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1.
Bioorg Chem ; 95: 103523, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31911305

RESUMO

It has been shown that inclusion of CF3O and CHF2O groups to drug candidates often improve their pharmacological properties, especially metabolic stability, membrane permeability and PK profile. Moreover, the unique non-spherical structure of the OCHF2 group can provide interesting and beneficial characteristics. Accordingly, new 3rd-generation taxoids, bearing 3-OCF3 or 3-OCF2H (and 3-CH3 for comparison) at the C2 benzoate moiety, were synthesized and their potencies against drug-sensitive and drug-resistant cancer cell lines examined. In this study, our previous SAR studies on 3rd-generation taxoids were expanded to disclose that CH3, CF3O and CHF2O groups are well tolerated at this position and enhance potency, especially against MDR-cancer cell lines so that these taxoids can virtually overcome MDR. These new taxoids exhibit up to 7 times higher cytotoxicity (IC50) than paclitaxel against drug-sensitive cancer cell lines (MCF7 and LCC6-WT) and 2-3 orders of magnitude higher potency than paclitaxel against drug-resistant ovarian, breast and colon cancer cell lines with MDR-phenotype (NCI/ADR, LCC6-MDR and LDL-1), as well as pancreatic cancer cell line, CFPAC-1. Since it has been shown that a bulky group at this position reduces potency, it is noteworthy that rather bulky CF3O and CHF2O groups are well tolerated. Molecular modeling analysis indicated the favorable van der Waals interactions of CF3O and CHF2O groups in the binding site. It is also worthy of note that new taxoids, bearing a CHF2O group at the C2 benzoate position (1-06 series), exhibited the highest potencies against MDR-cancer cell lines and cancer stem cell (CSC)-enriched cancer cell lines. These new 3rd-generation taxoids are promising candidates for highly potent chemotherapeutic agents, as well as payloads for tumor-targeting drug conjugates such as antibody-drug conjugates (ADCs).

2.
Surg Endosc ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823047

RESUMO

BACKGROUND: Previous retrospective studies have shown that laparoscopic spleen-preserving D2 total gastrectomy (LSTG) for advanced upper third gastric cancer (AUTGC) is safe. However, all previous studies were underpowered. We therefore conducted a prospective, multicenter study to evaluate the technical safety and feasibility of LSTG for patients with AUTGC. METHODS: Patients diagnosed with AUTGC (cT2-4a, N-/+, M0) underwent LSTG at 19 institutions between September 2016 and October 2017 were included. The number of No. 10 lymph node (LN) dissections, metastasis rates, intraoperative and postoperative complications were investigated. RESULTS: A total of 251 patients were enrolled in the study, and 242 patients were eligible for the per protocol analysis. The average numbers of No. 10 LN dissections and metastases were 2.4 and 0.1, respectively. Eighteen patients (7.4%) had No. 10 LN metastases, and among patients with advanced gastric cancer, the rate of No. 10 LN metastasis was 8.1% (18/223). pN3 status was an independent risk factor for No. 10 LN metastasis. Intraoperative complications occurred in 7 patients, but no patients required conversion to open surgery or splenectomy. The overall postoperative complication rate was 13.6% (33/242). The major complication and mortality rates were 3.3% (8/242) and 0.4% (1/242), respectively. The number of retrieved No. 10 LNs, No. 10 LN metastasis and TNM stage had no significant influence on postoperative complication rates. CONCLUSION: LSTG for AUTGC was safe and effective when performed by very experienced surgeons, this technique could be used in patients who needed splenic hilar lymph node dissection.

3.
Surg Endosc ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31741161

RESUMO

BACKGROUND: As a key landmark during laparoscopic right colectomy, the classification and variation of the gastrocolic trunk of Henle (GTH) remains to be clarified. The aim of this nationwide multicenter study was to describe the characteristics of the GTH intra-operatively during laparoscopic right colectomies. METHODS: Three hundred seventy-one patients who underwent laparoscopic right colectomies from January 2018 to March 2019 in 25 hospitals across China were enrolled in the study. The length of the GTH, the classification with a precise description of confluent tributaries, and other variations were analyzed. RESULTS: Of the 371 patients, 363 had a GTH. The proportion of type-0, type-I, type-II, and type-III was 15.2% (n = 55), 54.8% (n = 199), 25.3% (n = 92), and 4.7% (n = 17), respectively. The average length of the GTH was 8.5 mm, ranging from 2 to 30 mm. CONCLUSIONS: This is the first multicenter study with a large sample by which the GTH was classified based on laparoscopic intraoperative observation. Variations in the GTH were classified into four types based on the number of colic drainage veins (right colic, superior right colic, middle colic, accessory middle colic, and ileocolic veins), among which the right colic vein was the most common. The length of the GTH was relatively short, and thus might carry a risk of bleeding. Further clinical data should be correlated with the characteristics of the GTH.

4.
BMC Med Inform Decis Mak ; 19(1): 193, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615569

RESUMO

BACKGROUND: Several heart failure (HF) risk models exist, however, most of them perform poorly when applied to real-world situations. This study aimed to develop a convenient and efficient risk model to identify patients with high readmission risk within 90 days of HF. METHODS: A multivariate logistic regression model was used to predict the risk of 90-day readmission. Data were extracted from electronic medical records from January 1, 2017 to December 31, 2017 and follow-up records of patients with HF within 3 months after discharge. Model performance was evaluated using a receiver operating characteristic curve. All statistical analysis was done using R version 3.5.0. RESULTS: A total of 350 patients met the inclusion criterion of being readmitted within in 90 days. All data sets were randomly divided into derivation and validation cohorts at a 7/3 ratio. The baseline data were fairly consistent among the derivation and validation cohorts. The variables most clearly related to readmission were logarithm of serum N-terminal pro b-type natriuretic peptide (NT-proBNP) level, red cell volume distribution width (RDW-CV), and Charlson comorbidity index (CCI). The model had good discriminatory ability (C-statistic = 0.73). CONCLUSIONS: We developed and validated a multivariate logistic regression model to predict the 90-day readmission risk for Chinese patients with HF. The predictors included in the model are derived from electronic medical record (EMR) admission data, making it easier for physicians and pharmacists to identify high-risk patients and tailor more intensive precautionary strategies.


Assuntos
Registros Eletrônicos de Saúde , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapia , Readmissão do Paciente , Adulto , Idoso , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Alta do Paciente , Fragmentos de Peptídeos/sangue , Curva ROC , Medição de Risco
5.
J Mater Chem B ; 7(34): 5230-5236, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31378805

RESUMO

Flexible hydrogel-based sensors have attracted significant attention due to promising applications of wearable devices. However, fabricating a flexible hydrogel combining toughness, stickiness, anti-freezing capability and conductivity is still a great challenge. Here, casein and LiCl are successfully introduced into a polyacrylamide hydrogel to prepare a tough and adhesive PAAm/casein hydrogel, which exhibits good mechanical properties and excellent reversible adhesive behavior for diverse materials and human skin. Due to the presence of conductive ions, the PAAm/casein hydrogel exhibits high conductivity (0.0753 S cm-1) and anti-freezing properties (-21 °C). Moreover, the PAAm/casein hydrogel as a flexible wearable strain sensor is sensitive to both large-scale human motions (e.g., joint bending) and tiny physiological signals (e.g., speaking). It is envisioned that the strategy would provide novel inspiration for the development of flexible wearable protein-driven hydrogel devices.

6.
Zhongguo Zhong Yao Za Zhi ; 44(10): 2118-2123, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31355570

RESUMO

The aim of this paper was to investigate the mechanism and effect of psoralen and isopsoralen in the treatment of lipid accumulation in LO2 cells. Human LO2 cells nonalcoholic fatty liver models were established by using palmitic acid( PA). Then psoralen and isopsoralen were administered for intervention. Intracellular triglyceride( TG) and total cholesterol( TC) content,the cell supernatant alanine aminotransferase( ALT) and aspartate aminotransferase( AST) levels were determined by enzyme method. Cell supernatant proinflammatory cytokines( IL-6,TNF-α) and chemokines( IL-8,MCP-1) were determined by ELISA method. Western blot method was conducted to detect the protein expression of intracellular nuclear factor( NF-κB) p65 phosphorylation( p-p65),nonphosphorylated protein( p65),and transforming factor TGF-ß1. Result showed that as compared with the model group,intracellular TG and TC levels,the cell supernatant ALT and AST levels,proinflammatory cytokines and chemokines were decreased( P < 0. 01,P <0. 05); the p-p65/p65 ratio and TGF-ß1 protein expression were also significantly decreased( P< 0. 01,P< 0. 05) in psoralen intervention group. As compared with the model cells,intracellular TG content had no significant changes,but all the other indexes were reduced( P<0. 01,P<0. 05) in the cells of isopsoralen intervention group. Psoralen exhibited better effect than isopsoralen( P< 0. 01,P<0. 05). It is concluded that psoralen could improve the adipogenesis of LO2 cells induced by PA; both psoralen and isopsoralen are effective in ameliorating LO2 cells injury induced by PA,reducing inflammation via inhibiting the activation of NF-κB and down-regulating the expression of TGF-ß1.


Assuntos
Ficusina/farmacologia , Furocumarinas/farmacologia , Metabolismo dos Lipídeos , NF-kappa B/metabolismo , Linhagem Celular , Humanos , Hepatopatia Gordurosa não Alcoólica
7.
PLoS One ; 14(6): e0218619, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31237895

RESUMO

(-)-Incarvillateine (INCA) is a natural product that has garnered attention due to its purported analgesic effects and historical use as a pain reliever in China. α-Truxillic acid monoesters (TAMEs) constitute a class of inhibitors targeting fatty acid binding protein 5 (FABP5), whose inhibition produces analgesia in animal models. The structural similarity between INCA and TAMEs motivated us to assess whether INCA exerts its antinociceptive effects via FABP inhibition. We found that, in contrast to TAMEs, INCA did not exhibit meaningful binding affinities toward four human FABP isoforms (FABP3, FABP4, FABP5 and FABP7) in vitro. INCA-TAME, a putative monoester metabolite of INCA that closely resembles TAMEs also lacked affinity for FABPs. Administration of INCA to mice produced potent antinociceptive effects while INCA-TAME was without effect. Surprisingly, INCA also potently suppressed locomotor activity at the same dose that produces antinociception. The motor suppressive effects of INCA were reversed by the adenosine A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine. Collectively, our results indicate that INCA and INCA-TAME do not inhibit FABPs and that INCA exerts potent antinociceptive and motor suppressive effects at equivalent doses. Therefore, the observed antinociceptive effects of INCA should be interpreted with caution.


Assuntos
Alcaloides/farmacologia , Analgésicos/farmacologia , Locomoção/efeitos dos fármacos , Monoterpenos/farmacologia , Nociceptividade/efeitos dos fármacos , Receptores A2 de Adenosina/metabolismo , Agonistas do Receptor A2 de Adenosina/farmacologia , Antagonistas do Receptor A2 de Adenosina/farmacologia , Animais , Proteínas de Ligação a Ácido Graxo/metabolismo , Humanos , Masculino , Camundongos , Ligação Proteica , Teobromina/análogos & derivados , Teobromina/farmacologia
8.
Invest New Drugs ; 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31124054

RESUMO

Intrinsic chemoresistance is the main reason for the failure of human pancreatic ductal adenocarcinoma (PDAC) therapy. To identify the candidate protein, we compared the protein expression profiling of PDAC cells and its distinct surviving cells following primary treatment with gemcitabine (GEM) and 5-fluorouracil (5-FU) by two-dimensional electrophoresis combined with liquid chromatography-mass spectrometry or mass spectrometry. A total of 20 differentially expressed proteins were identified, and annexin A1 (ANXA1) was analyzed for further validation. The functional validation showed that the downregulation of ANXA1 contributes to GEM and 5-FU resistance in PDAC cells through protein kinase C/c-Jun N-terminal kinase/P-glycoprotein signaling pathway. Our findings provide a platform for the further elucidation of the underlying mechanisms of PDAC intrinsic chemoresistance and demonstrated that ANXA1 may be a valid marker for anticancer drug development.

9.
Ann Pharmacother ; 53(10): 1005-1019, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31129978

RESUMO

Background: Adverse drug outcomes in the elderly have led to the development of lists of potentially inappropriate medications (PIMs), such as the Beers criteria, and these PIMs have been studied widely; however, it is still unclear whether PIM use is predictive of adverse outcomes in older people. Objective: To qualitatively examine the associations between exposure to PIMs from the general Beers criteria and the Screening Tool of Older Persons' Prescriptions list and adverse outcomes, such as adverse drug reactions (ADRs)/adverse drug events (ADEs), hospitalization, and mortality. Methods: Specified databases were searched from inception to February 1, 2018. Two reviewers independently selected studies that met the inclusion criteria, assessed study quality, and extracted data. Data were pooled using Stata 12.0. The outcomes were ADRs/ADEs, hospitalization, and mortality. Results: A total of 33 studies met the inclusion criteria. The combined analysis revealed a statistically significant association between ADRs/hospitalizations and PIMs (odds ratio [OR] = 1.44, 95% CI = 1.33-1.56; OR = 1.27, 95% CI = 1.20-1.35), but no statistically significant association was found between mortality and PIMs (OR = 1.04; 95% CI = 0.75-1.45). It is interesting to note that the results changed when different continents/criteria were used for the analysis. Compared with the elderly individuals exposed to 1 PIM, the risk of adverse health outcomes was much higher for those who took ≥2 PIMs. Conclusion and Relevance: We recommend that clinicians avoid prescribing PIMs for older adults whenever feasible. In addition, the observed associations should be generalized to other countries with different PIM criteria with caution.

10.
Phys Rev E ; 99(2-1): 022120, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30934271

RESUMO

Scale dependence of electrostatic and magnetostatic properties is investigated in the setting of spatially random linear lossless materials with statistically homogeneous and spatially ergodic random microstructures. First, from the Hill-Mandel homogenization conditions adapted to electric and magnetic fields, uniform boundary conditions are formulated for a statistical volume element (SVE). From these conditions, there follow upper and lower mesoscale bounds on the macroscale (effective) electrical permittivity and magnetic permeability. Using computational electromagnetics methods, these bounds are obtained through numerical simulations for composites of two types: (i) two-dimensional (2D) random checkerboard (two-phase) microstructures and (ii) analogous 3D random (two-phase) media. The simulation results demonstrate a scale-dependent trend of these bounds toward the properties of a representative volume element (RVE). This transition from SVE to RVE is described using a scaling function dependent on the mesoscale δ, the volume fraction v_{f}, and the property contrast k between two phases. The scaling function is calibrated through fitting the data obtained from extensive simulations (∼10000) conducted over the aforementioned parameter space. The RVE size of a given microstructure can be estimated down to within any desired accuracy using this scaling function as parametrized by the contrast and the volume fraction of two phases.

11.
Cancer Manag Res ; 11: 1697-1704, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863178

RESUMO

Gastric cancer is the third most common cause of cancer-related deaths and is the fifth highest incidence of cancer worldwide, especially in Eastern Asia, Central and Eastern Europe, and South America. Currently, surgery is the only curative treatment for gastric cancer; however, digestive tract reconstruction after distal gastrectomy for gastric cancer is controversial due to the postoperative complications such as reflux gastritis. There is an increasing trend toward laparoscopic uncut Roux-en-Y (URY) for radical gastrectomy. However, evidence on the feasibility of this procedure in patients undergoing laparoscopic radical distal gastrectomy is still absent. Thus, a prospective randomized trial is warranted. This is a prospective, multicenter, two-arm randomized controlled trial in which 210 patients will be randomly assigned to two groups: laparoscopic URY (n=105) and laparoscopic Billroth II plus Braun anastomosis (n=105). Each participant must be pathologically diagnosed with gastric cancer and undergo laparoscopic radical gastrectomy at Xijing Hospital and other four hospitals. The laparoscopic URY procedure is based on the Billroth II gastrojejunostomy plus Braun anastomosis, and then blocked the jejunum input loop at the stump-jejunal anastomosis. The patients' demographic and pathological characteristics will be recorded. The total and oral nutritional intake, general data, total serum protein, serum albumin, blood glucose, and temperature will be recorded before surgery and at the time of hospitalization. Postoperative adverse events will also be recorded, as well as at follow-up appointments at three months and six months after surgery. The rate of reflux gastritis will represent the primary endpoint, and other secondary endpoints, which are all recorded.

12.
J Org Chem ; 84(7): 4000-4008, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30864430

RESUMO

An "on water" organocatalytic cyanoarylmethylation of aryl acetonitrile to isatins is developed, giving products in high yields and up to excellent diastereoselectivities. A remarkable enhancement of reaction rates and diastereoselectivities by water was observed under mild conditions. Moreover, this approach provides a highly efficient and environmentally benign access to thermodynamic 3-hydroxy-3-cyanomethyl oxindoles.

13.
Chem Commun (Camb) ; 55(22): 3274-3277, 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30810124

RESUMO

Polymer film materials with smart wetting surfaces can be widely used in aerospace, petrochemicals, shipbuilding, automotives, energy saving, environmental protection and other fields. Here, the wettability of conjugated polymer poly(3-hexylthiophene) (P3HT) films was accurately controlled by an electric field polarization technique, and transition of the films from being hydrophobic to hydrophilic was successfully achieved. The water contact angle of the P3HT films could be changed from 105.9° to 75.6° by the effect of the electric field. More importantly, the contact angle of the P3HT films' surfaces could be precisely controlled by adjusting the electric field strength. The molecular orientation of the conjugated polymers under electric field is investigated to explain this novel phenomenon, which will expand the application scope and improve the properties of conjugated polymers greatly.

14.
J Asian Nat Prod Res ; 21(8): 813-819, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29962231

RESUMO

A new diphenolic derivative asperdiphenol A (1), along with nine known compounds (2-10), was isolated from the marine-derived fungus Aspergillus niger 102. Their structures were elucidated on the basis of spectroscopic analysis including NMR and MS spectrometry. Compound 1 was suggested to be a chiral mixture by the specific rotation and chiral HPLC. Compound 1 was evaluated for its anti-inflammatory, antibacterial, and cytotoxic activity.


Assuntos
Aspergillus niger/metabolismo , Ciclopentanos/isolamento & purificação , Fenóis/isolamento & purificação , Animais , Linhagem Celular Tumoral , Ciclopentanos/química , Ciclopentanos/farmacologia , Fermentação , Espectroscopia de Ressonância Magnética , Biologia Marinha , Camundongos , Fenóis/química , Fenóis/farmacologia , Células RAW 264.7
15.
Plant Cell Rep ; 38(2): 243-253, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30535511

RESUMO

KEY MESSAGE: Seed germination rate and oil content can be regulated at theGDSL transcriptional level by eitherAtGDSL1 orBnGDSL1 inB. napus. Gly-Asp-Ser-Leu (GDSL)-motif lipases represent an important subfamily of lipolytic enzymes, which play important roles in lipid metabolism, seed development, abiotic stress, and pathogen defense. In the present study, two closely related GDSL-motif lipases, Brassica napus GDSL1 and Arabidopsis thaliana GDSL1, were characterized as functioning in regulating germination rate and seed oil content in B. napus. AtGDSL1 and BnGDSL1 overexpression lines showed an increased seed germination rate and improved seedling establishment compared with wild type. Meanwhile, the constitutive overexpression of AtGDSL1 and BnGDSL1 promoted lipid catabolism and decreased the seed oil content. While RNAi-mediated suppression of BnGDSL1 (Bngdsl1) in B. napus improved the seed oil content and decreased seed germination rate. Moreover, the Bngdsl1 transgenic seeds showed changes in the fatty acid (FA) composition, featuring an increase in C18:1 and a decrease in C18:2 and C18:3. The transcriptional levels of six related core enzymes involved in FA mobilization were all elevated in the AtGDSL1 and BnGDSL1 overexpression lines, but strongly suppressed in the Bngdsl1 transgenic line. These results suggest that improving the seed germination and seed oil content in B. napus could be achieved by regulating the GDSL transcriptional level.


Assuntos
Brassica napus/crescimento & desenvolvimento , Brassica napus/genética , Germinação/genética , Óleos Vegetais/metabolismo , Proteínas de Plantas/química , Sementes/crescimento & desenvolvimento , Sementes/genética , Transcrição Genética , Motivos de Aminoácidos , Sequência de Aminoácidos , Arabidopsis/genética , Ácidos Graxos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Metabolismo dos Lipídeos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Plântula/genética , Plântula/crescimento & desenvolvimento
16.
Cell Death Dis ; 10(1): 2, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30578411

RESUMO

CUL1 is an essential component of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex. Our previous study has showed that CUL1 is positively associated with poor overall and disease-specific survival of breast cancer patients. Here, we further explored its roles in breast cancer metastasis. Our data showed that CUL1 significantly promoted breast cancer cell migration, invasion, tube formation in vitro, as well as angiogenesis and metastasis in vivo. In mechanism, the human gene expression profiling was used to determine global transcriptional changes in MDA-MB-231 cells, and we identified autocrine expression of the cytokines CXCL8 and IL11 as the target genes of CUL1 in breast cancer cell migration, invasion, metastasis, and angiogenesis. CUL1 regulated EZH2 expression to promote the production of cytokines, and finally significantly aggravating the breast cancer cell metastasis and angiogenesis through the PI3K-AKT-mTOR signaling pathway. Combined with the previous report about CUL1, we proposed that CUL1 may serve as a promising therapeutic target for breast cancer metastasis.


Assuntos
Comunicação Autócrina , Neoplasias da Mama/metabolismo , Proteínas Culina/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Regulação Neoplásica da Expressão Gênica , Interleucina-11/biossíntese , Interleucina-8/biossíntese , Proteínas de Neoplasias/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proteínas Culina/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Interleucina-11/genética , Interleucina-8/genética , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Proteínas de Neoplasias/genética
17.
Chin J Cancer Res ; 30(5): 500-507, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30510361

RESUMO

Objective: Infra-pyloric artery (IPA) is an important anatomical landmark in treatment of gastric cancer and is the key vessel for pylorus-preserving gastrectomy and subgroup of infra-pyloric lymph nodes. However, its anatomical variation is not thoroughly understood. Our study aimed to clarify the origination of the IPA. Methods: We did this prospective, multicenter, open-label, observational study at gastric surgery departments of 34 hospitals in China. Gastric cancer patients aged 18 years or older and scheduled to undergo elective total or distal gastrectomy were assigned. During the surgery, IPA dissecting and exposing the origination point with photographs or video clips were required. The primary outcome was the origination of the IPA. Analysis of variance, χ2 tests and Fisher's tests were used to analyze the differences between groups. The study is registered at Clinicaltrials.gov (No. NCT03071237). Results: Between May 8 and July 31, 2017, 429 patients were assigned for the study, and 419 (97.7%) patients had the IPA dissected and recorded through photograph or video and were included in the primary outcome analysis. The median age was 62 years old, and 73.7% were male. Among the patients, 78.5% received laparoscopic surgery. Single IPA origination was identified in 398 (95.0%) patients, including gastroduodenal artery (GDA) in 154 (36.8%) patients, anterior superior pancreaticoduodenal artery (ASPDA) in 130 (31.0%) patients, and right gastroepiploic artery (RGEA) in 114 (27.2%) patients. Fifteen (3.6%) patients were identified with multiple IPA and 6 (1.4%) patients were identified as IPA absence. The differences in the distribution of surgical approach (P=0.003) and geographic area (P=0.030) were statistically significant. No difference was shown in sex, age, gastrectomy type, tumor location, and clinical T, N and M stage. Conclusions: Our study found that the IPA originates from GDA, ASPDA and RGEA in similar proportions. Laparoscopic surgery may be more helpful in dissection of the IPA than open surgery.

18.
Nat Biotechnol ; 36(9): 847-856, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30102295

RESUMO

The efficacy of chimeric antigen receptor (CAR) T cell therapy against poorly responding tumors can be enhanced by administering the cells in combination with immune checkpoint blockade inhibitors. Alternatively, the CAR construct has been engineered to coexpress factors that boost CAR-T cell function in the tumor microenvironment. We modified CAR-T cells to secrete PD-1-blocking single-chain variable fragments (scFv). These scFv-secreting CAR-T cells acted in both a paracrine and autocrine manner to improve the anti-tumor activity of CAR-T cells and bystander tumor-specific T cells in clinically relevant syngeneic and xenogeneic mouse models of PD-L1+ hematologic and solid tumors. The efficacy was similar to or better than that achieved by combination therapy with CAR-T cells and a checkpoint inhibitor. This approach may improve safety, as the secreted scFvs remained localized to the tumor, protecting CAR-T cells from PD-1 inhibition, which could potentially avoid toxicities associated with systemic checkpoint inhibition.


Assuntos
Receptor de Morte Celular Programada 1/imunologia , Receptores de Antígenos Quiméricos/imunologia , Anticorpos de Cadeia Única/imunologia , Linfócitos T/imunologia , Animais , Humanos , Camundongos , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Asian J Androl ; 20(6): 587-592, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30004039

RESUMO

Once-daily tadalafil administration has been well established; however, studies about tadalafil once-daily treatment in the Chinese population are lacking. In this phase 4, postmarketing study, we ascertained the long-term safety and effectiveness of tadalafil 2.5 mg and 5.0 mg once daily in Chinese men with erectile dysfunction (n = 635). The primary endpoint of the study was safety at 12 months as assessed by the proportion of patients experiencing at least one treatment-emergent adverse event (serious or nonserious). The secondary endpoints included safety and effectiveness, measured by the International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores. Similar adverse events to the known safety profile of tadalafil, such as nasopharyngitis, upper respiratory tract infection, headache, and dizziness, were detected. No new cardiovascular safety concerns were observed. After 3 months of treatment, significant increases in IIEF-EF domain scores were detected for both 2.5-mg (least squares [LS] mean change: 6.3; 95% confidence interval [CI]: 5.4-7.1; P < 0.001) and 5.0-mg (LS mean change: 7.4; 95% CI: 6.8-7.9; P < 0.001) tadalafil doses, and significance was maintained up to 12 months. In addition, approximately 40% of patients regained normal erectile function (IIEF-EF ≥26) following 1 year of tadalafil once-daily treatment. The findings in this study provide evidence for the extended effectiveness and tolerability of tadalafil, demonstrating no new safety concerns, in a Chinese population and make once-daily tadalafil administration a viable option for improving sexual performance and satisfaction in Chinese men with erectile dysfunction.


Assuntos
Disfunção Erétil/tratamento farmacológico , Inibidores da Fosfodiesterase 5/efeitos adversos , Inibidores da Fosfodiesterase 5/uso terapêutico , Tadalafila/efeitos adversos , Tadalafila/uso terapêutico , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Inibidores da Fosfodiesterase 5/administração & dosagem , Vigilância de Produtos Comercializados , Estudos Prospectivos , Tadalafila/administração & dosagem , Resultado do Tratamento , Adulto Jovem
20.
J BUON ; 23(3): 820-825, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30003757

RESUMO

PURPOSE: The purpose of this study was to analyze the clinical efficacy and complications of endoscopic submucosal dissection (ESD) and laparoscopic resection of stromal tumors, and to explore the clinical value and complications of stromal tumors treated with ESD. METHODS: 146 patients with gastric stromal tumors (GSTs) treated in our hospital from January 2012 to January 2016 were retrospectively analyzed. Patients were divided into the ESD group and the laparoscopic surgery group (LS). The operation time, postoperative recovery time of diet, postoperative exhaust time, etc were observed and analyzed. All the measurement indexes were described as mean ± standard deviation. The t-test of two independent samples was used for the hypothesis test. Chi-square test was used for comparison of the percent data between the two groups and p<0.05 indicated significant difference. RESULTS: The postoperative diet recovery time, postoperative exhaust time, hospital stay and hospitalization cost of the ESD group were better compared with the LS group (p<0.001). There was no significant difference in operative time between the ESD and LS group (p>0.05), while the operation time in ESD group was longer than in the LS group (p<0.05). The operation time of gastric body and antrum stromal tumors was shorter than in the ESD group group (p<0.05). There were no significant differences in tumor diameter, mitotic number and Flether classification between the groups (p>0.05). No significant difference in the incidence of postoperative bleeding, incision infection and recurrence rate was noticeable between the groups (p>0.05). CONCLUSIONS: Endoscopic treatment of GSTs is safe and feasible, and may be better than laparoscopic resection.


Assuntos
Neoplasias Gastrointestinais/cirurgia , Tumores do Estroma Gastrointestinal/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Feminino , Gastroscopia/métodos , Humanos , Laparoscopia/métodos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento
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