Survival Analysis of Glioblastoma Multiforme

Introduction: To evaluate the survival of Glioblastoma Multiforme (GBM). Material and Methods: Patients witha pathological diagnosis of Glioblastoma Multiforme (GBM) between 1 January 1994 and 30 November 2013, wereretrospectively reviewed. Inclusion criteria: 1) GBM patients with confirmed pathology, 2) GBM patients were treatedby multimodality therapy. Exclusion criteria: 1) GBM patients with unconfirmed pathology, 2) GBM patients with spinalinvolvement, 3) GBM patients with incomplete data records. Seventy-seven patients were treated by multimodalitytherapy such as surgery plus post-operative radiotherapy (PORT), post-operative Temozolomide (TMZ) concurrent withradiotherapy (CCRT), post-operative CCRT with adjuvant TMZ. The overall survival was calculated by the Kaplan-Meiermethod and the log-rank test was used to compare the survival curves. A p-value of ≤ 0.05 was considered to bestatistically significant. Results: Seventy-seven patients with a median age of 53 years (range 4-76 years) showeda median survival time (MST) of 12 months. In subgroup analyses, the PORT patients revealed a MST of 11 monthsand 2 year overall survival (OS) rates were 17.2%, the patients with post-operative CCRT with or without adjuvantTMZ revealed a MST of 23 months and 2 year OS rates were 38.2%. The MST of patients by Recursive PartitioningAnalysis (RPA), classifications III, IV, V, VI were 26.8 months, 14.2 months, 9.9 months, and 4.0 months, (p <0.001).Conclusions: The MST of the patients who had post-operative CCRT with or without adjuvant TMZ was better thanthe PORT group. The RPA classification can be used to predict survival. Multimodality therapy demonstrated the mosteffective treatment outcome. Temozolomide might be beneficial for GBM patients in order to increase survival time.     

Radiotherapy-related Tiredness in Patients with Glioblastoma Multiforme (GBM)

Tiredness may be caused by the brain injury due to the tumor or the treatment in patients with glioblastomamultiforme (GBM). Some patients describe a sense of tiredness particularly after radiation or oral chemotherapy.To evaluate tiredness level of patients with GBM during preoperative, postoperative and radiotherapy we hereeamined a sample of 38 patients. Data were collected over six months in a neurosurgery clinic. Patients assignedto Group I were given a booklet and information about radiotherapy, oral temozolomide and tiredness. GroupII received only the booklet. The chi-squared test were used to determine differences in tiredness betweenGroup I and Group II, with Spearman’s correlation for post-radiotherapy results (3 and 6 months postoperative).In conclusion, the level of tiredness was assessed to be significantly better in Group I than in Group II. Levels oftiredness in patients with GBM were greatly affected by the radiotherapy and oral chemotherapy (temozolomide).     

Glioblastoma Multiforme: A Review of its Epidemiology and Pathogenesis through Clinical Presentation and Treatment

Glioblastoma multiforme (GBM) is one of the most malignant types of central nervous system tumors. Despite advances in treatment modalities it remains largely incurable. The objective of our review is to provide a holistic picture of GBM epidemiology, etiology, pathogenesis, clinical findings and treatment. A literature search was conducted for GBM at PubMed and Google Scholar, with relevant key words like glioblastoma multiforme, pathogenesis, signs and symptoms, treatment etc., and papers published until 2015 were reviewed. It was found that radiation and certain genetic syndromes are the only risk factors identified to date for GBM. Depending on the tumor site patients may present to the clinic with varying symptoms. To confirm the presence and the extent of tumor, various invasive and non-invasive imaging techniques require employment. The literature survey revealed the pathogenesis to involve aberrations of multiple signaling pathways through multiple genetic mutations and altered gene expression. Although several treatment options are available, including surgery, along with adjuvant chemo- and radio-therapy, the disease has a poor prognosis and patients generally succumb within 14 months of diagnosis.     

Understanding the role of cytokines in Glioblastoma Multiforme pathogenesis

Cytokines play a significant role in cancer diagnosis, prognosis and therapy. The immune system’s failure to recognize the malignant tumor cells and mount an effective response may be the result of tumor-associated cytokine deregulation. Glioblastoma Multiforme (GBM) has a characteristic cytokine expression pattern, and abnormalities in cytokine expression have been implicated in gliomagenesis. Within the heterogeneous GBM microenvironment, the tumor cells, normal brain cells, immune cells, and stem cells interact with each other through the complex cytokine network. This review summarizes the current understanding of the functions of key cytokines on GBM, and highlights potential therapeutic applications targeting these cytokines.     

Evaluation of Nestin and EGFR in Patients with Glioblastoma Multiforme in a Public Hospital in Iran

Introduction: Glioblastoma multiforme (GBM) is a grade IV glioma and accounts for 15% of all primary brain tumors. This GBM has a median survival range of less than 2 years after diagnosis and it is highly vascularized by neoformed vessels. Neoangiogenesis is a crucial factor in the malignant tumoral behavior and prognosis of patients and Nestin protein belongs to class VI which is expressed in endothelial cells of neoformed vessels in GBM. Our study shows the correlation between EGFR mutation and Nestin expression in endothelial of neoformed vessels in GBM. Methods: We analyzed 40 GBM samples by immunohistochemistry staining. The immunohistochemical expression of EGFR in tumoral cells and Nestin in endothelial cells in paraffin sections were analyzed. EGFR scoring was the based on staining intensity. Score 0 shows No staining, Score1, mild to moderate staining and score2 sever staining. Microvascular density (MVD) was evaluated with Nestin-immunoreactive. Results: The mean of MVD was 14.6 ±8.25. Nestin-MVD was significantly higher in GBM with sever vascular prolifration (p-value=0.01). EGFR was expressed in 92.5% of samples. The EGFR scoring for tumoral tissue was 7.5%(score:0), 22.5% (score:1) and 70% (score:2). There was a significant relationship between EGFR expression and MVD (p-value=0.017). Conclusion: We suggest that some important mutations as like as EGFR in GBM is responsible for inducing angiogenesis and vascular proliferation. Nestin overexpression as a novel marker might reflect the extent of neoangiogenesis, thus target therapy against EGFR pathway and anti angiogenic may be useful for GBM treatment.     

Overexpression of TRPM7 is Associated with Poor Prognosis in Human Ovarian Carcinoma

Background: The melastatin-related transient receptor potential 7 channel (TRPM7) is a nonselectivecation channel that has been shown to promote tumor metastasis and progression. In this study, we determinedthe expression of TRPM7 in ovarian carcinomas and investigated its possible prognostic value. Materials andMethods: Samples were collected from 138 patients with ovarian cancer. Expression of TRPM7 was assessed byreal-time PCR and immunohistochemistry, expressed with reference to an established scoring system and relatedto clinical pathological factors. Kaplan-Meier survival analysis was applied to estimate disease-free survival(DFS) and overall survival (OS). Univariate and multivariate cox regression analyses were performed to correlateTRPM7 expression levels with DFS and OS. Results: TRPM7 was highly expressed in ovarian carcinoma andsignificantly associated with decreased disease-free survival (DFS: median 20 months vs. 42 months, P=0.0002)and overall survival (OS: median 27 months vs. 46 months, P<0.001). Conclusion: Overexpression of TRPM7expression is significantly associated with poor prognosis in patients with ovarian cancer.     

OLC1在肺鳞癌组织中的过表达与患者的不良预后相关

背景与目的 OLC1(overexpressed in lung cancer 1)是本实验室前期工作中筛选克隆出的一个新型肺癌相关基因.它在肺癌和其它恶性肿瘤中均有较高表达,并与食管鳞癌、卵巢癌、乳腺癌、结直肠癌患者的不良预后相关.本研究旨在检测OLC1在肺鳞癌(squamous cell carcinoma,SCC)和腺癌(adenocarcinoma,ADC)患者肿瘤组织中的表达情况,研究其与肺癌患者预后之间的关系.方法 分别对108例肺鳞癌和90例肺腺癌的癌组织进行免疫组织化学染色,检测OLC1蛋白的表达水平,分析OLC1的表达水平与临床特征及预后的关系.结果 OLC1在肺腺癌组织中的过表达率显著高于鳞癌(87.5%vs 55.3%,P<0.001).OLC1在癌组织中的过表达与肺腺癌患者的预后无显著相关性,与肺鳞癌患者的预后关系的单因素分析显示两者存在相关性(P=0.042),而多因素分析则显示OLC1过表达与鳞癌患者预后的相关性无统计学意义(P=0.05).结论 OLC1在肺腺癌组织中的过表达高于鳞癌,在癌组织中的过表达仅与鳞癌患者的不良预后相关,但不能作为影响预后的独立危险因素.     

Glioblastoma multiforme with an abscess: case report and literature review

An intratumoral or peritumoral microbial intracranial abscess is an infrequent diagnosis. The development of this complication may not be preceded by apparent local or general infection in all cases. To identify this diagnosis by radiological (MRI) or laboratory investigations is very intricate. Nevertheless, the recommended life-saving strategy is early surgery with resolution of both the tumor and infection. If subsequent oncological treatment is required, it has to be adjusted for prevention of re-inflammation. The described patient suffered from an intracranial abscess superimposed on a Glioblastoma Multiforme. The confirmed etiological agent was Staphylococcus aureus. The suspected route of microbial migration and colonization in this tumor was bacteremia via agents from thrombophlebitis. The patient is in a good condition following surgery, antimicrobial treatment, and radiotherapy.     

脑多形性胶质母细胞瘤水肿带大小与预后相关性的分析

目的评价肿瘤外周水肿带对脑多形性胶质母细胞瘤(GBM)的预后影响。方法回顾性分析74例接受适形放射治疗(CRT)多形性胶质母细胞瘤患者的资料。所有患者均经病理组织学证实,其中62例患者经手术全切或次全切术,12例仅行立体定向活检术。55例采用了不同方式的化疗,另外19例患者行单纯放疗,放疗剂量均为60Gy。结果中位生存期为13.9个月,1、2及3年总生存率分别为57.0%、18.0%和12.9%。水肿带最大径≤70mm者中位生存期为19.9个月,>70mm者为9.9个月(P<0.0001);水肿带与肿瘤最大径比值(E/T)≤1.8与>1.8者中位生存期分别为16.6个月和9.9个月(P=0.0004)。中位肿瘤进展时间为7.8个月,1、2年的局部控制率分别为22.4%和8.2%。结论肿瘤边缘水肿带大小以及与肿瘤的比值是影响GBM预后的重要因素,提示水肿带应包括在照射野内,同时在不增加并发症的前提下是否应进一步提高水肿带照射剂量?     

Role of microRNAs in Predicting the Prognosis of Cervical Cancer Cases: A Systematic Review and Meta-Analysis

Aim: There is growing evidence for the possible use of microRNAs (miRNAs) in cancers as diagnostic as well as prognostic biomarkers in the present era of Personalized Medicine. The objective of the present systematic review and meta-analysis was to assess the prognostic role of microRNAs in uterine cervical cancers. Methods: A systematic review and meta-analysis was carried out searching electronic databases for published articles between January 2009 and August 2020 based on standard systematic review guidelines. Meta-analysis was performed by pooling the hazard ratio (HR) with 95% confidence interval (CI) to assess the prognostic value of deregulated miRNAs by the random-effects model. Results: In the present meta-analysis, the aberrant expression of 14 microRNAs in 1,526 uterine cervical cancer cases before definitive therapy from 14 case-control studies were assessed. The pooled HR of two miRNAs, miRNA-155 and miRNA-224 which were upregulated in cervical cancer tissues was 1.76 (95% CI 1.27-2.45) revealing significant association with overall poor survival. Meanwhile, the pooled HR was 1.53 (95% CI 0.94-2.94) when all the deregulated miRNAs in cervical cancer tissues were evaluated. The pooled HR of downregulated miRNAs was 1.46 (95% CI 0.81, 2.64). Meanwhile, the pooled HR of three upregulated miRNAs-425-5p, 196a, 205 in the serum sample was 1.37 (95% CI 0.45 -4.20). Conclusion: The downregulation of aberrant miRNAs was not associated with poor overall survival rates.     

Autophagy Inhibition Promotes Gambogic Acid-induced Suppression of Growth and Apoptosis in Glioblastoma Cells

Objective: To investigate the effects of gambogic acid (GA) on the growth of human malignant glioma cells.Methods: U251MG and U87MG human glioma cell lines were treated with GA and growth and proliferationwere investigated by MTT and colony formation assays. Cell apoptosis was analyzed by annexin V FITC/PI flowcytometry, mitochondrial membrane potential assays and DAPI nuclear staining. Monodansylcadaverine (MDC)staining and GFP-LC3 localisation were used to detect autophagy. Western blotting was used to investigate themolecular changes that occurred in the course of GA treatment. Results: GA treatment significantly suppressedcell proliferation and colony formation, induced apoptosis in U251 and U87MG glioblastoma cells in a timeanddose-dependent manner. GA treatment also lead to the accumulation of monodansylcadaverine (MDC)in autophagic vacuoles, upregulated expressions of Atg5, Beclin 1 and LC3-II, and the increase of punctatefluorescent signals in glioblastoma cells pre-transfected with GFP-tagged LC3 plasmid. After the combinationtreatment of autophagy inhitors and GA, GA mediated growth inhibition and apoptotic cell death was furtherpotentiated. Conclusion: Our results suggested that autophagic responses play roles as a self-protective mechanismin GA-treated glioblastoma cells, and autophagy inhibition could be a novel adjunctive strategy for enhancingchemotherapeutic effect of GA as an anti-malignant glioma agent.     

Increased Expression of Thymidylate Synthetase (TS), Ubiquitin Specific Protease 10 (USP10) and Survivin is Associated with Poor Survival in Glioblastoma Multiforme (GBM)

Background The limited success of empirically designed treatment paradigms for patients diagnosed with glioblastoma multiforme (GBM) emphasizes the need for rationally designed treatment strategies based on the molecular profile of tumor samples and their correlation to clinical parameters.Methods In the current study, we utilize a novel real-time quantitative low density array (RTQ-LDA) to identify differentially expressed genes in de novo GBM tissues obtained from patients with distinctly different clinical outcomes. Total RNA was isolated from a cohort of 21 GBM specimens obtained from patients with either good (long-term survival (LTS) >36 months post surgery, n = 8) or poor (died of the disease (DOD) <24 months post surgery, n = 13) prognosis. Non-neoplastic brain tissue (n = 5) was obtained from patients who underwent surgery for refractory epilepsy. Demographic data was assessed for correlation with survival using Cox proportional hazards models. Sufficient RNA was available to use RTQ-LDA to quantify the expression of 93 independent genes in 5␣LTS, 4 DOD, and 5 non-neoplastic brain samples. The eight differentially expressed genes identified by RTQ-LDA in LTS versus DOD (P ≤ 0.050) were subsequently quantified in all 21 GBM samples by real-time quantitative PCR (RTQ).Results A correlation between younger patients and good prognosis was demonstrated (P ≤ 0.05). The combination of RTQ-LDA and RTQ identified thymidylate synthetase (TS), ubiquitin specific protease 10 (USP10), and survivin as significantly over-expressed (P ≤ 0.050) in DOD compared to LTS patients. Ribonucleotide reductase subunit M2 (RRM2) was identified as tumor-specific, but not associated with survival.Conclusions Taken collectively, TS, USP10, survivin and RRM2 may be useful as prognostic indicators and/or in the development of rationally designed treatment protocols.     

GSTP-1基因遗传变异对术后接受替莫唑胺联合放疗的脑胶质瘤患者预后的影响

目的 探讨谷胱甘肽S-转移酶P-1（GSTP-1）基因遗传变异对术后接受替莫唑胺联合放疗的脑胶质瘤患者预后的影响。方法 收集患者外周血进行GSTP-1基因多态性位点基因分型。收集部分患者接受化疗前的新鲜外周血单核细胞提取RNA进行GSTP-1 mRNA表达实验。对多态性位点和其他变量进行相关性分析。结果 Ile105Val位点在研究人群中的分布频率为：G/G型68.00%（119例）,G/A型29.14%（51例）,A/A型2.86%（5例）,最小等位基因频率为0.17,该位点基因型分布频率符合Hardy-Weinberg平衡（P=0.868）。G/A+A/A型和G/G基因型患者的中位无进展生存期（PFS）分别为4.4和6.9月,差异有统计学意义（P=0.005）。G/A+A/A型和G/G基因型患者的中位总生存期（OS）分别为11.0和15.3月,差异有统计学意义（P<0.001）。G/A+A/A基因型对OS具有独立的影响意义（OR=1.68, P=0.011）。G/A+A/A基因型患者的GSTP-1 mRNA表达较G/G型高（P<0.001）。结论 GSTP-1基因Ile105Val位点可能通过影响GSTP-1基因mRNA表达进而影响接受替莫唑胺联合放疗的胶质瘤患者预后。     

Overexpression of Tbx3 Predicts Poor Prognosis of Patients with Resectable Pancreatic Carcinoma

Background: To determine the expressions of Tbx3, a member of subgroup belonging to T-box family, andits prognostic value in pancreatic carcinoma. Materials and Methods: We determined the expression levels ofTbx3 on both mRNA and protein levels in 30 pairs of fresh tumor tissues and paratumor tissues by quantitativereal-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. In addition, protein levelof Tbx3 were identified using immunochemistry in 80 pairs of paraffin-embedded specimen. The correlationsbetween Tbx3 expression and various clinicopathological parameters as well as overall survival were evaluated.Results: Tbx3 mRNA and protein levels in tumor tissues were significantly higher than in the paratumor tissuesby qRT-PCR (0.05 ±0.007 vs. 0.087±0.001, p<0.001) and western blotting (1.134±0.043 vs. 0.287±0.017, p<0.001).The statistical analysis based on immunohistochemical evaluation suggested that Tbx3 aberrant expressionwas significantly associated with several conventional clinicopathological variables, such as gender, age, tumorposition, preoperative CA19-9 level, pathological T staging and N staging. Univariate and multivariate analysesrevealed that Tbx3 expression was an independent prognostic factor for overall survival (<0.001). Conclusions:Our results suggest that overexpression of Tbx3 is associated with poor prognosis of pancreatic cancer patients.However, additional clinical trials are needed to accurately validate this observation.     

ZMYND11在多形型胶质母细胞瘤中的表达及意义

目的 探讨ZMYND11在多形性胶质母细胞瘤（GBM）中的表达及意义。方法 收集河北医科大学第二医院GBM患者术中肿瘤标本20例（肿瘤组）,重度脑外伤患者正常脑组织标本20例（对照组）,对上述标本进行Western blot及qRT-PCR实验,检测并比较两组ZMYND11的表达;利用ZMYND11过表达的慢病毒转染GBM的细胞系U87细胞使其ZMYND11过表达,通过CCK、Transwell及流式细胞分析检测ZMYND11对U87细胞在增殖、侵袭及凋亡方面的作用;将ZMYND11过表达的U87细胞接种至裸鼠内进行体内试验。结果 肿瘤组中ZMYND11的表达量明显低于对照组（P<0.001）; ZMYND11过表达可明显抑制U87细胞的增殖及侵袭并促进其凋亡,体内实验显示ZMYND11可明显抑制肿瘤的生长。结论 ZMYND11可抑制GBM的发生与发展。     

MRI Manifestions Correlate with Survival of Glioblastoma Multiforme Patients

Objective To identify the correlation between magnetic resonance manifestation and survival of patients with glioblastoma multiforme(GBM). Methods The magnetic resonance imaging(MRI) images of 30 glioblastoma patients were collected.Imaging features including degrees of contrasted area,edema surrounding the tumor,and intensity in T2-weighted imaging were selected to determine their correlation with patient survival.The relationship between imaging and survival time was studied using SPSS 19.0 software.KaplanMeier survival analysis and log-rank test were used to compare the survival curves. Results Patients with <5%contrasted enhancement area of tumor had longer overall survival(OS) than those with >5%contrasted enhancement area of tumor.Patients without edema surrounding the tumor had longer OS than those with edema.Patients with tumor of hyperintensity and/or isointensity in T2-weighted imaging had longer OS than those with hyperintensity and/or isointensity and hypointensity. Conclusions Some MR imaging features including degrees of contrasted area,edema surrounding the tumor,and intensity in T2- weighted imaging are correlated with the survival of patients with GBM.These features can serve as prognostic indicators for GBM patients.     

Overexpression of MMSET is Correlation with Poor Prognosis in Hepatocellular Carcinoma

The multiple myeloma SET domain (MMSET) involved in the t(4;14)(p16;q32) chromosomal translocation encodes a histone lysine methyltransferase. High expression of MMSET is common translocation in multiple myeloma (MM) and is associated with the worst prognosis. Recent studies have shown that overexpression of MMSET is significant in other tumor types compared to their normal tissues. However, little is known about its role in hepatocellular carcinoma (HCC). In these study we investigate the expression of MMSET in HCC and to make correlations with clinicopathologic features. Twenty-eight pairs of HCC and adjacent non-tumor tissues, and eight normal liver tissues were collected for MMSET detection by western blotting and real time-PCR analysis. Immunohistochemistry was used to determine the expression of MMSET in HCC and adjacent non-tumor tissues from 103 patients. Overexpression of MMSET was significantly associated with Edmondson stage, vascular invasion. Moreover, Kaplan-Meier curves showed that MMSET upregulated was associated with shorter overall survival and disease-free survival in HCC patient. In conclusion, our study demonstrates for the first time that overexpression of MMSET is an independent prognostic factor and is correlated with poor survival in HCC patients.     

Involvement of MicroRNA-198 Overexpression in the Poor Prognosis of Esophageal Cancer

Objective: This study aimed to investigate whether the miR-198 expression level is related to clinicopathologicalfactors and prognosis of esophageal cancer. Methods: MicroRNA was extracted from esophageal cancer patientswho underwent surgery for assessment using the Taqman@ MicroRNA assay. The correlation between miR-198expression and clinicopathological features was analyzed, and the significance of miR-198 as a prognostic factorand its relationship with survival was determined. Results: MicroRNA-198 (miR-198) expression was higher inpatients with poor prognosis than those with good prognosis (P < 0.05). Kaplan-Meier analysis results showedthat the miR-198 expression level had a significant correlation with survival time (P = 0.030) and that patientswith a higher expression of miR-198 had a shorter survival time. Cox multi-factor model analysis showed thatpatient prognosis (P = 0.014), tumor length (P = 0.040) and expression (P = 0.012), and survival time had asignificant correlation; the corresponding risks were 7.268, 1.246, and 3.524, respectively. Conclusion: miR-198 overexpression is involved in the poor prognosis of esophageal cancer and can be used as a biomarker forselection of cases requiring especial attention.