[Operative management of continuous erection of the penis--reconstruction of collateral venous circulation].
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Publications and source records attributed to Y Seo.
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The effect of combined use of a derivative of nitrosourea, ACNU, with recombinant human tumor necrosis factor (rhTNF) on the radiation-induced antiproliferative effect was examined using Meth A tumor cells. The radiation-induced antiproliferative effect was slightly augmented by the simultaneous addition of ACNU at 10 micrograms/ml in 5 Gy and 15 Gy irradiated groups. The antiproliferative effect was augmented in parallel with the radiation dose by the addition of rhTNF. Further augmentation of the proliferation inhibition was observed when both of ACNU (10 micrograms/ml) and 10 U/ml of rhTNF were added in combination with irradiation. Similar augmentation was observed when the target cells were treated with ACNU prior to irradiation and the addition of rhTNF.
A method for peroxidase labeling of the monomeric subunit (IgMs) of ABO blood group specific mouse monoclonal IgM is described. IgM was purified from a commercial monoclonal anti-B blood grouping reagent by a combination of salt precipitation, euglobulin precipitation, and gel filtration. IgM was mildly reduced with L-cysteine to yield SH-bearing IgMs. Finally, IgMs was conjugated to horseradish peroxidase, into which SH-reacting maleimide groups had been introduced using N-succinimidyl 6-maleimidohexanoate, through the selective reaction between SH of IgMs and maleimide groups of peroxidase.
Renin-producing tumors of extrarenal origin are rare in children. An 8-year-old boy with hepatoblastoma and hypertension associated with a high plasma renin level is reported. After chemotherapy, the plasma renin level normalized and the hypertension spontaneously resolved. The patient underwent surgery, and a right trisegmentectomy of the liver and a partial resection of the second and third segments were performed. The tumor was as shown the source of renin by immunohistochemical study and reverse transcriptase-polymerase chain reaction.
We investigated the possible mechanisms of hyperthermic enhancement of actinomycin D (AMD) cytotoxicity in a neoplastic cell line. The hyperthermic enhancement of AMD cytotoxicity depended on both the temperature and the sequence of the administration. The percentage survival of simultaneous treatment of either 42 or 43 degrees C hyperthermia with 5 micrograms/ml AMD was 42% or 2.2%, respectively, and the amount of AMD in the DNA (DNA-bound AMD) of simultaneous hyperthermia at either 42 or 43 degrees C was 16.5 or 27.2 ng/10(6) cells, respectively. The percentage survival of sequential treatment of 5 micrograms/ml AMD following either 42 or 43 degrees C hyperthermia was 55 or 46%, respectively. The amount of DNA-bound AMD of sequential hyperthermia at either 42 or 43 degrees C was 10.8 or 21.7 ng/10(6) cells, respectively. In addition, the percentage survivals of the S-phase and G1-phase cells concomitantly treated with 43 degrees C hyperthermia and 5 micrograms/ml of AMD were 1.4 and 92%, respectively, and the amounts of DNA-bound AMD of these S-phase and G1-phase cells were 28.2 and 1.6 ng/10(6) cells. These findings suggested that an increased amount of AMD in DNA was responsible for the hyperthermic enhancement of AMD cytotoxicity. When the G1-phase cells were treated with 5 micrograms/ml AMD alone, without hyperthermia, the amount of AMD in acid-soluble fraction of the G1-phase cells was quite low (0.3 ng/10(6) cells). However, concomitant hyperthermia treatment with AMD at the G1-phase significantly increased the AMD amount (1.6 ng/10(6) cells at 42 degrees C, and 3.1 ng/10(6) cells at 43 degrees C) up to a level equal to that in asynchronous (1.7 ng/10(6) cells) and S-phase cells (2.1 ng/10(6) cells) simultaneously treated with hyperthermia and AMD. It was suggested that hyperthermia altered the membrane permeability of the G1-phase cells. The increase of the AMD amount in the DNA might thus be the result of higher intracellular drug concentration.
It is important to reduce a systemic stress during regional hyperthermia against upper abdominal malignancies. A 50 mg indomethacin suppository was administered to five patients with intrahepatic tumour 30 min before hyperthermia. Oral temperature only rose to 37.8 degrees C, heart rate increased to just 110/min, and systolic blood pressure only increased to 134 mmHg. Under these conditions, epinephrine and norepinephrine rose to only 0.09 and 0.25 ng/ml, respectively, which were within normal limits. In addition, prostaglandin E2 (PGE2) did not increase at all. However, when these same five patients were not pretreated with indomethacin, parameters monitoring the systemic condition rose profoundly during hyperthermia. Systemic stress during hyperthermia against upper abdominal malignancies was reduced by the indomethacin pretreatment.
Bone metastases diffusely invading the bone marrow from gastric cancer often manifest a rapid clinical course and the prognosis is very poor due to hematologic disorders such as DIC (disseminated intravascular coagulation) and/or MAHA (microangiopathic hemolytic anemia). The objective of this study was to clarify the clinicopathological features and prognosis of patients with gastric cancer in whom diffuse bone metastasis associated with hematologic disorders were evident. Thirty-eight patients with bone metastasis from a primary gastric cancer were thus selected and placed into 2 groups consisting of 15 with diffuse bone metastasis with DIC and/or MAHA, and 23 patients who had bone metastasis without hematological disorders. We compared the clinicopathological features and prognosis between the two groups. The clinicopathological features in patients with diffuse bone metastasis accompanied by hematologic disorders were significantly related to undifferentiated adenocarcinoma, a relatively younger age, elevated levels of serum ALP-BI and LDH, and a lower frequency of extraosseous metastasis. The median survival time after manifestation was 2 and 11 months for the patients with or without hematologic disorders, respectively. The prognosis was significantly worse in cases of DIC with the median survival being only one month. Since, prognosis of diffuse bone metastasis from gastric cancer is significantly poor, close attention should be directed to the specific clinicopathologic features related to diffuse bone metastasis plus hematologic disorders. Regarding high risk patients, a regular follow-up of the serum chemistry levels and a bone scan will aid in the early detection of the disease.
We present a patient with pancreatoblastoma along with a discussion of various cross-sectional imaging features. The tumor was a large multilocular cystic mass with solid components in the left retroperitoneal space. There were fine internal echoes on ultrasonography, and the signal intensity was high on both T1- and T2-weighted MR images in most of the locules, suggesting the presence of hemorrhagic debris. Among the various retroperitoneal organs displaced by the tumor, only the pancreatic tail was inseparable from the mass, suggesting that the pancreatic tail was the origin of the tumor. Pancreatoblastoma should be included in the differential diagnosis when a large left upper quadrant mass with these imaging features is seen in infants and young children.
Two cases of hepatocellular carcinoma (HCC) with ring calcification are reported together with their CT findings. HCC in both cases showed little early enhancement followed by delayed enhancement on dynamic CT. The pathologic specimen in one case showed HCC with fairly abundant fibrosis, and calcification was noted underneath the thick fibrous capsule, which might explain the enhancement pattern on CT.
Among 145 patients with carcinoma of the pancreas who had been admitted to three institutions between 1976 and 1985, 117 were entered into a prognostic factor analysis system according to Cox's proportional hazards model. The treatment was classified into four modalities: bypass surgery, single-dose intraoperative radiotherapy (IOR), IOR combined with external irradiation, and resection with or without various radiations. The most important prognostic factors for treatment were identified as location of tumor, TNM stage, and relief of back pain. Adjusting the imbalances among the treatment groups using Cox's model, the superiority of IOR with external irradiation was confirmed for both bypass and single-dose IOR. With this adjustment, the survival rates proved to be more meaningful than the simple Kaplan-Meier estimates.
An in vitro assay method for predicting the hormonal response of primary cultured cells was used in 38 women with breast carcinoma. The response to 17 beta-estradiol (E2) was compared with other hormone treatments, such as tamoxifen (TAM), estracyt (EC) and bestrabucil (BB). The response to the E2-conjugated drugs (EC and BB) and TAM showed a good correlation with the response to E2 (p < 0.01). Coincidental rates of EC and BB response (stimulatory, insensitive, and inhibitory) with E2 response were 47% (16/34) and 53% (16/30) of cases, respectively. Cells showing an inhibitory response to E2 were also inhibited by EC and BB in 60% (6/10) and 100% (8/8) of cases, respectively. In premenopausal women, 28% (5/18) and 43% (6/14) of cases were inhibited by EC and BB, respectively, whereas in postmenopausal women 44% (7/16) and 56% (9/16) of cases showed inhibition with EC and BB, respectively. The inhibitory response to the E2-conjugated drugs was not significantly different between pre- and post-menopausal women. Cells resistant to inhibition by TAM were inhibited by EC and BB, respectively, in 17% (4/24) and 30% (6/20) of cases. These results indicate that E2-conjugated drugs may inhibit the growth of breast cancer cells and that their inhibitory actions might be different from those of TAM.
The combined chemotherapy of SN-38, active metabolite of CPT-11, and 5-FU in vitro was examined using human cell lines and primarily cultured cells obtained at surgery. The percent survival of the Suit-2 cell line treated with a single modality of SN-38 at the concentration of 0.95-61 nM was 70% to 86%, while, when treated with SN-38 and 5-FU, the percent survival of these cells decreased at even 1 microM of 5-FU. The enhanced ratios (percent survival at 0 nM SN-38/percent survival at 61 nM SN-38) at 1 microM and 4 microM of 5-FU were 1.56 and 1.33, respectively. The enhanced ratio became lower when the concentration of 5-FU was increased. When topoisomerase I activity in Suit-2 cells incubated with 5-FU was examined, 5-FU at a high dose (> or = 4 microM) in the medium caused a strong inhibition of the relaxation of Suit-2 DNA by topoisomerase I, but 5-FU at low dose (< or = 2 microM) barely inhibited topoisomerase I activity. These results indicated that topoisomerase I synthesis in the Suit-2 cell line might be suppressed by a high dose of 5-FU in the medium but not by a clinically achievable level of 5-FU. The cancer cells obtained from clinical cancer tissues were treated with these drugs at a clinically achievable dose in the medium. Judging from the results of a sensitivity test, in 7 out of 10 cases, the percent survivals under the combined treatment were lower than those estimated under the single modality treatment. Therefore, by the addition of 5-FU, the antitumor effect of CPT-11 would seem to be further enhanced.
The difference in growth response between neoplastic and contact-sensitive normal cells was investigated by cell growth curve, colony forming efficiency and flow cytometric analysis. Neoplastic cells (MKN-28, MKN-45, and MCF-7), treated with paclitaxel at a concentration of 0.01 mM, showed growth inhibition, low colony-forming efficiency and a prolonged G2+M phase accumulation. Normal cells (Balb/c 3T3 cells and human fibroblasts originating from stomach cancer tissue), treated with paclitaxel at a concentration of less than 0.5 microM, showed no growth inhibition and no decrease in colony-forming efficiency. Normal cells treated with 1 microM of paclitaxel showed low accumulation in G2+M phases. The results show that paclitaxel at concentrations ranging from 0.01 to 0.5 microM had a cytotoxic effect against neoplastic cells but not against normal cells, such as fibroblasts around the cancer cells.
CPT-11 is a derivative of camptothecin, a topoisomerase-I inhibitor with marked cytotoxic activity. We examined the cytotoxicity of CPT-11 and its metabolite SN-38 for primary gastrointestinal carcinoma and various recurrent carcinomas which were cultured on contact-sensitive plates (CSPs). The response rate of seven gastrointestinal carcinomas for either CPT-11 or SN-38 was 71% (5/7). The response was higher than those for other anticancer agents, including adriamycin (ADM), cisplatinum (CDDP) and 5-fluorouracil (5-FU). The mean percent survival of these tumor cells was 69% when incubated with 25 ng/ml of SN-38, which was the lowest survival for all the anticancer drugs tested. IN the case of recurrent carcinomas, the response rate to either CPT-11 or SN-38 was 60% (3/5), and was higher than the rates for MMC, CDDP or 5-FU. The mean percent survival of the recurrent carcinoma cells was 76% in the presence of 25 ng/ml SN-38, and this was once again the lowest survival rate. CPT-11 had a stronger inhibitory effect against one carcinoma than SN-38 when a clinical drug concentration was added to the culture medium, suggesting that CPT-11 itself was cytotoxic. IN addition, one carcinoma with a low response to CDDP also showed no response to CPT-11, but was very occurred because of decreased conversion of CPT-11 to SN-38. Our results suggest that CPT-11 may be a useful agent for the treatment of both primary gastrointestinal cancer and various recurrent carcinomas.
We investigated the cytotoxic potentiation by folinic acid (FA) of two fluoropyrimidines, 5-fluorouracil (FUra) and 5'-deoxy-5-fluorouracil (5'-dFUrd), against two human neoplastic cell lines (HeLa and KSE-2 cells). The concentrations of fluoropyrimidine (2-10 microM) and FA (1 microM) in media were based on clinically achievable levels, and the duration of culture was relatively long (6 days). The cytotoxic activity of fluorouridine and FA was evaluated by both clonogenic efficiency and thymidylate synthase (TS) inhibition rate of the cells. After combined treatment with 2 microM 5'-dFUrd and 1 microM FA the clonogenic efficiencies of the two cell lines were significantly lower than those after treatment with 5'-dFUrd alone (p < 0.01). Moreover, the TS inhibition rates of these two human cell lines after combined treatment with 10 microM 5'-dFUrd and 1 microM FA were significantly higher than those after treatment with 5'-dFUrd alone (p < 0.01). However, when these two cell lines were exposed to FUra, concomitant treatment with FA did not enhance cytotoxicity. These differences in the cytotoxic properties of FUra and 5'-dFUrd in response to the addition of FA ascribed to the fact that during 2-3 days and 5-6 days after treatment, intracellular concentrations of 5'-dFUrd produced by combined treatment with 10 microM 5'-dFUrd and 1 microM FA were higher than those associated with 10 microM 5'-dFUrd achieved by combined treatment with 5'-dFUrd and FA was also higher than that of FUra during combined treatment with FUra plus FA and that of 5'-dFUrd during treatment with 5'-dFUrd alone. There was no statistically significant difference in intracellular FUra concentrations between combined treatment with FUra plus FA and treatment with FUra alone. Prolonged treatment with 5'-dFUrd and FA in clinically feasible concentrations was thus more effective than the combination of FUra and FA in two human neoplastic cell lines.
We examined the activity of paclitaxel against primary cultured cells from gastrointestinal neoplasmas, such as stomach, colon, hepatocellular and pancreatic cancer, and estimated the clinical use of paclitaxel. Antitumor activity, expressed as reduction in cell survival rates mediated by anticancer agents, was measured using [3H]thymidine incorporation into primary cell cultured. Percent survival rates for stomach, colon and hepatocellular cancer cells in the presence of 0.5 microM paclitaxel were 68.1%, 58.4% and 65.1%, respectively. Proportions of gastrointestinal cancer cases having percent survival rates of < or = 70% for paclitaxel, CDDP, MMC and ADM were 48.3%, 17.4%, 28.0% and 21.1%, respectively. The rate for paclitaxel was the highest of all. The proportion of stomach, colon, liver and pancreatic cancer cases having a percent survival rate of < or = 70% in the percentage of paclitaxel were 55.6%, 66.7%, 50.0% and 20.0%, respectively. In particular, the proportions of stomach and colonal cases having survival rates of < or = 70% for paclitaxel in spite of having survival rates of > 70% for other anticancer drugs were 75% (3/4) and 50% (2/4), respectively. From these results, it is probable that paclitaxel will demonstrate clinical activity in gastrointestinal tract cancers, such as stomach, colon, hepatocellular and pancreatic cancer.
The usefulness of lymphocyte subset change as an indicator for predicting survival time and the effectiveness of combined treatment with an immunopotentiator, lentinan, and carboplatin (CBDCA) were investigated. Of 13 patients with advanced unresectable cancer entered in this study, 9 were administered 2 mg/body lentinan and 450 mg/m2 CBDCA, and 4 were administered a single modality of CBDCA. The mean survival time of all 13 cases was 9.89 months. Lymphocyte subsets of CD11(-)CD8(+), CD11(+)CD8(+), CD57(-)CD16(+) and CD57(+)CD16(+,-) were measured by two-color flow cytometry. In five cases surviving longer than 9.89 months, CD11(-)CD8(+)/CD11(+)CD8(+) on post-treatment showed an increase two-fold higher than on pre-treatment, but in all cases surviving less than 9.89 months the rate on post-treatment did not increase two fold higher than on pre-treatment. The mean (1.78) of (post-treatment/pre-treatment) ratios of CD57(-)CD16(+)/CD57(+) in long survival cases was significantly higher (p < 0.01) than that (0.46) in short survival cases. Moreover, the mean of (post-treatment/pre-treatment) ratios of CD11(-)CD8(+)/CD11(+)CD8(+) and CD57(-) CD16(+)/CD57(+) showed a good correlation with survival time. These results indicate that changes of lymphocyte subsets of killer T cell/suppressor T cell and natural killer cell on posttreatment compared to pre-treatment are clinically useful indicators for predicting and monitoring the effectiveness of combined treatment with lentinan and CBDCA.
In 55 gastrointestinal cancer patients the mean change ratios for platelets were, respectively, 1.22 +/- 0.75 and 0.67 +/- 0.45, in the romurtide administration (30 cases) and non-administration (25 cases) groups, [statistically significant difference (p < 0.005)]. The number of cases in each group with a decrease in platelet count was 13 (43%) and 20 (80%) with and without romurtide, respectively. The difference was statistically significant, (p < 0.01). In addition, the number of cases with a marked decrease ( < 6 x 10(4)/mm3) in platelet count was 2 (7%) and 7 (28%) with and without romurtide, respectively, reaching statistical significance (p < 0.05). For patients treated with a bolus administration of 450 mg/m2 carboplatin (27 cases), the mean change ratios for leukocytes and platelets in the romurtide administration group (13 cases) were 1.10 +/- 0.52 and 1.23 +/- 0.59, respectively. Meanwhile, in the romurtide non-administration group the mean change ratios for leukocytes and platelets were, respectively, 0.74 +/- 0.27 and 0.74 +/- 0.42, a statistically significant reduction (p < 0.05) compared with the romurtide administration group. The number of cases with an increase in the number of lymphocytes after i.v. administration was significantly more than that observed after s.c. administration (p < 0.01). These results indicate that romurtide has a restorative effect on thrombocytopenia similar to that displayed for leukocytopenia when given as concomitant therapy with anticancer drugs and/or irradiation in patients undergoing intensive treatment for gastrointestinal cancer.