13-cis Retinoic Acid Treatment of a Patient With Chemotherapy Refractory Nephroblastomatosis

Witt, Olaf; Hämmerling, Susanne; Stockklausner, Clemens; Schenk, Jens Peter; Günther, Patrick; Behnisch, Wolfgang; Hamad, B.; Mulla, Naima Ali Al; Kulozik, Andreas E.

doi:10.1097/mph.0b013e3181979c70

Cited by 20 publications

(15 citation statements)

References 20 publications

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“…Together with the strong growth suppression observed in vitro for all retinoids tested this clearly hints at a possible therapeutic utility of such a treatment. This is supported by the impressive clinical success of retinoid treatment in one case report of nephroblastomatosis, a WT precursor lesion, where a significant decline of kidney volumes was observed over a period of 1 year [11]. The comparatively poor response seen for ws592, a culture derived from mesoblastic nephroma, an early childhood tumor separate from WT, suggests that the effects observed with our cultures of classical WT may be rather specific and not due to general or unspecific effects of retinoids on cultured human cells and it may further set this tumor apart from classical WT.…”

Section: Discussionmentioning

confidence: 88%

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Retinoic acid pathway activity in wilms tumors and characterization of biological responses in vitro

Wegert¹,

Bausenwein²,

Kneitz

et al. 2011

Mol Cancer

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BackgroundWilms tumor (WT) is one of the most common malignancies in childhood. With current therapy protocols up to 90% of patients can be cured, but there is still a need to improve therapy for patients with aggressive WT and to reduce treatment intensity where possible. Prior data suggested a deregulation of the retinoic acid (RA) signaling pathway in high-risk WT, but its mode of action remained unclear.ResultsThe association of retinoid signaling and clinical parameters could be validated in a large independent tumor set, but its relevance in primary nephrectomy tumors from very young children may be different. Reduced RA pathway activity and MYCN overexpression were found in high risk tumors as opposed to tumors with low/intermediate risk, suggesting a beneficial impact of RA especially on advanced WT. To search for possible modes of action of retinoids as novel therapeutic options, primary tumor cell cultures were treated in vitro with all-trans-RA (ATRA), 9cis-RA, fenretinide and combinations of retinoids and a histone deacetylase (HDAC) inhibitor. Genes deregulated in high risk tumors showed opposite changes upon treatment suggesting a positive effect of retinoids. 6/7 primary cultures tested reduced proliferation, irrespective of prior RA signaling levels. The only variant culture was derived from mesoblastic nephroma, a distinct childhood kidney neoplasm. Retinoid/HDAC inhibitor combinations provided no synergistic effect. ATRA and 9cis-RA induced morphological changes suggestive of differentiation, while fenretinide induced apoptosis in several cultures tested. Microarray analysis of ATRA treated WT cells revealed differential expression of many genes involved in extracellular matrix formation and osteogenic, neuronal or muscle differentiation. The effects documented appear to be reversible upon drug withdrawal, however.ConclusionsAltered retinoic acid signaling has been validated especially in high risk Wilms tumors. In vitro testing of primary tumor cultures provided clear evidence of a potential utility of retinoids in Wilms tumor treatment based on the analysis of gene expression, proliferation, differentiation and apoptosis.

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Section: Discussionmentioning

confidence: 88%

“…in childhood neuroblastoma [9,10]. Until today next to nothing is known about retinoids as therapeutic agents in WT, since only one case of 13 cis -RA treatment of nephroblastomatosis, a WT precursor lesion, [11] and administration of fenretinide in one patient with WT [12] have been reported.…”

Section: Introductionmentioning

confidence: 99%

Retinoic acid pathway activity in wilms tumors and characterization of biological responses in vitro

Wegert¹,

Bausenwein²,

Kneitz

et al. 2011

Mol Cancer

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“…treated cultured Wilms tumor cells with ATRA and observed the reversion of gene expression patterns that are associated with high risk and relapse. There is in addition a case report of a child being successfully treated with 13‐cis retinoid after a relapse of a bilateral nephroblastomatosis . Especially in tumors that are resistant to conventional therapy, ATRA‐induced growth inhibition might hence be used as alternative or additional therapeutic intervention.…”

Section: Resultsmentioning

confidence: 99%

DrugTargetInspector: An assistance tool for patient treatment stratification

Schneider

Stöckel

Kehl

et al. 2016

Intl Journal of Cancer

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Cancer is a large class of diseases that are characterized by a common set of features, known as the Hallmarks of cancer. One of these hallmarks is the acquisition of genome instability and mutations. This, combined with high proliferation rates and failure of repair mechanisms, leads to clonal evolution as well as a high genotypic and phenotypic diversity within the tumor. As a consequence, treatment and therapy of malignant tumors is still a grand challenge. Moreover, under selective pressure, e.g., caused by chemotherapy, resistant subpopulations can emerge that then may lead to relapse. In order to minimize the risk of developing multidrug-resistant tumor cell populations, optimal (combination) therapies have to be determined on the basis of an in-depth characterization of the tumor's genetic and phenotypic makeup, a process that is an important aspect of stratified medicine and precision medicine. We present DrugTargetInspector (DTI), an interactive assistance tool for treatment stratification. DTI analyzes genomic, transcriptomic, and proteomic datasets and provides information on deregulated drug targets, enriched biological pathways, and deregulated subnetworks, as well as mutations and their potential effects on putative drug targets and genes of interest. To demonstrate DTI's broad scope of applicability, we present case studies on several cancer types and different types of input -omics data. DTI's integrative approach allows users to characterize the tumor under investigation based on various -omics datasets and to elucidate putative treatment options based on clinical decision guidelines, but also proposing additional points of intervention that might be neglected otherwise. DTI can be freely accessed at https://dti.bioinf.uni-sb.de.

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“…Interstitial fibrosis is the main cause of end stage renal failure. Retinoids are believed to inhibit inflammatory and proliferative pathways (24)(25)(26)(27)(28). Lehrke et al (25) suggested that the natural retinoic acid and 13cis retinoic acid conserve renal formation and function in rat mesangioproliferative glomerulonephritis and that all retinoid agonists with different subtypes are profoundly efficient in reducing renal damage and proliferation of mesangial cells.…”

Section: Discussionmentioning

confidence: 99%

Isotretinoin is a Safety Therapy on Kidney: A Retrospective Study

Parlak¹,

Ünal²,

Aksoy³

2018

tdd

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Objective: Isotretinoin is widely used in severe acne treatment. The drug leads to several adverse effects; skin and mucous membranes are frequently affected. It may also cause serious and fatal adverse effects like kidney damage. The aim of this study is to determine the safety of isotretinoin usage on kidney functions in patients with acne vulgaris. Methods: Eighty six patients with severe acne vulgaris and receiving 0.5 mg/kg/day of isotretinoin treatment were included in the study and evaluated retrospectively. Serum urea, creatinine, complete blood count, aspartate aminotransferase, alanine aminotransferase, lipid profile datas were obtained from patient files. Glomerular filtration rate (GFR) was measured at the baseline of treatment, 3 rd and 6 th months of treatment. Results: We detected significant increases in levels of creatinine on the third month (p=0.041), but it was not clinically significant, and there was no significant difference in creatinine levels at 6 th month. There were no significant differences among the baseline, 3 rd month (p=0.066) and 6 th month (p=0.429) of GFR values. Conclusion:We think that isotretinoin is safe for the kidneys but patients with high creatinine levels at the baseline of treatment should be closely followed up.Amaç: Şiddetli akne tedavisinde isotretinoin yaygın olarak kullanılmaktadır. İlaç çok sayıda yan etki oluşturmaktadır; deri ve mukoz membranlar ise sıklıkla etkilenmektedir. Ayrıca böbrek hasarı gibi ciddi ve ölümcül yan etkiler de görülebilmektedir. Bu çalışmanın amacı, akne vulgarisli hastalarda isotretinoin kullanımının böbrek fonksiyonları üzerindeki güvenilirliğini değerlendirmektir. Yöntemler: Şiddetli aknesi olan ve 0,5 mg/kg/gün isotretinoin tedavisi alan 86 hasta çalışmaya alındı ve geriye dönük değerlendirildi. Serum üre, kreatinin, tam kan sayımı, aspartat aminotransferaz, alanin aminotransferaz, lipit profil verileri hasta dosyalarından elde edildi. Glomerüler filtrasyon hızı (GFR) tedavi başlangıcında, tedavinin 3. ve 6. ayında hesaplandı. Bulgular: Tedavinin 3. ayında kreatinin değerlerinde anlamlı artış gözlendi (p=0,041); ancak klinik olarak anlamlı değildi, tedavinin 6. ayında ise kreatinin değerlerinde anlamlı farklılık yoktu. Başlangıç, 3. ay (p=0,066) ve 6. ay (p=0,429) GFR değerleri arasında anlamlı farklılık görülmedi. Sonuç: İsotretinoinin böbrekler için güvenilir olduğunu düşünüyoruz; ancak tedavi başlangıcında kreatin değeri yüksek olan hastalar yakın takip edilmelidir. Anahtar kelimeler: İsotretinoin, akne vulgaris, kreatinin, üre, böbrek fonksiyonu, böbrek hastalığında diyet modifikasyonu Öz

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13-cis Retinoic Acid Treatment of a Patient With Chemotherapy Refractory Nephroblastomatosis

Cited by 20 publications

References 20 publications

Retinoic acid pathway activity in wilms tumors and characterization of biological responses in vitro

Retinoic acid pathway activity in wilms tumors and characterization of biological responses in vitro

DrugTargetInspector: An assistance tool for patient treatment stratification

Isotretinoin is a Safety Therapy on Kidney: A Retrospective Study

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