Assessing the Impact of Charged Particle Radiation Therapy for Head and Neck Adenoid Cystic Carcinoma: A Systematic Review and Meta-Analysis.

Purpose: Head and neck adenoid cystic carcinoma (HNACC) is a radioresistant tumor. Particle therapy, primarily proton beam therapy and carbon-ion radiation, is a potential radiotherapy treatment for radioresistant malignancies. This study aims to conduct a meta-analysis to evaluate the impact of charged particle radiation therapy on HNACC. Methods: A comprehensive search was conducted in Pubmed, Cochrane Library, Web of Science, Embase, and Medline until December 31, 2022. The primary endpoints were overall survival (OS), local control (LC), and progression-free survival (PFS), while secondary outcomes included treatment-related toxicity. Version 17.0 of STATA was used for all analyses. Results: A total of 14 studies, involving 1297 patients, were included in the analysis. The pooled 5-year OS and PFS rates for primary HNACC were 78% (95% confidence interval [CI] = 66-91%) and 62% (95% CI = 47-77%), respectively. For all patients included, the pooled 2-year and 5-year OS, LC, and PFS rates were as follows: 86.1% (95% CI = 95-100%) and 77% (95% CI = 73-82%), 92% (95% CI = 84-100%) and 73% (95% CI = 61-85%), and 76% (95% CI = 68-84%) and 55% (95% CI = 48-62%), respectively. The rates of grade 3 and above acute toxicity were 22% (95% CI = 13-32%), while late toxicity rates were 8% (95% CI = 3-13%). Conclusions: Particle therapy has the potential to improve treatment outcomes and raise the quality of life for HNACC patients. However, further research and optimization are needed due to the limited availability and cost considerations associated with this treatment modality.

Effect of 1,4-Dioxane Solvent on ß-Glucuronidation Using Methyl 1,2,3,4-Tetra-O-acetyl-ß-D-glucuronate as the Glycosyl Donor.

A facile and selective ß-D-glucuronidation of alcohols, such as (-)-menthol, cholestanol, (+)- and (-)-borneols, and 2-adamantanol, using commercially available methyl 1,2,3,4-tetra-O-acetyl-ß-D-glucuronate as the glycosyl donor and trimethylsilyl bis(trifluoromethanesulfonyl)imide (Tf2NTMS) (0.5 equivalent) as the activator in 1,4-dioxane at 60 °C gave products in moderate yields. The addition of MS4A increased the ß : α ratios of D-glucuronides when cholestanol, (+)-borneol, and 2-adamantanol were used as the acceptor substrate.

UBA2 as a Prognostic Biomarker and Potential Therapeutic Target in Glioma.

BACKGROUND: Gliomas are characterized by aggressive behavior, leading to severe disability and high mortality. Ubiquitin-like modifier activating enzyme 2 (UBA2) is a subunit of the E1-activating enzyme involved in the SUMOylation (SUMO, small ubiquitin-related modifier) of numerous proteins. Although the abnormality of UBA2 is linked to the progression of various tumor types, the role of UBA2 in glioma is still unknown. METHODS: A bioinformatic analysis using several public databases was conducted to examine the expression level, clinicopathological correlations, and prognostic significance of UBA2 in glioma. The correlation between UBA2 expression and drug sensitivity in cancers was also explored. Multiple cellular experiments were conducted to validate the role of UBA2 in glioma. RESULTS: Analysis of multiple databases and cellular experiments revealed that UBA2 was overexpressed in glioma tissues and cell lines, respectively. UBA2 expression in gliomas correlated with World Health Organization (WHO) grade, IDH gene status, 1p19q deletion, histological type, and immune cell infiltration in glioma. UBA2 expression in carcinomas also correlated with drug sensitivity. Kaplan-Meier analysis revealed that high expression of UBA2 predicted poorer survival in glioma patients. A nomogram model containing UBA2 expression was constructed for clinical practice. Knockdown of UBA2 was observed to suppress glioma cell progression and sensitize glioma cells to irradiation in vitro. CONCLUSION: Overall, this research showed that UBA2 might be involved not only in the development of glioma but also in the regulation of immunity, drug sensitivity, and radiosensitivity. Therefore, UBA2 may be a potential target for therapy and a candidate biomarker for glioma diagnosis and prognosis.

Carbon ion irradiation combined with PD-1 inhibitor trigger abscopal effect in Lewis lung cancer via a threshold dose.

Background and goal: Carbon ion beam is radio-biologically more efficient than photons and is beneficial for treating radio-resistant tumors. Several animal experiments with tumor-bearing suggest that carbon ion beam irradiation in combination with immunotherapy yields better results, especially in controlling distant metastases. This implies that carbon ion induces a different anti-tumor immune response than photon beam. More complex molecular mechanisms need to be uncovered. This in vivo and in vitro experiment was carried out in order to examine the radio-immune effects and the mechanism of action of carbon ion beam versus X-ray in combination with PD-1 inhibitors. Methods and Materials: Lewis lung adenocarcinoma cells and C57BL/6 mice were used to create a tumor-bearing mouse model, with the non-irradiated tumor growing on the right hind leg and the irradiated tumor on the left rear. 10Gy carbon ion beam or X-ray radiation, either alone or in combination with PD-1 inhibitor, were used to treat the left back tumor. The expression of molecules linked to immunogenicity and the infiltration of CD8+ T lymphocytes into tumor tissues were both identified using immunohistochemistry. IFN-ß in mouse serum was measured using an ELISA, while CD8+ T cells in mouse peripheral blood were measured using flow cytometry. Lewis cells were exposed to different dose of X-ray and carbon ion. TREX1, PD-L1, and IFN-ß alterations in mRNA and protein levels were identified using Western blot or RT-PCR, respectively. TREX1 knockdown was created by siRNA transfection and exposed to various radiations. Using the CCK8 test, EdU assay, and flow cytometry, changes in cell viability, proliferation, and apoptosis rate were discovered. Results: Bilateral tumors were significantly inhibited by the use of carbon ion or X-ray in combination with PD-1, particularly to non-irradiated tumor(p<0.05). The percentage of infiltrating CD8+ T cells and the level of IFN-ß expression were both raised by 10Gy carbon ion irradiation in the irradiated side tumor, although PD-L1 and TREX1 expression levels were also elevated. Lewis cell in vitro experiment further demonstrated that both X-ray and carbon ion irradiation can up-regulate the expression levels of PD-L1 and TREX1 with dose-dependent in tumors, particularly the trend of up-regulation TREX1 is more apparent at a higher dose in carbon ion, i.e. 8 or 10Gy, while the level of IFN-ß is decreased. IFN-ß levels were considerably raised under hypofractionated doses of carbon ion radiation by gene silencing TREX1. Conclusions: By enhancing tumor immunogenicity and increasing CD8+T infiltration in TME through a threshold dosage, X-ray or carbon ion radiation and PD-1 inhibitors improve anti-tumor activity and cause abscopal effect in Lewis lung adenocarcinoma-bearing mice. TREX1 is a possible therapeutic target and prognostic marker.

Facile Preparation of L-Iduronic Acid and α-L-Iduronidation Using Methyl 1,2,3,4-Tetra-O-acetyl-α-L-iduronate as Glycosyl Donor.

Methyl 1,2,3,4-tetra-O-acetyl-α-L-iduronate was prepared from methyl 1,2,3,4-tetra-O-ß-D-glucuronate in two steps: Ferrier's photobromination and subsequent radical reduction with tris(trimethylsilyl)silane. The obtained methyl 1,2,3,4-tetra-O-acetyl-α-L-iduronate was a good glycosyl donor for the L-iduronidation when bis(trifluoromethanesulfonic)imide was employed as the activator. The reaction afforded the α-isomer as the major product, the configuration of which is the same as that of the L-iduronic acid unit in heparin and heparan sulfate.

Efficacy and safety of particle therapy for inoperable stage II-III non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Particle therapy, mainly including carbon-ion radiotherapy (CIRT) and proton beam therapy (PBT), has dose distribution advantages compared to photon radiotherapy. It has been widely reported as a promising treatment method for early non-small cell lung cancer (NSCLC). However, its application in locally advanced non-small cell lung cancer (LA-NSCLC) is relatively rare, and its efficacy and safety are inconclusive. This study aimed to provide systematic evidence for evaluating the efficacy and safety of particle therapy for inoperable LA-NSCLC. METHODS: To retrieve published literature, a systematic search was conducted in PubMed, Web of Science, Embase, and Cochrane Library until September 4, 2022. The primary endpoints were local control (LC) rate, overall survival (OS) rate, and progression-free survival (PFS) rate at 2 and 5 years. The secondary endpoint was treatment-related toxicity. The pooled clinical outcomes and 95% confidence intervals (CIs) were calculated by using STATA 15.1. RESULTS: Nineteen eligible studies with a total sample size of 851 patients were included. The pooled data demonstrated that the OS, PFS, and LC rates at 2 years of LA-NSCLC treated by particle therapy were 61.3% (95% CI = 54.7-68.7%), 37.9% (95% CI = 33.8-42.6%) and 82.2% (95% CI = 78.7-85.9%), respectively. The pooled 5-year OS, PFS, and LC rates were 41.3% (95% CI = 27.1-63.1%), 25.3% (95% CI = 16.3-39.4%), and 61.5% (95% CI = 50.7-74.6%), respectively. Subgroup analysis stratified by treatment type showed that the concurrent chemoradiotherapy (CCRT, PBT combined with concurrent chemotherapy) group had better survival benefits than the PBT and CIRT groups. The incidence rates of grade 3/4 esophagitis, dermatitis, and pneumonia in LA-NSCLC patients after particle therapy were 2.6% (95% CI = 0.4-6.0%), 2.6% (95% CI = 0.5-5.7%) and 3.4% (95% CI = 1.4-6.0%), respectively. CONCLUSIONS: Particle therapy demonstrated promising efficacy and acceptable toxicity in LA-NSCLC patients.

Biological effects of cancer stem cells irradiated by charged particle: a systematic review of in vitro studies.

PURPOSE: The existence of cancer stem cells (CSCs) is closely related to tumor recurrence, metastasis, and resistance to chemoradiotherapy. In addition, given the unique physical and biological advantages of charged particle, we hypothesized that charged particle irradiation would produce strong killing effects on CSCs. The purpose of our systematic review is to evaluate the biological effects of CSCs irradiated by charged particle, including proliferation, invasion, migration, and changes in the molecular level. METHODS: We searched PubMed, EMBASE, and Web of Science until 17 march 2022 according to the key words. Included studies have to be vitro studies of CSCs irradiated by charged particle. Outcomes included one or more of radiation sensitivity, proliferation, metastasis, invasion, and molecular level changes, like DNA damage after been irradiated. RESULTS: Eighteen studies were included in the final analysis. The 18 articles include 12-carbon ion irradiation, 4-proton irradiation, 1 α-particle irradiation, 1-carbon ion combine proton irradiation. CONCLUSION: Through the extraction and analysis of data, we came to this conclusion: CSCs have obvious radio-resistance compared with non-CSCs, and charged particle irradiation or in combination with drugs could overcome this resistance, specifically manifested in inhibiting CSCs' proliferation, invasion, migration, and causing more and harder to repair DNA double-stranded breaks (DSB) of CSCs.

Does particle radiation have superior radiobiological advantages for prostate cancer cells? A systematic review of in vitro studies.

BACKGROUND: Charged particle beams from protons to carbon ions provide many significant physical benefits in radiation therapy. However, preclinical studies of charged particle therapy for prostate cancer are extremely limited. The aim of this study was to comprehensively investigate the biological effects of charged particles on prostate cancer from the perspective of in vitro studies. METHODS: We conducted a systematic review by searching EMBASE (OVID), Medline (OVID), and Web of Science databases to identify the publications assessing the radiobiological effects of charged particle irradiation on prostate cancer cells. The data of relative biological effectiveness (RBE), surviving fraction (SF), standard enhancement ratio (SER) and oxygen enhancement ratio (OER) were extracted. RESULTS: We found 12 studies met the eligible criteria. The relative biological effectiveness values of proton and carbon ion irradiation ranged from 0.94 to 1.52, and 1.67 to 3.7, respectively. Surviving fraction of 2 Gy were 0.17 ± 0.12, 0.55 ± 0.20 and 0.53 ± 0.16 in carbon ion, proton, and photon irradiation, respectively. PNKP inhibitor and gold nanoparticles were favorable sensitizing agents, while it was presented poorer performance in GANT61. The oxygen enhancement ratio values of photon and carbon ion irradiation were 2.32 ± 0.04, and 1.77 ± 0.13, respectively. Charged particle irradiation induced more G0-/G1- or G2-/M-phase arrest, more expression of γ-H2AX, more apoptosis, and lower motility and/or migration ability than photon irradiation. CONCLUSIONS: Both carbon ion and proton irradiation have advantages over photon irradiation in radiobiological effects on prostate cancer cell lines. Carbon ion irradiation seems to have further advantages over proton irradiation.

EZH2 as a Prognostic Factor and Its Immune Implication with Molecular Characterization in Prostate Cancer: An Integrated Multi-Omics in Silico Analysis.

Prostate cancer (PCa) is a type of potentially fatal malignant tumor. Immunotherapy has shown a lot of potential for various types of solid tumors, but the benefits have been less impressive in PCa. Enhancer of zeste homolog 2 (EZH2) is one of the three core subunits of the polycomb repressive complex 2 that has histone methyltransferase activity, and the immune effects of EZH2 in PCa are still unclear. The purpose of this study was to explore the potential of EZH2 as a prognostic factor and an immune therapeutic biomarker for PCa, as well as the expression pattern and biological functions. All analyses in this study were based on publicly available databases, mainly containing Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), UCSCXenaShiny, and TISIDB. We performed differential expression analysis, developed a prognostic model, and explored potential associations between EZH2 and DNA methylation modifications, tumor microenvironment (TME), immune-related genes, tumor mutation burden (TMB), tumor neoantigen burden (TNB), and representative mismatch repair (MMR) genes. We also investigated the molecular and immunological characterizations of EZH2. Finally, we predicted immunotherapeutic responses based on EZH2 expression levels. We found that EZH2 was highly expressed in PCa, was associated with a poor prognosis, and may serve as an independent prognostic factor. EZH2 expression in PCa was associated with DNA methylation modifications, TME, immune-related genes, TMB, TNB, and MMR. By gene set enrichment analysis and gene set variation analysis, we found that multiple functions and pathways related to tumorigenesis, progression, and immune activation were enriched. Finally, we inferred that immunotherapy may be more effective for PCa patients with low EZH2 expression. In conclusion, our study showed that EZH2 could be a potentially efficient predictor of prognosis and immune response in PCa patients.

A Facile α-Glucuronidation Using Methyl 1,2,3,4-Tetra-O-acetyl-D-glucuronate as Glycosyl Donor.

Some terpenyl 2,3,4-tri-O-acetyl-α-D-glucuronide methyl esters were facilely synthesized from commercially available methyl 1,2,3,4-tetra-O-acetyl-ß-D-glucuronate and terpenoid alcohols in the presence of bis(trifluoromethanesulfonyl)imide (Tf2NH) in dichloromethane (DCM) in good yields. The predominant α-selectivity at the anomer position is caused via transition state in which the neighboring group participation of the methoxycarbonyl group at C-6 stabilizes the oxonium intermediate by forming 1C4 conformation. The intermediate accelerates the glucuronidation reaction despite the use of the acetyl group, which is not a good activating group in general glycosylation reactions, as the activating group.

Brain metastases of lung cancer: comparison of survival outcomes among whole brain radiotherapy, whole brain radiotherapy with consecutive boost, and simultaneous integrated boost.

PURPOSE: Radiotherapy is the mainstay for treating brain metastasis (BM). The objective of this study is to evaluate the overall survival (OS) of patients with BM of lung cancer treated with different radiotherapy modalities. METHODS: Patients with BM of lung cancer who underwent radiotherapy between July 2007 and November 2017 were collected, and their baseline demographics, clinicopathological characteristics and treatments were recorded. Survival was estimated by the Kaplan-Meier method and compared by using the log-rank test. Univariate and multivariate analysis of the prognostic factors were performed using the Cox proportional hazard regression model. RESULTS: A total of 144 patients were enrolled, of whom 77 underwent whole-brain radiotherapy (WBRT), 39 underwent whole brain radiotherapy with consecutive boost (WBRT + boost), and 28 underwent integrated simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT). The OS in SIB-IMRT group was significantly longer than that in WBRT group (median OS 14 (95% confidence interval [CI] 8.8-19.1) vs.7 (95% CI 5.5-8.5) months, log-rank p < 0.001) and WBRT + boost group (median OS: 14 (95% CI 8.8-19.1) vs.11 (95% CI 8.3-13.7) months, log-rank p = 0.037). Multivariable analysis showed that mortality risk of patients treated with SIB-IMRT decrease by 56, 59, 64 and 64% in unadjusted model (hazard ratio [HR] = 0.44; 95% CI 0.28-0.70, p < 0.001), model 1 (HR = 0.41; 95% CI 0.26-0.65, p < 0.001), model 2 (HR = 0.36; 95% CI 0.21-0.61, p < 0.001), and model 3 (HR = 0.36; 95% CI 0.21-0.61, p < 0.001). CONCLUSIONS: For patients with BM of lung cancer, SIB-IMRT seems to be associated with a more favorable prognosis.

RALY may cause an aggressive biological behavior and a dismal prognosis in non-small-cell lung cancer.

RALY is a member of the heterogeneous nuclear ribonucleoprotein (hnRNP), an RNA-binding protein that plays a role in mRNA splicing and metabolism, may be involved in tumorigenesis and development. Some studies have shown that RALY plays a role in promoting cancer in a variety of tumors. However, the biological function and molecular mechanism of RALY in non-small cell lung cancer (NSCLC) remain unknown. TCGA databases were used to gather RALY expression data in NSCLC, the results indicate that RALY is highly expressed in cancer tissue of NSCLC patients. Then we demonstrated that RALY gene expression was notably upregulated in NSCLC tissue and cell lines (A549 and SK-MES-1), and was associated with lymph node metastasis (P = 0.007) and poorer overall survival in NSCLC patients. Subsequently, RALY in A549 and SK-MES-1 cells was knocked down by lentivirus to analyze the consequences of RALY on the biological behavior of NSCLC cell lines. Our results indicated that RALY knockdown impaired NSCLC cells proliferation, migration, and invasion, as well as arrested cells in G1 phase, and the reintroduction of RALY recused its biological phenotype. Furthermore, RALY knockdown down-regulated the expression levels of c-Myc, Cyclin D1, CDK4, MMP9, Rho A ,Rho C, N-cadherin and ß-catenin, and up-regulated the expression levels of P27, Rho B and E-cadherin. Therefore, targeting RALY could be a promising molecular target for NSCLC treatment.

Primitive Neuroectodermal Tumor of the Prostate with Notalgia and Paraplegia as the Initial Symptoms: A Case Report and Literature Review.

Primitive neuroectodermal tumor (PNET) is a rare and highly malignant neoplasm composed of small round cells, which frequently occurs in children and adolescents. PNET originating from the prostate is even rarer. We report a case of PNET of the prostate with notalgia and paraplegia as the initial symptoms. Positron emission tomography-computed tomography scanning showed hypodense and hypermetabolism on the prostate; subsequently, we ascertained the diagnosis by transrectal ultrasound-guided biopsy. The patient underwent local vertebral radiotherapy combined with five courses of systematic chemotherapy. Disease progressed after 11 months, and the overall survival was 17 months.

Successful cryopreservation of whole sheep ovary by using DMSO-free cryoprotectant.

PURPOSE: The study aims to assess the protective effects of dimethyl sulfoxide (DMSO)-free solution based on trehalose on the cryopreservation of a whole sheep ovary and evaluate its use as an efficient cryoprotectant. METHOD: Twenty-one ovaries collected from 6- to 8-month-old non-pregnant female sheep were randomly distributed into three groups, namely, a fresh group, a DMSO-free group, and a DMSO group. The morphology, cell apoptosis (by hematoxylin and eosin (HE) staining and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assay), and mRNA transcript of Bcl-2-associated X protein (BAX) and cold inducible RNA-binding protein (CIRP) (by real-time PCR) of the thawed sheep ovaries and fresh controls were tested to establish a criterion for appraising the results of the cryopreservation. RESULTS: (i) The histological assessment indicated that the structure of the DMSO-free ovaries remained largely intact and comparable to those of the fresh control groups; whereas, significant damage was observed in the ovaries of the DMSO group (P < 0.05). (ii) The TUNEL assay and mRNA transcript of the BAX assessment showed that the apoptosis parameter in the fresh group was the lowest among all the groups (P < 0.05), and the parameter in the DMSO-free group was significantly lower than that in the DMSO group (P < 0.05). (iii) The level of the CIRP transcripts increased the most in the DMSO-free group followed by the DMSO group and the fresh control group (P < 0.05). CONCLUSIONS: These results indicate that a DMSO-free cryoprotectant solution, especially a trehalose cryoprotectant, is an efficient cryoprotectant and has a beneficial effect on the cryopreservation of whole sheep ovaries.