Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The malignant mesothelioma is an aggressive form of cancer with a mean survival rate of less than a year. Moreover, environmental exposure to minerals is an important factor in the development of malignant mesothelioma (MM), especially the mineral asbestos, which has a well-documented role in MM, and more recently, the mineral erionite has been proven to be a strong carcinogenic inducer of MM. In addition, the virus simian virus 40 has been implicated as a co-carcinogenic player in MM. However, the molecular mechanisms involved in the pathogenesis of this cancer are still not fully understood. Indeed, it is known that several genes are altered or mutated in MM, among those are p16(INK4A), p14(ARF), and neurofibromatosis type II. Furthermore, TP53 has been reported to be mutated in the majority of the cancers; however, in MM, it is very uncommon mutations in this gene. Also, the PTEN gene has been shown to play an important role in endometrial cancer and glioblastoma, although the role of PTEN in MM has yet to be established. Taken altogether, this review focuses on the historical aspects, molecular mechanisms, interaction with other genes and proteins, and the role of these genes in MM. Lastly, this review questions the cancer theory of the two hits because the functions of both PTEN and TP53 are not fully explained by this theory.
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PMID:The function, mechanisms, and role of the genes PTEN and TP53 and the effects of asbestos in the development of malignant mesothelioma: a review focused on the genes' molecular mechanisms. 2408 73

Increasing evidence indicated that dysregulation of microRNAs (miRNAs) were involved with human disease including cancer. Recently, miR-595 was reported as a tumor promoter in malignant mesothelioma. However, the underlying mechanism of miR-595 in human glioblastoma (GBM) cells have not been well elucidated. Therefore, in this study, we investigated the biological functions and molecular mechanisms of miR-595 in human GBM. MiR-595 expression was significantly upregulated in GBM tissues and cells. We modified miR-595 levels in GBM cells and investigated their effects on the cell proliferation by MTT, colony formation and anchorage-independent growth assays. We found that miR-595 significantly increased GBM cell proliferation. Bioinformatic analysis predicted that miR-595 may target the 3'-UTR of SOX7and suppressed its translation, and further confirmed by luciferase assay. In sum, these observations together indicated that miR-595 played a critical role in carcinogenesis by suppression of SOX7, and may serve as a therapeutic target for the treatment of GBM.
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PMID:MiR-595 targeting regulation of SOX7 expression promoted cell proliferation of human glioblastoma. 2713 48

Podoplanin (PDPN)/Aggrus is a type-I transmembrane sialoglycoprotein, which possesses a platelet aggregation-stimulating (PLAG) domain. The O-glycosylation on Thr52 of human PDPN (hPDPN) is critical for the interaction of hPDPN with C-type lectin-like receptor-2 (CLEC-2), resulting in platelet aggregation. Many anti-hPDPN monoclonal antibodies (MAbs) against PLAG domains and non-PLAG domains have been established; however, mouse anti-PLAG2/3 MAb, the epitope of which is consistent with rat anti-PLAG2/3 MAb NZ-1, has not been established. NZ-1 inhibits the hPDPN-CLEC-2 interaction and is also useful for anti-PA tag MAb. We recently established CasMab technology to produce MAbs against membranous proteins. Herein, we produced a novel anti-hPDPN MAb, LpMab-13, which binds to PLAG2/3 domains. LpMab-13 recognized endogenous hPDPN of cancer cells, including glioblastoma, oral cancer, lung cancer, and malignant mesothelioma, and normal cells such as lymphatic endothelial cells and podocytes of kidney in Western blot, flow cytometry, and immunohistochemistry. LpMab-13 recognized glycan-deficient hPDPN in flow cytometry, indicating that the interaction between LpMab-13 and hPDPN is independent of its glycosylation. The minimum epitope of LpMab-13 was identified as Ala42-Asp49 of hPDPN using Western blot and flow cytometry. The combination of different epitope-possessing MAbs could be advantageous for the hPDPN-targeting diagnosis and therapy.
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PMID:Establishment of Mouse Monoclonal Antibody LpMab-13 Against Human Podoplanin. 2714 66

Podoplanin (PDPN)/Aggrus is a type-I transmembrane sialoglycoprotein, which possesses a platelet aggregation-stimulating (PLAG) domain. The O-glycosylation on Thr52 of human PDPN (hPDPN) is critical for the interaction of hPDPN with C-type lectin-like receptor-2 (CLEC-2), resulting in platelet aggregation. Many anti-hPDPN monoclonal antibodies (MAbs) against PLAG domains and non-PLAG domains have been established; however, mouse anti-PLAG2/3 MAb, the epitope of which is consistent with rat anti-PLAG2/3 MAb NZ-1, has not been established. NZ-1 inhibits the hPDPN-CLEC-2 interaction and is also useful for anti-PA tag MAb. We recently established CasMab technology to produce MAbs against membranous proteins. Herein, we produced a novel anti-hPDPN MAb, LpMab-13, which binds to PLAG2/3 domains. LpMab-13 recognized endogenous hPDPN of cancer cells, including glioblastoma, oral cancer, lung cancer, and malignant mesothelioma, and normal cells such as lymphatic endothelial cells and podocytes of kidney in Western blot, flow cytometry, and immunohistochemistry. LpMab-13 recognized glycan-deficient hPDPN in flow cytometry, indicating that the interaction between LpMab-13 and hPDPN is independent of its glycosylation. The minimum epitope of LpMab-13 was identified as Ala42-Asp49 of hPDPN using Western blot and flow cytometry. The combination of different epitope-possessing MAbs could be advantageous for the hPDPN-targeting diagnosis and therapy.
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PMID:Establishment of Mouse Monoclonal Antibody LpMab-13 Against Human Podoplanin. 2732 60

ABBV-321 (serclutamab talirine), a next-generation EGFR-targeted antibody-drug conjugate (ADC) incorporates a potent pyrrolobenzodiazepine (PBD) dimer toxin conjugated to the EGFR-targeting ABT-806 affinity-matured AM1 antibody. ABBV-321 follows the development of related EGFR-targeted ADCs including depatuxizumab mafodotin (depatux-m, ABT-414), ABT-806 conjugated to monomethyl auristatin F (MMAF), and ABBV-221 (losatuxizumab vedotin), AM1 antibody conjugated to monomethyl auristatin E (MMAE). The distinct tumor selectivity of ABBV-321 differentiates it from many previous highly active antibody PBD conjugates that lack a therapeutic window. Potency of the PBD dimer, combined with increased binding of AM1 to EGFR-positive tumor cells, opens the possibility to target a wide array of tumors beyond those with high levels of EGFR overexpression or amplification, including those insensitive to auristatin-based ADCs. ABBV-321 exhibits potent antitumor activity in cellular and in vivo studies including xenograft cell line and patient-derived xenograft glioblastoma, colorectal, lung, head and neck, and malignant mesothelioma tumor models that are less sensitive to depatux-m or ABBV-221. Combination studies with ABBV-321 and depatux-m suggest a promising treatment option permitting suboptimal, and potentially better tolerated, doses of both ADCs while providing improved potency. Collectively, these data suggest that ABBV-321 may offer an extended breadth of efficacy relative to other EGFR ADCs while extending utility to multiple EGFR-expressing tumor indications. Despite its highly potent PBD dimer payload, the tumor selectivity of ABBV-321, coupled with its pharmacology, toxicology, and pharmacokinetic profiles, support continuation of ongoing phase I clinical trials in patients with advanced EGFR-expressing malignancies.
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PMID:Targeting Multiple EGFR-expressing Tumors with a Highly Potent Tumor-selective Antibody-Drug Conjugate. 3284 77