Medulloblastoma development: tumor biology informs treatment decisions

Gopalakrishnan, Vidya; Tao, Rong; Dobson, Tara; Brugmann, William; Khatua, Soumen

doi:10.2217/cns.14.58

Cited by 18 publications

(14 citation statements)

References 111 publications

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“…1 Medulloblastoma is a primitive neuroectodermal-derived brain tumor in the CNS and the most common malignant brain tumor in children. 4 Medulloblastoma is sensitive to a wide range of chemotherapeutic medicines, such as cisplatin, 5 procarbazine, 6 methotrexate, 7 and cyclophosphamide. 4 Medulloblastoma is sensitive to a wide range of chemotherapeutic medicines, such as cisplatin, 5 procarbazine, 6 methotrexate, 7 and cyclophosphamide.…”

Section: Introductionmentioning

confidence: 99%

Retracted: Triptolide inhibits the proliferation and migration of medulloblastoma Daoy cells by upregulation of microRNA‐138

Zhang

Liu

et al. 2018

J of Cellular Biochemistry

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Medulloblastoma is a primitive neuroectodermal-derived brain tumor and the most common malignant brain tumor in children. Triptolide (TPL) is the major active component extracted from Tripterygium wilfordii Hook F. This study aimed to explore the effects of TPL on medulloblastoma cell proliferation, migration, and apoptosis, as well as the underlying possible molecular mechanism. Viability, proliferation, and apoptosis of Daoy cells were measured using cell counting kit-8 assay, 5-bromo-2'-deoxyuridine incorporation assay, and Guava Nexin assay, respectively. Cell migration was detected using two-chamber transwell assay and wound healing assay. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to determine the relative expression of microRNA-138 (miR-138) in Daoy cells. Cell transfection was used to change the expression of miR-138 in cells. Western blot analysis was used to analyze the expression of key factors involved in cell apoptosis, cell migration, the phosphatidylinositol 3-kinase (PI3K)/protein kinase 3 (AKT) pathway, and the Notch pathway in Daoy cells. We found that TPL significantly inhibited the viability, proliferation, and migration of Daoy cells but promoted Daoy cell apoptosis. The expression levels of matrix metalloproteinases (MMP)-2 and MMP-9 after TPL treatment were decreased. The expression of miR-138 in Daoy cells after TPL treatment was increased. Suppression of miR-138 obviously reversed the TPL-induced Daoy cell proliferation, migration inhibition, and cell apoptosis enhancement, as well as the inactivation of the PI3K/AKT and Notch pathways. Cyclin-dependent kinase 6 (CDK6) was a direct target gene of miR-138, which might be involved in the antitumor effects of TPL on Daoy cells. In conclusion, our study verified that TPL exerted anticancer effects on medulloblastoma cells possibly via upregulating miR-138 and inactivating the PI3K/AKT and Notch pathways.

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Section: Introductionmentioning

confidence: 99%

Retracted: Triptolide inhibits the proliferation and migration of medulloblastoma Daoy cells by upregulation of microRNA‐138

Zhang

Liu

et al. 2018

J of Cellular Biochemistry

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“…Adjuvant radiotherapy with CSI and a local boost are usually given, and often combined with systemic chemotherapy to control or prevent distant metastasis (10). The current consensus of medulloblastoma grouping has moved from histologically to genetically defined subgroups as a result of better understanding of medulloblastoma biology (12). Four genetic (molecular) groups of medulloblastoma are now widely accepted: wingless (WNT)-activated, sonic hedgehog (SHH)-activated, and the numerically designated "group 3" and "group 4" (13).…”

Section: Discussionmentioning

confidence: 99%

“…Four genetic (molecular) groups of medulloblastoma are now widely accepted: wingless (WNT)-activated, sonic hedgehog (SHH)-activated, and the numerically designated "group 3" and "group 4" (13). New risk stratifications and therapeutic combinations have been developed for medulloblastomas to individualize treatment approaches (12). Because of the limited patient numbers, there is no data available for developing molecular or genetic subtypes of pineoblastomas.…”

Section: Discussionmentioning

confidence: 99%

Treatment outcomes for pediatric pineoblastoma: a single institute experience in Taiwan

Kang¹,

Lin²,

Lee³

et al. 2018

Ther Radiol Oncol

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Background: Our purpose was to evaluate the clinical outcomes of pediatric pineoblastoma patients after multimodality treatment. Methods: The medical records of 11 children with pineoblastomas treated at Taipei Veterans General Hospital between 1991 and 2006 were retrospectively reviewed. There were 7 females (63.6%) and 4 males (36.4%) with a median age at diagnosis of 5.25 years (range, 1.47-16.8 years). Age, sex, symptoms, pathological findings, treatment modalities, failure patterns, recurrence date, death date, and toxicities were recorded. Survival curves were estimated with the Kaplan-Meier method, and univariate Cox proportional hazards models were used to identify possible risk factors. Results: The median overall survival was 2.3 years, with 2-and 5-year survival rates of 63.6% and 36.4%, respectively. Eight patients (72.7%) died after serial treatments, and extensive seeding with multi-organ failure was the most common failure pattern. Three patients (27.2%) were alive without disease recurrence. Kaplan-Meier survival curves showed a significant difference (P<0.05) when compared by age at diagnosis (over or under 3 years old) (P=0.0014). Two out of the three long-term survivors received stereotactic biopsy, craniospinal irradiation (CSI) with focal boost, and chemotherapy without radical surgery. Conclusions: Our results showed survival was associated with age at diagnosis. Long-term survival can be achieved for patients who receive radiotherapy plus chemotherapy. Further studies are needed to determine the best treatment options for pediatric pineoblastoma patients.

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“…Northcott et al and Liu et al published excellent reviews highlighting the genomics of the four subgroups and would be an excellent resource for further specifics, including genetic pathways implicated in tumorigenesis. Stratification of MB into molecularly segregated subgroups allowed for critical debates regarding de‐escalation in treatment of specific groups, namely, the WNT subgroup . The WNT subgroup is the least aggressive of all the subgroups with only 5% to 10% metastases at diagnosis and a mean OS of 95%.…”

Section: Medulloblastoma Stratification and Its Effects On Overall Sumentioning

confidence: 99%

Medulloblastoma: Challenges and advances in treatment and research

Martirosian

Neman

2018

Cancer Reports

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Background: Medulloblastoma (MB) is a pediatric brain tumor occurring in the posterior fossa. MB is a highly heterogeneous tumor, which can be grouped into four main subgroups: WNT, SHH, Group 3, and Group 4. Each subgroup is different both in its implicated pathways and pathology, as well as how they are treated in the clinic. Recent Findings: Standard protocol for MB treatment consists of maximal safe resection, followed by craniospinal radiation (in patients 3 years and older) and adjuvant chemotherapy. Advances in clinical stratification of this tumor have allowed establishment of treatment de-escalation trials aimed at reducing long-term side effects. However, there have been few advances in identifying novel therapeutic strategies for MB patients due to difficulties in creating chemotherapeutics that can bypass the blood-brain-barrier-among other factors. On the other hand, with the help of whole genome sequencing technologies, molecular pathways involved in MB pathogenesis have become clearer and have helped drive MB research. Regardless, this advance in research has yet to translate to the clinic, which may be due to the inability of current in vivo and in vitro models to accurately recapitulate this heterogeneous tumor in humans.Conclusions: There have been significant advances in knowledge and treatment of medulloblastoma over the last few decades. Whole genome sequencing has helped elucidate clear differences between the subgroups of MB, allowing physicians to better tailor treatments to each patient in an effort to reduce long-term sequelae. However, there are still many more obstacles to overcome, including less cytotoxic therapies in the clinic and better modeling systems to accurately replicate this disease in the laboratory. Scientists and physicians must work in a more cohesive manner to create translatable results from the laboratory to the clinic-helping improve therapies for medulloblastoma patients.

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Medulloblastoma development: tumor biology informs treatment decisions

Cited by 18 publications

References 111 publications

Retracted: Triptolide inhibits the proliferation and migration of medulloblastoma Daoy cells by upregulation of microRNA‐138

Retracted: Triptolide inhibits the proliferation and migration of medulloblastoma Daoy cells by upregulation of microRNA‐138

Treatment outcomes for pediatric pineoblastoma: a single institute experience in Taiwan

Medulloblastoma: Challenges and advances in treatment and research

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