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Biomedical subjects

M Tani

Publications and source records attributed to M Tani.

At least 469 records · Page 26Linked to original sources

Primary tracheoesophageal shunt operation for postlaryngectomy speech with sphincter mechanism.

This paper describes a primary voice restoration technique designed to eliminate the problem of aspiration commonly encountered in rehabilitation procedures following laryngectomy. This technique, utilized in 16 patients, consists of a unique combination of tracheal flap for voice production and bilateral esophageal constrictor muscle flaps to prevent aspiration. Fourteen patients developed satisfactory tracheoesophageal speech; of them 12 had normal deglutition without problems of aspiration. On radiographic examination, the bilateral esophageal muscle flaps, in combination with the dilatation and elevation of the cervical esophagus, provide a sphincter mechanism that prevents tracheal reflux during deglutition.

Adult↗

MACOP-B regimen followed by involved-field radiation therapy in early-stage aggressive non-Hodgkin's lymphoma patients: 14-year update results.

A single-center, retrospective study was conducted to evaluate therapeutic results of the MACOP-B third-generation chemotherapy regimen followed by involved-field radiation therapy in a stage I-II aggressive non-Hodgkin's lymphoma (NHL) patients. From 1986 to 1995, 118 consecutive patients with the diagnosis of aggressive NHL, stage I-IE or II-IIE, with or without bulky disease were treated with MACOP-B regimen followed, when appropriate, by 30-36 Gy involved-field radiation therapy. The complete response (CR) rate was 95% after the combined modality treatment (97% for stage I-IE and 93% for stage II-IIE). Patients with bulky disease had a CR rate of 92%. Treatment was well tolerated and no deaths occurred from acute toxicity. After a median follow-up of 68 months, 24 (21%) patients relapsed. The 14-year projected relapse-free and overall survival rates were 78% and d 69%, respectively. MACOP-B regimen with/without involved-field radiation therapy provides a safe and effective combined modality treatment for early-stage aggressive NHL, with the possibility to definitively cure two thirds of the patients.

Adolescent↗

Active and inactive renin-like enzymes in the arterial wall of the spontaneously hypertensive rat.

Renin-like enzyme(s) in the arterial wall of the spontaneously hypertensive rat (SHR) were activated markedly by either acidic pH or treatment of proteolytic enzymes (trypsin and glandular kallikrein). The highest concentration of renin-like enzyme (active form) was localized in the renal artery (2.51 +/- 0.59 ng angiotensin I generated/mg of protein per h, mean +/- S.D.), followed by the mesenteric (1.58 +/- 0.31), the carotid (1.44 +/- 0.27) and the major aortic trunk (0.20 +/- 0.10), while the highest concentration of the inactive renin-like enzyme was localized in the major aortic trunk (0.97 +/- 0.18), followed by the carotid (0.72 +/- 0.41), the renal (0.71 +/- 0.31) and the mesenteric (0.60 +/- 0.29) arteries. In addition, the active renin-like activity from the mesenteric and the carotid arteries of SHR rats was higher significantly than that of age-matched normotensive Wistar-Kyoto (WKY) rats, despite a similar concentration of total renin-like enzyme of the corresponding arteries of both groups. These results suggest that increased interconversion of the inactive to the active renin-like enzymes in the arterial wall of SHR rats may result in local vasospasm through generation of angiotensin II, which may contribute in part at least to systemic hypertension of SHR rats.

Animals↗

Absence of mutatins in the analysis of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic humangastric cancer using genomic DNA and intron primers.

Mutations in the transforming growth factor beta type II receptor (TGFbetaRII) gene have been detected in several human cancers that represent the phenotype of genomic instability. To establish a basis for diagnosis of cancer patients, we previously determined the exon-intron organization of the TGFbetaRII gene. The results indicated that TGFbetaRII protein is encoded by 567 codons in 7 exons. In this study, we further determined the nucleotide sequences surrounding these 7 exons and designed 8 sets of intron-based primers to examine the entire coding region of the TGFbetaRII gene. By using these primers, we screened for mutations of the TGFbetaRII gene in DNAs of 32 sporadic gastric cancer patients in whom one case showed MI+ (3.1%) at two loci. We found no mutations, and these data support other recent evidence that TGFbetaRII mutations rarely occur except in colon and gastric tumors with MI.

Chromosome Mapping↗

P-glycoprotein expression and chemosensitivity in highly purified fresh human gastrointestinal cancer cells.

BACKGROUND/AIMS: Colorectal cancer is one of the tumors most refractory to treatment by chemotherapy. One of the major problems associated with cancer chemotherapy is drug-resistance of tumor cells, and resistance to doxorubicin (DOX) is mainly due to the effect of P-glycoprotein. We have tried to prove the correlation between P-glycoprotein expression and DOX-sensitivity in highly purified fresh human colorectal cancer and, moreover, to prove the differentiation of P-glycoprotein expression between the different kinds of cancers, including gastric cancer. METHODOLOGY: The present study was designed to quantify P-glycoprotein expression by flow cytometry, and DOX-sensitivity by MTT assay in highly purified fresh human tumor cells obtained from 29 cancer patients including 13 colorectal cancers and 16 gastric cancers. RESULTS: DOX-sensitivity decreased in proportion to P-glycoprotein expression in colorectal cancer. P-glycoprotein expression in colorectal cancer was higher than that in gastric cancer. Particularly, P-glycoprotein expression in colorectal cancer in the DOX low-sensitivity group was higher than in the DOX high-sensitivity group. CONCLUSIONS: The chemotherapeutic management of patients with colorectal cancer might be more effective if we can circumvent the effect of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Multidisciplinary treatment for gastric cancer patients by chemoimmunotherapy.

BACKGROUND/AIMS: Gastric cancer is a virulent disease with a poor prognosis despite multidisciplinary treatment. The present study was designed to clarify the clinical effects of chemoimmunotherapy for patients with advanced gastric cancer. METHODOLOGY: The enrolled gastric cancer patients had distant metastases including liver (n = 2) and peritoneal dissemination (n = 21). The patients had received the chemotherapy according to the results of chemosensitivity test and adoptive immunotherapy by activated killer cells. RESULTS: There were no severe toxicities, except fever and mild myelo-suppression. Four patients had complete response (17.4%) and 10 patients had partial response (43.5%). The performance status was improved in responders (p < 0.01, from 2.6 +/- 0.5 to 1.4 +/- 0.7); however, this was not changed in non-responders (from 2.2 +/- 0.9 to 2.0 +/- 1.2). The survival of responders was longer than that of non-responders (p < 0.05, 198 +/- 69 days vs. 104 +/- 68 days). CONCLUSIONS: It was clarified that responders by chemoimmunotherapy had a good quality of life and longer survival.

Aged↗

Neutrophil functions and cytokine production in patients with gastric cancer.

BACKGROUND/AIMS: One of the most important factors in the prevention of postoperative infection is the patient's own capacity to protect against infection. Neutrophils play a major role in this protection through phagocytosis and superoxide generation. Inflammatory cytokines are suitable for estimating the degree of surgical stress. The present study was designed to elucidate whether neutrophil functions are impaired in gastric cancer patients, and are related with cytokine production after surgery. METHODOLOGY: Phagocytosis and superoxide generation by neutrophils was studied in 84 patients with gastric cancer by flow cytometry. IL-6, IL-8 and tumor necrosis factor alpha were studied in 18 patients with gastric cancer by enzyme-linked immunosolubent assay. RESULTS: In gastric cancer patients phagocytosis was not impaired, whereas superoxide generation was lower than benign diseases and it was inhibited relative to the clinical stage. Moreover, superoxide generation was correlated with the nutritional parameters and was more suppressed in 7 patients who suffered from postoperative infection than in 40 patients whose postoperative course were uneventful. The fluctuation of superoxide generation correlated well with the serum cytokine levels in the postoperative course and its correlation was clarified in vitro. Nine patients with gastric cancer received intravenous hyperalimentation, and their superoxide generation was increased. CONCLUSIONS: Superoxide generation by neutrophils was suppressed in gastric cancer patients and it is suggested that nutritional support prevents postoperative infection via the augmentation of superoxide generation.

Aged↗

In vitro antitumor effect of topoisomerase-I inhibitor, CPT-11, on freshly isolated human gastric and colorectal cancer.

CPT-11 is a comptothecin analogue which has shown a broad spectrum of strong antitumor effect against various cancers, including gastroenterological malignancies. In the present study, the antitumor effect of CPT-11 was determined by MTT assay for freshly isolated human gastric and colorectal cancer cells, especially highly purified tumor cells. Twenty-three patients with gastric cancer, and 32 patients with colorectal cancer were enrolled in this study. Three gastric and 3 colonic cancer cell lines were used to study the antitumor effect of CPT-11, and freshly isolated cancer cells from 3 patients with gastric cancer were investigated. The in vitro antitumor effect was tested by MTT assay, and showed % inhibition rate. CPT-11 and SN-38 showed the antitumor effect as a dose dependent matter for human gastric and colorectal tumor cells in vitro. From the results of chemosensitivity for freshly isolated gastric and colorectal tumor cells, antitumor effect of SN-38 was as strong as other conventional anticancer agents. It was demonstrated that the MTT assay was appropriate for the analysis of the antitumor effects of CPT-11 and SN-38, and that CPT-11 may be a worthwhile choice as an anticancer agent against gastric and colorectal cancer.

Antineoplastic Agents↗

Effect of continued stretching of the affected arm in patients with cerebrovascular diseases by examining H-reflex characteristics.

To investigate excitability of spinal neural function during stretching excises in patients with cerebrovascular disease (CVD), H-reflex was analyzed before, during and after 1 min. continued stretching of the affected arm. 10 hemiparesis patients with hypertonus and hyperreflex, mean age of 53.2 years were tested. H-reflex was recorded from the abductor pollicis brevis on the affected side after stimulation of median nerve in supine position. The persistence, amplitude and amplitude ratio of H/M during stretching were lower than those before and after in the patients with moderately increased muscle tonus. In patients with slightly and markedly increased, H-reflex was same before, during and after continued stretching. It is suggested that excitability of spinal neural function during 1 min. continued stretching was inhibited in the patients with moderately increased muscle tonus caused by CVD.

Adult↗

Non-T cell disturbance causes the suppression of the autologous mixed lymphocyte reaction in patients with gastric carcinoma.

We investigated the accessory function of non-T cells to autoreactive T cells in autologous mixed lymphocyte reaction (AMLR) and clarified the cause of the suppression of autoreactivity in patients with gastric carcinoma. The response of T cells in the AMLR in gastric cancer patients was significantly suppressed compared with that in controls. In patients in whom the AMLR of the spleen was suppressed more than that of the peripheral blood, the degree of stimulation of non-T cells from the spleen was remarkably suppressed, on the other hand, in patients in whom AMLR of the peripheral blood was suppressed more than the spleen, the degree of stimulation from the peripheral blood was remarkably suppressed. The expression of HLA-DR antigens on non-T cells of gastric cancer patients was lower than that of controls. AMLR was considerably decreased in controls by the treatment non-T cells with anti-HLA-DR MoAb, but not in cancer patients. Treatment of non-T cells from the spleen of gastric cancer patients with IFN-gamma remarkably improved T cell proliferation in the AMLR. IFN-gamma also enhanced the expression of HLA-DR antigens on non-T cells. The disturbance of non-T cells was not biased to a specific population. These disturbances of non-T cells suppressed the AMLR independently of stage status. Therefore, the immunological abnormality of non-T cells manifested by reduced accessory function to autoreactive T cells may cause impaired immunological surveillance against tumors and permit cancer cell growth.

Antibodies, Monoclonal↗

Polysaccharide preparation PSK augments the proliferation and cytotoxicity of tumor-infiltrating lymphocytes in vitro.

We have investigated whether or not polysaccharide preparation PSK directly augments the proliferation and cytotoxicity of tumor-infiltrating lymphocytes (TILs). TILs were separated from 10 patients with gastrointestinal cancer (5 gastric cancers, 3 colon cancers and 2 pancreatic cancers). TILs were cultured with IL-2 and PSK for 7 days. The DNA synthesis of TILs was augmented by incubation with 100 micrograms/ml of PSK, which was similar to serum level with oral administration of PSK in cancer patients. The effect of PSK in DNA synthesis was also found by elimination of non-T cells. Furthermore, we established TIL clones and examined the effect of PSK on TILs clones. The DNA synthesis was augmented by PSK in CD4 positive and CD8 positive TIL clones without non-T cells, suggesting that PSK acts directly on TILs. We examined the cytotoxic activities of TILs by the 4-h and 16-h 51Cr release assay. PSK did not affect the cytotoxic activity of TILs against autologous tumor cells and KATO-III cells in the 4h 51Cr release assay, whereas PSK induced high lysability of TILs against autologous tumor cells in the 16-h 51Cr release assay. We studied the ability of PSK to induce cytokines from TILs using a double chamber plate. The DNA synthesis of tumor cells was more suppressed by the mixed-tumor cell culture supernatants of TILs cultured with PSK, compared to that of TILs cultured without PSK. It is suggesting that PSK induced long term killing activity of TILs by induction of cytotoxic cytokines. Thus, PSK augmented the proliferative response of TILs without interaction of T cells and non-T cells and induced cytotoxic cytokines of TILs.

Cell Division↗

In vitro augmentation of cytotoxic activity of peripheral blood lymphocytes and spleen cells of cancer patients by ubenimex.

Ubenimex is used for the immunotherapy of malignant diseases as a biological response modifier (BRM) and shows beneficial effects as an adjuvant treatment. In the present study, the in vitro effects of ubenimex on the cytotoxic activity of peripheral blood lymphocytes (PBL) and spleen cells of cancer patients and the mechanism of killer cell activation were investigated. Cytotoxic activity against K562, KATO-III and autologous tumor cells was augmented by in vitro sensitization with ubenimex (p < 0.05). The optimal concentration of ubenimex for induction of cytotoxic activity was 1 micrograms/ml, similar to serum levels after clinical oral administration. The major population of killer cells activated by ubenimex recognizing K562 was CD16+, and those recognizing KATO-III were mainly CDA+ or CD8(5) cels and CD16+ NK cells, while CDA5 or CD8+T cells comprised the majority of killer cells which showed autologous tumor-killing activity. Augmentation of the cytotoxic activity of mononuclear cells by ubenimex was blocked by both anti-IL-1 beta Ab and anti-IL-2 AB. However, the expression of IL-2 receptor (p55, p75) on effector cells was not altered. Ubenimex augmented not only NK activity but also autologous tumor killing activity of PBL and spleen cells via macrophage activation. These activities of ubenimex may be clinically beneficial as an adjuvant treatment.

Adjuvants, Immunologic↗

Ubenimex treatment enhances the susceptibility of gastric cancer cell lines to lymphokine-activated killer cells.

We investigated the direct effects of ubenimex on the modification of gastric carcinoma cell lines' susceptibility to killer cells, and the mechanism of its action. The susceptibility of both MKN-45 cells and KATO-III cells to LAK cells was enhanced by treatment with ubenimex for 48 h (p < 0.05), and the optimal concentration for this effect was 10 micrograms/ml. The susceptibility of ubenimex treated KATO-III cells to CD3+ LAK cells, especially to those also expressing CD8, was enhanced. DNA synthesis of tumor cells was not impaired by treatment with ubenimex at all concentrations tested. The binding rate of LAK cells and ubenimex-treated KATO-III cells was similar to that between LAK cells and untreated KATO-III cells. Moreover, no alterations in the expression of any antigen related to mononuclear cell-binding to tumor cells were induced by ubenimex. Lysis or the inhibition of DNA synthesis of tumor cells by LAK cell supernatant was enhanced by ubenimex. These results suggested that the mechanism responsible for the augmentation of tumor cell susceptibility by ubenimex may be a result of the alteration of their sensitivity to some Iytic factors released by LAK cells. Thus ubenimex shows not only an indirect host-mediated anti-tumor activity but also a direct effect on tumor cells, modifying their susceptibility to killer cells, and this may explain why ubenimex shows beneficial clinical effects as an adjuvant treatment.

Adjuvants, Immunologic↗

Augmentation of lymphokine-activated killer cell activity by lentinan.

Lymphokine-activated killer (LAK) activity stimulated by interleukin 2 (IL-2) and/or lentinan was examined in the peripheral blood of 9 healthy subjects and 7 cancer patients. After 4 and 8 days culture, LAK killer activity stimulated by IL-2 and lentinan against autologous tumor and K562 cells was greater than that stimulated by IL-2 alone. The optimal concentration of lentinan for the generation of killer cells ranged from 25-500 ng/ml, a level which can be achieved in vivo by the administration of clinical doses of this agent. The expression of CD25 antigen, the alpha chain of the IL-2 receptor on the activated killer cells was increased by lentinan. Thus it was shown that LAK cells stimulated with IL-2 plus lentinan had strong cytotoxicity and might be useful as effector cells for adoptive immunotherapy.

Cytotoxicity, Immunologic↗

In vitro antitumor activity of 4'-O-tetrahydropyranyladriamycin on human gastric cancer cells.

The antitumor activity of 4'-O-tetrahydropyranyladriamycin (THP-ADM) was assessed in established gastric cancer cell lines, including MKN-28, moderately differentiated adenocarcinoma and KATO-III, signet ring cell carcinoma and freshly excised human gastric cancer cells, using the MTT assay. The inhibition rates of THP-ADM were identical to those of adriamycin (ADM) in established gastric cancer cell lines, and the chemosensitivity of MKN-28 was higher than KATO-III. In fresh human gastric cancer cells obtained from 27 patients the inhibition rates of THP-ADM were identical to those of ADM, and there was a significant correlation of inhibition rates ADM and THP-ADM. These results indicate that THP-ADM should be a potent candidate to replace ADM in cancer chemotherapy.

Adenocarcinoma↗

Etoposide enhances the antitumor effects of cisplatin in gastric cancer cells.

We studied the combination effect of cisplatin(CDDP) plus etoposide(VP-16) in an established gastric cancer cell line, KATO-III, and also highly purified fresh human tumor cells obtained from 55 gastric cancer patients, using MTT assay. The synergistic effects of CDDP plus VP-16 were shown by both the fractional product method and median effect plot analysis in KATO-III cells, and by fractional product method in fresh human gastric cancer cells. The combination with CDDP and VP-16 showed the synergistic antitumor effects in not only KATO-III cells, but also fresh human gastric cancer cells. The antitumor effects of CDDP were enhanced by early exposure of VP-16 in KATO-III cells. The combination effects of CDDP and VP-16 were more potent in poorly differentiated gastric cancer, compared with well-differentiated cell types. Thus, it is suggested that the combination of CDDP plus VP-16 is useful in the anticancer chemotherapy of gastric cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗