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1.
Zhonghua Bing Li Xue Za Zhi ; 53(7): 691-696, 2024 Jul 08.
Article in Zh | MEDLINE | ID: mdl-38955700

ABSTRACT

Objective: To investigate the clinical and pathological characteristics of breast cancer with HER2 low expression. Methods: The data from 3 422 patients with invasive breast cancer which archived in Peking Union Medical College Hospital between April 2019 and July 2022 were retrospectively reviewed. Among them, 136 patients were treated with neoadjuvant chemotherapy. The tumor size, histological type, tumor differentiation, lymph node metastasis, Ki-67 index, the status of estrogen receptor, progesterone receptor and HER2 as well as pathological complete response (pCR) rate were collected. Results: The HER2 status of 3 286 patients without neoadjuvant therapy, 616 (616/3 286, 18.7%) score 0, 1 047 (1 047/3 286, 31.9%) score 1+, 1 099 (1 099/3 286,33.4%) score 2+ and 524 (524/3 286,15.9%) score 3+ by immunohistochemistry (IHC). Among the 1 070 IHC 2+ cases, 161 were classified as HER2 positive by reflex fluorescence in situ hybridization (FISH) assay. In our cohort, 1 956 cases of HER2-low (IHC 1+ and IHC 2+/FISH-) breast cancer were identified. Compared to the HER2 IHC 0 group, HER2-low tumors more frequently occurred in patients with hormone receptor (HR) positive (P<0.001), Ki-67 index below 35% (P<0.001), well or moderate differentiation (P<0.001) and over the age of 50 (P=0.008). However, there were no significant differences in histological type, tumor size, and lymph node metastasis between HER2-low and HER2 IHC 0 group. For patients who had neoadjuvant therapy, the pCR rate in the patients with HER2-low was lower than those with HER2 IHC 0 (13.3%, 23.9%), but there was no significant difference. Although HER2-low breast cancers showed a slightly lower pCR rate than HER2 IHC 0 tumors, no remarkable difference was observed between tumors with HER2-low and HER2 IHC 0 regardless of hormone receptor status. Conclusions: The clinicopathological features of HER2-low breast cancers are different from those with HER2 IHC 0. It is necessary to accurately distinguish HER2-low breast cancer from HER2 IHC 0 and to reveal whether HER2-low tumor is a distinct biological entity.


Subject(s)
Breast Neoplasms , Lymphatic Metastasis , Receptor, ErbB-2 , Receptors, Estrogen , Humans , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Receptor, ErbB-2/metabolism , Female , Retrospective Studies , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Neoadjuvant Therapy , In Situ Hybridization, Fluorescence , Immunohistochemistry , Middle Aged , Adult , Ki-67 Antigen/metabolism
2.
Zhonghua Bing Li Xue Za Zhi ; 53(5): 464-469, 2024 May 08.
Article in Zh | MEDLINE | ID: mdl-38678327

ABSTRACT

Objective: To investigate HER2 mRNA expression in breast cancer with HER2 immunohistochemistry (IHC) 0 and to analyze the feasibility of distinguishing between the tumor with HER2 µltra-low expression and the one without expression of HER2 (no staining by IHC) by HER2 mRNA level preliminarily. Methods: HER2 mRNA was analyzed by reverse transcription digital PCR in 41 cases of formalin-fixed paraffin-embedded surgical tissue samples of invasive breast cancer obtained between January 2020 and March 2023 at Peking Union Medical College Hospital. The cohort included 21 HER2 IHC 1+ and 20 IHC 0 (12 ultra-low and 8 non-expression of HER2). HER2 mRNA expression level was quantitatively evaluated by the FAM (HER2)/VIC (reference gene) ratio. Results: The expression of HER2 mRNA for the cases with 1+, ultra-low, and non-expression of HER2 by IHC was 0.30 to 1.78 (average 0.90, median 0.82), 0.55 to 1.51 (average 0.93, median 0.90) and 0.22 to 0.78 (average 0.41, median 0.36), respectively. For the mean and median HER2 mRNA levels, there was no significant difference between HER2 IHC 1+ and HER2 ultra-low expression diseases (P=0.757). A remarkable difference in HER2 gene expression was found between the tumors with 1+ and non-expression of HER2 by IHC (P=0.002). And, HER2 ultra-low cases contained statistically higher levels of HER2 mRNA compared with non-expression of HER2 subgroup by IHC (P=0.001). Conclusions: Based on HER2 mRNA, HER2 non-expression and HER2 weak expression (including HER2 IHC 1+ and ultra-low) belong to two different types of the tumor and the disease with HER2 IHC 1+ and HER2 ultra-low expression may be the same. It is necessary to further test the performance of HER2 mRNA detection for stratifying the HER2 weak expression subgroup and to determine the threshold.


Subject(s)
Breast Neoplasms , Immunohistochemistry , Receptor, ErbB-2 , Female , Humans , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Immunohistochemistry/methods , Receptor, ErbB-2/metabolism , Receptor, ErbB-2/genetics , RNA, Messenger/metabolism , RNA, Messenger/genetics
3.
Clin Radiol ; 78(6): 437-443, 2023 06.
Article in English | MEDLINE | ID: mdl-37028999

ABSTRACT

AIM: To develop a high-accuracy low-dose computed tomography (LDCT) lung nodule diagnosis system by combining artificial intelligence (AI) technology with the Lung CT Screening Reporting and Data System (Lung-RADS), which can be used in the future AI-aided diagnosis of pulmonary nodules. MATERIALS AND METHODS: The study comprised the following steps: (1) the best deep-learning segmentation method for pulmonary nodules was compared and selected objectively; (2) the Image Biomarker Standardization Initiative (IBSI) was used for feature extraction and to determine the best feature reduction method; and (3) a principal component analysis (PCA) and three machine learning methods were used to analyse the extracted features, and the best method was determined. The Lung Nodule Analysis 16 dataset was applied to train and test the established system in this study. RESULTS: The competition performance metric (CPM) score of the nodule segmentation reached 0.83, the accuracy of nodule classification was 92%, the kappa coefficient with the ground truth was 0.68, and the overall diagnostic accuracy (calculated by the nodules) was 0.75. CONCLUSION: This paper summarises a more efficient AI-assisted diagnosis process of pulmonary nodules, and has better performance compared with the previous literature. In addition, this method will be validated in a future external clinical study.


Subject(s)
Lung Neoplasms , Multiple Pulmonary Nodules , Solitary Pulmonary Nodule , Humans , Artificial Intelligence , Lung Neoplasms/diagnostic imaging , Tomography, X-Ray Computed/methods , Multiple Pulmonary Nodules/diagnostic imaging , Diagnosis, Computer-Assisted/methods , Solitary Pulmonary Nodule/diagnostic imaging , Radiographic Image Interpretation, Computer-Assisted
4.
Zhonghua Zhong Liu Za Zhi ; 38(5): 351-6, 2016 May 23.
Article in Zh | MEDLINE | ID: mdl-27188607

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the effects of Rad9 mutants with impaired DNA mismatch repair (MMR) function on the tumorigenesis of colorectal cancer. METHODS: The colorectal cancer tumor samples were collected from 100 patients. The mutation profiles of human Rad9 (hRad9) gene in these samples were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing. The plasmid of pFLAG-hRad9 (L101M) was constructed following the QuickChange mutagenesis procedure and transfected into mRad9-deleted mouse cells (mRad9(-/-) cells). The expression of hRad9 protein was measured by western blot analysis. The MMR activity in live cells was detected by flow cytometry using the reporter plasmid for MMR function. RESULTS: Mutation from Leu to Met at the residue 101 (L101M) of hRad9 gene was detected in 7 of the 100 samples. The mismatch repair efficiency of mRad9(-/-)+ L101M cells (mRad9-deleted mouse cells with ectopic expression of L101M hRad9 gene) was (34.0±5.6)%, which was significantly lower than that in the mRad9(-/-)+ hRad9 cells [mRad9-deleted mouse cells with ectopic expression of hRad9 gene, (48.0±7.5)%, P<0.05]. After N-nitroso-N-methylurea (MNU) treatment, the survival rate of mRad9(-/-)+ L101M cells was (33.7±5.9)%, which was significantly higher than that in the mRad9(-/-)+ hRad9 cells [(21.3±4.7)%, P<0.05]. Thus, ectopic expression of L101M hRad9 gene resulted in significantly reduced MMR activity and increased resistance to MNU. Furthermore, ectopic expression of hRad9 gene with mutation at the target residues of post-translational modification in mRad9(-/-) cells also led to a reduced MMR activity. CONCLUSION: Rad9 mutants with impaired DNA mismatch repair function may promote tumorigenesis of colorectal cancer.


Subject(s)
Cell Cycle Proteins/genetics , Colorectal Neoplasms/genetics , DNA Mismatch Repair , Mutation , Animals , Cell Cycle Proteins/metabolism , Cell Transformation, Neoplastic , Humans , Mice , Reverse Transcriptase Polymerase Chain Reaction
6.
Clin Exp Obstet Gynecol ; 42(5): 653-6, 2015.
Article in English | MEDLINE | ID: mdl-26524817

ABSTRACT

OBJECTIVES: To investigate whether the time of embryo transfer (ET) affect the oocyte-to-baby rate. MATERIALS AND METHODS: The database was retrospectively analyzed including total number of oocytes collected and corresponding oocyte-to-live baby born (LBB) rate. Then the relationship between different time of embryo transfer and oocyte-to-baby rate was compared. In a year period all patients undergoing infertility treatment were included in the study. The outcome parameters were total number of oocytes collected and corresponding oocyte-to-LBB. RESULTS: For patients under the age of 35 years, there was no increase in oocyte-to-LBB regardless of the time of ET. For patients older than 35 years, the oocyte use rate increased significantly when embryo was transferred on day 2. Oocyte-to-baby rates were also analyzed after grouping patients on the number of oocytes retrieved per cycle. For patients < 35 years, the oocyte- to -LBB rate increased significantly on day 3 if < ten oocytes were obtained. whereas for patients > 35 years, the oocyte-to-baby rate was best on day 2 when about 15 oocytes were retrieved. CONCLUSIONS: This retrospective analysis demonstrated the relationship between the time of ET and ooctye-to-baby rate that is indicative of a more biologically efficient reproductive system.


Subject(s)
Embryo Transfer , Oocytes/physiology , Adult , Age Factors , Cryopreservation , Female , Fertilization in Vitro , Humans , Pregnancy , Pregnancy Rate , Retrospective Studies , Time Factors
8.
Zhonghua Liu Xing Bing Xue Za Zhi ; 45(6): 892-898, 2024 Jun 10.
Article in Zh | MEDLINE | ID: mdl-38889992

ABSTRACT

Medical and preventive integration effectively bridges the gap between "treating diseases" and "preventing diseases". Over the years, medical and preventive integration research has focused on chronic and chronic infectious diseases, with insufficient attention to acute ones. Confronting newly emerging infectious diseases establishing continuous monitoring, early warning, emergency response, and appropriate treatment will be a key focus for developing and reforming the healthcare system. Interoperability and sharing of medical and health data are essential prerequisites for bridging the gap between medical treatment and disease prevention and are also important for promoting intelligent surveillance and early warning of infectious diseases. Informatization is necessary to achieve efficient collaboration between medical treatment and disease prevention. Reviewing the development of medical and health informatization in the United States and Europe, this paper compares and discusses the problems and challenges in developing medical and health informatization in China. The aim is to provide references for the development of medical and health informatization and the innovation of medical and preventive integration mechanisms in the country.


Subject(s)
Public Health , China , Humans , Public Health Informatics , Delivery of Health Care
9.
Zhonghua Liu Xing Bing Xue Za Zhi ; 45(3): 455-463, 2024 Mar 10.
Article in Zh | MEDLINE | ID: mdl-38514324

ABSTRACT

Objective: To introduce the progress in research of rash and fever syndrome (RFS) surveillance and early warning both at home and abroad, and provide reference for surveillance and prevention of RFS in China. Methods: The keywords "fever" "rash" and "surveillance" and others were used for a literature retrieval by using China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed and Web of Science. The languages of literatures were limited in Chinese and English. The key information of the literatures were collected and analyzed with Excel. Results: A total of 36 study papers (21 in Chinese and 15 in English) were included. The studies mainly focused on the pathogen surveillance of RFS (n=19). The pathogens included measles virus, varicella-zoster virus, rubella virus, enterovirus, human B19 virus, dengue virus, streptococcus group A, Salmonella typhi and Salmonella paratyphoid,human herpesvirus, mumps virus and adenovirus. Eight studies were about the surveillance in major events, such as sport game, World Expo and religious gathering, or sudden natural disasters, such as earthquake and tropical storm, during 2010-2015. Eight studies focused on case or epidemic surveillance, most of which were studies from other counties. The surveillance sites were medical institutions. RFS was diagnosed according to the International Classification of Diseases, 9th (ICD-9) and symptoms descripted in chief-complaint. Only one study in Mongolia conducted RFS epidemic prediction. The analysis methods of 36 papers included simple descriptive analysis, time-based early warning models (such as regression analysis, fixed threshold method, Hugh Hart control chart method and cumulative sum control chart method) and time series analysis method. Conclusions: In the future, RFS surveillance system should cover both known pathogens and emerging pathogens. Automatic surveillance using information capture and intelligent modelling can be applied to improve the sensitivity and specificity of RFS surveillance and early warning.


Subject(s)
Enterovirus Infections , Epidemics , Exanthema , Paratyphoid Fever , Humans , Sentinel Surveillance , Enterovirus Infections/epidemiology , Paratyphoid Fever/epidemiology , Syndrome , Exanthema/epidemiology
10.
J Vet Pharmacol Ther ; 36(5): 486-93, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23406022

ABSTRACT

The pharmacokinetic profile of meloxicam in clinically healthy koalas (n = 15) was investigated. Single doses of meloxicam were administered intravenously (i.v.) (0.4 mg/kg; n = 5), subcutaneously (s.c.) (0.2 mg/kg; n = 1) or orally (0.2 mg/kg; n = 3), and multiple doses were administered to two groups of koalas via the oral or s.c. routes (n = 3 for both routes) with a loading dose of 0.2 mg/kg for day 1 followed by 0.1 mg/kg s.i.d for a further 3 days. Plasma meloxicam concentrations were quantified by high-performance liquid chromatography. Following i.v. administration, meloxicam exhibited a rapid clearance (CL) of 0.44 ± 0.20 (SD) L/h/kg, a volume of distribution at terminal phase (Vz ) of 0.72 ± 0.22 L/kg and a volume of distribution at steady state (Vss ) of 0.22 ± 0.12 L/kg. Median plasma terminal half-life (t(1/2)) was 1.19 h (range 0.71-1.62 h). Following oral administration either from single or repeated doses, only maximum peak plasma concentration (C(max) 0.013 ± 0.001 and 0.014 ± 0.001 µg/mL, respectively) was measurable [limit of quantitation (LOQ) >0.01 µg/mL] between 4-8 h. Oral bioavailability was negligible in koalas. Plasma protein binding of meloxicam was ~98%. Three meloxicam metabolites were detected in plasma with one identified as the 5-hydroxy methyl derivative. This study demonstrated that koalas exhibited rapid CL and extremely poor oral bioavailability compared with other eutherian species. Accordingly, the currently recommended dose regimen of meloxicam for this species appears inadequate.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Phascolarctidae/metabolism , Thiazines/pharmacokinetics , Thiazoles/pharmacokinetics , Administration, Oral , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/blood , Chromatography, High Pressure Liquid/methods , Chromatography, High Pressure Liquid/veterinary , Chromatography, Reverse-Phase/methods , Chromatography, Reverse-Phase/veterinary , Female , Injections, Intravenous/veterinary , Injections, Subcutaneous/veterinary , Male , Meloxicam , Phascolarctidae/blood , Thiazines/administration & dosage , Thiazines/blood , Thiazoles/administration & dosage , Thiazoles/blood
11.
Hong Kong Med J ; 17(1): 26-32, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21282823

ABSTRACT

OBJECTIVE: To compare the long-term outcome of open and laparoscopic surgery for Dukes' B and C rectal cancer in a regional hospital in Hong Kong. DESIGN: Retrospective study. SETTING: A regional hospital in Hong Kong. MAIN OUTCOME MEASURES: Survival and local recurrence rates. PATIENTS: Patients with Dukes' B and C rectal cancers underwent elective curative open or laparoscopic surgery during the period December 2000 to December 2006. RESULTS: A total of 222 patients (open surgery, n=133; laparoscopic surgery, n=89) were assessed. The overall 3- and 5-year survival rates for all patients were 72% and 58%, respectively. Local recurrence rates were similar in both groups. Laparoscopic group had better overall survival (P=0.014), however. The overall 3-year survival rates were 79% and 68% in the laparoscopic and open groups, respectively. The corresponding 5-year rates were 75% and 52%. Multivariate analysis also demonstrated that laparoscopic surgery was a significant independent factor for better survival. Chemotherapy, local recurrence, lymph node metastasis, and poorly differentiated tumour were significantly associated with survival. CONCLUSION: Laparoscopic surgery for Dukes' B and C rectal cancer was associated with more favourable survival than with open surgery.


Subject(s)
Laparoscopy/methods , Rectal Neoplasms/surgery , Aged , Female , Humans , Male , Rectal Neoplasms/mortality , Retrospective Studies , Survival Rate , Treatment Outcome
12.
BJOG ; 117(8): 990-6, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20536432

ABSTRACT

OBJECTIVE: The aim of the study was to determine the efficacy of uterine artery embolisation (UAE) combined with local methotrexate (MTX) for the treatment of caesarean scar pregnancy, compared with other traditional modalities, and to investigate the complications associated with this treatment. DESIGN: A retrospective cohort study. SETTING: A large obstetrics and gynaecology unit within a university hospital in China. SAMPLE: Women who were diagnosed with a caesarean scar pregnancy between January 2003 and December 2008, and who had informative case records, were included in the study. METHODS: We reviewed the results for all women who received one of three treatments: dilation and curettage (D&C) (11 patients; group A), systemic MTX (17 patients; group B), and UAE and local MTX (38 patients; group C). MAIN OUTCOME MEASURES: The main outcome measures were success rate, blood loss, time for beta human chorionic gonadotrophin (beta-hCG) to decline to normal values, and the duration of hospital stay. Success was defined as a complete recovery with no severe complications and with the preservation of fertility. RESULTS: A total of 66 women diagnosed with caesarean scar pregnancy between January 2003 and December 2008 were identified, and their data were analysed. The success rate in group C was significantly higher than that in groups A and B after adjusting for beta-hCG level (89.5 versus 27.3 and 58.8%, respectively; P < 0.001). The mean blood loss in group C was lower than in the other two groups (240.5 versus 855.5 and 639.4 ml, respectively; P = 0.008 and 0.009, respectively). The average time for beta-hCG to decline to normal values was significantly shorter in group C than in group B (28.1 versus 44.3 days; P = 0.021). A significantly shorter duration of hospital stay was observed in group C compared with group B (12.5 versus 22.0 days; P = 0.024). CONCLUSIONS: UAE combined with local MTX is of benefit to women wishing to preserve fertility, and is suitable for use as the primary treatment for caesarean scar pregnancy.


Subject(s)
Abortifacient Agents, Nonsteroidal/administration & dosage , Cesarean Section/adverse effects , Cicatrix/therapy , Methotrexate/administration & dosage , Pregnancy Complications/therapy , Uterine Artery Embolization/methods , Administration, Topical , Adult , Chorionic Gonadotropin, beta Subunit, Human/metabolism , Combined Modality Therapy/methods , Female , Humans , Middle Aged , Pregnancy , Pregnancy Complications, Cardiovascular/therapy , Pregnancy, Ectopic/therapy , Retrospective Studies , Young Adult
13.
J Vet Pharmacol Ther ; 33(6): 595-604, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21062313

ABSTRACT

Koalas (n = 43) were treated daily for up to 8 weeks with enrofloxacin: 10 mg/kg subcutaneously (s.c.), 5 mg/kg s.c., or 20 mg/kg per os (p.o.); or marbofloxacin: 1.0-3.3 mg/kg p.o., 10 mg/kg p.o. or 5 mg/kg s.c. Serial plasma drug concentrations were determined on day 1 and again at approximately 2 weeks, by liquid chromatography. The median (range) plasma maximum concentrations (C(max) ) for enrofloxacin 5 mg/kg s.c. and 10 mg/kg s.c. were 0.83 (0.68-1.52) and 2.08 (1.34-2.96) µg/mL and the median (range) T(max) were 1.5 h (1-2) and 1 h (1-2) respectively. Plasma concentrations of orally dosed marbofloxacin were too low to be quantified. Oral administration of enrofloxacin suggested absorption rate limited disposition pharmacokinetics; the median (range) C(max) for enrofloxacin 20 mg/kg p.o. was 0.94 (0.76-1.0) µg/mL and the median (range) T(max) was 4 h (2-8). Oral absorption of both drugs was poor. Plasma protein binding for enrofloxacin was 55.4 ± 1.9% and marbofloxacin 49.5 ± 5.3%. Elevations in creatinine kinase activity were associated with drug injections. Enrofloxacin and marbofloxacin administered at these dosage and routes are unlikely to inhibit the growth of chlamydial pathogens in vivo.


Subject(s)
Anti-Bacterial Agents/pharmacology , Fluoroquinolones/pharmacology , Fluoroquinolones/pharmacokinetics , Phascolarctidae/metabolism , Administration, Oral , Animals , Anti-Bacterial Agents/administration & dosage , Enrofloxacin , Female , Fluoroquinolones/administration & dosage , Fluoroquinolones/blood , Injections, Subcutaneous/veterinary , Intestinal Absorption , Male , Phascolarctidae/blood
14.
Neuropsychobiology ; 60(3-4): 195-203, 2009.
Article in English | MEDLINE | ID: mdl-19893336

ABSTRACT

Users of the popular party drug 3,4-methylenedioxymethamphetamine (MDMA) sometimes report combining MDMA with gamma-hydroxybutyrate (GHB) to enhance the pleasurable effects of both drugs. However, very few studies have examined the influences of this drug combination. The present study investigated the development of locomotor sensitization in laboratory rats given 7 once-weekly exposures to either MDMA, GHB or their combination (MDMA/GHB). The drugs were administered at a high ambient temperature (28 degrees C) to mimic nightclub conditions. MDMA (5 mg/kg), given once weekly, produced a progressively greater locomotor and hyperthermic response over time. In contrast, GHB (500 mg/kg) administered weekly produced consistent low levels of locomotor activity and few changes in body temperature. Rats receiving the mixture of MDMA (5 mg/kg) and GHB (500 mg/kg) showed asymptotic levels of sensitized locomotor activity similar to those seen in rats given MDMA alone, but the development of locomotor sensitization was delayed by coadministered GHB. GHB also delayed the development of MDMA-induced hyperthermia. After a washout period of 5 weeks, rats pre-exposed to MDMA, GHB and MDMA/GHB showed no hyperactivity when tested drug-free in the context in which they had previously received drugs, but displayed a sensitized locomotor response to a low challenge dose of MDMA (2.5 mg/kg). The response to a low dose of methamphetamine (0.5 mg/kg) did not differ among groups. Neurochemical analysis using high-performance liquid chromatography revealed few lasting changes in serotonin, dopamine or their metabolites in the striatum or prefrontal cortex of MDMA- or GHB-pre-exposed rats. These results indicate that GHB modulates the locomotor and hyperthermic response to acute MDMA and that pre-exposure to GHB can sensitize the locomotor response to low doses of MDMA.


Subject(s)
Central Nervous System Agents/pharmacology , Hallucinogens/pharmacology , Locomotion/drug effects , N-Methyl-3,4-methylenedioxyamphetamine/pharmacology , Sodium Oxybate/pharmacology , Animals , Body Temperature , Central Nervous System Agents/administration & dosage , Chromatography, High Pressure Liquid , Corpus Striatum/chemistry , Corpus Striatum/drug effects , Dopamine/analysis , Drug Interactions , Hallucinogens/administration & dosage , Male , N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage , Prefrontal Cortex/chemistry , Prefrontal Cortex/drug effects , Rats , Rats, Wistar , Serotonin/analysis , Sodium Oxybate/administration & dosage , Temperature
16.
Photodiagnosis Photodyn Ther ; 3(4): 247-58, 2006 Dec.
Article in English | MEDLINE | ID: mdl-25046989

ABSTRACT

The photodynamic properties of pyropheophorbide-a methyl ester (MPPa), a semi-synthetic photosensitizer derived from chlorophyll a, were evaluated in a human nasopharyngeal carcinoma HONE-1 cell line. MPPa was non-toxic to the HONE-1. At the concentrations of 0.5-2µM, MPPa-mediated a drug dose-dependent photocytotoxicity in the HONE-1 cells. Confocal microscopy revealed a subcellular localization of MPPa in mitochondria and the Golgi apparatus. MPPa PDT-induced apoptosis was associated with the collapse of mitochondrial membrane potential, release of cytochrome c, the up-regulation of endoplasmic reticulum (ER) stress proteins (calnexin, Grp 94 and Grp78), and the activation of caspases-3 and -9. The photocytotoxicity was reduced by the corresponding specific caspase inhibitors. MPPa PDT-treated HONE-1 cells also up-regulated the gene expression of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and beta-chemokines (MIP-1ß, MPIF-1, and MPIF-2). These results suggest that the MPPa may be developed as a chlorophyll-based photosensitizer for the treatment of nasopharyngeal carcinoma.

17.
Toxicol Mech Methods ; 16(1): 13-9, 2006.
Article in English | MEDLINE | ID: mdl-20021036

ABSTRACT

Changes in cellular energy and redox states in the C6 glioma cells exposed to increasing concentrations of either Zn or Se were studied to examine whether different elements cause different patterns of changes in cellular metabolism. Following a 3-h exposure, both Zn and Se(+4) caused dose-dependent decreases in cell viability and total adenosine nucleotides (TAN = ATP + ADP + AMP). In addition, Zn caused a dose-dependent increase in cellular ATP/TAN and a decrease in the ADP/TAN and AMP/TAN. These changes resulted in a significant increase in energy charge potential (ECP = [ATP + 0.5ADP]/TAN). Se(+4), on the other hand, caused a dose-dependent decrease in ATP/TAN but an increase in both ADP/TAN and AMP/TAN, resulting in a dose-dependent decrease in ECP. Both Zn and Se(+4) caused a dose-dependent decrease in GSH/GSSG and an increase in GSH + GSSG when compared to TAN. In contrast to Zn and Se(+4), the nontoxic Se(+6) caused no significant changes in cellular energy states but reduced the GSH/GSSG ratio from 3.14 +/- 0.49 to 2.05 +/- 0.29, which could be explained by the effect of Se on enzymes responsible for GSH metabolism. As the cellular ATP level has been considered an important element that mediates the mode of cell death, it was suggested that a significant increase in ATP/TAN upon exposure to Zn would indicate that cell death occurred via apoptosis, while Se(+4) caused a different pattern of cell death. This was confirmed by the appearance of cells with fragmented nucleus in cells treated with Zn, but not Se(+4) and Se(+6). The results demonstrated that different chemicals caused different patterns of metabolic changes. The correlation between metabolic changes and the mode of cell death was discussed.

18.
Oncogene ; 20(55): 7945-53, 2001 Nov 29.
Article in English | MEDLINE | ID: mdl-11753677

ABSTRACT

Treatment of SENCAR mouse skin with dibenzo[a,l]pyrene results in abundant formation of abasic sites that undergo error-prone excision repair, forming oncogenic H-ras mutations in the early preneoplastic period. To examine whether the abundance of abasic sites causes repair infidelity, we treated SENCAR mouse skin with estradiol-3,4-quinone (E(2)-3,4-Q) and determined adduct levels 1 h after treatment, as well as mutation spectra in the H-ras gene between 6 h and 3 days after treatment. E(2)-3,4-Q formed predominantly (> or =99%) the rapidly-depurinating 4-hydroxy estradiol (4-OHE(2))-1-N3Ade adduct and the slower-depurinating 4-OHE(2)-1-N7Gua adduct. Between 6 h and 3 days, E(2)-3,4-Q induced abundant A to G mutations in H-ras DNA, frequently in the context of a 3'-G residue. Using a T.G-DNA glycosylase (TDG)-PCR assay, we determined that the early A to G mutations (6 and 12 h) were in the form of G.T heteroduplexes, suggesting misrepair at A-specific depurination sites. Since G-specific mutations were infrequent in the spectra, it appears that the slow rate of depurination of the N7Gua adducts during active repair may not generate a threshold level of G-specific abasic sites to affect repair fidelity. These results also suggest that E(2)-3,4-Q, a suspected endogenous carcinogen, is a genotoxic compound and could cause mutations.


Subject(s)
DNA Adducts/genetics , DNA Damage/genetics , DNA Repair/genetics , Estradiol/analogs & derivatives , Genes, ras/genetics , Mutagenesis/genetics , Skin/metabolism , Animals , Artifacts , Base Sequence , DNA Adducts/chemistry , DNA Adducts/drug effects , DNA Damage/drug effects , DNA Mutational Analysis , DNA Repair/drug effects , Estradiol/chemistry , Estradiol/pharmacology , Female , Mice , Mice, Inbred SENCAR , Mutagens/chemistry , Mutagens/pharmacology , Nucleic Acid Heteroduplexes/drug effects , Nucleic Acid Heteroduplexes/genetics , Point Mutation/genetics , Polymerase Chain Reaction , Skin/drug effects
19.
J Neurosurg ; 69(5): 707-11, 1988 Nov.
Article in English | MEDLINE | ID: mdl-3183731

ABSTRACT

A biomembrane was developed from pig peritoneum treated with 0.65% glutaraldehyde. This was evaluated for use as a dural substitute in an animal model and in a patient population. After being treated with the glutaraldehyde solution, the biomembrane lost its antigenicity while its collagen underwent an irreversible cross-linking reaction, causing it to become a stable nonviable polymer resistant to absorption by the host. The biomembrane was used experimentally in 43 procedures on 20 dogs and was applied clinically in 614 patients. The results demonstrated that it is an acceptable material for the repair of dural defects, with the following advantages: 1) it is nontoxic to the body and brain tissues, with minimal tissue reaction; 2) its biophysical properties facilitate watertight closure with sutures; 3) its distensibility makes it suitable for decompressive surgical dural repair; and 4) its visceral surface is extremely smooth, causing virtually no adhesions with the brain tissue while the outer surface readily heals with the subcutaneous tissue.


Subject(s)
Bioprosthesis , Dura Mater/surgery , Adolescent , Adult , Animals , Central Nervous System Diseases/surgery , Child , Dogs , Dura Mater/ultrastructure , Fever/etiology , Humans , Microscopy, Electron , Middle Aged , Postoperative Complications , Swine
20.
Physiol Behav ; 82(2-3): 357-68, 2004 Sep 15.
Article in English | MEDLINE | ID: mdl-15276799

ABSTRACT

Lactic acid accumulation in the caecum and colon resulting from the fermentation of carbohydrates can lead to deleterious effects in ruminant and monogastric animals, including humans. In the present study, we examined the behavioural effects of two types of commonly consumed foods: soluble and fermentable carbohydrates (FCs). Thirty-six male Wistar rats were fed either a commercial rat and mouse chow, a soluble carbohydrate (SC)-based diet or an FC-based diet. Social interaction, anxiety, aggression and locomotor activity were examined by employing a social interaction test and a light/dark emergence test, while physical parameters of hindgut fermentation were examined after sacrifice, either 3 or 21 h after feeding. Results showed that anxiety (spending less time in the light compartment during the light/dark emergence test) and aggression (increased fighting during the social interaction test) were increased following raised concentrations of fermentation end products, such as lactic acid and volatile fatty acids (VFAs) in the caecum of rats. These associations occurred regardless of dopamine and 5-HT concentrations in the prefrontal cortex (PFC) and provide evidence supporting a general effect of FCs on behaviour. Possible mechanisms of action along with similarities between a rat and human model of acidosis are discussed.


Subject(s)
Aggression/physiology , Anxiety/metabolism , Cecum/metabolism , Colon/metabolism , Dietary Carbohydrates/metabolism , Fermentation/physiology , Acetates/analysis , Animal Feed , Animals , Carbohydrates/chemistry , Cecum/chemistry , Colon/chemistry , Dietary Fiber/metabolism , Dopamine/metabolism , Feces/chemistry , Lactic Acid/analysis , Male , Motor Activity/physiology , Prefrontal Cortex/metabolism , Random Allocation , Rats , Rats, Wistar , Serotonin/metabolism , Social Behavior
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