Fruquintinib plus paclitaxel versus placebo plus paclitaxel for gastric or gastroesophageal junction adenocarcinoma: the randomized phase 3 FRUTIGA trial.

The vascular endothelial growth factor pathway plays a key role in the pathogenesis of gastric cancer. In the multicenter, double-blind phase 3 FRUTIGA trial, 703 patients with advanced gastric or gastroesophageal junction adenocarcinoma who progressed on fluorouracil- and platinum-containing chemotherapy were randomized (1:1) to receive fruquintinib (an inhibitor of vascular endothelial growth factor receptor-1/2/3; 4 mg orally, once daily) or placebo for 3 weeks, followed by 1 week off, plus paclitaxel (80 mg/m2 intravenously on days 1/8/15 per cycle). The study results were positive as one of the dual primary endpoints, progression-free survival (PFS), was met (median PFS, 5.6 months in the fruquintinib arm versus 2.7 months in the placebo arm; hazard ratio 0.57; 95% confidence interval 0.48-0.68; P < 0.0001). The other dual primary endpoint, overall survival (OS), was not met (median OS, 9.6 months versus 8.4 months; hazard ratio 0.96, 95% confidence interval 0.81-1.13; P = 0.6064). The most common grade ≥3 adverse events were neutropenia, leukopenia and anemia. Fruquintinib plus paclitaxel as a second-line treatment significantly improved PFS, but not OS, in Chinese patients with advanced gastric or gastroesophageal junction adenocarcinoma and could potentially be another treatment option for these patients. ClinicalTrials.gov registration: NCT03223376 .

Inducing enhanced neutralizing antibodies against broad SARS-CoV-2 variants through glycan-shielding multiple non-neutralizing epitopes of RBD.

Introduction: Since the outbreak of SARS-CoV-2, vaccines have demonstrated their effectiveness in resisting virus infection, reducing severity, and lowering the mortality rate in infected individuals. However, due to the rapid and ongoing mutations of SARS-CoV-2, the protective ability of many available vaccines has been challenged. Therefore, there is an urgent need for vaccines capable of eliciting potent broadly neutralizing antibodies against various SARS-CoV-2 variants. Methods: In this study, we developed a novel subunit vaccine candidate for SARS-CoV-2 by introducing a series of shielding glycans to the Fc-fused receptor-binding domain (RBD) of the prototypic spike protein. This approach aims to mask non-neutralizing epitopes and focus the immune response on crucial neutralizing epitopes. Results: All modified sites were confirmed to be highly glycosylated through mass spectrometry analysis. The binding affinity of the glycan-shielded RBD (gsRBD) to the human ACE2 receptor was comparable to that of the wildtype RBD (wtRBD). Immunizing mice with gsRBD when combined with either Freund's adjuvant or aluminum adjuvant demonstrated that the introduction of the glycan shield did not compromise the antibody-inducing ability of RBD. Importantly, the gsRBD significantly enhanced the generation of neutralizing antibodies against SARS-CoV-2 pseudoviruses compared to the wtRBD. Notably, it exhibited remarkable protective activity against Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529), approximately 3-fold, 7- fold, and 17-fold higher than wtRBD, respectively. Discussion: Our data proved this multiple-epitope masking strategy as an effective approach for highly active vaccine production.

A clinical decision support system to predict the efficacy for EGFR-TKIs based on artificial neural network.

BACKGROUND: The efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) was affected by numerous factors. In the study, we developed and validated an artificial neural network (ANN) system based on clinical characteristics and next-generation sequencing (NGS) to support clinical decisions. METHODS: A multicenter retrospective non-interventional study was conducted. 240 patients from three hospitals with advanced non-small cell lung cancer (NSCLC) and EGFR mutation were tested by NGS before the first treatment. All patients received formal EGFR-TKIs treatment. Five different models were individually trained to predict the efficacy of EGFR-TKIs based on one medical center with 188 patients. Two independent cohorts from other medical centers were collected for external validation. RESULTS: Compared with logistic regression, four machine learning methods showed better predicting abilities for EGFR-TKIs. The inclusion of NGS tests improved the predictive power of models. ANN performed best on the dataset with mutations TP53, RB1, PIK3CA, EGFR mutation sites, and tumor mutation burden (TMB). The prediction accuracy, recall and AUC were 0.82, 0.82, and 0.82, respectively in our final model. In the external validation set, ANN still showed good performance and differentiated patients with poor outcomes. Finally, a clinical decision support software based on ANN was developed and provided a visualization interface for clinicians. CONCLUSION: This study provides an approach to assess the efficacy of NSCLC patients with first-line EGFR-TKI treatment. Software is developed to support clinical decisions.

Intrathyroidal Thymic Carcinoma: A Retrospective Case Series Study.

OBJECTIVE: Intrathyroidal thymic carcinoma (ITC) is a rare low-grade malignant thyroid tumor. There is neither sufficient understanding of this tumor nor its clinical treatment. This study is to explore the clinicopathological features, treatment, and prognosis of ITC and thereby provide a reference for the diagnosis and treatment of the disease. METHODS: The clinical, pathological, therapeutic, and prognostic data of 13 patients with ITC were retrospectively analyzed. RESULTS: The case series comprised 7 males and 6 females, with an average age of 51.9 ± 10.1 years. After surgical resection, all patients received post-operative neck radiotherapy at dosages of 60-66 Gy. Five patients with level VI lymph node metastasis additionally received 6 courses of cisplatin chemotherapy. All patients were followed-up for 21-132 months (median = 66 months), and all of them survived without recurrence or metastasis. CONCLUSIONS: The diagnosis of ITC depends mainly on pathological and immunohistochemical results, particularly CD5 positive staining. Surgical resection is the preferred primary treatment modality which can be supplemented with radiotherapy and chemotherapy to reduce the risk of recurrence and metastasis.

Gut Bacteria Erysipelatoclostridium and Its Related Metabolite Ptilosteroid A Could Predict Radiation-Induced Intestinal Injury.

It is difficult to study the intestinal damage induced by space radiation to astronauts directly, and few prediction models exist. However, we can simulate it in patients with pelvic tumor radiotherapy (RT). Radiation-induced intestinal injury (RIII) is common in cancer patients who receieved pelvic and abdominal RT. We dynamically analyzed gut microbiota and metabolites alterations in 17 cervical and endometrial cancer patients after pelvic RT. In patients who later developed grade 2 RIII, dysbiosis of gut microbiota and metabolites were observed. Univariate analysis showed that Erysipelatoclostridium and ptilosteroid A were related to the occurrence of grade 2 RIII. Notably, a strong positive correlation between gut bacteria Erysipelatoclostridium relative abundance and gut metabolite ptilosteroid A expression was found. Furthermore, combinations of Erysipelatoclostridium and ptilosteroid A could provide good diagnostic markers for grade 2 RIII. In conclusion, gut bacteria Erysipelatoclostridium and its related metabolite ptilosteroid A may collaboratively predict RIII, and could be diagnostic biomarkers for RIII and space radiation injury.

Differential expression of Tim3 protein in colorectal cancer associated with MSI and Braf mutation.

Tim3 is a negative immune checkpoint molecule and plays a crucial part in tumor-induced immune suppression. Tim3 is a cell surface molecule expressed on T cells marking dysfunctional CD8+ cells in various kinds of cancers. Tim3 expression was mainly reported in tumor-infiltrating lymphocytes (TILs). There are few studies focusing on the expression of Tim3 in tumor cells. Immunohistochemistry was performed to determine Tim3 expression level. The relationships between Tim3 expression in colorectal cancer cells and in tumor-infiltrating lymphocytes and cilicopathological parameters were statistically analyzed. Tim3 was differentially detected in TILs and in colorectal cancer cells. Positive expression of Tim3 in colorectal cancer cells was associated with tumor location (P=0.001), depth of tumor invasion (P<0.001), lymph node metastasis (P=0.001), TNM stage (P=0.001), MSI (P=0.008), and Braf V600E mutation (P=0.001). On the other hand, positive expression of Tim3 in TILs was only related to depth of tumor invasion (P<0.001). Positive expression of Tim3 in both colorectal cancer cells and TILs was associated with depth of tumor invasion (P<0.001), lymph node metastasis (P=0.002), TNM stage (P=0.002), MSI (P=0.039), and Braf V600E mutation (P=0.009). Kaplan-Meier survival analysis showed that Tim3 expression in colorectal cancer and in TILs was significantly associated with patient overall survival (OS) rate (P=0.039, and 0.001). Tim3 may be a potential prognostic marker and a therapy target for colorectal cancer.

A Pan-Cancer Study of KMT2 Family as Therapeutic Targets in Cancer.

OBJECTIVE: Exome sequencing studies have shown that the histone-lysine N-methyltransferase 2 (KMT2) gene is one of the most commonly mutated genes in a range of human malignancies and is linked to some of the most common and deadly solid tumors. However, the connection between this gene family's function and tumor type, immunological subtype, and molecular subtype dependency is still unknown. METHODS: We examine the expression patterns of the histone-lysine N-methyltransferase 2 (KMT2) gene, as well as their relationship to patient survival. We also used a pan-cancer analysis to link their function to immunological subtypes, the tumor microenvironment, and treatment sensitivity. RESULTS: Using the TCGA pan-cancer data, researchers looked at and examined KMT2 expression patterns and their links to patient survival and the tumor microenvironment in 33 cancer types. The expression of the KMT2 family changes significantly across and within cancer types, indicating significant inter- and intracancer heterogeneity. Patients' overall survival was often linked to the expression of KMT2 family members. However, the direction of the link differed depending on the KMT2 isoform and cancer type studied. Notably, in all cancer types examined, nearly all KMT2 family members were substantially linked with overall survival in patients with renal clear cell carcinoma (KIRC). Furthermore, all KMT2 genes have a strong relationship with immune infiltrate subtypes, as well as varying degrees of stromal cell infiltration and tumor cell stemness. Finally, we discovered that higher expression of KMT2s, particularly KMT2F and KMT2G, was linked to greater chemotherapeutic sensitivity in several cell lines. CONCLUSIONS: The necessity to investigate each KMT2 member as a distinct entity inside each particular cancer type is highlighted by our comprehensive investigation of KMT2 gene expression and its relationship with immune infiltrates, tumor microenvironment, and cancer patient outcomes. Our research also confirmed the identification of KMT2 as a potential therapeutic target in cancer, but further laboratory testing is required.

CCR4 is a prognostic biomarker and correlated with immune infiltrates in head and neck squamous cell carcinoma.

BACKGROUND: Increased evidence has indicated that the tumour microenvironment plays an essential in the development, treatment and prognosis of head and neck squamous cell carcinoma (HNSC). Recent studies have indicated CC chemokine receptor 4 (CCR4) plays an essential role in tumor invasion and other adverse biological behavior. This study used data from the Cancer Genome Atlas (TCGA) database to explore the role of CCR4 in HNSC and its clinical significance. METHODS: The gene expression and clinical data of HNSC patients in the TCGA database were extracted. Gene Expression Profiling Interactive Analysis (GEPIA) was used to analyze the expression of CCR4 in tumor and non-tumor tissue. Kaplan-Meier survival analysis was used to analyze the relationship between CCR4 expression and overall survival rate (OS), disease-specific survival (DSS), and progression-free interval (PFI) in HNSC. A logistic regression model was used to analyze the relationships between various clinical factors and CCR4 expression. Gene Set Enrichment Analysis (GSEA) was used to explore the potential role of CCR4 in HNSC. Additionally, we explored the relationship between CCR4 and immune infiltration. RESULTS: The expression of CCR4 in HNSC was not significantly different from that in normal tissue. The expression level of CCR4 in wild-type TP53 was higher than that in mutant TP53. Cox regression analysis showed the expression level of CCR4 was related to the patient's tumor grade and Tumor-Node-Metastasis (TNM) stage. CCR4 expression level is an independent prognostic factor. CCR4 is positively correlated with immune infiltration and immune checkpoints expression levels. The results of GSEA revealed that the high CCR4 expression group genes were enriched in allograft rejection, inflammatory response, IL-6/JAK/STAT3 signaling, interferon gamma response, and KRAS signaling up. Low CCR4 expression group genes were enriched in oxidative phosphorylation, MYC targets v1, DNA repair, reactive oxygen species pathway, and P53 pathway. Further, our study indicated CCR4 can also predict the prognosis of radiotherapy patients. CONCLUSIONS: Our study found that CCR4 was a prognostic marker related to HNSC immune infiltration, and patients with high expression of CCR4 had a better prognosis.

Numerical Simulations of Calcium Sulphate Scaling in Full-Scale Brackish Water Reverse Osmosis Pressure Vessels Using Computational Fluid Dynamics.

Coal mine waters often have high salinity, hardness and alkalinity. The treatment of coal mine water requires careful management of multi-stage reverse osmosis (RO) systems to achieve effective recovery of water for domestic reuse, as well as zero liquid discharge to minimise the impact to the local environment. Design of RO systems for coal mine water treatment has been limited to the use of commercial design packages provided by membrane manufacturers, which do not provide insights into the impact of operating parameters such as feedwater salinity, concentrations of sparingly soluble salts, feed pressure and their interactions with different RO modules on the fouling/scaling potential of RO membranes. This also restricts the use of novel RO products and the delivery of an optimum design based on real needs. In this work, a mathematical model was developed to simulate a standard brackish water RO pressure vessel consisting six full-size RO membrane elements, using computational fluid dynamics (CFD). The model can be used to predict the permeate flowrate, water recovery levels, as well as the spatial information of the accumulation and scaling potential of sparingly soluble salts on the membrane surface. The results obtained from the model showed good agreement with the results obtained from the commercial RO design software WAVE. The CFD model was then used to predict the scaling threshold on various positions of a full-scale RO element, at different operating conditions, using parametric simulations based on Central Composite Designs. Outputs from this work not only provide insights into the microscopic flow characteristics of multiple full-scale elements in the RO pressure vessel, but also predicts the position where scaling would occur, at different feed conditions, for any RO products.

Clinicopathological characteristics and survival outcomes in neuroendocrine prostate cancer: A population-based study.

OBJECTIVE: This study aimed to investigate the clinicopathological features and the survival outcomes of neuroendocrine prostate cancer (NEPC). METHODS: Within the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute, we identified a total of 510 patients with NEPC between 2006 and 2015. Age-adjusted incidence rates were evaluated in the study by the SEER∗Stat Software version 8.3.6. Kaplan-Meier analysed assessed overall survival (OS) after stratification according to marital status, age, histologic subtype, metastatic status, and treatment. The significant differences were assessed in a log-rank test. Univariate and multivariate cox hazard regression analysis were performed to determine independent predictors of OS. RESULTS: From a total of 560,124 patients with prostate cancer diagnosed between 2006 and 2015, we identified 510 cases of de novo NEPC. Regarding histology, among all the NEPC, 329 (64.5%) patients were diagnosed as small cell carcinoma, 181 (39.8%) were nonsmall cell carcinoma. The overall age-adjusted incidence of NEPC statistically significantly increased from 0.321/1,000,000 person-years in 2006 to 0.587/1,000,000 person-years in 2015. The median OS in our study cohort was 9 months (95% CI, 8-10 months). Multivariate cox regression analysis showed that age, histologic subtype, and stage were independent prognostic factors for NEPC patients. The majority of NEPC (78.2%) were metastatic at diagnosis. In terms of treatment, for metastatic tumor patients, chemotherapy was the most effective therapy. Chemotherapy increased the OS of patients with regional (distant) metastases from 8 months (5 months) to 13.5 months (9 months). CONCLUSION: NEPC is extremely rare but the incidence of NEPC has been increasing in the past years. The prognosis of NEPC is poor because most cases are diagnosed at metastatic stage. The patients with metastases are typically treated with chemotherapy and chemotherapy shows survival benefits in both regional and distant metastatic tumor patients.

The long noncoding RNA CRYBG3 induces aneuploidy by interfering with spindle assembly checkpoint via direct binding with Bub3.

Aneuploidy is a hallmark of genomic instability that leads to tumor initiation, progression, and metastasis. CDC20, Bub1, and Bub3 form the mitosis checkpoint complex (MCC) that binds the anaphase-promoting complex or cyclosome (APC/C), a crucial factor of the spindle assembly checkpoint (SAC), to ensure the bi-directional attachment and proper segregation of all sister chromosomes. However, just how MCC is regulated to ensure normal mitosis during cellular division remains unclear. In the present study, we demonstrated that LNC CRYBG3, an ionizing radiation-inducible long noncoding RNA, directly binds with Bub3 and interrupts its interaction with CDC20 to result in aneuploidy. The 261-317 (S3) residual of the LNC CRYBG3 sequence is critical for its interaction with Bub3 protein. Overexpression of LNC CRYBG3 leads to aneuploidy and promotes tumorigenesis and metastasis of lung cancer cells, implying that LNC CRYBG3 is a novel oncogene. These findings provide a novel mechanistic basis for the pathogenesis of NSCLC after exposure to ionizing radiation as well as a potential target for the diagnosis, treatment, and prognosis of an often fatal disease.

Camrelizumab plus gemcitabine and oxaliplatin (GEMOX) in patients with advanced biliary tract cancer: a single-arm, open-label, phase II trial.

BACKGROUND: Immune checkpoint inhibitors monotherapy has been studied in patients with advanced biliary tract cancer (BTC). The aim of this study was to assess the efficacy and safety of camrelizumab, plus gemcitabine and oxaliplatin (GEMOX) as first-line treatment in advanced BTC and explored the potential biomarkers associated with response. METHODS: In this single-arm, open-label, phase II study, we enrolled stage IV BTC patients. Participants received camrelizumab (3 mg/kg) plus gemcitabine (800 mg/m2) and oxaliplatin (85 mg/m2). Primary endpoints were 6-month progression-free survival (PFS) rate and safety. Secondary endpoints were objective response rate (ORR), PFS and overall survival (OS). Exploratory endpoints included association between response and tumor mutational burden (TMB), blood TMB, dynamic change of ctDNA and immune microenvironment. RESULTS: 54 patients with advanced BTC were screened, of whom 38 eligible patients were enrolled. One patient withdrew informed consent before first dose treatment. Median follow-up was 11.8 months. The 6-month PFS rate was 50% (95% CI 33 to 65). Twenty (54%) out of 37 patients had an objective response. The median PFS was 6.1 months and median OS was 11.8 months. The most common treatment-related adverse events (TRAEs) were fatigue (27 (73%)) and fever (27 (73%)). The most frequent grade 3 or worse TRAEs were hypokalemia (7 (19%)) and fatigue (6 (16%)). The ORR was 80% in patients with programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥1% versus 53.8% in PD-L1 TPS <1%. There was no association between response and TMB, blood TMB, immune proportion score or immune cells (p>0.05), except that PFS was associated with blood TMB. Patients with positive post-treatment ctDNA had shorter PFS (p=0.007; HR, 2.83; 95% CI 1.27 to 6.28). CONCLUSION: Camrelizumab plus GEMOX showed a promising antitumor activity and acceptable safety profile as first-line treatment in advanced BTC patients. Potential biomarkers are needed to identify patients who might respond to camrelizumab plus GEMOX. TRIAL REGISTRATION NUMBER: NCT03486678.

A Phase III, randomized, double-blind, placebo-controlled, multicenter study of fruquintinib in Chinese patients with advanced nonsquamous non-small-cell lung cancer - The FALUCA study.

OBJECTIVES: Fruquintinib is an orally active kinase inhibitor that selectively targets the vascular endothelial growth factor (VEGF) receptor. A Phase II trial has demonstrated a significant benefit in progression-free survival (PFS) for fruquintinib-treated patients with locally advanced/metastatic nonsquamous non-small-cell lung cancer (NSCLC) who have progressed after second-line chemotherapy. This Phase III trial is a randomized, double-blind, multicenter trial to confirm fruquintinib's efficacy in the same patient population. MATERIALS AND METHODS: From December 2015 to February 2018, 730 patients were screened, of whom 527 were enrolled into the study. Participants were randomized 2:1 to receive fruquintinib (n = 354) or placebo (n = 173) once daily for 3 weeks on-treatment, and 1 week off-treatment. Patients were stratified according to epidermal growth factor receptor mutation status and prior use of VEGF inhibitors. Primary endpoint was overall survival (OS). RESULTS: Median OS was 8.9 months for the fruquintinib group and 10.4 months for placebo group (hazard ratio [HR] 1.02; 95 % confidence interval [CI], 0.82-1.28; P = 0.841), with median PFS of 3.7 months and 1.0 months, respectively (HR 0.34; 95 % CI, 0.28-0.43; P < 0.001). Objective response rate and disease control rate were 13.8 % and 66.7 % for fruquintinib, and 0.6 % and 24.9 % for placebo, respectively (P < 0.001). Hypertension was the most frequent treatment-emergent adverse event (≥grade 3) observed in fruquintinib-treated patients (21.0 %). Post hoc analysis revealed that fruquintinib prolonged the median OS for patients who did not receive subsequent antitumor therapy: 7.0 months versus 5.1 months for placebo (HR 0.65; 95 % CI, 0.46-0.91; P = 0.012). Patients receiving fruquintinib also reported improvements in quality of life for most functional scales measured by EORTC QLQ-C30 and LC13 questionnaires. CONCLUSION: Although the study did not meet its primary endpoint, fruquintinib could be effective in combination with other agents for the treatment of patients with NSCLC who have failed second-line chemotherapy.

NLK interacts with 14­3­3ζ to restore the expression of E­cadherin.

The Nemo­like kinase (NLK), a conserved serine/threonine kinase, plays a critical role in the regulation of a variety of transcription factors, with important roles in determining cell fate. Although recent studies have demonstrated decreased expression patterns of NLK in various types of human cancer, the functional mechanism of NLK in cancer development has not been elucidated. Here, in the present study overexpression of NLK was found to inhibit the growth and migration of the non­small cell lung cancer A549 cell line. NLK was subsequently found to interact with 14­3­3ζ (also known as YWHAZ), which is responsible for E­cadherin silencing during epithelial­mesenchymal transition (EMT). Furthermore, NLK overexpression was able to restore the expression of E­cadherin inhibited by 14­3­3ζ. Notably, NLK interacts with 14­3­3ζ and prevents its dimerization, which is essential for 14­3­3ζ stability and function. By fusing two copies of the 14­3­3ζ gene, via a Gly­rich linker, a non­dissociable dimer of 14­3­3ζ was formed. It was found that NLK was unable to restore the expression of E­cadherin inhibited by the overexpression of the fused dimer of 14­3­3ζ. In addition, the increased ability of migration induced by the overexpression of fused 14­3­3ζ dimer could not be altered by NLK overexpression. The results from the present study indicate that NLK is a negative regulator of 14­3­3ζ and plays a tumor suppressive role in the inhibition of cancer cell migration.

Treatment strategies for metastatic gastric cancer: chemotherapy, palliative surgery or radiotherapy?

Aim: This study explored whether chemotherapy combined with palliative surgery and/or radiotherapy is a possible treatment for metastatic gastric cancer. Materials & methods: Patients were divided into groups according to treatments. COX models were used to explore prognostic factors. Kaplan-Meier models and log-rank tests were used to analyze outcomes. Outcomes were analyzed before and after propensity score matching. Results: Chemotherapy combined with gastrectomy or metastasectomy prolongs the survival time compared with chemotherapy alone (p < 0.05). Chemotherapy combined with gastrectomy plus metastasectomy and/or radiation therapy also prolongs the survival time (p < 0.05). Conclusion: Chemotherapy combined with gastrectomy could be a more effective treatment for metastatic gastric cancer. Chemotherapy combined with gastrectomy plus metastasectomy and/or radiation therapy could also be a promising treatment.

Alpinumisoflavone suppresses human Glioblastoma cell growth and induces cell cycle arrest through activating peroxisome proliferator-activated receptor-γ.

As a common subtype of malignant gliomas, glioblastoma multiforme (GBM) is associated with poor prognosis. This study is aimed to examine the anticancer activities of alpinumisoflavone (AIF) and its underlying mechanisms. Our results demonstrated that AIF inhibited the proliferation of GBM cells (U373 and T98G) in a time and dose-dependent manner. In addition, flow cytometry analysis not only confirmed AIF arrested cell cycle at the G0/G1 phase but also the induced apoptosis of U373 and T98G cells. Western blotting also confirmed that AIF altered the expression levels of cell cycle-related proteins. Further mechanism studies revealed that AIF inhibited cell proliferation, induced G0/G1 phase arrest and induced apoptosis of U373 and T98G cells through activating PPARγ, as evidenced by the fact that GW9662 (PPARγ inhibitor) could effectively reverse the effects of AIF on U373 and T98G cells. Furthermore, the in vivo study also revealed that AIF suppressed tumor growth and caused cell cycle arrest. Collectively, these results highlighted the potential use of AIF in the treatment of GBM.

The Cell Cycle G2/M Block Is an Indicator of Cellular Radiosensitivity.

BACKGROUND: Determination of the radiosensitivity of a specific tumor is essential to its precision tumor radiotherapy, but the measurement of cellular radiosensitivity with a routine colony forming assay is both labor- and time-consuming. An alternative option allowing rapid and precise prediction of radiosensitivity is necessary. METHODS: In this study, we exposed 4 in vitro cultured cell lines to various doses of X-rays or carbon ions and then measured their radiosensitivities with a routine colony-forming assay, and monitored the kinetics of cell cycle distribution with routine propidium iodine staining and flow cytometry. RESULTS: Based on the results, we correlated cellular radiosensitivity with a dynamic assay of cell cycle distribution, specifically, the negative correlation of cellular radiosensitivity with the accumulated G2/M arrested cells at 48 hours after exposure. The higher the proportion of accumulated G2/M arrested cells at 48 hours after exposure, the lower the radiosensitivity of the cell line, that is, the higher radioresistance of the cell line. CONCLUSION: These findings provide an optional application of regular cell cycle analysis for the prediction of tumor radiosensitivity.