Keizo Yamamura

Clinical and photobiological characteristics of xeroderma pigmentosum complementation group F: a review of cases from Japan

A 61‐year‐old female patient with xeroderma pigmentosum (XP), registered as XP46KO, was assigned to complementation group F by the cell fusion‐complementation method. The XP46KO fibroblasts in culture exhibited a defective DNA repair capacity of 10–15% unscheduled DNA synthesis and a 3‐fold sensitivity to the lethal effect of 254 nm ultraviolet light compared with normal cells. The patient had mild clinical symptoms consisting of numerous pigmented freckles and a small number of scborrheic keratosis‐like papules. She had no skin cancers in the sun‐exposed areas of the skin and so far no neurological abnormalities. A review of 11 Japanese group F patients revealed very mild skin symptoms with no ocular or neuro‐psychiatric abnormalities. Single skin cancers occurred in only 3 of the 11 patients with an average age of 52 years for their first skin malignancy.

Selective Thermal Neutron Capture Therapy and Diagnosis of Malignant Melanoma: From Basic Studies to First Clinical Treatment

As melanoma genesis occurs in pigment cells, accentuated melanogenesis concurrently occurs in principlel. Thus, harnessing this accentuation of melanogenesis, we developed a new mutually-dependent two-step therapy, in which melanogenesis-seeking compounds first specifically target melanoma cells, enabling the powerful second step to selectively destroy the targeted cells. Our new thermal neutron capture therapy2,3,4,5(NCT) uses a 10B-dopa(melanin substrate) analogue, 10B1-p-boronophenylalanine (10B1-BPA) which accumulates preferentially in melanoma cells6,7. The cells then are irradiated with thermal neutrons to induce the 10B(n, α)7Li reaction which releases energy of 2.33MeV to a distance of 10~14μ, the diameter of melanoma cells. Extensive in vitro and in vivo radiobiological analysis8 confirmed the highly enhanced killing effect of 10B1-BPA. Measurements of the accumulating capacity of 10B1-BPA into melanoma cells in vitro and in vivo using both chemical and prompt gamma ray spectrometry7 assay showed its high affinity for these cells9.

Enhancement of tumor growth by basement membrane: Modulation of growth and angiogenesis by laminin-derived synthetic peptides

The study of human cancers has been impaired by a lack of good animal models. Human cancers are difficult to grow in culture, and the use of immunologically deficient mice has had limited success in propagating human tumors [1]. If a tumor is able to grow in a mouse, its ability to subsequently survive in culture is enhanced. We and others have found much greater take and growth of both murine and human tumor cells and primary isolates in mice when the cells are premixed with a basement membrane extract (Matrigel) and injected subcutaneously [2, 3, 4, 5]. In addition, we have been able to further increase the growth of solid tumors by the inclusion of a synthetic angiogenic peptide derived from the laminin A chain [6]. In contrast, anti-angiogenic peptides reduce the tumor growth even when intra-peritoneal injections of the peptide are initiated several days after tumor growth has begun [3]. Although these subcutaneous tumors do not frequently metastasize, the growth of such tumors is an important first step in developing animal models to study the metastatic and phenotypic properties of human cancer.

Further in Vitro Radiobiological Analysis on 10B-BPA BNCT of Malignant Melanoma: Correlation of Determined 10B-Content and Cell Killing Effect

The successful application of boron neutron capture therapy (BNCT) for melanoma depends on the following points, (1) high accumulation of 10B in target melanoma cells (approcimately 20 ppm) and (2) high tumor/normal tissue10B ratio, theoretically greater than 5.