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H Furue

Publications and source records attributed to H Furue.

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

[Cancer of the liver, pancreas, gallbladder, and bile duct].

In cancer of the liver, pancreas, gallbladder, and bile duct, symptoms and signs are non-specific compared with benign conditions. Early detection is difficult and long term survivors are extremely low. The role of systemic chemotherapy in patients with these malignancies is only palliative. Prolongation of survival has not been demonstrated with any single agent or with any combination chemotherapy. However, in some instances, useful symptomatic palliation may occur even without an objective partial response. Quality of life is an important parallel endpoint in these malignancies. In advanced cancer of the liver, numerous alternative therapies have been investigated. These include pharmacologically based chemotherapeutic delivery methods, percutaneous alcohol injection, TAE, TACE, etc. However, further rigorous investigations will be warranted. It is hoped that successful chemotherapeutic agents or other modalities can be developed and combined with limited efficacy of surgery and radiotherapy. In this respect, newer, more active chemotherapy regimens are clearly needed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Capsaicin facilitates excitatory but not inhibitory synaptic transmission in substantia gelatinosa of the rat spinal cord.

Actions of capsaicin were examined on synaptic transmissions in the substantia gelatinosa (SG) of adult rat spinal cord slices using the whole-cell patch-recording technique. Bath-applied capsaicin at a concentration of 2 microM activated a slow inward current (having an amplitude of 33 pA at -70 mV), which was accompanied by an increase in the frequency of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs; by 234%); these actions were blocked by a capsaicin-receptor antagonist, capsazepine (10 microM). The capsaicin-induced increase in sEPSC frequency was resistant to tetrodotoxin (0.5-1 microM). On the other hand, capsaicin (2 microM) did not affect either glycine- or gamma-aminobutyric acid-mediated spontaneous synaptic transmission. The results indicate that capsaicin enhances excitatory but not inhibitory synaptic transmission, possibly through a direct action on primary afferent terminals in the SG. As the SG has been thought to participate in nociceptive pathway, it is suggested that such a presynaptic action of capsaicin contributes to nociceptive transmissions.

Animals↗
PubMed1998

A method for in-situ tight-seal recordings from single taste bud cells of mice.

In order to investigate taste transduction mechanisms, we developed a method to irrigate the receptor and basolateral membranes of mouse taste bud cells with different solutions under tight-seal recording conditions. A peeled tongue epithelium with taste bud cells was mounted on a recording platform designed to separate irrigating solutions for each membrane. The mucosal surface (receptor membrane side) of the peeled epithelium facing an inner chamber was always irrigated with deionized water or stimulating solutions, and the serosal surface (basolateral membrane side) was irrigated with a physiological saline solution. A recording electrode was placed on the basolateral membrane of a taste bud cell under an upright-microscope with a x 40-water-immersed objective. Investigated taste bud cells generated action potentials, and 1 M glucose, 200 mM NaCl, and 10 mM quinine elicited inward current. Irrigation with deionized water for more than 1 h had no effect. The resistance of the peeled tongue epithelium was 1570 +/- 343 omega cm2. These results show that the peeled tongue epithelium protects basolateral membranes from deionized water or stimulating solutions as the tongue epithelium does in situ and that this method is suitable to investigate the role of each membrane in taste transduction.

Action Potentials↗
PubMed1998

[Unknown primary cancer].

Unknown primary cancers (UPCs) are heterogeneous group of tumors with widely varying clinical features. Majority of patients with UPC do not respond to systemic therapy and show an unfavorable median survival duration. However, some subgroups are responsive to treatment. The definition of these subgroups is based on the organ sites involved at the time of presentation and/or on the histologic findings. These subgroups include patients with squamous cell carcinoma involving the high- or mid-cervical lymph node, female patients with adenocarcinoma involving the axillary lymph nodes, selected female patients with peritoneal carcinomatosis, patients with histology of poorly differentiated or undifferentiated carcinomas, and patients with poorly differentiated neuroendocrine carcinomas. Identification of these specific patients who may have clinical and pathological features of highly treatable unknown primary carcinoma is required. However, for most responsive UPCs, the tumor origin, biology and precise lineage are not yet fully clarified. On the other hand, a large group of patients with insensitive tumor remains. Research into the molecular characterization of UPC cells will improve our understanding of metastases from UPC and will resolve eventually this important clinical problem.

Adenocarcinoma↗
PubMed1998

[Phase I study of orally administered UFT plus l-leucovorin].

A Phase I study of UFT plus l-LV was conducted in 29 patients (pts) with G.I. cancer on a multicenter cooperative study. UFT and l-LV were given orally in two divided doses for 28 consecutive days, followed by a 14 day-rest period. UFT was fixed in three doses, 250, 313 and 375 mg/m2/day, and l-LV was increased in dose from 25 to 50 and to 100 mg/body/days. Dose-limiting toxicities were anorexia, diarrhea, and nausea/vomiting. The maximum tolerated dose of UFT was 375 mg/m2/day, and l-LV 25 mg/body/day. Severe myelotoxicity was not observed. There were three responders (PR) out of 21 pts with measurable disease at UFT doses of 313 mg/m2/day and l-LV 50 and 100 mg/body/day. Responses observed were abdominal mass (rectal ca), liver metastasis (pancreas ca) and metastasis of liver and lymph-node (gastric ca). As a result of pharmacokinetics, plasma concentrations of 5-methyl-THF were maintained > 1.0 microM for over 5 hours that was considered to have a modulating effect on the plasma concentration. In doses of 50 mg and 100 mg/body/day of l-LV. No accumulations in plasma were observed in patient treated in 28 days by l-LV/UFT therapy. It was suggested UFT and l-LV did not interfere with each other's absorption. A Phase II study is recommended, with doses of 313 mg/m2/day of UFT and 50 or 100 mg/body/day of l-LV.

Administration, Oral↗
PubMed1998

[Phase I clinical study of oxaliplatin].

Oxaliplatin is a new platinum derivative. A multicentric phase I study was conducted with a monotherapy of Oxaliplatin. A total of 20 patients were enrolled who had histologically proven 6 ovarian cancers, 5 uterine cervix cancers, 3 lung cancers, 3 breast cancers, 1 endometrial cancer, 1 gastric cancer, and 1 colorectal cancer. Oxaliplatin was administered as a 2-hour infusion at doses of 20, 40, 80, 130, and 180 mg/m2 every 3 weeks, for a total of 30 cycles. A dose-related and reversible peripheral sensory neuropathy was the dose-limiting toxicity with minimal hematotoxicity and no nephrotoxicity. No hydration was needed. The plasma platinum concentration was biphasically decreased. Cmax and AUC were dose-dependent. T1/2 beta was 31.3 hours. The recommended dose for further studies was 130 mg/m2. A partial response was observed in endometrial cancer.

Adult↗
PubMed1998

[Phase I study of raltitrexed (ZD-1694)].

A multicenter cooperative phase I study of ZD-1694 (raltitrexed), a novel, folate-based thymidylate synthase (TS) inhibitor, was conducted with single and repeated doses in 30 patients with various malignant tumors. ZD-1694 was intravenously infused over 15 minutes. In the single-dose study, the initial dose was fixed at 1.0 mg/m2 (1n), and the dose was escalated stepwise up to 3.5 mg/m2 (3.5 n). Based on the results of the single-dose study, in the repeated-dose study, doses of 2.5 n and 3 n were infused every three weeks (3 weeks/one course). In principle, patients received 2 courses or more. Of the 29 eligible patients, 16 were in the single-dose study and 13 in the repeated-dose study. Adverse reactions were evaluated in all eligible patients. In the single-dose study, neutropenia, nausea/vomiting, diarrhea, and transaminase (GOT, GPT) increases, of grade 3 or higher, occurred at high doses of 3 n and 3.5 n. These were regarded as dose-limiting toxicities (DLT). DLT of grade 3 or higher were observed in 1 of 4 patients given 3 n and 2 of 4 patients given 3.5 n. These results suggested that the maximum tolerated dose (MTD) of ZD-1694 was 3.5 n (3.5 mg/m2). In the repeated-dose study, DLT of grade 3 or higher was observed in no more than one third of each dose group, 2 of the 6 patients given 2.5 n and 2 of the 7 patients given 3 n. These results suggested that 3 n (3.0 mg/m2), a dose nearer to MTD, was the recommended dose for the phase II study. Although transaminase increases were observed in all patients, in 12 of them the increase was grade 2 or lower and reversible. A pharmacokinetic investigation showed the mean elimination half life of ZD-1694 plasma concentration was 91.5 hours in the single-dose group and 119.1 hours in the repeated dose group. It was suggested that ZD-1694 is metabolized to polyglutamates after uptake and retained in the cells for a long duration. However, no accumulation was seen in plasma concentration of ZD-1694 following repeated doses at 3-weekly intervals. One PR was observed in a patient with colorectal cancer receiving 2.5 n in the repeated-dose study. Based on these results, the recommended dosage and administration for the phase II study of ZD-1694 was 3 n (3.0 mg/m2) intravenously infused over 15 minutes every 3 weeks.

Adult↗
PubMed1997

In situ tight-seal recordings of taste substance-elicited action currents and voltage-gated Ba currents from single taste bud cells in the peeled epithelium of mouse tongue.

We investigated the taste responses of single taste-bud cells (TBCs) in mice by applying stimuli only on receptor membranes acclimated to deionized water under tight-seal cell-attached voltage-clamp conditions, while their basolateral membranes were irrigated with a physiological saline solution. For this irrigation, we developed a new method: a peeled-tongue epithelium with TBCs mounted on a recording chamber where the peeled epithelium separated the irrigating solutions for each membrane as it separated in situ. Although no quinine-elicited action potentials had been reported, TBCs elicited a long-lasting train of biphasic currents derived from the action potentials in response to 10 mM quinine, in addition to responses to 10 mM HCl, or 200 mM NaCl dissolved in deionized water. These results indicate that quinine as well as HCl and NaCl depolarizes TBCs and generate action potentials. Under whole-cell recording conditions, TBCs generated action potentials, and voltage-gated currents such as LVA and HVA Ca currents, TTX-sensitive Na currents, and TEA/4-AP-sensitive K currents on depolarization. These voltage-gated channels were shown to exist predominantly on the basolateral membranes. We discussed the receptor mechanisms and the role of taste substance-elicited action potentials.

Action Potentials↗
PubMed1997

[Bropirimine (U-54461S) early phase II clinical studies--to investigate the efficacy and safety of bropirimine treatment on various malignant tumors (urological, hematologic, and dermal cancers)].

Early Phase II clinical studies with bropirimine (U-54461S) having interferon (IFN) inducing and direct antiproliferative activities were conducted in patients with various solid tumors or hematologic neoplasm at 34 institutions nationwide. To investigate the safety and efficacy of the treatment, bropirimine was orally administered to the patients at the dose of 1g every two hours, three times a day for three consecutive days with a four day drug-free interval. Among the 65 patients registered, 60 patients were eligible and 44 patients completed bropirimine treatment in accordance with the respective protocols. Complete response (CR) was observed in 7 cases, and partial response (PR) was observed in 4 cases, so the efficacy rate was 25.0% (7 CRs + 4 PRs/44). Classified by target tumors, the efficacy rates were 12.9% (6 CRs/14) in bladder CIS, 33.3% 1 CR/3) in superficial bladder cancer. 11.1% 1 PR/9) in renal cell carcinoma, and 42.9% (3 PRs/7) in malignant lymphoma, respectively. Adverse drug reactions frequently observed were influenza-like symptoms such as fever (60.0%) and generalized malaise (21.7%), gastrointestinal symptoms like anorexia (56.7%) and nausea/vomiting (43.3%), and adverse effects on the circulatory system such as tachycardia (15.0%) and abnormalities in ECG (11.7%). Most of these symptoms were relieved or improved. Abnormalities in laboratory tests observed frequently were adverse effects on the liver such as elevations in GPT (33.3%), in GOT (31.7%), and in LDH (18.3%) or on the blood system like a decrease in RBC (18.3%), leukopenia (26.7%), or neutropenia (25.0%). In conclusion, bropirimine treatment proved to be effective for bladder CIS in particular, suggesting that it will be promising for use in the treatment of the disease.

Adult↗
PubMed1997

[Oncologic emergencies].

Many complications are frequently associated in patients with cancer which require immediate treatment. Oncologic emergencies are widely varying, which include superior vena cava syndrome, intracranial hypertension, spinal cord compression, metabolic emergencies, surgical emergencies, urologic emergencies, etc. In the treatment of these emergencies, the decision is most difficult because the usual responses and criteria for decision making are altered, and specific expertise is necessary. In patient with cancer, a situation in which complex problems are frequent, and the use of more sophisticated studies may be critical in defining and following acute, emergent problems. Furthermore, poor host "reserve" may make earlier decision-making essential, even though apparent risks are greater and diagnosis may be less certain. In this review, pathogenesis, manifestation, diagnosis, and treatment of principal oncologic emergencies (hypercalcemia, hyponatremia, tumor hypoglycemia, DIC, and cardiac tamponade) were evaluated from the view point of medical oncology.

Cardiac Tamponade↗
PubMed1997

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

1. The clinical efficacy and safety of the 2 mg granisetron tablet were assessed in 32 mainly lung cancer patients who were to receive treatment with anticancer drugs including CDDP. 2. One 2 mg granisetron tablet was administered prophylactically one hour before the start of CDDP administration. 3. Based on the development of nausea and vomiting in 24 hours after the start of CDDP administration, the study medication was judged to be "remarkably effective" or "effective" in 71.0% (22/31) of cases. 4. The study medication was judged to be "safe" in 96.9% (31/32) of cases, without causing any adverse reactions. 5. The above results indicate that the 2 mg granisetron tablet is safe and useful.

Adult↗
PubMed1997

[TUT-7 phase I clinical study. TUT-7 Study Group].

A phase I study with TUT-7, a new anthracycline antitumor antibiotic, was conducted in 35 malignant tumor patients at 11 institutions nationwide. The study was initiated with a single dose at 100 mg/body which was equivalent to 2n, then the dose as escalated up to 700 mg/body in accordance with the modified Fibonacci's scheme. The dose limiting factor (DLF) was considered to be leukopenia, and maximum tolerated dose (MTD) was 700 mg/ body. The consecutive days dosing study subsequently conducted started with 25 mg/body/day, and the dose level was escalated up to 150 mg /body/day. TUT-7 was orally administered for seven (7) to fourteen (14) consecutive days in principle. It was considered that DLF was leukopenia and MTD was 100 mg/body/day for consecutive days dosing. The study indicated that serum drug concentrations reached their plateaus on the 5th day after initiation of TUT-7 treatment and the accumulation of this compound was low. With these findings, a regimen with a dose of 100 mg/body/day orally administered for 14 consecutive days was recommended for early phase II studies.

Administration, Oral↗
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

[TUT-7 early phase II clinical study for various solid tumors and hematologic malignancies].

An early Phase II study with TUT-7 (menogaril), a new anthracycline antitumor antibiotic, was conducted in patients with various malignant tumors at 81 departments of 65 institutions nationwide. One course of TUT-7 treatment consisted of seven (7) or fourteen (14) consecutive days of administration at 75 or 100 mg/body/day with two-week drug withdrawal; at least two courses of treatment were given in principle. Among the 165 patients registered, 145 patients were eligible and 128 patients were evaluable for antitumor efficacy. In 11 patients with malignant lymphoma, one (1) had CR and five (5) had PR (54.5%); in three (3) patients with prostate cancer, one (1) had PR (33.3%); and in 12 patients with uterine cervical cancer, two (2) had PR (16.7%). Adverse drug reactions frequently observed were digestive organ disorders (anorexia and nausea/vomiting) and malaise. The abnormality in laboratory tests observed frequently was myelosuppression (leukopenia and neutropenia).

Adult↗
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↗
PubMed1996

Feasibility of salvage chemotherapy for refractory or relapsed non-Hodgkin's lymphoma with two topoisomerase II inhibitors, MST-16 and VP-16. MST-16 Study Group.

A feasibility study was carried out on the treatment for refractory and relapsed non-Hodgkin's lymphomas with a combination of two oral topoisomerase II inhibitors, MST-16 and VP-16. On the basis of the synergistic activity in preclinical studies and the schedule dependency in these drugs, low-dose and long-term administration was planned. For the anticipated myelosuppression, two different regimens were designed as an open label trial in this study. In Regimen I, 400 mg of MST-16 combined with 25 mg of VP-16 was administered daily. With this regimen, the response rate (RR)/median time to tumor progression (TTP) in all evaluable patients was 50% (2/4)8.5 months in low grade (indolent) lymphoma and 60% (6/10)/5.2 months in intermediate/high grade (aggressive) lymphomas. In Regimen II, 400 mg of MST-16 combined with 25 mg of VP-16 was administered intermittently (3 days a week or every other day). With this regimen, there was an RR/median TTP of 60% (3/5)/7.0 months in indolent lymphoma and 33.3% (4/12)/1.1 months in aggressive lymphoma. A major side effect in both of these regimens was myelosuppression, with the incidence of grades 3 and 4 toxicity being higher in Regimen I than in Regimen II. The other side effects were uncommon and not severe. These findings indicated that two regimens were tolerated well and were promising for refractory and relapsed aggressive non-Hodgkin's lymphomas. To define the anti-tumor activity and safety of these regimens precisely, large-scale prospective randomized trials are necessary.

Adolescent↗
PubMed1996

[The development of a new QOL Questionnaire on chemotherapy - induced emesis and vomiting--investigation of reliability and validity. Group for Investigation of QOL Questionnaire for Anti-Emetics Used in Cancer Chemotherapy. Joint Research Group for Tropisetron Double-Blind Comparative study].

A new questionnaire on QOL of patients with chemotherapy-induced emesis and vomiting was developed, and its reliability and validity were investigated in the present multi-center clinical trial. The questionnaire consisted of 15 items which included descriptive questions on appetite, feeling, sleep, mental fatigue, anxiety, pain, sputum, respiratory distress, nausea, vomiting, abdominal condition, daily life in a hospital and relationship with family, a linear analogue scale representing influence of nausea and vomiting on patient's life during 24 hours, and a face scale as the global scale. Data from 98 patients with cancer were analyzed by principal component analysis and correlation analysis. The results were summarized as follows: 1) Recollect rate was 78.1% and complete response rate was 86.0% in this QOL measurement. 2) A clear correlation was observed between appetite, feeling, nausea, vomiting and the physiological scale, between sleep, mental fatigue, anxiety, pain, abdominal condition and the psychological scale, between sputum, respiratory distress and the respiratory condition related scale, between daily life in hospital and the active scale, between relationship with family and the social relation scale. These results satisfied internal consistency. 3) As for test-retest reliability, the total score of 13 descriptive items between the day before and two days before the start of chemotherapy showed no significant difference. 4) The 13 items were grouped into physiological, the psychological, the respiratory condition related, the active and the social relation scales, and these scales belonged to a different dimension. 5) The linear analogue scale, the face scale and the total scores of 13 descriptive items correlated respectively with all of items except item of, relationship with family. 6) As for concurrent validity, vomiting frequency, severity of nausea and anorexia correlated with the physiological scale. Severity of nausea and anorexia also correlated with the psychological and active scales. 7) As a result of investigation of sensitivity, the total score of the 13 descriptive items, the linear analogue scale representing influence of nausea and vomiting on patient's life during 24 hours and the face scale revealed the poorest levels 2-3 days after chemotherapy but recovered thereafter. The aggravation of QOL of patients treated with chemotherapy was reduced in the anti-emetic administration group compared with the placebo administration group. These results suggested that this new questionnaire developed for chemotherapy-induced emesis and vomiting had sufficient validity and reliability to reflect the effects of anti-emetic drug.

Aged↗