• 제목/요약/키워드: Glioblastoma multiforme

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악성 성상세포종에서 표피성장인자 수용체 과발현의 임상적 의의 (Clinical Implications of the Epidermal Growth Factor Receptor Overexpression in the High-grade Astrocytomas)

  • 홍성언;강진오;이혜경;양문호;임언;조경삼
    • Radiation Oncology Journal
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    • 제14권2호
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    • pp.87-93
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    • 1996
  • 목적 : 악성 성상세포종에서 표피 성장 인자 수용체의 과발현의 빈도와 예후 인자로서 가능성을 조사하기 위하여 본 연구를 시행하였다. 대상 및 방법 : 조직학적으로 악성 성상세포종으로 확진되고 방사선 치료를 받은 23명(역형성성상세포종 7예, 다형성 교아세포종 16예)의 파라핀 블록에 antihuman EGFR polyclonal antibody를 이용하여 면역염색을 시행하였다. 결과 : 표피 성장 인자 수용체는 역형성 성상세포종에서는 7예중 2예에서 양성이었고 다형성 교아세포종은 16예중 9예에서 양성으로 양군간의 발현 빈도의 차이는 통계적으로 유의하지 않았다 (p=0.44). 55세 미만의 환자는 11예중 3예에서 양성이었고 55세 이상은 12예중 8예에서 양성이었다(p=0.141). 표피 성장 인자 수용체 음성인 역형성 성상세포종 환자의 평균 생존기간(중앙값)은 37개월이었다. 다형성 교아세포종 환자의 평균 생존 기간은 표피 성장 인자 수용체 음성 군은 중앙값 11개월, 양성 군은 중앙값 7개월이었으나 두 군간의 통계적인 차이는 없었다(p=0.17). 결론 : 55세 이상 연령군에서 표피성장인자 수용체의 과발현의 빈도가 높았다. 다형성 교아세포종 환자의 생존율은 표피성장인자 수용체 과발현에 의하여 감소하였으나 유의한 영향을 받지 않았다.

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Effects of Copper Reduction on Angiogenesis-Related Factors in Recurrent Glioblastoma Cases

  • Jazayeri, Shima;Feli, Alireza;Bitaraf, Mohammad Ali;Dodaran, Masoud Solaymani;Alikhani, Mazdak;Hosseinzadeh-Attar, Mohammad Javad
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권10호
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    • pp.4609-4614
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    • 2016
  • Purpose: To evaluate the therapeutic effects of copper reduction on angiogenesis-related factors in patients with glioblastoma multiforme treated by gamma knife radiosurgery. Materials and Methods: In the present block randomized, placebo-controlled trial, fifty eligible patients with a diagnosis of glioblastoma multiforme who were candidates for gamma knife radiosurgery were randomly assigned into two groups to receive daily either 1gr penicillamine and a low copper diet or placebo for three months. The intervention started on the same day as gamma knife radiosurgery. Serum interleukin-6 (IL-6), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), vascular endothelial growth factor (VEGF) and copper levels were measured at baseline and after the intervention. The serum copper level was used as the final index of compliance with the diet. In order to control probable side effects of intervention, laboratory tests were conducted at the beginning, middle and end of the study. Results: The patients had a mean age and Karnofsky Performance Scale of 43.7 years and 75 respectively. Mean serum copper levels were significantly reduced in intervention group. Mean survival time was 18.5 months in intervention group vs. 14.9 in placebo group. VEGF and IL-6 levels in the intervention group were also significantly reduced compared to the placebo group and $TNF-{\alpha}$ increased less. Conclusions: It seems that reducing the level of copper in the diet and dosing with penicillamine leads to decline of angiogenesis-related factors such as VEGF, IL-6 and $TNF-{\alpha}$. Approaches targeting angiogenesis may improve survival and can be used as a future therapeutic strategy.

Inhibitory effect of temozolomide on apoptosis induction of cinnamaldehyde in human glioblastoma multiforme T98G cell line

  • Hedieh Abband;Sara Dabirian;Adele Jafari;Mehran Nasiri;Ebrahim Nasiri
    • Anatomy and Cell Biology
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    • 제57권1호
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    • pp.85-96
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    • 2024
  • Glioblastoma is the most common primary malignant brain tumor in adults. Temozolomide (TMZ) is an FDA-approved drug used to treat this type of cancer. Cinnamaldehyde (CIN) is a derivative of cinnamon extract and makes up 99% of it. The aim of this study was to investigate the in vitro combined effect of CIN and TMZ on human glioblastoma multiforme T98G cell line viability. In this study, we used 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-tertazolium bromide (MTT) method to evaluate the extent of IC50, acridine orange, Giemsa and Hoechst staining to evaluate the manner of apoptosis and the Western blotting method to examine the expression change of apoptotic proteins. Our results show that TMZ has an inhibitory effect on CIN when both used in combination at concentrations of 300 and 100 µM (P<0.05) and has a cytotoxic effect when used alone at the same concentrations (P<0.05). The western blotting result showed that TMZ at concentrations of 2,000 and 1,000 µM significantly increased Bax expression and decreased Bcl2 expression (P<0.05), indicating that TMZ induced apoptosis through the mitochondrial pathway. However, CIN had no effect on Bax and Bcl2 expressions, thus causing apoptosis from another pathway. Also, the Bax:Bcl2 expression ratio at concentrations combined was lower than that for TMZ 1,000 µM and higher than that for CIN 150 and 100 µM (P<0.05), which confirms the inhibitory effect of TMZ on CIN. From the present study, we conclude that TMZ in combination with CIN has an inhibitory effect on increasing the cytotoxicity rate.

Comparison of Linear Accelerator and Helical Tomotherapy Plans for Glioblastoma Multiforme Patients

  • Koca, Timur;Basaran, Hamit;Sezen, Duygu;Karaca, Sibel;Ors, Yasemin;Arslan, Deniz;Aydin, Aysen
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권18호
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    • pp.7811-7816
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    • 2014
  • Background: Despite advances in radiotherapy, overall survival of glioblastoma multiforme (GBM) patients is still poor. Moreover dosimetrical analyses with these newer treatment methods are insufficient. The current study is aimed to compare intensity modulated radiation therapy (IMRT) linear accelerator (linac) and helical tomotherapy (HT) treatment plans for patients with prognostic aggressive brain tumors. Material and Methods: A total of 20 GBM patient plans were prospectively evaluated in both linac and HT planning systems. Plans are compared with respect to homogenity index, conformity index and organs at risk (OAR) sparing effects of the treatments. Results: Both treatment plans provided good results that can be applied to GBM patients but it was concluded that if the critical organs with relatively lower dose constraints are closer to the target region, HT for radiotherapeutical application could be preferred. Conclusion: Tomotherapy plans were superior to linear accelerator plans from the aspect of OAR sparing with slightly broader low dose ranges over the healthy tissues. In case a clinic has both of these IMRT systems, employment of HT is recommended based on the observed results and future re-irradiation strategies must be considered.

Therapeutic effects of dihydroartemisinin and transferrin against glioblastoma

  • Kim, Suk Hee;Kang, Seong Hee;Kang, Bo Sun
    • Nutrition Research and Practice
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    • 제10권4호
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    • pp.393-397
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    • 2016
  • BACKGROUND/OBJECFTIVES: Artemisinin, a natural product isolated from Gaeddongssuk (artemisia annua L.) and its main active derivative, dihydroartemisinin (DHA), have long been used as antimalarial drugs. Recent studies reported that artemisinin is efficacious for curing diseases, including cancers, and for improving the immune system. Many researchers have shown the therapeutic effects of artemisinin on tumors such as breast cancer, liver cancer and kidney cancer, but there is still insufficient data regarding glioblastoma (GBM). Glioblastoma accounts for 12-15% of brain cancer, and the median survival is less than a year, despite medical treatments such as surgery, radiation therapy, and chemotherapy. In this study, we investigated the anti-cancer effects of DHA and transferrin against glioblastoma (glioblastoma multiforme, GBM). MATERIALS/METHODS: This study was performed through in vitro experiments using C6 cells. The toxicity dependence of DHA and transferrin (TF) on time and concentration was analyzed by MTT assay and cell cycle assay. Observations of cellular morphology were recorded with an optical microscope and color digital camera. The anti-cancer mechanism of DHA and TF against GBM were studied by flow cytometry with Annexin V and caspase 3/7. RESULTS: MTT assay revealed that TF enhanced the cytotoxicity of DHA against C6 cells. An Annexin V immune-precipitation assay showed that the percentages of apoptosis of cells treated with TF, DHA alone, DHA in combination with TF, and the control group were $7.15{\pm}4.15%$, $34.3{\pm}5.15%$, $66.42{\pm}5.98%$, and $1.2{\pm}0.15%$, respectively. The results of the Annexin V assay were consistent with those of the MTT assay. DHA induced apoptosis in C6 cells through DNA damage, and TF enhanced the effects of DHA. CONCLUSION: The results of this study demonstrated that DHA, the derivative of the active ingredient in Gaeddongssuk, is effective against GBM, apparently via inhibition of cancer cell proliferation by a pharmacological effect. The role of transferrin as an allosteric activator in the GBM therapeutic efficacy of DHA was also confirmed.

산화철 나노입자의 U373MG 세포 독성평가 및 방사선 세포생존 곡선에 미치는 영향에 대한 연구 (A Research on Superparamagnetic Iron Oxide Nanoparticles' Toxicity to U373MG Cell and its Effect on the Radiation Survival Curve)

  • 강성희;김정환;김도경;강보선
    • 한국방사선학회논문지
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    • 제6권6호
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    • pp.507-513
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    • 2012
  • 본 연구는 초상자성 산화철 나노입자 (SPIONs)의 세포독성평가 및 SPIONs를 uptake한 뇌신경교종 (glioblastoma multiforme, GBM) 세포의 방사선 세포생존곡선을 구하기 위해 수행되었으며, 본 연구의 결과는 양성자선과 SPIONs 이용한 GBM의 양성자선 치료선량 정보 등 양성자선 치료효과를 개선하기 위한 기초자료로 활용될 수 있을 것이다. SPIONs의 세포독성을 평가는 in vitro 실험 후 MTT 분석법을 이용하여 수행하였다. 독성평가 결과 $1{\sim}100{\mu}g/ml$의 농도에서는 세포생존율의 유의한 차이가 나타나지 않았다. 하지만 $200{\mu}g/ml$의 농도에서는 세포생존율이 74.2%로 감소하며 세포독성을 나타냈다. SPIONs가 uptake 된 U373MG세포와 uptake 되지 않은 U373MG세포에 0~5 Gy의 양성자선을 조사하여 각각에 대한 세포생존곡선을 측정한 결과를 분석하여 SPIONs가 uptake된 U373MG세포의 세포생존율이 더 급격히 감소함을 알 수 있었다. 결론적으로 SPIONs가 uptake 된 세포에서는 보다 적은 선량으로도 세포사멸을 유도할 수 있음을 알 수 있었다. 따라서 GBM에 SPIONs를 타겟팅하면 양성자선을 이용한 뇌신경교종 치료효과를 개선할 수 있음을 보였다.

Should Adjuvant Radiotherapy Be Recommended for Pediatric Craniopharyngiomas?

  • Dadlani, Ravi;Ghosal, Nandita;Hegde, Alangar Sathya
    • Journal of Korean Neurosurgical Society
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    • 제55권1호
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    • pp.54-56
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    • 2014
  • Intracranial tumors secondary to radiotherapy are rare. In this group gliomas are the rarest. Only 6 cases of glioblastoma multiforme (GBM) have been reported in patients undergoing radiotherapy (RT) for craniopharyngiomas of which only 4 have been in children less than 18 years of age. In recent years RT has become a mainstay of adjuvant therapy for recurrent or partially excised craniopharyngiomas. We report a child of 12 years who had previously undergone RT for a suprasellar craniopharyngioma and presented 10 years later with a GBM. This is the 5th pediatric case in literature demonstrating a GBM after RT for a craniopharyngioma. The implications of subjecting the pediatric population to RT for a benign lesion versus the outcome of gross total removal and management of RT induced tumors is discussed and the need to avail of safer alternatives such as stereotactic radiosurgery is stressed.

Evaluation of JC and Cytomegalo Viruses in Glioblastoma Tissue

  • Afshar, Reza Malekpour;Mollaei, Hamid Reza;Zandi, Bahare;Iranpour, Maryam
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권11호
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    • pp.4907-4911
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    • 2016
  • Glioblastoma multiforme (GBM) is the most aggressive of the gliomas, a collection of tumors arising from glia in the central nervous system. Possible associations between the human cytomegalovirus (HCMV) and the JC virus with GBM are now attracting interest. Our present aim was to investigate the prevalence of the two viruses in Iranian patients from Kerman's cities in the south of Iran. In addition, the expression rates of pp65, large T antigen and p53 proteins were assessed and their relation with GBM evaluated using reverse transcription real time PCR (rReal Time PCR). A total of 199 patients with GBM cancer were enrolled, with $mean{\pm}SD$ ages of $50.0{\pm}19.5$ and $50.7{\pm}19.6$ years for males and females, respectively. The P53 rate was dramatically low suggesting an aetiological role,. Large T antigen expression was found in JC positive samples, while the PP65 antigen was observed in patients positive for CMV and JC. HCMV products and JC virus with oncogenic potential may induce the development of various tumors including glioblastomas. The JC virus produces an early gene product, T-antigen, which has the ability to associate with and functionally inactivate well-studied tumor suppressor proteins including p53 and pRB.

Effect of glucose level on chemical hypoxia- and hydrogen peroxide-induced chemokine expression in human glioblastoma cell lines

  • Jung, Yieun;Ahn, So-Hee;Park, Sang Hui;Choi, Youn-Hee
    • The Korean Journal of Physiology and Pharmacology
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    • 제21권5호
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    • pp.509-518
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    • 2017
  • Glioblastoma multiforme (GBM) is the most common primary intracranial tumor in adults and has poor prognosis. The GBM-specific tumor microenvironment (TME) plays a crucial role in tumor progression, immune escape, local invasion, and metastasis of GBM. Here, we demonstrate that hypoxia, reactive oxygen species (ROS), and differential concentration of glucose influence the expression of cytokines and chemokines, such as IL-6, IL-8, and IP-10, in human glial cell lines. Treatment with cobalt chloride ($CoCl_2$) and hydrogen peroxide ($H_2O_2$) significantly increased the expression levels of IL-6, IL-8, and IP-10 in a dose-dependent manner in CRT-MG and U251-MG astroglioma cells, but not in microglia cells. However, we found strikingly different patterns of expression of cytokines and chemokines between $H_2O_2$-treated CRT-MG cells cultured in low- and high-glucose medium. These results suggest that astroglioma and microglia cells exhibit distinct patterns of cytokine and chemokine expression in response to $CoCl_2$ and $H_2O_2$ treatment, and different concentrations of glucose influence this expression under either hypoxic or oxidant-enriched conditions.