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Treatment of novel IL17A inhibitor in glioblastoma implementing 3rd generation co-culture cell line and patient-derived tumor model

Khan MSS, Asif M, Basheer MKA, Kang CW, Al-Suede FS, Ein OC, et al.

Eur J Pharmacol, 2017 May 15;803:24-38.
PMID: 28322833 DOI: 10.1016/j.ejphar.2017.03.031

Despite many treatment options, cancer remains a growing problem and has become the second leading cause of death globally. Here, we present fluorescence molecular tomography (FMT) data regarding the reversion of third generation co-cultured U87+DBTRG and patient-derived GBM tumor model after treatment with novel IL17A inhibitor named FLVM and FLVZ (organic derivatives of caffeic acid). FMT was used to determine tumor angiogenesis volume (assessment of number of blood vessel; the expression of angiogenic factors CD34 and other angiogenic cancer bio-markers) in U87+DBTRG and patient-derived gliomas. Immunohistochemistry was used to determine microvessel density [CD34], and cell proliferation [Ki67]. Western blot was used to assess the interleukin 17A [IL17A], vascular endothelial growth factor [VEGF] and hypoxia-inducible factor-1α [HIF-1α]. Antibody array was used to assess the cancer bio-markers in co-cultured U87+DBTRG gliomas. Animal survival was found to be significantly increased (P<0.0001) after FLVM treatment compared with control-IL17A. After FMT detection, FLVM, administered orally, was found to decrease tumor growth (P<0.0001). FLVM and FLVZ administration resulted in significant decreases in tumor hypoxia [HIF-1α (P<0.05)], angiogenesis [CD34 (P<0.05)], VEGF, IL17A and cell proliferation [Ki67 (P<0.05)] and caused a significant increase of Bax, caspase and FasL (P<0.05), compared with untreated animals. Additionally, Leptin, LPL (P<0.01), FFA (P<0.05) and adipogenesis were downregulated and no additive toxicity was found in mice except calorie-restriction like effect. Use of FLVM can be considered as a novel inhibitor of IL17A for the treatment of human gliomas.
A phase II randomized, double-blind, placebo-controlled study of Nuvastatic (C50SEW505OESA), a standardized rosmarinic acid-rich polymolecular botanical extract formulation to reduce cancer-related fatigue in patients with solid tumors

Ng ML, Majid AMSA, Yee SM, Natesan V, Basheer MKA, Gnanasekaran A, et al.

Support Care Cancer, 2024 May 06;32(6):331.
PMID: 38710920 DOI: 10.1007/s00520-024-08536-w

AIM: We evaluated the efficacy and safety of Nuvastatic™ (C5OSEW5050ESA) in improving cancer-related fatigue (CRF) among cancer patients.
METHODS: This multicenter randomized double-blind placebo-controlled phase 2 trial included 110 solid malignant tumor patients (stage II-IV) undergoing chemotherapy. They were randomly selected and provided oral Nuvastatic™ 1000 mg (N = 56) or placebo (N = 54) thrice daily for 9 weeks. The primary outcomes were fatigue (Brief Fatigue Inventory (BFI)) and Visual Analog Scale for Fatigue (VAS-F)) scores measured before and after intervention at baseline and weeks 3, 6, and 9. The secondary outcomes were mean group difference in the vitality subscale of the Medical Outcome Scale Short Form-36 (SF-36) and urinary F2-isoprostane concentration (an oxidative stress biomarker), Eastern Cooperative Oncology Group scores, adverse events, and biochemical and hematologic parameters. Analysis was performed by intention-to-treat (ITT). Primary and secondary outcomes were assessed by two-way repeated-measures analysis of variance (mixed ANOVA).
RESULTS: The Nuvastatic™ group exhibited an overall decreased fatigue score compared with the placebo group. Compared with the placebo group, the Nuvastatic™ group significantly reduced BFI-fatigue (BFI fatigue score, F (1.4, 147) = 16.554, p

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