Clinical prognostic factors in adults with astrocytoma: Historic cohort

Wegman-Ostrosky, Talía; Reynoso-Noverón, Nancy; Mejía-Pérez, Sonia Iliana; Sánchez-Correa, Thalía Estefania; Álvarez-Gómez, Rosa María; Vidal-Millán, Silvia; Cacho-Díaz, Bernardo; Sánchez‐Corona, José; Herrera-Montalvo, Luis Alonso; Corona-Vázquez, Teresa

doi:10.1016/j.clineuro.2016.05.002

Cited by 25 publications

(12 citation statements)

References 23 publications

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“…Glioblastoma (GBM) has among the highest mortality rates for primary brain tumors and remains poorly manageable. Despite the hype surrounding recent therapies (1)(2)(3)(4)(5), median life expectancy following diagnosis remains poor for most GBM patients (6)(7)(8)(9). Survival is slightly better, however, for younger GBM patients compared to older GBM patients and for patients with GBM tumors that express IDH1 mutations (10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report

et al. 2021

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Background: Successful treatment of glioblastoma (GBM) remains futile despite decades of intense research. GBM is similar to most other malignant cancers in requiring glucose and glutamine for growth, regardless of histological or genetic heterogeneity. Ketogenic metabolic therapy (KMT) is a non-toxic nutritional intervention for cancer management. We report the case of a 32-year-old man who presented in 2014 with seizures and a right frontal lobe tumor on MRI. The tumor cells were immunoreactive with antibodies to the IDH1 (R132H) mutation, P53 (patchy), MIB-1 index (4–6%), and absent ATRX protein expression. DNA analysis showed no evidence of methylation of the MGMT gene promoter. The presence of prominent microvascular proliferation and areas of necrosis were consistent with an IDH-mutant glioblastoma (WHO Grade 4).Methods: The patient refused standard of care (SOC) and steroid medication after initial diagnosis, but was knowledgeable and self-motivated enough to consume a low-carbohydrate ketogenic diet consisting mostly of saturated fats, minimal vegetables, and a variety of meats. The patient used the glucose ketone index calculator to maintain his Glucose Ketone Index (GKI) near 2.0 without body weight loss.Results: The tumor continued to grow slowly without expected vasogenic edema until 2017, when the patient opted for surgical debulking. The enhancing area, centered in the inferior frontal gyrus, was surgically excised. The pathology specimen confirmed IDH1-mutant GBM. Following surgery, the patient continued with a self-administered ketogenic diet to maintain low GKI values, indicative of therapeutic ketosis. At the time of this report (May 2021), the patient remains alive with a good quality of life, except for occasional seizures. MRI continues to show slow interval progression of the tumor.Conclusion: This is the first report of confirmed IDH1-mutant GBM treated with KMT and surgical debulking without chemo- or radiotherapy. The long-term survival of this patient, now at 80 months, could be due in part to a therapeutic metabolic synergy between KMT and the IDH1 mutation that simultaneously target the glycolysis and glutaminolysis pathways that are essential for GBM growth. Further studies are needed to determine if this non-toxic therapeutic strategy could be effective in providing long-term management for other GBM patients with or without IDH mutations.

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Section: Introductionmentioning

confidence: 99%

Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report

et al. 2021

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“…Today, gliomas still represent a serious and discouraging brain tumor; despite the diversity of treatment modalities, generally, the prognosis for patients is still poor (i.e., fatality and sequelae). Even with surgical resection and aggressive treatment with chemotherapy and radiotherapy, the prognosis for patients with astrocytomas remains very poor [15].…”

Section: Biologic Behaviormentioning

confidence: 99%

“…The current standard of care for glioblastoma patients consists of maximal safe resection, followed by radiotherapy, and concurrent chemotherapy with Temozolomide [15,41,42]. Despite substantial clinical research efforts over the past decades, therapeutic progress has been marginal [43]; added benefits from Temozolomide [44] and bevacizumab [45] are modest, and patient overall survival remains poor.…”

Section: Functional and Therapeutics Implicationsmentioning

confidence: 99%

Functional and Therapeutic Implications of Mitochondrial Network and Mitochondria-Associated Membranes: The Glioma’s Case

Arismendi-Morillo¹,

Castellano-Ramírez²,

Seyfried³

2019

Glioma - Contemporary Diagnostic and Therapeutic Approaches

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Even today, despite the surgery, radiotherapy, and chemotherapy, gliomas prognosis is still poor. There is a great need to develop new therapies. The understanding of the structural and functional characteristics of mitochondrial network (MN) and mitochondriaassociated membranes (MAM) in gliomas is essential for the design of future therapeutic strategies. A huge range of ultrastructural findings is observed in MN and MAM in the human gliomas. These findings imply that a majority of glioma cells are incompetent to produce an adequate amount of energy by means of oxidative phosphorylation and compensatory increases in glycolytic ATP production. Regarding MAM, a "MAM-rich" cell (well-differentiated glioma cells) and "MAM-deficient" cells (glioma like-stem cells) exist. The quantity of MAM could be linked to the functional or metabolic state of the different glioma cells. MAM-resident mTORC2 is a major regulator tumor growth and drug resistance. If sufficient nutrients are present, glioblastoma cells maintain mTORC2 signaling to drive cell proliferation and survival. Consequently, the replacement of fermentable fuels like glucose with non-fermentable fuels like ketone bodies becomes a logical approach. The vision must be targeting the cellular signaling pathways and metabolic reprogramming. Whatever the modality, a holistic and feasible approach must be developed.

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“…2 The average survival of patients with astrocytoma depends on the histological grade, 7 years for patients with astrocytoma grade II, 3 years for grade III, and 12-15 months for patients with glioblastoma, even with the standard treatment (radiotherapy + temozolomide). 4 The National Institute of Neurology and Neurosurgery (INNN) reports that in Mexico, 9% of all brain tumors are GBM, 5 which present an incidence of 3.5 per 100,000 habitants 6 and, particularly for the Mexican population, the average of diagnosis is 49 years old. 6 Some factors support the development of astrocytomas, for example, the activated pathways of NFκB, PI3K/AKT and the expression of progesterone receptor (PR).…”

Section: Introductionmentioning

confidence: 99%

“…4 The National Institute of Neurology and Neurosurgery (INNN) reports that in Mexico, 9% of all brain tumors are GBM, 5 which present an incidence of 3.5 per 100,000 habitants 6 and, particularly for the Mexican population, the average of diagnosis is 49 years old. 6 Some factors support the development of astrocytomas, for example, the activated pathways of NFκB, PI3K/AKT and the expression of progesterone receptor (PR). 7,8 Regarding PR, immunohistochemical analysis revealed higher detection of this receptor in GBM compared with lower-grade malignant tumors; 9 furthermore, blocking this receptor with RU486 antagonist reduces proliferation, migration, and invasion of GBM derived cell lines.…”

Section: Introductionmentioning

confidence: 99%

Progesterone Receptor Together with PKCα Expression as Prognostic Factors for Astrocytomas Malignancy

Arcos-Montoya¹,

Wegman-Ostrosky²,

Mejía-Pérez³

et al. 2021

OTT

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Introduction: Astrocytomas are the most common and aggressive primary brain tumors, and they are classified according to the degree of malignancy on a scale of I to IV, in which grade I is the least malignant and grade IV the highest. Many factors are related to astrocytomas progression as progesterone receptor (PR), whose transcriptional activity could be regulated by phosphorylation by protein kinase C alpha (PKCα) at the residue Ser400. Our aim was to investigate if PR phosphorylation together with PKCα expression could be used as a prognostic factor for astrocytomas malignancy. Methods: By immunofluorescence, we detected the content of PKCα, PR and its phosphorylation at Ser400 in 46 biopsies from Mexican patients with different astrocytoma malignancy grades; by bioinformatic tools using TCGA data, we evaluated the expression of PR and PKCα mRNA according to astrocytoma malignancy grades. For all statistical analyses, significance was p<0.05. Results: We detected a positive correlation between the tumor grade and the content of PKCα, PR and its phosphorylation at Ser400, as well as the intracellular colocalization of these proteins. Interestingly, using an in silico assay, we found that the PR and PKCα expression at mRNA level has an inverse ratio with astrocytomas tumor grade. Discussion: These results indicate that PR and its phosphorylation at Ser400 site, as well as PKCα and their colocalization, could be considered as possible malignancy biomarkers for astrocytomas grades I-IV.

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Clinical prognostic factors in adults with astrocytoma: Historic cohort

Cited by 25 publications

References 23 publications

Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report

Ketogenic Metabolic Therapy, Without Chemo or Radiation, for the Long-Term Management of IDH1-Mutant Glioblastoma: An 80-Month Follow-Up Case Report

Functional and Therapeutic Implications of Mitochondrial Network and Mitochondria-Associated Membranes: The Glioma’s Case

Progesterone Receptor Together with PKCα Expression as Prognostic Factors for Astrocytomas Malignancy

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