Search PubMed⌕ Search

Biomedical subjects

K Kumai

Publications and source records attributed to K Kumai.

At least 91 records · Page 5Linked to original sources

Identification of transferrin receptor in cervical and endometrial tissues.

The location of transferrin receptor (Tf.R) which is abundantly contained in proliferating cells and positional relationships of cells containing much Tf.R was observed on cervical and endometrial tissue sections by immunohistochemistry. In normal squamous epithelium, the parabasal cell layer was positive and the basal, intermediate, and superficial cell layers negative. This shows that the cells of the parabasal cell layer are proliferating most actively among those layers. Squamous carcinoma contained many positive cancer cells. But negative as well as positive cells were present, indicating that cancer cells proliferate under various conditions. Cancer cells infiltrating the stroma were made clear by Tf.R staining, and it became easier to identify them when only a few were present. Endometrial glandular cells in the basal layer stained only on the basal side of a cell regardless of the menstrual cycle, whereas in the functional layer glandular lumen side also stained positive in the secretory phase. Based on the present data, an immunohistochemical study of Tf.R seems useful to confirm the localization of proliferating cells and cancer cells and determine the conditions for cancer cell proliferation on the tissue sections.

Carcinoma, Squamous Cell↗

[Modified operation for early gastric cancer; rationale, technic and results].

During 1964 to 1976, standard operation, which consisted of subtotal or total gastric resection, extended dissection of lymph node and omentobursectomy, was performed for early gastric cancer. The result was satisfactory, i.e., 5 year relative survival rate was 95.2 per cent. But there were very few lymph-node metastases, which localized almost perigastric, no marked infiltration into the esophagus in cases of early cancer in the cardiac region. Macroscopic determination about the margin of the cancer was well compatible with microscopic one. The recurrent cases seemed to be due to hematogenous metastasis. These suggest that an extended lymph-node dissection, omentobursectomy and thoracotomy are not necessary for the early cancer. Proximal gastric resection and pylorus preserving gastric resection were indicated in some cases. In addition, the diagnosis of the early cancer, especially about the depth of invasion into the gastric wall, was accurate except for the early cancers which contained ulcerous lesion. Since 1977 modified operation for the early cancer has been applied. At this operation, lymph-node dissection was limited to perigastric region, omentobursectomy was omitted and the pancreas and spleen preserved. Through this method the operative time and blood unit have been much spared and the 5 year postoperative relative survival rate has improved, i.e., 100 per cent. It is concluded that the modified operation should be performed for the early gastric cancer.

Humans↗

Antitumor effect of adriamycin entrapped in liposomes conjugated with anti-human alpha-fetoprotein monoclonal antibody.

The monoclonal antibody, 19-F-12 (IgG2b), against human alpha-fetoprotein was conjugated to liposomes containing Adriamycin, and the therapeutic effects of the conjugate were experimentally studied using the alpha-fetoprotein-producing human hepatoma strain, Li-7, maintained in BALB/c nu/nu male mice. Three i.v. injections of liposomes containing Adriamycin (7.5 mg/kg) into tumor-bearing mice significantly inhibited the tumor growth, and the therapeutic effect of the antibody-conjugated liposomes was greater than that of unconjugated liposomes, as judged from the tumor weights and histological findings. Furthermore, the experiments were repeated with Adriamycin (4-5 mg/kg) in free form, since administration of Adriamycin (7.5 mg/kg) in free form was highly toxic for the mice. The results still indicated that the therapeutic effect of Adriamycin in 19-F-12 conjugated liposomes was superior to that of free Adriamycin or Adriamycin in unconjugated liposomes. In contrast to the treatment for Li-7 in nude mice, the therapeutic effect of Adriamycin in 19-F-12 conjugated liposomes was not much different from that of Adriamycin in normal mouse IgG (IgG2b fraction) conjugated liposomes against alpha-fetoprotein-negative human breast cancer strain MX1. Tissue distribution studies after i.v. injection of Adriamycin in various forms into mice revealed that preferential delivery of Adriamycin to tumors occurred to some extent with antibody-conjugated liposomes as compared to the unconjugated liposomes. In addition, reduction of the distribution of Adriamycin to the heart was achieved by administering the drug in the liposome-entrapped form, and this enabled the use of a higher dose (7.5 mg/kg) of Adriamycin without toxic side effect.

Animals↗

[New operative technic for resecting cardiac cancers with dissection of the lower mediastinal lymph nodes through transabdominal phrenotomy using an improved hook suspender and an autosuture surgical stapling instrument].

To obtain a sufficient operative field at the operation for cardiac cancer, especially with esophageal infiltration, thoracotomy or sternotomy has been added to laparotomy. These procedures are not easy and cause great stress in patients. Through our new technique, left sided thoracotomy and sternotomy can be eliminated in favor of transabdominal phrenotomy, which is able to be performed much easier to obtain a good operative field. In order to perform the phrenotomy, the diaphragm has to be stretched using our modified hook suspender, by which the costal arch is lifted strongly upward and cranially. With these procedures, about a 5cm long esophagus is able to be resected with lymph node dissection in the lower mediastinum without difficulty. No marked influence of the hook suspender as well as the phrenotomy has been recognized on respiratory and circulatory systems. The anastomosis between the esophagus and jejunum or residual stomach seems to be very difficult, because the site of the anastomosis is located quite deep in the mediastinum. This problem, however, can be completely resolved by means of a surgical stapling autosuture instrument.

Cardia↗

[Rational modified radical operation in early gastric cancer].

Extended dissection of regional lymph nodes, omentobursectomy, splenectomy and thoracotomy, which are performed on cases with advanced gastric cancer, are not necessary in radical operation for early gastric cancer, for the early cancer was revealed to have the metastasis to lymph node of slight degree and no metastasis to the peritoneum. This modified operation can provide us a decrease of either intraoperative blood loss or operation time, which seems to contribute to diminish the operative death and to improve the quality of postoperative life. The result was satisfactory: 5-year relative survival rate after the operation was 100.0%. Diagnostic accuracy for early cancer was also sufficient.

Humans↗

Multiple primary cancers in the stomach and another organ: frequency and the effects on prognosis.

Cases of multiple primary cancer (MPC) with gastric cancer were collected from 66 hospitals by questionnaires sent to 114 hospitals and institutions in Japan. Four hundred forty-five out of 22,163 gastric cancer patients who were operated on between 1966 and 1970 and had at least 10-year follow-up data were registered as having more than one cancer. The overall frequency was 2.0%. In 137 patients the MPCs were synchronous in 125 the MPC appeared after gastrectomy and 186 patients had a previous cancer before the diagnosis of gastric cancer. The most frequent association was cancer in the alimentary tract (53%), followed by uterus, breast and others in that order. In the patients with gastric cancer, the relative risk of a second cancer seemed to be twice as high as the incidence of cancer in the general population, especially in alimentary organs (four times as high) and in thyroid (nine times). Second malignancies were the first cause of death, except for recurrence or metastasis of the initial gastric cancer, and the importance of a follow-up system for cancer patients was indicated.

Adult↗

[Selective hepatic arterial infusion of liposomes containing antitumor agents].

To improve the targeting effect in cancer chemotherapy, liposomes containing Adriamycin (Lip-ADM) and monoclonal antibody-conjugated Lip-ADM (Lip-ADM = Ab) were prepared and examined experimentally and clinically. The liposomes used as biodegradable drug carriers, were prepared from a lipid mixture of egg yolk phosphatidylcholine, cholesterol and dipalmitoyl phosphatidic acid and Adriamycin (ADM) solution was added to prepare multilamellar vesicles (MLV). Small unilamellar vesicles (SUV) were prepared from MLV by sonication and monoclonal antibodies were conjugated to SUV by the SPDP method. Experimentally, antigen-specific acceleration of in vitro and in vivo anti-tumor effects was observed. As a high tissue distribution of Lip-ADM in the liver was observed and as sinusoidal capillaries, which are found in the liver, were expected to allow penetration of liposomes through the relatively large gaps in the endothelium into the underlying organ parenchymal cells, clinical application of Lip-ADM was started for patients with hepatic metastasis of gastrointestinal cancer by selective hepatic arterial infusion. Ten patients were treated by Lip-ADM which was administered at 8-30 mg/body cumulatively. No serious adverse reaction was observed except slight fever and leukocytopenia. The preliminary evaluation of anti-tumor effects on hepatic metastasis was LPR, 1MR, 6NC and 1PD. Repeat administrations of Lip-ADM or Lip-ADM = Ab using a retained infusion catheter and silicone reservoir were started in order to improve the more accelerated clinical effects.

Aged↗

[Statistical studies on multiple primary cancers including gastric cancers].

The incidence of cases with multiple primary cancers was analysed and it was found to have increased chronologically in autopsied cases. The incidence to have another cancer in the patients who underwent operations for gastric cancer was 2.0%, which seemed to be higher than the expect value in the general population. Regarding the cause of death after radical gastric surgery, the multiple primary cancer occupied the second position, the first being the recurrence of gastric malignancy.

Breast Neoplasms↗

Experimental and clinical studies on aclarubicin in the treatment of solid tumors.

Experimental and clinical studies were performed on aclarubicin in the treatment of solid tumors. In experimental cancer chemotherapy using human tumor xenografts transplanted to nude mice, aclarubicin showed a moderate antitumor effect (retardation of tumor growth) and nearly the same spectrum of activity in vivo as Adriamycin (doxorubicin). In in vitro sensitivity tests using 3H-thymidine uptake inhibition of a single cell suspension prepared from xenografts, aclarubicin showed a stronger inhibition than that of Adriamycin, mitomycin C and cyclophosphamide. In phase II clinical studies in patients with solid tumors, 3 intravenous dose schedules [schedule A: 20 mg (equal to 14 mg/m2) daily every other week, schedule B: 40 to 60 mg (28 to 42 mg/m2) twice a week, and schedule C: 60 to 100 mg (42 to 70 mg/m2) once a week] were investigated. Aclarubicin produced a 15 to 20% response rate for carcinomas of the stomach, lung, breast and ovary by schedules A and B. Dose-schedule limiting factors were digestive and hematologic toxicity.

Aclarubicin↗

Gastric microcirculatory disturbance and behaviour of leucocytes after thermal injury: intravital observation of arteriovenous shunting channels in the gastric submucosal layer.

In order to investigate the pathogenesis of acute gastric mucosal lesion after thermal injury, microcirculatory disturbance was assessed and observation of the behaviour of leucocytes was performed. Gastric blood flow decreased at 15 min post-thermal injury, and partially improved at 2 h; however, it decreased again at 5 h post-thermal injury. Mucosal microcirculatory disturbance was observed by using vascular labelling with monastral blue B. Deposits of monastral blue B were observed centring mainly on collecting venules but were also observed in the capillaries. Submucosal microcirculatory disturbance was observed through an intravital microscope. The irregularity of the wall and segmental constriction in the venules and presence of an arteriovenous shunting channel was observed in the submucosal layer at 5 h post-thermal injury. The percentage of rolling or sticking leucocytes that passed the confluence of a prevenule and a venule were significantly increased at 5 h after thermal injury. The present study revealed depression of gastric blood flow, mucosal and submucosal microcirculatory disturbance, and a significant increase of rolling and sticking leucocytes in the peripheral part of venules after thermal injury. Leucocyte-endothelial interactions may occur under such conditions and this interaction may play an important role in inducing the microcirculatory disturbance that results in an acute gastric mucosal lesion after thermal injury. The present study also demonstrated the possibility of intravital study of gastric submucosal arteriovenous shunting channels.

Animals↗

Chemosensitivity test is useful in evaluating the appropriate adjuvant cancer chemotherapy for stage III non-scirrhous and scirrhous gastric cancers.

A total of 183 cases with gastric cancer was retrospectively analyzed in terms of their chemosensitivity as determined by the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay and their survival rates after surgery. After the patients were stratified into scirrhous or non-scirrhous carcinoma groups, they were tested for stage III or IV gastric cancer. In these four cohorts, the patients were categorized into sensitive and insensitive groups determined by the MTT assay. The sensitive group was treated with at least one drug that had been shown to be effective in the MTT assay, and the insensitive group was given a drug that had been shown to be ineffective in the MTT assay. In stage III gastric cancer, the sensitive group showed a favorable survival compared to the insensitive group in scirrhous and non-scirrhous carcinoma, while this difference was diminished in stage IV gastric cancer. There were no survival benefits in the sensitive group in stage III gastric cancer, when they were not treated with adjuvant cancer chemotherapy. These results suggested that MTT assay would be useful in evaluating the appropriate adjuvant cancer chemotherapy for stage III scirrhous and non-scirrhous gastric cancer.

Adenocarcinoma, Scirrhous↗

Chemosensitivity testing of primary tumor cells from gastric cancer patients with liver metastasis can identify effective antitumor drugs.

The liver metastasis of gastric carcinoma is resistant to conventionally available treatment. Twenty patients with liver metastasis of gastric cancer were treated by arterial drug infusion using a reservoir and seven cases were treated with systemic chemotherapy. The resected primary gastric cancer specimen was used for chemosensitivity assay with 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) endpoint, and the patients were treated without reference to the results of the chemosensitivity assay. The mean survival period was assessed according to the histology of the primary lesion, the grade of liver metastasis and, the presence of peritoneal dissemination. No significant differences were observed in the primary tumor histology and grade of liver metastasis, but the survival period of the patients with liver metastasis and peritoneal dissemination was significantly shorter than that of the patients without peritoneal dissemination. Nine patients were treated with drugs that were effective in the chemosensitivity assay, and their responses included two complete responses and two partial responses; these patients showed a significantly prolonged survival period compared with patients treated with drugs that were not effective in the assay. The chemosensitivity assay is useful for evaluating the effectiveness of antitumor agents against liver metastasis of gastric cancer.

Adult↗

Thymidylate synthetase and dihydropyrimidine dehydrogenase levels in gastric cancer.

The measurement of thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) enzymatic activities and mRNA levels in tumors may be useful in predicting tumor sensitivity to 5-fluorouracil (5-FU). Forty-one patients with advanced gastric cancer gave informed consent and were enrolled in this study. Biopsy specimens of gastric cancer were obtained preoperatively through gastrofiberscopy and used to determine TS and DPD mRNA levels. We also measured TS and DPD enzymatic activities and mRNA levels in surgically resected gastric cancer samples, as well as in adjacent normal gastric mucosa. TS and DPD activities were measured using the TS-binding assay and a radioenzymatic assay, respectively, while mRNA levels were measured by semi-quantitative reverse transcription-PCR (RT-PCR) co-amplified with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard. In resected tumor specimens, TS and DPD activities ranged from 7.1 to 176.6 fmol/mg protein and from 3.6 to 99.8 pmol/min/mg protein, respectively, while TS and DPD mRNA levels ranged from 0.50 to 21.12 and from 0.014 to 7:22, respectively. There were no significant correlations between TS/DPD levels and other clinicopathological factors, except for low DPD mRNA levels in undifferentiated carcinoma. Both TS activity and mRNA levels were significantly higher in tumor tissues compared to normal adjacent mucosa. In contrast, there was no significant difference between tumoral and non-tumoral DPD activity, although tumor tissue showed significantly lower DPD mRNA levels than non-tumoral tissue. High tumoral TS mRNA levels in preoperative biopsy specimens from patients with stage III/IV was associated with poor survival outcome after surgery compared with patients with low tumoral TS mRNA levels. In contrast, DPD levels had no influence on prognosis. We conclude that high tumoral TS levels and low tumoral DPD mRNA may indicate the selective cytotoxicity of 5-FU on gastric cancer, and that tumoral TS mRNA levels may be a prognostic factor for patients with stage III/IV gastric cancer.

Aged↗