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1.
BMC Cancer ; 20(1): 385, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375688

RESUMO

BACKGROUND: Primary debulking surgery (PDS) and adjuvant chemotherapy is the standard treatment for advanced ovarian, fallopian or primary peritoneal cancer. However, neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) has been introduced as an alternative, showing similar efficacy and decreased postoperative complications compared with PDS. Although there is still no evidence for whether three or four cycles of NAC used clinically could be adequate, reducing one cycle of NAC is expected to remove more visible tumours and thereby improve prognosis. Thus, we proposed with this study to evaluate the efficacy and safety of reducing one cycle of NAC for advanced ovarian, fallopian or primary peritoneal cancer. METHODS: This study is a prospective, multi-centre, open-label, randomized phase III trial. A total of 298 patients with advanced ovarian, fallopian or primary peritoneal cancer will be recruited and randomly assigned to either three (control group) or two cycles of NAC (experimental group). After the NAC, we will conduct IDS with maximal cytoreduction and then administer the remaining three or four cycles for a total of six cycles of adjuvant chemotherapy. The primary end point is progression-free survival, and the secondary end points are time to tumour progression, overall survival, tumour response after NAC, IDS and adjuvant chemotherapy, radiologic investigation after IDS, tumour response by positron emission tomography-computed tomography after NAC, quality of life, adverse events, success rate of optimal cytoreduction, surgical complexity, postoperative complications and safety of IDS. We will assess these factors at screening, at every cycle of chemotherapy, at IDS, after the completion of chemotherapy, every 3 months for the first 2 years after the planned treatment and every 6 months thereafter for 3 years. DISCUSSION: We hypothesize that reducing one cycle of NAC will contribute to more resection of visible tumours despite 10% reduction of optimal cytoreduction, which could improve survival. Moreover, two cycles of NAC may increase postoperative complications by 5% compared with three cycles, which may be acceptable. TRIAL REGISTRATION: This study has been prospectively registered at ClinicalTrials.gov on Oct. 2nd, 2018 (NCT03693248, URL: https://clinicaltrials.gov/ct2/show/NCT03693248).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Quimioterapia Adjuvante/mortalidade , Neoplasias das Tubas Uterinas/tratamento farmacológico , Terapia Neoadjuvante/mortalidade , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário/patologia , Estudos de Casos e Controles , Neoplasias das Tubas Uterinas/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/patologia , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida , Adulto Jovem
2.
J Korean Med Sci ; 33(23): e166, 2018 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-29853821

RESUMO

BACKGROUND: The optimal endoscopic screening interval for early gastric cancer (EGC) detection still remains controversial. Thus, we performed this prospective study to clarify the optimal interval between endoscopic examinations for EGC detection. METHODS: A questionnaire survey for penultimate endoscopy and gastric cancer (GC) diagnosis interval was used; the findings were then analyzed. The patients were divided into two groups according to GC type and endoscopic examinations intervals. RESULTS: A total of 843 patients were enrolled. The endoscopic GC detection interval (P < 0.001), tumor location (P < 0.001), tumor size (P < 0.001), histology (P < 0.001), tumor stage (P < 0.001), and treatment modality (P < 0.001) showed significant differences in the univariate analysis between EGC and advanced gastric cancer (AGC). Endoscopic examination intervals below 2 years and 3 years were associated with higher proportions of EGC detection (adjusted odds ratio, 2.458 and 3.022, respectively) (P < 0.001). The patients with endoscopic examination to GC diagnosis interval of < 2 years showed significant differences in tumor size (P < 0.001), tumor stage (P < 0.001), and treatment modality (P < 0.001) compared to those with intervals of > 2 years and without screening. Similar results were observed in those with < 3-year intervals. CONCLUSION: Triennial endoscopic screening might be as effective as biennial screening in increasing the detection rate of EGC and the risk of subsequent curable endoscopic resections.


Assuntos
Neoplasias Gástricas/diagnóstico , Idoso , Antineoplásicos/uso terapêutico , Detecção Precoce de Câncer , Feminino , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Estudos Prospectivos , Estômago/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Fatores de Tempo
3.
Int J Gynecol Cancer ; 25(7): 1277-84, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26067858

RESUMO

OBJECTIVES: This study aimed to investigate the current management of endometrial hyperplasia (EH) in Korea. MATERIALS AND METHODS: This was an electronic survey, which included 40 questions, that was distributed to the members of the Korean Gynecologic Oncology Group in 2014. RESULTS: In total, 50 (69%) of 72 members responded to the survey. The oral progestogens were the most popular choices for managing EH without atypia (simple hyperplasia(SH), 64%; complex hyperplasia (CH), 52%). In the case of CH with atypia, most of the gynecologist respondents would perform hysterectomy (95.9%). For fertility preservation, the oral progestogens were the most popular choices (SH, 75.5%; CH, 56.3%), followed by the levonorgestrel-releasing intrauterine system (LNG-IUS). More than 70% of the respondents reported use of dilatation and curettage as a follow-up method. CONCLUSIONS: Our survey results show that most of Korean gynecologic oncologists still prefer oral progestogens for conservative management of EH, notwithstanding the many successful reports on the LNG-IUS. As a follow-up evaluation method, dilatation and curettage is mostly used. To identify the optimum therapy, a randomized controlled trial comparing the LNG-IUS with continuous oral progestogens is required. Furthermore, a large-scale prospective study to confirm the most reliable technique for follow-up evaluation is necessary.


Assuntos
Anticoncepcionais Femininos/uso terapêutico , Hiperplasia Endometrial/terapia , Histerectomia , Levanogestrel/uso terapêutico , Terapia Combinada , Gerenciamento Clínico , Hiperplasia Endometrial/patologia , Feminino , Seguimentos , Humanos , Dispositivos Intrauterinos Medicados , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , República da Coreia
4.
J Minim Invasive Gynecol ; 22(5): 785-91, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25757810

RESUMO

STUDY OBJECTIVE: To compare the operative outcomes of patients undergoing either single-port or multiport laparoscopic hysterectomy (LH). METHODS: Two hundred fifty-six women scheduled for LH for symptomatic myoma and/or adenomyosis from 8 tertiary teaching hospitals were randomized to single-port or multiport groups. Primary outcome was conversion and/or complication proportion of the planned procedure to determine whether the success proportion of the single-port approach was not inferior to that of the multiport approach. Secondary outcomes were postoperative pain and operative scar. RESULTS: Demographic parameters including age, body mass index, parity, and history of vaginal and cesarean delivery were comparable between the 2 groups. The primary outcome of a combined conversion and/or complication rate was similar between the single-port and multiport groups at 8% and 10.3%, respectively. Conversions were similar between the groups with 4% of single-port cases and .8% of multiport cases. Transfusions were the most frequent complication required in 4.0% of single-port cases and 7.9% of multiport cases, with no difference between the groups. Concerning secondary outcomes, postoperative pain score and patient and observer scar assessment were not different between the 2 groups. Although not a specific outcome measure, there was no difference between the groups in blood loss, operative time, and postoperative hospital stay. CONCLUSION: Single-port LH is not inferior to multiport LH in terms of conversion and/or complications rates, including transfusion. However, the single-port approach did not have any advantage over multiport LH with regard to pain or cosmetic outcomes. These findings were demonstrated by multi-institutional surgeons in Korea.


Assuntos
Adenomiose/cirurgia , Histerectomia , Laparoscopia , Leiomioma/cirurgia , Neoplasias Uterinas/cirurgia , Adulto , Feminino , Humanos , Histerectomia/métodos , Laparoscopia/métodos , Pessoa de Meia-Idade , Duração da Cirurgia , Dor Pós-Operatória/etiologia , Período Pós-Operatório , Estudos Prospectivos , República da Coreia , Resultado do Tratamento
5.
J Pers Med ; 14(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38929822

RESUMO

The purpose of this study was to establish the noninferiority of robotic single-site (RSS) surgery compared with multiport laparoscopic (MPL) surgery in surgical outcomes and overall survival for early endometrial cancer. This study was conducted retrospectively in a single center and included 421 patients who underwent either RSS (n = 146) or MPL (n = 275) surgery between 2014 and 2022. In terms of perioperative outcomes, the RSS group had a longer operating time than the MPL surgery group (mean (standard deviation [SD]) RSS 97.55 [29.79] vs. MPL 85.56 [26.13], p < 0.001). However, no significant differences in estimated blood loss or perioperative complications were found between the groups (p = 0.196 and p = 0.080, respectively). The patients in the RSS group were discharged earlier than those in the MPL group (mean [SD]): 4.06 [3.24] vs. 9.39 [4.76], p < 0.001). Regarding oncologic outcomes, no significant differences in the type of therapy, disease stage, tumor grade, histopathological type, or lymphovascular invasion were found between the groups. No statistically significant differences were found in the disease-free (p = 0.27) and overall survival rates (p = 0.5) either. In conclusion, this study suggests that RSS and MPL surgery are both safe and effective options for staging operations in patients with early-stage endometrial cancer.

6.
Mol Biol Rep ; 40(5): 3623-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23269624

RESUMO

Osteopontin (OPN) involves in the tumor-promoting or metastasis in human endometrial cancer. Depletion of OPN gene expression in endometrial cancer cells was significantly decreased in cell viability and the cells undergo apoptotic cell death. The status of OPN in THESC, RL95, Hec1A and Ishikawa cell lines were analyzed by RT-PCR and western blot. After OPN-siRNA transfection, mRNA and protein expression levels of OPN were determined in Hec1A and Ishikawa cells. Cell proliferation and cell cycle distribution were observed by MTT and flow cytometry analysis. DNA fragmentation assay was used to measure cell apoptosis. Cell migration was assessed by wound healing assay. Depletion of OPN gene expression in endometrial cancer cell lines (Hec1A and Ishikawa cells) reproducibly changed their ability of proliferation. Concomitant changes were seen in the expression of OPN binding cell surface receptors, cell cycle-regulatory genes, cell invasion and colony formation nature of the tumor cells. Decreased colonizing potential in the absence of OPN was reversed in the presence of recombinant OPN. Inhibition of anchorage-independent growth was observed in the presence of metabolic inhibitors of the PI3K, Src and integrin signaling cascades, which was ameliorated in the presence of exogenously added OPN. Our result showed the role of OPN in endometrial cancer, in particular on the malignancy-promoting aspects of OPN that may pave way for new approaches to the clinical management of endometrial cancer.


Assuntos
Transformação Celular Neoplásica/genética , Neoplasias do Endométrio/genética , Osteopontina/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Neoplasias do Endométrio/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Neoplásica/genética , Osteopontina/metabolismo
7.
J Korean Med Sci ; 28(4): 527-33, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23580227

RESUMO

Induction of apoptosis in target cells is a key mechanism by which chemotherapy promotes cell killing. The purpose of this study was to determine whether Indole-3-Carbinol (I3C) and Genistein in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induce apoptosis in endometrial cancer cell (Ishikawa) and to assess apoptotic mechanism. The MTT assay and flow cytometry were performed to determine cell viability and cell cycle. The induction of apoptosis was measured by caspase-3 activity test, DNA fragmentation assay, annexin V binding assay and western blot analysis. There was no effect in cell growth inhibition and cell cycle progression alone or in two-combination. However, the treatment of I3C and Genistein followed by TRAIL showed significant cell death and marked increase in sub-G1 arrest. Three-combination treatment revealed elevated expression of DR4, DR5 and cleaved forms of caspase-3, caspase-8, PARP. The Flip was found down regulated. Moreover, increase in caspase-3 activity and DNA fragmentation indicated the induction of apoptosis. The results indicate that I3C and Genistein with TRAIL synergistically induced apoptosis via death receptor dependent pathway. Our findings might provide a new insight into the development of novel combination therapies against endometrial cancer.


Assuntos
Anticarcinógenos/farmacologia , Apoptose/efeitos dos fármacos , Genisteína/farmacologia , Indóis/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Caspase 3/metabolismo , Caspase 8/metabolismo , Linhagem Celular Tumoral , Sinergismo Farmacológico , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Poli(ADP-Ribose) Polimerases/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo
8.
J Pers Med ; 13(5)2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37240903

RESUMO

BACKGROUND: The mainstay of treatment for early-stage cervical cancer is surgery; we present a 5-year experience of robotic single-site radical hysterectomy (RSRH) focused on surgical and oncologic outcomes. METHODS: This retrospective study included 44 cases of RSRH performed in patients with early-stage cervical cancer. RESULTS: The median follow-up period for the 44 patients was 34 months. The mean total operation time was 156.07 ± 31.77 min, while mean console time was 95.81 ± 24.95 min. Two cases had complications, which required surgical management, while four cases (9.1%) exhibited recurrence. The disease-free survival rate at 5 years was 90.9%. The sub-division analysis showed that Stage Ia2 and stage Ib1 patient sub-group showed better DFS than that of the stage Ib2 patient sub-group. The learning curve analysis showed that the CUSUM-T initially peaks at the sixth case then gradually decreases before rising and peaking at the 24th case. After 24th case, the CUSUM-T gradually decreases and reaches zero. CONCLUSION: The surgical outcomes of RSRH for early-stage cervical cancer treatment were safe and acceptable. However, RSRH could be considered carefully only in well-selected patient groups. Large-scale prospective studies are necessary in the future to validate the results.

9.
Int J Med Robot ; 17(4): e2255, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33817949

RESUMO

BACKGROUND: This study aimed to compare the surgical outcomes and cost of robotic single-site radical hysterectomy (RSSRH) versus robotic multiport radical hysterectomy (RMPRH) with pelvic lymph node dissection in early stage cervical cancer. METHODS: Sixty-two patients with early stage cervical cancer were recruited between November 2011 and July 2017 and underwent RSSRH (20 patients) and RMPRH (42 patients) for early stage cervical cancer using the da Vinci Si Surgical System (Intuitive Surgical). RESULTS: There were no significant difference between the two groups in most of parameters. However, postoperative hospital discharge and total hospital costs for RSSRH were significantly shorter than RMPRH (both p < 0.001). However, lymph node retrieval of RMPRH was significantly higher than RSSRH in (18.0 vs. 9.5, respectively; p < 0.001). CONCLUSIONS: RSSRH has comparable surgical outcomes to the RMPRH method. RSSRH could be considered a surgical option in a well-selected patient group.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Neoplasias do Colo do Útero , Feminino , Humanos , Histerectomia , Excisão de Linfonodo , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/cirurgia
10.
J Clin Med ; 10(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578930

RESUMO

This study aimed evaluate the feasibility of modified laparoscopic transabdominal cervicoisthmic cerclage (LTCC) and its impact on recurrent pregnancy loss (RPL) and is a retrospective observational cohort study of patients who underwent modified LTCC from 2003 to 2018 (n = 299). The surgery was performed at a mean gestational age of 12.5 weeks (range 10.5-17.5 weeks). Of the 299 patients, 190 were reported as having undergone abortion (one abortion: 91 (47.9%), two: 59 (31.1%), three or more: 40 (21.1%)) before the present pregnancy and prior to the surgery. The mean operation time was 47.4 min (range 15-100 min). We followed up with 205 of 299 patients and recorded their obstetric outcomes. There were 176 successful deliveries via cesarean section, and the fetal survival rate was 85.9% (176/205). The results of this study suggest that modified LTCC is a safe and feasible surgical option during pregnancy for patients with a history of RPL due to cervical factors.

11.
J Gynecol Oncol ; 32(6): e94, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34708596

RESUMO

Since the human papillomavirus (HPV) vaccine guidelines were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2011, 2016, and 2019, several recent studies on the efficacy and safety of HPV vaccines in middle-aged women and men have been reported. Furthermore, there has been an ongoing debate regarding the efficacy of the HPV vaccine in women with prior HPV infection or who have undergone conization for cervical intraepithelial neoplasia (CIN). We searched and reviewed studies on the efficacy and safety of the HPV vaccine in middle-aged women and men and the efficacy of the HPV vaccine in patients infected with HPV and those who underwent conization for CIN. The KSGO updated their guidelines based on the results of the studies included in this review.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/prevenção & controle , República da Coreia , Neoplasias do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/prevenção & controle
12.
Gynecol Oncol Rep ; 34: 100663, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33204794

RESUMO

BACKGROUND: Uterine smooth muscle tumor of uncertain malignant potential (STUMP) is a rare tumor belonging to a group of smooth muscle tumors that possess both benign and malignant features, complicating the diagnosis.Case report.We present the case of a 41-year-old primiparous woman who complained of heavy menstrual bleeding and severe pressure symptoms in the lower abdomen for 3 months. Magnetic resonance imaging revealed a large intramural myoma measuring 35 × 25 cm in the lower uterine corpus. A laparotomy including total hysterectomy was performed. Grossly, the uterine mass measured 38.5 × 35.4 × 20.4 cm in the largest diameter and weighed 18.3 kg. Pathological analysis revealed a uterine mass diagnosed as a smooth muscle tumor of uncertain malignant potential. The patient was normally discharged 7 days after surgery and decided to follow up without further treatment. At the time of this report, the patient had been followed up as an outpatient for 18 months without recurrence. CONCLUSION: Giant uterine STUMP is extremely rare and difficult to diagnose on physical examination and imaging findings alone. It is important to consider the possibility of an underlying malignancy when performing a preoperative examination and to perform frozen biopsy if malignancy is suspected. During follow-up, patients should undergo consultation with a gynecologic oncologist and should be surveilled closely because of the possibility of recurrence or metastasis.

13.
Obstet Gynecol Sci ; 62(3): 149-156, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31139590

RESUMO

OBJECTIVE: The aims of this study were to introduce surgical guidelines, and to evaluate the feasibility and safety of a robotic single-site staging (RSSS) operation for early-stage endometrial cancer. METHODS: Patients with a preoperative diagnosis of endometrial cancer (International Federation of Gynecology and Obstetrics stages IA to IB) from endometrial curettage and preoperative imaging studies were selected at Dongsan Medical Center from March 2014 to November 2015. All surgical procedures, including hysterectomy, salpingo-oophorectomy, bilateral pelvic node dissection, and cytology aspiration, were performed by robotic single-site instruments (da Vinci Si® surgical system; Intuitive Surgical, Sunnyvale, CA, USA). RESULTS: A total of 15 women with early-stage endometrial cancer underwent the RSSS operation. The median patient age and body mass index were 53 years (range, 37-70 years) and 25.4 kg/m2 (range, 18.3-46.4 kg/m2). The median docking time, console time, and total operative time were 8 minutes (range, 4-15 minutes), 75 minutes (range, 55-115 minutes), and 155 minutes (range, 125-190 minutes), respectively. The median retrieval of both pelvic lymph nodes was 9 (range, 6-15). There were no conversions to laparoscopy or laparotomy. CONCLUSION: The RSSS operation is feasible and safe in patients with early-stage endometrial cancer. In this study, operative times were reasonable, and the surgical procedure was well-tolerated by the patients. Further evaluation of patients with early-stage endometrial cancer should be performed in large-scale comparative studies using the laparoendoscopic, single-site staging operation to confirm the safety and benefits of the RSSS operation for early-stage endometrial cancer.

14.
J Gynecol Oncol ; 30(2): e31, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30740959

RESUMO

In 2016, 9-valent human papillomavirus (HPV) vaccine has been newly introduced in Korea, thus the need to develop recommendations for the vaccine has raised. Until we decide to develop a guideline, no further studies on the bi-valent or quadri-valent HPV vaccine have been announced. We searched and reviewed the literatures focused on the efficacy of 9-valent HPV vaccine, the ideal age of 3-dose schedule vaccination, the efficacy of 9-valent HPV vaccine in middle-aged women, the efficacy of the 2-dose schedule vaccination, the safety of 9-valent HPV vaccine, the possibility of additional 9-valent HPV vaccination, and cross-vaccination of 9-valent HPV vaccine. So, Korean Society of Gynecologic Oncology (KSGO) developed a guideline only for 9-valent HPV vaccine.


Assuntos
Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/prevenção & controle , Fatores Etários , Alphapapillomavirus/imunologia , Feminino , Humanos , Masculino , República da Coreia , Neoplasias do Colo do Útero/virologia
15.
Cancer Chemother Pharmacol ; 62(4): 689-97, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18074135

RESUMO

PURPOSE: We have investigated the effects of BRCA1 over-expression and knockdown on 5F-203-induced gene expression and cytotoxicity in human breast cancer cells. 5F-203 is a chemotherapeutic prodrug that both induces a p450 enzyme, CYP1A1, and is metabolically activated by CYP1A1. METHODS: We used several molecular biological techniques to confirm our findings. BRCA1 regulates sensitivity to 5F-203 by regulating the expression of CYP1A1 mRNA and its EROD activity. XRE-Luc reporter assays, semi-quantitative RT-PCR, Western blot analysis, EROD activity measurements, gene knockdown and MTT cell survival assays were used for this study. RESULTS: Our results show that the ability of 5F-203 treatments to increase CYP1A1 mRNA level and CYP1A1 enzymatic activity (EROD activity) are affected by BRCA1 protein levels. In addition, the ability of 5F-203 treatments to induce proteins, P53 and P53 target genes such as P21, is significantly decreased in BRCA1 knockdown cells, suggesting that BRCA1-related effects could at least partially explain why BRCA1 knockdown increases resistance to 5F-203-mediated cytotoxicity. We also observed altered expression of the two major transcription factors (AhR and ARNT) that affect CYP1A1 expression when BRCA1 protein levels are altered. CONCLUSION: BRCA1 is an important protein, which affects 5F-203-mediated cytotoxicity. Our findings are potentially clinically significant; they suggest that those patients most likely to respond to this new prodrug will have tumors containing normal amounts of BRCA1.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Citocromo P-450 CYP1A1/biossíntese , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Pró-Fármacos/farmacologia , Tiazóis/farmacologia , Ubiquitina-Proteína Ligases/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Citocromo P-450 CYP1A1/genética , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Indução Enzimática/efeitos dos fármacos , Feminino , Inativação Gênica , Humanos , RNA Interferente Pequeno/farmacologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
16.
Gynecol Endocrinol ; 24(5): 250-6, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18569028

RESUMO

OBJECTIVES: The objectives of the present study were to evaluate the expression level of ATP-sensitive potassium (K(ATP)) channels in smooth muscle cells in human uterine leiomyoma and the involvement of the channel in potentiating effect of estrogen on leiomyoma growth. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR and Western blot were used for the identification and quantification of K(ATP)-channel subunits in the control myometrial and leiomyoma cells. Furthermore, we measured the K(ATP)-channel activity in enzymatically isolated single uterine smooth muscle cells by whole-cell patch-clamp recordings. The estrogen-induced cell proliferation in leiomyoma was measured by the MTT assay. RESULTS: The subunits of K(ATP) channels (Kir6.1, Kir6.2, SUR2B) were more highly expressed in leiomyoma cells than in control cells. The whole-cell currents mainly through K(ATP) channels were also greater in the leiomyoma cells. Estrogen applied in the bath solution could acutely enhance the channel activity. Estrogen-induced proliferation of the leiomyoma cells was inhibited by pretreatment with glibenclamide, a K(ATP)-channel inhibitor. CONCLUSION: Estrogen may induce the proliferation of leiomyoma cells, at least in part, by activating the K(ATP) channel. Increased expression of the K(ATP) channel may be a causal factor for the high growth rate of uterine leiomyoma.


Assuntos
Estradiol/farmacologia , Canais KATP/biossíntese , Leiomioma/metabolismo , Neoplasias Uterinas/metabolismo , Adulto , Processos de Crescimento Celular/fisiologia , Receptor alfa de Estrogênio/biossíntese , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/biossíntese , Receptor beta de Estrogênio/genética , Feminino , Formazans/química , Glibureto/farmacologia , Humanos , Immunoblotting , Canais KATP/genética , Leiomioma/genética , Leiomioma/patologia , Pessoa de Meia-Idade , Técnicas de Patch-Clamp , Pinacidil/farmacologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sais de Tetrazólio/química , Regulação para Cima/efeitos dos fármacos , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia
17.
Mol Hum Reprod ; 13(11): 829-36, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17893092

RESUMO

The nuclear receptors PPARs (peroxisome proliferator-activated receptors) are transcription factors that play important roles in multiple disease conditions. The activation of PPARs by specific ligands is associated with growth suppression of several different types of human cancer, but the molecular mechanism responsible for this growth suppressive effect remains elusive. The aim of this study was to determine the distribution of PPARgamma protein/mRNA expression in uterine leiomyomas and to identify the PPARgamma induced signaling pathways responsible for the growth inhibition induced by treatment with ciglitizone, a synthetic ligand of PPARgamma, in view of identifying targets that could possibly affect the viability and proliferation of uterine leiomyoma cells. Dose-response studies on proliferation found that uterine leiomyoma was more sensitive to inhibition by ciglitizone treatments than normal myometrium. We also found that ciglitizone significantly stimulated gene expression driven by a PPAR-responsive element in cultured leiomyoma cells and reduced the survival of leiomyoma cells relative to the control cells. The reduced survival of ciglitizone treated leiomyoma cells resulted from a mechanism that involved the Fas receptor-mediated apoptosis signaling cascade. These results suggest that uterine leiomyomas growth and differentiation might be modulated through PPARgamma receptors and that PPARgamma ligands may be of potential use for uterine leiomyoma treatment.


Assuntos
Apoptose/efeitos dos fármacos , PPAR gama/antagonistas & inibidores , Tiazolidinedionas/farmacologia , Western Blotting , Caspase 8/metabolismo , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Leiomioma/genética , Leiomioma/metabolismo , Leiomioma/patologia , PPAR gama/genética , PPAR gama/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Neoplasias Uterinas/genética , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/patologia
18.
J Robot Surg ; 11(2): 139-143, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27550318

RESUMO

To describe a simple and efficient technique for suturing the vaginal cuff in robotic-assisted single-site hysterectomy using barbed suture and a straight needle. Consecutive patients undergoing robotic-assisted single-site hysterectomy from February 2014 to August 2015 at Dong San Hospital, Keimyung University were included. Surgeons used two barbed sutures in a running fashion to close the vaginal cuff. A barbed suture was exclusively used with a straightened needle in upward direction from posterior vaginal cuff to anterior vaginal cuff which played a pivotal role for closure. A total of 100 patients underwent robotic-assisted single-site hysterectomy. The total operation time was 132.5 min and vaginal cuff closure time was 12.0 min. There were no postoperative complications; vaginal cuff dehiscence, vaginal cuff infection, and vaginal bleeding that require surgical intervention or admission. The use of barbed suture with straightened needle to close the vaginal cuff in robotic-assisted single-site hysterectomy is easy to perform and demonstrates safety and efficacy. This technique offers secure, fast, and effective incision closure.


Assuntos
Histerectomia Vaginal/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Técnicas de Sutura , Vagina/cirurgia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Duração da Cirurgia
19.
Oncol Lett ; 13(4): 2817-2822, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28454472

RESUMO

The aim of the present study was to evaluate the in vitro effect of a heat shock protein (Hsp)90 inhibitor, SY-016, on the paclitaxel (PTX)-resistant human ovarian cancer cell line OVCAR-3PTX, and explore its mechanism of apoptosis. In the present study, SY-016 was used in combination with PTX to determine its effect on the cell proliferation and apoptosis of OVCAR-3PTX cells. The drug-resistant tumor cells were established in vitro by stepwise sequential exposure to increasing concentrations of PTX. The cell viability and cell cycle distribution were measured by MTT assay and flow cytometric analysis, respectively. The induction of apoptosis was measured by caspase-3 activity, DNA fragmentation and western blot analyses. The cell viability significantly decreased following treatment with PTX and SY-016 as compared with either drug alone. The DNA fragmentation assay revealed an induction of apoptosis. The results from the flow cytometric analysis revealed an increase in the percentage of cells in the G2/M phase. Downregulation of B-cell lymphoma (Bcl)-2, X-linked inhibitor of apoptosis protein, survivin, Akt, nuclear factor-κB and cyclin-dependent kinase 4, as well as upregulation of Bcl-2-associated X protein, were observed. SY-016 may contribute to the induction of apoptosis in OVCAR-3PTX cells. These results suggest that SY-016 in combination with PTX may be a beneficial chemotherapeutic strategy, particularly in patients with tumors refractory to PTX.

20.
Obstet Gynecol Sci ; 60(6): 549-557, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29184863

RESUMO

OBJECTIVE: The aim of our study is to compare the overall survival (OS), progression-free survival (PFS), and treatment-related morbidities between primary concurrent chemoradiation therapy (CCRT) vs. radical hysterectomy (RH) with or without tailored adjuvant therapy in patients with stages IB2 and IIA cervical cancer. METHODS: This was a retrospective study of 113 patients with IB2 or IIA cervical cancer treated with either primary CCRT (n=49) or RH (n=64) with or without tailored adjuvant therapy between 2002 and 2011 at Keimyung University Dongsan Medical Center. Patients in RH group was divided into those undergoing surgery alone (n=26) and those undergoing surgery with adjuvant therapy (n=38). RESULTS: The median follow up period was 66 months. The 5-year OS by treatment modality was 88.7% for the 64 patients in the RH group and 72.8% for 49 patients in the CCRT group (P=0.044). The 5-year PFS was 82.3% and 65.6% after RH group and CCRT group (P=0.048), respectively. Grade 3-4 complication was less frequent after RH alone (7.7%) than RH with adjuvant therapy (34.2%) or CCRT group (28.6%) (P=0.047). CONCLUSION: The RH group seems to be superior to the CCRT group in oncologic outcomes. However, considering the selection bias including tumor size, lymph node meta, and parametrial invasion in pretreatment magnetic resonance imaging, both treatment modalities are reasonable and feasible in cervical cancer IB2 and IIA. It is important to choose the appropriate treatment modality considering the age and general condition of the patient. Randomized controlled study is needed to confirm the result of our study and determine the optimal treatment.

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