RESUMO
Objective: To evaluate the relationships between the location and extent of diffusion of free intraperitoneal air by multi-slice spiral CT (MSCT) and between the location and size of acute gastrointestinal perforation. Methods: This was a descriptive case series. We examined abdominal CT images of 33 patients who were treated for intraoperatively confirmed gastrointestinal perforation (excluding appendiceal perforation) in the Department of General Surgery, Nanfang Hospital between January and September 2022. We identified five locations of intraperitoneal air: the subphrenic space, hepatic portal space, mid-abdominal wall, mesenteric space, and pelvic cavity. We allocated the 33 patients to an upper gastrointestinal perforation (n=23) and lower gastrointestinal perforation group (n=10) base on intraoperative findings and analyzed the relationships between the locations of free gas and of gastrointestinal perforation. Additionally, we established two models for analyzing the extent of diffusion of free gas in the abdominal cavity and constructed receiver operating characteristic (ROC) curves to analyze the relationships between the two models and the size of the gastrointestinal perforation. Results: In the upper gastrointestinal perforation group, free gas was located around the hepatic portal area in 91.3% (21/23) of patients: this is a significantly greater proportion than that found in the lower gastrointestinal perforation group (5/10) (P=0.016). In contrast, free gas was located in the mesenteric interspace in 8/10 patients in the lower gastrointestinal perforation group; this is a significantly greater proportion than was found in the upper gastrointestinal perforation group (8.7%, 2/23) (P<0.010). The sensitivity of diagnosis of upper gastrointestinal perforation base on the presence of hepatic portal free gas was 84.8% and the specificity 71.4%. Further, the sensitivity of diagnosis of lower gastrointestinal perforation base on the presence of mesenteric interspace free gas was 80.0% and the specificity 91.3%. The rates of presence of free gas in the subdiaphragmatic area, mid-abdominal wall, and pelvic cavity did not differ significantly between the two groups (all P>0.05). Receiver operating characteristic curves showed that when free gas was present in four or more of the studied locations in the abdominal cavity, the optimal cutoff for perforation diameter was 2 cm, the corresponding sensitivity 66.7%, and the specificity 100%, suggesting that abdominal free gas diffuses extensively when the diameter of the perforation is >2 cm. Another model revealed that when free gas is present in three or more of the studied locations, the optimal cutoff for perforation diameter is 1 cm, corresponding to a sensitivity of 91.7% and specificity of 76.2%; suggesting that free gas is relatively confined in the abdominal cavity when the diameter of the perforation is <1 cm. Conclusion: Identifying which of five locations in the abdominal cavity contains free intraperitoneal air by examining MSCT images can be used to assist in the diagnosis of the location and size of acute gastrointestinal perforations.
Assuntos
Cavidade Abdominal , Perfuração Intestinal , Trato Gastrointestinal Superior , Humanos , Tomografia Computadorizada Multidetectores , Tomografia Computadorizada Espiral , Fígado , Estudos RetrospectivosRESUMO
The aim of this study was to evaluate the efficacy of marsupialization treatment for odontogenic keratocyst (OKC) and unicystic ameloblastoma (UA) based on the three-dimensional volumetric change over time, and to determine the difference between OKC and UA in terms of the absolute volume reduction (AVR) and absolute shrinkage speed (ASS), and whether they are correlated with the preoperative volume, time after marsupialization (time between marsupialization and second treatment), and patient age. This was a retrospective cohort study with a sample size of 60 patients: 29 with OKC and 31 with UA. Pre- and post-marsupialization cone beam computed tomography images were analysed using Mimics software. The volume reduction and shrinkage speed were analysed and correlated with the preoperative volume, time after marsupialization, and demographic data. Descriptive univariable and multivariable statistics were computed; significance was set at P ≤ 0.05. The mean percentage volume reduction after marsupialization was 67.6 ± 9.6% for OKC and 63.3 ± 20.1% for UA. There was no significant difference in AVR or ASS between the OKC and UA groups. For OKC and UA, the preoperative volume (both P < 0.001) and time after marsupialization (P = 0.024 and P < 0.001, respectively) were associated with AVR. Moreover, for OKC and UA, the preoperative volume and time after marsupialization were also significantly associated with the ASS (all P < 0.001). For both lesions, patient age was not significantly related to AVR or ASS. Marsupialization appears to be a viable option to decrease the volume of OKC and UA. Age was found not to be associated with the volume reduction of either UA or OKC.
Assuntos
Ameloblastoma , Cistos Odontogênicos , Cistos Odontogênicos/diagnóstico por imagem , Cistos Odontogênicos/cirurgia , Tomografia Computadorizada de Feixe Cônico , Ameloblastoma/diagnóstico por imagem , Ameloblastoma/cirurgiaRESUMO
Objective: To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) with the novel Prizvalve® system in treating severe aortic stenosis. Methods: This is a single-center, prospective, single-arm, observational study. A total of 11 patients with severe aortic stenosis with high risk or inappropriate for conventional surgical aortic valve replacement (SAVR) were included, and TAVI was achieved with the Prizvalve® system between March 2021 and May 2021 in West China Hospital. Transthoracic echocardiography (TTE) was performed immediately after prosthesis implantation to evaluate mean transaortic gradient and maximal transaortic velocity. The device success rate was calculated, which was defined as (1) the device being delivered via the access, deployed, implanted and withdrawn, (2) mean transaortic gradient<20 mmHg (1 mmHg=0.133 kPa) or a maximal transaortic velocity<3 m/s post TAVI, and without severe aortic regurgitation or paravalvular leak post TAVI. TTE was performed at 30 days after the surgery, and all-cause mortality as well as the major cardiovascular adverse events (including acute myocardial infarction, disabling hemorrhagic or ischemic stroke) up to 30 days post TAVI were analyzed. Results: The age of 11 included patients were (78.1±6.3) years, with 8 males. A total of 10 patients were with NYHA functional class â ¢ or â £. Devices were delivered via the access, deployed, implanted and withdrawn successfully in all patients. Post-implant mean transaortic gradient was (7.55±4.08) mmHg and maximal transaortic velocity was (1.78±0.44) m/s, and both decreased significantly as compared to baseline levels (both P<0.05). No severe aortic regurgitation or paravalvular leak was observed post TAVI. Device success was achieved in all the 11 patients. No patient died or experienced major cardiovascular adverse events up to 30 days post TAVI. Mean transaortic gradient was (9.45±5.07) mmHg and maximal transaortic velocity was (2.05±0.42) m/s at 30 days post TAVI, which were similar as the values measured immediately post TAVI (both P>0.05). Conclusions: TAVI with the Prizvalve® system is a feasible and relatively safe procedure for patients with severe aortic stenosis and at high risk or inappropriate for SAVR. Further clinical studies could be launched to obtain more clinical experience with Prizvalve® system.
Assuntos
Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica , Estenose da Valva Aórtica/etiologia , Estenose da Valva Aórtica/cirurgia , Humanos , Masculino , Estudos Prospectivos , Substituição da Valva Aórtica Transcateter/métodos , Resultado do TratamentoRESUMO
A clear bone margin is essential for complete resection of the bone-involved tumour, but the evaluation of hard tissue takes time and is impractical intraoperatively. Bone marrow assessment remains controversial. The aim of this study was to investigate the diagnostic value of intraoperative bone marrow assessment for bone margins. PubMed and Web of Science were searched for studies published between 1990 and 2017. A systematic review was conducted. After quality assessment, 10 articles with 11 cohorts and 404 patients were identified. Sensitivity, specificity, and other measures were pooled for meta-analysis; the estimates for intraoperative bone marrow assessment were as follows: sensitivity 0.82 (95% confidence interval (CI) 0.62-0.93), specificity 0.99 (95% CI 0.96-1.00), positive likelihood ratio 109.79 (95% CI 22.99-524.34), negative likelihood ratio 0.18 (95% CI 0.08-0.42), and diagnostic odds ratio 241.82 (95% CI 90.33-647.38). Furthermore, sensitivity and specificity at the summary operating point of the summary receiver operating characteristic curve were 0.82 and 0.99, respectively, and the area under the curve was 0.99. Intraoperative bone marrow assessment was investigated by meta-analysis and shown to have a high level of overall accuracy for the diagnosis of bone margins.
Assuntos
Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Medula Óssea , Humanos , Margens de Excisão , Curva ROC , Sensibilidade e EspecificidadeRESUMO
The facial artery pedicle nasolabial island flap (FAPNIF) is widely used for oral and maxillofacial reconstruction. However, its use in reconstruction after malignant tumour resection is limited by the possibility of ipsilateral cervical lymph node metastasis along the facial artery. Through fine dissection, it was found that the contralateral FAPNIF can be used to repair the defect after buccal carcinoma resection. The aim of this study was to evaluate the clinical outcomes of the contralateral FAPNIF for buccal defect repair. From 2013 to 2016, 30 patients underwent the repair of a buccal defect with a contralateral FAPNIF after tumour resection. Clinical outcomes and complications were recorded and quality of life was evaluated preoperatively and at 3, 6, and 12 months postoperative. The flaps survived in all 30 cases. Mean mouth opening was 2.50±0.14cm at 1 month, 3.22±0.25cm at 6 months, and 3.35±0.23cm at 12 months postoperative. With regard to patient quality of life, adverse effects included impaired aesthetics, pain, and difficulty eating; these usually subsided within 1year after surgery. The contralateral FAPNIF is easily harvested and is a safe and effective option for the repair of medium-sized buccal defects after the resection of carcinoma.
Assuntos
Neoplasias Bucais/cirurgia , Procedimentos de Cirurgia Plástica , Artérias , Estética Dentária , Humanos , Qualidade de Vida , Retalhos CirúrgicosRESUMO
Primary intraosseous carcinoma (PIOC) is a rare but aggressive type of odontogenic tumour arising within the jawbone. Diagnosis criteria and treatment strategy remain difficult and controversial. The present study aimed to clarify the clinicopathological features and determine prognostic factors in management of PIOC. A retrospective study of 30 patients with PIOC, treated at the Hospital of Stomatology of Sun Yat-sen University between 2009 and 2017, was conducted. Clinical, histopathological and treatment modality data were collected. Follow-up data were recorded to determine prognostic factors. There were 19 males and 11 females with a mean age of 52.3 years. The most common location of the tumour was the mandible (90%). Having a history of tooth extraction or tooth mobility was the major characteristic symptom (63.3%), jaw swelling coming in second (53.3%). Half of the patients underwent surgery alone. The estimated 2-year overall survival rate (OS) and recurrence-free survival rate (RFS) were 61.3% and 40.1%, respectively. Higher histological grade was an independent risk factor for poor OS (hazard ratio (HR) 0.233 [0.059-0.915], P=0.037), while at pN+ stage for RFS, HR=5.627 [1.199-26.409], P=0.029. Because of its rarity and intrabony site, the classification, staging and treatment guidelines for PIOC should be further studied and established.
Assuntos
Neoplasias Maxilomandibulares/patologia , Tumores Odontogênicos/patologia , Adulto , Idoso , Feminino , Humanos , Neoplasias Maxilomandibulares/terapia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Tumores Odontogênicos/terapia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
The medial upper arm has previously been proposed as a potential free flap donor site, but the clinical application of such flaps in head and neck reconstruction has not been popular. The preliminary results of the clinical application of medial upper arm free flaps in oral cavity reconstruction are reported here. Five patients with oral cancer underwent surgical resection and neck dissection, with simultaneous reconstruction using a medial upper arm free flap. Functional outcomes were investigated using the University of Washington Quality of Life Questionnaire. Sensory-motor functions of the upper arm donor site were recorded before and after surgery. Four flaps were successfully transferred. One flap was abandoned during surgery because of a lack of perforators, and a forearm flap was used instead. All patients survived without loco-regional recurrence or distant metastasis. Functional outcomes, especially swallowing and speech, were satisfactory. The donor site scar was well hidden, with no functional impairment. This initial experience shows that the medial upper arm free flap represents an alternative perforator flap for oral cavity microsurgical reconstruction. The well-hidden scar and better texture match compared with other flaps make it suitable for oral cavity reconstruction.
Assuntos
Braço/irrigação sanguínea , Carcinoma Adenoide Cístico/cirurgia , Carcinoma de Células Escamosas/cirurgia , Retalhos de Tecido Biológico/irrigação sanguínea , Neoplasias Bucais/cirurgia , Procedimentos Cirúrgicos Bucais/métodos , Procedimentos de Cirurgia Plástica/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Qualidade de Vida , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Danshen (Salvia miltiorrhiza), a Chinese medicinal herb, consists of several functional components including tanshinones responsible for prevention of several chronic diseases. This study intends to prepare tanshinone extract and nanoemulsion from danshen and determine their inhibition effect on lung cancer cells A549. A highly stable tanshinone nanoemulsion composed of Capryol 90, Tween 80, ethanol and deionized water with the mean particle size of 14.2 nm was successfully prepared. Tanshinone nanoemulsion was found to be more effective in inhibiting A549 proliferation than tanshinone extract. Both nanoemulsion and extract could penetrate into cytoplasm through endocytosis, with the former being more susceptible than the latter. A dose-dependent response in up-regulation of p-JNK, p53 and p21 and down-regulation of CDK2, cyclin D1 and cyclin E1 expressions was observed with the cell cycle arrested at G0/G1 phase. The cellular microcompartment change of A549 was also investigated. The study demonstrated that tanshinone nanoemulsion may be used as a botanic drug for treatment of lung cancer.
Assuntos
Nanoestruturas , Células A549 , Abietanos , Ciclo Celular , Emulsões , Humanos , Neoplasias Pulmonares , Salvia miltiorrhizaRESUMO
OBJECTIVE: The treatment of large mandibular cystic lesions (diameter > 35 mm) is controversial. Few studies determine the inferior alveolar nerve function after decompression which is one of the major options for treating such lesions. We aim to investigate the recovery of inferior alveolar nerve function after decompression. METHODS: Twenty-two patients with large mandibular cystic lesions, diagnosed as keratocystic odontogenic tumor, ameloblastoma, or dentigerous cyst, were included. Inferior alveolar nerve function was observed by monitoring the pulp vitality of involved teeth (n = 64) with electric pulp test before decompression and 1, 3, 6, 9, 12, and 24 months after decompression, respectively. RESULTS: The pulp vitality of the involved teeth was significantly decreased before decompression. Recovery of pulp vitality could be observed after decompression, indicating the recovery of inferior alveolar nerve function. A majority (96.9%) of the vital pulp was preserved in the involved teeth after decompression. CONCLUSIONS: Recovery of inferior alveolar nerve function was remarkable in patients with large mandibular cystic lesions after decompression, indicated by the recovery of pulp vitality of involved teeth. When decompression is preferred, conservative therapy rather than root canal therapy is recommended for the teeth with root tip exposed in the cystic lesions and without pulposis.
Assuntos
Descompressão Cirúrgica , Doenças Mandibulares/fisiopatologia , Doenças Mandibulares/cirurgia , Nervo Mandibular/fisiologia , Cistos Odontogênicos/cirurgia , Adolescente , Adulto , Criança , Polpa Dentária/patologia , Teste da Polpa Dentária , Feminino , Humanos , Masculino , Doenças Mandibulares/terapia , Nervo Mandibular/fisiopatologia , Pessoa de Meia-Idade , Cistos Odontogênicos/terapia , Recuperação de Função Fisiológica , Tratamento do Canal Radicular , Extração Dentária , Adulto JovemRESUMO
OBJECTIVES: Adenoid cystic carcinoma (ACC) is one of the most common salivary gland cancers. The prognosis of adenoid cystic carcinoma is poor for its high frequency of distant metastases and insensitivity to chemotherapy or molecular therapies. This study investigated the effect of Obatoclax on adenoid cystic carcinoma cells and its cytotoxic mechanism. METHODS: Western blot, transmission electron microscopy, and pEGFP-LC3 plasmids transfection were carried out to detect autophagy in ACC cells treated with Obatoclax. 3-MA and RNA interference against Beclin 1 and ATG5 were used to inhibit autophagy. Then we used Western blot and Hochest 33342 staining for apoptosis assessment. Finally, cell viability was assessed by MTT assay. RESULTS: We found that Obatoclax induced cytoprotective autophagy which depended on ATG5 and partly on Beclin 1 in adenoid cystic carcinoma cells. Furthermore, pharmacologically inhibiting Obatoclax-induced autophagy promoted apoptosis. Downregulation of Beclin 1 or ATG5 attenuated the cytotoxicity of Obatoclax by suppressing both autophagy and apoptosis. Finally, when apoptosis was pharmacologically inhibited, autophagic cell death was initiated in adenoid cystic carcinoma cells treated with Obatoclax. CONCLUSION: In summary, Beclin 1 and ATG5 play important roles in regulating both Obatoclax-induced autophagy and apoptosis in adenoid cystic carcinoma.
Assuntos
Proteína 5 Relacionada à Autofagia/metabolismo , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Carcinoma Adenoide Cístico/tratamento farmacológico , Pirróis/farmacologia , Neoplasias das Glândulas Salivares/tratamento farmacológico , Autofagia/genética , Proteína 5 Relacionada à Autofagia/antagonistas & inibidores , Proteína 5 Relacionada à Autofagia/genética , Proteína Beclina-1/antagonistas & inibidores , Proteína Beclina-1/genética , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Indóis , Prognóstico , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologiaRESUMO
AIM: To study the lung cancer caused by smoking from RNA-seq data and its mechanism at molecular level. MATERIALS AND METHODS: We downloaded gene expression profile SRA (Sequence Read Archive) data from Gene Expression Omnibus database that included two samples: one was lung cancer tissue samples from smoker (GSM718710) and the other was from non-smoker (GSM718709). We analyzed differential expression of genes with packages software TopHat and Cufflinks, and did Gene Ontology (GO) function clustering of the differentially expressed genes by BLASTX. Then we utilized KEGG Orthology Based Annotation System (KOBAS) to make pathway annotation and do enrichment analysis of KEGG pathway. After that, we searched for probable alternative splicing of the selected differentially expressed genes and found closely-linked genes. RESULTS: we screened 1603 differentially expressed genes, most of which were involved in cellular processes. We also identified that the possible alternative splicing of gene FCGBP might have an important impact on lung cancer. CONCLUSIONS: These findings in this study may help better understand the relationship between smoking and lung cancer pathogenesis.
Assuntos
Moléculas de Adesão Celular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Pulmão/metabolismo , Fumar/genética , Processamento Alternativo , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Humanos , Análise de Sequência de RNARESUMO
In China, there are four types of liver abscesses (LAs) that meet the clinical criteria. Pyogenic liver abscesses (PLAs) and amoebic liver abscesses (ALAs) are two of the most common types of abscesses, followed by fungal liver abscesses (FLAs) and hydatid secondary liver abscesses (HsLAs). Diabetes mellitus (DM) is associated with the development of PLAs. However, there is a lack of population-based studies that have evaluated the underlying relationship between LAs (mainly PLAs and FLAs) and DM. We conducted a retrospective study based on a large population to identify the potential differences and factors that affect the mortality of PLA patients in DM and non-DM groups. Our results revealed that the prevalence of DM is 44.3% (158/357) in PLA patients and 35.3% (18/51) in FLA patients. Compared with the non-DM patients, statistically significant differences were found in DM patients according to symptomatology, clinical manifestations, laboratory findings, microbiological characteristics, antimicrobial resistance, clinical treatments and outcomes in relation to mortality. In addition, the status of antibiotic resistance to E. coli and K. pneumoniae, which were isolated from the patient samples, is severe in the area in which the study was conducted. Regarding the treatment of PLAs, our study indicated that broad-spectrum antimicrobial therapy and drug combinations should be recommended and initiated before the pathogens are cultured and identified. In the clinic, therapies that combine percutaneous drainage with antibiotics and surgery with antibiotics are the two most useful strategies for treating an LA. These two combined treatments resulted in satisfactory cure rates. In the DM and non-DM groups, the cure rates for percutaneous drainage with antibiotics were 90.3% and 92.0%, respectively, and the cure rates for surgery with antibiotics were 93.9% and 95.2%, respectively.
Assuntos
Diabetes Mellitus/microbiologia , Abscesso Hepático Piogênico/complicações , Adulto , Idoso , China , Farmacorresistência Bacteriana , Escherichia coli/isolamento & purificação , Feminino , Humanos , Klebsiella pneumoniae/isolamento & purificação , Abscesso Hepático Piogênico/microbiologia , Abscesso Hepático Piogênico/terapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: Abnormal myelopoiesis especially the expansion of myeloid-derived suppressor cells (MDSCs) is increasingly recognized as an important reason for the escape of tumor from immune surveillance. This study aims to investigate the role of this specific population of cells in oral cancer progression. MATERIALS AND METHODS: 4-Nitroquinoline 1-oxide (4NQO) was used to induce oral cancer in C57BL/6 mice. The tongue mucosa was examined by hematoxylin and eosin staining. The distribution of MDSCs in the spleen and peripheral blood and T cell subsets in the spleen was analyzed by flow cytometry. The expression of MDSCs in the tongue tissues was investigated by immunohistochemical staining, and the expression of arginase-1 (ARG-1) and NOS-2 in the tongue tissues was detected by real-time PCR. RESULTS: We found that during tumor progression, significantly increased frequency of MDSCs was observed in the spleens and peripheral blood of 4NQO-treated mice, and the frequency of MDSCs in the spleens was positively correlated with systemic CD3(+) CD8(+) T cells. Moreover, 4NQO-treated mice showed significantly higher MDSCs infiltration and ARG-1 mRNA level in the tumor site. CONCLUSIONS: Myeloid-derived suppressor cells contribute to oral tumor progression and represent a potential target for immunotherapy of oral cancer.
Assuntos
Carcinoma de Células Escamosas/imunologia , Células Mieloides/imunologia , Neoplasias da Língua/imunologia , Evasão Tumoral/imunologia , 4-Nitroquinolina-1-Óxido , Animais , Arginase/análise , Antígeno CD11b/imunologia , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/patologia , Feminino , Citometria de Fluxo , Tolerância Imunológica/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/análise , Receptores de Quimiocinas/imunologia , Linfócitos T Reguladores/imunologia , Neoplasias da Língua/induzido quimicamente , Neoplasias da Língua/patologiaRESUMO
BACKGROUND: Gene and stem cell therapies hold promise for the treatment of ischaemic cardiovascular disease. However, combined stem cell and angiogenic growth factor gene therapy for acute ischaemic myocardium has not been previously reported. This study hypothesized that combined stem cell and gene therapy would not only augment new vessels formation but also improve myocardial function in acute ischaemic myocardium. METHODS: Human angiopoietin-1 (Ang1) cDNA and VEGF(165) cDNA were ligated into AAV vector. The purified CD34(+) cells were obtained from human umbilical cord blood samples. Cord blood CD34(+) cells were transduced with AAV vector encoding either the human Ang1 (AAV-Ang1) or VEGF(165) (AAV-VEGF) cDNA alone, or both (AAV-Ang1 plus VEGF). Immediately after ligation of the left anterior descending coronary artery in male SCID mice, culture-expanded CD34(+) cells transduced with AAV-Ang1, AAV-VEGF or AAV-Ang1 plus VEGF were injected intramyocardially at the left anterior free wall. RESULTS: Western blot showed that Ang1 and VEGF protein expressions were enhanced in the CD34(+)cells transduced with AAV-Ang1 and AAV-VEGF, respectively. Infarct size significantly decreased and capillary density significantly increased after treatment with CD34(+)/AAV-Ang1 plus VEGF when compared with treatment by CD34(+) only. Combined therapy with CD34(+) and AAV-Ang1, CD34(+) and AAV-VEGF, CD34(+) and AAV-Ang1 plus VEGF, all showed significantly higher cardiac performance in echocardiography than the therapy with CD34(+) alone 4 weeks after myocardial infarction. CONCLUSIONS: Combined therapy with human umbilical cord blood CD34(+) cells and both Ang1 and VEGF genes reduced infarct size, attenuated the progression of cardiac dysfunction and increased capillary density in acute myocardial infarction in mice.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Terapia Genética/métodos , Infarto do Miocárdio/terapia , Angiopoietina-1/análise , Animais , Antígenos CD34/metabolismo , Modelos Animais de Doenças , Coração/fisiopatologia , Humanos , Masculino , Camundongos , Camundongos SCID , Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Neovascularização Patológica/fisiopatologia , RNA Mensageiro/análise , Transfecção , Fator A de Crescimento do Endotélio Vascular/análiseRESUMO
Multidrug resistance (MDR) is one of the main obstacles limiting the efficacy of chemotherapy treatment of tumours. One of the main causes of MDR is linked to the overexpression of P-glycoprotein (P-gp). This study aimed to characterise tetrandrine (Tet), a potent inhibitor of P-gp mediated MDR. Cytotoxicity was determined by the tetrazolium (MTT) assay. A MCF-7/adr cell xenograft model was established to investigate the effect of Tet on reversing MDR in vivo. Mechanistic experiments were conducted to examine the uptake, efflux and accumulation of doxorubicin (Dox) and Fura-2, and to assess lipid membrane fluidity. Tet potentiated the cytotoxicity of Dox; a 20.4-fold reversal of resistance was achieved in the presence of 2.5 micromol/l of Tet. Accumulation and efflux studies with the P-gp substrates, Dox and Fura-2, demonstrated that Tet inhibited the P-gp-mediated drug efflux. In addition, Tet lowered cell membrane fluidity in a concentration-dependent manner. In mice bearing the MDR MCF-7/adr cell xenografts, coadministration of Tet potentiated the antitumour activity of doxorubicin without a significant increase in toxicity. Tet was an extremely potent MDR modulator both in vitro and in vivo, without apparently enhancing the toxicity of the co-administered drugs. Hence, Tet holds great promise as a MDR modulator for the treatment of P-gp-mediated MDR cancers.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/efeitos dos fármacos , Adenocarcinoma/tratamento farmacológico , Alcaloides/uso terapêutico , Antineoplásicos/uso terapêutico , Benzilisoquinolinas , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/uso terapêutico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Animais , Antineoplásicos Fitogênicos/uso terapêutico , China , Relação Dose-Resposta a Droga , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Transplante Heterólogo , Células Tumorais CultivadasRESUMO
AIM: To explore the effect of atemoyacin-B (Ate) on overcoming multidrug resistance (MDR). METHODS: Bullatacin (Bul) was used as a positive control. Cytotoxic effects of Bul and Ate were studied with cell culture of human MDR breast adenocarcinoma cells, MCF-7/Dox and human KBv200 cells, and their parental sensitive cell lines MCF-7 and KB. Cytotoxicity was determined by tetrazolium (MTT) assay. The function of P-glycoprotein (P-gp) was examined by Fura 2-AM assay. Cellular accumulation of doxorubicin (Dox) was determined by fluorescence spectrophotometry. Apoptosis was measured by flow cytometry. RESULTS: IC50 of Ate for MCF-7/Dox, MCF-7, KBv200, and KB cells were 122, 120, 1.34, and 1.27 nmol.L-1, respectively. IC50 of Bul for MCF-7/Dox, MCF-7, KBv200, and KB cells were 0.60, 0.59, 0.04, and 0.04 nmol.L-1, respectively. The cytotoxicities of Bul and Ate to MDR cells were similar to those to parental sensitive cells. Bul and Ate markedly increased cellular Fura-2 and Dox accumulation in MCF-7/Dox cells, but not in MCF-7 cells. The rates of apoptosis in MDR cells were similar to those in sensitive cells induced by Ate. CONCLUSION: There was no cross-resistance of P-gp positive MCF-7/Dox and KBv200 cell lines to Bul and Ate as compared with their sensitive P-gp negative MCF-7 and KB cell lines. The mechanism of the circumvention of MDR was associated with the decrease of P-gp function and the increase of cellular drug accumulation in MDR cells.
Assuntos
4-Butirolactona/análogos & derivados , Adenocarcinoma/patologia , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/patologia , Álcoois Graxos/farmacologia , Furanos/farmacologia , 4-Butirolactona/farmacologia , Apoptose , Doxorrubicina/metabolismo , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Fura-2/metabolismo , Humanos , Células KB/efeitos dos fármacos , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA) and chemotherapy have been shown to have better outcome than those treated with conventional chemotherapy alone. However, the biological characteristics of leukemic cells and their clinical implications in patients treated with ATRA have not been well established. In this study, the biological and clinical features of 30 APL patients were reported. The risk factors for relapse and for occurrence of retinoic acid (RA) syndrome, which might cause morbidity or mortality of patients after ATRA treatment, were also analyzed. All patients showed 15;17 translocation by cytogenetic and/or gene analysis. Patients in this study had higher white blood cell (WBC) counts and a higher incidence of additional abnormalities than those from other areas. The ratio of long (L) form to short (S) form PML-RAR alpha fusion transcript was 1.8:1, a value lower than that of Latino patients but higher than that of Italians. Leukemic cells from four patients showed coexpression of T cell-associated antigen CD2 which was highly correlated with S form fusion transcript. Nine (36%) of the 25 patients treated with ATRA developed RA syndrome; all but one were successfully controlled by corticosteroid. Complete remission (CR) rate was 84%. Patients with high WBC counts tended to develop RA syndrome and had increased risk of relapse. Isochromosome for the long arm of the derivative chromosome 17, ider(17q), as an additional chromosomal abnormality was also associated with poor outcome in this study. In conclusion, APL in this study showed some different biological characteristics compared with those reported in other areas. High WBC count was a risk factor for relapse and development of RA syndrome after ATRA treatment. The prognostic implication of the presence of ider(17q) needs further clarification.
Assuntos
Antineoplásicos/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Tretinoína/uso terapêutico , Adolescente , Adulto , Idoso , Antígenos CD2/análise , Aberrações Cromossômicas , Feminino , Humanos , Hibridização in Situ Fluorescente , Leucemia Promielocítica Aguda/sangue , Leucemia Promielocítica Aguda/genética , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Fusão Oncogênica/genética , Prognóstico , RNA Mensageiro/análise , Recidiva , Tretinoína/efeitos adversosRESUMO
Translocation t(7;11)(p 15;p15) is an uncommon but recurrent chromosome aberration in acute myeloid leukaemia (AML). which occurs mostly in oriental patients and in AML M2 or, occasionally, M4 subtype. Recently, a consistent chimaeric fusion transcript NUP98-HOXA9 was found in several cases of t(7;11). Four AML cases with the chromosome abnormality in Taiwan are described. They were all adults with ages ranging from 30 to 41 years (median 36 years). Three of them were diagnosed as having AML M2; the remaining one as M4. Marked dyserythropoiesis was demonstrated in two patients. All four patients showed pan-myeloid antigen CD13 on the leukaemic cells, but none coexpressed lymphocyte-associated antigens and neither of the two patients studied for CD34 expression had positive staining. NUP98-HOXA9 fusion transcript was detected in both patients who had molecular analysis and the breakpoints on chromosome 11 and 7 respectively were similar to those previously reported. They all received conventional induction chemotherapy, but only one achieved a complete remission (CR) with short duration. This study and others reported in the literature suggest a racial or geographical predisposition among oriental patients to AML with t(7;11) and that this is associated with a poor prognosis. The molecular detection of NUP98-HOXA9 fusion transcript would be a useful method for the diagnosis of t(7;11) and also for monitoring disease status after treatment.