scholarly journals Advances in Immunotherapy for Glioblastoma Multiforme

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Boyuan Huang ◽  
Hongbo Zhang ◽  
Lijuan Gu ◽  
Bainxin Ye ◽  
Zhihong Jian ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Cancer Vaccines ◽  
Immune Checkpoint Blockade ◽  
First Line ◽  
Specific Cancer ◽  
Personalized Approach ◽  
Poor Outcomes ◽  
Temozolomide Chemotherapy ◽  
Primary Malignant Brain Tumor ◽  
First Line Treatment

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Patients with GBM have poor outcomes, even with the current gold-standard first-line treatment: maximal safe resection combined with radiotherapy and temozolomide chemotherapy. Accumulating evidence suggests that advances in antigen-specific cancer vaccines and immune checkpoint blockade in other advanced tumors may provide an appealing promise for immunotherapy in glioma. The future of therapy for GBM will likely incorporate a combinatorial, personalized approach, including current conventional treatments, active immunotherapeutics, plus agents targeting immunosuppressive checkpoints.

scholarly journals 5-FU promotes stemness of colorectal cancer via p53-mediated WNT/β-catenin pathway activation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yong-Hee Cho ◽  
Eun Ji Ro ◽  
Jeong-Su Yoon ◽  
Tomohiro Mizutani ◽  
Dong-Woo Kang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Strategy ◽  
First Line ◽  
The Poor ◽  
Pathway Activation ◽  
Discontinuation Of Treatment ◽  
Wnt Inhibitor ◽  
Poor Outcomes ◽  
Combinatorial Treatment ◽  
First Line Treatment

Abstract 5-Fluorouracil (5-FU) remains the first-line treatment for colorectal cancer (CRC). Although 5-FU initially de-bulks the tumor mass, recurrence after chemotherapy is the barrier to effective clinical outcomes for CRC patients. Here, we demonstrate that p53 promotes WNT3 transcription, leading to activation of the WNT/β-catenin pathway in ApcMin/+/Lgr5EGFP mice, CRC patient-derived tumor organoids (PDTOs) and patient-derived tumor cells (PDCs). Through this regulation, 5-FU induces activation and enrichment of cancer stem cells (CSCs) in the residual tumors, contributing to recurrence after treatment. Combinatorial treatment of a WNT inhibitor and 5-FU effectively suppresses the CSCs and reduces tumor regrowth after discontinuation of treatment. These findings indicate p53 as a critical mediator of 5-FU-induced CSC activation via the WNT/β-catenin signaling pathway and highlight the significance of combinatorial treatment of WNT inhibitor and 5-FU as a compelling therapeutic strategy to improve the poor outcomes of current 5-FU-based therapies for CRC patients.

scholarly journals Phase 2 clinical trial of VAL-083 as first-line treatment in newly-diagnosed MGMT-unmethylated glioblastoma multiforme (GBM): Halfway report

Glioma ◽  
2019 ◽  
Vol 2 (4) ◽  
pp. 167
Author(s):  
Dennis Brown ◽  
Zhong-ping Chen ◽  
Chengcheng Guo ◽  
Qunying Yang ◽  
Jiawei Li ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Glioblastoma Multiforme ◽  
Line Treatment ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
First Line ◽  
Phase 2 Clinical Trial ◽  
First Line Treatment

scholarly journals The therapeutic potential of curcumin for the treatment of glioblastoma multiforme

2020 ◽  
Vol 7 (1) ◽  
pp. 8-16
Author(s):  
T. I. Kushnir ◽  
N. E. Arnotskaya ◽  
I. A. Kudryavtsev ◽  
V. E. Shevchenko
Keyword(s):  
Cell Cycle ◽  
Glioblastoma Multiforme ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Chemotherapeutic Agents ◽  
Complementary Treatment ◽  
Adjuvant Temozolomide ◽  
Median Survival Rate ◽  
Temozolomide Chemotherapy ◽  
Primary Malignant Brain Tumor

Glioblastoma multiforme (GBM), a grade IV astrocytoma, is the most common and deadly type of primary malignant brain tumor, with a patien’s median survival rate ranging from 12 to 15 months. Over the last fifteen years, the treatment for GBM has included maximal safe surgical resection with combination radiotherapy and adjuvant temozolomide chemotherapy. The low efficacy of mentioned therapies has forced researchers to explore an appropriate alternative or complementary treatment for GBM. It has been shown that curcumin has therapeutic potentials to fight against GBM via affecting on cell proliferation, apoptosis, cell cycle, invasion and angiogenesis pathways. In addition, curcumin possess a synergistic impact with chemotherapeutic agents. Herein, we summarized the current findings on curcumin as potential therapeutic agent in the treatment of GBM.

Temozolomide combined with radiation as first-line treatment in primary glioblastoma multiforme: Phase I/II-study

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 1531-1531 ◽  
Author(s):  
S. E. Combs ◽  
S. Gutwein ◽  
D. Schulz-Ertner ◽  
M. Van Kampen ◽  
C. Thilmann ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase I ◽  
Line Treatment ◽  
First Line ◽  
Primary Glioblastoma ◽  
First Line Treatment

scholarly journals Progesterone Receptor Status Predicts Response to Progestin Therapy in Endometriosis

2018 ◽  
Vol 103 (12) ◽  
pp. 4561-4568 ◽  
Author(s):  
Valerie A Flores ◽  
Arne Vanhie ◽  
Tran Dang ◽  
Hugh S Taylor
Keyword(s):  
Progesterone Receptor ◽  
Predictive Value ◽  
Progesterone Receptor Status ◽  
First Line ◽  
Receptor Status ◽  
Academic Center ◽  
Polyclonal Igg ◽  
Personalized Approach ◽  
Progestin Therapy ◽  
First Line Treatment

Abstract Context Progestin-based therapy is the first-line treatment for managing endometriosis-associated pain. However, response to progestins is currently variable and unpredictable. Predictive markers for response to progestin-based therapy would allow for a personalized approach to endometriosis treatment. Objective We hypothesize that progesterone receptor (PR) levels in endometriotic lesions determine response to progestin-based therapy. Design Retrospective cohort study. Setting Academic center. Patients Fifty-two subjects with histologically confirmed endometriosis and a previous documented response to hormonal therapy were included. Interventions Immunohistochemistry was performed on sections of endometriotic lesions using a rabbit polyclonal IgG for detection of PR-A/B. Main Outcome Measures The Histo (H)-score was used for quantifying PR status. Response to progestin-based therapies was determined from review of the electronic medical record. Results H-score was higher in responders compared with nonresponders. Subjects were categorized into three groups: high (H-score > 80, n = 7), medium (H-score 6 to 80, n = 28), and low (H-score ≤ 5, n = 17) PR status. The threshold of PR > 80 was associated with a 100% positive predictive value. The threshold of PR < 5 was associated with a 94% negative predictive value. Conclusion PR status is strongly associated with response to progestin-based therapy. Receptor status in endometriosis could be used to tailor hormonal-based regimens after surgery, and negate trialing progestin-based therapy to determine resistance. Ascertainment of PR status may allow for a novel, targeted, precision-based approach to treating endometriosis.

scholarly journals STK11 and KEAP1 mutations as prognostic biomarkers in an observational real-world lung adenocarcinoma cohort

ESMO Open ◽  
2020 ◽  
Vol 5 (2) ◽  
pp. e000706 ◽  
Author(s):  
Simon Papillon-Cavanagh ◽  
Parul Doshi ◽  
Radu Dobrin ◽  
Joseph Szustakowski ◽  
Alice M Walsh
Keyword(s):  
Real World ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Poor Response ◽  
Immune Checkpoint Blockade ◽  
First Line ◽  
Real World Data ◽  
Prognostic Effect ◽  
Programmed Death ◽  
Poor Outcomes

IntroductionSomatic mutations in STK11 and KEAP1, frequently comutated in non-squamous non-small cell lung cancer (NSQ NSCLC), have been associated with poor response to immune checkpoint blockade (ICB). However, previous reports lack non-ICB controls needed to properly ascertain the predictive nature of those biomarkers. The objective of this study was to evaluate the predictive versus prognostic effect of STK11 or KEAP1 mutations in NSQ NSCLC.MethodsPatients diagnosed with stage IIIB, IIIC, IVA or IVB NSQ NSCLC from a real-world data cohort from the Flatiron Health Network linked with genetic testing from Foundation Medicine were retrospectively assessed. Real-world, progression-free survival (rwPFS) and overall survival (OS) were calculated from time of initiation of first-line treatment.ResultsWe analysed clinical and mutational data for 2276 patients including patients treated with anti-programmed death-1 (PD-1)/anti-programmed death ligand 1 (PD-L1) inhibitors at first line (n=574). Mutations in STK11 or KEAP1 were associated with poor outcomes across multiple therapeutic classes and were not specifically associated with poor outcomes in ICB cohorts. There was no observable interaction between STK11 mutations and anti-PD-1/anti-PD-L1 treatment on rwPFS (HR, 1.05; 95% CI 0.76 to 1.44; p=0.785) or OS (HR, 1.13; 95% CI 0.76 to 1.67; p=0.540). Similarly, there was no observable interaction between KEAP1 mutations and treatment on rwPFS (HR, 0.93; 95% CI 0.67 to 1.28; p=0.653) or OS (HR, 0.98; 95% CI 0.66 to 1.45; p=0.913).ConclusionOur results show that STK11-KEAP1 mutations are prognostic, not predictive, biomarkers for anti-PD-1/anti-PD-L1 therapy.

Temozolomide combined with radiation as first-line treatment in primary glioblastoma multiforme: Phase I/II-study

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 1531-1531 ◽  
Author(s):  
S. E. Combs ◽  
S. Gutwein ◽  
D. Schulz-Ertner ◽  
M. Van Kampen ◽  
C. Thilmann ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Phase I ◽  
Line Treatment ◽  
First Line ◽  
Primary Glioblastoma ◽  
First Line Treatment

scholarly journals Concurrent radiotherapy and temozolomide followed by temozolomide and sorafenib in the first-line treatment of patients with glioblastoma multiforme

Cancer ◽  
2010 ◽  
Vol 116 (15) ◽  
pp. 3663-3669 ◽  
Author(s):  
John D. Hainsworth ◽  
Thomas Ervin ◽  
Elke Friedman ◽  
Victor Priego ◽  
Patrick B. Murphy ◽  
...  
Keyword(s):  
Glioblastoma Multiforme ◽  
Line Treatment ◽  
First Line ◽  
Concurrent Radiotherapy ◽  
First Line Treatment
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