Poor Prognosis Research Articles

Subungual Melanoma with bone infiltration

Nail melanoma is rare and has a poor prognosis. It represents between 0.18 and 2.8% of all cutaneous melanomas. Amputation is usually performed for invasive nail melanoma, but not all invasive melanomas invade or attach to the distal phalanx. Our aim was to report a case of 56-year-old patient with history of a manipulated melanonychial band of the right big toe since 5 years presenting a nail melanoma with bone infiltration .Our patient illustrates the consequences of the late diagnosis of nail melanoma which led to a deep progression and the invasion of bone by the malignant melanocytes.

Talo-navicular dislocation with concomitant navicular fracture, a rare midfoot injury: A case report

Talon-navicular dislocation fracture is an extremely rare injury. It has a poor functional prognosis, since in most cases it is complicated by osteoarthritis of the talonavicular joint. We report a case of a closed talonavicular dislocation fracture in a 29-year-old patient following a road traffic accident. Reduction was performed urgently, with talo-navicular fixation using two k-wires. A cast was applied for 8 weeks, followed by rehabilitation sessions with good outcome at last follow-up

Potential of 6-mm-diameter fully covered self-expandable metal stents for unresectable malignant distal biliary obstruction: a propensity score-matched study

Background/Aims: To date, only thinner-diameter metal stents have been evaluated for unresectable malignant distal biliary obstruction (UR-MDBO). This study investigated the outcomes and optimal cohorts for a 6-mm-diameter fully covered self-expandable metal stent (FCSEMS) compared with those for a 10-mm-diameter FCSEMS.Methods: This single-center retrospective cohort study included patients who underwent initial transpapillary metal stenting for UR-MDBO. Propensity score matching (1:1) analysis was performed.Results: Of 133/68 patients who underwent 6-mm/10-mm-diameter FCSEMS deployment, 59 in each group were selected. The median time to recurrent biliary obstruction was not significantly different between the groups (p=0.46). In contrast, use of the 6-mm-diameter FCSEMS resulted in a significantly reduced incidence of stent-related adverse events (AEs) (p=0.016), especially cholecystitis (p=0.032), and patients aged <70 years were particularly affected by this significant reduction. Among the patients in the end-stage cohort who were unable to continue chemotherapy after FCSEMS deployment, the free rate of stent-related events, including recurrent biliary obstruction and stent-related AEs, was significantly higher in the 6-mm group (p=0.027).Conclusions: For UR-MDBO, a 6-mm-diameter FCSEMS can be an optimal and safe option in the younger cohort with a relatively high risk of AEs and in the end-stage cohort requiring safer drainage without interference from stent-related events during times of poor prognosis.

Biological correlates associated with high-risk breast cancer patients identified using a computational method

Using a novel unsupervised method to integrate multi-omic data, we previously identified a breast cancer group with a poor prognosis. In the current study, we characterize the biological features of this subgroup, defined as the high-risk group, using various data sources. Assessment of three published hypoxia signatures showed that the high-risk group exhibited higher hypoxia scores (p < 0.0001 in all three signatures), compared to the low-risk group. Our analysis of the immune cell composition using CIBERSORT and leukocyte fraction showed significant differences between the high and low-risk groups across the entire cohort, as well as within PAM50 subtypes. Within the basal subtype, the low-risk group had a statistically significantly higher spatial fraction of tumor-infiltrating lymphocytes (TILs) compared to the high-risk group (p = 0.0362). Our findings indicate that this subgroup with poor prognosis is driven by a distinct biological signature with high activation of hypoxia-related genes as well as a low number of TILs.

Assessing the diagnostic potential of SATB2 and β-catenin as biomarkers and therapeutic targets in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. The roles of the transcription factor special AT-rich binding protein-2 (SATB2) and β-catenin in PDAC have been a subject of controversy. We aimed to assess the diagnostic and prognostic impact of SATB2 and β-catenin in PDAC. We analyzed 44 paraffin-embedded tissue blocks along with corresponding blood and pancreatic tissues. We evaluated SATB2 expression using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). β-catenin was assessed using IHC and real-time polymerase chain reaction (qPCR). High SATB2 expression and low β-catenin expression were associated with a poor prognosis in PDAC, including advanced pathological tumor stage (pT-stage), pathological lymph node stage (pN-stage), and TNM stage. We found a positive correlation between SATB2 expression assessed by IHC and the concentration of SATB2 in both serum and tissue samples measured by ELISA. We observed a positive correlation between β-catenin expression assessed by IHC and β-catenin levels measured by qPCR. SATB2 and β-catenin could provide valuable insights into the development of pancreatic cancer, and targeting them may be beneficial for the prevention and treatment of PDAC. The levels of SATB2 in serum show promise for the diagnosis and tumor invasion of pancreatic cancer.

Pentraxin-3 as a novel prognostic biomarker in non-neutropenic invasive pulmonary aspergillosis patients.

The incidence of invasive pulmonary aspergillosis (IPA) in non-neutropenic patients is increasing. This study aimed to evaluate the clinical outcomes and risk factors for mortality in non-neutropenic IPA patients. We conducted a prospective, multicenter study from August 2020 to February 2024, enrolling 565 patients with suspected IPA. The study cohort comprised 195 IPA (non-neutropenic) cases and 370 non-IPA cases. Peripheral blood and bronchoalveolar lavage fluid (BALF) specimens were collected to measure pentraxin-3 (PTX3) levels. Additionally, demographic data, clinical characteristics, and antifungal therapy of each patient were recorded. We analyzed factors associated with 30- and 90-day mortality. IPA patients exhibited higher mortality rates compared to non-IPA patients, with 30-day rates of 26.15% versus 8.38% (P < 0.001) and 90-day rates of 34.36% versus 13.24% (P < 0.001). Higher plasma and BALF PTX3 levels were associated with poor prognosis in IPA patients. ROC curve analysis identified optimal PTX3 thresholds of 4.29 ng/mL in BALF (sensitivity, 67.1%; specificity, 81.4%) and 7.11 ng/mL in plasma (sensitivity, 73.4%; specificity, 82.8%) for predicting mortality. Multivariate Cox regression analysis confirmed PTX3 levels in plasma (hazard ratio [HR] 3.87, 95%CI [1.87-8.00], P＜0.001) and BALF (HR 2.40 [1.19-4.84], P = 0.014) were independent prognostic factors for IPA mortality. Additionally, positive galactomannan test results in both BALF and plasma were initially correlated with increased mortality in IPA patients. However, after adjusting for potential confounding factors, this correlation no longer remained statistically significant. In conclusion, PTX3 is a promising prognostic biomarker of mortality in IPA patients.IMPORTANCEStudies have confirmed the value of pentraxin-3 (PTX3) in the diagnosis of invasive pulmonary aspergillosis (IPA), yet its prognostic significance in IPA remains unclear. This study found that in non-neutropenic IPA patients, plasma and bronchoalveolar lavage fluid (BALF) levels of PTX3 are independently associated with poor outcomes. Furthermore, the optimal cutoff values of PTX3 for predicting a poor prognosis of IPA are 4.29 ng/mL in BALF and 7.11 ng/mL in plasma. These findings could help us better manage IPA in non-neutropenic patients, potentially enhancing the prognosis of patients with this condition.

SHP2 promotes the epithelial-mesenchymal transition in triple negative breast cancer cells by regulating β-catenin.

Growing evidence suggests that the tyrosine phosphatase SHP2 is pivotal for tumor progression. Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer, characterized by its high recurrence rate, aggressive metastasis, and resistance to chemotherapy. Understanding the mechanisms of tumorigenesis and the underlying molecular pathways in TNBC could aid in identifying new therapeutic targets. In this study, we conducted bioinformatics analysis of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases to examine PTPN11 (encoding SHP2) expression levels and perform survival analysis in TNBC. Additionally, we analyzed SHP2 levels in four TNBC cell lines and a normal breast epithelial cell line using Western blot. Furthermore, we knocked down SHP2 expression via RNA interference in three TNBC cell lines. To assess the impact of SHP2 on invasion and migration, we conducted transwell assays and wound healing experiments. An in vivo experiment utilizing a mouse xenograft model was also performed to evaluate tumor metastasis. Moreover, we detected the expression levels of epithelial-mesenchymal transition (EMT) biomarkers and investigated the mechanism between SHP2 and β-catenin using Western blot and immunofluorescence experiments. We found that high SHP2 expression was associated with a poor prognosis in patients with TNBC. The migratory and invasive abilities of TNBC cells in vitro, as well as the metastatic potential of TNBC in mouse xenograft models, were reduced after SHP2 depletion. Downregulation of SHP2 also decreased the expression of mesenchymal markers but induced upregulation of the epithelial marker E-cadherin. Additionally, SHP2 promoted β-catenin stability by inhibiting its degradation via the proteasome. Furthermore, c-Myc expression and GSK3β and AKT phosphorylation, which are involved in β-catenin signaling, were decreased in SHP2-depleted TNBC cells. Our study demonstrates that SHP2 is involved in migration, invasion, and EMT in TNBC cells by modulating β-catenin. Manipulating SHP2 expression or its target protein β-catenin may offer a novel approach to TNBC therapy.

Rare malignant ovarian tumors: a review.

There are many histologic types of gynecologic malignancies. I reviewed three rare ovarian tumor types that have poor prognoses. Ovarian mesonephric-like adenocarcinoma (MLA) is a newly described histological type known for its aggressive behavior. It is thought to arise from mesonephric duct remnants of the female genital tract and is typically associated with endometriosis. Although MLA has some similarities to endometrioid carcinoma, they have different prognoses. Recurrence of MLA is common, even in early stage cases, and distant metastases, especially in the lungs, are often seen. MLA is characterized by positive immunohistochemical-staining for TTF-1, GATA3, PAX2, and CD10, and negative staining for estrogen and progesterone receptors. Data on treatment for MLA are scarce, and further studies are needed. Adult granulosa cell tumors, the most common type of malignant ovarian sex cord-stromal tumors, have an indolent growth pattern. Chemotherapy, hormone therapy, and radiotherapy have all shown some efficacy. However, debulking surgery remains the most important treatment because tumor disruption or remnants are risk factors for recurrence. Late recurrence is also characteristic of this tumor. Malignant transformations of mature teratoma are suspected when the patient is relatively old and the tumor is large. Squamous cell carcinoma is the most common somatic malignancy. Treatment must be tailored to the transformed histology. Chemotherapy and radiation have shown some efficacy; however, the prognosis is extremely poor in advanced cases. Because these three types of ovarian tumors are rare, research on possible treatments has been difficult, but recent significant advances in drug therapy are expected to lead to the development of effective treatments.

Effect of SMARCA4 mutations on the outcomes of patients with advanced EGFR mutant lung adenocarcinoma

Objective: To investigate the impact of SMARCA4 mutations on the outcomes of patients with advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations. Methods: In the Memorial Sloan Kettering Cancer Center (MSK) MetTropism study, 960 patients with advanced EGFR-mutated lung adenocarcinoma were screened and included in the MSK cohort, composing of 313 males and 647 females, with a median [M(Q1, Q3)] age of 64 (56, 72) years. A retrospective analysis was conducted on the data of 178 patients with advanced EGFR-mutated lung adenocarcinoma who received EGFR tyrosine kinase inhibitors (TKIs) treatment in the Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, from January 2018 to December 2022. Among these patients, 69 were males and 109 were females, with a median age of 63 (54, 69) years. The follow-up of patients from the First Affiliated Hospital of Nanjing Medical University was conducted up to December 31, 2023, with a median follow-up time of 26.6 (95%CI: 24.6-28.6) months for the entire cohort, and 29 patients were lost to follow-up. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the relationship between SMARCA4 gene alternations and prognosis. Results: In the 960 patients of the MSK cohort with advanced EGFR-mutated lung adenocarcinoma, the SMARCA4 gene alternations rate was 4.2% (40/960). The median overall survival (OS) for patients without SMARCA4 gene alternations was 41.5 (95%CI: 35.6-47.3) months, which was superior to that of patients with SMARCA4 gene alternations [15.6 (95%CI: 7.9-23.4) months, P<0.001]. Patients with SMARCA4 gene alternations had a higher risk of mortality, with an HR (95%CI) of 1.97 (1.35 to 2.88). Among the 178 patients with advanced EGFR-mutated lung adenocarcinoma from the First Affiliated Hospital of Nanjing Medical University, the SMARCA4 gene alternations rate was 4.5% (8/178). The median progression-free survival (PFS) for patients without SMARCA4 gene alternations was 16.1 (95%CI: 12.2-20.0) months, which was superior to the median PFS of patients with SMARCA4 gene alternations [6.0 (95%CI: 1.3-10.7) months, P<0.001]. The median OS for patients without SMARCA4 gene alternations was 50.1 (95%CI: 28.1-72.1) months, which was also superior to the median OS of patients with SMARCA4 gene alternations [17.6 (95%CI: 15.4-19.8) months, P=0.001]. Conclusion: SMARCA4 alternation is an important factor associated with poor prognosis in patients with advanced EGFR-mutant lung adenocarcinoma.

S100A13-driven interaction between pancreatic adenocarcinoma cells and cancer-associated fibroblasts promotes tumor progression through calcium signaling

BackgroundCancer-associated fibroblasts (CAFs) are key components of the pancreatic adenocarcinoma (PAAD) tumor microenvironment (TME), where they promote tumor progression and metastasis through immunosuppressive functions. Although significant progress has been made in understanding the crosstalk between cancer cells and CAFs, many underlying mechanisms remain unclear. Recent studies have highlighted the importance of calcium signaling in enhancing interactions between tumor cells and the surrounding stroma, with the S100 family of proteins serving as important regulators. While the roles of some S100 proteins have been extensively studied, others, such as S100A13, remain less well understood.MethodsBioinformatic analysis was employed to predict the pathogenic potential of CAFs and S100A13. Stable S100A13 knockdown CAFs were generated using a short hairpin RNA system. Cellular viability and apoptosis rates were evaluated through CCK-8 and flow cytometry tests, respectively. Additionally, the wound healing and migration assays were conducted to assess the invasive and metastatic capabilities. Transcriptome analysis was conducted to identify differential gene expression and associated signaling pathways in PAAD cells derived from an indirect culture system. Furthermore, the protumoral role of S100A13 in PAAD was further verified using both 3D bioprinting and cell line-based xenograft tumor models.ResultsIn this study, we identified a strong association between S100A13, a calcium-binding protein, and CAFs in PAAD. Gene expression analysis revealed that S100A13 was highly expressed in CAFs and correlated with poor prognosis. Knockdown of S100A13 in CAFs reduced the metastatic potential of PAAD cells. In addition, S100A13 depletion impaired cell motility and calcium signaling pathways within the TME. Furthermore, silencing S100A13 in CAFs markedly slowed PAAD progression in both tumor spheroids and Balb/c nude mice.ConclusionsTogether, our findings underscore the critical role of CAFs-derived S100A13 in PAAD progression and suggest that targeting S100A13 may offer a promising therapeutic strategy for PAAD.

A new NCL-targeting aptamer-drug conjugate as a promising therapy against esophageal cancer

Esophageal cancer (EC) is one of the most common highly malignant tumors of the digestive system, with a poor prognosis under current treatment regimens. Nucleolin (NCL) is overexpressed in many tumors, and drugs specifically targeting NCL may offer a promising strategy for treating esophageal cancer. Here, we designed and prepared a novel aptamer-conjugated drug targeting NCL by AS1411 aptamer-human serum albumin (HSA)-the apoprotein of lidamycin (LDP)-active enediyne chromophore (AE), in order to achieve targeted treatment of esophageal cancer. The experimental results revealed that AS1411-HSA-LDP effectively binds to esophageal cancer cells and could be efficiently internalized by esophageal cancer cells. In the KYSE520 xenograft tumor nude mouse model, AS1411-HSA-LDP could be targeted and enriched in the tumor location for a long time. AS1411-HSA-LDP-AE exhibited a strong cell-killing activity in esophageal cancer cells, inhibited cell migration and invasion, and induced cell apoptosis. The animal studies confirmed that AS1411-HSA-LDP-AE exhibited a strong anti-tumor effect. These findings suggested that the novel NCL-targeting aptamer-drug conjugate constructed based on lidamycin exhibited a strong anti-tumor effect, providing a promising strategy for the targeted treatment of esophageal cancer.

HER2 regulates autophagy and promotes migration in gastric cancer cells through the cGAS-STING pathway.

In gastric cancer, the relationship between human epidermal growth factor receptor 2 (HER2), the cyclic GMP-AMP synthase-stimulator of the interferon genes (cGAS-STING) pathway, and autophagy remains unclear. This study examines whether HER2 regulates autophagy in gastric cancer cells via the cGAS-STING signaling pathway, influencing key processes such as cell proliferation and migration. Understanding this relationship could uncover new molecular targets for diagnosis and treatment. Through lentiviral transfection, cell counting kit-8 assays, colony formation, transwell migration, scratch assays, and siRNA, we found that HER2 overexpression suppresses the cGAS-STING pathway, inhibits autophagy, and enhances the migratory ability of gastric cancer cells. In contrast, HER2 knockdown activates the cGAS-STING pathway, promotes autophagy, and reduces cell migration. We further observed that the inhibition of autophagy using chloroquine (CQ) increases the migration ability of HER2-overexpressing cells. Moreover, interfering with STING expression reversed the migration defects caused by HER2 knockdown, underscoring the critical role of the cGAS-STING pathway in HER2-regulated cell migration. We also revealed that high STING expression in gastric cancer is significantly associated with poor prognosis. STING expression was identified as an independent prognostic factor for survival (hazard ratio, 1.942; 95% confidence interval, 1.06-3.54; P = 0.031). These results highlight the importance of HER2-driven regulation of autophagy through the cGAS-STING pathway in gastric cancer progression and its potential as a therapeutic target.

TP53 Mutations in Myeloproliferative Neoplasms: Context-Dependent Evaluation of Prognostic Relevance.

The clinical relevance of TP53 mutations (TP53MUT) in myeloproliferative neoplasms (MPN) and their prognostic interaction with MPN subtype designation has not been systematically studied. In the current study, 114 patients with MPN harboring TP53MUT (VAF ≥ 2%) were evaluated for overall survival (OS), calculated from the time of TP53MUT detection: chronic phase myelofibrosis (MF-CP; N = 61); blast-phase (MPN-BP; N = 31) or accelerated-phase (MPN-AP; N = 16) MPN, and polycythemia vera/essential thrombocythemia (PV/ET; N = 6). Sixty-five (57%) patients harbored International Consensus Classification (ICC)-defined multihit TP53MUT and 56 (49%) monosomal/complex karyotype (MK/CK). Majority of MPN-BP (90%) and MPN-AP (81%) while 39% of MF-CP and none of PV/ET patients harbored multihit TP53MUT. OS in MPN-BP and MPN-AP was equally dismal (median 6 vs. 4.5 months, respectively; p = 1.0), regardless of multihit configuration (p = 0.44), while OS in TP53MUT MPN-BP/AP (N = 47; median 4 months) was inferior to that of a separate cohort (N = 49) with TP53 wild-type MPN-BP/AP (median 11 months; p < 0.01). OS in MF-CP was significantly shorter with multihit versus non-multihit TP53MUT (median 10 vs. 35 months; HR 2.9; p < 0.01), independent of other MF-relevant genetic risk factors, including ASXL1/SRSF2/U2AF1 mutations. Multihit TP53MUT was also associated with inferior survival following allogeneic stem cell transplant (ASCT): median 9 months versus "not reached" in patients with (N = 9) versus without (N = 8) multihit TP53MUT (p < 0.01). The presence of multihit or non-multihit TP53MUT in MPN-BP/AP or multihit TP53MUT in MF-CP is associated with exceptionally poor prognosis and justifies inclusion into the ICC category of "myeloid neoplasms with mutated TP53." By contrast, detection of non-multihit TP53MUT, by itself, might not endanger short-term survival in MF-CP, PV, or ET.

Proteomic Characterization of NEDD4 Unveils Its Potential Novel Downstream Effectors in Gastric Cancer.

The E3 ubiquitin ligase neural precursor cell-expressed developmentally down-regulated 4 (NEDD4) is involved in various cancer signaling pathways, including PTEN/AKT. However, its role in promoting gastric cancer (GC) progression is unclear. This study was conducted to elucidate the role of NEDD4 in GC progression. We found that the inhibition of NEDD4 expression significantly reduced the migratory and proliferative abilities of GC cells, with minimal impact on the PTEN expression or p-AKT activation, suggesting that NEDD4 may exert its GC-promoting effects through alternative pathways. To gain novel insights into the role of NEDD4 in GC, we performed a comprehensive proteomic analysis to search for proteins with altered expression levels following NEDD4 gene knockdown, identifying a total of 3916 proteins. Pathway analysis of differentially expressed proteins (DEPs) indicated the potential involvement of NEDD4 in cancer-related metabolic pathways. Furthermore, the protein-protein interaction network of the DEPs revealed enriched core modules, highlighting key cellular processes and signaling pathways regulated by NEDD4 in GC. Additionally, we identified proteins whose expression was altered by NEDD4 inhibition, some of which were associated with poor prognosis in GC. These findings suggest that these proteins may act as downstream effectors that contribute to NEDD4-mediated GC progression.

Respiratory complex I-mediated NAD+ regeneration regulates cancer cell proliferation through the transcriptional and translational control of p21Cip1 expression by SIRT3 and SIRT7.

The role of the electron transport chain (ETC) in cell proliferation control beyond its crucial function in supporting ATP generation has recently emerged. In this study, we found that, among the four ETC complexes, the complex I (CI)-mediated NAD+ regeneration is important for cancer cell proliferation. In cancer cells, a decrease in CI activity by RNA interference (RNAi) against NADH:ubiquinone oxidoreductase core subunit V1 (NDUFV1) arrested the cell cycle at the G1/S phase, accompanying upregulation of p21Cip1 cyclin-dependent kinase inhibitor expression. Mechanistically, a decrease in the NAD+/NADH ratio downregulated SIRT3 and SIRT7 function, which suppressed p21Cip1 expression at the translational and transcriptional levels, respectively, resulting in the upregulation of the antiproliferative molecule. Importantly, high expression levels of the core subunits of CI correlated with poor prognosis in patients with the hormone receptor(+)/human epidermal growth factor receptor 2(-) (HR+/HER2-) subtype of breast cancer. Therefore, NDUFV1 and SIRT3/7 have emerged as promising therapeutic targets against this breast cancer subtype.

Predictive role of SLC1A5 in neuroblastoma prognosis and immunotherapy

BackgroundNeuroblastoma, a prevalent extracranial solid tumor in pediatric patients, demonstrates significant clinical heterogeneity, ranging from spontaneous regression to aggressive metastatic disease. Despite advances in treatment, high-risk neuroblastoma remains associated with poor survival. SLC1A5, a key glutamine transporter, plays a dual role in promoting tumor growth and immune modulation. However, its contributions to neuroblastoma biology remain largely unexplored.MethodsThis study utilized clinical neuroblastoma samples from 20 patients and 1310 cases from four public datasets to investigate SLC1A5 expression, biological function, and prognostic significance. Differential expression, Kaplan–Meier survival analysis, gene set enrichment analysis, and weighted correlation network analysis were conducted. Functional validation included qPCR, immunohistochemistry, Western blotting, and cell proliferation assays using the SLC1A5 inhibitor V-9302. A prognostic signature, SRPS, was constructed and validated using machine-learning approaches. Immune infiltration analysis was performed to evaluate the tumor immune microenvironment.ResultsSLC1A5 expression was significantly elevated in high-risk neuroblastoma and correlated with advanced stages and poor prognosis. GSEA revealed mTORC1 signaling enrichment in high SLC1A5 expression groups, validated by increased p-p70S6K levels in tumor samples and neuroblastoma cells. V-9302 treatment suppressed mTORC1 signaling and inhibited cell proliferation. Hub-genes were identified to form the SRPS model, which demonstrated superior prognostic performance compared to existing models. Immune infiltration analysis revealed a more immunosuppressive tumor microenvironment associated with high SLC1A5 expression. Additionally, SLC1A5 negatively regulated ST8SIA1, a gene crucial for GD2 biosynthesis, suggesting that SLC1A5 inhibition may enhance GD2-directed immunotherapies.ConclusionSLC1A5 plays a pivotal role in neuroblastoma by promoting tumor progression and shaping an immunosuppressive microenvironment. The SRPS model, incorporating SLC1A5-associated genes, offers robust prognostic utility. Targeting SLC1A5 through advanced drug delivery systems and combined metabolic-immunotherapeutic strategies may enhance treatment specificity and efficacy. These findings provide a foundation for novel therapeutic approaches to improve outcomes in high-risk neuroblastoma patients.

Programmed cell death-related gene IL20RA facilitates tumor progression and remodels tumor microenvironment in thyroid cancer

Programmed cell death (PCD) is a vital biological process that is essential for regulating cell progression and tumor microenvironment. This study aimed to explore the relationship between PCD-related genes expression and prognosis in thyroid cancer (THCA), especially IL20RA, as a potential prognostic marker for THCA. Data from The Cancer Genome Atlas (TCGA) database was utilized to develop a PCD-related risk prediction model based on LASSO regression along with univariate Cox regression. The correlation between PCD-related genes and immune cell infiltration was also assessed. The prognostic value of the key PCD-related gene for THCA was investigated by immunohistochemistry. The immune regulatory function and biological function of the key PCD related molecules were detected by cellular experiments. We identified four PCD-related genes (NPC2, E2F1, IL20RA, and TREM2) and constructed a risk model that exhibited excellent accuracy in predicting the prognosis of THCA. Moreover, we confirmed that high expression of IL20RA related to the poor prognosis of THCA. IL20RA promoted cell proliferation and IL20RA knockdown increased apoptosis and ferroptosis. Analysis of the immune microenvironment and detection of macrophages polarization showed that IL20RA promoted the polarization of M2 macrophages while reducing the polarization of M1. We constructed a prognostic prediction model and identified several PCD-related genes. The function of IL20RA which could potentially provide a foundation for additional investigations into diagnostic markers and treatment targets for THCA.

Halting Pancreatic Ductal Adenocarcinoma Progression and Metastasis by Neuron-Inhibitory Liposomes.

Pancreatic ductal adenocarcinoma (PDAC) remains an aggressive malignancy. The occurrence of perineural invasion is associated with neuropathic pain and poor prognosis of PDAC, underscoring the active participation of nerves and their potential as therapeutic targets. Lidocaine is a local anesthetic with antitumor properties in some tumors in the clinic. Nevertheless, its clinical application in PDAC is constrained by the insufficient tumor accumulation and potential neurovirulence associated with a high-dose regimen. Here, a tumor microenvironment-targeted and -responsive liposome was constructed to deliver lidocaine for restraining PDAC growth through single nerve regulation. By conjugation of a collagen binding peptide, the pH-responsive liposomes accumulate in the extracellular matrix. The released lidocaine selectively reduces neurite length and density, thereby indirectly halting the progression and metastasis of PDAC in an orthotopic mouse model without noticeable adverse effects. This study highlights the potential of anesthetic-based nanomodulation of crosstalk between nerve and tumor cells for PDAC treatment.

Polyoxometalate-based injectable coacervate inhibits HCC metastasis after incomplete radiofrequency ablation via scavenging ROS

BackgroundIncomplete radiofrequency ablation (iRFA) stimulates residual hepatocellular carcinoma (HCC) metastasis, leading to a poor prognosis for patients. Therefore, it is imperative to develop an effective therapeutic strategy to prevent iRFA-induced HCC metastasis.ResultsOur study revealed that iRFA induced an abnormal increase in ROS levels within residual HCC, which enhanced tumor cell invasiveness and promoted macrophage M2 polarization, ultimately facilitating HCC metastasis. Molybdenum-based polyoxometalate (POM) is an excellent ROS-scavenging nanocluster, but its size is too small to be easily cleared by the kidneys, limiting its effectiveness in scavenging iRFA-induced ROS. To overcome this limitation, we synthesized an injectable POM-loaded coacervate delivery system named POM@Coa, which can sustainably scavenge iRFA-induced ROS by slowly releasing POM. POM@Coa markedly reduced HCC invasiveness, reversed macrophage polarization from M2 to M1, and promoted the infiltration and activation of CD8+ T cells, ultimately inhibiting HCC metastasis. Importantly, POM@Coa showed superior therapeutic efficacy to free POM in the absence of systemic toxicity.ConclusionsPOM@Coa exhibits the potential to decrease HCC invasiveness and activate anti-tumor immunity, opening up new avenues for the safe and effective treatment and prevention of HCC metastasis when combined with RFA.

Disseminated nontuberculous mycobacteriosis due to Mycobacterium avium subsp. hominissuis infection in a reindeer from a zoo.

Bacteria in the Mycobacterium tuberculosis complex and nontuberculous mycobacteria may affect a variety of animal species under human care and pose public health risks as zoonotic pathogens. A case of sudden onset of lethargy and increased respiratory effort in a 5-y-old, intact female reindeer (Rangifer tarandus) under managed care had progressed to severe dyspnea despite aggressive treatment. The animal was euthanized due to poor prognosis. Postmortem findings included: disseminated miliary nodules in the lungs, pleura, small intestine, liver, and spleen; enlarged mesenteric lymph nodes; dilated mesenteric and serosal lymphatic vessels; and renal infarcts. Histologically, granulomatous lymphadenitis and lymphangitis with intrahistiocytic acid-fast bacilli were observed. Mycobacterium sp. DNA was detected in lung via real-time PCR. Mycobacterial culture and sequencing identified Mycobacterium avium subsp. hominissuis (MAH) within pulmonary lesions. Infection with MAH has been reported in humans and many animal species; this nontuberculous mycobacterial infection may be an emerging concern in animals under managed care. To our knowledge, MAH infection has not been reported previously in reindeer.