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1.
World J Surg ; 48(1): 151-162, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38686759

RESUMO

OBJECTS: This study was designed to explore the risk factors of lymph node metastasis (LNM) in distal gastric cancer with early stage, and to provide reference for the choice of treatment protocols. METHODS: In this retrospective observational study, 824 early distal gastric cancer (EDGC) cases who treated at our unit from 2010 to 2020 were selected as research objects. Subsequently, univariate and multivariate logistic regression analyses were conducted to investigate the associations between LNM and clinicopathological features. RESULTS: Of these 824 EDGC cases, 140 (17.0%) developed LNM, including 72 N1 stage and 68 N2-3 stage LNM. Multivariate logistic regression analysis identified the tumor diameter ≥1.75 cm (odds ratio (OR) = 2.361, p < 0.001), tumor location (OR = 1.552, p = 0.046), histological classification (p = 0.004), tumor infiltration depth (OR = 2.154, p = 0.001), and vascular infiltration (OR = 4.354, p < 0.001) as independent predictors for LNM. Logistic regression analyses based on 756 N0-1 LNM cases identified the smoking history (OR = 0.507, p = 0.043), tumor diameter ≥1.75 cm (OR = 2.265, p = 0.010), tumor location (OR = 1.834, p = 0.036), histological classification (p = 0.018), tumor infiltration depth (OR = 1.939, p = 0.034), and vascular infiltration (OR = 3.225, p < 0.001) as independent predictors for N1 LNM. Moreover, preoperative hypoalbuminemia (OR = 7.087, p = 0.015), significant preoperative weight loss (OR = 2.724, p = 0.023), tumor diameter ≥1.75 cm (OR = 5.484, p = 0.001), multiple tumors (OR = 9.986, p = 0.038), histological classification (p = 0.029), and vascular infiltration (OR = 33.704, p < 0.001) were proved to be associated with LNM for T1a tumors. CONCLUSIONS: The tumor diameter, location and infiltration depth, histological classification, and vascular infiltration were expected to be used as predictors of LNM in EDGC, and preoperative hypoalbuminemia, significant weight loss, tumor diameter and number, histological classification, and vascular infiltration were associated with LNM for T1a tumors.


Assuntos
Metástase Linfática , Estadiamento de Neoplasias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Masculino , Feminino , Estudos Retrospectivos , Fatores de Risco , Pessoa de Meia-Idade , Metástase Linfática/patologia , Idoso , Gastrectomia , Adulto
2.
Biochem Biophys Res Commun ; 670: 63-72, 2023 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-37276792

RESUMO

Gastric cancer (GC) is a highly prevalent and aggressive malignancy with a poor prognosis. Recent evidence suggested that metallothionein 1 M (MT1M) may play a critical role in cancer development, progression, and drug resistance; however, its role in GC remains largely unknown. In this study, we investigated the expression and function of MT1M in GC both in vitro and in vivo. We found that MT1M expression was significantly downregulated in GC tissues and cell lines. Decreased expression of MT1M was associated with worse clinical prognosis, particularly in patients treated with 5-fluorouracil. Low expression of MT1M was indicative of poor overall survival (OS, HR 0.56 [95% CI 0.37-0.84], P < 0.005), first progression survival (FP, HR 0.54 [95% CI 0.36-0.79], P < 0.005), and post-progression survival (PPS, HR 0.65 [95% CI 0.45-0.94], P < 0.05). We also demonstrated that overexpression of MT1M inhibited cell proliferation and induced apoptosis in GC cells and in tumor xenografts, and it improved chemosensitivity to 5-fluorouracil. Furthermore, we found that MT1M overexpression could inhibit stem cell characteristics by targeting GLI1 and affecting GLI1 ubiquitination. Collectively, these findings indicated that MT1M may act as a tumor suppressor in GC and could serve as a potential therapeutic target to attenuate stemness and chemotherapy resistance of GC.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Proteínas Hedgehog/metabolismo , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismo , Linhagem Celular Tumoral , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Metalotioneína/genética
3.
Br J Cancer ; 126(7): 1100-1107, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35027671

RESUMO

BACKGROUND: This systematic review and meta-analysis examined associations between serum levels of haemoglobin A1c (HbA1c) and glucose and the risk of gastric cancer. METHODS: MEDLINE, Embase, and Cochrane Library were searched for studies examining associations between serum levels of HbA1c or glucose and the risk of gastric cancer. Inclusion of studies, quality assessment, and data extraction were conducted independently by two authors. Pooled hazard ratios (HR) with 95% confidence intervals (CI) were synthesised using random-effects models. Cochran's Q test and I2 statistic were used to assess heterogeneity. RESULTS: Among 3473 identified studies, 12 were included. Of these, 5 studies examined HbA1c levels and 7 studies examined serum glucose levels. Serum HbA1c levels >6% were associated with an increased risk of gastric cancer (HR 1.36, 95% CI 1.06-1.74). When compared with the lowest glucose categories, the highest glucose categories were associated with a borderline increased risk of gastric cancer (HR 1.11, 95% CI 0.98-1.26). In subgroup analyses, studies that adjusted for Helicobacter pylori infection indicated stronger associations between elevated HbA1c levels and gastric cancer (HR 2.08, 95% CI 1.46-2.98) than those without such adjustment (HR 1.10, 95% CI 0.91-1.32). CONCLUSIONS: Long-standing poor glycaemic control may increase the risk of gastric cancer. REGISTRATION NUMBER: PROSPERO CRD42020157453.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Glucose , Hemoglobinas Glicadas , Infecções por Helicobacter/complicações , Humanos , Neoplasias Gástricas/epidemiologia
4.
Biochem Biophys Res Commun ; 627: 91-96, 2022 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-36030657

RESUMO

Gastric cancer is a one of the most common malignant tumors with poor prognosis worldwide. Leucine-rich G-protein-coupled receptor 5 (LGR5) is determined as a modulator of Wnt signaling cascade and R-spondins are a family of secretory agonists in the Wnt signaling and act as ligands to interact with LGR5. However, the function of Rspondin-1 in GC remains obscure. Here, we identified the effect of Rspondin-1 on GC progression. Rspondin-1 and LGR5 were upregulated in clinical gastric cancer tissues. CCK-8 assay revealed that the viability of GC cells was reduced by Rspondin-1 depletion and enhanced by Rspondin-1 overexpression. The depletion of Rspondin-1 decreased while the overexpression of Rspondin-1 increased the numbers of colony formation and Edu-positive GC cells. The depletion of Rspondin-1 attenuated the invasion and migration ability of GC cells. Moreover, sphere formation assays revealed that the knockdown of Rspondin-1 reduced the stemness of GC cells. The expression of cancer stem cell markers, including Nanog, OCT3/4, and SOX2 were suppressed by Rspondin-1 depletion in GC cells. Rspondin-1 induced tumor growth of gastric cancer cells in vivo. Mechanically, the cell viability and invasion suppressed by the depletion of Rspondin-1 in GC cells were rescued by LGR5 overexpression. Besides, the overexpression of LGR5 reversed Rspondin-1 knockdown-inhibited Nanog and OCT3/4 expression. Consequently, we concluded that Rspondin-1 contributes to the progression and stemness of gastric cancer by LGR5.


Assuntos
Neoplasias Gástricas , Trombospondinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Células-Tronco Neoplásicas/patologia , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Neoplasias Gástricas/patologia , Via de Sinalização Wnt
5.
Small ; 18(18): e2200364, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35229478

RESUMO

Cancer stem cells (CSCs) are a rare cell population in tumors that are responsible for tumor recurrence and metastasis. They are a priority as therapeutic targets, however, assays targeting CSCs have been limited by expanding and maintaining CSCs in vitro. Here, the authors find that gelatin methacryloyl (GelMA)-nanoclay hybrid hydrogels can induce and enrich colorectal CSCs assisted by three-dimensional (3D) bioprinting. The presence of the nanoclay increases the printability, Young's modulus, pore size, and cytocompatibility of the hydrogels. Bioprinted GelMA-nanoclay hydrogels promote the formation of spheroids expressing elevated levels of the stemness markers LGR5, CD133, CD26, and SOX2. Cancer cells grown in GelMA-nanoclay hydrogel possess higher self-renewal and differentiation capacity in vitro and higher tumorigenic capacity in vivo. GelMA-nanoclay hydrogels induce CSCs by stimulating the activation of the Wnt/ß-catenin signaling pathway. Further studies demonstrate that spheroids from GelMA-nanoclay hydrogels possess increased stemness, higher consistency, yield, and sensitivity to the anti-CSC compounds compared to the classic CSC-enrichment model. Collectively, this study may provide a valuable biomaterial and method for inducing and enriching CSCs, to facilitate the effective CSC-targeting drug screening.


Assuntos
Neoplasias Colorretais , Hidrogéis , Neoplasias Colorretais/tratamento farmacológico , Gelatina , Humanos , Hidrogéis/farmacologia , Metacrilatos , Células-Tronco Neoplásicas , Via de Sinalização Wnt , beta Catenina
6.
Neoplasma ; 69(2): 274-282, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34846157

RESUMO

This study was conducted to investigate the expression of the spindle assembly checkpoint kinase tyrosine/threonine kinase (TTK) in triple positive breast cancer (TPBC) and its effect on TPBC cells. We analyzed the status of TTK in 69 TPBC samples using immunohistochemistry. The correlation between TTK and clinicopathological parameters was analyzed using a chi-squared test. The prognostic value of TTK was evaluated using Kaplan-Meier survival curves. We analyzed the role of TTK in the invasion and proliferation of TPBC cells in vitro and in vivo. The mean age of the 69 patients with TPBC enrolled in this study was 53 years (range: 29-86 years). TTK expression was positively correlated with tumor size (p=0.034), p53 status (p=0.023), TNM stage ([p=0.023), and Ki-67 index (p<0.001). The Kaplan-Meier curves revealed that TTK expression was correlated with poor disease-free survival (p=0.001) and overall survival (p=0.050). Multivariate proportional hazard regression analyses showed that TTK and TNM staging were significant independent predictors of disease-free survival (p=0.007 and p=0.034, respectively). Additionally, TTK knockdown inhibited the invasion and proliferation of the BT474 TPBC cell line. The findings of this study indicate that TTK overexpression is associated with cancer progression and prognosis in patients with TPBC, whereas TTK knockdown inhibits the invasion and proliferation of TPBC cells. Thus, TTK might serve as a prognostic marker for TPBC.


Assuntos
Neoplasias da Mama , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Proteínas Serina-Treonina Quinases , Proteínas Tirosina Quinases/metabolismo , Treonina , Tirosina
7.
World J Surg Oncol ; 20(1): 356, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36348366

RESUMO

BACKGROUND: Gastric neuroendocrine neoplasm (g-NEN) is a rare but heterogeneous neoplasm, with an increasing incidence yearly. Conventional prognostic markers of g-NEN remain limited which could only be detected after surgery. There is an urgent need to explore new prognostic markers for g-NEN patients. This study aimed to investigate the prognostic value of platelet-to-lymphocyte, ratio (PLR) and the association between PLR and body mass index (BMI) in patients with gastric neuroendocrine neoplasms (g-NEN). METHODS: A retrospective cohort of patients with g-NEN from January 2001 through June 2016 was examined. The prognostic significance of PLR was determined by multiple regression analysis in different models. Stratified analysis was performed to examine the prognostic value of PLR at different BMI levels. RESULTS: In total, 238 patients were enrolled. Those with higher PLRs tended to undergo open surgery, had larger tumor sizes, were diagnosed more frequently with neuroendocrine carcinoma, and had higher tumor grades. PLR was significantly associated with the survival of patients with g-NEN. With PLR increased per standard deviation, the all-cause mortality risk of patients with g-NEN increased by 67%, 63%, and 54% in the crude (HR = 1.67, 95% CI 1.32-2.12, P < 0.001), minimally adjusted (HR = 1.63, 95% CI 1.28-2.08, P < 0.001), and fully adjusted (HR = 1.54, 95% CI 1.202-1.98, P = 0.001) models, respectively. Patients with higher PLR (quartile 4, ≥ 187) had a 1.8-fold increase in all-cause mortality risk compared with those with lower PLR (quartile 1-3, < 187). Furthermore, there was a significant interaction effect between BMI subgroups and PLR in predicting the survival of patients with g-NEN (PLR regarded as a continuous variable: all P for interaction < 0.05 in the crude, minimally adjusted, and fully adjusted models; PLR regarded as a categorical variable: P for interaction < 0.05 in the fully adjusted model). Patients with g-NEN with the characteristics of higher PLR (quartile 4, ≥ 187) and non-obesity (BMI < 25 kg/m2) had worse survival than others (P < 0.05). CONCLUSION: The inflammation marker PLR has an independent prognostic value for patients with g-NENs, and high PLR combined with non-obesity increases the mortality risk of these patients.


Assuntos
Tumores Neuroendócrinos , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Linfócitos/patologia , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Prognóstico , Neoplasias Gástricas/patologia , Plaquetas/patologia , Neutrófilos/patologia
8.
Biochem Biophys Res Commun ; 555: 61-66, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-33813277

RESUMO

It is vital to identify effective therapeutic targets and explore the underlying mechanisms to curb the progression of Gastric cancer (GC) and improve the prognosis of GC patients. Guanine-rich RNA sequence binding factor 1 (GRSF1) is a member of the RNA-binding protein family. The present study showed that GRSF1 knockdown suppressed GC cells proliferation, migration and invasion in vitro, while GRSF1 overexpression enhanced the proliferation, migration and invasion of GC cells. Meanwhile, knockdown of GRSF1 inhibited tumor growth and tumor metastasis in vivo. Furthermore, we demonstrated that GRSF1 induced epithelial-mesenchymal transition (EMT) and activated PI3K/AKT pathway in vitro and in vivo through gain and loss of function. In conclusion, we demonstrated that GRSF1 promotes tumorigenesis and EMT-mediated metastasis through PI3K/AKT pathway in GC. Our study for the first time identified the functions of GRSF1 serving as an oncogene in GC, which may be a potential effective therapeutic target and malignant indicator in GC.


Assuntos
Proteínas de Ligação a Poli(A)/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Masculino , Camundongos Endogâmicos BALB C , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas de Ligação a Poli(A)/genética , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Ensaios Antitumorais Modelo de Xenoenxerto
9.
J Transl Med ; 19(1): 432, 2021 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-34657624

RESUMO

BACKGROUND: Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide. Due to the dismal prognosis, identifying novel therapeutic targets in GC is urgently needed. Evidences have shown that miRNAs played critical roles in the regulation of tumor initiation and progression. GLI family zinc finger 2 (GLI2) has been reported to be up-regulated and facilitate cancer progression in multiple malignancies. In this study, we focused on identifying GLI2-targeted miRNAs and clarifying the underlying mechanism in GC. METHODS: Paired fresh gastric cancer tissues were collected from gastrectomy patients. GLI2 and miRNAs expression were detected in gastric cancer tissues and cell lines. Bioinformatics analysis was used to predict GLI2-targeted miRNAs and dual-luciferase reporter assay was applied for target verification. CCK-8, clone formation, transwell and flow cytometry were carried out to determine the proliferation, migration, invasion and cell cycle of gastric cancer cells. Tumorsphere formation assay and flow cytometry were performed to detail the stemness of gastric cancer stem cells (GCSCs). Xenograft models in nude mice were established to investigate the role of the miR-144-3p in vivo. RESULTS: GLI2 was frequently upregulated in GC and indicated a poor survival. Meanwhile, miR-144-3p was downregulated and negatively correlated with GLI2 in GC. GLI2 was a direct target gene of miR-144-3p. MiR-144-3p overexpression inhibited proliferation, migration and invasion of gastric cancer cells. Enhanced miR-144-3p expression inhibited tumorsphere formation and CD44 expression of GCSCs. Restoration of GLI2 expression partly reversed the suppressive effect of miR-144-3p. Xenograft assay showed that miR-144-3p could inhibit the tumorigenesis of GC in vivo. CONCLUSIONS: MiR-144-3p was downregulated and served as an essential tumor suppressor in GC. Mechanistically, miR-144-3p inhibited gastric cancer progression and stemness by, at least in part, regulating GLI2 expression.


Assuntos
MicroRNAs , Neoplasias Gástricas , Animais , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas Hedgehog , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Proteínas Nucleares , Neoplasias Gástricas/genética , Proteína Gli2 com Dedos de Zinco/genética
10.
Mol Cell Biochem ; 476(2): 757-765, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33099745

RESUMO

Human papillomavirus (HPV) infection is related to cancer growth of vaginal, cervical, vulva, penile, anogenital, and non-genital oropharyngeal sites. HPV, as a sexually transmitted virus, infects all sexes similarly but with more significant pathological risks in women. This accounts for high mortality due to late detection and poor prognosis. The initial development and eventual progress of this cancer type depend entirely on three main oncogenes E5, E6 and E7, constitutively expressed to lead to carcinogenesis. Despite an opportunity for pharmacological therapy, there is still a shortage of medical treatment that may remove HPV from infected lesions. This study offers a concise summary of the nature of the issue and the current status of work on potential lead molecules and therapeutic approaches that show the capacity of HPV therapies to counteract the roles of deregulation of E5, E6, and E7.


Assuntos
Interferons/uso terapêutico , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/tratamento farmacológico , Zinco/uso terapêutico , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Oligoelementos/uso terapêutico , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia
11.
Phys Chem Chem Phys ; 23(28): 15374-15383, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34259266

RESUMO

The use of the conventional pressure-composition-temperature (PCT) method to determine the thermodynamics of metal hydrides is a time-consuming process. This work presents an efficient method based on thermogravimetric analysis (TGA), to characterize the thermodynamic parameters. Through cycling catalyzed magnesium hydride in a TGA apparatus under a flowing gas with a constant hydrogen partial pressure, TGA curves can be used to determine absorption/desorption equilibrium temperatures. Based on the van't Hoff analysis, the reaction enthalpies and entropies can be derived from the equilibrium temperatures as a function of hydrogen pressure. Using the results of this work we calculated the hydrogenation and dehydrogenation enthalpies, which are 79.8 kJ per mol per H2 and 76.5 kJ per mol per H2, respectively. These values are in good agreement with those reported values using the PCT method. These results demonstrate that the TGA can be an efficient and effective method for measuring thermodynamic parameters of metal hydrides.

12.
Chin J Cancer Res ; 33(2): 232-242, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-34158742

RESUMO

OBJECTIVE: To avoid perioperative complications caused malnutrition, nutrition therapy is necessary in gastric outlet obstruction (GOO) patients. Compared to parenteral nutrition (PN), enteral nutrition (EN) is associated with many advantages. This study aimed to investigate whether preoperative EN has beneficial clinical effects compared to preoperative PN in gastric cancer patients with GOO undergoing surgery. METHODS: According to the methods of preoperative nutrition therapy, 143 patients were divided into EN group (n=42) and PN group (n=101) between January 2013 and December 2017 at the Chinese People's Liberation Army General Hospital. Multiple logistic regression models were used to assess the association between the methods of preoperative nutrition therapy and postoperative day of flatus passage. The generalized additive model and two-piecewise linear regression model were used to calculate the inflection point of the preoperative nutritional therapy time on the postoperative day of flatus passage in the PN group. RESULTS: EN shortened the postoperative day of flatus passage in gastric cancer patients with GOO, which is a protective factor, especially in patients who underwent non-radical operations and the postoperative day of flatus passage reduced when the preoperative PN therapy was up to 3 d and a longer PN therapy (>3 d) did not accelerate the postoperative recovery of gastrointestinal functions. CONCLUSIONS: Preoperative EN therapy would benefit gastric cancer patients with GOO by accelerating postoperative recovery. For patients with absolute obstruction, no more than 3-day PN therapy is recommended if patients can tolerate general anesthesia and surgery.

13.
Br J Cancer ; 122(12): 1837-1847, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32350414

RESUMO

BACKGROUND: Stearoyl-CoA desaturase-1 (SCD1) is reported to play essential roles in cancer stemness among several cancers. Our previous research revealed significant overexpression of SCD1 in primary gastric cancer stem cells (GCSCs), with its functional role still unknown. METHODS: We stably established three primary GCSCs by sphere-forming assays and flow cytometry. Protein quantification and bioinformatics analysis were performed to reveal the differential protein pattern. Lentivirus-based small-interfering RNA (siRNA) knockdown and pharmacological inhibition approaches were used to characterise the function and molecular mechanism role of SCD1 in the regulation of GC stemness and tumour metastasis capacity both in vitro and in vivo. RESULTS: SCD1 was found to increase the population of GCSCs, whereas its suppression by an SCD1 inhibitor or knockdown by siRNA attenuated the stemness of GCSCs, including chemotherapy resistance and sphere-forming ability. Furthermore, SCD1 suppression reversed epithelial-to-mesenchymal transition and reduced the GC metastasis probability both in vitro and in vivo. Downregulation of SCD1 in GCSCs was associated with the expression of Yes-associated protein (YAP), a key protein in the Hippo pathway, and nuclear YAP translocation was also blocked by the SCD1 decrease. CONCLUSIONS: SCD1 promotes GCSC stemness through the Hippo/YAP pathway. Targeting SCD1 might be a novel therapeutic strategy, especially to suppress GC metastasis and sensitise chemotherapy.


Assuntos
Adenocarcinoma/patologia , Células-Tronco Neoplásicas/patologia , Estearoil-CoA Dessaturase/metabolismo , Neoplasias Gástricas/patologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/metabolismo , Animais , Xenoenxertos , Via de Sinalização Hippo , Humanos , Masculino , Camundongos , Camundongos SCID , Invasividade Neoplásica/patologia , Metástase Neoplásica , Células-Tronco Neoplásicas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/fisiologia , Neoplasias Gástricas/metabolismo , Fatores de Transcrição/metabolismo , Células Tumorais Cultivadas , Proteínas de Sinalização YAP
14.
Jpn J Clin Oncol ; 50(10): 1108-1116, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32579167

RESUMO

BACKGROUND: Patient-derived xenograft model is a powerful and promising tool for drug discovery and cancer biology studies. The application of previous metastatic colorectal cancer models has been greatly limited by its low success rate and long time to develop metastasis. Therefore, in this study, we aim to describe an optimized protocol for faster establishment of colorectal cancer metastatic patient-derived xenograft mouse models. METHODS: Smaller micro tissues (˂150 µm in diameter) mixed with Matrigel were engrafted subcutaneously into NSG mice to generate the passage 1 (P1) patient-derived xenograft. The micro tumours from P1 patient-derived xenograft were then excised and orthotopically xenografted into another batch of NSG mice to generate a metastatic colorectal cancer patient-derived xenograft, P2. Haematoxylin and eosin and immunohistochemistry staining were performed to compare the characters between patient-derived xenograft tumours and primary tumours. RESULTS: About 16 out of 18 P1 xenograft models successfully grew a tumour for 50.8 ± 5.1 days (success rate 89.9%). Six out of eight P1 xenograft models originating from metastatic patients successfully grew tumours in the colon and metastasized to liver or lung in the NSG recipients for 60.9 ± 4.5 days (success rate 75%). Histological examination of both P1 and P2 xenografts closely resembled the histological architecture of the original patients' tumours. Immunohistochemical analysis revealed similar biomarker expression levels, including CDH17, Ki-67, active ß-catenin, Ki-67 and α smooth muscle actin when compared with the original patients' tumours. The stromal components that support the growth of patient-derived xenograft tumours were of murine origin. CONCLUSIONS: Metastatic patient-derived xenograft mouse model could be established with shorter time and higher success rate. Although the patient-derived xenograft tumours were supported by the stromal cells of murine origin, they retained the dominant characters of the original patient tumours.


Assuntos
Neoplasias Colorretais/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/metabolismo , Carcinogênese/patologia , Feminino , Xenoenxertos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica
15.
Surg Endosc ; 34(5): 2237-2242, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31376011

RESUMO

BACKGROUND: Laparoscopy is being increasingly applied as either a diagnostic or therapeutic intervention in the management of abdominal trauma. However, its outcomes in comparison with conventional laparotomy remain unclear, especially in terms of therapeutic management. METHODS: This retrospective cohort study included patients from three trauma centers in Beijing, China. Fifty-four patients undergoing laparoscopic interventions for abdominal trauma by experienced laparoscopists were enrolled in the laparoscopy group (LP group). Another 54 patients who underwent laparotomy (LT group) were matched according to the patients' baseline characteristics, causes of injury, and hemodynamic parameters. Perioperative clinical parameters and short-term survival were compared between these two groups. RESULTS: The baseline characteristics were comparable between these two groups (LP vs. LT: Age, p = 0.112; Sex, p = 0.820; Injury severity score, p = 0.158; Cause distribution, p = 0.840). The most common cause was traffic accident (36.1%) and the most frequent surgical intervention was bowel repair/resection (34.3%) in our study. The operation time was similar in these two groups (LP vs. LT: 202.2 ± 72.58 vs. 194.11 ± 82.95 min, p = 0.295) while post-operative complication rate was slightly reduced in LP group (7.7% vs. 13.5%) with no statistical significance (p = 0.383). Opioid use was lower in the LP than LT group (11.67 ± 4.08 vs. 26.0 ± 13.42 morphine equivalents (MEQ), p = 0.034). The hospital stay was significantly shorter in the LP group (13.48 ± 10.9 vs. 18.64 ± 14.73 days, p = 0.021). One patient in the LT group died of an intra-abdominal abscess and multiple organ dysfunction syndrome 19 days postoperatively, while all patients in the LP group recovered and were discharged. CONCLUSION: Laparoscopy is feasible and safe in treating abdominal trauma patients in hemodynamically stable conditions performed by experienced surgeons. Laparoscopy might have the advantages of reduced pain and quicker recovery with similarly favorable clinical outcomes.


Assuntos
Traumatismos Abdominais/cirurgia , Laparoscopia/métodos , Laparotomia/métodos , Traumatismos Abdominais/epidemiologia , Adulto , Pequim/epidemiologia , Feminino , Humanos , Escala de Gravidade do Ferimento , Laparoscopia/efeitos adversos , Laparotomia/efeitos adversos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Centros de Traumatologia , Resultado do Tratamento
16.
BMC Womens Health ; 20(1): 75, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32316946

RESUMO

BACKGROUND: Diverticulum, one of the long-term sequelae of cesarean section, can cause abnormal uterine bleeding, dysmenorrhea and chronic pelvic pain. Hysteroscopic resection of diverticula is thought to reduce abnormal uterine bleeding and chronic pelvic pain. In this study, we aim to describe the improvement after hysteroscopic resection of cesarean section diverticula (CSD) in women without childbearing intention, and to explore the variables associated with poor prognosis. METHODS: A retrospective cohort study of women aged 25-48 with CSD diagnosis by transvaginal ultrasonography (TVS) and hysteroscopy that were enrolled at Guangzhou Women and Children's Medical Center between June 2017 and December 2018. A total of 124 women met the inclusion criteria and all patients had undergone hysteroscopic resection and accepted a follow-up interview at the 3rd and 6th months postoperatively to record symptom improvement. RESULT: The mean of intraoperative blood loss and operative time of hysteroscopic resection were (12.94 ± 12.63) ml and (33.63 ± 6.87) min in 124 patients. Overall observed improvement rates of CSD symptom were 47.2 and 65.6% in the first 3 and 6 months, respectively. Multivariable logistic regression models revealed that timing of surgery < 14 days was a good prognostic factor associated with both 3-month improvement (OR, 16.59; 95% CI, 2.62-104.90; P = 0.003) and 6-month improvement (OR, 15.51; 95%CI, 1.63-148.00; P = 0.02); Patients with numbers of cesarean section (CS) ≥2 had a lower rate of improvement after 6 months of CSD repair surgery compared with patients who underwent one CS (OR, 8.29; 95%CI, 1.05-65.75; P = 0.04). CONCLUSIONS: A hysteroscopic repair might be an appropriate method for CSD in women who no childbearing intentions. The timing of surgery and the number of CS seems to be factors influencing the postoperative improvement of CSD.


Assuntos
Cesárea/efeitos adversos , Divertículo/cirurgia , Histeroscopia/métodos , Histeroscopia/estatística & dados numéricos , Doenças Uterinas/cirurgia , Adulto , Criança , China , Cicatriz/cirurgia , Feminino , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Histeroscopia/efeitos adversos , Pessoa de Meia-Idade , Gravidez , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Resultado do Tratamento
17.
Surg Endosc ; 33(2): 528-534, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30014325

RESUMO

BACKGROUND: Emerging evidence has demonstrated that either laparoscopic-assisted gastrectomy (LAG) or robotic-assisted gastrectomy (RAG) could be adopted as standard treatment for early gastric cancer. However, the long-term survival and recurrence rate after LAG or RAG for locally advanced gastric cancer (AGC) has seldom been reported. METHODS: We retrospectively analyzed the data from 339 patients who underwent LAG and 163 patients who underwent RAG from a prospectively established database in the Chinese People's Liberation Army General Hospital. We compared the short- and long-term oncological outcomes of the RAG group versus the LAG group in the entire cohort, and in a propensity score-matched cohort. RESULTS: Before propensity score matching (PSM), the two groups revealed comparable 3-year overall survival rates (OS, RAG vs. LAG: 76.1 vs. 81.7%, p = 0.118), and recurrence-free survival rates (RFS, RAG vs. LAG: 73.0 vs. 67.6%, p = 0.297). Similar results were obtained in the propensity score-matched cohort; the respective overall survival rates in the propensity score-matched RAG and LAG groups were 76.1 and 79.8% (p = 0.552), and the respective RFS rates were 73.0 and 68.7% (p = 0.386). After PSM, RAG was still associated with a significantly longer mean operating time (249.46 ± 63.26 vs. 232.17 ± 65.39 min, p = 0.008) and higher total costs (133.38 ± 41.62 vs. 95.34 ± 29.39 103 RMB, p < 0.001) than LAG; the two groups did not significantly differ in other surgical and oncological characteristics. CONCLUSION: Although there were some differences in the outcomes of RAG versus LAG in AGC patients, both RAG and LAG were similar in short-term recovery and long-term oncological outcomes.


Assuntos
Gastrectomia/métodos , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas/cirurgia , Idoso , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Duração da Cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Resultado do Tratamento
18.
Cancer Control ; 25(1): 1073274818765999, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29582668

RESUMO

BACKGROUND: An increasing amount of attention has been paid to minimally invasive function-preserving gastrectomy, with an increase in incidence of early gastric cancer in the upper stomach. This study aimed to compare oncological outcomes, surgical stress, and nutritional status between robot-assisted proximal gastrectomy (RAPG) and laparoscopy-assisted proximal gastrectomy (LAPG). METHODS: Eighty-nine patients were enrolled in this retrospective study between November 2011 and December 2013. Among them, 27 patients underwent RAPG and 62 underwent LAPG. Perioperative parameters, surgical stress, nutritional status, disease-free survival, and overall survival were compared between the 2 groups. RESULTS: Sex, age, and comorbidity were similar in the RAPG and LAPG groups. There were also similar perioperative outcomes regarding operation time, complications, and length of hospital stay between the groups. The reflux esophagitis rates following RAPG and LAPG were 18.5% and 14.5%, respectively ( P = .842). However, patients in the RAPG group had less blood loss ( P = .024), more harvested lymph nodes ( P = .021), and higher costs than those in the LAPG group ( P < .001). With regard to surgical stress, no significant differences were observed in C-reactive protein concentrations and white blood cell count on postoperative days 1, 3, and 7 between the groups ( Ps > .05). There appeared to be higher hemoglobin levels at 6 months ( P = .053) and a higher body mass index at 12 months ( P = .056) postoperatively in patients in the RAPG group compared with those in the LAPG group, but this difference was not significant. Similar disease-free survival and overall survival rates were observed between the groups. CONCLUSIONS: RAPG could be an alternative to LAPG for patients with early gastric cancer in the upper stomach with comparable oncological safety and nutritional status. Further well-designed, prospective, large-scale studies are needed to validate these results.


Assuntos
Gastrectomia/métodos , Estado Nutricional/fisiologia , Robótica/métodos , Neoplasias Gástricas/cirurgia , Feminino , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia
19.
Surg Endosc ; 32(3): 1422-1433, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29075971

RESUMO

BACKGROUND: As minimally invasive techniques advances, minimally invasive surgery (MIS) has emerged as an alternative modality for advanced gastric cancer. In this study, we compared the short- and long-term surgical outcomes of MIS and conventional open surgery for gastric cancer liver metastasis (GCLM) in terms of safety, feasibility, and efficacy. METHODS: This retrospective study used data from a prospective database at the Chinese People's Liberation Army General Hospital. From January 2006 to June 2016, 53 gastric cancer patients with synchronous liver metastasis accepted radical gastrectomy combined with either or both hepatectomy and radiofrequency ablation for liver metastases. The 53 patients enrolled in the study were divided into two groups: a conventional open surgery group (n = 42) and an MIS group (n = 11). Propensity score matching (PSM) analysis was performed to overcome possible bias. RESULTS: With PSM performed at a 1:3 ratio, 11 patients who received MIS were compared with 33 open surgery cases. Mean operation time was significantly longer for the MIS group compared with the open surgery group (301 vs. 236 min, P = 0.032), while the open surgery group had a larger estimated blood loss than the MIS group (421 vs. 196 ml, P = 0.019). Time to first flatus and postoperative complications, including Clavien-Dindo classification, were similar in the two groups. However, patients undergoing MIS had a significantly shorter time to first sips of water (P = 0.020) and soft diet (P = 0.020) compared with open surgery counterparts. Long-term outcomes were comparable between groups (P = 0.090) after adjustment by PSM analysis. CONCLUSIONS: MIS achieved superior short-term outcomes and comparable long-term outcomes compared with open surgery in GCLM patients. For experienced surgeons, both laparoscopic and robotic methods of MIS are reasonable approaches for the management of highly selected GCLM patients.


Assuntos
Adenocarcinoma/secundário , Hepatectomia/métodos , Laparoscopia , Neoplasias Hepáticas/secundário , Ablação por Radiofrequência/métodos , Procedimentos Cirúrgicos Robóticos , Neoplasias Gástricas/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Estudos de Viabilidade , Feminino , Seguimentos , Gastrectomia , Humanos , Tempo de Internação , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
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