No abstract available.
Thymidine

No abstract available.
Gastrointestinal Neoplasms* ; Thymidine Kinase* ; Thymidine*

No abstract available.
Clone Cells* ; Cloning, Organism* ; Thymidine*

Adenoviridae ; Humans ; Simplexvirus ; Thymidine Kinase

In a continuation of our studies to discover bioactive secondary metabolites from marine sources, we further investigated samples from a tryptamine and phenyl-alkane producing sponge, which resulted in the isolation of four uncommon small molecules and five nucleosides. Their structures were determined to be 7,8-dihydroimidazo[1,5-c]pyrimidin-5(6H)-one (1), 5-chlorocavernicolin (2), maleimide-5-oxime (3), 3-methylmaleimide-5-oxime (4), uridine (5), 2'-deoxyuridine (6), thymidine (7), adenine (8), and adenosine (9) by spectroscopic analyses. The isolated compounds were evaluated for inhibitory activity against soluble epoxide hydrolase (sEH) as well as the Wnt/beta-catenine signaling pathway.
Adenine ; Adenosine ; Nucleosides* ; Oximes* ; Porifera* ; Thymidine ; Uridine

BACKGROUND: Thymidine phosphorylase (TP) is an enzyme catalyzing the reversible phosphorolysis of thymidine to thymine and 2-deoxyribose-1-phosphate. TP plays a role in angiogenesis. Evidences suggest that infiltrating inflammatory cells adjacent cancer cells may affect tumor cell behavior. To evaluate each of these significances of TP expression in cancer cell and cancer-infiltrating inflammatory cells, we investigated TP expression patterns in cancer cells and infiltrating inflammatory cells adjacent cancer cells separately and the relationship between TP expression and angiogenesis or survival. METHODS: Immunohistochemistry assays were performed with anti-TP monoclonal antibody (Roche Japan) and anti-factor VIII polyclonal antibody (Dako) on 92 paraffin-embedded tissue samples from stomach cancer patients. A single pathologist scored the slides for percent positivity of tumor cells, intensity, localization and distribution of expression. TP reactivity in tumor cells (cancer) and infiltrating mononuclear cells adjacent cancer cells (matrix) was separately accessed. According to the pattern of TP expression, subjects were divided into 4 groups for further analysis: cancer(C;+)/matrix(M;+), cancer(+)/matrix(-), cancer(-)/matrix(+) and cancer(-)/matrix(-). With these 4 subsets of TP expression patterns, we evaluated cancer cell differentiation, intratumoral microvessel density, extent of tumor invasion, LN stage, and patient survival to find any differences among the subsets. RESULTS: Of 92 stomach cancer tissue, C/M(+/+), C/M(+/-), C/M(-/+), and C/M(-/-) were observed in 33patients, 19, 30, and 10, respectively. Microvessel density scores were higher in cancer(+)/matrix(-) group compared in cancer(-)/matrix(-) group (p=0.02). Of 4 TP expression subsets, other clinical factors such as histology, extent of tumor invasion, and LN metastasis were not associated with TP expression. CONCLUSION: This study suggested the TP in cancer-infiltrating inflammatory cell as well as cancer cells themselves may play an important role in angiogenesis as co-active factors in stomach cancer.
Cell Differentiation ; Humans ; Immunohistochemistry ; Microvessels ; Neoplasm Metastasis ; Prognosis* ; Stomach Neoplasms* ; Stomach* ; Thymidine Phosphorylase ; Thymidine* ; Thymine

OBJECTIVES: Angiogenesis is a critical factor in the progression of solid tumors, including cervical cancer. However, the association between the expression of thymidine phosphorylase(TP) and clinicopathological factors has scarcely been examined in cervical neoplasia. This study was performed to evaluate the level of TP expression in cervical intraepithelial neoplasia(CIN) and invasive cancer respectively, and to observe the relationship between expression of TP and various clinicopathological factors of cervical cancer. PATIENTS AND METHODS: Total 81 cervical biopsy specimens obtained from Jan. 1995 to Aug. 1996 at YUMC were evaluated for the expression of TP : among these, 9 were pathologically confirmed as benign, 6 as CIN I, 11 as CIN II, 12 as CIN III, and 43 as invasive squamous cell carcinoma(SCC) of uterine cervix. These specimens were immunostained to examine the expression of TP and the results of immunostaining were correlated with various clinicopathological factors of cervical cancer. RESULTS: TP expression progressively increased along a continuum from normal epithelium to invasive SCC(p<0.05) and TP expression in cancer cells was well correlated with pelvic lymph node metastasis(p<0.01), large tumor size(p<0.05) and advanced stage(p<0.05). Overall survival rate for 28 patients with TP-positive cervical cancer was significantly lower than that of 15 patients with TP-negative cervical cancer. CONCLUSIONS: With this study, we can speculate that TP might play a role in the growth and metastatic process of cervical neoplasia and be a possible prognostic factor of cervical cancer.
Biopsy ; Cervix Uteri ; Epithelium ; Female ; Humans ; Lymph Nodes ; Survival Rate ; Thymidine Phosphorylase* ; Thymidine* ; Uterine Cervical Neoplasms

Transduction of retroviral-mediated herpes simplex virus thymidine kinase(HSVtk) gene into tumor cells and subsequent ganciclovir(GCV) treatment have been used as an experimental and clinical therapeutic strategy. Because non-transduced tumor cells can be killed by small proportion of transduced cells, known as bystander effect. Increasing bystander effect is useful strategy of suicidal gene therapy using HSVtk gene. To get a better bystander effect, we transduced T98G gliobastoma cells with HSVtk gene, single and double transduction with different marker genes respectively. Double HSVtk gene transduced cell lines showed significantly increased HSVtk activity(83%) by measuring the intracellular amount of phosphrylated 3H-GCV comparing to the single HSVtk gene transduced cell lines. In vitro bystander effect, examined by coculturing with HSVtk gene transduced cells and HSVtk- negative pa rental cells, was significantly increased on double HSVtk gene transduced cell lines. These results suggest that increasing herpes simplex virus thymidine kinase activity by double transfer of HSVtk gene into tumor cells can be a useful strategy for treating cancer with suicidal gene therapy.
Bystander Effect* ; Cell Line ; Ganciclovir ; Genetic Therapy ; Simplexvirus ; Thymidine Kinase* ; Thymidine*

OBJECTIVE: We evaluated the relationship between the expression of Ki-67 and thymidine-phosphorylase (TP) according to the cancerous progression of uterine cervical cancer with immunohistochemical method. METHODS: The material was obtained from hysterectomized uterus and punched cervical specimen for two years from 1998 to 1999 at the Soonchunhyang Chunan hospital. The material included 15 normal epithelium, 13 CIN I/II, 21 CIN III, 15 microinvasive carcinoma and 13 invasive carcinoma. Monoclonal antibodies of Ki-67 and TP were used for immunohistochemical determination of cellular proliferation and angiogenic activity. RESULTS: 1. The positive rate of thymidine phosphorylase in each group of normal epithelium, CIN I/II, CIN III, microinvasive carcinoma and invasive carcinoma were 6.7%, 23.1%, 38.0%, 73.3%, 84.6% respectively. 2. The labeling indexes of Ki-67 in each group of normal epithelium. CIN I/II, CIN III, microinvasive carcinoma and invasive carcinoma were 2.0+/-0.7, 26+/-5.4, 41.2+/-10.1, 74.7+/-9.3 respectively. 3. There was statistically significant relationship between TP and Ki-67 expression. CONCLUSION: The above results indicates that the angiogenic activities and cellular proliferation indices increase according to the invasiveness of cervical cancer. We were able to reveal the expression of TP and Ki-67 and their relationship in cervical carcinoma.
Antibodies, Monoclonal ; Cell Proliferation ; Chungcheongnam-do ; Epithelium ; Thymidine Phosphorylase* ; Thymidine* ; Uterine Cervical Neoplasms ; Uterus

BACKGROUND: Calcipotriol(MC903), a new vitamin D(3) analogue, has been reported to be effective in the treatment of patients with psoriasis. OBJECTIVE: The purpose of this study is to examine the effects of calcipotriol on proliferation and differentiation of the keratinocytes in monolayer cultures and three-dimensional cultures. METHODS: Using moriolayer cultures, we examined morphological changes of keratinocytes and performed [(3)H]thymidine incorporation after calcipotriol was added into the medium. Using three dimensional cultures, we performed two experiments: one with cultures treated with calcipotriol immediately after the keratinocytes had been exposed to the air and another set of cultures treated with calcipotriol after three dimensional morphogenesis of the keratinocytes. We examined morphological changes of keraitinocytes and performed a immunohistochemical study for proliferation differentiation markers RESULTS: In monolayer cultures, at calcipotriol concentrations of 10(-9)M-10(-6)M, keratinocytes became larger, more irregular, and flattened in a dose-dependent manner. At 10(-9)M-10(-6)M, [3Hl thymidine incorporatiorn was decreased dose-dependently as compared to the control culture. In the first experiment using three-dimensional cultures, at 10(-9)M-10(-6)M, total epidermal layers were thinned. This was associated with thinnings of nucleated and horny layers in a dose dependent manner. In the seconcd experiment using three-dimensional cultures, at 10(-8)M-10(-6)M, nucleated layers were thinned in a dose dependent manner, but the horny layer was slightly thickened, as compared to the control culture. Immunohistochemical studies showed a reduction of differentiation markers such as keratin 1, involucrin, filaggrin, loricrin consistent with a thinning of nucleated layers in the epidermal architecture in both experiments. In the basal layer, at 10(-9)M-10(-6), PCNA-positive cells were and BrdU-positive cells were decreased dose-dependently as compared to the control culture. CONCLUSIONS: In this study, we demonstrated that at 10(-9)M-10(-6) calcipotriol inhibited keratinocytes proliferation and stimulated keratinocytes differentiation in a dose-dependent manner.
Antigens, Differentiation ; Humans* ; Keratin-1 ; Keratinocytes* ; Morphogenesis ; Psoriasis ; Thymidine ; Vitamins