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1.
ESMO Open ; 6(4): 100187, 2021 08.
Article in English | MEDLINE | ID: mdl-34118770

ABSTRACT

BACKGROUND: Precision and matched cancer medicine has the potential to complement the existing biomarker approaches in cancer treatment. However, despite their promising potential, certain negative results have highlighted their limitations in molecular biology-driven treatment strategies. This study aimed to evaluate the clinical benefits of precision therapies. MATERIALS AND METHODS: Three reviewers independently identified and assessed precision and matched cancer treatment studies published between January 2015 and December 2020. Clinical benefits of the treatments included in our cohort were assessed using two established frameworks; the European Society of Medical Oncology-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS) and the American Society of Clinical Oncology Value Framework. RESULTS: Of the 290 eligible studies, 130 were for lung cancer, 51 for solid tumors, 24 for melanoma, and 24 for breast cancer. The common targets were: epidermal growth factor receptor (N = 66), serine/threonine-protein kinase B-Raf (N = 40), anaplastic lymphoma kinase (ALK) (N = 34), breast cancer protein (N = 26), phosphatidylinositol-3 kinase/protein kinase B/phosphatase and tensin homolog (PI3K/AKT/PTEN) pathway (N = 19), receptor tyrosine-protein kinase erbB-2 (HER2) (N = 19), mitogen-activated protein kinase (RAS/RAF/MAPK) pathway (N = 18), programmed death-ligand 1 (N = 12), fibroblast growth factor receptor (N = 8), and others (N = 43). The ESMO-MCBS scales ranged from 0 to 4. Based on the clinical benefit values, tumor mutational burden/mismatch repair-deficient/microsatellite instability-high for immunotherapy, anaplastic lymphoma kinase, and neurotrophic receptor tyrosine kinase therapeutic targets were considered high, whereas RAS/RAF/MAPK and PI3K/AKT/PTEN were considered low. Additionally, we found a significant difference between each average score (P < 0.001). CONCLUSIONS: This study showed that precision and matched cancer therapies require further improvement. This is consistent with the views of the tumor board and of clinicians that precision strategies need to be revised to improve their therapeutic effects.


Subject(s)
Lung Neoplasms , Precision Medicine , Humans , Medical Oncology , Phosphatidylinositol 3-Kinase , Phosphatidylinositol 3-Kinases
2.
J Magn Reson ; 294: 128-132, 2018 09.
Article in English | MEDLINE | ID: mdl-30036813

ABSTRACT

We have been working on developing a low-cost tabletop NMR system. We reported that a field homogeneity as high as 50 ppm was achieved with a simple NMR magnet by employing two facing ferrite magnets with iron disks in between (Chonlathep et al., 2017). In this paper, we report two improvements added to our previous system: (1) an FPGA based signal processing unit to improve the S/N ratio and (2) a simple shimming mechanism to improve the field homogeneity. We obtained as high as 1 ppm field homogeneity in the best case. The signals from hydrogen nuclear spins in a methyl and carboxy group in acetic acid were resolved in NMR spectra.

3.
Int J Geriatr Psychiatry ; 28(3): 233-41, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22535710

ABSTRACT

OBJECTS: Identification of biomarkers for Alzheimer's disease (AD) is important for its early diagnosis and prevention and a key in advancing our understanding of its pathophysiology. The aim of this study was to determine whether systemic inflammatory interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) as well as hypertension (HT), diabetes mellitus (DM), and body mass index (BMI) are predictors of AD. METHODS: We performed a 10-year follow-up study on 133 elderly who were institutionalized in a nursing home. The associations of IL-1ß and IL-6 at both rest and agitation, as well as HT, DM, and BMI at baseline, were analyzed with the incidences of vascular dementia (VD) and AD during a 10-year follow-up period. RESULTS: The Kaplan-Meier method with log-rank test and Cox regression analyses for the total of 133 subjects showed significantly higher incidences of both VD and AD in subjects with DM or HT at baseline. Resting IL-1ß or IL-6 value, or agitation score, was not significantly associated with the subsequent development of VD or AD. The analyses of 40 subjects who had shown agitation at least once in the previous 3 months demonstrated that IL-1ß and IL-6 values at the agitation stage were significantly associated with AD, but not with VD. CONCLUSION: Our results indicate that systemic inflammatory IL-1ß and IL-6 at the agitation stage are risk factors for the development of AD, but not VD. Inflammatory mechanisms for AD seem to be causal and specific to the development of AD.


Subject(s)
Alzheimer Disease/blood , Dementia, Vascular/blood , Interleukin-1beta/blood , Interleukin-6/blood , Psychomotor Agitation/blood , Aged , Aged, 80 and over , Alzheimer Disease/epidemiology , Biomarkers/blood , Body Mass Index , Dementia, Vascular/epidemiology , Diabetes Mellitus/epidemiology , Female , Humans , Hypertension/epidemiology , Incidence , Japan/epidemiology , Male , Predictive Value of Tests , Psychomotor Agitation/epidemiology
4.
Int J Geriatr Psychiatry ; 25(6): 604-11, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19728317

ABSTRACT

OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly and is frequently accompanied by emotional disorder, including agitation. Although evidence of neuroendocrine immune and inflammatory functions during emotional changes has been accumulated, the pathogenic mechanisms in the development of agitation accompanied by AD remain to be elucidated. METHODS: To clarify the involvement of neuroendocrine and immune and inflammatory systems in agitation in AD, we examined agitation levels, circadian rhythms of behavior, cortisol, interleukin-1beta (IL-1beta), and natural killer cell activity (NKCA) in controls without dementia and 16 AD patients who were recognized to be easily agitated in their nursing homes. These behavioral and blood indicators were assessed according to the progress of the stage of agitation in 16 AD patients (stable, pre-agitation, and agitation stages). RESULTS: Elevations in night behavior and blood cortisol, IL-1beta and an reduced blood NKCA level in the evening were observed not only in the agitation stage, but also when stable in AD patients as compared to the control. Increased IL-1beta and decreased NKCA occurred in both the morning and evening in pre-agitation and agitation stages in AD. CONCLUSIONS: The increased IL-1beta and decreased NKCA with the progress of agitation in AD suggest that inflammation produces agitation and aggravates AD.


Subject(s)
Alzheimer Disease/immunology , Interleukin-1beta/blood , Killer Cells, Natural/immunology , Psychomotor Agitation/immunology , Aged , Alzheimer Disease/blood , Alzheimer Disease/complications , Analysis of Variance , Biomarkers/blood , Circadian Rhythm , Enzyme-Linked Immunosorbent Assay , Female , Humans , Hydrocortisone/blood , Male , Neuropsychological Tests , Psychomotor Agitation/blood , Psychomotor Agitation/etiology
5.
J Phys Chem A ; 109(21): 4766-71, 2005 Jun 02.
Article in English | MEDLINE | ID: mdl-16833819

ABSTRACT

The atmospheric chemistry of (CF3)2CHOCH3, a possible HCFC/HFC alternative, was studied using a smog chamber/FT-IR technique. OH radicals were prepared by the photolysis of ozone in a 200-Torr H2O/O3/O2 gas mixture held in an 11.5-dm3 temperature-controlled chamber. The rate constant, k1, for the reaction of (CF3)2CHOCH3 with OH radicals was determined to be (1.40 +/- 0.28) x 10(-12) exp[(-550 +/- 60)/T] cm3 molecule(-1) s(-1) by means of a relative rate method at 253-328 K. The value of k1 at 298 K was (2.25 +/- 0.04) x 10(-13) cm3 molecule(-1) s(-1). The random errors are reported with +/-2 standard deviations, and potential systematic errors of 15% could increase k(1). In considering OH-radical reactions, we estimated the tropospheric lifetime of (CF3)2CHOCH3 to be 2.0 months using the rate constant at 288 K. The degradation mechanism of (CF3)2CHOCH3 initiated by OH radicals was also investigated using FT-IR spectroscopy at 298 K. Products (CF3)2CHOC(O)H, CF3C(OH)2CF3, CF3C(O)OCH3, and COF(2) were identified and quantified. The branching ratio, k1a/k1b, was estimated to be 2.1:1 for reactions (CF3)2CHOCH3 + OH --> (CF3)2CHOCH2*+ H2O (k1a) and (CF3)2CHOCH3 + OH --> (CF3)2C*OCH3 + H2O (k1b).

6.
Phys Rev E Stat Nonlin Soft Matter Phys ; 64(5 Pt 1): 051806, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11735957

ABSTRACT

We study the effect of anisotropy of the Hele-Shaw cell on the viscous fingering instability in dilute polymer solutions with shear thinning. In isotropic cells, the tip-splitting instability is observed at the same pressure gradient for a fixed polymer concentration, whereas in anisotropic cells the side oscillation instability occurs at higher pressure gradient than the tip-splitting instability. Narrowing of the finger width in the isotropic cell is well correlated with the tip-splitting instability, whereas the finger width in the anisotropic cell is almost independent of the sample. The modified Darcy's law, where the constant viscosity is replaced by the shear thinning viscosity, gives good agreement with the experiments, irrespective of the cell and the fluid.

7.
J Biomater Sci Polym Ed ; 12(5): 503-14, 2001.
Article in English | MEDLINE | ID: mdl-11469781

ABSTRACT

Covalent immobilization of heparin has been developed to reduce the amount of heparin administered systematically during long-term dialysis. Recently, it was doubted partially because of the complexion during immobilization process. In this study, we investigated a novel method for specific immobilization of heparin on polysulfone (PSF) via free electron laser (FEL) irradiation. Laser wavelengths of 6.18 or 6.31 microm, the typical absorption bands of carboxyl groups of heparin and aromatic rings in PSF, respectively, were chosen to irradiate the thin heparin membrane formed on PSF surfaces. The amount of heparin immobilized on PSF was measured by the toluidine blue method. The binding of heparin on PSF was analyzed by X-ray photoelectron spectroscopy (XPS). The immobilization of heparin resulted in a hydrophilic surface on which decreased platelet adhesion was observed. The efficiency differences, depending on laser wavelengths, were discussed from the point of view of structural and environmental differences of light-absorbing groups.


Subject(s)
Biocompatible Materials/chemistry , Heparin/chemistry , Lasers , Polymers/chemistry , Sulfones/chemistry , Biocompatible Materials/radiation effects , Electron Probe Microanalysis , Heparin/pharmacology , Heparin/radiation effects , Humans , Methods , Platelet Adhesiveness/drug effects , Polymers/radiation effects , Sulfones/radiation effects , Surface Properties/drug effects , Water/metabolism
8.
Biochem Biophys Res Commun ; 280(4): 1077-84, 2001 Feb 02.
Article in English | MEDLINE | ID: mdl-11162637

ABSTRACT

The period of repair of hepatocytes injured by CCl4 and signaling proteins intrinsic to this period were examined. A 30 kDa polypeptide detected by immunoblot analysis using anti-phosphotyrosine antibody in livers from rats 48 to 72 h after administration of a single dose of CCl4 was identified as galectin-3 induced in cytoplasm of periportal hepatocytes and phosphorylated on tyrosine residue(s). Simultaneously, these hepatocytes induced p21(WAF1/Cip1/Sdi1) in the nucleus and the proliferating cell nuclear antigen in both the nucleus and the cytoplasm, suggesting that hepatocytes during this distinctive period are quiescent and repair cellular damage. Trabecular architecture of hepatocytes with the proliferating cell nuclear antigen only in the nucleus was found at 96 h. These findings indicate that galectin-3 is a novel member of signaling proteins downstream of tyrosine kinase, and suggest that it plays roles in supporting repair or survival of the injured hepatocytes rather than their proliferation that is likely to be initiated later than 72 h.


Subject(s)
Antigens, Differentiation/metabolism , Carbon Tetrachloride/pharmacology , Cyclins/metabolism , Hepatocytes/metabolism , Proliferating Cell Nuclear Antigen/metabolism , Tyrosine/metabolism , Animals , Antigens, Differentiation/chemistry , Blotting, Northern , Cloning, Molecular , Cyclin-Dependent Kinase Inhibitor p21 , Cytoplasm/metabolism , Fibrosis/metabolism , Galectin 3 , Immunoblotting , Immunohistochemistry , Liver/metabolism , Phosphorylation , Phosphotyrosine/metabolism , Rats , Rats, Wistar , Signal Transduction , Time Factors
9.
Biochem Biophys Res Commun ; 279(1): 282-7, 2000 Dec 09.
Article in English | MEDLINE | ID: mdl-11112453

ABSTRACT

The XmnI fragment, a highly repetitive DNA component, and animal and plant matrix or scaffold attachment region (MAR/SAR) were examined for similarity in interaction with nuclear scaffold. As the XmnI fragment bound a 130 kDa scaffold protein (P130) in vitro, various types of MAR/SAR fragments could bind 130 and 123 kDa scaffold proteins. The native XmnI and MAR/SAR fragments clearly augmented SV40 promoter-mediated luciferase gene transcription following transient transfection of recombinant plasmids into various types of recipient cells. In contrast, the XmnI fragment methylated at the cytosine base of the unique HindIII site, and a synthetic variant DNA deficient in base unpairing characteristic of MAR/SAR, could neither bind P130 nor augment this transcription. These two types of genomic regions appeared to have similar properties of interaction with nuclear scaffold, by which the activity of appropriately positioned promoter can be modulated.


Subject(s)
DNA-Binding Proteins/physiology , DNA/genetics , Nuclear Proteins/physiology , Repetitive Sequences, Nucleic Acid , Transcription, Genetic/physiology , Animals , Antigens, Nuclear , Cell Line , Cricetinae , DNA Methylation , Humans , Mice , Promoter Regions, Genetic , Protein Binding , Rats , Simian virus 40/genetics
10.
Colloids Surf B Biointerfaces ; 19(3): 237-247, 2000 Dec 30.
Article in English | MEDLINE | ID: mdl-10967497

ABSTRACT

The irradiation effects of oxygen on polysulfone have been investigated at energies of 20 keV, 150 keV and 2 MeV. The strong improvement of endothelial cell adhesion and proliferation is found on ion irradiated polysulfone at 20 keV. Such improvement is declined with increasing ion energy. The changes of surface color and free energy are strongly dependent on ion energy and dose. The formation of amorphous carbon phase is demonstrated by Raman spectroscopy and its degree is correspondent to the color changes observed. The formations of hydroxyl and carboxyl groups are confirmed by the attenuated total reflectance (ATR) FTIR spectroscopy. The depletions of heteroatoms are conjectured by detail analysis of X-ray photoelectron spectroscopy (XPS). Since no single one of these changes can be related directly to the improved adhesion and proliferation of endothelial cells on irradiated surface, we argue that the distribution of functional groups is crucial in promoting the adhesion of endothelial cells. Although the distribution cannot directly be detected at present, the irradiation effects were related to the results of TRIM simulation. The surface changes can be controlled by adjusting the size energy and dose of irradiating ion for the optimum morphology to cell adhesion.

11.
Colloids Surf B Biointerfaces ; 19(3): 249-256, 2000 Dec 30.
Article in English | MEDLINE | ID: mdl-10967498

ABSTRACT

A new process for surface modification of polymers with multi-source cluster deposition apparatus has been reported in our previous work. The apparatus simultaneously supplies reactant of ammonium sulfamate and activator of energetic Ar(+) ion. In this work chemical changes are analyzed on the basis of XPS spectra and the relations of contact angle and platelet adhesion with chemical changes are discussed. Polymer film, setting on a turning holder, was irradiated by Ar(+) ions during bombardment with ammonium sulfamate clusters. The Ar(+) ion source served for activation of polymer surface and a cluster ion source supplied ammonium sulfamate molecules to react with activated surface. After thorough washing with deionized sterile water, the modified surfaces were evaluated in terms of contact angle of water, elemental composition and binding state on XPS and platelet adhesion with platelet rich plasma (PRP). The modification of polysulfone decreased the contact angle of water on surfaces from 82.6 down to 34.5 degrees. The adhesion number of platelets were decreased to one-tenth of the original surface. Ammonium, amine, sulfate and thiophene combinations were formed on the modified surfaces. The primary studies showed successful modification of polysulfone with ammonium sulfamate by assistance of Ar(+) ion irradiation. The polar groups like N-sulfate were formed on surfaces and contribute to the decrease of surface contact angle and adhesion number of platelets. Since the same process can also be applied to other polymeric materials with various substrates, combining with the features of no solvent and no topographic changes, this method might be developed in a promising way for modification of polymers.

12.
Biochem Biophys Res Commun ; 273(1): 261-6, 2000 Jun 24.
Article in English | MEDLINE | ID: mdl-10873596

ABSTRACT

Acute phase responses to intragastric administration of a single dose of CCl(4) were examined with albumin mRNA turnover as a marker. Based on the combination of the changes in stability of albumin mRNA and activity of transcription of its gene, the entire course of liver injury was classified into three stages, the first stage for aggravation of injury until 9 h, the second from 9 to 24 h, and the third for repair of injury or regeneration of liver after 48 h. Liver S100 fractions from normal and CCl(4)-treated rats contained, in total, 11 polypeptides cross-linked with part of albumin mRNA, although they did not appear to be specific to this mRNA. Their profiles were altered together with the changes in stability of albumin mRNA in different stages. These findings suggest that the polypeptides with distinct properties play roles in physiologically significant processes involved in utilization and turnover of albumin mRNA, apparently altering its stability.


Subject(s)
Albumins/genetics , Carbon Tetrachloride/toxicity , Liver/drug effects , Liver/injuries , RNA Stability/drug effects , RNA-Binding Proteins/metabolism , Acute-Phase Reaction/genetics , Amanitins/pharmacology , Animals , Base Sequence , Binding, Competitive , Carbon Tetrachloride/administration & dosage , Chemical and Drug Induced Liver Injury , Gene Expression Regulation/drug effects , Half-Life , Liver/metabolism , Liver/pathology , Liver Diseases/classification , Liver Diseases/genetics , Liver Diseases/pathology , Male , Molecular Weight , Peptides/chemistry , Peptides/metabolism , Protein Binding/drug effects , RNA Probes/genetics , RNA Probes/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , RNA-Binding Proteins/chemistry , Rats , Rats, Wistar , Substrate Specificity , Time Factors , Transcription, Genetic/drug effects
13.
Yakugaku Zasshi ; 120(6): 520-33, 2000 Jun.
Article in Japanese | MEDLINE | ID: mdl-10860485

ABSTRACT

The nuclear matrix (nuclear scaffold), the RNA-protein skeleton of the nucleus, has a role in the organization and function of nuclear DNA. Nuclear processes associated with the nuclear matrix include transcription, replication, repair and splicing. We have purified a nuclear matrix protein, P130, which binds to several matrix attachment regions (MARs). Since the nucleotide sequence of P130 cDNA cloned by us was closely similar to that of matrin 3 cDNA cloned, except for two incorrect nucleotides within the matrin 3 coding region, and since the functions of matrin 3 were unknown, P130, referred to as P130/Mat3, was functionally characterized. The primary structure deduced for P130/Mat3 contained two DNA binding domains with C2H2-type zinc finger motif and two RNA binding domains. In addition, there were a nuclear localization signal and several phosphorylation sites for tyrosine or serine/threonine protein kinases, suggesting its multiple functions. MAR inserted upstream from the SV40 promoter in pMAR/luc assisted luciferase gene transcription in a transient expression system in Ac2F cells. Cotransfection of a plasmid carrying P130/Mat3 cDNA downstream from the CMV promoter into Ac2F cells produced this protein a level 4 times higher than that in wild-type Ac2F, causing 20 times higher luciferase activity from pMAR/luc than that induced by pMAR/luc alone. These findings indicated that MAR functions as a cis-element to which P130/Mat3 binds as one of the possible transactivators. Nuclear matrix proteins, which are tissue- and cell-type-specific, are altered with transformation and state of differentiation. We have shown that an MAR binding protein, P230, is detectable in rat hepatoma cells but not in normal liver, and suggested that this protein is a diagnostic and prognostic marker for liver cancer. It is clear that nuclear matrix proteins hold a considerable promise as diagnostic tools for pathologists. Present evidence, including our data, suggests that nuclear matrix proteins may be useful biomarkers of neoplastic disease in the serum, body fluids, and tissues. Nuclear matrix proteins are also potential candidates for the use as tumor prognostic factors and targets of anticancer drugs through apoptosis. We will discuss screening of drugs that interact with nuclear matrix proteins and influence nuclear events.


Subject(s)
DNA/genetics , Genome , Nuclear Matrix , Animals , Binding Sites , Biomarkers , DNA Repair , DNA-Binding Proteins/physiology , Humans , Neoplasms/diagnosis , Nuclear Matrix/chemistry , Nuclear Matrix/genetics , Transcription, Genetic
14.
JOP ; 1(4): 183-90, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11856860

ABSTRACT

CONTEXT: We studied behavior of the subcutaneously implanted pancreatic tumors and the process of metastasis using syngeneic Syrian golden hamsters. DESIGN: HaP-T1, a cell line derived from nitrosamine-induced pancreatic cancer in Syrian golden hamsters was used for this experiment. Thirty-five animals were divided into two groups: subcutaneous cell inoculation and subcutaneous tissue implantation. The tumor tissue was obtained from subcutaneously implanted cancer cells. One month after implantation, the tumors were resected and studied histopathologically. The animals were followed-up weekly by palpation of the peripheral lymph nodes in order to identify local recurrence. After death, necropsy was performed. Liver, lungs and pancreas specimens were taken for histopathogical study and detection of K-ras point mutation using the PCR/RFLP method. RESULTS: The mean survival time in the subcutaneous cell inoculation group was 151+/-17.5 days, and in the subcutaneous tissue implantation group was 137 +/-12.9 days. During the follow-up, 13 subcutaneously cell inoculated hamsters (86.7%) had right axillary lymph node metastasis while subcutaneously tissue implanted hamsters did not show any palpable lymph nodes. After necropsy, 10 of the 20 subcutaneously tissue implanted animals (50%) showed metastases in the lungs at the histopathological level. However, 16 of the 20 subcutaneously tissue implanted animals (80%) showed K-ras point mutation in the lung specimens. The lungs of the animals of the subcutaneous cell inoculation group did not show any metastases. No metastases were found in the liver or the pancreas in either group. CONCLUSION: This study suggests that homologous subcutaneous cell inoculation and subcutaneous tissue implantation models showed completely different patterns of metastasis. These models may aid further research to clarify the mechanisms of metastasis in pancreatic cancer.


Subject(s)
Neoplasm Transplantation/pathology , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/secondary , Skin Neoplasms/pathology , Animals , Cricetinae , Female , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Lung Neoplasms/pathology , Lung Neoplasms/secondary , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Male , Mesocricetus , Neoplasm Recurrence, Local/pathology , Neoplasm Seeding , Neoplasms, Experimental/pathology , Neoplasms, Experimental/secondary , Tumor Cells, Cultured/transplantation
15.
Yakugaku Zasshi ; 119(10): 763-72, 1999 Oct.
Article in Japanese | MEDLINE | ID: mdl-10518460

ABSTRACT

The spectral karyotyping (SKY) method is a novel molecular cytogenetic technique which simultaneously discerns entire chromosomes. In order to elucidate the origins of micronuclei induced under hyperthermic conditions in human lymphocyte culture, peripheral blood cells were cultured at 40 degrees C or 42 degrees C for 3-24 h, using the cytokinesis-block method with cytochalasin B. The induced micronuclei were identified by the fluorescence in situ hybridization (FISH) and SKY methods. At 42 degrees C for more than 6 h, the frequency of occurrence of micronuclei in binucleated cells rose with increasing incubation time. By the FISH method, 83.3% of micronuclei induced in 24 h culture at 42 degrees C were shown to be positive for the human centromeric probes. By the SKY method, each micronucleus induced under the hyperthermic conditions was identified unequivocally and shown to contain a specific chromosome. These results suggest that the micronuclei induced under the hyperthermic conditions in human lymphocyte culture contain chromosomes which do not migrate to the poles at the anaphase of the cell cycle because of the breakdown of the spindle apparatus.


Subject(s)
Cytogenetic Analysis , In Situ Hybridization, Fluorescence/methods , Lymphocytes/cytology , Micronuclei, Chromosome-Defective , Temperature , Cells, Cultured , Chromosome Aberrations , Chromosomes, Human , Humans , Spindle Apparatus
16.
Biochem Pharmacol ; 57(12): 1415-22, 1999 Jun 15.
Article in English | MEDLINE | ID: mdl-10353263

ABSTRACT

To characterize the enhanced repair synthesis of defined DNA lesions, oligodeoxyribonucleotides were synthesized and inserted into plasmid DNA. The inserted plasmid DNA was treated with cis-diamminedichloroplatinum(II) (cisplatin) and subjected to in vitro DNA repair assay with soluble extract from the rat liver cell line Ac2F. All cisplatin adducts tested stimulated DNA repair synthesis. Moreover, two cisplatin-resistant cell lines, Ac2F-CR4 and Ac2F-CR10, were established by stepwise exposure of Ac2F cells to this drug. The DNA repair synthesis was enhanced 3- to 4-fold in the extract from cisplatin-resistant Ac2F cells relative to that from Ac2F cells. Such repair synthesis was suppressed by the specific DNA polymerase inhibitor aphidicolin. The results of the present study suggested that the enhanced repair activity induced by a cisplatin adduct can be detected by in vitro DNA repair assay with soluble cell extract.


Subject(s)
Cisplatin/pharmacology , Cross-Linking Reagents/pharmacology , DNA Adducts , DNA Repair/drug effects , Animals , Cell Extracts/pharmacology , Cell Line , Cell-Free System , Drug Resistance, Neoplasm/physiology , Liver/cytology , Luciferases/analysis , Oligonucleotides/genetics , Oligonucleotides/metabolism , Rats
17.
J Dent ; 27(4): 291-5, 1999 May.
Article in English | MEDLINE | ID: mdl-10193107

ABSTRACT

OBJECTIVES: To assess the usefulness of dimerized eugenol (bis-eugenol) in dentistry, the physical properties of zinc oxide eugenol cement (ZOE) with bis-eugenol and the cytotoxicity of bis-eugenol were studied. METHODS: Setting time, compressive strength, solubility and disintegration of ZOE cement with bis-eugenol according to the specifications of JDMAS315 were evaluated. The cytotoxicity of bis-eugenol and eugenol toward two different cell types, HGF (a primary culture of human gingival fibroblast) and HSG (a human epidermoid carcinoma cell line derived from a salivary gland) was evaluated by the MTT test and in terms of cell survival. RESULTS: Addition of bis-eugenol to ZOE did not decrease the physical properties when employed at the ratio of 9:1 or 6:1 (liquid ND:bis-eugenol, w/w). Bis-eugenol was less toxic than eugenol in the cell culture tests. CONCLUSIONS: The results of this assay demonstrated that bis-eugenol is useful in ZOE.


Subject(s)
Eugenol/chemistry , Zinc Oxide-Eugenol Cement/chemistry , Adenocarcinoma , Cell Survival/drug effects , Cells, Cultured , Chemical Phenomena , Chemistry, Physical , Dose-Response Relationship, Drug , Drug Combinations , Eugenol/toxicity , Fibroblasts/drug effects , Gingiva/cytology , Gingiva/drug effects , Humans , Salivary Gland Neoplasms , Tumor Cells, Cultured , Zinc Oxide-Eugenol Cement/toxicity
18.
J Long Term Eff Med Implants ; 9(4): 349-66, 1999.
Article in English | MEDLINE | ID: mdl-10847972

ABSTRACT

Fabricating maxillofacial prosthesis can be challenging. Placement of implants can have a dramatic effect on the stability and retention of the prosthesis in patients. This article provides clinical retrospective analysis of osseointegrated implants used for maxillofacial reconstruction. Patient charts and radiographs were reviewed to determine implant status, stability of prosthesis, and masticatory and speech function. Of the 104 implants placed, there were 4 implant failures. The overall survival rate for implants in this patient population was 96.1%. The stability of maxillofacial prostheses demonstrated significant improvement after anchorage to implants. Implant-borne maxillofacial prostheses are better stabilized and retained than non-implant-borne prostheses, providing an improved quality of life to patients requiring prosthesis rehabilitation of maxillofacial defects.


Subject(s)
Dental Implants , Maxillofacial Prosthesis , Adult , Aged , Bone Transplantation , Dental Implantation, Endosseous/psychology , Dental Implants/psychology , Dental Prosthesis Design/methods , Female , Humans , Male , Mastication , Maxillofacial Prosthesis/psychology , Middle Aged , Torque
19.
J Neurochem ; 71(6): 2638-41, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9832166

ABSTRACT

Effects of acute and chronic morphine treatment on the expression of diazepam binding inhibitor (DBI) mRNA in the mouse brain were examined. Cerebral DBI mRNA expression significantly increased in morphine-dependent mice, and this increase is more remarkable in morphine-withdrawn mice, whereas a single administration of morphine (50 mg/kg) produced no changes in the expression. Simultaneous administration of naloxone (3 mg/kg) with morphine completely abolished the increase in cerebral DBI mRNA expression observed in morphine-dependent and -withdrawn mice. These results indicate that a chronic functional interaction between morphine and opioid receptors has a critical role in increases in DBI mRNA expression.


Subject(s)
Brain/metabolism , Carrier Proteins/genetics , Morphine/administration & dosage , Narcotics/administration & dosage , RNA, Messenger/metabolism , Animals , Brain/drug effects , Diazepam Binding Inhibitor , Male , Mice , Morphine/pharmacology , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Narcotics/pharmacology , RNA, Messenger/antagonists & inhibitors , Time Factors
20.
Oral Oncol ; 34(5): 387-90, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9861346

ABSTRACT

We developed a new technique of superselective intra-arterial chemotherapy for tongue cancer using a modified (1.35 mm) angiographic catheter. The catheter was confirmed to be inserted into the lingual artery by the new technique. We measured the platinum concentrations in resected tumour tissues after infusion of carboplatin (CBDCA) at 20 mg/m2 over 30 min from 30 min before tumour resection in 12 patients with cancer of the tongue (6 patients: superselective intra-arterial infusion; 6 patients: conventional intra-arterial infusion). The mean platinum concentration in tumour tissue was 10.5 +/- 1.2 micrograms/g wet, which was more than twice higher than, and significantly different from, 4.3 +/- 3.8 micrograms/g wet by the conventional intra-arterial infusion method. This new superselective intra-arterial infusion method allows direct infusion of the anticancer agent into the artery supplying the tumour and is expected to become a new therapeutic modality for cancer of the tongue.


Subject(s)
Antineoplastic Agents/administration & dosage , Carboplatin/administration & dosage , Tongue Neoplasms/drug therapy , Antineoplastic Agents/metabolism , Carboplatin/metabolism , Humans , Infusions, Intra-Arterial/methods , Temporal Arteries , Tongue Neoplasms/metabolism
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