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Biomedical subjects

M Kitajima

Publications and source records attributed to M Kitajima.

At least 37 records · Page 2Linked to original sources
PubMed1995

[Chemotherapy and multimodality therapy in the treatment of esophageal cancer].

Many single-agent phase II studies for patients with esophageal cancer had been performed, and at least five agents with modest activity have been indentified, BLM, MMC, CDDP, VDS and MTX, that revealed no CR. Even in the phase II study of 254-S, a new anticancer platinum complex, with a response rate of 43%, CR could not be recognized. Only two regimens of combination chemotherapy have been studied extensively, CDDP/BLM/VDS and CDDP/5-FU. The combination of CDDP/5-FU has gained popularity and JEOG phase II study revealed a response rate of 36%. As surgical adjuvant therapy, postoperative adjuvant therapy has been common in Japan. The 4th JEOG phase III clinical trial, comparing surgery alone and postoperative chemotherapy of CDDP/VDS, showed no additive effect to surgery by postoperative chemotherapy with such a regimen. In western countries, neoadjuvant chemotherapy is frequent and most of the regimens include CDDP/5-FU. Pathological CR rates were less than 10%, and median survival terms were from eight to 28 months. The rationale for the concurrent use of chemotherapy and radiotherapy is to combine an agent that has an effect upon systemic micrometastases with a modality that enhances local tumor control. In addition, a number of chemotherapeutic agents have radiosensitizing effects. In western countries, more than 35 trials studying over 1400 patients have been reported. The majority of trials have employed CDDP/5-FU combined with RT to a total dose of 30Gy. Pathological CR rates were from 20 to 40% and median survival terms were from 12 to 29 months. Both neoadjuvant chemotherapy and chemoradiotherapy did not change operative morbidity or mortality, and there was a statistically significant increase in survival in complete responders. However, early and median survival seems improved but cure rates are not. Both therapies require further investigation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

A genetic linkage map of the mouse using an expanded production system of restriction landmark genomic scanning (RLGS Ver.1.8).

We have developed an expanded system (RLGS Ver.1.8) for producing RLGS patterns that result in a 16-fold increase in the number of gels produced and a 10-fold reduction in the total cost per gel. The major modifications include: 1) performing the blocking and labeling step without phenol extraction or ethanol precipitation; 2) minimizing the reaction volume and the enzyme units in each step; 3) developing a long vertical agarose disc gel electrophoresis for the 1st-dimension; and 4) developing a new apparatus for multiplex vertical 2nd-dimensional electrophoresis. RLGS Ver.1.8 was used with a new combination of restriction enzymes to identify variation for 209 loci between C57BL/6J and DBA/2J. Twenty-six BXD RI strains were analyzed and 195/209 loci were genetically mapped. These loci were mapped in one week of laboratory work by two people. This system provides an important tool for the genetic analysis of new loci in similar genetic resources.

Animals↗
PubMed1994

Combination chemotherapy with mitomycin C and cisplatin for advanced gastric cancer with multiple liver metastases.

A patient with advanced gastric cancer with multiple liver metastases was treated by reduction surgery at the primary site as well as by the intraarterial administration of mitomycin C (MMC) and cisplatin (CDDP) through a reservoir catheter inserted into the proper hepatic artery. After a palliative subtotal gastrectomy, MMC 8 mg/m2 was administered intraarterially (i.a.) followed by the administration of CDDP 80 or 40 mg/m2 i.a. with an interval of less than 1 week. After the completion of five courses of this regimen, a complete reduction of the hepatic tumors was achieved, while the level of serum carcinoembryonic antigen decreased to the normal range. The patient is currently alive with signs of disease recurrence at 17 months after initial diagnosis, while additional therapy with MMC + CDDP was continuously undergone until 17 months' after initial diagnosis with various interval. Although thrombocytopenia occurred during the treatment, it resolved within a few weeks after completing the combination chemotherapy without any specific treatment. The present case showed a better prognosis than we had expected, which suggested that combination chemotherapy with MMC and CDDP might thus be clinically useful because of its excellent antitumor activity and low toxicity.

Adenocarcinoma↗
PubMed1994

Gene expression of interstitial collagenase (matrix metalloproteinase 1) in gastrointestinal tract cancers.

Collagenolytic proteinases play an important pathological role in the invasion and metastasis of cancer cells. However, little is known about the role of interstitial collagenase (matrix metalloproteinase-1; MMP-1) in this process. To investigate the expression of the MMP-1 gene in cancer tissues, an in situ hybridization study was carried out in gastrointestinal tract cancers (one esophageal cancer, five gastric cancers, and four colorectal cancers), using a 35S-labeled MMP-1 cDNA probe. The MMP-1 gene was expressed in the stromal cells of fibrous tissue around cancer nests, especially at the margin of invasion and/or within the cancer nest; however, no definite expression within cancer cells was observed. Expression of the MMP-1 gene in the stromal cells was more common in well differentiated gastric adenocarcinoma than in poorly differentiated adenocarcinomas. These findings indicate that expression of the MMP-1 gene is greater in stromal cells that are closely associated with cancer cells, suggesting a pathophysiological role of MMP-1 in the invasion and metastasis of cancer cells.

Adenocarcinoma↗
PubMed1994

cDNA cloning and characterization of mitochondrial import stimulation factor (MSF) purified from rat liver cytosol.

We identified a liver cytosolic protein factor that stimulated the import of wheat germ lysate-synthesized precursor proteins into mitochondria. It was termed mitochondrial import stimulation factor or MSF [Hachiya, N. et al. (1993) EMBO J. 12, 1579-1586]. It consisted of 32-kDa (MSFL) and 30-kDa (MSFS) polypeptides as assessed by SDS-PAGE. MSF recognized the presequence portion of mitochondrial precursor proteins and catalyzed the depolymerization and unfolding of in vitro synthesized mitochondrial precursor proteins in an ATP-dependent manner. We report here the cDNA cloning and characterization of MSF. Microsequencing of MSFL and MSFS showed that they belonged to a highly conserved, widely distributed eukaryotic protein family, collectively designated as 14-3-3 proteins. We cloned the cDNA of MSFL and that of one component of MSFS (MSFS1) from a rat liver cDNA library. The cloned cDNAs were separately expressed in Escherichia coli and the expressed proteins were purified to homogeneity. The purified recombinant MSFL and MSFS1 stimulated mitochondrial import of adrenodoxin precursor (pAd) synthesized in vitro with wheat germ lysate translation system. Recombinant MSFL or MSFS1 had the ability to bind with denatured pAd and they kept the precursor in an import-competent state. Rabbit polyclonal antibodies raised against the recombinant proteins inhibited the import-stimulation activity of rat liver cytosol as well as that of authentic purified MSF. Identification of MSF as 14-3-3 proteins establishes a novel function for this family of proteins and indicates their role as cytosolic chaperones to aid many important cellular events.

14-3-3 Proteins↗
PubMed1994

[Clinical study of serum ErbB-2 protein using sandwich radioimmunometric assay (ErbB-2 IRMA 'Eiken')].

Sandwich radioimmunometric assay (ErbB-2 IRMA 'Eiken') was developed to determine the levels of c-erbB-2 oncogene product (ErbB-2 protein) in human sera, and a clinical investigation was carried out to evaluate this novel oncogene product. The mean serum concentration of the ErbB-2 protein determined from 364 donors was 4.0 +/- 0.69 ng/ml (mean +/- SD) for females and 4.5 +/- 0.96 ng/ml for males. Cut-off values were set at 5.4 ng/ml for females and 6.5 ng/ml for males. The positivities of serum ErbB-2 protein in patients with breast carcinoma were 13.0% for primary cases and 47.9% for recurrent cases. Patients with hepatic disorders also had positive serum ErbB-2 protein levels, ie, 43.8% (7/16) for hepatocellular carcinoma and 28.9% (11/38) for hepatitis and liver cirrhosis, although the increase was slight and barely exceeded 10 ng/ml. In comparison with the levels of other tumor markers, such as CEA, CA 15-3 and NCC-ST 439, the serum ErbB-2 level was shown to have poor correlations, and was thus assumed to be useful for combination with those tumor markers. In serial determinations of serum ErbB-2 protein in two patients with recurrent breast carcinoma, the antigen increased preceding the increases in the other tumor markers, thereby also showing usefulness as a monitoring marker for breast carcinoma. In conclusion, these results indicated that ErbB-2 measurement improves the assessment of breast cancer in combination with other tumor markers and is useful as a tool for monitoring the clinical condition and the response for treatment in breast cancer.

Aged↗
PubMed1994

[Clinical evaluation of serum ErbB-2 protein using enzyme immuno assay (ErbB-2 EIA [Nichirei])].

The levels of ErbB-2 protein in serum samples from patients with breast cancer, other various malignant tumors, and benign diseases were determined using the sandwich EIA for clinical evaluation. In 364 healthy blood donors, cut-off values were set at 5.4 ng/ml for females and 6.5 ng/ml for males. The positive rate of primary breast cancer was 13.0% (24/185) and that of recurrent breast cancer was 51.2% (62/121). No significant correlation was found between serum levels of ErbB-2 protein and other tumor markers, such as CEA, CA 15-3, and ST 439. Measurement of ErbB-2 protein in combination with these tumor markers showed increased sensitivities. The positive rates and levels of ErbB-2 protein in sera of patients with metastasis to multiple organs were significantly higher than those in patients with metastasis to only a single organ. In postoperative follow-up of two patients with recurrent breast cancer, the levels of ErbB-2 exceeded its cut-off value a few months earlier than did the other tumor markers. These results indicate that the measurement of the ErbB-2 protein in serum is useful for the diagnosis and a monitoring the relapse of breast carcinoma.

Biomarkers, Tumor↗
PubMed1994

[Abnormalities and clinical characteristics of growth factors and receptor systems in breast cancer].

Recent progress in molecular biology has revealed that the proliferation of breast cancer is controlled by various growth factors and their receptors. In particular, the amplifications and products of oncogenes which code growth factors and receptors can be different indicators of clinical malignancy from the conventional prognostic factors. We investigated the relation of c-erbB-2 and int-2 gene amplification, expression, ER and EGFR with clinical characteristics. In retrospective study, the cumulative 10-year survival rate of patients with c-erbB-2 and int-2 gene amplification was significantly lower than in patients without amplification. In 72 cases with tumor diameter less than 3.0 cm, which can be an indication of breast preservation surgery, the survival rates of patients in these gene amplified groups were significantly lower than in the non-amplified groups. As for prospective study, the results were the same as those from retrospective study. These data show that the cases with these gene amplification have a high biological malignancy and high risk of recurrence to distant organs, despite the small tumor diameter.

Breast Neoplasms↗
PubMed1994

[Clinical evaluation of ErbB-2 protein in tissue extract using an enzyme immuno assay (ErbB-2 EIA "Nichirei")].

ErB-2 protein levels in breast cancer tissue extracts were determined by an enzyme immuno assay (ErbB-2 EIA "Nichirei") using anti-c-erbB-2 monoclonal antibodies, and compared with the c-erbB-2 gene amplification detected by dot blot hybridization or differential PCR, and with the overexpression detected by immunostaining. The positivities of c-erbB-2 gene amplification and overexpression in breast cancer tissues were 25.0% (14/56) and 39.3% (46/117), respectively. The cut-off values of the Erb B-2 protein in tissue extract by EIA were set at 18.0 ng/mg-protein for gene amplification and 10.4 ng/mg-protein for overexpression, respectively, from the data of breast cancer tissues which were negative for c-erbB-2 gene. The accuracy of the ErbB-2 protein levels in tissue extract with c-erbB-2 gene amplification and overexpression were 90.6% and 79.2% using these cut-off values respectively. The result of c-erbB-2 gene amplification, overexpression, and ErbB-2 protein levels were significantly correlated with negative estrogen receptor (ER) and progesterone receptor (PgR) status in tissue cytosol fraction. These results indicate that measurement of ErbB-2 protein in tissue extract is useful to estimate the c-erbB-2 gene amplification and/or overexpression in breast cancer tissues.

Antibodies, Monoclonal↗
PubMed1994

[An early phase II clinical study of RP56976 (docetaxel) in patients with breast cancer].

An early phase II clinical study of RP56976 (docetaxel), a new anticancer agent of plant origin, was conducted in patients with breast cancer at 20 Japanese collaborative institutions. Docetaxel was administered at two or more doses of 60 mg/m2 by intravenous infusion with dose-free intervals of 3-4 weeks, and the efficacy and safety was evaluated. Of the 51 patients enrolled, 50 patients completed the scheduled course of treatment. Two patients showed a complete response (CR) and 19 showed a partial response (PR) with a response rate of 42.0%. The response rates based on the efficacy for metastatic lesions in soft tissue, liver and lung, were 46.2% (18/39), 37.5% (3/8), and 38.5% (5/13), respectively. Of the 50 patients who completed the study, 48 patients had previously been treated for the present malignancy. Forty-seven patients had previously been treated with chemotherapy and showed a response rate of 40.4% (19/47). The response rate in those who had received chemotherapy composed of anthracyclines and other agents was 44.1% (15/34). Grade 3 or more severe leukopenia and neutropenia developed in 43 patients (84.3%) and 48 patients (94.1%), respectively. Other adverse reactions which occurred in a Grade 3 or more severe form included nausea/vomiting (1 patient), anorexia (5 patients), diarrhea (4 patients), fatigue (2 patients), and alopecia (20 patients). Except for alopecia, most adverse reactions were generally transient and reversible without any specific treatment.

Adult↗
PubMed1994

Effect of acute lung injury and coexisting disorders on plasma concentrations of atrial natriuretic peptide.

OBJECTIVE: To clarify how plasma atrial natriuretic peptide concentrations vary with the severity of acute lung injury. The influence of coexisting diseases which trigger acute lung injury was also examined. DESIGN: Prospective study. SETTING: Intensive care unit of a university hospital. PATIENTS: Fifty patients who had standard risk factors for acute lung injury including sepsis syndrome, major surgery, prolonged hypotension, aspiration of gastric contents, and burns. Twenty-five of these patients had acute lung injury (group 3) caused by these disorders; the remaining 25 patients had risk factors only (group 2). Ten age-matched normal volunteers were selected as controls (group 1). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Plasma atrial natriuretic peptide concentration was measured in these patients and compared with the severity of acute lung injury. In group 3, a significant increase in the mean plasma atrial natriuretic peptide concentration was observed (188 +/- 78 pg/mL, p < .01) compared with group 2 (54 +/- 28 pg/mL) and the age-matched control group (30 +/- 8 pg/mL). This increase was related to the onset of acute lung injury and returned to control concentrations after recovery. Plasma atrial natriuretic peptide concentrations in group 3 correlated highly with a lung injury score representing the severity of acute lung injury (r2 = .45, p < .01), but did not correlate with other cardiopulmonary variables. CONCLUSION: The results suggest that severity of lung injury, but not other predisposing disorders, may be the key factor leading to the increase in plasma atrial natriuretic peptide concentrations observed in these patients.

Analysis of Variance↗
PubMed1993

Carbohydrate antigens and liver metastasis in colorectal cancer.

A comparative immunohistochemical study was performed to analyse the expression of cancer-associated carbohydrate antigens by primary and metastatic lesions of colon cancer. We used monoclonal antibodies which reacted with Lea, Lex and Tn as well as their sialylated derivatives. Twenty-one primary lesions in patients without metastasis and 26 primary and metastatic lesions in patients with liver metastasis were studied. Sialyl Lea was expressed by 57% of the primary lesions of patients without metastasis, 65% of the primary lesions of patients with metastasis and 73% of their liver metastases. Sialyl Lex was expressed by 60% of the primary lesions of patients with and without metastasis as well as by approximately 80% of the liver metastases. Sialyl Lea and sialyl Lex showed strong expressions in the liver metastases, significantly greater than in the primary lesions. The findings indicate the increased expressions of sialyl Lea and sialyl Lex to be correlated with liver metastasis of colorectal cancer.

Adenocarcinoma↗