Biomedical subjects

H Futami

Publications and source records attributed to H Futami.

At least 37 records · Page 2Linked to original sources

PubMed1997

Study of transmission routes of Helicobacter pylori in relation to seroprevalence of hepatitis A virus.

The seroprevalence of Helicobacter pylori in a group of 1,043 healthy Japanese people was compared with that of hepatitis A virus (HAV), which was used as a marker of fecal-oral exposure. No statistically significant relationship was observed between seropositivity for HAV and that for H. pylori. Therefore, the fecal-oral spread of H. pylori is of limited relevance in Japan.

Helicobacter Infections↗

PubMed1997

Percentage changes in serum pepsinogens are useful as indices of eradication of Helicobacter pylori.

OBJECTIVE: Eradication of Helicobacter pylori has been gaining significance for the treatment of gastroduodenal diseases. Establishment of a precise diagnostic method for H. pylori is of great value. The aim of this study was to establish a new method for precisely judging the eradication of this bacteria. METHODS: We measured serum pepsinogen I (PG I) and pepsinogen II (PG II) levels in 105 cases of peptic ulcer with H. pylori infection before and after anti-H. pylori treatment, determined percentage changes in serum PG I:PG II ratios before and 1 month after the treatment, and established cut-off values for them to distinguish success from failure of H. pylori eradication. Cut-off values for percentage changes in serum PG I:PG II ratios were tentatively set as +40%, +25%, and +10% when the serum PG I:PG II ratios before treatment were less than 3.0, not less than 3.0 but less than 5.0, and not less than 5.0, respectively. RESULTS: With these cut-off values, the sensitivity, specificity, and validity for determination of eradication of H. pylori-on the basis of culture, histology, the rapid urease test, and a polymerase chain reaction method-were 100.0%, 93.1%, and 96.2%, respectively. These cut-off values could be applied to both gastric ulcer and duodenal ulcer. CONCLUSION: Our findings suggest that percentage changes in serum PG I:PG II ratios are useful as indices for distinguishing success from failure in eradication therapy for H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1996

UCN-01, 7-hydroxyl-staurosporine, inhibits kinase activity of cyclin-dependent kinases and reduces the phosphorylation of the retinoblastoma susceptibility gene product in A549 human lung cancer cell line.

UCN-01 (7-hydroxyl-staurosporine), which was initially developed as a selective protein kinase C inhibitor, has an anti-tumor effect on several human cancer cell lines in vivo. In this study, we examined whether this compound has an inhibitory effect on cell cyclin-dependent kinases (cdks) in vitro and in vivo using A549 human lung adenocarcinoma cell line. UCN-01 inhibited the retinoblastoma susceptibility gene product (pRB) kinase activity of three types of cdks (cdk 2, 4 and 6) with 50% inhibitory concentration values of 42, 32, and 58 nM, respectively, in vitro. Moreover, the amount of phosphorylated pRB was reduced by UCN-01 at a concentration of 100 nM in the living cells. Flow cytometric analysis showed that UCN-01 inhibited cell cycle progression at G1 to S transition in A549 cells at the concentration of 100 nM. These results suggest that inhibition of pRB phosphorylation by UCN-01 might lead to inhibition of the cell cycle and thereby contribute to antitumor activity of this compound.

Alkaloids↗

PubMed1996

Quantitative study of Helicobacter pylori in gastric mucus by competitive PCR using synthetic DNA fragments.

Helicobacter pylori is closely related to upper gastrointestinal diseases, and the precise evaluation of H. pylori infection is necessary for the treatment of these diseases. The aim of the present study was to establish a method for the quantitative detection of H. pylori. We applied a competitive PCR method using various amounts of synthetic DNA fragments containing the same primer-binding and a subset of the same template sequences as the target competing for primer binding and amplification in order to quantify H. pylori in gastric mucus. The results obtained by this method were compared with the results of histological examination, the rapid urease test, bacterial culture, the [13C]urea breath test, and urea and ammonia measurements in gastric juice. As the quantity of H. pylori in gastric mucus increased, the rates of positivity of histological examination, the rapid urease test, and bacterial culture increased. The quantity of H. pylori in gastric mucus was also significantly correlated with the results of the [13C]urea breath test and was negatively correlated with the urea/ammonia ratio in gastric juice. The competitive PCR method provides an objective measure of the quantity of H. pylori and makes it possible to distinguish true negatives from false negatives due to incomplete PCR and true positives from false positives due to contamination. This method is very useful for the precise evaluation of gastric H. pylori infection.

Adult↗

PubMed1996

Inhibition of lymphatic metastasis in a syngeneic rat fibrosarcoma model by an angiogenesis inhibitor, AGM-1470.

We examined whether lymphatic metastasis was inhibited by the potent angiogenesis inhibitor AGM-1470 [O-(chloroacetyl-carbamoyl)fumagillol, TNP-470] using a rat lymphatic metastasis model. Clone A of the rat fibrosarcoma AS653HM, when inoculated into the footpads of syngeneic rats, highly and preferentially metastasized to lymph nodes. In contrast, when AGM-1470 was administered subcutaneously to rats bearing the tumor cells, the tumor growth and incidence of metastasis in the lymph nodes were reduced in a dose- and schedule-dependent manner. Similar inhibition of lymphatic metastasis was also observed in the rats in which treatment with AGM-1470 was initiated following resection of the primary tumor in the foot, indicating that the treatment with AGM-1470 inhibited the progression of lymphatic metastasis at the metastatic sites of the lymph nodes. These results suggest that AGM-1470 can be a potential agent to prevent lymphatic metastasis.

Animals↗

PubMed1995

The role of angiogenesis in the tumor growth of Syrian hamster pancreatic cancer cell line HPD-NR.

BACKGROUND/AIMS: New therapeutic approach is required for pancreatic cancer, one of the most intractable malignancies. The role of angiogenesis in the tumor growth of a Syrian hamster pancreatic cancer cell line HPD-NR, which closely resembles its human counterpart, was investigated. METHODS: Angiogenic activity was measured as stimulation of growth of human umbilical vein endothelial cells (HUVEC), and angiogenic factors produced by HPD-NR cells were identified by reverse-transcription polymerase chain reaction and Northern blot analysis. Then in vitro and in vivo antitumor effects of a potent angiogenesis inhibitor, O-(chloroacetylcarbamoyl)fumagillol (AGM-1470), were examined. RESULTS: The conditioned medium of HPD-NR cells stimulated the growth of HUVEC, and four hamster angiogenic factors were detected with an overexpression of transforming growth factor alpha and vascular endothelial growth factor messenger RNAs. AGM-1470 specifically inhibited the growth of HUVEC and that of HPD-NR tumors in vivo with decreased vascularity of the tumors but not the growth of HPD-NR cells in vitro. CONCLUSIONS: The results suggest that angiogenesis plays an important role in tumor growth of HPD-NR cells and can be a new target of medical therapy for pancreatic cancer.

Animals↗

PubMed1995

Effects of lansoprazole with or without amoxicillin on ulcer healing: relation to eradication of Helicobacter pylori.

We studied the effects of lansoprazole with or without amoxicillin on the quality of ulcer healing in relation to eradication of Helicobacter pylori. Ulcer healing rates for lansoprazole 30 mg q.d. alone (group A) were 100% for duodenal ulcers (DU; n = 20) and 92% for gastric ulcers (GU; n = 15). The healing rates for lansoprazole 30 mg plus amoxicillin 1-2 g q.d. (group B) were 100% for both DU (n = 20) and GU (n = 12). Endoscopic findings after treatment showed that the red scar/white scar ratio in group A was 16/4 for DU and 12/1 for GU. The red scar/white scar ratio in group B was 4/16 for DU and 6/6 for GU. The numbers of H. pylori in gastric mucus did not change throughout the course of treatment in group A but decreased significantly, without H. pylori relapse, in group B. Changes in ammonia concentration in gastric juice, as well as serum gastrin and pepsinogen I and II levels, differed between group A and group B. Concomitant treatment with lansoprazole and high-dose amoxicillin eradicated H. pylori and modified gastric secretory function, resulting in high-quality ulcer healing.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1995

A novel somatic point mutation of the RET Proto-oncogene in tumor tissues of small cell lung cancer patients.

We examined whether the novel point mutation from GCC (Ala) to GAC (Asp) at codon 664 in exon 11 of RET proto-oncogene, which we had found in two small cell lung carcinoma (SCLC) cell lines, existed in genomic DNA of tumor tissues of the two SCLC patients from whom these SCLC cell lines were derived. Sequence analysis revealed that point mutation identical to that of the SCLC cell lines was present in amplified alleles of single-strand conformational variants in genomic DNA of the tumor tissues, whereas it was not detected in genomic DNA of non-tumor tissues of the patients. These results indicate that this mutation had initially occurred in the SCLC patients and was of somatic origin.

ACTH Syndrome, Ectopic↗

PubMed1995

FUS/TLS-CHOP chimeric transcripts in liposarcoma tissues.

Myxoid liposarcoma and malignant fibrous histiocytoma (MFH) are common soft tissue sarcomas of adulthood. Histopathologically they often show intratumor heterogeneity. In some cases, differential diagnosis of liposarcoma and MFH is difficult. It has been reported that myxoid liposarcomas are characterized by chromosomal translocation t (12; 16) (q13; p11), and that this results in two types (type I and type II) of FUS/TLS-CHOP fusion transcripts. In this study, the FUS/TLS-CHOP chimeric transcripts in seven malignant soft tissue tumors of Asian patients were analyzed by reverse transcription-polymerase chain reaction, DNA blot hybridization and nucleotide sequencing. One myxoid liposarcoma and two round cell liposarcomas possessed a chimeric transcript whose fusion point was the same as that of the type I fusion transcript reported previously for myxoid liposarcoma. We were thus able to detect the type I FUS/TLS-CHOP fusion transcript in clinical specimens of liposarcoma from Asian patients, including the first examples of round cell liposarcoma. These results suggest that the detection of FUS/TLS-CHOP chimeric transcripts or chimeric genes can be used as a diagnostic tool for the pathological diagnosis of liposarcomas.

Adult↗

PubMed1992

Prevention of acute chemotherapy-induced death in mice by recombinant human interleukin 1: protection from hematological and nonhematological toxicities.

Previous studies have demonstrated that interleukin 1 (IL-1) can protect most mice from the acute lethal toxicity mediated by high doses of radiation and/or some chemotherapeutic drugs. The results presented herein demonstrate that the pretreatment of mice with recombinant human interleukin 1 alpha (rhIL-1 alpha) protects mice from the lethal effects of several myelotoxic chemotherapeutic drugs, including 5-fluorouracil (5FUra), cyclophosphamide, cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II), and 1,3-bis-(2-chloroethyl)-1-nitrosourea. However, pretreatment with rhIL-1 alpha was not effective against the acute lethal toxicity generated by doxorubicin and cisplatin. The chemoprotective effects appear to be at least partially due to myeloprotection/restoration, since the recovery of myeloid colony-forming units and the total cellularity in the bone marrow and spleen were accelerated in the rhIL-1 alpha-pretreated mice. However, the chemoprotective effects of rhIL-1 alpha are apparently not limited to myeloprotection, since pretreatment with rhIL-1 alpha protects mice against the lethal toxicity of both 5FUra and cyclophosphamide, yet bone marrow transplants rescue mice treated with 5FUra but not those treated with cyclophosphamide. The chemoprotective effects of rhIL-1 alpha may be at least partially indirect, since the efficacy of chemoprotection by rhIL-1 alpha is reduced in athymic mice, and interleukin 6, but not tumor necrosis factor alpha, can substitute for rhIL-1 alpha in chemoprotection from 5FUra.

Animals↗

PubMed1992

Cytokine induction and therapeutic synergy with interleukin-2 against murine renal and colon cancers by xanthenone-4-acetic acid derivatives.

Derivatives of xanthenone-4-acetic acid (XAA) have been found to have similar activity to flavone-8-acetic acid against transplantable solid tumors. Some of these compounds were compared to flavone acetic acid (FAA) in their ability to induce cytokines as well as to mediate antitumor effects against murine renal cancer (Renca) and a mouse colon cancer (MCA-38). 5-Methyl-XAA and 5-chloro-XAA proved to be more potent than FAA on a mg/kg basis for induction of the genes for IFN alpha, IFN gamma, and TNF alpha, and for IFN and TNF activities in the sera of treated mice. These effects were sharply dose dependent. On the other hand, 7-methyl-XAA, which has no antitumor activity, did not induce these genes. In addition, 5-methyl-XAA and 5-chloro-XAA but not 7-methyl-XAA synergized with recombinant human interleukin-2 (rhIL-2) for the treatment of Renca and MCA-38. Doses of the active derivatives that failed to induce cytokines also exhibited no therapeutic synergy with rhIL-2. These results suggest that at least some of the antitumor effects of these XAA derivatives are related to their ability to induce cytokines.

Animals↗

PubMed1991

Flavone acetic acid directly induces expression of cytokine genes in mouse splenic leukocytes but not in human peripheral blood leukocytes.

Flavone-8-acetic acid (FAA) is a flavonoid drug that augments mouse natural killer activity, induces cytokine gene expression, and synergizes with recombinant interleukin 2 for the treatment of murine renal cancer. However, FAA has been largely inactive in human clinical trials. In the present study we investigated the ability of FAA treatment to directly induce cytokine mRNA expression in total mouse splenic leukocytes and selected leukocyte subsets, as well as in total human peripheral blood leukocytes. Analysis of RNA isolated from FAA-treated mouse splenic leukocytes demonstrated that treatment with greater than or equal to 100 micrograms/ml of FAA induced expression of tumor necrosis factor alpha (TNF-alpha) mRNA by 1 h and induced maximal expression of TNF-alpha, alpha-interferon, and gamma-interferon mRNA within 3 h. The expression of all cytokine genes was diminished by 6 h. Interferon biological activity was detected in the supernatants of mouse splenic or peripheral blood leukocytes after treatment with FAA. These results correlate well with the previously reported induction of cytokine mRNA genes and biological activity by FAA in vivo. In contrast, FAA did not induce detectable mRNA expression or cytokine protein secretion by human peripheral blood leukocytes under similar conditions. These results demonstrate that FAA can directly stimulate cytokine gene expression in mouse but not in human leukocytes. Further studies performed with highly purified positively selected mouse CD4+ or CD8+ splenic T-lymphocytes, as well as purified B-cells, demonstrated that the FAA-induced expression of gamma-interferon mRNA was mainly induced in the CD8+ lymphocyte subset. alpha-Interferon mRNA was expressed largely in the B-cell population, while TNF-alpha mRNA was induced in all leukocyte subsets tested. Therefore, these results suggest that the immunomodulatory effects of FAA in mice are direct, but different cytokines are induced from different leukocyte subsets. Further, the data suggest that flavonoid compounds or analogues that stimulate cytokine gene expression in human cells might be therapeutically active in cancer patients.

Animals↗

PubMed1991

Effects of recombinant transforming growth factor-beta 1 on hematologic recovery after treatment of mice with 5-fluorouracil.

Transforming growth factor beta 1 (TGF-beta 1) has been shown to inhibit bone marrow colony formation after in vitro treatment as well as after in vivo administration to normal mice. These data suggest that TGF-beta might either protect, or further depress, progenitor cell levels in mice exposed to a cell cycle-active drug such as 5-fluorouracil (5FU). rTGF-beta 1 was administered repeatedly by either the i.v. or i.p. routes to mice during the hyperproliferative state of the bone marrow that occurs 7 to 9 days after the i.v. administration of 150 mg/kg 5FU. The formation of both multilineage and the more differentiated (CFU-c) colonies was inhibited by 20 to 40%/culture, and 66 to 93%/mouse. When multiple doses of rTGF-beta 1 were administered systemically immediately before the injection of 5FU, the resulting rebound in the number of CFU-c and multilineage colonies containing granulocyte, erythroid, megakaryocyte, and macrophage lineage colonies per culture was markedly inhibited by 30 to 77%, whereas the total number of CFU per mouse was inhibited up to 93%. This effect was maximal when rTGF-beta 1 was administered at daily doses of greater than or equal to 5 micrograms/mouse for at least 3 days. This inhibition of the recovery of the bone marrow from 5FU treatment induced by rTGF-beta 1 was a delayed transient response because by day 16 the progenitor cell numbers and bone marrow cellularity were identical to the 5FU-treated marrow controls.

Animals↗

PubMed1991

In vivo distribution and cytokine gene expression by enriched mouse LAK effector cells.

Lymphokine activated killer (LAK) cells administered in combination with interleukin 2 (IL2) can mediate antitumor activity in tumor-bearing mice and advanced cancer patients. Relatively little is known about the mechanism by which adoptively transferred LAK cells plus IL2 mediate these antitumor effects in vivo, and it remains unclear to what extent the actual LAK effector cells can accumulate in tumors. In the present study, enriched cytolytic LAK effector cells were obtained by fractionation of bulk LAK cell cultures on Percoll density gradients. About 95% of the total lytic activity was recovered from the 55% of cells isolated in fraction 2 (Fr2). The cells recovered in Fr2 are mostly large, proliferating lymphoblasts that express either the NK-associated surface markers NK1.1 (38%) or LGL-1 (31%), or the cytotoxic T cell phenotype, Lyt2 (39%). The cytolytic lymphoblasts obtained from Fr2 were radiolabelled with either 111Indium-Oxine (111InOx) which labels all cells in the population, or with 125Iododeoxyuridine (125IUdR) which labels only proliferating cells, and injected iv into mice bearing murine renal cancer (Renca). 111InOx-labeled Fr2 cells migrated mostly to spleen (28%) and liver (35%), with approximately 5% of the injected label detectable in the Renca-bearing kidney by 24 hrs. In contrast, Fr2 cells labeled with 125IUdR, which labels only the proliferating blasts thought to include the actual effector cells, exhibited a very different localization pattern. 125IUdR-Fr2 cells were retained in the lungs at higher levels than were 111InOx-Fr2 cells and very little label was detectable in liver (6%), spleen (3%), or tumor bearing kidney (2%) at 24 hrs. These results suggest that most of the large, proliferating lymphoblasts are cleared from the body by 24 hrs and very few localize into even large tumors. Subsequently, Northern blot analyses performed on bulk LAK cells revealed a potent induction of mRNA for TNF alpha by 6 hrs and for IFN gamma by 48 hrs. The intensity of gene expression for both cytokines was increased in Fr2 as compared to the unfractionated bulk LAK cells or to non-cytolytic cells obtained from Fr3. Overall, these results suggest that at least some of the antitumor effects mediated by LAK cells occur by the release of cytokines that synergize with exogenous IL2 for the activation of host effector cells.

Animals↗

PubMed1991

[Adriamycin, cisplatin and etoposide combination chemotherapy in non-small cell lung cancer].

Nineteen patients with non-small cell lung cancer (eight patients with adenocarcinoma, nine patients with squamous cell carcinoma, one patient with large cell carcinoma and one patient with sarcoma) who had not received previous chemotherapy were treated with a combination of adriamycin (30 mg/m2, i.v., on day 1), cisplatin (80 mg/m2, i.v., on day 1) and etoposide (70 mg/m2, i.v., on day 1-5). This chemotherapy regimen was repeated as long as possible for patients in whom PR was induced. Among all patients, CR was induced in none and 6 showed a PR (response rate 32%). However, 4 (56%) squamous cell carcinoma patients also showed PR. The median response duration in 6 PR patients was 28 weeks, and the median survival time in all patients was also 28 weeks. Mild to severe hematologic toxicities were induced and one patient died during myelosuppression. However almost all cases were reversible. Other toxicities included alopecia, nausea/vomiting, diarrhea, stomatitis, peripheral neuropathy and myocardial infarction which were reversible and manageable. The APVp therapy may be a valuable regimen for non-small cell lung cancer, especially squamous cell carcinoma.

Adult↗

PubMed1991

[A case of second-degree atrioventricular block caused by high dose cisplatin treatment].

A 56-year-old man was admitted to our hospital because of stage IV squamous cell carcinoma of the lung. He was treated with two courses of high dose cisplatin (40 mg/m2/day, day 1-5). On day 4 of each course, a second-degree atrioventricular block was observed, which disappeared after cisplatin treatment. This case suggests that, although the cardiotoxicity caused by cisplatin is believed to be rare, one should take special care in high dose usage.

Carcinoma, Squamous Cell↗

PubMed1990

Systemic alkalinization inhibits the ability of flavone acetic acid to augment natural killer activity, induce cytokine gene expression, and synergize with interleukin 2 for the treatment of murine renal cancer.

Flavone acetic acid (FAA) is an investigational drug that augments natural killer activity, induces the genes for alpha- and gamma-interferon (IFN) and tumor necrosis factor alpha, and synergizes with recombinant interleukin 2 for the successful treatment of murine renal cancer. However, in most clinical studies of FAA only minimal immunomodulatory effects have been reported. Most of the patients in these studies have also been given sodium bicarbonate to prevent possible nephrotoxicity. The current study was performed to determine whether alkalinization had any effects on FAA-induced immune modulation and therapeutic activity in mice. The results showed that alkalinization inhibited the treatment of murine renal cancer by FAA plus recombinant interleukin 2 such that the survival rate of 84% in nonalkalinized mice was reduced to 0 in mice that were alkalinized during treatment. Alkalinization also significantly inhibited the ability of FAA to augment both splenic and hepatic natural killer activity in a dose-dependent manner. In contrast, alkalinization did not inhibit the ability of polyinosinic:polycytidylic acid and poly-L-lysine stabilized in carboxymethyl cellulose, maleic anhydride divinyl ether, or Propionibacterium acnes to augment liver-associated natural killer activity. By Northern blot analysis, it was shown that the induction of mRNA for IFN-alpha, IFN-gamma, and tumor necrosis factor alpha by FAA in the spleen cells of mice was significantly reduced in alkalinized mice. Consistent with a reduction in the FAA-induced expression of the cytokine genes, alkalinization also resulted in a significant decrease in both the peak serum concentration and duration of detectable IFN activity following FAA treatment. Increasing the dose of FAA in alkalinized mice to 300 mg/kg overcame the deleterious effects of alkalinization for treatment of murine renal cancer by FAA plus recombinant interleukin 2. These results demonstrate that the process of alkalinization inhibits the immunomodulatory and immunotherapeutic effects of FAA in mice and suggest that alkalinization might have similar deleterious effects on FAA-induced immune stimulation in human clinical trials.

Adenocarcinoma↗

PubMed1990

Chemoprotective effects of recombinant human IL-1 alpha in cyclophosphamide-treated normal and tumor-bearing mice. Protection from acute toxicity, hematologic effects, development of late mortality, and enhanced therapeutic efficacy.

In this study, recombinant human IL-1 alpha (rhIL-1 alpha) was used to protect normal and tumor-bearing BALB/c mice from the acute toxicity caused by lethal doses of cyclophosphamide (Cy) and 5-fluorouracil. Pretreatment of mice for 7 days with 10,000 U/day of rhIL-1 alpha protected 70 to 100% of mice from the acute death induced by lethal doses of both Cy (380 mg/kg) and 5-fluorouracil (250 mg/kg). In contrast, post-treatment of mice with single or multiple doses of rhIL-1 alpha was not chemoprotective. Pretreatment of mice with rhIL-1 alpha increased the acute LD90 of Cy from 380 mg/kg to greater than 500 mg/kg in normal mice, an LD90 dose-modifying effect of at least 1.25, was accompanied by a more rapid recovery from neutropenia and a less severe reduction in the number of bone marrow single lineage monocyte, myeloid, or myelomonocytic colonies. Some of the mice (10 to 50%) that were successfully protected by pretreatment with rhIL-1 alpha died after day 50. These mice consistently presented with extensive pulmonary inflammation and fibrosis at death. Mice bearing murine renal cancer (Renca) were also protected from the acute toxic effects of Cy (450 mg/kg) by pretreatment with rhIL-1 alpha. Renca-bearing mice pretreated with rhIL-1 alpha and either sublethal (300 mg/kg) or lethal (450 mg/kg) doses of Cy exhibited enhanced survival times over those of untreated Renca-bearing mice. Interestingly, the cause of death in Renca-bearing mice that ultimately failed treatment with rhIL-1 alpha plus 300 mg/kg Cy was recurrent tumor, whereas most mice treated with rhIL-1 alpha plus 450 mg/kg Cy had no detectable tumor, although several died from late pulmonary inflammation and fibrosis. Thus, the dose escalation of Cy in rhIL-1 alpha-pretreated mice results in greater antitumor effects of Cy. However, the dose escalation of some cytotoxic agents allowed by the use of myelostimulatory agents can result in late fatal complications not detected in acute toxicity testing.

Animals↗