Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolizing enzyme, is induced under various pathological conditions, including viral and bacterial infection, allograft rejection, cerebral ischemia, and tumor growth. We have previously reported that the expression of IDO mRNA was increased in some clinical cases of hepatocellular carcinoma in which the recurrence-free survival rate in these IDO-positive patients was significantly higher than that in patients without IDO mRNA induction in tumors. Additionally, IDO expressed in tumors was localized not to the tumor cells but instead to tumor-infiltrating cells by immunohistochemistry. In this study, in order to elucidate the mechanisms underlying anti-tumor effect of IDO, we investigated whether IDO inhibitor (1-methyl-dl-tryptophan, 1MT) affects the growth of subcutaneous B16 tumors in mice. Subsequently, the activity of natural killer (NK) cells was investigated under the conditions of inhibited IDO activity in vivo and in vitro. IDO mRNA expression of B16 cells, B16 subcutaneous tumor, sprenocytes of mice, and human NK cells were studied by reverse transcription-polymerase chain reaction. B16 subcutaneous tumor growth with or without IDO inhibition was observed and cytotoxic activity of NK cells were investigated under the conditions of inhibited IDO activity in vivo and in vitro. IDO mRNA was expressed in B16 subcutaneous tumor, splenocytes of tumor bearing mice, co-cultured splenocytes with B16, and human NK cells. On day 14, after injection of B16 melanoma cells, the sizes of tumors in IDO-inhibited mice were significantly larger than those in control mice. The cytotoxic activity of mice NK cells was reduced by IDO inhibition in vivo. In vitro inhibition of IDO, NK activity was reduced in dose-dependent manner of 1MT. In conclusion, these results indicated that IDO plays an important role in anti-tumor immunity by regulating cytotoxic activity of NK cells.
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PMID:Inhibition of indoleamine 2,3-dioxygenase suppresses NK cell activity and accelerates tumor growth. 1467 22

Bacterial infection may adversely affect the hemostasis of patients with gastroesophageal variceal bleeding (GEVB). Antibiotic prophylaxis can prevent bacterial infection in such patients, but its role in preventing rebleeding is unclear. Over a 25-month period, patients with acute GEVB but without evidence of bacterial infection were randomized to receive prophylactic antibiotics (ofloxacin 200 mg i.v. q12h for 2 days followed by oral ofloxacin 200 mg q12h for 5 days) or receive antibiotics only when infection became evident (on-demand group). Endoscopic therapy for the GEVB was performed immediately after infection work-up and randomization. Fifty-nine patients in the prophylactic group and 61 patients in the on-demand group were analyzed. Clinical and endoscopic characteristics of the gastroesophageal varices, time to endoscopic treatment, and period of follow-up were not different between the two groups. Antibiotic prophylaxis decreased infections (2/59 vs. 16/61; P <.002). The actuarial probability of rebleeding was higher in patients without prophylactic antibiotics (P =.0029). The difference of rebleeding was mostly due to early rebleeding within 7 days (4/12 vs. 21/27, P =.0221). The relative hazard of rebleeding within 7 days was 5.078 (95% CI: 1.854-13.908, P <.0001). The multivariate Cox regression indicated bacterial infection (relative hazard: 3.85, 95% CI: 1.85-13.90) and association with hepatocellular carcinoma (relative hazard: 2.46, 95% CI: 1.30-4.63) as independent factors predictive of rebleeding. Blood transfusion for rebleeding was also reduced in the prophylactic group (1.40 +/- 0.89 vs. 2.81 +/- 2.29 units, P <.05). There was no difference in survival between the two groups. In conclusion, antibiotic prophylaxis can prevent infection and rebleeding as well as decrease the amount of blood transfused for patients with acute GEVB following endoscopic treatment.
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PMID:Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial. 1499 93

Rainbow trout (Onchorhynchus mikiss) possess two genes encoding putative leucine-rich repeat (LRR)-containing proteins similar to human TLR5. Molecular cloning of these two LRR proteins suggested the presence of a TLR5-like membrane form (rtTLR5M) and a soluble form (rtTLR5S). Here we elucidated the primary structures and the unique combinational functions of these fish versions of TLR5. The LRR regions of rtTLR5S and rtTLR5M exhibited 81% homology and relatively high (35.6 and 33.7%) homology to the extracellular domains of human TLR5 (huTLR5). Thus, two distinct genes encode the TLR5 orthologs in fish, one of which has a consensus intracellular domain (TIR). In order to test their functions, we constructed fusion proteins with the LRR region of rtTLR5S (S-chimera) or that of rtTLR5M and the TIR of huTLR5 (M-chimera). The S- and M-chimeras expressed in HeLa or CHO cells signaled the presence of Vibrio anguillarum flagellin, resulting in NF-kappaB activation. rtTLR5M was ubiquitously expressed, whereas rtTLR5S was predominantly expressed in the liver. In the hepatoma cell lines of the rainbow trout RTH-149, stimulation of rtTLR5M with V. anguillarum or its flagellin allowed the up-regulation of rtTLR5S. Flagellin-mediated NF-kappaB activation was more significant in the presence of or simultaneous expression of rtTLR5S. Therefore, a two-step flagellin response occurred for host defense against bacterial infection in fish: (a) flagellin first induced basal activation of NF-kappaB via membrane TLR5, facilitating the production of soluble TLR5 and minimal acute phase proteins, and (b) the inducible soluble TLR5 amplifies membrane TLR5-mediated cellular responses in a positive feedback fashion.
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PMID:Sensing bacterial flagellin by membrane and soluble orthologs of Toll-like receptor 5 in rainbow trout (Onchorhynchus mikiss). 1533 10

From an EST fragment of the rainbow trout that was predicted to contain leucine-rich repeats (LRR), we cloned the whole cDNA and identified a soluble form of TLR5 ortholog (rtTLR5S), which does not exist in the mouse and human. rtTLR5S was about 38% homologous to the extracellular domains of human (hu) and mouse (mo)TLR5, while rtTLR5S showed <25% homologous to those of other human or mouse TLRs. A chimera constructed of rtTLR5S and the intra-cellular TIR of huTLR5 expressed on HeLa cells signaled the presence of flagellin A and C from V. anguillarum, resulting in NF-kappaB activation. The mRNA of rtTLR5S was predominantly detected in the liver. The hepatoma cell line of the rainbow trout RTH149 that responded to flagellin, allowed to up-regulate rtTLR5S in response to V. anguillarum or its purified flagellin within 8 h. rtTLR5S, when co-expressed with membrane huTLR5 in HeLa cells, augmented huTLR5-mediated NF-kappaB activation in response to flagellin. These results, together with the genome information of the pufferfish Fugu (Fugu rubripes), suggest that in fish the soluble TLR5 is an acute-phase protein sensing bacterial infection via recognition of a variety of bacterial flagellins to augment NF-kappaB activation, and may be important for fish to survive from bacterial infection in the water.
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PMID:Fish soluble Toll-like receptor 5 (TLR5S) is an acute-phase protein with integral flagellin-recognition activity. 1570 48

Staphylococcus aureus is the leading cause of bacterial infection in liver transplant recipients. Preoperative nasal carriage of methicillin-resistant S. aureus (MRSA) is associated with a high risk of infection. We conducted a retrospective cohort study in order to identify independent risk factors for early-onset S. aureus infection after liver transplantation. Patients were screened preoperatively for methicillin-susceptible S. aureus (MSSA) and MRSA nasal carriage. Risk factor analysis was performed by univariate analysis followed by stepwise logistic regression. Of the 323 patients included, 63 (19.5%) patients developed S. aureus infection (36 MRSA, 27 MSSA) within 1 month of surgery. Variables significantly associated with infection in the univariate analysis were MRSA and MSSA nasal carriage, alcoholic cirrhosis, absence of hepatocellular carcinoma, decreased prothrombin ratio, and presence of ascites. In the multivariate analysis, MRSA carriage (odds ratio [OR]: 20.9, P < 0.0001), MSSA carriage (OR: 3.4, P = 0.0004), alcoholic cirrhosis (OR: 2.4, P = 0.01) and decreased prothrombin ratio (OR: 1.2, P = 0.01) were independent predictors of infection. Molecular typing showed that the infecting isolate was identical to the isolate from the nose in most patients. In conclusion, preoperative nasal carriage of MRSA and MSSA is an independent risk factor for S. aureus infection in liver transplant recipients. The infection is most often of endogenous origin. Alcoholic cirrhosis and the severity of liver failure are also associated with a high risk of infection.
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PMID:Risk factors for Staphylococcus aureus infection in liver transplant recipients. 1612 51

We have established a novel TCRalphabeta (TCRVbeta6)(+)CD4(-)CD8(-) T cell hybridoma designated B6HO3. When the B6HO3 cells were cocultured with bacterial-infected J774 macrophage-like cells, IFN-gamma production by B6HO3 cells was triggered through direct cell-cell contact with dying J774 cells infected with Listeria monocytogenes (LM), Shigella flexneri, or Salmonella typhimurium that expressed the type III secretion system, but not with intact J774 cells infected with heat-killed LM, nonhemolytic lysteriolysin O-deficient (Hly(-)) LM, plasmid-cured Shigella, or stationary-phase Salmonella. However, the triggering of B6HO3 cells for IFN-gamma production involved neither dying hepatoma cells infected with LM nor dying J774 cells caused by gliotoxin treatment or freeze thawing. Cycloheximide and Abs to H-2K(d), H-2D(d), Ia(d), CD1d, TCRVbeta6, and IL-12 did not inhibit the contact-dependent IFN-gamma response, indicating that this IFN-gamma response did not require de novo protein synthesis in bacterial-infected J774 cells and was TCR and IL-12 independent. Thus, in an as yet undefined way, B6HO3 hybridoma recognizes a specialized form of macrophage cell death resulting from bacterial infection and consequently produces IFN-gamma. Moreover, contact-dependent interaction of minor subsets of splenic alphabeta T cells, including NKT cells with dying LM-infected J774 and bone marrow-derived macrophage (BMM) cells, proved to provide an IFN-gamma-productive stimulus for these minor T cell populations, to which the parental T cell of the B6HO3 hybridoma appeared to belong. Unexpectedly, subsets of gammadelta T and NK cells similarly responded to dying LM-infected macrophage cells. These results propose that innate lymphocytes may possess a recognition system sensing macrophage cell "danger" resulting from bacterial infection.
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PMID:A novel functional T cell hybridoma recognizes macrophage cell death induced by bacteria: a possible role for innate lymphocytes in bacterial infection. 1675 4

The occurrence of complications marks a turn in the natural history of cirrhosis. The early management, the etiologic treatment of the subjacent disease, the methodological detection of hepatocarcinoma, the prophylaxis of digestive bleeding linked to portal hypertension, the control of ascite and prevention of hepato-renal syndrome allow to improve the prognosis of these patients. Moreover, bacterial infection represents one of the principal factor facilitating the occurrence of another complication. This is why any complication should be considered as secondary to bacterial infection until the refutation.
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PMID:[How to detect the complications of the cirrhosis?]. 1795 21

Liver transplantation with a part of the liver from a healthy living donor can be life saving for selected patients with end-stage liver failure. The experiences with the first 3 adult patients in the Netherlands were as follows. The first patient was a 56-year-old man with primary sclerosing cholangitis, who received half of the liver from his 53-year-old sister. Postoperatively, the donor developed a urinary tract infection, which was treated with antibiotics. The recipient developed fever and paralytic ileus 6 days after transplantation. Relaparotomy revealed minimal bile leakage from the cut surface of the liver, which was corrected with a suture. Three years after donation, both donor and recipient were doing well. The second patient was a 63-year-old man with hepatic cirrhosis due to hepatitis B, recurrent bleeding from varices, and hepatocellular carcinoma. The carcinoma was treated percutaneously with radiofrequency ablation. He was given a liver transplant from his 28-year-old son. The donor later developed transient ileus and mild liver function disorders. The recipient developed a bacterial infection of the ascites, which was treated with antibiotics, and later Candida-oesophagitis and a herpes simplex infection, which were also treated successfully. More than 2 years after donation and transplantation, both donor and recipient were in good condition. The third patient was a 42-year-old man with a chronic hepatitis B virus infection and 2 hepatocellular carcinomas. The donor was his 34-year-old sister-in-law. The recipient developed prolonged jaundice due to stenosis at the site of the bile duct anastomosis, for which a stent was placed. He was discharged in good condition but died 11 months later of cerebral metastases. One year after the procedure, the donor was doing well. The Rotterdam liver transplantation programme with living donors demonstrates that excellent results can be accomplished with minimal risk for the donor.
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PMID:[Liver transplantation with a living donor: the first 3 cases in Rotterdam]. 1849 25

Cardiac pacing often turns out to be the only effective treatment of severe, life-threatening arrhythmias. We performed 77 living-donor liver transplantations (LDLT) from 1999 to 2007. In these cases, three recipients experienced fatal arrhythmia and required temporary cardiac pacing during the perioperative period. The first case was a 68-year-old woman diagnosed with liver cirrhosis and hepatocellular carcinoma (HCC). Her Model for End-Stage Liver Disease (MELD) score was 34. We performed LDLT using a right lobe graft. She showed complete atrioventricular block with cardiac arrest at postoperative day (POD) 42 after a bacterial infection. We performed a resuscitation and instituted temporary cardiac pacing. However, she was dead at POD 43. Pathologic findings at autopsy showed a diffuse myocardial abscess, which caused the fatal arrhythmia. The second case was a 58-year-old man diagnosed with HCC and liver cirrhosis; his MELD score was 9. We performed LDLT using a right lobe graft. He showed atrial fibrillation after septic shock. He also showed sinus bradycardia with a cardiac arrest at POD 10. We performed resuscitation and emergent temporary pacing. He recovered and was alive without recurrence of arrhythmia or infection. The third case was a 58-year-old woman diagnosed with multiple HCC. During preoperative regular check-up, she was diagnosed to have cardiac hypertrophy and was started on beta-blockers as treatment for cardiac hypertrophy. However, severe bradycardia necessitated temporary cardiac pacing. LDLT was performed safely after implantation of a pacemaker. Early use of temporary cardiac pacing for severe arrhythmias may be effective to maintain the hemodynamic state in LDLT.
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PMID:Temporary cardiac pacing for fatal arrhythmia in living-donor liver transplantation: three case reports. 1892 69

Patients with chronic liver disease exhibit various cardiovascular and pulmonary complications. Hepatopulmonary syndrome results in dyspnea due to intrapulmonary arteriovenous shunting and ventilation-perfusion mismatch. Portopulmonary hypertension occurs in patients with portal hypertension. Intrathoracic portosystemic collateral vascular pathways develop in patients with portal hypertension to allow decompression of the portal vein into the systemic circulation. Hepatic hydrothorax may develop in patients with cirrhosis and ascites. Massive necrosis of the liver from any cause may be associated with acute hypoxic respiratory failure, necessitating ventilatory support. Bacterial infection is common in cirrhotic patients because of a compromised host defense system. Hepatocellular carcinoma may produce hematogenous lung metastases, intrathoracic lymph node metastases, direct intracardiac extension, and pulmonary embolism. Interferon therapy for treatment of chronic active hepatitis C may disturb cellular immune activation in some patients and contribute to the onset and progression of sarcoidosis. Awareness of the various thoracic manifestations in chronic liver disease can be helpful for making a differential diagnosis and planning proper management.
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PMID:Thoracic complications of liver cirrhosis: radiologic findings. 1944 18


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