Poor Prognosis Research Articles

Ovarian carcinoma in patients aged ≥80 years: A retrospective multicenter study of management and survival in the FRANCOGYN population

IntroductionThe aims of this study were to describe survival outcomes in patients with ovarian cancer aged ≥80 years and to explore predictors of poor prognosis. MethodsWe collected clinical, demographic, histologic, surgical and follow-up data for patients with ovarian cancer aged ≥80 years from a multicenter French cohort (FRANCOGYN) who underwent surgery from 1999 to 2019. Primary endpoints were overall survival (OS) and disease-free survival (DFS). We performed a descriptive analysis of demographic and clinical data and a survival time analysis and comparison using the Kaplan Meier method and log-rank test. ResultsOf 1671 patients treated for ovarian cancer during the study period, 83 were aged ≥80 years (median age at diagnosis, 83 years; range, 80–99). Median OS was 39.6 months (range, 23.64–60.24). Factors significantly associated with OS in the univariate analysis were adjusted Charlson comorbidity index (ACCI) (HR 2.32; 95% CI, 1.00–5.42 for ACCI >4), FIGO stage (HR 4.07 for FIGO stage >IIA; 95% CI, 1.43–11.54), debulking surgery (HR 0.40; 95% CI, 0.20–0.78), residual disease after surgery (HR 3.00; 95% CI, 1.31–6.87), and postoperative complications (HR 2.24; 95% CI, 1.04–4.81). Significant independent predictors of worse OS in the multivariate analysis were ACCI >4 (HR 4.96; 95% CI, 1.57–15.75), perioperative complications (HR 5.01; 95% CI, 1.32–18.95), and residual tumor after surgical debulking (HR 3.78; 95% CI, 1.23–11.61). ConclusionAge by itself should not refrain surgeons and oncologist from proposing surgical debulking and chemotherapy, as recommended by international guidelines for patients with ovarian cancer aged ≥80 years

Overall survival in TP53-mutated AML and MDS.

TP53 mutations in patients with AML and MDS frequently portend a poor prognosis, related to both p53 allele status and blast count. In 2022, the ICC and WHO released updated guidelines for classifying p53-mutated AML/MDS. The characteristics of p53 mutations, their associated co-mutations, and their effects on overall survival (OS) are not known in the context of these new guidelines. A retrospective chart review was undertaken for all patients with AML or MDS and at least one TP53 mutation detected on next generation sequencing (NGS) at Yale New Haven Hospital from 2015 to 2023. All patients (N = 210) met criteria for one of the 5 diagnostic classes based on WHO and ICC guidelines. Kaplan-Meier curves with associated log-rank testing and Cox proportional hazards model quantified the effects of clinical and molecular data on survival. Multi-hit pathogenic mutations were related to poorer OS in MDS but not AML using either the WHO (p = .02) or the ICC (p = .01) diagnostic criteria. The most significant predictors of OS in the sample overall were platelet count < 50K (HR: 2.01, 95% CI [1.47, 2.75], p < .001) and TP53 VAF ≤ 40% (HR: 0.68, 95% CI[0.50, 0.91], p = .01). Blast count ranges, complex karyotype, and p53 mutation type or location, showed no association with OS. In our cohort defined by the 2022 ICC and WHO criteria, VAF and thrombocytopenia, rather than blast count or p53 mutation features, significantly predicted OS. These results speak to each criteria's ability to identify cases of similarly aggressive disease biology and prognosis.

PTPN11 is a potential biomarker for type 2 diabetes mellitus complicated with colorectal cancer

Epidemiological surveys have shown that the incidence of type 2 diabetes mellitus (T2DM) and malignancies is rapidly increasing worldwide and has become a major disease that threatens human life. In this study, we quantitatively analyzed the proteome of tumor tissues and adjacent normal tissues from six patients withT2DM combined with colorectal cancer (CRC) and eight non-diabetic CRC, focusing on the effect of T2DM on tumor tissues. We analyzed the functional enrichment of differentially expressed proteins (DEPs) using clusterProfiler in R and the expression level of protein tyrosine phosphatase non-receptor type 11 (PTPN11) and other key proteins in the TIMER and GEPIA2 databases. The HPA database was used to validate PTPN11 protein expression. The correlation between PTPN11 expression and clinicopathological features was analyzed by UALCAN database. The impact of PTPN11 on clinical prognosis was evaluated utilizing Kaplan-Meier Plotter. The correlation between PTPN11 expression and tumor-infiltrated immune cells was investigated via TIMER and TISIDB databases. Gene set enrichment analysis (GSEA) was performed to examined the pathway of PTPN11 enrichment in CRC using data from The Cancer Genome Atlas (TCGA) database. Furthermore, small interfering (si) RNA was used to knock down PTPN11 in CRC cell line SW480. Western blot analysis was used to detect PTPN11 expression in tissue samples or cells and the effect of PTPN11 knockdown on key proteins related to PI3K/AKT and cell cycle pathway in SW480 cells. Cell proliferation and wound healing assays were used to detect the effects of cell proliferation and migration after knockdown of PTPN11 or treatment with high glucose. We found that metabolic pathways such as oxidative phosphorylation, glycolysis/gluconeogenesis, and insulin secretion were significantly enriched in tumor tissues from diabetic patients compared to non-diabetic patients. In addition, PTPN11, a marker gene associated with T2DM and CRC, were mined in diabetic tumor tissues. PTPN11 showed high expression in diabetic tumor tissues compared to normal tissues. High PTPN11 expression predicted poor prognosis in CRC. PTPN11 expression was strongly associated with immune infiltrating cells in CRC. GSEA analysis revealed that PTPN11 was enriched in cancer-related pathways. Western blotting analysis indicated that PTPN11 knockdown reduced the protein levels of p-PI3K, p-AKT, CDK1 and CYCLIN D, without altering PI3K and AKT protein levels. Cell proliferation and wound healing data showed that PTPN11 and high glucose could increase the proliferation and migration ability. These findings showed that PTPN11 may be a potential key biomarker for CRC in patients with diabetes, which will provide new potential targets for future intervention of T2DM complicated with CRC.

Predictors and Clinical Outcomes of True Mitral Stenosis in Patients Undergoing Transcatheter Aortic Valve Implantation

Abstract Aims Predictors of true degenerative mitral stenosis (MS) in patients with aortic stenosis who underwent transcatheter aortic valve implantation (TAVI) remain unknown. This study aimed to investigate the predictors and prognostic value of true degenerative MS in this population. Methods and results We retrospectively reviewed the records of 760 consecutive patients who underwent TAVI. The mitral valve area (MVA) was assessed using transthoracic echocardiography, and mitral valve calcification was assessed using multi-detector computed tomography. MS was defined as an MVA of ≤2.0 cm², and true MS was defined as moderate or severe MS following TAVI. In our TAVI cohort, we identified 72 (9.5%) patients with degenerative MS. Among these, true MS was observed in 38 (52.7%) patients. Echocardiographic data showed that the true MS group had a significantly lower MVA and higher trans-mitral gradient. The severity of mitral annular calcification was not significantly different between the two groups; however, the true MS group had significantly more posterior mitral leaflet (PML) and anterior mitral leaflet (AML) calcification. Multivariable logistic regression analysis showed that AML calcification was the independent predictor of true MS (adjusted OR, 9.23; 95% CI 2.84‒29.9). True MS was independently associated with poor prognosis (adjusted HR, 2.76; 95% CI 1.09‒6.98). Conclusions Approximately half of patients with concomitant degenerative MS who underwent TAVI had true MS, which was associated with a poor prognosis. Computed tomographic analysis of AML calcification was useful for predicting true MS.

AKAP12 positive fibroblast determines immunosuppressive contexture and immunotherapy response in patients with TNBC by promoting macrophage M2 polarization

BackgroundTriple-negative breast cancer (TNBC) is a molecular subtype of breast cancer with high aggressiveness and poor prognosis. Cancer-associated fibroblasts (CAFs) are major components of the TNBC microenvironment and play an...

Impact of Obesity on Gleason Score- Elderly and Very Elderly Patients with Prostate Cancer Indicated for Radical Radiotherapy

Introduction: Prostate cancer is an important public health concern in Brazil, especially among older men, with a significant mortality rate. In addition to advanced age, obesity emerges as a relevant risk factor, associated with a worse prognosis of the disease. Objective: To investigate the relationship between body mass index (BMI) and Gleason score in older and very older patients with prostate cancer indicated for radiotherapy treatment. Methods: Prospective, descriptive, and longitudinal study with 258 patients with prostate cancer, evaluating age, initial PSA, BMI, race, and Gleason Score. Result: Findings revealed an association between a higher BMI and a more aggressive degree of disease, as indicated by higher Gleason scores. Conclusion: Overweight and obese patients have a higher and more evident Gleason score in older patients compared to the very older, being more notable in the older. This study is one of the few studies to examine the link between BMI and poor prognosis in prostate cancer patients

Promotion of nerve regeneration and motor function recovery in SCI rats using LOCAS-iPSCs-NSCs

BackgroundSpinal cord injury (SCI) is a severe traumatic spinal condition with a poor prognosis. In this study, a scaffold called linearly ordered collagen aggregates (LOCAS) was created and loaded with induced pluripotent stem cells (iPSCs)-derived neural stem cells (NSCs) from human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) to treat SCI in a rat model.MethodsThe rats underwent a complete transection SCI resulting in a 3-mm break at either the T9 or T10 level of the spinal cord.ResultsScanning electron microscope analysis revealed a uniform pore structure on the coronal plane of the scaffold. The LOCAS had a porosity of 88.52% and a water absorption of 1161.67%. Its compressive modulus and stress were measured at 4.1 MPa and 205 kPa, respectively, with a degradation time of 10 weeks. After 12 weeks, rats in the LOCAS-iPSCs-NSCs group exhibited significantly higher BBB scores (8.6) compared to the LOCAS-iPSCs-NSCs group (5.6) and the Model group (4.2). The CatWalk analysis showed improved motion trajectory, regularity index (RI), and swing speed in the LOCAS-iPSCs-NSCs group compared to the other groups. Motor evoked potentials latency was lower and amplitude was higher in the LOCAS-iPSCs-NSCs group, indicating better neural function recovery. Histological analysis demonstrated enhanced neuronal differentiation of NSCs and nerve fiber regeneration promoted by LOCAS-iPSCs-NSCs, leading to improved motor function recovery in rats. The LOCAS scaffold facilitated ordered neurofilament extension and guided nerve regeneration.ConclusionsThe combination of LOCAS and iPSCs-NSCs demonstrated a positive therapeutic impact on motor function recovery and tissue repair in rats with SCI. This development offers a more resilient bionic microenvironment and presents novel possibilities for clinical SCI repair.

Ascites as a Predictive Factor in Malignancies in the Last Year of Life-Comparison Between Different Cancer Types.

Background: Ascites in malignancies is usually associated with poor prognosis, but the predictive value may vary between different cancer types. Objectives: The aim was to map the frequency and temporal pattern of paracentesis in patients with malignancies in relation to time to death and to evaluate the occurrence of ascites as a predictive factor in different cancer types, with a limitation to the last year of life. Design: A retrospective study based on registry data covering all care visits in the Stockholm Region, Sweden, for seven years was performed. All deceased subjects that had at least one registered paracentesis in the last year of life were included. Results: Of 23,056 subjects dying from cancer, 1863 had undergone paracentesis in the last year of life (8.0%). Ascites requiring paracentesis was most frequently seen in appendiceal cancer (38%), ovarian cancer (35%), cholangiocarcinoma (26%), hepatocellular carcinoma (19%), and pancreatic cancer (17%). The median time for the first paracentesis in all cancer types varied between 248 and 20 days before death. For ovarian cancer, the median time for first paracentesis differed significantly compared with upper gastro-intestinal (GI) cancers, 81 days compared with 30 days (p < 0.0001). Ascites in prostate cancer was rare,1.9%, but when present, a pronounced increase in the frequency of paracentesis was observed in the last three months of life. Conclusion: The occurrence of paracentesis in patients with advanced cancer is generally a sign that death is approaching within the coming months, especially in upper GI cancer. For ovarian and appendiceal cancers, ascites is less useful as a predictive tool.

Low SMARCD3 expression is associated with poor prognosis in patients with prostate cancer.

SWI/SNF complexes represent a family of multi-subunit chromatin remodelers that are affected by alterations in >20% of human tumors. While mutations of SWI/SNF genes are relatively uncommon in prostate cancer (PCa), the literature suggests that deregulation of various subunits plays a role in prostate tumorigenesis. To assess SWI/SNF functions in a clinical context, we studied the mutually exclusive, paralogue accessory subunits SMARCD1, SMARCD2, and SMARCD3 that are included in every known complex and are sought to confer specificity. Performing immunohistochemistry (IHC), the protein levels of the SMARCD family members were measured using a tissue microarray (TMA) comprising malignant samples and matching healthy tissue of non-metastatic PCa patients (n = 168). Moreover, IHC was performed in castration-resistant tumors (n = 9) and lymph node metastases (n = 22). To assess their potential role as molecular biomarkers, SMARCD1 and SMARCD3 protein levels were correlated with clinical parameters such as T stage, Gleason score, biochemical recurrence, and progression-free survival. SMARCD1 protein levels in non-metastatic primary tumors, lymph node metastases, and castration-resistant samples were significantly higher than in benign tissues. Likewise, SMARCD3 protein expression was elevated in tumor tissue and especially lymph node metastases compared to benign samples. While SMARCD1 levels in primary tumors did not exhibit significant associations with any of the tested clinical parameters, SMARCD3 exhibited an inverse correlation with pre-operative PSA levels. Moreover, low SMARCD3 expression was associated with progression to metastasis. In congruence with previous literature, our results implicate that both SMARCD1 and SMARCD3 may exhibit relevant functions in the context of prostate tumorigenesis. Moreover, our approach suggests a potential role of SMARCD3 as a novel prognostic marker in clinically non-metastatic PCa.

Impact of GAP score on surgical prognosis of non-small-cell lung cancer with usual interstitial pneumonia.

Post-surgical survival outcomes in patients with non-small-cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF) are expected to be worse than those in patients with other idiopathic interstitial pneumonias (IIPs). However, these remain unclear regarding patients with NSCLC and IPF histologically diagnosed as usual interstitial pneumonia [IPF(UIP)]. We aimed to assess the surgical and survival outcomes and identify prognostic factors in patients with NSCLC and IPF(UIP). This retrospective cohort study included patients with pathological stage I-III NSCLC and UIP. Prognostic factors and their association with lung cancer deaths (LCDs) and non-LCDs (NLCDs) were investigated. The overall survival of patients with UIP was significantly poorer than that of others with IIPs. The main causes of death were lung cancer (36%) and respiratory disease (44%). Multivariate analyses revealed the pathological stage of NSCLC ≥ II (hazard ratio [HR], 2.196; p = 0.009) and GAP stage ≥ II (HR, 2.821; p = 0.016) to be significant prognostic factors. NLCD incidence was significantly high in patients with GAP stage ≥ II. Recurrence occurred in 26 patients (36.1%); the period from recurrence to death was shorter in patients with IPF(UIP) than in patients without IPF(UIP). Patients with NSCLC and IPF(UIP) had poor prognosis after surgery. However, the prognosis varied greatly depending on the GAP stage. Considering the difficulty in managing post-surgical recurrence and high incidence of LCDs in patients with IPF(UIP), pursuing a radical resection is recommended in patients with GAP stage I. For patients with GAP stage ≥ II, comprehensive management of UIP is also necessary.

Spinal neurocutaneous melanosis.

Neurocutaneous melanosis is characterized by melanin-producing cells within the skin, leptomeninges, or brain parenchyma. It is a severe manifestation of congenital melanocytic nevus syndrome and can develop malignant melanomas. The disorder is commonly present in pediatric patients within the first two years of life and has a poor prognosis. We report a case of an 8-year-old male with epilepsy and cognitive deficit presenting spinal neurocutaneous melanosis.

Single-cell transcriptome analysis identifies a novel tumor-associated macrophage subtype predicting better prognosis in pancreatic ductal adenocarcinoma

BackgroundCharacterized by an immune-suppressive tumor microenvironment (TME), pancreatic ductal adenocarcinoma (PDAC) is well-known for its poor prognosis. Tumor associated macrophages (TAMs) play a critical role in PDAC TME. An in-depth understanding of TAMs is helpful to develop new strategies for immunotherapy.MethodsA large number of single-cell RNA sequencing data and bulk RNA sequencing data of PDAC were collected for systematic bioinformatics analysis. Characterize subtypes of TAMs at single-cell resolution and its effect on prognosis. Differential gene analysis and cell-cell communication were used to describe the effect on prognosis and validated by the TCGA dataset.ResultsWe used two prognosis-favorable genes, SLC12A5 and ENPP2, to identify a benign M2-like TAMs (bM2-like TAMs), which shared similarities with C1QC + TAMs, CXCL9+ TAMs and CD169+ TAMs, by analyzing scRNA-seq data and bulk RNA data of PDAC. The bM2-like TAMs were revealed to promote T cell activation and proliferation through ALCAM/CD6 interaction. Meanwhile, the bM2-like TAMs were responsible for stroma modeling by altering αSMA+/αSMA-cell ratio. On the contrast, the rest of the M2-like TAMs were defined as malignant M2-like TAMs (mM2-like TAMs), partly overlapping with SPP1+ TAMs. mM2-like TAMs were revealed to promote tumor progression by secretion of MIF and SPP1.ConclusionOur study used two prognosis-favorable genes to divide M2-like TAMs of PDAC into anti-tumor bM2-like TAMs and pro-tumor mM2-like TAMs. The bM2-like TAMs activate T cells through ALCAM/CD6 and generate prognosis-favorable αSMA+ myofibroblasts through secreting TGFβ, which brings insight into heterogeneity of TAMs, prognosis prediction and immunotherapy of PDAC.

FOXP3+/CD8+ ratio associated with aggressive behavior in RUNX3-methylated diffuse esophagogastric junction tumor.

The tumor immune microenvironment is increasingly becoming a key consideration in developing treatment regimens for aggressive cancers, with evidence that regulatory T cells (Tregs) attenuate the antitumor response by interrupting cytotoxic T cells (CD8+). Here, we hypothesized the prognostic relevance of the proportions of Tregs (marked by forkhead box protein 3 [FOXP3]) and CD8+ cells in diffuse, non-Epstein-Barr virus (EBV)/non-microsatellite instability (MSI)-high gastroesophageal adenocarcinomas (GEAs), which are clinically characterized as more aggressive, immunologically inactive tumors as compared with their intestinal counterparts. Cell-count ratios of FOXP3+/CD8+ expression were calculated at the intratumoral region and invasive margin discretely on digital images from 303 chemo-naive non-EBV/non-MSI-high esophagogastric junction (EGJ) adenocarcinomas. A significant modifying prognostic effect of tumor histology was observed between 5-year EGJ cancer-specific survival and the FOXP3+/CD8+ ratio at the invasive margin in pStage I-III tumors (p for interaction = 0.022; hazard ratio [HR] = 8.47 and 95% confidence interval [CI], 2.04-35.19 for high ratio [vs. low] for diffuse; HR = 1.57 and 95% CI, 0.88-2.83 for high ratio [vs. low] for intestinal). A high FOXP3+/CD8+ ratio at the invasive margin was associated with RUNX3 methylation (p = 0.035) and poor prognosis in RUNX3-methylated diffuse histological subtype (5-year EGJ cancer-specific survival, 52.3% for high and 100% for low, p = 0.015). Multiomics data from The Cancer Genome Atlas linked CCL28 with RUNX3-suppressed diffuse histological subtypes of non-EBV/non-MSI-high GEA. Our data suggest that a high FOXP3+/CD8+ ratio at the invasive margin might indicate tumor immune escape via CCL28, particularly in the RUNX3-methylated diffuse histological subtype.

Synergistic effects of anlotinib and DDP on breast cancer: targeting the VEGF/JAK2/STAT3 axis

BackgroundAnlotinib, a highly selective inhibitor of VEGFR2, has demonstrated significant anti-tumor effects in various cancers. However, its potential synergistic effects with DDP (cisplatin) in breast cancer (BRCA) remain to be fully elucidated. This study aims to discover the therapeutic efficacy of anlotinib on BRCA, specifically the synergistic effects with DDP, and to elucidate the underlying molecular mechanisms.MethodsBRCA cells were treated with anlotinib and/or DDP. The proliferation, migration and invasion capabilities of BRCA cells were evaluated using CCK-8 assays, cell cycle distribution, clone formation assays, wound healing assays and transwell assays. Cell apoptosis was detected by flow cytometry technique and Hoechst33342 fluorescence staining. The potential mechanism of anlotinib in the development of BRCA was predicted through bioinformatics analysis, and the mRNA or protein levels were subsequently quantified using qPCR, immunofuorescence and western blot. The anti-breast cancer efficacy of anlotinib was evaluated in vivo using a xenograft tumor model.ResultsOur findings reveal that increased VEGFA expression in BRCA patients is associated with poorer prognosis, underscoring the need for targeted therapeutic strategies. We also demonstrate that both anlotinib and DDP independently inhibit BRCA cell growth, migration, and invasion, while their combination exhibits a synergistic effect, significantly enhancing the inhibition of these oncogenic processes. This synergy is further evident through the induction of apoptosis and autophagy in BRCA cells. Mechanistically, anlotinib’s effectiveness is linked to its inhibition of the JAK2/STAT3 pathway, a critical axis in BRCA progression. In vivo study further support these results, showing that anlotinib markedly inhibits tumor growth in xenografted mice.ConclusionThis study confirms the efficacy of anlotinib or in combination with DDP and elucidates the mechanism behind anlotinib’s effectiveness, highlighting its role in inhibiting the JAK2/STAT3 pathway.

Identification of HSPG2 as a bladder pro-tumor protein through NID1/AKT signaling

PurposeHeparan sulfate proteoglycans (HSPGs) are complex molecules found on the cell membrane and within the extracellular matrix, increasingly recognized for their role in tumor progression. This study aimed to investigate the involvement of Heparan sulfate proteoglycan 2 (HSPG2) in the progression of bladder cancer.MethodsWe identified HSPG2 as a promoter of bladder tumor progression using single-cell RNA sequencing and transcriptome analysis of sequencing data from seven patient samples obtained from the Gene Expression Omnibus (GEO) database (GSE135337). Transcript profiles of 28 normal tissues and 407 bladder tumor tissues were analyzed for HSPG2 expression and survival outcomes using the Sanger tools and cBioPortal databases. HSPG2-overexpressing T24 and Biu-87 cell lines were generated, and cell proliferation and migration were assessed using CCK-8 and Transwell assays. Western blotting and immunostaining were performed to evaluate the activation of Nidogen-1 (NID1)/protein kinase B (AKT) signaling. Mouse models with patient-derived tumor organoids (HSPG2high and HSPG2low) were established to assess anticancer effects.ResultsOur results demonstrated a marked upregulation of HSPG2 in malignant bladder tumors, which correlated significantly with poor patient prognosis. HSPG2 overexpression consistently enhanced bladder tumor cell proliferation and conferred chemotherapy resistance, as shown in both in vitro and in vivo experiments. Mechanistically, HSPG2 upregulated NID1 expression, leading to the activation of the AKT pro-survival signaling pathway and promoting sustained tumor growth in bladder cancer.ConclusionThis study highlights the critical pro-tumor role of HSPG2/NID1/AKT signaling in bladder cancer and suggests its potential as a therapeutic target in clinical treatment.

Clinical Spectrum and Perspective in Bilateral Acute Retinal Necrosis: Systematic Review

Bilateral acute retinal necrosis (BARN) represents a broad ophthalmological field of severe retinal pathologies associated with poor visual prognosis and blindness. The purpose of this review is to examine the clinical spectrum in detail over the past few years, exploring laboratory and instrumental diagnosis, and providing useful and up-to-date guidance in this field. A systematic review of this field has been performed through the PRISMA guidelines, searching in the PUBMED database. Serological laboratory tests on blood or polymerase chain reaction (PCR) on aqueous humor or vitreous samples are crucial to identifying the underlying cause and choosing the timeliest strategic treatments. Often, the main cause remains herpesviruses, with Varicella zoster (VZV) predominating over the others. There are also other causes that one needs to be carefully aware of. Anatomical and functional recovery is unfavorable if they are not individuated in a quick time. Early diagnosis and timely treatment offer a better chance of visual improvement and the avoidance of complications. Complications worsen the visual prognosis over months and may require a surgical approach.

Investigating the Mechanisms of Anti-tumoral Effect of Combination Therapy of Calcitriol and Sodium Pentaborate Pentahydrate on HepG2 Hepatocellular Carcinoma Cells.

Hepatocellular carcinoma (HCC) is one of the most common primary liver cancers worldwide and is often associated with poor prognosis due to drug resistance. Combination therapies demonstrate superior efficacy at lower drug dosages on cancer cells compared to single treatments, resulting in less drug resistance in the cells. This study investigates the synergistic anti-tumoral effects of calcitriol, the biologically active form of vitamin D, and sodium pentaborate pentahydrate (NaB) on HepG2 cells. We examined the cell viability of NaB, calcitriol, or the combination of NaB and calcitriol on HepG2 cells and healthy human hepatic stellate cells (HHSC) using MTS. Our findings showed that combination therapy with 3.3mM NaB and 1µM calcitriol has a synergistic effect and a more cytotoxic effect on HepG2 cells. This combination significantly increased apoptosis and ROS levels compared to treatment alone with NaB or calcitriol. Gene expression and proteomics analysis revealed inhibition of DNA replication and the cell cycle process, further confirming the potent anti-proliferative effects of the combination therapy. When HepG2 cells were treated with a combination of 3.3mM NaB and 1µM calcitriol, mRNA levels of apoptosis-related genes AKT1 and MDM2 were downregulated, while p53 was upregulated. Additionally, cell cycle-related genes CDKN1A, GADD45A, and p27 were upregulated, whereas MCM2, MCM5, and MCM7 were downregulated. Furthermore, genes associated with the vitamin D receptor (VDR), including VDR and CYP24A1, were upregulated, while CYP27B1 was downregulated. Our proteomic analysis revealed decreased MCM2 and MCM5 protein expressions which was confirmed by western blotting. In conclusion, this study highlights the potential of NaB and calcitriol as a promising therapeutic strategy for HCC.

Long-term outcomes of transapical-transcatheter aortic valve replacement.

Transapical-transcatheter aortic valve replacement is one of the main interventions indicated for patients where access via peripheral vessels is challenging. However, there have been no reports on the long-term outcomes of this intervention. Here, we report the long-term outcomes of this intervention. Among 178 patients who underwent transapical-transcatheter aortic valve replacement between October 2009 and July 2023, 173 patients who underwent this intervention for native aortic stenosis were included in this study, and early and long-term results were evaluated. The mean age was 82.4 ± 6.4years, 52.6% were women, mean body area was 1.46 ± 0.17 m2, and the Society of Thoracic Surgeons Predicted Risk of Mortality was 11.2 ± 9.9%. In-hospital mortality was observed in three patients (1.7%). Mean follow-up duration was 4.3 ± 2.8years, and the survival rates at 1-, 3-, 5-, and 8-years were 84.9%, 67.1%, 47.0%, and 22.1%, respectively. Freedom from cardiovascular mortality at 1, 3, 5, and 8-years was 92.9%, 86.1%, 75.8%, and 53.5%, respectively. The freedom from disabling stroke rates at 1, 3, 5, and 8-years were 95.0%, 92.4%, 92.4%, and 90.8%, respectively. Multivariate analysis revealed that male (Hazard Ratio 1.85, 95%Confidence Interval 1.27-2.70, p = 0.0012) and hemodialysis (Hazard Ratio 1.64, 95%Confidence Interval 1.00-2.67, p = 0.049) were significant poor prognosis factors. Long-term outcomes of transapical-transcatheter aortic valve replacement were satisfactory. Despite the variety of available approaches, the role of transapical-transcatheter aortic valve replacement, which has low vascular impact, has not been completely lost.

Impact of fasting blood glucose on prognosis after acute large vessel occlusion reperfusion: results from a multicenter analysis

ObjectiveTo analyze the effect of fasting blood glucose levels after reperfusion of acute large vessel occlusion (ALVO) on patient functional prognosis.MethodsRetrospectively included ALVO patients from three large stroke centers in China, all of whom achieved vascular reperfusion after mechanical thrombectomy or bridging thrombolysis. The prognosis scores of all patients at 90 ± 7 days post-recanalization were categorized into a good prognosis group (mRS 0–2) and a poor prognosis group (mRS 3–6). The relationship between mean blood glucose levels at 72 h post-recanalization and prognosis was explored using multivariable logistic regression analysis. Then we measured the area under the ROC curve for all factors to assess their predictive performance.Results(1) Totally 2,056 patients were included in the study, with 1,488 males and 568 females. There were 1,370 patients in the good prognosis group (mRS 0–2) and 686 in the poor prognosis group (mRS 3–6). (2) The two groups exhibited significant differences in terms of age, preoperative mRS score, history of diabetes, and mean fasting blood glucose (MFBG) (p &amp;lt; 0.001). (3) With 90-day mRS as the outcome variable, all independent variables were included in Univariate and multivariate regression analyses analysis, and the results showed that: age, preoperative mRS score, history of diabetes, and MFBG are all independent predictors of prognosis after recanalization of ALVO, with MFBG demonstrating a higher predictive power than the other factors (AUC = 0.644).ConclusionVarious factors are correlated with the prognosis in patients who have undergone ALVO recanalization. Notably, the MFBG level demonstrates a significant predictive value for outcomes within the first 72 h following the recanalization procedure.

Clinical significance of CD155 expression in surgically resected lung squamous cell carcinoma.

Cluster of differentiation 155 (CD155) is expressed in many tumor types. CD155 is involved in the immune avoidance of tumor cells and contributes to tumor development and progression. Therefore, CD155 is a novel target for cancer immunotherapy. The clinical significance of CD155 expression in lung squamous cell carcinoma (LUSC) has not been fully elucidated. We performed a retrospective analysis of 264 patients with surgically resected LUSC. Immunohistochemistry was used to evaluate CD155 expression. The association of CD155 expression with clinicopathological features and clinical outcomes was assessed. We also analyzed the relationship between CD155 expression and programmed cell death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes. Among the 264 patients, 137 patients (51.9%) were classified in the high CD155 expression group. High CD155 expression was significantly associated with pleural invasion, vascular invasion, PD-L1 positivity, and high CD3, CD4, and CD8 expressions. In multivariate analysis, the presence of pleural invasion and PD-L1 positivity were independent predictors of high CD155 expression. Kaplan-Meier curve analysis showed that high CD155 expression was significantly associated with shorter disease-free survival and overall survival. In multivariate analysis, high CD155 expression was an independent poor prognostic factor for overall survival, but not for disease-free survival. Subgroup analyses revealed that the prognostic effect of CD155 expression was observed in the PD-L1 positive group but not the PD-L1 negative group. Our analysis revealed that high CD155 expression significantly predicted poor prognosis in patients with surgically resected LUSC, especially in patients with PD-L1-positive tumors.