- Research Article
- 10.1016/j.critrevonc.2026.105278
Harnessing synergy: Innovative combinations to overcome PARP inhibitor resistance in cancer treatment.
- Jun 01, 2026
- Critical reviews in oncology/hematology
- Yurun Huang + 3 more +3
Publications from 2021 to 2026
Showing 10 of 347 papers
Harnessing synergy: Innovative combinations to overcome PARP inhibitor resistance in cancer treatment.
Apolipoprotein J-mediated hepato-renal crosstalk drives renal injury in chronic kidney disease.
Overcoming MDSC-Mediated Immunosuppression in Hepatocellular Carcinoma: From Mechanisms to Novel Immunotherapeutic Approaches.
Background: Myeloid-derived suppressor cells (MDSCs) drive immunosuppression in the hepatocellular carcinoma (HCC) tumor microenvironment (TME), contributing to immune checkpoint blockade (ICB) resistance. This review explores underlying mechanisms and therapeutic strategies. Methods: We synthesize the recent literature on MDSC biology in HCC, focusing on signaling pathways, metabolic/epigenetic reprogramming, and novel interventions, including AI-driven analyses. Results: Key mechanisms include JAK-STAT3 activation for MDSC expansion, CXCL12-CXCR4 for recruitment, enhanced glycolysis/lipid metabolism for suppressive function, and epigenetic changes sustaining immunosuppression. Therapeutic approaches encompass inhibitors, differentiation promoters, metabolic modulators, transcriptional reprogramming, microbiome modulation, and combinations with ICB/locoregional therapies or standard chemoimmunotherapy, yielding improved outcomes in trials. Conclusions: Targeting MDSC redundancies via multi-modal strategies offers a roadmap for overcoming resistance, with AI enhancing biomarker-guided precision immunotherapy in HCC.
Read moreThe relationship between a body shape index and abdominal aortic calcification: a population-based study
Abdominal Aortic Calcification (AAC) is closely associated with visceral adiposity. The authors aimed to investigate the relationship between a Body Shape Index (ABSI) and AAC. Data were obtained from the 2013‒2014 cycle of the National Health and Nutrition Examination Survey (NHANES). Weighted multivariable regression, tests for trends, subgroup analysis, and smooth curves were used to explore the association between ABSI and AAC scores, as well as Severe Abdominal Aortic Calcification (SAAC). Receiver Operating Characteristic (ROC) curves were plotted to compare the predictive abilities of ABSI, Weight-adjusted Waist Index (WWI), Body Mass Index (BMI), Waist-to-Height Ratio (WHtR), and Waist Circumference (WC) for AAC and SAAC. A total of 2741 individuals were included in the present study. The weighted incidence of AAC was 29.12%, and SAAC was 7.94%. After fully adjusting for covariates, each one-unit increase in ABSI was associated with a 0.42-point increase in the AAC score (95% CI: 0.29, 0.63), and the risk of SAAC increased by 37% (95% CI: 1.12, 1.77). Smooth curves showed a nonlinear positive correlation between ABSI and AAC scores, as well as SAAC. No dependence was observed in the subgroup analysis. ROC analysis showed that ABSI was a stronger predictor than WWI, BMI, WHtR, and WC. ABSI has a positive correlation with AAC scores and SAAC. However, prospective studies are required to validate the present results.
Read moreDiagnostic and prognostic value of EphB2 in nasopharyngeal carcinoma
Nasopharyngeal carcinoma (NPC) is a subtype of head and neck carcinoma. This study aimed to investigate the diagnostic and prognostic significance of EphB2 in NPC. Serum and nasopharyngeal tissue samples were collected from 159 NPC patients and 159 individuals with chronic nasopharyngeal mucosal inflammation (control group). EphB2 expression in tissue samples was assessed by western blotting (WB) and immunofluorescence (IF); its concentration in serum was measured by enzyme-linked immunosorbent assay (ELISA). Survival rate differences were evaluated using Kaplan-Meier analysis and the log-rank test. Multivariate Cox regression was performed to identify prognosis-related factors. The diagnostic performance of EphB2 was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC). EphB2 expression was significantly elevated in both serum and tissue samples of NPC patients compared to controls. High EphB2 levels were significantly associated with TNM stage, tumor invasion depth, lymph node metastasis, distant metastases, EBV infection, and recurrence status. Kaplan-Meier survival curves showed that NPC patients with high levels of EphB2 or EBV(+) or recurrence had the poorest disease-free survival. Cox regression identified high EphB2 expression, EBV(+), and recurrence as independent predictors of poor prognosis in NPC. ROC analysis demonstrated that at an optimal cutoff of 7.079 ng/mL, serum EphB2 effectively distinguished NPC patients from controls, with an AUC of 0.904 (95 % CI: 0.866-0.942, P < 0.001), sensitivity of 79.9 %, and specificity of 98.7 %. The AUC for EBV infection alone was 0.767 (95 % CI: 0.714-0.821, P < 0.001), with a sensitivity of 71.1 % and specificity of 82.4 %. Combined detection of EphB2 and EBV infection improved the AUC to 0.922 (95 % CI: 0.891-0.954, P < 0.001), with 78.6 % sensitivity and 97.5 % specificity. Serum EphB2 represents a promising diagnostic and prognostic biomarker for NPC. The combination of EBV seropositivity and high EphB2 expression may be valuable for early NPC screening.
Read morePredicting Cyclosporine-Related Liver Injury in Pediatric Thalassemia after Hematopoietic Stem Cell Transplantation
Children with thalassemia often need a stem cell transplant, and cyclosporine is commonly used afterward to prevent transplant rejection. Although effective, cyclosporine can sometimes harm the liver, which may lead to serious health issues if not ide
Read moreProtective role of Bre1 in mitochondrial function and energy metabolism in Drosophila models of Parkinson's disease.
The second most common cause of autosomal recessive early-onset Parkinson's disease (PD) can be attributed to mutations in the PINK1 gene, malfunction of the mitochondria is the key pathological mechanism. Bre1 encodes an E3 ubiquitin ligase, with the discovery of Bre1's role in repairing mitochondrial damage, further investigation into its implications for PD is warranted. We used the PINK1B9 drosophila melanogaster as the PD model. The effects of Bre1 on PD phenotypes were evaluated based on the morphology of the wings and dorsal region, as well as flight ability. Immunostaining of dopaminergic neurons was used to examine neurodegeneration. Transcriptomes were used to detect the pathway directly involved. Mitochondrial structure and function were observed using electron microscopy, ATP detection, and an oxygen consumption assay. The detection of SOD activity and ROS were used to explicit the effects of Bre1 on oxidative stress. To identify the effects of Bre1 on glycolysis and tricarboxylic acid (TCA) cycle, we performed Western Blot and RT-PCR. We discovered that Bre1 overexpression significantly improved the phenotype of PD flies and protected their dopaminergic neurons from degeneration. More significantly, we observed that the overexpression of Bre1 markedly enhanced the respiratory capacity of mitochondrial Complex I and Complex II, elevated ATP levels, reduced ROS levels, and improved mitochondrial structural integrity. The Western Blot results demonstrate a significant increase in the critical glycolysis enzymes, Pfk and Pyk proteins. Moreover, qRT-PCR results showed a remarkably upregulation in the transcriptional level of OGDH, a critical rate-limiting enzyme in the TCA cycle. Therefore, our study suggests that Bre1 improves the phenotypes of PD model flies by attenuating mitochondrial damage and enhancing energy metabolism, offering a potential drug target for ameliorating the symptoms of PINK1 mutant autosomal recessive PD patients.
Read morePosterior Release Surgery Further Improves the Efficacy of Halo-Pelvic Traction in the Treatment of Patients With Severe Spinal Deformity
Objective: To explore the effect of posterior release surgery combined with halo-pelvic traction in improving spinal deformity and to evaluate the factors affecting the correction rate of scoliosis.Background: Spinal surgery is the preferred treatment for severe scoliosis and kyphosis, but direct primary corrective surgery carries significant risks and demands. Traction surgery has been shown to improve safety and spinal correction rates. However, traction surgery has a ceiling effect. In recent years, posterior release surgery has emerged as an emerging technique for spinal correction, but further research is needed to improve correction rates for severe scoliosis.Methods: Fifty-four patients with spinal deformity treated between April 2021 and December 2023 were divided into two treatment phases: a halo-pelvic traction phase (Phase I) and a posterior spinal release followed by a halo-pelvic traction phase (Phase II). The effects of Phase I and Phase II on scoliosis and kyphosis correction were retrospectively evaluated, and statistical analysis was performed to identify factors influencing scoliosis correction rates.Results: The first-stage scoliosis correction rate was 31.9%, and the kyphosis improvement rate was 23.1%. The second-stage scoliosis correction rate was 25.0%, and the kyphosis improvement rate was 19.5%. The overall scoliosis correction rate was 48.9%, and the kyphosis improvement rate was 38.0%. Statistical analysis showed that age, gender, and comorbidities (rib fusion or spinal fusion) were significant risk factors for scoliosis correction.Conclusion: Posterior release surgery combined with halo-pelvic traction can significantly improve the correction effect of patients with severe spinal deformity.
Read morePerioperative camrelizumab plus rivoceranib versus surgery alone in patients with resectable hepatocellular carcinoma at intermediate or high risk of recurrence (CARES-009): a randomised phase 2/3 trial.
Atypical presentation of cryptococcal meningitis in oncology patients: Case Report
Cryptococcal meningitis (CM) is a serious central nervous system (CNS) infection primarily affecting immuno-compromised individuals, including cancer patients. Although rare in oncology populations, it may present atypically and pose diagnostic challenges. We report two cases of malignancy-associated CM with non-classical features. The first involved a male with lung squamous cell carcinoma and multiple comorbidities, presenting with mild cerebrospinal fluid (CSF) pleocytosis and normal opening pressure. The second case involved a female with chronic lymphocytic leukemia and concurrent cryptococcal and purulent meningitis, showing marked leukocytosis and elevated CSF pressure. Neither had recent antitumor therapy. Despite similar initial symptoms of fever and headache, their clinical courses diverged: the male recovered with antifungal treatment, while the female had a poor response and discontinued therapy. These cases highlight the variable and atypical nature of CM in cancer patients and underscore the importance of early recognition and inclusion of fungal infections in the differential diagnosis for CNS complications, even in the absence of classical features.
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