Abstract:
:Despite an armamentarium that is wide in range, scope of action, and target, chemotherapy has limited success in colorectal cancer (CRC). Novel approaches are needed to overcome tumor barriers to chemotherapy that includes an abnormal tumor vasculature constituting a poor drug delivery system. We have previously shown that 5-methylselenocysteine (MSC) enhances therapeutic efficacy of irinotecan in various human tumor xenografts. We have recently demonstrated that MSC through vascular normalization leads to better tumor vascular function in vivo. In this study, we examined the role of MSC on tumor vasculature, interstitial fluid pressure (IFP) and drug delivery in 2 histologically distinct CRC xenografts, HCT-8 (uniformly poorly differentiated) and HT-29 (moderately differentiated tumor with avascular glandular regions). The presence of specific histologic structures as a barrier to therapy in these xenografts and their clinical relevance was studied using tissue microarray of human surgical samples of CRC. MSC led to a significant tumor growth inhibition, a reduced microvessel density, and a more normalized vasculature in both colorectal xenografts. While IFP was found to be significantly improved in HCT-8, an improved intratumoral doxorubicin delivery seen in both xenografts could explain the observed increase in therapeutic efficacy. Differentiated, glandular, avascular and hypoxic regions that contribute to tumor heterogeneity in HT-29 were also evident in the majority of surgical samples of CRC. Such regions constitute a physical barrier to chemotherapy and can confer drug resistance. Our results indicate that MSC could enhance chemotherapeutic efficacy in human CRC, especially in CRC with few or no hypoxic regions.
journal_name
Clin Colorectal Cancerjournal_title
Clinical colorectal cancerauthors
Bhattacharya A,Tóth K,Sen A,Seshadri M,Cao S,Durrani FA,Faber E,Repasky EA,Rustum YMdoi
10.3816/CCC.2009.n.025subject
Has Abstractpub_date
2009-07-01 00:00:00pages
155-62issue
3eissn
1533-0028issn
1938-0674pii
S1533-0028(11)70364-4journal_volume
8pub_type
杂志文章abstract::As new improvements in the treatment of colorectal cancer have become available, it has become important to understand the benefits of new therapies or the deleterious effects stemming from the increased risk of toxicity. In particular, a more rational approach to adjuvant chemotherapy for patients with stage II/III d...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/ccc.2006.n.019
更新日期:2006-05-01 00:00:00
abstract::Replacing infusional 5-fluorouracil (5-FU) leucovorin (LV) with oral capecitabine would be more convenient to patients, because it would lead to reduced hospital chair time and infusion-related toxicities. Previous trials with oral capecitabine-based regimens (other than XELOX [capecitabine/oxaliplatin]) have failed t...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2006.n.044
更新日期:2006-11-01 00:00:00
abstract:BACKGROUND:New treatment modalities and a growing understanding of the complex genetic tumor landscape have improved the outcome of colorectal cancer (CRC) patients. Nonetheless, more individualized treatment regimens, taking individual tumor characteristics into account, have been recently postulated and prognostic bi...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2018.02.008
更新日期:2018-06-01 00:00:00
abstract::The standard in rectal cancer has been to add adjuvant radiation therapy to surgery in patients with stage II and III disease. Total mesorectal excision has led to lower local recurrence rates, and, if properly performed, may make adjuvant radiation unnecessary for certain stage II and III patients, such as T3 N0 pati...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/CCC.2003.n.002
更新日期:2003-02-01 00:00:00
abstract:BACKGROUND:Few clinical studies have investigated the association between neutrophil-lymphocyte ratio (NLR) and treatment with cetuximab-based chemotherapy in metastatic colorectal cancer (mCRC). The NLR may reflect immune cells modulating specific cytokine signals in the tumor microenvironment; however, which immune-r...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2018.08.002
更新日期:2018-12-01 00:00:00
abstract::Modern chemotherapy combinations for metastatic colorectal cancer (mCRC) comprise infusional 5-fluorouracil (5-FU), leucovorin, and irinotecan or oxaliplatin. The fluoropyrimidine derivative capecitabine is at least as effective as 5-FU plus leucovorin bolus regimens. It displays a favorable toxicity profile and offer...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/CCC.2008.n.015
更新日期:2008-03-01 00:00:00
abstract:BACKGROUND:Similar epidemiologic characteristics suggest a common etiology for colon cancer (CC) and diverticular disease of the colon (DD). The relationship between the 2 diseases is still unclear, and the impact of DD in patients diagnosed with CC on disease-free survival (DFS) and overall survival (OS) is unknown. N...
journal_title:Clinical colorectal cancer
pub_type: 临床试验,杂志文章
doi:10.3816/ccc.2006.n.031
更新日期:2006-07-01 00:00:00
abstract::The discovery of the key role of the epidermal growth factor receptor (EGFR) and its downstream signaling effectors in the pathophysiology of colorectal cancer (CRC) has ushered in the clinical use of targeted therapies in the treatment of metastatic CRC (mCRC). The anti-EGFR monoclonal antibodies cetuximab and panitu...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.1016/j.clcc.2015.05.006
更新日期:2015-12-01 00:00:00
abstract::Microbiome (microbiota) is a community of all microorganisms inhabiting a specific site of the body, including pathogens, which distinguishes it from the physiological microflora. Intestinal dysbiosis plays a key role in the development of colorectal cancer. In the process of carcinogenesis, inflammation, immune respo...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.1016/j.clcc.2019.07.006
更新日期:2020-03-01 00:00:00
abstract:BACKGROUND:No biomarkers exist to predict benefit from antiangiogenic therapy in metastatic colorectal cancer patients. ACVRL1 (activin receptor like-protein 1) encodes for ALK1, a member of the transforming growth factor-β receptor family, which directs pathologic angiogenesis. We examined the intratumoral expression ...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2018.03.006
更新日期:2018-09-01 00:00:00
abstract::To evaluate, from a US payer perspective, the cost-effectiveness of treatment strategies for metastatic colorectal cancer (mCRC), we performed a systematic review of published cost-effectiveness analyses. We identified 14 papers that fulfilled our search criteria and revealed varying levels of value among current trea...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.1016/j.clcc.2015.10.002
更新日期:2016-03-01 00:00:00
abstract::This phase II study was designed to characterize the clinical activity of ISIS 3521 in patients with metastatic colorectal cancer (CRC). Sixteen patients with pretreated or refractory CRC were treated with ISIS 3521. Eleven patients were given a dose of 2.0 mg/kg per day, and 5 patients received 3.0 mg/kg per day give...
journal_title:Clinical colorectal cancer
pub_type: 临床试验,杂志文章
doi:10.3816/ccc.2004.n.026
更新日期:2004-11-01 00:00:00
abstract::Bevacizumab is a humanized monoclonal antibody approved by the US Food and Drug Administration for use in combination with fluorouracil (FU)-based chemotherapy for first-line treatment of patients with metastatic colorectal carcinoma (CRC). Its mechanism of action is inhibition of tumor angiogenesis by neutralizing va...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2010.n.008
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:The Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation (ICECREAM) study assessed the efficacy of cetuximab monotherapy compared with cetuximab combined with chemotherapy for quadruple wild-type (KRAS, NRAS, BRAF, or P13KCA exon 20) metastatic colorectal cancer. PATIENTS AND METHODS:Patients w...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clcc.2018.06.002
更新日期:2018-12-01 00:00:00
abstract:BACKGROUND:Metastatic colorectal cancer (CRC) outcomes continue to improve, but they vary significantly by race and ethnicity. We hypothesize that these disparities arise from unequal access to care. MATERIALS AND METHODS:The Harris Health System (HHS) is an integrated health delivery network that provides medical car...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2019.09.002
更新日期:2020-06-01 00:00:00
abstract:UNLABELLED:Two identical randomized controlled trials designed to optimize adjuvant treatment of colon cancer (CC) (n =855) and rectal cancer (RC) (n = 796) were performed. Long-term evaluation confirmed that the addition of folinic acid (FA) to 5-fluorouracil (5-FU) improved 7-year overall survival (OS) in CC but not ...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clcc.2012.07.005
更新日期:2013-03-01 00:00:00
abstract:INTRODUCTION:Patients with metastatic colorectal cancer (CRC) may present with oligometastatic lung lesions for which stereotactic ablative radiotherapy (SABR) can be utilized. This study aims to report efficacy and prognostic factors associated with colorectal lung metastases treated with SABR. MATERIAL AND METHODS:T...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2016.08.003
更新日期:2017-09-01 00:00:00
abstract:BACKGROUND:Recent trends have identified increasing number of young individuals with rectal and colon cancers. These individuals, who are younger than 50 years old, in most instances would not meet screening guidelines. We aimed to report the characteristics and trend of the rising proportion of young individuals being...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2018.10.002
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND:As more patients are screened for colorectal cancer a small but significant number of interval cancers develop after colonoscopy for colorectal cancer screening. MATERIALS AND METHODS:We reviewed records of 75,314 adult patients who underwent colonoscopy for screening or diagnostic purposes between 1998 and...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2014.11.001
更新日期:2015-03-01 00:00:00
abstract::The multiplicity of chemotherapy regimens currently available to treat colorectal cancer in the first-line setting precludes the identification of a single standard regimen for front-line therapy. The previous standard, 5-fluorouracil (5-FU), formerly the only agent with any significant activity against colorectal can...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/ccc.2004.s.002
更新日期:2004-06-01 00:00:00
abstract::Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal cancer of teh gastrointestinal tract. They are characterized by the expression of KIT. Therapeutically, metastatic GISTs are effectively treated by imatinib, a tyrosine kinase inhibitor (TKI) with activity against KIT and platelet-derived growth f...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/ccc.2006.s.005
更新日期:2006-11-01 00:00:00
abstract::Colorectal cancer (CRC), one of the most common malignancies worldwide, is often diagnosed at an advanced stage, and resistance to chemotherapeutic and existing targeted therapy is a major obstacle to its successful treatment. New targets that offer alternative clinical options are therefore urgently needed. Recently,...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.1016/j.clcc.2016.06.006
更新日期:2017-03-01 00:00:00
abstract:BACKGROUND:The efficacy and safety of the FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) regimen combined with aflibercept has not been studied in the first-line management of patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS:In the context of a prospective single-arm trial (NC...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,多中心研究
doi:10.1016/j.clcc.2018.06.003
更新日期:2018-12-01 00:00:00
abstract::Hepatic colorectal metastases present a challenging problem in patients with recurrent colorectal cancer. Twenty percent of patients with recurrence will have liver metastases as a component of their disease, and only 10% of these patients will have isolated liver metastases that are resectable. Although systemic chem...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/CCC.2003.n.010
更新日期:2003-05-01 00:00:00
abstract::Adult intussusception is a rare occurrence and, unlike in childhood, is usually associated with an underlying tumor. Although computed tomography (CT) imaging can identify an intussusception and point toward a cause, diagnosis is challenging if it is only intermittent. When an intussusception presents in the context o...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2008.n.028
更新日期:2008-05-01 00:00:00
abstract:PURPOSE:Capecitabine has shown similar efficacy to 5-fluorouracil (5-FU); a regimen containing 2 weeks of capecitabine/oxaliplatin (CapOx) has demonstrated noninferiority to infusional 5-FU/oxaliplatin/leucovorin (FOLFOX) for the treatment of metastatic colorectal cancer (mCRC). This phase II study explores the efficac...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.3816/CCC.2010.n.021
更新日期:2010-07-01 00:00:00
abstract:BACKGROUND:The optimal therapeutic strategy for metastatic colorectal cancer patients is still a matter of debate. There are no prognostic variables indicating how many lines individual patients ought to receive, and whether later lines could be effective even when earlier ones were not. PATIENTS AND METHODS:We retros...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2017.03.019
更新日期:2017-12-01 00:00:00
abstract::Epidermal growth factor receptor (EGFR) has been validated as an important target in the treatment of metastatic colorectal cancer (mCRC). While initial studies focused on the treatment of disease that was refractory to available chemotherapy agents, 2 recent themes have emerged: the use of KRAS mutation status to sel...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,评审
doi:10.3816/CCC.2010.s.006
更新日期:2010-06-01 00:00:00
abstract:INTRODUCTION:Bevacizumab improves outcome for patients with advanced colorectal cancer (CRC) when added to chemotherapy. The HORIZON I trial resulted in similar outcome with bevacizumab or cediranib, a small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF) receptor, as treatment of advanc...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clcc.2013.11.002
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:The safety of bevacizumab in older mCRC patients is poorly understood. The purpose of this analysis was to determine the prevalence, incidence, and risk factors for treatment-related AEs in older bevacizumab recipients. PATIENTS AND METHODS:Patients age ≥65 were identified from SEER-Medicare and categorized...
journal_title:Clinical colorectal cancer
pub_type: 杂志文章
doi:10.1016/j.clcc.2012.11.004
更新日期:2013-09-01 00:00:00