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)

Plachitin formed of both poly-N-acetyl-D-glucosamine (chitin) and cis-diamminedichloroplatinum (CDDP), was used as an arterial chemoembolization therapy against unresectable liver cancer. One gram of Plachitin contained 300 mg of CDDP. The Plachitin particle was 50-100 microns in diameter. Plachitin particles (50-100 mg) were injected via hepatic artery once or twice every week, and the total amount of 300 mg was considered one course of this therapy. The size and number of tumors were measured by computer tomography (CT). Pharmacokinetics of this drug was also assessed by serum and urine platinum (Pt) concentration. Three patients underwent the chemoembolization therapy using plachitin particles. Case 1 had multiple hepatocellular carcinomas. The tumor regression rate was 39% after two courses of this therapy. Serum alpha-fetoprotein (AFP) level decreased from 1,182 ng/ml to 300 ng/ml. Case 2 suffered from bile duct cystadenocarcinoma. After three courses of the therapy, the tumor regression rate was 84.4%. Serum carbohydrate antigen 19-9 (CA19-9) decreased from 731 U/ml to 75 U/ml. Case 3 had synchronous multiple liver metastases from sigmoid colon cancer. The tumor regression rate was 77% after one course of the therapy. Carcinoembryonic antigen (CEA) and CA19-9 decreased from 406 ng/ml to 65 ng/ml and from 4,800 U/ml to 790 ng/ml, respectively. The response rate of the 3 cases was 66.7%. The peak levels of the serum Pt concentration of three patients were 0-0.4 microgram/g throughout the therapy, but peak urine Pt concentrations were observed during one course of the therapy of three patients ranging from 0.5 microgram/g to 3.2 micrograms/g, and decreased gradually for three weeks after the first course. Adverse effects of Plachitin particles for arterial chemoembolization were epigastralgia, nausea, fever, and elevation of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. These adverse effects were observed in all patients, but were transient. Catheter obstruction occurred in one patient (case 2). Cholecystitis, pancreatic pseudocyst, and duodenal ulcer were noticed in case 3. No renal hypofunction was observed. Plachitin might be a useful agent for arterial chemoembolization therapy for primary and secondary liver cancer.
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PMID:[Intraarterial chemoembolization therapy for unresectable liver cancer using plachitin particles]. 794 46

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo2 ligand (Apo2L) has been identified as important in promoting programmed cell death in breast and colon cancer xenografts. More importantly, normal liver tissue appears not to be susceptible to the cytotoxic effects of TRAIL/Apo2L, although activation of the related Fas ligand receptor system is known to promote massive liver apoptosis terminating in fulminant hepatitis. In the present study, we investigated the therapeutic potential of TRAIL/Apo2L gene therapy in hepatocellular carcinoma (HCC) and evaluated its side effects in an immune-competent mouse model. Intratumoral administration of the TRAIL/Apo2L vector by electroporation elevated serum TRAIL/Apo2L through at least day 28 after gene therapy and significantly inhibited the growth not only of the HCC directly administered TRAIL/Apo2L vector, but also of distant subcutaneous HCC. In addition, intratumoral administration of the TRAIL/Apo2L vector inhibited spontaneous lung metastasis. Serum alanine aminotransferase was mildly elevated by TRAIL/Apo2L gene therapy, but without showing such histological signs as TUNEL staining. These results demonstrate that TRAIL/Apo2L gene therapy for HCC by electroporation in vivo is efficient without significant side effects, and is thus promising for use in future clinical trials.
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PMID:Electroporation-mediated tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo2L gene therapy for hepatocellular carcinoma. 1181 83

Cisplatin is one of the most effective chemotherapeutic agents and plays a major role in the treatment of a variety of human solid tumors. However, its toxicity limits the clinical use. Recently, the administration of antioxidants has been suggested to protect against cisplatin-induced nephrotoxicity. The present study was designed to estimate the antitumor activity of the licorice extract alone and in combination with cisplatin, and its protective potential against cisplatin-induced toxicity in a mouse xenograft model. The administration of the licorice extract significantly inhibited tumor growth in BALB/C mice inoculated with CT-26 colon cancer cells. The combination of the licorice extract and cisplatin diminished the therapeutic efficacy of cisplatin but promoted considerably antitumor activity of the licorice extract. In mice with cisplatin treatment for 15 d, the serum levels of blood urea nitrogen and creatinine remarkably were increased by kidney damage, and the serum alanine aminotransferase and aspartate aminotransferase levels were elevated by liver damage. The administration of the licorice extract plus cisplatin recovered these functional indices in the kidney and liver to almost the control levels. In addition, the administration of the licorice extract significantly reduced the cisplatin-induced oxidative stress. Taken together, the administration of the licorice extract inhibits the growth of mouse colon carcinoma without any adverse effects, and reduces the cisplatin-induced toxicity. Therefore, the licorice extract may be a candidate for an anticancer and chemopreventive agent. However, cancer patients with cisplatin therapy should avoid the supplementation of the licorice extract.
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PMID:Effects of the licorice extract against tumor growth and cisplatin-induced toxicity in a mouse xenograft model of colon cancer. 1797 99

A growing amount of attention has been focused on the investigation of the effects of chemopreventive agents on the inhibition of cancer cell growth and toxicity in combination with chemotherapeutics. The objective of this study was to determine whether isoliquiritigenin (ISL) has the potential to serve as a beneficial supplement during cisplatin chemotherapy. We found that the administration of ISL alone significantly reduced the size of the solid tumors in CT-26 cell-inoculated BALB/c mice, without any detectable induction of nephrotoxicity, hepatotoxicity, and oxidative stress, and ISL reduced the viability and DNA synthesis of CT-26 murine colon cancer cells in a dose-dependent manner. ISL did not affect the therapeutic efficacy of cisplatin. Furthermore, ISL suppressed cisplatin-induced kidney damage characterized by increases in serum creatinine and blood urea nitrogen, as well as cisplatin-induced liver damage characterized by increases in serum alanine aminotransferase and aspartate aminotransferase. The repeated oral administration of ISL prior to cisplatin treatment exerted a preventive effect on cisplatin-mediated increases in serum nitric oxide and tissue lipid peroxidation levels, and it recovered depleted GSH levels in the tissues. Therefore, supplementation with ISL may be an effective approach to counteracting the side effects of cisplatin therapy in cancer patients.
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PMID:Isoliquiritigenin inhibits tumor growth and protects the kidney and liver against chemotherapy-induced toxicity in a mouse xenograft model of colon carcinoma. 1836 95

Although chemotherapy has an important function in the treatment of most solid tumours, its clinical applications are limited by severe side effects such as nephrotoxicity, hepatotoxicity, ototoxicity and neurotoxicity. Recently, a growing amount of attention has been focused on the investigation of the effects of chemopreventive agents on the inhibition of cancer cell growth and toxicity in combination with chemotherapeutics. The aim of this study was to determine whether licochalcone A (LCA) has the potential to serve as a beneficial supplement during cisplatin chemotherapy. We found that the administration of LCA alone significantly inhibited the size of the solid tumours in CT-26 cell-inoculated Balb/c mice, without any detectable induction of nephrotoxicity, hepatotoxicity and oxidative stress. LCA also suppressed cell proliferation by reducing DNA synthesis of CT-26 murine colon cancer cells in a dose-dependent manner. LCA did not affect the therapeutic efficacy of cisplatin. Furthermore, LCA inhibited the cisplatin-induced kidney damage characterized by increases in the serum creatinine and blood urea nitrogen, as well as the cisplatin-induced liver damage characterized by increases in the serum alanine aminotransferase and aspartate aminotransferase. The repeated oral administration of LCA prior to cisplatin treatment exerted a preventive effect on the cisplatin-mediated increases in the serum nitric oxide and the tissue lipid peroxidation levels, and recovered the depleted reduced glutathione levels in the tissues. These results suggest that supplementation with LCA may be beneficial in counteracting the side effects of cisplatin therapy in cancer patients.
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PMID:Licochalcone A inhibits the growth of colon carcinoma and attenuates cisplatin-induced toxicity without a loss of chemotherapeutic efficacy in mice. 1848 61

We report a case of drug-induced liver injury associated with uracil/tegafur(UFT) + folinate (Uzel) therapy. A 73-year-old woman had undergone right hemicolectomy with ascending colon cancer in April 2008. Postoperative diagnosis was tub2, pSS, pN0, fStage II. We administered UFT + Uzel therapy(UFT 500 mg/day, Uzel 75 mg/day)as adjuvant chemotherapy after operation for 6 weeks. Two weeks after the first drug administration, she visited our hospital complaining of anorexia and general malaise. Laboratory data showed elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). She was admitted to the hospital with a diagnosis of grade 3 liver dysfunction. We supposed the cause of this liver dysfunction to be a drug-induced liver injury associated with UFT + Uzel, and administered drugs to the patient for liver protection. With time, the symptoms and elevation of AST, ALT and ALP recovered to the normal level. This case was diagnosed as drug-induced allergic liver injury by UFT, because the result of the drug lymphocyte stimulate test (DLST) was positive.
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PMID:[Drug-induced liver injury associated with uracil/tegafur + folinate therapy]. 1992 Mar 97

The prognosis of liver cancer remains poor, but recent advances in nanotechnology offer promising possibilities for cancer treatment. Novel adjuvant, amphiphilic nanoparticles (NPs) composed of L: -phenylalanine (Phe)-conjugated poly(gamma-glutamic acid) (gamma-PGA-Phe NPs) having excellent capacity for carrying peptides, were found to have the potential for use as a peptide vaccine against tumor models overexpressing artificial antigens, such as ovalbumin (OVA). However, the anti-tumor potential of gamma-PGA-Phe NPs vaccines using much less immunogenic tumor-associated antigen (TAA)-derived peptide needs to be clarified. In this study, we evaluated the effectiveness of immunization with EphA2, recently identified TAA, derived peptide-immobilized gamma-PGA-Phe NPs (Eph-NPs) against mouse liver tumor of MC38 cells (EphA2-positive colon cancer cells). Immunization of normal mice with Eph-NPs resulted in generation of EphA2-specific type-1 CD8+ T cells. Immunization with Eph-NPs tended to provide a degree of anti-MC38 liver tumor protection more than that observed for immunization with the mixture of EphA2-derived peptide and complete Freund's adjuvant (Eph + CFA). Neither Eph-NPs nor Eph + CFA vaccines inhibited tumor growth of BL6, EphA2-negative melanoma cells. Splenocytes isolated from MC38-bearing mice treated with Eph-NPs showed strong and specific cytotoxic activity against MC38 cells. Immunization with Eph + CFA induced liver damage as evidenced by elevation of serum alanine aminotransferase, while Eph-NPs vaccination did not exhibit any toxic damage to the liver. These results demonstrated that immunization with Eph-NPs displayed anti-tumor effects against liver tumor by generating acquired immunity equivalent to the toxic adjuvant CFA, suggesting that safe gamma-PGA-Phe NPs could be applied clinically for the vaccine treatment of liver cancer.
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PMID:EphA2-derived peptide vaccine with amphiphilic poly(gamma-glutamic acid) nanoparticles elicits an anti-tumor effect against mouse liver tumor. 1994 47

Regular consumption of fruits and vegetables is associated with reduced risks of certain cancers and other diseases in observational studies and animal models of human diseases. The aim of the present study was to investigate whether feeding of rats with whole raw apple has potentially chemopreventive properties by affecting markers of colon cancer. The end-point was preneoplastic changes in the colon known as aberrant crypt foci (ACF). Rats initiated with the colon carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) were given 0, 5, or 10 g apple/day for 13 wk. The group fed 5 g apple but not 10 g had a significantly lower number of ACF (P = 0.009) compared to the initiated control. DNA damage evaluated by the comet assay was significantly increased in leucocytes of DMH-treated animals (P = 0.021). No antigenotoxic effect of apple feeding was apparent in the colon. Apple feeding tended to lower DNA damage in the liver (P = 0.136 in DMH-initiated and P = 0.284 in noninitiated rats). Liver alanine aminotransferase was significantly increased in rats fed apples (P = 0.008 in DMH-initiated and P = 0.019 in noninitiated rats). In conclusion, feeding whole fresh apple may affect the occurrence of preneoplastic changes in the rat colon, but the effect was not gradual.
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PMID:The effect of apple feeding on markers of colon carcinogenesis. 2143 24

After extensive literature review utilizing PubMed and Medline searches, we present a rare case of oxaliplatin-induced grade 3/4 hepatocellular injury and ototoxicity. The patient is a 46-year-old female diagnosed with stage IIIC (pT3N2bM0) adenocarcinoma of the sigmoid colon. PET/CT prior to surgery and chemotherapy was negative for distant metastatic disease and baseline liver-associated enzymes were within normal limits. Following sigmoidectomy, patient began adjuvant chemotherapy with 5-florouracil, leucovorin, and oxaliplatin (mFOLFOX-6). Cycle 1 was complicated only by refractory nausea. However, cycle 2 was complicated by vertigo with refractory nausea, tinnitus, and marked elevation in liver enzymes in a hepatocellular pattern. Extensive workup was negative and the etiology of her symptoms and grade 3/4 hepatocellular injury was hypothesized to be the result of oxaliplatin. Aspartate aminotransferase and alanine aminotransferase decreased after two additional weeks off therapy and during cycle 3 in which oxaliplatin was held. She had no evidence of 5-florouracil toxicity. On cycle 4, oxaliplatin was restarted at 50% dose; symptoms and liver-associated enzymes remained stable. However, oxaliplatin was increased up to 75% full dose for cycle 5 with reported vertigo, tinnitus, nausea, and return of elevation in liver-associated enzymes. Oxaliplatin is a chemotherapy agent widely used in the treatment of many malignancies including colon cancer. Side effects include peripheral neuropathy, gastrointestinal toxicity, neutropenia, grade 1/2 hepatocellular injury, and hepatic vascular lesions. However, grade 3/4 hepatocellular injury and ototoxicity are extremely rare with the administration of oxaliplatin. Therefore, we present the unusual chemotherapy side effects.
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PMID:Oxaliplatin-induced hepatocellular injury and ototoxicity: a review of the literature and report of unusual side effects of a commonly used chemotherapeutic agent. 2233 69

Abnormal liver biochemical tests are present in up to 30% of patients with inflammatory bowel disease (IBD), and therefore become a diagnostic challenge. Liver and biliary tract diseases are common extraintestinal manifestations for both Crohn's disease and ulcerative colitis (UC), and typically do not correlate with intestinal activity. Primary sclerosing cholangitis (PSC) is the most common hepatobiliary manifestation of IBD, and is more prevalent in UC. Approximately 5% of patients with UC develop PSC, with the prevalence reaching up to 90%. Cholangiocarcinoma and colon cancer risks are increased in these patients. Less common disorders include autoimmune hepatitis/PSC overlap syndrome, IgG4-associated cholangiopathy, primary biliary cirrhosis, hepatic amyloidosis, granulomatous hepatitis, cholelithiasis, portal vein thrombosis, liver abscess, and non-alcoholic fatty liver disease. Hepatitis B reactivation during immunosuppressive therapy is a major concern, with screening and vaccination being recommended in serologically negative cases for patients with IBD. Reactivation prophylaxis with entecavir or tenofovir for 6 to 12 mo after the end of immunosuppressive therapy is mandatory in patients showing as hepatitis B surface antigen (HBsAg) positive, independently from viral load. HBsAg negative and anti-HBc positive patients, with or without anti-HBs, should be closely monitored, measuring alanine aminotransferase and hepatitis B virus DNA within 12 mo after the end of therapy, and should be treated if the viral load increases. On the other hand, immunosuppressive therapy does not seem to promote reactivation of hepatitis C, and hepatitis C antiviral treatment does not influence IBD natural history either. Most of the drugs used for IBD treatment may induce hepatotoxicity, although the incidence of serious adverse events is low. Abnormalities in liver biochemical tests associated with aminosalicylates are uncommon and are usually not clinically relevant. Methotrexate-related hepatotoxicity has been described in 14% of patients with IBD, in a dose-dependent manner. Liver biopsy is not routinely recommended. Biologics-related hepatotoxicity is rare, but has been shown most frequently in patients treated with infliximab. Thiopurines have been associated with veno-occlusive disease, regenerative nodular hyperplasia, and liver peliosis. Routine liver biochemical tests are recommended, especially during the first month of treatment. All these conditions should be considered in IBD patients with clinical or biochemical features suggestive of hepatobiliary involvement. Diagnosis and management of these disorders usually involve hepatologists and gastroenterologists due to its complexity.
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PMID:Hepatobiliary manifestations in inflammatory bowel disease: the gut, the drugs and the liver. 2425 64


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