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2.
Biomater Sci ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38687170

RESUMO

The effectiveness of photodynamic therapy (PDT) has been greatly restricted by the hypoxic tumor microenvironment and the susceptible resistance of monotherapy. Although nanodrugs based on transition metal complexes capable of integrating PDT with photoactivated chemotherapy (PACT) have garnered tremendous attention as promising candidates for overcoming the above limitations, the therapeutic efficacy of these nanodrugs is still hampered by inadequate loading of active pharmaceutical ingredients (APIs) and the inherent ability of cancer cells to repair damaged DNA. Herein, we developed a photoactivated full-API nanodrug, Ru-T FAND, by one-step self-assembly of RuDPB and TH287. By virtue of its 100 wt% API content and favorable stability in water, the Ru-T FAND exhibited improved cellular uptake behavior and intracellular 1O2 generation. Attractively, the Ru-T FAND with triple anti-cancer modalities can photogenerate 1O2, photo-release DPB ligand and inhibit the repair of DNA damage, ultimately enhancing its phototherapeutic effect on cancer cells. Importantly, the uncaged DPB ligand from RuDPB emits red fluorescence, enabling real-time monitoring of the drug's absorption, distribution and efficacy. Collectively, the presented photoactivated Ru-T FANDs with multiple anti-cancer mechanisms will expand new horizons for the development of safe, efficient and synergistic tumor phototherapy strategies.

3.
Phys Med Biol ; 69(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38316034

RESUMO

Objective. Ulceration of the small intestine, which has a high incidence, includes Crohn's disease (CD), intestinal tuberculosis (ITB), primary small intestinal lymphoma (PSIL), cryptogenic multifocal ulcerous stenosing enteritis (CMUSE), and non-specific ulcer (NSU). However, the ulceration morphology can easily be misdiagnosed through enteroscopy.Approach. In this study, DRCA-DenseNet169, which is based on DenseNet169, with residual dilated blocks and a channel attention block, is proposed to identify CD, ITB, PSIL, CMUSE, and NSU intelligently. In addition, a novel loss function that incorporates dynamic weights is designed to enhance the precision of imbalanced datasets with limited samples. DRCA-Densenet169 was evaluated using 10883 enteroscopy images, including 5375 ulcer images and 5508 normal images, which were obtained from the Shanghai Changhai Hospital.Main results. DRCA-Densenet169 achieved an overall accuracy of 85.27% ± 0.32%, a weighted-precision of 83.99% ± 2.47%, a weighted-recall of 84.36% ± 0.88% and a weighted-F1-score of 84.07% ± 2.14%.Significance. The results demonstrate that DRCA-Densenet169 has high recognition accuracy and strong robustness in identifying different types of ulcers when obtaining immediate and preliminary diagnoses.


Assuntos
Intestino Delgado , Úlcera , Humanos , Úlcera/diagnóstico por imagem , China , Intestino Delgado/diagnóstico por imagem , Diagnóstico Diferencial
4.
J Inorg Biochem ; 247: 112310, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37441921

RESUMO

Three ruthenium arene complexes, namely {[(η6-p-cymene)Ru(Cl)]2(dpb)}(PF6)2 (1), [(η6-p-cymene)Ru(dpb)Cl](PF6) (2) and [(η6-p-cymene) Ru(dpb)py](PF6) (3) (dpb = 2,3-bis(2-pyridyl)benzo-quinoxaline, py = pyridine), were synthesized and their antitumor properties were introduced. Complexes 1-3 were characterized by 1H NMR, MS, and elemental analysis. As a binuclear ruthenium structure, the absorption of metal ligand electron transfer (MLCT) of 1 extended to 700 nm. Complex 1 was significantly hydrolyzed under dark conditions. The cytotoxicity in vitro study showed that complexes 1 and 2 are more toxic to human lung cancer cells (A549) and human cervial cancer cells (Hela) than cisplatin. Moreover, there was almost no cross-resistance between complex 1-2 and cisplatin. Under the irradiation at 478 nm, complexes 1-3 all produced singlet oxygen (1O2), and the 1O2 quantum yield of complex 1 in PBS is the highest among complexes 1-3. Complex 1 also produced 1O2 under 600 nm light irradiation. DNA gel electrophoresis showed that 1 caused the photocleavage of plasmid DNA. The hydrolysis rate of complex 1 was accelerated under light (λ > 600 nm). And the phototoxicity of complex 1 to Hela cells under light (λ > 600 nm) was much greater than its dark toxicity, which may be due to its generation of 1O2 and the promotion of its hydrolysis under long-wave light irradiation.


Assuntos
Antineoplásicos , Complexos de Coordenação , Rutênio , Humanos , Cisplatino , Células HeLa , Linhagem Celular Tumoral , Rutênio/farmacologia , Rutênio/química , DNA/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Antineoplásicos/farmacologia , Antineoplásicos/química
5.
Gut ; 72(5): 855-869, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36690433

RESUMO

BACKGROUND AND AIMS: Current practice on Helicobacter pylori infection mostly focuses on individual-based care in the community, but family-based H. pylori management has recently been suggested as a better strategy for infection control. However, the family-based H. pylori infection status, risk factors and transmission pattern remain to be elucidated. METHODS: From September 2021 to December 2021, 10 735 families (31 098 individuals) were enrolled from 29 of 31 provinces in mainland China to examine family-based H. pylori infection, related factors and transmission pattern. All family members were required to answer questionnaires and test for H. pylori infection. RESULTS: Among all participants, the average individual-based H. pylori infection rate was 40.66%, with 43.45% for adults and 20.55% for children and adolescents. Family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces, with an average rate of 71.21%. In 28.87% (3099/10 735) of enrolled families, there were no infections; the remaining 71.13% (7636/10 735) of families had 1-7 infected members, and in 19.70% (1504/7636), all members were infected. Among 7961 enrolled couples, 33.21% had no infection, but in 22.99%, both were infected. Childhood infection was significantly associated with parental infection. Independent risk factors for household infection were infected family members (eg, five infected members: OR 2.72, 95% CI 1.86 to 4.00), living in highly infected areas (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and large families in a household (eg, family of three: OR 1.97, 95% CI 1.76 to 2.21). However, family members with higher education and income levels (OR 0.85, 95% CI 0.79 to 0.91), using serving spoons or chopsticks, more generations in a household (eg, three generations: OR 0.79, 95% CI 0.68 to 0.92), and who were younger (OR 0.57, 95% CI 0.46 to 0.70) had lower infection rates (p<0.05). CONCLUSION: Familial H. pylori infection rate is high in general household in China. Exposure to infected family members is likely the major source of its spread. These results provide supporting evidence for the strategic changes from H. pylori individual-based treatment to family-based management, and the notion has important clinical and public health implications for infection control and related disease prevention.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Criança , Adulto , Adolescente , Humanos , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/prevenção & controle , Família , Fatores de Risco , China/epidemiologia , Estudos Epidemiológicos , Prevalência
6.
Dig Dis Sci ; 66(6): 2075-2083, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32705437

RESUMO

BACKGROUND AND AIM: The management of pancreatic cystic lesions (PCLs) remains controversial. We performed a retrospective study to determine characteristics associated with advanced PCLs (A-PCLs) and whether these characteristics vary in different pathological types of PCLs. The additional diagnostic value of endoscopic ultrasound (EUS) was also evaluated. METHODS: Patients who underwent surgical resection for an identified PCLs by imaging modalities were included. A logistic regression model was developed to identify significant characteristics for A-PCLs. EUS data was assessed separately. RESULTS: Three hundred and fifty-three patients were included, and 125 patients (35.4%) were A-PCLs. The presence of main pancreatic duct (MPD) diameter ≥ 10 mm (odds ratio [OR], 11.7; 95% confidence interval [CI], 1.53-89.2; P = 0.018), mural nodules ≥ 5 mm (OR, 11.67; 95% CI, 2.3-59.05; P = 0.003), solid components within cysts (OR, 30.87; 95% CI, 7.23-131.7; P < 0.0001) and high serum CA19-9 levels (OR, 1.006; 95% CI, 1.001-1.011; P = 0.02) were independently associated with the presence of A-PCLs. The presence of septa was independently associated with the presence of non-A-PCLs (OR, 0.147; 95% CI, 0.04-0.6; P = 0.008). Males who had a history of tobacco abuse (P < 0.0001) and had a greatly dilated MPD (P < 0.0001) were more common in advanced intraductal papillary mucinous neoplasms (IPMC) patients. Solid pseudopapillary neoplasm (SPT) often occurred in young women (P < 0.0001), mostly asymptomatically (P < 0.0001) and with lower serum CA19-9 levels (P < 0.0001). In the 124 patients who underwent EUS-guided fine-needle aspiration (EUS-FNA), five additional characteristics (4 mural nodules and 1 MPD involvement) were identified by EUS imaging and 17 patients were identified with abnormal cytological results (13 atypical cells and 4 suspicious for malignancy cells) by EUS-FNA. CONCLUSION: On the basis of a retrospective study with large sample size, the presence of MPD ≥ 10 mm, mural nodules, solid components, and high serum CA19-9 levels were independently associated with the presence of A-PCLs. The high-risk characteristics may vary across different types of A-PCLs. EUS and EUS-FNA could provide additional diagnostic information for PCLs.


Assuntos
Cisto Pancreático/diagnóstico por imagem , Cisto Pancreático/cirurgia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cisto Pancreático/epidemiologia , Estudos Retrospectivos , Fatores de Risco
9.
J Clin Gastroenterol ; 55(9): 778-784, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33116065

RESUMO

BACKGROUND AND AIM: Gastric precancerous conditions are generally considered to play an essential role in the gastric carcinogenesis cascade. This study identified risk factors of gastric precancerous conditions in a nationwide multicenter cross-sectional study. METHODS: Individuals who made their visit to 115 hospitals in China for gastric cancer screening were recruited. Lifestyle habits and personal information were collected through a series of questionnaires. Serum biomarker test (pepsinogen I, pepsinogen II, gastrin-17, and anti-Helicobacter pylori immunoglobulin G antibody) and endoscopy were then performed. Risk factors for gastric precancerous conditions were identified by univariate and multivariate analyses. RESULTS: Of 14,929 subjects eligible for analysis, 4477 (30.0%) developed gastric precancerous conditions and 405 (2.71%) developed gastric cancer. In multiple logistic regression, precancerous conditions were associated with advanced age [odds ratio (OR)=1.027; 95% confidence interval (Cl), 1.023-1.032; P<0.001], male gender (OR=1.303; 95% Cl, 1.188-1.429; P<0.001), H. pylori infection (OR=1.377; 95% Cl, 1.272-1.490, P<0.001), and smoking (OR=1.142; 95% Cl, 1.005-1.298, P=0.004), whereas they were inversely correlated with white meat intake (OR=0.731; 95% Cl, 0.673-0.794; P<0.001) and pepsinogen I level (30 to 70 subgroup OR=1.536; 95% Cl, 1.163-2.028; P=0.002; <30 subgroup OR=1.354; 95% Cl, 1.206-1.520; P<0.001). Also, the authors observed a statistically lower prevalence of reflux esophagitis (2.8% vs. 4.7%) and of gastric polyps (11.0% vs. 13.7%) in H. pylori-infected population. CONCLUSIONS: Patients with H. pylori have a 1.4-fold higher risk of having gastric precancerous conditions. Besides, precancerous conditions were associated with advanced age, male gender, H. pylori infection, and smoking in a large population. However, regular white meat intake and higher pepsinogen I level were associated with reduced risk of having precancerous lesions.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Lesões Pré-Cancerosas , Neoplasias Gástricas , Estudos Transversais , Infecções por Helicobacter/complicações , Infecções por Helicobacter/epidemiologia , Humanos , Masculino , Pepsinogênio A , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/epidemiologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia
10.
Cell Death Discov ; 6(1): 136, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33298873

RESUMO

Pseudogene pituitary tumor-transforming 3 (PTTG3P) is emerging as a key player in the development and progression of cancer. However, the biological role and clinical significance of PTTG3P in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, we found that PTTG3P was significantly upregulated in PDAC tissues. Elevated PTTG3P expression correlated with larger tumor size and worse differentiation, and reduced overall survival. Bioinformatics and experimental evidence revealed that PTTG3P promoted malignant phenotypes and FoxM1 signaling pathway in PDAC cells. Mechanistically, PTTG3P functions as a microRNA sponge to positively regulate the expression of FoxM1 through sponging miR-132/212-3p. Moreover, it showed that FoxM1 transcriptionally activated PTTG3P expression, thus forming a feedback loop to promote the aggressiveness of PDAC cells. Taken together, our findings suggest that PTTG3P promotes PDAC progression through PTTG3P/miR-132/212-3p/FoxM1 feedforward circuitry and it may serve as a promising diagnostic marker or target for treatment in PDAC patients.

11.
J Gastroenterol Hepatol ; 35(12): 2103-2108, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32365410

RESUMO

BACKGROUND AND AIM: The effect of solid debris on walled-off necrosis (WON) drainage remains unknown. Our study evaluated the role of solid debris in endoscopic ultrasound (EUS)-guided drainage of WON compared lumen-apposing metal stent (LAMS) with double-pigtail plastic stent (DPPS). METHODS: We retrospectively evaluated consecutive patients with WON who underwent EUS-guided drainage in our endoscopic center over a 9-year period. The amount of solid debris in WON was assessed with computed tomography or magnetic resonance imaging and EUS images. RESULTS: From 2011 to 2019, 84 WON patients were included. In WON with < 20% solid debris, the short-term clinical success of LAMSs (96.8%) was significantly higher than DPPSs (66.7%) (P = 0.03), and LAMSs were safer than DPPSs with less early adverse events (P = 0.02) and late adverse events (P = 0.03). On multivariable analysis, DPPS (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.04-0.65; P = 0.01) and solid debris > 40% (OR, 0.11; 95% CI, 0.02-0.62; P = 0.01) were the predictors for failure of resolution of WON after adjusting for age and cyst size. The number of DPPSs used was significantly higher than LAMSs in managing WONs (P < 0.001). CONCLUSION: For WON with < 20% solid debris, LAMSs might superior to DPPSs in terms of efficacy and safety.


Assuntos
Drenagem/métodos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Pancreatite Necrosante Aguda/patologia , Pancreatite Necrosante Aguda/cirurgia , Plásticos , Stents Metálicos Autoexpansíveis , Stents , Cirurgia Assistida por Computador/métodos , Adulto , Endossonografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Segurança , Tomografia Computadorizada por Raios X , Resultado do Tratamento
12.
J Gastroenterol Hepatol ; 35(4): 624-629, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31788864

RESUMO

BACKGROUND AND AIM: China is a country with high prevalence of Helicobacter pylori (H. pylori) infection, which in turn is closely related to the occurrence of gastric cancer. Therefore, the risks of H. pylori infection and gastric cancer are highly overlapping, and the prevention and treatment of H. pylori infection are necessary to prevent gastric cancer. METHODS: Based on evidence-based medicine and the Delphi method, the National Clinical Medical Research Center for Digestive Disease along with the National Early Gastrointestinal Cancer Prevention and Treatment Center Alliance organized dozens of experts in the fields of digestive diseases, H. pylori research, gastric cancer surgery, epidemiology, health economics, and health management to discuss the relationship between H. pylori eradication and prevention and the treatment of gastric cancer. RESULTS: A preliminary consensus on the relationship between H. pylori infection and gastric cancer, H. pylori eradication and gastric cancer prevention, and H. pylori screening and eradication strategy was reached. The consensus further clarified the relationship between H. pylori and gastric cancer and how to formulate future prevention and control strategies for gastric cancer. CONCLUSIONS: This consensus could provide guidance on early detection, diagnosis, and treatment of H. pylori to reduce the occurrence of gastric cancer in China.


Assuntos
Consenso , Gastrite/tratamento farmacológico , Gastrite/microbiologia , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas/prevenção & controle , China/epidemiologia , Técnica Delphi , Medicina Baseada em Evidências , Gastrite/complicações , Gastrite/epidemiologia , Humanos , Programas de Rastreamento , Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia
13.
BMC Gastroenterol ; 19(1): 54, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30991953

RESUMO

BACKGROUND: Conventionally, disconnected pancreatic duct syndrome is treated surgically. Endoscopic management is associated with lesser morbidity and mortality than that observed with surgery and shows similar success rates. However, limited data are available in this context. We evaluated the efficacy of endotherapeutic management for this syndrome. METHODS: We prospectively obtained data of patients with disconnected pancreatic duct syndrome between September 2008 and January 2016. Demographic and clinical data were assessed, and factors affecting clinical outcomes were statistically analyzed. RESULTS: Thirty-one patients underwent 40 endoscopic transpapillary procedures, and 1 patient developed an infection after prosthesis insertion. Etiological contributors to disconnected pancreatic duct syndrome were abdominal trauma (52%) and acute necrotizing pancreatitis (48%). The median interval between the appearance of pancreatic leaks and disconnected pancreatic duct syndrome was 6.6 months (range 0.5-84 months). The median follow-up after the last treatment procedure was 38 months (range 17-99 months). Patients with complete main pancreatic duct disruption in the body/tail showed a low risk of pancreatic atrophy (P = 0.009). This study highlighted the significant correlation between endoscopic transpapillary drainage and clinical success (P = 0.014). CONCLUSIONS: Disconnected pancreatic duct syndrome is not an uncommon sequel of pancreatic injury, and much of the delayed diagnosis is attributable to a lack of knowledge regarding this disease. Endoscopic transpapillary intervention with ductal stenting is an effective and safe treatment for this condition.


Assuntos
Traumatismos Abdominais/complicações , Drenagem/métodos , Endoscopia , Pancreatopatias/etiologia , Pancreatopatias/cirurgia , Pancreatite Necrosante Aguda/complicações , Adulto , Idoso , Colangiopancreatografia Retrógrada Endoscópica , Drenagem/efeitos adversos , Feminino , Seguimentos , Humanos , Infecções/etiologia , Masculino , Pessoa de Meia-Idade , Pancreatopatias/diagnóstico por imagem , Ductos Pancreáticos/diagnóstico por imagem , Fístula Pancreática/diagnóstico por imagem , Fístula Pancreática/etiologia , Fístula Pancreática/cirurgia , Estudos Retrospectivos , Stents , Síndrome , Resultado do Tratamento , Adulto Jovem
14.
Technol Cancer Res Treat ; 18: 1533033818824314, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30803373

RESUMO

The role of microRNA-132 in human pancreatic ductal adenocarcinomas is still ambiguous. We explored the association between microRNA-132 and pancreatic ductal adenocarcinoma prognosis. The expression of microRNA-132 in 50 pancreatic ductal adenocarcinoma tissue samples and pancreatic ductal adenocarcinoma cell lines was examined, and the association between its expression and pancreatic ductal adenocarcinoma prognosis was assessed. Functional analysis and factors downstream of microRNA-132 were investigated. Kaplan-Meier survival curves showed that high expression of microRNA-132 was a significant prognostic factor for 1-year survival of patients with pancreatic ductal adenocarcinoma ( P = .028). Multivariate analysis for overall survival indicated that high expression of microRNA-132 was an independent prognostic factor for patients with pancreatic ductal adenocarcinoma ( P = .044). Low expression of microRNA-132 was associated with poor prognosis in pancreatic ductal adenocarcinoma. Ectopic expression of microRNA-132 significantly inhibited proliferation and promoted apoptosis of 2 pancreatic ductal adenocarcinoma cell lines. Bioinformatic analysis revealed that microRNA-132 may exert its effects on pancreatic ductal adenocarcinoma through downregulating mitogen-activated protein kinase 3 and nuclear transcription factor Y subunit α. The results of this study further our understanding of the relationship between microRNA-132 and pancreatic ductal adenocarcinoma by showing that microRNA-132 might inhibit the progression of pancreatic ductal adenocarcinoma by regulating mitogen-activated protein kinase and nuclear transcription factor Y subunit alpha.


Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/patologia , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , MicroRNAs/genética , Neoplasias Pancreáticas/patologia , Adenocarcinoma/genética , Adenocarcinoma/terapia , Apoptose , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/terapia , Ciclo Celular , Proliferação de Células , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Prognóstico , Taxa de Sobrevida
15.
Scand J Gastroenterol ; 54(1): 101-107, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30731044

RESUMO

BACKGROUND: To overcome the limitations of using cytological specimen alone for the diagnosis of challenging pancreatic lesions, biopsy needles have been developed to procure histological specimens during EUS, especially for the discrimination of several specific pancreatic tumors requiring adequate histological samples. The aim of this study was to compare the diagnostic yield of EUS-guided 22-gauge (G) fine needle aspiration (FNA) needles and 22G fine needle biopsy (FNB) needles for sampling pancreatic masses. METHODS: We conducted a retrospective study of all EUS-guided sampling performed between November 2012 and April 2016. 422 cases sampled with a 22G FNA needle (N = 254) or a 22G FNB needle (N = 168) were recruited for this study. The specimen quality analyses, technical characteristics, accuracy, sensitivity, specificity, positive predictive values (PPVs), and negative predictive values (NPVs) for the pancreatic masses were reviewed and compared. RESULTS: There was no significant difference in the procurement of adequate histological specimens (75.0% vs. 79.5%; p = .277) or the presence of diagnostic histological specimens (71.3% vs. 77.4%; p = .155) between FNA and FNB groups, respectively. There were also no significant differences in the accuracy, sensitivity, specificity, PPVs, or NPVs of the cytological, histological, and overall analyses for FNA and FNB groups in the diagnosis of pancreatic malignancy. However, 22G biopsy needles demonstrated a better histological diagnostic yield in the discrimination of pancreatic adenocarcinoma and non-adenocarcinoma pancreatic neoplasms than 22G FNA needles (69.8% vs. 57.9%, p = .033). CONCLUSIONS: 22G FNB needle demonstrated a better histological diagnostic yield in the differentiation between pancreatic adenocarcinoma and non-adenocarcinoma pancreatic neoplasms.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/instrumentação , Endossonografia , Agulhas , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , China , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Estudos Retrospectivos , Sensibilidade e Especificidade
16.
Gastroenterology ; 156(3): 722-734.e6, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30342032

RESUMO

BACKGROUND & AIMS: Cachexia, which includes muscle wasting, is a frequent complication of pancreatic cancer. There are no therapies that reduce cachexia and increase patient survival, so it is important to learn more about its mechanisms. The zinc transporter ZIP4 promotes growth and metastasis of pancreatic tumors. We investigated its effects on muscle catabolism via extracellular vesicle (EV)-mediated stimulation of mitogen-activated protein kinase 14 (p38 MAPK). METHODS: We studied nude mice with orthotopic tumors grown from human pancreatic cancer cell lines (AsPC-1 and BxPC-3); tumors were removed 8 days after cell injection and analyzed by histology. Mouse survival was analyzed by Kaplan-Meier curves. ZIP4 was knocked down in AsPC-1 and BxPC-3 cells with small hairpin RNAs; cells with empty vectors were used as controls. Muscle tissues were collected from mice and analyzed by histology and immunohistochemistry. Conditioned media from cell lines and 3-dimensional spheroid/organoid cultures of cancer cells were applied to C2C12 myotubes. The myotubes and the media were analyzed by immunoblots, enzyme-linked immunosorbent assays, and immunofluorescence microscopy. EVs were isolated from conditioned media and analyzed by immunoblots. RESULTS: Mice with orthotopic tumors grown from pancreatic cancer cells with knockdown of ZIP4 survived longer and lost less body weight and muscle mass than mice with control tumors. Conditioned media from cancer cells activated p38 MAPK, induced expression of F-box protein 32 and UBR2 in C2C12 myotubes, and also led to loss of myofibrillar protein myosin heavy chain and myotube thinning. Knockdown of ZIP4 in cancer cells reduced these effects. ZIP4 knockdown also reduced pancreatic cancer cell release of heat shock protein (HSP) 70 and HSP90, which are associated with EVs, by decreasing CREB-regulated expression of RAB27B. CONCLUSIONS: ZIP4 promotes growth of orthotopic pancreatic tumors in mice and loss of muscle mass by activating CREB-regulated expression of RAB27B, required for release of EVs from pancreatic cancer cells. These EVs activate p38 MAPK and induce expression of F-box protein 32 and UBR2 in myotubes, leading to loss of myofibrillar myosin heavy chain and myotube thinning. Strategies to disrupt these pathways might be developed to reduce pancreatic cancer progression and accompanying cachexia.


Assuntos
Caquexia/genética , Proteínas de Transporte de Cátions/genética , Vesículas Extracelulares/metabolismo , Neoplasias Pancreáticas/genética , Proteínas rab de Ligação ao GTP/genética , Animais , Caquexia/patologia , Linhagem Celular Tumoral , Vesículas Extracelulares/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Camundongos , Camundongos Nus , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Pancreatectomia/métodos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Distribuição Aleatória , Valores de Referência , Sensibilidade e Especificidade , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
BMC Med ; 16(1): 214, 2018 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-30463539

RESUMO

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, with increasing incidence. The mortality rate of pancreatic cancer is rising rapidly, and is projected to be the second most common of all malignant tumors by 2030. However, the diagnosis and therapy of pancreatic cancer remain a formidable challenge. Recently, enormous efforts have been made to develop several new methods for the early diagnosis and treatment of pancreatic cancer. We briefly introduce the most groundbreaking advances in pancreatic cancer diagnosis and clinical treatment strategies over the past 15 years, including surgery, chemotherapy, endoscopic therapy, immunotherapy and personalized medicine. The signaling pathways that are altered in the progression of pancreatic cancer, which may be used as therapeutic targets, are also discussed.


Assuntos
Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Humanos , Medicina de Precisão/métodos , Medicina de Precisão/tendências
19.
Oncogene ; 37(45): 6010, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30108331

RESUMO

Since the online publication of the above article, the authors have noted errors in the affiliations. The authors apologise for any inconvenience caused by this error. The html and online pdf versions have now been rectified and carry the corrected paper.

20.
Curr Med Sci ; 38(1): 137-143, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30074163

RESUMO

The different methods in differentiating biliary atresia (BA) from non-BA-related cholestasis were evaluated in order to provide a practical basis for a rapid, early and accurate differential diagnosis of the diseases. 396 infants with cholestatic jaundice were studied prospectively during the period of May 2007 to June 2011. The liver function in all subjects was tested. All cases underwent abdominal ultrasonography and duodenal fluid examination. Most cases were subjected to hepatobiliary scintigraphy, magnetic resonance cholangiopancreatography (MRCP) and a percutaneous liver biopsy. The diagnosis of BA was finally made by cholangiography or histopathologic examination. The accuracy, sensitivity, specificity and predictive values of these various methods were compared. 178 patients (108 males and 70 females with a mean age of 58±30 days) were diagnosed as having BA. 218 patients (136 males and 82 females with a mean age of 61 ±24 days) were diagnosed as having non-BA etiologies of cholestasis jaundice during the follow-up period in which jaundice faded after treatment with medical therapy. For diagnosis of BA, clinical evaluation, hepatomegaly, stool color, serum gamma-glutamyltranspeptidase (GGT), duodenal juice color, bile acid in duodenal juice, ultrasonography (gallbladder), ultrasonography (griangular cord or strip-apparent hyperechoic foci), hepatobiliary scintigraphy, MRCP, liver biopsy had an accuracy of 76.0%, 51.8%, 84.3%, 70.0%, 92.4%, 98.0%, 90.4%, 67.2%, 85.3%, 83.2% and 96.6%, a sensitivity of 83.1%, 87.6%, 96.1%, 73.7%, 90.4%, 100%, 92.7%, 27.5%, 100%, 89.0% and 97.4%, a specificity of 70.2%, 77.5%, 74.8%, 67.0%, 94.0%, 96.3%, 88.5%, 99.5%, 73.3%, 75.4% and 94.3%, a positive predictive value of 69.0%, 72.6%, 75.7%, 64.6%, 92.5%, 95.7%, 86.8%, 98.0%, 75.4%, 82.6% and 98.0%, and a negative predictive value of 83.6%, 8.5%, 95.9%, 75.7%, 92.3%, 100%, 84.2%, 93.7%, 100%, 84.0% and 92.6%, respectively. It was concluded that all the differential diagnosis methods are useful. The test for duodenal drainage and elements is fast and accurate. It is helpful in the differential diagnosis of BA and non-BA etiologies of cholestasis. It shows good practical value clinically.


Assuntos
Atresia Biliar/diagnóstico por imagem , Colestase/diagnóstico por imagem , Icterícia Neonatal/diagnóstico por imagem , Ácidos e Sais Biliares/análise , Atresia Biliar/sangue , Atresia Biliar/complicações , Atresia Biliar/patologia , Biomarcadores/análise , Biomarcadores/sangue , Colangiografia/efeitos adversos , Colangiografia/normas , Colangiopancreatografia por Ressonância Magnética/efeitos adversos , Colangiopancreatografia por Ressonância Magnética/normas , Colestase/sangue , Colestase/etiologia , Colestase/patologia , Diagnóstico Diferencial , Fezes/química , Feminino , Humanos , Lactente , Recém-Nascido , Icterícia Neonatal/sangue , Icterícia Neonatal/etiologia , Icterícia Neonatal/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Masculino , Sensibilidade e Especificidade , Ultrassonografia/efeitos adversos , Ultrassonografia/normas
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