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1.
Support Care Cancer ; 32(2): 121, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38252311

RESUMO

PURPOSE: Data indicates that clinicians might be under-prescribing opioids for patients with chronic cancer pain, and this could impact adequate pain management. Few studies have sought to understand healthcare provider (HCP) perceptions and practices regarding the prescription of opioids for chronic cancer pain. We assessed HCP perceptions and practices regarding opioid prescription for patients with chronic cancer pain since the onset of the COVID-19 pandemic. METHODS: An anonymous cross-sectional survey was conducted among 186 HCPs who attended an opioid educational event in April 2021 and 2022. RESULTS: Sixty-one out of 143 (44%) opioid prescribers reported reluctance to prescribe opioids for chronic cancer pain. In a multivariate logistic model, younger participants (log OR - 0.04, 95% CI - 0.085, - 0.004; p = 0.033) and pain medicine clinicians (log OR - 1.89, CI - 3.931, - 0.286; p = 0.034) were less reluctant, whereas providers who worry about non-medical opioid use were more reluctant to prescribe opioids (log OR 1.58 95% CI 0.77-2.43; p < 0.001). Fifty-three out of 143 (37%) prescribers had experienced increased challenges regarding opioid dispensing at pharmacies, and 84/179 (47%) of all respondents reported similar experience by their patients. Fifty-four out of 178(30%) were aware of opioid-related harmful incidents to patients or their families, including incidents attributed to opioid misuse by a household or family member. CONCLUSION: A considerable number of opioid prescribers were reluctant to prescribe opioids for patients with chronic cancer pain. Many reported challenges regarding dispensing of opioids at the pharmacies. These may be unintended consequences of policies to address the opioid crisis. Future measures should focus on addressing regulatory barriers without undermining the gains already made to combat the opioid crisis.


Assuntos
Dor do Câncer , Dor Crônica , Neoplasias , Transtornos Relacionados ao Uso de Opioides , Humanos , Analgésicos Opioides/uso terapêutico , Dor do Câncer/tratamento farmacológico , Estudos Transversais , Pandemias , Neoplasias/complicações , Dor Crônica/tratamento farmacológico , Pessoal de Saúde
2.
Res Sq ; 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37841840

RESUMO

PURPOSE: Data indicates that clinicians might be under-prescribing opioids for patients with chronic cancer pain, and this could impact adequate chronic pain management. Few studies have sought to understand healthcare provider (HCP) perceptions and practices regarding the prescription of opioids for chronic pain. We assessed HCP perceptions and practices regarding opioid prescription for patients with chronic pain since the onset of the COVID-19 pandemic. METHODS: An anonymous cross-sectional survey was conducted among 186 HCPs who attended an opioid educational event in April 2021 and 2022. RESULTS: 61/143(44%) opioid prescribers reported reluctance to prescribe opioids for chronic pain. In a multivariate logistic model, younger participants (log OR -0.04, 95% CI: -0.085, -0.004; p = 0.033) and pain medicine clinicians (log OR -1.89, CI: -3.931, -0.286; p = 0.034) were less reluctant, whereas providers who worry about non-medical opioid use (NMOU) were more reluctant to prescribe opioids (log OR 1.58 95% CI: 0.77-2.43; p < 0.001). 53/143(37%) respondents had experienced increased challenges regarding opioid dispensing at pharmacies, and 84/179(47%) reported similar experience by their patients. 54/178(30%) HCPs were aware of opioid-related harmful incidents to patients or their families, including incidents attributed to opioid misuse by a household or family member. CONCLUSION: A significant number of opioid prescribers were reluctant to prescribe opioids for patients with chronic pain. Many reported challenges regarding dispensing of opioids at the pharmacies. These may be unintended consequences of policies to address the opioid crisis. Future measures should focus on addressing regulatory barriers without undermining the gains already made to combat the opioid crisis.

3.
Int J Mol Sci ; 24(16)2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37628777

RESUMO

Members of the tripartite motif (TRIM)-containing protein family have been found to be involved in the progression of hepatocellular carcinoma (HCC). TRIM14 exerts a promotive impact on several cancers. This study aimed to explore the function and mechanism of TRIM14 in HCC. TRIM14 expression in HCC tissues and HCC cell lines was detected. The overexpression or knockdown model of TRIM14 was established in HCC cell lines. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, Transwell assay, RT-PCR, Western blot, and immunofluorescence were performed to verify the influence of TRIM14 on cell proliferation, sensitivity to chemotherapy drugs, apoptosis, migration, invasion, and autophagy. A xenograft tumor model was used to confirm the impact of TRIM14 on tumor cell growth. As shown by the data, TRIM14 level was notably higher in the tumor tissues of HCC patients than in the adjacent tissues. The overall survival rate of patients with a high TRIM14 expression was relatively lower than that of patients with a low TRIM14 expression. TRIM14 upregulation enhanced the proliferation, autophagy, migration, and invasion of HCC cells and chemoresistant HCC cells and decreased apoptosis. TRIM14 knockdown contributed to the opposite effects. In in vivo experiments, TRIM14 upregulation bolstered tumor growth. Western blot analysis revealed that TRIM14 upregulation boosted signal transducer and activator of transcription3 (STAT3) and hypoxia-inducible factor-1alpha (HIF-1α) expression, and TRIM14 knockdown suppressed their expression. Moreover, repressing STAT3 and HIF-1α could mitigate the tumor-promoting role of TRIM14 in HCC cells. Overall, TRIM14 facilitated malignant HCC development and induced chemoresistance in HCC cells by activating the STAT3/HIF-1α axis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Carcinoma Hepatocelular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Linhagem Celular , Modelos Animais de Doenças , Proteínas com Motivo Tripartido/genética , Peptídeos e Proteínas de Sinalização Intracelular , Fator de Transcrição STAT3/genética
4.
FASEB J ; 36(12): e22663, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36421017

RESUMO

Regardless of the improvements in diagnostic and therapeutic methods, the clinical outcomes of hepatocellular carcinoma (HCC) patients remain poor. Although accumulating evidence indicates that lncRNAs (long noncoding RNAs) are essential within the control of tumorigenesis and the metastasis of cancer, the underlying mechanisms remain largely unknown. This work explored the pattern of expression and functional significance of a newly found lncRNA, Ewing sarcoma-associated transcript 1 (EWSAT1), in HCC metastasis. The results indicated that EWSAT1 was upregulated significantly in HCC relative to that in normal tissues and was correlated with an aggressive phenotype and low patient survival. Functional experiments demonstrated that EWSAT1 could promote proliferation and HCC cell metastasis both in vitro and in vivo. Mechanistically, EWSAT1 binds directly to Yes-associated protein (YAP), promotes Sarcoma gene (Src)-induced phosphorylation of YAP, facilitates nuclear translocation of YAP, and consequently, activates the transcription of Hippo-YAP signaling target genes involved in cancer evolution. This study found that EWSAT1 plays a crucial role in HCC metastasis and that it has the potential to be a prognosis biomarker and a target for therapeutics.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Sarcoma de Ewing , Humanos , Carcinoma Hepatocelular/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Sarcoma de Ewing/genética , Neoplasias Hepáticas/metabolismo , Regulação Neoplásica da Expressão Gênica
5.
Int J Nurs Pract ; 28(6): e13081, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35855498

RESUMO

AIMS: This meta-analysis aimed to synthesize the available evidence on the effectiveness of psychoeducational interventions on family function among families after stroke. BACKGROUND: Family function may be improved by psychoeducational intervention, but findings about the effect of psychoeducation on family function among families after stroke have been mixed. METHODS: This was a meta-analysis carried out by searching five international electronic databases, including Cochrane Library, PubMed, EMBASE, Web of Science and CINAHL, as well as four national electronic databases, including Chinese Biological Medicine (CBM), China National Knowledge Infrastructure (CNKI), VIP and Wanfang. Two groups of researchers screened the studies independently, assessed the quality of the studies and extracted data. Meta-analysis was performed by using the RevMan 5.3 software. RESULTS: Five studies on psychoeducational interventions were included. Pooled analysis of these studies showed a small effect of the interventions on improving family function (WMD: -0.13, 95% CI: -0.24 to -0.01, P < 0.05). Subgroup analysis showed significant differences between the psychoeducation and control groups at 1 month postintervention (WMD: -0.12, 95% CI: -0.18 to -0.05, P < 0.05) and more than 6 months postintervention (WMD: -0.14, 95% CI: -0.24 to -0.04, P < 0.05). The psychoeducational interventions also had positive effect on improving the problem solving (WMD: -0.22, 95% CI: -0.14 to -0.03, P < 0.05) and communication (WMD: -0.23, 95% CI: -0.41 to -0.05, P < 0.05) functions of the family. There were significant differences in the group of dyad intervention (WMD: -0.14, 95% CI: -0.25 to -0.02, P < 0.05) and the group using face to face method (WMD: -0.58, 95% CI: -0.84 to -0.32, P < 0.05). CONCLUSIONS: Synthesized results demonstrated the favourable effect of psychoeducational interventions on the improvement of the family function among families after stroke, especially in terms of family problem solving and family communication. Future psychoeducational intervention research design should consider the combination of multiple intervention methods and the applicable population of intervention.


Assuntos
Acidente Vascular Cerebral , Humanos , Comunicação , China , Serviços de Saúde
6.
J Clin Lab Anal ; 35(12): e24071, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34741346

RESUMO

BACKGROUND: Liver hepatocellular carcinoma (LIHC) is a lethal cancer. This study aimed to identify the N6 -methyladenosine (m6 A)-targeted long non-coding RNA (lncRNA) related to LIHC prognosis and to develop an m6 A-targeted lncRNA model for prognosis prediction in LIHC. METHODS: The expression matrix of mRNA and lncRNA was obtained, and differentially expressed (DE) mRNAs and lncRNAs between tumor and normal samples were identified. Univariate Cox and pathway enrichment analyses were performed on the m6 A-targeted lncRNAs and the LIHC prognosis-related m6 A-targeted lncRNAs. Prognostic analysis, immune infiltration, and gene DE analyses were performed on LIHC subgroups, which were obtained from unsupervised clustering analysis. Additionally, a multi-factor Cox analysis was used to construct a prognostic risk model based on the lncRNAs from the LASSO Cox model. Univariate and multivariate Cox analyses were used to assess prognostic independence. RESULTS: A total of 5031 significant DEmRNAs and 292 significant DElncRNAs were screened, and 72 LIHC-specific m6 A-targeted binding lncRNAs were screened. Moreover, a total of 29 LIHC prognosis-related m6 A-targeted lncRNAs were obtained and enriched in cytoskeletal, spliceosome, and cell cycle pathways. An 11-m6 A-lncRNA prognostic model was constructed and verified; the top 10 lncRNAs included LINC00152, RP6-65G23.3, RP11-620J15.3, RP11-290F5.1, RP11-147L13.13, RP11-923I11.6, AC092171.4, KB-1460A1.5, LINC00339, and RP11-119D9.1. Additionally, the two LIHC subgroups, Cluster 1 and Cluster 2, showed significant differences in the immune microenvironment, m6 A enzyme genes, and prognosis of LIHC. CONCLUSION: The m6 A-lncRNA prognostic model accurately and effectively predicted the prognostic survival of LIHC. Immune cells, immune checkpoints (ICs), and m6 A enzyme genes could act as novel therapeutic targets for LIHC.


Assuntos
Adenosina/análogos & derivados , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , RNA Longo não Codificante/genética , Adenosina/genética , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/imunologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/imunologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , RNA Longo não Codificante/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
7.
Waste Manag ; 132: 142-150, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34332370

RESUMO

More food waste (FW) is desired to be treated in a certain processing period, while the degradation pattern of biochemical fractions during FW bioevaporation was significantly influenced by the organic loading (OL). Lower OL facilitated the lipids degradation, while higher OL favored the protein degradation. It was the more porous structure and abundant oxygen accelerated the lipids degradation, and the rapid proliferation of aerobic microorganisms compensated for the low protein degradation in lower OL. Detailly, 76.8% of the lipids was degraded in the trial with OL of 1.04 kg VSFW/kg TSBS (Trial A), but in the trial with OL of 3.16 kg VSFW/kg TSBS (Trial C) it was only 0.5%. For protein, the degradation was different that 17.5% of the protein was degraded in Trial A, whereas 69.1% was degraded in Trial C. Lipids degradation contributed 63.0% to the metabolic heat in Trial A, but its contribution in Trial C was only 0.5%. For protein, it contributed 4.1% to the metabolic heat in Trial A, but in Trial C it accounted for 53.6%. In addition, the degradation of carbohydrates (71.6-80.8%) and their contribution to metabolic heat (32.8-45.9%) were comparable in all trials, thus OL had little effect on carbohydrates degradation. Results from this study could provide important guideline for FW practical disposal during their biological treatment.


Assuntos
Eliminação de Resíduos , Reatores Biológicos , Carboidratos , Alimentos
8.
Am J Surg ; 222(2): 383-389, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33388133

RESUMO

BACKGROUND: The definition and prognostic value of a wide resection margin remains controversial. The aim of this study was to assess the relevance of resection margin length for survival following intrahepatic cholangiocarcinoma (ICC) resection. METHODS: Patients scheduled for curative resection for ICC between 2015 and 2018 were identified from an institutional database. Demographic data, pathological margin length, and oncologic outcomes were collected and analyzed. RESULTS: This study included 126 patients, of whom 78% underwent anatomical hepatectomy. The resection margin was <0.5, <1.0, and <1.5 cm in 73 (60%), 92 (73%), and 109 (87%) patients, respectively. A resection margin ≥1.0 cm was associated with favorable overall survival (OS) (HR: 0.403; 95% CI: 0.191-0.854; P = 0.018) and recurrence-free survival (RFS) (HR: 0.436; 95% CI: 0.232-0.817; P = 0.010). In the anatomical hepatectomy group, a resection margin ≥1.0 cm was an independent predictor of superior OS (HR: 0.451; 95% CI: 0.208-0.977; P = 0.043) and RFS (HR: 0.470; 95% CI: 0.242-0.914; P = 0.026). CONCLUSIONS: A resection margin ≥1.0 cm was associated with significantly improved survival in ICC. Therefore, a clear margin of at least 1.0 cm should be achieved during ICC resection.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Margens de Excisão , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
9.
J Cancer ; 12(1): 217-223, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391418

RESUMO

Background: Hepatocellular carcinoma (HCC) is one of the most leading causes of cancer-related mortality worldwide. Immune checkpoint inhibitors (ICIs) have been proved to be beneficial for advanced HCC. Tumor mutational burden (TMB) is an important predictor for efficacy of ICIs. However, the genetic landscape of Chinese HCC patients and the association between TMB and frequently mutated genes of HCC remain unclear. Methods: Whole-exome sequencing data of 369 liver tumors from the Cancer Genome Altas (TCGA) and next generation sequencing (NGS) data of 657 liver tumors from Chinese clinical dataset were included. Results: TP53 (61.8%) was the most frequently mutated gene in the Chinese cohort, followed by CTNNB1 (17.2%), RB1 (13.7%), and LRP1B (12.3%). The PI3K-Akt signaling (11.2%), the Rap1 signaling (8.1%), and Ras signaling (7.7%), were significantly mapped. LRP1B mutations were significantly associated with higher TMB in both TCGA cohort (P = 0.0003) and Chinese cohort (P = 0.0005). And TP53 mutations were also associated with higher TMB in the TCGA and Chinese cohort (P = 0.0005 and 0.0010, respectively). Prognosis analysis performed in TCGA cohort revealed LRP1B mutations were significantly associated with shorter overall survival (OS, median, 20.9 vs 61.7 months; HR, 2.22; P = 0.0012). TP53 mutation was an independent risk factor affecting both OS (HR 1.58, P = 0.0109) and PFS (HR 1.59, P = 0.0027). Conclusions: The results suggest that LRP1B or TP53 mutations are associated with higher TMB and a poor prognostic factor in HCC.

10.
J Transl Med ; 18(1): 273, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32631434

RESUMO

BACKGROUND: The genomic alterations of intrahepatic cholangiocarcinoma (ICC) in the Chinese population have not been fully revealed. Molecular profiling may provide a reference for clinical management, especially targeted therapy. METHODS: A retrospective study was conducted in 122 ICC patients. All patients' samples underwent next-generation sequencing (NGS), which analyzed 417 genes. The genetic characteristics, clinical management and therapeutic responses were analyzed. RESULTS: The most commonly mutated genes were TP53 (34%), KRAS (25%) and ARID1A (17%). Targeted agents were used referring to molecular profiling, in combination with chemotherapy. Twenty-two patients with wild-type KRAS/NRAS/BRAF were treated with cetuximab. The disease control and response rates were 78% and 47%, respectively, which were higher than those achieved with chemotherapy alone (72% and 11%, P = 0.16). Fifty-four patients underwent anti-VEGF treatment with bevacizumab. The disease control and response rates were 85% and 60%, respectively. Better therapeutic efficiency (P = 0.001) and longer progression-free survival (PFS) were observed in the bevacizumab-treated group compared to chemotherapy alone group (15.4 and 6.7 months, respectively; P = 0.04). The PFS of ten patients who underwent hepatectomy after combined treatment with chemotherapy and bevacizumab was longer than that of 139 patients who underwent surgical treatment (28.9 vs 18.0 months, P = 0.03). Two patients (1.6%) had signatures of microsatellite instability (MSI-H), and both benefited from immunotherapy. CONCLUSIONS: This study provides an overview of genetic alterations in Chinese ICC patients and indicates the potential clinical implications for NGS-based personalized therapies.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos , China , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/genética , Humanos , Mutação/genética , Estudos Retrospectivos
11.
Fam Pract ; 37(5): 581-591, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-32270181

RESUMO

BACKGROUND: There have been numerous measurement questionnaires to estimate the level of family resilience. However, we lack published evidence regarding the most appropriate family resilience questionnaire in different adversity domains. OBJECTIVE: This study critically assesses and contrasts the measurement properties of questionnaires measuring family resilience in two domains: health care domain and social domain. METHODS: Ten electronic databases were searched for studies concerning the establishment, adaptation or evaluation of the measurement properties of a family resilience assessment questionnaire. The methodological quality of included studies was assessed using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. On the basis of methodological quality and scoring criteria for the quality of questionnaires, the overall evidence of each questionnaire was rated. RESULTS: A total of 4084 initial studies were obtained, 23 of which met our inclusion criteria assessing 12 different questionnaires. The structural validity (23 studies) and internal consistency (22 studies) were the most frequently used measurement properties. Only two studies tested responsiveness, and the measurement error was not examined in any studies. The Family Resilience Assessment Scale (FRAS) and Italian version of the Walsh Family Resilience Questionnaire (Walsh-IT) showed positive evidence in health care domain. The FRAS performed well in social domain with specific adversity, and the Family Resilience Questionnaire (FRQ) received a good score in social domain without specific adversity. CONCLUSION: For health care domain, we recommend the FRAS and Walsh-IT. For social domain with specific adversity, we recommend the FRAS questionnaire. For social domain without specific adversity, the FRQ is recommended.


Assuntos
Saúde da Família , Resiliência Psicológica , Lista de Checagem , Atenção à Saúde , Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários
12.
Sensors (Basel) ; 19(14)2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31311084

RESUMO

Improperly grown trees may cause huge hazards to the environment and to humans, through e.g., climate change, soil erosion, etc. A proximity environmental feature-based tree health assessment (PTA) scheme is proposed to prevent these hazards by providing guidance for early warning methods of potential poor tree health. In PTA development, tree health is defined and evaluated based on proximity environmental features (PEFs). The PEF takes into consideration the seven surrounding ambient features that strongly impact tree health. The PEFs were measured by the deployed smart sensors surrounding trees. A database composed of tree health and relative PEFs was established for further analysis. An adaptive data identifying (ADI) algorithm is applied to exclude the influence of interference factors in the database. Finally, the radial basis function (RBF) neural network (NN), a machine leaning algorithm, has been identified as the appropriate tool with which to correlate tree health and PEFs to establish the PTA algorithm. One of the salient features of PTA is that the algorithm can evaluate, and thus monitor, tree health remotely and automatically from smart sensor data by taking advantage of the well-established internet of things (IoT) network and machine learning algorithm.


Assuntos
Saúde Ambiental , Internet das Coisas , Aprendizado de Máquina , Redes Neurais de Computação , Algoritmos , Bases de Dados Factuais , Humanos , Internet
13.
Hepatobiliary Surg Nutr ; 8(2): 129-137, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31098360

RESUMO

In addition to hepatocellular carcinoma, metastatic liver cancer (MLC) is another focus of hepatic surgeon. Good outcome of patients with liver metastasis (LM) from colorectal cancer or neuroendocrine tumor have been achieved. Ovarian cancer liver metastasis (OCLM) has its unique oncological characteristics and a variety of metastasis patterns, which brings a challenge to hepatic surgeon. Hepatic surgeons hold different views and techniques from gynecologists, which makes differences in the evaluation and treatment of the disease. We reviewed recent studies and, in combination with our own clinical experience, attempted to introduce the progress of surgical treatment of liver metastases from OC. In our experience, both preoperative imaging and surgical procedures are based on the assurance of R0 resection. R0 cytoreductive surgery (CRS) is the most favorable determinant for the prognosis of OC patients, and R0 liver resection (LR) is a component of R0 CRS. Gynecologists and hepatic surgeons should do their own preoperative and intraoperative evaluation for the extrahepatic and intrahepatic metastasis respectively. During the operation, regardless of the miliary nodules dissemination between the right hemidiaphragm and liver capsule, liver parenchymal infiltration (LPI) or liver parenchymal metastasis (LPM), 1-2 cm resection margin should be emphasized. For patients with liver portal lymph node metastasis (LPLNM), hepatic portal skeletonization should be performed, rather than portal lymph node dissection. The operation should be as radical as possible to ensure the patients to achieve good prognosis.

14.
Cell Physiol Biochem ; 47(6): 2199-2215, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29975948

RESUMO

BACKGROUND/AIMS: The Xi-Huang (XH) formula has been used for breast cancer treatment in traditional Chinese medicine (TCM) since 1740. In this study, we show that, XH extract could suppress the growth of breast cancer cells in vitro and in vivo, and that it preferentially inhibits cell growth of estrogen receptor positive (ER+) breast cancer cells. Presently, little is known about the potential mechanism of XH and our studies aim to elucidate its mechanism in breast cancer treatment. METHODS: Network-based systems biology and molecular docking analyses were performed to predict explicit targets of XH and active ingredients in XH. The effects of XH on cell viability, cell cycle, apoptosis in different breast cancer cell lines were analyzed in vitro. A model of transplanted tumors on nude mice was used to study the anticancer effect in vivo. Various techniques, including western blotting, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, co-immunoprecipitation and immunohistochemical were utilized to assess the expression of targets of XH in vitro and in vivo. RNA sequencing (RNA-seq) was performed to study the gene targets of XH. Furthermore, we analyzed of protein-ligand binding reactions by isothermal titration calorimetry (ITC). RESULTS: Using network-based systems biology and molecular docking analyses, we predicted that the major targets of XH were ERα and HSP90. Moreover, we found that, XH mediated its anti-cancer effects by promoting the disassociation of ERα and HSP90, resulting in the degradation of ERα and blockade of transport of ERα to the nucleus. XH also caused the dissociation of ERα and other oncoproteins via binding to HSP90. Some of the active ingredients in XH share a common cyclopentane hydrogen skeleton and were predicted to target ERα based on the structural similarity. CONCLUSIONS: XH, which has been used since 1740, has antiestrogenic effects in breast cancer via the targeting of ERα.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Receptor alfa de Estrogênio/metabolismo , Proteínas de Neoplasias/metabolismo , Animais , Neoplasias da Mama/patologia , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus
15.
Sci Rep ; 8(1): 7238, 2018 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-29740162

RESUMO

Increasing evidence has shown that Chinese herbal medicine (CHM) has promising therapeutic effects in colorectal cancer (CRC); however, the active ingredients and potential targets remain unclear. In this study, we aimed to investigate the relative molecular targets of the Chinese herbs that have been found effective in treating metastatic CRC (mCRC) based on clinical data and network pharmacology. In multivariate analysis CHM resulted an independent prognostic factor. The hazard ratio was 0.103 (95% confidence interval = 0.064-0.164; P < 0.001). Compared with the non-CHM group, the median survival time of the CHM group was also improved (40 versus 12 months; P < 0.001). Eighteen out of 295 herbs showed significant correlation with survival results (P < 0.05). Bioinformatics analysis indicated that the 18 herbs realize anti-CRC activity mainly through suppressing the proliferative activity of ERBB2, peroxisome proliferator-activated receptor gamma, and retinoid X receptor, suppressing angiogenesis via inhibition of VEGFR and VEGFA expression, inhibiting the phosphatidylinositol-3-kinase/AKT1 signaling pathway directly through SRC and AKT1, and reducing tumor necrosis factor-induced inflammation.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Neovascularização Patológica/prevenção & controle , Adulto , Idoso , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Biologia Computacional , Feminino , Humanos , Metástase Linfática , Masculino , Medicina Tradicional Chinesa/métodos , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Análise Multivariada , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , PPAR gama/antagonistas & inibidores , PPAR gama/genética , PPAR gama/metabolismo , Fosfatidilinositol 3-Quinase/genética , Fosfatidilinositol 3-Quinase/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptores X de Retinoides/antagonistas & inibidores , Receptores X de Retinoides/genética , Receptores X de Retinoides/metabolismo , Estudos Retrospectivos , Transdução de Sinais , Análise de Sobrevida , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/genética , Quinases da Família src/metabolismo
16.
J Surg Oncol ; 117(3): 409-416, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29044541

RESUMO

BACKGROUND AND OBJECTIVES: The Sendai consensus guidelines (SCG) and Fukuoka consensus guidelines (FCG) have been examined for their roles in predicting advanced neoplasia (AN) in pancreatic cystic neoplasm (PCN) patients with mixed results. We aim to evaluate the utilities of both guidelines in a Chinese cohort with preoperatively diagnosed mucinous PCNs. METHODS: One hundred ninety-seven patients who underwent resections from 2008 to 2015 in Zhong Shan Hospital, Fudan University for suspected PCNs were retrospectively reviewed. Receiver operating characteristic (ROC) curves were calculated and compared to measure diagnostic value. RESULTS: Fifty-five patients were diagnosed with AN pathologically. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the SCG high-risk (SCGHR ) criteria were 87.3%, 28.2%, 32.0%, 85.1%, and 44.7%, respectively, and for the FCG high-risk (FCGHR ) criteria, they were 40.0%, 95.8%, 78.6%, 80.5%, and 80.2%, respectively. ROC curve comparison analyses showed that the FCGHR were superior to the SCGHR (P = 0.02). The performance of the FCGHR was enhanced with CA19-9 incorporated (P = 0.004). CONCLUSIONS: The FCG were superior to the SCG in this retrospective analysis, which could be further improved by the incorporation of CA19-9. However, the practical safety remains uncertain because of missed invasive carcinoma cases.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Carcinoma Ductal Pancreático/diagnóstico , Cisto Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Adenocarcinoma Mucinoso/sangue , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/cirurgia , Antígeno CA-19-9/sangue , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgia , Consenso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cisto Pancreático/sangue , Cisto Pancreático/diagnóstico por imagem , Cisto Pancreático/cirurgia , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos
17.
Tumour Biol ; 39(3): 1010428317695913, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28351319

RESUMO

Splicing factor 3b subunit 4, a critical component of pre-message RNA splicing complex, has been reported to play an important part in the tumorigenesis. However, the expression pattern and biological role of splicing factor 3b subunit 4 in pancreatic cancer have never been investigated. In this study, we found that both the messenger RNA ( p < 0.001) and protein level of splicing factor 3b subunit 4 were decreased significantly in pancreatic cancer specimens compared with their adjacent normal tissues. Overexpression of splicing factor 3b subunit 4 in pancreatic cancer cells inhibited cell growth and motility in vitro, while suppressing splicing factor 3b subunit 4 expression promoted the proliferation and migration of pancreatic cancer cells. In addition, splicing factor 3b subunit 4 was found to inhibit the activity of signal transducer and activator of transcription 3 signaling via downregulating the phosphorylation of signal transducer and activator of transcription 3 on a tyrosine residue at position 705. Taken together, these findings demonstrated that splicing factor 3b subunit 4 acted as a suppressive role in pancreatic cancer and indicated that restoring the function of splicing factor 3b subunit 4 might be a strategy for cancer therapy.


Assuntos
Proliferação de Células/genética , Neoplasias Pancreáticas/genética , Fatores de Processamento de RNA/genética , Fator de Transcrição STAT3/biossíntese , Adulto , Idoso , Linhagem Celular Tumoral , Movimento Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Splicing de RNA/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais/genética
18.
Int J Surg Case Rep ; 5(12): 1151-3, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25437661

RESUMO

INTRODUCTION: Intrapancreatic accessory spleen is an uncommon congenital abnormality of the spleen with no indication for surgical intervention. Among the few cases reported, IPAS coexisted with a normal spleen. We here report the first case of IPAS arising a couple years after splenectomy with the appearance of an endocrine tumor of the pancreas. PRESENTATION OF CASE: A 62-year-old female presented with a one-week history of left upper quadrant discomfort. She had splenectomy for the treatment of hypersplenism caused by cirrhotic portal hypertension two years before this admission. Her physical examination was unremarkable and laboratory data was within the normal range. Both the ultrasonography and magnetic resonance image revealed a small oval-shaped mass in the tail of her pancreas with the diameter 2cm or less. A distal pancreatectomy was performed for the suspection of malignant neuroendocrine tumor of the pancreas. An intrapancreatic accessory spleen was confirmed by the pathologic examination. DISCUSSION: Intrapancreatic accessory spleen is one kind of congenital ectopic spleen without indication for operative intervention. We present the case to support that intrapancreatic accessory spleen may enlarge through a compensatory mechanism, and raise the awareness of this intrapacreatic entity to avoid unnecessary surgical operation. CONCLUSION: IPAS should be highly considered as a differential diagnosis while the lesion is no more than 2.5cm in diameter and/or other accessory spleens show around the splenic hilum.

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