Complete and Sustained Objective Response per RECIST to Irvalec (PM02734) in Undifferentiated Large Cell Esophageal Adenocarcinoma: A Case Report and a Review of the Literature

Salazar, Ramón; Cuadra, C.; Gil-Martín, Marta; Vandermeeren, Andrea; Alfaro, Vicente; Coronado, C.

doi:10.1159/000341104

Cited by 5 publications

(2 citation statements)

References 14 publications

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“…In fact, although the current World Health Organization Classification of Tumours of the Digestive System recognizes esophageal undifferentiated carcinomas as a distinct entity, the clinical and pathologic features are not described [8]. Within the literature, studies characterizing these neoplasms have been isolated to large epidemiological studies with little gross and histologic information or individual case reports that lack correlative clinical data [6,7,9–12,24]. To the best of our knowledge, our study represents the largest clinicopathological description of esophageal undifferentiated carcinomas.…”

Section: Discussionmentioning

confidence: 99%

Undifferentiated carcinoma of the esophagus: a clinicopathological study of 16 cases

et al. 2015

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Summary Undifferentiated carcinoma of the esophagus is a rare histologic variant of esophageal carcinoma. Using criteria based on studies of undifferentiated carcinomas arising at other sites, we have collected 16 cases of resected esophageal undifferentiated carcinomas. Patients ranged in age from 39 to 84 years (mean, 65.5 years) and were predominantly male (94%). The tumors were characterized by an expansile growth pattern of neoplastic cells organized in solid sheets and without significant glandular, squamous, or neuroendocrine differentiation. The neoplastic cells had a syncytial-like appearance, little intervening stroma, and patchy tumor necrosis. In a subset of cases, the tumor cells adopted a sarcomatoid (n = 2), rhabdoid (n = 1), or minor component (<5%) of glandular morphology (n = 3). In 1 case, reactive osteoclast-like giant cells were found interspersed among the neoplastic cells. Lymphovascular invasion, perineural invasion, and lymph node metastases were identified in 88%, 56%, and 81% of cases, respectively. In 12 (75%) specimens, the background esophageal mucosa was notable for Barrett esophagus. Consistent with the epithelial nature of these neoplasms, cytokeratin positivity was identified in all cases. In addition, SALL4 expression was present in 8 (67%) of 12 cases. Follow-up information was available for 15 (94%) of 16 patients, all of whom were deceased. Survival after surgery ranged from 1 to 50 months (mean, 11.9 months). Before death, 67% patients had documented locoregional recurrence and/or distant organ metastases. In summary, esophageal undifferentiated carcinomas are aggressive neoplasms and associated with a high incidence of recurrence and/or metastases and a dismal prognosis.

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Section: Discussionmentioning

confidence: 99%

Undifferentiated carcinoma of the esophagus: a clinicopathological study of 16 cases

et al. 2015

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“…Additionally, elisidepsin has been found to have synergistic effects when combined with several different conventional chemotherapeutic agents and tyrosine kinase inhibitors in cell lines and mouse xenograft models most likely due to its unique mechanism of action [ 6 , 7 ]. In clinical trials, elisidepsin has been shown to have a low toxicity profile [ 8 , 9 , 10 , 11 ] and preliminary assessment of its clinical efficacy showed interesting results in different solid tumors [ 8 , 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Reduces the Efficiency of Elisidepsin by Inhibiting Hydroxylation and Altering the Structure of Lipid Rafts

et al. 2013

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The mechanism of action of elisidepsin (PM02734, Irvalec®) is assumed to involve membrane permeabilization via attacking lipid rafts and hydroxylated lipids. Here we investigate the role of hypoxia in the mechanism of action of elisidepsin. Culturing under hypoxic conditions increased the half-maximal inhibitory concentration and decreased the drug’s binding to almost all cell lines which was reversed by incubation of cells with 2-hydroxy palmitic acid. The expression of fatty acid 2-hydroxylase was strongly correlated with the efficiency of the drug and inversely correlated with the effect of hypoxia. Number and brightness analysis and fluorescence anisotropy experiments showed that hypoxia decreased the clustering of lipid rafts and altered the structure of the plasma membrane. Although the binding of elisidepsin to the membrane is non-cooperative, its membrane permeabilizing effect is characterized by a Hill coefficient of ~3.3. The latter finding is in agreement with elisidepsin-induced clusters of lipid raft-anchored GFP visualized by confocal microscopy. We propose that the concentration of elisidepsin needs to reach a critical level in the membrane above which elisidepsin induces the disruption of the cell membrane. Testing for tumor hypoxia or the density of hydroxylated lipids could be an interesting strategy to increase the efficiency of elisidepsin.

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Population pharmacokinetics of kahalalide F in advanced cancer patients

Miguel-Lillo

Valenzuela

Peris-Ribera

et al. 2015

Cancer Chemother Pharmacol

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Complete and Sustained Objective Response per RECIST to Irvalec (PM02734) in Undifferentiated Large Cell Esophageal Adenocarcinoma: A Case Report and a Review of the Literature

Cited by 5 publications

References 14 publications

Undifferentiated carcinoma of the esophagus: a clinicopathological study of 16 cases

Undifferentiated carcinoma of the esophagus: a clinicopathological study of 16 cases

Hypoxia Reduces the Efficiency of Elisidepsin by Inhibiting Hydroxylation and Altering the Structure of Lipid Rafts

Population pharmacokinetics of kahalalide F in advanced cancer patients

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