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Biomedical subjects

A Tokunaga

Publications and source records attributed to A Tokunaga.

At least 73 records · Page 4Linked to original sources
PubMed1997

[Clinical evaluation of 2-mg granisetron tablet for nausea and vomiting induced by anticancer drugs including cisplatin].

The antiemetic effects on nausea and vomiting induced by anticancer drugs and safety of a 2-mg granisetron tablet were studied in cancer patients, particularly in the field of gynecology, who had been treated with anticancer drugs including cisplatin (CDDP) at 50 mg/m2 or more. The 1-mg granisetron tablet is already commercially available and used widely in clinical practice by oral administration of two tablets per dosage. In this investigation, the clinical efficacy, safety and usefulness of a 2-mg tablet, which can be taken more easily, were studied. The 2-mg granisetron tablet was judged to be "remarkably effective" or "effective" for nausea and vomiting in 22 (66.7%) of 33 patients. For safety, neither adverse experiences nor abnormal laboratory values were judged to be of clinical significance. The 2-mg granisetron tablet was considered "extremely useful" or "useful" in 22 (66.7%) of 33 patients. The above results confirmed the excellent antiemetic effect on nausea and vomiting induced by anticancer drugs including CDDP and the high degree of safety of a 2-mg granisetron tablet.

Adult↗
PubMed1997

[Prospect of gene therapy for metastatic foci of gastric cancer].

Surgical excision of both primary and metastatic tumors is the recommended therapy for gastric cancer. There are many cases of multiple metastasis to lymph nodes, disseminated metastasis of peritoneum, and post-operative systemic metastasis for which no surgical treatment is available. Cancer gene therapy is one of the promising new techniques. We injected the suicide gene, herpes simplex virus thymidine kinase (HSV-tk), directly into the tumor using gastrofiberscopy. Following GCV treatment caused tissue degeneration at the injection site and lymph nodes. These findings show that suicide gene therapy for gastric cancer may be effective for a metastatic tumor along with the primary tumor.

Animals↗
PubMed1997

[Current status and problems of home parenteral nutrition for terminal cancer patients from the viewpoint of indication].

Since June 1993, we have been performing home parenteral nutrition (HPN) for end-stage cancer patients. We studied how many patients could be treated with HPN, why they were not able to be treated with HPN in the terminal stage cancer patients, 158 cases, who admitted and died in our ward from June 1993 to April 1997. Eighty-six patients (54.4%) were considered to not be indicated for HPN, due to general weakness (28 cases), dyspnea (17 cases), need for medical care other than HPN (34 cases), and inability to understand this treatment (1 case). Fifty-six patients (35.4%) were considered to have been able to be treated with HPN and could have had returned home. Fifteen patients (26.8%) were given HPN. Four cases wanted to stay in the hospital after they knew the truth and the prognosis of their disease. Another four patients became weak while preparing for HPN and could not go home. Eighty percent of patients could not to be treated with HPN because of the factors of their family. Eight patients had no family to cared for them. Twelve patients were refused to the truth of their disease. The families of 13 cases refused to accept and care for them in their home. We may conclude that co-operation among patients, their family and the medical staff is the most important factor in providing HPN for end-stage cancer patients.

Adult↗
PubMed1996

Inhibitory effect of anti-epidermal growth factor receptor antibody on a human gastric cancer.

BACKGROUND: Blockading the putative epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha)/EGF receptor autocrine pathway with anti-EGF receptor monoclonal antibody (MoAb) might prevent the growth of tumor. METHODS: The present study was designed to examine the effect of MoAb 528 on the growth of an EGF receptor which was hyperproducing human gastric cancer cells in vitro and in vivo. RESULTS: Treatment with MoAb 528 inhibited the growth of cultured cells in a dose-dependent manner. Twenty micrograms of MoAb 528 given intraperitoneally after inoculation of 1 x 10(6) cells and 200 micrograms of the MoAb 528 given after inoculation of 1 x 10(7) cells to athymic mice inhibited the growth of the xenograft. Twenty micrograms of MoAb 528 from a miniosmotic pump, which releases its contents over 2 weeks, also prevented the growth of the xenograft when the treatment was started on the day after tumor inoculation. However, no inhibitory effect was observed when the treatment was started 3 weeks after inoculation. The binding capacity of 125I-EGF on the MoAb treated tumors was diminished in comparison with control tumors. CONCLUSIONS: The results suggest that MoAb 528 blocks the EGF or TGF-alpha/EGF receptor signal pathway, resulting in the inhibition of cancer cell growth. This MoAb 528 may therefore be an effective antitumor agent against human gastric cancer that shows expression of the EGF receptor.

Animals↗
PubMed1996

Genetic polymorphisms of the cancer related gene and Helicobacter pylori infection in Japanese gastric cancer patients. An age and gender matched case-control study.

BACKGROUND: Gastric cancer is a multistage process, each caused by numerous factors. The objective of this study was to elucidate the risk factors for gastric cancer by using molecular epidemiologic techniques and serum markers. METHODS: Serum pepsinogen I levels, pepsinogen I/pepsinogen II (I/II) ratios, serum IgG antibody against Helicobacter pylori (H. pylori), and genetic polymorphisms of cytochrome p450 2E1 (CYP2E1), glutathione-S-transferase M1 (GSTM1), and L-myc protooncogenes were analyzed in 82 persons with gastric cancer and in 151 age- and sex-matched controls, who were selected from 208 gastric cancer patients and 375 noncancer patients, respectively. Statistical analysis was performed to elucidate which risk factors for gastric cancer were contributing the most to gastric carcinogenicity. RESULTS: Serum pepsinogen I level (odds ratio [OR] = 1.81; 95% confidence interval [CI], 1.04-3.16) and pepsinogen I/II ratios (OR = 3.09; 95% CI, 1.74-5.49) were significantly associated with gastric cancer risk in a case-control study. Seropositivity of serum IgG antibody against H. pylori (OR = 1.25; 95% CI, 0.84-1.85) and specific genotypes of a L-myc genetic polymorphism (OR = 1.33; 95% CI, 0.59-2.99) were more commonly observed in gastric cancer cases, but this was not statistically significant. Specific genotypes of the CYP2E1 RsaI polymorphism and GSTM1 gene deletion were not associated with gastric cancer. CONCLUSIONS: Atrophic mucosal change, indicated by serum pepsinogen levels, is possible a risk factor for gastric cancer. H. pylori infection and genetic polymorphisms of CYP2E1, L-myc, and GSTM1 genetic polymorphisms were not risk factors in this study.

Adult↗
PubMed1996

[Mitomycin C-DNA adduct detection in rat organs and human liver].

Mitomycin C-DNA adduct formation was detected in rat organs and also in human tissues by 32P-postlabeling assay. The adduct levels were 1-4 adduct/ 10(8) nucleotides in the human liver after 20 mg of mitomycin C by intra-artery administration and which level was higher comparing with the levels in the rat liver after 10 times more dosages of mitomycin C administration by intra-venous injection. The levels in the human liver were maintained at least 56 days after administration. Organ-specific differences of adduct levels were observed in rat experiments: the adduct levels of liver, lung and kidney were stable but rapidly decreased in stomach and colon. These results, which were obtained from the experiments using the normal parts of each organs may indicate that the drug effectivity for adduct formation was sufficient with smaller dose in the stomach and colon, but disappeared quickly, mean while, the drug effectivity was undergoing in relatively high levels for longer periods in the liver lung and kidney. The analysis of human liver samples may suggest that the selective intra-artery injection induced stronger drug effectivity for adduct formation in human organs.

Adult↗
PubMed1996

[Phase II study of paclitaxel (BMS-181339) in patients with ovarian cancer by 3-hour intravenous infusion].

A phase II study of Paclitaxel in patients with ovarian cancer by 3-hour intravenous infusion was undertaken by a cooperative study group of 30 institutes. Of 66 cases enrolled, 57 cases were evaluable for efficacy, and 63 cases were evaluable for safety. In spite of the fact that all cases for efficacy evaluation were previously treated with chemotherapy including platinum-based drugs, 2 cases of complete response (CR) and 15 cases of partial response (PR) were observed, with a response rate of 29.8% (The 95% confidence interval of response rate was 18.4-43.4%). Paclitaxel also showed 28.2% (11/39) response rate in patients refractory to treatment by platinum-based drugs. Histologically, the response rates were 28.9% (11/38) in serous adenocarcinoma, 40.0% (2/5) in clear cell adenocarcinoma and 25.0% (1/4) in mucinous adenocarcinoma. As the major laboratory abnormalities, leukopenia, neutropenia and decrease in hemoglobin were observed with incidence rates of 98.4% (62/63), 95.2% (59/62) and 85.7% (54/63), respectively. However, these abnormalities were clinically manageable by either withdrawal of medication, administration of antibiotics, G-CSF or metachysis etc. In addition, thrombocytopenia, elevation in GOT and GPT were seen with moderate incidence. Peripheral neuropathy was a major adverse symptom with an incidence of 79.4% (50/63), followed by alopecia, myalgia, arthralgia and fever. However, the majority of these adverse reactions were less than grade 3. From these findings, we confirmed that 3-hour intravenous infusion of Paclitaxel was a clinically useful chemotherapeutic agent in patients with ovarian cancer.

Adult↗
PubMed1996

[Molecular mechanisms of chronic pain].

Peripheral noxious stimuli or tissue injury induce the release of excitatory amino acids (EAAs) and other neurotransmitters from primary afferent terminals in the spinal dorsal horn, which may lead to the expression of immediate early genes (IEGs) in dorsal horn neurons via activation of intracellular messengers including Ca2+ and various protein kinases. Various IEGs of fos, jun, and zinc finger families are differentially expressed in dorsal horn neurons in a time dependent manner. Protein products of these genes function as transcription factors and trigger long-lasting plastic changes in CNS neurons. Simultaneously, EAAs may activate the synthesis of prostanoids and NO, which may affect the sensitivity of dorsal horn neurons. In addition, peripheral chemical mediators such as 5-HT contribute to the peripheral hyperalgesia. These events may contribute to the establishment of persistent pain and hyperalgesia in a concerted manner. It is shown that pre-treatment, but not post-treatment, with local anesthetics or analgesics reduces expression of c-fos in spinal cord neurons and pain responses in animals, suggesting that the inhibition of intracellular events by pre-treatment with anesthetics and analgesics is effective for the reduction of persistent pain following tissue injury.

Animals↗
PubMed1996

[Role of peritoneal lavage smears and gastric wall brushing smears in gastric cancer surgery].

Examinations of peritoneal lavage smears (LC) and gastric wall brushing smear cytology (BC) appear to be important for determining accurately the stage of gastric cancer. We have been carrying out such examinations during gastric cancer surgery for 7 years. In the present study, we evaluated the results obtained from 287 patients with gastric cancer. Tumor invasion and peritoneal dissemination were correlated with a positive incidence of cancer cells in LC and/or BC. Gastric cancer showing serosal invasion was classified into positive for LC and/or BC and negative for LC and/or BC. Patients positive for LC and/or BC had a poorer prognosis. For future gastric cancer treatment, patients positive for peritoneal cytology are expected to be targeted for intensive treatment during or before surgery.

Adenocarcinoma↗
PubMed1996

[Expression of trefoil group antigen pS2 in human gastric cancer].

Expression of trefoil group antigen pS2 was examined immunohistochemically in resected stomachs from 121 patients with gastric cancer. Gastric cancer was classified as either undifferentiated or differentiated by histology, and was also divided into gastric type or non-gastric type by mucin-histochemistry. Immunoreactive pS2 was present in 20% of early cancers and 30% of advanced cancers (NS), and in 25% of undifferentiated and 15% of differentiated early cancers (NS), whereas the antigen was present in 38% of undifferentiated and 15% of differentiated advanced cancers (p = 0.04). Positivity for pS2 was found more often in gastric type early cancer (p = 0.04) as well as advanced cancer (p = 0.0002), and was also more frequent in cancers showing scirrhous (p = 0.04) and infiltrative growth (p = 0.03). Cancer positive for pS2 was characterized by mucin-histochemistry and microscopy as gastric type with scirrhous growth and diffuse infiltration, and thus the expression of pS2 in gastric cancer appears to be related to the growth of cancer with these characteristics.

Adenocarcinoma, Scirrhous↗
PubMed1995

Effects of local anaesthesia on formalin-induced Fos expression in the rat dorsal horn.

A subcutaneous injection of formalin into foot pad of the rat produces a bimodal nociceptive response including an early intense response in the first 5 min and a later moderate response that is exhibited from 20 to 60 min after injection. In this study, we investigated the effects of blocking the early phase and late phase input, respectively, on Fos-like immunoreactivity (Fos-LI) expression in dorsal horn neurones. Rats of the early phase block (EB) group were injected with 5% formalin (0.05 ml) into the footpad 5 min after a s.c. injection of 4% lidocaine (0.15 ml) into the angle. The rats of the late phase block (LB) group were injected with 5% formalin into the footpad 10 min before the s.c. injection of 3% prilocaine (0.20 ml) containing felypressin into the ankle. The rats of the control group were given the formalin injection alone. Fos-LI was detected in the dorsal horn 2 h after the formalin injection. The numbers of Fos-LI neurones in the dorsal horn of both EB and LB group were markedly decreased compared with the control group, being 31.3% (laminae I-III of EB), 37.1% (laminae I-III of LB), 13.9% (laminae IV-VI of EB) and 16.2% (laminae IV-VI of LB) of the control values. No significant difference was observed between EB and LB group. These findings suggested that the early and late phase contribute in concert to the induction of genetic changes in dorsal horn neurones after formalin injection.

Anesthesia, Local↗
PubMed1995

Clinical significance of epidermal growth factor (EGF), EGF receptor, and c-erbB-2 in human gastric cancer.

The EGF stimulation system for growth regulation is implicated in normal and neoplastic cell proliferation. The role of EGF, the EGF receptor, and c-erbB-2 in human gastric cancer is reviewed on the basis of several reports, which have been mainly oriented toward their clinical significance. EGF has been shown immunohistochemically to be present in 26% of gastric cancers (n = 395). The presence of EGF in gastric cancer is correlated with the degree of gastric wall invasion and lymph node metastasis. The 5-year survival of patients with EGF-positive tumors is worse than that of patients with EGF-negative tumors. The presence of EGF in human gastric cancer may therefore represent a higher malignant potential. Fifteen percent of gastric cancers (n = 352) were also shown to be positive for both EGF and the EGF receptor immunohistochemically, and the simultaneous occurrence of EGF and the EGF receptor suggests that these tumors grow in an autocrine fashion. Tumors exhibiting EGF and the EGF receptor simultaneously show a greater degree of local invasion and lymph node metastasis. Increased expression of EGF receptor protein in gastric cancer appears to be related to biologic aggressiveness, although gene amplification has occurred only to a small extent. Twelve percent of gastric cancers (n = 486) were found to be positive for c-erbB-2. This type of tumor has a frequent metastasis, and patients with c-erbB-2-positive cancer have a poorer prognosis than those with c-erbB-2-negative tumors. Selective blockade of the EGF receptor and c-erbB-2 from their ligands with monoclonal antibodies (MoAbs) inhibits the growth of human gastric cancer xenografts. These MoAbs may therefore be effective antitumor agents against gastric cancer showing overexpression of EGF receptors or c-erbB-2.

Epidermal Growth Factor↗
PubMed1995

Mucosal IgA antibody against Helicobacter pylori in chronic gastritis and intestinal metaplasia detected by the Tes-Tape method in resection specimens after gastrectomy for gastric cancer.

BACKGROUND: Subjects with atrophic body gastritis have a high prevalence of Helicobacter pylori seropositivity and a low prevalence of H. pylori infection. Disappearance of the organism appears to correlate with the development of intestinal metaplasia. To investigate this point, intestinal metaplasia was biochemically subclassified into complete and incomplete types by the Tes-Tape method, and tissue IgA and IgG antibodies against H. pylori were measured by enzyme-linked immunosorbent assay (ELISA). METHODS: Twenty-five stomachs resected for gastric cancer were examined using the Tes-Tape method. Serum H. pylori IgA and IgG antibodies and tissue IgA and IgG antibodies against H. pylori and tissue secretory IgA (sc-IgA) were examined in areas of intestinal metaplasia, nonmetaplastic gastric mucosa, and gastric carcinoma by ELISA: RESULTS: Tissue H. pylori IgA antibody was positive in 6 of 19 (32%) specimens taken from complete and 2 of 7 (29%) incomplete types of intestinal metaplasia and was positive in 6 of 14 (43%) nonmetaplastic gastric mucosa from the antrum and 14 of 23 (61%) from the body. Duodenal mucosa and cancer tissue were positive for tissue IgA antibody in 1 of 6 (17%) and 0 of 17 (0%), respectively. Tissue H. pylori IgG antibody was negative in all the tissues examined. sc-IgA in the areas of intestinal metaplasia was 120 +/- 65 (mean +/- standard error; ng/mg wet weight) and in the nonmetaplastic gastric mucosa was 113 +/- 72, showing no difference. Positivity and negativity of serum IgA and IgG antibodies against H. pylori coincided with presence or absence of tissue IgA antibody in nonmetaplastic gastric mucosa in 15 of 19 (79%) and 16 of 19 (84%) patients examined, respectively. CONCLUSION: Positivity rates of tissue IgA antibody against H. pylori were lower in the mucosa of intestinal metaplasia than in nonmetaplastic gastric mucosa and were negative in carcinoma. No significant difference in levels of sc-IgA between intestinal metaplasia and non-metaplastic gastric mucosa was found.

Antibodies, Bacterial↗
PubMed1995

Detection of Helicobacter pylori DNA in gastric juice by the polymerase chain reaction: comparison with findings in bacterial culture and the detection of tissue IgA and serum IgG antibodies against Helicobacter pylori.

The detection of Helicobacter pylori in gastric juice by the polymerase chain reaction (PCR) was undertaken in 124 patients with peptic ulcer or chronic gastritis. PCR products were evaluated by agarose gel electrophoresis and Southern hybridization of H. pylori-specific DNA sequences. Positive and negative results of the PCR analysis in 72 examinations were compared with those from bacterial culture, and with the detection of tissue IgA antibody against H. pylori by enzyme-linked immunosorbent assay ELISA; Serion, Wuerzburg, Germany, and detection of serum IgG antibody against H. pylori by ELISA; Radim Pomezia, Italy. Thirty-four PCR-positive samples evaluated by electrophoresis and hybridization coincided with positive samples in 56% of bacterial cultures, 59% of tissue IgA antibody identifications, and 94% of serum IgG antibody evaluations; 26 PCR-negative samples coincided with negative samples in 96% of bacterial cultures, 81% of tissue IgA antibody evaluations, and 38% of serum IgG assessments. We compared the detection achieved with the H. pylori PCR assay in gastric juice with that in biopsies taken from the antrum and upper corpus in 90 examinations, and found them to be both positive in 34 (38%) and 36 (40%) of specimens, both negative in 37 (41%) and 30 (33%) specimens, gastric juice-positive but biopsy-negative in 10 (11%) and 12 (13%) specimens, and vice versa in 9 (10%) and 12 (13%) specimens, when detected by electrophoresis and hybridization, respectively, showing equivalent detection rates. In relation to the type of disease, the positive PCR assay results with gastric juice, evaluated by electrophoresis and hybridization, respectively, were: gastric ulcer 34/53 (64%) and 39/53 (74%), duodenal ulcer 23/38 (61%) and 25/38 (66%), and chronic gastritis 20/33 (61%) and 23/33 (70%), showing no significant difference in positive rates between peptic ulcer and chronic gastritis. Of the samples of 16 patients with H. pylori-positive gastric juice by the PCR assay, 7 were negative by PCR assay analyzed by electrophoresis and hybridization after the completion of treatment H. pylori. However, after treatment, 3 were negative on electrophoresis but still had positive results with hybridization, indicating that a minimal number of bacilli may have still remained. Detection of H. pylori in gastric juice has potential advantages for examining H. pylori infection in the entire stomach and for follow up after treatment for the eradication of H. pylori.

Antibodies, Bacterial↗
PubMed1995

Prospective studies of the association between anticardiolipin antibody and outcome of pregnancy.

OBJECTIVE: To investigate the association of anticardiolipin antibody with the genesis of spontaneous abortion, fetal growth restriction (FGR), and preeclampsia. METHODS: Eight hundred sixty pregnant women constituted the study population. Anticardiolipin antibody was screened by enzyme-linked immunosorbent assay during the first trimester of pregnancy. The outcome of pregnancy in these women was analyzed prospectively, and the rate of occurrence of spontaneous abortion, preeclampsia, and FGR was compared in the anticardiolipin antibody-positive and -negative groups. RESULTS: Anticardiolipin antibody was positive in 60 of the 860 women (7.0%) and negative in 800 (93.0%). The rate of spontaneous abortions in the anticardiolipin antibody-positive group, 25.0%, was significantly higher than that in the anticardiolipin antibody-negative group, at 9.8% (P < .001; relative risk [RR] 2.56, 95% confidence interval (CI) 1.37-4.81). The rates of preeclampsia (11.7%) and FGR (11.7%) in the anticardiolipin antibody-positive group were also significantly higher than those in the -negative group (1.9 and 1.9%, respectively; for preeclampsia, P < .001; RR 6.22, 95% CI 2.43-16.0 and for FGR, P < .001; RR 6.22, 95% CI 2.43-16.0). CONCLUSIONS: Anticardiolipin antibody is associated with adverse outcomes of pregnancy such as spontaneous abortion, preeclampsia, and FGR.

Abortion, Spontaneous↗
PubMed1995

Cytochrome P4502E1 (CYP2E1) genetic polymorphism in a case-control study of gastric cancer and liver disease.

Cytochrome P4502E1 (CYP2E1) activates carcinogenic N-nitrosamines, benzene, urethane and other low molecular weight compounds. This enzyme is also inducible by ethanol, and metabolizes alcohol. A restriction fragment length polymorphism (RFLP) using the Rsa I restriction enzyme has been identified in the CYP2E1 transcription regulatory region; recent studies suggest that this polymorphism may affect gene expression. We investigated the frequency of the Rsa I RFLP in a Japanese population in relation to gastric cancer and liver disease susceptibility. The frequency of this polymorphism was determined in 150 gastric cancer, 16 hepatocellular cancer, 48 liver cirrhosis and 203 benign gastric disease (controls) patients. This preliminary study shows no association of the specific genotype with gastric cancer in all subjects (odds ratio = 1.04, 95% CI = 0.74-3.08 for the heterozygote and 0.57, 95% CI = 0.22-1.50 for the homozygous rare allele, respectively). To further confirm this lack of association, an age and gender matched case-control study should be performed. Separately, there was no association of the Rsa I RFLP with hepatocellular carcinoma (p = 0.911), but there was a suggested difference between the non-viral associated liver cirrhosis patients and control patients. Thus, this polymorphism may be related to ethanol metabolism and consequential liver diseases in a Japanese population.

Base Sequence↗