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1.
Asian J Endosc Surg ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34595840

RESUMO

INTRODUCTION: Seprafilm® has been used to prevent postoperative adhesion. However, it is challenging to insert and apply Seprafilm during laparoscopic surgery because of its fragility and sticky nature caused by moisture. Some studies have reported how to apply Seprafilm into a surgical site during laparoscopic surgery; however, some required special equipment with additional costs, and some were technically difficult to use. Herein, we introduced our simple method for applying Seprafilm during laparoscopic surgery. MATERIAL AND SURGICAL TECHNIQUE: Seprafilm was cut into three equal rectangle-shaped pieces and left to absorb moisture for a few minutes. All three pieces of Seprafilm were placed on the gauze, and the gauze was folded in half and grasped by forceps. The gauze with Seprafilm was inserted through a 12-mm trocar and placed at the surgical site close to the target place. The gauze functioned as a working station and prevented Seprafilm from directly attaching to the surrounding tissue, which allowed the surgeons to handle it with ease. The gauze was used to press Seprafilm onto the target area and could be easily removed through a 12-mm trocar. Through this method, Seprafilm was successfully applied in all cases and the average time of applying one sheet was 100 seconds. There was no small bowel obstruction within 30 days after surgery. DISCUSSION: This method neither requires special training nor special equipment only used for Seprafilm. Moreover, it can be easily introduced to every surgeon for the application of Seprafilm during laparoscopic surgery.

2.
Sci Rep ; 11(1): 17946, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504174

RESUMO

Fluorescence imaging of tumours facilitates rapid intraoperative diagnosis. Thus far, a promising activatable fluorescence probe for hepatocellular carcinoma (HCC) has not been developed. Herein, the utility of the fluorescence imaging of HCC using a ß-galactosidase (ß-Gal)-activatable fluorescence probe SPiDER-ßGal was examined. ß-Gal activity was measured in cryopreserved tissues from 68 patients. Live cell imaging of HCC cell lines and imaging of tumour-bearing model mice were performed using SPiDER-ßGal. Furthermore, fluorescence imaging was performed in 27 freshly resected human HCC specimens. In cryopreserved samples, ß-Gal activity was significantly higher in tumour tissues than in non-tumour tissues. Fluorescence was observed in HCC cell lines. In mouse models, tumours displayed stronger fluorescence than normal liver tissue. In freshly resected specimens, fluorescence intensity in the tumour was significantly higher than that in non-tumour liver specimens as early as 2 min after spraying. Receiver operating characteristic curves were generated to determine the diagnostic value of SPiDER-ßGal 10 min after its spraying; an area under the curve of 0.864, sensitivity of 85.2%, and specificity of 74.1% were observed for SPiDER-ßGal. SPiDER-ßGal is useful for the rapid fluorescence imaging of HCC. Fluorescence imaging guided by SPiDER-ßGal would help surgeons detect tumours rapidly and achieve complete liver resection.

3.
ACS Synth Biol ; 10(9): 2308-2317, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34351735

RESUMO

The development of microbes for conducting bioprocessing via synthetic biology involves design-build-test-learn (DBTL) cycles. To aid the designing step, we developed a computational technique that suggests next genetic modifications on the basis of relatedness to the user's design history of genetic modifications accumulated through former DBTL cycles conducted by the user. This technique, which comprehensively retrieves well-known designs related to the history, involves searching text for previous literature and then mining genes that frequently co-occur in the literature with those modified genes. We further developed a domain-specific lexical model that weights literature that is more related to the domain of metabolic engineering to emphasize genes modified for bioprocessing. Our technique made a suggestion by using a history of creating a Corynebacterium glutamicum strain producing shikimic acid that had 18 genetic modifications. Inspired by the suggestion, eight genes were considered by biologists for further modification, and modifying four of these genes proved experimentally efficient in increasing the production of shikimic acid. These results indicated that our proposed technique successfully utilized the former cycles to suggest relevant designs that biologists considered worth testing. Comprehensive retrieval of well-tested designs will help less-experienced researchers overcome the entry barrier as well as inspire experienced researchers to formulate design concepts that have been overlooked or suspended. This technique will aid DBTL cycles by feeding histories back to the next genetic design, thereby complementing the designing step.

4.
Esophagus ; 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34365578

RESUMO

BACKGROUND: In transmediastinal esophagectomy (TME) with equivalent lymphadenectomy to transthoracic procedure, an understanding of surgical anatomy in the deep mediastinum near the aortic arch or tracheal bifurcation is essential for the safe procedure. The present study aimed to evaluate the bronchial arteries (BAs) with preoperative 3D-CT in TME. METHODS: Seventy-nine patients with thoracic esophageal cancer undergoing TME were examined by preoperative 3D-CT to evaluate BA variations in the number, branching pattern, and mediastinal course. For the right BAs (RBAs) crossing the esophagus, the mediastinal courses in transcervical view were classified in relation to the esophagus and tracheobronchi and compared with surgical findings. RESULTS: A total of 107 RBAs (1.35/person) were confirmed on preoperative 3D-CT. Of these, 61 (57.0%) crossed the esophagus dorsally (type Ed), and the remaining 46 (43.0%) crossed the esophagus ventrally (type Ev). During the left transcervical procedure, all type Ed RBAs were identified and mostly preserved (57/61, 93.4%) whereas most type Ev RBAs were identified (39/46, 84.8%), but more than half were sacrificed (26/46, 56.5%) for lymphadenectomy. The blood loss during the transcervical procedure was 17.0 ± 55.8 ml. The total number of dissected mediastinal lymph nodes was 23.7 ± 9.3. There were no significant complications related to extensive lymphadenectomy. CONCLUSIONS: Preoperative 3D-CT evaluation is useful to understand the mediastinal courses of BAs specific to the transcervical approach, which may allow BAs to be handled more carefully according to the type during surgery, contributing to a safer procedure in the deep mediastinum.

5.
Int J Oncol ; 59(4)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34414448

RESUMO

The targeting of membrane proteins that are activated in cancer stem cells (CSCs) represents one of the key recent strategies in cancer therapy. The present study analyzed ion channel expression profiles and functions in pancreatic CSCs (PCSCs). Cells strongly expressing aldehyde dehydrogenase 1 family member A1 (ALDH1A1) were isolated from the human pancreatic PK59 cell line using fluorescence­activated cell sorting, and PCSCs were identified based on tumorsphere formation. Microarray analysis was performed to investigate the gene expression profiles in PCSCs. ALDH1A1 messenger RNA levels were higher in PCSCs compared with non­PCSCs. PCSCs were resistant to 5­fluorouracil and capable of redifferentiation. The results of the microarray analysis revealed that gene expression related to ion channels, including voltage­gated potassium channels (Kv), was upregulated in PCSCs compared with non­PCSCs. 4­Aminopyridine (4­AP), a potent Kv inhibitor, exhibited greater cytotoxicity in PCSCs compared with non­PCSCs. In a xenograft model in nude mice, tumor volumes were significantly lower in mice inoculated with PK59 cells pre­treated with 4­AP compared with those in mice injected with non­treated cells. The present results identified a role of Kv in the persistence of PCSCs and suggested that the Kv inhibitor 4­AP may have potential as a therapeutic agent for pancreatic carcinoma.

6.
J Surg Oncol ; 124(5): 791-800, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34196000

RESUMO

BACKGROUND: Oligometastasis, the presence of a small number of resectable metastatic tumors, usually has favorable outcomes. Here we examined whether the novel oligometastatic score (OLGS), which divides the number of colorectal liver metastases (CRLMs) by the time from colorectal resection to liver recurrence, better predicts CRLM patient survival than the commonly used clinical risk score. METHODS: A total of 143 patients who underwent curative hepatectomy for CRLMs between 2007 and 2018 were analyzed. We investigated their clinical characteristics and outcomes using OLGS. RESULTS: Of the 143 CRLM patients, 70 had synchronous CRLMs and 73 had metachronous CRLMs. Patients with metachronous CRLMs were divided into OLGS-low (n = 59) and OLGS-high (n = 14) subgroups. The 5-year overall survival (OS) rates after hepatectomy differed significantly between the subgroups (p < .001). In the multivariate Cox model, a high OLGS was an independent predictor of 5-year OS (p < .001), and the hazard ratio (HR) of the OLGS-high group (HR = 7.171) was higher than that of the high clinical risk score group (HR = 4.337). CONCLUSION: The OLGS, a simple and handy scoring system, better predicts the 5-year OS of patients with CRLMs after hepatectomy and warrants prospective validation.


Assuntos
Neoplasias Colorretais/mortalidade , Hepatectomia/mortalidade , Neoplasias Hepáticas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Software , Taxa de Sobrevida
7.
Gastric Cancer ; 24(6): 1278-1292, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34251542

RESUMO

BACKGROUND: The Na+/K+-ATPase alpha1 subunit (ATP1A1) is a critical component of Na+/K+-ATPase (NKA), a membrane pump that maintains a low intracellular Na+/K+ ratio and retains cellular volume and osmolarity. ATP1A1 was recently implicated in tumor behavior. Therefore, the present study investigated the role of ATP1A1 in patients with gastric cancer (GC). METHODS: Knockdown experiments were conducted on human GC cell lines using ATP1A1 siRNA, and its effects on proliferation, the cell cycle, apoptosis, and cellular movement were examined. Gene expression profiling was performed by a microarray analysis. Primary tumor samples from 192 GC patients who underwent gastrectomy were subjected to an immunohistochemical analysis. RESULTS: High ATP1A1 expression levels were observed in NUGC4 and MKN74 cells. Cell proliferation was suppressed and apoptosis was induced by the siRNA-induced knockdown of ATP1A1. The microarray analysis showed that knockdown of ATP1A1 leads to the up-regulated expression of genes involved in the interferon (IFN) signaling pathway, such as STAT1, STAT2, IRF1, and IRF9. Furthermore, the depletion of ATP1A1 altered the phosphorylation of the MAPK pathway. The immunohistochemical analysis revealed that the expression of ATP1A1 was associated with the histological type, venous invasion, and the pathological T stage. Furthermore, the prognostic analysis showed a relationship between high ATP1A1 expression levels and poor postoperative survival. CONCLUSIONS: ATP1A1 appears to regulate tumor progression by altering IFN signaling, and high ATP1A1 expression levels were associated with poor postoperative survival in GC patients. The present results provide novel insights into the function of ATP1A1 as a mediator and/or biomarker of GC.

8.
Photodiagnosis Photodyn Ther ; 35: 102420, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34242818

RESUMO

BACKGROUND: Accurate diagnosis of peritoneal metastasis in gastric cancer (GC) is important to determine the appropriate treatment. This study aimed to examine whether matrix metalloprotease-14 (MMP-14) was a candidate enzyme in fluorescence imaging for the diagnosis of peritoneal metastasis in GC. METHODS: GC and normal peritoneal (NP) tissues from 96 and 20 patients, respectively were evaluated for MMP-14 expression. Live cell imaging of GC cell lines (NUGC4, MKN45, MKN74, HGC-27, and Kato-III) was performed using the MMP-14-activatable fluorescence probe; BODIPY-MMP. Furthermore, the overall survival (OS) was calculated in all patients (n = 96). RESULTS: MMP-14 expression was significantly higher in GC tissues (median: 3.57 ng/mg protein; range:0.64-24.4 ng/mg protein) than in NP tissues (median: 1.34 ng/mg protein; median: 0.53-3.09 ng/mg protein) (P < 0.01). Receiver operating characteristic curves showed that the area under the curve, sensitivity, and specificity were 0.907, 84.4%, and 90.0%, respectively. In live cell imaging using the BODIPY-MMP, fluorescence was observed in five GC cell lines. In the analysis of OS, the high expression of the MMP-14 group had a significantly poorer OS rate than the low expression of the MMP-14 group (P = 0.02). In the multivariate analyses, MMP-14 expression was an independent risk factor for OS (hazard ratio: 2.33; 95 % confidence interval: 1.05-5.45; P = 0.04). CONCLUSION: MMP-14 is a promising enzyme in intraoperative fluorescence imaging for peritoneal metastasis in GC, especially in patients with poor prognosis.


Assuntos
Neoplasias Peritoneais , Fotoquimioterapia , Neoplasias Gástricas , Biomarcadores Tumorais , Humanos , Metaloproteinase 14 da Matriz , Neoplasias Peritoneais/diagnóstico por imagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Prognóstico , Neoplasias Gástricas/diagnóstico por imagem
9.
Surg Today ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34269851

RESUMO

PURPOSE: The significance of the duration of the recurrence-free survival after curative resection for colorectal cancer remains unclear. The purpose was to reveal the association between time to recurrence after surgery and the survival after recurrence. METHODS: Patients with stage II and III colorectal cancer who underwent curative resection between 2007 and 2015 were retrospectively reviewed (n = 645). Patients with recurrence after surgery (n = 133) were divided into 2 groups: early recurrence (within 13 months after surgery, n = 63) and late recurrence (more than 13 months after surgery, n = 70). The overall survival after recurrence and clinicopathological features were compared between early recurrence, late recurrence, and without recurrence groups. RESULTS: The overall survival after recurrence was significantly shorter in patients with early recurrence occurring at less than 13 months (hazard ratio: 1.70, p = 0.03). A high preoperative CA19-9 level (odds ratio [OR]: 2.38, p = 0.03), venous invasion (OR: 2.26, p = 0.03), and the absence of adjuvant chemotherapy (OR: 2.08, p = 0.04) were independently correlated with early recurrence. CONCLUSION: Early recurrence was associated with a poor prognosis after recurrence. Venous invasion correlated with early recurrence. Adjuvant chemotherapy may reduce the risk of early recurrence. These results indicate the importance of prudent surveillance and the aggressive application of adjuvant chemotherapy.

10.
World J Surg Oncol ; 19(1): 173, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118953

RESUMO

BACKGROUND: Since inflammation and the immune system contribute to the development and progression of malignancies, parameters that reflect a host's immune-inflammatory status may be useful prognostic indicators of gastric cancer (GC). The present study examined the clinical significance of a preoperative systemic immune-inflammation index (SII) for predicting postoperative survival outcomes in GC. METHODS: A total of 447 patients who underwent curative gastrectomy for GC were included in the present study. SII was calculated as platelet count × neutrophil count/lymphocyte count. The prognostic impact of preoperative SII was examined using univariate and multivariate analyses. RESULTS: Preoperative SII ranged between 105 and 4455 (median 474), and the optimal cutoff value for predicting overall survival (OS) was 395 based on a receiver operating characteristic curve. The 5-year OS rate of the SII ≥ 395 group was 80.0%, which was significantly worse than that (92.7%) of the SII < 395 group (p < 0.001). The multivariate analysis identified SII ≥ 395 (hazard ratio [HR] 2.95; 95% confidence interval [CI] 1.49-6.39; p = 0.001), heart disease (HR 2.14, 95% CI 1.07-4.07), C-reactive protein ≥ 0.5 (HR 2.45, 95% CI 1.15-4.94), pT4 (HR 4.46, 95% CI 2.44-8.14), and pN+ (HR 4.02, 95% CI 2.10-7.93) as independent predictors of worse OS. Peritoneal recurrence was more frequent in the high SII group than in the low SII group (p = 0.028). CONCLUSION: Preoperative SII may be a useful predictor of postoperative survival outcomes in GC. The meticulous surveillance of GC relapse, particularly peritoneal dissemination, is necessary for patients with SII ≥ 395 even after curative gastrectomy.


Assuntos
Neoplasias Gástricas , Humanos , Inflamação , Recidiva Local de Neoplasia , Neutrófilos , Prognóstico , Neoplasias Gástricas/cirurgia
11.
In Vivo ; 35(4): 2289-2296, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182508

RESUMO

BACKGROUND/AIM: The self-expanding metallic stent (SEMS) has recently been used for obstructive colorectal cancer (OCRC), and reports of its use are increasing. However, the long-term results of OCRC after using SEMS remain unclear. This study investigated the characteristics of SEMS compared to trans-anal tube (TAT) and clarified the long-term results and efficacy of SEMS for OCRC. PATIENTS AND METHODS: We analyzed 48 patients who required SEMS or TAT for emergent decompression of OCRC and underwent resection for OCRC between 2007 and 2019. The perioperative factors and long-term results in the two groups were evaluated. RESULTS: Patients with OCRC were divided into the SEMS (n=23) and the TAT group (n=25). No significant differences were seen in background factors, complications and the 5-year overall survival after surgery (p=0.3500) between the two groups. The clinical success of decompression (p=0.0072), oral intake (p<0.0001) and change in serum albumin (p<0.0001) from decompression to surgery were significantly better in the SEMS compares to the TAT group. CONCLUSION: The long-term outcomes in the SEMS group were not significantly different than in the TAT group, and nutritional status was better in patients with SEMS, suggesting that SEMS is very effective and may be the first-line treatment of OCRC.


Assuntos
Neoplasias Colorretais , Obstrução Intestinal , Stents Metálicos Autoexpansíveis , Neoplasias Colorretais/complicações , Neoplasias Colorretais/terapia , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Estudos Retrospectivos , Stents Metálicos Autoexpansíveis/efeitos adversos , Stents , Resultado do Tratamento
12.
Sci Rep ; 11(1): 10664, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34021168

RESUMO

Diagnosis of peritoneal metastasis in gastric cancer (GC) is essential for determining appropriate therapeutic strategies and avoiding non-essential laparotomy or gastrectomy. Recently, a variety of activatable fluorescence probes that can detect enzyme activities have been developed for cancer imaging. The aim of this study was to identify the key enzyme involved in peritoneal metastasis in GC. The enzymatic activity of gamma-glutamyl transpeptidase, dipeptidyl peptidase IV, and ß-galactosidase (ß-Gal) was assessed in lysates prepared from preserved human GC (n = 89) and normal peritoneal (NP; n = 20) samples. ß-Gal activity was significantly higher in the human GC samples than in NP samples, whereas no differences were observed in the activities of the other enzymes. Therefore, we used SPiDER-ßGal, a fluorescent probe that can be activated by ß-Gal, for imaging GC cell lines, peritoneal metastasis in a mouse model, and fresh human resected GC samples (n = 13). All cell lines showed fluorescence after applying SPiDER-ßGal, and metastatic nodules in the mice gradually developed high fluorescence that could be visualized with SPiDER-ßGal. The human GC samples showed significantly higher fluorescence than NP samples. ß-Gal is a useful target enzyme for fluorescence imaging of peritoneal metastasis in GC.

13.
Anticancer Res ; 41(5): 2441-2449, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952469

RESUMO

BACKGROUND/AIM: The regulation of gene expression by miRNAs plays an important role in cancer progression. Here, we investigated the role of miR-3663-3p in gastric cancer. PATIENTS AND METHODS: The relationship between miR-3663-3p expression, clinicopathological features and prognosis were retrospectively analyzed in 80 gastric cancer patients. RESULTS: miR-3663-3p expression was significantly lower in gastric cancer tissue than adjacent non-cancerous tissue (p=0.002). Recurrence free survival was significantly lower in patients with low miR-3663-3p expression (p=0.016). Low miR-3663-3p expression was also an independent predictive factor for recurrence (p=0.029). Overexpression of miR-3663-3p in gastric cancer cell lines significantly suppressed cell proliferation, migration/invasion, and induced G0/G1 arrest (p<0.01). Furthermore, overexpression of miR-3663-3p decreased Cyclin D1 mRNA and protein, and reduced the phosphorylation of Retinoblastoma (Rb) protein. CONCLUSION: miR-3663-3p is a clinically useful predictor of gastric cancer recurrence. It exhibits tumor suppressive features through limited entry into the cell cycle in a Cyclin D1-Rb dependent manner.


Assuntos
Ciclina D1/genética , MicroRNAs/genética , Proteínas de Ligação a Retinoblastoma/genética , Neoplasias Gástricas/genética , Ubiquitina-Proteína Ligases/genética , Idoso , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , Neoplasias Gástricas/patologia
14.
Anticancer Res ; 41(5): 2533-2542, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952481

RESUMO

BACKGROUND/AIM: This study aimed to investigate the impact of the inferior mesenteric artery (IMA) lymph node metastasis [IMALN (+)] on prognosis in left-sided colorectal cancer (LCRC). PATIENTS AND METHODS: A total of 285 patients with stage III LCRC and 118 patients with stage IV LCRC who underwent resection of primary tumor between 2005 and 2016 were included. RESULTS: IMALN (+) patients (n=10) had worse overall survival (OS) than patients without IMA lymph node metastasis [IMALN (-); n=275] in stage III LCRC (p=0.007). Multivariate analysis revealed that IMALN (+) was a prognostic factor in stage III LCRC (OS, HR=3.09, p=0.043). Conversely, there was no difference between the OS of IMALN (+) and stage IV LCRC with distant lymph node metastasis only [stage IV LCRC (LYM); n=21; p=0.434]. CONCLUSION: The prognosis of IMALN (+) was worse than that of IMALN (-); it was similar to that of stage IV LCRC (LYM).


Assuntos
Neoplasias Colorretais/diagnóstico , Metástase Linfática/diagnóstico , Artéria Mesentérica Inferior/patologia , Prognóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Masculino , Artéria Mesentérica Inferior/diagnóstico por imagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias
15.
Gastric Cancer ; 24(5): 1063-1075, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33864161

RESUMO

BACKGROUND: Leucin-rich repeat containing protein A (LRRC8A), a component of the volume-regulated anion channel (VRAC), is activated by cell swelling and mediates regulatory volume decrease. We previously reported the expression of and important roles for several ion transporters in various gastrointestinal cancers, which have potential as novel targets for cancer treatment; however, the significance of LRRC8A in gastric cancer (GC) remains unclear. MATERIALS AND METHODS: Knockdown experiments were performed by transfecting human GC cell lines with LRRC8A siRNA. Gene expression was then assessed using microarray analysis. Samples from 132 patients with GC were subjected to immunohistochemistry (IHC) for LRRC8A, and its relationships with clinicopathological factors and prognosis were examined. RESULTS: The knockdown of LRRC8A suppressed the proliferation and movement of cells and enhanced apoptosis. The results of the microarray analysis showed the up- or down-regulated expression of genes related to the p53 signaling pathway (JNK, p53, p21, Bcl-2, and FAS) in LRRC8A-knockdown cells. IHC revealed a correlation between the expression of LRRC8A and the pT status (p = 0.015), and multivariate analysis identified the strong expression of LRRC8A as an independent prognostic factor for 5-year survival in GC patients (p = 0.0231). CONCLUSIONS: The present results indicate that LRRC8A functions as a mediator of and/or biomarker for GC.

16.
Ann Surg Oncol ; 28(11): 6424-6436, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33710504

RESUMO

BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-dependent chloride (Cl-) anion conducting channel, and its role in esophageal squamous cell carcinoma (ESCC) was examined in the present study. METHODS: Overexpression experiments were conducted on human ESCC cell lines following the transfection of a CFTR plasmid, and changes in cell proliferation, the cell cycle, apoptosis, migration, and invasion were assessed. A microarray analysis was performed to examine gene expression profiles. Fifty-three primary tumor samples collected from ESCC patients during esophagectomy were subjected to an immunohistochemical analysis. RESULTS: Transfection of the CFTR plasmid into the ESCC KYSE 170 and KYSE 70 cell lines suppressed cell proliferation, migration, and invasion and induced apoptosis. The microarray analysis showed the up-regulated expression of genes involved in the p38 signaling pathway in CFTR plasmid-transfected KYSE 170 cells. Immunohistochemical staining revealed a relationship between the CFTR expression pattern at the invasive front and the pN category. A relationship was also observed between the weak expression of CFTR at the invasive front and a shorter postoperative survival in a prognostic analysis. CONCLUSIONS: The overexpression of CFTR in ESCC activated the p38 signaling pathway and was associated with a good patient prognosis. These results indicate the potential of CFTR as a mediator of and/or a biomarker for ESCC.


Assuntos
Carcinoma de Células Escamosas , Regulador de Condutância Transmembrana em Fibrose Cística , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Humanos
17.
World J Surg ; 45(5): 1561-1568, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33538878

RESUMO

BACKGROUND: A survival paradox between T4N0 (stage IIB/C) and T3N1 (stage IIIB) colon cancer has been rarely reported. The indication and regimen of adjuvant chemotherapy are separately described in the guidelines. This study aimed to elucidate the prognostic factors and investigate proper adjuvant treatment in colon cancer patients at these stages. METHODS: Patients who underwent R0 resection for pathological T4N0 (n = 49), T1-2N1 (n = 31), or T3N1 (n = 82) colon cancer between 2008 and 2016 at a single institute were retrospectively reviewed. The clinicopathological characteristics, status of adjuvant chemotherapy, and oncologic outcomes of patients with T4N0 tumors were compared with those of patients with T1-2N1 and T3N1 tumors. RESULTS: The biological characteristics of T4N0 tumors were more aggressive compared with the characteristics of T1-2N1 tumors and were similar to those of T3N1 tumors. The usage rate of oxaliplatin as an adjuvant chemotherapy was significantly lower in T4N0 patients than in T1-2N1 and T3N1 patients. The rate of local recurrence was the highest in patients with T4N0 tumors, and the survival outcomes for patients with T4N0 tumors were significantly worse compared with those of T1-2N1 patients and were similar to those of T3N1 patients. A multivariate analysis revealed that lack of adequate use of oxaliplatin for adjuvant chemotherapy was the only prognostic factor. CONCLUSIONS: T4N0 colon cancer had similar oncological characteristics and survival outcomes to T3N1 colon cancer. Systematic adjuvant chemotherapy, including oxaliplatin, should be incorporated into the therapy for T4N0 patients as well as T3N1 patients.


Assuntos
Neoplasias do Colo , Recidiva Local de Neoplasia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Fluoruracila/uso terapêutico , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos
18.
Ann Surg Oncol ; 28(9): 5384-5397, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33565032

RESUMO

BACKGROUND: Chloride channel 2 (CLCN2) was recently shown to affect tumor behavior. The present study examined the functions of CLCN2 in the regulation of genes that play a role in tumor progression, as well as its clinicopathological significance in esophageal squamous cell carcinoma (ESCC). METHODS: Knockdown experiments were conducted using CLCN2-small-interfering RNA, and changes in proliferation, survival, and cellular movement in human ESCC cell lines were investigated. A microarray analysis of gene expression profiles in CLCN2-depleted ESCC cells was conducted. Fifty-four primary ESCC samples were examined by immunohistochemistry (IHC). RESULTS: The strong expression of CLCN2 was detected in TE5 and KYSE70 cells. Downregulated expression of CLCN2 enhanced proliferation and decreased apoptosis, whereas its upregulation inhibited proliferation and increased apoptosis. The effects of lubiprostone, a CLCN2 activator, were also investigated. In lubiprostone-treated cells, proliferation was inhibited and apoptosis was increased. The microarray analysis demonstrated that interferon (IFN) signaling-related genes were downregulated in CLCN2-depleted cells. IHC showed the presence of CLCN2 in the cytoplasm and cell membranes of ESCC cells. The prognostic analysis revealed a relationship between weak CLCN2 expression and shorter overall survival. CONCLUSIONS: The present results indicate that tumor progression is regulated by CLCN2 through its effects on IFN signaling. Furthermore, weak CLCN2 expression was associated with poorer outcomes in ESCC patients. The present study will contribute to a clearer understanding of the role of CLCN2 as a mediator of ESCC, as well as its use as a biomarker for this cancer.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias de Cabeça e Pescoço , Apoptose , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Canais de Cloreto/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Prognóstico
19.
Esophagus ; 18(3): 461-467, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33599862

RESUMO

BACKGROUND: The aim of the present study was to evaluate subcarinal lymph node dissection in transmediastinal radical esophagectomy and subcarinal lymph node metastasis in patients with esophageal cancer. METHODS: Three hundred and twenty-three patients with primary esophageal cancer who underwent transmediastinal or transthoracic esophagectomy with radical two- or three-field lymph node dissection were retrospectively investigated. The clinicopathological characteristics of patients with subcarinal lymph node metastasis were analyzed in detail. RESULTS: The median of dissected subcarinal lymph nodes in transmediastinal and transthoracic esophagectomy groups was 6 and 7, respectively, and there was no significant difference between the two groups (p = 0.12). Of all patients, 26 (8.0%) were pathologically diagnosed as positive for subcarinal lymph node metastasis, whereas only 7 (26.9%) of those with metastasis were preoperatively diagnosed as positive. In addition, all patients with subcarinal lymph node metastasis had other non-subcarinal lymph node metastasis. By univariate analysis, subcarinal lymph node metastasis was found in larger (≥ 30 mm) and deeper (T3/T4a) primary lesions (p = 0.02 and 0.02, respectively), but it was not found in 49 patients with the primary lesion located in the upper thoracic esophagus. CONCLUSIONS: Subcarinal lymph nodes can be dissected in transmediastinal esophagectomy, almost equivalent to transthoracic esophagectomy. The tumor size, depth, and location may be predictive factors for subcarinal lymph node metastasis.

20.
Ann Surg Oncol ; 28(9): 5400-5411, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33566246

RESUMO

BACKGROUND: The membrane transporters activated in cancer stem cells (CSCs) are the target of novel cancer therapies for gastric cancer. The present study investigated ion channel expression profiles in gastric CSCs (GCSCs). METHODS: Cells strongly expressing CD44 were separated from MKN74 cells, a human gastric cancer cell line, by fluorescence-activated cell sorting (FACS), and GCSCs were identified based on tumorsphere formation. Gene expression profiles in GCSCs were examined by a microarray analysis. RESULTS: Among MKN74 cells, CD44 messenger RNA levels were higher in CSCs than in non-CSCs. These CSCs also exhibited resistance to cisplatin. The microarray analysis revealed that the expression of several genes related to voltage-gated Ca2+ channels (VGCCs), including CACNA2D1 and CACNB4, was upregulated. The cytotoxicities of the CACNA2D1 inhibitor amlodipine and the CACNB4 inhibitor verapamil were greater at lower concentrations in CSCs than in non-CSCs, and markedly reduced tumorsphere numbers. Tumor volumes were significantly smaller in a xenograft nude mouse model treated with amlodipine or verapamil in combination with cisplatin than in that treated with cisplatin alone. CONCLUSIONS: The present results indicate that VGCCs play a role in maintaining CSCs, and demonstrated the potential of their specific inhibitors, amlodipine and verapamil, as targeted therapeutic agents against gastric cancer.


Assuntos
Anlodipino , Neoplasias Gástricas , Anlodipino/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Receptores de Hialuronatos/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Verapamil/farmacologia
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