Prognostic significance of VEGF-A/VEGF-R and EGF in liver metastasis from colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15128-e15128
Author(s):  
Elena Alekseevna Nikipelova ◽  
Oleg I. Kit ◽  
Elena Mikhaylovna Frantsiyants ◽  
Valeria Bandovkina ◽  
Irina V. Kaplieva ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Liver Metastasis ◽  
Treatment Effectiveness ◽  
Prognostic Significance ◽  
R Ratio ◽  
Tumor Tissues ◽  
Resection Line

e15128 Background: Liver metastasis from colorectal cancer dramatically reduces the treatment effectiveness and affects survival. Early detection of metastasis allows increasing the median survival and improving the quality of life of patients. The purpose of the study was to reveal factors significant for the prognosis of liver metastasis from colorectal cancer. Methods: Levels of VEGF-A, VEGF-R and EGF were studied by ELISA in tumors and resection line tissues of 113 patients with colorectal cancer (rectal cancer n = 43, colon cancer n = 70). Results: VEGF-A and VEGF-R levels in all tumors were increased compared to the resection line. VEGF-A levels in 46.5% patients with rectal tumors and in 29% patients with colon tumors were 2.5 times higher than in other patients; the VEGF-A/VEGF-R ratio was 2.9 times higher as well. Besides, these patients showed an increase in EGF levels in tumors by 3.9 times (rectal cancer) and 4.2 times (colon cancer), compared to the resection line. The follow-up demonstrated that the patient cohort developed liver metastases during next 3 months. Conclusions: Neoangiogenesis is activated in rectal and sigmoid tumors, and increasing VEGF-А and EGF contribute to tumor progression and metastasis. The VEGF-A/VEGF-R ratio in tumor tissues in comparison with the resection line value can be a reliable factor for the prognosis of liver metastasis.

Prognostic significance of mesenteric tumor nodules in patients with stage III colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3566-3566
Author(s):  
D. S. Lo ◽  
A. Pollett ◽  
S. Gallinger ◽  
L. L. Siu ◽  
R. L. Burkes
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Tnm Staging ◽  
Stage Iii ◽  
Stage Iiic ◽  
Female Ratio ◽  
Mesenteric Tumor

3566 Background: Tumor nodules are occasionally found in adjacent mesentery of colorectal cancer specimens, but their prognostic significance is unclear. According to the TNM staging system, mesenteric nodules are classified as part of T or N categories, but clinically they are regarded to reflect a worse prognosis, more like M1. We investigated the clinical significance of mesenteric tumor nodules. Methods: We reviewed 786 patients with stage III colorectal cancer referred between 1995 and 1999. We standardized TNM staging by assigning N status based on number of definite lymph nodes. Mesenteric nodules were considered separately and not assigned to T or N categories. Survival analyses were performed. Results: Mesenteric tumor nodules were found in 116 patients (14.8%); 48 with colon cancer (41.4%) and 68 rectal cancer (58.6%). Mean age at surgery was 62.8±1.0 yrs (SE), and the male: female ratio was 1.2. All tumors were adenocarcinomas with an average size of 4.3±0.1 cm, and the majority were moderately differentiated. Resection margins were clear except in 7 cases. With respect to high risk features, 6 cases (5.2%) had bowel perforation, 12 (10.3%) obstructive symptoms, 41 (35.3%) lymphovascular invasion, and 11 (9.5%) were T4 lesions. Adjuvant chemotherapy was given to 84.8% of colon cancer patients. Two (2.9%) rectal cancer patients received neoadjuvant chemo-radiation, and 63 (92.6%) received adjuvant therapy; chemotherapy, radiation or both. In the cohort with mesenteric nodules, the median time to progression was 23.1 months; the median 5-yr disease free survival was 35%; and the median overall survival (OS) was 47.9 months, with 44% OS at 5 yrs. After TNM standardization, 19 (16.4%) patients were down-staged to either stage I or II, and their 5-yr OS was 60% (SEER Stage II 5 yr survival 82.5%). In the remaining cohort-patients with stage III disease after standardization, the 5-yr OS was 40% (SEER 5yr survival Stage IIIc 44.3%; Stage IV 8.1%). Conclusions: In comparison to SEER survival data, the presence of mesenteric nodules appears to worsen prognosis of any T/N0 disease to that of overall stage III disease. Patients with mesenteric nodules in the setting of any T/N1+ disease had prognosis similar to that of stage IIIC disease, but their prognosis was better than M1 disease. No significant financial relationships to disclose.

scholarly journals Single-Cell Analysis Reveals Characterization of Infiltrating T Cells in Moderately Differentiated Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xi Yang ◽  
Quan Qi ◽  
Yuefen Pan ◽  
Qing Zhou ◽  
Yinhang Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Peripheral Blood ◽  
Strong Correlation ◽  
Tumor Tissue ◽  
Cell Populations

ObjectiveThis study aimed to characterize the tumor-infiltrating T cells in moderately differentiated colorectal cancer.MethodsUsing single-cell RNA sequencing data of isolated 1632 T cells from tumor tissue and 1252 T cells from the peripheral blood of CRC patients, unsupervised clustering analysis was performed to identify functionally distinct T cell populations, followed by correlations and ligand-receptor interactions across cell types. Finally, differential analysis of the tumor-infiltrating T cells between colon cancer and rectal cancer were carried out.ResultsA total of eight distinct T cell populations were identified from tumor tissue. Tumor-Treg showed a strong correlation with Th17 cells. CD8+TRM was positively correlated with CD8+IEL. Seven distinct T cell populations were identified from peripheral blood. There was a strong correlation between CD4+TN and CD4+blood-TCM. Colon cancer and rectal cancer showed differences in the composition of tumor-infiltrating T cell populations. Tumor-infiltrating CD8+IEL cells were found in rectal cancer but not in colon cancer, while CD8+ TN cells were found in the peripheral blood of colon cancer but not in that of rectal cancer. A larger number of tumor-infiltrating CD8+ Tex (88.94%) cells were found in the colon cancer than in the rectal cancer (11.06%). The T cells of the colon and rectal cancers showed changes in gene expression pattern.ConclusionsWe characterized the T cell populations in the CRC tumor tissue and peripheral blood.

scholarly journals CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer

2020 ◽  
Author(s):  
Junwei Tang ◽  
Yifei Feng ◽  
Yuanjian Huang ◽  
Ziwei Xu ◽  
Dongsheng Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Liver Metastasis ◽  
Hepatic Metastasis ◽  
Vascular Invasion ◽  
Synchronous Liver Metastasis ◽  
Node Negative ◽  
Common Cancer ◽  
Tumor Tissues ◽  
Colorectal Cancer Patients

Abstract Background Colorectal cancer (CRC) is the fourth most common cancer in men and the third most common cancer in women worldwide. The incidence and mortality of CRC was increasing rapidly in China. Lymph node-negative colorectal cancer patients with synchronous liver metastasis (LNLM1) was defined as “skip” lymph vascular invasion on hepatic metastasis, who presenting poor prognosis. We aiming to investigate the potential mechanism for the “skip” lymph vascular invasion on hepatic metastasis in colorectal cancer. Methods The microarray was applied for screening the transcription landscape of circRNA in lymph node negative CRC patients with synchronous liver metastasis (LNLM1) or without liver metastasis (LNLM0). The gain- and loss-of-function experiments was conducted in CRC cell lines and animal models. The RNA pull-down, RNA immunoprecipitation n was further employed in exploring the detailed mechanism of circRNA and associated target genes. Results We identified the aberrant increased circRNA circ_0124554 (also entitled as circ-LNLM) in tumor tissues of LNLM1 patients comparing with either the tumor tissues of LNLM0 or adjacent tissues of LNLM1. Circ-LNLM1 expression was highly corrected with liver metastasis and vascular invasion. Ectopic expression of cytoplasmic located circ-LNLM could promote invasion of CRC cells and induced the liver metastasis in animal models through the direct binding with AKT. The phosphorylation of AKT (T308/S473) was activated due to the blocked ubiquitination site of Lys in 0-52aa peptide of circ-LNLM. Endogenous plasma expression of circ-LNLM induced poor prognosis of LNLM1 and could distinguish LNLM1 patients from LNLM0. Conclusions The circ-LNLM blocked the ubiquitination of AKT could promote the early metastasis especially for the lymph node-negative colorectal cancer patients with synchronous liver metastasis. The circ-LNLM might be prognosis and diagnosis biomarker for LNLM1 patients.

scholarly journals Analysis of Co-Expression Module of Liver Metastasis Genes in Colorectal Cancer and Mining of Potential High-Expression Biomarkers

2021 ◽  
Author(s):  
Xuehu Wang ◽  
Nie Li ◽  
Yun Wang ◽  
Xiaoping Yin ◽  
Yongchang Zheng
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Liver Metastasis ◽  
High Expression ◽  
Data Set ◽  
Colorectal Cancer Liver Metastasis ◽  
Functional Annotations ◽  
Public Data ◽  
Highly Correlated ◽  
Expression Module

Abstract AimsThe Hub genes highly related to the disease were found from the gene co-expression module, and the potential high expression genes were analyzed to predict the liver metastasis of colorectal cancer, so as to provide reference for subsequent targeted therapy.MethodsIn this study, we used the public data set of GEO database (GSE50760) to analyze the gene co-expression of liver metastasis of colon cancer, primary colon cancer and normal colon tissue (54 cases) and 50 cases of clinical cases. The functional annotations based on GO database are enriched, and the functional annotations of five gene modules are obtained through the enrichment of biological processes. Then the data mining is carried out to find the sub-networks with high adjacency in the gene co-expression network. At the same time, these sub-networks are annotated to find oncogenes related to liver metastasis of colorectal cancer.ResultsThis experiment found that KRAS, APC, FBXW7, PIK3CA, TP53 were highly correlated with liver metastasis of colorectal cancer. Finally, two protein genes STAT1 and MAPK1 were found by MCODE, which may be highly correlated with liver metastasis of colorectal cancer. Two new genes with high expression proteins found in this experiment have potential cancer, which has not been reflected in previous studies.ConclusionAccording to clinical data, KRAS, APC, FBXW7, PIK3CA, TP53 are related to colorectal cancer liver metastasis, and the analysis of the data set shows that STAT1 and MAPK1 are not only related to colorectal cancer liver metastasis oncogene but also related to clinically obtained genes.

scholarly journals Subsite-Specific Dietary Risk Factors for Colorectal Cancer: A Review of Cohort Studies

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Anette Hjartåker ◽  
Bjarte Aagnes ◽  
Trude Eid Robsahm ◽  
Hilde Langseth ◽  
Freddie Bray ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Cohort Studies ◽  
Distal Colon ◽  
Proximal Colon ◽  
Risk Estimates ◽  
Specific Risk ◽  
Dietary Components

Objective. A shift in the total incidence from left- to right-sided colon cancer has been reported and raises the question as to whether lifestyle risk factors are responsible for the changing subsite distribution of colon cancer. The present study provides a review of the subsite-specific risk estimates for the dietary components presently regarded as convincing or probable risk factors for colorectal cancer: red meat, processed meat, fiber, garlic, milk, calcium, and alcohol.Methods. Studies were identified by searching PubMed through October 8, 2012 and by reviewing reference lists. Thirty-two prospective cohort studies are included, and the estimates are compared by sex for each risk factor.Results. For alcohol, there seems to be a stronger association with rectal cancer than with colon cancer, and for meat a somewhat stronger association with distal colon and rectal cancer, relative to proximal colon cancer. For fiber, milk, and calcium, there were only minor differences in relative risk across subsites. No statement could be given regarding garlic. Overall, many of the subsite-specific risk estimates were nonsignificant, irrespective of exposure.Conclusion. For some dietary components the associations with risk of cancer of the rectum and distal colon appear stronger than for proximal colon, but not for all.

scholarly journals Clinicopathological Factors Influencing Lymph Node Yield in Colorectal Cancer: A Retrospective Study

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Elena Orsenigo ◽  
Giulia Gasparini ◽  
Michele Carlucci
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Cancer Patients ◽  
Rank Test ◽  
Lymph Node Yield ◽  
Log Rank Test ◽  
Lymph Node Retrieval

Many colorectal resections do not meet the minimum of 12 lymph nodes (LNs) recommended by the American Joint Committee on Cancer for accurate staging of colorectal cancer. The aim of this study was to investigate factors affecting the number of the adequate nodal yield in colorectal specimens subject to routine pathological assessment. We have retrospectively analysed the data of 2319 curatively resected colorectal cancer patients in San Raffaele Scientific Institute, Milan, between 1993 and 2017 (1259 colon cancer patients and 675 rectal cancer patients plus 385 rectal cancer patients who underwent neoadjuvant therapy). The factors influencing lymph node retrieval were subjected to uni- and multivariate analyses. Moreover, a survival analysis was carried out to verify the prognostic implications of nodal counts. The mean number of evaluated nodes was 24.08±11.4, 20.34±11.8, and 15.33±9.64 in surgically treated right-sided colon cancer, left-sided colon cancer, and rectal tumors, respectively. More than 12 lymph nodes were reported in surgical specimens in 1094 (86.9%) cases in the colon cohort and in 425 (63%) cases in the rectal cohort, and patients who underwent neoadjuvant chemoradiation were analysed separately. On univariate analysis of the colon cancer group, higher LNs counts were associated with female sex, right colon cancer, emergency surgery, pT3-T4 diseases, higher tumor size, and resected specimen length. On multivariate analysis right colon tumors, larger mean size of tumor, length of specimen, pT3-T4 disease, and female sex were found to significantly affect lymph node retrieval. Colon cancer patients with 12 or more lymph nodes removed had a significantly better long-term survival than those with 11 or fewer nodes (P=0.002, log-rank test). Rectal cancer patients with 12 or more lymph nodes removed approached but did not reach a statistically different survival (P=0.055, log-rank test). Multiple tumor and patients’ factors are associated with lymph node yield, but only the removal of at least 12 lymph nodes will reliably determine lymph node status.

Genetic epidemiology of colorectal cancer and associated cancers

Mutagenesis ◽  
2019 ◽  
Vol 35 (3) ◽  
pp. 207-219
Author(s):  
Hongyao Yu ◽  
Kari Hemminki
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Familial Risk ◽  
Shared Environment ◽  
Relative Risks ◽  
Swedish Family ◽  
Rectal Cancers ◽  
Common Risk Factors ◽  
Double Primary Cancers

Abstract We review here data on familial risk in colorectal cancer (CRC) generated from the Swedish Family-Cancer Database, the largest resource of its kind in the world. Although the concordant familial risk for CRC (i.e. CRC risk in families of CRC patients) has been reasonably well established, the studies on discordant familial risks (i.e. CRC risk in families with any other cancers) are rare. Because different cancers could be caused by shared genetic susceptibility or shared environment, data of associations of discordant cancers may provide useful information for identifying common risk factors. In analyses between any of 33 discordant cancers relative risks (RRs) for discordant cancers were estimated in families with increasing numbers of probands with CRC; in the reverse analyses, RRs for CRC were estimated in families with increasing numbers of probands with discordant cancers. In separate analyses, hereditary non-polyposis colorectal cancer (HNPCC) families were excluded from the study, based on HNPCC related double primary cancers, to assess the residual familial RRs. We further reviewed familial risks of colon and rectal cancers separately in search for distinct discordant associations. The reviewed data suggested that colon cancer was associated with a higher familial risk for CRC compared to rectal cancer. The previous data had reported associations of CRC with melanoma, thyroid and eye cancers. Nervous system cancer was only associated with colon cancer, and lung cancer only associated with rectal cancer. The reviewed data on discordant association may provide guidance to gene identification and may help genetic counseling.

scholarly journals Effect of Proton Pump Inhibitors on Colorectal Cancer

2020 ◽  
Vol 21 (11) ◽  
pp. 3877 ◽  
Author(s):  
Takamitsu Sasaki ◽  
Shiori Mori ◽  
Shingo Kishi ◽  
Rina Fujiwara-Tani ◽  
Hitoshi Ohmori ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Colon Cancer ◽  
Liver Metastasis ◽  
Cyclin D1 ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Aged People ◽  
Mitochondrial Volume ◽  
Risk Of Cancer

Proton pump inhibitors (PPIs) are administered commonly to aged people; however, their effect on colorectal cancer (CRC) has still not been fully elucidated. Here, we examined the effect of PPIs and consequent alkalization on CRC cells. PPI administration alkalized the fecal pH and increased serum gastrin concentration. PPI and pH8 treatment (alkalization) of CMT93 mouse colon cancer cells inhibited cell growth and invasion, increased oxidative stress and apoptosis, and decreased mitochondrial volume and protein levels of cyclin D1 and phosphorylated extracellular signal-regulated kinase (pERK) 1/2. In contrast, gastrin treatment enhanced growth and invasion, decreased oxidative stress and apoptosis, and increased mitochondrial volume and cyclin D1 and pERK1/2 levels. Concurrent treatment with a PPI, pH8, and gastrin increased aldehyde dehydrogenase activity and also enhanced liver metastasis in the BALB/c strain of mice. PPI administration was associated with Clostridium perfringens enterotoxin (CPE) in CRC lesions. CPE treatment activated yes-associated protein (YAP) signals to enhance proliferation and stemness. The orthotopic colon cancer model of CMT93 cells with long-term PPI administration showed enhanced tumor growth and liver metastasis due to gastrin and YAP activation, as indicated by gastrin receptor knockdown and treatment with a YAP inhibitor. These findings suggest that PPI promotes CRC growth and metastasis by increasing gastrin concentration and YAP activation, resulting in gut flora alteration and fecal alkalization. These findings suggest that PPI use in colorectal cancer patients might create a risk of cancer promotion.

Adjuvant chemotherapy with uracil-tegafur (UFT) for stage III colorectal cancer: Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4049-4049 ◽  
Author(s):  
T. Hamaguchi ◽  
K. Shirao ◽  
Y. Moriya ◽  
S. Yoshida ◽  
S. Kodaira ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Hazard Ratio ◽  
Stage Iii ◽  
Control Group ◽  
Significant Difference ◽  
Resected Stage

4049 Background: In the latter 1990s, no consensus was reached as to whether adjuvant chemotherapy was standard treatment for completely resected stage III colorectal cancer in Japan. At that time, we started two randomized controlled trials to clarify the role of adjuvant chemotherapy of stage III colon and rectal cancer in the same time. Methods: Patients with completely resected stage III cancer of the colon or rectum (PS, 0 to 2; age, 20 to 75 years; no other adjuvant therapy) were eligible for these trials. Patients were registered within 6 weeks after surgery and were randomly assigned to receive surgery alone (control group) or surgery followed by treatment with UFT (400 mg/m2/day), given for 5 consecutive days per week for 1 year (UFT group). The target number of patients was 500 for colon cancer and 400 for rectal cancer (hazard ratio = 0.67, one-sided a= 0.05, β= 0.2). The primary endpoint was relapse-free survival (RFS), and the secondary end point was overall survival (OS). Results: Between October 1996 and April 2001, a total of 334 patients with colon cancer and 276 with rectal cancer were enrolled. Four ineligible patients were excluded; data from the remaining 332 patients with colon cancer and 274 with rectal cancer were analyzed. The patients’ characteristics were similar in the groups. Analysis of the results of follow-up until March 2006, at least 5 years after surgery in all patients (median follow-up period, 6.2 years), showed no significant difference in RFS or OS in colon cancer. In rectal cancer, however, RFS and OS were significantly better in the UFT group than in the control group. The only grade 4 toxicity was diarrhea, occurring in 1 patient with colon cancer and 1 patient with rectal cancer. Conclusions: Postoperative adjuvant chemotherapy with UFT is well tolerated and improved RFS and OS in patients with stage III rectal cancer. In colon cancer, the expected benefits were not obtained (hazard ratio = 0.67). [Table: see text] No significant financial relationships to disclose.

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