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Biomedical subjects

M Ichihashi

Publications and source records attributed to M Ichihashi.

At least 127 records · Page 7Linked to original sources
PubMed1996

Doses of solar ultraviolet radiation correlate with skin cancer rates in Japan.

We analyzed trends in the disease rate of skin cancers in the 1976-80 and 1986-90 intervals in the 27 university hospitals in Japan. We also measured doses of solar ultraviolet (UV) radiation at Sapporo, Kobe and Miyazaki to evaluate the relationship between the two in Japan. The rates of basal cell carcinoma (BCC) and actinic keratosis (AK) were higher in 1986-90 than in 1976-80, whereas the rate of squamous cell carcinoma (SCC) was lower in 1986-90 than in the earlier period. The rates of SCC, BCC and AK in the southern part of Japan were about five times higher than those in the north, and the average daily UV dose measured with a Robertson-Berger meter in 1995 was about 1.8 times higher in Miyazaki than in Kobe. That measured by MS-210D UV dosimeter in Sapporo was about 0.53 times lower than in Kobe. These results demonstrate that solar UV dose is higher in the southern part of Japan than that in the northern part, explaining the higher rate of non-melanoma skin cancer in southern part of Japan. A significant increase of AK and BCC may reflect the trend of UV increase in Japan.

Dose-Response Relationship, Radiation↗
PubMed1995

Correlation between the number of melanosomes, tyrosinase mRNA levels, and tyrosinase activity in cultured murine melanoma cells in response to various melanogenesis regulatory agents.

Tyrosinase is the rate limiting enzyme critically associated with melanin synthesis. The melanosomes are specialized membrane-bound organelles within melanocytic cells in which melanin polymers are ultimately deposited. To determine whether tyrosinase correlates with the number of melanosomes, we examined the relationship between tyrosinase activity, tyrosinase mRNA levels, and the number of melanosomes in B16 murine melanoma cells, using melanogenesis regulatory agents. 12-O-Tetradecanoylphorbol-13-acetate (TPA) or linoleic acid decreased tyrosinase activity, while dibutyryl cyclic adenosine monophosphate (dbcAMP) or palmitic acid increased it. The tyrosinase mRNA levels were not always correlated with tyrosinase activity, i.e., TPA down-regulated, dbcAMP upregulated, while linoleic acid or palmitic acid did not alter the message levels, indicating that fatty acid regulation of melanogenesis was due to post-transcriptional events. The number of melanosomes changed when agents which modulate the tyrosinase gene expression were added, since TPA decreased, dbcAMP increased, and linoleic acid or palmitic acid did not alter their number. These results suggest that the number of melanosomes changed in relation to tyrosinase mRNA level but not to tyrosinase activity in response to melanogenesis regulatory agents.

Animals↗
PubMed1995

Trends in nonmelanoma skin cancer in Japan.

We compared the prevalence of skin cancer and solar keratosis (SK) in patients who attended 26 Japanese university hospitals between 1976-1980 with those who attended between 1986-1990 to investigate whether the incidence of skin cancer has increased or not. Age-adjusted incidence rates of basal cell carcinomas (BCC) and SK, but not squamous cell carcinomas (SCC), from 1986-1990 were higher than those from 1976-1980. In addition, a population-based incidence study was conducted in Kasai City, Hyogo prefecture, to establish the frequency of skin cancer and SK. A total of 4736 people over 20 years of age were examined. Two BCC and 36 SK patients were identified clinically and histopathologically. SCC was not found. Age-adjusted incidence rates of BCC and SK per 100,000 were 16.5 and 486.1, respectively. The BCC incidence rate in Kasai City was significantly higher than the incidence of Japanese nonmelanoma skin cancer (NMSC) reported by Gordon in 1976. Further, subjects classified as skin type I showed statistically higher SK prevalence rates compared to skin types II and III. The present study indicates that the prevalences of NMSC and SK in Japanese have increased during the last three decades and that skin type I may be a risk factor for NMSC in Japanese.

Adolescent↗
PubMed1995

Differential down-regulation of protein kinase C subspecies in normal human melanocytes: possible involvement of the zeta subspecies in growth regulation.

Normal human melanocytes are often grown in vitro in the continuous presence of 12-O-tetradecanoylphorbol-13-acetate (TPA) for growth in vitro. The expression of protein kinase C (PKC) subspecies, which are the major cellular receptors for phorbol esters, was examined in melanocytes after long-term treatment with TPA to investigate the role of PKC subspecies in TPA-dependent cell growth. The PKC enzyme activity detected in quiescent melanocytes was almost completely depleted in cells after incubation with 85 nM TPA for 48 h. Immunoblot analysis indicated that, among the PKC subspecies alpha, beta, delta, epsilon, and zeta expressed in quiescent cells, alpha-, beta-, delta-, and epsilon-PKC were significantly down-regulated, whereas zeta-PKC remained at detectable levels in TPA-treated cells. TPA did not significantly affect the expression or subcellular distribution of zeta-PKC in melanocytes. Immunoprecipitation assay revealed that the enzyme activity of zeta-PKC was increased in both the cytosol and particulate cell fractions, but the increase was much greater in the latter. The activation of zeta-PKC lasted for 24 to 48 h after the addition of TPA; thereafter, zeta-PKC activity returned to basal levels. DNA synthesis was shown to change concomitantly with the activation of zeta-PKC in TPA-treated cells. These results indicate that TPA induces not only the down-regulation of alpha-, beta-, delta-, and epsilon-PKC, but also long-term activation of zeta-PKC in melanocytes, and that activation of zeta-PKC parallels the growth of normal human melanocytes.

Cell Division↗
PubMed1995

Correlation of the clinical manifestations and gene mutations of Japanese xeroderma pigmentosum group A patients.

The gene responsible for xeroderma pigmentosum (XP) group A has recently been cloned and designated XPA gene. Previous studies have shown that most Japanese XPA patients have homozygous mutations for the splicing site of intron 3 of the XPA gene, which was recognized by restriction endonuclease (RE) AlwNI (AlwNI mutation). Other mutations found to date have been the nonsense mutation at codon 228 in exon 6, recognized by RE HphI (HphI mutation), and at codon 116 in exon 3, recognized by RE MseI (MseI mutation). Using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis, we examined the point mutations of the XPA gene in 16 XPA patients, their parents, and their four asymptomatic siblings. We found that eight patients were homozygous for the AlwNI mutation, two were compound heterozygotes for the AlwNI mutation and the HphI mutation, one was a compound heterozygote for the AlwNI mutation and the MseI mutation, three were compound heterozygotes for the AlwNI mutation and an unidentified mutation, and two were compound heterozygotes for the HphI mutation and an unidentified mutation. Investigation of their clinical features suggested that the four patients who were heterozygous for the HphI mutation and the AlwNI or an unidentified mutation had milder clinical manifestations such as later development of skin cancers and milder neurological deterioration, than those patients who were either homozygous for the AlwNI mutation or heterozygous for the AlwNI mutation and MseI mutation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Cyclin D and retinoblastoma gene product expression in actinic keratosis and cutaneous squamous cell carcinoma in relation to p53 expression.

Abnormality of the molecules regulating the cell cycle has been shown to lead cells to transformation. Recently, overexpression of cyclin D protein, one of the G1 cyclins, and the abnormality of the retinoblastoma gene have been found in various human cancers. We analyzed the expression of cyclin D, retinoblastoma gene product (pRB) and p53 in actinic keratoses (AKs) and cutaneous squamous cell carcinomas (SCCs) by immunohistochemistry to elucidate the role of these molecules in keratinocyte carcinogenesis. In the normal epidermis, a few cyclin D positive cells were seen mainly at the basal layer. In 11 seborrheic keratoses, no overexpression of cyclin D was observed. Twelve of 26 AKs (46%) and 27 of 45 SCCs (60%) showed cyclin D overexpression. A few pRB positive cells were seen in the basal layer and in the suprabasal spinous layer of the normal epidermis. An abnormality of pRB, loss of expression, was seen in 2 of 26 AKs (8%) and 7 of 45 SCCs (16%). p53 protein was positive in 12 of 26 AKs (46%) and 24 of 45 SCCs (53%). Forty-five SCCs examined were divided into 22 ultraviolet (UV)-related SCCs and 23 UV-unrelated SCCs. Though UV-related SCCs showed a significantly higher incidence of p53 positivity, as previously reported by us, no significant difference in cyclin D overexpression and loss of the pRB expression was observed between UV-related and UV-unrelated SCCs. These results suggest that cyclin D overexpression is frequently involved in keratinocyte carcinogenesis and that this is an early event, as well as p53 abnormality. In addition, abnormality of the retinoblastoma gene is also related to epidermal cell carcinogenesis, though the frequency is relatively low.

Carcinoma, Squamous Cell↗
PubMed1995

Reduction of ultraviolet-induced skin cancer in mice by topical application of DNA excision repair enzymes.

Ultraviolet (UV) irradiation produces two major photoproducts, cyclobutane pyrimidine dimers (CPD) and (6-4) photoproducts. T4 endonuclease V (T4N5), which specifically repairs CPD, is encapsulated in liposomes. A previous study has shown that UV-induced carcinogenesis in mice was suppressed by the application of T4N5 liposomes. To confirm the suppressive effect, we applied T4N5 liposomes with repeated UVB exposure to hairless mice. At the end of the experiment, mice treated with T4N5 liposomes had 3.5 +/- 1.3 tumors per mouse, and control mice had 6.3 +/- 2.8 tumors per mouse. In addition, the incidence of tumors was reduced in T4N5 liposome-treated mice compared with controls. The pathological diagnosis of the tumors was not significantly different between two groups. Immunohistochemical analysis of p53 protein in UV-induced tumors showed that nearly half of the tumors in both groups were positive. When the biopsied normal-looking skin taken during the experiment was stained with p53 antibody, there was no significant difference of the timing of p53 protein expression between the control mice and T4N5 liposome-treated mice. These results confirmed that CPD plays a pivotal role in UV carcinogenesis, although the molecular mechanisms of the suppression by T4N5 liposomes should be further clarified.

Administration, Topical↗
PubMed1995

[A case of malignant fibrous histiocytoma treated with intraarterial chemotherapy under complete venous isolation and charcoal hemoperfusion].

Herein reported is a case with malignant fibrous histiocytoma (MFH) at the left elbow treated successfully with intraarterial chemotherapy under complete brachial venous isolation and charcoal hemoperfusion (BVI-CHP). A 56-year-old man was admitted to our institution because of local recurrence at the left elbow 6 months after extended local resection combined with systemic chemotherapy. We treated the patient with a 15-min intraarterial infusion of adriamycin (100 mg/body) and cisplatin (30 mg/body) under a concomitant 30-min BVI-CHP. Two weeks after the first treatment, he received a repeated intraarterial infusion of adriamycin (80 mg/body) and cisplatin (50 mg/body) under BVI-CHP. The tumor became necrotic one week after the first treatment, resulting in 60% reduction in tumor diameter. In addition, angiography demonstrated a remarkable shrinkage of the tumor stain. Despite repeated intraarterial high-dose infusions of chemotherapeutic agents, systemic toxicities, such as leukopenia, nausea/vomiting and alopecia, were not observed. These results indicate that this approach offers a novel therapeutic option for malignant tumors in the extremities.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[Xeroderma pigmentosum].

Xeroderma pigmentosum (XP), an autosomal recessive disorder, is characterized by extreme sensitivity to sun exposure, a high incidence of skin cancer and frequent neurological abnormalities. Cells from XP patients of seven complementation groups (A-G) have defects in the nucleotide excision repair of UV damage, whereas the defect of another type, the XP variant, is not yet known. Recent discoveries of causative genes of XP have uncovered the molecular mechanisms of nucleotide excision repair. The analysis of gene mutation in XPA gene made a diagnosis of patients and carriers quicker and easier. Further, a relationship between the type of XPA gene mutation and clinical severity has also been uncovered. By analysing skin cancers developed on XP patients, the representative of UV-induced skin cancers, the molecular bases of UV skin carcinogenesis have also been rapidly discovered.

Animals↗
PubMed1994

bcl-2 expression in epidermal keratinocytic diseases.

BACKGROUND: The bcl-2 protein has been shown to suppress apoptosis, and overexpression of the bcl-2 protein has been reported in several malignant tumors. Skin is one of the largest organs in the body, and the most common human malignancies arise from keratinocytes in the epidermis. In this paper, the authors analyzed immunohistochemically the expression of the bcl-2 protein in several keratinocytic (KC) tumors and inflammatory skin disorders to investigate the role of bcl-2 in the development of benign and malignant skin tumors. METHODS: Seventy-two frozen tissues from patients with inflammatory KC proliferation (chronic dermatitis [CD] and psoriasis vulgaris [PV]), seborrheic keratosis (SK), carcinoma in situ of KC tumors (actinic keratosis [AK] and Bowen's disease [BD]), basal cell carcinoma (BCC), and squamous cell carcinoma (SCC), 2 SCC cell lines, and 20 normal skin were immunostained with an anti-bcl-2 monoclonal antibody. RESULTS: Tissue with normal KC, CD, PV, and SK scarcely expressed the bcl-2 protein. Seventy-three percent of tissue with BD, 25% with AK, 67% with BCC, and 100% with SCC showed obvious bcl-2 protein expression. bcl-2 expression of BCC, BD, and SCC was restricted to the involved lesions, and surrounding normal tissue with KCs were bcl-2 negative. Interestingly, tissue with atrophic AK expressed no bcl-2 protein (none of five cases), whereas tissue with hypertrophic AK reacted weakly with the anti-bcl-2 antibody (two of three cases). CONCLUSIONS: bcl-2 protein expression in patients with KC may be related to tumorigenic proliferation possibly due to enhanced cell survival, but not when inflammatory proliferation of keratinocytes is present.

Bowen's Disease↗
PubMed1994

Siblings with xeroderma pigmentosum complementation group A with different skin cancer development: importance of sun protection at an early age.

BACKGROUND: For patients with xeroderma pigmentosum (XP), strict protection from UV light exposure is the only way to prevent and retard skin cancer formation. OBJECTIVE: Our purpose was to learn how the timing of sun protection influences the clinical findings in patients with XP. METHODS: We studied two siblings with XP group A (XPA) who showed a significant difference in the age at onset of skin cancer development and in neurologic abnormalities. RESULTS: The elder sister had had her first basal cell carcinoma (BCC) at 13 years of age and had had multiple BCCs by 25 years of age. Her younger sister had her first BCC at 23 years of age. Neurologic impairment of the younger sister was much milder. The elder sister started strict sun protection at 4 years of age, whereas the younger began at 2 years of age. Analysis of the XPA complementing gene revealed that both patients had the identical mutation. CONCLUSION: In patients with XP the earlier sun protection begins the later skin cancer develops. Neurologic deterioration may also be reduced by earlier sun protection.

Adolescent↗
PubMed1994

Selective boron accumulation in human ocular melanoma vs surrounding eye components after 10B1-p-boronophenylalanine administration. Prerequisite for clinical trial of neutron-capture therapy.

We have developed neutron-capture therapy (NCT) for cutaneous malignant melanoma using a melanoma-seeking 10B-dopa, analogue, 10B1-para-boronophenylalanine (10B1-BPA). In order to explore the feasibility of applying NCT further to ocular melanoma, we investigated the boron concentrations in ocular melanomas and normal ocular tissues by 10B1-BPA administration to three patients, because success of NCT depends mainly upon selective boron accumulation in melanoma. In the first and second ocular melanoma patients, to whom 10B1-BPA fructose complex (total dose of 10B1-BPA: 170 mg/kg body weight) was administered orally in two divided doses, the boron concentrations in blood, vitreous body, sclera and retina choroidea were lower than that in melanoma examined. In the third conjunctival melanoma patient, to whom 10B1-BPA fructose complex (dose of 10B1-BPA: 85 mg/kg body weight) was administered by intravenous drip infusion, the average boron concentration in four melanoma samples was 17.7 ppm, which was estimated to be within the range necessary for melanoma eradication by thermal neutron irradiation. Boron uptake by lens, vitreous body, retina choroidea and sclera was much lower than that by melanoma. It was suggested that such a superficial ocular melanoma as iris melanoma can be destroyed by NCT, although vision may be affected--mainly due to cataract formation.

Boron↗
PubMed1994

The altered expression of alpha-smooth muscle actin in basal cell epithelioma and its surrounding stroma: with special reference to proliferating cell nuclear antigen expression and adenoid differentiation.

Altered expression of alpha-smooth muscle actin (alpha-SMA) is known to indicate the morphological, tumorigenic and immunological changes occurring in tumour and stromal cells. The purpose of this study was to analyse the dynamics of alpha-SMA expression in human basal cell epithelioma (BCE) cells and their surrounding stromal cells, in the process of differentiation towards cutaneous appendages such as hair, sebaceous, apocrine and eccrine glands. Using anti-alpha-SMA specific monoclonal antibody (MAb), 17 of 36 BCEs (47%) were shown to express alpha-SMA, despite the usual absence of alpha-SMA in all eukaryotic cells except muscle cells. Solid, adenoid and sclerosing types of BCE expressed alpha-SMA more frequently, and in greater amount, than cystic, keratotic and superficial types. Furthermore, the expression of alpha-SMA in BCE cells significantly paralleled the expression of proliferating cell nuclear antigen (PCNA) in these cells. Thus, the altered expression of alpha-SMA may reflect the growing properties of BCE cells under the specific cellular regulations for differentiation. In addition, we have found anti-alpha-SMA MAb-positive fibroblasts with smooth muscle differentiation (myofibroblasts) in desmoplastic stroma surrounding BCE nests in 13 of 36 cases (36%). Coincidental expression of alpha-SMA in both BCE cells and stromal cells was found in nine of the 13 cases (69%), indicating the possibility of the induction of myofibroblastic stromal changes in surrounding tissues by cytokines secreted from BCE cells [e.g. basic fibroblast growth factor (bFGF)-like factor].

Actins↗
PubMed1994

Stable and strong expression of basic fibroblast growth factor in naevus cell naevus contrasts with aberrant expression in melanoma.

It has been proposed that basic fibroblast growth factor (bFGF) is an autocrine growth factor of melanoma cells, in contrast with normal melanocytes where bFGF acts as a paracrine growth factor. As this notion is mostly based on the different requirements for bFGF in cultures of benign and malignant pigment cells in vitro, we performed an immunohistochemical study to examine bFGF expression in vivo, using paraffin sections from naevus cell naevi (NCN) and malignant melanoma (MM). All the NCN (n = 7) showed strong and homogeneous expression of bFGF protein, whereas the primary MMs (n = 5) showed heterogeneous expression, with a population of negative cells. Metastatic MMs (n = 5) also showed heterogeneous expression, and had a greater population of negative cells. These results suggest that bFGF has some, as yet unidentified, role in the growth of benign NCN, and that overexpression of bFGF is neither a prerequisite for melanoma genesis nor for progression to metastatic MM.

Antibodies, Monoclonal↗
PubMed1994

Tissue distribution of an immunogenic melanoma associated antigen, D-1.

A human melanoma-associated antigen immunogenic in patients was recently identified by screening an expression cDNA library constructed from cultured human melanoma cell line with sera from patients with melanoma. The nucleic acid sequence of the cloned D-1 cDNA has no significant homology with previously reported mammalian genes. The cDNA D-1 encodes a peptide of about 37 kDa, which showed fivefold higher reactivity with sera from patients with melanoma than with sera from normal donors. In order to detect D-1 gene expression in vivo, in-situ hybridization and immunostaining with cRNA probe and murine anti-D-1 sera were carried out on surgically removed tissues. Digoxigenin-labeled cRNA D-1 was exclusively hybridized with mRNA in the cytoplasm of melanoma cells but not with keratinocytes and fibroblasts adjacent to melanoma nests. Polyclonal anti-D-1 antibodies were obtained by immunization of Balb/c mice with recombinant D-1 peptide and clearly reacted with melanoma cells but not with keratinocytes and fibroblasts, similar to the results of in-situ hybridization. The above information will help to assess the suitability of recombinant D-1 peptide to implement active specific immunotherapy in patients with melanoma.

Animals↗
PubMed1994

PCNA expression and nucleolar organizer regions in malignant melanoma and nevus cell nevus.

The histogenesis of malignant melanoma with particular reference to the role of melanocytic nevus is still controversial in oncological pathology. In order to differentiate between the proliferative activity of malignant melanomas and benign melanocytic tumors, immunohistochemical analysis was carried out. We used monoclonal antibody PC10 to identify the Proliferating Cell Nuclear Antigen (PCNA), a highly conserved 36 KD acidic nuclear protein which correlates with cell proliferation, and the AgNOR method to stain the Nucleolar Organizer Regions (NORs) whose number and configurations may reflect protein synthesis activity. 47 cases of primary melanoma, 63 metastatic melanoma lesions, and 23 cases of nevi are included in this study. Spitz nevi showed a higher index of cell proliferation compared with other common benign nevi but a much lower index compared with malignant melanoma cells. The metastatic lesions of malignant melanomas had a higher index of proliferation and activity of cells than the primary lesions. Skin-metastatic lesions had higher indexes of cell proliferation and NOR activity than lymph node-metastatic lesions. These results support the idea that metastatic melanoma cells are derived from a more advanced stage of tumor progression. These data suggest that the combination of PCNA and AgNOR is an useful marker for differentiating benign melanocytic tumors from malignant melanomas.

Humans↗