Exploring the common targets of well-differentiated and dedifferentiated retroperitoneal liposarcoma via gene co-expression analysis.

Objective: This study aimed to identify common therapeutic targets for well-differentiated and dedifferentiated retroperitoneal liposarcoma. Methods: Patient clinical data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and survival differences were analyzed using the log-rank test. Gene expression data were sourced from the Gene Expression Omnibus (GEO) dataset GSE159659, with differential gene expression analysis conducted through GEO2R. Protein-protein interaction networks were developed using STRING and Cytoscape to identify key hub genes. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed using R, and transcription factors associated with the hub genes were predicted with TRRUST. Results: Significant survival differences were found between patients with well-differentiated and dedifferentiated retroperitoneal liposarcoma. Ninety-six differentially expressed genes with similar expression patterns were identified in both types. A protein-protein interaction network highlighted 12 hub genes and 24 transcription factors. Enrichment analysis pointed to the importance of lipid localization, storage, cytokine signaling, and metal ion absorption in both liposarcoma subtypes. Four potential therapeutic drugs were successfully predicted. Conclusion: This study identifies common molecular targets in well-differentiated and dedifferentiated retroperitoneal liposarcoma, providing new avenues for mechanistic studies and potential therapeutic development.

A case of H-type double gallbladder anomaly: A case report.

RATIONALE: Biliary system anomalies, such as duplicated gallbladders, are rare congenital conditions that present significant diagnostic challenges. Dr. Boyden's classification system, especially the H-type anomaly, offers vital insight into these variations. Failure to detect these anomalies preoperatively can increase the risk of surgical complications, making early identification crucial for surgical planning. PATIENT CONCERN: A 42-year-old male, asymptomatic, was incidentally found to have a gallbladder mass during routine imaging. An upper abdominal magnetic resonance imaging showed gallbladder wall thickening, gallstones, and a liver lesion. Despite the absence of symptoms, a laparoscopic cholecystectomy revealed an atrophied gallbladder with a cystic duct cyst, which was identified as an H-type double gallbladder anomaly. The surgery was completed without complications, and pathology confirmed the presence of gallstones and inflammation. DIAGNOSES: The patient was diagnosed with a duplicated gallbladder, classified as an H-type anomaly, following laparoscopic cholecystectomy. Preoperative imaging identified gallbladder wall thickening and gallstones, and further investigation during surgery confirmed the congenital anomaly. INTERVENTIONS: The patient underwent laparoscopic cholecystectomy for the removal of the gallbladder, and during the procedure, an H-type double gallbladder anomaly was discovered. The surgery proceeded without incident, ensuring the complete excision of the gallbladders. OUTCOMES: The case highlights the diagnostic difficulty of identifying duplicated gallbladders and the importance of advanced imaging techniques in detecting atypical anatomical variations. The successful laparoscopic removal of both gallbladders illustrates the current capabilities of minimally invasive surgery. Postoperative recovery was uneventful, and the pathology confirmed gallstones and inflammation. LESSONS: This case emphasizes the importance of recognizing biliary anomalies such as duplicated gallbladders to avoid complications during surgery. Preoperative identification, aided by imaging, and careful surgical planning are key to managing these rare conditions. The case contributes to the growing body of knowledge about biliary system anomalies and reinforces the need for comprehensive management strategies to ensure optimal patient outcomes.

Stimulator of Interferon Genes-Activated Biomimetic Dendritic Cell Nanovaccine as a Chemotherapeutic Booster to Enhance Systemic Fibrosarcoma Treatment.

Fibrosarcoma, a malignant mesenchymal tumor, is characterized by aggressive invasiveness and a high recurrence rate, leading to poor prognosis. Anthracycline drugs, such as doxorubicin (DOX), represent the frontline chemotherapy for fibrosarcoma, but often exhibit suboptimal efficacy. Recently, exploiting the stimulator of interferon genes (STING)-mediated innate immunity has emerged as a hopeful strategy for cancer treatment. Integrating chemotherapy with immunomodulators in chemo-immunotherapy has shown potential for enhancing treatment outcomes. Herein, we introduce an advanced dendritic cell (DC) nanovaccine, cGAMP@PLGA@CRTM (GP@CRTM), combined with low-dose DOX to enhance fibrosarcoma chemo-immunotherapy. The nanovaccine consists of poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating the STING agonist 2,3-cGAMP (cGAMP@PLGA, GP) as its core, and a calreticulin (CRT) high-expressing fibrosarcoma cell membrane (CRTM) as the shell. Exposing CRT on the vaccine surface aids in recruiting DCs and stimulating uptake, facilitating efficient simultaneous delivery of STING agonists and tumor antigens to DCs. This dual delivery method effectively activates the STING pathway in DCs, triggering sustained immune stimulation. Simultaneously, low-dose DOX reduces chemotherapy-related side effects, directly kills a subset of tumor cells, and increases tumor immunogenicity, thus further amplifying immune therapeutic performance. Hence, these findings demonstrate the potential of DC nanovaccine GP@CRTM as a booster for chemotherapy. Synergistically combining low-dose DOX with the DC nanovaccine emerges as a powerful chemo-immunotherapy strategy, optimizing systemic fibrosarcoma therapy.

Exploring the biological behavior differences between retroperitoneal and non-retroperitoneal liposarcomas.

Background: Liposarcoma is a malignant tumor that originates from adipose tissue and can occur in any part of the body. There is currently no clear conclusion on whether there are significant differences in prognosis between liposarcoma at different anatomical locations, especially retroperitoneal liposarcoma (RLPS) and non retroperitoneal liposarcoma (NRLPS). The aim of this study is to reveal whether there are differences in prognosis between these two locations of liposarcoma, and further explore the fundamental reasons behind these differences. Methods: We conducted an in-depth investigation into the factors affecting the prognosis of patients with liposarcoma by analyzing the data from the Surveillance, Epidemiology, and End Results Program (SEER) database. Then, we used propensity score matching (PSM) to balance these prognostic factors for comparative analysis of survival between RLPS and NRLPS. In addition, by analyzing transcriptome and whole exome data from TCGA and the Japan Genotypic Phenotype Archive (JGA), we identified genes with significant expression differences and explored changes in the immune microenvironment. Result: Through analysis of RLPS and NRLPS patients in the SEER database, we observed significant prognostic differences between the two groups, with RLPS exhibiting worse prognosis (p < 0.001). Even after adjusting for confounding factors through PSM, these survival rate differences remained significant, with RLPS still showing worse prognosis (p = 0.017). Furthermore, our analysis of transcriptomic data led to the identification of 467 differentially expressed genes. Additionally, we noted significant differences in the immune microenvironment and whole exome sequencing data between the two groups. Conclusion: There are significant differences between patients with RLPS and NRLPS. Therefore, from clinical research to treatment strategies, RLPS and NRLPS should be considered as two distinct types of tumors, necessitating differentiated approaches for their study and treatment.

Radiotherapy and surgery remain effective treatment options for retroperitoneal MPNST: a retrospective study based on SEER database.

Introduction: The proportion of retroperitoneal malignant peripheral nerve sheath tumours (RMPNST) in retroperitoneal tumors is less than 5%, but the mortality rate is very high. However, there is no relevant research focused on RMPNST only. Methods: We retrospectively analyzed data from the SEER database of patients with primary RMPNST from 2000 to 2019, by leveraging the advantages of the Seer database, we can explore the prognosis of such rare diseases. Kaplan-Meier method was used to construct the survival curve, and cox regression model was used to analyze the factors affecting the prognosis of patients. In addition, a model was developed to distinguish high-risk and low-risk patients. Results: This study included a total of 52 patients, with a median survival time of 39 months (95% CI 12.740-65.260) and a 5-year survival rate of 44.2% (95% CI 0.299-0.565). Radiotherapy (p = 0.004, OR: 1.475, 95% CI 0.718-3.033), metastasis disease (p = 0.002, OR: 5.596, 95% CI 2.449-47.079) and surgery (p = 0.003, OR: 5.003, 95% CI 0.011-0.409) were associated with overall survival (OS). The 5-year distant metastasis rate was 36% (95% CI 0.221-0.499). We used the above risk factors to separate patients into high and low groups and evaluate the results through the receiver operating characteristic (ROC) curve. This model is beneficial for guiding the selection of treatment strategies. Conclusion: The majority of RMPNST patients have a good prognosis after surgery, and the establishment of high-low group is helpful for clinical decision-making.

Osr2 functions as a biomechanical checkpoint to aggravate CD8+ T cell exhaustion in tumor.

Alterations in extracellular matrix (ECM) architecture and stiffness represent hallmarks of cancer. Whether the biomechanical property of ECM impacts the functionality of tumor-reactive CD8+ T cells remains largely unknown. Here, we reveal that the transcription factor (TF) Osr2 integrates biomechanical signaling and facilitates the terminal exhaustion of tumor-reactive CD8+ T cells. Osr2 expression is selectively induced in the terminally exhausted tumor-specific CD8+ T cell subset by coupled T cell receptor (TCR) signaling and biomechanical stress mediated by the Piezo1/calcium/CREB axis. Consistently, depletion of Osr2 alleviates the exhaustion of tumor-specific CD8+ T cells or CAR-T cells, whereas forced Osr2 expression aggravates their exhaustion in solid tumor models. Mechanistically, Osr2 recruits HDAC3 to rewire the epigenetic program for suppressing cytotoxic gene expression and promoting CD8+ T cell exhaustion. Thus, our results unravel Osr2 functions as a biomechanical checkpoint to exacerbate CD8+ T cell exhaustion and could be targeted to potentiate cancer immunotherapy.

Stereotactic Body Radiotherapy Combined With Lenvatinib With or Without PD-1 Inhibitors as Initial Treatment for Unresectable Hepatocellular Carcinoma.

PURPOSE: The aim of this study was to compare the clinical benefit and safety of the triple combination of stereotactic body radiotherapy (SBRT), lenvatinib, and programmed cell death protein 1 (PD-1) inhibitors with the dual combination of SBRT and lenvatinib in patients with unresectable hepatocellular carcinoma (uHCC). METHODS AND MATERIALS: Patients with uHCC who received SBRT in combination with lenvatinib and PD-1 inhibitors or SBRT in combination with lenvatinib alone as first-line treatment from October 2018 to July 2022 were reviewed in this study. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were intrahepatic PFS, extrahepatic PFS, and objective remission rate. In addition, safety profiles were assessed by analyzing treatment-related adverse events between the two groups to assess safety profiles. RESULTS: In total, 214 patients with uHCC who received combination therapy were included in this retrospective study. Among them, 146 patients received triple combination therapy of SBRT, lenvatinib, and PD-1 inhibitors (SBRT-L-P group), and 68 patients received dual therapy of SBRT and lenvatinib (SBRT-L group). The median OS times of the 2 groups were 31.2 months and 17.4 months, respectively (P < .001). The median PFS time was significantly longer in the SBRT-L-P group than in the SBRT-L group (15.6 months vs 8.8 months, P < .001). Additionally, the median intrahepatic PFS (17.5 vs 9.9 months, P < .001) and extrahepatic PFS (20.9 vs 11.6 months, P < .001) were significantly longer in the SBRT-L-P group than in the SBRT-L group. The objective remission rate in the SBRT-L-P group was higher than in the SBRT-L group (63.0 vs 39.7%, P = .002). The incidence and severity of treatment-related adverse events in the SBRT-L-P group were comparable to those in the SBRT-L group. CONCLUSION: The use of both lenvatinib and PD-1 inhibitors with SBRT in patients with uHCC was associated with improved overall survival compared with lenvatinib and SBRT alone with a manageable safety profile.

Immune characteristics of dedifferentiated retroperitoneal liposarcomas and the reliability of regional samples in evaluating their tumor immune microenvironments.

BACKGROUND: Tumor immunotherapy is a new treatment breakthrough for retroperitoneal liposarcoma (RPLS), which is highly invasive and has few effective treatment options other than tumor resection. However, the heterogeneity of the tumor immune microenvironment (TIME) leads to missed clinical diagnosis and inappropriate treatment. Therefore, it is crucial to evaluate whether the TIME of a certain part of the tumor reliably represents the whole tumor, particularly for very large tumors, such as RPLS. METHODS: We conducted a prospective study to evaluate the TIME in different regions of dedifferentiated RPLS (DDRPLS) by detecting the expressions of markers such as CD4+, CD8+, Foxp3+, CD20+, CD68+, LAMP3+, PD-1+ tumor-infiltrating lymphocytes (TILs), and PD-L1 in tumors and corresponding paratumor tissues via immunohistochemistry and RNA sequencing. RESULTS: In DDRPLS, very few TILs were observed. Differentially expressed genes were significantly enriched in cell part and cell functions, as well as the metabolic pathway and PI3K-Akt signaling pathway. In addition, for most tumors (70-80%), the TIME was similar in different tumor regions. CONCLUSIONS: For most tumors (70-80%), the TIME in any region of the tumor reliably represents the whole tumor. DDRPLS may regulate cell functions by modulating the metabolic and PI3K-Akt signaling pathways to promote its malignant behavior.

Multi-omics joint analysis revealed the metabolic profile of retroperitoneal liposarcoma.

Retroperitoneal liposarcoma (RLPS) is the main subtype of retroperitoneal soft sarcoma (RSTS) and has a poor prognosis and few treatment options, except for surgery. The proteomic and metabolic profiles of RLPS have remained unclear. The aim of our study was to reveal the metabolic profile of RLPS. Here, we performed proteomic analysis (n = 10), metabolomic analysis (n = 51), and lipidomic analysis (n = 50) of retroperitoneal dedifferentiated liposarcoma (RDDLPS) and retroperitoneal well-differentiated liposarcoma (RWDLPS) tissue and paired adjacent adipose tissue obtained during surgery. Data analysis mainly revealed that glycolysis, purine metabolism, pyrimidine metabolism and phospholipid formation were upregulated in both RDDLPS and RWDLPS tissue compared with the adjacent adipose tissue, whereas the tricarboxylic acid (TCA) cycle, lipid absorption and synthesis, fatty acid degradation and biosynthesis, as well as glycine, serine, and threonine metabolism were downregulated. Of particular importance, the glycolytic inhibitor 2-deoxy-D-glucose and pentose phosphate pathway (PPP) inhibitor RRX-001 significantly promoted the antitumor effects of the MDM2 inhibitor RG7112 and CDK4 inhibitor abemaciclib. Our study not only describes the metabolic profiles of RDDLPS and RWDLPS, but also offers potential therapeutic targets and strategies for RLPS.

Nomogram development and external validation for predicting overall survival and cancer-specific survival in patients with primary retroperitoneal sarcoma: a retrospective cohort study.

BACKGROUND: Primary retroperitoneal sarcoma (RPS) comprises over 70 histologic subtypes, yet there are limited studies that have developed prognostic nomograms for RPS patients to predict overall survival (OS) and cancer-specific survival (CSS). The objective of this study was to construct prognostic nomograms for predicting OS and CSS in RPS patients. METHODS: We identified a total of 1166 RPS patients from the Surveillance, Epidemiology and End Results (SEER) database, and an additional 261 cases were collected from a tertiary cancer center. The study incorporated various clinicopathological and epidemiologic features as variables, and prediction windows for overall survival (OS) and cancer-specific survival (CSS) were set at 3, 5, and 7 years. Multivariable Cox models were utilized to develop the nomograms, and variable selection was performed using a backward procedure based on the Akaike Information Criterion. To evaluate the performance of the nomograms in terms of calibration and discrimination, we used calibration plots, coherence index, and area under the curve. FINDINGS: The study included 818 patients in the development cohort, 348 patients in the internal validation cohort, and 261 patients in the external validation cohort. The backward procedure selected the following variables: age, French Federation of Cancer Centers Sarcoma Group (FNCLCC) grade, pre-/postoperative chemotherapy, tumor size, primary site surgery, and tumor multifocality. The validation results demonstrated that the nomograms had good calibration and discrimination, with C-indices of 0.76 for OS and 0.81 for CSS. Calibration plots also showed good consistency between the predicted and actual survival rates. Furthermore, the areas under the time-dependent receiver operating characteristic curves for the 3-, 5-, and 7-year OS (0.84, 0.82, and 0.78, respectively) and CSS (0.88, 0.88, and 0.85, respectively) confirmed the accuracy of the nomograms. INTERPRETATION: Our study developed accurate nomograms to predict OS and CSS in patients with RPS. These nomograms have important clinical implications and can assist healthcare providers in making informed decisions regarding patient care and treatment options. They may also aid in patient counseling and stratification in clinical trials.

SPTAN1/NUMB axis senses cell density to restrain cell growth and oncogenesis through Hippo signaling.

The loss of contact inhibition is a key step during carcinogenesis. The Hippo-Yes-associated protein (Hippo/YAP) pathway is an important regulator of cell growth in a cell density-dependent manner. However, how Hippo signaling senses cell density in this context remains elusive. Here, we report that high cell density induced the phosphorylation of spectrin α chain, nonerythrocytic 1 (SPTAN1), a plasma membrane-stabilizing protein, to recruit NUMB endocytic adaptor protein isoforms 1 and 2 (NUMB1/2), which further sequestered microtubule affinity-regulating kinases (MARKs) in the plasma membrane and rendered them inaccessible for phosphorylation and inhibition of the Hippo kinases sterile 20-like kinases MST1 and MST2 (MST1/2). WW45 interaction with MST1/2 was thereby enhanced, resulting in the activation of Hippo signaling to block YAP activity for cell contact inhibition. Importantly, low cell density led to SPTAN1 dephosphorylation and NUMB cytoplasmic location, along with MST1/2 inhibition and, consequently, YAP activation. Moreover, double KO of NUMB and WW45 in the liver led to appreciable organ enlargement and rapid tumorigenesis. Interestingly, NUMB isoforms 3 and 4, which have a truncated phosphotyrosine-binding (PTB) domain and are thus unable to interact with phosphorylated SPTAN1 and activate MST1/2, were selectively upregulated in liver cancer, which correlated with YAP activation. We have thus revealed a SPTAN1/NUMB1/2 axis that acts as a cell density sensor to restrain cell growth and oncogenesis by coupling external cell-cell contact signals to intracellular Hippo signaling.

Sonodynamic Therapy of NRP2 Monoclonal Antibody-Guided MOFs@COF Targeted Disruption of Mitochondrial and Endoplasmic Reticulum Homeostasis to Induce Autophagy-Dependent Ferroptosis.

The lethality and chemotherapy resistance of pancreatic cancer necessitates the urgent development of innovative strategies to improve patient outcomes. To address this issue, we designed a novel drug delivery system named GDMCN2,which uses iron-based metal organic framework (Fe-MOF) nanocages encased in a covalent organic framework (COF) and modified with the pancreatic cancer-specific antibody, NRP2. After being targeted into tumor cells, GDMCN2 gradually release the sonosensitizer sinoporphyrin sodium (DVDMS) and chemotherapeutic gemcitabine (GEM) and simultaneously generated reactive oxygen species (ROS) under ultrasound (US) irradiation. This system can overcome gemcitabine resistance in pancreatic cancer and reduce its toxicity to non-targeted cells and tissues. In a mechanistic cascade, the release of ROS activates the mitochondrial transition pore (MPTP), leading to the release of Ca2+ and induction of endoplasmic reticulum (ER) stress. Therefore, microtubule-associated protein 1A/1B-light chain 3 (LC3) is activated, promoting lysosomal autophagy. This process also induces autophagy-dependent ferroptosis, aided by the upregulation of Nuclear Receptor Coactivator 4 (NCOA4). This mechanism increases the sensitivity of pancreatic cancer cells to chemotherapeutic drugs and increases mitochondrial and DNA damage. The findings demonstrate the potential of GDMCN2 nanocages as a new avenue for the development of cancer therapeutics.

JMJD2D stabilises and cooperates with HBx protein to promote HBV transcription and replication.

Background & Aims: HBV infection is a global health burden. Covalently closed circular DNA (cccDNA) transcriptional regulation is a major cause of poor cure rates of chronic hepatitis B (CHB) infection. Herein, we evaluated whether targeting host factors to achieve functional silencing of cccDNA may represent a novel strategy for the treatment of HBV infection. Methods: To evaluate the effects of Jumonji C domain-containing (JMJD2) protein subfamily JMJD2A-2D proteins on HBV replication, we used lentivirus-based RNA interference to suppress the expression of isoforms JMJD2A-2D in HBV-infected cells. JMJD2D-knockout mice were generated to obtain an HBV-injected model for in vivo experiments. Co-immunoprecipitation and ubiquitylation assays were used to detect JMJD2D-HBx interactions and HBx stability modulated by JMJD2D. Chromatin immunoprecipitation assays were performed to investigate JMJD2D-cccDNA and HBx-cccDNA interactions. Results: Among the JMJD2 family members, JMJD2D was significantly upregulated in mouse livers and human hepatoma cells. Downregulation of JMJD2D inhibited cccDNA transcription and HBV replication. Molecularly, JMJD2D sustained HBx stability by suppressing the TRIM14-mediated ubiquitin-proteasome degradation pathway and acted as a key co-activator of HBx to augment HBV replication. The JMJD2D-targeting inhibitor, 5C-8-HQ, suppressed cccDNA transcription and HBV replication. Conclusion: Our study clarified the mechanism by which JMJD2D regulates HBV transcription and replication and identified JMJD2D as a potential diagnostic biomarker and promising drug target against CHB, and HBV-associated hepatocarcinoma. Impact and implications: HBV cccDNA is central to persistent infection and is a major obstacle to healing CHB. In this study, using cellular and animal HBV models, JMJD2D was found to stabilise and cooperate with HBx to augment HBV transcription and replication. This study reveals a potential novel translational target for intervention in the treatment of chronic hepatitis B infection.

Identification of MDM2 as a prognostic and immunotherapeutic biomarker in a comprehensive pan-cancer analysis: A promising target for breast cancer, bladder cancer and ovarian cancer immunotherapy.

BACKGROUND: The murine double minute 2 (MDM2) gene is a crucial factor in the development and progression of various cancer types. Multiple rigorous scientific studies have consistently shown its involvement in tumorigenesis and cancer progression in a wide range of cancer types. However, a comprehensive analysis of the role of MDM2 in human cancer has yet to be conducted. METHODS: We used various databases, including TIMER2.0, TCGA, GTEx and STRING, to analyze MDM2 expression and its correlation with clinical outcomes, interacting genes and immune cell infiltration. We also investigated the association of MDM2 with immune checkpoints and performed gene enrichment analysis using DAVID tools. RESULTS: The pan-cancer MDM2 analysis found that MDM2 expression and mutation status were observably different in 25 types of cancer tissue compared with healthy tissues, and prognosis analysis showed that there was a significant correlation between MDM2 expression and patient prognosis. Furthermore, correlation analysis showed that MDM2 expression was correlated with tumor mutational burden, microsatellite instability and drug sensitivity in certain cancer types. We found that there was an association between MDM2 expression and immune cell infiltration across cancer types, and MDM2 inhibitors might enhance the effect of immunotherapy on breast cancer, bladder cancer and ovarian cancer. CONCLUSIONS: The first systematic pan-cancer analysis of MDM2 was conducted, and it demonstrated that MDM2 was a reliable prognostic biomarker and was closely related to cancer immunity, providing a potential immunotherapeutic target for breast cancer, bladder cancer and ovarian cancer.

Lenvatinib with or without stereotactic body radiotherapy for hepatocellular carcinoma with portal vein tumor thrombosis: a retrospective study.

BACKGROUND AND OBJECTIVES: Patients with hepatocellular carcinoma (HCC) involving portal vein tumor thrombosis (PVTT) are presently lacking effective treatment options. We aimed to compare the efficacy and safety of lenvatinib with or without SBRT for HCC with PVTT. MATERIALS AND METHODS: This retrospective analysis included 37 patients treated with lenvatinib in combination with SBRT and 77 patients treated with lenvatinib alone from August 2018 to August 2021. Overall survival (OS), progression-free survival (PFS), intrahepatic PFS (IHPFS) and objective remission rate (ORR) were compared between the two groups, while adverse events (AEs) was analyzed between the two groups to assess safety profiles. RESULTS: Median OS, PFS and IHPFS were significantly prolonged in the combination treatment group compared with the single treatment group (median OS, 19.3 vs. 11.2 months, p < 0.001; median PFS: 10.3 vs. 5.3 months, p < 0.001; median IHPFS, 10.7 vs. 5.3 months, p < 0.001). Moreover, a higher ORR (56.8% vs. 20.8%, P < 0.001) were observed in the lenvatinib combined with SBRT group. In subgroup analyses of Vp1-2 and Vp3-4 group, median OS, PFS and IHPFS were also significantly longer in the lenvatinib combined with SBRT group than those in the lenvatinib alone group. AEs in the combined therapy group were mostly manageable and the incidence was not statistically significant compared to the monotherapy group. CONCLUSION: Lenvatinib plus SBRT had a significantly better survival benefit than lenvatinib monotherapy in the treatment of HCC patients with PVTT and was well tolerated.

Comparison of stereotactic body radiotherapy with and without lenvatinib for advanced hepatocellular carcinoma: a propensity score analysis.

PURPOSE: Lack of evidence on the benefit of stereotactic body radiotherapy (SBRT) in combination with lenvatinib for advanced hepatocellular carcinoma (HCC). Our research compared the efficacy and safety of SBRT plus lenvatinib versus SBRT alone in clinical practice for the treatment of advanced HCC. METHODS: Propensity score matching (PSM) analysis was used to reduce selection bias. Overall survival (OS), progression-free survival (PFS), intrahepatic PFS (IHPFS), and objective response rate (ORR) were compared between the two groups. Additionally, safety profiles were also evaluated in the two groups. RESULTS: After PSM, 35 patients from each group were selected and the date was compared. Compared with the SBRT alone group, the median OS, PFS, and IHPFS were significantly prolonged in SBRT plus lenvatinib group (median OS 16.8 vs. 11.0 months, pOS = 0.043; median PFS 9.1 vs. 3.7 months, pPFS < 0.001; median IHPFS 9.5 vs. 4.2 months, pIHPFS = 0.004). The 6- and 12-month OS rates were 91.4% and 68.6% in the combined therapy group and 82.9% and 48.6% in the monotherapy group, respectively. The 6- and 12-month PFS rates were 68.6% and 34.3% in the combined therapy group and 31.4% and 8.6% in the monotherapy group, respectively. Furthermore, a higher ORR was observed in SBRT plus lenvatinib group (54.29% vs. 22.86%, p = 0.007). Subgroup analysis of patients with macroscopic vascular invasion (MVI) also had similar results. Moreover, most adverse events (AEs) were mild-to-moderate and manageable in the SBRT plus lenvatinib group. CONCLUSION: SBRT plus lenvatinib is expected to significantly improve OS, PFS, IHPFS, and ORR for patients with advanced HCC when compared to SBRT alone, with manageable adverse effects.

Keratin19 promotes pancreatic cancer progression and poor prognosis via activating the Hedgehog pathway.

Pancreatic cancer is a serious threat to human health, with strong invasiveness, rapid progression and poor prognosis. Tumors expressing keratin 19 (K19) have stronger invasiveness and a worse prognosis. However, the role and mechanism of K19 in pancreatic cancer have remained largely elusive. In the present study, K19 expression was detected in pancreatic cancer tissues, its effect on proliferation, apoptosis and metastasis of pancreatic cancer at the cellular, in vivo preclinical and clinical levels was evaluated and its effect on the Hedgehog pathway was analyzed. K19 was significantly overexpressed in pancreatic cancer, promoted pancreatic cancer proliferation and metastasis, inhibited tumor cell apoptosis and was associated with poor prognosis. Mechanistically, these effects were mediated through the activation of the Hedgehog pathway. In conclusion, K19 may be a novel target molecule for pancreatic cancer treatment.

Prognosis of adenoid cystic carcinoma in head and neck region treated with different regimens-A single-centre study.

BACKGROUND: No study has evaluated the impact of regimen on recurrence, metastasis and survival in patients with adenoid cystic carcinoma (ACC). The present study aimed to compare the efficacy of radioactive seed implantation and other regimens in treating ACC, so as to investigate the clinical applicability of radioactive seed implantation and determine the indications for this regimen. METHODS: A total of 188 patients with ACC in oromaxillofacial region were allocated to four groups according to the treatment regimen: group 1 was treated with a combination of surgery and 125 I seed therapy, group 2 with a combination of surgery and external radiotherapy, group 3 with surgery, whereas group 4 was untreated. The Kaplan-Meier method was used to assess the survival rates, and the Cox regression analyses were used to identify the associated prognostic factors. RESULTS: The overall survival rates of 188 patients and groups 1, 2, 3 and 4 were 85.7%, 75%, 68.2% and 37.5%, respectively. Cox regression analysis revealed that age, T stage, N stage and regimen were independent prognostic factors of survival. Amongst patients with primary ACC, the efficacy of radioactive seed implantation was higher in those with perineural invasion than in those without. CONCLUSION: Patient age, T stage, N stage and regimen are independent prognostic factors of survival in patients with ACC. Patients treated with surgery combined with postoperative 125 I seed radiotherapy have a higher overall survival rate, and those with perineural invasion are more suitable for radioactive seed implantation therapy.

[Spatiotemporal distribution and multi-source characteristics of microplastics in the soil and water environment of Poyang Lake Wetland, China]. / 鄱阳湖湿地水土环境中微塑料的时空分布及多源性.

The increasing microplastics (MPs) pollution in freshwater wetlands has received global concerns. To investigate the spatiotemporal dynamics of MPs in the wetlands of Poyang Lake, surface water and sediment samples were collected from five rivers entering the lake as well as the confluence of Poyang Lake into the Yangtze River, in both dry and wet seasons. The MPs in water and sediment were extracted by the digestion-filtration method and flotation-separation-digestion-filtration method, respectively. Light microscope, Fourier transform infrared spectroscopy, and scanning electron microscope were used for microplastic characterization. The results showed that the abundance of MPs ranged from 32.1 to 127.3 n·L-1 in water samples, and from 533.3 to 1286.6 n·kg-1 in sediment samples during the wet season. In the dry season, the abundance of MPs ranged from 87.1 to 295.5 n·L-1 in water and from 460.0 to 1368.0 n·kg-1 in sediment. Compared with other freshwater wetlands, Poyang Lake had higher abundance of MPs. There were temporal and spatial differences among regions. The main forms of MPs included beads, fragment, film and fiber, and the corresponding polymer components were mainly polystyrene, polypropy-lene and polyethylene. Beads (35.7% in wet season and 52.0% in dry season) were the main form of MPs in water, while fragment (45.8% in wet season and 69.7% in dry season) was the main form of MPs in sediment. Small size (<0.1 mm) MPs were dominant (>50%) in water and sediment in both seasons. The abundance of MPs with different sizes decreased with the increases of size. The potential main sources of MPs in the wetlands of Poyang Lake included the discharge of industrial wastewater, discharge from urban and rural domestic sewage treatment plants, agricultural and fishing activities, and improper disposal of domestic wastes.

AKR1B10 accelerates the production of proinflammatory cytokines via the NF-κB signaling pathway in colon cancer.

Aldo-keto reductase family one, member B10 (AKR1B10) has been reported to be involved in the tumorigenesis of various cancers. It has been reported that colorectal cancer is closely associated with chronic inflammation, but the underlying molecular mechanisms are still elusive. In our study, we evaluated the relationship between AKR1B10 expression and clinicopathological characteristics of colon cancer and showed that AKR1B10 expression was significantly correlated with the T stage and clinical stage of colon cancer. Knockdown of AKR1B10 significantly decreased the expression of the inflammatory cytokines IL1α and IL6 induced by lipopolysaccharide by inhibiting the NF-κB signaling pathway. Furthermore, AKR1B10 depends on its reductase activity to affect the NF-κB signaling pathway and subsequently affect the production of inflammatory cytokines. In addition, knockdown of AKR1B10 effectively reduced cell proliferation and clonogenic growth, indicating the biological role of AKR1B10 in colon cancer. Together, our findings provide important insights into a previously unrecognized role of AKR1B10 in colon cancer.