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1.
J Magn Reson Imaging ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39304527

RESUMO

In patients with acute myocardial infarction (AMI), traditional clinical endpoints used to assess drug efficacy and prognosis include infarct size (IS), incidence of heart failure, and mortality rates. Although these metrics are commonly employed to evaluate outcomes in AMI patients, their utility is limited in small-scale studies. The introduction of the myocardial salvage index (MSI) reduces variability in assessments across multiple dimensions, thereby enhancing the sensitivity of outcome measures and reducing the required sample size. Moreover, MSI is increasingly utilized to evaluate drug efficacy, prognosis, and risk stratification in AMI patients. Although a variety of methodologies for measuring the MSI are currently available, the incorporation of these methods as clinical endpoints remains limited. In the clinical application of cardioprotective strategies, it is recommended that MSI be evaluated using late gadolinium enhancement measured along the endocardial surface length combined with IS in cardiac magnetic resonance. In dynamic single-photon emission computed tomography, an assessment of MSI using methods based on abnormalities in myocardial wall thickening combined with perfusion anomalies is advocated. This review comprehensively outlines the principles, advantages, and limitations of different MSI assessment methods and discusses the prospects and challenges of MSI in cardiac protective therapies. Additionally, we summarize recommended strategies for employing MSI as a clinical surrogate endpoint in various clinical scenarios, providing direction for future clinical practice and research. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 4.

2.
Colloids Surf B Biointerfaces ; 245: 114219, 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39293290

RESUMO

Osseointegration is significantly impeded in osteoporotic conditions due to the elevated levels of reactive oxygen species (ROS) and inflammation at the site of injury. To enhance bone regeneration in osteoporotic conditions, a modified polyether ether ketone (PEEK) implants was prepared, denoted as PEEK-PDA-Sr. The implants consisted of mussel adhesion layer with the conjugation of strontium (Sr) ions, which can constantly release Sr ions for up to 3 weeks. PEEK-PDA-Sr demonstrated excellent biocompatibility and effectively regulated intracellular ROS levels and macrophage differentiation. In addition, the PEEK-PDA-Sr facilitated the osteogenesis of bone marrow stromal cells (BMSCs). In the ovariectomized (OVX) rat model of osteoporosis, the PEEK-PDA-Sr exhibited raised osseointegration in the femoral bone defects. The PEEK-PDA-Sr can be used as an immunoregulator with enhanced osseointegration and osteogenesis both in vivo and in vitro, which provides an available approach to treat osteoporotic bone defects.

3.
J Bone Joint Surg Am ; 106(6): 492-500, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38109425

RESUMO

BACKGROUND: Many patients experience lower-extremity swelling following total knee arthroplasty (TKA), which impedes recovery. Diosmin is a semisynthetic flavonoid that is often utilized to treat swelling and pain caused by chronic venous insufficiency. We aimed to evaluate the efficacy and safety of diosmin in reducing lower-extremity swelling and pain as well as in improving functional outcomes following TKA. METHODS: This study was designed as a randomized, controlled multicenter trial and conducted in 13 university-affiliated tertiary hospitals. A total of 330 patients undergoing TKA were randomized to either receive or not receive diosmin postoperatively. The diosmin group received 0.9 g of diosmin twice per day for 14 consecutive days starting on the day after surgery, whereas the control group received neither diosmin nor a placebo postoperatively. The primary outcome was lower-extremity swelling 1, 2, 3, and 14 days postoperatively. The secondary outcomes were postoperative pain assessed with use of a visual analogue scale, Hospital for Special Surgery score, range of knee motion, levels of the inflammatory biomarkers C-reactive protein and interleukin-6, and complications. RESULTS: At all postoperative time points, diosmin was associated with significantly less swelling of the calf, thigh, and upper pole of the patella as well as with significantly lower pain scores during motion. However, no significant differences in postoperative pain scores at rest, Hospital for Special Surgery scores, range of motion, levels of inflammatory biomarkers, or complication rates were found between the diosmin and control groups. CONCLUSIONS: The use of diosmin after TKA reduced lower-extremity swelling and pain during motion and was not associated with an increased incidence of short-term complications involving the outcomes studied. However, further studies are needed to continue exploring the efficacy and safety of diosmin use in TKA. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Artroplastia do Joelho , Diosmina , Humanos , Artroplastia do Joelho/efeitos adversos , Diosmina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Coxa da Perna , Biomarcadores , Resultado do Tratamento
4.
J Cardiovasc Dev Dis ; 10(7)2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37504559

RESUMO

Cardiovascular disease morbidity/mortality are increasing due to an aging population and the rising prevalence of diabetes and obesity. Therefore, innovative cardioprotective measures are required to reduce cardiovascular disease morbidity/mortality. The role of necroptosis in myocardial ischemia-reperfusion injury (MI-RI) is beyond doubt, but the molecular mechanisms of necroptosis remain incompletely elucidated. Growing evidence suggests that MI-RI frequently results from the superposition of multiple pathways, with autophagy, ferroptosis, and CypD-mediated mitochondrial damage, and necroptosis all contributing to MI-RI. Receptor-interacting protein kinases (RIPK1 and RIPK3) as well as mixed lineage kinase domain-like pseudokinase (MLKL) activation is accompanied by the activation of other signaling pathways, such as Ca2+/calmodulin-dependent protein kinase II (CaMKII), NF-κB, and JNK-Bnip3. These pathways participate in the pathological process of MI-RI. Recent studies have shown that inhibitors of necroptosis can reduce myocardial inflammation, infarct size, and restore cardiac function. In this review, we will summarize the molecular mechanisms of necroptosis, the links between necroptosis and other pathways, and current breakthroughs in pharmaceutical therapies for necroptosis.

5.
J Cardiovasc Dev Dis ; 10(9)2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37754818

RESUMO

The cardiac variant of Fabry disease (FD) has high rates of missed diagnosis and misdiagnosis due to the lack of systemic symptoms. Here, we report a case of a 68-year-old female with delayed-onset FD presenting as concentric left ventricular hypertrophy (LVH) with right bundle branch block, atrial fibrillation, and diastolic dysfunction, which was first presented with coronary artery spasm. Early cardiac-specific signs are crucial for diagnosing this disease due to the lack of extracardiac indications and the late onset of symptoms. This case raises a new red flag that patients with unexplained LVH and its atypical electrocardiographic (ECG) manifestations accompanied by diastolic dysfunction should be considered for FD. We also recommend further refinement of examinations associated with Fabry disease, which will contribute to the early diagnosis and treatment of the disease.

6.
Front Bioeng Biotechnol ; 11: 1182187, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37207123

RESUMO

Polyetheretherketone (PEEK) has been used extensively in biomedical engineering and it is highly desirable for PEEK implant to possess the ability to promote cell growth and significant osteogenic properties and consequently stimulate bone regeneration. In this study, a manganese modified PEEK implant (PEEK-PDA-Mn) was fabricated via polydopamine chemical treatment. The results showed that manganese was successfully immobilized on PEEK surface, and the surface roughness and hydrophilicity significantly improved after surface modification. Cell experiments in vitro demonstrated that the PEEK-PDA-Mn possesses superior cytocompatibility in cell adhesion and spread. Moreover, the osteogenic properties of PEEK-PDA-Mn were proved by the increased expression of osteogenic genes, alkaline phosphatase (ALP), and mineralization in vitro. Further rat femoral condyle defect model was utilized to assess bone formation ability of different PEEK implants in vivo. The results revealed that the PEEK-PDA-Mn group promoted bone tissue regeneration in defect area. Taken together, the simple immersing method can modify the surface of PEEK, giving outstanding biocompatibility and enhanced bone tissue regeneration ability to the modified PEEK, which could be applied as an orthopedic implant in clinical.

8.
Colloids Surf B Biointerfaces ; 224: 113196, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36764204

RESUMO

Polyetheretherketone (PEEK) has been widely applied in biomedical engineering. However, the unsatisfactory bioactivity essentially limits the clinical application of PEEK. In this study, a simply immersing method was proposed to fabricate a dual-functional PEEK with antibacterial properties and enhanced bone integration. Firstly, the surface of PEEK was modified with a polydopamine (PDA) coating by incubating at dopamine solution. Afterward, the PEEK-PDA was modified with manganese (Mn) and silver (Ag) ions by the soaking method to fabricate the PEEK-PDA-Mn/Ag. The physicochemical capabilities of PEEK-PDA-Mn/Ag were further explored in the ions release, wettability, morphology, and element distributions. PEEK-PDA-Mn/Ag obviously accelerated the adhesion and distribution of MC3T3-E1 cells, indicating favorable biosafety in vitro. Meanwhile, the osteogenic properties of PEEK-PDA-Mn and PEEK-PDA-Mn/Ag were proved by the increased expression of osteogenic genes, alkaline phosphatase (ALP), and mineralization in vitro. Additionally, the wide antibacterial capabilities of PEEK-PDA-Mn/Ag were proved in both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) in vitro. Furthermore, the PEEK-PDA-Mn/Ag was antibacterial with capability in enhancing osseointegration in vivo. Overall, the simply immersing method can modify the surface of PEEK, giving the bioactivity, biocompatibility, and antibacterial ability to the composited PEEK, which could be applied as an orthopedic implant in clinical.


Assuntos
Osseointegração , Staphylococcus aureus , Escherichia coli , Polietilenoglicóis/química , Benzofenonas/farmacologia , Cetonas/farmacologia , Cetonas/química , Antibacterianos/farmacologia , Antibacterianos/química , Osteogênese , Bactérias , Íons
9.
Front Cardiovasc Med ; 10: 1195322, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37485278

RESUMO

Background: This study aims to evaluate the effectiveness and safety of low-dose (1.5 mg) fondaparinux for venous thromboembolism (VTE) prophylaxis in patients post-total knee arthroplasty (TKA). Methods: We retrospectively identified 314 patients who carried out the primary TKAs and received fondaparinux for VTE chemoprophylaxis between July 2020 and December 2021. A total of 141 TKA patients were excluded according to the exclusion criteria. Two groups of patients were established: the low-dose group included 84 patients who injected 1.5 mg of fondaparinux, and the regular-dose group included 89 patients who injected 2.5 mg of fondaparinux. The pre-operative blood analysis and coagulation assays were performed. The surgical time, the incidence of symptomatic VET, blood loss, wound complication, bleeding, drainage, and mortality of patients were determined and assessed. Results: The pre-operative blood analysis, body mass index, sex, age, and coagulation assays of patients in both groups were comparable. In terms of symptomatic pulmonary embolism and deep vein thrombosis, there was no significant difference (variation) between the two groups. However, patients in both groups showed a substantial difference in terms of blood loss, drain volume, wound complication, and transfusion rate. Conclusion: In prevention of VET in patients post-TKA, low-dose fondaparin is as effective as conventional dose fondaparinux. A significant decrease in blood loss, post-surgical transfusion rates, and wound complications were detected in patients given low-dose fondaparinux compared to those receiving regular-dose fondaparinux.

10.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(3): 259-264, 2019 Mar 15.
Artigo em Chinês | MEDLINE | ID: mdl-30874379

RESUMO

Objective: To evaluate the effectiveness of SRS-Schwab grade Ⅳ osteotomy combined with satellite rod for thoracolumbar old osteoporotic fracture with severe kyphosis. Methods: Between April 2013 and August 2016, 20 cases of thoracolumbar old osteoporotic fracture with severe kyphosis were treated with SRS-Schwab grade Ⅳ osteotomy combined with satellite rod. All the patients were females, aged 49-71 years (mean, 54.8 years). The disease duration was 6-28 months with an average of 14 months. The T value of bone density was -4.4 to -1.8 (mean, -2.8). The preoperative Cobb angle was (43.0±11.3)°. The vertebral compression fracture segment was T 12 in 9 cases, L 1 in 8 cases, and L 2 in 3 cases. Preoperative spinal cord function was evaluated by Frankel classification; there were 5 cases of grade D and 15 cases of grade E. The operation time, intraoperative blood loss, and perioperative complication were recorded. The Cobb angle for kyphosis and sagittal vertical axis (SVA) were recorded beforeoperation, at 3 months after operation, and at last follow-up. Oswestry disability index (ODI) was used to evaluate the effectiveness before operation and at last follow-up, and the evaluation indicators included pain degree, daily life self-care ability, extracting, walking, sitting, standing, sleeping, social activities, and traveling. Results: The operation time was 180-314 minutes (mean, 226 minutes). The intraoperative blood loss was 390-1 800 mL (mean, 750 mL). All the incisions healed by first intension without incision infection. Twenty patients were followed up 24-52 months, with an average of 30.9 months. During the follow-up period, no significant complication such as correction loss, nail breakage, rod breakage, pseudoarthrosis formation, or proximal and distal junctional kyphosis occurred. All patients were able to walk upright after operation, and the pain relieved significantly at 6 months after operation. Bone fusion achieved at 12 months after operation. The Frankel grade of nerve function improved from grade D to grade E at last follow-up in 5 patients with nerve damage before operation. At last follow-up, the indicator scores of ODI significantly improved when compared with preoperative values ( P<0.05). Cobb angle significantly improved at 3 months after operation and at last follow-up ( P<0.05) when compared with preoperative one, but there was no significant difference in the Cobb angles between 3 months after operation and last follow-up ( P>0.05). There was no significant difference in SVA between pre- and post-operation ( P>0.05). Conclusion: SRS-Schwab grade Ⅳ osteotomy combined with satellite rod for thoracolumbar old osteoporotic fracture with severe kyphosis is effective in achieving satisfactory clinical outcomes, as well as maintaining correction of kyphosis.


Assuntos
Fraturas por Compressão , Cifose , Fraturas por Osteoporose , Osteotomia , Fraturas da Coluna Vertebral , Idoso , Feminino , Fixação Interna de Fraturas , Fraturas por Compressão/cirurgia , Humanos , Vértebras Lombares , Pessoa de Meia-Idade , Fraturas por Osteoporose/cirurgia , Vértebras Torácicas , Resultado do Tratamento
11.
Pain Physician ; 22(5): E457-E465, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31561658

RESUMO

BACKGROUND: Scoliosis secondary to lumbar disc herniation (LDH) may occur in both adolescents and adults. As the spine is more flexible in adolescents than in adults, the curve features and curve evolution could be different between these 2 cohorts, which were unclear. OBJECTIVES: To compare the radiologic features of scoliosis secondary to LDH between adolescents and adults, and to further characterize the curve evolution after lumbar discectomy in 2 cohorts. STUDY DESIGN: A retrospective study. SETTING: An inpatient surgery center. METHODS: Patients with scoliosis secondary to LDH who underwent surgical intervention between 2010 and 2016 were reviewed. Radiographic parameters were measured on standing whole spine radiographs. The apical vertebral translation was measured on serial radiographs taken before surgery, one month and 6 months after surgery, and at last follow-up to evaluate the curve evolution. Meanwhile, the patients' reported outcomes were evaluated. According to age, patients were divided into adolescent and adult group. Comparisons between the 2 groups were made with regards to the preoperative and postoperative radiographic parameters and clinical outcomes. RESULTS: A total of 42 adolescent and 41 adult patients were included in this study. The incidence of scoliosis secondary to LDH in the adolescents was significantly higher than that in the adults. Adolescent patients present remarkably higher incidence of coronal balance as compared with the adult patients preoperatively. No significant difference was observed between the 2 groups in terms of preoperative radiographic parameters. A total of 85.7% of the adolescent patients and 92.7% of the adult patients achieved resolution of scoliosis within 6 months after surgery. LIMITATIONS: This was a retrospective study with a small series of cases and relatively short-term follow-up. CONCLUSIONS: The incidence of scoliosis secondary to LDH in adolescents is significantly higher than in adults. Moreover, adolescent patients are more likely to present coronal balance before surgery. The 2 cohorts could have comparable curve evolution, and resolution of scoliosis generally occurred within 6 months after surgery. KEY WORDS: Sciatic scoliosis, lumbar disc herniation, adolescent, adult, resolution, lumbar discectomy.


Assuntos
Discotomia/efeitos adversos , Vértebras Lombares/cirurgia , Escoliose , Adolescente , Feminino , Humanos , Incidência , Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Masculino , Radiografia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
Int J Clin Exp Med ; 8(6): 10086-90, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26309704

RESUMO

Treatment of adult tibiofibular fractures, especially severely comminuted fractures, is technically challenging due to the lack of reduction markers and difficulty in restoring the alignment. Fixation of the fibula can facilitate reduction of the tibia fracture and restoration of the lower-extremity alignment. However, there are few literatures mentioned using intramedullary nail fixation for fibular fractures. Twenty-three cases of tibiofibular fractures were treated with elastic nails fixation fibular fractures and intramedullary nail or plate stabilization tibial fractures between January 2012 and December 2012. Adult tibiofibular fractures with fibular neck fractures or fibular fracture line apart from the ankle joint surface within 8 cm was ruled out. There were 19 males and 4 females with an average age of 41 years (range, 21-59 years). The injury causes included 11 falls and 12 traffic accidents. The left side was involved in 11 cases and the right side was involved in 12 cases. Seventeen cases were closed fractures and 6 cases were open fractures, all were Gustilo type I and II fractures. According to the AO classification, six fractures were defined as type 42A, 11 as type 42B, and 6 as type 42C. The average interval between injury and surgery was 5.8 d (range, 3-22 d). The operation time of elastic nails fixation fibular fractures was 24 minutes (range, 15-42 minutes). Primary wound healing was achieved in all patients. No complications such as infection and wound necrosis occurred. Twenty-one patients were followed up for a mean follow-up period of 16.3 months (range, 12-26 months). The mean duration of fracture healing in the radiographs was 4.1 months (range, 3-8 months). No recurrent fracture dislocation and breakage of implant were observed. At the last follow-up visit, the lower-extremity alignment was excellent. Two degrees of varus deformity was found in 3 cases, and 2 degrees of valgus deformity was observed in 2 cases, but there were no serious varus or valgus deformity affecting the lower-extremity function or causing pain. The results of Tornetta's ankle function scoring were excellent in 17 cases, good in 3 cases, and fair in 1 case; and the good-to-excellent rate was 95.2%. In the case of adult tibiofibular fractures, elastic nails fixed fibular fracture is helpful to maintain and adjust the lower limbs axis, help tibial fracture reduction, and increase stability.

13.
World J Gastroenterol ; 9(7): 1415-20, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12854132

RESUMO

AIM: To study the role of Fas ligand (FasL) and Caspase-3 expression in carcinogenesis and progression of gastric cancer and molecular mechanisms of relevant immune escape. METHODS: FasL and Caspase-3 expression was studied in adjacent epithelial cells, cancer cells and lymphocytes of primary foci, and cancer cells of metastatic foci from 113 cases of gastric cancer by streptavidin-biotin-peroxidase (S-P) immunohistochemistry. Expression of both proteins in cancer cells of primary foci was compared with clinicopathological features of gastric cancer. The relationship between FasL expression in cancer cells and Caspase-3 expression in cancer cells or infiltrating lymphocytes of primary foci was investigated. RESULTS: Cancer cells of primary foci expressed FasL in 53.98 % (61/113) of gastric cancers, more than their adjacent epithelial cells (34.51 %, 39/113) (P=0.003, chi(2)=8.681), while the expression of Caspase-3 in cancer cells of primary foci was detected in 32.74 % (37/113) of gastric cancers, less than in the adjacent epithelial cells (50.44 %, 57/113) (P=0.007, chi(2)=7.286). Infiltrating lymphocytes of the primary foci showed positive immunoreactivity to Caspase-3 in 70.80 % (80/113) of gastric cancers, more than their corresponding adjacent epithelial cells (P=0.001, chi(2)=10.635) or cancer cells of primary foci (P=0.000, chi(2)=32.767). FasL was less expressed in cancer cells of metastases (51.16 %, 22/43) than in those of the corresponding primary foci (81.58 %, 31/38) (P=0.003, chi(2)=9.907). Conversely, Caspase-3 was more expressed in cancer cells of metastases (58.14 %, 25/43) than in those of the corresponding primary foci (34.21 %, 13/38) (P=0.031, chi(2)=4.638). FasL expression was significantly correlated with tumor size (P=0.035,rs=0.276), invasive depth (P=0.039, rs=0.195), metastasis (P=0.039, rs=0.195), differentiation (P=0.015, rs=0.228) and Lauren's classification (P=0.038, rs=0.196), but not with age or gender of patients, growth pattern or TNM staging of gastric cancer (P>0.05). In contrast, Caspase-3 expression showed no correlation with any clinicopathological parameters described above in cancer cells of the primary foci (P>0.05). Interestingly, FasL expression in primary gastric cancer cells paralleled to Caspase-3 expression in infiltrating lymphocytes of the primary foci (P=0.016, chi(2)=5.825). CONCLUSION: Up-regulated expression of FasL and down-regulated expression of Caspase-3 in cancer cells of primary foci play an important role in gastric carcinogenesis. As an effective marker to reveal the biological behaviors, FasL is implicated in differentiation, growth, invasion and metastasis of gastric cancer by inducing apoptosis of infiltrating lymphocytes. Chemical substances derived from the primary foci and metastatic microenvironment can inhibit the growth of metastatic cells by enhancing Caspase-3 expression and diminishing FasL expression.


Assuntos
Adenocarcinoma/imunologia , Adenocarcinoma/fisiopatologia , Caspases/genética , Glicoproteínas de Membrana/genética , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/fisiopatologia , Evasão Tumoral/fisiologia , Adenocarcinoma/secundário , Caspase 3 , Caspases/imunologia , Regulação para Baixo , Células Epiteliais/fisiologia , Proteína Ligante Fas , Feminino , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Metástase Linfática/imunologia , Linfócitos/fisiologia , Masculino , Glicoproteínas de Membrana/imunologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/secundário , Neoplasias Gástricas/secundário , Regulação para Cima
14.
World J Gastroenterol ; 9(8): 1662-6, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12918097

RESUMO

AIM: To investigate expression of PTEN in gastric cancer and to explore its roles in tumorigenesis and progression of gastric cancer. METHODS: Formalin-fixed and paraffin-embedded tissues of adjacent non-tumor mucosa and primary foci from 113 cases of gastric cancers were studied for the expression of PTEN and Caspase-3 and microvessel density (MVD) by streptavidin-peroxidase (S-P) immunohistochemistry with antibodies against PTEN, Caspase-3, and CD34. The relationship between PTEN and Caspase 3 expression and clinicopathological parameters of tumors was compared. RESULTS: Primary gastric cancer cells expressed PTEN less frequently than adjacent epithelial cells of primary foci (54.9 % vs 89.4 %; P=0.000, chi(2)=33.474). PTEN expression was significantly associated with invasive depth (P=0.003, rs=0.274), metastasis (P=0.036, rs=0.197), growth pattern (P=0.008, rs=0.282), Lauren's classification (P=0.000, rs=0.345), and histological classification (P=0.005, rs=0.262) of tumors, but not with tumor size (P=0.639, rs=0.045), Borrmann's classification (P=0.544, rs=0.070) or TNM staging (P=0.172, rs=0.129). PTEN expression was negatively correlated with MDV in primary gastric cancer (P=0.020, F=5.558). Primary gastric cancer cells showed less frequent immunoreactivity to Caspase-3 than adjacent epithelial cells of primary foci (32.7 % vs 50.4 %; P=0.007, chi(2)=7.286). Caspase-3 expression was dependent of PTEN expression in primary gastric cancer cells (P=0.000, chi(2)=15.266). CONCLUSION: Down-regulated expression of PTEN plays an important role in tumorigenesis, progression, growth, differentiation and angiogenesis of gastric cancer. Low expression of PTEN can decrease expression of Caspase-3 to disorder apoptosis of tumor cells, which might explain the molecular mechanisms of PTEN contributions to tumorigenesis and progression of gastric cancer.


Assuntos
Apoptose , Neovascularização Patológica , Monoéster Fosfórico Hidrolases/genética , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/patologia , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Caspase 3 , Caspases/metabolismo , Diferenciação Celular , Feminino , Mucosa Gástrica/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , PTEN Fosfo-Hidrolase , Monoéster Fosfórico Hidrolases/metabolismo , Neoplasias Gástricas/fisiopatologia , Neoplasias Gástricas/secundário , Proteínas Supressoras de Tumor/metabolismo
16.
Zhonghua Zhong Liu Za Zhi ; 26(7): 389-92, 2004 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-15355640

RESUMO

OBJECTIVE: To investigate the expression of PTEN and loss of heterozygosity (LOH) of its epigenetic microsatellite in gastric carcinoma and explore their roles in progression of gastric carcinoma. METHODS: LOH of epigenetic microsatellites of PTEN (D10S541, D10S583 and D10S1687) in advanced gastric cancer was detected by PCR-SSCP. Expression of PTEN mRNA and protein in normal gastric mucosa and gastric cancer was evaluated by RT-PCR and SABC immunohistochemistry, respectively. The relationship between expression of PTEN mRNA and protein and lymph node metastasis or LOH of microsatellites was discussed. RESULTS: LOH of D10S541, D10S583 and D10S1687 was found in 37.5% (21/56) of advanced gastric cancers. The positive rates of PTEN mRNA expression were 80.4% (45/56), 45.5% (5/11) and 32.1% (18/56) in normal mucosa, early and advanced gastric carcinomas, respectively, while 78.6% (44/56), 44.5% (5/11) and 28.6% (16/56) at the protein level. PTEN mRNA and protein were less frequently expressed in early and advanced gastric carcinomas than that in normal gastric mucosa (P < 0.05). There was positive correlation between PTEN mRNA expression and LOH of microsatellites in advanced gastric carcinomas. PTEN protein expression paralleled with its mRNA expression (P < 0.05). The expression of PTEN mRNA and protein was negatively correlated with lymph node metastasis of advanced gastric carcinomas (P < 0.05). CONCLUSION: Down-regulated expression of PTEN gene is found in different stages of gastric carcinoma, and is closely correlated with LOH of its epigenetic microsatellites, which probably is its underlying molecular mechanisms. It suggests that altered PTEN gene contributes to tumorigenesis and progression of gastric carcinomas.


Assuntos
Genes Supressores de Tumor , Perda de Heterozigosidade , Repetições de Microssatélites/genética , Monoéster Fosfórico Hidrolases/biossíntese , Neoplasias Gástricas , Proteínas Supressoras de Tumor/biossíntese , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática/genética , Estadiamento de Neoplasias , PTEN Fosfo-Hidrolase , Monoéster Fosfórico Hidrolases/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Proteínas Supressoras de Tumor/genética
17.
Pathol Int ; 53(10): 659-66, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14516315

RESUMO

To investigate the role of PTEN and matrix metalloproteinase-7 (MMP-7) expression in tumorigenesis and progression of gastric carcinoma, their expression in 113 gastric carcinomas was studied by immunohistochemistry. Microvessel density (MVD) was counted using the anti-CD34 antibody. The expressions of PTEN and MMP-7, and MVD were compared with the clinicopathological parameters of tumors, and the relationship between PTEN and MMP-7 expression and MVD was analyzed. It was found that PTEN was expressed less frequently in primary gastric carcinoma cells than in adjacent epithelial cells (P < 0.05), whereas this was reversed for MMP-7 (P < 0.05). PTEN expression was negatively correlated with invasion, metastasis, growth pattern, Lauren's classification and histological classification (P < 0.05). Matrix metalloproteinase-7 expression was positively associated with tumor size, Borrmann's classification, invasive depth, metastasis and TNM staging (P < 0.05), but negative with PTEN expression (P < 0.05). A positive correlation of MVD with tumor size, invasive depth, metastasis and TNM staging was found (P < 0.05). Microvessel density depended on decreased PTEN expression and increased MMP-7 expression (P < 0.05). The results of the present study suggested that down-regulated PTEN expression and up-regulated MMP-7 expression were greatly implicated in tumorigenesis and progression of gastric carcinoma. Close correlation between PTEN on MMP-7 expression provided a novel insight into the regulatory effects of PTEN on MMP-7 expression in gastric carcinoma.


Assuntos
Adenocarcinoma/enzimologia , Metaloproteinase 7 da Matriz/metabolismo , Neovascularização Patológica/enzimologia , Monoéster Fosfórico Hidrolases/metabolismo , Neoplasias Gástricas/enzimologia , Proteínas Supressoras de Tumor/metabolismo , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/classificação , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Técnicas Imunoenzimáticas , Masculino , Metaloproteinase 7 da Matriz/genética , Microcirculação , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Neovascularização Patológica/patologia , PTEN Fosfo-Hidrolase , Monoéster Fosfórico Hidrolases/genética , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/classificação , Neoplasias Gástricas/patologia , Proteínas Supressoras de Tumor/genética
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