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)

We have investigated the antitumor effects of synthetic MMP inhibitor MMI270 against postoperative lung metastasis from colon cancer in nude rat. The KM12SM human colon cancer cells were injected into the cecal wall, and at 5 weeks after the injection, the cecum was removed including the tumor. Then, 30 mg/kg of MMI270 was administered perorally twice per day for 2 or 4 weeks, either immediately after removal or after week 2 after the removal. At week 7 after the removal, lung metastasis was significantly inhibited by the early administration of MMI270 immediately after the tumor removal but not by the late administration. The survival rates were significantly higher in the rats treated by early administration of MMI270 compared to the survival rate in untreated rats. Moreover, no lung metastasis was detected in some rats with 24-weeks' survival treated by early administration. Lower microvessel density, lower PCNA Index and higher Apoptotic Index in the lung metastases of the rats treated with MMI270 were found compared to those in untreated rats. A beneficial effect of by early administration of MMI270 against postoperative lung metastases may be expected through inhibiting neovascularization of metastases in nude rat.
 ...
PMID:Efficacy of the MMP inhibitor MMI270 against lung metastasis following removal of orthotopically transplanted human colon cancer in rat. 1600 55

Receptor tyrosine kinases of the Eph family are upregulated in several different types of cancer. One family member in particular, the EphA2 receptor, has been linked to breast, prostate, lung and colon cancer, as well as melanoma. However, mechanisms by which EphA2 contributes to tumor progression are far from clear. In certain tumor cell lines, EphA2 receptor is underphosphorylated, raising the question of whether ligand-induced receptor phosphorylation and its kinase activity play a role in oncogenesis. To test directly the role of EphA2 receptor phosphorylation/kinase activity in tumor progression, we generated EphA2 receptor variants that were either lacking the cytoplasmic domain or carrying a point mutation that inhibits its kinase activity. Expression of these EphA2 mutants in breast cancer cells resulted in decreased tumor volume and increased tumor apoptosis in primary tumors. In addition, the numbers of lung metastases were significantly reduced in both experimental and spontaneous metastasis models. Reduced tumor volume and metastasis are not due to defects in tumor angiogenesis, as there is no significant difference in tumor vessel density between wild-type tumors and tumors expressing EphA2-signaling-defective mutants. In contrast, tumor cells expressing the EphA2 mutants are defective in RhoA GTPase activation and cell migration. Taken together, these results suggest that receptor phosphorylation and kinase activity of the EphA2 receptor, at least in part, contribute to tumor malignancy.
 ...
PMID:A kinase-dependent role for EphA2 receptor in promoting tumor growth and metastasis. 1610 80

A 54-year-old woman who had ascending colon cancer with multiple liver and lung metastases underwent rt. hemicolectomy and catheter insertion into the gastroduodenal artery for arterial infusion chemotherapy. On postoperative day 7, she had nausea and vomiting due to the enlarged multiple liver metastases on lateral segment. Intraarterial infusion of 5-FU 1,000 mg/m(2) for 5 hours weekly (WHF: weekly high-dose 5-FU) was started at first. After 3 courses, her symptoms improved, oral intake could be started, and liver metastases showed significant reduction on abdominal CT. Three months after surgery, bone scinti revealed multiple bone metastases. Combined HAI (5-FU: 600 mg/m(2)/3 hr) chemotherapy with UFT (400 mg/body) + CPT-11(80/body) and UFT (400 mg/body)/LV (75 mg/body) + CPT-11(100 mg/body) were effective for highly advanced colon cancer in terms of QOL. Eight months after surgery, she was doing well and the chemotherapy was continued. WHF therapy was effective for digestive symptoms due to liver metastasis.
 ...
PMID:[A case of colon cancer with multiple liver, lung and bone metastases successfully treated with combined weekly high-dose 5-FU (WHF) chemotherapy with UFT and CPT-11]. 1622 54

Artesunate (ART) is a derivative of artemisinin, the active principle of the Chinese herb Artemisia annua L. Artesunate is approved for the treatment of multidrug-resistant malaria and has an excellent safety profile. It has been shown that Artesunate, apart from its anti-malarial activity, has cytotoxic effects on a number of human cancer cell lines, including leukemia, colon cancer and melanoma. We report on the first long-term treatment of two cancer patients with ART in combination with standard chemotherapy. These patients with metastatic uveal melanoma were treated on a compassionate-use basis, after standard chemotherapy alone was ineffective in stopping tumor growth. The therapy-regimen was well tolerated with no additional side effects other than those caused by standard chemotherapy alone. One patient experienced a temporary response after the addition of ART to Fotemustine while the disease was progressing under therapy with Fotemustine alone. The second patient first experienced a stabilization of the disease after the addition of ART to Dacarbazine, followed by objective regressions of splenic and lung metastases. This patient is still alive 47 months after first diagnosis of stage IV uveal melanoma, a situation with a median survival of 2-5 months. Despite the small number of treated patients, ART might be a promising adjuvant drug for the treatment of melanoma and possibly other tumors in combination with standard chemotherapy. Its good tolerability and lack of serious side effects will facilitate prospective randomized trials in the near future.
 ...
PMID:Artesunate in the treatment of metastatic uveal melanoma--first experiences. 1627 63

We considered the appropriateness of RFA, which was performed in three cases of colorectal cancer with hepatic metastases accompanied by liver cirrhosis. Case 1 involved a patient with sigmoid colon cancer ss, n1 (+) with severe hepatic dysfunction and synchronous hepatic metastases (S5, S6, S8) in which RFA was performed. After 1 year and 6 months, recurrence (S3, S4) was detected in the residual liver, and the patient is currently undergoing the IFL (CPT-11/5-FU/Leucovorin) treatment. In case 2, following a partial hepatic resection, RFA was performed for cecal cancer ss, n2(+) with synchronous hepatic metastases (S5, S6, S8). After 11 months, recurrence (S5, S6, S7) occurred in residual liver and again RFA was performed following a partial hepatic resection. Lung metastases have occurred and currently IFL (CPT-11/5-FU/Leucovorin) and WHF treatments are underway. In case 3, 4 years and 8 months after cancer of the descending colon ss, n1 (+), RFA was performed on asynchronous hepatic metastases (S5, S7, S8). The patient died of peritonitis carcinomatosa one year after RFA. In all three cases, metastases were identified by dynamic CT as low density masses with no blood flow. Necrosis in all three metastases and local control had been achieved. There were no severe complications. Under the current conditions, local coagulation methods including RFA are appropriate in those cases in which resection are not possible such as multiple metastases with severe hepatic dysfunction, etc.
 ...
PMID:[Radiofrequency ablation (RFA) in colorectal cancer with hepatic metastases]. 1631 5

Comparative genomic hybridization was used to screen colorectal carcinomas for chromosomal aberrations that are associated with the metastatic phenotype of the lung. Specimens of 13 lung metastases, 6 primary tumors, 1 lymph node metastasis, 1 liver metastasis, and 1 ovarian metastasis were investigated and added to our CGH colon cancer tumor collective, comprising 85 tumor specimens from 56 patients (see CGH online tumor database at http://amba.charite.de/cgh). Lung metastases showed more alterations than liver metastases, particularly more deletions at 1p, 3p, 9q, 12q, 17q, 19p and 22q and gains at 2q, 5p, and chromosome 6. Comparing lung metastases with their corresponding primary tumors, particularly more deletions at 3p, 8p, 12q, 17q, and 21q21 and gains at 5p were observed. Based on our results, we wish to suggest a metastatic progression model. Specific subpopulations of metastatic cells have a distinct metastatic potential, which is reflected by a non-random accumulation of chromosomal alterations. Distinct alterations already exist within the primary tumor and this "ready to go package" gives the cells the metastatic potential to achieve the complex series of events needed for metastasis.
 ...
PMID:Chromosomal alterations in lung metastases of colorectal carcinomas: associations with tissue specific tumor dissemination. 1647 23

We report the complete response for one year of a patient with simultaneous multiple lung metastases from colon cancer who was treated using a combination of irinotecan (CPT-11) and uracil/tegafur (UFT)/Leucovorin (LV) using a schedule reported overseas. A 61-year-old woman was admitted to our hospital and diagnosed with ascending colon cancer and simultaneous multiple lung metastases. The patient underwent a right hemicolectomy and was treated with CPT-11 (150 mg/m(2)) on day 1 and oral UFT and oral LV on days 1-14. This treatment cycle was repeated every 3 weeks. A CT examination after 4 cycles of chemotherapy revealed a partial response of multiple lung metastases, and the next examination after 6 cycles revealed a complete response. The adverse effects observed during this chemotherapy regimen were leucopenia (grade 1), neutropenia (grade 2), vomiting (grade 2) and hair loss (grade 1). The patient is now receiving her 22nd cycle of chemotherapy, and her multiple metastases have shown a complete response for one year. The CPT-11 and UFT/LV combination therapy was well tolerated and was covered by the national health insurance system in Japan. This treatment may enable prolonged survival and improve quality of life in patients with metastatic colorectal cancer.
 ...
PMID:[Complete response to CPT-11 and UFT/LV combination therapy in a case with simultaneous multiple lung metastases from colon cancer]. 1677 Jan 4

In the management of hepatocellular carcinoma (HCC), a tumor thrombus occurrence between the hepatic vein and right ventricle is life threatening. We studied the effectiveness of radiation therapy to the venous thrombosis between the inferior vena cava and right ventricle. CASE 1: A 66-year-old man who suffered from no hepatic viral infection had hepatectomy of the huge HCC (over 20 cm) and recurrence at the post dperated liver and lung. After transarterial embolization, he suffered from dispnea and was found with tumor thrombus from the left hepatic vein to right atrium. Radiation therapy to the tumor thrombus was done and dispnea disappeared. He died by pneumonia at 5 months after the radiation. CASE 2: A 74-year-old woman who had hepatecomy and RFA for multiple HCC. For the recurrence of HCC, TAE and RFA were performed. After the tumor thrombus in the inferior vena cava, mammarian cancer was found and radiation therapy was performed. She died after 4 months from lung edema, but no growth of tumor thrombus was found. CASE 3: A 79-year-old man who had TAE, hepatectomy, RFA and MCT for multiple hepatoma. After these treatments, tumor thrombus at the right ventricle was found. Although he suffered from portal tumor thrombosis, lung metastases, bone metastases and colon cancer after the radiation therapy, he is still alive at the 19 month of treatments. Radiation therapy is safe and effective for venous tumor thrombosis of HCC.
 ...
PMID:[Effectiveness of radiation therapy to the venous thrombosis between the inferior vena cava and right ventricle]. 1721 13

New and more potent prodrugs of the 5-fluorouracyl family derived by hydroxymethylation or acyloxymethylation of 5-fluoro-1-(tetrahydro-2-furanyl)-2,4(1H,3H)-pyrimidinedione (tegafur, 1) are described. The anticancer activity of the butyroyloxymethyl-tegafur derivative 3 and not that of tegafur was attenuated by the antioxidant N-acetylcysteine, suggesting that the increased activity of the prodrug is in part mediated by an increase of reactive oxygen species. Compound 3 in an in vitro matrigel assay was found to be a more potent antiangiogenic agent than tegafur. In vivo 3 was significantly more potent than tegafur in inhibiting 4T1 breast carcinoma lung metastases and growth of HT-29 human colon carcinoma tumors in a mouse xenograft. In summary, the multifunctional prodrugs of tegafur display selectivity toward cancer cells, antiangiogenic activity, and anticancer activities in vitro and in vivo, superior to those of tegafur. 5-fluoro-1-(tetrahydro-2-furanyl)-2,4(1 H,3 H)-pyrimidinedione (tegafur, 1), the oral prodrug of 5-FU, has been widely used for treatment of gastrointestinal malignancies with modest efficacy. The aim of this study was to develop and characterize new and more potent prodrugs of the 5-FU family derived by hydroxymethylation or acyloxymethylation of tegafur. Comparison between the effect of tegafur and the new prodrugs on the viability of a variety of cancer cell lines showed that the IC50 and IC90 values of the novel prodrugs were 5-10-fold lower than those of tegafur. While significant differences between the IC50 values of tegafur were observed between the sensitive HT-29 and the resistant LS-1034 colon cancer cell lines, the prodrugs affected them to a similar degree, suggesting that they overcame drug resistance. The increased potency of the prodrugs could be attributed to the antiproliferative contribution imparted by formaldehyde and butyric acid, released upon metabolic degradation. The anticancer activity of the butyroyloxymethyl-tegafur derivative 3 and not that of tegafur was attenuated by the antioxidant N-acetylcysteine, suggesting that the increased activity of the prodrug is in part mediated by an increase of reactive oxygen species. Compound 3 in an in vitro matrigel assay was found to be a more potent antiangiogenic agent than tegafur. In vivo 3 was significantly more potent than tegafur in inhibiting 4T1 breast carcinoma lung metastases and growth of HT-29 human colon carcinoma tumors in a mouse xenograft. In summary, the multifunctional prodrugs of tegafur display selectivity toward cancer cells, antiangiogenic activity and anticancer activities in vitro and in vivo, superior to those of tegafur.
 ...
PMID:Novel prodrugs of tegafur that display improved anticancer activity and antiangiogenic properties. 1816 51

A 63-year-old woman was diagnosed as having a sigmoid colon cancer with synchronous unresectable multiple liver and lung metastases. After sigmoidectomy, she was treated with S-1 combined with CPT-11 as a down-staging chemotherapy. After 3 courses of chemotherapy, the liver and lung metastases reduced in size as partial response. In March 2005, extended right hepatectomy combined with MHV resection was performed. She was treated with 2 courses of chemotherapy after hepatectomy, and furthermore she underwent left lung upper lobectomy. She has been alive without any signs of recurrence for 33 months from the initial surgery. Recently, a progression of the systemic chemotherapy for colorectal cancer has been a promising modality to improve a poor prognosis for unresectable multiple liver or extrahepatic metastases from advanced colorectal cancer.
 ...
PMID:[A successful treatment with down-staging chemotherapy for sigmoid colon cancer with unresectable multiple liver and lung metastases]. 1821 89


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>