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BACKGROUND: To investigate whether carboplatin-liposomal paclitaxel neoadjuvant chemotherapy (NACT) benefits patients with locally advanced cervical cancer (LACC) through avoiding or delaying postoperative radiation. METHODS: A total of 414 patients with cervical cancer of International Federation of Gynecology and Obstetrics (FIGO 2009) stages IB2-IIA2 were included in the retrospective cohort study, who had received carboplatin-liposomal paclitaxel chemotherapy followed by radical surgery (NACT group) or primary radical surgery (PRS group) between 2007 and 2017 at our hospital. The baseline clinicopathological characteristics at diagnosis, postoperative pathological risk factors, and oncological outcomes after surgery, including postoperative radiation (as adjuvant treatment or treatment of recurrent diseases), progression-free survival (PFS), and overall survival (OS), were compared between the groups. Before treatment, the patients in the NACT group had significantly more advanced tumor stages and larger tumor sizes than those in the PRS group. RESULTS: The NACT reduced the tumor volumes remarkedly with a response rate of 62.4%, and the tumors in the NACT group were smaller than those in the PRS group when the patients were subjected to radical surgery. Furthermore, postoperative pathology examination revealed less frequent deep stromal invasion in the NACT group than in the PRS group. According to the presence of pathological risk factors for recurrence, 54.82% of women in the NACT group needed adjuvant radiotherapy, while 60.87% in the PRS group, and in fact, 33.00% of NACT patients and 40.09% of PRS patients received adjuvant radiation. In addition, 8.12% of NACT patients and 9.68% of PRS patients underwent radiotherapy after relapse. The cumulative postoperative radiation rate was significantly lower in the NACT group (P = 0.041), while the differences in 5-year OS and PFS were not statistically significant between the groups. CONCLUSIONS: NACT reduces the pathological risk factors and the use of radiation without compromising survival in patients with LACC, which may protect younger patients from radiation-related side effects and subsequently improve the quality of life. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN24104022.
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Terapia Neoadjuvante , Neoplasias do Colo do Útero , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Quimioterapia Adjuvante , Feminino , Humanos , Histerectomia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Paclitaxel , Qualidade de Vida , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologiaRESUMO
STUDY OBJECTIVE: The aim of our study was to determine if laparoscopic radical hysterectomy (LRH) can be routinely used for the treatment of early-stage cervical cancer. DESIGN: From May 2008, LRH was planned for all primarily operable cervical cancer patients after receiving informed consent in our department. The surgical and oncologic outcomes were retrospectively evaluated (Canadian Task Force classification III). SETTING: University teaching hospital. PATIENTS AND INTERVENTIONS: By August 2013, 404 patients with invasive cervical cancer were deemed operable, and all of them were subjected to upfront LRH, except 1 patient who insisted on open surgery. MEASUREMENTS AND MAIN RESULTS: The planned LRH was abandoned in 3 patients because of inoperability. The median operative time was 240 minutes (range, 100-410 minutes). The median blood loss was 300 mL (range, 50-800 mL). The median number of harvested pelvic lymph nodes was 23.5 (range, 11-54). Two patients had positive surgical margins. Intraoperative complications occurred in 7 of the patients, and a conversion to open surgery was mandatory for 2 patients (conversion rate = 0.5%). Postoperative urinary tract fistula developed in 3 patients. Sixty-nine patients underwent adjuvant therapy. The median duration of follow-up was 31 months (range, 7-69 months). Thirty patients developed recurrent disease with a median disease-free interval of 12 months (range, 6-23 months), and 24 died of disease. The estimated 3-year overall survival rate was 94.9% in the women with a tumor ≤ IB1 and 81.3% in those with a tumor >IB1, and the 3-year progression-free survival rates were 94.1% and 79.6%, respectively. CONCLUSION: LRH is adequate, safe, and feasible for women with cervical cancer, and it can be routinely used for the treatment of early-stage tumors as a primary modality.
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Histerectomia/métodos , Laparoscopia , Pelve/cirurgia , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Complicações Intraoperatórias/cirurgia , Excisão de Linfonodo , Linfonodos/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologiaRESUMO
OBJECTIVE: To compare the safety and efficacy after laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) in the treatment of patients with stage I a2-II b cervical cancer. METHODS: In a retrospective study, data were analyzed from patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ia2-II b cervical cancer underwent LRH or ARH at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; First Affiliated Hospital, School of Medicine, Shihezi University; and the Guizhou Provincial People's Hospital between 2000 and 2015. Perioperative outcomes and survival analysis were compared. RESULTS: (1) The FIGO stages, histotypes, metastasis of lymph nodes, lymph vascular space invasion and neoadjuvant chemotherapy significantly differed between the LRH group and the ARH group (all P<0.05). In order to eliminate the effects by the unbalanced data, stratified analysis was conducted based on FIGO stage. There were 861 patients in stage I a2-I b1 group, including 663 patients in LRH group and 198 patients in ARH group. And there were 668 patients in stage I b2-IIb group, including 389 patients in LRH group and 279 patients in ARH group. (2) In the patients with stage I a2- I b1 and I b2- II b tumor, there were no significant difference in age, histotype, differentiation degree, parametrial invasion, lymphvasular invasion space and neoadjvant chemotherapy between the LRH group and the ARH group (all P>0.05). For patients with stage I a2- I b1, the operation time in the LRH group was longer than that in the ARH group (P=0.027), and it showed less blood loss and lower blood transfusion rate in the LRH group than those in the ARH group (all P=0.000). The findings were similar in the patients with stage I b2-II b (all P=0.000). (3) There were no significant difference in intraoperative complications and postoperative complications between the LRH and the ARH group in the patients with stage I a2-I b1 and I b2-IIb, respectively (all P>0.05). (4) The median follow- up time was 24 months (range: 1 to 177 months), the recurrence rate was 3.6% (38/1 052) in LRH group and 3.1% (15/477) in ARH group,there was not significant difference (P>0.05). The estimated 3- year overall survival (OS) and the free-progression survival time (PFS) were respectively 92.4% and 91.5% in LRH group, and 91.8% and 91.5% in ARH group. There was no significant difference in the overall survival (P=0.738) or progress free survival (P=0.990) by log-rank test. Moreover, there were no significant difference in OS or PFS between the LRH group and the ARH group in patients with stage I a2- I b1 and I b2- II b, respectively (all P>0.05). CONCLUSION: LRH is safe and effective, and it could be used a routine way for the treatment of patients with stage I a2-IIb cervical cancer.
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Histerectomia/efeitos adversos , Laparoscopia/efeitos adversos , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Neoplasias do Colo do Útero/cirurgia , China/epidemiologia , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia/métodos , Histerectomia/mortalidade , Laparoscopia/métodos , Laparoscopia/mortalidade , Linfonodos/patologia , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Retrospectivos , Segurança , Análise de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: Emerging evidence has highlighted the biological significance of pyroptosis in tumor tumorigenesis and progression. Nonetheless, the potential roles of pyroptosis in tumor immune microenvironment and target therapy of ovarian cancer (OC) remain unknown. METHODS: In this study, with a series of bioinformatic and machine learning approaches, we comprehensively evaluated genetic alterations and transcriptome profiles of pyroptosis-associated genes (PYAGs) with TCGA-OV datasets. Consensus molecular clustering was performed to determine pyroptosis-associated clusters (PACs) and gene clusters in OC. Subsequently, component analysis algorithm (PCA) was employed to construct Pyrsig score and a highly accurate nomogram was established to evaluate its efficacy. Meanwhile, we systematically performed association analysis for these groups with prognosis, clinical features, TME cell-infiltrating characteristics, drug response and immunotherapeutic efficacy. Immunohistochemistry was conducted to verify molecular expression with clinical samples. RESULTS: The somatic mutations and copy number variation (CNV) of 51 PYRGs in OC samples were clarified. Two distinct PACs (PAC1/2) and three gene clusters (A/B/C) were identified based on 1332 OC samples, PAC1 and gene cluster A were significantly associated with favorable overall survival (OS), clinicopathological features and TME cell-infiltrating characteristics. Subsequently, Pyrsig score was successfully established to demonstrate the prognostic value and immune characteristics of pyroptosis in OC, low Pyrsig score, characterized by activated immune cell infiltration, indicated prolonged OS, increased sensitivity of some chemotherapeutic drugs and enhanced efficacy of anti-PD-L1 immunotherapy, Consequently, a nomogram was successfully established to improve the clinical applicability and stability of Pyrsig score. With clinical OC samples, GSDMD and GZMB proteins were validated highly expressed in OC and associated with immune infiltration and Pyrsig score, GZMB and CD8 proteins were regarded as independent prognostic factors of OC. CONCLUSION: This work revealed pyroptosis played a non-negligible role in prognosis value, clinicopathological characteristics and tumor immune infiltration microenvironment in OC, which provided novel insights into identifying and characterizing landscape of tumor immune microenvironment, thereby guiding more effective prognostic evaluation and tailored immunotherapy strategies of OC.
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Neoplasias Ovarianas , Piroptose , Feminino , Humanos , Piroptose/genética , Variações do Número de Cópias de DNA , Prognóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Imunoterapia , Microambiente Tumoral/genéticaRESUMO
The growth-inhibiting and apoptosis-inducing effects of WW domain-containing oxidoreductase (WWOX) gene on ovarian cancer cell line A2780 were investigated. The full length cDNA of human WWOX gene was amplified from normal human ovary tissues. The correct cDNA of full length WWOX was subcloned into eukaryocytic expression vector pCMV. After introduction of WWOX gene into cancer cells with liposome, the WWOX mRNA and protein level in the cancer cells were detected by reverse transcription polymerase chain reaction (RT-PCR) and immunoblotting. The growth activities of cancer cells were detected by Trypan blue staining. The clone formation assay in soft agar was employed to observe the proliferation of the cancer cells. Apoptosis was examined by DNA ladder and acridine orange-ethidium bromide fluorescent staining. The results showed that 72 h after WWOX gene transfection, the WWOX expression was increased significantly (P<0.01). The growth of ovarian cancer cells was decreased by 16.41% to 38.49% (P<0.01). The clone formation abilities were reduced (P<0.01). Some cancer cells presented the characteristic morphological changes of apoptosis with obvious ladder bands on electrophoresis. The apoptosis rate was (20.7+/-6.0)% (P<0.01). It was concluded that over-expression of WWOX gene could induce apoptosis and inhibit the growth of ovarian cancer cells, which might be potentially useful in the gene therapy of ovarian cancers.
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Apoptose/genética , Neoplasias Ovarianas/patologia , Oxirredutases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Terapia Genética , Humanos , Neoplasias Ovarianas/metabolismo , Oxirredutases/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Transfecção , Proteínas Supressoras de Tumor/genética , Oxidorredutase com Domínios WWRESUMO
OBJECTIVE: To construct a latent human soluble tumor necrosis factor receptor I (hsTNFRI) using the latency associated protein (LAP) of transforming growth factor-beta1 (TGF-beta1) fused via a matrix metalloproteinase (MMP) cleavage site to hsTNFRI so as to detect the latent biological activity of LAP-MMP-hsTNFRI fusion protein. METHODS: A double-stranded deoxyoligonucleotide coding for MMP cleavage site was cloned into plasmid pcDNA3.1. LAP and hsTNFRI cDNA were then inserted into both two sides of MMP cleavage site. After being transferred by LAP-MMP-hsTNFRI fusion gene with liposome, the expression of fusion protein in COS-7 cells was detected by RT-PCR and Western blot. The inhibitory effect of fusion protein upon cytotoxicity of TNF-alpha was detected by methyl thiazolyl tetrazolium (MTT) assay before and after the fusion protein incubated in MMP or peritoneal fluid from endometriosis patients. RESULTS: The recombinant plasmid LAP-MMP-hsTNFRI-pcDNA3.1 was constructed successfully and was expressed effectively in COS-7 cells. The MTT assay showed that there was no difference in the mortality rate of L929 cells between LAP-MMP-hsTNFRI-pcDNA3.1 and empty vector transfection groups (P > 0.05). The mortality rates of L929 cells with 800 ng/L TNF-alpha in LAP-MMP-hsTNFRI-pcDNA3.1 transfection group after incubation with MMP or peritoneal fluid from endometriosis patients were (44.5 +/- 2.4)% and (33.8 +/- 1.9)% respectively. And it was lower than the pre-incubation period (58.1 +/- 2.4)% (P < 0.05). CONCLUSION: The biological activity of LAP-MMP-hsTNFRI fusion protein can be made latent by LAP and activated by peritoneal fluid from endometriosis. Thus a new method has been provided for a targeted therapy of endometriosis.
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Endometriose/terapia , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/uso terapêutico , Líquido Ascítico/citologia , Linhagem Celular , Feminino , Vetores Genéticos , Humanos , Plasmídeos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/uso terapêutico , TransfecçãoRESUMO
OBJECTIVE: To assess the efficacy of platinum-based neoadjuvant chemotherapy (NACT) in patients with locally advanced cervical cancer (LACC) and investigate the pretreatment predictors of the response. PATIENTS AND METHODS: A total of 219 patients with International Federation of Gynecology and Obstetrics (FIGO 2009) stage IB2-IIA2 LACC who received platinum-based NACT from December 2007 to December 2017 were reviewed, and their clinical-pathological characteristics and follow-up data were retrospectively collected and analyzed. The baseline characteristics of age, FIGO stage, histology, tumor differentiation, tumor size, and clinical outcomes, including post-operative pathological risk factors, overall survival (OS), and progression-free survival (PFS) were compared between the responders and non-responders. RESULTS: The overall response rate was 58.9% (129/219), and 19 (8.7%) patients achieved pathologically complete remission. NACT responders showed significantly better OS and PFS than non-responders (POS= 0.002, PPFS= 0.002). The response to NACT was identified as an independent risk factor for OS (hazard ratio [HR] = 2.453, 95% confidence intervals [95% CI], 1.125-5.348, P = 0.024) and PFS (HR = 2.196, 95% CI, 1.183-4.076, P = 0.013), and patients with IB2/IIA1 and a tumor size of <5 cm tended to receive better response than patients with IIA2 (P = 0.004) and a tumor size of ≥5 cm (P = 0.027). CONCLUSION: The response rate of platinum-based NACT was approximately 60%. The response to NACT was an independent risk factor for prognosis, and patients with earlier stage and smaller tumor tended to respond better to NACT.
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OBJECTIVES: Lymph node metastasis (LNM) is an important determinant of prognosis in patients with cervical cancer. Members of the angiopoietin family have been demonstrated to regulate tumor-associated angiogenesis and lymphangiogenesis. This study aimed to investigate the expression levels of angiopoietin-1 (ANG1) and angiopoietin-2 (ANG2) in clinically early stage of cervical cancer along with their correlations with LNM. METHODS: In total, 124 human cervical cancer cases classified into stage IA-IIB in accordance with the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging criteria were included. ANG1 and ANG2 expression levels in the tumor sections were assessed by immunohistochemistry (IHC). Univariate and multivariate logistic regression models, including age at diagnosis, FIGO stage, tumor size, pathological type, histological grading, depth of stromal invasion, lymph-vascular space invasion (LVSI) and the expression status of ANG1 and ANG2, were used to evaluate the odds ratios (ORs) for LNM. RESULTS: ANG1 and ANG2 were positively expressed in 75 (60.5%) and 89 (71.8%) cervical cancers respectively, with predominant staining in the cytoplasm. ANG1 expression was significantly decreased in tumors with LNM, while no correlation was observed between ANG2 expression and LNM. More importantly, the multivariate logistic regression analysis demonstrated that high ANG1 expression was an independent protective factor of LNM (OR 0.107, 95% confidential interval [CI] 0.020~0.567), while LVSI was an independent risk factor of LNM (OR 34.313, 95% CI 5.914~199.092). CONCLUSION: ANG1 is associated with a significantly decreased risk of LNM in early stage cervical cancer. The predictive value and role of ANG1 in LNM needs to be further investigated in future studies.
Assuntos
Adenocarcinoma/metabolismo , Angiopoietina-1/metabolismo , Angiopoietina-2/metabolismo , Carcinoma de Células Escamosas/metabolismo , Linfonodos/metabolismo , Metástase Linfática/patologia , Neoplasias do Colo do Útero/metabolismo , Adenocarcinoma/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Neoplasias do Colo do Útero/patologiaRESUMO
OBJECTIVE: To compare clinical outcomes in laparoscopic and open radical hysterectomy with pelvic lymphadenectomy (LRH) in early cervical cancer without the selection bias. METHODS: One special retrospective study was conducted with more than 400 patients involved in laparoscopic procedure. RESULTS: Our results suggest that estimated blood loss and transfusion requirements were significantly lower in the LRH group. Postoperative hospital stay was also significantly shorter in the LRH group. Significant difference was found in the number of pelvic lymph nodes retrieved between the LRH and open radical hysterectomy with pelvic lymphadenectomy (ORH) groups. There were no differences in operating time, perioperative complications, progression-free survival, and overall survival between the LRH and ORH groups. CONCLUSION: LRH can be considered a safe and effective alternative to conventional open surgery (ORH) for early-stage cervical cancer.
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OBJECTIVE: Endometriosis is an estrogen-dependent disease, a steroid receptor-binding protein bearing the regulator of the G-protein signaling domain (SRB-RGS) can suppress the estrogen receptors-mediated transcriptional activities. We sought to determine whether overexpression of SRB-RGS suppresses the migration and invasion ability of endometrial stromal cells stimulated by 17ß-estradiol (E2). STUDY DESIGN: Endometrial stromal cells were obtained from endometriosis patients. SRB-RGS was overexpressed in the cells stimulated by E2. The migration and invasion ability of the cells were measured by migration assay and invasion assay, respectively. Western blot analysis was done to test the expression of matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF). RESULTS: Overexpression of SRB-RGS suppressed the migration and invasion ability of the stromal cells stimulated by E2; it also suppressed the expression of MMP-9 and VEGF, while the expression of TIMP-1 was increased. CONCLUSIONS: Overexpression of SRB-RGS suppresses the migration and invasion ability of the E2-stimulated endometrial stromal cells. The molecular mechanism is the reduced expression of MMP-9 and VEGF, and the increased expression of TIMP-1. These findings suggest that the coding gene of SRB-RGS is a promising target gene for endometriosis gene therapy.
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Movimento Celular/fisiologia , Endometriose/metabolismo , Estradiol/farmacologia , Células Estromais/metabolismo , Adulto , Movimento Celular/efeitos dos fármacos , Endometriose/patologia , Feminino , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Células Estromais/efeitos dos fármacos , Células Estromais/patologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: To compare outcomes after laparoscopic radical hysterectomy (LRH) and abdominal radical hysterectomy (ARH) for locally advanced cervical cancer (LACC)after neoadjuvant chemotherapy (NACT). METHODS: In a retrospective study, data were analyzed from patients with FIGO stage IB2-IIB cervical cancer who underwent LRH or ARH after NACT at Union Hospital, Wuhan, China, between January 2007 and August 2013.Perioperative outcomes and survival were compared. RESULTS: Overall, 99 patients who underwent LRH and 30 who underwent ARH were included. Compared with ARH patients, LRH patients presented with lower-stage tumors (P=0.013). Median operative time, number of harvested lymph nodes, and rate of positive surgical margins did not differ significantly between the groups, but LRH resulted in less blood loss (median 300mL [range 20-1100] vs 375mL [100-1200]; P=0.027). There were two intraoperative complications and 23 postoperative complications in the LRH group, and 12 postoperative complications in the ARH group. No conversions occurred in the LRH group; all complications were managed without severe sequelae. As of March 2014, recurrence had been noted for 6(6.1%) LRH patients and 2 (6.7%) ARH patients. CONCLUSION: LRH was similar to ARH in terms of safety, feasibility, and morbidity, with less blood loss among women with LACC undergoing NACT. Long-term outcomes need to be documented.
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Histerectomia/métodos , Laparoscopia/métodos , Neoplasias do Colo do Útero/terapia , Adulto , Perda Sanguínea Cirúrgica , Quimioterapia Adjuvante , Feminino , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Duração da Cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND: The second mitochondria-derived activator of caspases (Smac) is a novel proapoptotic gene, which plays an important role in the apoptosis-inducing effects of irradiation on tumor cells. The purpose of this study was to investigate the effects of extrinsic Smac gene transfer and its over-expression in radiotherapeutic sensitivities of cervical cancer cells. METHODS: After the Smac gene was transferred into the cervical cancer cell line HeLa, subcloned cells were obtained by persistent G418 selection. Cellular Smac gene expression was detected by RT-PCR and Western blot, while in vitro cell viabilities were detected by trypan blue staining assay. After treatment with X-ray irradiation, cellular radiotherapeutic sensitivities were investigated by tetrazolium bromide colorimetry. Cellular apoptosis and its rate were determined by electronic microscopy, annexin V-FITC and propidium iodide staining flow cytometry. The expression and activities of cellular caspase-3 were assayed by Western blot and colorimetry. RESULTS: Smac mRNA and protein levels in HeLa/Smac cells and the selected subclone cell line of cervical cancer were significantly higher than those of HeLa (P < 0.01). There was no significant difference in cellular viabilities between them (P > 0.05). However, after irradiation with 8 Gy X-ray, growth activities of HeLa/Smac were reduced by 22.42% (P < 0.01). When compared with those of HeLa, partial HeLa/Smac cells presented characteristic morphological changes of apoptosis under electronic microscope, with higher apoptosis rates (16.4% vs. 6.2%, P < 0.01); the caspase-3 expression levels in HeLa/Smac cells were improved significantly (P < 0.01), while its activities were increased by 3.42 times (P < 0.01). CONCLUSIONS: Stable transfer of the extrinsic Smac gene and its over-expression in cervical cancer cell line could significantly enhance the expression and activities of cellular caspase-3 and ameliorate apoptosis-inducing effects of irradiation on cancer cells, which was a novel strategy to improve radiotherapeutic effects on cervical cancer.
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Proteínas de Transporte/fisiologia , Proteínas Mitocondriais/fisiologia , Neoplasias do Colo do Útero/tratamento farmacológico , Apoptose/efeitos da radiação , Proteínas Reguladoras de Apoptose , Proteínas de Transporte/genética , Caspase 3 , Caspases/metabolismo , Feminino , Transferência Genética Horizontal , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas Mitocondriais/genética , Tolerância a Radiação , Neoplasias do Colo do Útero/enzimologia , Neoplasias do Colo do Útero/patologiaRESUMO
OBJECTIVE: To assess the efficacy and toxicity of the combination of paclitaxel plus carboplatin as neoadjuvant chemotherapy (NACT) for locally advanced cervical cancer (LACC) prior to radical hysterectomy and pelvic lymphadenectomy. METHODS: We reviewed patients with cervical cancer of the International Federation of Gynecology and Obstetrics (FIGO) stage IB2-IIB who underwent neoadjuvant chemotherapy (NACT) with paclitaxel plus carboplatin followed by radical hysterectomy (NACT group) or only received primary radical surgery (PRS group) in our hospital between Jan 2007 and Jan 2012. Toxicity, NACT response, surgery pathological factors and survival data were collected and analyzed. RESULTS: In the NACT group, the overall response rate was 71.3% (82/115). Eighteen (15.7%) patients achieved complete remission. Well differentiated tumors showed a more favorable response to NACT (P=0.011). Myelosuppression was the most common adverse effect (51.7%) and serious adverse effects were rare (3.4%). The median follow-up period was 44 months (range, 6-75). The NACT responders had significantly longer OS and PFS when compared to the non-NACT responders and patients in the PRS group. CONCLUSION: Patients with LACC can benefit from neoadjuvant chemotherapy with paclitaxel plus carboplatin when they have response to the chemotherapeutic agents.
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OBJECTIVE: To evaluate prognostic factors which have an influence on overall survival and to assess the rational application of retroperitoneal lymphadenectomy in patients with epithelial ovarian cancer. METHODS: The data of 131 patients treated between January 1990 and December 1998 in Union Hospital and Tongji Hospital were analyzed retrospectively. Survival was calculated using the Kaplan-Meier method and comparisons were performed using Log-rank test. Independent prognostic factors were identified by the Cox proportional hazards regression model. RESULTS: Univariate analysis showed that age, general conditions, menopausal status, stage, pathological types, location of the tumor, residual tumor and retroperitoneal lymphadenectomy were prognostic factors. Multivariate analysis showed that age, stage, residual tumor, retroperitoneal lymphadenectomy and the number of courses of chemotherapy were the most important prognostic factors. The survival rate could not be improved through retroperitoneal lymphadenectomy in the patients in early stage, advanced stage with residual tumor > 2 cm or those with mucinous adenocarcinoma (P > 0.05). Among patients in advanced stage cancer with a residual tumor = 2 cm, 5-year survival was 65% and 30% for patients who did and did not undergo lymphadenectomy, respectively (P < 0.01). Among patients with serous adenocarcinoma, 5-year survival was 61% and 31% for patients who did and did not undergo lymphadenectomy, respectively (P < 0.01). CONCLUSIONS: The prognosis of the patients with epithelial ovarian cancer may be influenced by age, stage, residual tumor, retroperitoneal lymphadenectomy and the number of courses of chemotherapy. Although retroperitoneal lymphadenectomy could improve the survival rate, it should be carried out selectively.
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Excisão de Linfonodo/métodos , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/mortalidade , Prognóstico , Espaço Retroperitoneal , Taxa de SobrevidaRESUMO
OBJECTIVE: The purpose of this study was to determine prognostic factors that have an impact on overall survival and to assess the rational application of retroperitoneal lymphadenectomy in patients with epithelial ovarian cancer. METHODS: A retrospective review was performed of 131 patients treated between Jan.1990 and Dec.1998 in Union Hospital and Tongji Hospital. Survival was calculated by Kaplan-Meier method and comparison was performed using Log-rank test. Independent prognostic factors were identified by the COX proportional hazards regression model. RESULTS: Multivariate analysis showed that the age, stage, residual tumor, retroperitoneal lymphadenectomy and the number of courses of chemotherapy were the most important prognostic factors. The overall 5-year survival was 66% and 41% for patients who did and did not undergo lymphadenectomy, respectively (P < 0.01). But the survival rate could not be improved through retroperitoneal lymphadenectomy in the patients with early stage, advanced stage whose residual tumor > 2 cm and those with mucinous adenocarcinoma (P > 0.05). Among patients with advanced stage whose residual tumor < or = 2 cm, 5-year survival was 65% and 30% for patients who did and did not undergo lymphadenectomy, respectively (P < 0.01). Among patients with serous adenocarcinoma, 5-year survival was 61% and 31% for patients who did and did not undergo lymphadenectomy, respectively (P < 0.01). CONCLUSIONS: The prognosis of the patients with epithelial ovarian cancer may be influenced by age, stage, residual tumor, retroperitoneal lymphadenectomy and the number of courses of chemotherapy. Although retroperitoneal lymphadenectomy could improve the survival rate, it should be carried out selectively.