Estrogen as a prognostic factor on liver metastasis from colorectal cancer.

506 Background: Estrogen plays an important role in some cancer. However, previous studies about the influence of estrogen on colorectal cancer (CRC) have been conflicting, especially rare reports on liver metastasis. This study tries to explore the prognostic impact of estrogen on CRC with liver metastasis. Methods: Eighty six patients with CRC including 43 synchronous liver metastases were studied. Estrogen receptor-beta (ER-beta) were assayed by immunohistochemistry (IHC) in liver metastasis tissues, colorectal cancer tissues and normal tissues. And the serum estrogens were detected by radioimmunoassay (RIA) in 30 patients with CRC including 14 synchronous liver metastases. After follow-up, the relationship between ERβ, estrogen and survival time were analyzed. Results: The positive rates of ER-beta in liver metastases tissues, CRC tissues and normal tissues were 39.5% (17/43), 39.5% (34/86) and 62.8% (54/86), respectively; and significant differences were found between liver metastasis (P=0.012) or CRC (P=0.002) with normal tissues. The 1-, 2-, 3-and 5-year survival rates for ER-beta positive patients were 97%, 79%, 71% and 51%, respectively comparing with 82%, 59%, 55% and 40%, respectively for ER-beta negative patients (P=0.190). In contrast, the 1-, 2-, 3- and 5-year survival rates in liver metastasis group were 77%, 37%, 31% and 23%, respectively; and 93%, 64%, 57% and 57%, respectively for ER-beta positive patients comparing with 67%, 19%, 14% and 7%, respectively for ER-beta negative patients (P=0.004). Serum estrogen levels in patients with liver metastases were significantly lower than those without liver metastasis (P=0.012) and Pearson Correlation showed that there was a moderate positive correlation between level of serum estrogen and survival time (P=0.006). Conclusions: CRC liver metastasis patients with positive ER-beta have a better survival, which indicates estrogen is a protective factor for CRC liver metastasis patients. But more study is needed to show estrogen would be a protective factor for CRC patients.

Download Full-text

The role of ccr5 polymorphism in colorectal cancer and liver metastasis in the Tunisian population

Archives of Biological Sciences ◽

10.2298/abs210817044w ◽

2021 ◽

pp. 44-44

Author(s):

Marwa Weslati ◽

Rahma Boughriba ◽

Donia Ounissi ◽

Meriam Hazgui ◽

Sonia Marghali

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Liver Metastases ◽

Protective Factor ◽

Significant Risk ◽

Tunisian Population ◽

Wild Type ◽

Ccr5 Expression ◽

Ccr5 Gene ◽

Mutational Status

Chemokines and their receptors are involved in cancer initiation and progression, including colorectal cancer (CRC) and liver metastasis formation. Our aim was to elucidate C-C chemokine receptor type 5 (CCR5) gene polymorphism (CCR5?32) impact on CRC and colorectal cancer liver metastases (CRLM) occurrence risk. We analyzed the CCR5 gene mutational status in 108 primary CRC cases, 35 CRLM and 248 healthy individuals, and evaluated CCR5 expression in healthy tissue and tumors. Rare allele ??32? was more frequent in controls (7.2% vs 2.8% in CRC). All 35 metastases had wild-type CCR5. Our analysis showed that CCR5 wild type has a significant risk of 2.73-fold (95% CI=1.22-7.31) to cause CRC while ?32 reduced the risks 0.36-fold (95% CI=0.13-0.82). For CRC, CCR5 correlated with left-sided tumors and liver metastases (P=0.040 and P= 0.039 respectively). As for CRLM, no correlation was found. Immunohistochemical profile analysis of CCR5 revealed a significant association with the male gender (P=0.049) and non-mucinous carcinomas (P< 0.001) in primary CRC. CCR5 expression revealed an association with the degree of tumor differentiation for both CRC and CRLM (P < 0.001). CCR5?32 might be a protective factor against CRC development and dissemination.

Download Full-text

Gut Microbiota Alteration Influences Colorectal Cancer Metastasis to the Liver By Remodeling the Liver Immune Microenvironment

10.21203/rs.3.rs-429405/v1 ◽

2021 ◽

Author(s):

na yuan ◽

Xiaoyan Li ◽

Meng Wang ◽

Zhilin Zhang ◽

Lu Qiao ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Gut Microbiota ◽

Liver Metastases ◽

Cancer Metastasis ◽

Pearson Correlation ◽

Control Group ◽

Immune Microenvironment ◽

Rdna Sequencing ◽

Key Factor

Abstract Background: The gut microbiota regulates the liver immune microenvironment in colorectal cancer (CRC) through gut-liver axis. Kupffer cells (KCs) contribute significantly to the formation of pre-metastatic niches (PMNs) for CRC liver metastasis. The aim of our study was to explore the effect of gut microbiota regulating KCs in CRC liver metastasis. Results: Mice treated with different antibiotics were divided into Control group, vancomycin (Vanc) group, colistin (Coli) group, and a group of ampicillin, streptomycin and colistin (ASC). Fewer liver metastases were identified in mice in the ASC group and Coli group than in those in the Control group (P = 0.003, P = 0.041, respectively). An increased proportion of Parabacteroides_goldsteinii, Bacteroides_vulgatus, Bacteroides_ thetaiotaomicron, Bacteroides_uniformis in mice of the Coli group were observed in 16S rDNA sequencing. Consistent with the Tax4Fun functional prediction, a prominent expansion of hepatic KCs was identified in mice in the ASC and Coli groups compared to those in the Control group (P = 0.001, P = 0.038, separately). Meanwhile, Bacteroides_vulgatus was a positive correlation with KCs contents (P = 0.011, r = 0.705). On the other hand, more liver metastases were observed in mice of the Vanc group than those in the Control group (P = 0.028). An increased abundance of Parabacteroides_distasonis, Proteus_mirabilis and a remarkable reduction of hepatic KCs were observed in mice in the Vanc group (P = 0.027). Pearson correlation analysis showed Proteus_mirabilis was a negative related to KCs contents (P = 0.028, r = 0.632). Conclusions: An increased abundance of Proteus_mirabilis and a decreased abundance of Bacteroides_vulgatus may be a key factor in CRC liver metastasis, which may be related to the reduction of KCs in the liver.

Download Full-text

Cytoreductive approach to peritoneal carcinomatosis originated from colorectal cancer: Turkish experience

Acta chirurgica iugoslavica ◽

10.2298/aci0602017f ◽

2006 ◽

Vol 53 (2) ◽

pp. 17-21 ◽

Cited By ~ 6

Author(s):

Mehmet Füzün ◽

Selman Sökmen ◽

Cem Terzi ◽

Aras Emre-Canda

Keyword(s):

Colorectal Cancer ◽

Lymph Nodes ◽

Liver Metastases ◽

Peritoneal Carcinomatosis ◽

Survival Time ◽

Median Survival ◽

Intraperitoneal Chemotherapy ◽

Survival Rates ◽

Complete Cytoreduction ◽

Mean Survival Time

Peritoneal carcinomatosis (PC) in contrast to lymph nodes and liver metastases was assumed as a terminal condition with no curative treatment options having a 5 to 9 months median survival rate until recently. Today, in properly selected patients, curative surgical treatment of PC is possible like resection of lymph nodes and liver metastases. Between 1996 and 2005, 29 patients who underwent cytoreductive surgery combined with intraperitoneal chemotherapy for PC originated from colorectal cancer (CRC) were analyzed prospectively at the Department of Surgery in Dokuz Eylul University Hospital. Mean age was 54 year (range, 23-75 years). There was no peroperative mortality in 29 patients. The morbidity rate was 41% (12/29) and 6 (20%) patients required reoperation(s) for major complications. Mean and median survival time was 34 and 21 months, respectively. The overall 1-year, 3-year, and 5-year survival rates were 72%, 13%, and 7%, respectively. Mean survival time was 56 months in patients with peritoneal cancer index (PCI) <10, and 22 months in patients with PCI >10 (P=0.075). The mean survival time was 62 months in patients with complete cytoreduction (CC)-0 score, 21 months in patients with CC-1 score, and 7 months in patients with CC-2 and 3 scores. Patients who had CC-0 score had better survival than patients having CC-1 and CC-2 scores (P = 0.003 and P = 0.000, respectively). Patients who had CC-0 and 1 scores had better survival than patients with CC-2 score (P = 0.000). The overall 1-year, 3-year, and 5-year survival rates for patients with CC-0 score were 87%, 37%, and 25%, respectively. There was a positive correlation between the PCI and CC score (P = 0.001, correlation coefficient = 0.585 with correlation is significant at level 0.01). Cytoreductive approach combined with intraperitoneal chemotherapy and systemic chemotherapy prolongs survival in selected patients with PC of CRC with acceptable morbidity and mortality. Prognosis is better in patients with limited disease and in whom complete cytoreduction is achieved. In patients with PC of CRC, the key issue is to select the patients in whom complete cytoreduction is feasible. Better patient assessment with new diagnostic tools such as (PET)-CT or PET-magnetic resonance imaging will be used to detect more precisely the patients with low tumor burden in the new feature.

Download Full-text

Inhibitory effect of an anti-prokineticin-1 antibody on liver metastasis in mice injected with human colorectal cancer cell lines

10.1101/2021.08.05.455319 ◽

2021 ◽

Author(s):

HIROKO KONO ◽

Takanori Goi ◽

Hidetaka Kurebayashi ◽

Kastuji Sawai ◽

Mitsuhiro Morikawa ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Liver Metastases ◽

Survival Time ◽

Cancer Cell ◽

Targeted Drugs ◽

Human Colorectal Cancer ◽

Metastatic Lesions ◽

Human Colorectal Cancer Cell ◽

Colorectal Cancer Cell Lines

Controlling hematogenous metastases is an effective treatment strategy for colorectal cancer. Multidisciplinary treatment for colorectal cancer has made great strides, and molecularly-targeted drugs have greatly improved the prognosis of patients. However, currently accepted molecularly-targeted therapeutic agents require concomitant use with anticancer agents. Thus, new molecularly-targeted drugs need to be developed. The prokineticin family of angiogenic factors has the potential of becoming target molecules. Among them, prokineticin-1 (PROK1) is involved in the promotion of angiogenesis, tumor growth, and liver metastases in colorectal cancer. We manufactured our own anti-PROK1 antibody and verified its effect in inhibiting liver metastases and prolonging survival. The method involved creating liver metastasis model mice using human colorectal cancer cell lines. These mice were divided into anti-PROK1 antibody administration and control groups. Mice were treated intraperitoneally with antibodies or phosphate-buffered saline (control) every 3 days. The number of liver metastatic lesions and survival time of each group were compared. The number of metastatic lesions decreased, and survival time was significantly prolonged in the antibody-treated group. Furthermore, using microarray and immunostaining in both groups, we confirmed the effect of administering the anti-PROK1 antibody on the oxidation, reduction, and apoptotic processes, and cell division of tumors, and that alterations were suppressed in 72.1% of the genes examined. The expression of transforming growth factor-β (TGF-β), a tumor suppressor gene, was increased. The increased expression of TGF-β via PROK1 antibody administration may suppress the cancer cell proliferation ability, leading to liver metastasis suppression and prolonging the survival time of mice.

Download Full-text

Simultaneous Resection of Primary Colorectal Cancer and Synchronous Liver Metastases: Contemporary Practice, Evidence and Knowledge Gaps

Oncology and Therapy ◽

10.1007/s40487-021-00148-2 ◽

2021 ◽

Author(s):

Dyre Kleive ◽

Eline Aas ◽

Jon-Helge Angelsen ◽

Erling A. Bringeland ◽

Arild Nesbakken ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastases ◽

Primary Colorectal Cancer ◽

Knowledge Gaps ◽

Synchronous Liver Metastases ◽

Simultaneous Resection ◽

Contemporary Practice

Download Full-text

Exosomal ANGPTL1 attenuates colorectal cancer liver metastasis by regulating Kupffer cell secretion pattern and impeding MMP9 induced vascular leakiness

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-020-01816-3 ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Kai Jiang ◽

Haiyan Chen ◽

Yimin Fang ◽

Liubo Chen ◽

Chenhan Zhong ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastasis ◽

Kupffer Cell ◽

Cell Secretion ◽

Gene Expressions ◽

Protein Levels ◽

Normal Tissues ◽

Mmp9 Expression ◽

Stat3 Signaling Pathway

Abstract Background Angiopoietin-like protein 1 (ANGPTL1) has been proved to suppress tumor metastasis in several cancers. However, its extracellular effects on the pre-metastatic niches (PMNs) are still unclear. ANGPTL1 has been identified in exosomes, while its function remains unknown. This study was designed to explore the role of exosomal ANGPTL1 on liver metastasis in colorectal cancer (CRC). Methods Exosomes were isolated by ultracentrifugation. The ANGPTL1 level was detected in exosomes derived from human CRC tissues. The effects of exosomal ANGPTL1 on CRC liver metastasis were explored by the intrasplenic injection mouse model. The liver PMN was examined by vascular permeability assays. Exosomal ANGPTL1 localization was validated by exosome labeling. The regulatory mechanisms of exosomal ANGPTL1 on Kupffer cells were determined by RNA sequencing. qRT-PCR, Western Blot, and ELISA analysis were conducted to examine gene expressions at mRNA and protein levels. Results ANGPTL1 protein level was significantly downregulated in the exosomes derived from CRC tumors compared with paired normal tissues. Besides, exosomal ANGPTL1 attenuated liver metastasis and impeded vascular leakiness in the liver PMN. Moreover, exosomal ANGPTL1 was mainly taken up by KCs and regulated the KCs secretion pattern, enormously decreasing the MMP9 expression, which finally prevented the liver vascular leakiness. In mechanism, exosomal ANGPTL1 downregulated MMP9 level in KCs by inhibiting the JAK2-STAT3 signaling pathway. Conclusions Taken together, exosomal ANGPTL1 attenuated CRC liver metastasis and impeded vascular leakiness in the liver PMN by reprogramming the Kupffer cell and decreasing the MMP9 expression. This study suggests a suppression role of exosomal ANGPTL1 on CRC liver metastasis and expands the approach of ANGPTL1 functioning.

Download Full-text