The relationship between prognosis and temporal muscle thickness in 102 patients with glioblastoma.

Temporal muscle thickness measured on 3D MRI has recently been linked to prognosis in glioblastoma patients and may serve as an independent prognostic indicator. This single-center study looked at temporal muscle thickness and prognosis in patients with primary glioblastoma. Overall survival was the major study outcome. For a retrospective analysis from 2010 to 2020, clinical data from 102 patients with glioblastoma at the Department of Oncology Radiotherapy of the First Affiliated Hospital of Dalian Medical University were gathered. Fifty-five cases from 2016 to 2020 contained glioblastoma molecular typing data, of which 45 were IDH wild-type glioblastomas and were analysed separately. TMT was measured on enhanced T1-weighted magnetic resonance images in patients with newly diagnosed glioblastoma.Overall patient survival (OS) was calculated by the Kaplan-Meier method and survival curves were plotted using the log-rank-sum test to determine differences between groups, and multifactorial analyses were performed using a Cox proportional-risk model.The median TMT for 102 patients was 6.775 mm (range: 4.95-10.45 mm). Patients were grouped according to median TMT, and the median overall survival (23.0 months) was significantly longer in the TMT > median group than in the TMT median group (P 0.001; Log-rank test). Analysing 45 patients with IDH wild type alone, the median overall survival (12 months) of patients in the TMT > median group was significantly longer than that of patients in the TMT ≤ median group (8 months) (P < 0.001; Log-rank test).TMT can serve as an independent prognostic factor for glioblastoma.

Effect of adjuvant radiotherapy on overall survival and breast cancer-specific survival of patients with malignant phyllodes tumor of the breast in different age groups: a retrospective observational study based on SEER.

PURPOSE: Malignant phyllodes tumor of the breast (MPTB) is a rare type of breast cancer, with an incidence of less than 1%. The value of adjuvant radiotherapy (RT) for MPTB has been controversial. The aim of the study was to explore the effect of radiotherapy on the long-term survival of female patients with MPTB at different ages. METHODS: Female MPTB patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2020. A Kaplan-Meier survival analysis was conducted to investigate the value of RT for the long-term survival of MPTB patients in different age groups. Additionally, univariate and multivariate Cox regression analyses were performed for overall survival (OS) and breast cancer-specific survival (BCSS) of MPTB patients. Furthermore, propensity score matching (PSM) was also performed to balance the differences in baseline characteristics. RESULTS: 2261 MPTB patients were included in this study, including 455 patients (20.12%) with RT and 1806 patients (79.88%) without RT. These patients were divided into four cohorts based on their ages: 18-45, 46-55, 56-65, and 65-80. Before adjustment, there was a statistically significant difference in long-term survival between RT-treated and non-RT-treated patients in the younger age groups (age group of 18-45 years: OS P = 0.019, BCSS P = 0.016; age group of 46-55 years: OS P < 0.001, BCSS P < 0.001). After PSM, no difference was found in long-term survival of patients in both younger and older groups regardless of whether they received RT (age group of 18-45 years: OS P = 0.473, BCSS P = 0.750; age group of 46-55 years: OS P = 0.380, BCSS P = 0.816, age group of 56-65 years: OS P = 0.484, BCSS P = 0.290; age group of 66-80 years: OS P = 0.997, BCSS P = 0.763). In multivariate COX regression analysis, RT did not affect long-term survival in patients with MPTB. CONCLUSION: There is no evidence that long-term survival of MPTB patients in specific age groups can benefit from RT.

Systematic review and metanalysis of neutrophil to lymphocyte ratio and prognosis in patients with nasopharyngeal carcinoma.

Background: Hematological parameters have been associated with prognosis in patients with nasopharyngeal carcinoma (NPC). The present meta-analysis investigated the utility of neutrophil-lymphocyte ratio (NLR) in the prognosis of patients with NPC. Methods: Multiple electronic databases, including PubMed, Embase, the Cochrane Library, and the Web of Science, were systematically searched for studies assessing the association between NLR and NPC from 2011 to 2021. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were utilized to estimate effect size. Use of a fixed effect or random effect model was based on heterogeneity stability was tested by sensitivity analysis, and the risk of bias was assessed by funnel plots. Random effects models were used based on the actual results. Because the NLR grouping criteria for the included studies differed, subgroup analyses were performed. Results: A search of the electronic databases identified 14 studies, encompassing 6693 patients, that met the selection criteria. NLR higher than the cutoff value was significantly associated with poorer OS [HR 1.760, 95% CI 1.470-2.120, p <0.00001] and PFS [HR 1.850, 95% CI 1.430-2.390, p = .006]. Sensitivity analysis showed that the results of the meta-analysis were relatively stable, and funnel plots were used to exclude the risk of bias. Conclusions: Elevated pretreatment NLR in peripheral blood is predictive of poorer OS and PFS in patients with NPC. NLR is an easily measured and important prognostic factor in patients with NPC.

Advances in the relationship between temporal muscle thickness and prognosis of patients with glioblastoma: a narrative review.

The most dangerous variety of glioma, glioblastoma, has a high incidence and fatality rate. The prognosis for patients is still bleak despite numerous improvements in treatment approaches. We urgently need to develop clinical parameters that can evaluate patients' conditions and predict their prognosis. Various parameters are available to assess the patient's preoperative performance status and degree of frailty, but most of these parameters are subjective and therefore subject to interobserver variability. Sarcopenia can be used as an objective metric to measure a patient's physical status because studies have shown that it is linked to a bad prognosis in those with cancers. For the purpose of identifying sarcopenia, temporal muscle thickness has demonstrated to be a reliable alternative for a marker of skeletal muscle content. As a result, patients with glioblastoma may use temporal muscle thickness as a potential marker to correlate with the course and fate of their disease. This narrative review highlights and defines the viability of using temporal muscle thickness as an independent predictor of survival in glioblastoma patients, and it evaluates recent research findings on the association between temporal muscle thickness and prognosis of glioblastoma patients.

A simplified non-coplanar volumetric modulated arc therapy for the whole brain radiotherapy with hippocampus avoidance.

Purpose: To evaluate the feasibility of using a simplified non-coplanar volumetric modulated arc therapy (NC-VMAT) and investigate its dosimetric advantages compared with intensity modulated radiation therapy (IMRT) and coplanar volumetric modulated arc therapy (C-VMAT) for hippocampal-avoidance whole brain radiation therapy (HA-WBRT). Methods: Ten patients with brain metastase (BM) were included for HA-WBRT. Three treatment plans were generated for each case using IMRT, C-VMAT, and NC-VMAT, respectively. Results: The dosimetric results of the three techniques complied roughly with the RTOG 0933 criteria. After dose normalization, the V30Gy of whole brain planned target volume (WB-PTV) in all the plans was controlled at 95%. Homogeneity index (HI) of WB-PTV was significantly reduced in NC-VMAT (0.249 ± 0.017) over IMRT (0.265 ± 0.020, p=0.005) and C-VMAT (0.261 ± 0.014, p=0.020). In terms of conformity index (CI), NC-VMAT could provide a value of 0.821 ± 0.010, which was significantly superior to IMRT (0.788 ± 0.019, p<0.001). According to D2% of WB-PTV, NC-VMAT could provide a value of 35.62 ± 0.37Gy, significantly superior to IMRT (36.43 ± 0.65Gy, p<0.001). According to D50% of WB-PTV, NC-VMAT can achieve the lowest value of 33.18 ± 0.29Gy, significantly different from IMRT (33.47 ± 0.43, p=0.034) and C-VMAT (33.58 ± 0.37, p=0.006). Regarding D2%, D98%, and Dmean of hippocampus, NC-VMAT could control them at 15.57 ± 0.18Gy, 8.37 ± 0.26Gy and 11.71 ± 0.48Gy, respectively. D2% and Dmean of hippocampus for NC-VMAT was significantly lower than IMRT (D2%: 16.07 ± 0.29Gy, p=0.001 Dmean: 12.18 ± 0.33Gy, p<0.001) and C-VMAT (D2%: 15.92 ± 0.37Gy, p=0.009 Dmean: 12.21 ± 0.54Gy, p<0.001). For other organs-at-risk (OARs), according to D2% of the right optic nerves and the right lenses, NC-VMAT had the lowest values of 31.86 ± 1.11Gy and 7.15 ± 0.31Gy, respectively, which were statistically different from the other two techniques. For other organs including eyes and optic chiasm, NC-VMAT could achieve the lowest doses, different from IMRT statistically. Conclusion: The dosimetry of the three techniques for HA-WBRT could roughly comply with the proposals from RTOG 0933. After dose normalization (D95%=30Gy), NC-VMAT could significantly improve dose homogeneity and reduce the D50% in the brain. Besides, it can reduce the D2% of the hippocampus, optic nerves, and lens. With this approach, an efficient and straightforward plan was accomplished.

Risk factor analysis and nomogram establishment and verification of brain astrocytoma patients based on SEER database.

Astrocytoma is a common brain tumor that can occur in any part of the central nervous system. This tumor is extremely harmful to patients, and there are no clear studies on the risk factors for astrocytoma of the brain. This study was conducted based on the SEER database to determine the risk factors affecting the survival of patients with astrocytoma of the brain. Patients diagnosed with brain astrocytoma in the SEER database from 2004 to 2015 were screened by inclusion exclusion criteria. Final screened brain astrocytoma patients were classified into low grade and high grade according to WHO classification. The risk factors affecting the survival of patients with low-grade and high-grade brain astrocytoma were analyzed by univariate Kaplan-Meier curves and log-rank tests, individually. Secondly, the data were randomly divided into training set and validation set according to the ratio of 7:3, and the training set data were analyzed by univariate and multivariate Cox regression, and the risk factors affecting the survival of patients were screened and nomogram was established to predict the survival rates of patients at 3 years and 5 years. The area under the ROC curve (AUC value), C-index, and Calibration curve are used to evaluate the sensitivity and calibration of the model. Univariate Kaplan-Meier survival curve and log-rank test showed that the risk factors affecting the prognosis of patients with low-grade astrocytoma included Age, Primary site, Tumor histological type, Grade, Tumor size, Extension, Surgery, Radiation, Chemotherapy and Tumor number; risk factors affecting the prognosis of patients with high-grade astrocytoma include Age, Primary site, Tumor histological type, Tumor size, Extension, Laterality, Surgery, Radiation, Chemotherapy and Tumor number. Through Cox regression, independent risk factors of patients with two grades were screened separately, and nomograms of risk factors for low-grade and high-grade astrocytoma were successfully established to predict the survival rate of patients at 3 and 5 years. The AUC values of low-grade astrocytoma training set patients were 0.829 and 0.801, and the C-index was 0.818 (95% CI 0.779, 0.857). The AUC values of patients in the validation set were 0.902, 0.829, and the C-index was 0.774 (95% CI 0.758, 0.790), respectively. The AUC values of high-grade astrocytoma training set patients were 0.814 and 0.806, the C-index was 0.774 (95% CI 0.758, 0.790), the AUC values of patients in the validation set were 0.802 and 0.823, and the C-index was 0.766 (95% CI 0.752, 0.780), respectively, and the calibration curves of the two levels of training set and validation set were well fitted. This study used data from the SEER database to identify risk factors affecting the survival prognosis of patients with brain astrocytoma, which can provide some guidance for clinicians.

[Retracted] Tripartite motif 16 inhibits hepatocellular carcinoma cell migration and invasion.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that various panels showing the western blotting data in Figs. 1D, 3A, 6A and C, 9B and 10A, the Transwell migration and invasion assays in Fig. 10C, and the H&E staining images from the lung portrayed in Fig. 5B were strikingly similar to data largely appearing in different form in other articles by different authors from different research institutions. Moreover, the data panels showing the Transwell migration and assay experiments in Figs. 3C and D and 4C and D showed several overlapping sections, such that the data appeared to have been selected from a small number of original sources to represent differently performed experiments. Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Oncology, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 48: 1639­1649, 2016; DOI: 10.3892/ijo.2016.3398].

Impact of Diets on Response to Immune Checkpoint Inhibitors (ICIs) Therapy against Tumors.

Immunotherapy has revolutionized the established therapeutics against tumors. As the major immunotherapy approach, immune checkpoint inhibitors (ICIs) achieved remarkable success in the treatment of malignancies. However, the clinical gains are far from universal and durable, because of the primary and secondary resistance of tumors to the therapy, or side effects induced by ICIs. There is an urgent need to find safe combinatorial strategies that enhance the response of ICIs for tumor treatment. Diets have an excellent safety profile and have been shown to play pleiotropic roles in tumor prevention, growth, invasion, and metastasis. Accumulating evidence suggests that dietary regimens bolster not only the tolerability but also the efficacy of tumor immunotherapy. In this review, we discussed the mechanisms by which tumor cells evade immune surveillance, focusing on describing the intrinsic and extrinsic mechanisms of resistance to ICIs. We also summarized the impacts of different diets and/or nutrients on the response to ICIs therapy. Combinatory treatments of ICIs therapy with optimized diet regimens own great potential to enhance the efficacy and durable response of ICIs against tumors, which should be routinely considered in clinical settings.

Characterization of the nasopharynx microbiota in patients with nasopharyngeal carcinoma vs. healthy controls.

PURPOSE: Nasopharyngeal carcinoma (NPC), an epithelial-originated malignant tumor, has a special geographic distribution. However, the etiology of NPC has not been examined in detail. Increasing pieces of evidence indicate that the microbiome may contribute to head and neck squamous cell carcinoma. Until now, there is limited information on the role of the microbiome in NPC, so we assessed variations in the nasopharynx microbiota of patients with NPC relative to the bacterial in health controls. METHODS: Nasopharynx lavage fluid (NLF) samples were collected from 11 NPC patients and 5 volunteer controls. 16S rRNA sequencing and comparative analyses of NLF bacterial microbiome between NPC patients and controls were performed. RESULTS: NLF microbial alpha-diversity by the Shannon index and Simpson index decreased significantly in the NPC patients when compared with the controls. Beta-diversity by principal component analysis exhibited separated patterns of the NPC patients and healthy controls. Thirty-one genera differed significantly between the NPC patient group and healthy control group. The abundance of 17 bacteria was correlated with primary tumor size and invaded lymph node size. Functional gene prediction analysis showed that 9 gene function pathways were significantly different between the two groups. CONCLUSION: Our results demonstrated that the nasopharynx microbiota in NPC patients was different from that of the healthy controls, suggesting that the nasopharynx microenvironment might be related to NPC.

RNF135, RING finger protein, promotes the proliferation of human glioblastoma cells in vivo and in vitro via the ERK pathway.

Ring finger protein 135 (RNF135), located on chromosome 17q11.2, is a RING finger domain-containing E3 ubiquitin ligase that was identified as a bio-marker and therapy target of glioblastoma. In our study, we confirmed that RNF135 was up-regulated in glioblastoma tissues compared with normal brain (NB) tissues, and that RNF135 knockdown inhibited proliferation and migration and led to cell cycle arrest in the G0/G1 phase in vivo. By lowering RNF135 expression, phosphorylated Erk and cell cycle protein CDK4 were down-regulated, while p27(Kip1) and p21(Waf1/Cip1) were up-regulated in U87 and U251 cells in vitro. In addition, using the immunofluorescence double labelling method, we found that RNF135 and P-Erk were co-localized in the cytoplasm and were highly expressed in glioblastoma samples compared with NB tissues. Moreover, the growth of U87 cell-transplanted tumours in nude mice was inhibited while transduced with Lv-shRNF135. Taken together, our findings demonstrate the biological effects of RNF135 in glioblastoma cell proliferation, migration and cell cycle, and its role in the progression of glioblastoma may be associated with the ERK signal transduction pathway.

Tripartite motif 16 inhibits hepatocellular carcinoma cell migration and invasion.

Tripartite motif 16 (TRIM16), a member of the RING B-box coiled-coil (RBCC)/tripartite totif (TRIM) protein family, has been demonstrated to have significant effects on tumor migration by previous studies, but its specific contribution to hepatocellular carcinoma (HCC) is currently unknown. The aim of this study was to evaluate the prognostic value of TRIM16 and investigate its functional roles in HCC. The expression of TRIM16 in HCC patient samples were examined using qRT-PCR and western blotting. HCC cell lines with either TRIM16 overexpression or knockdown were established. The effect of TRIM16 on HCC cell migration and invasion was investigated using these cells. Compared with paired normal liver tissues in clinical cancer samples, we found that the expression of TRIM16 was significantly downregulated in HCC lesions. We also found knockdown of TRIM16 promoted epithelial-mesenchymal transition (EMT) in a manner associated with HCC metastasis in vitro and in vivo. Mechanistically, TRIM16 inhibited ZEB2 expression, which in turn inhibited transcription of the pivotal ZEB2 target gene E-cadherin. RNA interference-mediated silencing of ZEB2 attenuated shTRIM16-enhanced cell migration and invasion. In conclusion, our findings define TRIM16 as an inhibitor of EMT and metastasis in HCC that predicts poor clinical outcomes.

Down-regulation of ribosomal protein S15A inhibits proliferation of human glioblastoma cells in vivo and in vitro via AKT pathway.

Ribosomal protein s15a (RPS15A), a highly conserved cytoplasmic protein, promotes mRNA/ribosome interaction in translation. Recent evidence showed that RPS15A is essential for tumor growth. RPS15A expression level was measured in glioblastoma tissue samples and normal brain (NB) tissue samples. RPS15A RNAi stable cell line U87 and U251 was generated by the pLVTHM-GFP lentiviral RNAi expression system. The knockdown efficiency was confirmed by quantitative real-time PCR and western blot. Molecular mechanisms and the effect of RPS15A on cell growth and migration were investigated by using western blot, MTT assay, wound healing assay, transwell migration assay, and tumorigenesis in nude mice. Here, we report that RPS15A is overexpressed in human glioblastoma tumor tissues. RPS15A knockdown inhibits proliferation and migration of glioblastoma cells in vitro. Knocking down RPS15A leads to the level of p-Akt decrease and cell cycle arrested in G0/G1 phase in U87 and U251 cells. Furthermore, the growth of glioblastoma cell-transplanted tumors in nude mice is inhibited by transduction with Lv-shRPS15A. Our findings indicate that RPS15A promotes cell proliferation and migration in glioblastoma for the first time. RPS15A might play a distinct role in glioblastoma and serve as a potential target for therapy.

HOXD9 promotes epithelial-mesenchymal transition and cancer metastasis by ZEB1 regulation in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor that severely threatens human health. The poor prognosis of HCC is mainly attributed to intrahepatic and extrahepatic metastases. HOXD9 proteins belong to a superfamily that regulates the development and control of many cellular processes, including proliferation, apoptosis, cell shape, and cell migration. HOXD9 can also function as an oncogene in several cancer cells. However, its biological function in human HCC requires further investigation. In this study, HOXD9 exhibited high expression in invasive HCC cells. HOXD9 overexpression can significantly enhance HCC cell migration, invasion, and metastasis, whereas silencing HOXD9 inhibits these processes. HOXD9 also promotes the epithelial-mesenchymal transition (EMT) of HCC cells. Microarray analysis suggests that ZEB1 can function as a downstream factor of HOXD9. HOXD9 can interact with the promoter region of ZEB1 and promotes ZEB1 expression. ZEB1 knockdown inhibits HOXD9-induced migration and invasion, as well as EMT in HCC cells. This study helps elucidates the oncogenic functions of HOXD9 in HCC.

Somatic mutations in myeloid cell leukemia-1 contribute to the pathogenesis of glioma by prolonging its half-life.

The identification of mutated genes in glioblastoma multiforme (GBM) is an essential step towards improving current understanding of the molecular mechanism underlying the disease and establishing novel targets for diagnostic and therapeutic purposes. The present study used direct sequencing to screen 20 malignancy-associated genes, which have either been well described in the literature or observed multiple times in human cancer sequencing, in cancerous and normal control tissue samples from 20 patients with histologically confirmed GBM. The investigation identified five somatic non-synonymous coding mutations in four candidate genes, with two located in the proline, glutamic acid, serine, threonine-rich region of myeloid cell leukemia sequence 1 (Mcl)-1, (D155G and L174S). The sample pool was then expanded by sequencing Mcl-1 in a further 43 patients with GBM and another somatic mutation in the same region, D155H, was identified. The subsequent functional investigation confirmed that these somatic mutations affected the degradation of Mcl-1, and the growth of glioma cells transfected with mutant plasmids was significantly accelerated compared with cells overexpressing wild-type Mcl-1. The mutational profiling of GBM in the present study revealed for the first time, to the best of our knowledge, several mutations in Mcl-1, and identified this gene as a novel therapeutic target for the treatment of GBM.

Expression and localization of estrogen receptor in human breast cancer and its clinical significance.

The aim of this study was to analyze the clinicopathologic significance of ERα protein that localized in the cell cytoplasm and/or cell membrane of human breast cancer and explore what kind of protein that the cytoplasm/membrane ERα belongs to. ERα expressions in 61 cases of breast cancer are detected by immunohistochemistry, grouping is performed according to the positive staining of different subcellular localizations, the expression levels of ERα66 and ERα36 in cancer tissues of groups with different subcellular localizations are detected by Western blot, and correlation between the indicators and its clinicopathologic significance are analyzed by combining with the clinical pathological parameters. Localization by immunohistochemical staining in breast cancer cells shows that there are two types of ERα­in the cell nucleus and/or the cell membrane; there are four groups as ER nuclear staining positive + membrane staining positive (N+/C+), 23 cases; ER nuclear staining positive + membrane staining negative (N+/C-), 16 cases; ER nuclear staining negative + membrane staining positive (N-/C+), 8 cases; and ER nuclear staining negative + membrane staining negative (N+/C+), 14 cases. ER expression in the cytoplasm and/or membrane of cancer cells is correlated with the high expression of HER-2, the lymphatic metastasis, and the late clinical stage. Western blot results show that ER protein in breast cancer tissues mainly consists of ERα66 and ERα36 bands, and among all the groups, all the cases from the N+/C+ group (n = 23) have both ERα66 and ERα36 expressions; in the N+/C- group, 14 cases of which only have the ERα66 expression without ERα36 expression and 2 cases of which have both ERα66 and ERα36 expression; all the cases from the N-/C+ group have only the ERα36 expression without ERα66 expression; and in the N-/C- group, there is no either ERα66 or ERα36 expression. The expression level of ERα36 relates to the age of patients, the menopause, the lymphatic metastasis, and the tumor size (p < 0.05), and no statistical significance was shown between it and the family history of patients as well as the clinical staging parameters (p > 0.05). The expression level of ERα66 relates to the tumor size of breast cancer and the clinical stages (p < 0.05), and no statistical significance was shown between it and the age of patients, the history of menopause, and the family history as well as the parameters of lymphatic metastasis (p > 0.05). ER protein expression of human breast cancer is localized in the cell nucleus and/or the cell membrane, with poor prognosis of cytoplasm/membrane-positive patients; ER protein that localized in the nucleus is mainly ERα66 and that localized in the cytoplasm and/or membrane is mainly ERα36.

MUC4 modulates human glioblastoma cell proliferation and invasion by upregulating EGFR expression.

Glioblastoma (GBM), the most common primary brain tumor, is the leading cause of deaths related to tumors in the central nervous system. The prognosis of GBM patients is currently poor, and the mechanisms underlying GBM genesis remain unclear. The expression of MUC4, a high-molecular-weight and highly glycosylated protein, has been studied in many cancers. However, information on MUC4 expression in GBM is limited. In this study, we found that MUC4 was overexpressed in GBM cell lines and tissues. The proliferation and invasive potential of GBM cells were significantly increased by the ectopic expression of MUC4. By contrast, RNA interference targeting MUC4 in GBM cells significantly decreased the proliferation and invasive potential of GBM cells. We also found that the expression of epidermal growth factor receptor (EGFR) was modulated by MUC4. EGFR inhibition by siRNA reversed the MUC4-induced proliferation and invasion. These results indicated that MUC4 expression in GBM was important in GBM cell proliferation and invasion, which may be partly associated with EGFR overexpression.