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1.
Exp Biol Med (Maywood) ; : 15353702211038511, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34514884

RESUMO

In breast cancer, tumor-associated macrophages with activated phenotypes promote tumor invasion and metastasis. The more aggressive mesenchymal-like breast cancer cells have a selective advantage, skewing macrophages toward the more immunosuppressive subtype. However, the mechanism underlying this shift is poorly understood. Cyclin D1b is a highly oncogenic variant of cyclin D1. Our previous study showed that non-metastatic epithelial-like breast cancer cells were highly metastatic in vivo when cyclin D1b was overexpressed. The present study determined whether cyclin D1b contributed to the interaction between breast cancer cells and macrophages. The results showed that cyclin D1b promoted the invasion of breast cancer cells in vitro. Specifically, through overexpression of cyclin D1b, breast cancer cells regulated the differentiation of macrophages into a more immunosuppressive M2 phenotype. Notably, tumor cells overexpressing cyclin D1b activated macrophages and induced migration of breast cancer cells. Further investigations indicated that SDF-1 mediated macrophage activation through breast cancer cells overexpressing cyclin D1b. These results revealed a previously unknown link between aggressive breast cancer cells and Tumor-associated macrophages, and highlighted the importance of cyclin D1b activity in the breast cancer microenvironment.

2.
Cancer Treat Res Commun ; 25: 100211, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33113437

RESUMO

PURPOSE: Triple-negative breast cancer (TNBC) is known for its higher recurrence rate in short-term (3-5 years) follow-up and limited systemic therapeutic methods (chemotherapy). Current literature debates over whether chemotherapy should be given to TNBC with a very early disease stage (T1a/bN0). This meta-analysis aimed to compare short-term recurrence rate between patients receiving adjuvant chemotherapy or not for this population. METHODS: We performed a comprehensive search in databases including PubMed, Web of Science, Embase, and Cochrane library from January 2008 to December 2019. Raw data on local or distance recurrence events was extracted, odds ratio (OR) values, 95% confidence interval (CI) values, and P values were then calculated. RESULTS: 9 studies out of 426 were included in the meta-analysis. Our main results showed that breast cancer recurrence rate in T1a/bN0 TNBC patients receiving chemotherapy was significantly lower than those without chemotherapy (OR 0.54, 95% CI 0.37-0.78, P = 0.001). Similar results were detected in the T1b group (OR 0.45, 95% CI 0.26-0.78). The main result remained stable after sensitivity analysis. No significant publication bias was found. CONCLUSIONS: Our results revealed that adjuvant chemotherapy reduced recurrence rate for T1mi/a/bN0 TNBC, especially for T1bN0. The benefit of chemotherapy for T1mi/aN0 disease is still debated.

3.
Cancer Lett ; 493: 236-244, 2020 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-32898601

RESUMO

Tumors harbor diverse compartments of cells with distinct metabolic properties and phenotypes, but the mechanism by which metabolic commensalism among distinct subsets of cancer cells affects tumor progression remains unclear. Colorectal cancer (CRC) has been reported to consist of cancer stem cells (CSCs) and differentiated cancer cells (non-CSCs). In the present study, organoid models were employed to show that CSCs and non-CSCs in CRC were characterized by distinct metabolic phenotypes. Treatment with either non-CSC-derived conditioned medium or exogenous lactate enhanced organoid-forming and tumor-initiating capacity of CSCs. In tumor regeneration assays with co-implanted CSCs and non-CSCs, the tumor-initiating activity was reduced when either monocarboxylate transporter (MCT)4 in non-CSCs or MCT1 in CSCs was silenced or inhibited. Mechanistically, oxiadative phosphorylation-derived reactive oxygen species in CSCs activated AKT-Wnt/ß-catenin signaling, which could be induced by lactate from non-CSCs. Overall, these results suggest that CSCs and non-CSCs possess distinct metabolic profiles and, unexpectedly, non-CSC-originated lactate promotes self-renewal of CSCs and thus contributes to CRC progression. Our findings establish a rationale for developing novel therapies targeting the metabolic commensalism between different cell populations in CRC.


Assuntos
Neoplasias Colorretais/patologia , Ácido Láctico/metabolismo , Células-Tronco Neoplásicas/patologia , Organoides/transplante , Animais , Diferenciação Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Transplante de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Organoides/citologia , Organoides/metabolismo , Fosforilação Oxidativa , Células Tumorais Cultivadas , Via de Sinalização Wnt
4.
Cell Death Dis ; 11(7): 610, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737283

RESUMO

Tumor heterogeneity is an important feature of malignant tumors, and cell subpopulations may positively interact to facilitate tumor progression. Studies have shown that hypoxic cancer cells possess enhanced metastatic capacity. However, it is still unclear whether hypoxic cancer cells may promote the metastasis of normoxic cells, which have greater access to the blood circulation. When cocultured with hypoxic CRC cells or treated with hypoxic CRC cell-derived CM, normoxic CRC cells possessed increased metastatic capacity. Furthermore, hypoxic CRC cell-derived CM was enriched in interleukin 8. Hypoxic CRC cell-derived CM and recombinant human IL-8 both enhanced the metastatic capacity of normoxic cells by increasing the phosphorylation of p65 and then by inducing epithelial-mesenchymal transition. Knockdown of IL-8 in hypoxic CRC cells or the use of an anti-IL-8 antibody attenuated the CM- or rhIL-8-induced prometastatic capacity of normoxic CRC cells. Inhibition or knockdown of p65 abrogated IL-8-induced prometastatic effects. Most importantly, hypoxia-treated xenograft tumors enhanced the metastasis of normoxic CRC cells. Hypoxic CRC cell-derived IL-8 promotes the metastatic capacity of normoxic cells, and novel therapies targeting the positive interactions between hypoxic and normoxic cells should be developed.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Interleucina-8/metabolismo , Transdução de Sinais , Fator de Transcrição RelA/metabolismo , Hipóxia Tumoral , Hipóxia Celular , Linhagem Celular Tumoral , Humanos , Invasividade Neoplásica , Metástase Neoplásica , Comunicação Parácrina
5.
Cryobiology ; 96: 45-49, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32861699

RESUMO

Patient derived xenograft (PDX) models provide an efficient way to study anti-tumor drug efficacy. In this respect, it is essential to study the optimal method needed to cryopreserve the starting cells obtained from tumor samples for PDX model generation. Cryopreservation of cells prior to xenografting is necessary for cross-verification of results obtained by xenografting and also for practical planning of experiments. In the present work, we studied the cryopreservation of colorectal carcinoma (CRC) cells isolated from patient tumor samples for generating their patient derived xenograft models. CRC therapeutics study is essential for early stage intervention and treatment of the disease. CRC cell lines do not ideally depict the molecular characteristics of patient CRC tumor samples. This necessitates the generation of CRC PDX models for drug discovery. We show that CRC cells isolated from patient tumor samples have comparable recovery, viability and growth with both conventional cryopreservation methods as well as Fibulas BioFlash Drive™. However, xenograft tumor formation was much more effective with Fibulas BioFlash Drive™ cryopreserved cells than with cells cryopreserved with conventional methods. Therefore, we put forward an effective way to cryopreserve primary cells obtained from patient tumor samples for PDX model generation in this study.


Assuntos
Neoplasias Colorretais , Criopreservação , Animais , Neoplasias Colorretais/tratamento farmacológico , Criopreservação/métodos , Características da Família , Xenoenxertos , Humanos , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Medicine (Baltimore) ; 99(22): e20511, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481473

RESUMO

BACKGROUND AND PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) usually experience recurrent acute exacerbations. These patients, especially those with stable COPD, require an effective intervention for treating exacerbations. This study aimed to evaluate the efficacy of Compound Caoshi silkworm granules (CCSGs) in stable COPD patients and to investigate their potential mechanism. METHODS: A randomized controlled trial was performed at Jinhua Hospital, Zhejiang University. Patients were enrolled in this study if they met the criterion of stable COPD. A total of 40 patients were randomly divided into the following 2 groups: Group A (n = 20, routine treatment (RT) group) and Group B (n = 20, RT plus CCSGs [RT plus CCSGs] group). The duration of treatment was 3 months. Stool samples were collected from all patients on day 0 and the gut microbiota was analyzed using 16s rRNA sequencing. The St. George's Respiratory Questionnaire (SGRQ) scores and lung function were assessed at month 0 and month 3. RESULTS: The components of gut microbiota differed between stable COPD patients and the healthy population. The RT plus CCSGs group showed improved SGRQ scores compared to the RT group. There was no difference in forced expiratory volume-one second, forced vital capacity, and forced expiratory volume-one second/forced vital capacity between the two groups. Furthermore, the abundance of gut microbiota in patients with the top 10 SGRQ scores (Group N) differed from the abundance of gut microbiota in those with the lowest 10 SGRQ scores (Group T). CONCLUSION: CCSGs have beneficial effects in the improvement of symptoms in stable COPD patients over a 3-month treatment period. The potential underlying mechanism may be attributable to the difference in gut microbiota among patients. However, more research is needed to confirm this conclusion.


Assuntos
Bombyx , Microbioma Gastrointestinal , Proteínas de Insetos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Masculino , Testes de Função Respiratória
7.
World J Clin Cases ; 8(4): 798-805, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32149063

RESUMO

BACKGROUND: Mesenteric phlebosclerosis (MP) is a rare disease of the colon. The clinical manifestations of this disease are nonspecific and it may easily be misdiagnosed. We report a case of MP with amyloidosis in the colonic vessel walls in a patient with hypertension who had been consuming Chinese medicinal liquor for 10 years. We also review the relevant literature and summarize the characteristics of MP in patients in mainland China. CASE SUMMARY: A 64-year-old man was referred to our department from his primary hospital because of abdominal pain, diarrhea, and fever for almost 10 d. Computed tomography showed colon wall thickening, with threadlike calcifications in the mesenteric vein in the transverse colon. Colonoscopy revealed purple-blue mucosa with multiple ulcers in the ascending and transverse colon. Biopsy showed thickening and calcification of the vein walls, perivascular and mucosal collagen degeneration, and amyloidosis. The patient had been consuming Chinese medicinal liquor, mainly that made from gardenia fruit, for 10 years. Based on these results, a diagnosis of MP with amyloidosis was made. After conservative treatment, the patient's discomfort subsided and he was followed closely. The use of Chinese herbal medicine was suspected to play a role in the pathogenesis of MP. CONCLUSION: The clinical manifestations of MP are nonspecific. Recognition of its typical imaging findings, including multiple calcifications on computed tomography and purple-blue mucosal discoloration on colonoscopy, is vital.

8.
J Appl Clin Med Phys ; 21(3): 45-51, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32043810

RESUMO

PURPOSE: Prescription practice in SRS plans for brain tumors differs significantly for different modalities. In this retrospective study, the strategies to optimize SRS plans for brain tumors with volumetric arc therapy (VMAT) were presented. METHODS: Fifty clinically treated cases were stratified by the maximum target size into two groups (≥ 2 cm in 25 cases and <2 cm but ≥1 cm in 25 cases), which were optimized using traditional LINAC MLC-based approaches with the average prescription isodose line (P-IDL) of (91.4 ± 0.6)%. Four to five plans have been created for each case with variation of the P-IDL from 65% to 90%. The optimization strategies to select an optimal P-IDL, to use tuning structures within the target and beyond as well as to use NTO (normal tissue objectives), were applied to all new plans. RESULTS: The optimal P-IDL was found to be around 75%. After applying the new optimization strategies with an average P-IDL of 74.8%, the mean modified gradient index (mGI) and V12 were reduced by 25% and 35%, respectively for both groups. The Paddick conformity index (PCI) was averagely improved by 8%. The average homogeneity index (HI) and focal index (FI) were increased by 22% and 50%, respectively. The mGI was inversely proportional to the PTV volumes. The shape of the dose distribution in target was also changed from concave to convex. The comparison of PCI with historical data from other institutes and modalities shows that the plans in this study have the best conformity near the target. CONCLUSIONS: With the new optimization strategies for VMAT SRS plan of brain tumor more conformal plans in both high and intermediate dose region (~50% of the PD) were created, in which the dose in the core of the target was notably increased while V12 and mGI were significantly decreased, and PCI was improved. The mGI was inversely proportional to the PTV volumes. The optimal P-IDL is around 75%. The average PCI is the best in this study compared with the published historical data. These strategies are applicable to treatment planning for multiple brain and liver tumors where sparing the tissue peripheral to the target is critical.


Assuntos
Neoplasias Encefálicas/cirurgia , Órgãos em Risco/efeitos da radiação , Radiocirurgia/normas , Planejamento da Radioterapia Assistida por Computador/normas , Radioterapia de Intensidade Modulada/métodos , Neoplasias Encefálicas/patologia , Humanos , Radiocirurgia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos
9.
Appl Opt ; 58(36): 9861-9869, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31873631

RESUMO

It is important to enhance the contrast and remove the speckle noise for optical coherence tomography (OCT) images. In this paper, we propose a selective retinex enhancement method based on the fuzzy c-means (FCM) clustering algorithm to enhance only the structure part in OCT images and combines with the block-matching 3D (BM3D) algorithm for filtering. In the proposed selective retinex enhancement method, we first calculate the feature image of the original image, which includes the mean value and standard deviation of each pixel in the original image and its correlation image. Second, by applying the FCM clustering algorithm to the feature image, a mask is generated that can distinguish the structure part from the background part in the OCT image. Then, the mask is applied to the multi-scale retinex algorithm, and only the structure part in the OCT image is enhanced. Moreover, the BM3D method is applied to filter the enhanced image. Experimental results demonstrate that the proposed method performs impressively in improving the contrast and removing the speckle noise of OCT images, and it provides better quantitative performance in terms of signal-to-noise ratio, contrast-to-noise ratio, equivalent number of looks, and the edge preservation parameter $ \beta $ß.

10.
BMC Infect Dis ; 19(1): 637, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315559

RESUMO

BACKGROUND: Rat bite fever (RBF), a severe infectious disease, can result from transmission of the pathogen Streptobacillus moniliformis (S. moniliformis) by rat bite. RBF diagnosis can be overlooked. CASE PRESENTATION: We present a case of RBF in a Chinese patient who was infected with S. moniliformis in mainland China. Meta-next generation sequencing (mNGS) was used to identify potential pathogens and detected S. moniliformis genome sequences in the pustular sample in less than 72 h. Then the diagnosis was validated by polymerase chain reaction analysis. Despite having severe RBF with complications, this 54-year-old male patient was successfully cured with penicillin as a result of timely pathogen-based diagnosis. CONCLUSIONS: Physicians should inquire about recent rat exposure and consider the possibility of RBF when a patient develops unexplained fever and rashes. mNGS is a new diagnostic technology and may identify RBF pathogens even when blood culture results are negative.


Assuntos
Febre por Mordedura de Rato/etiologia , Streptobacillus/patogenicidade , Animais , China , Exantema/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Penicilinas/uso terapêutico , Febre por Mordedura de Rato/tratamento farmacológico , Febre por Mordedura de Rato/microbiologia , Ratos , Streptobacillus/genética
11.
Int J Oncol ; 54(3): 893-904, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30664193

RESUMO

Three­dimensional (3D) cultures are indispensable for capturing tumor heterogeneity in colorectal cancer (CRC) in vitro. Although 3D cultures (such as sphere­forming assay and organoid culture) can partially preserve the morphological and molecular characteristics of primary CRC, whether these 3D cultures maintain the long­term stemness of cancer stem cells (CSCs) remains largely unknown. In the present study, spheres and organoids were generated side by side using individual primary CRC specimens, then respectively processed as serial passages. The results revealed that during serial passages, the percentage of CSCs (such as cluster of differentiation­133+ and Wnt+ cells) in organoids and the tumor­initiating capacity of organoid­derived cells were constant, while they gradually increased in the sphere­derived cells. Furthermore, during serial passages, resistance to chemotherapeutic agents (including 5­fluorouracil and oxaliplatin) in sphere­ and organoid­derived cells was evaluated. The results indicated that the percentage of chemoresistant cells was constant in serial organoid cultures; however, it gradually increased in the serial sphere­forming assays. Taken together, the results of the present study comprehensively demonstrate that, with regard to long­term culture in vitro, organoid culture may be useful in maintaining tumor heterogeneity and the levels of chemoresistant cells, while the sphere formation assay enriches for CSCs and chemoresistant cells.


Assuntos
Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos , Células-Tronco Neoplásicas/patologia , Organoides/patologia , Técnicas de Cultura de Tecidos/normas , Animais , Antineoplásicos/farmacologia , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Humanos , Camundongos , Camundongos SCID , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Organoides/efeitos dos fármacos , Organoides/metabolismo , Células Tumorais Cultivadas , Proteínas Wnt/metabolismo
12.
Clin Nutr ; 38(6): 2552-2557, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30573353

RESUMO

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is the most predominant chronic liver disease worldwide. Effect of coffee on NAFLD risk and its potential dose-response patterns were explored in the study. DESIGN: PubMed, Web of Science, MEDLINE, Cochrane and Embase were searched up to 10 April 2018. We performed pair-wise meta-analysis of <1 cup per day vs. 1-2 cups per days or >2 cups per day to pool the relative risks (RRs) and corresponding 95% confidence intervals (CIs). And dose-response analysis was used to estimate relationship of NAFLD occurrence with coffee intake. RESULTS: Seven articles were included with 4825 cases and 49,616 non-cases. Compared with <1 cup, 1-2 cups or >2 cups of coffee consumption per day were not significantly associated with NAFLD occurrence, and RR were 0.97 (95% CI: 0.85-1.11) and 0.88 (95%CI: 0.72-1.06). However, the summary RR of the highest versus lowest coffee consumption was 0.94 (95% CI: 0.92-0.97). Dose-response meta-analysis presented a non-linearity curve relationship of coffee and NAFLD occurrence while coffee consumption >3 cups per day reduced NAFLD significantly. CONCLUSION: Coffee intake level more than 3 cups was observed lower risk of NAFLD than <2 cups per day. Although the risk of NAFLD was inversely associated with coffee consumption, while relevance may not be very close and more observational studies would be needed to verify the relationship of coffee and NAFLD.


Assuntos
Café , Dieta/estatística & dados numéricos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
13.
Cell Physiol Biochem ; 51(5): 2111-2122, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30522100

RESUMO

BACKGROUND/AIMS: Sestrin 2 is associated with the pathophysiology of several diseases. The aim of this study was to investigate the effects and potential mechanisms of Sestrin 2 in rat hepatic stellate cells (HSCs) during liver fibrogenesis. METHODS: In this study, Sestrin 2 protein expression was detected in rat HSC-T6 cells challenged with transforming growth factor-ß (TGF-ß) and in mice treated with carbon tetrachloride (CCl4), a well-known model of hepatic fibrosis. Next, HSC-T6 cells and fibrotic mice were transfected with lentivirus. The mRNA expression levels of markers of liver fibrosis [alpha-smooth muscle actin (α-SMA) and collagen 1A1 (Col1A1)] were analyzed by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Cell death and proliferation were evaluated by the MTT assay, and biochemical markers of liver damage in serum [alanine transaminase (ALT) and aspartate transaminase (AST)] were also measured using a biochemical analyzer. Histopathological examination was used to evaluate the degree of liver fibrosis, and protein expression [phospho-adenosine monophosphate-activated protein kinase (p-AMPK), AMPK, phospho-mammalian target of rapamycin (p-mTOR), and mTOR] was determined by western blotting. RESULTS: We found that Sestrin 2 was elevated in both the HSC-T6 cell and hepatic fibrosis models. In vitro, overexpression of Sestrin 2 attenuated the mRNA levels of α-SMA and Col1A1, suppressed α-SMA protein expression, and modulated HSC-T6 cell proliferation. In vivo, overexpression of Sestrin 2 reduced the ALT and AST levels as well as the α-SMA and Col1A1 protein expression in the CCl4 model of liver fibrosis. Moreover, the degree of liver fibrosis was ameliorated. Interestingly, overexpression of Sestrin 2 increased p-AMPK but decreased p-mTOR protein expression. CONCLUSION: Our findings indicate that Sestrin 2 may attenuate the activation of HSCs and ameliorate liver fibrosis, most likely via upregulation of AMPK phosphorylation and suppression of the mTOR signaling pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Células Estreladas do Fígado/patologia , Cirrose Hepática/patologia , Proteínas Nucleares/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Animais , Linhagem Celular , Células Estreladas do Fígado/metabolismo , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Peroxidases , Fosforilação , Ratos
14.
Gastroenterol Res Pract ; 2018: 8620682, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30254671

RESUMO

Background: Type 2 diabetes mellitus (T2DM) patients are involved closely with cancer. This work aims to conduct a systematic review and network meta-analysis (NMA) to examine the effect of different types of statins on cancer incidence in patients with T2DM. Methods: We systematically searched the Cochrane Library, PubMed, Embase, and Wanfang databases from January 1999 to March 2017. We performed a pairwise meta-analysis to estimate the pooled ratios (ORs) and 95% confidence intervals (CIs). A NMA was performed to compare different types of statins. Results: Seven publications were included. In pairwise meta-analysis, the incidence of cancer in T2DM patients was reduced when simvastatin, atorvastatin, pravastatin, fluvastatin, lovastatin, rosuvastatin, and pitavastatin were used. In the result of NMA, the usage of simvastatin (RR 0.30 and 95% CI 0.16-0.56), atorvastatin (RR 0.29 and 95% CI 0.09-0.88), pravastatin (RR 0.34 and 95% CI 0.12-0.93), fluvastatin (RR 0.27 and 95% CI 0.09-0.83), rosuvastatin (RR 0.22 and 95% CI 0.10-0.49), and pitavastatin (RR 0.33 and 95% CI 0.20-0.57) was superior to the nonstatin groups. When compared with six other statins, rosuvastatin appeared to be the best one. Conclusions: Different statins can reduce the risk of cancer in patients with T2DM. Our analyses suggest that rosuvastatin may be more effective than others.

15.
J Vis Exp ; (138)2018 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-30175990

RESUMO

Phylogenetic analysis uses nucleotide or amino acid sequences or other parameters, such as domain sequences and three-dimensional structure, to construct a tree to show the evolutionary relationship among different taxa (classification units) at the molecular level. Phylogenetic analysis can also be used to investigate domain relationships within an individual taxon, particularly for organisms that have undergone substantial change in morphology and physiology, but for which researchers lack fossil evidence due to the organisms' long evolutionary history or scarcity of fossilization. In this text, a detailed protocol is described for using the phylogenetic method, including amino acid sequence alignment using Clustal Omega, and subsequent phylogenetic tree construction using both Maximum Likelihood (ML) of Molecular Evolutionary Genetics Analysis (MEGA) and Bayesian Inference via MrBayes. To investigate the origin of eukaryotic Sugars Will Eventually be Exported Transporters (SWEET) genes, 228 SWEETs including 35 SWEET proteins from unicellular eukaryotes and 57 SemiSWEET proteins from prokaryotes were analyzed. Interestingly, SemiSWEETs were found in prokaryotes, but SWEETs were found in eukaryotes. Two phylogenetic trees constructed using theoretically distinct methods have consistently suggested that the first eukaryotic SWEET gene might stem from the fusion of a bacterial SemiSWEET gene and an archaeal SemiSWEET gene. It is worth noting that one should be cautious to draw a conclusion based only on phylogenetic analysis, although it is useful to explain the underlying relationship between different taxa, which is difficult or even impossible to discern through experimental means.


Assuntos
Eucariotos/química , Proteínas de Membrana Transportadoras/genética , Filogenia , Sequência de Aminoácidos
16.
Mol Med Rep ; 18(4): 3997-4003, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30132575

RESUMO

Hypoxia serves a critical role in the pathogenesis of liver fibrosis. Hypoxia­inducible factor 1α (HIF1­α) is induced when cells are exposed to low O2 concentrations. Recently, it has been suggested that Rho­associated coiled­coil­forming kinase 1 (ROCK1) may be an important HIF1­α regulator. In the present study, it was analyzed whether crosstalk between HIF1­α and ROCK1 regulates cell proliferation and collagen synthesis in hepatic stellate cells (HSCs) under hypoxic conditions. For this purpose, a rat hepatic HSC line (HSC­T6) was cultured under hypoxic or normoxic conditions, and HIF1­α and ROCK1 expression was measured at different time points. Additionally, HSC­T6 cells were transfected with HIF1­α small interfering RNA (siHIF1­α), and measured protein expression and mRNA transcript levels of α­smooth muscle actin, collagen 1A1 and ROCK1. Collagen 3A1 secretion was also measured by ELISA. Cell proliferation was assessed by the MTT assay under these hypoxic conditions. The results indicated that a specific ROCK inhibitor, Y­27632, increased HIF1­α and ROCK1 expression over time in HSC­T6 cells in response to hypoxia. In addition, knockdown of HIF1­α inhibited HSC­T6 proliferation, suppressed collagen 1A1 expression, decreased collagen 3A1 secretion and attenuated ROCK1 expression. Notably, ROCK1 inhibition caused HSC­T6 quiescence, suppressed collagen secretion and downregulated HIF1­α expression. Collectively, these findings indicated that the interplay between HIF1­α and ROCK1 may be a critical factor that regulates cell proliferation and collagen synthesis in rat HSCs under hypoxia.


Assuntos
Colágeno/biossíntese , Células Estreladas do Fígado/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Quinases Associadas a rho/metabolismo , Animais , Hipóxia Celular , Linhagem Celular , Proliferação de Células , Regulação para Baixo , Técnicas de Silenciamento de Genes , Ratos , Regulação para Cima
17.
Curr Med Sci ; 38(3): 467-472, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30074214

RESUMO

Epithelial-to-mesenchymal transition (EMT) plays a critical role in cancer metastasis, and is relevant to the inflammatory microenvironment. Lipopolysaccharide (LPS), a cell wall constituent of gram-negative bacteria, has been reported to induce EMT of cancer cells through TLR4 signal. We previously reported that LPS promoted metastasis of mesenchymallike breast cancer cells with high expression of cyclin D1b. However, the role of cyclin D1b in LPS-induced EMT has not been fully elucidated. In the present study, we described that cyclin D1b augmented EMT induced by LPS in MCF-7 breast cancer cells. Cyclin D1b markedly amplified integrin αvß3 expression, which was further up-regulated under LPS stimulation. Our results showed ectopic expression of cyclin D1b promoted invasiveness of epithelial-like MCF-7 cells under LPS stimulation. Additionally, LPS-induced metastasis and EMT in MCF-7-D1b cells might depend on αvß3 expression. Further exploration indicated that cyclin D1b cooperated with HoxD3, a transcription factor promoting αvß3 expression, to promote LPSinduced EMT. Knockout of HoxD3 repressed LPS-induced EMT and αvß3 over-expression in MCF-7 cells with high expression of cyclin D1b. Specifically, all these effects were in a cyclin Dla independent manner. Taken all together, LPS up-regulated integrin αvß3 expression in MCF-7 cells with high expression of cyclin D1b and induced EMT in breast cancer cells, which highlights that cyclin D1b may act as an endogenous pathway participating in exogenous signal inducing EMT in breast cancer cells.


Assuntos
Processamento Alternativo/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ciclina D1/genética , Transição Epitelial-Mesenquimal/genética , Integrina alfaVbeta3/metabolismo , Lipopolissacarídeos/farmacologia , Processamento Alternativo/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Ciclina D1/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Fibrinogênio/farmacologia , Proteínas de Homeodomínio/metabolismo , Humanos , Células MCF-7 , Invasividade Neoplásica , Metástase Neoplásica , Fatores de Transcrição , Transfecção , Regulação para Cima/efeitos dos fármacos
18.
Exp Ther Med ; 15(6): 4838-4850, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29904396

RESUMO

The most suitable treatment regimen for autoimmune hepatitis (AIH) in adults remains unknown and requires further investigation. The current study therefore aimed to integrate evidence to provide hierarchies of the comparative efficacies of treatments measured by clinical and biochemical remission. A Bayesian-framework network meta-analysis of randomized controlled trials (RCTs) was preformed to compare eight treatments for AIH. Eligible RCTs were identified by searching Embase, Pubmed and the Cochrane Library for publications between 1966 and April 2017. All outcomes were independently extracted from the included studies by two authors. A total of six RCTs were subsequently included in the current study. The network of comparisons on remission indicated that patients treated with prednisone (pred) experienced significantly increased rates of remission compared with those treated with azathioprine [AZA; odds ratio (OR), 0.21; 95% confidence interval (CI), 0.06-0.71] and budesonide (bude) + AZA significantly increased remission compared with placebo treatment (OR, 36.66; 95% CI, 1.40-962.49) or AZA (OR, 10.30; 95% CI, 1.50-70.70). Based on the cumulative ranking probabilities, bude + AZA (89.4) was ranked first, pred (69.1) was ranked second, pred + AZA (63.2) was ranked third and placebo (7.8) treatment was ranked last. Bude + AZA may be the most appropriate candidate for the treatment of non-cirrhotic patients. However, bude + AZA as frontline therapy for AIH requires more large-scale studies with a longer duration of follow-up histology and a focus on dose-response. Additionally, development of other prospective treatments, which may be used as alternative therapy or first line therapy, and their subsequent evaluation in clinical RCTs is required.

19.
Oncogene ; 37(25): 3456-3470, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29559745

RESUMO

Chemoresistance remains a major obstacle to successful treatment of breast cancer. Although soluble tumor necrosis factor-α (sTNF-α) has been implicated in mediating drug-resistance in human cancers, whether transmembrane tumor necrosis factor-α (tmTNF-α) plays a role in chemoresistance remains unclear. Here we found that over 50% of studied patients expressed tmTNF-α at high levels in breast cancer tissues and tmTNF-α expression positively correlated with resistance to anthracycline chemotherapy. Alteration of tmTNF-α expression changed the sensitivity of primary human breast cancer cells and breast cancer cell lines to doxorubicin (DOX). Overexpression of N-terminal fragment (NTF) of tmTNF-α, a mutant form with intact intracellular domain of tmTNF-α to transmit reverse signals, induced DOX-resistance. Mechanistically, the tmTNF-α/NTF-ERK-GST-π axis and tmTNF-α/NTF-NF-κB-mediated anti-apoptotic functions were required for tmTNF-α-induced DOX-resistance. In a xenograft mouse model, the combination of tmTNF-α suppression with chemotherapy significantly enhanced the efficacy of DOX. Our data indicate that tmTNF-α mediates DOX-resistance through reverse signaling and targeting tmTNF-α may be beneficial for the treatment of DOX-resistant breast cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Membrana Celular/metabolismo , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Fator de Necrose Tumoral alfa/metabolismo , Animais , Antibióticos Antineoplásicos/farmacologia , Apoptose , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Adesão Celular , Proliferação de Células , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Transdução de Sinais , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/genética , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Oncotarget ; 8(45): 78466-78479, 2017 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-29108242

RESUMO

The concept of cancer stem cells has been proposed in various malignancies including colorectal cancer. Recent studies show direct evidence for quiescence slow-cycling cells playing a role in cancer stem cells. There exists an urgent need to isolate and better characterize these slow-cycling cells. In this study, we developed a new model to enrich slow-cycling tumor cells using cell-cycle inducer combined with cell cycle-dependent chemotherapy in vitro and in vivo. Our results show that Short-term exposure of colorectal cancer cells to chemotherapy combined with cell-cycle inducer enriches for a cell-cycle quiescent tumor cell population. Specifically, these slow-cycling tumor cells exhibit increased chemotherapy resistance in vitro and tumorigenicity in vivo. Notably, these cells are stem-cell like and participate in metastatic dormancy. Further exploration indicates that slow-cycling colorectal cancer cells in our model are less sensitive to cytokine-induced-killer cell mediated cytotoxic killing in vivo and in vitro. Collectively, our cell cycle inducer combined chemotherapy exposure model enriches for a slow-cycling, dormant, chemo-resistant tumor cell sub-population that are resistant to cytokine induced killer cell based immunotherapy. Studying unique signaling pathways in dormant tumor cells enriched by cell cycle inducer combined chemotherapy treatment is expected to identify novel therapeutic targets for preventing tumor recurrence.

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