scholarly journals Screening of Radiotracer for Diagnosis of Colorectal Cancer Liver Metastasis Based on MACC1-SPON2

2020 ◽  
Author(s):  
Hao Jiang ◽  
Wei Guo ◽  
Kuan Huang ◽  
Huijie Jiang ◽  
Rongjun Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Imaging ◽  
Liver Metastasis ◽  
Western Blot ◽  
Liver Metastases ◽  
Imaging Features ◽  
Expression Levels ◽  
Significant Difference ◽  
Metastasis Model

Abstract Background: metastasis-associated in colon cancer 1 (MACC1) and Spondin2 (SPON2) are newly discovered oncogenes, but little is known about their role in colorectal cancer(CRC) liver metastases. PET has become an important molecular imaging technology due to its high sensitivity and quantifiability. In particular, its targeted, specific molecular probes can detect biological behaviors. This study was designed to evaluate the different biological properties of 18F-FDG, 18F-FLT and 18F-FMISO PET. The value of the CRC liver metastasis model explores the correlation and potential mechanisms of three tracers uptakes with tumor-related biological characteristics. Methods: Human CRC cell lines(LoVo and HCT8), were cultured for in vitro radionuclide uptake experiments to compare the molecular imaging features of colorectal cancer cells with different metastatic potentials. Two kinds of cells were injected into the spleen of nude mice to establish a liver metastasis model. After the tumor formation, three kinds of tracer PET images were performed to evaluate the characteristics of live PET imaging of high and low liver metastasis colorectal cancer models. The expression levels of MACC1 and SPON2 in tissues were detected by immunohistochemistry and Western blot. Correlation between tracer uptake and expression of MACC1 and SPON2 in liver metastases was assessed by linear regression analysis. Results: The uptake rate of in vitro three tracers uptake experiments was: LoVo>HCT8. Micro-PET scan showed no significant difference between the 18F-FDG SUV values of the two cells (P>0.05); there was significant difference between the 18F-FLT and 18F-FMISO SUV values (P<0.05). All in vivo FLT and FMISO SUV values were significantly higher in LoVo tumors than in HCT8 tumors. The results of Western blot and immunohistochemistry showed that the expression levels of MACC1 and SPON2 in LoVo liver metastasis were higher than those in HCT8 (P<0.05). The 18F-FLT SUVmax ratio was significantly correlated with the expression of MACC1 and SPON2 in hepatic metastases (r=0.737, P=0.0026; r=0.842, P=0.0002). The 18F-FMISO SUVmax ratio was only significantly correlated with the expression of MACC1 in hepatic metastasis (r=0.770, P=0.0013). Conclusions: Early screening with 18F-FLT and 18F-FMISO tracers has important clinical value for the efficient diagnosis and treatment of colorectal cancer liver metastases.

scholarly journals Screening of radiotracer for diagnosis of colorectal cancer liver metastasis based on MACC1-SPON2

2021 ◽  
Author(s):  
Hao Jiang ◽  
Wei Guo ◽  
Kuan Huang ◽  
Huijie Jiang ◽  
Rongjun Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Imaging ◽  
Liver Metastasis ◽  
Western Blot ◽  
Liver Metastases ◽  
Imaging Features ◽  
Expression Levels ◽  
Significant Difference ◽  
Metastasis Model

Abstract Background Metastasis-associated in colon cancer 1 (MACC1) and Spondin2 (SPON2) are newly discovered oncogenes, but little is known about their role in colorectal cancer(CRC) liver metastases. PET has become an important molecular imaging technology due to its high sensitivity and quantifiability. In particular, its targeted, specific molecular probes can detect biological behaviors. This study was designed to evaluate the different biological properties of 18F-FDG, 18F-FLT, and 18F-FMISO PET. The value of the CRC liver metastasis model explores the correlation and potential mechanisms of three tracers uptakes with tumor-related biological characteristics. Methods Human CRC cell lines(LoVo and HCT8), were cultured for in vitro radionuclide uptake experiments to compare the molecular imaging features of colorectal cancer cells with different metastatic potentials. Two kinds of cells were injected into the spleen of nude mice to establish a liver metastasis model. After the tumor formation, three kinds of tracer PET images were performed to evaluate the characteristics of live PET imaging of high and low liver metastasis colorectal cancer models. The expression levels of MACC1 and SPON2 in tissues were detected by immunohistochemistry and Western blot. Correlation between tracer uptake and expression of MACC1 and SPON2 in liver metastases was assessed by linear regression analysis. Results The uptake rate of in vitro three tracers uptake experiments was LoVo > HCT8. Micro-PET scan showed no significant difference between the 18F-FDG SUV values of the two cells (P > 0.05); there was significant difference between the 18F-FLT and 18F-FMISO SUV values (P < 0.05). All in vivo FLT and FMISO SUV values were significantly higher in LoVo tumors than in HCT8 tumors. The results of Western blot and immunohistochemistry showed that the expression levels of MACC1 and SPON2 in LoVo liver metastasis were higher than those in HCT8 (P < 0.05). The 18F-FLT SUVmax ratio was significantly correlated with the expression of MACC1 and SPON2 in hepatic metastases (r = 0.737, P = 0.0026; r = 0.842, P = 0.0002). The 18F-FMISO SUVmax ratio was only significantly correlated with the expression of MACC1 in hepatic metastasis (r = 0.770, P = 0.0013). Conclusions Early screening with 18F-FLT and 18F-FMISO tracers has important clinical value for the efficient diagnosis and treatment of colorectal cancer liver metastases.

scholarly journals Radiomics and Radiogenomics in Evaluation of Colorectal Cancer Liver Metastasis

2022 ◽  
Vol 11 ◽  
Author(s):  
Yun Wang ◽  
Lu-Yao Ma ◽  
Xiao-Ping Yin ◽  
Bu-Lang Gao
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Texture Features ◽  
Biological Properties ◽  
Imaging Features ◽  
Current Application ◽  
Colorectal Cancer Liver Metastases ◽  
Colorectal Cancer Liver Metastasis ◽  
Non Invasive

Colorectal cancer is one common digestive malignancy, and the most common approach of blood metastasis of colorectal cancer is through the portal vein system to the liver. Early detection and treatment of liver metastasis is the key to improving the prognosis of the patients. Radiomics and radiogenomics use non-invasive methods to evaluate the biological properties of tumors by deeply mining the texture features of images and quantifying the heterogeneity of metastatic tumors. Radiomics and radiogenomics have been applied widely in the detection, treatment, and prognostic evaluation of colorectal cancer liver metastases. Based on the imaging features of the liver, this paper reviews the current application of radiomics and radiogenomics in the diagnosis, treatment, monitor of disease progression, and prognosis of patients with colorectal cancer liver metastases.

scholarly journals Metformin Intake Suppresses The Degree of Liver Metastasis From Colorectal Cancer In Diabetic Patients But Does Not Improve Their Prognosis

2021 ◽  
Author(s):  
Akira Saito ◽  
Joji Kitayama ◽  
Hisanaga Horie ◽  
Koji Koinuma ◽  
Hideyuki Ohzawa ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Hepatic Metastases ◽  
Stage Iv ◽  
University Hospital ◽  
Diabetic Patients ◽  
Significant Difference ◽  
Patients With Diabetes

Abstract Background: Metformin reduces the risk of, and mortality from, colorectal cancer in patients with diabetes mellitus. However, the effect of metformin on patients with stage IV disease is unknown. In the present study we reviewed the clinical features and outcomes of patients with diabetes mellitus and stage IV colorectal cancer (M1, liver metastases) treated with or without metformin.Methods: The 202 patients with colorectal cancer and macroscopic liver metastasis who were treated in the Department of Surgery or Department of Clinical Oncology at Jichi Medical University Hospital from January 2006 through June 2019 were surveyed treatment of diabetes, clinical and pathological factor and prognosis of these patients. Results: We retrospectively examined the effect of metformin use on outcomes in 32 patients with liver metastases from colorectal cancer. Hepatic metastases were stage H1 in 8/8 patients taking metformin and stage H2-3 in 17/24 non-users. Of 22 patients who underwent colectomy, colorectal tumors were pT4 in 5 metformin users, and pT2-3 in 10/17 non-users. The mean survival of metformin users and non-users was equal (28.0 mo vs 29.3 mo, p>.05). No significant difference was detected when survival was compared between 6 metformin users and 19 non-users who received systemic chemotherapy. Conclusion: These results suggest that metformin has less potent anti-tumor effects in patients with advanced stage disease. Metformin for the treatment of patients with metastatic colorectal cancer requires further study.

scholarly journals LncRNA MIR17HG promotes colorectal cancer liver metastasis by mediating a glycolysis-associated positive feedback circuit

Oncogene ◽  
2021 ◽  
Author(s):  
Senlin Zhao ◽  
Bingjie Guan ◽  
Yushuai Mi ◽  
Debing Shi ◽  
Ping Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Metastatic Tumor ◽  
Feedback Circuit ◽  
Colorectal Cancer Liver Metastasis ◽  
Positive Feedback Circuit

AbstractGlycolysis plays a crucial role in reprogramming the metastatic tumor microenvironment. A series of lncRNAs have been identified to function as oncogenic molecules by regulating glycolysis. However, the roles of glycolysis-related lncRNAs in regulating colorectal cancer liver metastasis (CRLM) remain poorly understood. In the present study, the expression of the glycolysis-related lncRNA MIR17HG gradually increased from adjacent normal to CRC to the paired liver metastatic tissues, and high MIR17HG expression predicted poor survival, especially in patients with liver metastasis. Functionally, MIR17HG promoted glycolysis in CRC cells and enhanced their invasion and liver metastasis in vitro and in vivo. Mechanistically, MIR17HG functioned as a ceRNA to regulate HK1 expression by sponging miR-138-5p, resulting in glycolysis in CRC cells and leading to their invasion and liver metastasis. More interestingly, lactate accumulated via glycolysis activated the p38/Elk-1 signaling pathway to promote the transcriptional expression of MIR17HG in CRC cells, forming a positive feedback loop, which eventually resulted in persistent glycolysis and the invasion and liver metastasis of CRC cells. In conclusion, the present study indicates that the lactate-responsive lncRNA MIR17HG, acting as a ceRNA, promotes CRLM through a glycolysis-mediated positive feedback circuit and might be a novel biomarker and therapeutic target for CRLM.

scholarly journals Oncolytic peptides DTT-205 and DTT-304 induce complete regression and protective immune response in experimental murine colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karianne Giller Fleten ◽  
J. Johannes Eksteen ◽  
Brynjar Mauseth ◽  
Ketil André Camilio ◽  
Terje Vasskog ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Cell Lines ◽  
Checkpoint Inhibitors ◽  
Inhibitory Effect ◽  
Systemic Effect ◽  
Intratumoral Injection ◽  
Complete Regression ◽  
Future Drug

AbstractOncolytic peptides represent a novel, promising cancer treatment strategy with activity in a broad spectrum of cancer entities, including colorectal cancer (CRC). Cancer cells are killed by immunogenic cell death, causing long-lasting anticancer immune responses, a feature of particular interest in non-immunogenic CRC. Oncolytic peptides DTT-205 and DTT-304 were administered by intratumoral injection in subcutaneous tumors established from murine CRC cell lines CT26 and MC38, and complete regression was obtained in the majority of animals. When cured animals were rechallenged by splenic injection of tumor cells, 1/23 animals developed liver metastases, compared to 19/22 naïve animals. Treatment with both peptides was well tolerated, but monitoring post-injection hemodynamic parameters in rats, less extensive changes were observed with DTT-205 than DTT-304, favoring DTT-205 for future drug development. DTT-205 was subsequently shown to have strong in vitro activity in a panel of 33 cancer cell lines. In conclusion, both peptides exerted a strong inhibitory effect in two immunocompetent CRC models and induced a systemic effect preventing development of liver metastases upon splenic rechallenge. If a similar effect could be obtained in humans, these drugs would be of particular interest for combinatory treatment with immune checkpoint inhibitors in metastatic CRC.

Evaluation of Histopathological Heterogeneity After Preoperative Chemotherapy in Patients With Liver Metastases from Colorectal Cancer

2021 ◽  
Author(s):  
Nobuhisa matsuhashi ◽  
Hiroyuki Tomita ◽  
Takazumi Kato ◽  
Yoshinori Iwata ◽  
Satoshi Matsui ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Surgical Oncology ◽  
Resected Specimen ◽  
Histopathological Changes ◽  
School Of Medicine ◽  
Response To Chemotherapy ◽  
Grade 3 ◽  
The Right

Abstract Background: Patients with liver metastases from colorectal cancer (CRLMs) frequently receive chemotherapy prior to liver resection. Histopathological assessment of the resected specimen can evaluate the response to chemotherapy. This study analyzed the correlation between histopathological changes in the primary site and liver metastases. Patients and Methods: This study comprised 45 patients with resectable CRLMs at the Surgical Oncology Department of Gifu University School of Medicine from January 2006 to August 2015. Results: The study included 24 men and 21 women. The primary colonic tumor was located in the right side in 13 (28.9%) patients and the left side in 32 (71.9%) patients. We evaluated patients with metastatic colorectal cancer (31/45) after excluding those in whom histopathological heterogeneity between the primary and liver metastasis changed to grade 3 after chemotherapy. We compared the group which underwent hepatectomy after chemotherapy (n=25) with that underwent hepatectomy alone (n=6). In 16 (53.3%) out of 25 patients, histopathological heterogeneity of the liver metastasis was lost (p=0.04). Conclusion: Chemotherapy appears to change histopathological heterogeneity.Our study suggests that the change of intratumoral heterogeneity reflect by the response of chemotherapy.

scholarly journals Genome-Wide Scan for Copy Number Alteration Association with Relapse-Free Survival in Colorectal Cancer with Liver Metastasis Patients

2018 ◽  
Vol 7 (11) ◽  
pp. 446 ◽  
Author(s):  
Po-Sheng Yang ◽  
Hsi-Hsien Hsu ◽  
Tzu-Chi Hsu ◽  
Ming-Jen Chen ◽  
Cin-Di Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Liver Metastases ◽  
Copy Number ◽  
Copy Number Alteration ◽  
Gene Signature ◽  
Comparative Genomic ◽  
Relapse Free Survival ◽  
Cgh Array ◽  
Free Survival

Predicting a patient’s risk of recurrence after the resection of liver metastases from colorectal cancer is critical for evaluating and selecting therapeutic approaches. Clinical and pathologic parameters have shown limited accuracy thus far. Therefore, we combined the clinical status with a genomic approach to stratify relapse-free survival in colorectal cancer liver metastases patients. To identify new molecular and genetic signatures specific to colorectal cancer with liver metastasis (CRCLM) patients, we conducted DNA copy number profiling on a cohort of 21 Taiwanese CRCLM patients using a comparative genomic hybridization (CGH) array. We identified a three-gene signature based on differential copy number alteration between patients with different statuses of (1) recurrence and (2) synchronous metastasis. In relapse hotspot regions, only three genes (S100PBP, CSMD2, and TGFBI) were significantly associated with the synchronous liver metastasis factor. A final set of three genes—S100PBP, CSMD2, TGFBI—significantly predicted relapse-free survival in our cohort (p = 0.04) and another CRCLM cohort (p = 0.02). This three-gene signature is the first genomic signature validated for relapse-free survival in post-hepatectomy CRCLM patients. Our three-gene signature was developed using a whole-genome CGH array and has a good prognostic position for the relapse-free survival of CRCLM patients after hepatectomy.

scholarly journals Bevacizumab in neoadjuvant treatment of patients with liver metastases from colorectal carcinoma

2010 ◽  
Vol 18 (3) ◽  
pp. 75-78
Author(s):  
Ivan Nikolic ◽  
Svetlana Pavin ◽  
Biljana Kukic ◽  
Bogdan Bogdanovic ◽  
Miroslav Ilic ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastases ◽  
Neoadjuvant Treatment ◽  
Hepatic Metastases ◽  
Response Rates ◽  
Control Group ◽  
Significant Difference ◽  
Experimental Group ◽  
Selection Of Patients ◽  
Selection Of

Background: Liver metastases are the leading cause of death in patients with colorectal cancer. Despite advances in chemotherapy, surgical resection of hepatic metastases is still considered the only curative options. However, the majority of patients have inoperable disease at presentation. Perioperative chemotherapy is the most successful way for improved selection of patients for resection. The aim of the study was to demonstrate if and to what extent does bevacizumab, introduced in chemotherapy, increase response rates, and development of liver metastases. Methods: Our study included 50 patients who were divided in two groups. The experimental group included patients who were treated with bevacizumab plus chemotherapy, and the control group included patients who were treated with chemotherapy only. Results: The comparison showed that the patients who were treated with bevacizumab became candidates for resection of liver metastases in higher percentage (85%:52%). In addition, distribution of patients regarding the development of metastases resulted in statistically significant difference. Ratio between the patients with good response from the experimental and the control group was 67%:39%. Ratio of patients with stable disease was 26%:48%, and of patients with progressive disease, it was 7%:3%. The estimate of margin after resection was statistically insignificant. Conclusion: Bevacizumab in combination with chemotherapy in therapy of liver metastases from primary colorectal cancer improves and increases response rates and development of liver metastases.

scholarly journals FSH Promotes Rat Follicle Development Through Inhibition of the Hippo Signalling Pathway

2021 ◽  
Author(s):  
Tairen Chen ◽  
Mengjing Wu ◽  
Yuting Dong ◽  
Bin Kong ◽  
Yufang Cai ◽  
...  
Keyword(s):  
Western Blot ◽  
In Vitro Culture ◽  
Granulosa Cells ◽  
Signalling Pathway ◽  
Control Group ◽  
Follicle Development ◽  
Follicle Growth ◽  
Expression Levels ◽  
Hippo Signalling

Abstract Purpose: Whether FSH promotes follicle growth by inhibiting the Hippo signalling pathway.METHODS: Ovaries were cultured in vitro into a control group (no intervention), an FSH group (0.3 IU/mL FSH), and a VP group (10 µg/mL vetiporfin). HE staining and follicle counts were performed at each stage after 3 hours of in vitro culture. Immunohistochemistry was performed to study the expression levels of LATS2, YAP, PLATS2, and PYAP, and their expression levels in each group were also analysed by Western blot.The number of secondary follicles was significantly increased in the FSH group, the arrangement of granulosa cells was neater, the nuclear fixation was reduced, and the number of atretic follicles was decreased in the VP group. The number of secondary follicles was significantly increased, the number of atretic follicles was reduced, and granulosa cell nuclear consolidation was reduced in the VP+FSH group. Immunohistochemistry showed that LATS2 and YAP expression levels were significantly increased and PLATS2 and PYAP expression levels were relatively decreased in the FSH group, PYAP and PLATS2 expression levels were significantly increased and YAP expression was significantly decreased in the VP group, and YAP and LATS2 expression levels were significantly increased and PYAP and PLATS2 expression levels were significantly decreased in the VP+FSH group. By Western blot, LATS2 and YAP were elevated and PYAP and PLAT2 were decreased in the FSH group, LATS2 and YAP were decreased and PYAP and PLATS were significantly elevated in the VP group, and LATS2 and YAP were elevated and PYAP and PLATS2 were decreased in the VP+FSH group.CONCLUSION: FSH promotes follicle development by inhibiting the Hippo signalling pathway.

The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

Chemotherapy ◽  
2022 ◽  
pp. 1-10
Author(s):  
Cheng Yang ◽  
Na Xie ◽  
Zhifei Luo ◽  
Xiling Ruan ◽  
Yixin Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Poor Prognosis ◽  
Cancer Metastasis ◽  
Mrna Level ◽  
Normal Mucosa ◽  
Tnm Stage ◽  
Expression Levels ◽  
Normal Tissues

<b><i>Introduction:</i></b> We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). <b><i>Methods:</i></b> CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. <b><i>Results:</i></b> Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. <b><i>Conclusion:</i></b> CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.

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