Animal models of colorectal cancer with liver metastasis

Oh, Bo Young,Hong, Hye Kyung,Lee, Woo Yong,Cho, Yong Beom Elsevier 2017 Cancer letters Vol.387 No.-

<P><B>Abstract</B></P> <P>Liver metastasis is a leading cause of death in patients with colorectal cancer. Investigating the mechanisms of liver metastasis and control of disease progression are important strategies for improving survival of these patients. Liver metastasis is a multi-step process and relevant models representing these steps are necessary to understand the mechanism of liver metastasis and establish appropriate treatments. Recently, the development of animal models for use in metastasis research has greatly increased; however, there is still a lack of models that sufficiently represent human cancer. Thus, in order to select an optimal model for of a given study, it is necessary to fully understand the characteristics of each animal model. In this review, we describe the mouse models currently used for colorectal cancer with liver metastasis, their characteristics, and their pros and cons. This may help us specify the mechanism of liver metastasis and provide evidence relevant to clinical applications.</P> <P><B>Highlights</B></P> <P> <UL> <LI> No animal model is fully representative of metastasis in human cancer. </LI> <LI> Spontaneous liver metastasis models represent all steps of metastasis. </LI> <LI> Experimental liver metastasis models are highly reproducible and consistent. </LI> <LI> PDX models are useful for predicting patient-specific drug response. </LI> <LI> GEMMs represent the natural course of cancer, but liver metastases seldom develop. </LI> </UL> </P>

HCV, Acute, LT : Liver Abscess Mimicking Liver Metastasis

( Ki You Myo ),( Byung Su Kim ),( Jun Hwa Song ),( Yong Kook Lee ),( Jeong Bae Park ),( Jeong Ill Suh ) 대한간학회 2013 춘·추계 학술대회 (KASL) Vol.2013 No.1

Background: In patient with mass in liver, it will suspected as hepatoma, cholangiocarcinoma, liver metastasis or liver abscess. Differential diagnosis of these disease is not simply. We present a case of liver abscess that mimicked metastasis in patient with liver mass. Case: A 77-year-old woman was visited to an OPD for evaluation and biopsy of liver mass. The patient had no history of alcoholic use. She had abdominal pain and febrile sense before 3 days. She visited local medical clinic and about 5cm sized liver mass was detected in liver ultrasonography. She was transferred to our hospital. Initial vital sign were: blood pressure 110/70 mmHg, heart rate of 88 beats/min, respiratory rate of 20 breaths/min, and temperature of 36.8 μL. The patient was alert and fully oriented. Laboratory studies revealed a white blood cell count 11,110/μL, hematocrit of 34.7%, platelets of 124,000, BUN of 27 mg/dL, creatinine of 0.8 mg/dL, AST of 53 IU/L, ALT of 62 U/L, serum albumin of 3.3 g/dL, alpha-fetoprotein of 0.6 ng/mL, CA19-9 of 14.760 U/mL. Initial abdominal computed tomography showed about 7×5 cm sized liver mass on left hepatic lobe. The patient made reservation for liver biopsy and taken antibiotics. After 2 weeks, the patient was visited to an OPD again for liver biopsy. Follow up abdominal computed tomography revealed that the mass had decreased in size to 3×2 cm. Follow up laboratory studies revealed a white blood cell count 6,840/μL, hematocrit of 32.5%, platelet 477,000, AST of 24 U/L, ALT of 10 U/L, serum albumin of 3.9 g/dL, CA19-9 of 6.6 U/mL, amoeba antibody was positive. We used metronidazole for 44 days, and the mass disappeared at follow up abdominal computed tomography. Now, the patient is still healthy without any complication. Conclusions: The reason of liver mass is variable. For new lesions in liver, biopsy is commonly performed to confirm the diagnosis. Liver abscess typically is the result of a pyogenic or amoebic infection and cause symptoms including fever and leukocytosis. But liver abscess does not have any pathognomonic imaging appearance. Infectious etiology is generally suspected based on a combination of clinical symptoms, laboratory abnormalities, medical history and corresponding imaging findings. Our case may serve as precautionary example that liver abscess can mimic metastasis. So, to diagnosis of liver mass we should consider another symptoms and signs.

Whole genome analysis for liver metastasis gene signatures in colorectal cancer

Ki, Dong Hyuk,Jeung, Hei-Cheul,Park, Chan Hee,Kang, Seung Hee,Lee, Gui Youn,Lee, Won Suk,Kim, Nam Kyu,Chung, Hyun Chul,Rha, Sun Young Alan R. Liss, Inc 2007 International journal of cancer Vol.121 No.9

<P>Liver metastasis is one of the major causes of death in colorectal cancer (CRC) patients. To understand this process, we investigated whether the gene expression profiling of matched colorectal carcinomas and liver metastases could reveal key molecular events involved in tumor progression and metastasis. We performed experiments using a cDNA microarray containing 17,104 genes with the following tissue samples: paired tissues of 25 normal colorectal mucosa, 27 primary colorectal tumors, 13 normal liver and 27 liver metastasis, and 20 primary colorectal tumors without liver metastasis. To remove the effect of normal cell contamination, we selected 4,583 organ-specific genes with a false discovery rate (FDR) of 0.0067% by comparing normal colon and liver tissues using significant analysis of microarray, and these genes were excluded from further analysis. We then identified and validated 46 liver metastasis-specific genes with an accuracy of 83.3% by comparing the expression of paired primary colorectal tumors and liver metastases using prediction analysis of microarray. The 46 selected genes contained several known oncogenes and 2 ESTs. To confirm that the results correlated with the microarray expression patterns, we performed RT-PCR with WNT5A and carbonic anhydrase II. Additionally, we observed that 21 of the 46 genes were differentially expressed (FDR = 2.27%) in primary tumors with synchronous liver metastasis compared with primary tumors without liver metastasis. We scanned the human genome using a cDNA microarray and identified 46 genes that may play an important role in the progression of liver metastasis in CRC. © 2007 Wiley-Liss, Inc.</P>

Does Liver Resection Provide Long-Term Survival Benefits for Breast Cancer Patients with Liver Metastasis? A Single Hospital Experience

김지예,윤동섭,박준성,이승아,김재근,정준,이희대 연세대학교의과대학 2014 Yonsei medical journal Vol.55 No.3

Purpose: Liver resection with colorectal liver metastasis widely accepted and has been considered safe and effective therapeutic option. However, the role of liver resection in breast cancer with liver metastasis is still controversial. Therefore, we reviewed the outcome of liver resection in breast cancer patients with liver metastasesin a single hospital experiences. Materials and Methods: Between January 1991 and December 2006, 2176 patients underwent breast cancer surgery in Gangnam Severance Hospital. Among these patients, 110 cases of liver metastases were observed during follow-up and 13 of these patients received liver resection with potential feasibility to achieve an R0 resection. Results: The median time intervalbetween initial breast cancer and detection of liver metastasis was 62.5 months (range, 13-121 months). The 1-year and 3-year overall survival rates of the 13 patients with liver resection were 83.1% and 49.2%, respectively. The 1-year and 3-year overall survival rates of patients without extrahepatic metastasis were 83.3% and 66.7% and those of patients with extrahepatic metastasis were 80.0% and 0.0%, respectively (p=0.001). Conclusion: Liver resection for metastatic breast cancer results in improved patient survival, particularly in patients with solitaryliver metastasis and good general condition.

임상 및 병리조직학적 특징에 따른 대장암의 간전이율

류동원,이승현,안병권,백승언 대한대장항문학회 2002 Annals of Coloproctolgy Vol.18 No.4

Immediate Results of Surgical Treatment of Metastasis of Colorectal Cancer of the Treatment

( Erlan Murzaliev ),( Bebezov Bakhadyr ),( Edir Surov ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: Evaluation of the results of surgical treatment of CRC metastasis in the liver. Methods: The results of treatment of 34 patients with metastases of colorectal cancer in the liver from 2010 to 2017 are analyzed. There were 19 men (55.8%), women-15 (44.1%). The average age of the patients was 37 ± 85 yearsold.There localization of metastasis are in the left lobe - 5 patients, right lobe - 24 patients and bilobate liver damage - 6 patients. According to the international mTNM classification IwatsukiS.C. with et al. 1986 metastasis of colorectal cancer in the liver patients were distributed as follows: mT2N0M0 (stage II) - 19, mT3N0M0 (III stage) - 10, mT4N0M0 (IVA stage) - 4 patients, mT4N1M1 (IVB stage) -1. Results: The following types of liver resection were performed: PGEGE-17, LGGE-2, atypical resections-2, bisegmentectomy -8, trisegmentectomy-3, LLE-1, explorative laparotomy-1. The average loss of blood was 798 ± 256ml., мinimal 200 ml. . 6 patients had hepatic insufficiency in the postoperative session, received conservative therapy; All patients received adjuvant chemotherapy according to the XELOX scheme, FOLFOX. Postoperative mortality was 2.9% (1 patient). Results: The following types of liver resection were performed: PGEGE-17, LGGE-2, atypical resections-2, bisegmentectomy -8, trisegmentectomy-3, LLE-1, explorative laparotomy-1. The average loss of blood was 798 ± 256ml., мinimal 200 ml. . 6 patients had hepatic insufficiency in the postoperative session, received conservative therapy; All patients received adjuvant chemotherapy according to the XELOX scheme, FOLFOX. Postoperative mortality was 2.9% (1 patient). Conclusions: The tactic of surgical treatment of metastatic liver cancer should be active, liver resection can be performed in patients with sufficient functional reserve of the organ.Performance of anatomic resections of the liver is more preferable. The closest results of treatment of this category of patients justify the proposed treatment tactics.

Aggressive surgical resection for concomitant liver and lung metastasis in colorectal cancer

Sung Hwan Lee,Sung Hyun Kim,Jin Hong Lim,Sung Hoon Kim,Jin Gu Lee,Dae Joon Kim,Gi Hong Choi,Jin Sub Choi,Kyung Sik Kim 한국간담췌외과학회 2016 한국간담췌외과학회지 Vol.20 No.3

Backgrounds/Aims: Aggressive surgical resection for hepatic metastasis is validated, however, concomitant liver and lung metastasis in colorectal cancer patients is equivocal. Methods: Clinicopathologic data from January 2008 through December 2012 were retrospectively reviewed in 234 patients with colorectal cancer with concomitant liver and lung metastasis. Clinicopathologic factors and survival data were analyzed. Results: Of the 234 patients, 129 (55.1%) had synchronous concomitant liver and lung metastasis from colorectal cancer and 36 (15.4%) had metachronous metastasis. Surgical resection was performed in 33 patients (25.6%) with synchronous and 6 (16.7%) with metachronous metastasis. Surgical resection showed better overall survival in both groups (synchronous, p=0.001; metachronous, p=0.028). In the synchronous metastatic group, complete resection of both liver and lung metastatic lesions had better survival outcomes than incomplete resection of two metastatic lesions (p=0.037). The primary site of colorectal cancer and complete resection were significant prognostic factors (p=0.06 and p=0.003, respectively). Conclusions: Surgical resection for hepatic and pulmonary metastasis in colorectal cancer can improve complete remission and survival rate in resectable cases. Colorectal cancer with concomitant liver and lung metastasis is not a poor prognostic factor or a contraindication for surgical treatments, hence, an aggressive surgical approach may be recommended in well-selected resectable cases.

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

Yuan Na,Li Xiaoyan,Wang Meng,Zhang Zhilin,Qiao Lu,Gao Yamei,Xu Xinjian,Zhi Jie,Li Yang,Li Zhongxin,Jia Yitao 거트앤리버 소화기연관학회협의회 2022 Gut and Liver Vol.16 No.4

Background/Aims:This study aimed to explore the effect of gut microbiota-regulated Kupffer cells (KCs) on colorectal cancer (CRC) liver metastasis. Methods: A series of in vivo and in vitro researches were showed to demonstrate the gut microbiota and its possible mechanism in CRC liver metastasis. Results: Fewer liver metastases were identified in the ampicillin-streptomycin-colistin and colistin groups. Increased proportions of Parabacteroides goldsteinii, Bacteroides vulgatus, Bacteroides thetaiotaomicron, and Bacteroides uniformis were observed in the colistin group. The significant expansion of KCs was identified in the ampicillin-streptomycin-colistin and colistin groups. B. vulgatus levels were positively correlated with KC levels. More liver metastases were observed in the vancomycin group. An increased abundance of Parabacteroides distasonis and Proteus mirabilis and an obvious reduction of KCs were noted in the vancomycin group. P. mirabilis levels were negatively related to KC levels. The number of liver metastatic nodules was increased in the P. mirabilis group and decreased in the B. vulgatus group. The number of KCs decreased in the P. mirabilis group and increased in the B. vulgatus group. In vitro, as P. mirabilis or B. vulgatus doses increased, there was an opposite effect on KC proliferation in dose- and time-dependent manners. P. mirabilis induced CT26 cell migration by controlling KC proliferation, whereas B. vulgatus prevented this migration. Conclusions: An increased abundance of P. mirabilis and decreased amount of B. vulgatus play key roles in CRC liver metastasis, which might be related to KC reductions in the liver.

Living donor liver transplantation for unresectable colorectal liver metastasis: Report of a case with 13-year follow-up without recurrence

Jin Uk Choi,Shin Hwang,Dong-Hwan Jung,Gil-Chun Park,Chul-Soo Ahn,Ki-Hun Kim,Deok-Bog Moon,Tae-Yong Ha,Gi-Won Song,Sung-Gyu Lee 한국간담췌외과학회 2020 Annals of hepato-biliary-pancreatic surgery Vol.24 No.2

The feasibility of liver transplantation (LT) for colorectal liver metastasis (CRLM) is still under investigation with only a limited number of LT cases in literature. CRLM is the most common type of liver metastasis, but it was considered as a contraindication to LT for a long time because of poor outcomes. We presented a case of living donor liver transplantation (LDLT) performed in a patient with liver cirrhosis and CRLM. The patient was a 49-year-old female with sigmoid colon cancer and synchronous multiple CRLM. She underwent anterior resection for sigmoid colon cancer and 7 sessions of chemotherapy for CRLM. She suffered from esophageal varix bleeding due to chemotherapy-associated liver cirrhosis. Because of liver cirrhosis and multiple CRLM, the patient underwent LDLT operation using a modified right lobe graft. Serum chorioembryonic antigen level was 220 ng/mL at LT. Explant liver pathology showed multiple metastatic adenocarcinomas of colonic origin, up to 4.7 cm in the greatest dimension. The patient did not receive any specific anti-tumor treatment after LT. She is doing well without any tumor recurrence to date for more than 13 years after the LDLT operation. The experience on our case and literature review suggest that CRLM is not always contraindicated for LT because some selected patients showed improved long-term survival outcomes.

A Synthetic Analog of Resveratrol Inhibits the Proangiogenic Response of Liver Sinusoidal Cells during Hepatic Metastasis

Olaso Elvira,Benedicto Aitor,Lopategi Aritz,Cossio Fernando P.,Arteta Beatriz 한국응용약물학회 2022 Biomolecules & Therapeutics(구 응용약물학회지) Vol.30 No.2

We utilized Fas21, a resveratrol analog, to modulate the function of hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) during the angiogenic phase of murine liver metastasis by B16 melanoma and 51b colorectal carcinoma. Preangiogenic micrometastases were treated with Fas21 (1 mg/kg/day) or vehicle during the development of intra-angiogenic tracts. Mice treated with Fas21 showed reduced liver tumor foci in both liver metastasis models. Micrometastases were classified immunohistochemically, as well as according to their position coordinates and connection to local microvasculature. The volume of liver occupied by sinusoidal-type foci, containing infiltrating angiogenic capillaries, decreased by ~50% in Fas21-treated mice compared to vehicle-treated ones in both tumor metastasis models. The volume of portal foci, containing peripheral neoangiogenesis within a discontinuous layer of myofibroblasts, was similar in all experimental groups in both tumor metastasis models, but displayed enhanced necrotic central areas devoid of angiogenesis following Fas21 treatment. As a result, sinusoidal tumors from mice treated with Fas21 showed a 50% reduction in desmin(+)/asma(+) HSCs and CD31(+) vessel density, and a 45% reduction in intrametastatic VEGF mRNA compared with sinusoidal tumors from vehicle-treated mice. Necrotic portal metastases increased 2-4-fold in treated mice. In vitro, Fas21 reduced VEGF secretion by HSCs and 51b cells dose-dependently. Additionally, HSCs migration in response to tumor soluble factors was dose-dependently diminished by Fas21, as was LSEC migration in response to HSCs and tumor soluble factors. Resveratrol analog Fas21 inhibits the proangiogenic response of HSCs and LSECs during the development of murine liver metastasis.