Abstract:
:The recurrence of colorectal cancer after chemotherapy is the leading cause of its high mortality. We propose that elucidating the mechanisms of tumor regrowth after chemotherapy in tumor-bearing mice may provide new insights into tumor relapse in cancer patients. We firstly report the identification of a chemokine, CXCL4, that plays an important role in the molecular mechanism of cancer regrowth after chemotherapy. A syngenic transplantation tumor model was established with murine colon cancer CT26 cells and treated with 5-FU. Genome-wide gene expression analysis determined that CXCL4 was transiently upregulated in the tumor model. Systemic overexpression of CXCL4 accelerated cancer growth in vivo, but not in vitro. Conversely, the anti-CXCL4 monoclonal antibody (CXCL4-mab) retarded tumor-regrowth after 5-FU treatment in immune-competent mice, but not nude mice. The CXCL4-mab treatment increased the local expression levels of IFN-γ and Gran-b genes in the tumor-bed, and elevated the function of CTLs against CT26 cells. Thus, the colon cancer cells in responding to the cytotoxic stress of 5-FU produce a high level of CXCL4, which suppresses antitumor immunity to confer the residual cancer cells an advantage for regrowth after chemotherapy. Our findings provide a novel target for developing therapeutics aiming to increase antitumor immunity after chemotherapy.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Zhang Y,Gao J,Wang X,Deng S,Ye H,Guan W,Wu M,Zhu S,Yu Y,Han Wdoi
10.1080/15384047.2015.1095404subject
Has Abstractpub_date
2015-01-01 00:00:00pages
1775-83issue
12eissn
1538-4047issn
1555-8576journal_volume
16pub_type
杂志文章abstract::The molecular regulation of growth and progression of hormone refractory breast and prostate cancers remains challenging. The Division of Cancer Biology, NCI organized a small "think tank" style workshop and invited scientists in relevant areas to assess the state of science on the biology of hormone refractory tumors...
journal_title:Cancer biology & therapy
pub_type:
doi:10.4161/cbt.8.21.9918
更新日期:2009-11-01 00:00:00
abstract::It has been reported that the local introduction of a promoter-less DNA containing the complementary DNA (cDNA) sequence of a gene could induce gene-specific silencing in plants. The feasibility of this kind of silencing in human cancer cells is as yet unknown. The current study was designed to investigate the anti-tu...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.10.6586
更新日期:2008-10-01 00:00:00
abstract:INTRODUCTION:Malignant cells are capable of an unlimited number of cell divisions, either through production of telomerase, or through the alternate lengthening of telomere (ALT) mechanism. Yeast cells with genomic instability have been shown to survive in the absence of telomerase by increased recombination events. We...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.12.1235
更新日期:2004-12-01 00:00:00
abstract::Mutationally activated and oncogenic versions of the ras genes were first identified in human tumors in 1982. This discovery prompted great interest in the development of anti-Ras strategies as novel, target-based approaches for cancer treatment. The three human ras genes represent the most frequently mutated oncogene...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.306
更新日期:2002-11-01 00:00:00
abstract:PURPOSE:Indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolic enzyme, plays an important role in immune escape through suppressing T-cell function. Since Vav1 signaling pathway regulates T cell homeostasis, this study was designed to test the hypothesis that IDO induces T-cell immunosuppression through inhibiting V...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.14.8882
更新日期:2009-07-01 00:00:00
abstract::Angiomyolipoma (AML) is classified as a perivascular epithelioid cell neoplasm, mostly occurring in the kidney. Twenty percent of patients with renal AML have tuberous sclerosis complex (TSC) caused by germline variation in the TSC1 or TSC2 gene. In this paper, we report the first case of renal AML harboring somatic m...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2019.1702406
更新日期:2020-04-02 00:00:00
abstract::WNT and FGF signaling pathways cross-talk during a variety of cellular processes, such as human colorectal carcinogenesis, mouse mammary tumor virus (MMTV)-induced carcinogenesis, E2A-Pbx-induced leukemogenesis, early embryogenesis, body-axis formation, limb-bud formation, and neurogenesis. Canonical WNT signals are t...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.5.9.3151
更新日期:2006-09-01 00:00:00
abstract::The selectively oncolytic mtHSV, a HSV icp34.5 mutant with lacz gene insertion, was proved that it was targeted for treating tumors but not other organs, however, its oncolytic mechanism is under confirmation. The results showed that HeLa cells could be lysed efficiently by mtHSV in vitro. In the flow cytometry and We...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.2.3628
更新日期:2007-02-01 00:00:00
abstract:OBJECTIVES:To evaluate the 6-mo overall survival, safety and tolerability of lenalidomide in combination with standard gemcitabine as first-line treatment for patients with metastatic pancreatic cancer. METHODS:Eligibility included: previously untreated metastatic adenocarcinoma of the pancreas with metastases incurab...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,多中心研究
doi:10.4161/cbt.23625
更新日期:2013-04-01 00:00:00
abstract::Intestinal metaplasia of the gastric mucosa is an important component in the pathway to adenocarcinoma. The mechanisms that induce the progression from intestinal metaplasia to cancer have not been elucidated. High dietary salt has been known as one of the risk factors for gastric cancer development in humans. Therefo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.4.6.1734
更新日期:2005-06-01 00:00:00
abstract::Targeting FGFRs is one of the most promising therapeutic strategies in squamous non-small cell lung cancer (SQCC). However, different FGFR genomic aberrations can be associated with distinct biological characteristics that result in different clinical outcomes or therapeutic consequences. Currently, the full spectrum ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1480294
更新日期:2018-01-01 00:00:00
abstract::Drug resistance has always been the main problem in osteosarcoma treatment, and hypoxia seems to be one of the many causes for drug resistance. Therefore, in this study, we investigated how hypoxia triggers chemotherapy resistance in osteosarcoma. We first screened hypoxia- and normoxia- cultured osteosarcoma cells in...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1294285
更新日期:2017-03-04 00:00:00
abstract::Tumors with identical phenotype can have markedly different biologic behavior. The differentiation between hemangioblastoma, a benign vascular brain tumor, and renal cell carcinoma (RCC), a malignant tumor that can metastasize to the brain, is a well-known pathological quandary. We report a 59-year-old female with von...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.3.3673
更新日期:2007-03-01 00:00:00
abstract::Colon cancer is the third most common cancer and third most common cause of cancer-related death in the USA according to 2008 American Cancer Society statistics. The carcinogenesis of colon cancer has been associated with both genetics and environmental factors. It has been found that several signal pathways, includin...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.8.14.8983
更新日期:2009-07-01 00:00:00
abstract::Head and neck cancer arises from a series of molecular alterations progressive from dysplasia to carcinoma in situ, and finally invasive carcinoma. Risk factors associated with head and neck cancer include tobacco, alcohol and viral infection. There are genetic alterations in pre-cancerous cells that contribute to tra...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.9.1.10905
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Mutations that activate the PI3K/AKT/mTOR pathway are relatively common in urothelial (bladder) cancers, but how these pathway mutations affect AKT dependency is not known. We characterized the relationship between AKT pathway mutational status and sensitivity to the effects of the selective AKT kinase inhib...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.21793
更新日期:2012-11-01 00:00:00
abstract::IL-15 has been actively investigated for its potential in tumor immunotherapy. To enhance the anti-tumor activity of IL-15, the novel PFC-1 construct was designed, which comprises the following 3 parts: (1) IL-15Rα fused with IL-15 to enhance IL-15 activity, (2) an Fc fragment to increase protein half-life, and (3) an...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1071739
更新日期:2015-01-01 00:00:00
abstract::Methylthioadenosine phosphorylase (MTAP), a key enzyme in the catabolism of 5'-deoxy-5'-methylthioadenosine (MTA), catalyzes the formation of adenine and 5-methylthioribose-1-phosphate. MTAP is expressed in all cells throughout the body, but a significant percentage of human tumors have lost MTAP expression, thereby m...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.21115
更新日期:2012-09-01 00:00:00
abstract::Chronic arsenic treatment induces epithelial-mesenchymal transition (EMT) and promotes tumorigenicity, but the mechanism is unclear. MiR-100 has been shown to be involved in this biologic process. In this study, we hypothesize that inactivation of miR-100 combined with low concentration of arsenic exposure could promo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1345393
更新日期:2017-12-02 00:00:00
abstract::The irreversible ERBB1/2/4 inhibitor neratinib has been shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET, PDGFRα and mutant RAS proteins via autophagic degradation. Neratinib interacted in an additive to synergistic fashion with the approved PARP1 inhibitor niraparib to kill ov...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1436024
更新日期:2018-06-03 00:00:00
abstract::Both Pten and Nras are downstream mediators of receptor tyrosine kinase activation that plays important roles in controlling cell survival and proliferation. Here, we investigated whether and how Pten loss cross-talks with Nras activation in driving liver cancer development in mice. Somatic disruption of hepatic Pten ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1323597
更新日期:2017-07-03 00:00:00
abstract:BACKGROUND:Unlike papillary thyroid cancer (PTC), anaplastic thyroid carcinoma (ATC) is extremely aggressive and rapidly lethal without effective therapies. However, the differences of master regulators and regulatory networks between PTC and ATC remain unclear. Methods: Three representative datasets comprising 32 ATC,...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1803009
更新日期:2020-09-01 00:00:00
abstract:BACKGROUND:Primary brain tumors have always been associated with high morbidity and mortality. Glioma is the most common type of malignant brain tumors,with a high probability of recurrence after surgical excision and with poor prognosis.The purpose of this study was to compare the therapeutic efficacy of computed tomo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.20834
更新日期:2012-08-01 00:00:00
abstract::Although HER2-targeted therapy has been shown to prolong the survival of patients with HER2-positive breast cancer, most patients eventually progress due to drug resistance. Novel treatment options are urgently needed to overcome resistance to HER2-targeted therapy. The VEGF/VEGFR (Vascular endothelial growth factor a...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2020.1743159
更新日期:2020-07-02 00:00:00
abstract::Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, are the first targeted therapy drugs approved for the treatment of advanced non-small-cell lung cancer (NSCLC). Interestingly, treatment with these small molecule, reversible EGFR-TKIs leads to more positive respo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.9.8.11881
更新日期:2010-04-15 00:00:00
abstract::Epigenetics are defined, in broad-terms, as alterations in gene expression without changes in DNA sequence. While histone modifications and DNA methylation are two classical means to regulate gene expression, miRNA has also recently been documented to govern gene expression in normal as well as cancer cells. In this r...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.7.9.6992
更新日期:2008-09-01 00:00:00
abstract::Because of its high mortality rate, ovarian cancer is a leading cause of death among women and a highly unmet medical need. New therapeutic agents that are effective and well tolerated are needed and cancer antigen-specific monoclonal antibodies that have direct pharmacologic effects or can stimulate immunological res...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.26106
更新日期:2013-11-01 00:00:00
abstract::Hypoxia, a common phenomenon in human solid tumors, is associated with invasion and metastasis in various tumors. Hypoxia inducible factors (HIFs) are key molecules in the hypoxic response, and regulate the activation of specific genes, which mediate many of the adaptations to hypoxia. CC chemokine receptor 7 (CCR7) h...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.4.7332
更新日期:2009-02-01 00:00:00
abstract::The Forkhead Box transcription factor FoxM1 regulates expression of genes that promote cell cycle progression, and it plays essential roles in the development of liver, lung, prostate and colorectal tumors. Thiazolidinediones (TZDs) activate the peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activa...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.9.12.11710
更新日期:2010-06-15 00:00:00
abstract::Hypoxia is known to play important role in cancer biology. In sarcomas, hypoxia-induced protein biomarkers such as Hypoxia Inducible Factor-1a (HIF-1a), vascular endothelial growth factor (VEGF), and Erythropoietin (Epo) have been previously reported in only a few studies. Moreover, the biologic significance and rel...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.9.4.10744
更新日期:2010-02-01 00:00:00