Diagnostic microchip to assay 3D colony-growth potential of captured circulating tumor cells

Microfluidic technology has been successfully applied to isolate very rare tumor-derived epithelial cells (circulating tumor cells, CTCs) from blood with relatively high yield and purity, opening up exciting prospects for early detection of cancer. However, a major limitation of state-of-the-art CTC-chips is their inability to characterize the behavior and function of captured CTCs, for example to obtain information on proliferative and invasive properties or, ultimately, tumor re-initiating potential. Although CTCs can be efficiently immunostained with markers reporting phenotype or fate (e.g. apoptosis, proliferation), it has not yet been possible to reliably grow captured CTCs over long periods of time and at single cell level. It is challenging to remove CTCs from a microchip after capture, therefore such analyses should ideally be performed directly on-chip. To address this challenge, we merged CTC capture with three-dimensional (3D) tumor cell culture on the same microfluidic platform. PC3 prostate cancer cells were isolated from spiked blood on a transparent PDMS CTC-chip, encapsulated on-chip in a biomimetic hydrogel matrix (QGel™) that was formed in situ, and their clonal 3D spheroid growth potential was assessed by microscopy over one week in culture. The possibility to clonally expand a subset of captured CTCs in a near-physiological in vitro model adds an important element to the expanding CTC-chip toolbox that ultimately should improve prediction of treatment responses and disease progression.

Impact of a modified dietary plan on the health related quality of life of minority participants in the Women's Healthy Eating and Living (WHEL) Study

Advances in medical technology, in genetics, and in clinical research have led to early detection of cancer, precise diagnosis, and effective treatment modalities. Decline in cancer incidence and mortality due to cancer has led to increased number of long-term survivors. However, the ethnic minority population has not experienced this decline and still continues to carry a disparate proportion of the cancer burden. Majority of the clinical research including survivorship studies have recruited and continue to recruit a convenient sample of middle- to upper-class Caucasian survivors. Thus, minorities are underrepresented in cancer research in terms of both clinical studies and in health related quality of life (HRQOL) studies. ^ Life style and diet have been associated with increased risk of breast cancer. High vegetable low fat diet has been shown to reduce recurrence of breast cancer and early death. The Women's Healthy Eating and Living Study is an ongoing multi-site randomized controlled trial that is evaluating the high-vegetable low fat diet in reducing the recurrence of breast cancer and early death. The purpose of this dissertation was to (1) compare the impact of the modified diet on the HRQOL during the first 12-month period on specific Minorities and matched Caucasians; (2) identify predictors that significantly impact the HRQOL of the study participants; and (3) using the structural equation modeling assess the impact of nutrition on the HRQOL of the intervention group participants. Findings suggest that there are no significant differences in change in HRQOL between Minorities and Caucasians; between Minorities in the intervention group and those in the comparison group; and between women in the intervention group and those in the comparison group. Minority indicator variable and Intervention/Comparison group indicator variable were not found to be good predictors of HRQOL. Although the structural equation models suggested viable representation of the relationship between the antecedent variables, the mediating variables and the two outcome variables, the impact of nutrition was not statistically significant to be included in the model. This dissertation, by analyzing the HRQOL of minorities in the WHEL Study, attempted to add to the knowledge base specific to minority cancer survivors. ^

Detection of Biological CO2 and 1,3-Pentadiene Using Non-refrigerated Low-Cost MWIR Detectors

The early detection of spoiling metabolic products in contaminated food is a very important tool to control quality. Some volatile compounds produce unpleasant odours at very low concentrations, making their early detection very challenging. This is the case of 1,3-pentadiene produced by microorganisms through decarboxylation of the preservative sorbate. In this work, we have developed a methodology to use the data produced by a low-cost, compact MWIR (Mid-Wave IR) spectrometry device without moving parts, which is based on a linear array of 128 elements of VPD PbSe coupled to a linear variable filter (LVF) working in the spectral range between 3 and 4.6 ?m. This device is able to analyze food headspace gases through dedicated sample presentation setup. This methodology enables the detection of CO2 and the volatile compound 1,3-pentadiene, as compared to synthetic patrons. Data analysis is based on an automated multidimensional dynamic processing of the MWIR spectra. Principal component and discriminant analysis allow segregating between four yeast strains including producers and no producers. The segregation power is accounted as a measure of the discrimination quality.

Presentation and detection of invasive melanoma in a high-risk population

Background: Early detection of melanoma has been encouraged in Queensland for many years, yet little is known about the patterns of detection and the way in which they relate to tumor thickness. Objective: Our purpose was to describe current patterns of melanoma detection in Queensland. Methods: This was a population-based study, comprising 3772 Queensland residents diagnosed with a histologically confirmed melanoma between 2000 and 2003. Results: Almost half (44.0%) of the melanomas were detected by the patients themselves, with physicians detecting one fourth (25.3%) and partners one fifth (18.6%). Melanomas detected by doctors were more likely to be thin (\0.75 mm) than those detected by the patient or other layperson. Melanomas detected during a deliberate skin examination were thinner than those detected incidentally. Limitations: Although a participation rate of 78% was achieved, as in any survey, nonresponse bias cannot be completely excluded, and the ability of the results to be generalized to other geographical areas is unknown. Conclusion: There are clear differences in the depth distribution of melanoma in terms of method of detection and who detects the lesions that are consistent with, but do not automatically lead to, the conclusion that promoting active methods of detection may be beneficial. ( J Am Acad Dermatol 2006;54:783-92.)

Acoustic and Magnetic Techniques for the Isolation and Analysis of Cells in Microfluidic Platforms

Cancer comprises a collection of diseases, all of which begin with abnormal tissue growth from various stimuli, including (but not limited to): heredity, genetic mutation, exposure to harmful substances, radiation as well as poor dieting and lack of exercise. The early detection of cancer is vital to providing life-saving, therapeutic intervention. However, current methods for detection (e.g., tissue biopsy, endoscopy and medical imaging) often suffer from low patient compliance and an elevated risk of complications in elderly patients. As such, many are looking to “liquid biopsies” for clues into presence and status of cancer due to its minimal invasiveness and ability to provide rich information about the native tumor. In such liquid biopsies, peripheral blood is drawn from patients and is screened for key biomarkers, chiefly circulating tumor cells (CTCs). Capturing, enumerating and analyzing the genetic and metabolomic characteristics of these CTCs may hold the key for guiding doctors to better understand the source of cancer at an earlier stage for more efficacious disease management.

The isolation of CTCs from whole blood, however, remains a significant challenge due to their (i) low abundance, (ii) lack of a universal surface marker and (iii) epithelial-mesenchymal transition that down-regulates common surface markers (e.g., EpCAM), reducing their likelihood of detection via positive selection assays. These factors potentiate the need for an improved cell isolation strategy that can collect CTCs via both positive and negative selection modalities as to avoid the reliance on a single marker, or set of markers, for more accurate enumeration and diagnosis.

The technologies proposed herein offer a unique set of strategies to focus, sort and template cells in three independent microfluidic modules. The first module exploits ultrasonic standing waves and a class of elastomeric particles for the rapid and discriminate sequestration of cells. This type of cell handling holds promise not only in sorting, but also in the isolation of soluble markers from biofluids. The second module contains components to focus (i.e., arrange) cells via forces from acoustic standing waves and separate cells in a high throughput fashion via free-flow magnetophoresis. The third module uses a printed array of micromagnets to capture magnetically labeled cells into well-defined compartments, enabling on-chip staining and single cell analysis. These technologies can operate in standalone formats, or can be adapted to operate with established analytical technologies, such as flow cytometry. A key advantage of these innovations is their ability to process erythrocyte-lysed blood in a rapid (and thus high throughput) fashion. They can process fluids at a variety of concentrations and flow rates, target cells with various immunophenotypes and sort cells via positive (and potentially negative) selection. These technologies are chip-based, fabricated using standard clean room equipment, towards a disposable clinical tool. With further optimization in design and performance, these technologies might aid in the early detection, and potentially treatment, of cancer and various other physical ailments.

Men's knowledge and attitudes about cervical cancer screening in Kenya.

BACKGROUND: A number of studies have identified male involvement as an important factor affecting reproductive health outcomes, particularly in the areas of family planning, antenatal care, and HIV care. As access to cervical cancer screening programs improves in resource-poor settings, particularly through the integration of HIV and cervical cancer services, it is important to understand the role of male partner support in women's utilization of screening and treatment. METHODS: We administered an oral survey to 110 men in Western Kenya about their knowledge and attitudes regarding cervical cancer and cervical cancer screening. Men who had female partners eligible for cervical cancer screening were recruited from government health facilities where screening was offered free of charge. RESULTS: Specific knowledge about cervical cancer risk factors, prevention, and treatment was low. Only half of the men perceived their partners to be at risk for cervical cancer, and many reported that a positive screen would be emotionally upsetting. Nevertheless, all participants said they would encourage their partners to get screened. CONCLUSIONS: Future interventions should tailor cervical cancer educational opportunities towards men. Further research is needed among both men and couples to better understand barriers to male support for screening and treatment and to determine how to best involve men in cervical cancer prevention efforts.

EULAR Recommendations for Women's Health and the Management of Family Planning, Assisted Reproduction, Pregnancy and Menopause in Patients with Systemic Lupus Erythematosus and/or Antiphospholipid Syndrome

OBJECTIVES: Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). METHODS: Systematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus. RESULTS: Family planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease. CONCLUSIONS: Recommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.

Influência do tratamento de radioterapia na qualidade de vida dos doentes com cancro de mama

RESUMO: Introdução – A evolução tecnológica permitiu uma deteção precoce do cancro e, consequentemente, uma abordagem terapêutica mais eficaz e efetiva, resultando no aumento da sobrevida dos doentes. Assim, pretende-se avaliar a influência da radioterapia na qualidade de vida dos doentes com cancro da mama. Metodologia – 47 participantes que efetuaram radioterapia no Centro Hospitalar Barreiro-Montijo preencheram os dois questionários, o EORTC QLQ-C30 e o QLQ-BR23, antes de iniciar radioterapia e no último dia do tratamento. Os resultados foram analisados através do programa informático SPSS, versão 19.0. Resultados – Observou-se um ligeiro decréscimo na qualidade da saúde global no segundo momento de avaliação. Verificou-se uma diminuição nas escalas sintomática e funcional no segundo momento de avaliação. Em relação ao questionário QLQ-BR23, na escala sintomática, observou-se uma diminuição nos efeitos secundários resultantes da radioterapia no último momento de avaliação. Discussão dos Resultados – Os resultados obtidos no questionário QLQ-C30 revelam que a avaliação global da saúde dos doentes não é influenciada pelo tratamento de radioterapia. Em relação ao questionário QLQ-BR23, os sintomas relacionados com a mama e o braço tiveram um aumento ligeiramente significativo no segundo momento de avaliação, sendo estes associados à radioterapia. De acordo com os resultados obtidos, a radioterapia não influencia a qualidade de vida em doentes com cancro da mama.

Selecting control genes for RT-QPCR using public microarray data.

Background: Gene expression analysis has emerged as a major biological research area, with real-time quantitative reverse transcription PCR (RT-QPCR) being one of the most accurate and widely used techniques for expression profiling of selected genes. In order to obtain results that are comparable across assays, a stable normalization strategy is required. In general, the normalization of PCR measurements between different samples uses one to several control genes (e. g. housekeeping genes), from which a baseline reference level is constructed. Thus, the choice of the control genes is of utmost importance, yet there is not a generally accepted standard technique for screening a large number of candidates and identifying the best ones. Results: We propose a novel approach for scoring and ranking candidate genes for their suitability as control genes. Our approach relies on publicly available microarray data and allows the combination of multiple data sets originating from different platforms and/or representing different pathologies. The use of microarray data allows the screening of tens of thousands of genes, producing very comprehensive lists of candidates. We also provide two lists of candidate control genes: one which is breast cancer-specific and one with more general applicability. Two genes from the breast cancer list which had not been previously used as control genes are identified and validated by RT-QPCR. Open source R functions are available at http://www.isrec.isb-sib.ch/similar to vpopovic/research/ Conclusion: We proposed a new method for identifying candidate control genes for RT-QPCR which was able to rank thousands of genes according to some predefined suitability criteria and we applied it to the case of breast cancer. We also empirically showed that translating the results from microarray to PCR platform was achievable.

Gériatrie [Review in geriatric medicine 2011].

In 2011, new tools to evaluate life expectancy are available. Controversy about PSA-based screening for prostate cancer is still going on, with new data from the US Preventive services task force. A brief behavioral treatment for insomnia can be efficient and durable. Gliptines are be useful to avoid treatment-induced hypoglycemia in diabetic patients. New Alzheimer diagnostic criteria, including biomarkers, have been published.

Optimizing urothelial cell preparation for the human urinary micronucleus assay.

Biological monitoring of early genotoxic effects in urothelial cells using the urinary micronucleus (MNu) assay is promising for early detection of cancer, such as bladder carcinoma. But many problems are encountered, the major being the poorly differential staining of cells, particularly in women having an important amount of squamous cells. We have optimized the protocol and obtained a differential staining of the cell types present in urine on 10 subjects. Following Carnoy I fixation and Papanicolaou staining, urothelial cells were blue while most squamous cells were pink. This differential staining allowed for optimization of the MNu assay on a single urine void, for both females and males. Even if our MNu means were comparable to the literature, the great variation in reported MNu results could reside in the ability of scorers to distinguish correctly between urothelial and squamous cells. When monitoring exposed populations, this erroneous distinction could largely influence the results, even more in women’s urine samples. Given a situation where exposure would not increase micronuclei frequency in vaginal squamous cells, their erroneous analysis in the MNu assay could mask an early genotoxic effect. Therefore, as transitional cell carcinoma of the bladder originates from transformed urothelial cells, restricting micronuclei analysis to urothelial cells could yield a more precise estimate of cancer risk in exposed populations. Moreover, it is hoped that the improvements proposed in this paper will allow for an easier implementation of the MNu assay in various set-ups and enhance its specificity, since MNu are considered a suitable biomarker.

Gingival squamous cell carcinoma: a case report

Squamous cell carcinoma is a malignant epithelial neoplasm characterized by variable clinical manifestations. When located in the gingiva, this neoplasm may mimic common inflammatory lesions. The aim of this study was to report a case of atypical squamous cell carcinoma, in which the patient had no risk factors for the development of this neoplasm. A 61 year old Caucasian female was seen with a 3 month history of a rapidly growing, painful nodule in the gingiva adjacent to tooth #11. Clinical examination revealed a proliferative lesion in the vestibular marginal gingiva of teeth #11 and #12, presenting with purulent exudation. Thus, in view of the clinical symptoms and differential diagnosis of an infectious granulomatous process and malignant neoplasm, an incisional biopsy was obtained from the lesion. The diagnosis of squamous cell carcinoma was made and fourteen days after incisional biopsy, healing was found to be unsatisfactory. The patient was referred for treatment consisting of surgical excision of the tumour. A removable partial denture was fabricated for rehabilitation, one month after surgery of the maxilla; the patient was submitted to dissection of the regional lymph nodes and radiotherapy for an additional 3 months. Three years after the end of treatment, the patient continues to be followed-up and does not show any sign of recurrence. Gingival squamous cell carcinoma is a condition which chance of cure is higher when carcinomatous lesions are diagnosed and treated early. In this instance dentists play an important role in early detection of gingival squamous cell carcinoma.

Exame colorretal : conhecimentos e sentimentos dos utentes submetidos ao rastreio

INTRODUÇÃO: O câncer colorretal é a terceira causa de morte no mundo e requer diagnóstico precoce. OBJETIVO: Determinar a influência das variáveis sociodemográficas sobre o nível de conhecimento e sentimentos desencadeados nos utentes submetidos ao primeiro exame colonoscópico. MÉTODOS: Estudo transversal, observacional, primário, aberto em centro único realizado com 100 participantes, entre 1 e 24 de dezembro de 2015, utilizando instrumento de colheita dos dados composto por 22 perguntas para caracterização sociodemográfica dos pacientes, e determinação dos conhecimentos e sentimentos despertados pela colonoscopia. Após organização dos dados, procedeu-se à análise com o pacote estatístico Epi Info 7, na versão 7.1.5.2, empregando parâmetros da Estatística Descritiva. RESULTADOS: A maioria dos utentes (81%) afirmou ter pouco ou nenhum conhecimento sobre a colonoscopia, obtido junto a diversos agentes, dos quais o médico não era o mais frequente. O nível de conhecimento auto-perceptível não teve relação com a especificação de risco da colonoscopia, idade de rastreio e repetição do exame. As dificuldades mais frequentes foram o preparo do cólon, vergonha, medo de diagnóstico de câncer e da sedação. As variáveis sexo, escolaridade, estado civil e situação profissional mantiveram associação com sentimento de vergonha, angústica, segurança durante a colonoscopia e a percepção de repetir o exame caso necessário. CONCLUSÃO: Aumentar a adesão dos utentes à colonoscopia exige considerar suas características para contribuir com menor sofrimento, cabendo à enfermagem um papel relevante na melhoria dos cuidados. Palavras-chave: Câncer colorretal. Colonoscopia. Conhecimento.

Discovering Hands - México

El modelo de Discovering Hands ha sido reconocido internacionalmente como un proyecto innovador que se ha expandido por diferentes países del mundo, como Austria, y se ha empezado a estudiar la propuesta en países como República Checa, India y Colombia. (Discovering Hands, 2016). Esto se debe a que no solo mejora el tratamiento de cáncer de mama, sino que también reduce los costos totales de tratamiento de la enfermedad y aumenta la fuerza laborar de los países donde esté presente. Al representar una gran oportunidad en diferentes aspectos, se quiso desarrollar un estudio de factibilidad del modelo de negocio en tres países de América Latina, Colombia –donde ya se encuentra en marcha un proyecto piloto liderado por la CAF en Cali - , Argentina y México. El presente trabajo consiste en dicho estudio de factibilidad, focalizado en México; por medio de este se buscaron tres cosas primordiales, conocer y estudiar el contexto del mercado y situación de salud en el país, analizar los datos recogidos, con el fin de proponer soluciones para disminuir una de las principales causas de muerte en el país. Actualmente en México el 52% de casos de cáncer de mama diagnosticados sucede en etapas tardías, aumentando el riesgo de muerte de los pacientes (Colima, 2013). Con el estudio se logró identificar una oportunidad potencial para Discovering Hands siendo su estrategia un recurso adicional para contribuir a mejorar el diagnóstico precoz de cáncer de mama en el país y debido a esto se presenta un modelo de negocio adaptable a las necesidades mexicanas