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1.
Nutrients ; 13(7)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34371859

RESUMO

Almost two in three patients who are aged 75 years and older and scheduled for surgery for colorectal cancer (CRC) are undernourished. Despite evidence that perioperative nutritional management can improve patients outcomes, international guidelines are still insufficiently applied in current practice. In this stepped-wedge cluster-randomized study of five surgical hospitals, we included 147 patients aged 70 years or older with scheduled abdominal surgery for CRC between October 2013 and December 2016. In the intervention condition, an outreach team comprising a geriatrician and a dietician visited patients and staff in surgical wards to assist with the correct application of guidelines. Evaluation, diagnosis, and prescription (according to nutritional status) were considered appropriate and strictly consistent with guidelines in 39.2% of patients in the intervention group compared to only 1.4% in the control group (p = 0.0002). Prescription of oral nutritional supplements during the perioperative period was significantly improved (41.9% vs. 4.1%; p < 0.0001). However, there were no benefits of the intervention on surgical complications or adverse events. A possible benefit of hospital stay reduction will need to be confirmed in further studies. This study highlights the importance of the implementation of quality improvement interventions into current practice for the perioperative nutritional management of older patients with CRC.


Assuntos
Avaliação Geriátrica/métodos , Desnutrição/terapia , Terapia Nutricional/métodos , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodos , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/complicações , Neoplasias Colorretais/fisiopatologia , Neoplasias Colorretais/cirurgia , Suplementos Nutricionais , Feminino , Humanos , Masculino , Desnutrição/complicações , Política Nutricional , Terapia Nutricional/normas , Estado Nutricional , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios/normas , Período Pré-Operatório , Melhoria de Qualidade , Resultado do Tratamento
2.
Elife ; 102021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34342264

RESUMO

Colorectal cancer (CRC) remains a leading cause of cancer death, and its mortality is associated with metastasis and chemoresistance. We demonstrate that oxaliplatin-resistant CRC cells are sensitized to TRAIL-mediated apoptosis. Oxaliplatin-resistant cells exhibited transcriptional downregulation of caspase-10, but this had minimal effects on TRAIL sensitivity following CRISPR-Cas9 deletion of caspase-10 in parental cells. Sensitization effects in oxaliplatin-resistant cells were found to be a result of increased DR4, as well as significantly enhanced DR4 palmitoylation and translocation into lipid rafts. Raft perturbation via nystatin and resveratrol significantly altered DR4/raft colocalization and TRAIL sensitivity. Blood samples from metastatic CRC patients were treated with TRAIL liposomes, and a 57% reduction of viable circulating tumor cells (CTCs) was observed. Increased DR4/lipid raft colocalization in CTCs was found to correspond with increased oxaliplatin resistance and increased efficacy of TRAIL liposomes. To our knowledge, this is the first study to investigate the role of lipid rafts in primary CTCs.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/fisiopatologia , Resistencia a Medicamentos Antineoplásicos/genética , Oxaliplatina/farmacologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/genética , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Microdomínios da Membrana/metabolismo , Pessoa de Meia-Idade , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Regulação para Cima
3.
Int J Mol Sci ; 22(13)2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34281166

RESUMO

Cetuximab is a common treatment option for patients with wild-type K-Ras colorectal carcinoma. However, patients often display intrinsic resistance or acquire resistance to cetuximab following treatment. Here we generate two human CRC cells with acquired resistance to cetuximab that are derived from cetuximab-sensitive parental cell lines. These cetuximab-resistant cells display greater in vitro proliferation, colony formation and migration, and in vivo tumour growth compared with their parental counterparts. To evaluate potential alternative therapeutics to cetuximab-acquired-resistant cells, we tested the efficacy of 38 current FDA-approved agents against our cetuximab-acquired-resistant clones. We identified carfilzomib, a selective proteosome inhibitor to be most effective against our cell lines. Carfilzomib displayed potent antiproliferative effects, induced the unfolded protein response as determined by enhanced CHOP expression and ATF6 activity, and enhanced apoptosis as determined by enhanced caspase-3/7 activity. Overall, our results indicate a potentially novel indication for carfilzomib: that of a potential alternative agent to treat cetuximab-resistant colorectal cancer.


Assuntos
Neoplasias Colorretais/metabolismo , Oligopeptídeos/farmacologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Animais , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cetuximab/farmacologia , Neoplasias Colorretais/fisiopatologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Oligopeptídeos/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Resposta a Proteínas não Dobradas/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Commun Biol ; 4(1): 657, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34079064

RESUMO

Claudin-2 promotes breast cancer liver metastasis by enabling seeding and early cancer cell survival. We now demonstrate that Claudin-2 is functionally required for colorectal cancer liver metastasis and that Claudin-2 expression in primary colorectal cancers is associated with poor overall and liver metastasis-free survival. We have examined the role of Claudin-2, and other claudin family members, as potential prognostic biomarkers of the desmoplastic and replacement histopathological growth pattern associated with colorectal cancer liver metastases. Immunohistochemical analysis revealed higher Claudin-2 levels in replacement type metastases when compared to those with desmoplastic features. In contrast, Claudin-8 was highly expressed in desmoplastic colorectal cancer liver metastases. Similar observations were made following immunohistochemical staining of patient-derived xenografts (PDXs) that we have established, which faithfully retain the histopathology of desmoplastic or replacement type colorectal cancer liver metastases. We provide evidence that Claudin-2 status in patient-derived extracellular vesicles may serve as a relevant prognostic biomarker to predict whether colorectal cancer patients have developed replacement type liver metastases. Such a biomarker will be a valuable tool in designing optimal treatment strategies to better manage patients with colorectal cancer liver metastases.


Assuntos
Biomarcadores Tumorais/fisiologia , Claudinas/fisiologia , Neoplasias Colorretais/secundário , Neoplasias Hepáticas/patologia , Animais , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Adesão Celular/genética , Adesão Celular/fisiologia , Claudinas/antagonistas & inibidores , Claudinas/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/fisiopatologia , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Células HT29 , Hepatócitos/patologia , Xenoenxertos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/fisiopatologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/secundário , Camundongos , Camundongos SCID , Domínios PDZ/genética , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
5.
Int J Comput Assist Radiol Surg ; 16(8): 1335-1345, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33891254

RESUMO

PURPOSE: The introduction of novel endoscopic instruments is essential to reduce trauma in visceral surgery. However, endoscopic device development is hampered by challenges in respecting the dimensional restrictions, due to the narrow access route, and by achieving adequate force transmission. As the overall goal of our research is the development of a patient adaptable, endoscopic anastomosis manipulator, biomechanical and size-related characterization of gastrointestinal organs are needed to determine technical requirements and thresholds to define functional design and load-compatible dimensioning of devices. METHODS: We built an experimental setup to measure colon tissue compression piercing forces. We tested 54 parameter sets, including variations of three tissue fixation configurations, three piercing body configurations (four, eight, twelve spikes) and insertion trajectories of constant velocities (5 mms-1, 10 mms-1,15 mms-1) and constant accelerations (5 mms-2, 10 mms-2, 15 mms-2) each in 5 samples. Furthermore, anatomical parameters (lumen diameter, tissue thickness) were recorded. RESULTS: There was no statistically significant difference in insertion forces neither between the trajectory groups, nor for variation of tissue fixation configurations. However, we observed a statistically significant increase in insertion forces for increasing number of spikes. The maximum mean peak forces for four, eight and twelve spikes were 6.4 ± 1.5 N, 13.6 ± 1.4 N and 21.7 ± 5.8 N, respectively. The 5th percentile of specimen lumen diameters and pierced tissue thickness were 24.1 mm and 2.8 mm, and the 95th percentiles 40.1 mm and 4.8 mm, respectively. CONCLUSION: The setup enabled reliable biomechanical characterization of colon material, on the base of which design specifications for an endoscopic anastomosis device were derived. The axial implant closure unit must enable axial force transmission of at least 28 N (22 ± 6 N). Implant and applicator diameters must cover a range between 24 and 40 mm, and the implant gap, compressing anastomosed tissue, between 2 and 5 mm.


Assuntos
Colonoscopia/métodos , Neoplasias Colorretais/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Experimentais , Reto/cirurgia , Anastomose Cirúrgica/métodos , Animais , Fenômenos Biomecânicos , Neoplasias Colorretais/fisiopatologia , Pressão , Suínos
6.
J Microbiol ; 59(2): 202-216, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33527319

RESUMO

5-Fluorouracil (5-FU) is an essential drug in systemic chemotherapy treatments for colorectal cancer (CRC). Despite the development of several treatment strategies over the past decades, the patient benefits of 5-FU-based therapies have been compromised by the development of chemoresistance. Differences in treatment responses among CRC patients may be due to genetic and epigenetic factors unique to individuals. Therefore, important factors for realizing personalized medicine are to accurately understand the causes and mechanisms of drug resistance to 5-FU-based therapies and to identify and validate prognostic biomarkers. Gut microbes that interact directly with the host contribute to human health and cancer control. Lactobacillus plantarum, in particular, has the potential to be a therapeutic agent by producing bioactive compounds that may benefit the host. Here, we investigated the gamma-aminobutyric acid (GABA) and GABAB receptor (GABABR)-dependent signaling pathway as a treatment option for 5-FU-resistant HT-29 cells. GABA-producing L. plantarum activates anti-proliferative, anti-migration, and anti-invasion effects against 5-FU-resistant HT-29 cells. The inhibitory effects of GABA-producing L. plantarum are mediated via GABABR. Activated GABABR induces apoptosis through the inhibition of cAMP-dependent signaling pathways and cellular inhibitor of apoptosis protein 2 (cIAP2) expression. Thus, the GABAergic system has potential in 5-FU-resistant HT-29 cells as a predictive biomarker. In addition, GABA-producing L. plantarum is promising as an adjuvant treatment for 5-FU-resistant CRC, and its intervention in neurobiological signaling imply new possibilities for chemoprevention and the treatment of colon cancer-related diseases.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Colorretais/fisiopatologia , Fluoruracila/farmacologia , Lactobacillus plantarum/metabolismo , Probióticos/administração & dosagem , Receptores de GABA/metabolismo , Ácido gama-Aminobutírico/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Células HT29 , Humanos , Metástase Neoplásica , Receptores de GABA/genética , Transdução de Sinais/efeitos dos fármacos
8.
Cancer Immunol Immunother ; 70(10): 2781-2793, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33634371

RESUMO

TIGIT is a lymphocyte surface receptor, which is mainly expressed on the surface of CD8+T cells. The role of TIGIT in colorectal cancer and its expression pattern in colorectal cancer infiltrating lymphocytes are still controversial. This study aimed at identifying the function of TIGIT in colorectal cancer. Patients with colorectal cancer showed significantly higher TIGIT+CD8+T cell infiltration in tumor tissues, metastases compared with paired PBMC and normal tissues through flow cytometry. TIGIT+CD8+T cells showed an exhausted phenotype and expressed low levels of killer cytokines IFN-γ, IL-2, TNF-α. In addition, more inhibitory receptors such as PD-1, LAG-3, and TIM-3 were expressed on the surface of TIGIT+CD8+T cells. TGF-ß1 could promote the expression of TIGIT and inhibit CD8+T cell function in vitro. Moreover, the accumulation of TIGIT+T cells in tumors was associated with advanced disease, predicted early recurrence, and reduced survival rates in colorectal cancer patients. Our results indicate that TIGIT can be a biological marker for the prognosis of colorectal cancer, and TIGIT can be used as a potential target for treatment.


Assuntos
Neoplasias Colorretais/complicações , Regulação Neoplásica da Expressão Gênica/genética , Receptores Imunológicos/genética , Neoplasias Colorretais/fisiopatologia , Feminino , Humanos , Masculino , Prognóstico
9.
Int J Sports Med ; 42(10): 924-929, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33634458

RESUMO

Colorectal cancer is now a frequently treatable illness for most and a chronic disease for many. The number of people living with a diagnosis of colorectal cancer is thus expected to rise. Yet even after successful treatment, colorectal cancer survivors, mostly the elderly, frequently experience health problems and impaired health-related quality of life. We investigated the cross-sectional association between physical fitness, measured with the 6-min walk test, 30-second chair-stand test, and isometric handgrip strength, as well as health-related quality of life, in a cohort of colorectal cancer patients (n=71, mean [SD] age 67±10 years, 63% men; 35, 39 and 25% in stages I, II and III, respectively). Greater performance in the 6-minute walk test and 30-second chair-stand test was associated with higher levels of global health status (p<0.001, p=0.001 respectively), higher functioning (p<0.001) and lower levels of symptomatology (p<0.001; pain and fatigue). Additionally, greater 6-min walk test performance was associated with a better cognitive function (p=0.005). Our results suggest that greater aerobic fitness and lower-extremity muscle strength are cross-sectionally associated with higher levels of global health status, higher functioning and lower levels of symptomatology such as pain and fatigue in colorectal cancer patients.


Assuntos
Sobreviventes de Câncer , Neoplasias Colorretais/fisiopatologia , Aptidão Física , Qualidade de Vida , Idoso , Estudos Transversais , Teste de Esforço , Fadiga , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Dor
10.
Med Sci Monit ; 27: e927935, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33518699

RESUMO

BACKGROUND Thyroid nodules (TNs) and metabolic syndrome (MS) have been individually associated with colorectal polyps. However, the potential joint relationship between them in relation to colorectal polyps has not been fully evaluated. This study aimed to validate the association of TNs/MS and colorectal polyps/adenomas and to determine the risk of colonic polyps in patients with TNs/MS. MATERIAL AND METHODS A retrospective study was conducted on patients undergoing routine health checks in the First Affiliated Hospital of Wenzhou Medical University from July 2014 to August 2017. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for colorectal polyps/adenomas after adjusting for confounding factors. Then patients were divided into 4 groups according to whether they had TNs or MS. Relative excess risks of interaction, attributable proportion, and synergy index were used to determine the additive interaction of TNs and MS on colorectal polyps/adenomas. RESULTS A total of 4514 eligible patients were included in this study. TNs and MS were confirmed to be independent risk factors for colorectal polyps/adenomas. Compared with the group of TNs(-)/MS(-), the odds ratios of TNs(+)/MS(+) in colorectal polyps (odds ratio [OR]: 3.031, 95% confidence interval [CI]: 2.262-4.062, P<0.05) or adenomas (OR: 2.894, 95% CI: 2.099-3.990, P<0.05) were significantly increased, and there was an interactive additive effect between TNs and MS. CONCLUSIONS TNs and MS have an associative and superimposing effect on the increased occurrence of colorectal adenomas. Colonoscopy screening should be advocated for patients with both of these diseases.


Assuntos
Pólipos do Colo/complicações , Síndrome Metabólica/epidemiologia , Nódulo da Glândula Tireoide/epidemiologia , Adulto , China , Pólipos do Colo/fisiopatologia , Colonoscopia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/fisiopatologia , Feminino , Humanos , Modelos Logísticos , Masculino , Programas de Rastreamento , Síndrome Metabólica/complicações , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Razão de Chances , Neoplasias Retais/complicações , Neoplasias Retais/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Nódulo da Glândula Tireoide/complicações , Nódulo da Glândula Tireoide/fisiopatologia
11.
Nat Rev Gastroenterol Hepatol ; 18(6): 393-410, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33514916

RESUMO

The enteric nervous system (ENS) is the largest division of the peripheral nervous system and closely resembles components and functions of the central nervous system. Although the central role of the ENS in congenital enteric neuropathic disorders, including Hirschsprung disease and inflammatory and functional bowel diseases, is well acknowledged, its role in systemic diseases is less understood. Evidence of a disordered ENS has accumulated in neurodegenerative diseases ranging from amyotrophic lateral sclerosis, Alzheimer disease and multiple sclerosis to Parkinson disease as well as neurodevelopmental disorders such as autism. The ENS is a key modulator of gut barrier function and a regulator of enteric homeostasis. A 'leaky gut' represents the gateway for bacterial and toxin translocation that might initiate downstream processes. Data indicate that changes in the gut microbiome acting in concert with the individual genetic background can modify the ENS, central nervous system and the immune system, impair barrier function, and contribute to various disorders such as irritable bowel syndrome, inflammatory bowel disease or neurodegeneration. Here, we summarize the current knowledge on the role of the ENS in gastrointestinal and systemic diseases, highlighting its interaction with various key players involved in shaping the phenotypes. Finally, current flaws and pitfalls related to ENS research in addition to future perspectives are also addressed.


Assuntos
Sistema Nervoso Entérico/fisiopatologia , Neoplasias Colorretais/fisiopatologia , Diabetes Mellitus/fisiopatologia , Dieta , Sistema Nervoso Entérico/embriologia , Acalasia Esofágica/genética , Acalasia Esofágica/fisiopatologia , Mucosa Gástrica/fisiologia , Microbioma Gastrointestinal/fisiologia , Doença de Hirschsprung/genética , Doença de Hirschsprung/fisiopatologia , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/fisiopatologia
12.
Sci Rep ; 11(1): 136, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420228

RESUMO

Recent research indicated the potential of cold physical plasma in cancer therapy. The plethora of plasma-derived reactive oxygen and nitrogen species (ROS/RNS) mediate diverse antitumor effects after eliciting oxidative stress in cancer cells. We aimed at exploiting this principle using a newly designed dual-jet neon plasma source (Vjet) to treat colorectal cancer cells. A treatment time-dependent ROS/RNS generation induced oxidation, growth retardation, and cell death within 3D tumor spheroids were found. In TUM-CAM, a semi in vivo model, the Vjet markedly reduced vascularized tumors' growth, but an increase of tumor cell immunogenicity or uptake by dendritic cells was not observed. By comparison, the argon-driven single jet kINPen, known to mediate anticancer effects in vitro, in vivo, and in patients, generated less ROS/RNS and terminal cell death in spheroids. In the TUM-CAM model, however, the kINPen was equivalently effective and induced a stronger expression of immunogenic cancer cell death (ICD) markers, leading to increased phagocytosis of kINPen but not Vjet plasma-treated tumor cells by dendritic cells. Moreover, the Vjet was characterized according to the requirements of the DIN-SPEC 91315. Our results highlight the plasma device-specific action on cancer cells for evaluating optimal discharges for plasma cancer treatment.


Assuntos
Neoplasias Colorretais/terapia , Neônio/farmacologia , Gases em Plasma/farmacologia , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/fisiopatologia , Humanos , Morte Celular Imunogênica/efeitos dos fármacos , Camundongos , Neônio/química , Estresse Oxidativo/efeitos dos fármacos , Fagocitose , Gases em Plasma/química , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Esferoides Celulares
13.
Asian Pac J Cancer Prev ; 22(1): 131-137, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33507690

RESUMO

INTRODUCTION: The present study aimed to determine the alterations in the serum levels of tumor markers used to evaluate cardiac, renal and liver function, and detect the interleukin (IL)-18 rs1946518 polymorphism in breast (BC), colorectal (CRC) and prostate cancer (PCa) patients. METHODS: Blood samples were collected from 65 female BC, 116 CRC, 79 PCa and 88 myocardial infarction (MI) patients, and 110 healthy individuals to determine the concentration of tumor and cardiac markers. Furthermore, the IL-18 rs1946518 polymorphism was assessed using amplification refractory mutation system (ARMS)-PCR. RESULTS: The serum levels of the tumor markers cancer antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and total prostate-specific antigen (TPSA) were significantly increased in cancer patients compared with healthy controls. Furthermore, the activity of high-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase­myocardial band (CK-MB) was enhanced in MI patients, however, their activity was unchanged in cancer patients. The activity of alkaline phosphatase (ALP), and the serum concentration of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and urea were markedly elevated in CRC and PCa patients, respectively, compared with the control group. Although, no significant differences were observed in the -607 C/A polymorphism and allele frequency of IL-18 among BC, CRC patients and healthy individuals, the odds ratio (OR) was 1.75 for both C and A allele in BC patients. Therefore, the -607 C/A polymorphism could be considered as a risk factor for BC. CONCLUSION: The aforementioned results suggested that tumor markers could be considered as excellent biomarkers for the early detection of BC, CRC and PCa, whereas the concentration of liver enzymes could serve as an alternative indicator for the diagnosis of CRC and PCa. Additionally, the rs1946518 polymorphism in the IL-18 gene could be considered as a risk factor for the occurrence of BC, CRC and PCa.
.


Assuntos
Neoplasias da Mama/fisiopatologia , Neoplasias Colorretais/fisiopatologia , Cardiopatias/patologia , Interleucina-18/genética , Nefropatias/patologia , Hepatopatias/patologia , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/fisiopatologia , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Feminino , Seguimentos , Cardiopatias/etiologia , Cardiopatias/metabolismo , Humanos , Nefropatias/etiologia , Nefropatias/metabolismo , Hepatopatias/etiologia , Hepatopatias/metabolismo , Masculino , Prognóstico
14.
Br J Cancer ; 124(7): 1231-1236, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33462361

RESUMO

BACKGROUND: The faecal immunochemical test (FIT) was introduced to triage patients with low-risk symptoms of possible colorectal cancer in English primary care in 2017, underpinned by little primary care evidence. METHODS: All healthcare providers in the South West of England (population 4 million) participated in this evaluation. 3890 patients aged ≥50 years presenting in primary care with low-risk symptoms of colorectal cancer had a FIT from 01/06/2018 to 31/12/2018. A threshold of 10 µg Hb/g faeces defined a positive test. RESULTS: Six hundred and eighteen (15.9%) patients tested positive; 458 (74.1%) had an urgent referral to specialist lower gastrointestinal (GI) services within three months. Forty-three were diagnosed with colorectal cancer within 12 months. 3272 tested negative; 324 (9.9%) had an urgent referral within three months. Eight were diagnosed with colorectal cancer within 12 months. Positive predictive value was 7.0% (95% CI 5.1-9.3%). Negative predictive value was 99.8% (CI 99.5-99.9%). Sensitivity was 84.3% (CI 71.4-93.0%), specificity 85.0% (CI 83.8-86.1%). The area under the ROC curve was 0.92 (CI 0.86-0.96). A threshold of 37 µg Hb/g faeces would identify patients with an individual 3% risk of cancer. CONCLUSIONS: FIT performs exceptionally well to triage patients with low-risk symptoms of colorectal cancer in primary care; a higher threshold may be appropriate in the wake of the COVID-19 crisis.


Assuntos
Neoplasias Colorretais/diagnóstico , Fezes/química , Sangue Oculto , Atenção Primária à Saúde , Anemia Ferropriva/complicações , Neoplasias Colorretais/complicações , Neoplasias Colorretais/fisiopatologia , Inglaterra , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Sensibilidade e Especificidade , Perda de Peso
16.
Magn Reson Imaging ; 75: 116-123, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32987123

RESUMO

Development of a deterministic algorithm for automated detection of the Arterial Input Function (AIF) in DCE-MRI of colorectal cancer. Using a filter pipeline to determine the AIF region of interest. Comparison to algorithms from literature with mean squared error and quantitative perfusion parameter Ktrans. The AIF found by our algorithm has a lower mean squared error (0.0022 ±â€¯0.0021) in reference to the manual annotation than comparable algorithms. The error of Ktrans (21.52 ±â€¯17.2%) is lower than that of other algorithms. Our algorithm generates reproducible results and thus supports a robust and comparable perfusion analysis.


Assuntos
Algoritmos , Artérias/diagnóstico por imagem , Artérias/fisiopatologia , Circulação Sanguínea , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/fisiopatologia , Imageamento por Ressonância Magnética , Automação , Meios de Contraste , Humanos , Processamento de Imagem Assistida por Computador , Reprodutibilidade dos Testes
17.
Nutr Rev ; 79(1): 88-97, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32679587

RESUMO

Excessive gut luminal iron contributes to the initiation and progression of colorectal cancer. However, emerging evidence suggests that reduced iron intake and low systemic iron levels are also associated with the pathogenesis of colorectal cancer. This is important because patients with colorectal cancer often present with iron deficiency. Iron is necessary for appropriate immunological functions; hence, iron deficiency may hinder cancer immunosurveillance and potentially modify the tumor immune microenvironment, both of which may assist cancer development. This is supported by studies showing that patients with colorectal cancer with iron deficiency have inferior outcomes and reduced response to therapy. Here, we provide an overview of the immunological consequences of iron deficiency and suggest ensuring adequate iron therapy to limit these outcomes.


Assuntos
Anemia Ferropriva/complicações , Neoplasias Colorretais/etiologia , Ferro/metabolismo , Microambiente Tumoral/imunologia , Animais , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/fisiopatologia , Humanos , Estado Nutricional
18.
Int J Mol Sci ; 21(22)2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33266494

RESUMO

Colorectal cancer (CRC) is the fourth leading cause of cancer mortality worldwide. Aberrant activation of WNT/ß-catenin signaling present in the vast majority of CRC cases is indispensable for CRC initiation and progression, and thus is a promising target for CRC therapeutics. Hispolon is a fungal-derived polyphenol with a pronounced anticancer effect. Several hispolon derivatives, including dehydroxyhispolon methyl ether (DHME), have been chemically synthesized for developing lead molecules with stronger anticancer activity. Herein, a DHME-elicited anti-CRC effect with the underlying mechanism is reported for the first time. Specifically, DHME was found to be more cytotoxic than hispolon against a panel of human CRC cell lines, while exerting limited toxicity to normal human colon cell line CCD 841 CoN. Additionally, the cytotoxic effect of DHME appeared to rely on inducing apoptosis. This notion was evidenced by DHME-elicited upregulation of poly (ADP-ribose) polymerase (PARP) cleavage and a cell population positively stained by annexin V, alongside the downregulation of antiapoptotic B-cell lymphoma 2 (BCL-2), whereas the blockade of apoptosis by the pan-caspase inhibitor z-VAD-fmk attenuated DHME-induced cytotoxicity. Further mechanistic inquiry revealed the inhibitory action of DHME on ß-catenin-mediated, T-cell factor (TCF)-dependent transcription activity, suggesting that DHME thwarted the aberrantly active WNT/ß-catenin signaling in CRC cells. Notably, ectopic expression of a dominant-active ß-catenin mutant (∆N90-ß-catenin) abolished DHME-induced apoptosis while also restoring BCL-2 expression. Collectively, we identified DHME as a selective proapoptotic agent against CRC cells, exerting more potent cytotoxicity than hispolon, and provoking CRC cell apoptosis via suppression of the WNT/ß-catenin signaling axis.


Assuntos
Apoptose , Neoplasias Colorretais/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , Antineoplásicos/farmacologia , Basidiomycota/química , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/fisiopatologia , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética
19.
PLoS One ; 15(12): e0239201, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33270661

RESUMO

PURPOSE: Quality of life in colorectal cancer patients may be affected by colostomy and treatment, but relevant studies are still scarce and contradictory. The present study aimed to evaluate the association between colostomy time and treatment type with quality of life in colorectal cancer patients. METHODS: A prospective observational study of 41 patients with colorectal cancer was conducted on three occasions T0, T1 and T2 (0-2; 3-5 and 6-8 months after ostomy surgery, respectively). The treatments prescribed were: surgery alone, chemotherapy or radiotherapy, or chemoradiotherapy. European Organization for Research and Treatment of Cancer questionnaires were used to evaluate quality of life. Worsening clinical changes were evaluated considering difference in scores between times of surgery ≥±9 points. RESULTS: Regarding ostomy surgery, scores in physical function improved between T0 and T1 and these better scores were maintained at T1 to T2. The same was observed for urinary frequency, appetite loss and dry mouth. Chemoradiotherapy was associated with worse scores for global health status, nausea and vomiting, bloating and dry mouth. Although significant differences were not observed in some domains in the Generalized Estimating Equations analysis, patients showed noticeable changes for the worse in the pain, anxiety, weight concern, flatulence and embarrassment domains during these periods. CONCLUSIONS: Colostomy improved quality of life at 3-5 months in most domains of quality of life and remained better at 6-8 months after surgery. Chemoradiotherapy had a late negative influence on quality of life. Health teams could use these results to reassure patients that this procedure will improve their quality of life in many functional and symptomatic aspects.


Assuntos
Neoplasias Colorretais/fisiopatologia , Neoplasias Colorretais/cirurgia , Colostomia/efeitos adversos , Estomia/efeitos adversos , Idoso , Quimiorradioterapia/efeitos adversos , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida
20.
BMJ Case Rep ; 13(12)2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33370932

RESUMO

A 58-year-old woman presented with a 1-week history of lower limb bruising. She had a medical history of recurrent metastatic colon cancer with a sigmoid colectomy and complete pelvic exenteration leading to colostomy and urostomy formation. She had malignant sacral mass encroaching on the spinal cord. This caused a left-sided foot drop for which she used an ankle-foot orthosis. She was on cetuximab and had received radiotherapy to the sacral mass 1 month ago. On examination, there were macular ecchymoses with petechiae on the lower limbs. There was sparing of areas that had been compressed by the ankle-foot orthosis. Bloods showed mild thrombocytopaenia and anaemia with markedly raised inflammatory markers. Coagulation studies consistent with inflammation rather than disseminated intravascular coagulation. She was found to have Klebsiella bacteraemia secondary to urinary source. Skin biopsy showed dermal haemorrhage without vessel inflammation. Vitamin C levels were low confirming the diagnosis of scurvy.


Assuntos
Ácido Ascórbico , Colectomia/efeitos adversos , Neoplasias Colorretais , Equimose , Desnutrição , Apoio Nutricional/métodos , Escorbuto , Antineoplásicos Imunológicos/uso terapêutico , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/sangue , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Colectomia/métodos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/fisiopatologia , Neoplasias Colorretais/secundário , Neoplasias Colorretais/terapia , Diagnóstico Diferencial , Equimose/sangue , Equimose/diagnóstico , Equimose/etiologia , Feminino , Humanos , Klebsiella/isolamento & purificação , Extremidade Inferior , Desnutrição/etiologia , Desnutrição/terapia , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Exenteração Pélvica/efeitos adversos , Exenteração Pélvica/métodos , Escorbuto/sangue , Escorbuto/etiologia , Escorbuto/fisiopatologia , Escorbuto/terapia , Pele/patologia , Resultado do Tratamento , Vitaminas/administração & dosagem
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