Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
1.
Transl Oncol ; 14(12): 101229, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34592589

RESUMO

Tumour metastasis accounts for over 90% of cancer related deaths. The platelet is a key blood component, which facilitates efficient metastasis. This study aimed to understand the molecular mechanisms involved in tumour-platelet cell interactions. The interaction between cancer cells and platelets was examined in 15 epithelial cell lines, representing 7 cancer types. Gene expression analysis of EMT-associated and cancer stemness genes was performed by RT-PCR. Whole transcriptome analysis (WTA) was performed using Affymetrix 2.0ST arrays on a platelet co-cultured ovarian model. Platelet adhesion and activation occurred across all tumour types. WTA identified increases in cellular movement, migration, invasion, adhesion, development, differentiation and inflammation genes and decreases in processes associated with cell death and survival following platelet interaction. Increased invasive capacity was also observed in a subset of cell lines. A cross-comparison with a platelet co-cultured mouse model identified 5 common altered genes; PAI-1, PLEK2, CD73, TNC, and SDPR. Platelet cancer cell interactions are a key factor in driving the pro-metastatic phenotype and appear to be mediated by 5 key genes which have established roles in metastasis. Targeting these metastasis mediators could improve cancer patient outcomes.

2.
Mol Cancer ; 20(1): 59, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789677

RESUMO

Cancer cells that transit from primary tumours into the circulatory system are known as circulating tumour cells (CTCs). These cancer cells have unique phenotypic and genotypic characteristics which allow them to survive within the circulation, subsequently extravasate and metastasise. CTCs have emerged as a useful diagnostic tool using "liquid biopsies" to report on the metastatic potential of cancers. However, CTCs by their nature interact with components of the blood circulatory system on a constant basis, influencing both their physical and morphological characteristics as well as metastatic capabilities. These properties and the associated molecular profile may provide critical diagnostic and prognostic capabilities in the clinic. Platelets interact with CTCs within minutes of their dissemination and are crucial in the formation of the initial metastatic niche. Platelets and coagulation proteins also alter the fate of a CTC by influencing EMT, promoting pro-survival signalling and aiding in evading immune cell destruction. CTCs have the capacity to directly hijack immune cells and utilise them to aid in CTC metastatic seeding processes. The disruption of CTC clusters may also offer a strategy for the treatment of advance staged cancers. Therapeutic disruption of these heterotypical interactions as well as direct CTC targeting hold great promise, especially with the advent of new immunotherapies and personalised medicines. Understanding the molecular role that platelets, immune cells and the coagulation cascade play in CTC biology will allow us to identify and characterise the most clinically relevant CTCs from patients. This will subsequently advance the clinical utility of CTCs in cancer diagnosis/prognosis.


Assuntos
Coagulação Sanguínea , Plaquetas/metabolismo , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Animais , Biomarcadores , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Comunicação Celular/genética , Comunicação Celular/imunologia , Gerenciamento Clínico , Suscetibilidade a Doenças , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/imunologia , Humanos , Neoplasias/sangue , Neoplasias/complicações , Neoplasias/etiologia , Neoplasias/patologia
3.
Breast Cancer Res Treat ; 181(3): 571-580, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32378053

RESUMO

PURPOSE: The association between pathological complete response (pCR) in patients receiving neoadjuvant chemotherapy (NAC) for breast cancer and Circulating Tumour Cells (CTCs) is not clear. The aim of this study was to assess whether CTC enumeration could be used to predict pathological response to NAC in breast cancer as measured by the Miller-Payne grading system. METHODS: Twenty-six patients were recruited, and blood samples were taken pre- and post-NAC. CTCs were isolated using the ScreenCell device and stained using a modified Giemsa stain. CTCs were enumerated by 2 pathologists and classified as single CTCs, doublets, clusters/microemboli and correlated with the pathological response as measured by the Miller-Payne grading system. χ2 or ANOVA was performed in SPSS 24.0 statistics software for associations. RESULTS: 89% of patients had invasive ductal carcinoma (IDC) and 11% invasive lobular carcinoma (ILC). At baseline 85% of patients had CTCs present, median 7 (0-161) CTCs per 3 ml of whole blood. Post-chemotherapy, 58% had an increase in CTCs. This did not correlate with the Miller-Payne grade of response. No significant association was identified between the number of CTCs and clinical characteristics; however, we did observe a correlation between pre-treatment CTC counts and body mass index, p < 0.05. CONCLUSIONS: Patients with a complete response to NAC still had CTCs present, suggesting enumeration is not sufficient to aid surgery stratification. Additional characterisation and larger studies are needed to further characterise CTCs isolated pre- and post-chemotherapy. Long-term follow-up of these patients will determine the significance of CTCs in NAC breast cancer patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Terapia Neoadjuvante/mortalidade , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/metabolismo , Estudos de Coortes , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Células Neoplásicas Circulantes/efeitos dos fármacos , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Taxa de Sobrevida
4.
Artigo em Inglês | MEDLINE | ID: mdl-29312142

RESUMO

Growth hormone (GH) promotes growth in children, but is also essential for bone strength, body composition, metabolic factors, such as lipid profile, and maintenance of quality of life. The Merck KGaA (Germany) funded "360° GH in Europe" meeting, held in Lisbon, Portugal, in June 2016, comprised three sessions entitled "Short Stature Diagnosis and Referral," "Optimizing Patient Management and Adherence," and "Managing Transition." The scientific program covered all stages of pediatric GH treatment, and reported here are the outcomes of the third session of the meeting, which considered transition from pediatric GH treatment to teenage and young adult GH therapy. A large number of patients with chronic diseases, including GH deficiency, drop out of therapy during the transition period. Multiple factors are associated with this, such as lack of understanding of the disease process, insufficient knowledge of treatment options, the patient becoming more independent, and requirement for interaction with a new set of health-care workers. Education regarding disease management and treatment options should be provided from an early age and right through the transition period. However, endocrine specialists will view the transition period differently, depending on whether they are pediatric endocrinologists who mainly deal with congenital diseases, in which auxology is important, or adult endocrinologists who are more concerned with body composition and metabolic factors. View points of both a pediatric and an adult endocrine specialist are presented, together with a case study outlining practical aspects of transition. It was noted in the meeting discussion that having one person to guide a patient through transition from an early age is important, but may be constrained by various factors such as finances, and options will differ by country.

5.
Artigo em Inglês | MEDLINE | ID: mdl-21430238

RESUMO

In the 1990s, an interdisciplinary group including pediatricians, anthropologists, health educators, psychologists, and statisticians developed and evaluated an HIV prevention intervention targeting early adolescents living in public housing developments in the USA. The intervention, "Focus on Kids," (FOK) was effective in reducing risk behaviors, intentions, and perceptions and ultimately was included in the Center for Disease Control's portfolio of effective adolescent programs, "Programs that Work." Learning about FOK and concerned about the need for a structured program to address high rates of teen pregnancy and risk for HIV, professionals from the Ministries of Health of The Bahamas approached the researchers about collaborating to develop a program for Bahamian youth. A partnership developed which has spanned over a decade and led to the development of an intervention program targeting Bahamian children in grade six, a 10-session adolescent HIV prevention program entitled "Focus on Youth in the Caribbean" (FOYC). Two programs including a video and parent discussion were developed for their parents. Caribbean Informed Parents and Children Together (CImPACT) emphasizes the importance of parent-child communication about sexuality and "Goal for It" (GFI) emphasizes the importance of planning ahead. The US-Bahamian team evaluated these interventions through a randomized, controlled 3-celled longitudinal trial (36 months follow-up) involving 15 elementary schools in The Bahamas. The programs have been shown to be effective. This article describes the context in which the epidemic occurred, events leading up to the collaboration and the issues, decisions, processes, and relationships that we have developed that have allowed it to succeed.


Assuntos
Infecções por HIV , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Região do Caribe , Infecções por HIV/prevenção & controle , Humanos , Comportamento de Redução do Risco , Comportamento Sexual
6.
J Phys Chem A ; 109(2): 347-55, 2005 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-16833353

RESUMO

Product distribution studies of the OH radical and Cl atom initiated oxidation of CF3CH2CH2OH in air at 1 atm and 298 +/- 5 K have been carried out in laboratory and outdoor atmospheric simulation chambers in the presence and absence of NOx. The results show that CF3CH2CHO is the only primary product and that the aldehyde is fairly rapidly removed from the system. In the absence of NOx the major degradation product of CF3CH2CHO is CF3CHO, and the combined yields of the two aldehydes formed from CF3CH2CH2OH are close to unity (0.95 +/- 0.05). In the presence of NOx small amounts of CF3CH2C(O)O2NO2 were also observed (<15%). At longer reaction times CF3CHO is removed from the system to give mainly CF2O. The laser photolysis-laser induced fluorescence technique was used to determine values of k(OH + CF3CH2CH2OH) = (0.89 +/- 0.03) x 10(-12) and k(OH + CF3CH2CHO) = (2.96 +/- 0.04) x 10(-12) cm3 molecule(-1) s(-1). A relative rate method has been employed to measure the rate coefficients k(OH + CF3CH2CH2OH) = (1.08 +/- 0.05) x 10(-12), k(OH + C6F13CH2CH2OH) = (0.79 +/- 0.08) x 10(-12), k(Cl + CF3CH2CH2OH) = (22.4 +/- 0.4) x 10(-12), and k(Cl + CF3CH2CHO) = (25.7 +/- 0.4) x 10(-12) cm3 molecule(-1) s(-1). The results from this investigation are discussed in terms of the possible importance of emissions of fluorinated alcohols as a source of fluorinated carboxylic acids in the environment.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...