scholarly journals Early Initiation of Temozolomide Therapy May Improve Response in Aggressive Pituitary Adenomas

2021 ◽  
Vol 12 ◽  
Author(s):  
Liza Das ◽  
Nidhi Gupta ◽  
Pinaki Dutta ◽  
Rama Walia ◽  
Kim Vaiphei ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Dna Methyltransferase ◽  
Early Recognition ◽  
Staining Intensity ◽  
Median Number ◽  
Early Initiation ◽  
Lower Percentage ◽  
Positive Staining ◽  
Methylguanine Dna Methyltransferase ◽  
Postmeiotic Segregation

IntroductionAggressive pituitary adenomas (APAs) are, by definition, resistant to optimal multimodality therapy. The challenge lies in their early recognition and timely management. Temozolomide is increasingly being used in patients with APAs, but evidence supporting a favorable response with early initiation is lacking.MethodsThis was a single-center study of all patients with APAs who received at least 3 cycles of temozolomide (150–200 mg/m2). Their baseline clinico-biochemical and radiological profiles were recorded. Immunohistochemical evaluation for cell-cycle markers O6-methylguanine-DNA methyltransferase (MGMT), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), MutL homolog 1 (MLH1), and postmeiotic segregation increased 2 (PMS2) was performed, and h-scores (product of the number of positive cells and staining intensity) were calculated. Response was assessed in terms of radiological response using the RECIST criteria. Patients with controlled disease (≥30% reduction in tumor volume) were classified as responders.ResultsThe study comprised 35 patients (48.6% acromegaly, 37.1% prolactinomas, and 14.3% non-functioning pituitary adenomas). The median number of temozolomide (TMZ) cycles was 9 (IQR 6–14). Responders constituted 68.6% of the cohort and were more likely to have functional tumors, a lower percentage of MGMT-positive staining cells, and lower MGMT h-scores. There was a significantly longer lag period in the initiation of TMZ therapy in non-responders as compared with responders (median 36 vs. 15 months, p = 0.01). ROC-derived cutoffs of 31 months for the duration between diagnosis and TMZ initiation, low-to-intermediate MGMT positivity (40% tumor cells), and MGMT h-score of 80 all had a sensitivity exceeding 80% and a specificity exceeding 70% to predict response.ConclusionEarly initiation of TMZ therapy, functional tumors, and low MGMT h-score predict a favorable response to TMZ in APAs.

scholarly journals Salvage therapy with temozolomide in patients with aggressive or metastatic pituitary adenomas: experience in six cases

2010 ◽  
Vol 163 (6) ◽  
pp. 843-851 ◽  
Author(s):  
Marco Losa ◽  
Elena Mazza ◽  
Maria Rosa Terreni ◽  
Ann McCormack ◽  
Anthony J Gill ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Tumor Size ◽  
Pituitary Adenomas ◽  
Dna Methyltransferase ◽  
Response Assessment ◽  
Pituitary Carcinoma ◽  
Consecutive Series ◽  
Positive Staining ◽  
Hormone Levels ◽  
Wide Range

ObjectiveThe prognosis of either pituitary carcinoma or aggressive pituitary adenoma resistant to standard therapies is poor. We assessed the efficacy of treatment with temozolomide, an oral second-generation alkylating agent, in a consecutive series of six patients with aggressive pituitary adenomas.DesignThis was a 1-year prospective study of temozolomide therapy in six consecutive patients with pituitary carcinoma (one case) or atypical pituitary adenoma (five cases) resistant to standard therapies. There were three males and three females. Age at enrollment ranged between 52 and 64 years. Temozolomide was given orally at a dose of 150–200 mg/m2 per day for 5 days every 4 weeks for a maximum of 12 cycles.MethodsResponse assessment was based on measurable change in tumor size, as assessed on magnetic resonance imaging, and hormone levels. Response was defined as reduction of at least 50% of tumor size and hormone levels.ResultsFour patients completed the 12 cycles of temozolomide treatment, as planned. Two patients stopped the drug after 3 and 6 months respectively because of the progression of disease. Two patients responded to temozolomide, while the remaining two patients had stable disease. Immunohistochemistry for O6-methylguanine-DNA methyltransferase (MGMT) in tumor sample showed a partial association with treatment response.ConclusionsTemozolomide treatment has a wide range of efficacy in patients with pituitary carcinoma or locally aggressive pituitary adenoma. Positive staining for MGMT seems likely to predict a lower chance of response.

O6-methylguanine DNA methyltransferase immunoexpression in nonfunctioning pituitary adenomas

Cancer ◽  
2009 ◽  
Vol 115 (5) ◽  
pp. 1070-1080 ◽  
Author(s):  
Georg Widhalm ◽  
Stefan Wolfsberger ◽  
Matthias Preusser ◽  
Adelheid Woehrer ◽  
Mark R. Kotter ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Dna Methyltransferase ◽  
Nonfunctioning Pituitary Adenomas ◽  
Methylguanine Dna Methyltransferase

scholarly journals Evaluation of 06-methylguanine-DNA methyltransferase expression in children and adolescent pituitary adenoma

2020 ◽  
Author(s):  
Xueming Shen ◽  
Yakun Yang ◽  
Zuocheng Yang ◽  
Ning Liu ◽  
Xueling Qi ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Children And Adolescents ◽  
Pituitary Adenomas ◽  
Dna Methyltransferase ◽  
Tumor Type ◽  
Treatment Needs ◽  
Ki 67 ◽  
Children And Adolescent ◽  
Methylguanine Dna Methyltransferase ◽  
Mgmt Protein

Abstract BackgroundTemozolomide can be used in the treatment of pituitary adenoma. Its efficacy can be evaluated by the expression of 06-methylguanine-DNA methyltransferase (MGMT). However, the previous study population was mainly adult. This study was the first to evaluate the expression of MGMT in children and adolescents with pituitary adenomas.MethodsThe clinical features and biological characteristics of 38 cases of pituitary adenoma in children and adolescents were analyzed retrospectively. The expression of MGMT, Ki-67, p53 was marked by immunohistochemical staining.ResultsIn this cohort, the expression of MGMT protein is 16/38 (42.11%). The low expression rate of MGMT in children and adolescent somatotroph adenomas was only 11.11%, which was much lower than that of adults. Ki-67 expression range of 1% -10%（mean 4.24 ± 2.71%）. The positive rate of p53 was 22/38 (57.89%). The statistical analysis showed that the expression of MGMT was related to the diameter of the tumor (P=0.01), the diameter of the tumor was large, and the expression of MGMT was high. The expression of MGMT was not associated with age, sex, tumor type, invasiveness, texture, apoplexy, recurrence, and expression of p53 and Ki-67.ConclusionSomatotroph adenomas, large-diameter children and adolescent pituitary adenomas may be not suitable for temozolomide treatment. To determine whether temozolomide responds to salvage therapy in children and adolescents with pituitary adenomas, MGMT expression should be assessed in all pituitary adenomas, the time span between specimen collection and temozolomide treatment needs to be considered because of the instability of MGMT protein expression.

Posttranslational Regulation of O6-Methylguanine-DNA Methyltransferase (MGMT) and New Opportunities for Treatment of Brain Cancers

2016 ◽  
Vol 16 (6) ◽  
pp. 455-464 ◽  
Author(s):  
Kalkunte S. Srivenugopal ◽  
Amit Rawat ◽  
Suryakant K. Niture ◽  
Ameya Paranjpe ◽  
Chinavenmani Velu ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Posttranslational Regulation ◽  
Methylguanine Dna Methyltransferase

Effect of O6-Substituted Guanine Analogs on O6-methylguanine DNA-methyltransferase Expression and Glioblastoma Cells Viability

2016 ◽  
Vol 13 (1) ◽  
pp. 28-39 ◽  
Author(s):  
Patrick-Denis St-Coeur ◽  
Marc Cormier ◽  
Veronique LeBlanc ◽  
Pier Morin ◽  
Mohamed Touaibia
Keyword(s):  
Dna Methyltransferase ◽  
Glioblastoma Cells ◽  
Methylguanine Dna Methyltransferase

scholarly journals Purification, structure, and biochemical properties of human O6-methylguanine-DNA methyltransferase.

1990 ◽  
Vol 265 (25) ◽  
pp. 14754-14762
Author(s):  
G. Koike ◽  
H. Maki ◽  
H. Takeya ◽  
H. Hayakawa ◽  
M. Sekiguchi
Keyword(s):  
Dna Methyltransferase ◽  
Biochemical Properties ◽  
Methylguanine Dna Methyltransferase

scholarly journals Molecular and Circulating Biomarkers of Brain Tumors

2021 ◽  
Vol 22 (13) ◽  
pp. 7039
Author(s):  
Wojciech Jelski ◽  
Barbara Mroczko
Keyword(s):  
Brain Tumors ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Extracellular Vesicles ◽  
Dna Methyltransferase ◽  
Growth Factor Receptor ◽  
Response To Treatment ◽  
Liquid Biopsies ◽  
Methylguanine Dna Methyltransferase ◽  
The Central Nervous System

Brain tumors are the most common malignant primary intracranial tumors of the central nervous system. They are often recognized too late for successful therapy. Minimally invasive methods are needed to establish a diagnosis or monitor the response to treatment of CNS tumors. Brain tumors release molecular information into the circulation. Liquid biopsies collect and analyze tumor components in body fluids, and there is an increasing interest in the investigation of liquid biopsies as a substitute for tumor tissue. Tumor-derived biomarkers include nucleic acids, proteins, and tumor-derived extracellular vesicles that accumulate in blood or cerebrospinal fluid. In recent years, circulating tumor cells have also been identified in the blood of glioblastoma patients. In this review of the literature, the authors highlight the significance, regulation, and prevalence of molecular biomarkers such as O6-methylguanine-DNA methyltransferase, epidermal growth factor receptor, and isocitrate dehydrogenase. Herein, we critically review the available literature on plasma circulating tumor cells (CTCs), cell-free tumors (ctDNAs), circulating cell-free microRNAs (cfmiRNAs), and circulating extracellular vesicles (EVs) for the diagnosis and monitoring of brain tumor. Currently available markers have significant limitations.While much research has been conductedon these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature.

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