Expression of programmed death ligand-1 and programmed death 1 in hepatocellular carcinoma and its clinical significance.

OBJECTIVE: To investigate the correlation between the expression of programmed death 1 (PD-1) and PD ligand-1 (PD-L1) in hepatocellular carcinoma (HCC) and clinical parameters. MATERIALS AND METHODS: The study comprised tumor sections from 45 HCC patients treated with curative resection, which were evaluated for PD-1 and PD-L1 protein expression by immunohistochemistry. RESULTS: PD-1 and PD-L1 expression was increased in cancers compared to adjacent normal tissues, with a positive rate of 37.78% (17/45) and 62.22% (28/45), respectively, which was positively correlated with the tumor stage and lymph node metastasis, negatively with postoperative prognosis. PD-1 positivity was most frequently observed in stromal tumor-infiltrating lymphocytes. The number of PD-1 positive lymphocyte was correlated with PD-L1 positive expression. CONCLUSION: PD-L1 and PD-1 are overexpressed in HCC tissues. PD-L1 expression plays a critical role in the pathogenesis of human HCC, suggesting that it might be used as a new biomarker to predict the disease progression and prognosis.

Effects of diphenylhydantoin on killer cell activity and other immunological functions. A sequential study including the interaction of Corynebacterium parvum in melanoma patients.

The effects of a single Phenytoin dose, given to patients with malignant melanoma, upon peripheral blood counts, serum immunoglobulins, lymphocyte subpopulations and lymphocytotoxicity (using Chang target cells) were recorded. Sequential blood samples were taken before and 10, 14, 34, 38 and 58 h after the Phenytoin. Early reductions (P less than 0.05) in lymphocyte count, NK, K and PHA induced cytotoxicity, when compared with initial, pre-Phenytoin values were noted. Immunisation with i.v. C. parvum prevented the reductions occurring after a second dose of Phenytoin. Indeed, significant increases above the values of samples taken immediately before the second dose, were observed in T cells, PHA blastogenesis, NK and K cell Cytotoxicity. The second dose did however cause some immunosuppression; the increase in T cells, NK and PHA induced cytotoxicity above initial values expected from previous investigations were not observed. The immunosuppression, particularly of killer cell function, occurring after phenytoin could have implications for the pathogenesis of malignancy and transplacental carcinogenesis, reported as following Phenytoin exposure.

Moduretic-induced metabolic acidosis and hyperkalaemia.

A patient who developed significant metabolic acidosis and severe hyperkalaemia while taking Moduretic (amiloride and hydrochlorothiazide) is reported. During the period of hyperkalaemia (maximum potassium 7-6 mmol/l) the patient's whole body potassium content was normal. His acid-base balance and serum potassium returned to normal some 10 days after stopping the drug. The possible mechanism of acidosis and hyperkalaemia in this patient is discussed.

Dantrolene and lymphocytic lymphoma.

A patient is reported who was on prolonged treatment with dantrolene for spastic paraplegia; he developed a malignant lymphoma which led to his death.

Lack of effect of immunotherapy with BCG and Corynebacterium parvum on hepatic drug hydroxylation in man.

Serial serum diphenylhydantoin and urinary 5-(p-hydroxphenyl)-5-phenylhydantoin concentrations were determined in 8 patients with malignant disease and 4 healthy volunteers on 2 separate occasions after an oral dose of diphenylhydantoin (500 mg). No significant difference was observed between metabolism before and 10 days after immunization with BCG or Corynebacterium parvum. Volunteers without intervening immunization similarly showed no difference.