Search PubMed⌕ Search

Biomedical subjects

M Ichihashi

Publications and source records attributed to M Ichihashi.

At least 145 records · Page 8Linked to original sources
PubMed1994

Enhanced therapeutic effect on murine melanoma and angiosarcoma cells by boron neutron capture therapy using a boronated metalloporphyrin.

We have already achieved successful treatment of several human patients with malignant melanoma by boron neutron capture therapy (BNCT) using 10B1-paraboronophenylalanine (10B1-BPA). In this communication we used a new compound, a manganese boronated protoporphyrin (Mn-10BOPP), and compared it to 10B1-BPA.HCl with respect to uptake in murine melanoma and angiosarcoma cells as well as to their respective cell killing effects using BNCT. Mn-10BOPP was found to be 3 to 10 times more effectively taken up by melanoma cells and angiosarcoma cells than 10B1-BPA.HCl when the content of 10B was measured by the new method, inductively coupled plasma-mass spectrometry (ICP-MS). In addition, melanoma cells and angiosarcoma cells preincubated with Mn-10BOPP were 15 to 20 times more efficiently killed by BNCT than cells preincubated with 10B1-BPA.HCl. These results suggest that Mn-10BOPP is a suitable compound for BNCT of not only malignant melanoma but also angiosarcoma.

Animals↗
PubMed1994

[Neutron capture therapy for cancer].

Boron neutron capture therapy (BNCT) is a selective radiotherapy using boron-10 which absorbs thermal neutrons and releases high LET alpha particles by 10B(n, alpha)7Li reaction. In this paper, the present status of BNCT for malignant melanoma was introduced. As a melanoma-targetting 10B-compound, 10B-paraboronophylalanine (BPA) was used. It was administered by multiple subcutaneous injection or intravenous drip infusion. We adopted the maximum tolerance dose to the skin as a therapeutic dose regardless of the tumor 10B concentration, because we cannot directly measure it. For this purpose, an approximation of skin concentration was made using blood data just after the administration. We treated 14 melanoma patients in this way and obtained good local control of the tumor with tolerable skin reaction. More experience with logical analysis and basic research is necessary for further development of this therapy.

Boron Compounds↗
PubMed1994

Boron neutron capture therapy of malignant melanoma using 10B-paraboronophenylalanine with special reference to evaluation of radiation dose and damage to the normal skin.

A treatment regimen for boron neutron capture therapy of malignant melanomas is described using 10B-paraboronophenylalanine as the tumor-targeting compound. As a therapeutic dose, we adopted the maximum tolerable dose for the skin regardless of tumor 10B concentration. In practice, the maximum neutron fluence should be decided prior to starting irradiation. For this purpose, the kinetics of the concentration of 10B in the blood and skin and the skin-to-blood ratios were analyzed in the six patients who received 170 mg/kg of the compound intravenously, and skin concentrations during irradiation were predicted using a standard skin factor curve. This yields a skin concentration at time T based on the blood concentration at time 0. We calculated the maximum tolerable fluence yielding but not exceeding 18 RBE-Gy by assuming that the RBE of 14N(n,p)14C and 10B(n, alpha)7Li reaction for skin damage is 2.5. Actual skin reactions in three of five patients treated with the therapy were, as predicted, within tolerable limits, and we were able to obtain complete tumor regression in four cases. The results indicate that application of our logical approach will be useful for subsequent cases and further development of this therapy.

Aged↗
PubMed1994

[A case of malignant localized chest wall mesothelioma accompanying with abdominal aortic aneurysm].

The patient was a 78-year-old man with a history of large painful left lower lateral chest wall tumor that was fist sized, while he had large abdominal aortic aneurysm. Because of high age, two staged operation was done. Initially chest wall tumor was resected. The defect was 11 x 11 cm in sized. The reconstruction of the defect was made with Marlex mesh. The microscopical findings was biphasic malignant mesothelioma. Fourty one days later abdominal aortic aneurysm was excised and the aorta was reconstructed using a Y shaped artificial graft. Post-operative course was uneventful.

Aged↗
PubMed1993

Partial improvement of Olmsted syndrome with etretinate.

An 11-year-old Japanese boy with Olmsted syndrome was seen at our clinic. He had a sharply marginated, painful keratoderma with a red border on his palms and soles. Flexion contractures of the fingers were also observed. Hyperkeratotic plaques were present below the lower lip, on the elbows and knees, and in the sacral area. Localized alopecia, leukokeratosis on the tongue, shortness of stature, and laxity of the large joints corresponded to the clinical features of Olmsted syndrome. Treatment with etretinate was effective for the palms and fingers, but resulted in no improvement of the keratoderma of the soles. Because of periosteal thickening of the tibia, presumably caused by etretinate, therapy was terminated one year after it began.

Child↗
PubMed1993

Decreased expression of human melanoma-associated antigen ME491 along the progression of melanoma pre-canceroses to invasive and metastatic melanomas.

ME491 expression was examined by immunohistochemistry in the different stages of various types of human malignant melanomas. In addition, the primary and metastatic lesions in five patients were studied to compare the ME491 antigen expression between these lesions in a single patient. A large proportion of cells from melanoma pre-canceroses showed strong ME491 expression, whereas the proportion of negatively stained tumour cells increased in the melanomas invading the dermis and in metastatic melanomas. In addition, a comparison of five sets of primary tumour and its metastatic lesion revealed decreased expression of this antigen in metastases. These results show that the reduction or loss of ME491 antigen expression is associated with increased invasiveness and metastatic ability of human malignant melanoma, suggesting that ME491 may act as an anti-metastatic gene.

Adult↗
PubMed1993

Expression of p53 protein is an early event in ultraviolet light-induced cutaneous squamous cell carcinogenesis.

BACKGROUND AND DESIGN: p53 Is known to be a tumor-suppressor gene and has been suggested to play an important role for multistep carcinogenesis of cutaneous squamous cell carcinoma (SCC). To evaluate the role of ultraviolet light (UV) in p53 mutation in squamous cell carcinogenesis, paraffin-embedded sections of SCCs were immunohistochemically stained with the CM-1 antibody for p53 protein. Positive staining suggests mutation of the p53 gene since the mutant p53 protein gains prolonged half-life to be detectable by this method. The specimen included SCCs induced by UV (SCCs on sun-exposed areas, SCCs on patients with xeroderma pigmentosum), roentgen rays, scar, and miscellaneous causes. In addition, solar keratoses that are precancerous lesions of UV-related SCCs were also analyzed. RESULTS: Fourteen (54%) of 26 UV-related SCCs were positive, whereas five (19%) of 26 UV-unrelated SCCs were positive. Among the UV-related SCCs, five (45%) of 11 well-differentiated SCCs and nine (60%) of 15 moderately to poorly differentiated SCCs were positive. Eleven (48%) of 23 solar keratoses were positive for p53. CONCLUSIONS: These results indicate that UV acts as a mutagen for the p53 gene, and this event may occur at a relatively early stage of multistep UV carcinogenesis.

Carcinoma, Squamous Cell↗
PubMed1992

4-Borono-2-[18F]fluoro-D,L-phenylalanine: a possible tracer for melanoma diagnosis with PET.

The potential of 4-borono-2-[18F]fluoro-D,L-phenylalanine ([18F]FBPA), a flurodinated derivative of a target compound for boron neutron capture therapy, for melanoma imaging by positron emission tomography (PET) was studied using animal models. A high uptake of [18F]FBPA was found in murine B16 melanoma or in Greene's melanoma No. 179, a melanotic cell line in hamsters, for the first 6 h after injection. Whole body autoradiography using [18F]FBPA gave a clear image of the B16 tumor. The acid-insoluble 18F in the B16 increased to 27% by 6 h, and most of the free 18F was detected as [18F]FBPA in both B16 and plasma. In the hamster models, No. 179 showed a 1.7 times higher uptake than amelanotic Greene's melanoma No. 178 at 6 h post-injection, although both melanomas indicated similar metabolic activities when examined by a tracer uptake study using L-[14C]methionine, 2-deoxy-D-[14C]glucose and [3H]thymidine. [18F]FBPA may be a very promising PET tracer for melanoma imaging.

Animals↗
PubMed1992

A unique in vivo assessment of 4-[10B]borono-L-phenylalanine in tumour tissues for boron neutron capture therapy of malignant melanomas using positron emission tomography and 4-borono-2-[18F]fluoro-L-phenylalanine.

A unique in vivo approach to assessing the concentrations of 4-[10B]borono-L-phenylalanine (L-BPA), a melanoma targeting compound for boron neutron capture therapy (BNCT), was investigated using L-BPA labelled with positron-emitting 18F (half-life = 110 min), i.e., 4-[10B]borono-2-[18F]fluoro-L-phenylalanine (L-[18F]FBPA). High melanoma uptake of L-[18F]FBPA was reduced slightly by competition with L-BPA in the two animal models of the murine B16 melanoma and the melanotic Greene's melanoma No. 179 in hamsters. In mice given L-[18F]FBPA and L-BPA, the concentrations of 10B in B16 estimated from 18F radioactivity were lower than those measured by inductively coupled plasma-atomic emission spectroscopy. Lower estimated values were dependent on the time after injection and on the loading dose of L-BPA. The estimated 10B concentrations for Green's melanomas were comparable to the measured values. Positron emission tomography (PET) using L-[18F]FBPA allowed Greene's melanomas to be clearly visualized. In conclusion, when L-[18F]FBPA is used as a probe for L-BPA in BNCT of malignant melanomas, the melanoma can be localized and the 10B concentrations in tissues can be assessed in vivo using 18F radioactivity by PET.

Animals↗
PubMed1992

Intracellular glutathione and its metabolizing enzyme activities in a metastatic variant melanoma cell line.

Levels of glutathione peroxidase (GSH-PX), glutathione-S-transferase (GST), gamma-glutamyl transpeptidase (gamma GTP) and glutathione reductase (GR) activities in the B16-F10 metastatic melanoma cell line are higher than those in non-metastatic B-16 murine melanoma cells. An inverse relationship was observed between the level of reduced glutathione (GSH) and metastatic capacity. Interferon (IFN), an antitumour and antimetastic agent, reduced the experimental metastatic capacity of B16-F10 cells while increasing the intracellular GSH content. This was associated with a fall in activity of GSH-metabolizing enzymes. These results suggest a correlation of intracellular GSH and its metabolizing enzymes with malignant transformation.

Animals↗
PubMed1992

Dysplastic nevus syndrome: melanoma-prone disease.

Regardless of subsequent clinical courses of patients with dysplastic nevi (DN), substantial evidence supporting DN as one of the melanoma-prone diseases is not yet available, especially in sporadic DN, due to the lack of genetic information other than retrospective studies in clinical observation. This study aimed at the immunohistological characterization of sporadic DN distinct from common nevi (CN) and at the evaluation of the potentially of sporadic DN for malignant transformation. We considered our results together with previous immunological and epidemiological reports. We noted the following three immunohistological characteristics. 1) Proliferating cell nuclear antigen (PCNA), one of the markers for active cell division, could be detected on DN cells in junctional nests of only one among ten DN examined but not on CN cells at all. 2) The altered expression of alpha-smooth muscle actin (alpha-Sma), often observed in melanoma cells, could not be detected in DN cells. However, anti-alpha-Sma monoclonal antibody (MoAb) clearly demonstrated distinctive hypervascularity in the stroma surrounding DN when compared with CN. 3) ME491 antigen, which is known to be expressed mainly in the radial growth phase of melanoma, was detected with similar intensity on both DN and CN. These data indicate that DN has a somewhat higher potentiality than CN for cell division and secretion of some cytokines which can induce hypervascularity in the surrounding stroma, but that DN has not yet undergone the significant phenotypic changes observed in melanoma cells. Further advancements in understanding molecular events in DN cells will be of great benefit in setting DN in the multiple oncogenic spectrum from pigment cells to melanoma.

Actins↗
PubMed1992

Role of excision repair in UVB-induced depletion and recovery of human epidermal Langerhans cells.

Skin exposure to UVB radiation deprives the antigen-presenting function and OKT6 monoclonal antibody-binding characteristics of Langerhans cells. Decrease of Langerhans cell population could be relevant to immune surveillance disturbance in the UV-exposed skin. Patients with xeroderma pigmentosum exhibit a thousandfold higher risk for sunlight-induced skin cancers than patients with normal skin, and also have various defects in cellular immunity. Therefore, studies of numerical and structural changes in epidermal Langerhans cells of patients with xeroderma pigmentosum after UVB irradiation compared with normal subjects may contribute to understanding the role of antigen-presenting cells in photocarcinogenesis. The effect of UVB radiation on OKT6+ Langerhans cells was studied in epidermal sheets obtained from irradiated normal subjects (36 and 49 years old) and subjects with xeroderma pigmentosum complementation group A (21 years old), complementation group D (32 years old), and variant (35 and 60 years old). Langerhans cell densities in chronically sunlight-exposed skin were remarkably reduced in patients with xeroderma pigmentosum group A but only slightly in those with xeroderma pigmentosum variant and in normal subjects compared with covered skin. Structural changes were substantial in Langerhans cells of chronically exposed patients with xeroderma pigmentosum group A but fewer in subjects with other xeroderma pigmentosum groups and in normal subjects. A single irradiation of three times the minimal erythema dose induced a large reduction of Langerhans cells from 3 to 7 days in all subjects. However, subsequent reappearance and return to preirradiated levels was delayed more in patients with xeroderma pigmentosum group A than in those with xeroderma pigmentosum variant and normal subjects. These results indicate (1) an essential role for excisional repair in the UVB-induced depletion, recovery, and maintenance of the epidermal Langerhans cell population, and (2) a possible, but not confirmed, relationship between depletion of Langerhans cells and earlier photocarcinogenesis in xeroderma pigmentosum.

Antibodies, Monoclonal↗
PubMed1991

Malignant schwannoma associated with xeroderma pigmentosum in a patient belonging to complementation group D.

A 43-year-old man with xeroderma pigmentosum, XP97TO, was allocated to complementation group D. He had had moderate photosensitivity at age 1 year and freckles by age 6 but no neurologic abnormalities. Nevertheless, his fibroblasts in culture had the XP-D phenotype. They showed a sevenfold hypersensitivity to killing by 254 nm ultraviolet radiation and a diminished level (29%) of unscheduled DNA synthesis. Phototesting revealed delayed maximum erythema at 72 hours after UVB exposure and a lowered minimal erythema dose. Lentigo maligna developed on the patient's face, and a rapidly growing malignant schwannoma was found on the left trigeminal nerve. This may be the first case of a peripheral nervous tissue neoplasm in xeroderma pigmentosum.

Adult↗
PubMed1991

Synthesis and radiation dosimetry of 4-borono-2-[18F]fluoro-D,L-phenylalanine: a target compound for PET and boron neutron capture therapy.

The 18F-labeling of 4-borono-D-L-phenylalanine (BPA), a potential target compound for cancer treatment with boron neutron capture therapy, is described. By direct fluorination of BPA with [18F]AcOF or [18F]F2 followed by HPLC separation, 4-borono-2-[18F]fluoro-D,L-phenylalanine was prepared with radiochemical yields of 25-35% and with a radiochemical purity of over 99%. The tissue distribution study showed that the compound has potential as a tracer for pancreas imaging with positron emission tomography. Radiation dosimetry is also described.

Animals↗
PubMed1991

4-Borono-2-[18F]fluoro-D,L-phenylalanine as a target compound for boron neutron capture therapy: tumor imaging potential with positron emission tomography.

We studied the tumor uptake and metabolism of 4-borono-2-[18F]fluoro-D,L-phenylalanine ([18F]FBPA), an 18F-labeled target compound for boron neutron capture therapy. In mice bearing FM3A mammary carcinoma, the accumulation of [18F]FBPA in the FM3A for the first 2 h, and its decrease in all other tissues, resulted in high FM3A-to-tissue uptake ratios. In the FM3A, the tracer was stable for metabolic alteration, which was in contrast to the gradual increase of protein-bound radioactivity in plasma. Imaging of FM3A was demonstrated by whole body autoradiography. [18F]FBPA has potential for use as a PET tracer for tumor imaging with high contrast, even in the pancreas.

Animals↗
PubMed1991

A mechanism for relief of replication blocks by activation of unused origins and age-dependent change in the caffeine susceptibility in xeroderma pigmentosum variant.

The first XP16KO-I (age 42 without cancer) and the second XP16KO-II (age 52 after carcinogenesis) skin fibroblasts of a xeroderma pigmentosum variant (XPV) were studied. First, caffeine had no effect on XP16KO-I cells, but it potentiated UV killing and inhibited the recovery of DNA synthesis and the elongation of nascent DNA after UV irradiation in XP16KO-II cells, indicating an age-dependent change from caffeine resistance to sensitivity. These results confirmed a previous similar change in an unrelated XPV subject and the existence of 2 XPV subgroups, caffeine-sensitive and -resistant. Further, processing of post-excision breaks was also slightly more defective in XP16KO-II than in XP16KO-I cells. Second, nascent DNA pulse-labeled at 1.5 h after 5 J/m2 indicated an initial complete blockage of elongation by each dimer in XP16KO-II cells and less complete blocks in XP16KO-I and normal cells. The nascent DNA in 5 J/m2-irradiated XP16KO-II cells was 4 microns (8 x 10(6) Da) long for the peak fraction, with a possible range up to 20 microns of average replicon size, indicating activation of at least 4 microns-spaced new origins around 1.5 h post irradiation. Post-labeling chase without caffeine allowed nearly normal elongation to the present maximum molecular weight of 2.60-2.80 x 10(8) in 3-4 h in irradiated XP16KO-I and -II cells. Thus, the activation of unused origins at shorter spaces is a main mechanism for relief and the reduction of almost all unreplicated regions or blocks initially formed by 2 dimers in trans on both leading strands between converging forks. Post-labeling addition of 1 mM caffeine increased perpetuated blocks to a frequency of about 10% of the initial number of dimers in 4 h in XP16KO-II cells, but not in XP16KO-I and normal cells.

Adult↗