Hypoxia-induced lncRNA ANRIL promotes cisplatin resistance in retinoblastoma cells through regulating ABCG2 expression.

This study was designed to explore the role and mechanism of long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) in regulating DDP resistance in Rb cells under hypoxia and to validate whether HIF-1α was involved in this process. The interaction between HIF-1α and the promoter of ANRIL was analyzed using ChIP assay. Cell proliferation and apoptosis, as well as protein levels of drug resistance-related proteins (ABCG2 and MDR1) were examined to evaluate DDP resistance in Rb cells. The interactions between miR-328 and ANRIL as well as miR-328 and ABCG2 were analyzed using dual-luciferase reporter assays. Upon hypoxia, HIF-1α directly bound to the ANRIL promoter region to transcriptionally activate ANRIL. The hypoxia-induced ANRIL promoted Rb cell resistance to DDP, as evidenced by facilitation of cell proliferation, inhibition of cell apoptosis and upregulation of ABCG2 and MDR1. Mechanistically, ANRIL promoted Rb cell resistance to DDP by acting as a sponge of miR-328 to upregulate expression of ABCG2, which was confirmed as a direct target of miR-328. Collectively, hypoxia-induced ANRIL promotes DDP resistance in Rb cells by sponging miR-328 to upregulate ABCG2 expression. PMID: 32173903 [PubMed - as supplied by publisher]
Source: Clinical and Experimental Pharmacology and Physiology - Category: Drugs & Pharmacology Authors: Tags: Clin Exp Pharmacol Physiol Source Type: research

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Conclusion: Even in the absence of genetic testing, screening for children with high risk for Rb is effective in enhancing early diagnosis, improving visual outcome, and increasing eye salvage rate with limited exposure to treatment burden. PMID: 32432497 [PubMed - as supplied by publisher]
Source: Ophthalmic Genetics - Category: Opthalmology Tags: Ophthalmic Genet Source Type: research
M. Benbrook Cervical cancer is caused by high-risk human papillomavirus (HPV) types and treated with conventional chemotherapy with surgery and/or radiation. HPV E6 and E7 proteins increase phosphorylation of retinoblastoma (Rb) by cyclin D1/cyclin dependent kinase (CDK)4/6 complexes. We hypothesized that cyclin D1 degradation by the SHetA2 drug in combination with palbociclib inhibition of CDK4/6 activity synergistically reduces phosphorylated Rb (phospho-Rb) and inhibits cervical cancer growth. The effects of these drugs, alone, and in combination, were evaluated in SiHa and CaSki HPV-positive and C33A HPV-negative c...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
CONCLUSION: We have demonstrated neural stem cell/CSC markers that facilitate the maintenance of cancer stem cells. Developing therapies targeting these factors will help in overcoming resistance and improving retinoblastoma treatment. PMID: 32364077 [PubMed - as supplied by publisher]
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research
Condition:   Retinoblastoma Intervention:   Drug: Melphalan Sponsor:   Washington University School of Medicine Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Abstract Retinoblastomas represent 6% of all malignant tumors in children under 5 years old, which untreated lead to blindness in the affected eye and death due to metastases. The main symptoms are leukocoria and strabismus, which if possible, always necessitate a clarification within 1 week for exclusion of a retinoblastoma. The most frequent differential diagnoses are Coats' disease and persistent fetal vasculature (PFV) as well as other intraocular tumors, in particular astrocytomas. Systemic chemotherapy, if necessary in combination with laser hyperthermia, local chemotherapy and brachytherapy are the most imp...
Source: Der Ophthalmologe - Category: Opthalmology Authors: Tags: Ophthalmologe Source Type: research
ConclusionUnilateral raised intraocular pressure, iris neovascularization, or both may be the presenting features of intraocular tumors. High degree of suspicion and a thorough examination reveals the definitive diagnosis.
Source: International Ophthalmology - Category: Opthalmology Source Type: research
ConclusionsOur demographic and basic clinical data for advanced RB are comparable to other similar reports. The tumor growth pattern correlates well with the type of seeding observed in enucleated globes with RB. Less tumor differentiation is a relative risk of massive choroidal invasion. It is advocated to implement the AJCC 8th edition by ocular pathologists worldwide aiming to histopathologically classify the RB tumor in cases for selective adjuvant chemotherapy.
Source: International Ophthalmology - Category: Opthalmology Source Type: research
Abstract Endovascular microcatheter-based intraarterial (ophthalmic artery) chemotherapy is becoming widely used for the clinical treatment of intraocular retinoblastoma due to its apparent increased efficacy compared with traditional intravenous chemotherapy; however local ocular complications are not uncommon. Carboplatin is a chemotherapeutic agent used in both intravenous and intraarterial chemotherapy. We used rabbits to assess pharmacokinetics and ocular and systemic toxicity after intraarterial carboplatin infusion. Subsequent to unilateral intraarterial administration of carboplatin, severe unilateral or b...
Source: Comparative Medicine - Category: Zoology Authors: Tags: Comp Med Source Type: research
Contributors : Mirjana Kessler ; Karen Hoffmann ; Hans Mollenkopf ; Thomas Meyer ; Hilmar BergerSeries Type : Expression profiling by arrayOrganism : Homo sapiensHigh-grade serous ovarian cancer (HGSOC) creates a unique clinical challenge due to late detection, limited therapeutic options and wide-spread resistance to chemotherapy, all of which lead to very low survival rates. It is now widely recognized that this cancer emerges as metastasis from the fallopian tube and the lack of suitable in vitro disease models poses a major obstacle for efforts to improve our understanding of this deadly disease. We used organoids of h...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research
ConclusionsWithin a 3-year follow-up period, IVC plus IAC produced no additional benefit over primary IAC for treating advanced intraocular retinoblastoma in terms of local tumor control and extending survival. Longer follow-up periods are required to assess long-term efficacy.
Source: Cancer Chemotherapy and Pharmacology - Category: Cancer & Oncology Source Type: research
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