1.The cytotoxic effect,cell cycle perturbations and apoptosis of paclitaxel in human bladder cancer lines
Jiang ZHU ; Xu-Dong YAO ; Xiao-Da TANG ; Al ET
China Oncology 1998;0(04):-
Purpose:To determine the efficacy of paclitaxel in human bladder cancer lines and to investigate the mechanism by which paclita xel induce apoptosis in human bladder cancer cells. Methods:BIU-87, 5637, T24 and EJ bladder cancer cell lines wer e cultured by techniques of cell culture in vitro. The cytotoxic activity an d apoptosis induction abilities of paclitaxel were analyzed by MTT and Annexin- V assay as well as DNA cytometry , respectively. The effects on the cell cycle w ere assessed by flow cytometry of propidium iodide. The expressions of Bcl-2, B ax, p53 and Caspase3 proteins were determined by flow cytometry immunofluorescen ce. Results:Paclitaxel dose-dependent inhibition of cell prolifera tion was seen.Paclitaxel induced G_2/M arrest (71.29% and 64.57%) which was maximal in 5637 and EJ cell lines. While paclitaxel at 1?g/ml concentration ex posure to 5637 12h, 14h and 48h respectively, the apoptosis rates of the respect ive times were 5.0%, 12.9%, 27.6%. The expression of genes p53 and Bcl-2 was no t influenced, whereas the expression of Bax and Caspase3 had increases time-dep endently after exposure to paclitaxel. The analysis of Annexin-V showed a drama tic dose-dependent increase of apoptosis. Conclusions:Paclitaxel inhibited bladder cancer cells prolifera tion and had more effect on those cells whose grade was lower and doubling time was longer. Paclitaxel could block G_2/M arrest, and induce apoptosis by th e path of Bcl-2/Bax in bladder cancer cell lines.
2.Some controversial conditions in the management of chronic prostatitis/chronic pelvic pain syndrome.
National Journal of Andrology 2003;9(6):403-406
Chronic prostatitis (CP)/chronic pelvic pain syndrome (CPPS) is a common problem of medically controversial condition that causes considerable morbidity and impact on life. Although there are many competing causes proposed, the etiology and pathogenesis of CP/CPPS remain unclear. The causative factors underlying the CPPS are not fully understood. The optimal management of CP/CPPS is still unknown. The guideline of diagnosis and management of CP/CPPS based on evidence base medicine is not yet established. Many problems are still not resolved, such as the significance of leukocytes and the role of inflammation in CP/CPPS, the significance of bacteria presence and the role of infection in CP/CPPS, the correlation between leukocytes/bacteria and severity of symptoms, how to divide the subgroups of CP/CPPS, the role of antimicrobial therapy in the treatment of men with CP/CPPS, why patients with category IIIb complain of symptoms, while those with category IV complain of none. Although CP/CPPS is now achieving greater recognition, well-designed studies with large sample size should be performed.
Chronic Disease
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Humans
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Male
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Pelvic Pain
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etiology
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microbiology
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therapy
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Prostatitis
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etiology
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microbiology
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therapy
3.Progress in small-molecule inhibitors of Bcl-2 family proteins.
Yong TANG ; Da-yong ZHANG ; Xiao-ming WU
Acta Pharmaceutica Sinica 2008;43(7):669-677
Apoptosis is an essential factor in keeping homeostasis of the organism. Apoptosis is regulated by a series of cytokines. Bcl-2 family proteins are key regulators of apoptosis. The Bcl-2 family includes both anti- and pro-apoptotic proteins with opposing biological functions. Their interaction regulates the transmission of the apoptosis signal. High expression of anti-apoptotic members such as Bcl-2 and Bcl-xL are commonly found in human cancers. In recent years, following the disclosing of the crystal structures of Bcl-2 family proteins, researchers have paid attention to the development of the small molecule inhibitors of Bcl-2 family proteins. This article reviews the progress in this field from the view of drug design.
Antimycin A
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chemistry
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pharmacology
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Antineoplastic Agents
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chemistry
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pharmacology
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Apoptosis
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drug effects
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Benzopyrans
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chemistry
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pharmacology
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Biphenyl Compounds
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chemistry
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pharmacology
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Cell Line, Tumor
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Drug Design
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Drugs, Chinese Herbal
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chemistry
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pharmacology
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Gossypol
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chemistry
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pharmacology
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Humans
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Nitriles
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chemistry
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pharmacology
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Nitrophenols
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chemistry
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pharmacology
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Piperazines
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chemistry
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pharmacology
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Proto-Oncogene Proteins c-bcl-2
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antagonists & inhibitors
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pharmacology
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Structure-Activity Relationship
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Sulfonamides
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chemistry
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pharmacology
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Thiazoles
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chemistry
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pharmacology
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bcl-X Protein
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antagonists & inhibitors
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pharmacology
4.Protective effect of melatonin on oxidative stress inducing hair follicle injury in scald rat.
Jun ZHANG ; Da-Hai HU ; Gang CHEN ; Xiao-Zhi BAI ; Chao-Wu TANG
Chinese Journal of Burns 2009;25(2):129-132
OBJECTIVETo investigate the protective effect of melatonin on residual hair follicle cells of scald rats at early stage.
METHODSEighteen male Sprague-Dawley rats were randomly divided into scald group, treatment group, sham group , with 6 rats in each group. The rats in scald group and treatment group were subjected to 30% TBSA partial thickness scald on the back, and were resuscitated with balanced solution after 1 hour, while those in sham group were immersed in water at 37 degrees C for 25 s to simulate scald, and did not receive fluid replacement. Rats in treatment group were intraperitoneally injected with 10 mg/kg melatonin solution at 1 minute, 8 hours and 12 hours after scald, while those in sham group and scald group were given equal volume of 1% alcohol sodium-isotonic saline instead. Tissue samples were harvested at 6, 12 and 24 post scald hours (PSH) for determination of MDA and GSH levels. Apoptosis of residul hair follicle was detected by TUNEL method and immunohistochemistry of caspase-3.
RESULTSThe level of MDA in scald group at each time point was much higher than that in sham group (P < 0.01) and treatment group (P < 0.05), and it peaked at 12 PSH. The changes in GSH were just opposite to that of MDA. Under fluorescence microscope, the residual hair follicle cells were blue, and the apoptotic cells appeared green. The apoptosis rate in scald group at 6, 12, 24 PSH was obviously higher than that in sham (P < 0.01) and treatment groups (P < 0.05), which was (20.2 +/- 3.4)% vs (4.3 +/- 2.3)% vs (10.9 +/- 3.2)%, (31.2 +/- 3.6)% vs (5.1 +/- 2.5)% vs (19.1 +/- 3.7)%, (22.4 +/- 2.7)% vs (4.1 +/- 2.4)% vs (13.1 +/- 3.4)%, respectively. The score of caspase-3 positive cell in scald group was higher than those in sham group (P < 0.01) and treatment group (P < 0.05).
CONCLUSIONSThere is obvious correlation between oxidative stress and apoptosis rate of hair follicle cells in rats with partial thickness scald. Early administration of melatonin may have anti-apoptosis ability for residual hair follicle cells by attenuation of oxidative stress.
Animals ; Apoptosis ; Burns ; drug therapy ; metabolism ; Hair Follicle ; cytology ; metabolism ; Male ; Melatonin ; therapeutic use ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley
5.Androgen receptor isoforms in LNCaP cell and human prostate.
National Journal of Andrology 2002;8(3):169-172
OBJECTIVESTo investigate the androgen receptor (AR) isoforms expression in human benign and malignant prostatic tissues and LNCaP cells.
METHODSUsing high resolution isoelectric focusing (IEF), the different expression of AR isoforms were demosntrated in human benign and malignant prostatic tissues and LNCaP cells.
RESULTSData were obtained from 41 AR-positive BPH, three prostatic cancer specimens, and LNCaP cells. From these materials, three types of AR isoforms were detected with pI values at 6.5, 6.0 and 5.3. In the case of BPH tissues, 15 (36.5%) specimens expressed all the three types of isoforms at pI 6.5, 6.0 and 5.3, and 10 (24.4%) samples contained isoforms at pI 6.5 and 5.3, five (12.2%) samples indicated isoforms at pI 6.5 and 6.0, four (9.8%) showed the isoforms at pI 6.0 and 5.3. Of all the 41 specimens, two (4.9%) and two (4.9%) as well as three (7.3%) denoted the isoforme at pI 6.5, 6.0 and 5.3 respectively. As for three prostatic cancer specimens, one sample showed all the three types of AR isoforms at pI 6.5, 6.0, 5.3, but another specimen expressed at pI 6.5 and 6.0, and only one failed to indicate any types of isoforms. LNCaP cells expressed all three types of AR isoforms at pI 6.5, 6.0 and 5.3. Binding of 3H-dihydrotestosterone to these three types of isoforms was inhibited by the addition of 100-fold excess of DHT and testosterone. No effect of progesterone, oestradiol and diethylstilboestrol on tritiated hormone binding was observed.
CONCLUSIONSThe expression of AR isoforms is different among various patients and different between BPH and LNCaP cells, though no clear explanation could be induced for this. These results suggest the possibility of explaining effective hormonal therapy to prostatic disease in the future.
Humans ; Male ; Prostate ; metabolism ; Protein Isoforms ; metabolism ; Receptors, Androgen ; metabolism ; Tumor Cells, Cultured
6.Effects of delta-opioid receptor stimulation on survival of cultured myocardial cells upon to serum deprivation.
Da-Peng WANG ; Hong-Xin WANG ; Bo TANG ; Xiao-Chun YU
Chinese Journal of Applied Physiology 2008;24(3):274-278
AIMTo study upon to serum deprivation if delta-opioid receptor activation has direct effect on cultured impaired cardiomyocytes survival.
METHODSMyocardial cells of neonatal rats were cultured in vitro. The cell viability was determined with crystal violet staining uptake. The percentage of S + G2 + M in cell cycle was determined by flow cytometry. Apoptosis rates were determined by flow cytometry (FCM). The expression of Caspase-3 were investigated by Western blotting.
RESULTSMyocardial cells of neonatal rats were cultured of serum-free in vitro, apoptotic index was significantly increased, the expression of Caspase-3 was significantly increased, free-serum induced apoptosis in cardiac myocytes after 48 h. At concentrations of 10 nmol x L(-1) - 10 micromol x L(-1), a delta opoid receptor agonist [D-Ala2, D-Leu5]-enkephalin DADLE promoted the myocardial cells survival, in a concentration-dependent manner. The optimal response was achieved at 0.1 micromol x L(-1), which increase survival index of cardiac myocyte, percentage of S + G2 + M in cell cycle, decrease apoptotic index of cardiac myocyte, and the expression activate caspase-3. Delta-opioid receptor antagonist naltrindole at 10 micromol x L(-1) inhibited the promoting effects of DADLE, which decrease survival index of cardiac myocyte, and percentage of S + G2 + M in cell cycle, increase apoptotic index of cardiac myocyte and the expression of Caspase-3.
CONCLUSIONThe protective of delta-opioid receptor activation can promote survival in cultured impaired myocardial cells.
Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Survival ; drug effects ; Cells, Cultured ; Culture Media, Serum-Free ; Enkephalin, Leucine-2-Alanine ; pharmacology ; Female ; Male ; Myocytes, Cardiac ; cytology ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid, delta ; agonists
7.Anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways act as potent immunoregulatory cells in vitro and vivo.
Yong CAI ; Pei-jun ZHOU ; Xiao-da TANG
Chinese Medical Journal 2004;117(8):1178-1183
BACKGROUNDThis study was to evaluate whether anergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro and prolong cardiac allograft survival after adoptive transfer.
METHODSAnergic cells were induced in vitro by the addition of anti-CD154 and anti-CD80 monoclonal antibodies (mAbs) to primary MLR (mixed lymphocyte reaction) consisting of BALB/c as responder and C3H as stimulator. Anergic cells were added to a newly formed MLR in assessing the regulatory capacity and antigen specificity of anergic cells. The ability of anergic cells to respond to antigen and/or exogenous recombinant mouse interleukin-2 (rmIL-2) was tested. For in vivo studies, anergic cells were intravenously injected into 3.0-Gy gamma-irradiated BALB/c mice immediately after heterotopic abdominal cardiac transplantation. To prolong allograft survival, recipient mice injected with anergic cells received rapamycin therapy [1 mg.day(-1).kg(-1)].
RESULTSAnergic cells strongly suppressed the proliferation of naicaron;ve BALB/c splenocytes against the original (C3H) stimulator in a dose-dependent manner, but they failed to suppress the proliferation of naicaron;ve BALB/c splenocytes against the third-party (C57BL/6J) stimulator. The anergic state was reversed by both original (C3H) stimulator and additional exogenous IL-2. In in vivo studies, untreated irradiated BALB/c mice rejected C3H cardiac allografts with a mean survival time of (8.6 +/- 1.1) days, whereas those injected with the anergic cells rejected the allografts with a mean survival time of (11.8 +/- 1.9) days, which was slightly longer than that of the untreated mice. The protocol based on anergic cells injection plus rapamycin therapy could prolong allograft survival significantly [(29.6 +/- 4.4) days].
CONCLUSIONSAnergic cells induced by the blockade of CD40-CD154 and CD28-B7 costimulatory pathways can act as potent immunoregulatory cells in vitro, and prolong cardiac allograft survival after adoptive transfer in the presence of rapamycin therapy. This procedure might be clinically useful for prolonging allograft survival if optimal protocols are developed.
Animals ; Antibodies, Monoclonal ; pharmacology ; B7-1 Antigen ; physiology ; CD28 Antigens ; physiology ; CD40 Antigens ; physiology ; CD40 Ligand ; physiology ; Graft Survival ; Heart Transplantation ; Lymphocyte Activation ; Lymphocyte Culture Test, Mixed ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory ; immunology ; Transplantation, Homologous
8.ERK1/2 signaling pathway is involved in 15-hydroxyeicosatetraenoic acid-induced hypoxic pulmonary vasoconstriction.
Chang-Lian LÜ ; Hong YE ; Xiao-Bo TANG ; Da-Ling ZHU
Acta Physiologica Sinica 2005;57(5):605-611
Hypoxia-induced 15-hydroxyeicosatetraenoic acid (15-HETE) is an essential mediator to constrict pulmonary arteries (PA). The signaling pathway involved in 15-HETE-induced PA vasoconstriction remains obscure. The aim of the present study was to test the hypothesis that hypoxic PA constriction induced by 15-HETE was possibly regulated by the extracellular signal-regulated kinase-1/2 (ERK1/2) pathway. PA ring tension measurement, Western blot and immunocytochemistry were used in the study to determine the possible role of ERK1/2 in 15-HETE-induced PA vasoconstriction. The organ bath for PA rings tension study was employed. Adult male Wistar rats were raised in hypoxic environment with fractional inspired oxygen (FIO2, 0.12) for 9 d. PA 1~1.5 mm in diameter were dissected and cut into 3 mm long rings for tension study. ERK1/2 up-stream kinase (MEK) inhibitor PD98059, which blocks the activation of ERK1/2, was used. The results showed that pretreatment of PD98059 significantly blunted 15-HETE-induced PA vasoconstrictions in the rings from hypoxic rat. Moreover, in endothelium-denuded rings, PD98059 also significantly attenuated 15-HETE-induced vasoconstriction. Phosphorylation of ERK1/2 in pulmonary arterial smooth muscle cells (PASMCs) of rat was enhanced evidently when stimulated by 15-HETE. Thus, the data suggest that ERK1/2 signaling pathway is involved in 15-HETE-induced hypoxic pulmonary vasoconstriction.
Animals
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Flavonoids
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pharmacology
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Hydroxyeicosatetraenoic Acids
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antagonists & inhibitors
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pharmacology
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Hypoxia
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physiopathology
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MAP Kinase Signaling System
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physiology
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Male
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Muscle, Smooth, Vascular
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cytology
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Myocytes, Smooth Muscle
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drug effects
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Pulmonary Artery
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cytology
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drug effects
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physiopathology
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Rats
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Rats, Wistar
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Vasoconstriction
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drug effects
9.Characteristic pattern of human prostatic growth with age.
Shu-Jie XIA ; Xiao-Xin XU ; Jian-Bao TENG ; Chun-Xiao XU ; Xiao-Da TANG
Asian Journal of Andrology 2002;4(4):269-271
AIMTo study the characteristic pattern of the age-related growth of the human prostate gland.
METHODSThe volume (weight) of the prostate in 1,601 males, aged from newborn to 92 years, was determined by B-ultrasonography.
RESULTSProstatic volume determination by B-ultrasonography in 1601 males (1301 normal subjects and 300 BPH patients) pointed out that the age-stratified growth of human prostate could be categorized into 4 life stages: (1) the first slow growing phase (from newborn to 9 years): the prostate grows slowly at a rate of 0.14 g per year; (2) the first rapid growing phase (from 10 to 30 years): the prostate grows at a rate of 0.84 g per year; (3) the second slow growing phase (from 30 to 50 years), the prostate grows at a rate of 0.21 g per year; (4) the second rapid growing phase (from 50 to 90 years): the prostate grows at one of the following rates: in one group the growth rate is of 0.50 g per year and in the other 1.20 g per year, leading to benign prostatic hyperplasia (BPH).
CONCLUSIONThe volumes of the prostate are different in different age groups and it grows with age at different rates in four life phases. The prostate growth in phases can be expressed by the following equation: Y=19.36+1.36X'-0.58X'(2+0.33X'3), where Y = prostate volume, X = age (up to 70 years), X'=(X-35.5)/10.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Organ Size ; Prostate ; anatomy & histology ; diagnostic imaging ; growth & development ; Ultrasonography
10.Surgical treatment of metastatic spinal tumors by anterial approach.
Wei GUO ; Akbar ; Xiao-dong TANG ; Nan LI ; Shun TANG ; Da-sen LI
Acta Academiae Medicinae Sinicae 2005;27(2):179-184
OBJECTIVETo investigate the efficacy of surgical treatment of the patients with metastatic spinal tumors by anterial decompression and stabilization.
METHODSFrom December 1997 to December 2003, 93 patients (40 women and 53 men) with metastatic spinal tumors were treated in our department. The locations of the tumor included, thoracic vertebra (53 cases), lumbar vertebra (33 cases), and cervical region (7 cases). The original tumors included lung cancer (21 cases), renal cancer (13 cases), prostate cancer (8 cases), hepatic cancer (5 cases), breast cancer (13 cases), thyroid cancer (5 cases), gastrointestinal tumor (3 cases), and multiple myeloma (8 cases). However, no primary tumor was found in the rest of 17 cases. Among 54 of 93 patients who presented with neurological dysfunction, 16 patients completely paralyzed and others incompletely paralyzed. The follow-up time ranged from 10 to 72 months.
RESULTSPain was relieved in 87 of 93 patients (93.5%) and neurological function was improved in 47 of the 54 patients. Among 16 completely paralyzed patients, 7 patients experienced a neurological function improvement (from Frankel grade A or B to C or D after decompression). The average amount of blood transfused was 3000 ml. No severe complications were seen in our series. The one-year survival rate was 85% (79 cases).
CONCLUSIONSThe integrity of the spinal column structure and neurological function should be considered firstly in the treatment of spinal metastasis. Thorough resection of metastatic tumor and stable internal fixation by anterior approach should be performed when single or two vertebra are involved. In order to alleviate paralysis, promote spinal stability, and improve the quality of life, urgent decompression should be performed on patient with spinal metastasis.
Breast Neoplasms ; pathology ; surgery ; Decompression, Surgical ; methods ; Female ; Follow-Up Studies ; Humans ; Internal Fixators ; Kidney Neoplasms ; pathology ; surgery ; Lumbar Vertebrae ; surgery ; Lung Neoplasms ; pathology ; surgery ; Male ; Spinal Neoplasms ; secondary ; surgery ; Thoracic Vertebrae ; surgery