Expression pattern and prognostic significance of myosin light chain 9 (MYL9): a novel biomarker in glioblastoma

2019 ◽  
Vol 72 (10) ◽  
pp. 677-681 ◽  
Author(s):  
Banavathy S Kruthika ◽  
Harsha Sugur ◽  
Kanuri Nandaki ◽  
Arivazhagan Arimappamagan ◽  
Kondaiah Paturu ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
The Cancer Genome Atlas ◽  
Newly Diagnosed ◽  
Paired Samples ◽  
Idh1 R132h ◽  
Recurrent Gbm

AimsTumour recurrence is inevitable in glioblastoma (GBM) and mostly noted in the peritumoural brain zone (PT). In our previous microarray-based study, we identified Myosin Light Chain 9 (MYL9) as a highly expressed gene in the PT of GBM. Therefore, we aimed to study the expression pattern and clinical significance of MYL9 in GBM.MethodsPatient samples included three retrospective cohorts: 25 GBM cases with differential biopsies of tumour core and PT, 62 retrospective cases of newly diagnosed GBM with survival information and 20 paired samples (newly diagnosed and recurrent GBM). All tumour tissues, archived as formalin fixed paraffin embedded blocks were retrieved and immunohistochemistry for MYL9 and IDH1 R132H was performed. MYL9 expression was correlated with patient prognosis in our cohort and in The Cancer Genome Atlas (TCGA) and Rembrandt cohorts. It was further evaluated in the 20 paired samples of GBM.ResultsMYL9 showed a cytoplasmic membranous staining of tumour cells. The staining pattern was variable and patchy within tumours. Higher MYL9 expression was associated with poor overall and progression-free survival in our and in TCGA and Rembrandt cohorts. The expression of MYL9 was higher in IDH1 R132H immunonegative cases.ConclusionsWe show MYL9 as a novel biomarker, variably expressed in GBM. The association of high MYL9 expression with poor prognosis in newly diagnosed GBM patients and increased expression in recurrent GBM is indicative of its role in conferring tumour aggressiveness.

TAMI-19. IMMUNOHISTOLOGICAL ANALYSIS OF ANGIOGENIC FACTORS OTHER THAN VEGF IN GLIOBLASTOMAS IN RELATION TO THE USE OF BEVACIZUMAB

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi202-vi202
Author(s):  
Taketo Ezaki ◽  
Ryota Tamura ◽  
Toshihide Tanaka ◽  
Yuki Kuranari ◽  
Keisuke Miyake ◽  
...  
Keyword(s):  
Growth Factor ◽  
Performance Status ◽  
Progression Free Survival ◽  
Angiogenic Factors ◽  
In Situ Observation ◽  
Newly Diagnosed ◽  
Naive Group ◽  
Paired Samples ◽  
Initial Surgery ◽  
Effective Group

Abstract Although bevacizumab was shown to improve progression-free survival and performance status of the patients with high-grade gliomas, clinical trials consistently showed lack of benefit in terms of patients’ overall survival. The recurrent tumors are inevitably more aggressive and invasive as compared with the original tumors, and the in-situ observation in actual human specimens is essential to elucidate the mechanism of resistance. In Japan, bevacizumab was approved not only for recurrent but also for newly diagnosed cases. The safety as well as efficacy of resection following neoadjuvant bevacizumab has been reported, and a phase II study is currently ongoing (UMIN-000025579). In the present study, the expression of angiogenic factors other than VEGF (basic fibroblast growth factor (bFGF), placenral growth factor (PlGF), angiopoietin1/2 and ephrinA2) was investigated by immunohistochemistry to be compared among tumors with no previous bevacizumab treatment, those resected following bevacizumab, and those refractory to bevacizumab. Fifty-nine samples from 42 patients were included; 24 of newly diagnosed glioblastomas with no previous bevacizumab (naïve group), 16 resected following neoadjuvant bevacizumab (effective group), and 6 resected after recurrence or autopsied (refractory/autopsied group). 12 were paired samples (8 naïve and refractory, 4 effective and refractory). The expression of PlGF significantly increased in the effective group as compared with the naïve group (p=0.003). In the paired specimens, there was a trend towards increased expression of PlGF in the second specimens (refractory/autopsied group) as compared with the specimens of initial surgery (p=0.083). Angiopoietin1, angiopoietin2 and ephrinA2 were characteristically expressed in the microvessels less than 15μm. The increased expression of PlGF might be associated with the recurrence after bevacizumab.

scholarly journals Outcomes with early response to first-line treatment in patients with newly diagnosed multiple myeloma

2019 ◽  
Vol 3 (5) ◽  
pp. 744-750 ◽  
Author(s):  
Nidhi Tandon ◽  
Surbhi Sidana ◽  
S. Vincent Rajkumar ◽  
Morie A. Gertz ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Light Chain ◽  
Progression Free Survival ◽  
Early Response ◽  
Stage Iii ◽  
Newly Diagnosed ◽  
Best Response ◽  
Light Chain Disease ◽  
The Impact

Abstract We evaluated the impact of achieving a rapid response in 840 newly diagnosed multiple myeloma patients from 2004 to 2015. Rates of very good partial response (VGPR) or better were 29% (240/840) after 2 cycles of treatment, 42% (350/840) after 4 cycles of treatment, and 66% (552/840) as best response. Early responders after 2 cycles of treatment had higher rates of light chain disease, anemia, renal failure, International Staging System (ISS) stage III disease, and high-risk cytogenetics, especially t(4;14), and were more likely to have received triplet therapy and undergo transplant. Median progression-free survival (PFS) and overall survival (OS) were not different among patients with ≥VGPR and <VGPR after 2 cycles (PFS, 28 vs 30 months, P = .6; OS, 78 vs 96 months, P = .1) and 4 cycles (PFS, 31 vs 29 months; OS, 89 vs 91 months, P = .9), although both were improved, with ≥VGPR as best response (PFS, 33 vs 22 months, P < .001; OS, 102 vs 77 months, P = .003). On multivariate analysis stratified by transplant status, achievement of ≥VGPR after 2 cycles was not associated with improved PFS (hazard ratio [95% confidence interval]; transplant cohort, 1.1 [0.7-1.6]; nontransplant cohort, 1.2 [0.8-1.7]) or OS (transplant cohort, 1.6 [0.9-2.9]; nontransplant cohort, 1.5 [1.0-2.4]). Covariates in the model included high-risk cytogenetics, ISS stage III, triplet therapy, creatinine ≥2 mg/dL, light chain disease, and age. Although patients with high-risk disease are more likely to achieve early response, a rapid achievement of a deep response by itself does not affect long-term outcomes.

Future Directions in Glioblastoma Therapy

2012 ◽  
pp. 108-111 ◽  
Author(s):  
Howard Colman
Keyword(s):  
Large Scale ◽  
Antiangiogenic Therapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Recurrent Glioblastoma ◽  
The Cancer Genome Atlas ◽  
Antiangiogenic Agents ◽  
Molecular Heterogeneity ◽  
Newly Diagnosed ◽  
Tumor Subtypes

Overview: The standard of care for both newly diagnosed and recurrent glioblastoma (GBM) patients has changed significantly in the past 10 years. Surgery followed by radiation and concurrent and adjuvant temozolomide is now the well-established standard treatment for newly diagnosed GBM. More recently, bevacizumab has become a mainstay of treatment for recurrent GBM. However, despite these advances and significant improvements in patient outcomes, the management and treatment of GBM patients remains a challenging and frustrating endeavor. Difficulties in interpretation of imaging changes after initial treatment, as well as the effects of antiangiogenic agents like bevacizumab on MRI characteristics, can make even the determination of disease progression complicated in multiple situations. Although a high percentage of patients benefit from antiangiogenic therapy in terms of radiographic response and progression-free survival, the effects of bevacizumab on prolonging overall survival remain controversial. Furthermore, tumor progression after treatment with antiangiogenic agents carries a particularly poor prognosis and there is a general lack of effective therapies for this group of patients. These limitations in terms of standard treatments contrast with a relative wealth of new information regarding the molecular underpinnings of GBM. Data from several large-scale efforts to molecularly profile GBM tumors including The Cancer Genome Atlas (TCGA) project have helped define specific molecular subtypes of GBM with distinct biology and clinical outcomes. These findings are helping to refine our understanding of the molecular heterogeneity and pathogenesis of these tumors and provide a basis for the future development of rational and targeted therapies for specific tumor subtypes.

Phase II trial for patients with newly diagnosed glioblastoma (GBM) treated with carmustine wafers followed by concurrent radiation therapy (RT), temozolomide (TMZ), and bevacizumab (BV), then followed by TMZ and BV post-RT.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13015-e13015 ◽  
Author(s):  
Tulika Ranjan ◽  
Katherine B. Peters ◽  
Gordana Vlahovic ◽  
Lloyd M Alderson ◽  
James Emmett Herndon ◽  
...  
Keyword(s):  
Wound Infection ◽  
Cerebral Edema ◽  
Progression Free Survival ◽  
Newly Diagnosed ◽  
Carmustine Wafers ◽  
Venous Thromboembolic Events ◽  
Venous Thromboembolic ◽  
Newly Diagnosed Glioblastoma ◽  
Grade 3 ◽  
Recurrent Gbm

e13015^ Background: Standard treatment for GBM includes RT and TMZ, followed by six cycles of TMZ, for a median overall survival (OS) and progression-free survival (PFS) of 14.6 and 6.9 months, respectively. BV is FDA approved for recurrent GBM and carmustine wafers are approved for newly diagnosed and recurrent GBM. We evaluated the safety and efficacy of carmustine wafers insertion followed by concurrent RT, TMZ and BV, followed by TMZ and BV for newly diagnosed GBM patients. Methods: Treatment consisted of: Part A- carmustine wafers insertion at resection followed by RT and TMZ at 75 mg/m2/day. BV at 10 mg/kg every two weeks started at least 28 days post-operatively. Part B- Patients received 12 cycles of TMZ (200 mg/m2on days 1-5 of a 28-day cycle) and BV every two weeks (day 1 and 15). Results: Forty one patients of a planned accrual of 72 were enrolled. The study was closed early due to six grade 4-5 toxicities related to study intervention, which met the safety criteria to discontinue the trial. Three patients had grade 4 cerebral edema and one each had grade 4 fatigue, wound infection and meningitis. Median age was 56 years (range, 27-77 years) and 28 patients were men. Of 41 patients, 36 completed part A and 31 started part B. Eleven patients are still on study and 4 have completed part B. Twenty six patients are off study due to progression (n = 16), adverse events (n = 8) and consent withdrawal (n = 2). At a median follow-up of 12.6 months (95% CI: 10.8-15.6 months) the median PFS is 11.3 months (95% CI: 9.2-12.9 months) and the median OS is 16.1 months (95% CI: 15.8 months- ∞). Grade 3-5 toxicities so far include: thrombocytopenia (grade 3, n = 2; grade 4, n = 2), stroke (grade 3, n = 1; grade 5, n = 1), infection (grade 3, n = 2), meningitis (grade 3, n = 1; grade 4, n=1), venous thromboembolic events (grade 3, n = 5), cerebral edema (grade 4, n = 3), fatigue (grade 4, n = 1), enterocolitis (grade 3, n = 1), and wound infection (grade 3, n = 2; grade 4, n = 1). Conclusions: For the patients who did well post carmustine wafers insertion, the treatment was tolerable and median PFS and OS has improved. Updated survival and toxicity results will be presented. Clinical trial information: NT01186406.

Prognostic significance of t(11;14) expression by FISH in patients with newly diagnosed multiple myeloma in the era of novel therapies.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19525-e19525
Author(s):  
Miguel Gonzalez Velez ◽  
Ricardo Daniel Parrondo ◽  
Tracy Andrews ◽  
Narjust Duma ◽  
Joshua Ryan Richter ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Novel Therapies ◽  
Newly Diagnosed ◽  
Seer Data ◽  
Worse Prognosis

e19525 Background: Rearrangements of the immunoglobulin heavy chain (IGH) on chromosome 14 are identified by FISH in about 15-20% of patients (pts) with newly diagnosed multiple myeloma (MM). Historically there is variation on the significance on prognosis of these rearrangements: typically, t(4;14), t(14;16) and t(14;20) have high risk (HR), and t(11;14) have standard risk (SR). A recent study (Kaufman et al, Leukemia. 2016 30:633-9) suggests that t(11;14) may confer a worse prognosis We report the prognostic significance of t(11;14) in a single-institution MM cohort. Methods: 87 pts with t(11;14) by CD 138 selected FISH at diagnosis were identified, pts without symptomatic MM were excluded. Cox regression was used for statistical analysis. Progression free survival (PFS), and overall survivals (OS) from diagnosis and post autologous stem cell transplant (ASCT) were analyzed by Kaplan-Meier. Results: Median age at diagnosis was 62 years, 45 pts (52%) were male, and 24 pts (27%) had ISS 3. All pts received either a proteasome inhibitor or an immunomodulatory agent, and 42 (48%) received triplet treatment as induction. Sixty-nine (79%) pts had ASCT, and overall response rate (ORR, partial response or better) post ASCT was 73%. For pts with HR FISH (defined as t(14;16), p53 del, 1q21 gain or 1p del) compared to SR FISH, the ORR post ASCT was 70% vs 77% (p = 0.67). OS from diagnosis was 93% at 3 years, 74% at 4 years and 51% at 5 years. Seven patients (8%) developed plasma cell leukemia, and there was no association between HR and SR FISH (p = 0.66). In multivariate analysis, ISS stage was an independent risk factor for mortality; pts with stage 3 had 7.3 times (CI: 1.16-36.4) and 5.7 times (CI: 1.63-20.0) the risk of mortality than pts with stage 1 and 2. Having an ASCT reduced mortality by 87% (CI: 0.04-0.41). Conclusions: Despite the use of novel therapies the OS at 5 years of our pts with MM was not significantly improved compared to SEER data from 1992-2013 (51% vs 48.5%). Pts with t(11;14) who had ASCT had increased survival compared to those who did not. Our results suggest that t(11;14) may confer a worse prognosis. Further prospective studies evaluating the risk of t(11;14) are warranted.

scholarly journals PD-L1 and prognosis in patients with malignant pleural mesothelioma: a meta-analysis and bioinformatics study

2020 ◽  
Vol 12 ◽  
pp. 175883592096236
Author(s):  
Liu Jin ◽  
Weiling Gu ◽  
Xueqin Li ◽  
Liang Xie ◽  
Linhong Wang ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Malignant Pleural Mesothelioma ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
The Cancer Genome Atlas ◽  
Cochrane Library ◽  
Pleural Mesothelioma ◽  
Significant Prognostic Factor ◽  
Tcga Dataset

Background: The prognostic value of programmed death-ligand 1 (PD-L1) expression in patients with malignant pleural mesothelioma (MPM) has been controversial according to previous investigations. Therefore, we conducted a meta-analysis to assess the potential prognostic significance of PD-L1 expression in MPM. Methods: PubMed, Embase, Web of Science, Scopus, and the Cochrane Library were thoroughly searched for relevant original articles published before 9 April 2020. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were calculated. The results of the meta-analysis were verified using The Cancer Genome Atlas (TCGA) dataset. Results: In total 16 studies were included in our meta-analysis. A high PD-L1 expression was associated with a poor OS (HR = 1.53, 95% CI = 1.28–1.83, p < 0.001), but not a grave PFS (HR = 1.07, 95% CI = 0.82–1.39, p = 0.643) in MPM. Furthermore, the PD-L1 expression correlated with the sarcomatoid + biphasic type of MPM (odds ratio = 4.32, 95% CI = 2.16–8.64, p < 0.001). TCGA data indicated that PD-L1 was a significant prognostic factor for OS (HR = 2.069, 95% CI = 1.136–3.769, p = 0.0175), but not for PFS (HR = 1.205, 95% CI = 0.572–2.539, p = 0.624), which was in accordance with the results of the meta-analysis. Conclusion: A high PD-L1 expression is a significant prognostic factor for poor OS of patients with MPM. We therefore suggest that PD-L1 expression levels can be used to predict the clinical outcomes of patients with MPM in the future.

Association of VEGFA SNP rs2010963 with prognosis and prediction of vascular toxicity of bevacizumab in recurrent glioblastomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2028-2028
Author(s):  
Anna Luisa Di Stefano ◽  
Giuseppe Lombardi ◽  
Jaime Gallego Perez-Larraya ◽  
Blandine Boisselier ◽  
Marianne Labussiere ◽  
...  
Keyword(s):  
General Population ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Vascular Events ◽  
Vascular Toxicity ◽  
Prognosis And Prediction ◽  
Functional Single Nucleotide Polymorphism ◽  
Grade 3 ◽  
The Impact ◽  
Recurrent Gbm

2028 Background: VEGFA has become an attractive target in high grade gliomas but there is no predictor of response or toxicity to anti-VEGF therapy. We investigated here the association between functional single nucleotide polymorphism (SNP) +405 G>C (rs2010963), located in 5’ untranslated terminal region of VEGFA gene, survival, response to bevacizumab (BVZ), and vascular toxicity. Methods: The rs2010963 was analyzed in blood DNA using a Taqman SNP Genotyping Assay and confronted to Progression Free Survival (PFS), Overall Survival (OS) in the general population of gliomas, and -for the glioblastomas (GBM) treated with BVZ at recurrence- with Response, PFS, and thrombo-hemorragic events. Results: In the general population of 954 gliomas stratified per grade (362 grade 2, 269 grade 3, 323 grade 4) there was no association between rs2010963 and OS or PFS. In the population of 123 recurrent GBM treated with BVZ, we observed a favourable trend in PFS associated with the C allele of rs2010963 (5.4 vs 4.2 months, p = 0.07). Most importantly the CC genotype was associated with the occurrence of thrombo-hemorragic events (6/16 vs 2/107 in CG+GG, p <0.0001). Conclusions: Our data suggest that rs2010963 status has not prognostic significance in gliomas, but is associated with vascular events in recurrent GBM treated with BVZ. The impact of rs2010963 on response to BVZ needs to be further investigated.

scholarly journals Laser interstitial thermal therapy for newly diagnosed and recurrent glioblastoma

2016 ◽  
Vol 41 (4) ◽  
pp. E12 ◽  
Author(s):  
Jonathan G. Thomas ◽  
Ganesh Rao ◽  
Yvonne Kew ◽  
Sujit S. Prabhu
Keyword(s):  
Median Survival ◽  
Progression Free Survival ◽  
Primary Brain Tumor ◽  
Recurrent Glioblastoma ◽  
Thermal Therapy ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Laser Interstitial Thermal Therapy ◽  
Median Progression Free Survival ◽  
Recurrent Gbm

OBJECTIVE Glioblastoma (GBM) is the most common and deadly malignant primary brain tumor. Better surgical therapies are needed for newly diagnosed GBMs that are difficult to resect and for GBMs that recur despite standard therapies. The authors reviewed their institutional experience of using laser interstitial thermal therapy (LITT) for the treatment of newly diagnosed or recurrent GBMs. METHODS This study reports on the pre-LITT characteristics and post-LITT outcomes of 8 patients with newly diagnosed GBMs and 13 patients with recurrent GBM who underwent LITT. RESULTS Compared with the group with recurrent GBMs, the patients with newly diagnosed GBMs who underwent LITT tended to be older (60.8 vs 48.9 years), harbored larger tumors (22.4 vs 14.6 cm3), and a greater proportion had IDH wild-type GBMs. In the newly diagnosed GBM group, the median progression-free survival and the median survival after the procedure were 2 months and 8 months, respectively, and no patient demonstrated radiographic shrinkage of the tumor on follow-up imaging. In the 13 patients with recurrent GBM, 5 demonstrated a response to LITT, with radiographic shrinkage of the tumor following ablation. The median progression-free survival was 5 months, and the median survival was greater than 7 months. CONCLUSIONS In carefully selected patients with recurrent GBM, LITT may be an effective alternative to surgery as a salvage treatment. Its role in the treatment of newly diagnosed unresectable GBMs is not established yet and requires further study.

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