Volume 27, Issue 4

Introduction Hand sarcomas are rare malignancies requiring a careful balance between oncologic control and functional preservation. This systematic review aims to evaluate optimal therapeutic strategies, with a focus on radiotherapy (RT). Content A systematic search was conducted using PubMed, Cochrane, and Scopus to identify relevant studies on hand sarcomas from database inception to 31 October 2024. Eligible study designs included randomized controlled trials, cohort studies, case-control studies, case series, and case reports, published in English. Exclusion criteria encompassed studies involving non-human subjects, unavailable full texts, systematic reviews, editorials, conference abstracts, and studies with inadequate follow-up or focusing on pediatric populations. The quality of the included studies was evaluated using the Joanna Briggs Institute checklist. Case reports were categorized by treatment modality. Following data aggregation, survival outcomes were analyzed using Kaplan-Meier curves. Statistical comparisons between groups were conducted using log-rank tests, with a p-value <0.05 considered statistically significant. Cohort-level analyses were not performed due to limitations in the available data. 25 studies met the inclusion criteria, including 10 case reports, 3 case series, seven cohort studies with granular data, and five additional cohort studies. Data synthesis revealed that adding radiotherapy to surgery and chemotherapy improved local control (LC), disease-free survival (DFS), and overall survival (OS), though not significantly. The addition of radiotherapy to surgery resulted in a favorable separation of the curves for LC and OS, with no difference observed for DFS. However, none of these differences reached statistical significance. Radiotherapy with surgery significantly improved DFS and OS compared to surgery with chemotherapy, with a non-significant improvement in LC. Multimodal therapy did not significantly differ from surgery plus radiotherapy alone in LC, DFS, and OS. Surgical resection was positively correlated with OS. From cohort studies, factors negatively affecting outcomes included tumor size, advanced stage, histology, and positive margins. Summary and Outlook This systematic review confirms surgery as the cornerstone of treatment. While benefits in LC may be somewhat masked, radiotherapy improves DFS and OS compared to chemotherapy, supporting its use despite toxicity. No benefit was observed from chemotherapy, although its tailored use may be considered on a case-by-case basis. Treatment should consider tumor characteristics, histology, metastatic potential, margins, and patient-specific factors. Future research should refine protocols to improve outcomes in this complex disease.

Social determinants of health (SDOH) profoundly shape breast cancer treatment pathways and outcomes. Variables such as race, socioeconomic status, and insurance coverage significantly influence the timeliness, accessibility, and quality of surgical care. This narrative review aims to critically examine how SDOH influences breast cancer surgical trajectories and outcomes in the United States. By synthesizing current epidemiological evidence, the review explores the impact of these non-medical factors on time to surgery, procedure selection, access to reconstruction, postoperative complications, and quality of life. Racial and socioeconomic disparities persist across the continuum of care, with marginalized populations experiencing greater delays, lower rates of breast-conserving surgery, and decreased access to reconstruction. Insurance status, particularly lack of private coverage, is consistently associated with inferior outcomes and reduced access to standard treatments. Despite the growing body of evidence, major clinical guidelines still fail to integrate SDOH into decision-making frameworks, underscoring the need for systemic changes to promote equitable care.

Cancer remains one of the most prevalent causes of mortality worldwide and thus necessitates the development of novel therapeutic strategies. Snake venom, consisting of a complex mixture of bioactive proteins and peptides, has demonstrated significant anti-cancer effects such as cytotoxicity, angiogenesis inhibition, and apoptosis induction. However, its clinical applicability is restrained due to stability concerns and off-target toxicity. The current review aims to investigate the potential of employing silica nanoparticles (SiO 2 NPs) as a vehicle for administering snake venom to enhance therapeutic efficacy while reducing systemic toxicity. Snake venom conjugated SiO 2 NP shave gained attention recently due to their biocompatibility, stability, and optimal loading efficiency. In vitro investigations on cancer cell lines revealed a considerable increase in cytotoxicity and induction of apoptosis as compared to free snake venom, with greater selectivity for malignant cells. Furthermore, apoptotic cell death through overproduction of reactive oxygen species (ROS)has also been shown in preliminary in vivo models. The main aim of this review article is to highlight that combining snake venom and SiO 2 NPs can work in conjunction to provide tailored cancer treatment. This novel strategy not only overcomes the drawbacks of traditional treatments but also opens up the possibilities for more preclinical and clinical research on the application of venom-based nanotherapeutics in oncology.

Objectives Rectal cancer is a significant global health concern, with radiotherapy playing a crucial role in treatment. However, optimal fractionation regimens remain debated, particularly with newer treatment techniques such as the use of Halcyon-based radiotherapy. This study aims to compare dosimetric and radiobiological parameters between two radiotherapy regimes for rectal cancer: 50 Gy/25 fractions and 50.4 Gy/28 fractions. Methods A retrospective analysis of 28 treatment plans was conducted. Group A (10 plans) received 50 Gy/25 fractions, while Group B (18 plans) received 50.4 Gy/28 fractions. The study evaluated parameters including dose volume histograms (DVH), conformity index (CI), homogeneity index (HI), tumor control probability (TCP), normal tissue complication probability (NTCP), equivalent uniform dose (EUD), and biologically effective dose (BED) across the two groups. Results No significant dose differences were found in normal tissues between the groups. However, it demonstrated a significantly higher conformity index (CI) for the planning target volume (0.98 ± 0.01 vs. 0.96 ± 0.02, p=0.007) and biologically effective dose (BED) (71.82 ± 0.32 vs. 70.08 ± 0.08, p<0.001). Additionally, Group A exhibited a higher normal tissue complication probability (NTCP) for the bladder (0.03 ± # vs. 0.02 ± #, p=0.004). Conversely, Group B had a lower tumor control probability (TCP) compared to Group A. Conclusions Group A offers better tumor coverage and comparable TCP but has a higher NTCP, indicating a potential increase in normal tissue complications compared to Group B. While the study provides valuable dosimetric and radiobiological insights, its retrospective nature and limited sample size pose constraints on generalizability.

Objectives To date, few studies have investigated the potential application of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) in the diagnosis of periampullary duodenal lesions (PADLs). This study aimed to investigate the diagnostic value of CH-EUS in PADLs and compare parameters of time intensity-curve (TIC) in pathological difference. Methods We enrolled individuals with preliminary assessment as PADLs, and conducted B mode endoscopic ultrasound (B-EUS) and CH-EUS successively. The patients were divided into benign lesion (BL) and malignant lesion (ML) groups according to the pathology. McNemar’s test was used to compare the diagnostic value of these examinations. Differential analysis between BL and ML groups is conducted to find TIC parameters that show a significant difference for pathology prediction. Results 20 PADLs patients were finally included. Echo intensity and uniformity showed no significant difference between the BL and ML groups. In contrast, different modes of blood supply showed statistical significance (p=0.014). Furthermore, 6 parameters including the differences in intensity gain (ΔI gain ; p<0.001), time used from basic to peak status (|ΔT peak |; p=0.027), rate of elevation (ER; p<0.001), the velocity of elevation (ΔVE; p<0.001) and decrease within 90 s (ΔVD 2 ; p=0.041) between neoplasm and control tissue, and the AUC during the wash-in period of lesion tissue (WiAUC (lesion); p=0.043) differed from BL group to ML group. The diagnostic efficacy of CH-EUS TIC quantitative data for PADLs was: sensitivity 88.9 %, specificity 100 %, PPV 100 %, NPV 91.70 %, and accuracy 95 %. Conclusions The quantitative TIC parameters from CH-EUS were of great significance in the pathology difference of PADLs, and demonstrated promising potential as a complementary clinical diagnostic approach.

Objectives Given the lack of a unified and comprehensive approach for the early prognostic assessment of fetal sacrococcygeal teratoma (SCT), this study aimed to evaluate the utility of ultrasound feature-based scoring in treatment decision-making and prognostic evaluation of fetal SCT, and to construct a predictive model that can provide imaging-based evidence for the early intervention and individualized management of SCT in clinical practice. Methods 90 cases of fetal SCT that met the inclusion criteria were retrospectively analyzed. Ultrasound feature data were extracted, including tumor volume, proportion of solid tumor components (PST), tumor volume to fetal weight ratio (TFR), solid tumor volume to head volume ratio (STV/HV), tumor growth rate (TGR), blood supply grade (BSG), polyhydramnios, increased cardiothoracic ratio (ICR), placental thickening, and Altman’s classification. Univariate and multivariate logistic regression analyses were conducted to identify the independent risk factors. On the basis of these factors, a prognostic prediction model was constructed and visualized using a nomogram. Results Three independent risk factors for poor prognosis in fetal SCT were identified: ICR, BSG III, and TGR. ICR (area under the curve [AUC]=0.785, 95 % CI: 0.697–0.873; accuracy=0.833; sensitivity=0.606; specificity=0.965), BSG (AUC=0.901, 95 % CI: 0.829–0.972; accuracy=0.900; sensitivity=0.848; specificity=0.930), and TGR (AUC=0.833, 95 % CI: 0.744–0.922; accuracy=0.822; sensitivity=0.667; specificity=0.912) each demonstrating good predictive performance. The combined model yielded an AUC of 0.967 (95 % CI: 0.940–0.997), with an accuracy of 0.911, sensitivity of 0.909, and specificity of 0.912, outperforming any individual factor. A nomogram was developed to enable intuitive prognostic risk assessment and timely clinical decision-making. Conclusions The proposed ultrasound feature-based prognosis prediction model can effectively predict the risk of poor prognosis in fetal SCT, particularly during the mid-trimester, providing a reliable tool for clinical decision-making and early intervention. This model is expected to provide important imaging data for the personalized treatment of SCT fetuses.

Objectives Heat shock protein family A (Hsp70) member 9 (HSPA9) is a mitochondrial chaperone protein that belongs to the heat shock protein 70 family. HSPA9 is expressed across various malignancies. However, the intricate relationship and mechanisms between HSPA9 and glioma remain unclear. This study aims to elucidate the molecular mechanisms by which HSPA9 influences glioma progression through transcriptomic and proteomic analysis. Methods HSPA9 expression in glioma patient tissues was validated by histopathological analysis and Western blotting. Subsequently, stable HSPA9-overexpressing and HSPA9-knockdown U-87 MG and U251 MG cell lines were generated. To investigate the downstream effects, transcriptomic and proteomic sequencing was performed on HSPA9-knockdown U-87 MG cells. Bioinformatics analysis was then applied to identify enriched pathways associated with the differentially expressed genes and proteins. Finally, key metabolites related to these pathways were quantified. Results Immunohistochemistry and Western blotting revealed a significant elevation of HSPA9 expression in glioma tissues, indicating its potential as a molecular marker for this malignancy. Integrated transcriptomic-proteomic analysis detected 496 downregulated genes and 276 upregulated proteins in HSPA9-knockdown U-87 MG cells. Pathway enrichment analysis indicated that these differentially expressed molecules were primarily enriched in energy metabolism-related pathways. Metabolic assays using commercial kits demonstrated that knockdown of HSPA9 reduced lactate levels in both U-87 MG and U251 MG cells, accompanied by increased glucose and ATP levels. Conversely, in HSPA9-overexpressing U-87 MG and U251 MG cell lines, α-ketoglutarate (α-KG) levels were consistently decreased. Conclusion The results demonstrated that HSPA9 could drive glioma cells from oxidative phosphorylation toward glycolytic metabolism, thereby accelerating tumor cell proliferation. This study provides novel insights into the influence of HSPA9 on the initiation and progression of glioma through gene and protein expression. Further research needs to be conducted to investigate the potential therapeutic target of HSPA9 in glioma.

Objectives Annexin A2 (Anxa2) has been implicated in regulating tumor progression. However, the role in driving thyroid cancer development is unclear. Herein, this study aimed to investigate the possible role of Anxa2 in the pathogenesis of thyroid cancer. Methods The expression of Anxa2 in thyroid cancer was retrieved from bioinformatics data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Additionally, 16 paired papillary thyroid carcinoma (PTC) tissue samples and another three unpaired PTC tissues were collected from Taipei Medical University (TMU), and commercially available complementary (c)DNA and tissue arrays of thyroid cancer were also obtained. Results Anxa2 mRNA expression was increased in PTC in datasets of the GEO database. Additionally, the Anxa2 transcript was increased in PTC, and its expression related to the BRAF mutation, a young age onset, tumor size, lymph node invasion, and advanced disease in the TCGA database. Moreover, the increase in Anxa2 messenger (m)RNA in PTC was also validated from both a TMU cohort (PTC=19, normal=16, p<0.001) and a commercial cDNA array (PTC=32, normal=5; p<0.001). In the cDNA array analysis, Anxa2 mRNA levels were associated with tumor expansion (p=0.013) and advanced staging (p=0.044). However, despite the Anxa2 protein being increased in PTC (PTC=36, normal=8; p<0.001), no significant associations with tumor staging or extent (p=0.053) were observed. Conclusions Anxa2 transcript and protein expressions were upregulated in PTC. Its expression levels were associated with unfavorable clinical parameters. Further, well-designed studies are needed to clarify the underlying mechanisms of Anxa2 in thyroid tumorigenesis.

Objectives Although immunotherapy improves the prognosis of many current advanced malignancies, many patients still do not respond or develop resistance after immunotherapy. The key point of cancer immunotherapy is whether the immune system can recognize the tumor as a foreign body. However, lung adenocarcinoma (LUAD) is a tumor with weak immunogenicity, and many patients do not benefit from immunotherapy. This study aimed to optimize the adoptive cell immunotherapy process and propose a new pipeline for LUAD immunotherapy. Methods This study optimized the process of adoptive cell immunotherapy by adding individualized and enhanced whole tumor cell antigens (WTCAs) modified by chemotherapeutics, irradiation, or freezing. Venous blood from lung adenocarcinoma patients was collected to extract peripheral blood mononuclear cells (PBMCs). This study also verified the efficacy of the new strategy for LUAD immunotherapy by Flow Cytometry analysis, EdU proliferation assay, Annexin V-FITC/PI apoptosis assay, and Animal models in vivo and in vitro , etc. Results WTCAs could enhance the proliferation of immune-effective CD8 + cells and inhibit the apoptosis of immune-effective CD8 + cells, especially for X-ray-induced WTCA. The efficacy of WTCAs-induced cell immunotherapy for LUAD in vitro and vivo was prominent. Tumor size was significantly reduced by adoptive cell immunotherapy, whether specific or non-specific. In contrast, WTCAs-induced immune cells induced by 4 Gy X-ray irradiation or high-dose cisplatin (10 μg/mL) had a more effective tumor inhibition capability than all other groups (p<0.001). Conclusion The adoptive tumor-specific immune cells activated by X-ray-induced WTCA could elicit the most effective tumor inhibition. This study provides new ideas for future individualized cell immunotherapy of LUAD.

Objectives The incidence of colorectal cancer (CRC) continues to rise steadily, imposing a substantial disease burden on countries worldwide. This study aims to analyze the changing trends in CRC disease burden attributed to dietary risk factors, providing a foundation for strategies to mitigate the burden of CRC arising from dietary influences. Methods Using data from the Global Burden of Disease (GBD) 2021 study, CRC mortality rates and Disability-Adjusted Life Years (DALYs) attributed to specific dietary risk factors (including diets low in calcium, milk, whole grains, or fiber, and diets high in red meat and processed meat) were analyzed across five countries: the United States, Italy, China, Japan, India. The average annual percentage change (AAPC) was calculated using Joinpoint 5.0 software to illustrate the variations in CRC burden across different time frames and age groups. Results In 2021, dietary risk factors contributed to more than 65 % of the age-standardized mortality rate (ASMR) for CRC across the five countries. From 1990 to 2021, ASMR and age-standardized DALYs attributable to dietary risks for CRC declined across five countries: the United States [AAPC (95 % CI): −1.52 (−1.64, −1.40), −1.23 (−1.49, −0.97)], Italy [AAPC (95 % CI): −1.05 (−1.15, −0.95), −1.19 (−1.28, −1.10)], China [AAPC (95 % CI): −0.81 (−0.99, −0.63), −0.88 (−1.03, −0.72)], Japan [AAPC (95 % CI): −0.54 (−0.73, −0.36), −0.66 (−0.89, −0.42)], and India [AAPC (95 % CI): −0.03 (−0.41, 0.35), −0.19 (−0.34, −0.03)]. The United States and Italy demonstrated the most significant reductions in CRC disease burden related to diets low in milk (AAPC: −1.77 vs. −1.87), whole grain (AAPC: −1.28 vs. −1.13), and high in red meat (AAPC: −1.27 vs. −1.18) and processed meat (AAPC: −0.86 vs. −0.98) (p<0.05). Conversely, China and Japan experienced a higher CRC disease burden linked to diets low in calcium (AAPC: −3.07 vs. −0.91) and milk (AAPC: −0.58 vs. −0.78) (p<0.05). Notably, in the United States, CRC burden exhibited a trend toward affecting younger populations. Conclusions Poor dietary habits significantly contribute to the CRC disease burden, with diets low in milk and whole grains, and high in meat identified as major risk factors. Promoting healthy eating habits is essential to reduce this burden and improve public health outcomes.

Objectives It is unclear how body mass index (BMI) affects individuals with hepatocellular carcinoma (HCC) receiving lenvatinib and programmed death receptor 1 (PD-1) inhibitors and transcatheter arterial chemoembolization (TACE). This study aims to evaluate the impact of BMI on the efficacy and safety of TACE with systemic therapies in HCC patients. Methods A retrospective analysis was performed involving 102 patients receiving TACE alongside lenvatinib and PD-1 inhibitors. Key endpoints, including overall survival (OS) and progression-free survival (PFS), were analyzed, comparing overweight (BMI≥24 kg/m 2 ) and non-overweight (BMI<24 kg/m 2 ) individuals. Prognostic variables for OS and PFS were identified through Cox regression analyses (univariable and multivariable). The nonlinear association between mortality risk and BMI was evaluated using the RCS curve. A subgroup analysis was conducted to determine whether diabetes affects the survival of HCC patients in various BMI groups. Results The overweight group showed longer median OS (23.82 vs. 12.45 months, p=0.028) and median PFS (15.01 vs. 10.02 months, p=0.035) than the non-overweight group. Multivariable Cox analysis revealed that being overweight was a protective prognostic factor for OS and PFS. A U-shaped correlation between BMI and mortality risk was identified, with the risk reaching its nadir at a BMI of 24.13–26.37 kg/m 2 . However, the study’s retrospective design and small sample size limit the generalizability of these findings. Conclusion Being overweight was related to improved OS and PFS in HCC patients receiving TACE plus lenvatinib and PD-1 inhibitors. In individuals with HCC, a BMI between 24.13 and 26.37 is protective for OS.

Objectives Among the large number of members in the aldo-keto reductase families, aldo-keto reductase family one member C3 (AKR1C3) has been identified as a key player in hepatocellular carcinoma (HCC) progression, yet the specific regulatory mechanisms are still being unraveled. We aimed to validate the effects of AKR1C3 on cholesterol and bile acid (BA) metabolism both in vivo and in vitro , and to investigate its novel mechanisms in HCC progression. Methods The differential expression of AKR1C3 in HCC and normal liver tissues was assessed using a public database and validated through cell experiments. The effects of AKR1C3 on liver cancer cell proliferation, migration, and invasion were verified using a cell counting kit-8 (CCK-8) assay, a plate clone formation experiment, and Transwell assays. The specific mechanism was predicted by RNA sequencing, and pathway proteins were validated by western blotting. Subcutaneous tumor formation experiments were used to confirm the effect of AKR1C3 on liver cancer proliferation in nude mice. Furthermore, the effect of AKR1C3 on lung metastasis was evaluated through the pulmonary metastasis model. Results AKR1C3 is overexpressed in liver cancer and is positively correlated with poor prognosis. HCC cells showed a marked reduction in both proliferative activity and metastatic potential (migration and invasion) after AKR1C3 knockdown. RNA sequencing suggested that AKR1C3 was involved in cholesterol and BA metabolism. Western blotting showed that AKR1C3 promoted the expression of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase (HMGCR) and cholesterol 7α-hydroxylase (CYP7A1). Subsequently, knocking down AKR1C3 decreased cholesterol and BA levels. In vivo experiments confirmed that AKR1C3 knockdown inhibits tumor growth, suppresses lung metastasis, and lowers cholesterol and BA levels. Conclusions AKR1C3 promotes cholesterol and BA synthesis through the HMGCR–CYP7A1 axes, thus accelerating liver cancer pathogenesis.

Objectives The first-line treatment for castration-resistant prostate cancer (CRPC) is docetaxel (Doc); nevertheless, chemoresistance frequently occurs. Inhibitors of programmed cell death protein-1 (PD-1) can prevent immunological escape mediated by programmed cell death ligand-1 (PD-L1). Although the synergistic effect of propranolol (Pro) with PD-1 inhibitors has been demonstrated in melanoma, Pro’s role in Doc-resistant prostate cancer has yet to be investigated. Here, this study aimed to investigate how Pro regulates PD-L1 in Doc-resistant prostate cancer cells. Methods Bioinformatics was used to analyze PD-L1 expression and its correlation with β-adrenergic receptor (β-AR). Doc-resistant prostate cancer cells were constructed using a concentration-escalation method, and CCK-8 and colony formation assays were used to verify the construct status. The expression of PD-L1 was examined using flow cytometry and RT-qPCR. Additionally, a co-culture system was established to analyze changes in cytokines using ELISA and to assess apoptosis by flow cytometry. Results We established docetaxel-resistant PC3 and DU145 cell lines, which exhibited significantly upregulated PD-L1 expression (42.5 % increase in PC3-DR, p<0.05; 46.4 % in DU-DR, p<0.0001) by flow cytometry. Propranolol treatment induced apoptosis in resistant cells (47.8 % increase in PC3-DR, p<0.01; 67.3 % in DU-DR, p<0.01) and reduced IFN-γ secretion in co-culture systems (16.7 % decrease in PC3-DR, p<0.01; 24.3 % in DU-DR). Notably, Pro downregulated PD-L1 expression (6.9 % in PC3-DR, p<0.05; 3.9 % in DU-DR, p<0.01), and its combination with anti-PD-1 enhanced apoptosis vs. anti-PD1 alone (19.3 % increase in PC3-DR, p<0.0001; 41.1 % in DU-DR, p<0.01). These results imply that, especially in patients with PD-L1 overexpression, the Pro/anti-PD-1 combination may provide a unique treatment approach for Doc-resistant prostate cancer. Conclusions This research in docetaxel-resistant prostate cancer demonstrated that Pro decreases PD-L1 expression in Docetaxel-Resistant prostate cells, suggesting a potential immunotherapy approach.