New Developments in Interventional Oncology

Kallini, Joseph R.; Gabr, Ahmed; Abouchaleh, Nadine; Ali, Rehan; Riaz, Ahsun; Lewandowski, Robert J.; Salem, Riad

doi:10.1097/ppo.0000000000000226

Cited by 14 publications

(9 citation statements)

References 82 publications

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“…The main cause of mortality is recurrence and metastasis of the tumor, even after a successful surgical resection and postoperative therapy. Some 60% of patients suffer from metastasis during the course of CRC 3,4. Consequently, it is necessary to fully understand the mechanism of metastasis or develop an effective biomarker for early diagnosis.…”

Section: Introductionmentioning

confidence: 99%

<p>The β-galactoside α2,6-sialyltranferase 1 (ST6GAL1) inhibits the colorectal cancer metastasis by stabilizing intercellular adhesion molecule-1 via sialylation</p>

Zhou¹,

Zhang²,

Zou³

et al. 2019

CMAR

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Background: Colorectal cancer (CRC) is one of the most frequent malignancies of the digestive system. Elevated expression of β-galactoside α2,6-sialyltranferase 1 (ST6GAL1) has been observed in multiple cancers. But the mechanism of how ST6GAL1 might affect cancer cells remains to be clarified. Our previous study recognized intercellular adhesion molecule-1(ICAM-1) as a probable substrate of ST6GAL1 through mass spectrometry (MS) analysis. ICAM-1 is related to tumor metastasis in various cancers. Methods: First, ST6GAL1 was overexpressed and knocked down to perform transwell and wound healing assays, and the results were further confirmed in vivo. Based on the results of MS, GO and KEGG analysis were applied to reveal the connection between ST6GAL1 and ICAM-1. Immunoblot and tissue microarrays were administered to investigate the expression of ICAM-1 in different stages of CRC. Next, PCR, lectin precipitation and cycloheximide (CHX) were used to demonstrate the mechanism of ST6GAL1 on ICAM-1. Moreover, we investigated the sialylation on soluble ICAM in serum and its connection to tumor staging. Results: Overexpression of ST6GAL1 inhibited the migratory ability, while knockdown of ST6GAL1 cells had the reverse effect. Moreover, nude mice injected with ST6GAL1-knockdown cells harvested more liver metastases. Based on the GO and KEGG analysis, data from TCGA database showed a positive correlation between ST6GAL1 and ICAM-1. ICAM-1 also demonstrated a significant decrease in stage III/IV compared with stage I/II tumors. Our results revealed that ST6GAL1 could increase the stability of ICAM-1 through sialylation but had little influence on transcriptional level. Additionally, results of serum lectin precipitation revealed a correlation between the level of sialylation on soluble ICAM and CRC staging. Conclusion: This study illustrated that ST6GAL1 inhibited the metastatic ability of CRC by stabilizing ICAM-1 via sialylation and demonstrated a correlation between CRC staging and the sialylation on soluble ICAM-1 in serum.

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Section: Introductionmentioning

confidence: 99%

<p>The β-galactoside α2,6-sialyltranferase 1 (ST6GAL1) inhibits the colorectal cancer metastasis by stabilizing intercellular adhesion molecule-1 via sialylation</p>

Zhou¹,

Zhang²,

Zou³

et al. 2019

CMAR

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“…1-3 More than 50% of CRC patients develop metastatic disease to their liver over the course of their life, 4 and liver metastasis is a leading cause of death from CRC. 5-7 Unfortunately, surgical resection of isolated liver metastases of CRC (LM-CRC) is curative in only 20%-30% of patients, 8 , 9 and systemic therapy provides limited survival benefit.…”

Section: Introductionmentioning

confidence: 99%

Blockade of LAG3 enhances responses of tumor-infiltrating T cells in mismatch repair-proficient liver metastases of colorectal cancer

et al. 2018

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Purpose: Liver metastasis develops in >50% of patients with colorectal cancer (CRC), and is a leading cause of CRC-related mortality. We aimed to identify which inhibitory immune checkpoint pathways can be targeted to enhance functionality of intra-tumoral T-cells in mismatch repair-proficient liver metastases of colorectal cancer (LM-CRC). Methodology: Intra-tumoral expression of multiple inhibitory molecules was compared among mismatch repair-proficient LM-CRC, peritoneal metastases of colorectal cancer (PM-CRC) and primary CRC. Expression of inhibitory molecules was also analyzed on leukocytes isolated from paired resected metastatic liver tumors, tumor-free liver tissues, and blood of patients with mismatch repair-proficient LM-CRC. The effects of blocking inhibitory pathways on tumor-infiltrating T-cell responses were studied in ex vivo functional assays. Results: Mismatch repair-proficient LM-CRC showed higher expression of inhibitory receptors on intra-tumoral T-cells and contained higher proportions of CD8+ T-cells, dendritic cells and monocytes than mismatch repair-proficient primary CRC and/or PM-CRC. Inhibitory receptors LAG3, PD-1, TIM3 and CTLA4 were higher expressed on CD8+ T-cells, CD4+ T-helper and/or regulatory T-cells in LM-CRC tumors compared with tumor-free liver and blood. Antibody blockade of LAG3 or PD-L1 increased proliferation and effector cytokine production of intra-tumoral T-cells isolated from LM-CRC in response to both polyclonal and autologous tumor-specific stimulations. Higher LAG3 expression on intra-tumoral CD8+ T-cells associated with longer progression-free survival of LM-CRC patients. Conclusion: Mismatch repair-proficient LM-CRC may be more sensitive to immune checkpoint inhibitors than mismatch repair-proficient primary CRC. Blocking LAG3 enhances tumor-infiltrating T-cell responses of mismatch repair-proficient LM-CRC, and therefore may be a new promising immunotherapeutic target for LM-CRC.

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“…Almost 22% of all CRC patients already have liver or other distance organ metastasis at the first time of diagnosis [ 2 ]; however, radical surgery resection, which includes both primary and metastatic tumors, can only be performed in few of these patients. Depending on the data of National Comprehensive Cancer Network (NCCN), active chemotherapy should be recommended to unresectable stage IV CRC patients, and palliative surgical resection is considered for those who develop symptomatic disease, such as bowel obstruction, severe bleeding, or perforation [ 3 ]. The alternative strategy is to perform a palliative surgical resection of primary tumor first, which will prevent related complications; then, systemic chemotherapy should be administered to treat any metastatic disease.…”

Section: Introductionmentioning

confidence: 99%

Primary tumor location as a predictor of the benefit of palliative resection for colorectal cancer with unresectable metastasis

Zhang

Ma²,

et al. 2017

World J Surg Onc

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BackgroundIt is still under debate that whether stage IV colorectal cancer patients with unresectable metastasis can benefit from primary tumor resection, especially for asymptomatic colorectal cancer patients. Retrospective studies have shown controversial results concerning the benefit from surgery. This retrospective study aims to evaluate whether the site of primary tumor is a predictor of palliative resection in asymptomatic stage IV colorectal cancer patients.MethodsOne hundred ninety-four patients with unresectable metastatic colorectal cancer were selected from Sun Yat-sen University Cancer Center Database in the period between January 2007 and December 2013. All information was carefully reviewed and collected, including the treatment, age, sex, carcinoembryonic antigen, site of tumor, histology, cancer antigen 199, number of liver metastases, and largest diameter of liver metastasis. The univariate and multivariate analyses were used to detect the relationship between primary tumor resection and overall survival of unresectable stage IV colorectal cancer patients.ResultsOne hundred twenty-five received palliative resection, and 69 received only chemotherapy. Multivariate analysis indicated that primary tumor site was one of the independent factors (RR 0.569, P = 0.007) that influenced overall survival. For left-side colon cancer patients, primary tumor resection prolonged the median overall survival time for 8 months (palliative resection vs. no palliative resection: 22 vs. 14 months, P = 0.009); however, for right-side colon cancer patients, palliative resection showed no benefit (12 vs. 10 months, P = 0.910).ConclusionsThis study showed that left-side colon cancer patients might benefit from the primary tumor resection in terms of overall survival. This result should be further explored in a prospective study.

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New Developments in Interventional Oncology

Cited by 14 publications

References 82 publications

<p>The β-galactoside α2,6-sialyltranferase 1 (ST6GAL1) inhibits the colorectal cancer metastasis by stabilizing intercellular adhesion molecule-1 via sialylation</p>

<p>The β-galactoside α2,6-sialyltranferase 1 (ST6GAL1) inhibits the colorectal cancer metastasis by stabilizing intercellular adhesion molecule-1 via sialylation</p>

Blockade of LAG3 enhances responses of tumor-infiltrating T cells in mismatch repair-proficient liver metastases of colorectal cancer

Primary tumor location as a predictor of the benefit of palliative resection for colorectal cancer with unresectable metastasis

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