Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

No standard has been established for salvage therapy in gemcitabine refractory advanced urothelial cancer. We report the complete response to FOLFOX4 therapy of a metastatic urothelial cancer patient, for whom adjuvant gemcitabine plus cisplatin combination chemotherapy had failed. A 54-year-old male patient with urothelial cancer (transitional cell carcinoma) in the right kidney underwent three rounds of adjuvant gemcitabine-cisplatin chemotherapy after extensive radical nephrectomy. However, he had new liver, lung metastases and synchronous two separate primary colon cancer. The lung metastasis lesion was confirmed as a metastatic urothelial cancer via percutaneous transthoracic needle biopsy (PTNB). Liver and lung metastasis lesions disappeared after the 4th cycle of FOLFOX4 chemotherapy. In addition, colon cancer also disappeared after the 8th cycle of FOLFOX4 chemotherapy. The patient was still showing a complete response after 4 months. Clinical trials using the FOLFOX regimen as salvage therapy for gemcitabine-refractory advanced urothelial cancer are warranted.
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PMID:Complete response to FOLFOX4 therapy in a patient with advanced urothelial cancer: a case report. 2008 86

Metastasis relies on angiogenesis for tumor expansion. Tumor angiogenesis is restrained by a variety of endogenous inhibitors, including thrombospondin 1 (TSP1). The principal antiangiogenic activity of TSP1 resides in a domain containing three TSP1 repeats (3TSR), and TSP1 cleavage is regulated, in part, by the metalloproteinase ADAMTS1. In this study, we examined the role of TSP1 and ADAMTS1 in controlling metastatic disease in the liver and lung. TSP1 overexpression inhibited metastatic growth of colon or renal carcinoma cells in liver but not lung. Metastatic melanoma in liver grew more rapidly in Tsp1-null mice compared with controls, whereas in lung grew similarly in Tsp1-null mice or controls. Recombinant TSP1 was cleaved more efficiently in lysates from liver than lung. ADAMTS1 inhibition by neutralizing antibody, small interfering RNA, or genetic deletion abrogated cleavage activity. To confirm that lack of cleavage of TSP1 ablated its antiangiogenic function in the lung, we generated colon cancer cells stably secreting only the 3TSR domain and found that they inhibited formation of both liver and lung metastases. Collectively, our results indicate that the antiangiogenic activity of TSP1 is differentially regulated by ADAMTS1 in the liver and lung, emphasizing the concept that regulation of angiogenesis is varied in different tissue environments.
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PMID:Variable inhibition of thrombospondin 1 against liver and lung metastases through differential activation of metalloproteinase ADAMTS1. 2010 48

The aim of study was to investigate the pattern of mediastinal lymph node metastases in patients with colorectal cancer metastasis. Twenty-four pulmonary metastasectomies with mediastinal lymphadenectomies were performed on 19 patients (14 unilateral and five bilateral operations). The metastases were centrally localised in eight cases; the primary tumour was colon cancer in 15 patients and rectal cancer in nine cases. The number and the localisation of metastases were recorded, as the clinico-pathological data of the primary tumours. The results were compared with the pattern of metastases in mediastinal lymph nodes. The data were subjected to statistical processing with the chi(2)-test and Mann-Whitney test. Mediastinal lymph node metastases were confirmed in eight cases (33.3%). The proportion of positive lymph nodes was significantly higher for central metastases (62.5% vs. 18.8%, P=0.032). When the pathological stage of the primary tumour was more advanced, the proportion of lymph node metastases displayed a statistically not significant increase. The pattern of lymph node metastases did not correlate with the localisation of the lung metastases, disease-free interval and the diameter of the greatest pulmonary metastasis. The frequency of lymph node metastasis is relatively high, therefore, mediastinal lymphadenectomy during the resection of colorectal cancer metastases is necessary.
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PMID:Is the mediastinal lymphadenectomy during pulmonary metastasectomy of colorectal cancer necessary? 2040 83

MMP11 expression is a poor prognosis factor in human carcinomas. Although it has been shown to favor primary tumor development, its role in metastatic processes remains unclear. We studied the hematogenous metastatic activity of C26 mouse colon cancer cells injected into the tail vain of wild-type or MMP11-deficient mice during 2 months. Using X-ray computed tomography to image metastasis development in recipient living mice, lung metastases were found to occur earlier and to grow faster in wild-type mice. Histological analyses of the lung, liver, kidney, adrenal gland, mammary gland, ovary and salivary gland, performed at the end of experiment, also showed lower numbers of metastases in wild-type mice, regardless of organ. Lung metastases showed similar Factor VIII-positive vascular networks regardless of the mouse MMP11 status. However, those found in MMP11-deficient mice also exhibited vessel-like structures that did not express Factor VIII, Lyve-1 and vimentin, and were not stained with PAS. Consequently, they did not correspond to vascular or lymphatic vessels or to vascular mimicry channels. Collectively, these results revealed significant spatio-temporal variability that is dependent on host MMP11 status. Furthermore, they point-out the paradoxical role of MMP11 in favoring the onset and growth of lung metastases but limiting lung foci number, and inhibiting the cancer cell dissemination to other organs. These data highlight the complexity of the metastatic process in which the same factor can play activator or repressor functions depending on the metastatic step.
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PMID:Matrix metalloproteinase 11/stromelysin-3 exerts both activator and repressor functions during the hematogenous metastatic process in mice. 2020 94

Selenium has cancer-preventive activity that is mediated, in part, through selenoproteins. The role of the 15-kDa selenoprotein (Sep15) in colon cancer was assessed by preparing and using mouse colon CT26 cells stably transfected with short hairpin RNA constructs targeting Sep15. Metabolic (75)Se labeling and Northern and Western blot analyses revealed that >90% of Sep15 was downregulated. Growth of the resulting Sep15-deficient CT26 cells was reduced (P < 0.01), and cells formed significantly (P < 0.001) fewer colonies in soft agar compared with control CT26 cells. Whereas most (14 of 15) BALB/c mice injected with control cells developed tumors, few (3 of 30) mice injected with Sep15-deficient cells developed tumors (P < 0.0001). The ability to form pulmonary metastases had similar results. Mice injected with the plasmid-transfected control cells had >250 lung metastases per mouse; however, mice injected with cells with downregulation of Sep15 only had 7.8 +/- 5.4 metastases. To investigate molecular targets affected by Sep15 status, gene expression patterns between control and knockdown CT26 cells were compared. Ingenuity Pathways Analysis was used to analyze the 1,045 genes that were significantly (P < 0.001) affected by Sep15 deficiency. The highest-scored biological functions were cancer and cellular growth and proliferation. Consistent with these observations, subsequent analyses revealed a G(2)-M cell cycle arrest in cells with targeted downregulation of Sep15. In contrast to CT26 cells, Sep15-targeted downregulation in Lewis lung carcinoma (LLC1) cells did not affect anchorage-dependent or anchorage-independent cell growth. These data suggest tissue specificity in the cancer-protective effects of Sep15 downregulation, which are mediated, at least in part, by influencing the cell cycle.
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PMID:Deficiency in the 15-kDa selenoprotein inhibits tumorigenicity and metastasis of colon cancer cells. 2038 23

Tumor-associated macrophages (TAMs) encourage and coordinate neoplastic growth. In late stage human lung adenocarcinoma, TAMs exhibited mixed M1 (classical; argI(low)iNOS(high)) and M2 (alternative; argI(high)iNOS(low)) polarization based on arginine metabolism. In several murine cancer models including chemically and genetically-induced primary lung tumors, prostate tumors, colon xenografts, and lung metastases, TAMs expressed argI(high)iNOS(low) early during tumor formation; argI(low)iNOS(high) polarization also occurred during malignancy in some models. In a chemically-induced lung tumor model, macrophages expressed argI(high)iNOS(low) within one week after carcinogen treatment, followed by similar polarization of bone marrow-derived monocytes (BDMCs) a few days later. TAMs surrounding murine prostate tumors also expressed argI(high)iNOS(low) early during tumorigenesis, indicating that this polarization is not unique to neoplastic lungs. In a human colon cancer xenograft model, the primary tumor was surrounded by argI(high)iNOS(low)-expressing TAMs, and BDMCs also expressed argI(high)iNOS(low), but pulmonary macrophages adopted argI(high)iNOS(low) polarization only after tumors metastasized to the lungs. Persistence of tumors is required to maintain TAM polarization. Indeed, in both conditional mutant Kras- and FGF10-driven models of lung cancer, mice expressing the transgene develop lung tumors that regress rapidly when the transgene is silenced. Furthermore, pulmonary macrophages expressed argI(high)iNOS(low) on tumor induction, but then returned to argI(low) iNOS(low) (no polarization) after tumors regressed. Manipulating TAM function or depleting TAMs may provide novel therapeutic strategies for preventing and treating many types of cancer.
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PMID:Tumor progression stage and anatomical site regulate tumor-associated macrophage and bone marrow-derived monocyte polarization. 2043 Oct 28

Adverse events associated with bevacizumab (BV) were haemorrhage, impaired wound healing and arterial thromboembolism. We report 2 patients with colorectal cancer who underwent percutaneous coronary intervention (PCI) for unstable angina soon after administration of chemotherapy including BV. CASE 1: A 74-year-old male with rectal cancer and simultaneous liver metastases was admitted to our hospital for unstable angina. Before admission he had received 4 courses of chemotherapy including BV. He had no coronary risk factors besides old age. Since coronary angiography (CAG) revealed significant stenosis in the mid-left circumflex coronary artery, PCI with a coronary stent was performed without any complications. CASE 2: A 67-year-old male with colon cancer and liver and lung metastases was referred to our Dept. of Internal Medicine for unstable angina. Before referral, he had undergone 28 courses of chemotherapy including BV. He had a history of familial hyperlipidemia and smoking. Since CAG revealed significant stenoses in the proximal left anterior descending coronary artery, PCI with coronary stents was performed without any complications. These 2 patients had no angina after PCI. PCI with coronary stent was safely performed in this patient with unstable angina soon after administration of chemotherapy including BV.
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PMID:[Two cases of unstable angina in patients treated with bevacizumab]. 2064 38

Various tumors metastasize to the lung, and they are often detected as multiple nodules. We report on two cases of such multiple lung metastases combined with primary lung cancer: a myxoid liposarcoma in the right thigh and a colon cancer. In each case, a pulmonary metastasectomy revealed that one of the tumors was primary lung cancer. Regardless of recent advances in computed tomography for detecting small pulmonary nodules and ground-glass opacity components, which indicate possible primary lung cancer, the preoperative differential diagnosis for either metastatic or primary lung cancers is usually difficult because they are too small to obtain enough tissue for diagnosis, except by surgery. When nodules are removed and diagnosed as lung metastasis combined with primary lung cancer, additional treatment should be considered depending on the prognosis of each disease.
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PMID:Lung metastases from various malignancies combined with primary lung cancer. 2094 70

XELOX for metastatic colorectal cancer has been approved last year in Japan and used to manage some cases of metastatic colorectal cancer at our hospital. We thought that this regimen has some merits in the patient's quality of life (QOL). Case 1: A 66-year-old man who had been diagnosed sigmoid colon cancer with retroperitoneal invasion. Case 2: A 67-year-old man who had been diagnosed Sigmoid colon cancer with multiple lung metastases. Therefore, both of them have been diagnosed as metastatic sigmoid colon cancer. Although two cases started with XELOX + bevacizumab, there was no toxicity of grade 3 or 4 for both, and we thought that the patients' QOL had been kept. Now, two cases are followed tightly as their chemotherapeutic response is being PR or NC.
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PMID:[Our experiences of XELOX + bevacizumab for two cases of metastatic sigmoid colon cancer]. 2122 23

A 77-year-old woman had a laparoscope assisted ileocecal resection for ascending colon cancer with multiple lung metastases in December 2003. The patient who had postoperative complication such as anastomotic leakage left the hospital in March 2004. UFT was administered from April 2004 to June 2006. One year after administration of UFT, CT showed the lung metastases had been disappeared and the level of CEA was decreased below normal. Recurrence was not observed for 62 months.
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PMID:[A case of lung metastases of colon cancer demonstrating complete response for more than five years after treatment with UFT]. 2122 29


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