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Fulltext Polymodal therapy for high grade gliomas: a case report of favourable outcomes following intraoperative radiation therapy

Zamzuri I, Rahman GI, Muzaimi M, Jafri AM, Nik Ruzman NI, Lutfi YA, et al.

Med J Malaysia, 2012 Feb;67(1):121-2.
PMID: 22582564 MyJurnal

High grade gliomas, frequently with their infiltrative nature, often make the outcome from neurosurgical intervention alone unsatisfactory. It is recognized that adjuvant radiochemotherapy approaches offer an improved prognosis. For these reasons, we opted for surgical debulking, intraoperative radiation therapy (IORT) in combination with whole brain irradiation therapy and chemotherapy (temozolamide cycles) in the management of a 42 year-old lady with Glioblastoma Multiforme (GBM). Her troublesome symptoms improved after 3 months of this polymodal therapy and remained independently functional for more than two years.

Matched MeSH terms: Brain Neoplasms/therapy*
Analysis of brain tumours suitable for curability via gene therapy in North East Malaysia

Abdullah J, Isa MN

Stereotact Funct Neurosurg, 1999;73(1-4):19-22.
PMID: 10853092

Two hundred primary brain tumours in both adults and children from the year 1990 to 1998 presenting for treatment to the Neurosurgical Division of the Hospital of the University of Sciences Malaysia were studied retrospectively. Volumes of tumours were taken from CT scans with contrast using two formulas and divided into 4 groups: (1) less than 20 cm(3), (2) 20-50 cm(3), (3) 50-100 cm(3) (4) larger than 100 cm(3). The majority of the brain tumours were in the volume range of 50-100 cm(3), and are thus potentially curable with retroviral gene therapy.

Matched MeSH terms: Brain Neoplasms/therapy*
Metastatic endodermal sinus tumor of cerebellum and brainstem

Sinniah D, Chee CP, Pathmanathan R, Nuruddin R

Med. Pediatr. Oncol., 1988;16(1):57-61.
PMID: 3340064
Matched MeSH terms: Brain Neoplasms/therapy
Fulltext Newcastle disease virus interaction in targeted therapy against proliferation and invasion pathways of glioblastoma multiforme

Abdullah JM, Mustafa Z, Ideris A

Biomed Res Int, 2014;2014:386470.
PMID: 25243137 DOI: 10.1155/2014/386470

Glioblastoma multiforme (GBM), or grade IV glioma, is one of the most lethal forms of human brain cancer. Current bioscience has begun to depict more clearly the signalling pathways that are responsible for high-grade glioma initiation, migration, and invasion, opening the door for molecular-based targeted therapy. As such, the application of viruses such as Newcastle disease virus (NDV) as a novel biological bullet to specifically target aberrant signalling in GBM has brought new hope. The abnormal proliferation and aggressive invasion behaviour of GBM is reported to be associated with aberrant Rac1 protein signalling. NDV interacts with Rac1 upon viral entry, syncytium induction, and actin reorganization of the infected cell as part of the replication process. Ultimately, intracellular stress leads the infected glioma cell to undergo cell death. In this review, we describe the characteristics of malignant glioma and the aberrant genetics that drive its aggressive phenotype, and we focus on the use of oncolytic NDV in GBM-targeted therapy and the interaction of NDV in GBM signalling that leads to inhibition of GBM proliferation and invasion, and subsequently, cell death.

Matched MeSH terms: Brain Neoplasms/therapy*
Fulltext Meningioma--the Sarawak General Hospital experience

Wong SH, Chan SH

Med J Malaysia, 2002 Dec;57(4):467-73.
PMID: 12733172

The aim of this study was to determine the factors for the large size of intracranial meningiomas at the time of presentation to the Sarawak General Hospital. The data was collected prospectively from 1/3/2000 to 28/2/2001. During this period a total of 57 cases of intracranial tumours were operated upon. Twenty of these cases (35%) were meningioma, making meningioma the most common intracranial tumour operated in the Neurosurgery service here with one to two cases operated per month. Headache was the most common symptom. The average duration of symptoms before the diagnosis was made was twenty-five months, the longest being fifteen years. The patients needed an average of seven visits prior to the diagnosis.

Matched MeSH terms: Brain Neoplasms/therapy
Fulltext Challenges and Perspectives of Standard Therapy and Drug Development in High-Grade Gliomas

Chelliah SS, Paul EAL, Kamarudin MNA, Parhar I

Molecules, 2021 Feb 22;26(4).
PMID: 33671796 DOI: 10.3390/molecules26041169

Despite their low incidence rate globally, high-grade gliomas (HGG) remain a fatal primary brain tumor. The recommended therapy often is incapable of resecting the tumor entirely and exclusively targeting the tumor leads to tumor recurrence and dismal prognosis. Additionally, many HGG patients are not well suited for standard therapy and instead, subjected to a palliative approach. HGG tumors are highly infiltrative and the complex tumor microenvironment as well as high tumor heterogeneity often poses the main challenges towards the standard treatment. Therefore, a one-fit-approach may not be suitable for HGG management. Thus, a multimodal approach of standard therapy with immunotherapy, nanomedicine, repurposing of older drugs, use of phytochemicals, and precision medicine may be more advantageous than a single treatment model. This multimodal approach considers the environmental and genetic factors which could affect the patient's response to therapy, thus improving their outcome. This review discusses the current views and advances in potential HGG therapeutic approaches and, aims to bridge the existing knowledge gap that will assist in overcoming challenges in HGG.

Matched MeSH terms: Brain Neoplasms/therapy*
Fulltext Peroxisome proliferator-activated receptor gamma: promising target in glioblastoma

Gupta G, Singhvi G, Chellappan DK, Sharma S, Mishra A, Dahiya R, et al.

Panminerva Med, 2018 Sep;60(3):109-116.
PMID: 30176701 DOI: 10.23736/S0031-0808.18.03462-6

Glioblastoma, also known as glioblastoma multiforme, is the most common and worldwide-spread cancer that begins within the brain. Glioblastomas represent 15% of brain tumors. The most common length of survival following diagnosis is 12 to 14 months with less than 3% to 5% of people surviving longer than five years. Without treatment, survival is typically 3 months. Among all receptors, special attention has been focused on the role of peroxisome proliferator-activated receptors (PPARs) in glioblastoma. PPARs are ligand-activated intracellular transcription factors. The PPAR subfamily consists of three subtypes encoded by distinct genes named PPARα, PPARβ/δ, and PPARγ. PPARγ is the most extensively studied subtype of PPAR. There has been interesting preliminary evidence suggesting that diabetic patients receiving PPARγ agonists, a group of anti-diabetics, thiazolidinedione drugs, have an increased median survival for glioblastoma. In this paper, the recent progresses in understanding the potential mechanism of PPARγ in glioblastoma are summarized.

Matched MeSH terms: Brain Neoplasms/therapy*
Normal pregnancy after successful treatment of choriocarcinoma with cerebral metastases. A case report

Sivanesaratnam V, Sen DK

J Reprod Med, 1988 Apr;33(4):402-3.
PMID: 2452881

Pregnancy after treatment of choriocarcinoma with cerebral metastases is uncommon. We treated a patient successfully with less-toxic chemotherapeutic agents than those advocated by others together with whole brain irradiation. She subsequently had two uneventful pregnancies.

Matched MeSH terms: Brain Neoplasms/therapy
Fulltext Virus vector-mediated genetic modification of brain tumor stromal cells after intravenous delivery

Volak A, LeRoy SG, Natasan JS, Park DJ, Cheah PS, Maus A, et al.

J Neurooncol, 2018 Sep;139(2):293-305.
PMID: 29767307 DOI: 10.1007/s11060-018-2889-2

The malignant primary brain tumor, glioblastoma (GBM) is generally incurable. New approaches are desperately needed. Adeno-associated virus (AAV) vector-mediated delivery of anti-tumor transgenes is a promising strategy, however direct injection leads to focal transgene spread in tumor and rapid tumor division dilutes out the extra-chromosomal AAV genome, limiting duration of transgene expression. Intravenous (IV) injection gives widespread distribution of AAV in normal brain, however poor transgene expression in tumor, and high expression in non-target cells which may lead to ineffective therapy and high toxicity, respectively. Delivery of transgenes encoding secreted, anti-tumor proteins to tumor stromal cells may provide a more stable and localized reservoir of therapy as they are more differentiated than fast-dividing tumor cells. Reactive astrocytes and tumor-associated macrophage/microglia (TAMs) are stromal cells that comprise a large portion of the tumor mass and are associated with tumorigenesis. In mouse models of GBM, we used IV delivery of exosome-associated AAV vectors driving green fluorescent protein expression by specific promoters (NF-κB-responsive promoter and a truncated glial fibrillary acidic protein promoter), to obtain targeted transduction of TAMs and reactive astrocytes, respectively, while avoiding transgene expression in the periphery. We used our approach to express the potent, yet toxic anti-tumor cytokine, interferon beta, in tumor stroma of a mouse model of GBM, and achieved a modest, yet significant enhancement in survival compared to controls. Noninvasive genetic modification of tumor microenvironment represents a promising approach for therapy against cancers. Additionally, the vectors described here may facilitate basic research in the study of tumor stromal cells in situ.

Matched MeSH terms: Brain Neoplasms/therapy*
Challenges in the Management of Childhood Intracranial Germ Cell Tumors in Middle-Income Countries: A 20-Year Retrospective Review From a Single Tertiary Center in Malaysia

Rajagopal R, Leong SH, Jawin V, Foo JC, Ahmad Bahuri NF, Mun KS, et al.

J Pediatr Hematol Oncol, 2021 Oct 01;43(7):e913-e923.
PMID: 33633029 DOI: 10.1097/MPH.0000000000002116

BACKGROUND: A higher incidence of pediatric intracranial germ cell tumors (iGCTs) in Asian countries compared with Western countries has been reported. In Malaysia, the literature regarding pediatric iGCTs have been nonexistent. The aim of this study was to review the management, survival, and long-term outcomes of pediatric iGCTs at a single tertiary center in Malaysia.
PATIENTS AND METHODS: We retrospectively reviewed data from patients below 18 years of age with iGCTs treated at the University Malaya Medical Center (UMMC) from 1998 to 2017.
RESULTS: Thirty-four patients were identified, with a median follow-up of 3.54 years. Sixteen (47%) patients had pure germinoma tumors (PGs), and the remaining patients had nongerminomatous germ cell tumors (NGGCTs). The median age was 12 years, with a male:female ratio of 4.7:1. Abnormal vision, headache with vomiting, and diabetes insipidus were the commonest presenting symptoms. Twenty-eight patients received initial surgical interventions, 24 were treated with chemotherapy, and 28 received radiotherapy. Eight patients experienced relapses. The 5- and 10-year event-free survival rates were similar at 61.1%±12.6% and 42.9%±12.1% for PG and NGGCT, respectively. The 5- and 10-year overall survival rates were the same at 75.5%±10.8% and 53.3%±12.3% for PG and NGGCT, respectively. Four patients died of treatment-related toxicity. Most of the survivors experienced good quality of life with satisfactory neurologic status.
CONCLUSIONS: The survival rate of childhood iGCTs in UMMC was inferior to that reported in developed countries. Late diagnosis, poor adherence to treatment, and treatment-related complications were the contributing factors. Although these results highlight a single institution experience, they most likely reflect similar treatment patterns, outcomes, and challenges in other centers in Malaysia.

Matched MeSH terms: Brain Neoplasms/therapy*