Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.144
Filtrar
1.
Nat Commun ; 12(1): 5006, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408135

RESUMO

Obesity is a strong risk factor for cancer progression, posing obesity-related cancer as one of the leading causes of death. Nevertheless, the molecular mechanisms that endow cancer cells with metastatic properties in patients affected by obesity remain unexplored.Here, we show that IL-6 and HGF, secreted by tumor neighboring visceral adipose stromal cells (V-ASCs), expand the metastatic colorectal (CR) cancer cell compartment (CD44v6 + ), which in turn secretes neurotrophins such as NGF and NT-3, and recruits adipose stem cells within tumor mass. Visceral adipose-derived factors promote vasculogenesis and the onset of metastatic dissemination by activation of STAT3, which inhibits miR-200a and enhances ZEB2 expression, effectively reprogramming CRC cells into a highly metastatic phenotype. Notably, obesity-associated tumor microenvironment provokes a transition in the transcriptomic expression profile of cells derived from the epithelial consensus molecular subtype (CMS2) CRC patients towards a mesenchymal subtype (CMS4). STAT3 pathway inhibition reduces ZEB2 expression and abrogates the metastatic growth sustained by adipose-released proteins. Together, our data suggest that targeting adipose factors in colorectal cancer patients with obesity may represent a therapeutic strategy for preventing metastatic disease.


Assuntos
Tecido Adiposo/citologia , Reprogramação Celular , Neoplasias do Colo/fisiopatologia , Células-Tronco Neoplásicas/citologia , Nicho de Células-Tronco , Tecido Adiposo/metabolismo , Animais , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos SCID , MicroRNAs/genética , MicroRNAs/metabolismo , Metástase Neoplásica , Células-Tronco/citologia , Células-Tronco/metabolismo , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo
2.
Ann Agric Environ Med ; 28(2): 291-299, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34184513

RESUMO

INTRODUCTION: Due to the fact that lymphocytes NK (natural killer cells) are the first line of defence of the body against cancer, one of the goals of modern immunotherapy is the enhancement of their natural activities for the effective recognition, detection, and elimination of cancer cells. OBJECTIVE: The aim of the study was to evaluate the influence of selected phytochemicals (curcumin and resveratrol) and plant extracts (chlorella and goji berries) on NK cells viability and proliferation, as well as cytotoxic activity against colon cancer - one of the most common cancer worldwide. MATERIAL AND METHODS: The impact of phytochemicals, viability and proliferation of plant extracts on NK cells was examined in NK-92 cells using both LDH and MTT assays. The immunomodulatory properties of selected compounds were tested against human colon cancer cell line LS180 using the MTT test. RESULTS: Extracts of chlorella and goji berries significantly increased NK cell proliferation, while curcumin and resveratrol did not affect this process. Curcumin, as well as extracts of chlorella and goji berries, did not impact NK viability, while resveratrol significantly increased it. LDH test revealed the cytotoxic effect of chlorella extract and curcumin in NK-92 cell cultures. On the contrary, goji berries extract significantly decreased LDH level, while resveratrol did not affect the integrity of NK cell membranes. Studies conducted in co-cultures NK cells, also directly eliminated colon cancer cells. CONCLUSIONS: Performed studies revealed immunomodulatory properties of goji berries extract, which improved viability and proliferation of NK cells, and above all, significantly increased their ability to recognize and eliminate colon cancer cells.


Assuntos
Neoplasias do Colo/fisiopatologia , Curcumina/farmacologia , Fatores Imunológicos/farmacologia , Células Matadoras Naturais/efeitos dos fármacos , Lycium/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Resveratrol/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Chlorella/química , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/imunologia , Frutas/química , Humanos , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia
3.
Ann Clin Lab Sci ; 51(2): 271-276, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33941570

RESUMO

Here we present the case of a 73-year-old male with rectal adenocarcinoma with heterotopic ossification (HO). Cancer-associated HO in the digestive system is rare. Thus, the precise mechanism and clinicopathological significance of HO have not yet been defined. To clarify the molecular mechanisms of HO, we analyzed the expression levels of signaling molecules related to epithelial-mesenchymal transition (EMT) that lead to ossification in the tumor cells discriminating the ossified area (HO-area) and non-ossified area (non-HO area). Expression levels of BMP4 were elevated in both areas, whereas BMP2 was specifically increased in the HO-area by qPCR. EMT-related molecules such as Snail and Slug were especially higher in the HO-area. By immunohistochemistry, the expression of Smad4, nuclear staining of ß-catenin, and the phosphorylated form of GSK-3ß were detectable in both areas, and GSK-3ß was highly phosphorylated in the HO-area. The tumor growth rate was extremely high, with the Ki-67 labeling index at 90%. In the HO-area, osteoblasts with alkaline phosphatase expression were distributed surrounding the tumor cells. This is the first demonstration of the involvement of EMT in HO of colon cancer through BMP/SMAD and WNT/ß-catenin signaling pathways, which are especially prominent in the HO-area leading to the osteogenic property.


Assuntos
Proteína Morfogenética Óssea 2/genética , Transição Epitelial-Mesenquimal/fisiologia , Ossificação Heterotópica/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/fisiopatologia , Idoso , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/fisiopatologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Masculino , Osteoblastos/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo
4.
Biochemistry (Mosc) ; 86(3): 262-274, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33838628

RESUMO

Altered expression of cellular redox genes and proteins contributes to invasion, metastasis, and drug resistance in cancer. NADPH oxidase (NOX) isoforms are the pro-oxidant enzymes that generate ROS as a primary product. Dysregulation of NOX activity and expression alters ROS generation, which either directly or indirectly modulates cell death and survival signaling during the progression of cancer. Nuclear factor erythroid 2-related factor 2 (Nrf-2) is an inducible transcription factor, which transcribes an array of antioxidant genes and protects cancer cells from the oxidative stress. Both NOXs and Nrf-2 participate in the regulation of cellular redox homeostasis; but their dysregulation promotes oxidative stress, which contributes to the progression of different types of cancer. Indeed, the role of NOX isoforms and Nrf-2 in developing the drug resistance in cancer is largely unknown. In the present study, we have explored the association of NOX isoforms and Nrf-2 signaling with the MDR1 gene expression in colon carcinoma cells (HCT-116/R). The MDR1 gene was overexpressed to develop resistant HCT-116/R cells and the NOX activation and ROS generation were monitored. We also assessed the role of NOX isoforms and Nrf-2 in the 5-fluorouracil (5-FU) mediated apoptotic cell death of HCT-116/R cells. The HCT-116/R cells demonstrated higher expression of HIF-1α, Nrf-2, and HO-1 and were highly resistant to 5-FU; they also displayed upregulated expression and activity of NOX-2, as well as elevated ROS levels. Interestingly, the treatment with HDC, a specific NOX-2 inhibitor, reduced the ROS levels in HCT-116/R cells. The treatment with HDC and ML-385 (specific inhibitor of Nrf-2) augmented the 5-FU-mediated apoptotic cell death of HCT-116/R cells, which suggests that NOX-2 and Nrf-2 are involved in the development of the chemoresistant phenotype of these cells. Taken together, NOX-2 and Nrf-2 are associated with developing drug resistance of colorectal cancer cells and might be potential targets to overcome drug resistance during cancer therapy.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Neoplasias do Colo/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/farmacologia , NADPH Oxidase 2/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Apoptose , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/fisiopatologia , Fluoruracila/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Estresse Oxidativo , Isoformas de Proteínas , Transdução de Sinais
5.
Commun Biol ; 4(1): 400, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767328

RESUMO

During the final stages of cell division, newly-formed daughter cells remain connected by a thin intercellular bridge containing the midbody (MB), a microtubule-rich organelle responsible for cytokinetic abscission. Following cell division the MB is asymmetrically inherited by one daughter cell where it persists as a midbody remnant (MB-R). Accumulating evidence shows MB-Rs are secreted (sMB-Rs) into the extracellular medium and engulfed by neighbouring non-sister cells. While much is known about intracellular MB-Rs, sMB-Rs are poorly understood. Here, we report the large-scale purification and biochemical characterisation of sMB-Rs released from colon cancer cells, including profiling of their proteome using mass spectrometry. We show sMB-Rs are an abundant class of membrane-encapsulated extracellular vesicle (200-600 nm) enriched in core cytokinetic proteins and molecularly distinct from exosomes and microparticles. Functional dissection of sMB-Rs demonstrated that they are engulfed by, and accumulate in, quiescent fibroblasts where they promote cellular transformation and an invasive phenotype.


Assuntos
Neoplasias do Colo/fisiopatologia , Vesículas Extracelulares/fisiologia , Animais , Citocinese , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Microtúbulos/metabolismo , Organelas/metabolismo , Células Tumorais Cultivadas
6.
Int J Mol Sci ; 22(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33670920

RESUMO

The impact of tumour associated stroma on cancer metastasis is an emerging field. However, cancer associated genes in peritumoral adipose tissue (pAT) in human colon cancer have not been explored. The aim of this study was to identify differentially expressed genes (DEGs) associated with cancer pathways in mesenteric pAT compared with adjacent adipose tissue. In total, nine patients with colon cancer pathological stage T2/T4 were employed in this study. DEGs were identified in 6 patients employing Nanostring PanCancer Pathway Panel and pathway enrichment analyses were performed. Differential expression of the 5 most up-regulated and 2 down regulated genes was validated with qRT-PCR. Results showed collagen type I alpha 1 chain (COL1A1) p = 0.007; secreted frizzled related protein (SFRP2) p = 0.057; fibroblast growth factor 7 (FGF7) not significant (ns); phospholipase A2, group IIA (PLA2G2A) ns; nerve growth factor receptor (NGFR) ns; lymphoid enhancer binding factor 1 (LEF1) p = 0.03; cadherin 1, Type 1, E-cadherin (epithelial) (CDH1) 0.09. Results have highlighted down-regulation of the Wingless/Integrated (Wnt) pathway in mesenteric pAT compared to distal adipose tissue. Highly upregulated genes in mesenteric pAT were involved in extracellular matrix (ECM)-receptor interactions and focal adhesion. Highly down regulated genes were involved in the cell cycle. Immunohistochemistry revealed differential distribution of COL1A1 showing maximum levels in tumour tissue and gradually decreasing in distant adipose tissue. COL1A1 and down regulation of Wnt pathway may have a role in local invasion and distant metastasis. COL1A1 may represent a stromal prognostic biomarker and therapeutic target in colon cancer.


Assuntos
Tecido Adiposo/metabolismo , Colágeno Tipo I/genética , Neoplasias do Colo/fisiopatologia , Regulação Neoplásica da Expressão Gênica , Mesentério , Microambiente Tumoral/genética , Tecido Adiposo/patologia , Idoso , Idoso de 80 Anos ou mais , Matriz Extracelular , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Via de Sinalização Wnt
7.
Hum Cell ; 34(3): 932-944, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33559868

RESUMO

Although colon cancer is a leading and typical gastrointestinal tumor, there is little published data on the underlying molecular mechanisms of endoplasmic reticulum (ER) stress. Here, we investigated the role of ERO1α and its impact on microRNA (miR)-101 expression and ER stress in colon cancer cells. Cell ER stress was established by treating RKO or HT-29 cells with 1 µM thapsigargin (THG). Cell biological behaviors were detected using CCK-8, bromodeoxyuridine assay, flow cytometry and western blot. We also investigated the expression of ERO1α and miR-101 after THG treatment using RT-qPCR. Moreover, effects of ERO1α and miR-101 on ER stress of colon cancer cells were detected. Additionally, miR-101 impact on EZH2 expression and relevance of this regulation was confirmed by RT-qPCR and luciferase reporter. The regulation of miR-101/EZH2 axis and Wnt/ß-catenin pathway in ER stress were investigated. Our results demonstrated that THG induced ER stress in colon cancer cells. Silencing ERO1α further promoted ER stress-induced cell apoptosis. ERO1α knockdown up-regulated miR-101 expression and promoted colon cancer cell apoptosis via regulating miR-101. Surprisingly, miR-101 negatively regulated EZH2 expression via miRNA-mRNA targeting. Moreover, ER stress promoted colon cancer cell apoptosis via regulating miR-101/EZH2 axis. Wnt/ß-catenin pathway was also involved in the regulation of ERO1α/miR-101/EZH2 in ER stress of colon cancer cells. These findings illustrated that silencing ERO1α regulated ER stress-induced apoptosis via miR-101/EZH2 axis in RKO and HT-29 cells.


Assuntos
Apoptose/genética , Neoplasias do Colo/genética , Neoplasias do Colo/fisiopatologia , Estresse do Retículo Endoplasmático/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Glicoproteínas de Membrana/fisiologia , MicroRNAs/metabolismo , Oxirredutases/fisiologia , Linhagem Celular Tumoral , Neoplasias do Colo/patologia , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Células HT29 , Humanos , MicroRNAs/genética , Via de Sinalização Wnt/genética , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismo
8.
Dig Dis ; 39(2): 106-112, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32599599

RESUMO

BACKGROUND: The objective of this study was to compare functional and surgical outcomes of patients undergoing ileocecal resection for Crohn's disease (CD) to patients undergoing oncological right colectomy. METHODS: Retrospective single-center cohort study including consecutive patients undergoing right colectomy for adenocarcinoma (oncological resection) or CD (mesentery-sparing resection) between July 2011 and November 2017. Outcome measures were pathological details (lymph node yield), postoperative recovery (pain levels, return to flatus and stool, intake of fluids, weight change, and mobilization), and early (30-day) outcomes (surgical/medical complications, hospital stay, readmissions). RESULTS: A total of 195 patients (153 [78%] with cancer and 42 [22%] with CD) were included. Overall compliance with the institutional enhanced recovery protocol was comparable between the 2 groups (compliance ≥70%: 60% in CD patients vs. 62% in cancer, p = 0.458). The adenocarcinoma group had a larger lymph node yield than the CD group (26 ± 13 vs. 2.4 ± 5, respectively, p < 0.001). While the CD group experienced significantly more pain (3.7 ± 1.9/10 vs. 2.8 ± 2.5/10, p = 0.007, patients requiring opioids: 65 vs. 28%, p = 0.001), return of flatus (2.3 ± 1.2 days vs. 2.4 ± 2.8 days, p = 0.642) and stool (4.1 ± 6.0 vs. 3.0 ± 1.8 days, p = 0.292) was no different in both groups. No difference was observed regarding postoperative complications, length of stay, and readmission rate. CONCLUSION: This study revealed no differences in both functional and surgical outcomes in CD and cancer patients undergoing mesentery-sparing or formal oncological right colectomy, respectively.


Assuntos
Adenocarcinoma/fisiopatologia , Adenocarcinoma/cirurgia , Colectomia , Neoplasias do Colo/fisiopatologia , Neoplasias do Colo/cirurgia , Doença de Crohn/fisiopatologia , Doença de Crohn/cirurgia , Adulto , Idoso , Recuperação Pós-Cirúrgica Melhorada , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento
9.
Am J Physiol Gastrointest Liver Physiol ; 320(1): G117-G124, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33174455

RESUMO

Motility of the large bowel may be grossly subdivided in two types of contractile activity: low-amplitude single or cyclic propagated waves and high-amplitude propagated activity. The latter is mainly apt to shift relatively large amounts of colonic contents, and it is related to defecation. The main component of this propagated activity is represented by the radiologically identified mass movements that have a manometric equivalent known as high-amplitude propagated contractions (HAPC). The present article reviews origins and characterization of HAPC in the time course of colonic motility investigations, and correlates it with technological advancements in recent years, putting into perspective the future possible options to better detect and investigate these important physiological events.


Assuntos
Colo/fisiologia , Neoplasias do Colo/patologia , Motilidade Gastrointestinal/fisiologia , Contração Muscular/fisiologia , Neoplasias do Colo/fisiopatologia , Humanos , Manometria/métodos
10.
J Agric Food Chem ; 69(2): 686-697, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33369397

RESUMO

Targeting autophagy and lysosome may serve as a promising strategy for cancer therapy. Tea polysaccharide (TP) has shown promising antitumor effects. However, its mechanism remains elusive. Here, TP was found to have a significant inhibitory effect on the proliferation of colon cancer line HCT116 cells. RNA-seq analysis showed that TP upregulated autophagy and lysosome signal pathways, which was further confirmed through experiments. Immunofluorescence experiments indicated that TP activated transcription factor EB (TFEB), a key nuclear transcription factor modulating autophagy and lysosome biogenesis. In addition, TP inhibited the activity of mTOR, while it increased the expression of Lamp1. Furthermore, TP ameliorated the lysosomal damage and autophagy flux barrier caused by Baf A1 (lysosome inhibitor). Hence, our data suggested that TP repressed the proliferation of HCT116 cells by targeting lysosome to induce cytotoxic autophagy, which might be achieved through mTOR-TFEB signaling. In summary, TP may be used as a potential drug to overcome colon cancer.


Assuntos
Autofagia/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Camellia sinensis/química , Neoplasias do Colo/fisiopatologia , Lisossomos/metabolismo , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Morte Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Células HCT116 , Humanos , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genética
11.
J Agric Food Chem ; 68(50): 14978-14987, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33140648

RESUMO

Caffeic acid phenethyl ester (CAPE) has various biological activities but low water solubility and poor bioavailability. In this study, CAPE was encapsulated in skim milk powder (SMP) by spray drying warm aqueous ethanol solutions with different mass ratios of SMP and CAPE. The loading capacity and encapsulation efficiency were up to 10.1 and 41.7%, respectively. Differential scanning calorimetry and X-ray diffraction results confirmed the loss of crystallinity of CAPE after encapsulation. Fourier-transform infrared and fluorescence spectroscopy results indicated the hydrophobic binding between CAPE and caseins. Scanning electron microscopy and static light scattering results showed spherical capsules with an average diameter of around 26 µm. The CAPE loaded in SMP microcapsules showed significantly improved in vitro bioaccessibility and antiproliferation activity against human colon cancer cells compared to free CAPE. The simple, scalable, and low-cost approach in the present study may be significant for industrial encapsulation of CAPE and other lipophilic bioactive compounds.


Assuntos
Ácidos Cafeicos/química , Ácidos Cafeicos/farmacologia , Composição de Medicamentos/métodos , Leite/química , Álcool Feniletílico/análogos & derivados , Animais , Disponibilidade Biológica , Bovinos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/fisiopatologia , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia
12.
Cell Biol Int ; 44(11): 2307-2314, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32767706

RESUMO

Ferritinophagy is a form of selective autophagy responsible for degrading intracellular ferritin, mediated by nuclear receptor coactivator 4 (NCOA4). NCOA4 plays significant roles in systemic iron homeostasis, and its disruption leads to simultaneous anemia and susceptibility to iron overload. The importance of iron colorectal cancer pathogenesis is well studied; however, the role of ferritinophagy in colon cancer cell growth has not been assessed. Disruption of ferritinophagy via NCOA4 knockout leads to only marginal differences in growth under basal and iron-restricted conditions. Moreover, NCOA4 played no significant role in cell death induced by 5-fluorouracil and erastin. Western blotting analysis for ferritin and transferrin receptor 1 found a dose-dependent effect on expression in both proteins in wild-type and NCOA4 knockout cell lines, but further investigation revealed no difference in growth response when treated at both high and low doses. Our data demonstrate a marginal role for ferritinophagy in growth both under normal and cytotoxic conditions in colon cancer cells, as well as a possible compensatory mechanism in colon cancer cells in response to ferroptosis induction.


Assuntos
Neoplasias do Colo/metabolismo , Ferritinas/metabolismo , Coativadores de Receptor Nuclear/metabolismo , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Neoplasias do Colo/fisiopatologia , Ferritinas/fisiologia , Homeostase/efeitos dos fármacos , Humanos , Ferro/metabolismo , Distúrbios do Metabolismo do Ferro , Coativadores de Receptor Nuclear/genética , Espécies Reativas de Oxigênio/metabolismo
13.
Sci Rep ; 10(1): 12803, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32733047

RESUMO

Biophysical studies on single cells have linked cell mechanics to physiology, functionality and disease. Evaluation of mass and viscoelasticity versus cell cycle can provide further insights into cell cycle progression and the uncontrolled proliferation of cancer. Using our pedestal microelectromechanical systems resonant sensors, we have developed a non-contact interferometric measurement technique that simultaneously tracks the dynamic changes in the viscoelastic moduli and mass of adherent colon (HT-29) and breast cancer (MCF-7) cells from the interphase through mitosis and then to the cytokinesis stages of their growth cycle. We show that by combining three optomechanical parameters in an optical path length equation and a two-degree-of-freedom model, we can simultaneously extract the viscoelasticity and mass as a function of the nano-scaled membrane fluctuation of each adherent cell. Our measurements are able to discern between soft and stiff cells across the cell cycle and demonstrated sharp viscoelastic changes due to cortical stiffening around mitosis. Cell rounding before division can be detected by measurement of mechanical coupling between the cells and the sensors. Our measurement device and method can provide for new insights into the mechanics of single adherent cells versus time.


Assuntos
Neoplasias da Mama/patologia , Ciclo Celular/fisiologia , Neoplasias do Colo/patologia , Viscosidade , Neoplasias da Mama/fisiopatologia , Neoplasias do Colo/fisiopatologia , Elasticidade , Feminino , Células HT29 , Humanos , Células MCF-7 , Masculino , Mitose
14.
BMC Gastroenterol ; 20(1): 269, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32799796

RESUMO

BACKGROUND: Cancer patients are at increased risk of novel coronavirus disease 2019 (COVID-19). Currently, surgeries for cancer patients with COVID-19 are generally suggested to be properly delayed. CASE PRESENTATION: We presented a 69-year-old Chinese female colon cancer patient with COVID-19, the first case accepted the surgical treatment during the pandemic in China. The patient developed a fever on January 28, 2020. After treatments with Ceftriaxone and Abidol, her fever was not moderated yet. A repeat chest computed tomography (CT) scan showed significantly exacerbated infectious lesions with a positive result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid. An abdomen CT scan indicated the tumor of ascending colon with local wrapped changes. She was diagnosed with 'Severe novel coronavirus pneumonia' and 'Incomplete bowel obstruction: Colon cancer?'. After actively anti-inflammatory and anti-viral therapies, a right colectomy with lymph node dissection was performed on March 11, followed by a pathological examination. The patient successfully recovered from COVID-19 pneumonia and incomplete bowel obstruction after surgery without any postoperative related complications and was discharged on the 9th day after operation. Significant degeneration, necrosis and slough of focal intestinal and colonic mucosal epithelial cells were observed under microscope. No surgeons, nurses or anesthetists in our team were infected with SARS-CoV-2. CONCLUSIONS: It is meaningful and imperative to share our experience of protecting health care personnels from SARS-CoV-2 infection and providing references for optimizing treatment of cancer patients, at least for the operative intervention with absolute necessity or surgical emergency, during the outbreak of COVID-19.


Assuntos
Betacoronavirus/isolamento & purificação , Colectomia/métodos , Neoplasias do Colo , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Idoso , COVID-19 , Colo Ascendente/diagnóstico por imagem , Colo Ascendente/patologia , Neoplasias do Colo/diagnóstico , Neoplasias do Colo/patologia , Neoplasias do Colo/fisiopatologia , Neoplasias do Colo/cirurgia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Feminino , Humanos , Controle de Infecções/métodos , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/fisiopatologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Pneumonia Viral/virologia , SARS-CoV-2 , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
15.
Nat Commun ; 11(1): 3606, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32681016

RESUMO

Mitochondrial metabolism has emerged as a promising target against the mechanisms of tumor growth. Herein, we have screened an FDA-approved library to identify drugs that inhibit mitochondrial respiration. The ß1-blocker nebivolol specifically hinders oxidative phosphorylation in cancer cells by concertedly inhibiting Complex I and ATP synthase activities. Complex I inhibition is mediated by interfering the phosphorylation of NDUFS7. Inhibition of the ATP synthase is exerted by the overexpression and binding of the ATPase Inhibitory Factor 1 (IF1) to the enzyme. Remarkably, nebivolol also arrests tumor angiogenesis by arresting endothelial cell proliferation. Altogether, targeting mitochondria and angiogenesis triggers a metabolic and oxidative stress crisis that restricts the growth of colon and breast carcinomas. Nebivolol holds great promise to be repurposed for the treatment of cancer patients.


Assuntos
Antagonistas Adrenérgicos/farmacologia , Indutores da Angiogênese/farmacologia , Neoplasias da Mama/fisiopatologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/fisiopatologia , Mitocôndrias/efeitos dos fármacos , Nebivolol/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Feminino , Humanos , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , ATPases Mitocondriais Próton-Translocadoras/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Proteínas/genética , Proteínas/metabolismo
16.
Scand J Med Sci Sports ; 30(10): 1918-1929, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32599670

RESUMO

BACKGROUND: This pilot trial explores the feasibility of measuring muscle contractile properties in patients with cancer, effects of exercise during chemotherapy on muscle contractile properties and the association between changes in contractile muscle properties and perceived fatigue. METHOD: Patients who received (neo)adjuvant chemotherapy for breast or colon cancer were randomized to a 9-12 week exercise intervention or a waitlist-control group. At baseline and follow-up, we measured knee extensor strength using maximal voluntary contraction (MVC), contractile muscle properties of the quadriceps muscle using electrical stimulation, and perceived fatigue using the Multidimensional Fatigue Inventory. Feasibility was assessed by the proportion of patients who successfully completed measurements of contractile muscle properties. Exercise effects on muscle contractile properties were explored using linear regression analyses. Between-group differences >10% were considered potentially relevant. Pearson correlation (rp ) of changes in contractile muscle properties and changes in perceived fatigue was calculated. RESULTS: Twenty two of 30 patients completed baseline and follow-up assessments. Measurements of contractile properties were feasible except for muscle fatigability. We found a potentially relevant between-group difference in the rate of force development favoring the intervention group (1192 N/s, 95% CI = -335; 2739). Change in rate of force development was negatively correlated with change in perceived general (rp  = -0.54, P = .04) and physical (rp  = -0.59, P = .02) fatigue. CONCLUSION: Chemotherapy induces a decrease in the rate of force development, which may reflect a larger loss in type II muscle fibers. This may be attenuated with (resistance) exercise. The increase in the rate of force development was related to a decrease in perceived fatigue.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Exercício Físico/fisiologia , Contração Muscular/fisiologia , Músculo Quadríceps/fisiopatologia , Neoplasias da Mama/fisiopatologia , Quimioterapia Adjuvante , Neoplasias do Colo/fisiopatologia , Estudos de Viabilidade , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Contração Muscular/efeitos dos fármacos , Fadiga Muscular/fisiologia , Terapia Neoadjuvante , Países Baixos , Projetos Piloto , Músculo Quadríceps/efeitos dos fármacos , Listas de Espera
17.
J Food Sci ; 85(7): 2186-2197, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32567699

RESUMO

Yerba Mate (Ilex paraguariensis St. Hill. Aquifoliaceae) is a native South American tree and has a large amount of bioactive compounds. Colorectal cancer (CRC) is one of the so-called westernized diseases and is the third most common cancer in both men and women. Efficient strategies for the treatment of CRC are extensively being explored including dietary intervention. The objective of our research was to evaluate the effects of Yerba Mate extract on cell proliferation, invasive capacity of tumor cells, and angiogenesis. For this, in vitro and in vivo experimentation was carried out using CRC models. The extract was generated by aqueous extraction and prepared according to traditional American procedure of preparing mate infusion. In vitro results showed that the Yerba Mate extract inhibits CT26 and COLO 205 cell proliferation with IC50 values of 0.25 and 0.46 mg/mL, respectively. We demonstrated by TUNEL assay that one of the mechanisms by which Yerba Mate extract decreases cell proliferation is by induction of apoptosis. In a murine syngeneic tumor model, oral administration of Yerba Mate extract in a dose of 1.6 g/kg/day significantly inhibited angiogenesis and tumor growth without affecting biological parameters or body weight. Our findings suggest that Yerba Mate may be a promising agent for the treatment of colon cancer and could be used as an herbal medicine or functional food ingredient. PRACTICAL APPLICATION: Considering the chemical composition and presence of phenolic compounds with their free-radical scavenging activities and bioactivities against colon cancer cells, Yerba Mate can be a promising candidate as healthy food sources in human nutrition, and also be considered a natural source of potential antitumor agents. Taking into account the economic importance of Yerba Mate in Argentina, this vegetable would have a greater commercial value as a functional food.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Ilex paraguariensis/química , Extratos Vegetais/administração & dosagem , Animais , Antineoplásicos Fitogênicos/química , Argentina , Peso Corporal/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/fisiopatologia , Humanos , Camundongos , Fenóis/administração & dosagem , Fenóis/química , Fitoterapia , Extratos Vegetais/química
18.
Surg Today ; 50(12): 1633-1643, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32556551

RESUMO

PURPOSE: The prognostic nutritional index (PNI) is calculated using the serum albumin and peripheral lymphocyte counts. We sought to assess the correlation between the preoperative PNI and postoperative outcomes in patients with colon cancer treated with laparoscopic surgery. METHODS: We included 896 colon cancer patients who underwent curative laparoscopic colectomy between January 2013 and March 2016. To identify any predictors of the postoperative outcomes, we compared the clinical characteristics and immunonutritional parameters, including the PNI, between patients classified as the Clavien-Dindo grade 2 or higher (n = 99) with those classified as grade 0 or 1 (n = 797). RESULTS: A longer surgical time and a preoperative low PNI (< 49.8) (odds ratio; 1.913, p = 0.002) were independent predictors of postoperative complications according to a multivariate analysis. A preoperative low PNI was significantly associated with an older age, a lower performance status, a lower BMI, higher CEA levels, an advanced T status, lymph node metastasis, a longer operative time, a higher blood loss, a larger tumor size, treatment with a combined resection, a longer time to bowel recovery, a longer postoperative hospital stay, and a poor overall survival. CONCLUSIONS: A preoperative low PNI was found to be significantly associated with the incidence of postoperative complications, an advanced tumor status, and a poor prognosis. Further research is needed to understand how to best clinically utilize this promising parameter.


Assuntos
Colectomia/métodos , Neoplasias do Colo/cirurgia , Endoscopia Gastrointestinal/métodos , Laparoscopia/métodos , Avaliação Nutricional , Fenômenos Fisiológicos da Nutrição/fisiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Neoplasias do Colo/fisiopatologia , Feminino , Humanos , Incidência , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Prognóstico , Albumina Sérica , Resultado do Tratamento
19.
Biomed Pharmacother ; 127: 110232, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32559854

RESUMO

Interleukin (IL)-33 is a member of the IL-1 family, participating in both helper T1 (Th1)- and Th2-type immune responses, but its ambiguous effects on tumor growth and related immune mechanisms remain unclear. Here, we report that recombinant mouse IL-33 (mIL-33) significantly inhibited colon cancer growth and metastasis to lung and liver in a murine CT26 or MC38 tumor-cell engraftment model. This effect could be associated with CD4+ T cells and CD40 L signaling, as depletion of CD4+ T cells or blocking CD40 L signaling in vivo partly abolished the antitumor function of IL-33. In addition, IL-33 treatment upregulated CD40 L expression on tumor-infiltrating lymphocytes, and promoted the activation of CD4+ T, CD8+ T and natural killer cells via CD40 L signaling. Furthermore, IL-33 was sufficient to induce the ST2 expression on CD4+ T cells, but not on CD8+ T and natural killer cells, indicating that IL-33 acted on CD4+ T cells via a positive-feedback loop. Our findings shed new light on the IL-33-mediated antitumor effects and mechanisms of Th1 action, and also suggest that IL-33 may serve as an activator to boost anticancer immune responses in singular or combinatory therapies.


Assuntos
Ligante de CD40/biossíntese , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Neoplasias do Colo/fisiopatologia , Proteína 1 Semelhante a Receptor de Interleucina-1/fisiologia , Interleucina-33/fisiologia , Animais , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/fisiologia , Proteína 1 Semelhante a Receptor de Interleucina-1/biossíntese , Interleucina-33/farmacologia , Camundongos , Transdução de Sinais/fisiologia , Linfócitos T/metabolismo , Linfócitos T/fisiologia , Regulação para Cima
20.
J Nat Prod ; 83(4): 1238-1248, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32223193

RESUMO

Seven new daphnane-type diterpenoids, daphgenkins A-G (1-7), and 15 known analogues (8-22) were isolated from the flower buds of Daphne genkwa. Their structures and absolute configurations were elucidated by spectroscopic data and calculated ECD analyses. The cytotoxicities of all daphnane-type diterpenoids (1-22) obtained were evaluated against three human colon cancer cell lines (SW620, RKO, and LoVo). Compounds 1, 12, and 13 exhibited cytotoxic effects against the SW620 and RKO cell lines, with IC50 values in the range of 3.0-9.7 µM. The most active new compound, 1, with an IC50 value of 3.0 µM against SW620 cells, was evaluated further for its underlying molecular mechanism. Compound 1 induced G0/G1 cell cycle arrest, leading to the induction of apoptosis in SW620 cells. Also, it induced cancer cell apoptosis by an increased ratio of Bax/Bcl-2, activated cleaved caspase-3 and caspase-9, and upregulated PARP. Finally, compound 1 significantly inhibited PI3K/Akt/mTOR signaling in SW620 cells. Together, the results suggest that compound 1 may be a suitable lead compound for further biological evaluation.


Assuntos
Antineoplásicos/farmacologia , Neoplasias do Colo/fisiopatologia , Daphne/química , Diterpenos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Caspase 3/química , Caspase 3/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Diterpenos/química , Diterpenos/isolamento & purificação , Humanos , Estrutura Molecular , Fosfatidilinositol 3-Quinases/química , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/química , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...