RESUMO
The Spaceborne Global Lightning Location Network (SGLLN) serves the purpose of identifying transient lightning events occurring beneath the ionosphere, playing a significant role in detecting and warning of disaster weather events. To ensure the effective functioning of the wideband electromagnetic pulse detector, which is a crucial component of the SGLLN, it must be tested and verified with specific signals. However, the inherent randomness and unpredictability of lightning occurrences pose challenges to this requirement. Consequently, a high-power electromagnetic pulse radiation system with a 20 m aperture reflector is designed. This system is capable of emitting nanosecond electromagnetic pulse signals under pre-set spatial and temporal conditions, providing a controlled environment for assessing the detection capabilities of SGLLN. In the design phase, an exponentially TEM feed antenna has been designed firstly based on the principle of high-gain radiation. The feed antenna adopts a pulser-integrated design to mitigate insulation risks, and it is equipped with an asymmetric protective loading to reduce reflected energy by 85.7%. Moreover, an innovative assessment method for gain loss, based on the principle of Love's equivalence, is proposed to quantify the impact of feed antenna on the radiation field. During the experimental phase, a specialized E-field sensor is used in the far-field experiment at a distance of 400 m. The measurements indicate that at this distance, the signal has a peak field strength of 2.2 kV/m, a rise time of 1.9 ns, and a pulse half-width of 2.5 ns. Additionally, the beamwidth in the time domain is less than 10°. At an altitude of 500 km, the spaceborne detector records a signal with a peak field strength of approximately 10 mV/m. Particularly, this signal transformed into a nonlinear frequency-modulated signal in the microsecond range across its frequency spectrum, which is consistent with the law of radio wave propagation in the ionosphere. This study offers a stable and robust radiation source for verifying spaceborne detectors and establishes an empirical foundation for investigating the impact of the ionosphere on signal propagation characteristics.
RESUMO
Covalent organic frameworks (COFs) are appealing photocatalysts for toxic chemical degradation. Great efforts have been devoted to regulate the photocatalytic performance of COFs by tuning their organic building blocks, but the relationship between COF linkage and photochemical properties has rarely been explored. Herein, we report the synthesis and characterisation of a novel aminal-linked porphyrinic COF, namely Por-Aminal-COF. Por-Aminal-COF (0.25â mol %) showed excellent photocatalytic activity toward the detoxification of the sulfur mustard simulant with a half-life (t1/2 ) of 5â min, which is far lower than that of traditional imine-linked Por-COF (t1/2 =16â min). Transient absorption spectroscopy indicated that the aminal linkages of Por-Aminal-COF facilitated the intersystem crossing process. Thus, Por-Aminal-COF showed higher triplet-state generation efficiency compared with Por-COF, consequently promoting the activation of oxygen molecular to singlet oxygen.
RESUMO
Hedyotis diffusa polysaccharides, as the main component and an important bioactive substance of Hedyotis diffusa, are effective immunomodulators with various pharmacological activities, including antitumour, anti-inflammatory, antioxidant, anti-fatigue and immunity-enhancing activities. The total polysaccharides extracted from Hedyotis diffusa and Scutellaria barbata have great effects in treating liver cancer, gastric cancer, rectal cancer, glioma and nasopharyngeal carcinoma. Moreover, different materials and extraction methods result in differences in the structure and bioactivity of Hedyotis diffusa polysaccharides. Therefore, this paper summarizes the isolation, purification, structural characteristics, pharmacological activities, and combined action of Hedyotis diffusa polysaccharides to provide a reference for further study.
Assuntos
Hedyotis/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/farmacologia , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Bronchopulmonary dysplasia (BPD) is characterized by impaired vascular and alveolar development, and the underlying molecular mechanisms have remained elusive. MicroRNAs are important players in various biological functions including the pathogenesis of BPD. The present study aimed to examine the expression of miR-203a-3p in the peripheral blood of BPD patients and elucidate the mechanisms underlying miR-203a-3p-mediated progression of BPD. We examined the expression of miR-203a-3p in the peripheral blood of BPD patients and found that miR-203a-3p was up-regulated in the patients. Additionally, the mRNA expression levels of vascular endothelial growth factor A (VEGFA) and hypoxia-inducible factor-1alpha were down-regulated in the BPD patients. Further in vitro studies showed that miR-203a-3p suppressed the expression of VEGFA in RLE-6TN cells by targeting the VEGFA 3' untranslated region. Overexpression of miR-203a-3p inhibited the viability of RLE-6TN cells and induced cell apoptosis, whereas the knockdown of miR-203a-3p exerted opposite effects. VEGFA treatment significantly attenuated the increase in the RLE-6TN cell apoptotic rates induced by miR-203a-3p overexpression; while VEGFA knockdown significantly increased the cell apoptotic rates of RLE-6TN cells, which was partially reversed by the treatment with miR-203a-3p inhibitor. Furthermore, miR-203a-3p was up-regulated, whereas VEGFA was down-regulated in the lung tissues of BPD rats, and sequestration of the expression of miR-203a-3p prevented hyperoxia-induced lung damage, increased VEGFA mRNA and protein expression levels, and promoted the protein expression of ERK, PI3K, and p38 in the lung tissues of BDP rats. In summary, the findings of our study indicate that miR-203a-3p knockdown alleviates hyperoxia-induced lung tissue damage in the BPD rat model, and its effect may be associated with the up-regulation of VEGF.
Assuntos
Displasia Broncopulmonar/metabolismo , MicroRNAs/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Displasia Broncopulmonar/genética , Displasia Broncopulmonar/patologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , MicroRNAs/genética , MicroRNAs/fisiologia , Ratos , Ratos Sprague-Dawley , Transfecção , Regulação para CimaRESUMO
OBJECTIVE: To explore the clinical efficacy of C3 expanded half lamina excision combined with unilateral open door laminoplasty for multiple segmental cervical spinal cord compression syndrome. METHODS: The clinical data of 58 patients with multiple segmental cervical spinal cord compression syndrome underwent surgical treatment between September 2014 and May 2018 were retrospectively analyzed. There were 34 males and 24 females with a mean age of 64.4 years old (ranged from 46 to 78 years old). Among them, 28 cases received the surgery of C3 expanded half lamina excision combined with C4-C7 unilateral open-door laminoplasty (improvedgroup), and 30 cases received a single C3-C7 unilateral open-door laminoplasty (traditional group). Operation time, intraoperative blood loss, complications including C5 nerve root palsy and axial symptoms were compared between two groups. To evaluate the situation of the imaging indicators by measuring the space available for the spinal cord through cross sectional MRI of cervical spine at the narrowest segment of C3 (including intervertebral disc levels of C3, 4). Pre- and post-operative Japanese Orthopedic Association(JOA) score, Neck Disability Index(NDI) score, and improvement rate of neurological function, were recorded and analyzed between the two groups. RESULTS: All the patients were followed up for 12 to 18 months with an average of(14.5±1.8) months for improved group and (14.5±1.9) months for traditional group, and no significant difference was found between the two groups (P>0.05). There was no significant difference in intraoperative blood loss and C5 nerve root palsy between the two groups (P>0.05). The operation time (119±10) min vs (126±12) min and axial symptoms 7.1%(2/28) vs 26.6%(8/30) was significant difference between the two groups (P<0.05). Preoperative and postoperative space available for the spinal cord of C3 was (93.61±9.02) mm3 and (153.50±12.76) mm3 respectively, which was obtained obvious improvement in all patients(P<0.05). At the final follow up, JOA scores of improved group and traditional group were 14.36±1.70 and 14.03±1.82 respectively, and NDI scores were 10.36±2.55 and 12.47±3.46 respectively, there was significant difference between two groups (P<0.05). However, there was no significant difference between two groups for the improvement rate (68.36±0.12)%VS (65.01±0.12)%of neurological function(P>0.05). CONCLUSION: C3 expanded half lamina excision combined with unilateral open-door laminoplasty is an effective method to treat multiple segmental cervical spinal cord compression syndrome, for it can not only fully relieved spinal cord compression, but also achievedgood effect in preventing complications such as axial symptoms by reducing stripping of muscles from C2 spinous process.
Assuntos
Laminoplastia , Compressão da Medula Espinal , Idoso , Vértebras Cervicais/cirurgia , Estudos Transversais , Feminino , Humanos , Laminectomia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Hedyotis diffusa is a well-known traditional Chinese herbal medicine. The polysaccharides extracted from H. diffusa (HDP) exhibit a range of pharmacological activities. Transfusion of cytokine-induced killer (CIK) cell is one type of adoptive cellular immunotherapy, which is becoming an important method of cancer immunotherapy. In this present study, we investigate the immunostimulatory effect of HDP on CIK cells. CIK cells were generated by culturing and stimulating peripheral blood monocytes of healthy volunteers. They were treated with HDP at three different concentrations (10, 50, and 100⯵g/mL). The effect of HDP on CIK cell populations, intracellular cytokine production, and apoptosis was examined by flow cytometry. The antitumor effect of HDP on CIK cells was determined by cytotoxicity assay. Furthermore, the effect of HDP on the antitumor activity of CIK cells in a mouse model was investigated. HDP increased the percentage of CD3+CD56+ CIK cells but did not significantly change the percentage of CD4+, CD8+, or CD4+CD25+ CIK cells. The HDP-treated CIK cells showed a greater ability to kill tumor cells, as well as higher production of interferon-γ and tumor necrosis factor-α, compared with the no-HDP-treated CIK cells. The HDP-treated CIK cells also found a lower apoptosis level in vitro. Moreover, HDP combined with CIK cells had a stronger inhibitory effect on tumor growth in the mouse model compared with the CIK or HDP treatment alone. In conclusion, the results indicated that HDP enhanced the antitumor activity of CIK cells and could be used for cancer immunotherapy combined with CIK cell therapy.
Assuntos
Antineoplásicos/farmacologia , Células Matadoras Induzidas por Citocinas/efeitos dos fármacos , Células Matadoras Induzidas por Citocinas/imunologia , Hedyotis/química , Polissacarídeos/imunologia , Polissacarídeos/farmacologia , Células A549 , Animais , Apoptose/efeitos dos fármacos , Apoptose/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Antígeno CD56/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Citotoxicidade Imunológica/efeitos dos fármacos , Citotoxicidade Imunológica/imunologia , Células HCT116 , Humanos , Imunoterapia Adotiva/métodos , Interferon gama/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Dioscin, a typical saponin, is widely present in the family of Dioscoreaceae, Liliaceae, Caryophyllaceae and Rosaceae, especially in Dioscoreaceae, including Discorea nipponica Makino, Dioscorea zingiberensis C. H. Wright and Dioscorea panthaica Prain et Burkill. Traditional Chinese medicine reported that dioscin plays a role in expectorant, relaxing the muscles and stimulating the blood circulation, aiding digestion and diuresis. With the development of science and technology in recent years, some new extraction and separation techniques and methods have been applied to the study of dioscin, and more and more pharmacological effects were found. Modern pharmacology studies have confirmed that dioscin had some activities on desensitization, anti-inflammatory, lipid-lowering, anti-tumor, hepatoprotection and anti-viral. After oral administration, dioscin is metabolized to diosgenin, which is the true active ingredient and is an important raw material to synthesize steroid hormone drugs. Therefore, the studies on dioscin are valueable and promising. In this review, we make a summary on the researches of dioscin including the extraction technology, separation and prepara- tion, chemical synthesis, drug metabolism, determination and pharmacological researches.
Assuntos
Produtos Biológicos/farmacologia , Diosgenina/análogos & derivados , Extratos Vegetais/farmacologia , Animais , Produtos Biológicos/efeitos adversos , Produtos Biológicos/química , Diosgenina/efeitos adversos , Diosgenina/química , Diosgenina/farmacologia , Humanos , Extratos Vegetais/efeitos adversos , Extratos Vegetais/químicaRESUMO
Dioscin, a natural steroid saponin, has been widely investigated. However, its anti-cancer activities on human lung cancer cells are still unknown. In the present paper, the inhibitory effects of dioscin were investigated, and the results showed that dioscin inhibited the proliferation of human A549, NCI-H446 and NCI-H460 cancer cells. DNA damage and cell apoptosis in dioscin-treated cells were found through single cell gel electrophoresis and in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. Furthermore, dioscin caused mitochondrial structure changes and blocked cell cycle at S phase based on transmission electron microscope and flow cytometry analysis. In addition, dioscin treatment caused the release of cytochrome c from mitochondria into cytosol. The activities of Caspase-3 and -9 in dioscin-treated groups were significantly increased compared with control group. Western blotting analysis showed that dioscin significantly down-regulated the expressions of Bcl-2 and Bcl-xl, and up-regulated the expressions of Bax, Bak and Bid. Our results indicate that dioscin has anticancer activities against human lung cancer cells through inducing cell cycle arrest, DNA damage and activating mitochondrial signal pathway.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Dano ao DNA , Diosgenina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/ultraestrutura , Adenocarcinoma de Pulmão , Proteínas Reguladoras de Apoptose/agonistas , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/metabolismo , Carcinoma de Células Grandes/ultraestrutura , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citosol/efeitos dos fármacos , Citosol/metabolismo , Citosol/ultraestrutura , Diosgenina/farmacologia , Humanos , Concentração Inibidora 50 , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/ultraestrutura , Microscopia Eletrônica de Transmissão , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Transporte Proteico/efeitos dos fármacos , Fase S/efeitos dos fármacos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/ultraestruturaRESUMO
Alterations in energy metabolism play a major role in cancer development. Aconitase (ACO2) is an essential enzyme located in the mitochondria and catalyzes the interconversion of citrate and isocitrate in the tricarboxylic acid cycle. Recent studies suggest that the expression of ACO2 may be altered in certain types of cancer. The purpose of this study was to examine ACO2 expression in clinical tumor specimens from patients with gastric cancer and to evaluate the clinical relevance of ACO2 expression in gastric cancer. A total of 456 paraffin-embedded gastric cancer tissues and 30 pairs of freshly frozen tissues were used in this study. Real-time quantitative reverse transcription polymerase chain reaction, western blotting, and immunohistochemical staining were performed to measure ACO2 expression in tumor tissues and matched adjacent non-tumorous tissues. The results showed that the expression of ACO2 was significantly down-regulated in gastric cancer tissues compared with matched adjacent nontumorous tissues and was associated with clinical stage (p = 0.001), T classification (p = 0.027), N classification (p = 0.012), M classification (p = 0.002), and pathological differentiation states (p = 0.036). Patients with lower ACO2 expression had a shorter survival time than those with higher ACO2 expression. Univariate and multivariate analyses indicated that ACO2 expression functions as an independent prognostic factor (p < 0.001). Our data suggested that ACO2 could play an important role in gastric cancer and may potentially serve as a prognostic biomarker.
Assuntos
Aconitato Hidratase/antagonistas & inibidores , Biomarcadores Tumorais/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica , Proteínas Mitocondriais/antagonistas & inibidores , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/enzimologia , Aconitato Hidratase/biossíntese , Aconitato Hidratase/genética , Idoso , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/biossíntese , Proteínas Mitocondriais/genética , Prognóstico , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Neoplasias Gástricas/genética , Taxa de Sobrevida/tendênciasRESUMO
OBJECTIVE: To evaluate the early outcome of anterior cervical discectomy and fusion (ACDF) using a Zero-profile implant system (Zero-P) for interbody fusion in the treatment of cervical spondylosis. METHODS: Between March 2010 and June 2011, 25 patients with cervical spondylosis underwent ACDF with Zero-P. There were 13 males and 12 females with an average age of 44.2 years (range, 26-67 years), including 14 cases of nerve root cervical spondylosis, 6 cases of spinal cervical spondylosis, and 5 cases of mixed cervical spondylosis. The disease duration was 3-120 months (median, 25 months). Single segment was involved in 20 cases, 2 segments in 4 cases, and 3 segments in 1 case. A total of 31 Zero-P were implanted (3 at C3, 4, 8 at C4, 5, 12 at C5, 6, and 8 at C6, 7). Primary cervical operation was performed in 23 cases and re-operation in 2 cases. Before and after operation, the height of intervertebral space and the cervical Cobb angle were measured; clinical outcome was evaluated using visual analogue scale (VAS) score for pain in the neck and upper limb, and Japanese Orthopaedic Association (JOA) score for myelopathy; and intervertebral fusion and the incidence of dysphagia were also observed. RESULTS: All incisions healed by first intention. All the patients were followed up 12-16 months (mean, 13.9 months). Interbody bone fusion was obtained, and the fusion time was 2.7-6.0 months (mean, 3.8 months). Three patients had dysphagia after operation; symptom disappeared at 1 week and 3 months after operation in 2 cases and 1 case, respectively. No fixation loosening, subsidence, or breakage occurred. The height of intervertebral space was significantly improved (P < 0.05) from (4.5 +/- 0.5) mm at preoperation to (6.0 +/- 0.7) mm at 1 week and (5.7 +/- 0.6) mm at 12 months after operation; the cervical Cobb angle was significantly improved (P < 0.05) from (11.9 +/- 6.1) degrees at preoperation to (21.2 +/- 4.1) degrees at 1 week and (20.2 +/- 3.7) degrees at 12 months after operation; and there was no significant difference between at 1 week and 12 months after operation (P > 0.05). The VAS score was significantly reduced (P < 0.05) from 7.1 +/- 0.8 at preoperation to 1.9 +/- 0.8 at 3 months and 1.0 +/- 0.5 at 12 months after operation; the JOA score was significantly increased (P < 0.05) from 9.6 +/- 1.3 at preoperation to 13.5 +/- 1.0 at 3 months and 14.9 +/- 1.0 at 12 months after operation; and there was significant difference between at 3 months and at 12 months after operation (P < 0.05). CONCLUSION: The early outcome of ACDF using a Zero-P in the treatment of cervical spondylosis is satisfactory and reliable, and it can restore and maintain the cervical alignment and disc height, and disc has low incidence of postoperative dysphagia.
Assuntos
Vértebras Cervicais/cirurgia , Próteses e Implantes , Fusão Vertebral/instrumentação , Espondilose/cirurgia , Adulto , Idoso , Vértebras Cervicais/patologia , Descompressão Cirúrgica/instrumentação , Descompressão Cirúrgica/métodos , Transtornos de Deglutição/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Retrospectivos , Fusão Vertebral/métodos , Espondilose/patologia , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the clinical application and therapeutic effect of open vertebroplasty for thoracolumbar metastatic tumor. METHODS: From September 2003 to December 2009, 21 patients with thoracolumbar metastatic tumor underwent the surgical procedure of posterior spinal cord decompression and open vertebroplasty combined with short-segmental pedicle screw fixation during the same intervention. There were 14 males and 7 females, ranging in age from 48 to 73 years with the mean of 59.5 years and ranging in course of disease from 1 to 4 months with an average of 2.5 months. The primary focus of the tumor of 19 cases were established, lung carcinoma was in 8 cases, breast cancer in 4 cases, prostate carcinoma in 4 cases, hepatocarcinoma in 2 cases and thyroid carcinoma in 1 case. The primary focus of 2 cases could not be established. The spinal function according to Frankel grade, grade B was in 4 cases, C in 6, D in 5, E in 6. The lumbar-back pain, height of anterior and posterior vertebral body, Cobb angle and spinal function were recorded before and after operation. RESULTS: The operation of all patients was successful, there were no severe complications and aggravation of spinal function. The VAS score of lumbar-back pain decreased from 8.78 +/- 0.45 preoperatively to 2.25 +/- 0.36 postoperatively. Among 16 cases combined with pathological fracture, the height of anterior spinal vertebral body increased from (12.7 +/- 2.1) mm preoperatively to (19.5 +/- 3.9) mm postoperatively; the height of posterior spinal vertebral body increased from (14.1 +/- 1.8) mm preoperatively to (20.3 +/- 2.3) mm postoperatively; Cobb angle decreased from (26.0 +/- 8.9) degrees preoperatively to (6.0 +/- 0.9) degrees postoperatively. There was significant difference above items between before and after operation (P < 0.05). The spinal function according to Frankel grade at final follow up, grade C was in 2 cases, D in 4, E in 15. All patients were followed up from 5 to 28 months with an average of 14 months, there was no loosening and breakage of internal fixity, 15 cases died during follow-up period. CONCLUSION: The surgical intervention can effectively preserve spinal instability and alleviate the spinal cord symptoms, improve the life quality of patients. It may provide an alternative treatment for patients in poor general health and shorter life expectancy.
Assuntos
Vértebras Lombares/patologia , Metástase Neoplásica/terapia , Neoplasias da Coluna Vertebral/cirurgia , Vértebras Torácicas/patologia , Vertebroplastia/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/fisiopatologia , Neoplasias da Coluna Vertebral/patologia , Resultado do TratamentoRESUMO
Loss of heterozygosity or mutation at the p53 tumor suppressor gene locus is frequently associated with advanced human prostate cancer. Hence, replacement p53 gene therapy may prove to be efficacious for this disease. While many mutations result in p53 molecules with oncogenic properties, other variants may possess wild-type properties with increased tumor suppressor activity. We have chosen to investigate the activity of a naturally occurring variant p53 molecule, p53(R172L), carrying an arginine-to-leucine mutation at codon 172. We demonstrate that p53(R172L) can differentially activate expression of genes involved in cell cycle control and apoptosis in vitro. Transgenic mice expressing a subphysiological level of a p53(R172L) minigene (PB-p53(R172L)) in the prostate epithelium were generated and bred to the transgenic adenocarcinoma mouse prostate (TRAMP) model of prostate cancer. While PB-p53(R172L) transgenic mice developed normally with no detectable prostate gland phenotype, we observed a significant increase in the apoptotic index in the prostate glands of TRAMP x PB-p53(R172L) F1 mice. We noted an increase in the expression of Bax in the bigenic mice concomitant with the reduced incidence and rate of tumor growth and increased survival. While low-level expression of the p53(R172L) variant had no obvious influence on normal prostate tissue, it was able to significantly inhibit prostate cancer progression in the context of a genetically predisposed model system. This suggests that additional tumor-related events specifically influence the ability of the variant p53(R172L) molecule to inhibit tumor growth. These studies support gene therapy strategies employing specific p53 variants.