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1.
Front Cardiovasc Med ; 11: 1396865, 2024.
Article in English | MEDLINE | ID: mdl-38952542

ABSTRACT

Background: Previous research has demonstrated the validity of the triglyceride-glucose (TyG) index as a robust measure of insulin resistance (IR) and its association with coronary artery disease (CAD). The objective of this study is to elucidate the relationship between the TyG index and the prognosis of patients underwent percutaneous coronary intervention (PCI) through a comprehensive systematic review and meta-analysis. Our goal is to provide a thorough analysis of the available evidence to offer more clarity on this association. Methods: A systematic and thorough search was carried out in the PubMed, Embase, Cochrane Library, and Web of Science databases, covering studies published in English from the beginning until October 1, 2023. The focus of the search was to gather relevant studies pertaining to the occurrence of major adverse cardiovascular events (MACE). To address the variability among the included studies, random or fixed effect models were utilized to summarize the hazard ratios (HR). In cases where heterogeneity was detected, subgroup or sensitivity analyses were performed to explore potential sources. To evaluate publication bias, the Egger or Begg test was employed. Results: This study incorporated a total of 17 studies. Individuals with the highest TyG index exhibited an elevated risk of major adverse cardiovascular events (MACEs) compared to those with the lowest TyG index (HR = 1.69; 95% CI: 1.47-1.95; P < 0.001). When analyzing the TyG index as a continuous variable, each standard deviation increase was associated with an HR of 1.60 (95% CI: 1.48-1.73; P < 0.001). Moreover, in patients diagnosed with acute coronary syndrome (ACS), higher TyG index levels showed a trend of increased risk of MACE (HR = 1.54; 95% CI: 1.27-1.86; P < 0.001). Furthermore, an elevated TyG index was found to be associated with a higher risk of in-stent restenosis (HR = 1.62; 95% CI: 1.29-2.03; P < 0.001), new-onset atrial fibrillation (HR = 2.97; 95% CI: 2.10-4.06; P = 0.014), and a reduction in quantitative flow ratio (HR = 1.35; 95% CI: 1.101-1.592; P = 0.005). Subgroup analysis indicated the risk of MACE was comparable between varied durations of follow-up (P = 0.11). Furthermore, regression analysis revealed that the positive association between TyG index and the risk of MACE did not differ between individuals with or without diabetes (P = 0.23). Conclusion: An increase in the TyG index may lead to a higher vulnerability to major adverse cardiovascular events (MACE) in patients underwent PCI and there was no significant difference in the risk of major adverse cardiovascular events (MACE) between diabetic and non-diabetic individuals.

2.
Sci Rep ; 13(1): 11769, 2023 07 20.
Article in English | MEDLINE | ID: mdl-37474710

ABSTRACT

Esophageal stricture is a debilitating condition that negatively impacts patients' quality of life after undergoing endoscopic mucosal resection (EMR). Despite its significance, this disease remains underexplored due to the lack of a stable animal model. Under direct visualization with choledochoscopy, we retrogradely damaged the esophageal mucosal layer through the gastrostomy to create a rat model of esophageal stricture. The development of histological defects in the mucosal layer was assessed over a 2-week period after model induction. Then the models were evaluated using X-ray barium radiography, Hematoxylin-Eosin, Masson's trichrome, Sirius red, and Victoria blue staining, multiphoton microscopic imaging. Additionally, the molecular mechanisms of esophageal stricture were explored by conducting RNA transcriptome sequencing, PCR, immunohistochemistry, and immunofluorescence staining. We successfully established fifteen rat models of esophageal stricture by injuring the mucosal layer. In the model group, the mucosal defect initially occurs and subsequently repaired. The epithelium was absent and was plastically remodeled by collagen during the acute inflammatory phase (Day 1), proliferation phase (Day 7), anaphase of proliferation (Day 10), and plastic remodeling phase (Day 14). We observed increased expression of COL1A1, acta2, FGF, IL-1, and TGF-ß1 pathway in the model group. We established a highly repeatable rat model of esophageal stricture, and our results suggest that the mucosal defect of the esophagus is a critical factor in esophageal stricture development, rather than damage to the muscularis layer. We identified Atp4b, cyp1a2, and gstk1 as potential targets for treating esophageal stricture, while the TGF-ß pathway was found to play an important role in its development.


Subject(s)
Esophageal Neoplasms , Esophageal Stenosis , Humans , Rats , Animals , Quality of Life , Mucous Membrane/pathology , Esophageal Mucosa/pathology , Esophageal Neoplasms/pathology
4.
Int J Ophthalmol ; 12(12): 1908-1916, 2019.
Article in English | MEDLINE | ID: mdl-31850177

ABSTRACT

AIM: To ensure the diagnostic value of computer aided techniques in diabetic retinopathy (DR) detection based on ophthalmic photography (OP). METHODS: PubMed, EMBASE, Ei village, IEEE Xplore and Cochrane Library database were searched systematically for literatures about computer aided detection (CAD) in DR detection. The methodological quality of included studies was appraised by the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2). Meta-DiSc was utilized and a random effects model was plotted to summarize data from those included studies. Summary receiver operating characteristic curves were selected to estimate the overall test performance. Subgroup analysis was used to identify the efficiency of CAD in detecting DR, exudates (EXs), microaneurysms (MAs) as well as hemorrhages (HMs), and neovascularizations (NVs). Publication bias was analyzed using STATA. RESULTS: Fourteen articles were finally included in this Meta-analysis after literature review. Pooled sensitivity and specificity were 90% (95%CI, 85%-94%) and 90% (95%CI, 80%-96%) respectively for CAD in DR detection. With regard to CAD in EXs detecting, pooled sensitivity, specificity were 89% (95%CI, 88%-90%) and 99% (95%CI, 99%-99%) respectively. In aspect of MAs and HMs detection, pooled sensitivity and specificity of CAD were 42% (95%CI, 41%-44%) and 93% (95%CI, 93%-93%) respectively. Besides, pooled sensitivity and specificity were 94% (95%CI, 89%-97%) and 87% (95%CI, 83%-90%) respectively for CAD in NVs detection. No potential publication bias was observed. CONCLUSION: CAD demonstrates overall high diagnostic accuracy for detecting DR and pathological lesions based on OP. Further prospective clinical trials are needed to prove such effect.

6.
J Zhejiang Univ Sci B ; 20(3): 205-218, 2019.
Article in English | MEDLINE | ID: mdl-30829009

ABSTRACT

Spinal cord injury (SCI), which is much in the public eye, is still a refractory disease compromising the well-being of both patients and society. In spite of there being many methods dealing with the lesion, there is still a deficiency in comprehensive strategies covering all facets of this damage. Further, we should also mention the structure called the corticospinal tract (CST) which plays a crucial role in the motor responses of organisms, and it will be the focal point of our attention. In this review, we discuss a variety of strategies targeting different dimensions following SCI and some treatments that are especially efficacious to the CST are emphasized. Over recent decades, researchers have developed many effective tactics involving five approaches: (1) tackle more extensive regions; (2) provide a regenerative microenvironment; (3) provide a glial microenvironment; (4) transplantation; and (5) other auxiliary methods, for instance, rehabilitation training and electrical stimulation. We review the basic knowledge on this disease and correlative treatments. In addition, some well-formulated perspectives and hypotheses have been delineated. We emphasize that such a multifaceted problem needs combinatorial approaches, and we analyze some discrepancies in past studies. Finally, for the future, we present numerous brand-new latent tactics which have great promise for curbing SCI.


Subject(s)
Pyramidal Tracts/pathology , Regenerative Medicine/methods , Spinal Cord Injuries/therapy , Animals , Astrocytes/cytology , Axons/physiology , Cell Transplantation , Disease Models, Animal , Electric Stimulation , Humans , Microglia/cytology , Motor Neurons/cytology , Nerve Regeneration , Neuroglia/cytology , Neuronal Plasticity , Neurons/cytology , Oligodendroglia/cytology , Recovery of Function
7.
J Foot Ankle Surg ; 55(3): 529-34, 2016.
Article in English | MEDLINE | ID: mdl-26874831

ABSTRACT

The present study investigated the clinical outcomes of the posterior midline approach in the treatment of 34 patients with significantly calcified insertional Achilles tendinopathy. The posterior midline approach was applied for the surgical treatment of 34 patients with chronic significantly calcified insertional Achilles tendinopathy after failed conservative treatment. Gastrocnemius recession was performed simultaneously for patients with gastrocnemius contracture. The Fowler-Philip angle and parallel pitch lines were measured before surgery, and the visual analog scale, Tegner score, and Victorian Institute of Sport tendon study group score were recorded before and after surgery. The mean follow-up period was 45.2 ± 17.7 (range 24 to 84) months. After surgery, the visual analog scale score had decreased notably, and the Tegner score and Victorian Institute of Sport tendon study group score had increased significantly. The posterior midline approach can achieve satisfactory outcomes in the treatment of significantly calcified insertional Achilles tendinopathy, and gastrocnemius recession (Strayer procedure) should be performed for patients with gastrocnemius contracture to improve the surgical outcome.


Subject(s)
Achilles Tendon/surgery , Calcinosis/surgery , Muscle, Skeletal/surgery , Orthopedic Procedures/methods , Tendinopathy/surgery , Achilles Tendon/diagnostic imaging , Adult , Contracture/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pain Measurement
8.
Mol Med Rep ; 9(1): 345-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24173687

ABSTRACT

Although neoadjuvant chemotherapy has improved the survival rate of osteosarcoma patients, drug resistance remains a predominant obstacle to improving efficacy and necessitates the development of novel chemotherapeutical agents. The aim of this study was to investigate whether tetrandrine (TET) induces apoptosis in the U-2OS and MG-63 osteosarcoma cell lines and to further determine the underlying mechanism. This study investigated the effects of TET on osteosarcoma in vitro. To examine the antitumor effects of TET on osteosarcoma, the two osteosarcoma cell lines were treated with TET and subjected to apoptosis assays. The results revealed that TET induced the apoptosis of osteosarcoma cells in a time- and dose-dependent manner. Furthermore, the apoptosis of osteosarcoma cells was accompanied by increased cytochrome c (Cyto-C), apoptotic protease-activating factor (Apaf)-1, Bid and Bax activation and reduced Bcl-2 and Bcl-xl activation, demonstrating that the apoptosis may have occurred through the mitochondrial pathway. In conclusion, the results suggest that TET is a promising agent for osteosarcoma therapy.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Benzylisoquinolines/pharmacology , Caspases/metabolism , Antineoplastic Agents, Phytogenic/chemistry , Apoptotic Protease-Activating Factor 1/metabolism , BH3 Interacting Domain Death Agonist Protein/metabolism , Benzylisoquinolines/chemistry , Cell Line, Tumor , Cytochromes c/metabolism , Humans , Proto-Oncogene Proteins c-bcl-2/metabolism , Signal Transduction/drug effects , bcl-2-Associated X Protein/metabolism
9.
Cancer Biother Radiopharm ; 27(10): 701-10, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22849560

ABSTRACT

To examine the antitumor effects of gallic acid (GA) on osteosarcoma, two human osteosarcoma cell lines U-2OS and MNNG/HOS were treated by GA and subjected to cell proliferation and apoptosis assays. In addition, MNNG/HOS xenograft tumors were established in nude BALB/c mice to evaluate the anticancer capacity of GA in vivo. The results showed that GA inhibited the proliferation and induced the apoptosis of osteosarcoma cells, accompanied by the upregulation of p-38 activation and the downregulation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK1/2) activation. Additionally, p38 MAPK inhibitor abrogated GA-induced growth inhibition of osteosarcoma cells, whereas JNK or ERK1/2 inhibitors sensitized osteosarcoma cells to GA-induced growth inhibition. In vivo studies further showed that GA administration decreased xenograft tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the downregulation of PCNA and CD31 expression and upregulation of apoptosis in MNNG/HOS tumor tissues following GA treatment. This study demonstrates the antitumor efficacy of GA for osteosarcoma that is mediated by the modulation of cell proliferation, apoptosis, and angiogenesis. Our findings suggest that GA could be a potent agent for osteosarcoma intervention.


Subject(s)
Apoptosis/drug effects , Bone Neoplasms/drug therapy , Gallic Acid/pharmacology , MAP Kinase Signaling System/genetics , Mitogen-Activated Protein Kinase 8/genetics , Osteosarcoma/drug therapy , Animals , Antineoplastic Agents/pharmacology , Bone Neoplasms/enzymology , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Cell Growth Processes/drug effects , Cell Line, Tumor , Dose-Response Relationship, Drug , Enzyme Activation/drug effects , Female , Humans , MAP Kinase Kinase 4/antagonists & inhibitors , MAP Kinase Kinase 4/metabolism , Mice , Mice, Inbred BALB C , Mice, Nude , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/metabolism , Mitogen-Activated Protein Kinase 8/metabolism , Osteosarcoma/enzymology , Osteosarcoma/genetics , Osteosarcoma/pathology , Xenograft Model Antitumor Assays , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , p38 Mitogen-Activated Protein Kinases/metabolism
10.
Asian Pac J Cancer Prev ; 13(4): 1171-6, 2012.
Article in English | MEDLINE | ID: mdl-22799300

ABSTRACT

OBJECTIVE: The current study aimedto screen for possible factors which affect prognosis of chondrosarcoma. METHODS: Thirty seven cases were selected and analyzed statistically. The patients received surgical treatment at our hospital between December 2005 and March 2008. All of them had complete follow-up data. The survival rates were calculated by univariate analysis using the Kaplan-Meier method and tested by Log-rank. χ2 or Fisher exact tests were carried out for the numeration data. The significant indexes after univariate analysis were then analyzed by multivariate analysis using COX regression model. Based on the literature, factors of gender, age, disease course, tumor location, Enneking grades, surgical approaches, distant metastasis and local recurrence were examined. RESULTS: Univariate analysis showed that there were significant differences in Enneking grades, surgical approaches and distant metastasis related to the patients' 3-year survival rate after surgery (P<0.001). No significant difference was not found in gender, age, disease course, tumor location or local recurrence (P>0.05). Multivariate analysis showed that Enneking grade (P=0.007) and surgical approaches (P=0.010) were independent factors affecting the prognosis of chondrosarcoma, but distant metastasis was not (P=0.942). CONCLUSION: Enneking grades, surgical approaches and distant metastasis are risk factors for prognosis of chondrosarcoma, among which the former two are independent factors.


Subject(s)
Bone Neoplasms/pathology , Bone Neoplasms/surgery , Chondrosarcoma/pathology , Chondrosarcoma/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Bone Neoplasms/secondary , Child , Chondrosarcoma/secondary , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Neoplasm Grading , Neoplasm Staging , Prognosis , Proportional Hazards Models , Retrospective Studies , Survival Rate , Young Adult
11.
Anticancer Agents Med Chem ; 12(5): 554-63, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22263786

ABSTRACT

Genistein, a nontoxic flavonoid compound, has potent antitumor activity in various cancer cells. In the present study, we investigated whether genistein could be employed as a novel strategy to enhance the anti-tumor activity of gemcitabine using human osteosarcoma MNNG/HOS tumor model. In vitro, by MTT, electron microscopy, immunobloting and qRT-PCR assay, we found that the combination treatment of genistein and gemcitabine resulted in stronger growth inhibition and apoptosis induction through the downregulation of NF-κB activity and Akt activation in osteosarcoma cells. Moreover, the synergetic effects were observed when genistein was replaced by PI3K/Akt-pathway inhibitor (LY-294002) or NF-κB inhibitor (BAY11-7082). In vivo, the combination therapy augmented tumor growth inhibition through the down-regulation of NF-κB activity and Akt activation in xenografts. Taken together, these results provide in vitro and in vivo evidence that genistein abrogates gemcitabine-induced activation of NF-κB and increases the chemosensitization of osteosarcoma to gemcitabine. Combination therapy appears as a rational and novel approach for osteosarcoma treatment.


Subject(s)
Antineoplastic Agents/therapeutic use , Bone Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Down-Regulation/drug effects , Genistein/therapeutic use , Osteosarcoma/drug therapy , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Bone Neoplasms/genetics , Cell Line, Tumor , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Drug Synergism , Female , Gene Expression Regulation, Neoplastic/drug effects , Genistein/pharmacology , Humans , Mice , Mice, Inbred BALB C , NF-kappa B/genetics , Osteosarcoma/genetics , Proto-Oncogene Proteins c-akt/genetics , Signal Transduction/drug effects , Gemcitabine
12.
Cancer Chemother Pharmacol ; 69(2): 317-31, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21717192

ABSTRACT

PURPOSE: Matrine, one of the main active components of extracts from the dry roots of Sophora flavescens, has potent anti-tumor activity in various cancer cell lines. However, the activity of matrine against osteosarcoma remains unclear. In the present study, we examined the effects of matrine on human osteosarcoma cells and explored the underlying mechanism. METHODS: Four human osteosarcoma cell lines: MG-63, U-2OS, Saos-2, and MNNG/HOS were treated by matrine and subjected to MTT assay, annexin V-FITC/PI double staining, and TUNEL assay. The activation of caspases and the expression of pro-apoptotic and anti-apoptotic factors were examined by qRT-PCR and Western blot. In addition, MNNG/HOS xenograft tumors were established in female nude BALB/c mice, and matrine was intraperitoneally (i.p.) administered to evaluate the anti-cancer capacity of matrine in vivo. RESULTS: We found that matrine inhibited the proliferation and induced apoptosis of the four osteosarcoma cell lines in vitro and induced the activation of caspase-3, -8, and -9 in a dose-dependent manner. Furthermore, the pro-apoptotic factors Bax and Fas/FasL were upregulated, and the anti-apoptotic Bcl-2 was downregulated. More importantly our in vivo, studies showed that administration of matrine decreased tumor growth in a dose-dependent manner. Immunohistochemistry analysis demonstrated the downregulation of Bcl-2 and upregulation of Bax and Fas/FasL in MNNG/HOS tumor tissues following matrine treatment, consistent with the in vitro results. CONCLUSION: Our results demonstrate that matrine inhibits the proliferation and induces apoptosis of human osteosarcoma cells in vitro and in vivo. The induction of apoptosis appears to occur through the upregulation of Fas/FasL and Bax, downregulation of Bcl-2, and activation of caspase-3, -8, and -9, which then trigger major apoptotic cascades.


Subject(s)
Alkaloids/pharmacology , Apoptosis Regulatory Proteins/metabolism , Apoptosis/drug effects , Osteosarcoma/drug therapy , Quinolizines/pharmacology , Alkaloids/chemistry , Animals , Apoptosis Regulatory Proteins/genetics , Blotting, Western , Caspases/genetics , Caspases/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Down-Regulation/drug effects , Fas Ligand Protein/genetics , Fas Ligand Protein/metabolism , Female , Humans , Immunohistochemistry , Mice , Mice, Inbred BALB C , Mice, Nude , Molecular Structure , Osteosarcoma/metabolism , Osteosarcoma/pathology , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Quinolizines/chemistry , Reverse Transcriptase Polymerase Chain Reaction , Up-Regulation/drug effects , Xenograft Model Antitumor Assays , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism , fas Receptor/genetics , fas Receptor/metabolism , Matrines
13.
Orthopedics ; 34(12): e960-4, 2011 Dec 06.
Article in English | MEDLINE | ID: mdl-22146219

ABSTRACT

Cerebrotendinous xanthomatosis is a rare, autosomal-recessive, lipid-storage disease with accumulation of cholestanol in most tissues, particularly within the Achilles tendons. It has been characterized both clinically and biochemically, and recently from the molecular biological aspect as well. Juvenile cataract, childhood diarrhea, mental retardation, cerebellar ataxia, and tendon xanthomas are the most prominent features of this disease. Bilateral symmetrical firm masses of Achilles tendons may be the first symptom the patient recognizes because it can jeopardize his or her ability to walk. However, the treatment strategies for tendon tumors vary. In a recent case, we diagnosed the disease properly, according to the clinical manifestations and the radiological and laboratory examinations. The genetic mutation was characterized by analyzing sterol 27-hydroxylase from the patient's family (located on nucleotide 599) and led to a nonsense mutation. It is a unique type of mutation that has never been reported to our knowledge. Tendon lesions are characterized by the loss of muscle fibers and accumulation of lipid products. To help the patient regain the strength of the Achilles tendon and walking abilities, a large area of tendon tumor was excised, followed by reconstruction with a tibialis posterior allograft, which is the second strongest tendon in the foot and ankle. Although the use of this type of graft is uncommon, the final result was satisfactory. At the 10-month follow-up examination, the patient could walk easily without pain. This case report suggests that the surgical procedure will provide an alternative for the repair of large-area degenerative Achilles tendons.


Subject(s)
Achilles Tendon/pathology , Xanthomatosis, Cerebrotendinous/diagnosis , Achilles Tendon/physiopathology , Achilles Tendon/surgery , Adult , Ankle/pathology , Cholestanetriol 26-Monooxygenase/genetics , Codon, Nonsense , Diagnosis, Differential , Family Health , Female , Humans , Hypertrophy , Magnetic Resonance Imaging , Male , Mutation , Treatment Outcome , Xanthomatosis, Cerebrotendinous/genetics , Xanthomatosis, Cerebrotendinous/surgery
14.
Zhonghua Wai Ke Za Zhi ; 49(1): 79-82, 2011 Jan 01.
Article in Chinese | MEDLINE | ID: mdl-21418845

ABSTRACT

OBJECTIVE: To discuss the resection pseudoarthrosis for pelvic malignant tumors around acetabular. METHODS: From May 1997 to June 2005, 25 patients with malignant tumors around acetabular were treated surgically with resection pseudoarthrosis. The series comprised 15 males and 10 females with an average age of 42 years old (range from 16 to 75 years old). There were 4 osteosarcomas, 12 chondrosarcomas, 1 Ewing's sarcoma, 1 neuroectodermal tumor, 1 myeloma, 1 malignant fibrohistiocytoma, 2 synovial sarcomas, and 3 metastases. Pseudoarthrosis was performed after resection of pelvic malignant tumors around acetabular. The affected side was protected postoperatively by skin traction with 2 - 3 kg weight for 6 to 8 weeks. After then, the patients walked gradually with a cane. RESULTS: Among 25 patients, 6 had complications (24%). At a follow-up ranging from 3 to 10 years, 11 patients died of lung metastases, 2 relapsed, 12 remained alive free of disease. There was an average crispation of 5 cm (range from 2.5 to 7.5 cm). The patients were functionally evaluated according to Enneking's MSTS criteria in 1993. The average MSTS functional score was 17 points (12 to 19 points). After 3 months postoperative, the patients could sit normally, walk with a cane, and even walk limpingly without cane. CONCLUSIONS: Resection pseudoarthrosis for pelvic malignant tumors around acetabular results in good clinical results at the time of mid-term and long-term follow-up. And pseudoarthrosis is advisable especially for patients with malignant highly tumors around acetabular, poor soft tissue reconstruction condition, high risk for infection, poor economy.


Subject(s)
Acetabulum , Femur Head/surgery , Pelvic Neoplasms/surgery , Adolescent , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Young Adult
15.
Anticancer Drugs ; 21(3): 288-96, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20038829

ABSTRACT

Genistein, a nontoxic flavonoid compound, has potent antitumor activity in various cancer cell lines. This study was designed to investigate whether combination therapy with gemcitabine and genistein enhances antitumor efficacy in osteosarcoma cell lines (MG-63 and U2OS). Our results show that significant reduction in cell viability and corresponding induction of apoptosis were observed with combination treatment in both cell lines. On the molecular level, we found that gemcitabine alone can activate nuclear factor kappaB (NF-kappaB) in osteosarcoma, suggesting the potential mechanism of acquired chemoresistance. In contrast, genistein reversed the cancer's resistance to gemcitabine through the downregulation of NF-kappaB activity and the suppression of Akt. These findings suggest that the combination of gemcitabine and genistein enhanced the antitumor efficacy by abrogating the Akt/NF-kappaB pathway. The marked ability to induce apoptosis with a combination of gemcitabine and genistein suggests that this could be a rational and novel approach for osteosarcoma preclinical and clinical trials.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Protocols , Bone Neoplasms/drug therapy , Deoxycytidine/analogs & derivatives , Genistein/therapeutic use , NF-kappa B/antagonists & inhibitors , Osteosarcoma/drug therapy , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Apoptosis , Cell Line, Tumor , Cell Survival/drug effects , Deoxycytidine/therapeutic use , Drug Synergism , Humans , NF-kappa B/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Gemcitabine
16.
Chemotherapy ; 55(6): 433-40, 2009.
Article in English | MEDLINE | ID: mdl-19996588

ABSTRACT

AIMS: Studies on cancer biology have shown that overexpression of oncogenes (with or without functional loss of tumor suppressor genes), which is responsible for the progression of human malignancies via a multistep process, may be reduced by antisense technology. Caffeine enhances the effect of cisplatin (CDDP) chemotherapy on osteosarcoma cells. We constructed the recombinant adenovirus (Myc-AS) encoding the antisense c-myc fragment and investigated the synergic effect of caffeine and Myc-AS on the in vitro sensitivity of osteosarcoma MG-63 cells to cisplatin. METHODS: The recombinant adenovirus (Myc-AS) encoding the antisense c-myc fragment was constructed by cloning c-myc cDNA of about 750 bp in a reverse direction into adenovirus vector, then undergoing recombination, amplification and complementation in vivo. Myc-AS and caffeine were used either alone or in combination with CDDP to treat osteosarcoma MG-63 cells in vitro. Western blot, MTT, flow cytometry (FCM) and electron microscopy were used to evaluate the expression of c-myc protein, tumor cell proliferation in vitro and apoptosis and to perform cell cycle analysis. RESULTS: Myc-AS encoding antisense c-myc fragment was obtained with a titer of 2 x 10(9) pfu/ml. Myc-AS downregulated the expression of c-myc protein after transfecting MG-63 cells for 48 h, induced tumor cell apoptosis and inhibited tumor cell proliferation in vitro. Myc-AS or caffeine can enhance the cytotoxic effects of 2.0 and 5.0 microg/ml CDDP on MG-63 cells. Moreover, the significantly enhancing effect of the Myc-AS-caffeine combination on CDDP chemotherapy of MG-63 cells was not restricted to apoptosis but also decreased tumor cell proliferation in vitro. Expression of the apoptosis-associated bcl-2 gene was downregulated and bax was upregulated, with no changes in E2F-1 expression. FCM analysis showed that CDDP treatment induced a block in S phase, and caffeine reversed this block and accelerated cell progression through the S phase. CONCLUSIONS: Myc-AS can induce obvious G2/M phase arrest in transfected cells. Myc-AS combined with caffeine can enhance apoptosis induction and chemotherapeutic effects of CDDP on osteosarcoma MG-63 cells.


Subject(s)
Antineoplastic Agents/pharmacology , Caffeine/pharmacology , Cisplatin/pharmacology , Proto-Oncogene Proteins c-myc/administration & dosage , Adenoviridae/genetics , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , DNA, Antisense/administration & dosage , Drug Synergism , Flow Cytometry , Gene Expression Regulation, Neoplastic/drug effects , Genetic Vectors , Humans , Microscopy, Electron , Osteosarcoma/drug therapy , Osteosarcoma/metabolism
17.
Zhonghua Wai Ke Za Zhi ; 47(14): 1079-82, 2009 Jul 15.
Article in Chinese | MEDLINE | ID: mdl-19781274

ABSTRACT

OBJECTIVE: To observe the long-term result of fibula grafting for reconstruction of the distal radius after giant cell tumor excision. METHODS: From March 1994 to November 2004, 31 cases of fibula grafting for reconstruction of the distal radius for giant cell tumors performed were analysed. There were 12 males and 19 females. The patients were from 19 to 48 years old, and the mean age was 31 years. Twenty-four patients had Campanacci grade 3 lesions, and 7 patients had Campanacci grade 2 lesions. There were 6 cases of vascularized fibular grafting and 25 cases of non-vascularized fibular grafting. All cases were evaluated by clinical and radiologic examinations; the movement of the wrist and the grip strength was measured; the MSTS score and Mayo Wrist scores were calculated. RESULTS: Clinical follow-up time after reconstruction averaged 86.3 months, range from 41 to 169 months. The mean time for bone union at the host-graft junctions was 5.1 months range from 3 to 9 months in vascularized group and 10.3 months range from 7 to 15 months in non-vascularized group. One patient who had non-vascularized fibula grafting developed non-union at the host-graft junction, and one patient had local recurrence (3.2%). Five patients developed an wrist dislocation after surgery. The average movements of the wrist were: 67.3 +/- 9.4 degrees of extension, 31.2 +/- 5.1 degrees of flexion, 14.1 +/- 4.7 degrees of radial deviation, 19.4 +/- 3.9 degrees of ulnar deviation, 33.8 +/- 6.6 degrees of pronation, 15.3 +/- 4.0 degrees of supination. Average grip strength was 33.1 kg range from 15.5 to 52.1 kg. Compared with the contralateral side, there were accounted for 73%. MSTS score averaged 25.5 from 23 to 29, Mayo wrist score averaged 56 from 40 to 65. CONCLUSIONS: En bloc resection of giant cell tumor of the distal radius followed by reconstruction with a fibula graft is proved to be an effective method and results in a good functional outcome at long term follow-up evaluation. The stability of wrist is achieved by reconstruction of the capsule.


Subject(s)
Bone Neoplasms/surgery , Fibula/transplantation , Giant Cell Tumor of Bone/surgery , Radius , Adult , Bone Transplantation/methods , Female , Follow-Up Studies , Humans , Male , Middle Aged , Transplantation, Autologous , Treatment Outcome , Young Adult
19.
Zhonghua Wai Ke Za Zhi ; 46(12): 900-3, 2008 Jun 15.
Article in Chinese | MEDLINE | ID: mdl-19035147

ABSTRACT

OBJECTIVE: To study the limb salvage methods and treatment outcomes in malignant periacetabular bone tumors. METHODS: The data of 31 patients of periacetabular malignant tumors who had limb salvage surgery between January 1999 and December 2006 was retrospectively reviewed. There were 14 females and 17 males with a mean age of 53 years (range, 42-75 years). Twenty-four patients had chondrosarcomas, 4 patients had Ewing sarcomas, 1 patient had osteosarcoma, and the remaining 2 patients had metastatic disease. Sixteen patients had Types II pelvic resections, 5 patients had Types I and II pelvic resections, another 5 had Type I and III pelvic resections, and Type I , II and III pelvic resections in the remaining patients. Seventeen patients had reconstructions after tumor resection. RESULTS: The mean follow-up time for all patients was 52 months (range, 12-84 months). Fourteen patients were alive with no evidence of disease, 4 patients were alive with disease at the most recent follow-up, and 13 patients died of disease. The local recurrence rate and mortality rate in 24 patients with chondrosarcomas was 20.8% and 33.3% respectively. Two patients with metastatic disease died at 11 and 34 months postoperatively. One patient with osteosarcoma and 2 patients with Ewing sarcoma died of lung metastases. Enneking scoring system was used to evaluate the functional outcome in 18 alive patients. In 13 patients who had reconstructions, 6 were in excellent, 6 were in good, and 1 was in poor. While in 6 patients who had no reconstructions, 3 were in excellent, 2 were in good, and 1 was in poor. Minor complications occurred in 6 patients. CONCLUSIONS: Clear margin tumor resection with decreased local recurrence rate is critical for limb salvage surgery in periacetabular sarcomas. The ranges of tumor invasion and resection, the principle of individual treatment should be considered in functional reconstruction.


Subject(s)
Acetabulum , Bone Neoplasms/surgery , Adult , Aged , Arthroplasty, Replacement, Hip , Female , Follow-Up Studies , Humans , Limb Salvage , Male , Middle Aged , Retrospective Studies , Treatment Outcome
20.
Cell Biol Int ; 32(5): 494-501, 2008 May.
Article in English | MEDLINE | ID: mdl-18078766

ABSTRACT

Cyclooxygenase-2 (COX-2), involved in the inhibition of apoptosis and, the potentiation of cell growth, is frequently overexpressed in human malignancies including osteosarcoma (OS). We have attempted to identify the anti-proliferation of celecoxib, a selective COX-2 inhibitor, and the combination of celecoxib and cisplatin in MG-63 cells, and to explore the potential molecular mechanisms involved. MG-63 cells were treated with the combination of celecoxib and cisplatin or either agent alone for 48h in serum-supplemented medium. Celecoxib caused G1 phase arrest and significantly inhibited cell growth, as well as potentiating cisplatin-induced apoptosis. The effect was dose-dependent, and apoptotic changes such as DNA fragments and apoptotic bodies were observed. However, downregulation of COX-2 did not occur in cells treated with celecoxib. Phosphoinositide-3-kinase (PI3K)/Akt, survivin, bcl-2 were significantly downregulated in cells treated with the combination of celecoxib and cisplatin, and decreased survivin and bcl-2 levels were found in cells with wortmannin, a specific PI3K inhibitor. Moreover, the decreased expressions of procaspase-9, procaspase-3 and cleaved PARP-1 were detected by Western blot analysis. Therefore, celecoxib exerts its anti-tumor activities through COX-2-independent mechanisms, which may be PI3K/Akt-dependent, and survivin and bcl-2-related. PI3K may be at the center of the celecoxib effects, which play an essential role in the regulation of survivin and Bcl-2.


Subject(s)
Apoptosis/drug effects , Cyclooxygenase Inhibitors/pharmacology , Down-Regulation/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Pyrazoles/pharmacology , Sulfonamides/pharmacology , Androstadienes/pharmacology , Antineoplastic Agents/pharmacology , Celecoxib , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Cisplatin/pharmacology , Cyclooxygenase 2/genetics , Gene Expression Regulation, Enzymologic/drug effects , Humans , Inhibitor of Apoptosis Proteins , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Osteosarcoma , Phosphatidylinositol 3-Kinases/genetics , Phosphoinositide-3 Kinase Inhibitors , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Survivin , Wortmannin
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