Biomedical subjects

H Sato

Publications and source records attributed to H Sato.

At least 523 records · Page 29Linked to original sources

PubMed1999

Expression of E-cadherin in bone and soft tissue sarcomas: a possible role in epithelial differentiation.

The cadherin-mediated cell-cell adhesion system is now known to play a critical role in both the morphogenesis of cancer cells and suppression of their invasion. However, the pattern of expression of E-cadherin, the major cadherin of epithelial cells in bone and soft tissue sarcomas, remains unclear. This prompted us to study E-cadherin expression in a variety of bone and soft tissue sarcomas. Using the monoclonal antibody HECD-1, raised against the extracellular domain of E-cadherin, we observed immunoreactivity in 1 pleomorphic rhabdomyosarcoma, 2 of 5 diffuse mesotheliomas, 4 of 5 clear cell sarcomas, 1 of 5 epithelioid sarcomas, and 10 synovial sarcomas. Other types of bone and soft tissue sarcoma (4 osteosarcomas, 4 chondrosarcomas, 3 primitive neuroectodermal tumors, 1 fibrosarcoma, 4 malignant fibrous histiocytomas, 5 liposarcomas, 4 leiomyosarcomas, 6 alveolar and 5 embryonal rhabdomyosarcomas, 4 angiosarcomas, 4 malignant peripheral nerve sheath tumors, 2 extraskeletal myxoid chondrosarcomas, 2 extraskeletal osteosarcomas, and 3 alveolar soft part sarcomas) were completely negative for E-cadherin. Our findings indicate that E-cadherin is expressed in certain kinds of soft tissue sarcomas, especially those with epithelioid features, suggesting that E-cadherin plays a role in the constitution of their architecture.

Bone Neoplasms↗

PubMed1999

Disruption of gap junctional intercellular communication in human renal cancer cell lines.

OBJECTIVES: Gap junctional intercellular communication (GJIC) is believed to play an important role in the maintenance of cell homeostasis, and its disruption may be associated with carcinogenesis. However, GJIC has not been detected in many human cancers. We therefore studied the regulation of GJIC in human renal cancer cell lines. METHODS: We examined the human renal cancer cell lines, ACHN and NT, as well as Madin-Darby canine kidney (MDCK) cells as a positive control, using GJIC assays, Northern blotting to detect connexin 43 mRNA, immunofluorescent staining, and Western blotting of connexin 43 protein. RESULTS: GJIC of ACHN and NT was completely blocked. In ACHN cells, connexin 43 mRNA was not altered. However, connexin 43 protein was aberrantly localized and phosphorylated connexin 43 protein had disappeared. Both connexin 43 protein and its mRNA were undetectable in NT cells. CONCLUSIONS: GJIC in human renal cancer cell lines is impaired and various pathways may inhibit this mechanism in renal cancer. We believe that connexin plays an important role in renal carcinogenesis.

Carcinoma, Renal Cell↗

PubMed1999

Infection of the erythroid cell line, KU812Ep6 with human parvovirus B19 and its application to titration of B19 infectivity.

A human parvovirus B19 (B19) infectivity assay was developed using the erythroid cell line, KU812Ep6. KU812Ep6 was cloned for high efficiency infection with B19 in vitro, in the presence of erythropoietin by a limiting dilution method from the parent cell line, KU812. B19 was effectively propagated in KU812Ep6 and was detected for B19 antigens, VP1 and VP2. The titers of B19 positive sera measured with KU812Ep6 cells were in the range of 10(6) to 10(8) TCID50 ml. This KU812Ep6 infectivity assay had a 10(3)-10(4.5) higher sensitivity than the colony forming unit-erythroid (CFU-e) injury assay. It was calculated that one TCID50 needed 10(3) B19 genome copies, judging from the infectivity assay and semi-quantitative PCR. The KU812Ep6 infectivity assay was also used to determine infectivity of B19 in vitro, and to evaluate inactivation, as well as clearance of the virus. The inactivation of B19 by heating was carried out and infectivity declined from 10(4) TCID50 ml to < 10 TCID50 ml (lower limit of detection) at 60 degrees C for 3 h or at 70 degrees C for 30 min, but only decreased to 10(2.5) TCID50 ml at 50 degrees C for 8 h.

Antigens, Surface↗

PubMed1999

Emergence of resistance to acyclovir and penciclovir in varicella-zoster virus and genetic analysis of acyclovir-resistant variants.

We have characterized the differential actions of acyclovir and penciclovir against varicella-zoster virus (VZV) in cell culture by comparing the frequency of appearance of resistant viruses followed by their characterization. Cells were infected with cell-free virus and the cultures were successively treated with increasing concentrations of acyclovir or penciclovir. Drug-resistant viruses were selected in the presence of 6 microg/ml of acyclovir or penciclovir. The emergence frequency of resistant viruses was significantly higher following acyclovir exposure than following penciclovir exposure (Fisher's exact test, P<0.0001), possibly reflecting virus growth differences under these experimental conditions. Based on antiviral drug susceptibility and thymidine kinase (TK) activity assays, 11 acyclovir-resistant variants from seven experiments using three virus strains (Kawaguchi strain, Oka varicella vaccine strain and a clinical isolate from a zoster patient) were found to be TK-deficient. Sequence analysis of TK-deficient variants of the Kawaguchi strain revealed deletions that caused frameshifts, resulting in premature termination in the TK gene.

Acyclovir↗

PubMed1999

Effect of quadriceps exercise on synostosis following tibial osteotomy with internal fixation: a finite element simulation.

OBJECTIVE: To clarify the influence of quadriceps muscle exercises on the apposed bony surfaces of the tibia after a high tibial osteotomy. The study was designed so that the instability at the osteotomy could be evaluated by a finite element simulation. BACKGROUND: A detailed knowledge of the effects of quadriceps exercises on the healing tibia may lead to a solid rationale for exercise prescription. METHODS: Using a three-dimensional finite-element method, we calculated displacement at the site of surgical repair of a tibia with an osteotomy and fixation plate attached. Construction of the finite element model of the tibia and subsequent calculations were done with the aid of commercial software. Boundary and loading conditions were calculated for two situations: a straight leg raising exercise and a full knee extension beginning from 90 degrees of knee flexion. RESULTS: In the straight leg raising exercise, the surgically cut surfaces were apposed tightly, whether or not an external load was added. For the knee extension exercise, on the other hand, separation occurred when the lower leg began at a full vertical orientation of 90 degrees of knee flexion, but as the lower leg diverged from the vertical orientation, compression began to come into play and progressively increased. CONCLUSIONS: A position of 90 degrees of knee flexion with the lower leg vertical should be considered hazardous to the integrity of the surgically cut and apposed surfaces. RELEVANCE: Currently, the basis for deciding the timing and intensity of exercise is simply clinical experience. A more detailed knowledge of the effects of quadriceps exercise on the healing tibia may lead to a more solid rationale for exercise prescription in the postoperative care of a high tibial osteotomy.

Biomechanical Phenomena↗

PubMed1999

Policy and politics of smoking control in Japan.

The tobacco industry took root well before the hazards of its products were proven scientifically. As elsewhere, smoking control policy has not proceeded automatically nor smoothly in Japan. Examination of the past political process discloses that the failure to enact effective smoking control is attributable to several factors, including the political environment, administrative inadequacy and an inactive medical community. Especially remarkable in this failure have been: the political leverage of the tobacco industry; a lack of clear leadership by the health ministry; the successive rejection of law suits in the courts; and the relatively weak health advocacy groups in Japan. The Diet had been effectively immobilized by pro-tobacco interests and without support from the government, administrative agencies have remained inactive. Since the late 1970s, a series of smoking control measures has been introduced by government agencies, propelled by the social movement. However limited, the introduction of smoking control measures was accomplished with, or at least facilitated by the following: the advocacy of local and international groups and organizations; the continuous visibility of the issue in the media; and changing public attitudes. Involvement of the Diet and the Ministry of Health and Welfare (MHW) was essential in translating commitments into government action. Nevertheless, the resulting measures were not comprehensively legislated. Moreover, they were not subject to continuous evaluation. Consequently, they have been mostly ineffective in decreasing the prevalence of smoking among the populace. Clearly, leadership by the health ministry coupled with political support are the key to advancing effective smoking control.

Humans↗

PubMed1999

Effects of blocking non-N-methyl-D-aspartate receptors on visual responses of neurons in the cat visual cortex.

To elucidate the function of non-N-methyl-D-aspartate types of glutamate receptors in the primary visual cortex of the adult cat, we studied the effects of the iontophoretically applied glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione and D-amino-5-phosphonovalerate. Antagonists were applied with ejecting currents that selectively blocked non-N-methyl-D-aspartate receptors. Among 93 cells in which stable recordings were obtained, 6-cyano-7-nitroquinoxaline-2,3-dione reduced the visual response in all cells. The average response magnitude during 6-cyano-7-nitroquinoxaline-2,3-dione administration was reduced to 11.7% of the control (average ejecting current: 41.2 nA). The effect of 6-cyano-7-nitroquinoxaline-2,3-dione was obvious throughout all cortical layers. The effect of D-amino-5-phosphonovalerate on the visual response was tested in 14 cells and it was also effective in blocking the visual response: the average response magnitude during D-amino-5-phosphonovalerate administration was 45.0% of the control (average ejecting current: 41.4 nA). The effect of 6-cyano-7-nitroquinoxaline-2,3-dione on the response was compared in individual cells at both high and low firing rates in order to determine whether a differential effect exists on the level of firing activity of cells due to secondary inactivation of voltage-dependent N-methyl-D-aspartate receptors. However, no indication of response dependency on firing rate was seen with 6-cyano-7-nitroquinoxaline-2,3-dione. We suggest that excitatory transmission at the geniculocortical and corticocortical synapses seems to be strongly dependent on non-N-methyl-D-aspartate receptors throughout the primary visual cortex of the adult cat, and that both non-N-methyl-D-aspartate and N-methyl-D-aspartate type glutamate receptors function additively.

2-Amino-5-phosphonovalerate↗

PubMed1999

Role of microtubules in the contractile dysfunction of hypertrophied myocardium.

OBJECTIVES: We sought to determine whether the ameliorative effects of microtubule depolymerization on cellular contractile dysfunction in pressure overload cardiac hypertrophy apply at the tissue level. BACKGROUND: A selective and persistent increase in microtubule density causes decreased contractile function of cardiocytes from cats with hypertrophy produced by chronic right ventricular (RV) pressure overloading. Microtubule depolymerization by colchicine normalizes contractility in these isolated cardiocytes. However, whether these changes in cellular function might contribute to changes in function at the more highly integrated and complex cardiac tissue level was unknown. METHODS: Accordingly, RV papillary muscles were isolated from 25 cats with RV pressure overload hypertrophy induced by pulmonary artery banding (PAB) for 4 weeks and 25 control cats. Contractile state was measured using physiologically sequenced contractions before and 90 min after treatment with 10(-5) mol/liter colchicine. RESULTS: The PAB significantly increased RV systolic pressure and the RV weight/body weight ratio in PAB; it significantly decreased developed tension from 59+/-3 mN/mm2 in control to 25+/-4 mN/mm2 in PAB, shortening extent from 0.21+/-0.01 muscle lengths (ML) in control to 0.12+/-0.01 ML in PAB, and shortening rate from 1.12+/-0.07 ML/s in control to 0.55+/-0.03 ML/s in PAB. Indirect immunofluorescence confocal microscopy showed that PAB muscles had a selective increase in microtubule density and that colchicine caused complete microtubule depolymerization in both control and PAB papillary muscles. Microtubule depolymerization normalized myocardial contractility in papillary muscles of PAB cats but did not alter contractility in control muscles. CONCLUSIONS: Excess microtubule density, therefore, is equally important to both cellular and to myocardial contractile dysfunction caused by chronic, severe pressure-overload cardiac hypertrophy.

Animals↗

PubMed1999

Pravastatin restored the infarct size-limiting effect of ischemic preconditioning blunted by hypercholesterolemia in the rabbit model of myocardial infarction.

OBJECTIVES: We tested to find out whether pravastatin restores the infarct size (IS)-limiting effect of ischemic preconditioning (IP) and if it has any effect on the IP-induced activation of adenosine producing enzyme ecto-5'-nucleotidase which plays a key role in the IP-induced cardioprotection. BACKGROUND: The IS-limiting effect of IP is blunted by hypercholesterolemia. Recently, HMG-CoA reductase inhibitors are shown to have direct cytoprotective effects. METHODS: Rabbits were fed with a normal or cholesterol (1%) added diet with or without pravastatin (5 mg/kg/day) treatment. Infarct size was measured after 30 min occlusion and 3 h reperfusion of circumflex coronary artery with or without the IP procedure (5 min occlusion and 10 min reperfusion). Additionally, ecto-5'-nucleotidase activities of ischemic and nonischemic myocardium were measured immediately after IP procedure. RESULTS: This dose of pravastatin did not normalize the increased level of serum cholesterol. The IS-limiting effect of preceding IP (IS reduced from 36.7% to 9.6%, p < 0.001) was abolished by hypercholesterolemia (from 46.1% to 31.3%, p = NS) and restored by pravastatin treatment (from 35.2% to 9.4%, p < 0.001). Pravastatin treatment did not affect IS or the effect of IP under normocholesterolemia. The activation of ecto-5'-nucleotidase presented as the activity ratio of ischemic to nonischemic myocardium (3.1-fold in normocholesterolemia) was blunted by hypercholesterolemia (1.8-fold, p < 0.05) and restored by pravastatin treatment (2.9-fold). CONCLUSIONS: Pravastatin, at the dose serum cholesterol was not normalized, restored the IS-limiting effect of IP and IP-induced ecto-5'-nucleotidase activation, which were both blunted by hypercholesterolemia. The activation of ecto-5'-nucleotidase may be worth further investigation as a possible mechanism for the hypercholesterolemia-induced retardation and pravastatin-mediated restoration of the cardioprotective effect of IP.

5'-Nucleotidase↗

PubMed1999

Expression pattern of vascular endothelial growth factor isoform is closely correlated with tumour stage and vascularisation in renal cell carcinoma.

Vascular endothelial growth factor (VEGF) has five isoforms (VEGF206, 189, 165, 145 and 121). Increased VEGF expression in renal cell carcinoma (RCC) is associated with angiogenesis, but, it is not apparent which isoform is involved in this effect. We examined the isoform patterns of VEGF by reverse transcription-polymerase chain reaction (RT-PCR) in 47 RCCs. All showed increased VEGF expression as compared with extraneoplastic renal tissue. Four of the 47 RCCs showed VEGF121 alone, 10 showed VEGF121 + 165, and 33 showed the VEGF121 + 165 + 189 pattern. Patients with pathological stage pT3-4 RCC showed the VEGF121 + 165 + 189 isoform pattern at a significantly higher incidence (10/10, 100%) than those with pT0-2 (23/37, 62%) (P < 0.022). The VEGF121 + 165 + 189 isoform pattern was also significantly associated with high vessel counts and density (P = 0.0002, Mann-Whitney U test). These observations suggested that the VEGF189 mRNA isoform is closely associated with angiogenesis and results in the growth of RCC.

Blotting, Northern↗

PubMed1999

Pharmacodynamic analysis of the electrocardiographic interaction between disopyramide and erythromycin in rats.

Disopyramide (DP) is known to induce QT prolongation and Torsades de Pointes (TdP) when administered concomitantly with erythromycin (EM). To define and evaluate quantitatively the arrhythmogenic risk of the concomitant administration of DP and EM, we investigated the influence of EM on the pharmacokinetics and pharmacodynamics of DP in rats. The time profiles of change in QT interval and plasma concentration of each drug were evaluated during and after constant intravenous infusion of DP (6.0 or 15.0 mg/kg/h), EM (4.0 or 8.0 mg/kg/h), and coadministration of DP and EM (DP 6.0 mg/kg/h plus EM 4.0 mg/kg/h). Each agent induced QT prolongation at plasma concentrations within the therapeutic range in humans. DP-induced QT prolongation was proportional to its plasma concentration. In the case of EM, the Emax model with an "effect compartment" could explain the relationship between plasma EM concentrations and changes in QT interval. Although coadministration of EM with DP gave enhanced QT prolongation compared to dosing with DP alone, EM did not affect the pharmacokinetics of DP. In conclusion, it was shown that a pharmacodynamic interaction contributes to the electrocardiographic adverse reaction (i.e., QT prolongation) induced by coadministration of DP and EM in rats.

Animals↗

PubMed1999

Overexpression of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in metastatic MDCK cells transformed by v-src.

This article discusses the transformation of epithelial Madin-Durby canine kidney (MDCK) cells with v-src induced expression of membrane-type 1-matrix metalloproteinase (MT1-MMP) and metastatic growth in nude mice (Kadono Y et al., Cancer Res 1998; 58: 2240-44). To analyze genes associated with invasive phenotype of v-src MDCK cells, mRNA differential display was performed between control and the transformed cells. A clone 12', the expression of which was clearly up-regulated in the transformed cells, encoded a protein 81% homologous to human tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Northern hybridization showed that only MT1-MMP expression was enhanced and other matrix metalloproteinases (MMPs) were undetectable or rather repressed in the transformed cells. Proteolytic activity against type I gelatin was observed in v-src MDCK cells, which was inhibited only by TIMP-2 but not by TIMP-1. MDCK cells stably transfected with the MT1-MMP gene also degraded gelatin, which was selectively inhibited by TIMP-2. These results suggest that MT1-MMP, the expression of which is induced in v-src MDCK cells, degrades extracellullar matrix by itself rather than through the activation of progelatinase A, which in turn contributes to the metastasis of the transformed cells.

Animals↗

PubMed1999

Matrix metalloproteinase 9 is induced by the Epstein-Barr virus BZLF1 transactivator.

Type IV collagenases, matrix metalloproteinase (MMP) 2 and MMP9 are implicated in tumor invasion and metastasis. In patients with nasopharyngeal carcinoma (NPC), poor prognosis due to development of local and distant metastasis has been reported to be predicted by antibody titers against the Z protein which is an AP-1 family transcription factor encoded by the EBV BZLF1 immediate-early gene. Here we report that in patients with NPC, expression of Z in tumor cells correlates with advanced cervical lymph node metastasis which may suggest that Z affects tumor invasion and metastasis. We therefore tested if Z would induce expression of type IV collagenases. Transfection of Z expression plasmid into the C33A epithelial cell line increased expression of MMP9, but MMP2 expression was unaltered. Mutational analysis of the Z protein revealed that, in addition to all three functional domains of Z (dimerization domain, DNA binding domain, and activation domain), the carboxyl terminal 17 amino acids which stabilize the Z protein were necessary for induction of MMP9 expression. Analysis of the MMP9 promoter demonstrated that only AP-1 site close to the transcriptional start-site was essential for transactivation by Z. Previously we reported that Epstein-Barr virus latent membrane protein 1 (LMP1) stimulates MMP9 expression (Yoshizaki et al. Proc. Natl. Acad. Sci. 1998; 95: 3621-6). Thus, Z together with LMP1 may contribute to invasion and metastasis of NPC by inducing expression of MMP9.

DNA-Binding Proteins↗

PubMed1999

Genetic diagnosis of micrometastasis based on SCC antigen mRNA in cervical lymph nodes of head and neck cancer.

This study is designed to assess gene expression of squamous cell carcinoma antigen (SCCA) mRNA to detect micrometastases in cervical lymph nodes (LNs) of head and neck cancer. We examined the expression of SCCA mRNA in 12 primary tumors and 212 cervical LNs (101 LNs taken from 8 patients with tongue cancer, 71 from 7 patients with gingival cancer, 19 from 2 patients with laryngeal cancer, 9 from 2 patients with pharyngeal cancer, 7 from 1 patient with cancer of the buccal mucosa, and 5 from 1 patient with cancer of floor of the mouth). Detectability of metastatic LNs by nested and single reverse transcriptase-polymerase chain reaction (RT-PCR) was compared with semiserial sections (hematoxylin-eosin staining and keratin immunostaining). All primary tumors expressed SCCA mRNA. Of 198 histologically metastasis-negative nodes, SCCA mRNA was detected in 37 (18.7%) by nested PCR. Eleven micrometastatic foci in 9 LNs (4.6%) were discovered by semiserial sectioning. This suggests that SCCA mRNA is a promising tumor marker for detecting the micrometastases in cervical LNs of head and neck cancer.

Antigens, Neoplasm↗

PubMed1999

Analysis of antiplatelet effect of ticlopidine in humans: modeling based on irreversible inhibition of platelet precursors in bone marrow.

The relationship between plasma concentration of ticlopidine and its inhibitory effect on platelet aggregation in human was analyzed using a pharmacokinetic/pharmacodynamic (PK/PD) model. The data of plasma concentration and inhibitory effect on platelet aggregation were taken from the literature. A two-compartment open model was fitted to plasma ticlopidine concentrations. Assuming that ticlopidine acts on platelet precursors in the bone marrow, the apparent reaction rate constant of ticlopidine and platelet precursors (K), apparent transformation rate constant of platelet precursors (kr) and apparent elimination rate constant of platelets (ke) were estimated. The estimated values +/- S.D. were 1.01 +/- 1.08 ml micrograms-1 hr-1 for K, 0.265 +/- 0.259 hr-1 for kr and 0.0747 +/- 0.0112 hr-1 for ke. The antiaggregation effects of ticlopidine on platelets after administration of 100, 200, and 300 mg (bid for 8 days) were simulated using the PD parameters of K, kr, and ke. While the antiaggregation effect reached steady state within 3-4 days without dose dependency of the interval, the maximum effect increased with dose. Furthermore, changing the elimination rate constant of ticlopidine from the central compartment in the model significantly changed the duration of inhibitory effect of ticlopidine on platelet aggregation. Therefore, the reported long duration of antiplatelet effect after discontinuation of ticlopidine, which is believed to be irreversible binding to the platelet, might have been partially caused by the delayed plasma elimination after a long therapy of ticlopidine. On the other hand, the mean life-span of platelets in the blood estimated by 1/ke after administration of ticlopidine was 14 hr, far below the life-span of platelets in the blood. For a more detailed analysis of the antiplatelet effect of ticlopidine, the possible contribution of reversible binding of the drug to glycoprotein IIb/IIIa should be considered in future PK/PD models.

Blood Platelets↗

PubMed1999

Enhancement of membrane-type 1-matrix metalloproteinase (MT1-MMP) production and sequential activation of progelatinase A on human squamous carcinoma cells co-cultured with human dermal fibroblasts.

Matrix metalloproteinase 2 (MMP-2)/gelatinase A plays an important role in tumour invasion and metastasis. Since MMP-2 is secreted as an inactive form (proMMP-2) from tumour and neighbouring stroma cells, the activation process is necessary to express the enzymic activity for degradation of extracellular matrix components. We herein reported that the activation of proMMP-2 was induced in human squamous carcinoma cells co-cultured with normal human dermal fibroblasts. When A431 cells were co-cultured with human fibroblasts at various cell ratios, 72-kDa proMMP-2 was converted to a 62-kDa active form through the appearance of a 64-kDa intermediate. The activation of proMMP-2 by co-culture was also observed in other carcinoma cell lines, HSC-4 and SAS, but not in normal human keratinocytes. We characterized by in vitro invasion assay that A431 cells in co-culture preferentially invaded through Matrigel and the increased invasive activity was inhibited by exogenously adding tissue inhibitor of metalloproteinases 2. The augmented proMMP-2 activation by co-culture was achieved by the increase in membrane type 1-MMP (MT1-MMP) production along with that of its mRNA level. The predominant appearance of MT1-MMP was immunologically observed in A431 cells, but not human fibroblasts of the co-culture. Furthermore, epidermal growth factor (EGF) enhanced the co-culture-mediated proMMP-2 activation by increasing the production and gene expression of MT1-MMP, and thereby tumour invasive activity was further augmented. These results suggest that the cell-cell contact between carcinoma cells and normal fibroblasts enhances the production of MT1-MMP followed by sequential activation of proMMP-2 on the tumour cell surface, which may be closely implicated in tumour invasion in vivo.

Carcinoma, Squamous Cell↗

PubMed1999

Expression of proopiomelanocortin, corticotropin-releasing hormone (CRH), and CRH receptor in melanoma cells, nevus cells, and normal human melanocytes.

Proopiomelanocortin (POMC) is a 31 kDa prohormone that is processed to various bioactive peptides, including adrenocorticotropin (ACTH), melanotropins (alpha, beta, gamma-MSH), lipotropins, and endorphins. POMC is expressed not only in the pituitary gland but also in a variety of nonpituitary organs and tumors, including melanomas. We previously showed that normal human melanocytes produce and secrete alpha-MSH and ACTH, and furthermore, that advanced melanoma cells generally produce higher amounts of POMC peptides that correlate with tumor progression. To elucidate the mechanism of this upregulation, the expression of genes encoding corticotropin-releasing hormone (CRH) and its receptor, CRH-R, as well as POMC and the MSH receptor (MC1-R), was evaluated by reverse transcriptase-polymerase chain reaction using cultured human melanoma cells, nevus cells, and normal melanocytes. Our results show that all melanocytic cells express CRH, CRH-R, POMC, and MC1-R, with highest intensities in melanoma cells. Furthermore, immunohistochemistry shows that CRH as well as POMC is strongly expressed in advanced melanomas, such as vertically growing lesions of acral lentiginous, nodular and metastatic melanomas, in contrast to negative expression in nevus cells. These results indicate that tumor progression accentuates CRH, CRH-R, and POMC expression by melanoma cells.

Corticotropin-Releasing Hormone↗

PubMed1999

Analysis of c-kit exon 11 and exon 17 of urticaria pigmentosa that occurred in monozygotic twin sisters.

Genomic DNA extracted from peripheral blood mononuclear cells of monozygotic twin patients with urticaria pigmentosa was investigated for mutations of proto-oncogene c-kit. Neither the patients nor their families had genomic mutations in exon 11 or exon 17 of c-kit. The patients did not have any systemic involvement or bone marrow abnormalities. There are indications that some genetic factors may participate in the pathogenesis of urticaria pigmentosa in monozygotic twins. In the present patients, factors other than genomic faults in exon 11 and exon 17 of c-kit may be responsible for the pathogenesis.

Adult↗