1958年以来ヘマトポルフィリン水銀塩の制癌効果は,それを考案した飯島らをはじめ多数の臨床的及び基礎的蘇究の報告がなされている。
飯島らは担癌動物の肝に於ける著明な肝カタラーゼ活性の低下,銅第1分劃の上昇,フリーポルフィリン増加及び金属ポルフィリン減少などが所謂腫瘍物質によつて惹起されると思われる事実から,抗トキソホルモン作用を有する物質をもつて癌治療に応用しようとしてヘマトポルフィリン水銀を取り上げたことは,腫瘍細胞を直接攻撃する従来の抗癌剤と全く異つた観点に立つ点で極めて意義深いものがある。神前も癌患者の尿中ポルフィリン排泄量の増加,血中ポルフィリン量の上昇に注日し,癌に於てポルフイリン体平衡は金属ポルフィリンを減少させる状態にあるといい,ポルフィリン体分布の異常は癌発生の　1次的要因の　1つではないかと想定した。
我々も之等の説を継承する立場に於てヘマトポルフィリンの換りに生体内ポルフィリン体の　1つであるプロトポルフィリンのコパルト錯塩について癌の治療的応用を試みようとするものである。而して細胞内酸化触媒作用として重要な金属ポルフィリンのうち,最も安定な金属ポルフィリンであり且細胞内酸化の作用の顕著とされるコパルトポルフィリン体を選び,光感作用のないプロトポルフィリンの金属錯塩として使用した。他方,ポルフィリン体が癌治療物質として利用の端緒をなしたのはAULER,FIGGEらの云うポルフィリン体の新生腫蕩組織に対する親和性の問題である。即ち FIGGEらは動物の自然発生及び移植癌組織にポルフィリン体及び金属ポルフィリン体の蓄積を蛍光によつて確認している。今回はコバルトプ口卜ポルフィリンの治療的応用を検討するに先立ち動物移植癌に対する親和性について得た成績を報告する。

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The effect of pretreatment with protoporphyrin IX (PP) on the impairment of hepatic mitochondrial respiration induced by carbon tetrachloride (CCl₄) was studied in rats. Treatment of animals intraperitoneally with CCl₄ resulted in marked impairment of states 4 and 3 respirations, respiratory control and oxidative phosphorylation of mitochondria in the presence of succinate, β-hydroxybutyrate or glutamate as substrates. The PP, given intravenously, caused no alterations in those mitochondrial functions. The treatment with PP prior to the administration of CCl₄ inhibited the induction of mitochondrial respiratory impairment by CCl₄. CCl₄ increased markedly the contents of lipid peroxide in the liver but not those in the mitochondria. The increase of hepatic lipid peroxides by CCl₄ was markedly reduced by the pretreatment with PP. These results indicate that PP effectively protects the mitochondria from the functional disorder caused by CCl₄.

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In an established solid MH134 tumor in C3H/He mice, necrotic part increased in size after a time while viable part got smaller, At this stage, many lymph node metastases emerged stimulating the compensatory growth for the reduction of viable part. This fact appears to suggest that a well-established tumor bearing host can sustain a certain amount of viable part of tumor and that the emregence of metastases is, to some extent, delayed if the reduction of viable part is prevented. In fact, it was recently found that the viable part contains substances, inhibiting DNA-synthesis in MH134 cancer cell.
In an attempt to inhibit metastasis and recurrence, the primary tumor was removed and the viable part of this tumor was incubated for 7 hours under 37°C in 7% bicarbonate solution and was autotransplanted. The effect of 7% bicarbonate solution on the cancer cell is as follows:
1) According to our experiments in vitro, the bicarbonate treated cancer cell reduces its O₂ consumption reversibly. This fact indicates that the enzymatic activity of the bicarbonate treated autograft continues in the host for a while.
2) It prevents the reduction of tumor-graft that otherwise should have occurred in a well established MH134 tumor. This fact indicates that it stabilizes the viable part, releasing the inhibitor continuously against dispersed cancer cells in the tumor bearing host.
3) It has no effect upon the inhibitor of the viable part in vitro.
4) It inhibits the growth of tumor cell.
The result of this treatment was as follows:
(I) 149 mice bearing 2 to 3 weeks old MH134 tumor underwent removal of the tumor. 77 of them received bicarbonate-treated tumor autograft and 72 none. Survival rate during 300 days period after operation was threefold higher in the treated than in the controls. For example after 90 days it was 14/77(18.6%) in the treated and 4/72(5.6%) in the controls.
(1) In C3H mice of spontaneous mammary cancer, survival rate of the thus treated was 5/14 (35.7%) while 0/11 (0%) in the controls 154 days after radical mastectomy.
Autotransplantation of bicarbonate-treated tumor did not reverse the fall of serum albumin and the increase of alpha globulin, but it did rectify, to some extent, the fall of liver catalase activity the increase of serum lactic dehydrogenase and the involution of thymus. In such an occasion, splenomegaly was noted with accompanying lymphopoesis. Some clinical experience on 20 gastric cancer patients who have received this treatment is to be presented.

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Using a dog as an experimental animal, the metabolism of cobalt, nickel, zinc, manganese, and magnesium has been studied from normal to secondary hemorrhagic shock. The results are as follows:
1) The content of cobalt, nickel, zinc, manganese, and magnesium markedly decreased in the liver.
2) No marked change occured in the spleen.
3) Of vein serum, the magnesium content increased in a state of hemorrhagic shock.

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The content of ferritin iron was determined in a normal state and in hemorrhagic shock. The results are summarized as follows:
1) Normal ferritin obtained in the present experiments contains about 15-17% iron. These values seem to be slightly smaller compared with those obtained by other workers.
2) Ferritin of hemorrhagic shock shows markedly lower iron content. The nitrogen content remains almost constant independent of whether it is in a normal state or in a hemorrhagic shock.
3) These results show that the liberation of ferritin iron occurs in the hemorrhagic shock.

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The effect of some inorganic substances, nitrogen, carbon dioxide, and hydrogen gas, and copper, cobalt, nickel, zinc, manganese, tin, and magnesium, were studied in the ferritin-iron liberation. The results are summarized as follows:
1) Hydrogen gas promotes the ferritin-iron liberation. The effect of nitrogen and carbon dioxide gas was not clear.
2) The effect of copper, cobalt, nickel, manganese, zinc, and magnesium salt was not clear, but, in the existence of hydrogen gas, it seems that these salts slightly promote the ferritin-iron liberation.
3) Stannous chloride slightly promotes the ferritin-iron liberation. This may be due to the reducing activities.

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Using a dog as the experimental animal, the authors studied systematically the metabolism of iron and copper from normal to hemorrhagic shock state. By bleeding, the hypotential state continued for several hours, finally the animal fell into a sate of shock. The liver, spleen, and serum were chosen for this study.
1) The iron and copper content of the liver decreased markedly without any exception. No marked decrease of iron takes place during the hypotential state. Only when the state of shock was finally reached was iron liberated from the liver.
2) The serum iron value in vein distinctly decreased without any exception, while, in artery, the decrease was not so marked. In all cases, the serum iron level in artery was always more than that in the vein.
3) The variation of serum copper value was not always consistent. It is assumed that the general tendency is an increase. No difference could be observed in the content of vein serum and that of artery serum.

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Various drugs (anti-cancer agents, chelating agents, amino acids and salts) were injected i.p. with ⁶⁵Zn into Ehrlich ascites cancer-bearing mice, and after 1 hr its effect on the organ distribution of ⁶⁵Zn was investigated.
1. Mitomycin C (200 μgg/mouse), Toyomycin (50 μg/mouse) and Nitromin (500 μg/mouse) had no effects on the distribution of ⁶⁵Zn. Merphyrin (500 μg/mouse) caused a decrease in ⁶⁵Zn uptake by cancer cells without any effects in the other organs.
2. EDTA and BAL (each 1 mg/mouse) inhibited ⁶⁵Zn> uptake by cancer cells and conversely elevated its concentration in ascites supernatant. BAL elevated also ⁶⁵Zn concentration in other various organs. Tetracycline, dihydrothioctic acid and Na-thioglycolic acid (each 1 mg/mouse) did not affect the ⁶⁵Zn uptake by cancer cells.
3. Penicillamine (D-and DL-type, each 1 mg/mouse) caused a decrease of ⁶⁵Zn concentration in cancer cells with an increase of its concentration in the other organs. Cysteine, histidine and glycine (each 1 mg/mouse) had no effects on the ⁶⁵Zn distribution in every organs.
4. Various salts (each 0.1 ml of 3.5 ×10^-2M solution was injected per mouse) also affected organ distribution of ⁶⁵Zn. ZnSO₄, CoCl₂ and NiSO₄ inhibited the uptake of ⁶⁵Zn by cancer cells, however, MgCl₂, MnSO₄, FeCl<₂ and CuSO₄ had no effects on it. Organ distribution of ⁶⁵Zn was also affected by various salts without definite relationship between them.
5. In ascites cancer cells, the highest concentration of ⁶⁵Zn was found in supernatant fraction, next in nuclear and microsomal fraction. The mitochondrial fraction contained the lowest amount. All of the above drugs had no effect on the intracellular distribution pattern of ⁶⁵Zn in cancer cells.

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癒着現象が, フィブリンの折出→フィブリンのポリマー化→細胞浸潤, 線維芽細胞出現→コラーゲン線維網形成→細胞線維性癒着組織の完成, という過程を経て進行することに注目し, ヘパリン徐放で癒着の初期段階であるフィブリン折出を完全に阻止することによって, われわれは癒着防止に成功した。ヘパリンを含有し, 徐放する担体は, ヘパリン徐放後生体内に埋没され, あるいは吸収されることが望ましいことからコラーゲン膜をそれに利用した。動物実験として, 成犬の大腸漿膜に5cm平方の欠損を作り, この部をヘパリン化したヒト羊膜で覆い, 100%の抗癒着性を得た。60日以上の経過例では, ヘペリン化羊膜はすでに正常な漿膜細胞に覆われていた。従って, 作成した癒着防止膜を用いることによって, 初期はヘパリンの徐放により, その後は正常な漿膜細胞による天然の抗癒着力によって, 永久に癒着を阻止しつづけることが明らかとなった。

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