To evaluate the impact of early surgical intervention on outcomes in patients admitted non-electively for macroscopic hematuria, a clinical scenario with limited prior research.

We conducted a single-center, retrospective observational study including 261 consecutive patients admitted non-electively with a primary diagnosis of macroscopic hematuria to the Urology Department at Hospital Universitario 12 de Octubre, Spain, between January 2016 and June 2021. Patients were stratified into three groups: no surgical intervention, surgical intervention within 5 days, and surgical intervention after 5 days. Baseline characteristics, 365-day readmissions, and mortality were analyzed using binary logistic regression, zero-inflated Poisson, and Cox proportional hazards models.

The median age was 82 years and the median Charlson Comorbidity Index was 6. Crude 365-day readmission and mortality rates were 50.6% and 30.7%, respectively. Patients who underwent surgical intervention had lower 365-day mortality (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.32-0.97, p = 0.038) and readmission rates (odds ratio [OR] 0.28, 95% CI 0.15-0.54, p < 0.001). Significant risk factors for 365-day mortality included red blood cell transfusion (HR 2.12, 95% CI 1.29-3.49, p = 0.003), higher Charlson Comorbidity Index (HR 9.16, 95% CI 2.22-37.54, p = 0.002), and greater disease complexity (HR 2.35, 95% CI 1.63-3.39, p < 0.001). The single-center, retrospective design limits the generalizability of these findings.

In this cohort of elderly patients with substantial comorbidity, early surgical intervention, when clinically indicated, was associated with significantly reduced 365-day mortality and readmission rates.

In a resource limited setting, cabergoline remains an important part of medical management in acromegaly patients with persistent disease after surgery. Response to medical treatment may depend on the receptor expression in these tumors.

To study the dopamine receptor subtype2 (D2R) and somatostatin receptor subtypes2&5(SSTR2&SSTR5) expression in somatotropinomas by immunohistochemistry (IHC) and real time/quantitative polymerase chain reaction(qPCR). Also, to determine the relation between density of D2R expression and remission with cabergoline therapy.

This study included 30 patients with somatotropinomas who underwent surgery and had persistent disease post-surgery treated with cabergoline. Immunostaining and qPCR for D2R, SSTR2&5 were performed on archived GH secreting pituitary adenoma specimens. The clinical, biochemical and radiological details were collected from the hospital electronic medical records.

D2R was the predominantly expressed receptor followed by SSTR2 and SSTR5. The median(range) duration of cabergoline therapy was 20(6-72) months. 23% (7/30) of patients achieved normalization of IGF-I or GH < 1ng/ml (random/post glucose suppression) with cabergoline. Subjects with baseline IGF-1 < 1.5 times the upper limit of normal were more likely to achieve remission with cabergoline. D2R mRNA expression was significantly higher in patients in remission. On ROC curve analysis, a D2R ^ΔΔ CT of 19.2 (19-fold higher expression compared to normal tissue) predicted remission with cabergoline with a sensitivity of 71% and specificity of 74% (AUC 0.745).

D2 receptor profiling of growth hormone secreting pituitary tumors and post-operative IGF-1 level at 3 months are helpful to predict response to medical treatment with cabergoline.

The literature on squamous cell carcinoma associated with breast implants (BIA-SCC) is scarce and is limited primarily to case reports, nonsystematic and systematic reviews. There is no standard for diagnosis, staging, surgical treatment, or survival analysis.

We add to the literature the first case of BIA-SCC in Brazil. We also conducted a systematic review of the literature on BIA-SCC and subsequently proposed a clinical/surgical staging system based on disease-free survival (DFS) and overall survival (OS). The new staging system considers not only local invasion but also capsule rupture during surgery and the type of resection.

Survival and recurrence were evaluated in 17 patients. Nine patients experienced recurrence (mean 5.2 months; range 1-12 months), and six died (mean 8.2 months; range 2-17 months). The three patients who experienced prolonged survival underwent capsule resection, mastectomy, and chest wall resection, and one patient underwent capsulectomy despite the absence of extracapsular extension of the disease. The mean OS was 15.5 months (range 2-96 months), and the mean DFS was 13.5 months (range 0-96 months). The new clinical/surgical staging system had good prognostic value for OS (p < 0.001) and DFS (p < 0.001).

Squamous cell carcinoma associated with breast implants has a poor prognosis, making early preoperative diagnosis crucial. Total capsulectomy, without spillage of the contents of the capsule, followed by resection of adjacent tissue, may prevent local recurrence. In clinical-surgical staging, the surgeon should consider not only capsule infiltration but also the possibility of surgical injury and the type of resection.

Small cell carcinoma of cervix (SCCC) was a highly aggressive tumor with dismal prognosis. Current treatment strategies manifested poor survival outcomes and novel treatment options were needed exploration. We aimed to investigate several prognostic biomarkers for SCCC and conducted a novel risk-score system to predict cancer specific survival (CSS) in early-stage SCCC. Seven cell-cycle proteins were detected by immunohistochemistry in 88 SCCCs. Univariate and multivariate analysis were performed to identify prognostic proteins and establish a predicting model. Total patients were divided into two groups by the median risk-score: the high-risk group and the low-risk group. Logistic regression and Wilcoxon test were used to investigate the association between clinical variables and the risk-score system. Seven cell cycle proteins were overexpressed in SCCC. The expression of CDC20, MAD2L1, MCM2 and BUBR1 were correlated to survival outcomes with P < 0.05. A novel risk-score system consisting of CDC20, MAD2L1 and BUBR1 was significantly an independent prognostic factor for CSS and the high-risk group possessed worse survival (P < 0.001). The c-indexes for clinical model, risk-score system and the combined model were 0.668, 0.718 and 0.727, respectively. The AUCs for these three models were 0.730, 0.775 and 0.823, respectively. Furthermore, we discovered that patients with high-risk scores were inclined to possessing older age, parametrial invasion and higher FIGO stage (IIA vs IA/IB) with P < 0.05. This risk-score system consisting of CDC20, MAD2L1 and BUBR1 presented good discrimination and predictability for SCCC. Novel biomarkers in this study might have some merits in providing guidance of novel treatment strategies for SCCC.

RUNX2, a member of the RUNX transcription factor family, has been reported to promote epithelial-mesenchymal transition (EMT) in various malignancies, yet its role in glioma remains poorly understood. In this study, we systematically analyzed RUNX2 expression and clinical relevance in glioma using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets via the UALCAN web portal. Kaplan-Meier survival analyses and Wilcoxon rank-sum tests were employed to assess the prognostic significance of RUNX2. We further validated RUNX2 expression in glioma tissues and cell lines using RT-qPCR and Western blotting. Functional experiments, including CCK-8, wound healing, transwell invasion, and apoptosis assays, were conducted in U251 glioma cells with RUNX2 knockdown via siRNA. EMT-related proteins and components of the TGF-β/Smad pathway were examined by Western blot. In addition, we employed multiplex immunohistochemistry on 160 glioma specimens to analyze the spatial relationship between RUNX2 and EMT markers. Our results demonstrate that RUNX2 is significantly upregulated in glioma tissues and correlates with higher tumor grade, IDH-wildtype status, and poorer overall and disease-free survival. RUNX2 knockdown significantly inhibited glioma cell proliferation, migration, and invasion, while promoting apoptosis. Mechanistically, RUNX2 modulated the expression of EMT markers and activated the TGF-β1/Smad2/3 signaling axis. Collectively, our findings suggest that RUNX2 promotes EMT and malignant progression in glioma via the TGF-β/Smad pathway, and may serve as a potential therapeutic target and prognostic biomarker.

Immune checkpoint blockade (ICB) has made great progress in treating cancer, regulating the tumor immune microenvironment can improve the efficacy of ICB and has become a major focus. Pyroptosis, as a new form of cell death, has been reported in a few diseases to activate cellular immune responses due to the release of inflammatory factors. This may offer a new approach for regulating the tumor immune microenvironment. MT1JP plays an important role in gastric cancer, but its mechanism of pyroptosis and immunity is unclear. Bioinformatics analysis combined with qRT-PCR revealed the expression levels of MT1JP and miR-103a-3p in GC cells and tissues, and their interactions were revealed by dual-luciferase assay and rescue experiment. The effects of MT1JP on GC cell proliferation, invasion, and migration were assessed by CCK-8, EdU, Colony formation, Wound healing, and Transwell. Western blot, IHC, IF, and ELISA were used to assess the effects of MT1JP/miR-103a-3p in GC cell pyroptosis and immunity. MT1JP expression was downregulated and miR-103a-3p was upregulated in GC cells and tissues, the expression of MPDZ was downregulated in AGS and MKN-45. Overexpression of MT1JP inhibited GC cell proliferation, invasion, and migration. MT1JP directly targets and inhibits miR-103a-3p. MT1JP/miR-103a-3p induced the expression of pyroptosis-related proteins (GSDMD, NLRP3, Caspase1) and inflammatory factors (IL-1β, IL-18), activated the immune pathway Sting/IFN-β, and downregulated PD-L1. Based on bioinformatics analysis and preliminary exploration in this study, MPDZ may be a potential downstream target of miR-103a-3p. MT1JP/miR-103a-3p can induce pyroptosis, activate the immune response, and then inhibited the growth of gastric cancer, possibly acting through MPDZ. This explored a new anti-cancer method to regulate the tumor immune microenvironment.

Cuproptosis, a copper-dependent distinct form of cell death, holds a critical role in tumor development. However, further investigation is needed to elucidate the impact of the cuproptosis signaling on thyroid cancer. In this study, comprehensive bioinformatics analyses with six independent cohorts and in vitro experiments were performed to explore the expression, prognostic significance, and molecular function of the cuproptosis key regulator FDX1 in papillary thyroid carcinoma (PTC). LASSO regression analyses were utilized to screen the optimal combination of cuproptosis-related genes for constructing a Cox proportional-hazards model, and the cuproptosis-related risk score (CRRS) was calculated to stratify PTC patients in prognosis. The algorithm of ESTIMATE and ssGSEA were used to investigate the tumor immune microenvironment. Our results showed FDX1 was significantly downregulated in PTC, and its lower expression was closely associated with tumor recurrence. Based on six selected cuproptosis-related genes a predictive prognosis model was established and CRRS displayed a good prediction accuracy. Overexpression of FDX1 could promote cell death and inhibit the viability of tumor cells. Additionally, CYCS played a hub role in the cuproptosis regulatory network and could be upregulated with the overexpression of FDX1. Our study suggests that CRRS can serve as a good prognosis indicator and may provide new insights into cuproptosis-targeted therapies in PTC.

Malignant cells have in contrast to non-transformed cells de-regulated transcriptional networks. The activator protein-1 (AP-1) transcription factor complex is expressed in many cancer entities including adenocarcinomas and has been correlated to de-regulated transcription and tumor-promoting mechanisms. Despite complex treatment approaches, esophageal cancer is still associated with poor overall survival. There is an urgent need for better patient stratification to increase the outcome of the multimodal treatment. This study investigated the expression of two AP-1 factors, cJUN and JUNB, and their role in 735 patients with esophageal cancer undergoing surgery. We performed immunohistochemical stainings for cJUN and JUNB and correlated the expression to the clinical outcome. Patients with a high JUNB expression level correlate to a reduced overall survival (OS) compared to patients with a low expression. Furthermore, in the multivariate analysis high JUNB expression was shown to be an independent risk factor for reduced patient survival. In addition, subgroup analysis demonstrated a significantly reduced OS for high JUNB expression in the subgroup of patients with neoadjuvant treatment. Strikingly, tumors co-expressing cJUN and JUNB were associated with poorer overall survival compared to those expressing only one or neither of the transcriptions factors. Our study suggests JUN expression as a novel biomarker to stratify patients, especially in the subgroup of neoadjuvant treated patients. Our findings have translational implications as targeting JUN might complement current available multimodal treatment approaches.

Combinations of cancer drugs have the potential to overcome resistance, improve the response rate of existing drugs and reduce dose-limiting toxicity associated with single agents. Existing drug combination databases only provide response data, such as synergy scores between two drugs, without important contextual information to assist oncologists in matching their patients with these combinations in an evidence-based way. To address this gap, we developed a cancer drug combination database (named as OncoDrug+) by manually collecting and integrating drug combinations and corresponding evidences from FDA databases, clinical guidelines, clinical trials, clinical case reports, patient-derived tumor xenograft models, cell line models and bioinformatics predictions. OncoDrug+ includes 7895 data entries, covering 77 cancer types, including unique 2201 drug combination therapies, involving 1200 biomarkers, 763 published reports and seven types of evidence. Unlike many previous databases only include treatment regime and drug response data, OncoDrug+ provides detailed genetic evidences, pharmacological target information and evidence scores supporting each combination strategy, making evidence-based experimental or clinical applications of cancer drug combinations be possible.