[A study on estrogen receptor in human breast cancer by specific monoclonal antibody].
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Adult↗
Biomedical subjects
K Okui
Publications and source records attributed to K Okui.
Morphometric analysis of cytological atypia in colonic adenomas.
A total of 29 colorectal polyps were classified into those with mild, moderate, and severe dysplasia, and carcinoma. Morphometric analyses were performed on each group, determining; mean nuclear area (N-area), nuclear cytoplasmic (N/C) ratio, nuclear crowding index (Cx) and mean cellular area (C-area). N-area and N/C ratio increased in accordance with the progress of the atypical changes. Cx showed a gradual increase up to moderate dysplasia and a decline from severe dysplasia to carcinoma. N-area in severe dysplasia and carcinoma was distinctively larger than that in mild and moderate dysplasia. As for C-area, the value from normal to moderate dysplasia remained about the same, in contrast to the much higher levels in severe dysplasia and carcinoma. These results clearly indicated that the rise in N/C ratio from normal to moderate dysplasia depends mainly on nuclear crowding, but that from severe dysplasia to carcinoma on nuclear enlargement.
Adenoma↗
A histopathologic study of 102 cases of intrahepatic cholangiocarcinoma: histologic classification and modes of spreading.
In our survey of 102 cases of intrahepatic cholangiocarcinoma, 71 peripheral type cases and 31 hilar type cases were observed, the former being prone to metastasize to remote organs and lymph nodes when compared with the latter. These cases were histologically classified into nine histologic types according to the predominant features and rearranged into three groups (well-differentiated, less-differentiated, and uncommon). Although most of these cases were mucin-producing adenocarcinomas with variable grades of differentiation (92 of 102; 90%), several uncommon types were also encountered (ten of 102; 10%), such as adenosquamous, squamous, mucinous, or anaplastic carcinoma. Remote organ metastases were observed more frequently in the less-differentiated group than in the well-differentiated group. In regard to intrahepatic tumor spreading, expansion via sinusoidal spaces (93%), vascular (52%) or lymphatic (18%) involvement, perineural invasion (16%), replacing growth in the bile duct (12%), and permeation in the portal connective tissue (19%) were observed. The cholangiocarcinomas with the vascular involvement presented a higher tendency of intrahepatic as well as extrahepatic metastasis. For correct diagnosis and treatment of cholangiocarcinoma, it seems to be important to possess some knowledge of these histologic types, including their variations and patterns of intrahepatic spread.
Adenoma, Bile Duct↗
Enhancement of hyperthermochemotherapy for human gastric cancer in nude mice by thermosensitization with nitroimidazoles.
Hyperthermia for human gastric cancer xenotransplanted into the hindlegs of nude mice was performed to determine whether misonidazole (MISO) or metronidazole (MTR), derivatives of nitroimidazole, would intensify the antitumour effects of hyperthermia only, or combined with mitomycin C (MMC). MISO, MTR and MMC were given i.p. at doses of 500 mg kg-1, 500 mg kg-1 and 2.0 mg kg-1 respectively, and MISO or MTR was administered 45 min before MMC. Hyperthermia was applied twice at 48 h intervals, by means of a water bath at 43.5 +/- 0.1 degrees C for 23 min. Tumour tripling times following heat alone, MTR plus heat, and MISO plus heat were about 6.7, 8.0 and 7.9 days respectively, compared with 4.6 days for the control, but tumour regression occurred in the heat plus MISO group only. Tumour tripling times for MMC plus heat, MMC plus MTR plus heat, and MMC plus MISO plus heat were 9.6, 11.6 and 17.1 days respectively, compared to 4.6 days for the control and 6.7 days for heat alone. These data suggest that the antitumour activity of MMC plus MISO plus heat is an additive phenomenon.
Animals↗
Intraperitoneal hyperthermic perfusion combined with surgery effective for gastric cancer patients with peritoneal seeding.
Fifteen patients with far-advanced gastric cancer were given surgical treatment followed by intraperitoneal hyperthermic perfusion (IPHP) with mitomycin C (MMC) and misonidazole (MIS), a thermosensitizing drug. Immediately after extensive resection of the abdominal tumors, a 2-hour IPHP was performed at the inflow temperature of 44.7 to 48.7 C, using equipment designed for treatment of cancerous peritoneal seeding as a closed circuit, and under hypothermic general anesthesia at 30 to 31 C. In nine of the 15 patients with peritoneal seeding and/or ascites, cancerous ascites was absent after this treatment. In all cases, repeated cytologic examinations of the lavage from Douglas's pouch were negative. The postoperative courses were uneventful except for Patients 1 and 10, in whom slight leakage occurred. All patients were discharged and are in good health at the time of this writing, 7.2 +/- 4.6 months after the treatment. The Case 4 Patient recently died in a traffic accident. In all patients, transient hepatic dysfunction and hypoproteinemia occurred after the operation. This extensive surgery combined with IPHP using MMC and MIS was well tolerated and is a safe antitumor treatment for gastric cancer with peritoneal dissemination. Neurotoxicity due to MIS was nil.
Adult↗
[Combination intra-arterial chemotherapy with degradable starch microspheres and mitomycin C against inoperable hepatic metastases].
Intra-arterial hepatic infusion chemotherapy combined with degradable starch microspheres (DSM) and mitomycin C (MMC) was performed for 9 patients with inoperable hepatic metastases from alimentary tract primary cancer. DSM, 45 +/- 5 micron in average diameter, produces temporary obstruction of arterial blood flow in the arterio-capillary bed and are subsequently degraded by serum amylase with T 1/2 of about 30 min. This intra-arterial treatment was repeated 2.3 times on the average. The average dose of DSM in a single infusion was 721 +/- 194 mg and the average total dose of MMC was 34.4 +/- 22.3 mg. Antitumor effects were evaluated in terms of tumor regression measured by CT scan and sonography. An objective tumor response was shown in 4/9 patients (44.4%): PR, 2/9; MR, 2/9. Elevated serum CEA levels of more than 3.0ng/ml were decreased in 7/8 patients (87.5%). Marked declines in the CEA level of more than 50% were observed in 4/8 patients (50%). Nausea and vomiting as well as abdominal pain were experienced in 8/21 treatments (38.1%) and 5/21 (23.8%), respectively. Furthermore, fever (2/21 : 9.5%), hepatic dysfunction (2/21 : 9.5%), and leukopenia (1/21 : 4.8%) were observed. All these side effects, however, were mild and transient. Thus, these results suggest that combined intra-arterial administration of DSM and MMC favorably enhances the antitumor efficacy of MMC.
Carcinoma, Hepatocellular↗
[Chemosensitization with nitroimidazole to human gastric cancer transplanted into nude mice].
Combined chemotherapy for human gastric cancer Transplanted into nude mice has been performed to determine whether misonidazole (MIS) and metronidazole (MTR), derivatives of nitroimidazole, would enhance the antitumor activity of MMC. MTR, 500 mg/kg, MIS 500 mg/kg, and MMC 2.0 mg/kg were administered ip twice during a 48-hour interval. The antitumor efficacies of MMC only, MTR only, or MIS only were seen to be much the same as in the controls. The combined treatment with MMC and MTR surpassed the controls in antitumoral activity after the 12th day, whereas it did not surpass a regimen with MMC alone. The addition of MIS to MMC showed an enhanced antitumoral activity after the 10th day compared to the controls and, further, after the 10th day it exceeded the results of MMC only. Tumor tripling time in cases of MMC only, MTR only, MIS only, MMC plus MTR, and MMC plus MIS was 123, 132, 144, 144, and 178 hours, respectively, compared to 110 hours in the controls. Thus, these results suggest that MIS has a chemosensitizing activity under these conditions, while MTR has little activity.
Animals↗
[Enhancement of hyperthermochemotherapy with hypoxic cell radiosensitizers].
Hyperthermochemotherapy with hypoxic cell radiosensitizers has been carried out using human gastric cancer xenotransplanted into the nude mouse. Misonidazole (MIS) and metronidazole (MTR), hypoxic cell radiosensitizers, were administered singularly or in combination with an ip dose of 500 mg/kg each, and after 60 minutes, an ip dose of MMC of 2.0 mg/kg was given. Subsequently, hyperthermia was applied, twice at a 48-hour interval, by a water bath at 43.5 +/- 0.1 degrees C for 23 minutes. The antitumor activity of hyperthermia with MTR was similar to that of hyperthermia alone, whereas hyperthermia with MIS surpassed hyperthermia alone, at 0.03237 less than p less than 0.05038. Hyperthermia combined with MIS and MMC enhanced the antitumor effects, as compared to hyperthermia with MMC, and with MMC plus MTR. Tumor volumetric tripling times in case of MMC plus heat, MTR, MMC plus heat, and MIS, MMC plus heat were about 229, 213, and 398 hours, respectively, compared to about 110 hours in the control and 160 hours in the case of hyperthermia alone. Thus, these data suggest that the antitumor efficacy of hyperthermochemotherapy with MIS may be the result of a synergistic phenomenon of thermo-chemosensitization.
Animals↗
[Repeated intra-arterial chemotherapy combined with mitomycin C and degradable starch microspheres in inoperable metastatic hepatic cancer].
Intra-arterial chemotherapy combined with mitomycin C (MMC) and degradable starch microspheres (DSM) was prescribed repeatedly for 14 patients with inoperable hepatic metastasis. This intra-arterial treatment was repeated 2.7 times on the average. The average dose of DSM and MMC in a single infusion was 685 +/- 201 mg and 13.8 +/- 3.8 mg, respectively. To analyse the degradation time of DSM, MMC concentrations in the peripheral blood were measured by HPLC method. RI-angiography using 99mTc macroaggregated albumin(MAA) was performed to estimate the hemodynamic changes in the liver. Antitumor efficacy was evaluated in terms of tumor regression measured by CT scan. An objective tumor response was observed in 9/14 patients(64.2%): CR 1/14; PR 6/14; MR 2/14. Elevated CEA levels were decreased in 11/12 patients (91.7%). Based on the peripheral MMC blood levels after combined infusion with DSM and MMC, an occlusion of intrahepatic vessels with DSM continued at least for 30 minutes. Again, RI-angiography with 99mTc-MAA plus DSM revealed the increased accumulation in the tumor, compared to 99mTc-MAA only. Side effects possibly attributable to DSM were observed in 14/38 treatments, though they were slight and temporary. Thus, these results indicate that this combined intra-arterial infusion of DSM and MMC achieve, higher regional selectivity.
Combined Modality Therapy↗
[Extended treatment for gastric cancer patients with peritoneal seeding].
Fourteen patients with far-advanced gastric cancer were treated surgically followed by intraperitoneal hyperthermic perfusion (IPHP) with mitomycin C (MMC) and misonidazole (MIS), a thermosensitizing drug. Immediately after extensive resection of the abdominal tumors, a 2-hour IPHP was performed at the inflow temperature 47.4 +/- 0.5 degrees C and at the outflow temperature 45.3 +/- 0.5 degrees C, using equipment designed for treatment of cancerous peritoneal seeding, as a closed circuit, and under hypothermic general anesthesia at 31.2 +/- 0.5 degrees C. In 6 of the 14 patients, cancerous ascites was absent after IPHP. Repeated cytologic examination of the lavage from pelvic cul-de-sac were negative, in all cases. The postoperative courses were uneventful except for 2 patients, in whom slight leakage occurred. All patients were discharged, and 4 in the 14 patients died of recurrence in the liver, abdominal and/or pleural cavities 8.8 +/- 2.1 months after IPHP. The remaining 10 are in good health 12.1 +/- 3.1 months after IPHP. Transient hepatic dysfunction and hypoproteinemia occurred after hyperthermia in all cases. This extensive surgery combined with IPHP using MMC and MIS was well tolerated and is a safe anti-tumor treatment for gastric cancer with peritoneal dissemination. Neurotoxicity due to MIS was nil.
Combined Modality Therapy↗
[A case of successful operation of chronic dissecting aneurysm (DeBakey IIIb) complicated with frequent acute thrombo-embolism in the leg].
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Acute Disease↗
The presence of an aberrant type of human chorionic gonadotropin in patients with gastric or colorectal cancer.
Beta subunits of human chorionic gonadotropin (beta-hCG) and human chorionic gonadotropin-like substance (hCGLS) were measured radioimmunologically in the serum and malignant tissue from patients with gastrointestinal cancer. Since serum beta-hCG and hCGLS correlate closely to those in cancer tissues, it is assumed that these two gonadotropins originate from cancer tissues. The serum hCGLS levels in 54 patients with gastrointestinal cancer were significantly higher, when compared with the findings in 19 healthy volunteers and 10 peptic ulcer patients. The frequency of high levels of serum hCGLS accounted for 71 per cent of those with operable gastric cancer, 44 per cent of those with inoperable gastric cancer, 100 per cent of those with operable colorectal cancer, and 67 per cent of those with inoperable colorectal cancer. On the contrary, serum beta-hCG levels did not differ between the volunteers and the cancer patients. In the 17 sera and 15 cancer tissues assayed, beta-hCG did not correlate to hCGLS. Moreover, the high levels of beta-hCG in cancer patients occurred in only 1/14 (7.1 per cent) of the assayed serum, and in 5/14 (35.7 per cent) of the cancer tissue. The increased production of these two hCGs may result from neoplastic transformation of an unrestrained fetal genome responsible for hCG production during gestation. It is assumed that the increased producibility of a defective hCG, i.e., an aberrant hCG such as hCGLS, is characteristic of malignant tumors.
Chorionic Gonadotropin↗
Enhanced antitumor efficacy with a combination of hyperthermochemotherapy and thermosensitization with polyamine antimetabolites in nude mice.
In an attempt to enhance the antitumor effects of hyperthermochemotherapy, methylglyoxal-bis-guanylhydrazone (MGBG) and alpha-difluoromethylornithine (DFMO) were used in combination with hyperthermochemotherapy of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosoure a (ACNU) against human gastric cancer (ST-2) xenotransplanted into nude mice. After priming with DFMO and MGBG, ACNU was given ip and subsequently, a 23 minute-hyperthermia was carried out by placing the leg with the tumor into a water bath of a temperature of 43.5 +/- 0.1 degrees C. The second hyperthermic treatment was given in the same manner after 48 hours. MGBG and DFMO were administered for 4 successive days from the previous day of the first hyperthermia. In mice treated with DFMO plus MGBG, either tumor growth or tumor tripling time was much the same as in the control, while in mice given MGBG, DFMO plus heat, there was a diminution in tumor growth. Hyperthermia together with MGBG, DFMO plus ACNU brought about remarkable antiproliferative effects on ST-2 tumor growth, compared to three regimens with MGBG, DFMO plus heat, MGBG, DFMO plus ACNU, as well as ACNU plus heat. These data suggest that a combination of MGBG with DFMO leads to a favorable thermosensitization to the antitumor efficacy of ACNU.
Animals↗
Contradictory antitumor efficacies produced by the combination of DNA attacking drugs and polyamine antimetabolites.
The antitumor effects of two polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG), when combined with cis-diamminedichlroplatinum (CDDP) or mitomycin C (MMC), were studied using human gastric cancer cells xenotransplanted into nude mice. DFMO 1000 mg/kg and MGBG 50 mg/kg were given intraperitoneally for 6 successive days, while CDDP 3 mg/kg or MMC 2 mg/kg was given every second day. Although DFMO and MGBG plus MMC did suppress the tumor growth, the combination with CDDP led to no suppression, and rapid growth occurred after the cessation of therapy. The inhibition of tumoral DNA biosynthesis and a decline in polyamine levels, were also not observed. The polyamine antimetabolites when used with CDDP did not produce the desired antitumor efficacy, even though the platinum concentration in the tumor tissue was high. On the contrary, however, DFMO and MGBG when combined with MMC did suppress tumor growth, inhibited DNA biosynthesis, and tissue polyamine levels were low. These results suggest that though CDDP and MMC belong to a similar category of DNA attacking, bifunctional alkylating agents, the findings of these two drugs are contradictory. Here, the mechanism of action no doubt plays a contributory role.
Adenocarcinoma↗
Gastric cancer with synchronous unresectable hepatic metastasis and a positive response to chemotherapy--report of two cases.
We report herein the clinical events seen in two longterm survivors of gastric cancer with unresectable synchronous hepatic metastases. Partial gastrectomy was performed against the primary lesion and continuous intra-arterial infusion of anti-tumor drugs, followed by prolonged systemic antitumor drug treatment, were prescribed. A 43-year-old man with moderately-differentiated tubular adenocarcinoma had an uneventful course during his first 21 postoperative months. However, multiple liver metastases became manifest at 24 months and enlargement of the intrahepatic foci led to death 27 months after gastrectomy. A 51-year-old woman with moderately-differentiated tubular adenocarcinoma had an uneventful postoperative course and is now well with no signs of recurrence 6 years and 6 months after gastrectomy.
Adult↗
Modulation of vascular dynamics by spontaneous contraction of smooth muscle in the isolated carotid artery of the rat.
Possible roles of smooth muscle contractions in the vascular dynamics were studied in the isolated rat large artery which has previously been shown to generate spontaneous rhythmic contractions depending upon the extracellular Ca2+. A cylindrical segment of the common carotid artery was superfused externally and perfused intraluminally by Tyrode solution, and the steady state intraluminal pressure (P)-volume (V) relationship of the vessel was obtained. The pressure buffering characteristic (Windkessel effect) of the vascular wall was evaluated by measuring the intraluminal pressure swing during application of external alternating pressure (semi-triangular pressure pulse, 0-120 mmHg, 300 cycle/min, "dynamic pressure load") to the intraluminal space. Effects on these vascular dynamics of inhibition of spontaneous smooth muscle contraction during superfusion of the preparation with nominally Ca2+-free Tyrode solution were investigated. Spontaneous rhythmic fluctuations of the intraluminal pressure (0.2-1.0 mmHg, 2-25 cycle/min), presumably due to contractions of vascular smooth muscles, were detected. The Ca2+-free solution abolished these spontaneous changes in the intraluminal pressure and reduced the baseline intraluminal pressure. The volume distensibility (delta V/(V X delta P] of the preparation at higher intraluminal fluid volumes (or pressures, higher wall stretch) was increased by Ca2+-free solution. The magnitude of intraluminal pressure swing and the maximum rate of changes in the pressure during application of "dynamic pressure load" were decreased in Ca2+-free solution. The results suggest that the inhibition of spontaneous contractions of smooth muscle by Ca2+-free solution may increase the volume distensibility and pressure-buffering function of the large elastic artery.
Animals↗
[Antitumor effects of polyamine antimetabolites with polyamine-free diet].
To evaluate the antitumor efficacy of polyamine antimetabolites such as methylglyoxal-bis-guanylhydrazone (MGBG), ethylglyoxal-bis-guanylhydrazone (EGBG), and alpha-difluoromethylornithine (DFMO), the combined therapies of polyamine antimetabolites with a polyamine-free diet were studied. The combination of EGBG plus DFMO or MGBG plus DFMO showed a marked suppression of tumor growth with a polyamine-free diet; and, when compared, EGBG was slightly superior to MGBG. The inhibition of DNA biosynthesis was also parallel to the above-mentioned results. Furthermore, from an analysis for polyamine levels in tumor tissues, it was confirmed that the polyamine depletion can be maintained by polyamine antimetabolites in combination with a polyamine-free diet in vivo. Moreover, as EGBG has lesser side effects than MGBG, EGBG might be more suitable for clinical use.
Animals↗
[Antitumor efficacy of polyamine antimetabolites and mitomycin C under polyamine-free diet].
Treatment of nude mice xenografted with human gastric cancer was carried out by polyamine antimetabolites combined with mitomycin C (MMC) and polyamine-free diet. Polyamine antimetabolites, alpha-difluoromethylornithine (DFMO) and ethylglyoxal-bis-guanylhydrazone (EGBG), were given ip in a daily dose of 1,000 mg/kg and 20 mg/kg, respectively, for 6 consecutive days. MMC 2.0 mg/kg was administered every other day. The polyamine-free diet was given from 4 days before start of the treatment through the end of the study. Although the tumor growth rate of the control group given polyamine-free diet was similar to that given normal diet, in the mice treated with EGBG, DFMO plus MMC, the antitumor effect in the polyamine-free diet group was superior to the normal diet group. In comparison with tumor growth suppression due to EGBG plus DFMO or MMC only, the polyamine-free diet group showed better result than the normal diet group to some extent. In mice treated with EGBG, DFMO plus MMC, tumor tissue spermine levels in the polyamine-free diet group were significantly depressed, compared to the normal diet group. Furthermore, marked suppression of DNA biosynthesis was observed in mice given EGBG, DFMO plus MMC together with the polyamine-free diet. These results suggest that combined treatments of polyamine antimetabolites and MMC revealed a marked enhancement of antitumor effects, under conditions of polyamine depletion, which may be responsible for the alteration in DNA structure.
Animals↗