scholarly journals Perspectives on Immunotherapy of Metastatic Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yongjiu Dai ◽  
Wenhu Zhao ◽  
Lei Yue ◽  
Xinzheng Dai ◽  
Dawei Rong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Liver Metastasis ◽  
Experimental Design ◽  
Poor Prognosis ◽  
Response Rate ◽  
Traditional Treatment ◽  
The Poor ◽  
New Thinking ◽  
New Treatment

Colorectal cancer, especially liver metastasis, is still a challenge worldwide. Traditional treatment such as surgery, chemotherapy and radiotherapy have been difficult to be further advanced. We need to develop new treatment methods to further improve the poor prognosis of these patients. The emergence of immunotherapy has brought light to mCRC patients, especially those with dMMR. Based on several large trials, some drugs (pembrolizumab, nivolumab) have been approved by US Food and Drug Administration to treat the patients diagnosed with dMMR tumors. However, immunotherapy has reached a bottleneck for other MSS tumors, with low response rate and poor PFS and OS. Therefore, more clinical trials are underway toward mCRC patients, especially those with MSS. This review is intended to summarize the existing clinical trials to illustrate the development of immunotherapy in mCRC patients, and to provide a new thinking for the direction and experimental design of immunotherapy in the future.

A Rare Case of Stage IV Adrenocortical Carcinoma with Acute Adrenocortical Dysfunction After Trans-Catheter Arterial Chemo-Embolization (TACE)

2020 ◽  
Author(s):  
Zhilong Wang ◽  
Xin Sun ◽  
Fengli Zhang ◽  
Ting Wang ◽  
Ping Li
Keyword(s):  
Liver Metastasis ◽  
Adrenocortical Carcinoma ◽  
Poor Prognosis ◽  
Rare Case ◽  
Stage Iv ◽  
Postoperative Recurrence ◽  
Tumor Burden ◽  
Case Presentation ◽  
Embolization Therapy ◽  
New Treatment

Abstract Background: Adrenocortical carcinoma(ACC) is a rare and highly invasive endocrine malignant tumor with poor prognosis and insensitivity tochemotherapy, which don't have effective treatment. Although Surgical resection is considered to be the main treatment for ACC, postoperative recurrence and metastasis have become the most important factors of death. Therefore, local treatments such as trans-catheter arterial chemo-embolization, radiofrequency ablation become be new treatment for ACC. Trans-catheter arterial chemo-embolization therapy for ACC patients with liver metastasis has good efficacy and can effectively reduce the tumor burden of patients, which is considered to be safe and easy for patients. Case presentation: We report a 47-year-old female patient diagnosed with stage Ⅳ ACC with liver metastases, who developed symptoms of acute adrenocortical dysfunctions after hepatic arterial catheter chemo-embolization.Conclusion: Trans-catheter arterial chemo-embolization therapy for ACC patients with liver metastasis is not completely safe, and there is a certain probability that it will lead to secondary adrenal dysfunction. Hydrocortisone supplementation can effectively alleviate the symptoms.

scholarly journals The mechanism of the premetastatic niche facilitating colorectal cancer liver metastasis generated from myeloid-derived suppressor cells induced by the S1PR1–STAT3 signaling pathway

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Qi Lin ◽  
Li Ren ◽  
Mi Jian ◽  
Pingping Xu ◽  
Jun Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
T Cell ◽  
Liver Metastasis ◽  
Signaling Pathway ◽  
Mouse Models ◽  
Poor Prognosis ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Premetastatic Niche

Abstract The tumor-derived factors involved in the expansion and accumulation of myeloid-derived suppressor cells (MDSCs) in metastatic dissemination of colorectal cancer (CRC) to the liver has not been studied. Immunohistochemistry was used to detect sphingosine-1-phosphate receptor 1 (S1PR1) and signal transducer and activator of transcription-3 (STAT3) in human colorectal tumors. IL-6 and interferon-γ were detected by enzyme-linked immunosorbent assay (ELISA). Tumor growth, invasion, and migration were evaluated by MTT, transwell, and wound healing assays, respectively. Subcutaneous tumor-bearing and CRC liver metastasis (CRLM) nude mouse models were constructed. The percentage of MDSCs was measured using multicolor flow cytometry. Western blot assay was used to evaluate S1PR1 and p-STAT3 expression in MDSCs after separation from the liver and tumor by magnetic antibody. T-cell suppression assay was detected by carboxyfluorescein succinimidyl ester (CFSE). Aberrant co-expressed S1PR1 and p-STAT3 was correlated with metachronous liver metastasis and poor prognosis in CRC. A mutual activation loop between S1PR1 and STAT3 can enhance CRC cell proliferation, migration, and invasion in vitro and in vivo. The expression of p-STAT3 and its downstream proteins can be regulated by S1PR1. p-STAT3 was the dependent signaling pathway of S1PR1 in the promotion of cell growth and liver metastasis in CRC. The level of IL-6 and the associated MDSCs stimulated by the S1PR1–STAT3 correlated with the number of liver metastatic nodes in the CRLM mouse models and patients. Increased CD14+HLA-DR−/low MDSCs from CRLM patients inhibited autologous T-cell proliferation and predict poor prognosis. The S1PR1–STAT3–IL-6–MDSCs axis operates in both tumor cells and MDSCs involved in the promotion of growth and liver metastasis in CRC. MDSCs induced by S1PR1–STAT3 in CRC cells formed the premetastatic niche in the liver can promote organ-specific metastasis.

scholarly journals Integrated analysis of genes associated with poor prognosis of patients with colorectal cancer liver metastasis

Oncotarget ◽  
2017 ◽  
Vol 8 (15) ◽  
pp. 25500-25512 ◽  
Author(s):  
Zhenyuan Qian ◽  
Guobing Zhang ◽  
Guangyuan Song ◽  
Ji Shi ◽  
Lijie Gong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Poor Prognosis ◽  
Integrated Analysis ◽  
Colorectal Cancer Liver Metastasis

scholarly journals High expression of ZEB1 correlates with liver metastasis and poor prognosis in colorectal cancer

2012 ◽  
Vol 5 (2) ◽  
pp. 564-568 ◽  
Author(s):  
GUANG-JUN ZHANG ◽  
TONG ZHOU ◽  
HONG-PENG TIAN ◽  
ZUO-LIANG LIU ◽  
SHU-SEN XIA
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Poor Prognosis ◽  
High Expression

Increased incidence of adverse events after concomitant hepatic arterial infusion plus systemic chemotherapy and bevacizumab for colorectal cancer with liver metastasis.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 591-591
Author(s):  
S. Sadahiro ◽  
T. Suzuki ◽  
Y. Maeda ◽  
A. Tanaka ◽  
K. Okada ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Adverse Events ◽  
Phase I ◽  
Systemic Chemotherapy ◽  
Response Rate ◽  
Hepatic Arterial Infusion ◽  
Progression Free Survival ◽  
Arterial Infusion ◽  
Grade 3

591 Background: FOLFOX+bevacizumab (BEV) is the standard systemic chemotherapy for metastatic colorectal cancer (CRC). We investigated the combination of FOLFOX4 and hepatic arterial infusion (HAI) in patients who had isolated liver metastasis from CRC. We also compared efficacy and safety between this combination therapy and its concomitant use with BEV. Methods: Twenty-five patients entered a phase I/II trial of HAI (5-FU 250 mg/d, leucovorin 25 mg/d; d1-7, q2w) combined with FOLFOX4. Fourteen other patients with a similar background received HAI + FOLFOX4 combined with BEV and the two regimens were compared. Results: In the phase I/II study, the recommended doses for FOLFOX were as follows: L-OHP, 85 mg/m2; l-LV, 100 mg/m2; 5-FU (bolus), 400 mg/m2; and 5-FU (infusion), 600 mg/m2. Sixteen patients who received this regimen showed a response rate of 93.8% (2 CR and 13 PR), a median progression-free survival of 323 days, and a one-year survival rate of 93.7%. In the subsequent phase II trial of HAI + FOLFOX4 with BEV, 14 patients were enrolled and the response rate was 78.6% (2 CR and 9 PR). The outcome was inferior when BEV was used concomitantly. The median numbers of doses were 10 (range: 1-27) for FOLFOX4 and 9 (1-27) for HAI without BEV, whereas the corresponding numbers with BEV were 8 (1-12) and 2 (0-9), respectively. There was a marked decrease in the number of HAI procedures when BEV was used. Thrombosis occurred in 8 patients who received concomitant BEV, which was the most common reason for cessation of HAI. Other adverse events (≥Grade 3) were neutropenia (n=7; 43.8%) and thrombocytopenia (n=2; 12.5%) without BEV or neutropenia (n=7; 43.8%) and diarrhea (n=1; 7.1%) with BEV, and no marked difference was seen between the two regimens. Both regimens were well tolerated. Severe neuropathy was only observed in 1 patient (6.3%; Grade 3) who received concomitant BEV. Conclusions: In the present study, HAI + FOLFOX combined with BEV caused thrombosis and disturbance of wound healing, thereby increasing the incidence of complications and making it difficult to continue treatment. These findings suggest that BEV should not be administered with HAI therapy. No significant financial relationships to disclose.

scholarly journals Recruitment of CCR2+tumor associated macrophage to sites of liver metastasis confers a poor prognosis in human colorectal cancer

2018 ◽  
Vol 7 (9) ◽  
pp. e1470729 ◽  
Author(s):  
Julie G Grossman ◽  
Timothy M Nywening ◽  
Brian A Belt ◽  
Roheena Z Panni ◽  
Bradley A Krasnick ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Poor Prognosis ◽  
Human Colorectal Cancer ◽  
Tumor Associated Macrophage

scholarly journals Multimodal Treatment in Glioblastomas

2021 ◽  
Author(s):  
Ercan Çetin ◽  
Serdar Kabataş
Keyword(s):  
Overall Survival ◽  
Multimodal Treatment ◽  
Poor Prognosis ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Modalities ◽  
Tumor Vaccines ◽  
Tumor Treating Fields ◽  
The Poor ◽  
New Treatment

Glioblastomas are the most common primary brain tumors. Despite aggressive resection, radiotherapy and concomitant chemotheraphy overall survival is 14-16 months, and 5 year survivial rate is only 2%. The poor prognosis required development of new treatment modalities. Tumor Treating Fields, molecularly targetted drugs, antiangiogenic molecules, immune checkpoint inhibitors, tumor vaccines, Chimeric Antigen Receptor-T cell, viral theraphy and oncolytic viruse and mesenchymal stem cell vectors are some of the modalities that are currently being developed.

Meta-analysis of randomized trials testing the biochemical modulation of fluorouracil by methotrexate in metastatic colorectal cancer. Advanced Colorectal Cancer Meta-Analysis Project.

1994 ◽  
Vol 12 (5) ◽  
pp. 960-969 ◽  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Clinical Trials ◽  
Regression Model ◽  
Randomized Clinical Trials ◽  
Tumor Response ◽  
Advanced Colorectal Cancer ◽  
Response Rate ◽  
Meta Analysis ◽  
Biochemical Modulation

PURPOSE Even though fluorouracil (5FU) remains the standard treatment of advanced colorectal cancer, almost 90% of patients treated with 5FU alone do not achieve an objective response to chemotherapy. Biochemical modulation of 5FU by methotrexate (MTX) is an attempt to increase the sensitivity of tumor cells to 5FU. However, despite the inclusion of several hundreds of patients in randomized clinical trials, no definitive evidence is available on the clinical benefit of 5FU/MTX over 5FU alone. A meta-analysis was performed to assess this benefit objectively and quantitatively for tumor response rate and overall survival. DESIGN The meta-analysis was based on individual data of 1,178 patients included in eight randomized clinical trials comparing 5FU alone with 5FU/MTX. Patient data were provided by all principal investigators. The analyses were performed by an independent secretariat, and then discussed with all collaborators. RESULTS Tumor response rate was 10% for patients allocated to 5FU alone (complete response [CR] rate, 2%; partial response [PR] rate, 8%) compared with 19% for patients allocated to 5FU/MTX (CR rate, 3%; PR rate, 16%). This difference was highly significant, with an overall response odds ratio (OR) of 0.51 (95% confidence interval [CI], 0.37 to 0.70) (P < .0001). Median overall survival times were 9.1 months and 10.7 months in the 5FU-alone and 5FU/MTX groups, respectively. This difference was also statistically significant, with an overall survival OR of 0.87 (95% CI, 0.77 to 0.98) (P = .024). Logistic regression model and Cox regression model showed that performance status and randomized treatment were the only two significant predictors of tumor response and survival. CONCLUSION It is concluded that the modulation of 5FU by MTX doubles the response rate to 5FU, and yields a small improvement in survival.

Aberrant expression of USP22 is associated with liver metastasis and poor prognosis of colorectal cancer

2010 ◽  
Vol 103 (3) ◽  
pp. 283-289 ◽  
Author(s):  
Yan-Long Liu ◽  
Yan-Mei Yang ◽  
Hui Xu ◽  
Xin-Shu Dong
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Poor Prognosis ◽  
Aberrant Expression
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