Experimental study was done to investigate the effect of combination therapy of recombinant interferon alpha-2a (IFN-alpha) and 13-cis-retinoic acid(13cRA) or all-transretinoic acid(TRA) on the in vitro and in vivo proliferation of human renal carcinoma cell line(CURC-2). 13cRA inhibited the in vitro proliferation of CURC-2 significantly at tolerable serum concentration in human(0.000001mole) and IC50 of 13cRA was found to be about 0.000003 mole. TRA did not inhibit the in vitro proliferation of CURC-2 significantly at tolerable serum concentration and IC50 of TRA was found to be too high(0.00003mole) to be administered in vivo. IFN-alpha inhibited in vitro proliferation of CURC-2 significantly with IC50 of about 500 unit/ml. Combined administration of low concentration of IFN-alpha(300 unit/ml) and 13cRA (0.000001mole) showed significant synergistic antiproliferative effect (79%, p<0.01 ) compared to single administration of IFN-alpha(29%) and 13cRA(29%). Combined administration of IFN-alpha and TRA showed underadditive effect. Combined administration of IFN-alpha(50,000 unit s.c./mouse/day) and 13cRA (0.5 mg p.o./mouse/day) to nude mouse significantly decreased the incidence(p<0.05) and tumor weight(p<0.001) of subcutaneously implanted CURC-2 cells and showed significant synergistic effect(p<0.05) compared to 13cRA or IFN-alpha single administration. 13cRA-administered animals did not show toxic sign of hypervitaminosis A. These results suggest that IFN-alpha and 13cRA show significant synergistic antiproliferative effect both in vitro and in vivo on human renal carcinoma cells and that combination therapy of IFN-alpha and 13cRA may become effective and safe adjuvant therapy for renal cell carcinoma. Based on the results of this study, clinical trials of combination therapy of IFN-alpha and 13cRA are ongoing in patients with renal cell carcinoma.
Animals ; Carcinoma, Renal Cell* ; Humans ; Hypervitaminosis A ; Inhibitory Concentration 50 ; Interferon-alpha* ; Interferons* ; Mice ; Mice, Nude ; Tretinoin*

Vitamin D deficiency rickets became quite rare now-a-days and also more rare in incidence complicated by hypervitaminosis A which was found at Pusan Childrens Charity Hospital. This patient was 1 year old female who developed hypervitaminosis A during the vitamin therapy because of its misuse of vitamin D and A compounds. Also a brief review of the literature is done along with presentation of the case.
Busan ; Charities ; Child ; Female ; Humans ; Hypervitaminosis A ; Incidence ; Rickets ; Vitamin D ; Vitamin D Deficiency ; Vitamins

The influence of vitamin A acetate on the induction of bladder carcinogenesis by N-butyl-N-(4- hydroxybutyl) nitrosamine(BBN) was studied in male Wistar rats. Animals were divided into 4 groups : Group I and II received BBN and/or vitamin A acetate for 12 and 20 weeks. respectively. Group I and II were further divided into 3 subgroups : Subgroup a received BBN only, subgroup b BBN and vitamin A acetate in 100 IU per gram diet and subgroup c BBN and vitamin A acetate in 200 IU per gram diet, respectively. Group E received only vitamin A acetate and Group IV only basal diet. Animals were killed at 20 weeks after first carcinogen exposure and bladder was examined by both light and electron microscopy. At the two dose levels. vitamin A acetate significantly reduced the incidence and extent of carcinoma in Group I, as well as in Group X Vitamin A acetate of lower and higher dosage were nearly same in the inhibitory effect of development of carcinoma. Vitamin A acetate did not reduce the incidence of papilloma, but reduced the extent of papilloma in group I significantly. Vitamin A acetate also reduced the incidence of high grade neoplasm and deeply invasive cancer. Hypervitaminosis A did not develop at both lower and higher dosage of vitamin A acetate. Cancer cells in animals which received both vitamin A acetate and BShl often showed cytolysis, pyknosis and disruption of cellular membrane. The present findings indicate that vitamin A acetate inhibits or delays the development of bladder carcinoma without significant toxicity.
Animals ; Carcinogenesis* ; Diet ; Humans ; Hypervitaminosis A ; Incidence ; Male ; Membranes ; Microscopy, Electron ; Papilloma ; Rats* ; Rats, Wistar ; Urinary Bladder Neoplasms ; Urinary Bladder* ; Vitamin A* ; Vitamins*

To elucidate the early sequential morphogenetic progress of exencephaly and myeloschisis, rat embryos whose mothers had been treated with hypervitaminosis A were studied at 1-day interval from gestation day 10.5 to 15.5. In exposed animals sequential change was found in both exencephaly and myeloschisis as the embryos grew up. The 10.5-day old exencephalic embryos had still widely open cephalic neural tubes. Exencephalic embryos older than 13.5 days of gestation showed strikingly severe eversion and overgrowth of the cephalic neuroepithelium, thus failed in forming normal primitive brain. The convex dorsal surface of the exencephaly was covered with ependyma, which was connected directly with surrounding surface eqithelium at the periphery. The earliest morphologically recognized myeloschisis was in the 13.5-day old embryos. In myeloschisis, divergence at the roof plate and eversion of the spinal neural tube, disorganized overgrowth of the neuroepithelium, malformed and misplaced spinal ganglia and nerve roots, and absence of the neural arch and dermal covering were characteristic. It is suggested that exencephaly results from failure of the cephalic neural tube closure which is followed by eversion and overgrowth of the neuroepithelium. And failure in closure of the posterior neuropore and disturbance in the development of the tail bud probably play major role in the morphogenesis of myeloschisis.
Animals ; *Embryonic and Fetal Development ; Female ; Hypervitaminosis A ; Neural Tube Defects/chemically induced/*pathology ; Pregnancy ; Rats ; Rats, Inbred Strains ; Spinal Cord/*abnormalities/embryology