Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 541
Filtrar
1.
Ann Surg Oncol ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34855064

RESUMO

BACKGROUND: Transient receptor potential vanilloid 2 (TRPV2) is a highly Ca2+-permeable ion channel that is involved in a number of cellular processes. It is expressed in various human cancers; however, the role of TRPV2 in gastric cancer (GC) remains poorly understood. METHODS: TRPV2 gene expression was knocked down in GC cell lines by small-interfering RNA (siRNA), and the biological roles of TRPV2 in the proliferation, migration, and invasion of GC cells were then investigated. The gene expression profile of GC was elucidated using a microarray analysis. TRPV2 expression in tumor tissue sections was analyzed by immunohistochemistry. RESULTS: The migration and invasion abilities of GC cells were inhibited by the knockdown of TRPV2. Moreover, the microarray assay revealed that TRPV2 was associated with the transforming growth factor (TGF)-ß signaling pathway. Immunohistochemical staining showed that the strong expression of TRPV2 correlated with lymphatic invasion, venous invasion, pathological T (pT), pathological N (pN), and a poor prognosis in GC patients. CONCLUSIONS: TRPV2 appeared to promote tumor migration and invasion via the TGF-ß signaling pathway, and the strong expression of TRPV2 was associated with a worse prognosis in GC patients.

2.
Surg Today ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34817683

RESUMO

PURPOSE: Recent studies have highlighted the importance of understanding trends in blood glucose levels. We examined the differences in blood glucose fluctuations according to the reconstruction method used after distal gastrectomy (DG) in patients with non-diabetic gastric cancer (GC). METHODS: Sixty-one patients who underwent DG followed by either Billroth 1 (B1) or Roux-en-Y (R-Y) reconstruction were enrolled in this study. We used flash continuous glucose monitoring (CGM), a new technique for assessing glycemic control, to document the post-gastrectomy glycemic profile. Immediately before discharge, a CGM sensor was placed subcutaneously to evaluate blood glucose trends for 2 weeks. RESULTS: The coefficient of variation of glucose levels was significantly higher in the Roux-en-Y (R-Y) group than in the Billroth I (B-I) group (p = 0.0260). The time below range (TBR, glucose levels of < 70 mg/dL) was also significantly higher in the R-Y group (p = 0.0115). Logistic regression analysis revealed that preoperative casual glucose levels of < 100 mg/dL and R-Y reconstruction were independently correlated with risk factors for a postoperative nocturnal TBR of > 30% (p = 0.006 and 0.042, respectively). CONCLUSION: Our findings provide new insights into the post-DG reconstruction method selected for patients with non-diabetic gastric cancer by assessing postoperative blood glucose fluctuations using flash CGM.

3.
Am J Cancer Res ; 11(10): 4947-4955, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765302

RESUMO

Preoperative Prognostic Nutritional Index (PNI) could be a crucial factor for the prognosis of colorectal cancer (CRC). However, the clinical impact of postoperative PNI is still unclear, and there have been no reports on the significance of postoperative PNI in patients undergoing adjuvant chemotherapy (AC). We retrospectively analysed 227 consecutive patients who underwent AC after radical surgery for high-risk stage II or stage III CRC. PNI value was calculated before radical surgery and before the introduction of AC. In our study, patients with a low PNI value before surgery showed significantly poorer long-term outcomes than those with a high PNI value. Next, we divided the patients into four groups: patients with a high PNI value before surgery and remained after surgery (Group High-High), a high PNI value before surgery but decreased after surgery (Group High-Low), a low PNI value before surgery but recovered after surgery (Group Low-High), and a low PNI value but did not recover after surgery (Group Low-Low). Although the patients in Group Low-Low showed significantly poorer long-term outcomes than those in Group High-High, the prognosis of patients in Group Low-High was the same as that of patients in Group High-High. In addition, in patients with recurrence after AC, those with a high PNI value at the time of recurrence showed a significantly better survival after recurrence than patients with a low PNI value. Postoperative PNI value could be a prognostic biomarker for CRC patients undergoing AC. Even though the PNI value was low before the surgery, recovery of PNI value by the introduction of AC could improve the prognosis of CRC patients.

4.
Am J Cancer Res ; 11(10): 5038-5044, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765310

RESUMO

Postoperative complications contribute to recurrences and poor long-term outcomes for gastric cancer patients, especially among the elderly. However, the prognostic effect of postoperative complications on non-cancer-related death in elderly patients with gastric cancer has not been reported. Two hundred and twenty elderly (> 75 years of age) patients with stage I gastric cancer were retrospectively identified from consecutive admissions between 1995 and 2020. Non-cancer-related death following gastrectomy occurred in 13.6% (30/220) of patients. Non-cancer-related death was associated with respiratory disease in 46.7% (14/30) of cases. Although there was no association with any preoperative comorbidities, postoperative complications [P < 0.001, HR 4.16 (95% CI: 1.91-9.02)] and open gastrectomy [P=0.002, HR 3.87 (95% CI: 1.54-9.66)] were independently associated with a poorer prognosis for non-cancer-related death. Poor nutritional status [P=0.028, OR 4.25 (95% CI: 1.17-15.4)] was an independent risk factor for postoperative complications. Postoperative complications shortened life expectancy from 8.8 years to 6.1 years. Specifically, postoperative complications shortened life expectancy from 6.7 years to 3.9 years in elderly patients over 80 years of age. Postoperative complications and open gastrectomy affected the incidence of non-cancer-related death among elderly patients with gastric cancer, primarily attributed to respiratory disease. Efforts should be made to perform minimally invasive surgery, improve preoperative nutrition, and avoid postoperative complications.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34729630

RESUMO

PURPOSE: Although a central venous catheter (CVC) is often needed perioperatively for intraoperative and nutritional management of esophageal cancer (EC), the catheter placement impacts the risk of venous thrombosis. We examined the risks of thrombus formation by catheter type, placement, and duration. METHODS: In total, 226 patients with EC were enrolled in this retrospective study. Patients were classified into one of three groups: those with a conventional CVC (cCVC), a peripherally inserted central catheter (PICC), or an antithrombogenic agent-coated PICC (secPICC). The thrombus formation and clinicopathological features were examined. RESULTS: The frequency of all types of thrombosis was significantly lower in the secPICC group (p < 0.01). Although deep vein thrombosis was frequent in the cCVC group, catheter thrombosis was frequent in the PICC group. In a univariate analysis in patients with the PICC and secPICC groups, less thrombus formation was observed in the secPICC (p = 0.01), short placement time (p = 0.02), and right-sided placement (p < 0.01). Furthermore, a multivariate analysis revealed that secPICC (p = 0.049) and right-sided placement (p = 0.04) significantly reduced rates of thrombus formation. CONCLUSION: In patients with EC, secPICC and right-sided placement reduce perioperative venous thrombus formation.

6.
J Gastrointest Surg ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725783

RESUMO

BACKGROUND: Malnutrition leads to accelerated tumor progression through the suppression of tumor immunity. The present study examined the significance of the preoperative prognostic nutritional index (PNI) for predicting postoperative survival outcomes in gastric cancer (GC). METHODS: A total of 447 patients who underwent curative gastrectomy for GC were included in the present study. PNI was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte counts (per mm3). The prognostic impact of preoperative PNI was examined using two multivariate analysis models. RESULTS: The optimal cutoff value of preoperative PNI for predicting overall survival (OS) was 48 based on a receiver operating characteristic curve. The 5-year OS rate was 59.5% in the PNI<48 group and 91.3% in the PNI≥48 group (p<0.001). In the first multivariate survival analysis where all explanatory variables were composed of preoperative factors alone, a PNI<48 (hazard ratio [HR] 3.33; 95% confidence interval [CI] 2.01-5.56, p<0.001), upper-third GC and cT2-T4 were identified as independent indicators of a poor OS. In the second survival analysis where explanatory variables were composed of preoperative, intraoperative, and pathological factors, a PNI<48 (HR 2.80; 95% CI 1.65-4.78, p<0.001), hypertension, open gastrectomy, intraoperative blood loss≥100g, pT2-T4, and pN+ were independent prognostic factors. CONCLUSION: Preoperative PNI may be a useful predictor of postoperative survival outcomes both before and immediately after surgery in GC. Appropriate perioperative interventions and the meticulous surveillance of GC relapse are necessary for patients with PNI<48.

8.
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.

9.
Oncol Rep ; 46(6)2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34713298

RESUMO

Anterior gradient 2 (AGR2) reportedly promotes tumor growth and has an unfavorable impact on survival in several cancers. However, no comprehensive functional analysis of AGR2 in esophageal squamous cell carcinoma (ESCC) has been performed. In the present study, the function and clinical significance of AGR2 were examined using ESCC cell lines and clinical samples. AGR2 was upregulated in EC tissue and ESCC cell lines. The downregulation of AGR2 suppressed cell proliferation and increased the proportion of G2/M­phase cells and phosphorylation of p53 in TP53­wild­type ESCC and osteosarcoma cells. However, these changes were not observed in TP53­mutant ESCC cells. In addition, immunohistochemistry results demonstrated that high AGR2 and low p53 expression levels in ESCC tissues were correlated with a worse prognosis. These results suggested that although AGR2 enhanced cell proliferation by inhibiting p53 phosphorylation in TP53­wild­type ESCC, the same mechanism did not regulate cell functions in TP53­mutant ESCC. Thus, AGR2 served an important role in ESCC progression and might be a useful prognostic marker in patients with TP53­wild­type ESCC.

10.
Eur J Cancer ; 157: 373-382, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34563992

RESUMO

BACKGROUND: Transarterial chemoembolisation (TACE) is a treatment option for hepatocellular carcinoma (HCC), but the optimum agent for TACE remains unclear. We compared the efficacy of TACE with cisplatin versus with epirubicin in patients with unresectable HCC. METHODS: This multicentre, randomised, phase 2/3 trial was performed at 21 hospitals in Japan. Patients with liver-confined HCC, performance status 0-2, and Child-Pugh class A/B were randomised to receive TACE with cisplatin or epirubicin. Patients were stratified in accordance with the institution, Child-Pugh class, tumour size, tumour thrombosis, α-fetoprotein and prior treatment. The primary end-point was overall survival in the intention-to-treat population. Tumour response was evaluated in accordance with the Response evaluation criteria in solid tumours criteria. FINDINGS: Between 2008 and 2012, 455 patients were randomly assigned to undergo TACE with cisplatin (n = 228) or epirubicin (n = 227). Eleven patients were ineligible, and 444 patients were included in the full analysis. Twelve patients not receiving TACE were excluded, and 432 patients were included in the safety analysis set. In phase 2, disease control rates in cisplatin (91·7%) and epirubicin (91·8%) groups exceeded the predefined threshold of 70%, and the study proceeded to phase 3. After a median follow-up of 32·7 months (IQR = 15·3-49·3), median overall survival periods were 2·93 years (95% CI 2·60-3·79) and 2·74 years (95%CI 2·26-3·21), respectively (hazard ratio 0·90 [95% CI 0·71-1·15], p = 0·22). Median times to treatment failure were 1·38 and 1·46 years (hazard ratio 1·09 [95% CI 0·88-1·35], p = 0·88), response rates were 65·3% and 60·6% (p = 0·31), and serious adverse event rates were 49·8% and 48·3% (p = 0·56), respectively. No treatment-related deaths occurred in either group. INTERPRETATION: In our phase 2/3 randomised trial, cisplatin is not significantly superior to epirubicin in TACE for patients with HCC.

11.
Sci Rep ; 11(1): 17946, 2021 09 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.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/enzimologia , Corantes Fluorescentes/metabolismo , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/enzimologia , Imagem Óptica/métodos , beta-Galactosidase/metabolismo , Idoso , Animais , Carcinoma Hepatocelular/patologia , Modelos Animais de Doenças , Feminino , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Sensibilidade e Especificidade
12.
J Cancer ; 12(19): 5960-5966, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34476010

RESUMO

Background: Adjuvant chemotherapy (AC) following curative gastrectomy for stage II/III gastric cancer (GC) is recommended in Japan. However, for various reasons, patients cannot always start AC at the appropriate time. This study was designed to investigate the effect of the postoperative interval until adjuvant chemotherapy (PIAC) and cumulative S-1 dose on prognosis. Methods: Between 2008 and 2014, consecutive 81 GC patients who underwent postoperative S-1 monotherapy were enrolled in this study. Results: Postoperative complications of Clavien-Dindo grade II or higher and postoperative peak C-reactive protein of 8.1 mg/dl or higher were significantly associated with delayed AC. The cut-off value of PIAC selected to most effectively stratify prognosis was 7 weeks. For relapse-free survival (RFS), patients with PIAC ≥ 7 weeks had an insignificantly poorer prognosis than those with PIAC < 7 weeks. A multivariate analysis showed that PIAC ≥ 7 weeks [p = 0.024; hazard ratio (HR) 2.45] and the cumulative S-1 dose/body surface area (BSA) ≥ 12,000 mg/m2 [p = 0.004; HR 3.27] were independent prognostic factors. In patients with the cumulative S-1 dose/BSA ≥ 12,000 mg/m2, there were no prognostic differences between patients with and without PIAC ≥ 7 weeks. Conclusions: Seven weeks after surgery could be a limit indicator starting AC. A cumulative S-1 dose/BSA of more than 12,000 mg/m2 might be a key dose for diminishing the poor prognostic effects of delaying AC.

13.
Int J Mol Sci ; 22(18)2021 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-34576284

RESUMO

5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence is widely used for the intraoperative detection of malignant tumors. However, the fluorescence emission profiles of the accompanying necrotic regions of these tumors have yet to be determined. To address this, we performed fluorescence and high-performance liquid chromatography (HPLC) analyses of necrotic tissues of squamous cancer after 5-ALA administration. In resected human lymph nodes of metastatic squamous cell carcinoma, we found a fluorescence peak at approximately 620 nm in necrotic lesions, which was distinct from the PpIX fluorescence peak at 635 nm for viable cancer lesions. Necrotic lesions obtained from a subcutaneous xenograft model of human B88 oral squamous cancer also emitted the characteristic fluorescence peak at 620 nm after light irradiation: the fluorescence intensity ratio (620 nm/635 nm) increased with the energy of the irradiation light. HPLC analysis revealed a high content ratio of uroporphyrin I (UPI)/total porphyrins in the necrotic cores of murine tumors, indicating that UPI is responsible for the 620 nm peak. UPI accumulation in necrotic tissues after 5-ALA administration was possibly due to the failure of the heme biosynthetic pathway. Taken together, fluorescence imaging of UPI after 5-ALA administration may be applicable for the evaluation of tumor necrosis.


Assuntos
Ácido Aminolevulínico/administração & dosagem , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Uroporfirinas/metabolismo , Idoso , Ácido Aminolevulínico/uso terapêutico , Animais , Carcinoma de Células Escamosas/tratamento farmacológico , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Biológicos , Necrose , Espectrometria de Fluorescência
14.
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.

15.
Am J Cancer Res ; 11(7): 3628-3644, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354864

RESUMO

Evaluation of the functional aspects if the tumor immune microenvironment (TIME), such as the recently introduced cytolytic activity score (CYT) index have been under the spotlight in cancer research; however, clinical relevance of immune cell killing activity in breast cancer has never been analyzed in large patient cohorts. We hypothesized that CYT reflects the immune activity of TIME and can predict patient survival. A total of 7533 breast cancer patients were analyzed as both discovery and validation cohorts. We found that high CYT was associated with advanced histological grade and triple-negative breast cancer (TNBC). High CYT in tumors was significantly associated with better survival in TNBC, but unexpectedly, not in other breast cancer subtypes. High CYT TNBC included both favorable immune-related, as well as unfavorable (suppressive) inflammation-related gene sets, and characterized by high infiltration with T cells and B cells. High CYT TNBC was associated with high homologous recombination deficiency and low somatic copy number alteration score and less mutant allele tumor heterogeneity, but not with tumor mutation burden (TMB). Although CYT was not associated with pathological complete response after neoadjuvant chemotherapy, it was significantly associated with high expression of multiple immune checkpoint molecules. In conclusion, CYT of TNBC is associated with enhanced anti-cancer immunity, less intra-tumoral heterogeneity, and with better survival.

16.
J Anus Rectum Colon ; 5(3): 319-326, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395946

RESUMO

Objectives: Recent findings suggest that the combination of mechanical bowel preparation (MBP) and preoperative oral antibiotics (OA) decreases the risk of surgical site infection (SSI) in colorectal surgery; however, this remains controversial. The present study examined the efficacy of OA plus MBP in laparoscopic colorectal cancer (CRC) surgery using propensity score matching (PSM). Methods: A total of 1080 patients with CRC underwent MBP followed by laparoscopic surgery between 2007 and 2019. OA was administered to all patients with CRC who underwent colectomy from 2018. PSM was performed to compare the effects of OA plus MBP (OA) versus MBP only (non-OA) on the rate of superficial SSI. Results: Overall, 128 patients received OA. Significant differences were observed in age, the American Society of Anesthesiologists performance status (ASA-PS), liver disease, and preoperative serum albumin (Alb) between the OA and non-OA groups. The enrolled patients were matched using PSM into two groups based on the following factors: sex, age, body mass index, ASA-PS, diabetes mellitus, liver disease, Alb, and tumor location, which resulted in the disappearance of significant differences. A univariate analysis showed that blood loss of 100 g or more, non-OA, and preoperative chemotherapy or radiation correlated with SSI (p = 0.021, 0.010, 0.038). A multivariate analysis of these three variables identified blood loss of 100 g or more and non-OA as independent risk factors for SSI (hazard ratio (HR): 3.238, p = 0.031; HR: 2.547, p = 0.033). Conclusions: The present study revealed that OA plus MBP markedly reduced SSI rate. OA with MBP needs to be adopted in laparoscopic CRC surgery.

17.
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.

18.
Anticancer Res ; 41(7): 3657-3665, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230164

RESUMO

BACKGROUND/AIM: We attempted to stratify prognosis using the modified Journal of Hepato-Biliary-Pancreatic Sciences (mJHBPS) nomogram upon identification of colorectal liver metastasis (CRLM) and to investigate which strategy is better, surgery first (SF) or chemotherapy first (CF), in each risk group. PATIENTS AND METHODS: A total of 137 patients with CRLM who underwent resection of the primary tumor were included. Patients with brain, bone, or perihilar lymph node metastases were excluded. Patients were scored using the mJHBPS nomogram upon identification of CRLM. Prognosis was investigated using event-free survival (EFS) and overall survival (OS). RESULTS: The nomogram allowed stratification of patients using EFS and OS: low-risk (0-6 score, n=38), medium-risk (7-11 score, n=42), and high-risk (12≥ score, n=57). In the low-risk group, the EFS and OS of the CF group were significantly poorer than those of the SF group (p=0.019 and p=0.014, respectively). CF was an independent prognostic factor for both EFS and OS. CONCLUSION: The mJHBPS nomogram can stratify CRLM patients with sufficient differences in EFS and OS. SF was recommended for patients in the low-risk group.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Fígado/patologia , Idoso , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Nomogramas , Pâncreas/patologia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
19.
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
20.
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.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...