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Biomedical subjects

Y Ariyoshi

Publications and source records attributed to Y Ariyoshi.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Recent advances of supportive therapy for cancer patients].

Over 25 years ago survival was the sole aim in the management of cancer patients. However, over the past 25 years quality of life (QOL) as well as survival has become increasingly important in the treatment of cancer. In other words, treatment modalities without good QOL are no longer accepted. Thus, supportive therapies for cancer patients are very important. These supportive therapies fall into two categories. One is the management of adverse events induced by cancer therapies such as surgery, radiotherapy or chemotherapy. Adverse events induced by the administration of anti-cancer drugs in particular must be managed to maintain QOL. The second category is the management of pain, cachexia, metabolic disorders or mental depression induced by the existence of cancer. Over these 25 years major advances have been observed in the supportive therapy for cancer patients. These include the development of colony-stimulating factor (CSF) agents and the anti emetic agents such as serotonin-receptor inhibitors. These two agents have contributed to the relief of drug-induced adverse events. Opioids have been frequently used to relieve cancer pain. Hypercalcemia accompanying cancer are very easily treated with bisphosphonate agents. In the present paper, the advances in supportive therapy for cancer patients that have been made during these 25 years will be reviewed.

Antiemetics↗
PubMed1999

[CA125].

Explore the source record for details and available documents.

Adult↗
PubMed1998

Clinical implications of p53 autoantibodies in the sera of patients with non-small-cell lung cancer.

BACKGROUND: The presence of autoantibodies to p53 protein has been associated with the presence of p53 (also known as TP53) gene mutations in primary tumors and with poor prognosis. This study was undertaken to determine the clinical significance of p53 autoantibodies in patients with non-small-cell lung cancer (NSCLC). METHODS: We studied 188 consecutive patients with NSCLC who underwent pulmonary resection and for whom preoperative serum was available. The presence of p53 autoantibodies, detected by use of two amino-terminal and two carboxy-terminal peptides (20-30 mers) as antigens and an enzyme-linked immunosorbent assay, was related to various clinicopathologic parameters and to overexpression of p53 protein in the primary tumor. For 22 patients who had p53 autoantibodies before surgery, we also examined sera taken during postoperative follow-up. Reported P values are two-sided. RESULTS: Autoantibodies to p53 protein were detected in 38 patients. Patients with squamous cell carcinoma, those with more advanced disease (stage III-IV), and those with tumors that overexpressed p53 had a significantly higher incidence of p53 autoantibodies (P = .05,.0079, and .02, respectively). In all but one of the patients with postoperative serum samples, the antibody titer declined after surgery; however, there was no relationship between clinical course and this change in antibody titer. In addition, there was no relationship between the presence of p53 autoantibodies and overall survival in 171 patients who underwent potentially curative resection (P = .28); however, 13 patients with autoantibodies to amino-terminal peptides had a worse overall survival (P = .02). CONCLUSIONS: In NSCLC, the incidence of p53 autoantibodies is associated with histologic type, stage, and p53 overexpression--but not with patient survival. Our data do not support the clinical utility of p53 autoantibodies as diagnostic or prognostic markers in patients with NSCLC.

Adult↗
PubMed1998

Chemical synthesis and characterization of the sweet protein mabinlin II.

The sweet protein mabinlin II isolated from the seeds of Capparis masaikai consists of the A chain with 33 amino acid residues and the B chain composed of 72 residues. The B chain contains two intramolecular disulfide bonds and is connected to the A chain through two intermolecular disulfide bridges. The A chain was synthesized by the stepwise fluoren-9-ylmethoxycarbonyl (Fmoc) solid-phase method in a yield of 5.9%, while the B chain was synthesized by a combination of the stepwise Fmoc solid-phase method and fragment condensation in a yield of 6.0%. Disulfide formation and combination of the A and B chains followed by purification by ion-exchange high-performance liquid chromatography (HPLC) gave mabinlin II in a yield of 47.4%. The characterization of the synthetic mabinlin II by HPLC, electrospray ionization mass spectrometry, amino acid analysis, and disulfide bond determination fully supported the expected structure. A 0.1% solution of the synthetic mabinlin II had an astringent-sweet taste.

Amino Acid Sequence↗
PubMed1998

Structure of an enantiomeric protein, D-monellin at 1.8 A resolution.

The D-enantiomer of a potently sweet protein, monellin, has been crystallized and analyzed by X-ray crystallography at 1.8 A resolut ion. Two crystal forms (I and II) appeared under crystallization conditions similar, but not identical, to the crystallization conditions of natural L-monellin. There are four molecules per asymmetric unit in crystal form I and one in crystal form II. Crystal form I is not reproducible and is equivalent to that of monoclinic L-monellin. Intermonomer contacts in crystal form II are very different from those found in natural L-monellin crystals. The backbone trace of D-monellin resembles very closely the mirror image of that of L-monellin, but the N- and C-terminus backbones as well as several side-chain conformations of D-monellin are different from those of natural L-monellin. Most of these apparent differences may be attributable to the crystal packing differences.

Crystallography, X-Ray↗
PubMed1998

Role of hydrophobic amino acids in gurmarin, a sweetness-suppressing polypeptide.

The sweetness-suppressing polypeptide gurmarin isolated from Gymnema sylvestre consists of 35 amino acid residues and contains three intramolecular disulfide bonds. Nuclear magnetic resonance analysis showed that the hydrophobic side chains of Tyr-13, Tyr-14, Trp-28, and Trp-29 in gurmarin are oriented outwardly. Together with the hydrophobic side chains of Leu-9, Ile-11, and Pro-12, they form a hydrophobic cluster, and therefore these hydrophobic groups are assumed to act as the site for interaction with the receptor protein. To examine the roles of these hydrophobic amino acids, they were replaced by Gly. The resulting [Gly13,14,28,29] gurmarin and [Gly9,11,13,14,28,29]-gurmarin did not suppress the responses to sucrose, glucose, fructose, or Gly. This result strongly suggests that these hydrophobic amino acids are involved in the interaction with the receptor protein.

Amino Acid Sequence↗
PubMed1998

Synthesis, characterization, and sweetness-suppressing activities of gurmarin analogues missing one disulfide bond.

The sweetness-suppressing polypeptide gurmarin isolated from Gymnema sylvestre consists of 35 amino acid residues and includes three intramolecular disulfide bonds. The roles of the three disulfide bonds were investigated by replacing each with two alanine residues by solid-phase synthesis. Nine analogues of [Ala3,18]gurmarin, [Ala10,23]gurmarin, and [Ala17,33]-gurmarin were obtained. Three analogues had native disulfide bonds, while the other six had non-native disulfide bonds. The three analogues with native disulfide bonds suppressed the response to sucrose, but not those to glucose, fructose, saccharin, or glycine in rats. In contrast, the six analogues with non-native disulfide bonds did not suppress the responses to any of these sweeteners. These results suggest that the native disulfide bonds of gurmarin are necessary for interaction with the receptor protein, and that the sucrose-specific receptor site is present in rats.

Amino Acid Sequence↗
PubMed1998

Determining whether a parotid tumor is in the superficial or deep lobe using magnetic resonance imaging.

PURPOSE: This study examined the usefulness of magnetic resonance imaging (MRI) in assessing whether parotid tumors were located in the superficial or deep lobe. PATIENTS AND METHODS: Eight patients with parotid gland tumors underwent MRI using a spin echo pulse sequence. T1- and T2-weighted images were obtained. To assess tumor localization in the parotid gland, two anatomic landmarks were used: 1) a line connecting the lateral surface of posterior belly of digastric muscle and lateral surface of the cortical bone of ascending ramus (facial nerve [FN] line) and 2) the relationship to the retromandibular vein (RV). Results of all MRI examinations were compared with the surgical findings. RESULTS: Seven of eight cases were correctly diagnosed using the FN line criterion. Five of eight cases were correctly diagnosed using the RV criterion. CONCLUSION: MRI is an excellent modality to show tumor localization in the parotid gland.

Adenocarcinoma↗
PubMed1998

Phase II study of irinotecan combined with cisplatin in patients with previously untreated small-cell lung cancer. West Japan Lung Cancer Group.

PURPOSE: Irinotecan (CPT-11) is effective against small-cell lung cancer (SCLC) as monotherapy. Cisplatin is also a key drug against SCLC. We conducted a phase II study of CPT-11 combined with cisplatin to evaluate the efficacy and toxicity of this regimen in patients with previously untreated SCLC. PATIENTS AND METHODS: Seventy-five patients with previously untreated SCLC were enrolled onto the study. CPT-11 60 mg/m2 was administered intravenously on days 1, 8, and 15 in combination with cisplatin 60 mg/m2 on day 1 every 28 days. Four courses of chemotherapy followed by thoracic irradiation were given to patients with limited disease (LD) and six courses to patients with extensive disease (ED). RESULTS: The overall response rate was 84%, with a complete response (CR) rate of 29%. Forty patients with LD achieved an overall response rate of 83% and a CR rate of 30% and 35 patients with ED achieved an overall response rate of 86% and a CR rate of 29%. The median response duration was 8.0 months for LD patients and 6.6 months for ED patients. The median survival was 14.3 months for LD patients and 13.0 months for ED patients. The major grade 3 or 4 toxicities were neutropenia (77%), leukopenia (45%), diarrhea (19%), and anemia (39%). Two patients died with concomitant neutropenia and diarrhea. CONCLUSION: This is a new active regimen for SCLC, especially ED-SCLC, with acceptable toxicity. A phase III study that compares CPT-11/cisplatin with etoposide/cisplatin for ED-SCLC is now being conducted.

Adult↗
PubMed1998

Phase III study of intensive weekly chemotherapy with recombinant human granulocyte colony-stimulating factor versus standard chemotherapy in extensive-disease small-cell lung cancer. The Japan Clinical Oncology Group.

PURPOSE: To evaluate the therapeutic significance of cisplatin, vincristine, doxorubicin, and etoposide (CODE) plus granulocyte colony-stimulating factor (G-CSF) compared with cyclophosphamide, doxorubicin, and vincristine, alternating with cisplatin and etoposide (CAV/PE) for extensive-disease (ED) small-cell lung cancer (SCLC). PATIENTS AND METHODS: Two hundred twenty-seven patients were randomized. CODE consisted of cisplatin 25 mg/m2 weekly for 9 weeks; vincristine 1 mg/m2 on weeks 1, 2, 4, and 6; and doxorubicin 40 mg/m2 and etoposide 80 mg/m2 for 3 days on weeks 1, 3, 5, 7, and 9. G-CSF 50 micrograms/m2 was administered on the days when chemotherapy was not administered. CAV/PE consisted of cyclophosphamide 800 mg/m2; doxorubicin 50 mg/m2; and vincristine 1.4 mg/m2 on day 1, which alternated every 3 weeks with cisplatin 80 mg/m2 on day 1 and etoposide 100 mg/m2 on days 1 to 3. RESULTS: Overall response rates were 77% for the CAV/PE arm and 84% for the CODE arm respectively (15% complete response in both arms). The median survival times were 10.9 months in the CAV/PE arm and 11.6 months in the CODE arm (P = .1034). The achieved dose-intensity for CODE was approximately twice that for CAV/PE for those drugs common to both arms. The incidence of leukopenia did not differ between the two arms, but anemia and thrombocytopenia had a significantly higher incidence in the CODE arm. Four treatment-related deaths from neutropenic fever occurred in the CODE arm. CONCLUSION: The CODE group had a similar median survival to the CAV/PE group. It does not appear that CODE is a useful approach to improve survival in ED SCLC.

Adult↗
PubMed1997

Structure and dynamic studies by NMR of the potent sweet protein monellin and a non-sweet analog. Evidence on the importance of residue AspB7 for sweet taste.

Monellin, an intensely sweet protein and a non-sweet analog in which the AspB7 in monellin has been replaced with AbuB7 were studied by NMR. The results of our investigations show that the 3-dimensional structure of these two proteins are very similar indicating that the lack of the beta-carboxyl group in the AbuB7 analog is responsible for the loss of sweet potency. Selectively labeled monellin was prepared by solid-phase peptide synthesis by incorporating 15N-labeled amino acids into 10 key positions including AspB7. The internal mobility of these 10 key residues in monellin was estimated by the method of model-free analyses and our NMR studies show that AspB7 is the most flexible of these 10 residues. The flexibility of the AspB7 side chain may be important for receptor binding.

Amino Acid Sequence↗
PubMed1997

Crystallization and preliminary X-ray analysis of D-monellin.

D-Monellin is a chemically synthesized protein composed of all D-amino acids. It has an amino-acid sequence identical to L-monellin, a natural protein with potent sweetness. Two crystal forms of D-monellin were obtained. Both crystals were grown under conditions similiar to those used to crystallize natural L-monellin. Crystal form I has similar, but not identical, cell parameters to natural L-monellin and diffracts to 2.7 A resolution. Crystal form II is very different and diffracts to 1.7 A resolution using synchrotron radiation.

Journal Article↗
PubMed1997

Intermittent hepatic arterial infusion of high-dose 5FU on a weekly schedule for liver metastases from colorectal cancer.

PURPOSE: We performed phase I and II studies to examine the usefulness of intermittent hepatic arterial infusion of high-dose 5-fluorouracid (5-FU) for patients with liver metastasis from colorectal cancer. METHODS: As the phase I study, 1000, 1250 and 1500 mg/m2 of 5-FU were administered over 5 h by hepatic arterial infusion on a weekly schedule to establish the recommended dose. Based on the results of the phase I study, the phase II study was performed to confirm the efficacy of the recommended dose thus obtained. RESULTS: In the phase I study, the dose-limiting factors of this therapy were gastrointestinal and central nervous system toxicities, and the recommended dose was judged to be 1000 mg/m2. In the phase II study, 1000 mg/m2 of 5-FU was administered over 5 h once a week on an outpatient basis, and this therapy was repeated as long as possible. The response rate was 78% (25/32), with an overall median survival time of 25.8 months (without extrahepatic lesions 25.9 months; with extrahepatic lesions 17.3 months). CONCLUSIONS: (1) Compared with conventional continuous infusion, the advantages of this therapy were that it caused no decrease in the patient's quality of life as a result of being permanently equipped with a pump and it thus enabled more cost-effective use of the pump, (2) The phase II study on 32 patients showed that this therapy caused no serious toxicities, with a response rate of 78% and a survival time of 25.8 months, which exceeded the results with conventional continuous infusion. If the reproducibility of these results is established in further studies involving multicenter collaboration, this therapy will be able to become the standard local chemotherapy for liver metastases from colorectal cancer. (3) Important problems remaining to be solved are improvement of the technical aspects and studies of combined use with systemic chemotherapy. Furthermore, to finally determine the position of this therapy in the treatment system for liver metastasis from colorectal cancer, it is necessary to conduct comparative trials versus systemic chemotherapy, using the survival time as the end-point.

Antimetabolites, Antineoplastic↗
PubMed1997

Lifestyle and anti-Helicobacter pylori immunoglobulin G antibody among outpatients.

Since eradication of Helicobacter pylori (H. pylori) is thought to be a preventive measure against stomach cancer, several studies have examined factors associated with the infection. This paper reports the association of the infection with lifestyle factors observed in a hospital-based case-control study. Cases were 140 anti-H. pylori IgG antibody-positive outpatients (75 males and 65 females). Controls were 52 antibody-negative outpatients (22 males and 30 females). Both groups had undergone gastroscopy at Aichi Cancer Center Hospital between February 1995 and February 1997, and lifestyle data collected on the first visit were linked to calculate odds ratios. A strong association was observed with smoking among males; age-adjusted odds ratio (OR) = 7.85, 95% confidence interval (CI), 2.03-30.4. Rice breakfast (OR = 3.74; 95% CI, 1.30-10.8) and soybean paste soup (every day vs. occasionally, OR = 5.24; 95% CI, 1.80-15.2) were also associated with antibody positivity in males, but not in females. In females, pickled Chinese cabbage (> or = 1/week vs. < or = 3/month, OR = 2.82; 95% CI, 1.06-7.48) and lettuce (> or = 1/week vs. < or = 3/month, OR = 2.90; 95% CI, 1.09-7.76) were significantly associated with positivity. Multivariate analysis gave similar estimates for the above factors. Although the association between smoking and H. pylori infection has not been detected in past studies of a general population, except one recent one, this study on outpatients suggested a possible association. Smoking may work as a cofactor disturbing incidental eradication of H. pylori by antibacterial agents administered for other reasons.

Adult↗
PubMed1997

[Clinical efficacy of GG032X tablets, a new dosage form of ondansetron (fast dispersing tablet), on cisplatin-induced nausea and emesis].

The inhibitory effects of GG032X tablets, a new dosage form (fast dispersing tablet) of ondansetron, 5-HT2 receptor antagonist, on nausea and emesis induced by cisplatin (CDDP), were investigated along with safety and usefulness. Subjects were chemotherapy patients starting CDDP administration for the first time, who were receiving a high single dose of CDDP (50 mg/m2 or more and intravenous drip infusion of less than 4 hours), or lower multiple doses of CDDP (a single dose of 10 mg/m2 or more, administered intravenously for 3-5 consecutive days). GG032X tablets were administered orally 1-2 hours before CDDP administration. In lower multiple doses of CDDP, GG032X tablets and CDDP were administered, as much as possible, at the same respective time when they were administered on the first day. Efficacy of GG032X tablets was evaluated in terms of inhibitory effect on nausea and emesis 24 hours after administration of a high single dose of CDDP, and of the inhibitory effect on nausea and emesis during the study period (3-5 days) in lower multiple doses of CDDP. Efficacy, safety and usefulness were evaluated in accordance with the evaluation criteria used in the clinical study of already-approved ondanstron tablets. In a high single dose of CDDP, the cases judged "effective" or better in the investigation of the inhibitory effect of the drug on nausea and emesis, accounted for 52.9% (63/119 cases). As for the overall safety rating, the cases judged as "safe" accounted for 87.0% (107/123 cases), and as a "minor safety problem" accounted for 13.0% (16/123 cases). As for the usefulness rating, the cases judged "useful" or better accounted for 52.1% (62/119 cases). Major adverse effects included headache, fever, atrial fibrillation and increases in total bilirubin, GOT and GPT values. None of these was serious, and the patients recovered without any treatment or by nosotropic therapy. Meanwhile, in lower multiple doses of CDDP, the inhibitory effect judged "effective" or better accounted for 70.6% (12/17 cases). As for the overall safety rating, all cases were judged "safe". In terms of usefulness, those cases judged "useful" or better accounted for 70.6% (12/17 cases). No adverse effect was observed. Study results of these two groups were almost the same as those for already-approved ondansetron tablets. According to the results of questionnaires for the patients who participated in the study and took GG032X tablets, the drug was found to be easy to take and had favorable results. Based on the above results, GG032X tablets were evaluated as having the same inhibitory effect as the already-approved ondansetron tablets against CDDP-induced nausea and emesis, and were considered safe and clinically useful.

Administration, Oral↗
PubMed1997

[Phase I study of S-1. S-1 Study Group].

We have conducted Phase I study of a novel oral antitumor agent of fluorinated pyrimidines, S-1, in which tegafur (FT) is combined with two classes of modulator, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) at a molar ratio of FT:CDHP:Oxo = 1:0.4:1 as a multi-center study with 16 institutions nationwide. Two administration methods, once and twice daily administrations, were evaluated. As a result, MAD was determined as 150 mg/body/day approximately 200 mg/body/day and 75 mg/body x2/day approximately 100 mg/body x2/day, respectively. DLF was myelosuppression, mainly consisting of leukopenia in the two administrations. Most adverse reactions observed, including myelosuppression, disappeared by discontinuation of administration, and recovery was in about 2 weeks. Adverse reactions other than myelosuppression which induced the discontinuation were rash and vomiting. Other adverse reactions observed were anorexia, malaise, diarrhea and stomatitis. Diarrhea and stomatitis were mild (Grade 1), except those observed at a dose of 200 mg/body/day, and did not induce discontinuation of administration. Based on these findings and pharmacokinetic evaluation, the recommended dose and administration for Early Phase II studies were determined as twice daily administration of 75 mg/body for 28 consecutive days with 14 days rest (1 course).

Administration, Oral↗