PURPOSE: This study was designed to investigate effect of the etoposide on expression of cell cycle regulatory proteins and apoptosis-related proteins in human skin fibroblast (HSF). MATERIALS AND METHODS: HSF cells were treated with etoposide. After treatment, expression patterns of cell cycle regulatory proteins and apoptosis-related proteins were analyzed by using Immunoprecipitation-Western blot method and RT-PCR. RESULTS: Immediately after etoposide treatment, E2F-1 was up- regulated following MDM2 down-regulation. After E2F-1 up-regulation, p53 and p21WAF1 level was markedly increased without or with mRNA up-regulation, respectively. Consistent with these results, cell cycles arrested in mainly G1 phase 24 hr after etoposide treatment. However, HSF cells progressed into apoptosis 72 hr after etoposide treatment. In this process, caspase-3 activation and Bax up-regulation were observed. CONCLUSION: In early response of etoposide treatment, E2F-1 plays an important role in p53 accumulation through MDM2 down- regulation. The increased p53 induce an increase of p21WAF1 level through p21WAF1 mRNA up-regulation. However, after long term treatment of etoposide, HSF cells resulted in apoptotic cell death through caspase-3 activation and Bax up-regulation.
Apoptosis ; Caspase 3 ; Cell Cycle Proteins ; Cell Cycle* ; Cell Death ; Down-Regulation ; Etoposide ; Fibroblasts* ; G1 Phase ; Genes, p53 ; Humans* ; RNA, Messenger ; Skin* ; Up-Regulation

Cancer is considered to occur through abnormal growth and differentiation processes, in which oncogenes and tumor suppressor genes are deeply related. Cellular responses to DNA-damaging agents are believed to be critical determinants of human tumorigenesis. Cell cycle arrests and DNA repair following DNA damage require the coordination of multiple gene products that, as a whole, serve to maintain the integrity of the genome. Within the cell cycle, both G1-S and G2-M phase transitions are under constant surveillance by checkpoint genes for the protection of cells from either exogenous or endogenous DNA-damaging agents. p53 tumor suppressor gene mediates cell cycle perturbations in response to DNA damage, and play a role in cell death, genetic stability, and cancer susceptibility. Recently, gene therapy with p53 tumor suppressor gene is expected as a new effective therapeutic strategy in many kinds of cancer. By using retroviral vector system, we transduced p53 tumor suppressor gene into human osteosarcoma cells, and analysed its growth suppression and apoptosis inducing effects. Combined effects of p53 gene therapy with chemotherapeutic agent or radiation were also analysed. Titer of ecotrophic p53 retrovirus was 5.0x10/ml, and that of amphotrophic p53 retrovirus was 2.0x10/ml when NIH3T3 cells were used as target cells. Human osteosarcoma cells infected with amphotrophic p53 retroviruses showed increased p21waf1 gene expression, which acts as a major cyclin-dependent kinase inhibitor in DNA damage responses. In normal DMEM media, human skin fibroblasts infected with amphotrophic p53wt retroviruses showed very slow growing (1.7 fold increase in doubling time) and very low saturation density (50% decrease in cell density). In media containing chemotherapeutic agent, human osteosarcoma cells infected with p53wt retroviruses died rapidly; 75% of them died within 4 days and all of them died within 10 days of incubation with chemotherapeutic agent. Their DNAs were extracted and electrophoresed in agarose gel, and we identified DNA ladders characteristic of apoptotic cell death. When human osteosarcoma cells infected with p53 retroviruses were irradiated with ultraviolet light, more than 95% of cancer cells died within 1 day; whereas mock infected cells showed only less than 5% of cell death. These findings suggest that retroviral vector mediated p53 tumor suppressor gene transfer into cancer cells can suppress tumor cell growth and decrease tumor cell density effectively. These findings also suggest that effective induction of tumor cell apoptosis can be obtained when p53 gene therapy is used in combination with chemotherapy or radiotherapy.
Apoptosis ; Carcinogenesis ; Cell Count ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Death ; DNA ; DNA Damage ; DNA Repair ; Drug Therapy ; Fibroblasts ; Gene Expression ; Genes, p53 ; Genes, Tumor Suppressor* ; Genetic Therapy* ; Genome ; Humans ; Oncogenes ; Osteosarcoma ; Phase Transition ; Phosphotransferases ; Radiotherapy ; Retroviridae* ; Sepharose ; Skin ; Ultraviolet Rays ; Zidovudine

Cholangiocarcinoma frequently metastasizes to several internal organs but rarely to the skin. We report a case of a cutaneous metastasis of cholangiocarcinoma in a 59-year-old female who had asymptomatic, firm, ulcerative nodules and papules on the scalp. She had been diagnosed with cholangiocarcinoma 3 years earlier, and histopathologic examination of the cutaneous lesion showed well differentiated tubular adenocarcinoma.
Adenocarcinoma ; Cholangiocarcinoma ; Female ; Humans ; Middle Aged ; Neoplasm Metastasis ; Scalp ; Skin ; Ulcer

PURPOSE: We analyzed the gene status of p16INK4A, p15INK4B and MTAP (methylthio adenosine phophorylase) in Korean hepatdegrees Cellular carcinoma (HCC) to investigate whether the inactivation of these genes participated in hepatdegrees Carcinogenesis, and evaluated MTAP-targeted chemotherapy in MTAP-deficient cell lines. MATERIAL AND METHODS: We examined eleven primary HCC and 8 SNU cell lines using PCR, Southern blot analysis, PCR-SSCP, DNA sequencing, methylation-specific PCR, Western blot analysis, MTT assay, and crystal violet staining. RESULTS: Mutations or deletion of the p16INK4A, 15INK4B, and MTAP genes were rare, but methylation of the p16INK4A promoter region was common in HCC. The base alterations of 3' untranslated region of p16INK4A exon 3 were also detected in 3 samples. In SNU cells, p16INK4A was not detectable, when treated with demethylating agent, high levels of re-expressed p16INK4A protein were detected. In MTAP-targeted chemotherapy experiment, methylthioadeno sine (MTA) was able to rescue MTAP positive cell lines but not MTAP negative cell lines from growth inhibition by depletion of methionine and MTX treatment. CONCLUSION: These results suggest that de novo methylation of the p16INK4A promoter region seems to play an important role in the pathogenesis of HCC. And treatment of MTX, combined with methionine depletion in the presence of MTA, may be a high selective treatment for MTAP negative HCC.
3' Untranslated Regions ; Adenosine ; Blotting, Southern ; Blotting, Western ; Carcinogenesis ; Cell Line ; Cyclin-Dependent Kinase Inhibitor p16 ; Drug Therapy ; Exons ; Gentian Violet ; Methionine ; Methylation ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Sequence Analysis, DNA ; Pemetrexed

Fluorescein has been used for decades in ophthalmology for fluorescence angiography and it is the only fluorophore routinely used in experimental dermatology for in vivo study of the skin. It absorbs blue light, with peak absorption and excitation wavelengths between 465 and 490 nm and fluoresces at yellow-green wavelengths of 520~530 nm. The most common side effects are nausea and vomiting, and other adverse events such as a vasovagal response, cardiac or respiratory effects, neurologic manifestations or allergy, including anaphylaxis, were also reported. But a photosensitive reaction to fluorescein is very rare. We report here on a case of photoallergic dermatitis due to fluorescein after fluorescence angiography.
Absorption ; Anaphylaxis ; Dermatitis, Photoallergic ; Dermatology ; Fluorescein ; Fluorescein Angiography ; Hypersensitivity ; Light ; Nausea ; Neurologic Manifestations ; Ophthalmology ; Skin ; Vomiting

Hyperacute or acute accelerated rejection caused by preformed antibody in sensitized patients resulted in increased waiting period and complicated posttransplant hospital course. Intravenous immunoglobulin (IVIG) has known to have anti cytotoxic effect by blocking the anti HLA antibody. PURPOSE: We investigated the effect of IVIG on hyperacute and acclerated rejection of the heart graft in the presensitized rat. METHODS: Recipients (Wistar) were sensitized from repeated allo (Lewis) skin graft and followed by heterotopic allo cardiac transplantation. A guinea pig was used for the xenotransplantation model. IVIG (Green Cross kappa, 400 mg/kg in allotransplantation, 800 mg/kg in xenotransplantation) was given just before heart transplantation. Graft survival and donor specific IgG, IgM and complement were measured. RESULTS: Graft survival was 7.2 days in non sensitized allogenic heart transplantation (n=9), 1.3 days in sensitized allogenic recipients (n=7). Graft survival was prolonged from 1.3 days to 4.4 days with IVIG treatment (n=5). As for xenogenic transplantation, graft survival was prolonged from 30 min to 7.4 hr with IVIG treatment (n=5). Donor specific IgG and IgM and complement increment were blocked by IVIG during the IVIG treatment. Donor specific IgG and Ig M and complement were increased after the cessation of IVIG treatment. CONCLUSION: IVIG was able to prolong the graft survival of the sensitized allograft and xenograft. Suppression of the donor specific IgG, IgM and complement might be one of the underlying mechanisms. A further studies have to follow to clarify the more detailed mechanism.
Allografts ; Animals ; Complement System Proteins ; Graft Survival ; Guinea Pigs ; Heart Transplantation* ; Heart* ; Heterografts ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulins* ; Immunoglobulins, Intravenous ; Rats* ; Skin ; Tissue Donors ; Transplantation, Heterologous ; Transplants

A 40-year-old male had a history of tinea pedis, which had been treated with itraconazole. One week later fever and pruritic, multiple, symmetric, erythematous papules developed, some of which became confluent, producing plaques on his face, trunk, and limbs. The skin biopsy showed subcorneal and spongiform pustules. One month later we had patch tests with itraconazole and other drugs. The result of the patch test using itraconazole was a (++) reaction that showed erythematous macules, papulovesicles and patch (after 48 hours). So, we report here a rare case of acute generalized exanthematous pustulosis (AGEP) that manifests as generalized erythema, erythema multiforme and amicrobial pustules with fever due to itraconazole.
Acute Generalized Exanthematous Pustulosis ; Adult ; Biopsy ; Erythema ; Erythema Multiforme ; Extremities ; Fever ; Humans ; Itraconazole ; Male ; Patch Tests ; Skin ; Tinea Pedis

OBJECTIVETo investigate the association between M235T variant of angiotensinogen (AGT) gene and the blood pressure response to benazepril in a hypertensive cohort.

METHODSBenazepril (10-20 mg/day) was administered for 6 weeks to 251 essential hypertensives. Polymerase chain reaction (PCR) combined with restriction enzyme digestion was used to detect the polymorphism and the patients were classified as MM, MT or TT genotype. The changes in systolic and diastolic blood pressure (SBP and DBP) were analyzed for association with genotypes at the AGT gene locus.

RESULTSThe MM genotype was observed in 23 patients (9.2%), the MT genotype in 104 patients (41.4%) and the TT genotype in 124 patients (49.4%). There was no association between these polymorphisms and the blood pressure responses in the total 251 patients. But based on the analysis stratified by age, the association between these polymorphism and the DBP responses was found in the old patients (> or = 60 years old) subgroup, the reduction in DBP was significantly greater in patients carrying the MM compared to MT or TT genotypes (14.8 +/- 4.8 mm Hg vs. 7.9 +/- 7.7 mm Hg or 9.8 +/- 6.4 mm Hg respectively; ANOVA, P = 0.034).

CONCLUSIONThe M235T polymorphism of the AGT gene was shown to influence the responses to benazepril in old hypertensive patients (> or = 60 years old). Thus, specific genotypes might predict the response to specific antihypertensive treatment.

Aged ; Angiotensinogen ; genetics ; Antihypertensive Agents ; therapeutic use ; Benzazepines ; therapeutic use ; Female ; Genotype ; Humans ; Hypertension ; drug therapy ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

Both duodenal ulcer and gastric cancer are common, and it is well known that the pathophysiology of the two is different. The presence of a duodenal ulcer is believed to protect against the development of a gastric malignancy. However gastric cancer may occur in the presence of active or chronic duodenal ulcer disease. Although rare in incidence of coexistence of duodenal ulcer and gastric cancer, physician must be alert to the strange association of duodenal ulcer and gastric cancer. Here, we present 3 cases with coexistence of duodenal ulcer and gastric cancer, diagnosed by endoscopy.
Duodenal Ulcer* ; Endoscopy ; Incidence ; Stomach Neoplasms*

Tinea cruris is a superficial dermatophyte infection of the groin. It is the second most common dermatophytosis. Scrotal dermatophystosis develops in low frequency in spite of extensive infection in nearby sites such as groin and thigh. The lesions are usually finely scaly and faint erythematous patch. In our case, the patient presented with erythematous lichenified plaques on the scrotum and groin. It was definitely diagnosed as dermatophytosis caused by Trichophyton rubrum. Although scrotal fungal infection is rare, dermatophyte infection should be suspected in cases with scaly lesions on the scrotum.
Arthrodermataceae ; Groin ; Humans ; Scrotum ; Thigh ; Tinea ; Trichophyton