Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Background: Brain metastases from colorectal cancer (CRC) are uncommon. There has been relatively little published on the host and tumor factors that might lead to this clinical scenario. We reviewed all cases of brain metastases from CRC at Dartmouth-Hitchcock Medical Center over a more than 20-year period to establish incidence and to identify patient and cancer characteristics which were associated with their development. Patients and Methods: We present a retrospective review of 39 confirmed cases of brain metastases from CRC diagnosed between 1984 and 2006. Immunohistochemical staining for CXCR4 was performed on all available brain metastasis biopsy specimens. Results: The incidence of brain metastases from CRC was 2.3%. Left-sided primary colon tumors predominated. The majority of patients had pulmonary metastases at the time brain metastases were identified, and those with preexisting pulmonary metastases had progression of that disease. All patients were symptomatic from brain metastases, and the cerebellum was the most common area of brain involvement. Immunohistochemical analysis confirmed strong expression of CXCR4 in all brain metastases sampled. Conclusion: The incidence of brain metastases from CRC is low. Primary tumor in the left colon, long-standing pulmonary metastases, especially those with recent progression, and CXCR4 expression by tumor cells are all associated with increased risk of brain metastases. Increased survival among patients with metastatic CRC will likely result in an increased incidence of brain metastases. Further characterization of the role of tumor and host factors might yield better insight into the development, and potentially the prevention, of this devastating situation.
Clin Colorectal Cancer 2009 Mar
PMID:Brain metastases from colorectal cancer: risk factors, incidence, and the possible role of chemokines. 1942 3

The identification of prognostic determinants of colorectal cancer (CRC), including prediction of occult metastasis, is of urgent consideration, based on the tremendous differences in outcome and survival between patients who present with metastasis or develop metastasis versus those patients with organ-confined or nonrecurrent disease. Currently, a great deal of attention has been focused on using gene expression profiles of tumor specimens as a launch point for prognostic biomarker discovery. In our study, we chose to focus on functional protein-based pathway biomarkers as a new information archive because it is these proteins that form the functional signaling networks that control cell growth, motility, apoptosis, survival, and differentiation. We used reverse-phase protein microarray analysis of laser capture microdissected CRC tumor specimens to profile broad cell signaling pathways from patients who presented with liver metastasis versus patients who remained recurrence free after follow-up. Our results indicate that members of the EGFR and COX2 signaling pathways appear differentially activated in the primary tumors of patients with synchronous metastatic disease. If validated in larger study sets, this pathway defect might be useful as a prognostic clinical tool as well as a guide to potential therapeutic intervention strategies that target occult disease and/or preventative measure.
Clin Colorectal Cancer 2009 Mar
PMID:Multiplexed Cell Signaling Analysis of Metastatic and Nonmetastatic Colorectal Cancer Reveals COX2-EGFR Signaling Activation as a Potential Prognostic Pathway Biomarker. 1942 5

When patients with colorectal cancer are monitored after resection of primary or metastatic disease, an elevated carcinoembryonic antigen (CEA) level is usually an indicator of recurrent disease. Positron emission tomography (PET) scans are often used to locate the site of recurrences when computed tomography scans do not show the presence of disease. This case highlights an important cause of a falsely elevated CEA with abnormal PET imaging.
Clin Colorectal Cancer 2009 Jul
PMID:Elevated carcinoembryonic antigen and sarcoidosis masquerading as metastatic colon cancer. 1963 34

In the past 10 years, overall survival and disease-free survival of patients with colorectal cancer (CRC) has improved substantially because of a combination of factors: (1) more accurate staging as a result of advances in imaging technology; (2) refinements in surgical technique; (3) 'curative' metastasectomy for patients with limited metastatic disease; (4) improvements in radiation therapy planning and greater precision of radiation therapy delivery; and (5) increasing chemotherapeutic options, including antiangiogenic and vascular targeting drugs. In this era of 'personalized medicine', the increasingly individualized treatment of patients with CRC has highlighted the need for functional imaging techniques in addition to conventional anatomic-based imaging. This review discusses the contribution of positron emission tomography to the clinical management of CRC. In addition, evolving techniques such as dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), DCE computed tomography (perfusion CT), diffusion-weighted MRI, and blood oxygenation level-dependent MRI that might have a future role will be covered.
Clin Colorectal Cancer 2009 Apr
PMID:Functional imaging of colorectal cancer: positron emission tomography, magnetic resonance imaging, and computed tomography. 1973 68

The identification of prognostic determinants of colorectal cancer (CRC), including prediction of occult metastasis, is of urgent consideration, based on the tremendous differences in outcome and survival between patients who present with metastasis or develop metastasis versus those patients with organ-confined or nonrecurrent disease. Currently, a great deal of attention has been focused on using gene expression profiles of tumor specimens as a launch point for prognostic biomarker discovery. In our study, we chose to focus on functional protein-based pathway biomarkers as a new information archive because it is these proteins that form the functional signaling networks that control cell growth, motility, apoptosis, survival, and differentiation. We used reverse-phase protein microarray analysis of laser capture microdissected CRC tumor specimens to profile broad cell signaling pathways from patients who presented with liver metastasis versus patients who remained recurrence free after follow-up. Our results indicate that members of the EGFR and COX2 signaling pathways appear differentially activated in the primary tumors of patients with synchronous metastatic disease. If validated in larger study sets, this pathway defect might be useful as a prognostic clinical tool as well as a guide to potential therapeutic intervention strategies that target occult disease and/or preventative measure.
Clin Colorectal Cancer 2009 Apr
PMID:Multiplexed cell signaling analysis of metastatic and nonmetastatic colorectal cancer reveals COX2-EGFR signaling activation as a potential prognostic pathway biomarker. 1973 73

Oxaliplatin is a third-generation platinum compound that is commonly used for the treatment of colorectal cancer (CRC) both in the adjuvant and metastatic disease settings. Oxaliplatin-based chemotherapy is presently limited by cumulative dose-dependent neurotoxicity. We had previously reported on 2 patients who developed oxaliplatin-induced immune thrombocytopenia (OITP) during their tenth and seventeenth FOLFOX (5-fluorouracil/leucovorin/ oxaliplatin) cycles. Herein, we report on a third patient who developed severe thrombocytopenia after 28 cycles of modified FOLFOX6 (mFOLFOX) chemotherapy. A 60-year-old white woman with metastatic CRC, who had partial sigmoidectomy and colostomy, presented with bleeding from stoma site, on cycle 28, day 1 of mFOLFOX6, 7.5 hours after completion of the oxaliplatin infusion. Laboratory data revealed marked thrombocytopenia with a nadir platelet count of zero. Due to concern for OITP, the patient's serum was sent to BloodCenter of Wisconsin, Inc. (Diagnostic Laboratories; Milwaukee, WI). Serologic testing for oxaliplatin-dependent platelet antibodies was performed using flow cytometry in the presence of various concentrations of oxaliplatin. Laboratory tests for autoimmune hemolysis and disseminated intravascular coagulation (DIC) were negative. Oxaliplatin-dependent platelet reactive antibodies were detected in the patient's serum, confirming the diagnosis of OITP. The diagnosis of OITP should be entertained in patients receiving oxaliplatin for prolonged periods of time even though there are other more common causes of thrombocytopenia in these patients, including chemotherapy-induced myelosuppression, bone marrow involvement with tumor, and DIC.
Clin Colorectal Cancer 2009 Oct
PMID:Oxaliplatin-induced immune thrombocytopenia: another cumulative dose-dependent side effect? 1982 13

Oxaliplatin-based chemotherapy regimens are currently a standard of care for the treatment of colorectal cancer (CRC) in both the adjuvant treatment and metastatic disease settings. Significant improvements in outcomes have been achieved with oxaliplatin-based combinations in these settings when compared with administration of 5-fluorouracil alone. Pathologic evaluation of normal liver from patients undergoing neoadjuvant oxaliplatin treatment has identified histologic evidence of sinusoidal injury, although the effect of this finding on patient outcomes after hepatic resection appears to be minimal. This article describes the use of oxaliplatin-based chemotherapy in 6 patients with stage III or IV CRC who developed evidence of noncirrhotic portal hypertension. These patients developed complications of portal hypertension including esophageal or hemorrhoidal varices with bleeding, splenomegaly with associated thrombocytopenia, and ascites. In each case, oxaliplatin-induced hepatic sinusoidal injury was identified as the most likely factor contributing to the development of noncirrhotic portal hypertension. The literature on hepatic sinusoidal injury after oxaliplatin is reviewed and the proposed pathophysiology is discussed.
Clin Colorectal Cancer 2009 Oct
PMID:Portal hypertension associated with oxaliplatin administration: clinical manifestations of hepatic sinusoidal injury. 1982 14

Aberrant activation of the Src family of tyrosine kinases has been implicated in the development and progression of colorectal cancer (CRC). As a result, Src inhibitors are now being studied as possible therapeutic agents to treat metastatic disease. In this review, we discuss the effects of aberrant Src activation in CRC, Src as a target of single-agent drug therapy, and Src as a target of combination therapy with epidermal growth factor receptor inhibition and cytotoxic chemotherapy. The greatest potential for clinically relevant benefit most likely lies in combination regimens. Further evaluation with biomarkers will continue to define the molecular phenotype of patients with CRC who will benefit the most from Src-based therapy.
Clin Colorectal Cancer 2010 Apr
PMID:The SRC family of protein tyrosine kinases: a new and promising target for colorectal cancer therapy. 2037 2

In March 2010, a randomized trial called Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) was launched and is open to recruitment. The evidence for pulmonary metastasectomy reviewed in this supplement includes no randomized trials. Claims for a survival benefit for patients undergoing this surgery rely on case series. Furthermore, there is little documentation of any symptoms attributable to pulmonary metastases that are alleviated or obviated by metastasectomy. The PulMiCC study aims are to examine whether or not surgical resection of pulmonary metastases from colorectal cancer lengthens survival and to record systematically the harms and benefits of such surgery and quality of life.
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PMID:Pulmonary metastasectomy in colorectal cancer: the PulMiCC trial. 2050 65

Long-term survival with colorectal liver metastases (CLM) usually requires surgical resection, despite considerable improvements in systemic chemotherapy that have extended median survival with metastatic colorectal cancer from 6 months to in excess of 2 years. Multidisciplinary management is now the norm in the perioperative setting, and chemotherapy has become part of an accepted treatment paradigm. Systemic and intrahepatic chemotherapy can shrink inoperable disease to the point of resection, and a combination of neoadjuvant and adjuvant chemotherapy improves disease-free survival for patients with operable CLM. A greater understanding of the biology of colorectal metastasis has revealed many new potential targets, and carefully designed clinical trials are required to investigate these and other existing biologic therapies in this setting. In this article we discuss the biology of colorectal cancer metastases, the rationale for perioperative chemotherapy, and the recent and ongoing investigation of perioperative chemotherapy in the management of CLM.
Clin Colorectal Cancer 2010 Jun
PMID:Improving response and outcomes for patients with liver-limited metastatic colorectal cancer. 2063 Aug 49


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