Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 120
Filtrar
1.
Radiat Oncol ; 15(1): 72, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252781

RESUMO

BACKGROUND: The optimal adjuvant treatment for stage III endometrial cancer in the era of modern radiotherapy remains undefined. We investigated the benefit of adjuvant radiotherapy for women who underwent optimal resection for stage III endometrial cancer in the era of modern radiotherapy. METHODS: We retrospectively reviewed patients with endometrial cancer who were treated between 2010 and 2018. Adjuvant treatment included radiotherapy by modern radiotherapy techniques (intensity-modulated or volumetric modulated arc radiotherapy), chemotherapy, or both. Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed via multivariate Cox proportional hazards models. RESULTS: One hundred sixty-one patients were initially included (52, 9, and 100 with stages IIIA, IIIB, and IIIC cancer, respectively); 154 patients (96%) received adjuvant therapy. Such adjuvant treatment was associated with improved RFS (p = 0.014) and OS (p = 0.044) over surgery alone. Adjuvant radiotherapy by modern radiotherapy techniques led to low incidence of acute (25%) and chronic (7%) grade ≥ 2 gastrointestinal toxicity. On univariate analysis, non-endometrioid histology and grade 3 status were associated with higher risks of tumor recurrence and death, whereas adjuvant radiotherapy alone or in combination chemotherapy reduced their risks. On multivariate analysis, non-endometrioid histology was associated with increased recurrence (hazard ratio [HR], 2.95; p = 0.009), whereas adjuvant radiotherapy alone or with chemotherapy was associated with lower recurrence (HR, 0.62; p = 0.042). Patients > 60 years of age (p = 0.038) as well as those with endometrioid histology (p = 0.045), lymphovascular space invasion (p = 0.031), and ≥ 2 positive lymph nodes (p = 0.044) benefited most from adjuvant radiotherapy. CONCLUSIONS: Modern adjuvant radiotherapy (intensity-modulated or volumetric modulated arc radiotherapy) alone or with chemotherapy should be considered for women with optimally resected stage III endometrial cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04251676. Registered 24 January 2020. Retrospectively registered.


Assuntos
Neoplasias do Endométrio/radioterapia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos Retrospectivos
2.
J Immunother Cancer ; 7(1): 313, 2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31753019

RESUMO

BACKGROUND: The standard treatment for epithelial ovarian carcinoma (EOC) is surgery followed by platinum/paclitaxel-based chemotherapy, but the overall survival rate is poor. The purpose of this study was to investigate the therapeutic potential of chemotherapy combined with inhibition of B and T lymphocyte attenuator (BTLA) for clinical use to treat EOC. METHODS: Initially, we evaluated the potential application of chemotherapy combined with anti-BTLA antibody in an animal model. We then analyzed the distribution and regulation of BTLA expression on immunocytes in vitro. Finally, we examined the correlation between BTLA expression levels in cancerous tissues and prognosis in 254 EOC cases. RESULTS: The combination of chemotherapy and anti-BTLA antibody for inhibiting BTLA significantly reduced peritoneal tumor volume and extended survival in tumor-bearing mice. In addition, BTLA could be identified mostly on B lymphocytes, especially on CD19hi B cells, rather than on T lymphocytes and natural killer cells. Under regulation of interleukins 6 and 10, more BTLA+CD19hi B lymphocytes could be induced through AKT and STAT3 signaling pathways. Detectable BTLA expression in ovarian cancerous tissues was associated with worse disease-free and overall survivals of EOC patients. CONCLUSIONS: BTLA detected in cancerous tissues can predict poor outcome of EOC patients. Inhibition of BTLA combined with chemotherapy can elevate immune activation and generate potent anti-tumor effects. Thus, the combination of chemotherapy and anti-BTLA antibody may hold potential clinical application for the treatment of EOC patients. TRIAL REGISTRATION: The Trial Registration Number was NCT00854399.

3.
Cancers (Basel) ; 11(9)2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31546897

RESUMO

The immuno-inhibitory checkpoint PD-L1, regulated by tumor cells and antigen-presenting cells (APCs), dampened the activation of T cells from the PD-1/PD-L1 axis. PD-L1-expressing APCs rather than tumor cells demonstrated the essential anti-tumor effects of anti-PD-L1 monotherapy in preclinical tumor models. Using the murine tumor model, we investigated whether anti-PD-L1 antibody increased the antigen-specific immune response and anti-tumor effects induced by the antigen-specific protein vaccine, as well as the possible mechanisms regarding activation of APCs. Anti-PD-L1 antibody combined with the PEK protein vaccine generated more potent E7-specific immunity (including the number and cytotoxic activity of E7-specific cytotoxic CD8+ T lymphocytes) and anti-tumor effects than protein vaccine alone. Anti-PD-L1 antibody enhanced the maturation of dendritic cells and the proportion of M1-like macrophages in tumor-draining lymph nodes and tumors in tumor-bearing mice treated with combinatorial therapy. PD-L1 blockade overturned the immunosuppressive status of the tumor microenvironment and then enhanced the E7 tumor-specific antigen-specific immunity and anti-tumor effects generated by an E7-specific protein vaccine through modulation of APCs in an E7-expressing small tumor model. Tumor-specific antigen (like HPV E7 antigen)-specific immunotherapy combined with APC-targeting modality by PD-L1 blockade has a high translational potential in E7-specific cancer therapy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31323767

RESUMO

Adjuvant treatment in advanced-stage (stages III /IV) endometrial carcinomas in terms of tumor grades has not yet been explored. We retrospectively analyzed 194 patients with advanced-stage endometrioid endometrial carcinoma who received surgery, followed by adjuvant therapy, at National Taiwan University Hospital between January 1, 2000 and August 31, 2017. Adjuvant therapies included radiation (RT), chemotherapy alone (CT), and combined modality treatment (CMT: radiation and chemotherapy). The prognostic factors were determined from multivariate survival analyses using Cox regression models. Progression-free survival (PFS) and overall survival (OS) times were estimated with the Kaplan-Meier method. The median follow-up was 45.5 months (range: 6.2-207.9). In grade 1/2 endometrioid carcinoma, neither adjuvant CT nor CMT could prolong PFS significantly compared to RT (CT: HR 1.59, 95% CI 0.64-3.97; CMT: HR 2.03, 95% CI 0.72-5.74). Notably, maximal cytoreduction independently improved PFS (HR 0.31, 95% CI 0.10-0.90). No particular adjuvant treatment provided an OS advantage over the others for grade 1/2 endometrioid carcinomas. However, for grade 3 endometrioid carcinoma, CMT showed OS benefits (HR 0.15, 95% CI 0.03-0.89) compared to RT and CT. In conclusion, maximal cytoreduction should be the goal in patients with grade 1/2 advanced-stage endometrioid carcinomas. Based on our results, patients with grade 3 endometrioid carcinomas might benefit from adjuvant CMT.


Assuntos
Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Quimioterapia Adjuvante , Terapia Combinada , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Estudos Retrospectivos , Taiwan/epidemiologia , Útero/patologia
5.
Cancers (Basel) ; 11(5)2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31052575

RESUMO

The life span of dendritic cells (DCs) can become short following induced activation, which is associated with metabolic transition due to the regulation of mechanistic target of rapamycin (mTOR). The purpose of this study was to investigate the potential of inhibiting mTOR to modulate DC functions for elevating the anti-tumor effects of DNA vaccines. Therefore, the influences of various inhibitors of mTOR (mTORi) on the expressions of DC maturation markers, the abilities of antigen presenting and processing of BMM-derived DCs and the tumor killing effects of E7-specific CD8+ T lymphocytes activated by BMM-derived DCs were in vitro examined. The anti-tumor effects of connective tissue growth factor (CTGF)/E7 DNA vaccine and/or mTORi were also in vivo analyzed. In our study, suppressive effects of mTORi on the DC maturation markers expressed on BMMCs could be reversed. The mTORi-treated mature BMM-derived DCs tended to be non-apoptotic. These mTORi-treated BMM-derived DCs could have better antigen presenting and processing abilities. The E7-specific cytotoxic CD8+ T lymphocytes could have more potent tumoricidal activity following activation of mTORi-treated BMM-derived DCs. For tumor-bearing mice, those treated with CTGF/E7 DNA vaccine and mTORi indeed can have higher percentages of mature DCs in the TME, better disease control and longer survivals. Consequently, application of mTORi can be a pharmacological approach for temporally increasing life span, antigen presenting and antigen processing of DCs to strengthen the therapeutic outcome of cancer immunotherapy.

6.
Front Pharmacol ; 10: 426, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31105567

RESUMO

In this retrospective study, we investigated adverse events and outcomes in patients treated with bevacizumab for ovarian, fallopian tube, or primary peritoneal cancers at a single hospital. We determined the cumulative incidences of various bevacizumab-related adverse events and the correlation between dose and adverse event incidences. We analyzed data from 154 patients that received 251 rounds of bevacizumab as first-line, first salvage, >2 salvage treatments. Adverse events of any grade were observed in 121 (78.6%) patients; at least one grade 3 or 4 adverse event occurred in 32 (20.8%) patients. The two most common events were proteinuria (38.3%) and hypertension (33.8%). The first-line treatment group displayed significantly higher frequencies of hypertension (52.7% vs. 18.9% vs. 15.5%, p < 0.001), wound complications (9.1% vs. 0% vs. 1.2%, p = 0.010), arthralgia (29.1% vs. 11.3% vs. 8.3%, p = 0.003), and reduced range of joint motion (14.5% vs. 5.7% vs. 3.6%, p = 0.046), compared to those in the first and >2 lines salvage groups, respectively (Kruskal-Wallis test). The cumulative incidences of all grades and grades 3/4 of hypertension cumulative incidence plateaued at around 30% for all grades and 10% for grades 3 and 4, at bevacizumab doses above 8080 and 3510 mg, respectively. The proteinuria cumulative incidence plateaued at around 35% for all grades and 3% for grades 3 and 4, at bevacizumab doses above 11,190 and 4530 mg, respectively. We concluded that, in this realistic clinical population, different kinds and higher cumulative incidences of adverse events were observed compared to those reported in previous clinical trials. Moreover, bevacizumab doses showed cumulative toxicity and plateau effects on hypertension and proteinuria.

7.
Asian Pac J Cancer Prev ; 20(5): 1377-1387, 2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-31127896

RESUMO

Objective: Three vaccines are available to Taiwanese young girls for cervical cancer (CC) prevention. Here we evaluate the cost-effectiveness of the two-dose (2D) AS04-adjuvanted HPV-16/18 vaccine (2D-AS04-HPV- 16/18v)+screening compared with a screening programme alone, with 2D human papillomavirus 6/11/16/18 vaccine (2D-4vHPVv)+screening, and with 2D/three-dose (3D) human papillomavirus 6/11/16/18/31/33/45/52/58 vaccine (9vHPVv)+screening, for Taiwan universal mass vaccination. Methods: A static Markov cohort model simulated the natural history of human papillomavirus (HPV) infection and CC screening for a 12-year-old cohort of Taiwanese girls (N=120,000). The model ran in 1-year cycles over the cohort's lifetime. Vaccine efficacy irrespective of HPV type was considered in the analysis for each vaccine. Input data were obtained from published literature, local databases, government reports and websites, and expert opinion. The analysis incorporated direct medical costs only, with an annual discount rate of 3.0%. The threshold was determined as 1 Gross Domestic Product per capita (New Taiwan dollar [NT$] 727,818; year 2016). Results: The 2D-AS04-HPV-16/18v+screening yielded 0.0365 quality-adjusted life year (QALY) gained at an additional cost of NT$ 5,770 per person compared with the screening programme alone. This resulted in an incremental cost-effectiveness ratio well below the threshold. Compared with 2D-4vHPVv+screening and 2D/3D-9vHPVv+screening, discounted results demonstrated additional QALYs gained at lower cost for 2D-AS04-HPV- 16/18v+screening, making it dominant over both 2D-4vHPVv+screening and 2D/3D-9vHPVv+screening. Conclusions: Vaccinating Taiwanese girls with 2D-AS04-HPV-16/18v in addition to screening to prevent CC is cost-effective compared with using a screening programme alone and the dominant option compared with 2D-4vHPVv+screening and 2D/3D-9vHPVv+screening.


Assuntos
Análise Custo-Benefício , Detecção Precoce de Câncer/economia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/economia , Vacinas contra Papillomavirus/economia , Neoplasias do Colo do Útero/economia , Vacinação/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Cadeias de Markov , Pessoa de Meia-Idade , Papillomaviridae/classificação , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Prognóstico , Anos de Vida Ajustados por Qualidade de Vida , Taxa de Sobrevida , Taiwan/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Adulto Jovem
8.
Cancers (Basel) ; 11(2)2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30823599

RESUMO

Epithelial ovarian cancer patients usually relapse after primary management. We utilized the support vector machine algorithm to develop a model for the chemo-response using the Cancer Cell Line Encyclopedia (CCLE) and validated the model in The Cancer Genome Atlas (TCGA) and the GSE9891 dataset. Finally, we evaluated the feasibility of the model using ovarian cancer patients from our institute. The 10-gene predictive model demonstrated that the high response group had a longer recurrence-free survival (RFS) (log-rank test, p = 0.015 for TCGA, p = 0.013 for GSE9891 and p = 0.039 for NTUH) and overall survival (OS) (log-rank test, p = 0.002 for TCGA and p = 0.016 for NTUH). In a multivariate Cox hazard regression model, the predictive model (HR: 0.644, 95% CI: 0.436⁻0.952, p = 0.027) and residual tumor size < 1 cm (HR: 0.312, 95% CI: 0.170⁻0.573, p < 0.001) were significant factors for recurrence. The predictive model (HR: 0.511, 95% CI: 0.334⁻0.783, p = 0.002) and residual tumor size < 1 cm (HR: 0.252, 95% CI: 0.128⁻0.496, p < 0.001) were still significant factors for death. In conclusion, the patients of high response group stratified by the model had good response and favourable prognosis, whereas for the patients of medium to low response groups, introduction of other drugs or clinical trials might be beneficial.

9.
Artigo em Inglês | MEDLINE | ID: mdl-30795566

RESUMO

We aimed to determine prognostic factors of early stage (I/II) epithelial ovarian carcinoma (EOC) including clinicopathologic and chemotherapeutic regimens. Four hundred and thirty-seven women who underwent primary staging surgery with adjuvant chemotherapy between January 1, 2000 and December 31, 2010 were retrospectively reviewed and analyzed from two medical centers. The prognostic factors were determined from multivariate survival analyses using Cox regression models. The majority of women were diagnosed with stage Ic (244/437, 55.8%). The histopathologic types were clear cell (37.5%), endometrioid (27.2%), serous (14.0%), and mucinous (13.3%). Fifty-seven percent (249/437) of the women received taxane-based (platinum plus paclitaxel) regimens and 43.0% received non-taxane (platinum plus cyclophosphamide) regimens as frontline adjuvant chemotherapy. Clear cell tumors (adjusted Hazard ratio (aHR) 0.37, 95% confidence interval (CI) 0.21⁻0.73, p = 0.001) showed better 5-year disease-free survival (DFS) than serous tumors. Women diagnosed at FIGO (International Federation of Gynecology and Obstetrics) stage II (aHR 5.97, 95% CI = 2.47⁻14.39, p < 0.001), grade 3 tumor without clear cell (aHR 2.28, 95% CI = 1.02⁻5.07, p = 0.004) and who received 3⁻5 cycles of non-taxane regimens (aHR 3.29, 95% CI = 1.47⁻7.34, p = 0.004) had worse 5-year overall survival (OS). Clear cell histology treated with taxane-based regimens showed significantly higher 5-year DFS (91.2% vs. 82.0%, aHR = 0.45, 95% CI = 0.21⁻0.93, p = 0.043) and 5-year OS (93.5% vs. 79.0%, aHR = 0.30, 95% CI = 0.13⁻0.70, p = 0.005) than those treated with non-taxane-based regimens. We conclude that stage, tumor grade, and chemotherapeutic regimens/cycles are independent prognostic factors for early stage ovarian cancer.


Assuntos
Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Adulto , Idoso , Carcinoma Epitelial do Ovário/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/cirurgia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
10.
Artigo em Inglês | MEDLINE | ID: mdl-30769847

RESUMO

The objective of this article was to report the clinicopathological characteristics, treatment modalities, and outcomes of patients with clear cell carcinoma (CCC) of the abdominal wall. Medical records of six patients diagnosed with CCC of the abdominal wall between May 2003 and May 2018 at the National Taiwan University Hospital were reviewed. All patients had prior obstetric or gynecologic surgeries. The primary clinical presentation was enlarging abdominal masses at previous surgical scars. Four patients underwent initial/primary surgeries with/without adjuvant chemotherapy. One patient received neoadjuvant chemotherapy followed by surgical intervention and adjuvant chemotherapy, the other received chemotherapy and sequential radiotherapy without any surgical intervention. Two of four patients undergoing initial/primary surgeries had disease recurrence and the remaining two cases without initial surgery experienced disease progression during primary treatment. Inguinal lymph nodes were the most frequent sites of recurrence. In conclusion, previous obstetric or gynecologic surgery can be a risk factor for CCC of the abdominal wall. Complete resection of abdominal wall tumor and suspected intra-abdominal lesions with hysterectomy and bilateral inguinal lymph nodes dissection may be the primary treatment. Adjuvant chemotherapy would be considered for potential benefits. For patients without bilateral inguinal lymph nodes dissection, careful inguinal lymph node palpation during postoperative surveillance is necessary. More cases are still needed to elucidate the clinical management of this disease.


Assuntos
Parede Abdominal/fisiopatologia , Adenocarcinoma de Células Claras/etiologia , Adenocarcinoma de Células Claras/cirurgia , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Procedimentos Cirúrgicos Obstétricos/efeitos adversos , Adenocarcinoma de Células Claras/fisiopatologia , Adulto , Idoso , Feminino , Hospitais Universitários , Humanos , Pessoa de Meia-Idade , Gravidez , Taiwan
11.
Cancer Lett ; 444: 20-34, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30543813

RESUMO

We determined the anti-tumor effects and possible mechanisms of an antigen-specific DNA vaccine combined with PD-1 or CTLA-4 blockade. Using the HPV16 E6/E7+ syngeneic mouse tumor model, we investigated whether anti-CTLA-4 antibody (Ab) or anti-PD-1 Ab increases the antigen-specific anti-tumor effects and immune response induced by CTGF/E7 chimeric DNA vaccine and the possible mechanisms. Anti-PD-1 Ab or anti-CTLA-4 Ab combined with E7-specific DNA vaccine generated more potent antigen-specific immunity, including anti-E7 Abs and the number and cytotoxic activity of E7-specific cytotoxic CD8+ T lymphocytes, and anti-tumor effects than E7-specific DNA vaccine alone. In addition, the number of systemic and intratumoral Tregs was lower with the anti-PD-1 or anti-CTLA-4 Ab and E7-specific DNA vaccine. Furthermore, anti-PD-1 and anti-CTLA-4 Abs could enhance the maturation and abilities of intratumoral DCs to activate E7-specific cytotoxic CD8+ T cells. Immune checkpoint blockade overcomes the immunosuppressive status of the tumor-microenvironment to enhance the antigen-specific immunity and anti-tumor effects generated by an antigen-specific DNA vaccine. Antigen-specific immunotherapy combined with immune checkpoint blockade can be a novel strategy in clinical cancer therapy.


Assuntos
Anticorpos Monoclonais/farmacologia , Antígeno CTLA-4/imunologia , Células Dendríticas/imunologia , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/imunologia , Animais , Antígenos de Neoplasias/imunologia , Apoptose , Linfócitos T CD8-Positivos/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Proliferação de Células , Feminino , Humanos , Imunoterapia , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/patologia , Neoplasias/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Células Tumorais Cultivadas , Microambiente Tumoral , Vacinas de DNA/administração & dosagem , Vacinas de DNA/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Int J Gynecol Pathol ; 38(5): 470-473, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30085939

RESUMO

Ewing sarcoma and peripheral primitive neuroectodermal tumor constitute the Ewing family of tumors (EFT). EFTs primarily arising in the ovary are extremely rare. We report the case of a 22-yr-old nulliparous woman with a primary EFT in the ovary that initially presented as a 3-cm teratoma-like ovarian tumor, with rapid progression to a 15-cm-sized tumor with liver metastasis in 3 mo. The patient underwent suboptimal debulking surgery and salvage chemotherapy with vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide. In conclusion, primary EFT in the ovary is extremely rare with highly aggressive behavior and poor outcome for metastatic disease. Demonstration of EWSR1 rearrangement, observed in a variety of soft tissue tumors, is very helpful in the diagnosis of EFT when interpreted on the basis morphology and immunohistochemistry.


Assuntos
Tumores Neuroectodérmicos Primitivos Periféricos/patologia , Neoplasias Ovarianas/patologia , Sarcoma de Ewing/patologia , Adulto , Feminino , Humanos , Tumores Neuroectodérmicos Primitivos Periféricos/terapia , Neoplasias Ovarianas/terapia , Sarcoma de Ewing/terapia
13.
Endocr Relat Cancer ; 26(1): 73-88, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30121622

RESUMO

The role of chitinase-3-like protein 1 (CHI3L1) in ovarian cancer and the possible mechanisms were elucidated. CHI3L1 is a secreted glycoprotein and associated with inflammation, fibrosis, asthma, extracellular tissue remodeling and solid tumors. Our previous study showed CHI3L1 could be a potential prognostic biomarker for epithelial ovarian cancer and could protect cancer cells from apoptosis. Therefore, clinical data and quantitation of CHI3L1 of ovarian cancer patients, tumor spheroid formation, side-population assays, Aldefluor and apoptotic assays, ELISA, RT-PCR, immunoblotting and animal experiments were performed in two ovarian cancer cells lines, OVCAR3 and CA5171, and their CHI3L1-overexpressing and -knockdown transfectants. High expression of CHI3L1 was associated with poor outcome and chemoresistance in ovarian cancer patients. The mRNA expression of CHI3L1 in CA5171 ovarian cancer stem-like cells was 3-fold higher than in CA5171 parental cells. CHI3L1 promoted the properties of ovarian cancer stem-like cells including generating more and larger tumor spheroids and a higher percentage of ALDH+ in tumor cells and promoting resistance to cytotoxic drug-induced apoptosis. CHI3L1 could induce both the Akt (essential) and Erk signaling pathways, and then enhance expression of ß-catenin followed by SOX2, and finally promote tumor spheroid formation and other properties of ovarian cancer stem-like cells. OVCAR3 CHI3L1-overexpressing transfectants were more tumorigenic in vivo, whereas CA5171 CHI3L1-knockdown transfectants were not tumorigenic in vivo. CHI3L1 critically enhances the properties of ovarian cancer stem-like cells. CHI3L1 or CHI3L1-regulated signaling pathways and molecules could be potential therapeutic targets in ovarian cancer.


Assuntos
Proteína 1 Semelhante à Quitinase-3 , Neoplasias Ovarianas/patologia , Animais , Linhagem Celular Tumoral , Proteína 1 Semelhante à Quitinase-3/genética , Proteína 1 Semelhante à Quitinase-3/metabolismo , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Camundongos SCID , Pessoa de Meia-Idade , Células-Tronco Neoplásicas , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Esferoides Celulares , beta Catenina/metabolismo
14.
Epigenomics ; 10(11): 1397-1413, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30324802

RESUMO

AIM: To investigate the CDH1, DLEC1 and SFRP5 gene methylation panel for advanced epithelial ovarian carcinoma (EOC). MATERIALS & METHODS: One hundred and seventy-seven advanced EOC specimens were evaluated by methylation-specific PCR. We also used The Cancer Genome Atlas dataset to evaluate the panel. RESULTS: The presence of two or more methylated genes was significant in recurrence (hazard ratio [HR]: 1.91 [1.33-2.76]; p = 0.002) and death (HR: 1.96 [1.26-3.06]; p = 0.006) in our cohort. In The Cancer Genome Atlas dataset, the presence of two or three methylated genes was significant in death (HR: 1.59 [1.15-2.18]; p = 0.0047) and close to the significance level in recurrence (HR: 1.37 [0.99-1.88]; p = 0.058). CONCLUSION: The CDH1, DLEC1 and SFRP5 methylation panel is a potential prognostic biomarker for advanced EOC.


Assuntos
Antígenos CD/genética , Biomarcadores Tumorais/genética , Caderinas/genética , Carcinoma Epitelial do Ovário/genética , Metilação de DNA , Proteínas do Olho/genética , Proteínas de Membrana/genética , Neoplasias Ovarianas/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Análise de Sobrevida
15.
PLoS One ; 13(10): e0204950, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30335786

RESUMO

We aimed to identify factors predicting parametrial invasion in early-stage cervical cancer patients undergoing radical hysterectomy. We recruited women with invasive cervical cancer who underwent radical hysterectomy at a single medical institute from 2000-2011. The clinical and pathological characteristics and outcomes were retrospectively recorded, and the risk factors for parametrial invasion were analyzed. We enrolled 339 patients, including 7 with stage IA1 carcinomas, 10 with stage IA2, 266 with stage IB1, 39 with stage IB2, 14 with stage IIA1, and 3 with stage IIA2. The majority (237/339, 69.9%) had squamous cell carcinoma, while 32 (12.4%) had parametrial invasion. The 16 patients with stage IB1 tumors and parametrial invasion were older (55.9±9.5vs. 49.0±9.9 years, p = 0.005, Mann-Whitney U test), and had deeper cervical stromal invasion (9.59±4.87 vs. 7.47±5.48 mm, p = 0.048, Mann-Whitney U test), larger tumor size (2.32±1.15 vs. 1.74±1.14cm, p = 0.043, Mann-Whitney U test), higher incidences of lymphovascular space invasion (87.5% vs. 28.8%, p<0.001, chi-square test), and greater lymph node metastasis (68.8% vs. 10.8%, p<0.001, chi-square test) than the 260 patients without parametrial invasion. Among the patients with stage IB1 tumor size >2 cm,10% had parametrial invasion and 24.2% had lymph node metastasis compared with only 4% and 9.4% of stage IB1 patients with a tumor size <2 cm, respectively. Only one (0.9%) of the 109 patients aged less than 50 years had parametrial invasion compared with 6 (9.7%) of the 62 patients aged over 50 years. Patients with stage IA2 and IB1 tumors <2 cm may not need radical hysterectomy owing to the low incidence of parametrial invasion.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias do Colo do Útero/patologia , Adulto , Fatores Etários , Idoso , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Histerectomia , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Neoplasias do Colo do Útero/cirurgia , Adulto Jovem
16.
J Gynecol Oncol ; 29(5): e76, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30022636

RESUMO

OBJECTIVE: Choice of hysterectomy and adjuvant treatment for International Federation of Gynecology and Obstetrics (FIGO) 2009 stage II endometrioid endometrial cancer (EEC) is still controversial. Aims of this study were to evaluate survival benefits and adverse effects of different hysterectomies with or without adjuvant radiotherapy (RT), and to identify prognostic factors. METHODS: The patients at 14 member hospitals of the Taiwanese Gynecologic Oncology Group from 1992 to 2013 were retrospectively investigated. Patients were divided into simple hysterectomy (SH) alone, SH with RT, radical hysterectomy (RH) alone, and RH with RT groups. Endpoints were recurrence-free survival (RFS), overall survival (OS), disease-specific survival (DSS), adverse effects and prognostic factors for survival. RESULTS: Total of 246 patients were enrolled. The 5-year RFS, OS, DSS and recurrence rates for the entire cohort were 89.5%, 94.3%, 96.2% and 10.2%, respectively. Patients receiving RH had more adverse effects including blood loss (p<0.001), recurrent urinary tract infections (p=0.013), and leg lymphedema (p=0.038). Age over 50-year (HR=9.2; 95% confidence interval [CI]=1.2-70.9) and grade 3 histology (HR=7.28; 95% CI=1.45-36.6) were independent predictors of OS. Grade 3 histology was an independent predictor of RFS (HR=5.13; 95% CI=1.38-19.1) and DSS (HR=5.97; 95% CI=1.06-58.7). Patients receiving adjuvant RT had lower locoregional recurrence (p=0.046), but no impact on survival. CONCLUSION: Different treatment modalities yield similar survival outcomes. Patients receiving SH with RT had lower locoregional recurrent with acceptable morbidity. Age and tumor grading remained significant predictors for survival among patients with FIGO 2009 stage II EEC.


Assuntos
Carcinoma Endometrioide/terapia , Neoplasias do Endométrio/terapia , Adulto , Fatores Etários , Idoso , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/secundário , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histerectomia/efeitos adversos , Histerectomia/métodos , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Prognóstico , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
17.
J Gynecol Oncol ; 29(4): e55, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29770625

RESUMO

OBJECTIVE: To investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements. METHODS: Women with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152). RESULTS: There were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07-0.68; p=0.010). Women in their 40s-50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03-1.49; p=0.020). CONCLUSION: In women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years.


Assuntos
Células Escamosas Atípicas do Colo do Útero/citologia , Neoplasia Intraepitelial Cervical/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Distribuição por Idade , Idoso , Biópsia/estatística & dados numéricos , Neoplasia Intraepitelial Cervical/diagnóstico , Estudos de Coortes , Colposcopia/estatística & dados numéricos , Conização/estatística & dados numéricos , Crioterapia/estatística & dados numéricos , Detecção Precoce de Câncer , Feminino , Humanos , Incidência , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Gradação de Tumores , Teste de Papanicolaou/estatística & dados numéricos , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/terapia , Vigilância da População , Modelos de Riscos Proporcionais , Medição de Risco , Taiwan/epidemiologia , Neoplasias do Colo do Útero/diagnóstico , Adulto Jovem
18.
Oncotarget ; 9(23): 16501-16511, 2018 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-29662662

RESUMO

Health effect assessments based on natural killer (NK) cells are an important emerging area of human health. We recruited 90 forest staff members in Xitou, Taiwan and 110 urban staff members in Taipei to investigate the health effects of forest environment exposure on NK cells (CD3-/CD56+) and activating NK cells (CD3-/CD56+/CD69+) in humans. We also invited 11 middle-aged volunteers in a pilot study to participate in a five-day/four-night forest trip to Xitou forest to investigate the health effects of a forest trip on NK cells and activating NK cells. Results showed that NK cells were higher in the forest group (19.5 ± 9.1%) than in the urban group (16.4 ± 8.4%). In particular, the percentage of NK cells was significantly higher in the forest group than in the urban group among the subgroups of male, a higher body mass index (≥ 25 kg/m2), without hypertension, lower high-sensitivity C-reactive protein, hyperglycemia, without smoking habit, and with tea drinking habit. After the five-day trip in Xitou forest, the percentage of activating NK cells of the invited participants from Taipei increased significantly after the trip to Xitou forest (0.83 ± 0.39% vs. 1.72 ± 0.1%). The percentage of activating NK cells was 1.13 ± 0.43%, which was higher than the baseline value of 0.77 ± 0.38% before the forest trip among the seven subjects who participated in the follow-up study four days after returning to Taipei. This study suggests that exposure to forest environments might enhance the immune response of NK cells and activating NK cells in humans.

19.
Taiwan J Obstet Gynecol ; 57(2): 300-303, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29673677

RESUMO

OBJECTIVE: To evaluate the clinical presentations, diagnosis, management, and outcomes of torsion of the pedunculated subserous uterine leiomyoma. MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with subserous uterine leiomyomas undergoing surgeries at National Taiwan University Hospital from January 2001 to December 2015. RESULTS: Five cases of torsion of pedunculated subserous uterine leiomyoma were identified. All presented with sudden onset abdominal pain. Two patients received emergent surgeries, the other three cases received scheduled surgeries. The postoperative courses of these five women were uneventful without sequelae. CONCLUSIONS: Torsion of pedunculated subserous uterine leiomyoma is rare. Accurately diagnosing it prior to surgery is a major challenge. It should be one of the differential diagnosis in patients with uterine leiomyoma presenting with acute abdomen.


Assuntos
Leiomioma/complicações , Anormalidade Torcional/complicações , Neoplasias Uterinas/complicações , Dor Abdominal , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Histerectomia , Leiomioma/patologia , Leiomioma/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Taiwan , Anormalidade Torcional/cirurgia , Ultrassonografia , Miomectomia Uterina , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia
20.
Cancer Lett ; 425: 152-163, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29596890

RESUMO

As a tumor antigen, mesothelin (MSLN) can be identified in various malignancies. MSLN is potential for antigen-specific cancer vaccines. We generated a novel chimeric DNA vaccine using antigen-specific connective tissue growth factor lined with MSLN (CTGF/MSLN). The anti-tumor effects of the CTGF/MSLN DNA vaccine combined with anti-CD40 Ab and toll-like receptor 3 ligand-poly(I:C) were validated in an MSLN-expressing model. CTGF/MSLN DNA with anti-CD40Ab and poly(I:C) vaccinated mice demonstrated potent anti-tumor effects with longer survival and less tumor volumes. An increase in MSLN-specific CD8+ T cells and anti-MSLN Ab titers was also noted in CTGF/MSLN DNA with anti-CD40Ab and poly(I:C) vaccinated mice. The CTGF/MSLN DNA vaccine combined with immuno-modulator EGCG also generated potent anti-tumor effects. Immuno-modulators could enhance the antigen-specific anti-tumor effects of CTGF/MSLN DNA vaccine through promoting the DC maturation. In addition, MSLN-specific cell-based vaccine with AAV-IL-12 and the CTGF/MSLN DNA vaccine with anti-CD40Ab/polyp(I:C) generated more potent anti-tumor effects than the other combinational regimens. The results indicate that an MSLN-specific DNA vaccine combined with immuno-modulators may be an effective immunotherapeutic strategy to control MSLN-expressing tumors including ovarian and pancreastic cancers, and malignant mesothelioma.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Catequina/análogos & derivados , Fator de Crescimento do Tecido Conjuntivo/genética , Proteínas Ligadas por GPI/genética , Neoplasias Pulmonares/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Poli I-C/administração & dosagem , Vacinas de DNA/administração & dosagem , Animais , Anticorpos Monoclonais/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/imunologia , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Catequina/administração & dosagem , Catequina/imunologia , Linhagem Celular Tumoral , Células Dendríticas/imunologia , Sinergismo Farmacológico , Feminino , Neoplasias Pulmonares/imunologia , Mesotelioma/imunologia , Camundongos , Poli I-C/imunologia , Resultado do Tratamento , Vacinas de DNA/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA