and TAKAHASHI, M. Intratumoral Doxycycline for Skin Metastases of Human Malignancies. Tohoku J. exp. Med., 1987, 151(2), [241][242][243][244] As soon as its inducibility of lethality via prompt deprivation of heavy metals and HDL-cholesterol was born out, an intratumoral administration of doxycycline, an anti-prokaryotic agent, was undertaken in 7 patients presenting with skin metastases from a variety of malignancies. Complete remission of these lesions was attained in 6. The histological observation of elongated areas of acellularity along with central vessels appeared to suggest doxycycline-mediated cellular disintegration, resulting in empty tumor cords. Specific tumor selectivity of the treatment can be sustained by the intraand/or peri-tumoral confinement of the agent. The technique may constitute a novel mode of cancer cell elimination, anti-cancer effect ; doxycycline ; intra-tumoral injection ; skin metastasis Radiotherapy and surgery can be refrained especially when tumor metastases occur in the fields of the previous irradiation on account of probable induction of intractable radiation dermatitis and eventual radiation ulcers. Therefere, there has to be a novel technique that would facilitate treatment of local tumors without much untoward hazards to the host patients.Tetracyclines have been employed in the treatment of malignant pleurisy through induction of serosal fibrosis (Rubinson and Bolooki 1972). However, they have already been shown to be cell-killing in vitro , and we thought it worth-while to investigate the probable therapeutic effects of intratumoral injection of tetracyclines into skin metastases of human malignancies. MATERIALS AND METHODSThirty male Wistar rats of 6-months of age were fasted overnight, and were intraperitoneally injected with aliquots of normal saline or doses of doxycycline (50, 100 or 200 mg per rat). The concentrations of Cu and Zn were determined by atomic absorptiometry. The HDL-concentrations were estimated by the method of Noma et al. (1978).Doxycycline was injected into skin metastases from a variety of tumors (Table 2). Seven patients were treated by intratumoral injection of 0.3 to 0.6 ml or 6 to 12 mg of