Amplifying cancer treatment: advances in tumor immunotherapy and nanoparticle-based hyperthermia

In the quest for cancer treatment modalities with greater effectiveness, the combination of tumor immunotherapy and nanoparticle-based hyperthermia has emerged as a promising frontier. The present article provides a comprehensive review of recent advances and cutting-edge research in this burgeoning field and examines how these two treatment strategies can be effectively integrated. Tumor immunotherapy, which harnesses the immune system to recognize and attack cancer cells, has shown considerable promise. Concurrently, nanoparticle-based hyperthermia, which utilizes nanotechnology to promote selective cell death by raising the temperature of tumor cells, has emerged as an innovative therapeutic approach. While both strategies have individually shown potential, combination of the two modalities may amplify anti-tumor responses, with improved outcomes and reduced side effects. Key studies illustrating the synergistic effects of these two approaches are highlighted, and current challenges and future prospects in the field are discussed. As we stand on the precipice of a new era in cancer treatment, this review underscores the importance of continued research and collaboration in bringing these innovative treatments from the bench to the bedside

Polyadenosine diphosphate-ribose polymerase inhibitors: advances, implications, and challenges in tumor radiotherapy sensitization

Polyadenosine diphosphate-ribose polymerase (PARP) is a key modifying enzyme in cells, which participates in single-strand break repair and indirectly affects double-strand break repair. PARP inhibitors have shown great potential in oncotherapy by exploiting DNA damage repair pathways, and several small molecule PARP inhibitors have been approved by the U.S. Food and Drug Administration for treating various tumor types. PARP inhibitors not only have significant antitumor effects but also have some synergistic effects when combined with radiotherapy; therefore they have potential as radiation sensitizers. Here, we reviewed the advances and implications of PARP inhibitors in tumor radiotherapy sensitization. First, we summarized the multiple functions of PARP and the mechanisms by which its inhibitors exert antitumor effects. Next, we discuss the immunomodulatory effects of PARP and its inhibitors in tumors. Then, we described the theoretical basis of using PARP inhibitors in combination with radiotherapy and outlined their importance in oncological radiotherapy. Finally, we reviewed the current challenges in this field and elaborated on the future applications of PARP inhibitors as radiation sensitizers. A comprehensive understanding of the mechanism, optimal dosing, long-term safety, and identification of responsive biomarkers remain key challenges to integrating PARP inhibition into the radiotherapy management of cancer patients. Therefore, extensive research in these areas would facilitate the development of precision radiotherapy using PARP inhibitors to improve patient outcomes

Involved-field irradiation or elective-nodal irradiation in neoadjuvant chemo-radiotherapy for locally-advanced esophageal cancer: comprehensive analysis for dosimetry, treatment-related complications, impact on lymphocyte, patterns of failure and survival

PurposeTo compare the differences between involved-field irradiation (IFI) and elective nodal irradiation (ENI) in selecting the optimal target area for neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC).Materials and methodsWe retrospectively analyzed 267 patients with LA-ESCC, of whom 165 underwent ENI and 102 underwent IFI. Dosimetry, treatment-related complications, pathological responses, recurrence/metastasis patterns, and survival were compared between the two groups.ResultsThe median follow-up duration was 27.9 months. The R0 resection rates in the IFI and ENI groups were 95.1% and 92.7%, respectively (p=0.441), while the pathological complete response (pCR) rates were 42.2% and 34.5%, respectively (p=0.12). The ENI group received higher radiation doses to the heart (HV30:23.9% vs. 18%, p=0.033) and lungs (LV30:7.7% vs. 4.9%, p<0.001) than the IFI group. Consequently, the ENI group showed a higher incidence of grade 2 or higher radiation pneumonitis (30.3% vs. 17.6%, p=0.004) and pericardial effusion (26.7% vs. 11.8%, p=0.021) than the IFI group. Post-operation fistulas were observed in 3 (2.9%) and 17 cases (10.3%) in the IFI and ENI groups, respectively (p=0.026). In the multivariate analysis, smoking, positive lymph node involvement (pN+), and anastomotic fistula were independent predictors of overall survival (OS). The pN+ patients exhibited a greater propensity for recurrence compared to pN- patients, especially in the first year of follow-up (6.67% vs. 0.56%, p=0.003).ConclusionThe ENI group had a higher incidence of radiation-induced adverse events compared to the IFI group, likely due to the higher radiation doses to normal tissues. Considering the similar disease-free survival (DFS) and OS rates in the two groups, IFI may be suitable for nCRT in patients with LA-ESCC, although further prospective studies are warranted

Prognostic significance of cyclin-dependent kinase subunit 2 (CKS2) in malignant tumours: a meta-analysis and bioinformatic analysis

Objectives This study aimed to systematically elucidate the prognostic significance of cyclin-dependent kinase subunit 2 (CKS2) expression in various cancers and its correlation with their clinicopathological characteristics.Design In this meta-analysis and bioinformatic analysis, articles were identified through searches of multiple databases and meta-analysed according to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols. Data from The Cancer Genome Atlas were examined using UCSC Xena tools to further confirm the prognostic effect of CKS2.Data sources The PubMed, Embase, Web of Science and Cochrane Library databases were searched for articles published from their inception to 1 January 2023, using a combination of subject terms and free words, including ‘CKS2’, ‘cancer’, ‘tumor’, ‘neoplasm’, ‘carcinoma’, ‘malignancy’ and ‘prognosis’.Eligibility criteria The analysis included cohort or case–control studies, reported in English, with malignancy diagnoses confirmed by pathological methods, available HRs and 95% CIs for overall survival (OS) or extractable Kaplan-Meier curves, and a sample size of ≥20 patients. Reviews, commentaries, letters, conference reports, case reports, in vitro and animal studies, studies of CKS2 gene variants, studies with sample cases from public databases and studies with unavailable survival or duplicated data were excluded.Data extraction and synthesis Two researchers independently screened the articles, extracted the data and evaluated the quality of included studies using the Newcastle-Ottawa Scale. Meta-analysis and bioinformatic analyses were performed using the STATA and R software, respectively.Results The analysis included 13 retrospective studies encompassing 1348 cases across 10 cancer types. Nine studies involving 1124 patients examined the correlation between CKS2 expression levels and OS. A fixed-effects model analysis revealed a significant association between high CKS2 expression and reduced OS (HR=2.27, 95% CI=1.87 to 2.77, p<0.001). Furthermore, high CKS2 expression was significantly associated with advanced tumour stage (relative risk (RR) = 1.82, 95% CI=1.57 to 2.11, p<0.001), lymph node metastasis (RR=1.68, 95% CI=1.38 to 2.04, p<0.001), larger tumour size (RR=1.60, 95% CI=1.27 to 2.03, p<0.001) and lower differentiation grade (RR=1.57, 95% CI=1.29 to 1.90, p<0.001). CKS2 expression levels were not significantly correlated with patients’ age (RR=1.11, 95% CI=0.99 to 1.26, p=0.071) or sex (RR=0.98, 95% CI=0.90 to 1.07, p=0.653). An assessment of the articles showed no significant publication bias, confirming the robustness of these findings. The bioinformatic analysis further confirmed CKS2 upregulation in the examined cancer types and its association with poor OS in glioma (HR=1.97, 95% CI=1.78 to 2.18, p=3.70×10−42), liver hepatocellular carcinoma (HR=1.56, 95% CI=1.31 to 1.86, p=3.50×10−7) and lung adenocarcinoma (HR=1.27, 95% CI=1.10 to 1.48, p=1.70×10−3).Conclusions Elevated CKS2 expression is associated with poor prognosis in a subset of malignant tumours, highlighting its potential as a prognostic marker.PROSPERO registration number CRD42023394038

The pathogenesis and diagnosis of sepsis post burn injury

10.1093/burnst/tkaa047Burns and Trauma9tkaa04

Adjuvant gamma knife surgery and image-guided, intensity-modulated radiation therapy for the treatment of sacral chordomas

AimThe aim of this study was to confirm whether patients with sacral chordoma benefit from adjuvant radiotherapy and to determine the optimal photon radiotherapy module for comprehensive treatment.BackgroundChordoma is a rare slow-growing neoplasm arisen from cellular remnants of the notochord. About 50% occur in the sacrococcygeal region. Surgical resection and adjuvant radiation therapy are recommended treatment due to the improving local control rate.Materials and methods118 patients treated by surgery and adjuvant radiotherapy from August 2003 to May 2015 were retrospectively analyzed. All patients received surgical resection after diagnosis. Among these patients, 44 were treated by exclusive surgery, and 48 were treated with adjuvant image-guided, intensity-modulated radiation therapy (IG-IMRT). In addition, 26 patients were treated with gamma knife surgery (GKS) after surgical resection. The median follow-up was 54 months for all patients. Kaplan–Meier analysis was used to calculate recurrence-free survival (RFS) overall survival (OS).ResultsPatients treated with adjuvant radiotherapy had better RFS (p=0.014) than those treated exclusively by surgery. The patients in the IG-IMRT group exhibited better recurrence-free survival (p=0.01) than the GKS group. Moreover, in the IG-IMRT group, patients treated by higher dose were associated with better RFS (p=0.04). No significant difference in OS was found. No grade 3 late toxicity was found.ConclusionsWe confirmed that adjuvant radiotherapy improved RFS but not OS in sacral chordoma patients after surgery. Furthermore, favorable RFS and low adverse event rates were observed following IG-IMRT. Our results suggest that high dose IG-IMRT is an appropriate module of adjuvant radiotherapy for sacral chordoma patients

Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies

Reprogramming of glucose metabolism provides sufficient energy and raw materials for the proliferation, metastasis, and immune escape of cancer cells, which is enabled by glucose metabolism-related enzymes that are abundantly expressed in a broad range of cancers. Therefore, targeting glucose metabolism enzymes has emerged as a promising strategy for anticancer drug development. Although several glucose metabolism modulators have been approved for cancer treatment in recent years, some limitations exist, such as a short half-life, poor solubility, and numerous adverse effects. With the rapid development of medicinal chemicals, more advanced and effective glucose metabolism enzyme-targeted anticancer drugs have been developed. Additionally, several studies have found that some natural products can suppress cancer progression by regulating glucose metabolism enzymes. In this review, we summarize the mechanisms underlying the reprogramming of glucose metabolism and present enzymes that could serve as therapeutic targets. In addition, we systematically review the existing drugs targeting glucose metabolism enzymes, including small-molecule modulators and natural products. Finally, the opportunities and challenges for glucose metabolism enzyme-targeted anticancer drugs are also discussed. In conclusion, combining glucose metabolism modulators with conventional anticancer drugs may be a promising cancer treatment strategy

Solvent-pair surfactants enabled assembly of clusters and copolymers towards programmed mesoporous metal oxides

Abstract Organic-inorganic molecular assembly has led to numerous nano/mesostructured materials with fantastic properties, but it is dependent on and limited to the direct interaction between host organic structure-directing molecules and guest inorganic species. Here, we report a “solvent-pair surfactants” enabled assembly (SPEA) method to achieve a general synthesis of mesostructured materials requiring no direct host-guest interaction. Taking the synthesis of mesoporous metal oxides as an example, the dimethylformamide/water solvent pairs behave as surfactants and induce the formation of mesostructured polyoxometalates/copolymers nanocomposites, which can be converted into metal oxides. This SPEA method enables the synthesis of functional ordered mesoporous metal oxides with different pore sizes, structures, compositions and tailored pore-wall microenvironments that are difficult to access via conventional direct organic-inorganic assembly. Typically, nitrogen-doped mesoporous ε-WO3 with high specific surface area, uniform mesopores and stable framework is obtained and exhibits great application potentials such as gas sensing