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1.
J Hand Surg Eur Vol ; : 1753193420901441, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000613

RESUMO

In selective ulnar and median nerve transfers, donor nerve fascicles should be harvested in an area where motor and sensory fascicles are intermingled to minimize motor or sensory deficits. We aimed to define such an area for ulnar and median nerve harvesting through microanatomical dissection and histology in 12 fresh adult cadaveric upper extremities. Anatomically, we studied the arrangement, localization, and histological features of fascicle groups in two nerves at eight segments of the upper arms. Histological sections were examined to confirm the findings of the anatomical dissections. We found that sensory and motor fascicles were mixed proximally to the third most distal segment of the ulnar nerve and to the fourth most distal segment of the median nerve. We conclude that harvesting a part of the ulnar or median nerve proximal to these levels minimizes donor nerve deficits.

2.
Neural Regen Res ; 14(12): 2132-2140, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31397352

RESUMO

Direct coaptation of contralateral C7 to the upper trunk could avoid the interposition of nerve grafts. We have successfully shortened the gap and graft lengths, and even achieved direct coaptation. However, direct repair can only be performed in some selected cases, and partial procedures still require autografts, which are the gold standard for repairing neurologic defects. As symptoms often occur after autografting, human acellular nerve allografts have been used to avoid concomitant symptoms. This study investigated the quality of shoulder abduction and elbow flexion following direct repair and acellular allografting to evaluate issues requiring attention for brachial plexus injury repair. Fifty-one brachial plexus injury patients in the surgical database were eligible for this retrospective study. Patients were divided into two groups according to different surgical methods. Direct repair was performed in 27 patients, while acellular nerve allografts were used to bridge the gap between the contralateral C7 nerve root and upper trunk in 24 patients. The length of the harvested contralateral C7 nerve root was measured intraoperatively. Deltoid and biceps muscle strength, and degrees of shoulder abduction and elbow flexion were examined according to the British Medical Research Council scoring system; meaningful recovery was defined as M3-M5. Lengths of anterior and posterior divisions of the contralateral C7 in the direct repair group were 7.64 ± 0.69 mm and 7.55 ± 0.69 mm, respectively, and in the acellular nerve allografts group were 6.46 ± 0.58 mm and 6.43 ± 0.59 mm, respectively. After a minimum of 4-year follow-up, meaningful recoveries of deltoid and biceps muscles in the direct repair group were 88.89% and 85.19%, respectively, while they were 70.83% and 66.67% in the acellular nerve allografts group. Time to C5/C6 reinnervation was shorter in the direct repair group compared with the acellular nerve allografts group. Direct repair facilitated the restoration of shoulder abduction and elbow flexion. Thus, if direct coaptation is not possible, use of acellular nerve allografts is a suitable option. This study was approved by the Medical Ethical Committee of the First Affiliated Hospital of Sun Yat-sen University, China (Application ID: [2017] 290) on November 14, 2017.

3.
Gastroenterol Rep (Oxf) ; 7(3): 193-198, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31217983

RESUMO

Background: In addition to the stepwise manner of lymph-node metastasis from the primary tumour, the skip lymph-node metastasis (SLNM) was identified as a low-incidence metastasis of gastric cancer (GC). So far, both the mechanism and outcome of SLNM have not been elucidated completely. The purpose of this study was to analyse the clinical significance and the potential mechanism of SLNM in GC patients who had lymph-node metastasis. Methods: Clinicopathological data and follow-up information of 505 GC patients who had lymph-node metastasis were analysed to demonstrate the significance of SLNM in evaluating the prognostic outcome. According to the pathological results, all GC patients who had lymph-node metastasis were categorized into three groups: patients with the perigastric lymph-node metastasis, patients with the perigastric and extragastric lymph-node metastasis and patients with SLNM.Results: Among the 505 GC patients who had lymph-node metastasis, 24 (4.8%) had pathologically identified SLNM. The location of lymph-node metastasis was not significantly associated with 5-year survival rate and overall survival (OS) (P = 0.194). The stratified survival analysis results showed that the status of SLNM was significantly associated with the OS in patients with pN1 GC (P = 0.001). The median OS was significantly shorter in 19 pN1 GC patients with SLNM than in 100 patients with perigastric lymph-node metastasis (P < 0.001). The case-control matched logistic regression analysis results showed that tumour size (P = 0.002) was the only clinicopathological factor that may predict SLNM in pN1 GC patients undergoing curative surgery. Among the 19 pN1 GC patients with SLNM, 17 (89.5%) had metastatic lymph nodes along the common hepatic artery, around the celiac artery or in the hepatoduodenal ligament. Conclusions: SLNM may be considered a potentially practicable indicator for prognosis among various subgroups of pN1 GC patients.

4.
Oncol Lett ; 17(1): 1245-1252, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30655891

RESUMO

Hypoxia is an important factor that results in failure of chemotherapy for the majority of solid tumor types, particularly for gastric cancer. In the present study, mesenchymal stem cells (MSCs), which have the ability to migrate to cancer tissues were used as a vehicle to supply oxygen to gastric cancer. The hemoglobin genes were transfected into MSCs as MSC-hemo groups. Subsequently, MSC-hemo groups were induced by isopropyl-b-D-thiogalactopyranoside and hemin to express hemoglobin. The hemoglobin was detected by western blotting method. Following this, the MSC-hemo groups were placed in an atmosphere containing 100% oxygen and were used to investigate the effect of the function of the oxygen-laden MSC-hemo group on gastric cancer chemotherapy with an MTT assay. As a first approach to investigate the possibility of MSCs as a vehicle to supply oxygen to anoxic cancer types, including gastric, liver, breast cancer, the results indicated that the oxygen-laden MSC-hemo group significantly enhanced the effect of chemotherapeutic treatments on gastric cancer cells. Utilizing MSCs as a svehicle to supply oxygen to the solid tumor may be a novel method to improve the hypoxia conditions of tumor tissues and improve the effect of chemotherapy on tumor cells.

5.
Mol Med Rep ; 19(3): 1471-1480, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30628681

RESUMO

γδ T cells are a subset of unconventional T cells that serve a critical role in infectious diseases and various types of cancer. Cell therapy with genetically­modified γδ T cells is regarded as a promising tool for tumor treatment. However, since γδ T cells constitute a minority of T cells, their large­scale expansion is difficult to realize in an efficient and cost­effective manner. In the present study, based on previous studies, culture protocols for γδ T cells were tested using different combinations of isopentenyl pyrophosphate and interleukin 2 in order to satisfy different experimental purposes. One protocol was demonstrated to be the most suitable for lentiviral transduction. These results greatly reinforce the promising prospects of using γδ T cells in basic research and for clinical applications.


Assuntos
Técnicas de Cultura de Células/métodos , Proliferação de Células , Subpopulações de Linfócitos T/citologia , Linfócitos T/citologia , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Lentivirus/genética , Receptores de Antígenos de Linfócitos T gama-delta/genética , Transdução Genética
6.
Chin J Integr Med ; 25(6): 416-424, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30484020

RESUMO

OBJECTIVE: To investigate the potential mechanisms that curcumin reverses 5-fluorouracil (5-FU) multidrug resistance (MDR). METHODS: Cell growth and the inhibitory rate of curcumin (2-25 µg/mL) and/or 5-FU (0.05-1000 µg/mL) on human colon cancer HCT-8 and HCT-8/5-FU (5-FU-resistant cell line) were determined using cell counting kit-8 (CCK-8) assay. Apoptosis and cell cycle after 5-FU and/or curcumin treatment were detected by flow cytometry (FCM) and transmission electron microscopy (TEM). The expression of the multidrug resistance related factors p-glycoprotein (P-gp) and heat shock protein 27 (HSP-27) genes and proteins were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting (WB), respectively. RESULTS: The inhibitory rate of curcumin or 5-FU on HCT-8 and HCT-8/5-FU cells proliferation at exponential phase were in a dosedependent manner, HCT-8 cell line was more sensitive to curcumin or 5-FU when compared the inhibitory rate of HCT-8/5-FU. The 50% inhibitory concentration (IC50) of combination 5-FU and curcumin (4.0 µg/mL) in HCT-8/5-FU was calculated as 179.26 µg/mL, with reversal fold of 1.85. Another IC50 of combination 5-FU and curcumin (5.5 µg/mL) in HCT-8/5-FU was calculated as 89.25 µg/mL, with reversal fold of 3.71. Synergistic effect of 5-FU and curcumin on HCT-8 and HCT-8/5-FU cells were found. The cell cycle analysis performed by FCM showed that HCT-8 and HCT-8/5-FU cells mostly accumulated at G0/G1 phase, which suggested a synergistic effect of curcumin and 5-FU to induce apoptosis. FCM analysis found that the percentage of apoptosis of cells treated with curcumin, 5-FU and their combination were significantly increased compared to the control group (P<0.05), and the percentage of apoptosis of the combination groups were slightly higher than other groups (P<0.05). The mRNA levels of P-gp (0.28±0.02) and HSP-27 (0.28±0.09) in HCT-8/5-FU cells treated with combination drugs were lower than cells treated with 5-FU alone (P-gp, 0.48±0.07, P=0.009; HSP-27, 0.57±0.10, P=0.007). The protein levels of P-gp (0.25±0.06) and HSP-27 (0.09±0.02) in HCT-8/5-FU cells treated with combination drugs were decreased when compared to 5-FU alone (P-gp, 0.46±0.02, P=0.005; HSP-27, 0.43±0.01, P=0.000). CONCLUSIONS: Curcumin can inhibit the proliferation of human colon cancer cells. Curcumin has the ability of reversal effects on the multidrug resistance of human colon cancer cells lines HCT-8/5-FU. Down-regulation of P-gp and HSP-27 may be the mechanism of curcumin reversing the drug resistance of HCT-8/5-FU to 5-FU.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Apoptose/efeitos dos fármacos , Neoplasias do Colo/patologia , Curcumina/farmacologia , Regulação para Baixo/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/farmacologia , Proteínas de Choque Térmico HSP27/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/ultraestrutura , Regulação para Baixo/efeitos dos fármacos , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP27/metabolismo , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
7.
Chin J Integr Med ; 24(8): 573-578, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29790064

RESUMO

OBJECTIVE: To investigate the efficacy of integrated Chinese and Western medicine (IM) in the treatment of metastatic colorectal cancer (mCRC) in a cohort study. METHODS: The survival outcome of patients receiving IM was compared with that of patients receiving Western medicine alone. The study design was adopted with "continuous administration of Chinese medicine for ⩾ 3 months" as the exposure factor. Patients who met this exposure factor were assigned to the IM cohort (Group A, 110 patients). Patients who did not meet this exposure factor were assigned to the Western medicine cohort (Group B, 225 patients). The overall survival (OS), progression-free survival (PFS), and 1st year, 2nd year, and 3rd year survival in the two cohorts were compared. RESULTS: The median OS in Group A and B were 18 months [95% confidence interval (CI) 15-21] and 16 months (95% CI 14-18), respectively, and the median PFS in Group A and B were 6 months (95% CI 4-7) and 5 months (95% CI 4-6), respectively. No statistically significant differences were observed between the groups (P=0.186, P=0.223). Group A demonstrated significantly longer OS and PFS than Group B in the following subgroups: female patients, patients with lesions in the right half of the colon, and those who received first-line treatment (P<0.05). In the subgroup of elderly patients (age>65 years), the OS in Group A was longer than that in Group B (P<0.05). CONCLUSION: IM could prolong the survival of patients with mCRC. (Registry No. ChiCTR-IOR-17010497).


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Integrativa , Idoso , Estudos de Coortes , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
8.
Bioorg Med Chem Lett ; 28(3): 394-399, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29275936

RESUMO

Akt, also known as protein kinase B (PKB), is a serine/threonine kinase that promotes survival and growth in response to extracellular signals. Akt1 has been demonstrated to play vital roles in cardiovascular diseases, but the role of Akt2 in cardiomyocytes is not fully understood. This study investigated the effect of Akt2 knockdown on tunicamycin (TM)-induced cytotoxicity in cardiomyocytes and the underlying mechanisms with a focus on the JNK-Wnt pathway. TM treatment significantly increased the expression of Akt2 at both mRNA and protein levels, which was shown to be mediated by the induction of reactive oxygen species (ROS). Knockdown of Akt2 expression via siRNA transfection markedly increased cell viability, decreased lactate dehydrogenase (LDH) release and reduced cell apoptosis after TM exposure. The results of western blot showed that downregulation of Akt2 also attenuated the TM-induced activation of the unfolded protein response (UPR) factors and ER stress associated pro-apoptotic proteins. In addition, Si-Akt2 transfection partially prevented the TM-induced decrease in nuclear localization of ß-catenin. By using the selective inhibitor SP-600,125 to inhibit JNK phosphorylation, we found that knockdown of Akt2-induced protection and inhibition of ER stress was mediated by reversing TM-induced decrease of Wnt through the JNK pathway. In summary, these data suggested that Akt2 play a pivotal role in regulating cardiomyocyte survival during ER stress by modulating the JNK-Wnt pathway.


Assuntos
Regulação para Baixo/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Tunicamicina/farmacologia , Apoptose/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Modelos Moleculares , Estrutura Molecular , Miócitos Cardíacos/metabolismo , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Relação Estrutura-Atividade , Tunicamicina/química , Via de Sinalização Wnt/efeitos dos fármacos
9.
World J Gastroenterol ; 23(33): 6119-6127, 2017 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-28970727

RESUMO

AIM: To investigate the molecular mechanisms of gastric carcinogenesis. METHODS: We used label-free quantification technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify differentially expressed proteins in 160 specimens of normal gastric mucosa, gastric mucosa with mild dysplasia, moderate dysplasia, severe dysplasia, and early mucosal gastric cancer (GC) collected at the Second Hospital of Lanzhou University from 2010 to 2015. Immunohistochemistry was used to verify the differentially expressed proteins detected by LC-MS/MS. RESULTS: With a threshold of a 1.2-fold change and a P-value < 0.05 between mild dysplasia, moderate dysplasia, severe dysplasia or early mucosal GC and matched normal gastric mucosa tissues, proteomic analysis identified 365 significantly differentially expressed proteins. ERGIC1 expression decreased, while DNA-PKcs expression increased gradually along with different stages of GC initiation based on the tendency of fold change. The expression patterns of ERGIC1 and DNA-PKcs revealed by immunohistochemistry were consistent with the LC-MS/MS results. CONCLUSION: The results suggest that aberrant ERGIC1 and DNA-PKcs expression may be involved in GC initiation.


Assuntos
Carcinogênese/patologia , Diferenciação Celular , Proteína Quinase Ativada por DNA/metabolismo , Proteínas Nucleares/metabolismo , Neoplasias Gástricas/patologia , Proteínas de Transporte Vesicular/metabolismo , Adulto , Idoso , Cromatografia Líquida de Alta Pressão/métodos , Regulação para Baixo , Feminino , Mucosa Gástrica/patologia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteômica/métodos , Espectrometria de Massas em Tandem/métodos , Regulação para Cima
10.
Front Immunol ; 8: 983, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28861087

RESUMO

Mycobacterium tuberculosis/human immunodeficiency virus (MTB/HIV) coinfection presents a special challenge to the prevention and treatment of tuberculosis and HIV/AIDS. Adoptive transfer of high-affinity T cell receptor (TCR) gene-modified T cells against MTB and HIV antigens is a promising approach to treating MTB/HIV coinfected patients whose cellular immunity is obviously disordered. We have previously successfully identified that a bispecific TCR screened out from peripheral blood mononuclear cells of a HLA-A*0201+ healthy individual using the complementarity determining region 3 (CDR3) spectratype analysis recognizes both MTB Ag85B199-207 and HIV-1 Env120-128 peptide. However, it has not been known how residues on CDR3 loops, which have been shown to play a leading role in antigen binding and specificity contribute to the bispecific TCR contact with the peptide-major histocompatibility complex (MHC) complexes. In this study, we provided an extensive investigation of residues in the predicted CDR3 of the bispecific TCR beta (ß) chain using alanine scanning mutagenesis. Our data showed that three of the five substituted residues (G115A, T116A, A117G) in CDR3ß of the bispecific TCR caused a significantly diminished T cell response to antigen, whereas the remaining two substituted residues (D114A, S118A) resulted in completely eliminated response, thus identifying the two residues that were particularly critical for the recognition of peptide-MHC in the bispecific TCR. These findings will provide an imperative foundation for generating an improved high-affinity bispecific TCR for use in T cell adoptive immunotherapy for MTB/HIV coinfected individuals.

11.
Oncol Rep ; 36(1): 223-30, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27176873

RESUMO

Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal carcinoma and remains the leading cause of cancer-related death worldwide. DEAD-box RNA helicases play critical roles in cellular metabolism and in many cases have been implicated in cellular proliferation and neoplastic transformation. DDX46 belongs to DEAD-box helicase family, the expression pattern of DDX46 in ESCC tissues and the biologic role in ESCC progression have not been implicated previously. In this study, DDX46 expression in human ESCC and adjacent normal tissues were explored using immunohistochemistry, and ESCC cell lines compared with normal esophageal epithelium cell were quantified using real­time PCR. Next, lentivirus-mediated RNA interference was applied to silence DDX46 in TE-1 and Eca-109 cells. Cell growth was monitored using high content screening. Cell viability was measured by MTT assay. Cell colony-forming capacity was measured by colony formation assay. Cell cycle progression and apoptosis were determined by flow cytometry. Further, the stress and apoptosis signaling antibody array kit was used to detect the changes of signaling molecules in TE-1 cells after DDX46 knockdown. We found that DDX46 was significantly upregulated in ESCC tissues and cells compared with normal tissues and cells. DDX46 knockdown led to decreased proliferation and increased apoptosis in TE-1 and Eca-109 cells. Moreover, DDX46 silencing resulted in apoptotic induction via decreased phosphorylation of Akt and IκBα, as well as negative regulation of NF-κB signaling. In conclusion, these results demonstrate that DDX46 knockdown inhibited cell growth, and induced apoptosis, suggest that DDX46 is critical for ESCC cells proliferation. In addition, this study provides a foundation for further study into the clinical potential diagnosis and novel therapeutic target for ESCC.


Assuntos
Apoptose/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Proliferação de Células/genética , RNA Helicases DEAD-box/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Ribonucleoproteína Nuclear Pequena U2/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Epitélio/patologia , Carcinoma de Células Escamosas do Esôfago , Esôfago/patologia , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes/métodos , Humanos , Lentivirus/genética , NF-kappa B/genética , Proteínas Proto-Oncogênicas c-akt/genética , Interferência de RNA/fisiologia , Transdução de Sinais/genética , Regulação para Cima/genética
12.
J Cell Mol Med ; 20(10): 1984-98, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27113787

RESUMO

Tuberculosis (TB) and human immunodeficiency virus type 1 (HIV-1) infection are closely intertwined, with one-quarter of TB/HIV coinfected deaths among people died of TB. Effector CD8(+) T cells play a crucial role in the control of Mycobacterium tuberculosis (MTB) and HIV-1 infection in coinfected patients. Adoptive transfer of a multitude of effector CD8(+) T cells is an appealing strategy to impose improved anti-MTB/HIV-1 activity onto coinfected individuals. Due to extensive existence of heterologous immunity, that is, T cells cross-reactive with peptides encoded by related or even very dissimilar pathogens, it is reasonable to find a single T cell receptor (TCR) recognizing both MTB and HIV-1 antigenic peptides. In this study, a single TCR specific for both MTB Ag85B199-207 peptide and HIV-1 Env120-128 peptide was screened out from peripheral blood mononuclear cells of a HLA-A*0201(+) healthy individual using complementarity determining region 3 spectratype analysis and transferred to primary CD8(+) T cells using a recombinant retroviral vector. The bispecificity of the TCR gene-modified CD8(+) T cells was demonstrated by elevated secretion of interferon-γ, tumour necrosis factor-α, granzyme B and specific cytolytic activity after antigen presentation of either Ag85B199-207 or Env120-128 by autologous dendritic cells. To the best of our knowledge, this study is the first report proposing to produce responses against two dissimilar antigenic peptides of MTB and HIV-1 simultaneously by transfecting CD8(+) T cells with a single TCR. Taken together, T cells transduced with the additional bispecific TCR might be a useful strategy in immunotherapy for MTB/HIV-1 coinfected individuals.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Epitopos/imunologia , HIV-1/imunologia , Mycobacterium tuberculosis/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Transdução Genética , Sequência de Aminoácidos , Antígenos/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Sequência de Bases , Citotoxicidade Imunológica , Vetores Genéticos/metabolismo , Humanos , Interferon gama/metabolismo , Lectinas Tipo C/metabolismo , Peptídeos/imunologia , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/genética , Fator de Necrose Tumoral alfa/metabolismo
13.
Curr Stem Cell Res Ther ; 11(5): 434-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26496889

RESUMO

The incidence of gastric cancer is third most prevalent among all malignant tumors in China. The conventional therapies for advanced gastric cancer are futile. Targeted gene therapy has become a promising alternative approach. Mesenchymal stem cells (MSCs) can be used as potential cellular vehicles for cancer therapy in vivo. This review will summarize the published data about the application of MSC-based targeted therapy for gastric cancer, and discuss some of the challenges associated with this method.


Assuntos
Terapia Genética , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Neoplasias Gástricas/terapia , Animais , Humanos , Terapia de Alvo Molecular
14.
Am J Cancer Res ; 4(6): 924-33, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25520880

RESUMO

We have previous found a positive correlation between post-therapy TCR repertoire normalization and remission of colorectal cancer (CRC) patients following fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or Rh-endostatin therapy. To further define the TCR repertoire diversity changes following treatment in CRC patients, and confirm its potential prognostic value, the present study extended the sample size of follow-up and used an alternative therapy regime to investigate changes of TCR repertoires following Erbitux plus FOLFIRI therapy. Inclusion and exclusion criteria have been established to screen out 26 patients to receive Erbitux plus FOLFIRI therapy. Efficacy and toxicity assessment have been made for them after 3 months' treatment as well as the TCR repertoire diversity has been determined. A CDR3 complex scoring system was used to quantify the diversity of TCR repertoire. The results showing that the diversity of CD4(+) T cells in PR group was significantly higher than that of SD and PD groups, and the difference was enlargement after treatment. The diversity of CD8(+) T cells in PR group has no difference before and after treatment, but significant decrease in SD and PD group after treatment. In conclusion, analysis the diversity of T cell repertoire has an important prognosis value for CRC patients.

15.
Asian Pac J Cancer Prev ; 15(9): 4067-70, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24935598

RESUMO

BACKGROUND: The Chinese Hui ethnic group has diverse origins, including Arab, Persian, Central Asian, and Mongol. The standardized mortality rate of gastric cancer in the Hui population is higher than the overall Chinese population. In this study, we investigated whether COX-2-765G>C polymorphism, an extensively studied polymorphism, contributes to gastric cancer and its precursor lesions (GPL) in the Chinese Hui ethnic group. MATERIALS AND METHODS: COX-2-765G>C polymorphism was determined by pyrosequencing in 100 gastric cancer cases, 102 gastric cancerand its precursor lesions cases and 105 controls. Data were statistically analyzed using Chi-square tests and logistic regression models. RESULTS: Among the Chinese Hui ethnic group COX-2 -765 C allele carriers were at increased risk for gastric cancer (OR=1.977, 95%CI=1.104-3.541). We also found an interaction between COX-2 -765 C carriers and Helicobacter pylori infection and eating pickled vegetables. CONCLUSIONS: Our findings suggest a multi-step process of gene-environment interaction contributes to gastric carcinogenesis.


Assuntos
Carcinogênese/genética , Ciclo-Oxigenase 2/genética , Comportamento Alimentar , Infecções por Helicobacter/patologia , Neoplasias Gástricas/genética , Sequência de Bases , China , Dieta , Grupos Étnicos/genética , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Lesões Pré-Cancerosas/genética , Risco , Análise de Sequência de DNA , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/mortalidade , Inquéritos e Questionários
16.
Zhong Xi Yi Jie He Xue Bao ; 10(4): 406-15, 2012 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-22500714

RESUMO

OBJECTIVE: To explore the characteristic genomics of syndrome of liver-kidney yin deficiency in peripheral blood mononuclear cells of hepatocellular carcinoma (HCC) patients. METHODS: HCC patients with or without syndrome of liver-kidney yin deficiency were enrolled into the experimental group and the control group, respectively; their gene expression profiles were evaluated by a whole-genome Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. The differentially expressed mRNAs were then selected by Gene Ontology (GO) and pathway analyses, respectively. Based on the results of GO and pathway analyses, gene coexpression networks were built according to the normalized signal intensity of specifically expressed genes. Finally, the results from microarray were confirmed by real-time fluorescence quantitative polymerase chain reaction and Western blot methods. RESULTS: The results showed that a set of 615 mRNAs were differentially expressed in the HCC patients with syndrome of liver-kidney yin deficiency. By GO enrichment analysis, the genes for anti-apoptosis, regulation of cell cycle, transmembrane transport, etc. were up-regulated or down-regulated in the experimental group. Another functional analysis of mRNAs by KEGG revealed that 10 signal transduction pathways were up-regulated and 16 were down-regulated, such as antigen processing and presentation, cell cycle, and protein export. Based on the above results, we constructed coexpression networks to determine which genes may play pivotal role in HCC patients with syndrome of liver-kidney yin deficiency. Some critical genes, including SEC62 (SEC62 homolog (S. cerevisiae)), CCNB1 (cyclin B1) and BIRC3 (baculoviral IAP repeat-containing 3), which rank the top 3 in |δ normalized degree| were chosen. Of another 60 samples, we found that the mRNA expressions of SEC62, CCNB1 and BIRC3 were significantly lower in HCC patients with syndrome of liver-kidney yin deficiency than those without syndrome of liver-kidney yin deficiency (P<0.01). Also, the protein expressions of SEC62, CCNB1 and BIRC3 were significantly lower (P<0.01). CONCLUSION: Gene chip technique allows rapid and high-throughput screening for different gene expression in HCC patients with or without liver-kidney yin deficiency syndrome. The results of this study further confirm the hypothesis on the essence of syndrome, namely, a kind of deviation from the normal state in multigene style on the levels of both mRNA and protein.


Assuntos
Carcinoma Hepatocelular/genética , Leucócitos Mononucleares/metabolismo , Neoplasias Hepáticas/genética , Medicina Tradicional Chinesa , Adulto , Idoso , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Expressão Gênica , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Genômica , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Deficiência da Energia Yin
17.
World J Gastroenterol ; 18(48): 7262-70, 2012 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-23326131

RESUMO

AIM: To clarify the role of activated Notch2 in the invasiveness of gastric cancer. METHODS: To investigate the invasiveness of silencing Notch2 gene expression, we established a Notch2 small interfering RNA (siRNA) transfected cell line using the MKN-45 gastric cancer cell line. After the successful transfection confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, migration and invasion assays were employed to evaluate the aggressiveness of the gastric cancer. RT-PCR and Western blottings were employed to confirm the down-regulation of Notch2 and to evaluate the expression of epithelial mesenchymal transition-related gene matrix metallopeptidase 9 (MMP9), Akt, p-Akt. To confirm the relationship between PI3K-Akt and MMP9, the PI3K inhibitor LY294002 was used to treat MKN-45 cells. RESULTS: Notch2 expression was dramatically decreased after Notch2 siRNA transfection (100.00% ± 9.74% vs 11.61% ± 3.85%, P < 0.01 by qRT-PCR). There was also a marked reduction of Notch target gene Hes1 (100.00% ± 4.74% vs 61.61% ± 3.58%, P < 0.05) at the mRNA, indicating an inhibition of Notch signaling. Inhibition of Notch signaling was also confirmed by the marked reduction of Notch2 intracellular domain at the protein levels (100.00% ± 9.74% vs 65.61% ± 7.58%, P < 0.05). Down-regulation of Notch2 by siRNA enhanced tumor cell invasion (100.00% ± 21.64% vs 162.22% ± 16.84%, P < 0.05) and expression of MMP9 (1.56 fold, P < 0.05), and activated the pro-MMP9 protein to its active form (1.48 fold, P < 0.05). There was no significant difference in the protein levels of Akt between the two groups (100.00% ± 10.87% vs 96.61% ± 7.33%, P > 0.05), while down-regulation of Notch2 elevated p-Akt expression (100.00% ± 9.87% vs 154.61% ± 13.10%, P < 0.05). Furthermore, p-Akt and MMP9 was down-regulated in response to the inhibitor LY294002 (p-Akt 100.00% ± 8.87% vs 58.27% ± 5.01%, P < 0.05; MMP9 100.00% ± 9.17% vs 50.03% ± 4.88%, P < 0.05). CONCLUSION: Notch2 may negatively regulate cell invasion by inhibiting the PI3K-Akt signaling pathway in gastric cancer.


Assuntos
Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Metaloproteinase 9 da Matriz/metabolismo , Receptor Notch2/metabolismo , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Movimento Celular , Cromonas/farmacologia , Humanos , Morfolinas/farmacologia , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais
18.
Zhonghua Wei Chang Wai Ke Za Zhi ; 14(7): 516-9, 2011 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-21792762

RESUMO

OBJECTIVE: To evaluate the prognostic value of metastatic lymph node ratio (MLR) for patients with gastric cancer. METHODS: Data collected from 1247 patients with gastric cancer who underwent radical surgery (pT4 cases were excluded) at the First Affiliated Hospital of Nanjing Medical University between 2005 and 2009 were analyzed retrospectively. MLR was compared to pathological N staging (pN) in terms of prognostic accuracy, homogenicity, and applicability. RESULTS: MLR and pN were both positively correlated with the number of retrieved lymph nodes(both P<0.01). Significant differences were found in 5-year cumulative survival rate (5-YCSR) among different pN stages and MLR classification(all P<0.01). Multivariable analysis showed that both pN and MLR were independent prognostic factors(both P<0.01). The area under ROC curve(AUC) of MLR was larger than pN, however the difference was not statistically significant(P>0.05). There were significant differences in 5-YCSR among different MLR stages within the same pN stages(P<0.05), but not among different pN stages within the same MLR stage(P>0.05). Significant differences in 5-YCSR were also found among different retrieved-node groups within the same pN stage (P<0.05), but not within the same MLR stages (P>0.05). CONCLUSIONS: MLR is an independent prognostic factor for patients with gastric cancer. The prognostic homogenicity and applicability of MLR are better than those of pN, however the prediction accuracy is not favorable.


Assuntos
Linfonodos/patologia , Metástase Linfática/patologia , Neoplasias Gástricas/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico
19.
Chin Med J (Engl) ; 124(24): 4193-7, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22340386

RESUMO

BACKGROUND: Hepatitis B virus infection is closely related to hepatocellular carcinoma (HCC). Cyclooxygenase-2 (COX-2) is overexpressed in HCC and considered to play a role in hepatic carcinogenesis. In this study, we analyzed the polymorphism of COX-2 promoter -899G/C in healthy controls, chronic hepatitis B (CHB) patients, liver cirrhosis patients, and hepatocellular carcinoma (HCC) patients, to investigate the relationship between COX-2 -899G/C polymorphism and the risk for hepatitis B-related liver cancer in a Chinese population from Gansu province. METHODS: Patients were divided into four groups: 300 patients with CHB, 300 patients with liver cirrhosis, 300 patients with HCC, and 300 healthy controls. The polymorphism of COX-2 -899G/C was detected by PCR-TaqMan probes. The results were analyzed by SPSS 17.0. RESULTS: The COX-2 -899G/C genotypes were GG, GC, and CC. Frequencies in CHB were 87.00%, 12.67%, 0.33%; in liver cirrhosis were 85.33%, 14.00%, 0.67%; in HCC were 77.00%, 21.67%, 1.33%; and in healthy controls were 90.67%, 9.00%, 0.33%, respectively. COX-2 -899C carriers may have an increased risk for hepatitis B-related liver cancer. Compared with the frequency of GG genotype, there were significant differences in the frequency of GC genotype between HCC and healthy control groups (OR = 2.835, 95%CI: 1.751 - 4.589); HCC and CHB groups (OR = 1.933, 95%CI: 1.248 - 2.994); and HCC and liver cirrhosis groups (OR = 1.175, 95%CI: 1.119 - 2.628). Stratification analyses showed that COX-2 -899C allele carriers with a drinking history are more susceptible to develop HCC. CONCLUSION: COX-2 -899C genotype may increase the susceptibility of individuals to hepatitis B-related liver cancer in Gansu province, China.


Assuntos
Carcinoma Hepatocelular/genética , Ciclo-Oxigenase 2/genética , Hepatite B/genética , Neoplasias Hepáticas/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Carcinoma Hepatocelular/etiologia , Feminino , Predisposição Genética para Doença , Hepatite B/etiologia , Humanos , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade
20.
World J Gastroenterol ; 16(37): 4738-46, 2010 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-20872977

RESUMO

AIM: To investigate the effects of superoxide dismutase (SOD) polymorphisms (rs4998557, rs4880), Helicobacter pylori (H. pylori) infection and environmental factors in gastric cancer (GC) and malignant potential of gastric precancerous lesions (GPL). METHODS: Copper-zinc superoxide dismutase (SOD1, CuZn-SOD)-G7958A (rs4998557) and manganese superoxide dismutase (SOD2, Mn-SOD)-Val16Ala (rs4880) polymorphisms were genotyped by SNaPshot multiplex polymerase chain reaction (PCR) in 145 patients with GPL (87 cases of gastric ulcer, 33 cases of gastric polyps and 25 cases of atrophic gastritis), 140 patients with GC and 147 healthy controls. H. pylori infection was detected by immunoblotting analysis. RESULTS: The SOD1-7958A allele was associated with a higher risk of gastric cancer [odds ratio (OR) = 3.01, 95% confidence intervals (95% CI): 1.83-4.95]. SOD2-16Ala/Val genotype was a risk factor for malignant potential of GPL (OR = 2.04, 95% CI: 1.19-3.49). SOD2-16Ala/- genotype increased the risk of gastric cancer (OR = 2.85, 95% CI: 1.66-4.89). SOD1-7958A/- genotype, SOD2-16Ala/- genotype, alcohol drinking, positive family history and type I H. pylori infection were associated with risk of gastric cancer, and there were additive interactions between the two genotypes and the other three risk factors. SOD2-16Ala/Val genotype and positive family history were associated with malignant potential of GPL and jointly contributed to a higher risk for malignant potential of GPL (OR = 7.71, 95% CI: 2.10-28.22). SOD1-7958A/- genotype and SOD2-16Ala/- genotype jointly contributed to a higher risk for gastric cancer (OR = 6.43, 95% CI: 3.20-12.91). CONCLUSION: SOD1-7958A/- and SOD2-16Ala/-genotypes increase the risk of gastric cancer in Chinese Han population. SOD2-16Ala/-genotype is associated with malignant potential of GPL.


Assuntos
Predisposição Genética para Doença , Polimorfismo Genético , Neoplasias Gástricas , Superóxido Dismutase/genética , Adulto , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Grupos Étnicos/genética , Feminino , Infecções por Helicobacter/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia
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