scholarly journals Pharmacokinetic parameters from 3-Tesla DCE-MRI as surrogate biomarkers of antitumor effects of bevacizumab plus FOLFIRI in colorectal cancer with liver metastasis

2011 ◽  
Vol 130 (10) ◽  
pp. 2359-2365 ◽  
Author(s):  
Yoshinori Hirashima ◽  
Yasuhide Yamada ◽  
Ukihide Tateishi ◽  
Ken Kato ◽  
Mototaka Miyake ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
3 Tesla ◽  
Pharmacokinetic Parameters ◽  
Antitumor Effects ◽  
Dce Mri

scholarly journals New insights into colorectal cancer liver metastasis carcinogenesis and its effect with moxibustion

2021 ◽  
Author(s):  
Yafang Song ◽  
Lixia Pei ◽  
Jing Guo ◽  
Yi Zhuang ◽  
Yuhang Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Molecular Targets ◽  
Rna Seq ◽  
Antitumor Effects ◽  
Significant Differential Expression ◽  
Cell Injection ◽  
Suspension Array ◽  
Model Control ◽  
Hct 116

Background: Chemotherapeutic drugs creates severe adverse reactions for colorectal cancer. Moxibustion confers clinical benefits for postoperative patients undergoing chemotherapy, it will fill the blank period of western medicine treatment and provide useful help for tumor patients to prevent recurrence and metastasis, but the physiological mechanisms behind the antitumor effects are unclear. This study was aimed to determine the effect and characterize the differential cytokines and gene expression profiles in intrasplenic transplanted GFP-HCT-116 cells-induced tumors model by Pre-Mox, Post-Mox and Pre-Post-Mox intervention. Methods: Human CRC cells with GFP fluorescence were implanted via intrasplenic injection into Balb/c nude mice spleens. Moxibustion stimulation was applied to the BL18 and ST36 acupoints. The model control (MC) group were given no treatment. Pre-Mox mice were received moxibustion for 2 weeks before HCT-116 cell injection. Post-Mox mice received moxibustion for 3 weeks after CRC cell injection. Pre-Post-Mox mice received moxibustion for 5 weeks (2 weeks before and 3 weeks after CRC cell injection). Peripheral bloods were collected, pooled and assayed using a RayBio mouse inflammation antibody array. Multi-Analyte Suspension Array was opted for verification. RNA isolated from liver paracancerous tissues from the control group and the experimental groups was subjected to RNA-seq, and then screened out significant differences for in-depth verification. RESULTS: The results showed that moxibustion stimulation increased the survival rate and decreased CRC liver metastasis. With the help of Multi-Analyte Suspension Array and RNA-seq, we screened significant differential expression of cytokines and RNA, then further verified them. The metastasis rate decreased significantly from 100% (10/10, MC group) to 50% (6/12, Pre-Mox group), to 46% (6/13, Post-Mox group), and further to 25% (3/12, Pre-Post-Mox group). Cytokine chips were used significant differences were found in MIP-3α, MDC, IL-6, and IL-1a. Transcriptomic analysis suggested that the low-dose combination of Pre-Mox and Post-Mox modulated larger gene sets than the single treatment. We identified a small subset of genes, like APOA4, IGFBP5, IGFBP6, TIMP1, and MGP, as potential molecular targets involved in the preventive action of the combination of Pre-Mox and Post-Mox. Conclusions: Taken together, the current results provide the first evidence in support of the chemopreventive effect of a combination of Pre-Mox and Post-Mox in CRC. Moreover, the cytokines and transcriptional profile obtained in our study may provide a framework for identifying the mechanisms underlying the carcinogenesis process from colonic cancer to liver metastasis as well as the cancer inhibitory effects and potential molecular targets of Pre-Post-Mox.

Stem cell gene Girdin: a potential early liver metastasis predictor of colorectal cancer

2012 ◽  
Vol 39 (9) ◽  
pp. 8717-8722 ◽  
Author(s):  
Chen Liu ◽  
Hongpeng Xue ◽  
Yixia Lu ◽  
Baorong Chi
Keyword(s):  
Colorectal Cancer ◽  
Stem Cell ◽  
Liver Metastasis ◽  
Cell Gene ◽  
Stem Cell Gene

scholarly journals Liver Immune Microenvironment and Metastasis from Colorectal Cancer-Pathogenesis and Therapeutic Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2418
Author(s):  
Xuezhen Zeng ◽  
Simon E. Ward ◽  
Jingying Zhou ◽  
Alfred S. L. Cheng
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Cancer Patients ◽  
High Recurrence Rate ◽  
Immune Microenvironment ◽  
Liver Sinusoidal Endothelial Cells ◽  
Premetastatic Niche ◽  
Cancer Pathogenesis ◽  
Colorectal Cancer Patients ◽  
The Impact

A drastic difference exists between the 5-year survival rates of colorectal cancer patients with localized cancer and distal organ metastasis. The liver is the most favorable organ for cancer metastases from the colorectum. Beyond the liver-colon anatomic relationship, emerging evidence highlights the impact of liver immune microenvironment on colorectal liver metastasis. Prior to cancer cell dissemination, hepatocytes secrete multiple factors to recruit or activate immune cells and stromal cells in the liver to form a favorable premetastatic niche. The liver-resident cells including Kupffer cells, hepatic stellate cells, and liver-sinusoidal endothelial cells are co-opted by the recruited cells, such as myeloid-derived suppressor cells and tumor-associated macrophages, to establish an immunosuppressive liver microenvironment suitable for tumor cell colonization and outgrowth. Current treatments including radical surgery, systemic therapy, and localized therapy have only achieved good clinical outcomes in a minority of colorectal cancer patients with liver metastasis, which is further hampered by high recurrence rate. Better understanding of the mechanisms governing the metastasis-prone liver immune microenvironment should open new immuno-oncology avenues for liver metastasis intervention.

scholarly journals PD-L1 targeting and subclonal immune escape mediated by PD-L1 mutations in metastatic colorectal cancer

2021 ◽  
Vol 9 (7) ◽  
pp. e002844
Author(s):  
Alexander Stein ◽  
Donjete Simnica ◽  
Christoph Schultheiß ◽  
Rebekka Scholz ◽  
Joseph Tintelnot ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cell ◽  
Metastatic Colorectal Cancer ◽  
Multispectral Imaging ◽  
Standard Treatment ◽  
Immune Escape ◽  
Killer Cell ◽  
Cell Killing ◽  
Antitumor Effects ◽  
High Affinity

BackgroundIn patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC), immune checkpoint blockade is ineffective, and combinatorial approaches enhancing immunogenicity need exploration.MethodsWe treated 43 patients with predominantly microsatellite stable RAS/BRAF wild-type mCRC on a phase II trial combining chemotherapy with the epidermal growth factor receptor antibody cetuximab and the programmed cell death ligand 1 (PD-L1) antibody avelumab. We performed next-generation gene panel sequencing for mutational typing of tumors and liquid biopsy monitoring as well as digital droplet PCR to confirm individual mutations. Translational analyses included tissue immunohistochemistry, multispectral imaging and repertoire sequencing of tumor-infiltrating T cells. Detected PD-L1 mutations were mechanistically validated in CRISPR/Cas9-generated cell models using qRT-PCR, immunoblotting, flow cytometry, complement-dependent cytotoxicity assay, antibody-dependent cytotoxicity by natural killer cell degranulation assay and LDH release assay as well as live cell imaging of T cell mediated tumor cell killing.ResultsCirculating tumor DNA showed rapid clearance in the majority of patients mirroring a high rate of early tumor shrinkage. In 3 of 13 patients expressing the high-affinity Fcγ receptor 3a (FcγR3a), tumor subclones with PD-L1 mutations were selected that led to loss of tumor PD-L1 by nonsense-mediated RNA decay in PD-L1 K162fs and protein degradation in PD-L1 L88S. As a consequence, avelumab binding and antibody-dependent cytotoxicity were impaired, while T cell killing of these variant clones was increased. Interestingly, PD-L1 mutant subclones showed slow selection dynamics reversing on avelumab withdrawal and patients with such subclones had above-average treatment benefit. This suggested that the PD-L1 mutations mediated resistance to direct antitumor effects of avelumab, while at the same time loss of PD-L1 reduced biological fitness by enhanced T cell killing limiting subclonal expansion.ConclusionThe addition of avelumab to standard treatment appeared feasible and safe. PD-L1 mutations mediate subclonal immune escape to avelumab in some patients with mCRC expressing high-affinity FcγR3a, which may be a subset experiencing most selective pressure. Future trials evaluating the addition of avelumab to standard treatment in MSS mCRC are warranted especially in this patient subpopulation.Trial registration numberNCT03174405.

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 Review of Intra-Arterial Therapies for Colorectal Cancer Liver Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1371
Author(s):  
Justin Kwan ◽  
Uei Pua
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Treatment Strategies ◽  
Current Evidence ◽  
Unresectable Liver Metastasis ◽  
Hepatic Arterial Chemotherapy ◽  
Chemotherapy Infusion ◽  
Systemic Side Effects ◽  
Local Disease Control ◽  
Line Setting

The liver is frequently the most common site of metastasis in patients with colorectal cancer, occurring in more than 50% of patients. While surgical resection remains the only potential curative option, it is only eligible in 15–20% of patients at presentation. In the past two decades, major advances in modern chemotherapy and personalized biological agents have improved overall survival in patients with unresectable liver metastasis. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies such as hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are treatment strategies which are increasingly being considered to improve local tumor response and to reduce systemic side effects. Currently, these therapies are mostly used in the salvage setting in patients with chemo-refractory disease. However, their use in the first-line setting in conjunction with systemic chemotherapy as well as to a lesser degree, in a neoadjuvant setting, for downstaging to resection have also been investigated. Furthermore, some clinicians have considered these therapies as a temporizing tool for local disease control in patients undergoing a chemotherapy ‘holiday’ or acting as a bridge in patients between different lines of systemic treatment. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future.

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