Antitumoral effects of 9-cis retinoic acid in adrenocortical cancer

Szabó, Dorottya; Baghy, Kornélia; Szabó, Péter M.; Zsippai, Adrienn; Marczell, Istvan; Nagy, Zoltán; Varga, Vivien; Éder, Katalin; Tóth, Sára; Buzás, Edit I.; Falus, András; Kovalszky, Ilona; Patócs, Attila; Rácz, Kàroly; Igaz, Péter

doi:10.1007/s00018-013-1408-z

Cited by 22 publications

(16 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the other potential pathways that can be suggested by microRNA studies, retinoic acid signaling in ACC [56] might be of interest, and our in vitro and xenograft studies support the potential applicability of 9-cis-retinoic acid in ACC treatment [93]. Other, but currently unvalidated pathways such as aryl hydrocarbon and integrin signaling [56] might also include targets that could be exploited in therapy.…”

Section: Indirect Targets: Pathways Affected By Micrornasmentioning

confidence: 88%

MicroRNAs in adrenal tumors: relevance for pathogenesis, diagnosis, and therapy

Igaz

Nagy

et al. 2014

Cell. Mol. Life Sci.

Self Cite

View full text Add to dashboard Cite

Several lines of evidence support the relevance of microRNAs in both adrenocortical and adrenomedullary (pheochromocytomas) tumors. Significantly differentially expressed microRNAs have been described among benign and malignant adrenocortical tumors and different forms of pheochromocytomas that might affect different pathogenic pathways. MicroRNAs can be exploited as markers of malignancy or disease recurrence. Besides tissue microRNAs, novel data show that microRNAs are released in body fluids, and blood-borne microRNAs can be envisaged as minimally invasive markers of malignancy or prognosis. MicroRNAs might even serve as treatment targets that could expand the rather-limited therapeutic repertoire in the field of adrenal tumors. In this review, we present a critical synopsis of the recent observations made in the field of adrenal tumor-associated microRNAs regarding their pathogenic, diagnostic, and potential therapeutic relevance.

show abstract

Section: Indirect Targets: Pathways Affected By Micrornasmentioning

confidence: 88%

MicroRNAs in adrenal tumors: relevance for pathogenesis, diagnosis, and therapy

Igaz

Nagy

et al. 2014

Cell. Mol. Life Sci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Over the course of treatment, [D-Trp6]LHRH causes a surge of testosterone release at the beginning and then a reduction to levels similar to postcastration levels approximately 4 wk after injection (20,21). Retinoic acid is involved in the regulation of steroidogenesis, and its use significantly reduces cortisol secretion (19). [D-Trp6]LHRH and retinoic acid both influenced basal (Fig.…”

Section: Impact Of Lhrh Agonist [D-trp6]lhrh and Retinoic Acid On Enbmentioning

confidence: 98%

“…Adrenocortical cells express receptors for both LHRH and retinoic acid (18,19). The LHRH agonist [D-Trp6]LHRH is clinically approved for the treatment of hormone-dependent cancers, predominantly prostate cancer.…”

Section: Impact Of Lhrh Agonist [D-trp6]lhrh and Retinoic Acid On Enbmentioning

confidence: 99%

Transplantation of bovine adrenocortical cells encapsulated in alginate

Balyura

Gelfgat

Ehrhart‐Bornstein

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Current treatment options for adrenal insufficiency are limited to corticosteroid replacement therapies. However, hormone therapy does not replicate circadian rhythms and has unpleasant side effects especially due to the failure to restore normal function of the hypothalamic-pituitary-adrenal (HPA) axis. Adrenal cell transplantation and the restoration of HPA axis function would be a feasible and useful therapeutic strategy for patients with adrenal insufficiency. We created a bioartificial adrenal with 3D cell culture conditions by encapsulation of bovine adrenocortical cells (BACs) in alginate (enBACs). We found that, compared with BACs in monolayer culture, encapsulation in alginate significantly increased the life span of BACs. Encapsulation also improved significantly both the capacity of adrenal cells for stable, long-term basal hormone release as well as the response to pituitary adrenocorticotropic hormone (ACTH) and hypothalamic luteinizing hormone-releasing hormone (LHRH) agonist, [D-Trp6]LHRH. The enBACs were transplanted into adrenalectomized, immunodeficient, and immunocompetent rats. Animals received enBACs intraperitoneally, under the kidney capsule (free cells or cells encapsulated in alginate slabs) or s.c. enclosed in oxygenating and immunoisolating βAir devices. Graft function was confirmed by the presence of cortisol in the plasma of rats. Both types of grafted encapsulated cells, explanted after 21-25 d, preserved their morphology and functional response to ACTH stimulation. In conclusion, transplantation of a bioartificial adrenal with xenogeneic cells may be a treatment option for patients with adrenocortical insufficiency and other stress-related disorders. Furthermore, this model provides a microenvironment that ensures 3D cell-cell interactions as a unique tool to investigate new insights into cell biology, differentiation, tissue organization, and homeostasis.adrenal | alginate encapsulation | cell transplantation | LHRH A drenal insufficiency is the failure of adrenocortical cells to produce adequate amounts of glucocorticoids and/or mineralocorticoids. These steroid hormones play a central role in the body's homeostasis of energy, salt, and fluid; thus, adrenal insufficiency is a potentially life-threatening condition. The most relevant causes of adrenal insufficiency are autoimmune disorders (up to 80%); infectious diseases; hereditary factors; traumatic, metabolic, or neoplastic conditions; or surgical bilateral adrenalectomy, sometimes due to a compulsory therapeutic strategy in the treatment of adrenal tumors or congenital adrenal hyperplasia

show abstract

“…A number of drugs developed for other malignant diseases have been assessed as potential therapies for ACC, but the results to date have been disappointing ( Table S3 , supporting information).…”

Section: Treatment Of Recurrent and Metastatic Diseasementioning

confidence: 99%

Diagnosis, treatment and outcome of adrenocortical cancer

Mihai

2015

British Journal of Surgery

View full text Add to dashboard Cite

Background: Adrenocortical cancer (ACC) is a rare disease with a dismal prognosis. The majority of patients are diagnosed with advanced disease and raise difficult management challenges.Methods: All references identified in PubMed, published between 2004 and 2014, using the keywords 'adrenocortical cancer' or 'adrenal surgery' or both, were uploaded into a database. The database was interrogated using keywords specific for each field studied.Results: In all, 2049 publications were identified. There is ongoing debate about the feasibility and oncological outcomes of laparoscopic adrenalectomy for small ACCs, and data derived from institutional case series have failed to provide an evidence level above expert opinion. The use of mitotane (1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane) in combination with chemotherapy in the treatment of metastatic disease has been assessed in an international randomized trial (FIRM-ACT trial) involving patients with ACC. Based on this trial, mitotane plus etoposide, doxorubicin and cisplatin is now the established first-line cytotoxic therapy owing to a higher response rate and longer median progression-free survival than achieved with streptozocin-mitotane. For patients with tumours smaller than 5 cm and with no signs of lymph node or distant metastases, survival is favourable with a median exceeding 10 years. However, the overall 5-year survival rate for all patients with ACC is only 30 per cent. Conclusion:Open and potentially laparoscopic adrenalectomy for selected patients is the main treatment for non-metastatic ACC, but the overall 5-year survival rate remains low.Cutting edge articles are invited by the BJS Editorial Team, and focus on how current research and innovation will affect future clinical practice.

show abstract

Antitumoral effects of 9-cis retinoic acid in adrenocortical cancer

Cited by 22 publications

References 57 publications

MicroRNAs in adrenal tumors: relevance for pathogenesis, diagnosis, and therapy

MicroRNAs in adrenal tumors: relevance for pathogenesis, diagnosis, and therapy

Transplantation of bovine adrenocortical cells encapsulated in alginate

Diagnosis, treatment and outcome of adrenocortical cancer

Contact Info

Product

Resources

About