Vaccination with dendritic cells loaded with allogeneic brain tumor cells for recurrent malignant brain tumors induces a CD4+IL17+ response

Glioblastoma multiforme (GBM) is a highly vascularized and invasive neoplasm. The methanol extract ofAngelica sinensis(AS-M) is commonly used in traditional Chinese medicine to treat several diseases, such as gastric mucosal damage, hepatic injury, menopausal symptoms, and chronic glomerulonephritis. AS-M also displays potency in suppressing the growth of malignant brain tumor cells. The growth suppression of malignant brain tumor cells by AS-M results from cell cycle arrest and apoptosis. AS-M upregulates expression of cyclin kinase inhibitors, including p16, to decrease the phosphorylation of Rb proteins, resulting in arrest at the G0-G1phase. The expression of the p53 protein is increased by AS-M and correlates with activation of apoptosis-associated proteins. Therefore, the apoptosis of cancer cells induced by AS-M may be triggered through the p53 pathway. Inin vivostudies, AS-M not only suppresses the growth of human malignant brain tumors but also significantly prolongs patient survival. In addition, AS-M has potent anticancer effects involving cell cycle arrest, apoptosis, and antiangiogenesis. Thein vitroandin vivoanticancer effects of AS-M indicate that this extract warrants further investigation and potential development as a new antibrain tumor agent, providing new hope for the chemotherapy of malignant brain cancer.

Download Full-text

IMMU-12. PHASE I/II TRIAL OF IMMUNOTHERAPY WITH FUSIONS OF DENDRITIC CELLS AND TUMOR CELLS FOR RELAPSED OR REFRACTORY BRAIN TUMORS IN CHILDREN AND YOUNG ADULTS

Neuro-Oncology ◽

10.1093/neuonc/noaa222.368 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii362-iii362

Author(s):

Masayoshi Yamaoka ◽

Yasuharu Akasaki ◽

Jun Takei ◽

Masaharu Akiyama ◽

Tetsunori Tasaki ◽

...

Keyword(s):

Overall Survival ◽

Dendritic Cells ◽

Young Adults ◽

Brain Tumor ◽

Brain Tumors ◽

Tumor Cells ◽

Progression Free Survival ◽

Cervical Region ◽

Free Survival ◽

Children And Young Adults

Abstract BACKGROUND/OBJECTIVES Relapsed or refractory brain tumors in childhood continue to have a dismal prognosis in spite of intensive multidisciplinary treatment. Cancer immunotherapy is newly developed to be expected as next promising treatment for highly aggressive pediatric cancer. This trial was designed to evaluate the safety and effectiveness of an immunotherapy with fusions of dendritic cells (DCs) and tumor cells in patients with malignant brain tumors. METHODS Patients with histopathologically confirmed malignant and recurrent/refractory brain tumor were eligible for this immunotherapy trial. Autologous cultured tumor cells obtained from surgical specimens were fused with autologous DCs using polyethylene glycol. The fusion cells (FC) were inoculated intradermally in the cervical region and repeated 3–10 times in each 28–84 days cycle. Treatment-related toxicity, progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS Six patients were enrolled, three with high grade glioma and three with ependymoma. Median age at first course of immunotherapy was 10 years (range 8–25 years) and median follow-up time from the first course of immunotherapy was 13.5 months (range 3–33 months). All patients with immunotherapy were well tolerated to this treatment with no adverse events except local erythema in injected site. Median progression free survival and overall survival were 18 months and 18.5 months, respectively. CONCLUSIONS FC immunotherapy with autologous DCs and tumor cells for brain tumor in children and young adults were extremely well tolerated and showed encouraging responses in this series. Further phase II study of FC immunotherapy is planned to improve survival and reduce treatment related morbidity.

Download Full-text

Brain Tumor Treatment: 2017 Update

Cancer and Clinical Oncology ◽

10.5539/cco.v7n1p30 ◽

2018 ◽

Vol 7 (1) ◽

pp. 30

Author(s):

Adri Chakraborty ◽

Jennifer Han ◽

Cristina Faltas ◽

Natalia Coleman

Keyword(s):

Stem Cells ◽

Brain Tumor ◽

Brain Tumors ◽

Tumor Cells ◽

Cell Types ◽

High Recurrence Rate ◽

Tumor Initiating Cells ◽

Malignant Brain Tumors ◽

Current Therapies ◽

Adults And Children

Malignant brain tumors are a heterogeneous group of diseases arising from different cell types that affect both adults and children. The high recurrence rate of malignant brain tumors typically is due to reappearance of focal masses, indicating that a sub population of tumor cells are insensitive to current therapies and may be responsible for reinitiating tumor growth. It is generally agreed that the resistant tumor cells are comprised of cancer stem cells or tumor-initiating cells. While brain tumor stem cells (BTSCs) were first isolated within the last decade, much of the early research has been focused on identifying the BTSC markers and therapeutic targets. The challenge however, is to translate this knowledge to therapeutics. In the current review, we survey the remedial strategies to target BTSCs, which includes diagnostic, pharmacologic, immunologic, viral, and post-transcriptional approaches.

Download Full-text

Synthetic scorpion venom targets brain tumor cells

PsycEXTRA Dataset ◽

10.1037/e458452008-008 ◽

2006 ◽

Keyword(s):

Brain Tumor ◽

Tumor Cells ◽

Scorpion Venom ◽

Brain Tumor Cells

Download Full-text

LOCAL HYPERTHERMIA IN TREATMENT FOR MALIGNANT BRAIN TUMORS

Problems in oncology ◽

10.37469/0507-3758-2018-64-1-54-61 ◽

2018 ◽

Vol 64 (1) ◽

pp. 54-61

Author(s):

A. Ryabova ◽

O. Gribova ◽

V. Novikov ◽

E. Choinzonov ◽

Zh. Starceva ◽

...

Keyword(s):

Experimental Data ◽

Radiation Therapy ◽

Brain Tumors ◽

Tumor Cells ◽

Combined Treatment ◽

Complex Treatment ◽

Local Hyperthermia ◽

Malignant Brain Tumors ◽

Sensitizing Effect ◽

Methods Of Treatment

Unsatisfactory results of complex treatment for malignant brain tumors stimulate search of new effective methods of treatment. Radiation therapy is an integral part of the combined treatment but often does not influence lethally on resistant tumor cells. Thereby in recent decades there has been an active search for different modifiers, which can increase the sensitivity of tumors to chemotherapy and radiotherapy. One of the universal sensitizers is the local hyperthermia. Experimental data showed that the effect of high temperatures had both a direct damaging effect on tumor cells and a sensitizing effect. The literature review given in the article provides an overview of the existing methods of the local hyperthermia for brain tumors treatment.

Download Full-text

DIPG-60. PILOT STUDY OF CIRCULATING TUMOR CELLS IN PEDIATRIC HIGH GRADE BRAIN TUMORS

Neuro-Oncology ◽

10.1093/neuonc/noaa222.105 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii299-iii299

Author(s):

Wafik Zaky ◽

Long Dao ◽

Dristhi Ragoonanan ◽

Izhar Bath ◽

Sofia Yi ◽

...

Keyword(s):

Brain Tumor ◽

Brain Tumors ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Pediatric Brain Tumor ◽

Pediatric Brain Tumors ◽

Disease Assessment ◽

Liquid Biopsies ◽

Capture Method ◽

Pediatric Brain

Abstract BACKGROUND Despite its increasing use, circulating tumor cells (CTCs) have not been studied in pediatric brain tumors. METHODS Cell surface vimentin (CSV) is a marker for CTC detection. We developed an automated CSV-based CTC capture method for pediatric brain tumor using the Abnova Cytoquest platform. PBMCs isolated from blood samples from 52 brain tumor patients were processed to isolate CSV+ CTCs. Captured cells were then stained for CSV and CD45 and scanned to determine the number of CTCs. DIPG samples were additionally examined for H3K27M expression on CSV+ cells. Long term cancer survivors were used as a control cohort. RESULTS 86.4% of all the samples exhibited between 1–13 CSV+ CTCs, with a median of 2 CSV+ CTCs per sample. Using a value of ≥ 1 CTC as a positive result, the sensitivity and specificity of this test was 83.05% and 60.0% respectively. 19 DIPG samples were analyzed and 70% (13 samples) were positive for 1–5 CTCs. Five of these 7 positive CSV+ CTCs DIPG samples were also positive for H3K27M mutations by immunohistochemistry (71%). Mean survival in days for the CTC positive and negative DIPG samples were 114 and 211 days, respectively (p= 0.13). CONCLUSION This is the first study of CTCs in pediatric CNS tumors using an automated approach. Patients with brain tumors can exhibit CSV+ CTCs within peripheral blood. The use of specific molecular markers such as H3K27M can improve the diagnostic capability of liquid biopsies and may enable future disease assessment for personalized therapy.

Download Full-text