCC ascites. RNAseq data showed that lactate regulated genes expression involving PD-L1 expression and NETs formation, suggesting that ascitic lactate might be responsible for tumor progression in TME. Then, NETs-related markers including calprotectin, dsDNA, CitH3, MPO and MPO-DNA were found dramatically elevated in malignant ascites. Next, correlation analysis revealed that ascitic NETs levels positively correlated with LDH, a classic ascitic biochemical indicator. Furthermore, we identified the diagnostic values of NETs in discriminating malignant ascites from benign ascites. Conclusions: Our findings highlighted that elevated ascitic NETs served as a biomarker in HCC patients with malignant ascites, which provided useful insights for both clinical and basic research for malignant ascites diagnosis and management. [ABSTRACT FROM AUTHOR]

We computationally predicted all phosphorylation sites in the sequence of the human laminin γ1-chain (LAMC1), and computationally identified, for the first time, all kinases for experimentally observed phosphorylated residues of the LAMC1 and all missense deleterious LAMC1 mutations found in different cancer types that interfere with LAMC1 phosphorylation. Also, we mapped the above data to all the biologically functional interaction sequences of the LAMC1. Five kinases (CKII, GPCRK1, PKA, PKC, and CKI) are most enriched for LAMC1 phosphorylation, and the significance of ecto-kinases in this process was emphasized. PKA and PKC targeted more residues inside and close to functional interaction sequences compared with other kinases and in the functional interaction sequence RPESFAIYKRTR. Most phosphorylation-interfering mutations were found in cutaneous melanoma and uterine endometrioid carcinoma. The mutation R255H interfered with the experimentally observed phosphorylation of LAMC1 inside the functional interaction sequence TDIRVTLNRLNTF, while the mutations S181Y and S213Y interfered with the experimentally observed phosphorylation of LAMC1 outside the functional interaction sequences. Mutations R359C,H, R589H, R657C,H, R663I,G, and T1207 interfered with the predicted phosphorylation inside or close to the functional interaction sequences, whereas other mutations interfered outside. PKA- and PKC-predicted phosphorylation was mostly interfered with by mutations inside functional interaction sequences. Phosphorylation-interfering mutations and functional interaction sequences were suggested to promote specific cancer types or cancer progression in general. [ABSTRACT FROM AUTHOR]

Conventional therapies for metastatic cancers have limited efficacy. Recently, cancer therapies targeting noncancerous cells in tumor microenvironments have shown improved clinical outcomes in patients. However, further advances in our understanding of the metastatic tumor microenvironment are required to improve treatment outcomes. Adipocytes are distributed throughout the body, and as a part of the metastatic tumor microenvironment, they interact with cancer cells in almost all organs. Adipocytes secrete various factors that are reported to exert clinical effects on cancer progression, including engraftment, survival, and expansion at the metastatic sites. However, only a few studies have comprehensively examined their impact on cancer cells. In this review, we examined the impact of adipocytes on cancer by describing the adipocyte-secreted factors that are involved in controlling metastatic cancer, focusing on adipokines, such as adiponectin, leptin, visfatin, chemerin, resistin, apelin, and omentin. Adipocyte-secreted factors promote cancer metastasis and contribute to various biological functions of cancer cells, including migration, invasion, proliferation, immune evasion, and drug resistance at the metastatic sites. We propose the establishment and expansion of "adipo-oncology" as a research field to enhance the comprehensive understanding of the role of adipocytes in metastatic cancers and the development of more robust metastatic cancer treatments. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is a brain tumor with poor prognosis. Dexmedetomidine (Dex) regulates the biological behaviors of tumor cells to accelerate or decelerate cancer progression. Objective: We investigated the effects of Dex on the migration, invasion, and glycolysis in GBM. Methods: The concentration of Dex was determined using the cell counting kit-8 assay. The impacts of Dex on biological behaviors of GBM cells were assessed using Transwell assay, XF96 extracellular flux analysis, and western blot. The expression of c-Myc was examined using reverse transcription-quantitative polymerase chain reaction. The lactylation or stability of c-Myc was measured by western blot after immunoprecipitation or cycloheximide treatment. Results: We found that Dex (200 nM) inhibited GBM cell viability, migration, invasion, and glycolysis. C-Myc was highly expressed in GBM cells and was decreased by Dex treatment. Moreover, Dex suppressed lactylated c-Myc levels via suppressing glycolysis, thereby reducing the protein stability of c-Myc. Sodium lactate treatment abrogated the effects of Dex on the biological behaviors of GBM cells. Conclusion: Dex suppressed the migration, invasion, and glycolysis of GBM cells via inhibiting lactylation of c-Myc and suppressing the c-Myc stability, suggesting that Dex may be a novel therapeutic drug for GBM treatment. [ABSTRACT FROM AUTHOR]

Copy number variation (CNV) is an essential genetic driving factor of cancer formation and progression, making intelligent classification based on CNV feasible. However, there are a few challenges in the current machine learning and deep learning methods, such as the design of base classifier combination schemes in ensemble methods and the selection of layers of neural networks, which often result in low accuracy. Therefore, an adaptive bilinear dynamic cascade model (Adap-BDCM) is developed to further enhance the accuracy and applicability of these methods for intelligent classification on CNV datasets. In this model, a feature selection module is introduced to mitigate the interference of redundant information, and a bilinear model based on the gated attention mechanism is proposed to extract more beneficial deep fusion features. Furthermore, an adaptive base classifier selection scheme is designed to overcome the difficulty of manually designing base classifier combinations and enhance the applicability of the model. Lastly, a novel feature fusion scheme with an attribute recall submodule is constructed, effectively avoiding getting stuck in local solutions and missing some valuable information. Numerous experiments have demonstrated that our Adap-BDCM model exhibits optimal performance in cancer classification, stage prediction, and recurrence on CNV datasets. This study can assist physicians in making diagnoses faster and better. [ABSTRACT FROM AUTHOR]

At present, the role of many long non-coding RNAs (lncRNAs) as tumor suppressors in the formation and development of cervical cancer (CC) has been studied. However, lncRNA prostate cancer gene expression marker 1 (PCGEM1), whose high expression not only aggravates ovarian cancer but also can induce tumorigenesis and endometrial cancer progression, has not been studied in CC. The objective of this study was to investigate the expression and the underlying role of PCGEM1 in CC. The relative expression of PCGEM1 in CC cells was detected by real-time PCR. After the suppression of PCGEM1 expression by shRNA, the changes in the proliferation, migration, and invasion capacities were detected via CCK-8 assay, EdU assay, and colony formation assay wound healing assay. Transwell assay and the changes in expressions of epithelial-to-mesenchymal transition (EMT) markers were determined by western blot and immunofluorescence. The interplay among PCGEM1, miR-642a-5p, and kinesin family member 5B (KIF5B) was confirmed by bioinformatics analyses and luciferase reporter assay. Results showed that PCGEM1 expressions were up-regulated within CC cells. Cell viabilities, migration, and invasion were remarkably reduced after the suppression of PCGEM1 expression by shRNA in Hela and SiHa cells. N-cadherin was silenced, but E-cadherin expression was elevated by sh-PCGEM1. Moreover, by sponging miR-642a-5p in CC, PCGEM1 was verified as a competitive endogenous RNA (ceRNA) that modulates KIF5B levels. MiR-642a-5p downregulation partially rescued sh-PCGEM1's inhibitory effects on cell proliferation, migration, invasion, and EMT process. In conclusion, the PCGEM1/miR-642a-5p/KIF5B signaling axis might be a novel therapeutic target in CC. This study provides a research basis and new direction for targeted therapy of CC. [ABSTRACT FROM AUTHOR]

Parathyroid carcinoma (PC) is a rare malignancy, often characterized by the unregulated secretion of parathyroid hormone. The sequelae of severe hypercalcemia together with direct complications from tumor dissemination in patients with advanced disease are usually fatal. Due to its rarity, formal studies to guide the diagnosis and management of parathyroid carcinoma are lacking. However, recent data from case reports, case series, and registry studies suggest the emergence of new and effective treatment approaches for this understudied disease. We reviewed existing literature on the diagnosis and management of parathyroid carcinoma. Our findings suggest that traditional approaches such as surgical resection for both localized and metastatic diseases continue to play an important role in patient management. For patients with unresectable disease, newer systemic treatment approaches, including the use of temozolomide and tyrosine kinase inhibitors, may offer clinical benefit. [ABSTRACT FROM AUTHOR]

Rapid technological advances have allowed for molecular profiling across multiple omics domains for clinical decision-making in many diseases, especially cancer. However, as tumor development and progression are biological processes involving composite genomic aberrations, key challenges are to effectively assimilate information from these domains to identify genomic signatures and druggable biological entities, develop accurate risk prediction profiles for future patients, and identify novel patient subgroups for tailored therapy and monitoring. We propose integrative frameworks for high-dimensional multiple-domain cancer data. These Bayesian mixture model-based approaches coherently incorporate dependence within and between domains to accurately detect tumor subtypes, thus providing a catalog of genomic aberrations associated with cancer taxonomy. The flexible and scalable Bayesian nonparametric strategy performs simultaneous bidirectional clustering of the tumor samples and genomic probes to achieve dimension reduction. We describe an efficient variable selection procedure that can identify relevant genomic aberrations and potentially reveal underlying drivers of disease. Although the work is motivated by lung cancer datasets, the proposed methods are broadly applicable in a variety of contexts involving high-dimensional data. The success of the methodology is demonstrated using artificial data and lung cancer omics profiles publicly available from The Cancer Genome Atlas. [ABSTRACT FROM AUTHOR]

Objectives: To develop a comprehensive scale that measures the three burden types of any treatment, including expected, unexpected (complications), and need for ancillary procedures. Methods: A panel of experts created a scale that assessed the burden of all aspects of treatment, including hospitalization, anesthesia, surgery, and follow-up. The total score is defined as the burden score (BS). BS was calculated retrospectively for patients in three clinical scenarios in urology, each with two acceptable treatment options: patients with a small renal mass (T1a) treated with either partial nephrectomy (PN, 139 patients) or percutaneous ablation (PA, 83 patients), patients with bladder cancer (stages T2-4a, N0, M0) treated with radical cystectomy (RC, 162 patients) or trimodal therapy (TMT, 88 patients), and patients with upper ureteral stones ≤ 10 mm treated with either ureteroscopy (137 patients) or extracorporeal shock-wave lithotripsy (SWL, 150 patients). Results: Both PN and PA provided excellent oncological results (5-year recurrence-free survival ≥ 97%) and low complication rates. However, the BS of PN was more than twice that of PA (27.3 ± 7.7 vs. 12.5 ± 6.4, p < 0.01). RC and TMT showed identical 3-year disease-specific survival rates (73%), but the BS of TMT was significantly lower (53.8 ± 11.1 vs. 42.0 ± 11.6, p < 0.01). Both ureteroscopy and SWL have achieved high stone-free rates (≥ 97%) and low complication rates. However, the BS of ureteroscopy was significantly lower (7.8 ± 3 vs. 9.0 ± 3.5, p < 0.01). Conclusion: PA treatment for small renal masses, TMT for muscle-invasive bladder cancer, and ureteroscopy for upper ureteral stones provided similar success rates to those of PN, RC, and SWL, but with significantly lower BS. This tool can assist in patient consultation when multiple treatment options are available. The concept of BS can be extended to other fields of medicine. [ABSTRACT FROM AUTHOR]

Background: Breast cancer remains the most common invasive cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options. Trastuzumab (Tz) is typically used to treat HER2-positive breast cancers, but its potential in TNBC is unclear. Objectives: To investigate the effects of trastuzumab on cell viability, apoptosis, cell cycle progression, and gene expression in TNBC cell lines compared with HER2-positive and normal cell lines. Design: This is an in vitro experimental pre-clinical study using cultured cancer cell lines. Methods: MDA-MB-231 and 4T1 (TNBC), MCF-7 (HER2 -positive), and HSF (normal) cell lines were treated with 20 μg/mL trastuzumab for 24 hours. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, apoptosis by flow cytometry, cell cycle progression by DNA content analysis, and gene expression by qPCR. Results: Trastuzumab significantly reduced cell viability and induced apoptosis in TNBC cell lines, comparable to effects in HER2-positive MCF-7 cells. Cell cycle analysis revealed G2/M phase arrest in TNBC cells. Gene expression analysis showed upregulation of ERBB2, NOTCH1, EGFR, PIK3CA, and PTEN in MDA-MB-231 cells, while 4T1 cells exhibited downregulation of most genes except NOTCH1. Conclusion: This study provides initial evidence for trastuzumab's potential therapeutic effects in TNBC, despite low HER2 expression. The observed cytotoxicity, apoptosis induction, and cell cycle modulation in TNBC cells warrant further investigation into trastuzumab's mechanisms of action in HER2 -negative contexts and its potential repurposing for TNBC treatment. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most frequently diagnosed malignancy among women. It is characterized by a high level of heterogeneity that emerges from the interaction of several cellular and soluble components in the tumor microenvironment (TME), such as cytokines, tumor cells and tumor-associated immune cells. Tumor necrosis factor (TNF) receptor 2 (TNFR2) appears to play a significant role in microenvironmental regulation, tumor progression, immune evasion, drug resistance, and metastasis of many types of cancer, including BC. However, the significance of TNFR2 in BC biology is not fully understood. This review provides an overview of TNFR2 biology, detailing its activation and its interactions with important signaling pathways in the TME (e.g., NF-κB, MAPK, and PI3K/Akt pathways). We discuss potential therapeutic strategies targeting TNFR2, with the aim of enhancing the antitumor immune response to BC. This review provides insights into role of TNFR2 as a major immune checkpoint for the future treatment of patients with BC. [ABSTRACT FROM AUTHOR]

Protein interactions are fundamental for all cellular metabolic activities. Cytoplasmic linker protein 170 (CLIP170) plays diverse roles in cellular processes and the development of malignant tumors. Renal cell carcinoma (RCC) poses a significant challenge in oncology owing to its invasive nature, metastatic potential, high recurrence rates, and poor prognosis. However, the specific mechanisms and roles of CLIP170 underlying its involvement in RCC progression remain unclear. The findings of this study revealed a significant upregulation of CLIP170 in RCC tumor tissues. Elevated CLIP170 expression correlated positively with advanced clinical and pathological stages and was associated with poor overall survival in RCC patients. Functional assays in vitro demonstrated that elevated CLIP170 levels enhanced RCC cell proliferation, migration and invasion. Mechanistically, 4D-label free proteomics library identified that CLIP170 increased the level of FOSL1 in the Wnt signaling pathway. Immunoprecipitation and molecular docking were performed to unveil that CLIP170 formed a complex with β-catenin, inhibiting β-catenin degradation via the ubiquitin–proteasome pathway. Elevated β-catenin levels within RCC cells played a central role in promoting the transcriptional expression of FOSL1, thereby facilitating RCC cell proliferation and epithelial–mesenchymal transition (EMT) progression. In vivo investigations corroborated these findings, illustrating that CLIP170 regulated β-catenin and FOSL1 expression, driving tumor growth in RCC. This study highlights the crucial role of CLIP170 in promoting FOSL1 expression by preventing β-catenin ubiquitination and degradation, thus promoting RCC tumor progression. It suggests the CLIP170/β-catenin/FOSL1 axis as a potential therapeutic target for RCC treatment. [ABSTRACT FROM AUTHOR]

Introduction: Tumor microenvironments (TMEs) encompass complex ecosystems of cancer cells, infiltrating immune cells, and diverse cell types. Intercellular and intracellular signals within the TME significantly influence cancer progression and therapeutic outcomes. Although computational tools are available to study TME interactions, explicitly modeling tumor progression across different cancer types remains a challenge. Methods: This study introduces a comprehensive framework utilizing single-cell RNA sequencing (scRNA-seq) data within a multilayer network model, designed to investigate molecular changes across glioma progression stages. The heterogeneous, multilayered network model replicates the hierarchical structure of biological systems, from genetic building blocks to cellular functions and phenotypic manifestations. Results: Applying this framework to glioma scRNA-seq data allowed complex network analysis of different cancer stages, revealing significant ligand‒receptor interactions and key ligand‒receptor-transcription factor (TF) axes, along with their associated biological pathways. Differential network analysis between grade III and grade IV glioma highlighted the most critical nodes and edges involved in interaction rewiring. Pathway enrichment analysis identified four essential genes— PDGFA (ligand), PDGFRA (receptor), CREB1 (TF), and PLAT (target gene)—involved in the Receptor Tyrosine Kinases (RTK) signaling pathway, which plays a pivotal role in glioma progression from grade III to grade IV. Discussion: These genes emerged as significant features for machine learning in predicting glioma progression stages, achieving 87% accuracy and 93% AUC in a 3-year survival prediction through Kaplan-Meier analysis. This framework provides deeper insights into the cellular machinery of glioma, revealing key molecular relationships that may inform prognosis and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC), characterized by a high incidence rate, poses significant clinical challenges owing to its poor prognosis despite advancements in diagnostic and therapeutic approaches. Therefore, a comprehensive understanding of the molecular mechanisms driving GC progression is crucial for identifying predictive markers and defining treatment targets. Deubiquitinating enzymes (DUBs), also called deubiquitinases, function as reverse transcriptases within the ubiquitin-proteasome system to counteract protein degradation. Recent findings suggest that DUB dysregulation could be a crucial factor in GC pathogenesis. In this review, we examined recent research findings on DUBs in the context of GC, elucidating their molecular characteristics, categorizations, and roles while also exploring the potential mechanisms underlying their dysregulation in GC. Furthermore, we assessed the therapeutic efficacy of DUB inhibitors in treating malignancies and evaluated the prevalence of aberrant DUB expression in GC. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is one of the deadliest malignant tumors. Despite significant advances in RCC treatment over the past decade, complete remission is rarely achieved. Consequently, there is an urgent need to explore and develop new therapies to improve the survival rates and quality of life for patients. In recent years, the development of tumor organoid technology has attracted widespread attention as it can more accurately simulate the spatial structure and physiological characteristics of tumors within the human body. In this review, we summarize the main methods currently used to construct kidney cancer organoids, as well as their various biological and clinical applications. Furthermore, combining organoids with other technologies, such as co-culture techniques and microfluidic technologies, can further develop organoids and address their limitations, creating more practical models. This approach summarizes the interactions between different tissues or organs during tumor progression. Finally, we also provide an outlook on the construction and application of kidney cancer organoids. These rapidly evolving kidney cancer organoids may soon become a focal point in the development of in vitro clinical models and therapeutic research for kidney cancer. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion This study aimed to assess the value of a HPV E6/E7 mRNA assay (Aptima® HPV [AHPV]) for primary cervical cancer screening combined with menopausal status.A total of 16 917 women underwent AHPV testing and had complete histopathological results at the Affiliated Hospital of Jining Medical University China between January 1, 2017 and March 31, 2022. We evaluated the performance of different screening strategies and combined strategies, as well as evaluations of different menopausal states.When identifying LSIL+ (includes low‐ and high‐grade squamous intraepithelial lesions and invasive cervical cancer [ICC]), the sensitivity (91.2%) and negative predictive value (NPV; 96.6%) were significantly higher for AHPV than for liquid‐based cytology assay (LBC; 33.2% and 84.7% for sensitivity and NPV, respectively). Furthermore, the co‐testing strategy (cytology combined with AHPV), when compared with AHPV, achieved a slightly higher sensitivity (93.6% vs. 91.2%, respectively, P < 0.001), a similar specificity (61.3% vs. 62.7%, respectively, P = 0.014), a similar positive predictive value (PPV; 37.5% vs. 37.8%, respectively, P = 0.709) and a similar NPV (97.5% vs. 96.6%, respectively, P = 0.001). Moreover, AHPV (when compared with menopausal women) achieved a higher sensitivity (93.5% vs. 77.7%, respectively, P < 0.001), a higher NPV (97.3% vs. 93.9%, respectively, P < 0.001), a similar PPV (37.8% vs. 37.0%, respectively, P = 0.618) and a slightly lower specificity (60.7% vs. 72.1%, respectively, P < 0.001) in premenopausal women. These results were similar when identifying HSIL+ (includes high‐grade squamous intraepithelial lesion and ICC).The present study suggests that initial screening with HPV E6/E7 mRNA testing rather than combined screening is a suitable candidate for cervical cancer screening in China (especially for premenopausal women) based on economic reasons. [ABSTRACT FROM AUTHOR]

Studying specific subpopulations of cancer-derived extracellular vesicles (EVs) could help reveal their role in cancer progression. In cancer, an increase in reactive oxygen species (ROS) happens which results in lipid peroxidation with a major product of 4-hydroxynonenal (HNE). Adduction by HNE causes alteration to the structure of proteins, leading to loss of function. Blebbing of EVs carrying these HNE-adducted proteins as a cargo or carrying HNE-adducted on EV membrane are methods for clearing these molecules by the cells. We have referred to these EVs as Redox EVs. Here, we utilize a surface tension-mediated extraction process, termed exclusion-based sample preparation (ESP), for the rapid and efficient isolation of intact Redox EVs, from a mixed population of EVs derived from human glioblastoma cell line LN18. After optimizing different parameters, two populations of EVs were analyzed, those isolated from the sample (Redox EVs) and those remaining in the original sample (Remaining EVs). Electron microscopic imaging was used to confirm the presence of HNE adducts on the outer leaflet of Redox EVs. Moreover, the population of HNE-adducted Redox EVs shows significantly different characteristics to those of Remaining EVs including smaller size EVs and a more negative zeta potential EVs. We further treated glioblastoma cells (LN18), radiation-resistant glioblastoma cells (RR-LN18), and normal human astrocytes (NHA) with both Remaining and Redox EV populations. Our results indicate that Redox EVs promote the growth of glioblastoma cells, likely through the production of H2O2, and cause injury to normal astrocytes. In contrast, Remaining EVs have minimal impact on the viability of both glioblastoma cells and NHA cells. Thus, isolating a subpopulation of EVs employing ESP-based immunoaffinity could pave the way for a deeper mechanistic understanding of how subtypes of EVs, such as those containing HNE-adducted proteins, induce biological changes in the cells that take up these EVs. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) recapitulate the developmental and homeostatic behaviors of tissue resident macrophages (TRMs) to promote tumor growth, invasion and metastasis. TRMs arise in the embryo and colonize developing tissues, initially to guide tissue morphogenesis and then to form complex networks in adult tissues to constantly search for threats to homeostasis. The macrophage growth factor, colony-stimulating factor-1 (CSF-1), which is essential for TRM survival and differentiation, is also responsible for the development of the unique motility machinery of mature macrophages that underpins their ramified morphologies, migratory capacity and ability to degrade matrix. Two CSF-1-activated kinases, hematopoietic cell kinase and the p110δ catalytic isoform of phosphatidylinositol 3-kinase, regulate this machinery and selective inhibitors of these proteins completely block macrophage invasion. Considering tumors co-opt the invasive capacity of TAMs to promote their own invasion, these proteins are attractive targets for drug development to inhibit tumor progression to invasion and metastasis. [ABSTRACT FROM AUTHOR]

Engrailed 2 (EN2) is a homeodomain-containing protein whose aberrant expression is observed in various cancer types, yet its role in breast cancer remains unclear. This study investigates the roles and mechanisms of EN2 in breast cancer progression. Using online dataset analysis, we assessed the correlation between EN2 expression and breast cancer progression and chemotherapeutic sensitivity. Functional assays, including RT-qPCR, Western blot, cell viability, transwell migration and invasion, spheroid formation, and flow cytometry, were conducted to explore EN2's role. Mechanistic insights were obtained through luciferase reporter assays, ChIP, and Caspase 3 activity detection. Our results showed that EN2 is highly expressed in breast cancer patients, negatively correlating with survival rates and positively with disease progression and reduced chemotherapy sensitivity. Functional experiments confirmed EN2's oncogenic role, and it was found to promote the expression of the oncogenic Tenascin-C (TNC) gene. Notably, EN2 directly interacts with the super-enhancer region within the TNC locus. Elevated TNC expression mitigated the effects of EN2 knockdown on breast cancer cell progression. Our study unveils a novel mechanism by which EN2 regulates the TNC locus super-enhancer, thereby activating oncogenic pathways in breast cancer. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) plays a crucial role in cancer development and metastasis. This review summarizes the current research on how the TME promotes metastasis through molecular pathways, focusing on key components, such as cancer-associated fibroblasts, immune cells, endothelial cells, cytokines, and the extracellular matrix. Significant findings have highlighted that alterations in cellular communication within the TME enable tumor cells to evade immune surveillance, survive, and invade other tissues. This review highlights the roles of TGF-β and VEGF signaling in promoting angiogenesis and extracellular matrix remodeling, which facilitate metastasis. Additionally, we explored how metabolic reprogramming of tumor and stromal cells, influenced by nutrient availability in the TME, drives cancer progression. This study also evaluated the therapeutic strategies targeting these interactions to disrupt metastasis. By providing a multidisciplinary perspective, this study suggests that understanding the molecular basis of the TME can lead to more effective cancer therapies and identify potential avenues for future research. Future research on the TME should prioritize unraveling the molecular and cellular interactions within this complex environment, which could lead to novel therapeutic strategies and personalized cancer treatments. Moreover, advancements in technologies such as single-cell analysis, spatial transcriptomics, and epigenetic profiling offer promising avenues for identifying new therapeutic targets and improving the efficacy of immunotherapies, particularly in the context of metastasis. [ABSTRACT FROM AUTHOR]

Background: Increasing evidence suggests that the CXC chemokine receptor 6 (CXCR6) is involved in tumor progression and the regulation of tumor immunity. However, its role in muscle-invasive bladder cancer (MIBC) remains largely unexplored. Methods: Data from 391 MIBC patients in the TCGA, 212 patients from GEO, 131 patients from our center, 195 patients in the IMvigor210 cohort, and single-cell RNA sequencing (scRNA-seq) data from 9 bladder cancer patients (GSE222315) were analyzed. Additionally, data from the GEPIA 2, TISCH2, TIMER2.0, and UALCAN platforms were utilized to investigate the prognostic and immunotherapeutic significance of CXCR6 in MIBC. Results: We observed that CXCR6 expression was significantly reduced in bladder cancer tumors and correlated with tumor stage and grade. Low CXCR6 expression was associated with poor recurrence-free survival (RFS) and overall survival (OS) in the TCGA cohort, a finding validated in both the meta-GEO dataset and our center's cohort. Multivariate analysis confirmed that low CXCR6 expression was an independent predictor of poor OS and RFS. A nomogram incorporating CXCR6 expression and other independent prognostic factors was developed to accurately predict 3- and 5-year OS. Gene set enrichment analysis indicated that immune activation-related pathways were significantly enriched in tumors with high CXCR6 expression. CIBERSORT analysis revealed that CXCR6 expression was positively correlated with CD8+ T cells, CD4+ T cells, activated NK cells, M1 macrophages, and activated dendritic cells in TCGA, findings further validated by TIMER2.0. scRNA-seq data showed that CXCR6 was predominantly expressed in T and NK cells and facilitated T/NK-myeloid interaction via the CXCR6-CXCL16 axis. Importantly, CXCL16+ macrophages and dendritic cells recruited CXCR6+ T and NK cells, which exhibited enhanced cytotoxicity, thereby amplifying anti-tumor immunity. Clinically, in the IMvigor210 immunotherapy cohort, higher CXCR6 expression was associated with improved anti-PD-L1 therapeutic outcomes. Conclusion: Our findings highlight CXCR6 as a critical biomarker for predicting prognosis and immunotherapeutic response in MIBC. [ABSTRACT FROM AUTHOR]

Background: Cisplatin resistance is the leading cause of mortality in muscle-invasive bladder cancer (MIBC) cases. Previous evidence suggests that abnormal epitranscriptome modifications are associated with reduced chemotherapy responses. However, the exact underlying mechanism remains largely unknown. Methods: Insulin-like growth factor-2 mRNA-binding protein 2 (IMP2) was identified by clustered regularly interspaced short palindromic repeats (CRISPR) data screening, single-cell RNA-sequencing and sample analysis. To evaluate the regulatory role of IMP2, functional studies were conducted both in vitro and in vivo. To elucidate the underlying mechanisms, various techniques including immunofluorescence, fluorescent in situ hybridization, RNA pull-down, coimmunoprecipitation, and RNA immunoprecipitation were used. Results: Our study revealed that IMP2 was overexpressed in chemoresistant MIBC and lung metastasis tissues. IMP2 inhibition markedly enhanced the sensitivity of BC cells to cisplatin both in vitro and in vivo. Mechanistically, IMP2 enhanced the mRNA stability of IPO4 and SLC7A11 in a m6A-dependent manner, augmenting the nuclear translocation of C/EBPδ to activate PRKDC-mediated DNA damage repair in response to cisplatin. Moreover, IMP2 upregulated SLC7A11 levels and suppressed cisplatin-induced ferroptosis. Combining ferroptosis and apoptosis inhibitors completely reversed cisplatin resistance caused by IMP2 overexpression. LINC00941, which was induced by HIF-1α-mediated transcriptional activation, specifically bound IMP2 and protects it from degradation. Conclusions: This work demonstrated a novel mechanism involving the IMP2-IPO4/SLC7A11 pathway as a promising treatment target for cisplatin-resistant bladder cancer. [ABSTRACT FROM AUTHOR]

Mitochondria are dynamic organelles integral to metabolic processes, coordination of essential biological pathways, and oncogenesis and tumor progression. Recent studies have revealed that mitochondria can be transferred between cells via multiple mechanisms, implicating their involvement in the pathogenesis and progression of ovarian cancer. This review provides a comprehensive analysis of intercellular mitochondrial transfer within the context of ovarian cancer and its tumor microenvironment. We also propose targeted pathways and therapeutic strategies that could be utilized to modulate diseases associated with mitochondrial transfer therapy. Finally, we examine recent advancements in this field and identify several unresolved questions. [ABSTRACT FROM AUTHOR]

Mitochondrial‐nuclear communication plays a vital role in maintaining cellular homeostasis. MOTS‐c, a short peptide derived from the 12S rRNA of mitochondrial DNA, has been suggested as a retrograde mitochondrial signal. Although recent clinical studies have suggested a possible link between MOTS‐c and human cancer, the role of MOTS‐c in tumorigenesis has yet to be investigated. Here, MOTS‐c levels are found to be reduced in both serum and tumor tissues from ovarian cancer (OC) patients, which are associated with poor patients' prognosis. Exogenous MOTS‐c inhibits the proliferation, migration and invasion of OC cells, and induces cell cycle arrest and apoptosis. Mechanistically, MOTS‐c interacts with LARS1 and promotes its ubiquitination and proteasomal degradation. In addition, USP7 was identified as a deubiquitinase of LARS1, and MOTS‐c can attenuates USP7‐mediated LARS1 deubiquitination by competing with USP7 for binding to LARS1. Besides, LARS1 was found to be increased and play an important oncogenic function in OC. More importantly, MOTS‐c displays a marked anti‐tumor effect on OC growth without systemic toxicity in vivo. In conclusion, this study reveals a crucial role of MOTS‐c in OC and provides a possibility for MOTS‐c as a therapeutic target for the treatment of this manlignacy. [ABSTRACT FROM AUTHOR]

LACTB is identified as a tumor suppressor in several tumors. However, preliminary study reveals that LACTB is overexpressed in osteosarcoma and indicates poor prognosis. Two missense mutations (rs34317102 and rs2729835) exist simultaneously in 92.31% of osteosarcoma patients and cause M5L and R469K double mutations in LACTB, suggesting the biologic function of LACTB protein may be altered in osteosarcoma. Moreover, LACTBM5L+R469K overexpression can promote malignant progression in different tumors, which suggests that the M5L and R469K mutations confer oncogene‐like functions to LACTB. Mechanistically, LACTBM5L+R469K not only reduces the wild type p53 via enhancing PSMB7 catalytic activity, but also protects p53R156P protein from lysosomal degradation, which suggesting LACTBM5L+R469K is a dual‐regulator for wt‐p53 and mutant p53, and derive oncogene‐like functions. More importantly, clavulanate potassium, a bacterial β‐lactamase inhibitor, can inhibit osteosarcoma proliferation and sensitize osteosarcoma to cisplatin by binding and blocking LACTBM5L+R469K. These findings revealed that the M5L and R469K double mutations can diminish the tumor suppressive ability of wild type LACTB and provide oncogene‐like functions to LACTB. Inhibiting LACTBM5L+R469K can suppress the progression of osteosarcoma harbouring wild‐type or mutant p53. Clavulanate potassium is a promising drug by targeting LACTBM5L+R469K‐p53 pathway for the treatment of osteosarcoma patients. [ABSTRACT FROM AUTHOR]