جستجوی مقالات مرتبط با کلیدواژه "glioblastoma multiform" در نشریات گروه "پزشکی"
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مجله دانشکده پزشکی دانشگاه علوم پزشکی مشهد، سال شصت و هفتم شماره 4 (پیاپی 196، مهر و آبان 1403)، صص 1089 -1109
مقدمه:
گلیوبلاستوما یکی از بدخیم ترین تومورهای مغزی است که به عنوان تومورهای اولیه اپیتلیال عصبی نیز شناخته می شود. تومورهای بدخیم گلیوبلاستوما در حدود 40%-20 موارد از تومورهای مغزی را شامل می شوند. ژن LMO1 در موقعیت 11P15.4 قرار دارد و به عنوان انکوژن در برخی سرطان ها معرفی می شود. این مطالعه، برای اولین بار در ایران، جهت شناسایی و بررسی ارتباط جهش های ژن LMO1 با گلیوبلاستوما ، انجام شده است.
روش کار:
در این تحقیق، از تکنیک Touchdown PCR و روش تعیین توالی DNA، در 35 نمونه ی خون افراد مبتلا به گلیوبلاستومای مولتی فرم و 40 نمونه شاهد استفاده شد. همچنین آنالیزهای بیوانفورماتیکی، برای بررسی اثر پاتوژنسیتی تغییرات نوکلئوتیدی در این ژن انجام شد. نتایجطی این مطالعه، چهار جهش نقطه ای شناسایی شد که دو تا از جهش های جدید، بدمعنی بوده و منجر به تغییر اسیدآمینه در یکی از دامین های مهم پروتئین می شدند (p.M135K و p.N148H) که نشان دهنده اهمیت بالقوه بیماریزایی آنها است. نتایج مطالعه ما در چندین پایگاه داده بیوانفورماتیکی، پیش بینی کرد که هر دو این جهش ها بر عملکرد پروتئین اثرگذار هستند، بگونه ای که می توانند این دامین را مختل کرده و عملکرد آن را دچار نقص کنند. همچنین، یک تغییر نوکلئوتیدی هم در ناحیه 3'UTR این ژن مشاهده شد (c.*74A>G) که در جایگاه اتصال دو miRNA تنظیمی قرار دارد و پیش بینی می شود بتواند اتصال این miRNAها به توالی هدف را مختل کند.
نتیجه گیریاین یافته ها، پیش بینی می کنند که هرگونه جهش در دامین های حساسLIM در ژنLMO1 به طور قابل توجهی با بیماریزایی گلیوبلاستومای مولتی فرم مرتبط هستند و به احتمال زیاد بر عملکرد این کوفاکتور نسخه برداری تاثیر بسزایی دارند.
کلید واژگان: تومورهای مغزی, تعیین توالی, گلیوبلاستومای مولتی فرم, ژن Touchdown PCR, LMO1IntroductionGlioblastoma is one of the most malignant brain tumors, which is also known as primary neuroepithelial tumors. Glioblastoma malignant tumors include 20-40% of brain tumors. The LMO1 gene is located at position 11P15.4 and is introduced as an oncogene in some cancers. This study was conducted for the first time in Iran to identify and investigate the relationship between LMO1 gene mutations and glioblastoma.methodIn this research, the Touchdown PCR technique and DNA sequencing method were used in 35 blood samples of people with glioblastoma multiforme and 40 control samples. Bioinformatics analyses were also performed to investigate the pathogenic effect of nucleotide changes in this gene.
ResultsIn this study, four point mutations were identified, of which two of the new mutations were misense and led to amino acid changes in one of the important domains of the protein (p.M135K and p.N148H), which indicates their potential pathogenicity. Our results of bioinformatics databases predicted that both of these mutations affect protein function, such that they can disrupt this domain and impair its function. Also, a nucleotide change was observed in the 3'UTR region of this gene (c.*74A>G), which is located at the binding site of two regulatory miRNAs and is expected to disrupt the binding of these miRNAs to the target sequence.
ConclusionThese findings predict that any mutations in the LIM-sensitive domains in the LMO1 gene are significantly related to the pathogenesis of glioblastoma and most likely have a significant impact on the function of this transcriptional cofactor.
Keywords: Brain Tumors, Sequencing, Glioblastoma Multiform, LMO1 Gene, Touchdown PCR -
مقدمه
علی رغم دهه ها تلاش در تشخیص و درمان تومورهای مغزی، همچنان این نوع تومورها، در بین کشنده ترین انواع سرطان ها دسته بندی می شوند. فعال شدن آنزیم تلومراز، به عنوان یک عامل اساسی در نامیرایی این سلول ها شناخته شده است. ژن TERT با بیان زیرواحد کاتالیتیک آنزیم، به عنوان مهم ترین تنظیم کننده فعالیت تلومراز معرفی شده است. جهش های نقطه ای در ناحیه پروموتری ژن TERT، به ویژه در نقاط داغ پروموتر، می توانند نفش مهمی در اتصال فاکتورهای رونویسی فعال کننده و مهار اتصال فاکتورهای تنظیم منفی ژن TERT و درنهایت، تنطیم بیان این ژن ایفا کنند. این پژوهش، با هدف شناسایی و بررسی بیوانفورماتیکی جهش های ناحیه پروموتری ژن TERT در تومور مغزی بدخیم گلیوبلاستوما انجام شده است.
روش بررسیاین مطالعه به روش مورد - شاهدی انجام گرفته است و 35 فرد مبتلا به تومور مغزی گلیوبلاستومای مولتی فرم و 40 فرد به عنوان نمونه های کنترل بررسی شدند. در این پژوهش، از تکنیک Touchdown PCR و روش تعیین توالی مستقیم DNA، جهت تشخیص جهش های ناحیه پروموتر ژن TERT در افراد مبتلا به گلیوبلاستوما استفاده شد. هم چنین آنالیزهای بیوانفورماتیکی، برای بررسی اثر پاتوژنسیتی تغییرات نوکلئوتیدی این ناحیه ژنی انجام شد.
نتایجطی این مطالعه، 3 جهش نقطه ای در ناحیه هسته پروموتر ژن TERT شناسایی شد (c.*146C>T، c.*144C>G و c.*143G>C) که از بین آن ها، 2 جهش برای اولین بار در بیماران گلیوبلاستومای مولتی فرم مشاهده شد و یک جهش دیگر نیز در نقطه ی داغ هسته پروموتری ژن (c.*146C>T) واقع شده بود.
نتیجه گیریدر این مطالعه، اثر پاتوژنسیتی جهش های ناحیه پروموتر TERT به عنوان بیومارکر گلیوبلاستوما بررسی شد. چنین یافته هایی، این احتمال را افزایش می دهند که جهش های سوماتیکی در مناطق تنظیم کننده، ممکن است رویدادهای القایی مهمی در روند سرطان زایی باشند.
کلید واژگان: تومور مغزی, تلومراز, گلیوبلاستومای مولتی فرم, ژن TERT, Touchdown PCRJournal of Shaeed Sdoughi University of Medical Sciences Yazd, Volume:32 Issue: 3, 2024, PP 7645 -7659IntroductionBrain tumors are considered to be one of the most dangerous types of cancer, despite decades of research and treatment efforts. The activation of the telomerase enzyme is a critical factor in the immortality of these cells. Mutations in the promoter region of the TERT gene, particularly in the promoter hot spots, can influence the binding of activating transcription factors and inhibit the binding of negative regulatory factors of the TERT gene, ultimately regulating the gene's expression. This study aimed to identify and investigate the mutations of the TERT gene promoter region in glioblastoma, a malignant brain tumor, using bioinformatics.
MethodsA study was conducted using the case-control method where 35 patients with glioblastoma multiform brain tumor were examined along with 40 people who were examined as control samples. In this research, the Touchdown PCR technique and direct DNA sequencing were used to detect mutations in the promoter region of the TERT gene in patients with glioblastoma. Furthermore, bioinformatic analyses were conducted to investigate the pathogenic effect of nucleotide changes in this gene region.
ResultsIn the core region of the TERT gene promoter, three-point mutations were identified (c.*146C>T، c.*144C>G and c.*143G>C). Two of these mutations were novel and have been observed for the first time in glioblastoma multiform. The remaining mutation was located in the promoter core's hot spot of the gene. This mutation was known as c.*146C>T.
ConclusionIn this research, the harmful impact of TERT promoter region mutations as a biomarker for glioblastoma was examined. These findings suggest that mutations in regulatory regions, as well as coding sequences, could be significant contributory factors in the process of carcinogenesis.
Keywords: Brain Tumor, Telomerase, Glioblastoma Multiform, TERT Gene, Touchdown PCR, Bioinformatics -
IntroductionGlioblastoma multiforme is the foremost common harmful tumor of the central nervous system that specifically influences the brain and is resistent to common therapies such as surgery, radiotherapy and chemotherapy. The aim of this study was to examine the viability of perseverance preparing and Nano-curcumin supplementation on the expression of miR-21 and P53 qualities in brain tumor tissue in a creature demonstrate of glioblastoma multiforme.MethodsIn this experiment, 35 8-week-old male Wistar rats were divided into seven groups with 5 rats each: healthy control group, 4-week-old healthy, control group cancer, 4-week-old cancer group and training group, Nano-curcumin group and training-Nano-curcumin group. Cancer cells were injected into the right frontal cortex of mice using a pump at a depth of 2.5 mm. One week later, mice entered the treadmill training program (4 weeks) and Nano-curcumin was administered orally at a dose of 80 mg/kg (28 days). Gene expression was measured using real-time fluorescent quantitative PCR and used for analysis.spss software.ResultsThe expression of miR-21 gene in the training group, Nano-curcumin, and training group Nano-curcumin was lower than that of the control cancer at 4 weeks (P = 0.001). Moreover, the expression of P53 gene in the Nano-curcumin training group and Nano-curcumin training group was higher in cancer cells and 4-week blood-eating cancer than in the control group (P = 0.001).ConclusionEndurance training and curcumin administration appear to reduce tumor growth in mice with brain tumors by modulating the expression of miR-21 and p53 genes.Keywords: Glioblastoma multiform, miR-21, P53
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Background
Medical images of cancer patients are usually evaluated qualitatively by clinical specialists which makes the accuracy of the diagnosis subjective and related to the skills of clinicians. Quantitative methods based on the textural feature analysis may be useful to facilitate such evaluations. This study aimed to analyze the gray level co‑occurrence matrix (GLCM)‑based texture features extracted from T1‑axial magnetic resonance (MR) images of glioblastoma multiform (GBM) patients to determine the distinctive features specific to treatment response or disease progression.
Methods20 GLCM‑based texture features, in addition to mean, standard deviation, entropy, RMS, kurtosis, and skewness were extracted from step I MR images (obtained 72 h after surgery) and step II MR images (obtained three months later). Responded and not responded patients to treatment were classified manually based on the radiological evaluation of step II images. Extracted texture features from Step I and Step II images were analyzed to determine the distinctive features for each group of responsive or progressive diseases. MATLAB 2020 was applied to feature extraction. SPSS version 26 was used for the statistical analysis. P value < 0.05 was considered statistically significant.
ResultsDespite no statistically significant differences between Step I texture features for two considered groups, almost all step II extracted GLCM‑based texture features in addition to entropy M and skewness were significantly different between responsive and progressive disease groups.
ConclusionsGLCM‑based texture features extracted from MR images of GBM patients can be used with automatic algorithms for the expeditious prediction or interpretation of response to the treatment quantitatively besides qualitative evaluations.
Keywords: Glioblastoma multiform, gray level co‑occurrence matrix, texture feature, treatmentresponse -
Background
Since EGFR inhibitors show a limited therapeutic effect on Glioblastoma multiforme patients, the EGFR/MAPK/STAT5/FN14 signaling pathway becomes vulnerable to the invasive GBM cell population and may be a suitable target for the treatment of GBM. Nanocurcumin consumption and exercise training are probably effective interventions in this signaling pathway.
ObjectivesThis study aimed to investigate the simultaneous effects of exercises training and Nanocurcumin consumption on the EGFR/MAPK/STAT5/FN14/FN14 pathway in the tumor tissue of GBM model rats.
MethodsIn this study, 40 male Wistar rats were randomly assigned to five groups: 1- control (CON), 2- glioblastoma multiform (GBM), 3- glioblastoma multiform+concurrent training (GBM+CT), 4- glioblastoma multiform+nanocurcumin (GBM+NC), and 5- glioblastoma multiform+nanocurcumin+concurrent training (GBM+NC+CT) groups. The target groups performed aerobic training (20 - 35 minutes at 18 m/min) along with resistance training (climbing the ladder in three sets repeated four times) and received Nanocurcumin at the rate of 100 mg.kg-1.day-1 for four weeks. Gene expression was measured by real-time PCR. Two-way analysis of variance was used for analyzing data.
ResultsAccording to our study results, concurrent training significantly reduced the expressions of EGFR, MAPK, STAT5, and Fn14, mRNA compared with GBM group (P < 0.05). Furthermore, nanocurcumin significantly reduced the expressions of EGFR, MAPK, as well as Fn14, mRNA compared with GBM group (P < 0.05). Nanocurcumin+Concurrent training decreased the expressions of EGFR, MAPK, STAT5 as well as Fn14, and mRNA compared with the GBM group (P < 0.05). A significant reduction was recorded for all mRNA expression levels in the GBM+NC+CT group compared with those in the GBM+NC group (P < 0.05).
ConclusionsIn sum, combined exercises and nano curcumin consumption may have been adopted as a non-pharmacological strategy to modulate the expression of EGFR/MAPK/STAT5/FN14 genes in tumor tissue of glioblastoma multiform.
Keywords: Nanocurcumin, Concurrent Training, Glioblastoma Multiform, EGFR, MAPK, STAT5, FN14 Pathway -
Background & Objective
Glioblastoma Multiforme is a very aggressive primary brain cancer that has a median overall survival even if the treatment period is less than 1 year. Despite progress in glioblastoma diagnosis and treatment, the prognosis of patients with glioblastoma still remains poor. Recently, it has been detected that stem cell therapies are an effective method for brain tumor cell targeting. Also, the anti-inflammatory and anti-apoptotic activity of taurine against cancerous cells has been found.
Materials & MethodsIn this study, we employed taurine as an anti-cancer drug and PDLSCs as a potential agent for improving anti-cancer drug efficiency. Then, we investigated their effect on the glioma tumor cells in in-vitro 2D cell culture and in vivo.
ResultsTaurine had the best apoptotic activity on the C6 glioblastoma cells at the concentration of 80 μM after 72h post-treatment. The obtained results showed that a combination of taurine/PDLSCs induced the expression of caspase-3, caspase-8, and IL-17Ra and down-regulated the expression of Bcl-2 and IL-17Ra. Uses of taurine and PDLSCs suppress the migration of the cancerous C6 cells after 48h and show good potential in the suppression of GBM metastasis.
ConclusionThe taurine at concentration of 80µM has a strong potential in decreasing the viability of cancerous C6 Glioblastoma cells. Therefore, taurine and PDLSCs combination, due its therapeutic efficacy, has a considerable potential to be a successful method to glioblastoma brain cancer treatment.
Keywords: Glioblastoma Multiform, Taurine, Periodontal Ligament Stem Cells, Apoptosis -
Background and Aim
Glioblastoma multiforme (GBM) is the most common malignant and invasive tumor of the brain. The relation between prognosis and survival of GBM patients with Epidermal Growth Factor Receptor (EGFR) expression is challenging. Thus, we aimed to evaluate the prognosis and survival of patients with GBM and its relationship with EGFR expression.
Materials and MethodsThis single-arm cohort study was conducted on 70 patients with GBM during 2012-2018 in Shahid Rahnemoon and Mortaz hospitals. The immunohistochemistry technique was applied to paraffin blocks of brain tumors for examining EGFR expression. Other data were extracted from medical records. To determine the survival rate, the Kaplan–Meier curves were used. A chi-square test was used for the analysis of data. Statistically, p-value <0.05 was assumed significant.
ResultsThe mean survival of patients with GBM was 22.3 ± 2.5 months (95% CI=17.41 - 27.10). In addition, 1, 2- and 5-year survival rates were 90%, 30% and 5%, respectively. The mean survival of patients with negative and positive EGFR was 27.4±7.3 and 20.6±2.4 months, respectively. Besides, 11.1% and 14.3% of patients in negative and positive EGFR groups were alive. There was no significant difference in patient’s survival in terms of EGFR expression (p=0.36). No significant difference was seen between the two groups (EGFR positive and negative groups), regarding the frequency of age, sex, tumor’s anatomical location, and place of living (p>0.05).
ConclusionBased on our study, it seems that the GBM tumor was associated with poor prognosis and a low survival rate. It was also found that the expression of the EGFR gene did not affect the survival rate of patients with GBM. Therefore, its use as a predictor factor for survival and prognosis is questionable.
Keywords: Epidermal growth factor receptor, Glioblastoma multiform, Prognosis -
Background
Glioblastoma Multiforme (GBM) is the most common and deadly type of primary brain tumor in adults. Magnetic Resonance Spectroscopy (MRS) is a non-invasive imaging technique used to study metabolic changes in the brain tumors. Some metabolites such as Phosphocholine, Creatine, NAA/Cr, and Pcho/Cr have been proven to show a diagnostic role in GBM. The present study was conducted to analyze important metabolites using MRS multivoxel in GBM tumor.
MethodsIn this study, information was collected from 8 individuals diagnosed with GBM using Siemens multivoxel MRS with a magnetic field strength of 3 T. Data were obtained by Point-Resolved Spectroscopy (PRESS) protocol with TE=135 ms and TR=1570 ms. NAA, Pcho, Cr, Ala, Gln, Gly, Glu, Lac, NAAG, and Tau metabolites were extracted and evaluated statistically.
ResultsGiven total number of normal voxels and total number of all voxels, levels of Cr, Glu, NAA, NAAG, and Gly/Tau ratio in healthy voxels were significantly higher than tumoral voxels (p=0.005, p=0.03, p<0.001, p<0.001 and p=0.041, respectively). In contrast, levels of Gly, Gln, Tau, Lac/Cr, Pcho/Cr, Pcho/NAA, Lac/NAA, and Gln/Glu ratios in tumoral voxels were significantly more than healthy voxels (p=0.001, p=0.037, p<0.001, p=0.010, p<0.001, p<0.001, and p=0.024, respectively). However, levels of Lac and Pcho had no significant difference in the two types of voxels.
ConclusionIn summary, compared to patients with glioblastoma with 1H-MRS, the Pcho/Cr and Pcho/NAA ratios, and NAAG are the most important parameters to differentiate between tumoral and normal voxels.
Keywords: Glioblastoma multiform, Magnetic resonance spectroscopy, Neurochemical profiles, Voxel -
BackgroundGlioblastoma multiform (GBM) is the most common and most malignant of the glial tumors that begins primarily in brain tissue. Genetic background could be considered as an important predisposing factor in GBM. Autocrine motility factor receptor (AMFR) is a cytokine receptor that participates in a lot of physiologic and pathologic processes like: Cellular motility and metastasis. So, it seems that this protein has an essential role in pathophysiology of several cancers and could be a potential diagnostic and or therapeutic target in GBM. Te aim of this study is to investigate the association of AMFR (rs2440472, rs373191257) gene polymorphism and GBM in a representative Iranian population.Materials and MethodsTis study includes 81 cases of GBM and 117 control subjects. After DNA extraction, polymerase chain reaction ? high resolution melting reaction was performed. For each single nucleotide polymorphisms, 12 samples were selected for sequencing. Data was analyzed using Chi?square test and Logistic regression.ResultsFor rs2440472, frequency of GG genotype in the case group was increased compared to the control group (51.9% vs. 34.2% respectively, P = 0.013). After adjusting for sex and age by logistic regression our results were the same (P = 0.017, odds ratio = 2.056). Allelic frequencies for rs2440472 among cases and controls were not signifcantly di?erent (P = 0.058). For
rs373191257, genotypic and allelic frequencies were not signifcantly di?erent between two groups.ConclusionOur results showed
the possible association between the AMFR rs2440472 gene polymorphism with susceptibility to GBMKeywords: Autocrine motility factor receptor, cancer, glioblastoma multiform, polymorphism, single nucleotide polymorphisms How to cite this article: Eishi Osk -
BackgroundGlioblastoma Multiform has been a common and fatal brain tumor. In this regard, there was ambiguity around patient survival rates in Iran que to data insufficiency. In this study, we have analyzed the overall and progression free survival in GBM patients at Milad Tehran hospital.MethodsIn this retrospective study, we have considered survival, clinical characteristics and prognostic factors in 123 primary GBM patients who underwent surgical procedure (Biopsy or Resection) between February 2010 and June 2015 at Milad hospital, Tehran, Iran. All patients have pathologically proven as primary GBM. The overall survival and progression free survival has calculated using the Kaplan-Meier method. The Cox proportional hazards model has used for univariate analysis of prognostic factors. Age, gender, first symptom of the disease, tumor location and size, treatment protocol, and surgery have considered in the Cox model as prognostic factor.ResultsOne hundred and one patients have been studied. The mean age of the patients was 52.12 1.64, 67% of the patients were male, and 20% of the patients has not included in adjuvant therapy due to the patients low performance status after surgery. Patient median survival time was approximately 10.1 (6.3 - 11.8); 80% of the patient survive more than a month; and 57% of the patient has survived for six month, and one year survival of the patients was about 37%. Median progression free survival time was about 6.3 month, one-month progression free survival was 70%, and six months and one year progression free survival rates were 50% and 26%, respectively. Patients higher than 50 years have shown significant, 2 times more chance of death (HR = 2.00 CI 95% (1.3 - 3.2)) or disease progression (HR 1.94 CI 95% (1.3 - 3.2)). Correspondingly, patients who has not included in adjuvant therapy had 3.9 CI 95% ( 2.3 - 6.8) more hazard of death and 2.8 CI 95% (1.6 - 4.8) more chances of disease progression than who included in adjuvant therapy with TMZ and radiotherapy. Gender, symptom, tumor location or surgery type have not significantly affected patient prognosis.ConclusionsGBM patients survival would be quite poor. Nevertheless, this result was similar to the other reports from other centers and countries.Keywords: Glioblastoma Multiform, Survival, Prognosis, Iran
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Background and AimGlioblastoma multiforme (GBM), the highest grade glioma (grade IV), is the most malignant form of astrocytoma in adults. This study aimed at evaluating the relationship between demographic, clinical and medical factors with GBM outcome.
Methods & Materials/Patients: Through a cross-sectional design, 58 patients with newly diagnosed GBM were studied from 1999 to 2015 in Guilan province (North of Iran). Demographic, clinical and medical data including age, gender, score of Karnofsky Performance Scale (KPS), status at discharge, extent of resection (EOR) and administration of post operative radio-chemotherapy were recorded in an individual questionnaire. The data were analyzed using chi-square and fisher exact tests.ResultsOf all patients, 35 (60.3%) cases were men and 23 (39.7%) were women. Age range (at the time of diagnosis of GBM) was 18-82 years (54.86±16.34). The most common side and location of tumor were left hemisphere and frontal lobe, respectively. 41 patients (70.7%) received total surgical resection. Half of patients were treated with simultaneous post operative radiation therapy and chemotherapy.11 (19%) of all cases died. About 41 (70.6%) of patients demonstrated KPS 50-70.ConclusionGBM is a frequent malignant brain tumor with male predominance and high occurrence in age range of ≥50 years. The number of dead patients increases with decreased KPS. Total surgical resection followed by concomitant radiation therapy and chemotherapy were common standard therapeutic regimens.Keywords: Glioblastoma Multiform, Extent of Resection, Radiotherapy, Chemotherapy -
BackgroundGliomas are the most common primary brain tumors of the central nervous system. Among a number of different bio-molecular events, molecular connections between oxidative stress pathways and their development is prevalent. Oxidative stress is the consequence of an imbalance between pro-oxidant factors and antioxidant defense. This imbalance may lead to DNA damage and changes in growth and function of cells in the brain. Many evidences show that reactive oxygen species in the mammalian brain are directly responsible for cell and tissue function and dysfunction. A brain tumor is correlated with oxidative stress. In this study, we determine the pro-oxidant – antioxidant balance in patients with grade IV brain tumors (glioblastoma multiforme) by the pro-oxidant – antioxidant assay.MethodsWe collected sera from 50 patients with high grade (IV) glioblastoma multiform and 49 healthy subjects. The pro-oxidant - antioxidant assay was measured.ResultsThere was a significant increase in pro-oxidant - antioxidant values in patients (158.10±85.71 HK unit) compared to the control group (74.54±33.54 HK; P=0.001.ConclusionThe pro-oxidant - antioxidant balance assay can show a high level of pro-oxidants in the sera of patients with glioblastoma which indicates the presence of oxidative stress in this group.Keywords: Glioblastoma multiform, Oxidative stress, PAB assay
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Radiation induced sarcoma is a rare but recognized complication of radiotherapy and is associated with poor prognosis, frequently occurs 5 years after completion of treatment. We report radiation-induced sarcoma in a 42 years old male, involving the left parietooccipital scalp region following treatment of brain tumor with craniotomy and post-operative radiation with 60Co machine. Diagnosis of radiation induced sarcoma was confirmed by history, latency period and biopsy. This Radiation induced malignancy was diagnosed only 2 years after completion of Radiotherapy for primary lesion.Keywords: Radiation induced sarcoma, brain tumor, glioblastoma multiform
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زمینه و هدفبا وجود پیشرفت در زمینه های تشخیص و درمان سرطان ها، هنوز میزان بقای مبتلایان به گلیوبلاستوما مالتی فورم (GBM) بهبود قابل توجهی نیافته است و درمان های دیگری در کنار درمان های رایج پیشنهاد شده است. یکی از این درمان ها، کنترل و توقف آنژیوژنز تومور از طریق داروها بوده تا از این طریق بتوان سرعت رشد سلول های بدخیم را مهار نمود. سنجش تراکم عروق کوچک (MVD) تکنیکی است که در آن عروق خونی رنگ پذیر شده توسط ایمونوهیستوشیمی، شمارش می گردند. امروزه از موش های بی موی فاقد ایمنی سلولی به طور گسترده ای در تحقیقات سرطان جهت ایجاد مدل تومورهای زنوگرافت استفاده می شود. هدف از این مطالعه، سنجش تراکم عروق کوچک در تومورهای زنوگرافت بومی حاصله از کاشت گلیوبلاستوما مالتی فورم بیماران در موش بوده تا از این مدل ها بتوان در تحقیقات داروهای مهارکننده آنژیوژنز استفاده نمود.روش بررسینمونه های توموری تازه از سه بیمار مبتلا به GBM اخذ و بعد از آماده سازی اولیه، به شکل هتروتاپیک در پهلوی موش های بی مو کاشته شد. دو ماه بعد موش ها قربانی و تومورها به آزمایشگاه پاتولوژی منتقل شده و پس از اطمینان از نوع تومور، میزان MVD-CD34 با شمارش نواحی Hot spot در 22 نمونه تعیین گردید.یافته هامیزان تراکم عروق کوچک در این تومورها به طور میانگین 1/2±30 شمارش شد.نتیجه گیریاز مدل زنوگرافت بومی گلیوبلاستوما مالتی فورم می توان در مطالعات پیش بالینی داروهای مهارکننده آنژیوژنز بر اساس فارماکوژنومیکس بیماران ایرانی استفاده نمود. هم چنین در آینده این امکان وجود دارد که از این مدل ها بتوان در پیش بینی میزان حساسیت یا مقاومت نسبت به داروهای مهارکننده آنژیوژنز به منظور درمان انفرادی سرطان استفاده نمود.
کلید واژگان: گلیوبلاستوما مالتی فورم, مدل زنوگرافت, آنژیوژنز, تراکم عروق کوچکBackgroundDespite advances in cancer diagnosis and treatment, survival rate of patients suffering from glioblastoma multiform (GBM) has not been significantly improved. Therefore, novel therapeutic adjuncts to routine therapies have been suggested over time. Inhibition of angiogenesis by antiangiogenic drugs is one of the new approaches to inhibit the growth of malignant cells. Microvessel density (MVD) assay is a technique performed by counting immunohistochemically-stained blood vessels. Nowadays, athymic nude mice are widely used for the establishment of xenograft tumor models in cancer research. The aim of this study was to evaluate the MVD of autochthonous xenograft models of GBM isolated from Iranian patients for use in pharmaceutical research on antiangiogenic drugs.MethodsFresh tumor samples of GBM were obtained from three patients in Cancer Institute of Tehran University of Medical Sciences in Fall of 2010 and Winter of 2011. After preliminary processing, minced tumor samples were implanted heterotopically on flanks of athymic nude mice. Two months later, the animals were sacrificed and the xenograft tumor samples were sent to the pathology laboratory. After establishing the proof of the xenograft tumor type, MVD-CD34, an endothelial cell marker, was assessed by counting hot spot areas in 22 samples.ResultsThe mean number of microvessels in these xenograft tumor models was 30±2.1.ConclusionThese autochthonous xenograft models of GBM can be used in preclinical settings for research on antiangiogenic drugs regarding a pharmacogenomics-based treatment regimen for the Iranian population. Moreover, such models can be used in future studies for determining the sensitivity or resistance to antiangiogenic drugs in individualized cancer therapy.Keywords: Angiogenesis, CD34, glioblastoma multiform, microvessel density, xenograft model
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