Monitoring response to cytostatic cisplatin in a HER2(+) ovary cancer model by MRI and in vitro and in vivo MR spectroscopy

Pisanu, Maria Elena; Ricci, Alessandro; Paris, Luisa; Surrentino, E; Liliac, Ludmila; Bagnoli, Marina; Canevari, Silvana; Mezzanzanica, Delia; Podo, Franca; Canese, Rossella

doi:10.1038/bjc.2013.758

Cited by 24 publications

(44 citation statements)

References 53 publications

(88 reference statements)

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“…13 This study suggested that MARCH1 regulates cellular processes, not only in immunity, but also in cell signal transduction. [22][23][24]36 Previous studies have shown an ADC increase following targeted agent treatment with cisplatin in an ovarian cancer model, 37 sorafenib in breast cancer xenografts 38 and irinotecan in colon carcinoma xenografts. In this regard, here, we demonstrated that MARCH1 deletion does affect the biomarker of HCC tumours.…”

Section: Discussionmentioning

confidence: 99%

“…The ADC value, as a non-invasive biomarker and a sensitive biomarker to predict early treatment responses in various malignant tumours derived from DW-MRIs, was used to assess tumour cellularity, necrosis, cell apoptosis and cell density. [22][23][24]36 Previous studies have shown an ADC increase following targeted agent treatment with cisplatin in an ovarian cancer model, 37 sorafenib in breast cancer xenografts 38 and irinotecan in colon carcinoma xenografts. 39 Hence, we used DW-MRI to monitor the therapy response of the HCC xenografts under different therapy conditions.…”

Section: Discussionmentioning

confidence: 99%

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MARCH1 encourages tumour progression of hepatocellular carcinoma via regulation of PI3K‐AKT‐β‐catenin pathways

Xie

Dai

et al. 2019

J Cellular Molecular Medi

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Membrane‐associated RING‐CH‐1 (MARCH1) is a membrane‐anchored E3 ubiquitin ligase that is involved in a variety of cellular processes. MARCH1 was aberrantly expressed as a tumour promoter in ovarian cancer, but the signalling about the molecular mechanism has not yet been fully illuminated. Here, we first determined that MARCH1 was obviously highly expressed in human hepatocellular carcinoma samples and cells. In addition, our findings demonstrated that the proliferation, migration and invasion of hepatocellular carcinoma were suppressed, but the apoptosis was increased, as a result of MARCH1 knockdown by either siRNA targeting MARCH1 or pirarubicin treatment. Conversely, the proliferation, migration and invasion of hepatocellular carcinoma were obviously accelerated, and the apoptosis was decreased, by transfecting the MARCH1 plasmid to make MARCH1 overexpressed. Moreover, in vivo, the results exhibited a significant inhibition of the growth of hepatocellular carcinoma in nude mice, which were given an intra‐tumour injection of siRNA targeting MARCH1. Furthermore, our study concluded that MARCH1 functions as a tumour promoter, and its role was up‐regulated the PI3K‐AKT‐β‐catenin pathways both in vitro and in vivo. In summary, our work determined that MARCH1 has an important role in the development and progression of hepatocellular carcinoma and may be used as a novel potential molecular therapeutic target in the future treatment of hepatocellular carcinoma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MARCH1 encourages tumour progression of hepatocellular carcinoma via regulation of PI3K‐AKT‐β‐catenin pathways

Xie

Dai

et al. 2019

J Cellular Molecular Medi

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“…The majority of ovarian cancer studies in mouse models use xenografts that are obtained either after subcutaneous implantation (19) or intraperitoneal injection of cancer cells (20). To mimic the tumor microenvironment, more recent models involved direct injection of cells into the ovarian intrabursa (21, 22).…”

Section: Discussionmentioning

confidence: 99%

Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism

Penet¹,

Krishnamachary²,

Wildes³

et al. 2016

Front. Oncol.

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Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here, we have assessed the effect of pantethine on tumor growth and metabolism using magnetic resonance imaging and high-resolution proton magnetic resonance spectroscopy (MRS) in a model of ovarian cancer. To evaluate treatment strategies, it is important to use models that closely mimic tumor growth in humans. Therefore, we used an orthotopic model of ovarian cancer where a piece of tumor tissue, derived from an ovarian tumor xenograft, is engrafted directly onto the ovary of female mice, to maintain the tumor physiological environment. Treatment with pantethine, the precursor of vitamin B5 and active moiety of coenzyme A, was started when tumors were ~100 mm3 and consisted of a daily i.p. injection of 750 mg/kg in saline. Under these conditions, no side effects were observed. High-resolution 1H MRS was performed on treated and control tumor extracts. A dual-phase extraction method based on methanol/chloroform/water was used to obtain lipid and water-soluble fractions from the tumors. We also investigated effects on metastases and ascites formation. Pantethine treatment resulted in slower tumor progression, decreased levels of phosphocholine and phosphatidylcholine, and reduced metastases and ascites occurrence. In conclusion, pantethine represents a novel potential, well-tolerated, therapeutic tool in patients with ovarian cancer. Further in vivo preclinical studies are needed to confirm the beneficial role of pantethine and to better understand its mechanism of action.

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“…Compared with the parental cell line, SKOV3.ip cells are characterized by a more aggressive phenotype, including faster in vivo tumor growth and increased overexpression of human epidermal growth factor receptor‐2 (HER2+++). These features, along with the already known EGFR++, HER3+/−, HER4+/−, p53‐null and PTEN+/− profile typical of the SKOV3 cells, are associated with a low responsiveness of SKOV3.ip cells to cisplatin …”

Section: Introductionmentioning

confidence: 90%

“…In vivo MRI technologies, including diffusion‐weighted MRI (DWI) and localized MRS, have been successfully applied by our group, shortly after the in vivo administration of either conventional or innovative drugs, for the identification of their induced functional changes and metabolic alterations in preclinical models, and even in the presence of tumor growth inhibition rather than tumor shrinkage . Clinical DWI applications also showed encouraging results in the imaging of a variety of gynecological cancer lesions …”

Section: Introductionmentioning

confidence: 99%

Integration of MRI and MRS approaches to monitor molecular imaging and metabolomic effects of trabectedin on a preclinical ovarian cancer model

et al. 2018

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Although several drugs are available to treat recurrences of human epithelial ovarian cancer (EOC), clinical responses often remain short lived and lead to only marginal improvements in patients' survival. One of the new drugs proposed for recurrent platinum-resistant EOC patients is trabectedin (Trab), a marine-derived antitumor agent initially isolated from the tunicate Ecteinascidia turbinata and currently produced synthetically. Predictive biomarkers of therapy response to this drug and the potential use of non-invasive functional MRI and MRS approaches for an early assessment of Trab efficacy have not yet been evaluated, although they might be relevant for improving the clinical management of EOC patients. In the present work we combined functional and spectroscopic magnetic resonance technologies, such as in vivo diffusion-weighted MRI and 1 H MRS, with ex vivo high resolution MRS (HR-MRS) metabolomic analyses, with the aim of identifying new pharmacodynamic markers of Trab effectiveness on well characterized, highly aggressive human SKOV3.ip (a HER2-enriched cell variant derived from SKOV3 cells) EOC xenografts. In vivo treatment with Trab (three consecutive weekly 0.2 mg/kg i.v. injections) resulted in the following: (1) a significant reduction of in vivo tumor growth, along with the formation in cancer lesions of diffuse hyper-intense areas detected by T 2 -weighted MRI and attributed to necrosis, in agreement with histopathology findings; (2) significant increases in the apparent diffusion coefficient mean and median values versus saline-treated control tumors; and (3) a significant reduction in the cholinecontaining metabolites' signal detected by quantitative in vivo MRS. Multivariate and quantitative HR-MRS analyses on ex vivo tissue samples revealed Trab-induced alterations in phospholipid and glucose metabolism identified as a decrease in phosphocholine and an increase in lactate. Collectively, these data identify Trab-

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Monitoring response to cytostatic cisplatin in a HER2(+) ovary cancer model by MRI and in vitro and in vivo MR spectroscopy

Cited by 24 publications

References 53 publications

MARCH1 encourages tumour progression of hepatocellular carcinoma via regulation of PI3K‐AKT‐β‐catenin pathways

MARCH1 encourages tumour progression of hepatocellular carcinoma via regulation of PI3K‐AKT‐β‐catenin pathways

Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism

Integration of MRI and MRS approaches to monitor molecular imaging and metabolomic effects of trabectedin on a preclinical ovarian cancer model

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