amphotericin-b and Carcinoma--Hepatocellular

Pleurostomophora richardsiae is a dematiaceous mold that causes subcutaneous cystic phaeohyphomycosis. Few cases of invasive P richardsiae infection have been reported. Hepatic artery thrombosis following organ transplantation caused by a fungal organism is also very rare. We present here a 57-year-old man with refractory ascites and liver failure following liver transplantation for treatment of hepatocellular carcinoma. Abdominal computed tomography demonstrated total occlusion of hepatic artery and blood clot in the portal vein and inferior vena cava. P richardsiae was isolated from blood culture and the blood clot in his liver. The patient was treated successfully with a 4-week course of amphotericin B deoxycholate and liver retransplantation.

Topics: Abdomen; Amphotericin B; Antifungal Agents; Ascomycota; Carcinoma, Hepatocellular; Deoxycholic Acid; Drug Combinations; Hepatic Artery; Humans; Liver; Liver Neoplasms; Liver Transplantation; Male; Middle Aged; Phaeohyphomycosis; Portal Vein; Thrombosis; Tomography, X-Ray Computed; Treatment Outcome

We describe a case of a 62-year-old diabetic woman with hepatocellular carcinoma due to chronic hepatitis B virus infection. Two weeks after orthotopic liver transplantation, endoscopy for massive upper gastrointestinal bleeding revealed a large necrotic area in the gastric fundus. The patient underwent emergency resection. Histopathologically, angioinvasive mold infection compatible with mucormycosis was diagnosed in a large area of necrosis, mimicking an atypically localized gastric ulcer. Foreign bodies originating from transarterial chemoembolization (TACE) performed 7 and 8 months earlier and 40 days before transplantation were identified in the submucosal tissue. The patient was treated with liposomal amphotericin B (LAB) for 5 weeks, followed by 7 weeks of posaconazole. Follow-up biopsies after 1 and 5 months confirmed successful treatment. Review of the radiological images of the TACE procedure showed that some of the TACE material had been diverted to the stomach via an accessory gastric branch originating from the left hepatic artery. TACE agents may be associated with chronic, refractory gastroduodenal ulcers. We hypothesize that the ischemic lesion was first colonized with presumed Mucorales mold and invasive growth was promoted by the posttransplantation immunosuppression. Careful exploration of extrahepatic collaterals during TACE may prevent this complication.

Topics: Amphotericin B; Antifungal Agents; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Diabetes Complications; Female; Hepatitis B, Chronic; Histocytochemistry; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Neoplasms; Liver Transplantation; Microscopy; Middle Aged; Mucorales; Mucormycosis; Stomach Diseases; Triazoles

Alteration of the oxidative stress of hepatocellular carcinoma (HCC) cells can influence the expressions of genes favored angiogenesis. Quinone reductase 2 which can activate quinones leading to reactive oxygen species production is a melatonin receptor known as MT3. Prazosin prescribed for benign prostate hyperplasia and hypertension is a potent antagonist for MT3. This study was to investigate the influence of therapeutic concentrations of prazosin (0.01 and 0.1μM) on cell proliferation and differential expressions of CCL2, CCL20, CXCL6, CXCL10, IL8 and IL6 genes related to inflammation and/or oxidative stress in human HCC cell lines. Two HCC cell lines including one without susceptible to amphotericin B-induced oxidative stress (cell line A; HCC24/KMUH) and one with this effect (cell line B; HCC38/KMUH) were investigated by 0.01 and 0.1μM prazosin. The premixed WST-1 cell proliferation reagent was applied for proliferation assay. Differential expressions of genes were examined by quantitative reverse transcriptase-polymerase chain reaction. Our results showed that both 0.01 and 0.1μM prazosin did not influence cell proliferation in both cell lines. Both 0.01 and 0.1μM prazosin in cell line A and 0.01μM prazosin in cell line B did not cause differential expressions of tested genes. However, 0.1μM prazosin caused remarkable up-regulation of IL6 gene and slightly up-regulation of CCL2 gene in cell line B. In conclusion, high therapeutic concentration of prazosin can up-regulate angiogenic IL6 and CCL2 genes in human HCC cells susceptible to amphotericin B-induced oxidative stress. Clinical application of prazosin in patients with HCC should consider this possibility.

Topics: Amphotericin B; Carcinoma, Hepatocellular; Cell Culture Techniques; Cell Proliferation; Chemokine CCL2; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic; Humans; Interleukin-6; Liver Neoplasms; Neovascularization, Pathologic; Oxidative Stress; Prazosin; Reverse Transcriptase Polymerase Chain Reaction; Tetrazolium Salts; Up-Regulation

This study was to investigate whether melatonin (MLT) at pharmacologic concentrations (1 and 100 μM) had potential to influence the expressions of angiogenic (CCL2, CXCL6, IL8) and angiostatic (CXCL10) chemokine genes in two hepatocellular carcinoma (HCC) cell lines with different characteristics (cell line A, HCC24/KMUH, without susceptible to amphotericin B (AmB)-induced oxidative stress; cell line B, HCC38/KMUH, susceptible to AmB-induced oxidative stress). Differential expression of gene was investigated by quantitative reverse transcriptase-polymerase chain reaction. Two genes related to oxidative stress (SOD2, VNN3) were also studied. One and 100 μM MLT up-regulated CCL2, IL8 and CXCL10 genes in cell line A but down-regulated CCL2, CXCL6, IL8 and SOD2 genes in cell line B. CXCL10 gene was up-regulated by 1 and 100 μM MLT in both cell lines. SOD2 gene was down-regulated by 1 and 100 μM MLT only in cell line B. The magnitudes of gene expression fold changes of CCL2 and IL8 genes in cell line A and CCL2, CXCL6, IL8 and SOD2 genes in cell line B were similar between 1 and 100 μM MLT. The magnitudes of gene expression fold change of up-regulated CXCL10 gene in both cell lines were smaller in 100 μM MLT than in 1 μM MLT. In conclusion, the responses of angiogenic chemokine genes to MLT were mainly determined by the characteristics of cancer cells. The concentration of MLT may be the main determinant for the response of angiostatic CXCL10 gene to MLT. Clinical application of MLT in patients with HCC should consider these effects.

Topics: Amidohydrolases; Amphotericin B; Carcinoma, Hepatocellular; Cell Adhesion Molecules; Cell Line, Tumor; Chemokines; Coloring Agents; Down-Regulation; Gene Expression Regulation, Neoplastic; GPI-Linked Proteins; Humans; Liver Neoplasms; Melatonin; Oxidative Stress; Reverse Transcriptase Polymerase Chain Reaction; Superoxide Dismutase; Tetrazolium Salts; Thiazoles; Up-Regulation

Amphotericin B (AmB) has a discordant influence on epirubicin (4'-epidoxorubicin) cytotoxicity in hepatocellular carcinoma (HCC). This indicates that the cellular function of HCC may be significantly influenced by AmB. Whether the influence of AmB on HCC has any possibility to influence cancer growth has not been studied. This study was to try and clarify this issue.. Two HCC cell lines including one without augmentation of the epirubicin cytotoxicity by AmB (cell line A; HCC24/KMUH) and one with this effect (cell line B; HCC38/KMUH) were studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and whole human genome microarray (experimental group: 2.5 microg mL(-1) AmB).. Differential expressions of genes induced by AmB in two cell lines had no influence on cell proliferation as determined by MTT assay. Only cell line B showed up-regulation of genes related to oxidative stress, acute phase reaction, cytokine-cytokine receptor interaction and complement and coagulation cascades. Among the chemokine genes up-regulated by AmB, five genes (CCL2, CXCL1, CXCL5, CXCL6, IL8) were angiogenic. Cell line B also showed up-regulation of one angiogenic C10orf10 gene and down-regulation of one angiostatic chemokine gene (CXCL10). Up- or down-regulation of other genes in cell line A and B did not show any evidence to promote angiogenesis.. AmB has the capacity to concomitantly up-regulate angiogenic genes in HCC cells susceptible to AmB-induced oxidative stress.

Topics: Amphotericin B; Antifungal Agents; Carcinoma, Hepatocellular; Gene Expression Regulation, Neoplastic; Humans; Oxidative Stress; Reverse Transcriptase Polymerase Chain Reaction; Tumor Cells, Cultured; Up-Regulation

The purpose of this prospective study was to investigate whether amphotericin B (AmB) had any potential role in the systemic chemotherapy of primary hepatic malignancy using cancer cells collected by the authors' method of primary culture.. The specimens obtained by ultrasound-guided fine-needle aspiration biopsy (22 G) from 15 patients with hepatocellular carcinoma (HCC) and one with cholangiocarcinoma were plated into culture flask without disaggregation by trypsin-ethylenediamine tetra-acetic acid solution. Six patients with HCC and one patient with cholangiocarcinoma (7/16, 44%) had successful culture and the cancer cells at the 4th passage were continuously exposed to therapeutic ranges of epirubicin (0, 0.5, 1.0, 1.5, 2.0 microg/mL) with or without the combination of 2.5 microg/mL AmB for 24 h. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to evaluate the effects of the drugs. A human HCC cell line (HA 22T/VGH) was studied for comparison.. Addition of AmB showed no influence on epirubicin cytotoxicity in two patients (one partial resistant HCC and one epirubicin-sensitive cholangiocarcinoma; 25%), augmentation of the epirubicin cytotoxicity in two patients (one total resistant HCC, partial resistant HA 22T/VGH cell line and one epirubicin-sensitive HCC; 37.5%), and decrease of epirubicin cytotoxicity in the remaining three (one partial resistant and two epirubicin-sensitive HCC; 37.5%).. Amphotericin B has a discordant influence on epirubicin cytotoxicity in primary cultured hepatic malignant cells. Application of AmB in the systemic chemotherapy of primary hepatic malignancy should be limited to patients with positive AmB effect evaluated by an in vitro sensitivity test such as the present method.

Topics: Adult; Aged; Amphotericin B; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biopsy, Fine-Needle; Carcinoma, Hepatocellular; Cell Culture Techniques; Cell Proliferation; Cholangiocarcinoma; Drug Interactions; Drug Therapy, Combination; Epirubicin; Female; Follow-Up Studies; Humans; Liver Neoplasms; Male; Middle Aged; Prospective Studies; Treatment Outcome; Tumor Cells, Cultured

Infected graft transplantation is an unwelcome complication that may lead to serious consequences in the immunosuppressed host. It can be caused by infection of the donor or by contamination of the organ during harvest, preservation and handling, or at transplantation. With current donor evaluation protocols, the risk of transmitting infections by exogenous contaminated grafts seems to be more frequent than true donor-transmitted infections. Nevertheless, although rare and usually free of clinically significant sequelae, if contamination is by some virulent organisms such as Staphylococcus aureus, gram-negative bacilli, or fungi, severe complications may occur. We report the clinical outcome of liver, heart, and kidney recipients from a single donor. Both renal allografts had to be removed because of renal artery rupture secondary to Candida albicans infection. Careful donor evaluation before transplantation, unusually early presentation of mycosis leading to anastomotic renal artery disruption, the histopathologic findings of the grafts, and the absence of Candida infection in the liver and heart recipients make us believe that exogenous contamination of the grafts occurred during donor procedure, kidney processing, or at transplantation. In summary, because infected grafts can lead to serious complications, besides careful donor screening, it is important to achieve early recognition of contaminated organs by culturing the perfusate to start specific antibiotic or antifungal therapy after transplantation if necessary and avoid the rare but, in this case, fatal consequences of these infections.

Topics: Adolescent; Adult; Amphotericin B; Anastomosis, Surgical; Aneurysm, Ruptured; Antifungal Agents; Candidiasis; Carcinoma, Hepatocellular; Female; Heart Transplantation; Humans; Kidney Failure, Chronic; Kidney Transplantation; Liver Neoplasms; Liver Transplantation; Male; Middle Aged; Renal Artery; Reoperation; Tissue Donors; Ultrasonography

The effects of amphotericin B, ketoconazole, and adenine arabinoside on production of hepatitis B surface antigen (HBsAg) particles by the human hepatoma cell line PLC/PRF/5 were examined. In addition, the effects of these drugs on cellular protein synthesis were determined. These drugs caused a dose-dependent decrease in HBsAg production that was paralleled by a decrease in cellular protein synthesis. Ketoconazole was the most active of these drugs and the most specific, causing a 72% reduction in HBsAg production with only a 38% reduction in protein synthesis. These data suggest that further studies evaluating ketoconazole for the treatment of chronic hepatitis B virus infection in animals are warranted.

Topics: Amphotericin B; Antigens, Neoplasm; Antiviral Agents; Carcinoma, Hepatocellular; Cell Line; Depression, Chemical; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Hepatitis B; Hepatitis B Surface Antigens; Humans; Ketoconazole; Liver Neoplasms; Neoplasm Proteins; Vidarabine

Two clonal lines of rat hepatoma cells, in tissue culture, that have steroid-inducible tyrosine aminotransferase (TAT) activities were shown to have different responses to amphotericin B. One of the cell lines (HTC) was relatively resistant to the growth-inhibiting effects of amphotericin B and demonstrated an inhibition of only its steroid-inducible TAT activity when exposed to the antifungal agent. In contrast, not only was the other cell line (MHC) sensitive to amphotericin B during its growth, but uninduced and induced enzyme activities were affected. During the first few hours after the exposure of MHC cells to amphotericin B, both basal and dexamethasone-induced TAT activity were reduced; with continued exposure, enzyme activity increased over that of untreated cells and was superinduced in the presence of maximal, stimulating amounts of steroid. The mechanisms by which enzyme activity is induced by amphotericin B are probably different from those mediated by steroids.

Topics: Amphotericin B; Carcinoma, Hepatocellular; Cells, Cultured; Liver Neoplasms; Time Factors; Tyrosine Transaminase

Topics: Adrenal Glands; Agammaglobulinemia; Amphotericin B; Brain; Carcinoma; Carcinoma, Hepatocellular; Cryptococcosis; Cryptococcus; Diabetes Complications; Granuloma; Humans; Immunologic Deficiency Syndromes; Kidney Neoplasms; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged