PubMed HealthSearch

Biomedical subjects

S Akaishi

Publications and source records attributed to S Akaishi.

At least 19 recordsLinked to original sources

Targeting chemotherapy using antibody-combined liposome against human pancreatic cancer cell-line.

Anti-tumor effect of Adriamycin (ADM)-encapsulated and CA19-9 antibody-conjugated artificial lipid membrane follicle liposomes against a human pancreatic cancer cell-line PK-1 was studied in vitro and in vivo. The liposome compound (lipo c ADM = Ab) showed a stronger cell damage than ADM-encapsulated liposome (lipo c ADM) and free ADM, especially when the contact time was short and the concentration was low. The intra-tumor concentration of ADM in the group of i.v. injection of lipo c ADM = Ab showed the highest value, over twice those of lipo c ADM and free ADM after 120 hr. Lipo c ADM = Ab showed a significant inhibitory effect on the tumor growth inhibition test in vivo, and the final tumor weight at the 19th day was 27% in the group of lipo c ADM = Ab and 52% in the group of free ADM as compared with the control. The targeting chemotherapy using liposomes was demonstrated to have a stronger anti-tumor effect than the administration of anti-cancer drug alone owing to enhanced tumor accessibility and good targeting.

Animals

[Transfer of carmofur (HCFU) to the serum, bile, pancreatic juice and pancreatic tumor tissue in the cases of peri-pancreatic head cancer].

The concentrations of carmofur, 1-hexyl-carbamoyl-5-fluorouracil (HCFU), in the serum, bile, pancreatic juice and pancreatic tumor tissue were studied in 18 cases of peri-pancreatic head cancer with drainages of the pancreatic and biliary ducts after pancreatico-duodenectomy. As a result, high concentrations of HCFU and 5-FU were detected in the serum, bile and pancreatic juice after a per-oral administration of HCFU, 200 mg: HCFU was high in the order of serum > bile and pancreatic juice, and 5-FU in the order of bile, serum and pancreatic juice. Two hours after administration, 5-FU concentration in the bile and serum attained to the maximum levels of 0.45 and 0.19 micrograms/ml, respectively, which demonstrated a lasting transfer of 5-FU to the bile at high concentration. HCFU and 5-FU levels in the tumor tissue were 0.079 and 0.024 micrograms/g, respectively. In conclusion, antitumor effect against the malignant tumors of the pancreatobiliary system can be expected by peroral administration of carmofur.

Administration, Oral

Growth-inhibitory effect of combination chemotherapy for human pancreatic cancer cell lines.

Sensitivities to anti-tumor drugs, mitomycin C (MMC), aclarubicin hydrochloride (ACR), doxorubicin hydrochloride (ADR), cisplatin, and 5-fluorouracil (5FU), were examined using PK-1, -8, -9, -12, -14, and -16 cell lines derived from human pancreatic cancer. These cell lines showed different sensitivities to each of the above anti-tumor drugs. The concentrations required for 50% growth-inhibition (IC50) after 2 hours of exposure were 0.096 to 0.35 micrograms/ml for MMC, 0.0074 to 0.0076 micrograms/ml for ACR, 0.033 to 0.23 micrograms/ml for ADR, 0.35 to 1.9 micrograms/ml for cisplatin, and 21 to 42 micrograms/ml for 5FU, IC50 of each anti-tumor drug decreased significantly after 48 hours of exposure. The combination of any two out of MMC, ACR, and 5FU showed synergistic inhibition of the growth of PK-1 and PK-8 cell lines. These results show that MMC, ACR, ADR, cisplatin, and 5FU have sufficient anti-tumor effect against six human pancreatic cancer cell lines even at clinically achievable concentrations and exposure times, and chemotherapy for pancreatic cancers requires naturally effective drug delivery into cancer tissues.

Aclarubicin

[Experimental study of the intra-operative radiation therapy in pancreatic cancer].

The radiosensitivity of pancreatic cancer, optimum dose of irradiation and the effect of 1-[(4'-Hydroxy-2'-Butenoxy) Methyl]-2-Nitrosoimidazole (RK-28) on irradiation were investigated using an experimental pancreatic cancer of hamster and the following results were obtained: i) The mean lethal dose (Do) and the 50% tumor control dose (TCD50) against the pancreatic cancer were 3.5 Gy and 73.7 +/- 6.9 Gy, respectively. These results indicate that the pancreatic cancer is resistant to irradiation, which could be explained by the existence of hypoxic cells consisting of 35% of the tumor. ii) The dose of intraoperative irradiation (10-40 Gy) seemed to be insufficient to bring long-term anti-tumor effect and long-term survival since that dose resulted in only temporary regression of the tumor. iii) The hypoxic cell sensitizer (RK28), which is known to specifically enhance the sensitivity of hypoxic cells to irradiation, lowered TCD50 of the pancreatic cancer to 53.8 +/- 1.57Gy. Therefore, RK-28 was effective in the treatment of the experimental pancreatic cancer (the enhancement ratio: 1.37). When combined with 30 or 40 Gy of irradiation, which is applicable to intraoperative irradiation, RK-28 induced a longer period of tumor suppression and a higher tumor regression ratio than irradiation alone. These results indicate that RK-28 significantly increases the effect of intraoperative irradiation and this combination therapy could possibly induce remarkable effect on tumor regression and long-term survival.

Adenocarcinoma

[Effects of urokinase on the transfer of 1-hexylcarbamoyl-5-fluorouracil (HCFU) into the blood, bile and pancreatic juice].

We studied effects of urokinase (Uronase) on the transfer of an oral anticancer agent, 1-hexylcarbamoyl-5-fluorouracil (HCFU) into blood, bile and pancreatic juice in 5 patients in whom pancreaticoduodenectomy has been performed for cancer of the periampullary region, and who had been simultaneously provided with drainage of the bile duct and pancreatic duct. Following oral administration of 500 mg of HCFU, HCFU and 5-FU concentrations in blood reached a peak at 2 hours, those in bile at 4 hours, and those in pancreatic juice at 4 to 6 hours. The administration of 24,000 IU of urokinase in combination with HCFU resulted in increased HCFU and 5-FU concentrations in blood, bile and pancreatic juice--the HCFU concentration in bile increased to 3 times and that in pancreatic juice, to about 5 times the level in the some counterparts in urokinase--untreated patients. These changes seemed to have resulted from the acceleration by urokinase of distribution of the anticancer agent into the organs.

Administration, Oral

Homicidal and camouflaged carbon monoxide poisoning in Japan.

There were 1,985 fatal cases of CO poisoning in the Tohoku district of Japan in the period from 1969 to 1980. Among them, 1,322 cases were suicidal, 662 accidental, and one homicidal, in which a man killed his wife with the self-made CO gas to obtain by fraud a large amount of life insurance. Our nationwide survey revealed four other cases of homicidal CO poisoning and two cases of camouflaged CO poisoning. The police and police surgeons should be cautious enough in cases of CO poisoning.

Adult

Isoelectric focusing studies on the PGM1 subtypes in the northern Japanese population.

The distribution of the human red cell phosphoglucomutase (PGM1) subtypes in samples from Japanese population (n = 277) living in the Miyagi Prefecture, the northern part of Japan, was investigated by applying the thinlayer polyacrylamide gel isoelectric focusing. In our population sample all the ten common phenotypes were demonstrated, and the estimated allele frequencies for the genes PGM1+1, PGM1-1, PGM2+1, and PGM2-1 were 0.671, 0.107, 0.161, and 0.061, respectively. Family studies (n = 40) indicated an autosomal codominant inheritance and confirmed the four alleles. The new system will increase the probability of exclusion in paternity cases among Japanese to 29.4% compared with 14.3% if the two allele system is used.

Female

Physico-chemical properties and local toxic effects of injectables.

In Japan, many cases of muscle contracture as a sequela of injections have been reported. We studied the physico-chemical properties and muscle-damaging potential of many injectables which are commonly used in hospitals. Contrary to our expectations, the pH of the injectables was found to range widely from 1.4 to 12.8, and the osmotic ratio from 0.2 to 36. It was also found that their hemolytic potential was closely related to the severity of the muscle lesions in animal experiments and that there were many injectables with strong muscle-damaging potentials. Therefore, doctors should be informed of the physico-chemical properties and tissue-damaging potential of each injectable; pharmaceutical companies should exert all possible efforts to improve injectables; and doctors should keep the administration of intramuscular injections to a minimum and use them only in cases of actual need.

Animals