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

Human thymidine phosphorylase (dThdPase) is an angiogenic factor identical to platelet-derived endothelial cell growth factor (PD-ECGF). Thymidine phosphorylase is also a converting enzyme of the prodrug 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil (5-FU) in tumors. To assess the role of dThdPase in targeting chemotherapy, we examined the relationship between the expression of dThdPase and the sensitivity of 5'-DFUR in cancer cell lines, and also examined whether transfection of dThdPase cDNA enhanced the drug-sensitivity to 5'-DFUR with or without angiogenesis in breast cancer cells. Thirteen human cancer cell lines consisting of 4 breast cancer, 6 gastric cancer, and 3 colon cancer cell lines were used. Expression of dThdPase was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). In vitro drug-sensitivity was assessed by MTT assay, and anti-tumor effect in vivo was assessed using nude mouse xenografts. Intratumoral microvessel density was evaluated by immunohistochemical staining to factor VIII related antigen. Transfection of dThdPase cDNA was performed using pcDNA3 expression vector encoding its cDNA by the lipofection method. An inverse relationship between the expression of dThdPase and the IC50 values of 5'-DFUR was observed (p=0.1278, rho=-0.440) in the 13 cancer cell lines. Transfection of dThdPase cDNA into MCF-7 breast cancer cells resulted in an approximately 2.6- and 10-fold increase of the expression of dThdPase mRNA and its enzyme activity, respectively, compared to the control vector alone. The sensitivity to 5'-DFUR in the transfected cells was increased approximately 20-fold compared to the parent cells and control vector alone, and the sensitivity to 5-FU was also somewhat increased. In contrast, the sensitivity to ADM, CDDP, and VP-16 was not different between the transfected and control cells. In nude mice xenografts of the transfected cells, treatment with 5'-DFUR had a significant anti-tumor effect compared to those of the untreated transfected cells and control vector alone treated with 5'-DFUR (p<0.01). Intratumoral microvessel density in the transfected cells was not significantly increased with or without treatment with 5'-DFUR compared to control vector alone. The high expression of dThdPase was correlated with an increase in the sensitivity to 5'-DFUR in gastrointestinal and breast cancer cell lines. The introduction of dThdPase cDNA in breast cancer cells enhanced the sensitivity to 5'-DFUR without an increase of tumor angiogenesis, and targeting chemotherapy of dThdPase may be a good tumor-specific and personalized therapy for improving the poor prognosis of cancer patients who show high expressions of dThdPase.
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PMID:Effects of introduction of dThdPase cDNA on sensitivity to 5'-deoxy-5-fluorouridine and tumor angiogenesis. 1263 76

Acquired hemophilia A (AHA) is a rare coagulation disorder due to the development of an autoantibody against and inhibitor of coagulation factor VIII. It has been reported that immunosuppressive therapy with corticosteroids, cyclophosphamide, azathioprine and vincristine are effective to decrease this inhibitor. When corticosteroids and cytotoxic drugs are ineffective, cyclosporine A (CyA) may be effective as a second-line salvage therapy. Except for postpartum conditions, AHA usually occurs in elderly patients who are often already suffering from diabetes mellitus, ischemic heart disease and/or hyperlipidemia. However, immunosuppressive and cytotoxic drugs may have adverse effects on these patients. We report on a 66-year-old man who developed AHA after colon cancer resection (factor VIII inhibitor: 61 Bethesda units/ml, aPTT : 97.9 s). Since he already had both diabetes mellitus and ischemic heart disease, we abandoned treatment with corticosteroids and oral cyclophosphamide was started, but was switched to CyA because of leukopenia. Within 3 months of starting the CyA treatment, aPTT levels returned to normal and 4 further months were required for complete eradication of the inhibitor. This case revealed that CyA is as effective as corticosteroids for AHA. For patients with AHA who have unfavorable complications due to corticosteroids and cytotoxic drugs, CyA could be a potential first-line drug.
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PMID:[Cyclosporine A as an effective treatment for a patient with acquired hemophilia A complicated with diabetes mellitus and ischemic heart disease]. 1644 Jul 70

Acquired hemophilia A is a rare and potentially fatal condition of coagulopathy caused by autoantibodies against clotting factor VIII (factor VIII inhibitor). We report a case of a 63-year-old woman, who presented with a sudden onset of severe hemorrhagic tendency with exclusively prolonged activated partial thromboplastin time (APTT). She was diagnosed with acquired hemophilia A due to a decrease in factor VIII activity and a high titer of factor VIII inhibitor. Hemorrhage was well controlled by recombinant activated factor VII. Although the level of factor VIII inhibitor did not decline with prednisolone and cyclophosphamide, it became undetectable with rituximab. In parallel with controlling hemorrhage, malignancy, which may cause acquired hemophilia A, was searched for and sigmoid colon cancer was found. After the eradication of factor VIII inhibitor, surgical resection was performed uneventfully. Thereafter, acquired hemophilia A has been in complete remission without any additional therapy. The present case suggests the efficacy of rituximab for refractory acquired hemophilia A and the importance of the identification of underlying diseases that can cause acquired hemophilia A.
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PMID:Acquired hemophilia A with sigmoid colon cancer: successful treatment with rituximab followed by sigmoidectomy. 1948 33

We report a rare case of subarachnoid hemorrhage (SAH) in a man who acquired factor VIII inhibitor and suffered coagulopathy a month after disease onset. Acquired factor VIII inhibitors in patients without hemophilia is a rare disease characterized by severe bleeding as a result of antibody against factor VIII. A 61-year-old male, who had a past history of hypertension, underwent resection for colon cancer at the local hospital. Ten days after surgery he suffered septic shock that required intensive use of antibiotics. Two days after this episode, he had a sudden loss-of-consciousness attack, and was referred to our hospital with the diagnosis of SAH. Emergency angiography revealed a dissecting aneurysm at the right intracranial vertebral artery distal to the origin of the posterior inferior cerebellar artery. The aneurysm was successfully treated with endovascular parent artery occlusion. However, after a placing ventriculo-peritoneal shunt a month later, he developed severe coagulopathy due to acquired factor VIII inhibitor.
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PMID:[A case of subarachnoid hemorrhage complicated by acquired hemophilia]. 1999 54

We report a case of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) concomitant with acquired von Willebrand syndrome. A 33-year-old man developed motor and sensory polyneuropathy with electrophysiological conduction slowing. At this time, M-protein was absent He was diagnosed with CIDP and received intravenous immunoglobulin and subsequent oral corticosteroids, which resulted in almost complete remission for over 10 years. At the age of 44, he presented with chronic anemia. Laboratory tests and colonoscopy revealed that he had acquired von Willebrand syndrome with monoclonal gammopathy of undetermined significance (IgG lambda type) and colon cancer. Bleeding symptoms were.resolved with intravenous immunoglobulin, but not with supplementation of factor VIII. Shortly after successful excision of the cancer, CIDP and acquired von Willebrand syndrome simultaneously recurred. Intravenous immunoglobulin produced rapid improvement of both neurological and hematological abnormalities. Concurring CIDP and acquired von Willebrand syndrome in the present case may indicate that the conditions have a partly common immunological background including monoclonal gammopathy and a potential common autoantibody-mediated mechanism. Alternatively, dysfunction of von Willebrand factor may increase blood-nerve barrier permeability, inducing the recurrence of CIDP.
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PMID:[A case of chronic inflammatory demyelinating polyradiculoneuropathy concomitant with acquired von Willebrand syndrome]. 2170 30

We report a case of multiple hepatic epithelioid hemangioendothelioma( EHE) mimicking hepatic metastasis of colon cancer. A 71-year-old man was referred to our hospital for further evaluation of multiple hepatic tumors. Enhanced CT scan was not performed because of renal dysfunction. Total colonoscopy revealed a type 1 cancer at the rectosigmoid junction. We therefore diagnosed the hepatic tumors as metastases from rectal cancer. Anterior resection was performed and postoperative chemotherapy targeting the hepatic tumors was carried out. Unfortunately, the size of the hepatic tumors increased. We therefore performed lateral segmentectomy and partial hepatectomies (11 lesions). The macroscopic findings indicated basically localized tumor without diffuse infiltration. Microscopically, spindle and oval-shaped cells with abundant eosinophilic cytoplasm were observed; immunohistochemical staining was positive for factor VIII and CD34. These data were conclusive for EHE. EHE of the liver is a rare neoplasm of which little is currently known. We herein report a case of EHE in the liver, misdiagnosed as colorectal metastatic tumor.
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PMID:[A case of multiple hepatic epithelioid hemangioendothelioma mimicking metastatic hepatic tumor]. 2326 60


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