Impact of sarcopenia and obesity on overall survival in patients with head and neck cancer receiving radiotherapy: A longitudinal study.

PURPOSE: To analyze the impact of sarcopenia and obesity on overall survival (OS) in patients with head and neck cancer (HNC) receiving radiotherapy (RT). METHODS: This prospective longitudinal study recruited 494 patients using convenient sampling. Weight and body composition were assessed before RT (T1), and at the end of RT (T2) using bioelectrical impedance analysis (BIA). The appendicular skeletal mass index was used to define sarcopenia, while the body mass index and fat mass index were used to define obesity. Patient OS was followed and described using Kplan-Meier analysis. Cox proportional hazard regression was used to analyze influencing factors of OS. RESULTS: The median follow-up time was 26.2 months (IQR: 18.4-34.4 months). Multivariable models indicated that sarcopenia/obesity type assessed at T1 was not significantly associated with OS. Multivariable models involving body composition at T2 showed that age (P < 0.001), tumor site (P = 0.003), tumor stage (P = 0.024), and sarcopenia/obesity type (P = 0.040) were significantly associated with OS, while sarcopenic patients without obesity at T2 had worse OS. CONCLUSIONS: Patients with sarcopenia and no obesity at the end of RT might have worse OS. Healthcare professionals should enhance HNC patients' management during RT, helping them maintain a certain amount of muscle mass and fat mass to improve their survival.

Epidermal growth factor receptor­targeted antibody nimotuzumab combined with chemoradiotherapy improves survival in patients with locally advanced head and neck squamous cell carcinoma: a propensity score matching real-world study.

Patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) have poor survival outcomes. The real-world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)-based chemoradiotherapy in patients with LA-HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3-year overall survival (OS) rate. Log-rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow-up time was 54.2 (95% confidence interval [CI]: 52.7-55.9) months. The study group was associated with improved OS (hazard ratio [HR] = 0.75, 95% CI: 0.57-0.99, p = 0.038) and progression-free survival (PFS) (HR = 0.74, 95% CI: 0.58-0.96, p = 0.021). Subgroup analysis revealed that aged 50-60 year, IV, N2, radiotherapy dose ≥ 60 Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab-related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA-HNSCC patients in an IMRT era.

A real-world evaluation of tislelizumab in patients with head and neck cancer.

Background: Various studies support the use of programmed cell death protein 1 (PD-1) blockades, also known as immune checkpoint inhibitors (ICIs), to treat head and neck cancer (HNC). Tislelizumab is a humanised immunoglobulin G4 (IgG4) monoclonal antibody with a high affinity and specificity for PD-1. However, the "real-world" clinical evidence of tislelizumab for HNC is limited. Methods: In this study, the medical records of 39 patients with head and neck squamous cell carcinoma (HNSCC) or nasopharyngeal carcinoma (NPC) who received tislelizumab between January 2021 and March 2022 were reviewed retrospectively. Tislelizumab was administered to 15 patients during neoadjuvant therapy (Group 1), five patients during adjuvant therapy (Group 2), 14 patients during consolidation therapy (Group 3), and five patients during salvage therapy (Group 4). The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS). Results: The median age of enrolled patients was 55 (range, 28-83) years. The median follow-up time was 27.1, 26.1, 28.6, and 20.9 months for Groups 1, 2, 3, and 4, respectively. The mean PFS and OS of Groups 1, 2, 3, and 4 were 21.5 and 22.8; 24.1 and 24.2; 26.9 and 28.1; and 13.9 and 17.1 months, respectively. In Groups 1 and 4, the objective response rate (ORR) was 86.7% and 60%, respectively. Meanwhile, except for one (2.6%) patient with grade 4 enteritis, the other observed non-haematological adverse events (AEs) were ≤ grade 2. Conclusions: Tislelizumab demonstrated promising efficacy and tolerability in patients with HNSCC or NPC in a real-world setting, consistent with previous reports.

Adult head and neck rhabdomyosarcoma: radiotherapy- based treatment, outcomes, and predictors of survival.

BACKGROUND: Adult head and neck rhabdomyosarcoma (HNRMS) is an exceptionally rare malignancy, and there is a paucity of data and research dedicated to understanding its characteristics and management in adult populations. This study aimed to assess the outcomes and identify survival predictors in adult HNRMS. METHODS: We retrospectively evaluated 42 adult patients (> 16 years) with HNRMS who received radiotherapy (RT)-based treatment at our institute between 2008 and 2022. We analysed the clinical characteristics and prognosis of these patients, including the locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS), using the Kaplan-Meier method. The chi-square and Fisher's exact tests were used to analyse differences between groups for dichotomous and categorical variables, respectively. Survival rates were calculated using the Kaplan-Meier method. Prognostic variables were assessed through univariate Cox analyses. RESULTS: The median patient age was 28 years (range, 16-82 years). Alveolar RMS was the most common histological type, observed in 21 patients (50.0%), followed by embryonal in 16 patients (38.1%). The anatomic sites of origin were orbital in one (2.4%), parameningeal in 26 (61.9%), and non-orbital/non-parameningeal in 15 (35.7%) patients. Nineteen patients (45.2%) had regional lymph node metastasis, and five patients (11.9%) presented with distant metastatic disease. Distant metastasis (n = 17) was the primary cause of treatment failure. At a median follow-up of 47.0 months, the 5-year LRFS, PFS, and OS rates were 69.0%, 39.7%, and 41.0%, respectively. Univariate analysis revealed that tumour size, lymph node involvement, and the local treatment pattern (surgery and RT vs. RT alone) were significant predictors of survival. CONCLUSIONS: The main failure pattern in patients with HNRMS receiving RT-based treatment was distant metastasis. Tumour size > 5 cm and lymph node involvement were predictors of worse LRFS. Multimodality local treatment, combining surgery and RT, is effective and provides survival benefits.

Prognostic factors analysis of diffuse midline glioma.

PURPOSE: This study retrospectively analyzes cases of diffuse midline glioma treated with radiotherapy, with the aim of investigating the prognosis of the tumor and its influencing factors. METHODS: From January 2018 to November 2022, we treated 64 patients who were pathologically diagnosed with diffuse midline glioma. Among them, 41 underwent surgical resection, and 23 underwent biopsy procedures. All patients received postoperative radiotherapy. We followed up with the patients to determine the overall survival rate and conducted univariate and multivariate analyses on relevant indicators. RESULTS: The median survival time for the entire patient group was 33.3 months, with overall survival rates of 92.9%, 75.4%, and 45.0% at 1 year, 2 years, and 3 years, respectively. Univariate and multivariate analyses indicated that older patients had a better prognosis. CONCLUSION: Patient age is an independent prognostic factor for patients with diffuse midline glioma undergoing radiation therapy.

Clinical Advances and Future Directions of Oncolytic Virotherapy for Head and Neck Cancer.

Oncolytic viruses (OVs), without harming normal tissues, selectively infect and replicate within tumor cells, to release immune molecules and tumor antigens, achieving immune-mediated destruction of tumors and making them one of the most promising immunotherapies for cancer. Many clinical studies have demonstrated that OVs can provide clinical benefits for patients with different types of tumors, at various stages, including metastatic and previously untreatable cases. When OVs are used in combination with chemotherapy, radiotherapy, immunotherapy, and other treatments, they can synergistically enhance the therapeutic effects. The concept of oncolytic virotherapy (OVT) was proposed in the early 20th century. With advancements in genetic engineering, genetically modified viruses can further enhance the efficacy of cancer immunotherapy. In recent years, global research on OV treatment of malignant tumors has increased dramatically. This article comprehensively reviews the findings from relevant research and clinical trials, providing an overview of the development of OVT and its application in the clinical treatment of head and neck cancer. The aim is to offer insights for future clinical and fundamental research on OVT.

Identification of potential biomarkers in cancer testis antigens for glioblastoma.

OBJECTIVE: To screen and validate cancer testis antigens (CTAs) as potential biomarkers and explore their molecular mechanisms in glioblastoma (GBM). METHODS: Ribonucleic acid sequencing (RNA-seq) and bioinformatics analyses were utilized to screen the highly expressed CTAs in GBM. Correlation analysis was used to identify potential biomarkers associated with tumor purity and prognosis. Immunohistochemistry was applied for detection of protein expression. Protein-protein interaction (PPI) network construction, functional enrichment analysis, and binding domain prediction were performed to investigate the underlying molecular mechanisms of GBM. RESULTS: A total of 8 highly expressed CTAs were identified in GBM. One of them was PDZ-binding kinase (PBK). PBK messenger RNA (mRNA) was most highly expressed in GBM and associated with tumor purity and prognosis, PBK protein expression was also significantly increased in GBM tissues and correlated with p53 expression. Functional enrichment analysis revealed that the PBK related genes were predominantly enriched in cell cycle pathway with 38 genes enriched. The proteins encoding by these 38 genes were performed by binding domain prediction analysis, which demonstrated 15 proteins interacting with PBK. Most of these proteins were up regulated in GBM. CONCLUSION: PBK is highly expressed in GBM. It may serve as a potential biomarker for GBM targeting therapy and the cell cycle modulator by interacting with certain key molecules of cell cycle in GBM.

Predictive effect of pretreatment nutritional risk and GLIM-defined malnutrition on the nutrition impact symptom clusters in patients with head and neck cancer undergoing radiotherapy.

BACKGROUND: Evidence supporting predictive effects of pretreatment nutritional risk and nutritional status on nutrition impact symptom (NIS) clusters during radiotherapy in patients with head and neck cancer (HNC) is insufficient. METHODS: At baseline (T1 ), we collected severity and interference of NIS (Head and Neck Patient Symptom Checklist), nutritional risk, and nutritional status. During (T2 ) and at the end of radiotherapy (T3 ), we re-evaluated NIS. Symptom clusters were identified by exploratory factor analysis using mean scores of NIS severity at T2 and T3 . Predictive effects were explored by generalized estimating equations. RESULTS: Five hundred thirty-seven patients were recruited and 334 of them completed. Four clusters were identified; the oropharyngeal symptom cluster was the most severe and had the greatest interference with diet. Patients with pretreatment nutritional risk or malnutrition experienced more severe oropharyngeal symptom cluster. CONCLUSIONS: Pretreatment nutritional risk or malnutrition could predict the oropharyngeal symptom cluster in patients with HNC undergoing radiotherapy.

High Expression of Fibronectin 1 Predicts a Poor Prognosis in Glioblastoma.

OBJECTIVE: Glioblastoma multiforme (GBM), the most malignant intracranial neoplasm, is associated with a high mortality and recurrence rate due to the aggressive nature and heterogeneity of the tumor. Some of the molecular markers involved in the tumorigenesis of GBM are essential in prognosis, diagnosis, and treatment. Due to the limitations of therapeutic effects, this study aims to explore novel biomarkers with prognostic value and to provide new insights into therapeutic targets. METHODS: The expression profile of mRNAs in GBM was detected by RNA-sequencing, and differentially expressed genes were identified by integrating the data from RNA-seq results and the GEPIA2 database. Of the total 40 hub genes, FN1, P4HB, and PPIB showed prognostic significance based on both GEPIA2 and CGGA databases. The validation of FN1, P4HB, and PPIB expression by qPCR and correlation analysis with clinicopathological features were performed in 41 GBM tissues from our institution. RESULTS: Kaplan-Meier analysis revealed that FN1 and P4HB expressions levels were related to the overall survival (OS) of GBM patients (P<0.05). Multivariate analysis showed that FN1 overexpression (HR=9.199, P=0.002) was an independent and unfavorable prognostic factor for GBM patients. The median survival time was 8.5 months and 21 months for high and low expressions of FN1, respectively. CONCLUSION: It was suggested that FN1 could be an ideal target for prognosis and a potential therapeutic target in GBM.

Association between body composition and survival in head and neck cancer patients undergoing radiotherapy.

BACKGROUND: Body composition may influence the prognosis of head and neck cancer (HNC) patients. To find out the most crucial factors in this relationship, we explored the association between body composition and survival. METHODS: In this prospective longitudinal study, HNC patients who underwent radiotherapy (RT) from March 2017 to December 2018 were recruited. The association between body composition and survival was analyzed using Cox proportional hazard regression. RESULTS: Final analysis included 316 patients, with a median follow-up of 34.4 months. Multivariable analysis revealed that weight loss 6 months before RT and body composition changes during RT did not affect the survival outcome. However, patients with low appendicular skeletal muscle mass index (ASMI) before RT exhibited poor overall survival (OS). ASMI before RT was an independent prognostic factor for OS. CONCLUSIONS: Body composition loss was common during RT, and ASMI before RT independently influenced the survival outcomes of HNC patients.

FMR1NB Involved in Glioma Tumorigenesis Is a Promising Target for Prognosis and Therapy.

OBJECTIVE: Cancer/testis antigen FMR1NB is aberrantly expressed in various types of cancer, but not in normal tissues except for testis. This study aimed to investigate the expression and functional role of FMR1NB in glioma. METHODS: The expression of FMR1NB mRNA and protein was determined using RT-PCR and immunohistochemistry, respectively, in glioma specimens from 83 patients at follow-up. The effects of siRNA-mediated FMR1NB silencing on malignant biological behaviors were evaluated in glioma cell lines A172 and U251. RESULTS: FMR1NB mRNA and protein expression was detected in 58.8% (77/131) and 46.34% (57/123) of glioma tissues, respectively. FMR1NB protein was positively correlated with World Health Organization grade and found to be an independent prognostic marker for poor outcome. Knockdown of FMR1NB induced apoptosis and suppressed proliferation, adhesion, migration, and invasion by modulating the expression of cyclin A, CDK2, caspase-3, E-cadherin, and N-cadherin in A172 and U251 cells. CONCLUSION: Our findings suggest that FMR1NB contributes to the tumorigenesis of glioma cells and may represent a potential prognostic biomarker and an attractive therapeutic target in glioma.

Pretherapy platelet-to-lymphocyte ratio as a prognostic parameter for locally advanced hypopharyngeal cancer patients treated with radiotherapy combined with chemotherapy.

PURPOSE: This study aimed to identify whether the platelet-to-lymphocyte ratio (PLR) correlated with the prognosis of patients with locally advanced hypopharyngeal squamous cell carcinoma (LA-HPSCC) undergoing radiotherapy combined with chemotherapy. METHODS: This study enrolled 103 patients diagnosed with LA-HPSCC and treated with radiotherapy combined with chemotherapy between 2008 and 2021. The optimal PLR cut-off value was chosen from the receiver operating characteristic (ROC) curve analysis. According to the cut-off value of PLR, patients were divided into two groups: a low PLR group (< 133.06) and a high PLR group (≥ 133.06). Propensity score matching (PSM) was used to balance the confounding factors between the two PLR groups. Univariate and multivariate Cox proportional hazard regression models, the Kaplan-Meier curve by the log-rank test, and univariate and multivariate Fine-Gray competing risk models were all used for assessment. RESULTS: After PSM, 27 pairs were left, and the high PLR group correlated with higher local failure (sHR 6.91, 95% CI 2.14-22.35, p = 0.001) in the multivariate Fine-Gray competing risk model. Moreover, the low PLR group had a significantly longer 3-year progression-free survival (43.7% vs. 29.2%, p = 0.038) and overall survival (55.1% vs. 32.1%, p = 0.034) than the high PLR group had. Multivariate Cox analysis showed that a low PLR was an independent protective factor for PFS (HR 0.43, 95% CI 0.21-0.92, p = 0.019) and OS (HR 0.46, 95% CI 0.22-0.96, p = 0.039) in patients with LA-HPSCC. CONCLUSION: Pretherapy PLR might be a factor in predicting the risk of local failure and survival in LA-HPSCC patients undergoing radiotherapy combined with chemotherapy.

Nutritional counseling was insufficient to maintain dietary intake and nutritional status in head and neck cancer patients undergoing radiotherapy: A historical control study for future intervention in China.

Objective: To determine whether nutritional counseling (NC) affects the dietary intake and nutritional status of head and neck cancer (HNC) patients undergoing radiotherapy (RT) in China. Methods: This historical control study enrolled 139 HNC patients in the NC group and 146 patients in the control group. Before RT, the latter received usual education about side effects. The former received three sessions (T1, before RT; T2, 3 weeks of RT; and T3, 6 to 7 weeks of RT) of individualized NC. Outcome measures were dietary intake, weight, body composition, and nutritional status. Generalized estimating equation (GEE) models were used to analyze intergroup differences. Results: The NC group had higher energy (P â€‹< â€‹0.001) and protein intake (P â€‹= â€‹0.003). However, some patients in the NC group still could not reach 60% of the recommended caloric goals (22.3% at T2 and 32.4% at T3) or protein goals (23.0% at T2 and 27.3% at T3). Although the NC group had a lower weight loss rate (ߠ​= â€‹-0.555, P â€‹= â€‹0.037), they still lost 6.15% â€‹± â€‹4.08% of weight at T3. At T2, more patients in the control group lost ≥ 5% of weight (26.0% vs 15.8%, P â€‹= â€‹0.049). More patients in the control group had malnutrition (P â€‹= â€‹0.045), but 77% of the NC group had malnutrition at T3. Conclusions: NC could effectively improve dietary intake, weight loss, and malnutrition in HNC patients receiving RT. Nevertheless, only NC was insufficient to maintain adequate intake and well-nourished status. We should adopt intensive nutritional intervention with a multidisciplinary team to enhance patients' nutritional status.

Immunohistochemistry Study of OY-TES-1 Location in Fetal and Adult Human Tissues.

OY-TES-1 is reportedly involved in carcinogenesis and spermatogenesis. However, the tissue distribution of OY-TES-1 in the normal human body remains elusive. This study detected OY-TES-1 expression in human fetal and adult normal tissues by immunohistochemistry. We identified a general principle of OY-TES-1 expression. The expression of OY-TES-1 was found in neurons, smooth muscle cells, and cardiac muscle cells from both fetuses and adults. The connective tissue showed no specific staining throughout the fetal and adult samples. With OY-TES-1-positive staining of the epithelium irregular, OY-TES-1 was strongly expressed in the epithelium of the skin and bladder, as well as hepatocytes, pancreatic islets, and acinous cells during the fetal stage but was not detected in the postnatal period. In contrast to the epithelium of blood vessels, the fetal and adult central hepatic vein and glomeruli showed negative expression of the OY-TES-1 protein. Sex-dimorphism was observed in the distribution of OY-TES-1 in male and female germ cells. Collectively, our results indicate that OY-TES-1 is a member of the cancer-testis antigen and autoantigen, with tissue-specific and period-specific expression patterns, revealing potential contributions of OY-TES-1 to the diagnosis and therapeutic treatment for neoplasms and infertility.

GLIM Criteria-Defined Malnutrition Informs on Survival of Nasopharyngeal Carcinoma Patients Undergoing Radiotherapy.

Studies regarding malnutrition in patients with nasopharyngeal carcinoma (NPC) using the Global Leadership Initiative in Malnutrition (GLIM) criteria are still limited. Our study aimed to investigate the prevalence of malnutrition using the GLIM criteria in NPC patients receiving radiotherapy and explore the relationship between pre-radiotherapy (pre-RT) malnutrition and survival. A total of 113 NPC patients were enrolled for nutritional assessment using the GLIM criteria at different radiotherapeutic time points, and related toxicities were graded. Regarding the results, 19 patients (16.8%) were malnourished before radiotherapy and 103 patients (91.2%) were malnourished at the end of radiotherapy. Among the phenotypic GLIM criteria, low fat-free muscle index (FFMI) before radiotherapy was associated with mucositis and radiodermatitis (p < 0.05). Importantly, patients with malnutrition before radiotherapy had significantly poorer 2-year progression free survival (PFS) than the patients being well-nourished (62.1% vs. 88.9%, p = 0.015). From the multivariate Cox regression model, being-well nourished before radiotherapy was the protective factor for PFS (HR: 0.27; 95%CI: 0.089-0.85; p = 0.023) and male was the risk factor for PFS (HR: 7.25; 95%CI: 1.548-34.00; p = 0.012). In conclusion, malnutrition according to the GLIM criteria is common in NPC patients undergoing radiotherapy, and pre-RT malnutrition is correlated with survival.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2022.2044059.

Clinical characteristics and prognosis of patients with hypopharyngeal cancers with multiple primary cancers: A propensity score matched analysis.

PURPOSE: This study aimed to identify the clinical characteristics of hypopharyngeal squamous cell carcinoma (HPSCC) patients with multiple primary cancers (MPCs) and to compare differences between patients with metachronous and synchronous MPCs. MATERIAL AND METHODS: This study included 219 patients with HPSCC treated at our center between 2008 and 2020; the clinical characteristics and prognosis of 66 patients with MPCs were analyzed. Propensity score matching (PSM) was used to balance the factors between patients with synchronous and metachronous MPCs. RESULTS: Sixty-six patients with HPSCC (66/219, 30.1%) experienced MPCs, of which 29 were synchronous and 37 were metachronous. The esophagus (n = 39, 59.1%), lung (n = 10, 15.2%), and oropharynx (n = 4, 6.1%) were the three most common sites of MPCs in both the synchronous and metachronous groups. More patients with synchronous MPCs were stage T1-2 (82.8% vs. 59.5%, P = 0.041) compared to those with metachronous MPCs. Among the 24 pairs of patients after PSM, patients with metachronous MPCs had higher 3-year progression-free survival (PFS) (52.5% vs. 16.3%, P < 0.001) and overall survival (OS) (58.5% vs. 22.1%, P = 0.001) than those with synchronous cancers. Multivariate Cox analysis showed that patients with synchronous MPCs had shorter PFS (HR 4.45, 95% CI 1.819-10.885, P = 0.001) and OS (HR 3.918, 95% CI 1.591-9.645, P = 0.003). CONCLUSION: MPCs are common among patients with HPSCC, and patients with metachronous MPCs had better survival than those with synchronous MPCs. Clinicians should be aware of the possibility of MPCs in patients with HPSCC and optimize treatment to improve outcomes.

The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence-based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.

The prevalence of sarcopenia and relationships between dietary intake and muscle mass in head and neck cancer patients undergoing radiotherapy: A longitudinal study.

PURPOSE: Our study aims to investigate dietary intake characteristics and their association with skeletal muscle mass in head and neck cancer patients treated with radiotherapy. METHODS: From March 2017 to August 2018, patients with head and neck cancer who received radiotherapy at our affiliated hospital were enrolled. Dietary intake was assessed through 24-hr dietary recall and skeletal muscle mass was evaluated by bioelectrical impedance analysis at three-time points. Appendicular skeletal muscle mass was adjusted for height squared defined sarcopenia and correlated with dietary intake by generalized estimating equations (GEE). RESULTS: This study sample comprised 287 patients [median age: 54 years; 187 (65.2%) men]. Median dietary intake at post-treatment was 14.95 kcal/kg/day energy and 0.63 g/kg/day protein. Skeletal muscle mass decreased significantly in all patients. The prevalence of sarcopenia increased from 24.4% before treatment to 46.7% at the end of treatment. Exploratory univariate GEE analysis revealed that radiotherapy time-point, male-gender, age ≥60 and decreased dietary energy intake significantly impacted on muscle loss represented by the appendicular skeletal muscle index. After controlling covariates, dietary energy intake was only positively associated with muscle loss in women (P = 0.013, 95% CI = 0.003-0.027) but not in men (P = 0.788, 95% CI = -0.007-0.009). CONCLUSION: While the loss in skeletal muscle is more prevalent in men receiving radiotherapy, the effects of dietary energy intake were only associated with women. A prospective randomized clinical trial is required to identify the appropriate amount of dietary energy supplement by gender in cancer patients treated with radiotherapy.

Tanshinone IIA sensitizes TRAIL-induced apoptosis in glioblastoma through inducing the expression of death receptors (and suppressing STAT3 activation).

OBJECTIVE: This work was designed to explore whether the combination of Tanshinone IIA (T-IIA) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has a direct anti-cancer effect in glioblastoma (GBM) and the possible mechanisms. METHODS: GBM cells (U-87 and U-251 MG) were treated with T-IIA or/and TRAIL, or the expression of death receptors (DRs), DR4 and DR5, was suppressed in GBM cells. The activity of GBM cells was determined by MTT, and the apoptosis was assessed by Hoechst33342 staining and flow cytometry. The expression levels of cleaved caspase-3/8/9, phosphorylated (p)-STAT3 as well as DR4 and DR5 in GBM cells were assessed by Western blotting. A nude mouse xenograft model was constructed to evaluate the effects of T-IIA and TRAIL cotreatment on tumor growth and apoptosis in vivo. RESULTS: After T-IIA treatment, GBM cells resumed the sensitivity to TRAIL-induced apoptosis dependent on inhibition of p-STAT3 and activation of DR4, DR5 and caspases. DR4 or/and DR5 knockdown significantly abated the co-effect of T-IIA and TRAIL on GBM cell apoptosis and proliferation. Furthermore, T-IIA and TRAIL cotreatment markedly inhibited the growth of transplanted tumor and activated U87 cell apoptosis in nude mice. CONCLUSION: T-IIA increases TRAIL-induced apoptosis by downregulating STAT3 and upregulating DR4 and DR5, indicating T-IIA therapy as a novel treatment strategy for TRAIL-resistant GBM.