Oncolytic herpes viral therapy is effective in the treatment of hepatocellular carcinoma cell lines

The rising incidence of hepatocellular carcinoma (HCC) in western countries, along with the poor prognosis offered by present-day treatment modalities, makes novel therapies for this disease necessary. Oncolytic herpes simplex viruses (HSV) are replication-competent viruses that are highly effective in the treatment of a wide variety of experimental models of human malignancies. This study seeks to investigate the effectiveness of oncolytic herpes viruses in the treatment of primary HCC cell lines. Sixteen commercially available human HCC cell lines were studied. G207 is an attenuated, replication-competent, oncolytic HSV engineered to selectively replicate within cancer cells. Cell lines were tested for viral sensitivity to G207 and their ability to support viral replication using standard cytotoxicity and viral replication assays. Eleven of 16 cell lines were moderately to highly sensitive to G207 viral oncolysis. HCC cell lines additionally demonstrated the ability to support viral replication in vitro with as high as 800-fold amplification of the administered viral dose observed. G207 is cytotoxic to, and efficiently replicates within, HCC cell lines in vitro. From these data, we suggest that oncolytic HSV therapy may have a role in the treatment of HCC, and in vivo studies are warranted. Presented in part at the 2005 American Hepato-Pancreato-Biliary Association Congress, Hollywood, Florida, April 14–17, 2005. Supported by grants R01CA75461 and R01CA72632 from the National Institutes of Health, and by grant MBC-99366 from the American Cancer Society (Yuman Fong).     

Cathodes for fuel cells using proton-conducting Li2SO4–Al2O3 electrolyte

The performances of three widely different cathode materials (Pt, strontium-doped lanthanum manganite (LSM), and NiO) have been compared for use with proton conducting Li₂SO₄–Al₂O₃ composite electrolyte, using H₂S–air and H₂–air fuel cells operating at 600 °C. Surface analysis and electrochemical techniques were used to characterize fresh and used electrode materials. Pt or LSM cathodes each became covered with Li₂SO₄ and Al₂O₃ and, as a consequence, the fuel cells showed poor performance. In contrast, the NiO cathode catalyst did not become covered with Li₂SO₄ and good fuel cell performance was achieved. Exceptionally good current densities of over 100 mA/cm² and power densities of over 30 mW/cm² were obtained for H₂S–air fuel cells having Mo–Ni–S anode catalysts. Slight agglomeration of NiO particles during fuel cell operation had only a minor effect on performance.     

Primary carcinoma of gallbladder in Yazd, Iran: A 14-year study (1992–2006)

Aim: To investigate the clinico‐pathological profile and stage of disease at presentation of patients with carcinoma of the gallbladder diagnosed during 1992–2006 in Iran. Methods: During this study period 34 consecutive patients with gallbladder carcinoma were identified using a pathology‐based tumor database. The data extracted for each study patient included their gender, age at diagnosis, signs and symptoms, presence of gallstones and histopathological pattern of the gallbladder carcinoma and the UICC/AJCC TNM staging system was used for labeling the stages of the disease. Results: The median age of the 34 patients studied was 69.50 with most between 61 and 70 years of age. The age range of the men was between 53 and 80 years with a median age of 71.50 years and that of the women was between 33 and 79 years with a median age of 68.50 years. The most common symptom was pain in the right hypochondrium. More women had gallstones (15/34) than men (3/10). Adenocarcinoma was the most common histopathological type (91.18%) with the commonest subtype being papillary (47.06%). Eighteen patients had stage IB and stage IIA (52.94%) carcinomas whereas stages IIB and III were observed in six (17.6%) and seven cases (20.6%), respectively. Only three cases (8.82%) were seen in stage IV. The follow up of gall bladder carcinoma (GBC) patients in this study ranged from 6 to 60 months. However, there was a progressive reduction of patients attending follow‐up oncology clinic, particularly by those who had stages III and IV of the disease. Conclusion: Most patients (52.94%) presented with early disease (stage IB and IIA) which carries a good prognosis. Early detection of GBC and a national consensus for the evidence‐based management of GBC in Iran should be the major components of a strategy aimed at improving therapeutic outcome.     

Urinary cyclic AMP response to bovine parathyroid hormone during treatment with neuroleptics

The urinary cyclic AMP response to bovine parathyroid hormone and urinary concentrating ability (max Uosm) after des-amino-D -arginine vasopressin were studies in nine volunteers and seven patients receiving long-term neuroleptic treatment. Max Uosm was lower in the patient group (770 ± 70 mosmol/kg) compared with the controls (948 ± 152 mosmol/kg) but the trend to a lower cAMP response to bovine PTH was not statistically significant. These results suggest that, although adenylate cyclase inhibition may contribute, other mechanisms are also important in the genesis of reduced uring concentrating ability in patients treated with psychotropic drugs.     

Portsite and intraabdominal metastases of unsuspected gallbladder carcinoma after laparoscopic cholecystectomy: Report of a case

We herein report a rare case of portsite metastasis of gallbladder carcinoma which occurred after laparoscopic cholecystectomy. A 64-year-old man underwent laparoscopic cholecystectomy at another hospital for symptomatic cholecystolithiasis. The histological examination revealed an adenocarcinoma of the gallbladder infiltrating the entire wall. Despite the physician's advice the patient refused any additional treatment. Thirteen months after surgery he visited our hospital because of a palpable mass at the scar of the right trocar incision. The nodule was removed and histological examination confirmed metastasis from the gallbladder carcinoma.     

Validation of silver-stained nucleolar organizer regions for evaluation of invasive character of urinary bladder carcinoma in rats and mice

A series of 8 rat and 16 mouse invasive bladder carcinomas were investigated for the presence of silverstained nucleolar organizer regions (AgNORs) to clarify whether this parameter is applicable to the estimation of their invasive character. With regard to number of AgNORs per cell, neither rat nor mouse carcinomas showed any difference between invasive and noninvasive sites within the same tumor. However, the frequency of cancer cells bearing bizarre dots, irregular in size and shape, was significantly higher at sites of actual invasion. Quantitative data generated using an image analyzer revealed significantly lower values for NOR roundness and significantly larger NOR size in invasive sites than in noninvasive sites in all groups. Double staining for the proliferation marker proliferating cell nuclear antigen (PCNA) and AgNORs was performed on eight rat carcinomas and a close correlation between the two was confirmed. Thus the number of AgNORs in PCNA-positive cells was significantly greater than in PCNA-negative cells. Furthermore, a particularly strong correlation was observed for incidences of PCNA-positive cells and bizarre dots (P<0.01). The quantitative data also demonstrated significant differences in size and shape of dots. It is concluded that AgNORs have diagnostic value for the invasive character of bladder carcinomas.     

A randomized placebo-controlled study of enalapril in the treatment of erythrocytosis after renal transplantation

BACKGROUND: Erythrocytosis is a common complication of renal transplantationwith an incidence of up to 17%. It is associated with an increasedrisk of complications due to thromboembolic events and has traditionallybeen treated by intermittent venesection. More recently, angiotensin-convertingenzyme inhibitors have been shown to cause a fall in haematocritin a number of groups of subjects and some uncontrolled studieshave shown these drugs to be of possible therapeutic benefitin post renal transplant erythrocytosis. METHODS: We performed a randomized double-blind placebo-controlled studyin 25 patients with post-transplant erythrocytosis. Subjectsreceived either 2.5 mg of enalapril daily or a placebo for 4months and all patients completed the study period without anyserious adverse effects. RESULTS: Haematocrit fell from 52.7 (±SEM 0.7) to 47.1 (±1.8) at 1 month and 46.1 (± 1.2) after 4 months in patientsreceiving enalapril, with no change in the placebo group (P=0.004).We did not demonstrate any change in serum erythropoietin ineither group. CONCLUSION: Angiotensin-converting enzyme inhibitors are a safe and effectiveform of treatment for erythrocytosis developing after renaltransplantation. The mechanism of action, however, is not mediatedby changes in erythropoietin production and remains uncertain.