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71.
Biweekly administration regimen of docetaxel combined with CPT-11 in patients with inoperable or recurrent gastric cancer 总被引:2,自引:0,他引:2
Takashi Yoshioka Yuh Sakata Masanori Terashima Kouji Sekikawa Makio Gamoh Yasushi Mitachi Soh Saitoh Ryunosuke Kanamaru 《Gastric cancer》2003,6(3):153-158
Background. Both docetaxel (TXT) and irinotecan (CPT-11) are active chemotherapeutic agents for gastric cancer. We designed a biweekly administration regimen of TXT combined with CPT-11 for 4 weeks as one cycle in patients with inoperable or recurrent gastric cancer, and conducted a dose-escalation study.
Methods. Patients with histologically confirmed gastric cancer were treated with the regimen. The dosage levels of TXT and CPT-11 were as follows: level 1, 30mg/m2 and 50mg/m2; level 2, 35 and 50mg/m2; level 3, 40 and 50mg/m2; level 4, 40 and 60mg/m2; and level 5, 50 and 60mg/m2. The dose escalation was based on the dose-limiting toxicity (DLT) observed during the first cycle.
Results. Grade 4 neutropenia was observed at level 3, but no other DLT was observed at less than level 4 during the first cycle. However, three patients at level 3 could not continue treatment without a decrease in the dosage after the second cycle. Based on these results, level 2 was considered to be the clinically recommended dosages.
Conclusion. Biweekly TXT and CPT-11 was well tolerated. The recommended dosages of TXT and CPT-11 for a phase II trial are 35mg/m2 and 50mg/m2, respectively. 相似文献
72.
Shabtai M Ye H Kono K Takayam T Terashima K Tsukuda K Frischer Z Waltzer WC Malinowski K 《Urologic oncology》2003,21(1):27-32
The presence of tumor infiltrating lymphocytes (TIL) has been attributed to the host cell mediated immune response against the evolving malignancy. However, due to specific evasive and escape mechanisms, the immune competent cells are rendered ineffective. One such mechanism may be the production of immune suppressor substance(s), inhibiting lymphocyte proliferation, and subsequently, their transformation into effector cells. To evaluate a possible impact of RCC extract on lectin and alloantigen-induced proliferation of TIL and peripheral blood lymphocytes (PBL) from renal cell carcinoma (RCC) patients and from healthy control human subjects. Tumor extract and TIL were derived from 13 patients with RCC undergoing radical nephrectomy. Tumor infiltrating lymphocytes and PBL from these patients were activated with Concanavalin A (Con-A), Phytohemoglutinine (PHA) or Pokeweed (PW) and the rate of blastogenesis was measured by (3)H Thymidine incorporation. The same procedure was used in assay with PBL from control healthy blood donors. There was a significant reduction (88.6%) in the proliferative response to ConA of TIL compared to PBL from the same patients (P = 0.007). A similar decrease was seen following stimulation by PHA (85.8%, P = 0.01) and PW mitogen (78.5%, P = 0.001). A 79.5% decrease in response level of TIL to alloantigens compared to PBL from RCC patients (P = 0.021), was observed. Lectin induced proliferative response of RCC patients was significantly lower in the presence of RCC extract (82.9%) compared to normal kidney extract (P = 0.008). Alloantigenic stimulation of healthy individual PBL was also decreased significantly in the presence of RCC extract (92.9%, P = 0.0001) compared to normal kidney extract. Similarly, lectin induced stimulation of healthy control PBL in the presence of RCC extract was significantly lower (83.2%, P = 0.003). Our data suggest that RCC extract contains an immune suppressive substance(s), capable of inhibiting lymphocyte proliferative response of tumor infiltrating lymphocytes as well as of PBL from patients and healthy individuals alike. This may be one of the mechanisms by which the tumor evades the transformation of lymphocytes into effector killer cells, and thus affects the biological inter-relationship between tumor and host. Identification of this substance and its gene may provide an effective anti-tumoral treatment modality. 相似文献
73.
Dissociable neural responses in the hippocampus to the retrieval of facial identity and emotion: an event-related fMRI study 总被引:1,自引:0,他引:1
In studies with brain-damaged patients and experimental animals, the medial temporal lobe, including the hippocampus and parahippocampal gyrus, has been found to play a critical role in establishing declarative or episodic memory. We measured the neural response in these structures, using event-related functional magnetic resonance imaging, while six healthy subjects performed the retrieval task for facial identity and emotion, respectively. Under the identity condition, the subjects participated in a yes/no recognition test for neutral faces learned before the scanning. Under the emotion condition, the subjects learned the faces with positive or negative expression and retrieved their expressions from neutral cue faces. The results showed that the left hippocampus is primarily involved in the identification of learned faces, and that the adjacent parahippocampal gyrus responds more to target than to distracter events. These results indicate a specific engagement of the left hippocampal regions in conscious recollection and identification of physiognomic facial features. The activity in the right hippocampus increased under both the identity and emotion conditions. The present results may relate with the functional model of face recognition in which the left hemisphere contributes to the processing of detailed features and the right hemisphere is efficient in the processing of global features. 相似文献
74.
Gruntenko NE Bownes M Terashima J Sukhanova MZh Raushenbach IY 《Insect molecular biology》2003,12(4):393-404
The link between reproduction and environmental signals is poorly understood at the physiological, genetic and molecular levels. We describe a mutant strain of Drosophila virilis that has altered responses to heat stress. Heat stress in wild-type females results in oocyte maturation delays, degradation of early vitellogenic egg chambers, inhibition of yolk protein gene expression in follicle cells and accumulation of mature oocytes. The mutant females have increased levels of ecdysteroids and decreased juvenile hormone degradation, and show all of the heat-stress-induced reproductive effects observed in wild-type flies, without exposure to heat stress. During oogenesis in mutant females following heat stress there is an increase in early vitellogenic oocyte degradation and some degradation of late egg chambers. 20-Hydroxyecdysone levels, but not juvenile hormone degradation, change following heat stress in mutant females. 相似文献
75.
Stabilizing and Solubilizing Effects of Sulfobutyl Ether β-Cyclodextrin on Prostaglandin E1 Analogue 总被引:1,自引:0,他引:1
Uekama Kaneto Hieda Yukako Hirayama Fumitoshi Arima Hidetoshi Sudoh Masao Yagi Akira Terashima Hiroshi 《Pharmaceutical research》2001,18(11):1578-1585
Purpose. Parent cyclodextrins are known to accelerate the degradations such as dehydration and isomerization of E-type prostaglandins in neutral and alkaline solutions. The objective of this study was to attempt the stabilization and solubilization of E1-type prostaglandin analogue in aqueous solution by biocompatible cyclodextrin derivatives.
Methods. The interaction of an E1-type prostaglandin, methyl 7-[(1R,2R,3R)-3-hydroxy-2-[(E)-(3S)-3-hydroxy-4-(m-methoxymethylphenyl)1-butenyl]-5-oxocyclopentyl]-5-thiaheptanoate (MEester) with cyclodextrins (CyDs) was studied by spectroscopies and the solubility method. The degradation of MEester was monitored by high-performance liquid chromatography.
Results.
1H-nuclear magnetic resonance spectroscopic studies indicated that MEester forms 1:1 inclusion complexes with -, -, and -CyDs in solutions, where -CyD interacts with the -side chain containing methyl ester moiety of the drug, whereas - and -CyDs preferentially include around the five-membered ring and both side chains of the drug. Parent -CyD and hydrophilic derivatives, such as 2-hydoxypropyl-- and --CyDs, sulfobutyl ether -CyD (SBE--CyD) and maltosyl -CyD showed higher solubilizing abilities against MEester over parent - and -CyDs. SBE--CyD and 2,6-dimethyl--CyD (DM--CyD) significantly decelerated the degradation of MEester, particularly the base-catalyzed dehydration, in neutral and alkaline solutions, whereas other CyDs accelerated the degradation. The acid-catalyzed degradation of MEester (pH < 3) was decelerated by the addition of CyDs, especially -CyD.
Conclusions. SBE--CyD with low hemolytic activity and low toxicity is useful as a pharmaceutical carrier for the preparation of injectable MEester, because of its higher stabilizing and solubilizing effects on MEester. Furthermore, SBE--CyD can be useful as a stabilizing agent for drugs, that are subject to base-catalyzed degradations, probably because of the electric repulsion between anionic charges of the sulfobutyl moiety and catalytic anionic species such as hydroxide ion. 相似文献
76.
Terashima M Fujita Y Sugano K Asano M Kagiwada N Sheng Y Nakamura S Hasegawa A Kakuta T Saito A 《Artificial organs》2001,25(3):209-212
Our aim was to develop bioartificial tubules using tubular epithelial cells and artificial membranes and evaluate the function of water and electrolyte transport by various tubular epithelial cells. The cells were cultivated onto extracellular matrix (ProNectin F) coating polycarbonate membrane. Water transport from the apical to the basolateral site of cells was examined using a modified Ussing chamber module. Water transport under colloidal osmotic pressure on the apical site and hydraulic pressure on the basolateral site were higher in JTC-12, LLC-PK1 cells than in MDCK cells. Water transport under osmotic plus hydraulic pressure was highest in LLC-PK1 cells. We made bioartificial tubules using LLC-PK1 cells and polysulfone hollow fiber cartridges. Water and Na ion transport function was high, and BUN and creatinine passage was recognized in these bioartificial tubules. BUN and creatinine concentrations of reabsorption fluid in these bioartificial tubules were significantly lower than those concentrations of control media and of noncell attached polysulfone hollow fiber cartridges. Though LLC-PK1 cells were more preferable cells for the use of bioartificial tubules in terms of water and electrolyte transport, the passage of BUN and creatinine was not appropriate for clinical use. To select more preferable cells for bioartificial tubules which transport water and electrolytes and do not induce passage of uremic toxins is necessary. 相似文献
77.
Nakamura K Sasaki M Kunitake N Kimura M Watanabe T Sasaki T Terashima H Kuwabara Y Sakai S Masuda K 《International journal of clinical oncology / Japan Society of Clinical Oncology》2001,6(6):302-305
Background. No effective follow-up strategy for non-Hodgkin's lymphoma (NHL) has been identified to date. The aim of this study was to
assess the value of a strict follow-up procedure in patients with NHL after they showed clinical remission.
Methods. One hundred and twenty-one patients with localized NHL of the head and neck who had achieved clinical remission after radiation
therapy and/or chemotherapy were followed with a strict follow-up strategy (consisting of a schedule of frequent office visits,
imaging studies, and blood tests, even if the patient was asymptomatic).
Results. Thirty-nine patients relapsed after remission. Twenty-two (56.4%) of the relapses were associated with symptoms. In the 17
patients with asymptomatic relapses (43.6%), an abnormal physical examination result initially indicated relapse in 10 patients.
The other tests that initially indicated relapse included scheduled computed tomography scans (3 patients), scheduled gallium
scans (2 patients), and serum lactate dehydrogenase levels (2 patients). According to the Ann Arbor stage at relapse, 72.7%
of the patients with symptomatic relapses were stage III or IV, while 70.6% of the patients with asymptomatic relapses were
stage I or II.
Conclusions. These results indicate that a strict follow-up procedure is effective in detecting asymptomatic relapses, which generally
involve a smaller tumor load than symptomatic relapses.
Received: May 10, 2001 / Accepted: October 26, 2001 相似文献
78.
Shirasaka T Aiba K Araki H Suzuki M Terashima M Mikami Y 《Gan to kagaku ryoho. Cancer & chemotherapy》1999,26(4):456-466
Highly effective treatment is required for patients with advanced GI cancer. Returning to the starting point for reconsideration of cancer chemotherapy, with the aim of attaining a therapy (self rescuing concept: SRC) with more potential efficacy and less toxicity than current therapy, we report two kinds of chemotherapy in the present paper. They were set up preclinically using the theory of 5-FU biochemical modulation, and demonstrated their usefulness in clinical practice. S-1 is a newly developed oral anti-cancer drug which is a combination of Tegafur (FT), a prodrug of 5-FU and two modulators (CDHP, an inhibitor of 5-FU degradation and Oxo, a selective inhibitor GI toxicity by 5-FU) at a molar ratio of 1:0.4:1. In combination with CDHP, 5-FU gradually released from FT remained longer in plasma, and consequently had high anti-tumor activity, while the combined Oxo significantly suppressed GI toxicity due to 5-FU. The response rate to S-1 of stomach cancer in a phase II study was 46.5% (60/129). Toxicity at more than G3 was less than 10%. In the combination therapy employing 5-FU by CVI (5-FU: 250-350 mg/body for 24 h, 4-6 wks) and low dose consecutive CDDP, CDDP acts mainly as a modulator of 5-FU (to increase 5-FU sensitivity for tumor by inhibition of intracellular Met incorporation). For this purpose, it was found that daily consecutive administration is required, even at low dose of CDDP (3-5 mg/body/day for 5 days). A high response rate (40-60%) was obtained for advanced GI cancer. Toxicity at more than G3 was less than 10%. On the other hand, the possibility has been suggested that so far as 5-FU is concerned, CVI every other day (500-750 mg/body/day for 3 days) is more favorable than long term CVI, with regard to decreasing GI and myelotoxicities based upon the difference in generation time between normal cell (GI mucous membrane and stem cell) and tumor cell cycles. The possibility is suggested that the above-mentioned chemotherapy can become a standard therapy for GI cancer. 相似文献
79.
K Kohshi Y Kinoshita H Imada N Kunugita H Abe H Terashima N Tokui S Uemura 《British journal of cancer》1999,80(1-2):236-241
The purpose of this non-randomized trial was to evaluate the efficacy of radiotherapy combined with hyperbaric oxygen (HBO) in patients with malignant glioma. Between 1987 and 1997, 29 patients in whom computerized tomography (CT) or magnetic resonance imaging (MRI) scans showed post-operative residual tumours were locally irradiated with nitrosourea-based chemotherapy. Treatments were consecutively combined with HBO at two institutions since 1991 and 1993. Fifteen patients were irradiated daily after HBO, and the periods of time from decompression to irradiation were within 15 and 30 min in 11 and four patients respectively. Fourteen other patients were treated without HBO. Tumour responses were assessed by CT or MRI scans and survival times were compared between the treated groups. In the HBO group, 11 of 15 patients (73%) showed > or = 50% tumour regression. All responders were irradiated within 15 min after decompression. In the non-HBO group, four of 14 patients (29%) showed tumour regression. The median survivals in patients with and without HBO were 24 and 12 months, respectively, and were significantly different (P < 0.05). No serious side-effects were observed in the HBO patients. In conclusion, irradiation after HBO seems to be a useful form of treatment for malignant gliomas, but irradiation should be administered immediately after decompression. 相似文献
80.
Terashima A Taniguchi T Nakai M Yasuda M Kawamata T Tanaka C 《Neuropharmacology》2000,39(10):1920-1928
Immunophilin-CsA and -FK506 complexes bind to calcineurin (CaN) and inhibit its phosphatase activity leading to enhancement of neuronal activities. However, inhibition of CaN activity is not the mediator of modulatory activity for IP3 and ryanodine receptors and does not mediate the neurotrophic actions of FK506. FK506 binding protein (FKBP)-12 also binds rapamycin, another immunosuppressant which does not affect CaN activity. Using whole-cell patch clamp techniques, excitatory postsynaptic currents (EPSCs) were recorded and we analyzed the effect of immunosuppressants on the synaptic potentiation induced by pairing weak presynaptic stimulation with postsynaptic depolarization in CA1 neurons of rat hippocampal slices. We found that postsynaptic application of rapamycin or FK506, at low concentrations, but not cyclosporin A, in conjunction with weak pairing stimulation, induced NMDA-dependent long-term potentiation (LTP). The rapamycin-induced LTP was blocked by chelating intracellular Ca(2+) or by inhibiting the intracellular Ca(2+) release. Thus, Ca(2+) release from intracellular Ca(2+) stores is required for the induction of LTP by weak pairing stimulation in the presence of rapamycin or FK506 at postsynaptic sites. We propose that postsynaptic FKBP-12 regulates synaptic transmission by stabilizing the postsynaptic Ca(2+) signaling mechanism in rat hippocampal CA1 neurons. 相似文献