Cytotoxic activity of gemcitabine, alone or in combination with mitotane, in adrenocortical carcinoma cell lines

Germano, Antonina; Rapa, Ida; Volante, Marco; Buono, Nicola Lo; Carturan, Sonia; Berruti, Alfredo; Terzolo, Massimo; Papotti, Mauro

doi:10.1016/j.mce.2013.08.023

Cited by 19 publications

(14 citation statements)

References 16 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gemcitabine in vitro demonstrated to be an active cytotoxic agent in ACC cells. Interestingly, efficacy in combination with mitotane was dependent on mitotane sensitivity of the ACC cell line (Germano et al 2014). In addition, the RRM1 gene appears to play a role in sensitivity to gemcitabine, independent of mitotane (Germano et al 2014).…”

Section: Future Directions and Pathway Driven Therapiesmentioning

confidence: 98%

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Creemers¹,

Hofland²,

Korpershoek³

et al. 2015

Endocrine-Related Cancer

View full text Add to dashboard Cite

Adrenocortical carcinoma (ACC) is a rare disease with a poor prognosis. Discrimination between ACCs and adrenocortical adenomas (ACAs) remains challenging, with the current gold standard being the Weiss score, consisting of several histopathological characteristics. However, new markers like Ki67, a marker for proliferation, and the staining of reticulins are promising not only as it comes to identifying malignancy but also as prognostic markers in patients with ACC. Currently, surgery is still the only curative treatment for ACC. Mitotane, an adrenolytic drug, is used in the adjuvant setting and in case of metastatic or advanced disease. Patients with progressive disease are frequently treated with mitotane, alone or in combination with etoposide, doxorubicine and cisplatin. Radiotherapy is indicated in selected cases. The low response rates and high toxicity of the systemic therapies emphasize the need for markers that enable the identification of responders and non-responders. Consequently, research is focusing on predictive factors varying from the expression of DNA repair genes to clinical patient characteristics. Subgroups of ACC with different prognosis have been identified based on transcriptome characteristics. As a conclusion from large molecular studies, ACCs appear to harbor many abnormalities compared to ACAs. Altered pathways driving ACC pathogenesis include the IGF, TP53 and the Wnt signaling pathway, allowing these as new potential targets for medical therapy. However, despite efforts in preclinical and clinical studies investigating efficacy of targeting these pathways, most novel therapies appear to be effective in only a subset of patients with ACC. New treatment concepts are therefore urgently needed.

show abstract

Section: Future Directions and Pathway Driven Therapiesmentioning

confidence: 98%

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Creemers¹,

Hofland²,

Korpershoek³

et al. 2015

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…1,2 Some attempts such as the combination of drugs and mitotane have been recommended as first-line therapy in advanced ACC, but the overall prognosis remains very limited. 3,4 In addition, the low target effects (from local low-dose drugs) and high side effects have also limited the utility of chemotherapeutic drugs. Therefore, development of new chemotherapeutic agent formulations is ongoing, such as tumor target nanoparticles-loaded anticancer drugs.…”

Section: Introductionmentioning

confidence: 99%

Development of biocompatible and VEGF-targeted paclitaxel nanodrugs on albumin and graphene oxide dual-carrier for photothermal-triggered drug delivery in vitro and in vivo

Deng¹,

Qiu²,

Wang³

et al. 2018

IJN

View full text Add to dashboard Cite

In this study, we performed the characterization and synthesis of biocompatible and targeted albumin and graphene oxide (GO) dual-carrier paclitaxel (PTX) nanoparticles for photothermal-triggered tumor therapy. PTX absorbed on GO nanosheets as cores were coated with human serum albumin (HSA), following surface conjugation with monoclonal antibodies (mAb) against vascular endothelial growth factor (VEGF; denoted as mAbVEGF) via polyethylene glycol linker to form targeted nanoparticles (PTX-GHP-VEGF). The spherical nanoparticles were 191±5 nm in size with good stability and biocompatibility. GO functioned as the first carrier and a near infrared absorber that can generate photothermal effects under 5-minute 808-nm laser irradiation to thermal trigger the release of PTX from the second carrier HSA nanoparticles. The mechanism of thermal-triggered drug release was also investigated preliminarily, in which the heat generated by GO induced swelling of PTX-GHP-VEGF nanoparticles which released the drugs. In vitro studies found that PTX-GHP-VEGF can efficiently target human SW-13 adrenocortical carcinoma cells as evaluated by confocal fluorescence microscopy as well as transmission electron microscopy, and showed an obvious thermal-triggered antitumor effect, mediated by apoptosis. Moreover, PTX-GHP-VEGF combined with near infrared irradiation showed specific tumor suppression effects with high survival rate after 100 days of treatment. PTX-GHP-VEGF also demonstrated high biosafety with no adverse effects on normal tissues and organs. These results highlight the remarkable potential of PTX-GHP-VEGF in photothermal controllable tumor treatment.

show abstract

“…One explanation for these findings may be a different interaction with the Ribonucleotide Reductase large Subunit 1 (RRM1) gene. Further investigations are needed to define the role of gemcitabine in ACC treatment 65 .…”

Section: Evidence Synthesismentioning

confidence: 99%

Adrenocortical carcinoma: The management of metastatic disease

Fay¹,

Elfiky²,

Teló³

et al. 2014

Critical Reviews in Oncology/Hematology

View full text Add to dashboard Cite

Adrenocortical cancer is a rare malignancy. While surgery is the cornerstone of the management of localized disease, metastatic disease is hard to treat. Cytotoxic chemotherapy and mitotane have been utilized with a variable degree of benefit and few long-term responses. A growing understanding of the molecular pathogenesis of this malignancy as well as multidisciplinary and multi-institutional collaborative efforts will result in better defined targets and subsequently, effective novel therapies.

show abstract

Cytotoxic activity of gemcitabine, alone or in combination with mitotane, in adrenocortical carcinoma cell lines

Cited by 19 publications

References 16 publications

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Future directions in the diagnosis and medical treatment of adrenocortical carcinoma

Development of biocompatible and VEGF-targeted paclitaxel nanodrugs on albumin and graphene oxide dual-carrier for photothermal-triggered drug delivery in vitro and in vivo

Adrenocortical carcinoma: The management of metastatic disease

Contact Info

Product

Resources

About