Development of an in vitro multicellular tumor spheroid model using microencapsulation and its application in anticancer drug screening and testing

In this study, an in vitro multicellular tumor spheroid model was developed using microencapsulation, and the feasibility of using the microencapsulated. multicellular tumor spheroid (MMTS) to test the effect of chemotherapeutic drugs was investigated. Human MCF-7 breast cancer cells were encapsulated in alginate-poly-L-lysine-alginate (APA) microcapsules, and a single multicellular spheroid 150 mu m in diameter was formed in the microcapsule after 5 days of cultivation. The cell morphology, proliferation, and viability of the MMTS were characterized using phase contrast microscopy, BrdU-Iabeling, MTT stain, calcein AM/ED-2 stain, and H&E stain. It demonstrated that the MMTS was viable and that the proliferating cells were mainly localized to the periphery of the cell spheroid and the apoptotic cells were in the core. The MCF-7 MMTS was treated with mitomycin C (MC) at a concentration of 0.1, 1, or 10 times that of peak plasma concentration (ppc) for up to 72 h. The cytotoxicity was demonstrated. clearly by the reduction in cell spheroid size and the decrease in cell viability. The MMTS was further used to screen the anticancer effect of chemotherapeutic drugs, treated with MC, adriamycin (ADM) and 5-fluorouracil (5-FU) at concentrations of 0.1, 1, and 10 ppc for 24, 48, and 72 h. MCF-7 monolayer culture was used as control. Similar to monolayer culture, the cell viability of MMTS was reduced after treatment with anticancer drugs. However, the inhibition rate of cell viability in MMTS was much lower than that in monolayer culture. The MMTS was more resistant to anticancer drugs than monolayer culture. The inhibition rates of cell viability were 68.1%, 45.1%, and 46.8% in MMTS and 95.1%, 86.8%, and 91.6% in monolayer culture treated with MC, ADM, and 5-FU at 10 ppc for 72 h, respectively. MC showed the strongest cytotoxicity in both MMTS and monolayer, followed by 5-FU and ADM. It demonstrated that the MMTS has the potential to be a rapid and valid in vitro model to screen chemotherapeutic drugs with a feature to mimic in vivo three-dimensional (3-D) cell growth pattern.

Clinical significance and prognostic value of urinary nucleosides in breast cancer patients

Objective: Thirteen urinary nucleosides, primarily degradation products of tRNA, were evaluated as potential tumor markers for breast cancer patients.

Anthropometry of the Breast Region: How to Measure?

Breast region measurements are important for research, but they may also become significant in the legal field as a quantitative tool for preoperative and postoperative evaluation. Direct anthropometric measurements can be taken in clinical practice. the aim of this study was to compare direct breast anthropometric measurements taken with a tape measure and a compass.Forty women, aged 18-60 years, were evaluated. They had 14 anatomical landmarks marked on the breast region and arms. the union of these points formed eight linear segments and one angle for each side of the body. the volunteers were evaluated by direct anthropometry in a standardized way, using a tape measure and a compass.Differences were found between the tape measure and the compass measurements for all segments analyzed (p > 0.05).Measurements obtained by tape measure and compass are not identical. Therefore, once the measurement tool is chosen, it should be used for the pre- and postoperative measurements in a standardized way.This journal requires that authors assign a level of evidence to each article. for a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Accelerated partial irradiation for breast cancer: Systematic review and meta-analysis of 8653 women in eight randomized trials

Background and purpose: Accelerated partial breast irradiation (APBI) is the strategy that allows adjuvant treatment delivery in a shorter period of time in smaller volumes. This study was undertaken to assess the effectiveness and outcomes of APBI in breast cancer compared with whole-breast irradiation (WBI). Material and methods: Systematic review and meta-analysis of randomized controlled trials of WBI versus APBI. Two authors independently selected and assessed the studies regarding eligibility criteria. Results: Eight studies were selected. A total of 8653 patients were randomly assigned for WBI versus APBI. Six studies reported local recurrence outcomes. Two studies were matched in 5 years and only one study for different time of follow-up. Meta-analysis of two trials assessing 1407 participants showed significant difference in the WBI versus APBI group regarding the 5-year local recurrence rate (HR = 4.54, 95% CI: 1.78-11.61, p = 0.002). Significant difference in favor of WBI for different follow-up times was also found. No differences in nodal recurrence, systemic recurrence, overall survival and mortality rates were observed. Conclusions: APBI is associated with higher local recurrence compared to WBI without compromising other clinical outcomes. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Influência da densidade de semeadura nas características agronômicas de cultivares de girassol.

RESUMO: O presente trabalho teve como objetivo avaliar a influência de densidades de semeadura de genótipos de girassol em suas características agronômicas. O experimento foi realizado no campo experimental do IFMT, Campus Campo Novo do Parecis - MT, entre os meses de fevereiro e junho de 2015. O delineamento experimental utilizado foi de blocos casualizados, em esquema fatorial 5 x 5, sendo cinco genótipos de girassol AGUARÁ 04, GNZ NEON, HÉLIO 251, SYN 045 e SYN 3950HO) e cinco populações de plantas (30.000, 37.500, 45.000, 52.500 e 60.000 plantas ha-1), com 3 repetições. Foram analisadas as características altura de planta, diâmetro da haste, tamanho do capítulo, massa de mil aquênios e produtividade de aquênios. Os dados obtidos foram submetidos à análise de variância, seguido de teste Tukey para cultivares e análise de regressão para as diferentes populações de plantas (p<0,05). O genótipo SYN 045 apresentou a maior produtividade de aquênios, 1.708,90 kg ha-1 enquanto que a população de 60.150 plantas ha-1 foi a que possibilitou a maior produtividade de aquênios, 2.391,92 kg ha-1. ABSTRACT: This study aimed to evaluate the influence of sowing density of sunflower genotypes on their agronomic characteristics. The experiment was conducted in the experimental field of IFMT, Campus Campo Novo do Parecis - MT, between February and June 2015. The experimental design was randomized blocks in a factorial 5 x 5, five sunflower genotypes (AGUARÁ 04, GNZ NEON, HÉLIO 251, SYN 045 and SYN 3950HO) and five plant populations (30,000, 37,500, 45,000, 52,500 and 60,000 plants ha-1) with 3 repetitions. Plant height, stem diameter, chapter length, mass thousand achenes and achenes productivity were analyzed. The data were submitted to analysis of variance followed by Tukey test for cultivars and regres. -

Desempenho morfoagronômico de genótipos de girassol cultivados na Chapada do Araripe, Pernambuco.

RESUMO: Com o objetivo de avaliar o desempenho agronômico de genótipos de girassol nas condições edafoclimáticas do primeiro semestre de 2015 na Chapada do Araripe, instalou-se um experimento na Estação Experimental do Instituto Agronômico de Pernambuco (IPA), no município de Araripina, Estado de Pernambuco. O delineamento foi o de blocos ao acaso, com quatro repetições e 13 tratamentos, correspondendo aos genótipos de girassol: M734, NTC 90, BRS G43, BRS G44, BRS G45, BRS G46, SYN 065, HLA 2013, HLA 2014, HLA 2015, HLA 2016, HLA 2017 e SYN 045. Avaliaram-se as seguintes características: sobrevivência final, floração inicial, maturação fisiológica, altura média do capítulo, peso de 1000 aquênios, diâmetro médio dos capítulos, produção final de aquênios, curvatura do capítulo e plantas acamadas, quebradas e atacadas por pássaros. Os genótipos apresentaram diferenças morfoagronômicas quando cultivados no primeiro semestre em condições edafoclimáticas da região do Araripe, com exceção da variável sobrevivência. O genótipo NTC 90 alcançou o maior peso de aquênios. Todos os genótipos, exceto HLA 2015, apresentaram elevado rendimento de grãos. Os caracteres plantas acamadas, quebradas, atacadas por pássaros ou a curvatura do capítulo não foram relacionadas às diferentes cultivares. ABSTRACT: The study aimed to evaluate the agronomic performance of different sunflower genotypes in edaphoclimatic conditions of Araripe region in the first semester of 2015. The experiment was established at the Experimental Station of Instituto Agronômico de Pernambuco (IPA), Araripina, Pernambuco, Brazil. Experimental design was a randomized blocks with thirteen treatments, corresponding to the sunflower genotypes: M734, NTC 90, BRS G43, BRS G44, BRS G45, BRS G46, SYN 065, HLA 2013, HLA 2014, HLA 2015, HLA 2016, HLA 2017 e SYN 045, with four replicates. The following characteristics were evaluated: final survival, early flowering, physiological maturity, average plant height, weight of 1,000 seeds, average flower diameter, final seed production, flower head curvature, lodged, broken and damaged by birds plants. The genotypes showed morphoagronomic differences when grown in the first semester of 2015 on edaphoclimatic conditions of the Araripe region, except for the variable survival. The NTC 90 genotype achieved the highest weight of head flower. All genotypes, except HLA 2015 showed high grain yield. The characters lodged, broken and damaged plants by birds or curvature of the head flower were not related to the different cultivars.

A novel breast tissue density classification framework

Oliver, A., Freixenet, J., Marti, R., Pont, J., Perez, E., Denton, E. R. E., Zwiggelaar, R. (2008). A novel breast tissue density classification framework. IEEE Transactions on Information Technology in BioMedicine, 12 (1), 55-65

Women's help seeking behaviour and the associated influencing factors on self discovery of a breast symptom

To investigate women’s help seeking behavior (HSB) following self discovery of a breast symptom and determine the associated influencing factors. A descriptive correlation design was used to ascertain the help seeking behavior (HSB) and the associated influencing factors of a sample of women (n = 449) with self discovered breast symptoms. The study was guided by the ‘Help Seeking Behaviour and Influencing Factors” conceptual framework (Facione et al., 2002; Meechan et al., 2003, 2002; Leventhal, Brissette and Leventhal, 2003 and O’Mahony and Hegarty, 2009b). Data was collected using a researcher developed multi-scale questionnaire package to ascertain women’s help seeking behavior on self discovery of a breast symptom and determine the factors most associated with HSB. Factors examined include: socio-demographics, knowledge and beliefs (regarding breast symptom; breast changes associated with breast cancer; use of alternative help seeking behaviours and presence or absence of a family history of breast cancer),emotional responses, social factors, health seeking habits and health service system utilization and help seeking behavior. A convenience sample (n = 449 was obtained by the researcher from amongst women attending the breast clinics of two large urban hospitals within the Republic of Ireland. All participants had self-discovered breast symptoms and no previous history of breast cancer. The study identified that while the majority of women (69.9%; n=314) sought help within one month, 30.1% (n=135) delayed help seeking for more than one month following self discovery of their breast symptom. The factors most significantly associated with HSB were the presenting symptom of ‘nipple indrawn/changes’ (p = 0.005), ‘ignoring the symptom and hoping it would go away’ (p < 0.001), the emotional response of being ‘afraid@ on symptom discovery (p = 0.005) and the perception/belief in longer symptom duration (p = 0.023). It was found that women who presented with an indrawn/changed nipple were more likely to delay (OR = 4.81) as were women who ‘ignored the symptoms and hoped it would go away’ (OR = 10.717). Additionally, the longer women perceived that their symptom would last, they more likely they were to delay (OR = 1.18). Conversely, being afraid following symptom discovery was associated with less delay (OR = 0.37; p=0.005). This study provides further insight into the HSB of women who self discovered breast symptoms. It highlights the complexity of the help seeking process, indicating that is not a linear event but is influenced by multiple factors which can have a significant impact on the outcomes in terms of whether women delay or seek help promptly. The study further demonstrates that delayed HSB persists amongst women with self discovered breast symptoms. This has important implications for continued emphasis on the promotion of breast awareness, prompt help seeking for self discovered breast symptoms and early detection and treatment of breast cancer, amongst women of all ages.

Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over.

PURPOSE: To compare the efficacy of paclitaxel versus doxorubicin given as single agents in first-line therapy of advanced breast cancer (primary end point, progression-free survival ¿PFS) and to explore the degree of cross-resistance between the two agents. PATIENTS AND METHODS: Three hundred thirty-one patients were randomized to receive either paclitaxel 200 mg/m(2), 3-hour infusion every 3 weeks, or doxorubicin 75 mg/m(2), intravenous bolus every 3 weeks. Seven courses were planned unless progression or unacceptable toxicity occurred before the seven courses were finished. Patients who progressed within the seven courses underwent early cross-over to the alternative drug, while a delayed cross-over was optional for the remainder of patients at the time of disease progression. RESULTS: Objective response in first-line therapy was significantly better (P =.003) for doxorubicin (response rate ¿RR, 41%) than for paclitaxel (RR, 25%), with doxorubicin achieving a longer median PFS (7.5 months for doxorubicin v 3.9 months for paclitaxel, P <.001). In second-line therapy, cross-over to doxorubicin (91 patients) and to paclitaxel (77 patients) gave response rates of 30% and 16%, respectively. The median survival durations of 18.3 months for doxorubicin and 15.6 months for paclitaxel were not significantly different (P =.38). The doxorubicin arm had greater toxicity, but this was counterbalanced by better symptom control. CONCLUSION: At the dosages and schedules used in the present study, doxorubicin achieves better disease and symptom control than paclitaxel in first-line treatment. Doxorubicin and paclitaxel are not totally cross-resistant, which supports further investigation of these drugs in combination or in sequence, both in advanced disease and in the adjuvant setting.

An EORTC-IDBBC phase I study of gemcitabine and continuous infusion 5-fluorouracil in patients with metastatic breast cancer resistant to anthracyclines or pre-treated with both anthracyclines and taxanes.

The aim of this study was to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and potential activity of combined gemcitabine and continuous infusion 5-fluorouracil (5-FU) in metastatic breast cancer (MBC) patients that are resistant to anthracyclines or have been pretreated with both anthracyclines and taxanes. 15 patients with MBC were studied at three European Organization for Research and Treatment of Cancer centres. 13 patients had received both anthracylines and taxanes. Gemcitabine was given intravenously (i.v.) on days 1 and 8, and 5-FU as a continuous i.v. infusion on days 1 through to 14, both drugs given in a 21-day schedule at four different dose levels. Both were given at doses commonly used for the single agents for the last dose level (dose level 4). One of 6 patients at level 4 (gemcitabine 1200 mg/m2 and 5-FU 250 mg/m2/day) had a DLT, a grade 3 stomatitis and skin toxicity. One DLT, a grade 3 transaminase rise and thrombosis, occurred in a patient at level 2 (gemcitabine 1000 mg/m2 and 5-FU 200 mg/m2/day). Thus, the MTD was not reached. One partial response and four disease stabilisations were observed. Only 1 patient withdrew from the treatment due to toxicity. The MTD was not reached in the phase I study. The combination of gemcitabine and 5-FU is well tolerated at doses up to 1200 mg/m2 given on days 1 and 8 and 250 mg/m2/day given on days 1 through to 14, respectively, every 21 days. The clinical benefit rate (responses plus no change of at least 6 months) was 33% with one partial response, suggesting that MBC patients with prior anthracycline and taxane therapy may derive significant benefit from this combination with minimal toxicity.

A joined analysis of two European Organization for the Research and Treatment of Cancer (EORTC) studies to evaluate the role of pegylated liposomal doxorubicin (Caelyx) in the treatment of elderly patients with metastatic breast cancer.

We have performed a retrospective analysis to evaluate the impact of age, using a 70 year cutoff, on the safety and efficacy of pegylated liposomal doxorubicin (Caelyx) given at 60 mg/m(2) every 6 weeks (treatment A) or 50 mg/m(2) every 4 weeks (treatment B) to 136 metastatic breast cancer patients in two EORTC trials, of whom 65 were 70 years of age or older. No difference in terms of toxicity was observed between younger and older patients treated with the 4-week schedule, while a higher incidence of hematological toxicity, anorexia, asthenia, and stomatitis was observed in older patients when the 6-week schedule was used. Antitumor activity was not affected by age. In the older cohort of patients, no dependence was found between the incidence of grade 3-4 toxicity or antitumor activity and patients' baseline performance status, number and severity of comorbidities, or number of concomitant medications. The higher therapeutic index of Caelyx 50 mg/m(2) every 4 weeks makes it, of the two dose schedules investigated, the preferred regimen in the elderly.

A randomised phase II study of two different schedules of pegylated liposomal doxorubicin in metastatic breast cancer (EORTC-10993).

One hundred and sixteen women with measurable metastatic breast cancer participated in a randomised phase II study of single agent liposomal pegylated doxorubicin (Caelyx) given either as a 60 mg/m2 every 6 weeks (ARM A) or 50 mg/m2 every 4 weeks (ARM B) schedule. Patients were over 65 years of age or, if younger, had refused or been unsuitable for standard anthracyclines. The aims of the study were to evaluate toxicity and dose delivery with the two schedules and obtain further information on the response rate of liposomal pegylated doxorubicin as a single agent in anthracycline nai ve advanced breast cancer. Twenty-six patients had received prior adjuvant chemotherapy (including an anthracycline in 10). Sixteen had received non-anthracycline-based first-line chemotherapy for advanced disease. One hundred and eleven patients were evaluable for toxicity and 106 for response. The delivered dose intensity (DI) was 9.8 mg/m2 (95% CI, 7.2-10.4) with 37 (69%) achieving a DI of >90% on ARM A and 11.9 mg/m2 (95% CI, 7.5-12.8) with 37 (65%) achieving a DI of >90% on ARM B. The adverse event profiles of the two schedules were distinctly different. Mucositis was more common with the every 6 weeks regimen (35% CTC grade 3/4 in ARM A, 14% in ARM B) but palmar plantar erythrodysesthesia (PPE) was more frequent with the every 4 weeks regimen (2% CTC grade 3/4 in ARM A, 16% in ARM B). Confirmed objective partial responses by RECIST criteria were seen with both schedules; 15/51 (29%) on ARM A and 17/56 (31%) on ARM B. Liposomal pegylated doxorubicin showed significant activity in advanced breast cancer with a generally favourable side-effect profile. The high frequency of stomatitis seen with 6 weekly treatment makes this the less preferred of the two schedules tested.