Identification of molecular pathways involved in oxaliplatin-associated sinusoidal dilatation

Agostini, Julie; Benoist, Stéphane; Seman, Marie; Julié, Catherine; Imbeaud, Sandrine; Letourneur, Franck; Cagnard, Nicolas; Rougier, Philippe; Brouquet, Antoine; Zucman‐Rossi, Jessica; Laurent‐Puig, Pierre

doi:10.1016/j.jhep.2011.10.023

Cited by 42 publications

(28 citation statements)

References 33 publications

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“…[21][22][23] A potential impact of bevacizumab treatment on oxaliplatin-induced SOS is backed by studies that demonstrate an involvement of angiogenesis pathways in this disease. 24,25 Although the present study does not demonstrate a protective influence of bevacizumab on SOS development, it is of importance that 88 % of patients received oxaliplatin-based chemotherapy together with bevacizumab. It is thus difficult to evaluate how anti-VEGF therapy affected the HA levels measured in the present study.…”

contrasting

confidence: 60%

Hyaluronic Acid as a Marker of Sinusoidal Obstruction Syndrome after Oxaliplatin-based Chemotherapy for Colorectal Liver Metastases: Don’t Forget the Tumor

Rahbari

Weitz

2013

Ann Surg Oncol

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A few decades ago, patients with colorectal cancer liver metastases were considered incurable, and treatment was mainly supportive. Treatment options for patients with metastatic colorectal cancer have changed greatly since then, as has the outcome of these patients. Although in the past survival of these patients was within the range of a few months, with no 5-year survivors, current studies report median survival rates of 20-25 months and 5-year survival rates of 30-60 %.1-4 What has happened? Numerous studies have taught us that in selected patients, surgical resection of metastases prolongs survival. As hepatic resection has evolved to a safe procedure even in patients requiring extended, complex, and/or two-stage resection for complete tumor clearance, its use has increased and has added to the improved long-term outcome. However, only approximately 15 % to 20 % of patients are initially amenable to potentially curative resection; therefore, further factors must have played a role in the marked improvement in survival. The development and increased use of effective chemotherapeutic regimens has contributed significantly to the treatment results we are currently documenting for metastatic colorectal cancer. Several phase III trials proved that the addition of oxaliplatin or irinotecan to the backbone of 5-fluorouracil (5-FU) and folinic acid is able to achieve objective response rates of 40-50 %.5-8 The antitumor activity of these combined chemotherapy regimens has clearly improved median survival rates compared to historic data of patients who received 5-FU monotherapy, which was the standard of care in the late 1980s. Moreover, these improved regimens rendered the disease of a higher proportion of patients resectable. Resectability rates in firstline chemotherapy trials with palliative intent range from 5 to 15 % and go up to 30 % in patients with more limited yet still unresectable disease receiving chemotherapy for the intent of downstaging.9 Furthermore, the addition of biological agents such as bevacizumab, a monoclonal antibody against the vascular endothelial growth factor (VEGF), and cetuximab or panitumumab, monoclonal antibodies against the epidermal growth factor receptor, seem to further enhance response and resectability rates. 10Although the effectiveness of modern chemotherapy protocols in patients with metastatic colorectal cancer is undisputed, issues associated with these regimens, such as acquired resistance and increased toxicity, remain important future challenges for interdisciplinary management. In particular, liver toxicity related to the administration of irinotecan-and oxaliplatin-containing regimens represents a significant concern; their development may interfere with the planned treatment concept. It has been demonstrated that preoperative chemotherapy correlates with significantly higher perioperative complications.11,12 Furthermore, the development of histological alterations in the liver parenchyma may impede the antitumor effects of systemic therapies. 13 The pathological ch...

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contrasting

confidence: 60%

Hyaluronic Acid as a Marker of Sinusoidal Obstruction Syndrome after Oxaliplatin-based Chemotherapy for Colorectal Liver Metastases: Don’t Forget the Tumor

Rahbari

Weitz

2013

Ann Surg Oncol

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“…Comparison with studies primarily focused on SI-associated transcriptome changes [11,15] is problematic, since no pathological evaluation of SI was performed in the present study. Pathways recognized to be important for SI development in a microarray study by Rubbia-Brandt et al did not overlap with our proteome analysis.…”

Section: Discussionmentioning

confidence: 98%

“…This is probably due to the use of both patients with and without FOLFOX treatment in the control group (without SI) in the microarray analysis [15]. Nevertheless, the classifying proteins showed small, but significant (Fisher exact test p -value 0.047) overlap with genes associated with SI in a microarray study by Agostini et al [11]. The overlap of three proteins, namely COL3A1, VCAN, and TMPRSS6, was significant, despite that only one third (26/81) of the original list of genes was identified in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Some patients develop SI after only a short period of treatment, while others do not develop SI despite prolonged treatment. This evokes the hypothesis of an individual susceptibility to oxaliplatin-induced injury [11]. The association of SI development with polymorphisms in the nucleotide excision repair genes ERCC2 [12], copper transporter ATP7B [13], and glutathione S-transferase M1 [14] supports the hypothesis.…”

Section: Introductionmentioning

confidence: 86%

“…Microarray studies attempting to investigate the whole panorama of changes associated with oxaliplatin-based treatment and SI development in humans show an involvement of angiogenesis, cellular adhesion, oxidative stress, and extracellular matrix components [11,15] together with activation of acute phase response, coagulation system, hepatic fibrosis, and hypoxic factors [15]. The role of the mentioned processes is supported by the findings of several studies focusing on particular pathways: angiogenesis [16], oxidative stress [16,17,18,19,20], extracellular matrix remodeling [21,22], and prothrombotic changes [11,23]. However, these changes can also be explained by the presence of CRLM itself [24].…”

Section: Introductionmentioning

confidence: 99%

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Global Proteome Changes in Liver Tissue 6 Weeks after FOLFOX Treatment of Colorectal Cancer Liver Metastases

et al. 2016

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(1) Oxaliplatin-based chemotherapy for colorectal cancer liver metastasis is associated with sinusoidal injury of liver parenchyma. The effects of oxaliplatin-induced liver injury on the protein level remain unknown. (2) Protein expression in liver tissue was analyzed—from eight patients treated with FOLFOX (combination of fluorouracil, leucovorin, and oxaliplatin) and seven controls—by label-free liquid chromatography mass spectrometry. Recursive feature elimination–support vector machine and Welch t-test were used to identify classifying and relevantly changed proteins, respectively. Resulting proteins were analyzed for associations with gene ontology categories and pathways. (3) A total of 5891 proteins were detected. A set of 184 (3.1%) proteins classified the groups with a 20% error rate, but relevant change was observed only in 55 (0.9%) proteins. The classifying proteins were associated with changes in DNA replication (p < 0.05) through upregulation of the minichromosome maintenance complex and with the innate immune response (p < 0.05). The importance of DNA replication changes was supported by the results of Welch t-test (p < 0.05). (4) Six weeks after FOLFOX treatment, less than 1% of identified proteins showed changes in expression associated with DNA replication, cell cycle entry, and innate immune response. We hypothesize that the changes remain after recovery from FOLFOX treatment injury.

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The significance of nonobstructive sinusoidal dilatation of the liver: Impaired portal perfusion or inflammatory reaction syndrome

et al. 2015

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Sinusoidal dilatation found in the absence of an impaired sinusoidal blood outflow has been so far of unclear significance. Sinusoidal dilatation may actually be a nonspecific feature of impaired portal venous blood inflow, whatever the cause, or a feature of severe systemic inflammatory reaction syndrome, whatever the cause. Sinusoidal dilatation is mainly located in the centrilobular area even in the absence of an outflow block. A predominantly periportal location is specifically found in oral contraceptive users, associated with an inflammatory condition. There is strong evidence for the association of sinusoidal dilatation and oxaliplatin-based chemotherapy but not for estroprogestative steroids or thiopurine derivatives. Exposure to anabolic androgen steroids appears to cause sinusoidal changes different from a mere sinusoidal dilatation. Conclusion: There is evidence of activation of the interleukin-6 and vascular endothelial growth factor pathways in sinusoidal dilatation, but the mechanisms linking the activation of these pathways with the microvascular changes must be identified. (HEPATOLOGY 2015;62:956-963) S inusoidal dilatation (SD) in the absence of postsinusoidal outflow block is characterized by enlarged hepatic sinusoids as a predominant histopathological feature.

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Identification of molecular pathways involved in oxaliplatin-associated sinusoidal dilatation

Cited by 42 publications

References 33 publications

Hyaluronic Acid as a Marker of Sinusoidal Obstruction Syndrome after Oxaliplatin-based Chemotherapy for Colorectal Liver Metastases: Don’t Forget the Tumor

Hyaluronic Acid as a Marker of Sinusoidal Obstruction Syndrome after Oxaliplatin-based Chemotherapy for Colorectal Liver Metastases: Don’t Forget the Tumor

Global Proteome Changes in Liver Tissue 6 Weeks after FOLFOX Treatment of Colorectal Cancer Liver Metastases

The significance of nonobstructive sinusoidal dilatation of the liver: Impaired portal perfusion or inflammatory reaction syndrome

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