Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 35
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Anticancer Res ; 41(8): 4047-4052, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281873

RESUMO

BACKGROUND/AIM: Tropomyosin-related kinase B (TrkB)/brain-derived neurotrophic factor (BDNF) signaling plays a role in inducing malignant phenotypes in several aggressive types of cancers. To create a conclusive therapy targeting TrkB/BDNF signaling in solid refractory cancers, the biological significance of TrkB/BDNF signaling was analyzed in pancreatic ductal adenocarcinoma (PDAC) cells. MATERIALS AND METHODS: Three PDAC cell lines were used as target cells to investigate proliferation and invasiveness. Small interfering RNA (siRNA) and the TrkB tyrosine kinase inhibitor k252a were used as TrkB/BDNF signaling inhibitors. RESULTS: All PDAC cell lines expressed TrkB and BDNF. When TrkB and BDNF were inhibited by siRNA or k252a, the invasiveness of PANC-1 and SUIT-2 cells significantly decreased. When TrkB was inhibited by siRNA or k252a, proliferation was significantly inhibited in PDAC cells. CONCLUSION: TrkB/BDNF signaling may be a new therapeutic target for PDAC. Therapies targeting TrkB/BDNF signaling may be a conclusive cancer therapy for refractory solid cancer.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Glicoproteínas de Membrana/metabolismo , Neoplasias Pancreáticas/metabolismo , Receptor trkB/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Carbazóis/farmacologia , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Alcaloides Indólicos/farmacologia , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/genética , Neoplasias Pancreáticas/patologia , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , RNA Interferente Pequeno/genética , Receptor trkB/antagonistas & inibidores , Receptor trkB/genética , Transdução de Sinais/efeitos dos fármacos
2.
Artigo em Inglês | MEDLINE | ID: mdl-34117530

RESUMO

PURPOSE: T1 gastric cancer (GC) with seven or more metastatic lymph nodes is extremely rare, and very few clinical studies have been conducted to evaluate the clinicopathological features of their recurrence. METHODS: We retrospectively analyzed the outcomes of T1 GC and T2-4 GC patients who had multiple nodal metastases after radical surgery from 2006 to 2020. Propensity score matching was performed to compare the two groups of patients. RESULTS: After propensity score matching, 18 of 22 patients in the T1 group and 36 of 144 patients in the T2-4 group were selected. Recurrence occurred in six patients (33.3%) in the T1 group. In the T1 group, the most common site of initial recurrence was bone (15.0%). The prevalence of bone recurrence was significantly higher in the T1 group than in the T2-4 group (P = 0.02). The median interval time between radical surgery and bone recurrence was 24 months, and the median survival time after bone recurrence was 14 months. CONCLUSION: Bone recurrence was more frequently identified as an initial recurrence site in T1 GC cases with multiple metastases after radical surgery compared with that in T2-4 GC cases. Careful attention should be paid to postoperative bone recurrence in the long-term postoperative course of these patients.

3.
J Exp Clin Cancer Res ; 40(1): 133, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858491

RESUMO

BACKGROUND: Pancreatic stellate cells (PSCs) occupy the majority of the pancreatic cancer microenvironment, contributing to aggressive behavior of pancreatic cancer cells (PCCs). Recently, anti-fibrotic agents have proven to be an effective strategy against cancer, but clinical trials have shown little efficacy, and the driving mechanism remains unknown. N-acetyl-cysteine (NAC) is often used for pulmonary cystic fibrosis. Pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, was habitually used for type II diabetes, but recently reported to inhibit metastasis of PCCs. However, few studies have focused on the effects of these two agents on cancer-stromal interactions. METHOD: We evaluated the expression of α-smooth muscle actin (α-SMA) and the number of lipid droplets in PSCs cultured with or without NAC. We also evaluated changes in invasiveness, viability, and oxidative level in PSCs and PCCs after NAC treatment. Using an indirect co-culture system, we investigated changes in viability, invasiveness, and migration of PSCs and PCCs. Combined treatment effects of NAC and Pioglitazone were evaluated in PSCs and PCCs. In vivo, we co-transplanted KPC-derived organoids and PSCs to evaluate the effects of NAC and Pioglitazone's combination therapy on subcutaneous tumor formation and splenic xenografted mouse models. RESULTS: In vitro, NAC inhibited the viability, invasiveness, and migration of PSCs at a low concentration, but not those of PCCs. NAC treatment significantly reduced oxidative stress level and expression of α-SMA, collagen type I in PSCs, which apparently present a quiescent-like state with a high number of lipid droplets. Co-cultured PSCs and PCCs mutually promoted the viability, invasiveness, and migration of each other. However, these promotion effects were attenuated by NAC treatment. Pioglitazone maintained the NAC-induced quiescent-like state of PSCs, which were reactivated by PCC-supernatant, and enhanced chemosensitivity of PCCs. In vivo, NAC and Pioglitazone's combination suppressed tumor growth and liver metastasis with fewer stromal components and oxidative stress level. CONCLUSION: NAC suppressed activated PSCs and attenuated cancer-stromal interactions. NAC induces quiescent-like PSCs that were maintained in this state by pioglitazone treatment.

4.
Surg Endosc ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616731

RESUMO

BACKGROUND: The addition of lateral pelvic lymph node dissection (LPLND) in rectal cancer surgery has been reported to increase the incidence of post-operative urinary retention. Here, we assessed the predictive factors and long-term outcomes of urinary retention following laparoscopic LPLND (L-LPLND) with total mesorectal excision (TME) for advanced lower rectal cancer. METHODS: This retrospective single-institutional study reviewed post-operative urinary retention in 71 patients with lower rectal cancer who underwent L-LPLND with TME. Patients with preoperative urinary dysfunction or who underwent unilateral LPLND were excluded. Detailed information regarding patient clinicopathologic characteristics, post-void residual urine volume, and the presence or absence of urinary retention over time was collected from clinical and histopathologic reports and telephone surveys. Urinary retention was defined as residual urine > 100 mL and the need for further treatment. RESULTS: Post-operative urinary retention was observed in 25/71 patients (35.2%). Multivariate analysis revealed that blood loss ≥ 400 mL [odds ratio (OR) 4.52; 95% confidence interval (CI) 1.24-16.43; p = 0.018] and inferior vesical artery (IVA) resection (OR 8.28; 95% CI 2.46-27.81; p < 0.001) were independently correlated with the incidence of urinary retention. Furthermore, bilateral IVA resection caused urinary retention in more patients than unilateral IVA resection (88.9% vs 47.1%, respectively; p = 0.049). Although urinary retention associated with unilateral IVA resection improved relatively quickly, urinary retention associated with bilateral IVA resection tended to persist over 1 year. CONCLUSION: We identified the predictive factors of urinary retention following L-LPLND with TME, including increased blood loss (≥ 400 mL) and IVA resection. Urinary retention associated with unilateral IVA resection improved relatively quickly. L-LPLND with unilateral IVA resection is a feasible and safe procedure to improve oncological curability. However, if oncological curability is guaranteed, bilateral IVA resection should be avoided to prevent irreversible urinary retention.

5.
Asian J Endosc Surg ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33145998

RESUMO

INTRODUCTION: The proportion of patients aged 75 years and over who undergo minimally invasive surgery for gastric cancer is increasing. However, the safety and feasibility of laparoscopic gastrectomy (LG) in this age group is controversial. This study aimed to evaluate whether LG is safe and effective in patients aged 75 years and over. METHODS: The study included 728 patients with early and advanced gastric cancer who underwent curative LG between 2009 and 2017; 166 of these patients (22.8%) were aged 75 or over. All surgeries were performed laparoscopically. Selected clinical factors were compared between the 166 patients aged 75 years and over and the 562 patients aged under 75 years. RESULTS: There were significant differences in presence of comorbidity, respiratory function and American Society of Anesthesiologists physical status scores between the older and younger groups. The older patients more frequently developed complications than the younger ones, particularly postoperative pneumonia. According to multivariate analyses of all participants, age, chronic obstructive pulmonary disease (COPD), and D2 lymphadenectomy were independent risk factors for postoperative pneumonia. Advanced stage and D2 lymphadenectomy were independent risk factors in the older group, whereas only COPD was an independent risk factor in the younger group. CONCLUSIONS: LG for gastric cancer can be safely performed in patients aged over 75 years with an acceptable complication rate. However, the present data suggest that care should be taken in selecting LG with D2 lymphadenectomy to treat advanced cancer in these patients because the risk of postoperative complications, especially postoperative pneumonia, increases.

6.
Surg Today ; 50(10): 1290-1296, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32358629

RESUMO

PURPOSE: There is no definite evidence of the feasibility and safety of laparoscopic distal gastrectomy (LDG) for patients who have undergone incomplete endoscopic resection (ER). We investigated the influence of ER prior to LDG by a propensity score matching analysis. METHODS: We retrospectively analyzed the outcomes of gastric cancer patients who underwent LDG with or without prior ER from 2000 to 2014. Propensity score matching was performed to compare the two groups of patients. RESULTS: After matching, 47 patients in the ER group and 94 patients in the non-ER group were selected from a total of 365 patients. A residual tumor was observed in 10 of 47 patients (21.3%). The mean number of dissected lymph nodes in the non-ER group (39.4 ± 14.5) was higher than that in the ER group (31.7 ± 13.5) (P = 0.003). However, other perioperative data, such as the operation time and blood loss volume were similar. The complication rate of the ER group (17.0%) and the non-ER group (9.6%) did not differ to a statistically significant extent (P = 0.2). Among these patients, 6 died during the 5-year follow-up period, but no patients showed signs of recurrence. CONCLUSION: ER prior to surgical resection showed no significant influence on postoperative complications or mortality. LDG can be safely performed to achieve radical resection after incomplete ER.


Assuntos
Endoscopia Gastrointestinal/métodos , Gastrectomia/métodos , Laparoscopia/métodos , Reoperação , Neoplasias Gástricas/cirurgia , Idoso , Estudos de Viabilidade , Feminino , Humanos , Excisão de Linfonodo/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Segurança , Neoplasias Gástricas/mortalidade , Falha de Tratamento , Resultado do Tratamento
7.
Surg Case Rep ; 6(1): 92, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32377803

RESUMO

BACKGROUND: The standard surgical method for symptomatic submucosal tumors (SMTs) or tumors with unclear biological behavior is enucleation. Minimally invasive approaches are usually considered appropriate for surgical enucleation; thus, thoracoscopic and laparoscopic enucleation is performed widely and safely. However, it is sometimes difficult to enucleate large and complicated esophageal tumors using thoracoscopic surgery, and even if rare, there is the risk of requiring thoracotomy or esophagectomy. In the present case, we enucleated a large and complicated leiomyoma safely using a new combined method with endoscopic and thoracoscopic procedures. CASE PRESENTATION: A 42-year-old woman presented to our hospital for a detailed examination of an abnormal finding in her health check-up chest X-ray images. She complained of upper abdominal pain after eating, and computed tomography revealed an esophageal tumor measuring 60 mm in length surrounding her lower thoracic esophagus. Esophagogastroduodenoscopy revealed a huge complicated SMT at the esophagogastric junction. Cytological examination with endoscopic ultrasound-guided fine-needle aspiration showed that the tumor was a leiomyoma. To enucleate this large and complicated esophageal SMT safely and without damaging the esophageal mucosa, we performed endoscopic and thoracoscopic procedures. We created a submucosal tunnel, endoscopically, and then performed thoracoscopic surgery to enucleate the tumor completely from the esophageal muscularis. Using these combined procedures, we were able to easily mobilize even a complicated tumor of this size from the mucosa and completed the surgery thoracoscopically without difficulty. As a result, the tumor was dissected safely with a minimal defect in the muscularis and without damaging the mucosa. Finally, we closed the defect in the esophageal muscularis with continuous sutures, thoracoscopically, and closed the entry of the submucosal tunnel using clips, endoscopically. CONCLUSIONS: Using these combined procedures, we safely enucleated a huge complicated esophageal SMT. The increased mobility of the tumor after creating the submucosal tunnel contributed to the minimal defect in the muscular layer and prevented injury to the esophageal mucosa, possibly leading to fewer postoperative complications such as esophageal stenosis and local infection.

8.
Oncoimmunology ; 9(1): 1724763, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117589

RESUMO

Tertiary lymphoid structures (TLSs), clusters of immune cells found around tumor tissue, have been shown to be associated with anti-tumor immunity, but the cellular composition within each TLS and whether the cellular composition of a TLS affects a patient's prognosis are poorly understood. In the present study, each TLS was categorized according to its cellular composition determined by a system of multiplex immunohistochemical staining and quantitative analysis, and the correlation between the category and prognosis was examined. Sixty-seven patients with curatively resected stage II/III colorectal cancer (CRC) were enrolled. A TLS, consisting of germinal center B cells, follicular dendritic cells, T helper (Th) cells, B cells, cytotoxic T cells, and macrophages, was confirmed in the tumor tissue of 58 patients (87%). The densities of Th cells and macrophages were significantly higher in relapsed patients than in not-relapsed patients (p = .043 and p = .0076). A higher ratio of Th cells was the most significant independent risk factor for disease relapse on multivariate analysis. The subset increasing in Th cells was GATA3+ Th2. A total of 353 TLSs was divided into five clusters according to immune cell composition. Among them, the Th-rich type TLS was significantly increased (p = .0009) in relapsed patients. These data suggest the possibility that Th cell-dominant composition might disturb the anti-tumor immune response, and the function of each TLS might differ depending on its composition.

9.
Surg Case Rep ; 6(1): 30, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32002705

RESUMO

BACKGROUND: According to the 2018 Japanese gastric cancer treatment guidelines (ver. 5), a reduced extent of lymphadenectomy (D1 or D1+) is indicated for cT1 N0 tumors that do not meet the criteria for endoscopic resection. However, early gastric cancer with multiple lymph node metastases is not unknown, and cases have been reported. We report a case of a patient with early gastric cancer and numerous nodal metastases who underwent laparoscopic proximal gastrectomy based on a preoperative diagnosis of T1 N0. CASE PRESENTATION: A 69-year-old woman underwent emergent endoscopic hemostasis for massive hematemesis of the stomach, and endoscopic examination showed ulceration with a visible vessel. Pathological biopsy examination of the ulcer identified poorly differentiated adenocarcinoma with signet ring cells. The patient was diagnosed with early gastric cancer that was not indicated for endoscopic resection because of the ulceration and histological type. Endoscopic ultrasound showed that the third layer was poorly demarcated at the ulcer scar, indicating invasion to the submucosal layer. Computed tomography did not reveal enlarged lymph nodes or distant metastasis. The preoperative diagnosis was early gastric cancer of the fundus without nodal metastasis, and laparoscopic proximal gastrectomy with D1+ lymphadenectomy was performed. The initial postoperative pathological diagnosis was intramucosal carcinoma without lymphovascular invasion; however, the presence of 26 lymph node metastases was revealed unexpectedly. Additional pathological examination of more resected specimens transected every 2-3 mm revealed that only one lesion contained a small number of cancer cells in the lymphatic duct below the muscularis mucosa. CONCLUSIONS: We report a case of early gastric cancer with 26 nodal metastases in which lymph node involvement was not identified prior to surgery. These findings indicate that the extent of lymphadenectomy and the surgical procedure should be carefully decided even in cT1 N0 early gastric cancer when several risk factors for lymph node metastasis are present.

10.
Asian J Endosc Surg ; 13(4): 582-585, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32097984

RESUMO

Recently, several scholars have demonstrated the efficacy of carbon ion radiotherapy (CIRT). To treat abdominal or pelvic tumors by CIRT, it is necessary to separate the tumor from the adjacent organs. Surgical placement of a GORE-TEX sheet as a spacer has been reported as a separation method. Usually, surgical spacer placement is done by open surgery. Here, we report a case of surgical spacer placement undertaken by a "pure" laparoscopic procedure. A 47-year-old man with recurrent sacral chordoma was referred for surgical spacer placement before CIRT. Laparoscopic dissection of the rectum and placement of a GORE-TEX sheet as a spacer were successfully performed. Surgical spacer placement by a pure laparoscopic procedure was safe and effective, and it seems to play an important part before CIRT.

11.
Int J Cancer ; 146(9): 2498-2509, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31344279

RESUMO

Oxaliplatin (l-OHP), a platinum-based drug, is a key chemotherapeutic agent for colorectal cancer (CRC), but drug resistance and toxic effects have been major limitations of its use. Synchrotron radiation X-ray fluorescence spectrometry (SR-XRF) is a rapid, nondestructive technique for monitoring the distribution of metals and trace elements in cells or tissue samples. We applied SR-XRF to visualize the distribution of platinum and other elements in 30 rectal cancer specimens resected from patients who received l-OHP-based preoperative chemotherapy and quantified platinum concentration in the tumor epithelium and stroma, respectively, using calibration curves. The platinum concentration in rectal cancer tissue ranged 2.85-11.44 ppm, and the detection limit of platinum was 1.848 ppm. In the tumor epithelium, the platinum concentration was significantly higher in areas of degeneration caused by chemotherapy than in nondegenerated area (p < 0.001). Conversely, in the tumor stroma, the platinum concentration was significantly higher in patients with limited therapeutic responses than in those with strong therapeutic responses (p < 0.001). Furthermore, multivariate analysis illustrated that higher platinum concentration in the tumor stroma was an independent predictive factor of limited histologic response (odds ratio; 19.99, 95% confidence interval; 2.04-196.37, p = 0.013). This is the first study to visualize and quantify the distribution of platinum in human cancer tissues using SR-XRF. These results suggest that SR-XRF analysis may contribute to predicting the therapeutic effect of l-OHP-based chemotherapy by quantifying the distribution of platinum.


Assuntos
Antineoplásicos/metabolismo , Oxaliplatina/metabolismo , Platina/metabolismo , Neoplasias Retais/metabolismo , Espectrometria por Raios X/métodos , Células Estromais/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Prognóstico , Neoplasias Retais/tratamento farmacológico , Estudos Retrospectivos , Células Estromais/efeitos dos fármacos , Síncrotrons
12.
J Gastroenterol Hepatol ; 35(3): 412-417, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31389626

RESUMO

BACKGROUND AND AIM: Indigo naturalis (IN) is a traditional Chinese herbal medicine reported to be effective in inducing remission in ulcerative colitis (UC). We conducted a retrospective observational study to investigate the efficacy and safety of IN for induction and maintenance therapy in patients with inflammatory bowel disease. METHODS: Data were collected from the electric medical records of patients with inflammatory bowel disease who had started IN treatment between March 2015 and April 2017 at Kyushu University Hospital. Clinical response and remission rates were assessed based on the clinical activity index determined by Rachmilewitz index or Crohn's disease (CD) activity index. Cumulative IN continuation rates were estimated using the Kaplan-Meier method. Overall adverse events (AEs) during follow-up were also analyzed. RESULTS: Seventeen UC patients and eight CD patients were enrolled. Clinical response and remission rates at week 8 were 94.1% and 88.2% in UC patients and 37.5% and 25.0% in CD patients, respectively. Clinical remission rates, as assessed through non-responders imputation analyses at weeks 52 and 104, were 76.4% and 70.4% in UC patients and 25.0% and 25.0% in CD patients, respectively. Ten patients (40%) experienced AEs during follow-up. Three patients (12%) experienced severe AEs, including acute colitis requiring hospitalization in two patients and acute colitis with intussusception requiring surgery in one patient. CONCLUSIONS: Indigo naturalis showed favorable therapeutic efficacy in UC, whereas its therapeutic efficacy in CD appeared to be modest. The risk of severe AEs should be recognized for IN treatment.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Índigo Carmim/química , Doenças Inflamatórias Intestinais/tratamento farmacológico , Fitoterapia , Adulto , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Seguimentos , Humanos , Doenças Inflamatórias Intestinais/mortalidade , Quimioterapia de Manutenção , Masculino , Indução de Remissão , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
13.
Surg Laparosc Endosc Percutan Tech ; 29(6): 493-497, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31107856

RESUMO

BACKGROUND: The combined resection of the vesical artery (VA) in laparoscopic lateral pelvic lymph node dissection (L-LPLD) was reported to facilitate the safe dissection of metastatic lymph nodes. However, whether or not the combined VA resection affects the urinary function remains controversial. PURPOSE: The purpose of the present study was to examine the risk factors for the postoperative urinary dysfunction (PUD) after L-LPLD followed by total mesorectal excision and to clarify the effects of the combined VA resection in L-LPLD on PUD. PATIENTS AND METHODS: L-LPLD was performed in 95 patients with advanced rectal cancer at Saga University Hospital and Kyushu University Hospital from January 2013 to December 2017. The risk factors for PUD after L-LPLD were investigated. RESULTS: The univariate analysis revealed that the combined resection of the inferior vesical artery (IVA) was a risk factor for PUD. To examine by the type of IVA resection, the incidence of PUD significantly increased with the bilateral IVA resection, but the unilateral IVA resection induced PUD on the same level with the preservation of IVA. CONCLUSIONS: Bilateral IVA resection in L-LPLD could increase the incidence of PUD. Thus, if possible, the preservation of the unilateral IVA through L-LPLD should be considered.


Assuntos
Artérias/cirurgia , Colectomia/métodos , Laparoscopia/métodos , Excisão de Linfonodo/métodos , Neoplasias Retais/cirurgia , Bexiga Urinária/fisiopatologia , Micção/fisiologia , Humanos , Linfonodos/patologia , Metástase Linfática , Estadiamento de Neoplasias , Pelve , Período Pós-Operatório , Neoplasias Retais/diagnóstico , Neoplasias Retais/secundário , Estudos Retrospectivos , Bexiga Urinária/irrigação sanguínea
14.
Anticancer Res ; 39(3): 1179-1184, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30842147

RESUMO

BACKGROUND/AIM: Small-cell lung cancer (SCLC) remains one of deadliest types of cancers. Cis-diamminedichloroplatinum (CDDP) is a key chemotherapeutic agent for SCLC, however, its therapeutic effect is limited. Recently, hypoxia in the cancer microenvironment has been suggested to influence the effect of cancer therapy. MATERIALS AND METHODS: Using small interfering RNA inhibition of leukocyte common antigen-related interacting protein alpha 4 (liprin-α4), and of hypoxia-inducible factor (HIF)-1α, proliferation, invasion, migration and chemosensitivity were investigated in SBC-5 SCLC cells, under normoxia and hypoxia. RESULTS: Liprin-α4 was found to contribute to proliferation, but not migration and invasion of SBC-5 cells both under normoxia and hypoxia. Inhibition of liprin-α4 increased chemosensitivity of SBC-5 cells under hypoxia. Liprin-α4 signaling occurs through mitogen-activated protein kinase pathways via activation of HIF1α expression. Inhibition of HIF1α reduced proliferation and increased chemosensitivity of SBC-5 cells under hypoxia. CONCLUSION: Liprin-α4 inhibition may enhance the effect of CDDP and liprin-α4 might be a novel therapeutic target in SCLC.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Pulmonares/terapia , RNA Interferente Pequeno/administração & dosagem , Proteínas Tirosina Fosfatases Semelhantes a Receptores/genética , Carcinoma de Pequenas Células do Pulmão/terapia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas Tirosina Fosfatases Semelhantes a Receptores/metabolismo , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/metabolismo
15.
Surg Endosc ; 33(1): 309-314, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29943055

RESUMO

BACKGROUND: Two ligation techniques can be applied in laparoscopy for left-sided colorectal cancer: (1) high-tie (HT), transection at the level of the inferior mesenteric artery (IMA); and (2) low-tie (LT), transection below the IMA, at the level of superior rectal artery (SRA), preserving the left colic artery (LCA). However, even with preoperative images, it can still be a challenge to identify these structures due to intraoperative individual conditions. In this study, we assess the use intraoperative ultrasonography (IOUS) to aid us in identifying the IMA and its branches to the SRA, LCA, and sigmoid artery. METHODS: We performed IOUS in 18 patients diagnosed with left-sided colorectal cancer. Preoperatively, a three-dimensional computed tomography (3D-CT) angiography was obtained in majority of the patients, to visualize the IMA and its branches. Two patients were contraindicated to receive a contrast study, hence, was unable to undergo 3D-CT angiography. The resected specimen was grossly examined for the study. The bifurcation types were identified and compared using different modalities: preoperative 3D-CT, IOUS, and gross examination of the resected specimen. RESULTS: The branching of the IMA revealed by IOUS was consistent to the findings preoperatively by the 3D-CT and postoperatively by the resected specimen. The IOUS result of the two patients without preoperative 3D-CT evaluation was also consistent with the post-operative bifurcation type. CONCLUSIONS: IOUS is an easy and feasible modality which aids in detecting the branching of the IMA during LT and HT ligation in laparoscopic left-sided colorectal surgery. It can serve as an adjunct modality for 3D-CT angiography and can also be considered a safe alternative option for cases wherein 3D-CT angiography is unavailable.


Assuntos
Neoplasias Colorretais/cirurgia , Cirurgia Colorretal/métodos , Laparoscopia/métodos , Ligadura/métodos , Artéria Mesentérica Inferior/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Artéria Mesentérica Inferior/cirurgia , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
16.
Arch Gerontol Geriatr ; 79: 185-191, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30269003

RESUMO

PURPOSE: To examine age-related factors influencing health-related quality of life (HR-QOL) among patients with lower rectal cancer during the 12-month period after sphincter-saving surgery (SSS). MATERIAL AND METHODS: In this 1-year longitudinal study, 137 patients (120 patients completed, and 82 aged ≥60 years) answered the European Organization for Research and Treatment of Cancer questionnaire (EORTC-C30/CR38) assessing their HR-QOL and related factors during the 12 months after SSS. RESULTS: No significant differences in HR-QOL were found before surgery. Only among those aged ≥60 years, global health status/QOL and cognitive functioning showed a significant decrease one month after surgery. At one month after SSS, the role functioning of groups <60 years old (which is negatively related to defecation problems, insomnia, and financial difficulties) was lower compared to those aged ≥60 years; and role functioning was significantly related to global health status/QOL. Six months after SSS, the global health status/QOL had recovered. In both groups, global health status/QOL was related to role and social functioning. Among participants aged <60 years, global health status/QOL was significantly related to emotional functioning, which is related to future perspective. Among participants aged ≥60 years only, global health status/QOL was significantly related to cognitive functioning; pain, financial difficulties, and defecation problems negatively influenced HR-QOL. Symptoms specific after SSS: defecation problems (in both group), micturition problems (only ≥60 years), and sexual problems (only<60 years) influenced HR-QOL. CONCLUSION: Health care providers should assess the influence of age-related factors during the early post-operative period after SSS to improve HR-QOL.


Assuntos
Nível de Saúde , Qualidade de Vida , Neoplasias Retais/cirurgia , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Japão , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
17.
Anticancer Res ; 38(8): 4543-4547, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30061220

RESUMO

BACKGROUND/AIM: Small cell lung cancer (SCLC) is still a deadly type of cancer for which there are few effective therapeutic strategies. Development of a new molecule targeting agent is urgently desired. Previously we showed that recombination signal binding protein for immunoglobulin-kappa-J region (RBPJ) and mastermind-like 3 (MAML3) are new therapeutic targets for pancreatic cancer. In the present study, we analyzed whether RBPJ/MAML3 inhibition could also be a new therapeutic strategy for SCLC. MATERIALS AND METHODS: Using silencing of RBPJ/MAML3, proliferation, invasion, migration and chemosensitivity of SBC-5 cells were investigated. RESULTS: RBPJ/MAML3 inhibition reduced Smoothened and HES1 expression, suggesting that RBPJ/MAML3 signaling was through Hedgehog and NOTCH pathways. In the analysis of cell functions, RBPJ/MAML3 inhibition significantly reduced proliferation and invasiveness via reduction of expression of matrix metalloproteinases. On the other hand, RBPJ/MAML3 inhibition also reduced chemosensitivity to cis-diamminedichlo-roplatinum and gemcitabine. CONCLUSION: These results suggest that RBPJ and MAML3 could be new therapeutic targets for SCLC, however, chemosensitivity may be reduced in combinational use with other chemo-therapeutic agents.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Nucleares/metabolismo , Carcinoma de Pequenas Células do Pulmão/metabolismo , Fatores de Transcrição/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Proteínas Hedgehog/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Metaloproteinases da Matriz/metabolismo , Invasividade Neoplásica/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Transativadores
18.
Anticancer Res ; 37(12): 6649-6654, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29187440

RESUMO

BACKGROUND/AIM: In pancreatic cancer, where the microenvironment is extremely hypoxic, analyzing signal transduction under hypoxia is thought to be significantly important. By investigating microarray analysis of pancreatic cancer cells cultured under both normoxia and hypoxia, we found that the expression of leukocyte common antigen-related (LAR)-interacting protein (liprin)-α4 was extremely increased under hypoxia compared to under normoxia. MATERIALS AND METHODS: In the present study, the biological significance of liprin-α4 in pancreatic cancer was investigated and whether liprin-α4 has potential as a therapeutic target for pancreatic cancer was estimated. RESULTS: Suppression of liprin-α4 reduced proliferation of pancreatic cancer cells both in vitro and in vivo. Inhibition of liprin-α4 also reduced invasiveness through the suppression of endothelial-mesenchymal transition. Stimulation by liprin-α4 was through phosphoinositide 3-kinase and mitogen-activated protein kinase signaling pathways. CONCLUSION: Liprin-α4 plays a pivotal role in inducing malignant phenotypes such as increased proliferation and invasion in pancreatic cancer, and that liprin-α4 could be a new effective therapeutic target for pancreatic cancer.


Assuntos
Carcinoma Ductal Pancreático/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/genética , Proteínas Tirosina Fosfatases Semelhantes a Receptores/genética , Animais , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Hipóxia Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Humanos , Hipóxia , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Interferência de RNA , Transdução de Sinais , Transplante Heterólogo
19.
Anticancer Res ; 37(9): 4987-4992, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28870922

RESUMO

BACKGROUND/AIM: Previously we have shown that tropomyosin-related kinase B (TRKB) and Hedgehog (Hh) signalling pathways induce malignant phenotypes in many cancer types. However, results from small cell lung cancer (SCLC) clinical trials using TRK and Hh inhibitors have been disappointing. One reason for this may be the existence of crosstalk between TRKB and Hh signalling pathways. In this study, we detected negative crosstalk between the TRKB and Hh-GLI1 signalling pathways. MATERIALS AND METHODS: The human small cell lung carcinoma cell line, SBC-5, was used. Using small interfering RNA to inhibit TRKB and Hh signalling, whether TRKB and Hh signaling contribute to proliferation and invasiveness in SBC-5 cells were investigated. RESULTS: TRKB expression in GLI1 siRNA-transfected SBC-5 cells was higher than that of control cells. GLI1-knockdown alone did not affect invasiveness of SBC-5 cells. However, combined knockdown of TRKB and GLI1 significantly decreased invasiveness. Moreover, combined TRKB and GLI1 knockdown inhibited proliferation and migration to a greater extent than when either was inhibited alone. CONCLUSION: These results suggest that Hh inhibition increases TrkB expression to counter tumor suppression in SBC-5 cells. The combined use of TRKB and Hh inhibitors may, therefore, be useful for the treatment of refractory SCLC.


Assuntos
Movimento Celular , Proliferação de Células , Proteínas Hedgehog/antagonistas & inibidores , Neoplasias Pulmonares/patologia , Glicoproteínas de Membrana/antagonistas & inibidores , Receptor trkB/antagonistas & inibidores , Carcinoma de Pequenas Células do Pulmão/patologia , Proteína GLI1 em Dedos de Zinco/antagonistas & inibidores , Apoptose , Proteínas Hedgehog/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , RNA Interferente Pequeno/genética , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/metabolismo , Células Tumorais Cultivadas
20.
Asian J Endosc Surg ; 10(2): 223-226, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28547931

RESUMO

Retrorectal tumors (RT) are uncommon and usually managed by open surgical excision. Laparoscopic excision for RT has been reported in only a small number of papers. We aimed to assess the laparoscopic approach for RT and to discuss the factors that made this procedure difficult. We performed laparoscopic excision using a five-trocar technique for neurogenic RT in three patients. Tumors were successfully excised laparoscopically in two patients. However, the third patient required open conversion because the tumor was strongly adhered to the sacrum and could not be mobilized by dissection, resulting in poor visualization of the dissected site. Laparoscopic excision for RT provides excellent intraoperative visualization and good cosmesis in selected patients, but firm adherence to the sacrum may cause difficulty with this procedure.


Assuntos
Conversão para Cirurgia Aberta/métodos , Ganglioneuroma/cirurgia , Laparoscopia/métodos , Neurilemoma/cirurgia , Neoplasias Retais/cirurgia , Adulto , Idoso , Feminino , Ganglioneuroma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neurilemoma/patologia , Neoplasias Retais/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...