Acceptance of relapse fears in breast cancer patients: effects of an act-based abridged intervention

Objective: Relapse fear is a common psychological scar in cancer survivors. The aim of this study is to assess the effects of an abridged version of Acceptance and Commitment Therapy (ACT) in breast cancer patients.Method: An open trial was developed with 12 non-metastatic breast cancer patients assigned to 2 conditions, ACT and waiting list. Interventions were applied in just one session and focused on the acceptance of relapse fears through a ‘defusion’ exercise. Interference and intensity of fear measured through subjective scales were collected after each intervention and again 3 months later. Distress, hypochondria and ‘anxious preocupation’ were also evaluated through standardized questionnaires.Results: The analysis revealed that ‘defusion’ contributed to decrease the interference of the fear of recurrence, and these changes were maintained three months after intervention in most subjects. 87% of participants showed clinically significant decreases in interference at follow-up sessions whereas no patient in the waiting list showed such changes. Statistical analysis revealed that the changes in interference were significant when comparing pre, post and follow-up treatment, and also when comparing ACT and waiting list groups. Changes in intensity of fear, distress, anxious preoccupation and hypochondria were also observed.Conclusions: Exposure through ‘defusion’ techniques might be considered a useful option for treatment of persistent fears in cancer patients. This study provides evidence for therapies focusing on psychological acceptance in cancer patients through short, simple and feasible therapeutic methods.

Effects of a positive emotion-based adjuvant psychological therapy in colorectal cancer patients: a pilot study

Objective: To examine the effectiveness of an “Enhancing Positive Emotions Procedure” (EPEP) based on positive psychology and cognitive behavioral therapy in relieving distress at the time of adjuvant chemotherapy treatment in colorectal cancer patients (CRC). It is expected that EPEP will increase quality of life and positive affect in CRC patients during chemotherapy treatment intervention and at 1 month follow-up.Method: A group of 24 CRC patients received the EPEP procedure (intervention group), whereas another group of 20 CRC patients did not receive the EPEP (control group). Quality of life (EORTC-QLQC30), and mood (PANAS) were assessed in three moments: prior to enter the study (T1), at the end of the time required to apply the EPEP (T2, 6 weeks after T1), and, at follow-up (T3, one-month after T2). Patient’s assessments of the EPEP (improving in mood states, and significance of the attention received) were assessed with Lickert scales.Results: Insomnia was reduced in the intervention group. Treatment group had better scores on positive affect although there were no significantly differences between groups and over time. There was a trend to better scores at T2 and T3 for the intervention group on global health status, physical, role, and social functioning scales. Patients stated that positive mood was enhanced and that EPEP was an important resource.Conclusions: CRC patients receiving EPEP during chemotherapy believed that this intervention was important. Furthermore, EPEP seems to improve positive affect and quality of life. EPEP has potential benefits, and its implementation to CRC patients should be considered.

Cell cycle-coupled expansion of AR activity promotes cancer progression

The androgen receptor (AR) is required for prostate cancer (PCa) survival and progression, and ablation of AR activity is the first line of therapeutic intervention for disseminated disease. While initially effective, recurrent tumors ultimately arise for which there is no durable cure. Despite the dependence of PCa on AR activity throughout the course of disease, delineation of the AR-dependent transcriptional network that governs disease progression remains elusive, and the function of AR in mitotically active cells is not well understood. Analyzing AR activity as a function of cell cycle revealed an unexpected and highly expanded repertoire of AR-regulated gene networks in actively cycling cells. New AR functions segregated into two major clusters: those that are specific to cycling cells and retained throughout the mitotic cell cycle ('Cell Cycle Common'), versus those that were specifically enriched in a subset of cell cycle phases ('Phase Restricted'). Further analyses identified previously unrecognized AR functions in major pathways associated with clinical PCa progression. Illustrating the impact of these unmasked AR-driven pathways, dihydroceramide desaturase 1 was identified as an AR-regulated gene in mitotically active cells that promoted pro-metastatic phenotypes, and in advanced PCa proved to be highly associated with development of metastases, recurrence after therapeutic intervention and reduced overall survival. Taken together, these findings delineate AR function in mitotically active tumor cells, thus providing critical insight into the molecular basis by which AR promotes development of lethal PCa and nominate new avenues for therapeutic intervention.

Development of polymeric drug delivery vehicles for targeted cancer therapy

The aim of my Ph. D. thesis is to generalize a method for targeted anti-cancer drug delivery. Hydrophilic polymer-drug conjugates involve complicated synthesis; drug-encapsulated polymeric nanoparticles limit the loading capability of payloads. This thesis introduces the concept of nanoconjugates to overcome difficulties in synthesis and formulation. Drugs with hydroxyl group are able to initiate polyester synthesis in a regio- and chemo- selective way, with the mediation of ligand-tunable Zinc catalyst. Herein, three anti-cancer drugs are presented to demonstrate the high efficiency and selectivity in the method (Chapter 2-4). The obtained particles are stable in salt solution, releasing drugs over weeks in controlled manner. With the conjugation of aptamer, particles are capable to target prostate cancer cells in vitro. These results open the gateway to evaluate the in vivo efficacy of nanoconjugates for target cancer therapy (Chapter 5). Mechanism study of the polymerization leads to the discovery of chemosite selective synthesis of prodrugs with acrylate functional groups. Functional copolymer-drug conjugates will expand the scope of nanoconjugates (Chapter 6). Liposome-aptamer targeting drug delivery vehicle is well studied to achieve reversible cell-specific delivery of non-hydoxyl drugs e.g. cisplatin (Chapter 7). New monomers and polymerization mechanisms are explored for polyester in order to synthesize nanoconjugates with variety on properties (Chapter 8). Initial efforts to apply this type of prodrugs will be focused on the preparation of hydrogels for stem cell research (Chapter 9).

Factors influencing Nigerian men's decision to undergo prostate specific antigen testing.

Background: Prostate cancer is a major cause of cancer death in Nigerian men. Attempts to reduce mortality from prostate cancer have focused mainly on early detection of the disease by the use of PSA testing. As a result of the increased incidence of prostate cancer in Nigeria despite the widespread availability of testing facilities, it became pertinent to understand the salient factors that prompt Nigerian men to go for prostate cancer testing. Objective: This study explores the factors that influence a group of Nigerian men’s decision to go for Prostate Specific Antigen (PSA) testing. Methods: Following ethical approval, semi structured interviews were conducted with a group of 10 men who had PSA test following consultation with their doctor with signs and symptoms at the University of Benin Teaching Hospital from July to August, 2010. Interview transcripts were analysed by employing steps proposed by Collaizi (1978). Results: Five themes were identified: the symptoms experienced, the influence of friends and relatives, older age associated with increased awareness, accessibility to testing services and the knowledge of the PSA test. Conclusion: The study revealed that there continues to be a considerable lack of awareness and knowledge about prostate cancer and screening.

Effects of radiation therapy on the structure and function of the pelvic floor muscles of patients with cancer in the pelvic area : a systematic review

Purpose Radiation therapy (RT) is often recommended in the treatment of pelvic cancers. Following RT, a high prevalence of pelvic floor dysfunctions (urinary incontinence, dyspareunia, and fecal incontinence) is reported. However, changes in pelvic floor muscles (PFMs) after RT remain unclear. The purpose of this review was to systematically document the effects of RT on the PFM structure and function in patients with cancer in the pelvic area. Methods An electronic literature search using Pubmed Central, CINAHL, Embase, and SCOPUS was performed from date of inception up to June 2014. The following keywords were used: radiotherapy, muscle tissue, and pelvic floor. Two reviewers selected the studies in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). Out of the 369 articles screened, 13 met all eligibility criteria. The methodological quality was assessed using the QualSyst scoring system, and standardized mean differences were calculated. Results Thirteen studies fulfilled all inclusion criteria, from which four were of good methodological quality. One presented strong evidence that RT affects PFM structure in men treated for prostate cancer. Four presented high-level evidence that RT affects PFM function in patients treated for rectal cancer. Meta-analysis was not possible due to heterogeneity and lack of descriptive statistics. Conclusion There is some evidence that RT has detrimental impacts on both PFMs’ structure and function. Implications for cancer survivors A better understanding of muscle damage and dysfunction following RT treatment will improve pelvic floor rehabilitation and, potentially, prevention of its detrimental impacts.

Effects of radiation therapy on the structure and function of the pelvic floor muscles of patients with cancer in the pelvic area : a systematic review

Purpose Radiation therapy (RT) is often recommended in the treatment of pelvic cancers. Following RT, a high prevalence of pelvic floor dysfunctions (urinary incontinence, dyspareunia, and fecal incontinence) is reported. However, changes in pelvic floor muscles (PFMs) after RT remain unclear. The purpose of this review was to systematically document the effects of RT on the PFM structure and function in patients with cancer in the pelvic area. Methods An electronic literature search using Pubmed Central, CINAHL, Embase, and SCOPUS was performed from date of inception up to June 2014. The following keywords were used: radiotherapy, muscle tissue, and pelvic floor. Two reviewers selected the studies in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). Out of the 369 articles screened, 13 met all eligibility criteria. The methodological quality was assessed using the QualSyst scoring system, and standardized mean differences were calculated. Results Thirteen studies fulfilled all inclusion criteria, from which four were of good methodological quality. One presented strong evidence that RT affects PFM structure in men treated for prostate cancer. Four presented high-level evidence that RT affects PFM function in patients treated for rectal cancer. Meta-analysis was not possible due to heterogeneity and lack of descriptive statistics. Conclusion There is some evidence that RT has detrimental impacts on both PFMs’ structure and function. Implications for cancer survivors A better understanding of muscle damage and dysfunction following RT treatment will improve pelvic floor rehabilitation and, potentially, prevention of its detrimental impacts.

Revisión sistemática utilidad de asa y calcio con o sin vitamina d en la prevención de cáncer colorrectal y la recurrencia de pólipos adenomatosos en paciente con riesgo de padecer esta patología

Introducción: El cáncer colorrectal es una patología con alto impacto en la salud pública, debido a su prevalencia, incidencia, severidad, costo e impacto en la salud mental y física del individuo y la familia. Ensayos clínicos realizados en pacientes con antecedente de infarto al miocardio que consumían ácido acetil salicílico (asa), calcio con y sin vitamina D, mostraron asociación entre el consumo de estos medicamentos y disminución en la incidencia en cáncer colorrectal y pólipos adenomatosos. Objetivo: Evaluar la literatura sobre el uso de asa, calcio con y sin vitamina D con relación a su impacto en la prevención del cáncer colorrectal y pólipos adenomatosos. Métodos: Se realizó revisión sistemática buscando ensayos clínicos realizados en pacientes con factores de riesgo para cáncer colorrectal y pólipos adenomatosos que usaron asa, calcio con y sin vitamina D fueron incluidos. Resultados: se escogieron 105 para la revisión sistemática. Conclusiones: Es necesario desarrollar más estudios que lleven a evaluar el efecto protector de la aspirina, calcio y vitamina D. En los artículos revisados la aspirina a dosis de 81 a 325 mg día se correlaciona con reducción de riesgo de aparición de CRC aunque la dosis ideal, el tiempo de inicio y la duración de la ingesta continua no son claros. Hacen falta estudios que comparen poblaciones con ingesta de asa a diferentes dosis.

Antitumor Activity Of Irradiated Riboflavin On Human Renal Carcinoma Cell Line 786-o.

Riboflavin (vitamin B2) is a precursor for coenzymes involved in energy production, biosynthesis, detoxification, and electron scavenging. Previously, we demonstrated that irradiated riboflavin (IR) has potential antitumoral effects against human leukemia cells (HL60), human prostate cancer cells (PC3), and mouse melanoma cells (B16F10) through a common mechanism that leads to apoptosis. Hence, we here investigated the effect of IR on 786-O cells, a known model cell line for clear cell renal cell carcinoma (CCRCC), which is characterized by high-risk metastasis and chemotherapy resistance. IR also induced cell death in 786-O cells by apoptosis, which was not prevented by antioxidant agents. IR treatment was characterized by downregulation of Fas ligand (TNF superfamily, member 6)/Fas (TNF receptor superfamily member 6) (FasL/Fas) and tumor necrosis factor receptor superfamily, member 1a (TNFR1)/TNFRSF1A-associated via death domain (TRADD)/TNF receptor-associated factor 2 (TRAF) signaling pathways (the extrinsic apoptosis pathway), while the intrinsic apoptotic pathway was upregulated, as observed by an elevated Bcl-2 associated x protein/B-cell CLL/lymphoma 2 (Bax/Bcl-2) ratio, reduced cellular inhibitor of apoptosis 1 (c-IAP1) expression, and increased expression of apoptosis-inducing factor (AIF). The observed cell death was caspase-dependent as proven by caspase 3 activation and poly(ADP-ribose) polymerase-1 (PARP) cleavage. IR-induced cell death was also associated with downregulation of v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homologue (avian)/protein serine/threonine kinase B/extracellular signal-regulated protein kinase 1/2 (Src/AKT/ERK1/2) pathway and activation of p38 MAP kinase (p38) and Jun-amino-terminal kinase (JNK). Interestingly, IR treatment leads to inhibition of matrix metalloproteinase-2 (MMP-2) activity and reduced expression of renal cancer aggressiveness markers caveolin-1, low molecular weight phosphotyrosine protein phosphatase (LMWPTP), and kinase insert domain receptor (a type III receptor tyrosine kinase) (VEGFR-2). Together, these results show the potential of IR for treating cancer.

Interferentes endócrinos no ambiente

Although the hypothesis that environmental chemicals may exhibit endocrine disrupting effects is not new, the issue has been a growing level of concern due to reports of increased incidences of endocrine-related disease in humans, including declining male fertility, and more significantly, to adverse physiological effects observed in wildlife where cause and effect relationships are more evident. The list of endocrine disrupting chemicals (EDCs) includes a range of anthropogenic compounds, phytoestrogens, naturally occurring sex steroids and synthetic estrogens. Within the aquatic environment, the presence of EDCs has concerned many scientists and water quality regulators. Discharge of effluents from treatment facilities is likely to be a significant source of input of contaminants to many systems, and the potential for concentration of hydrophilic compounds and transformation products within sludges has implications for their disposal. Then, understanding the processes and the fate of EDCs on the environment, as well as the mechanisms of endocrine disruption, may facilitate controlling or limiting exposure of both humans and the environment to these compounds.

Evaluation of Antiproliferative, Anti-Type 2 Diabetes, and Antihypertension Potentials of Ellagitannins from Strawberries (Fragaria x ananassa Duch.) Using In Vitro Models

Strawberries represent the main source of ellagic acid derivatives in the Brazilian diet, corresponding to more than 50% of all phenolic compounds found in the fruit. There is a particular interest in the determination of the ellagic acid content in fruits because of possible chemopreventive benefits. In the present study, the potential health benefits of purified ellagitannins from strawberries were evaluated in relation to the antiproliferative activity and in vitro inhibition of alpha-amylase, alpha-glucosidase, and angiotensin I-converting enzyme (ACE) relevant for potential management of hyperglycemia and hypertension. Therefore, a comparison among ellagic acid, purified ellagitannins, and a strawberry extract was done to evaluate the possible synergistic effects of phenolics. In relation to the antiproliferative activity, it was observed that ellagic acid had the highest percentage inhibition of cell proliferation. The strawberry extract had lower efficacy in inhibiting the cell proliferation, indicating that in the case of this fruit there is no synergism. Purified ellagitannins had high alpha-amylase and ACE inhibitory activities. However, these compounds had low alpha-glucosidase inhibitory activity. These results suggested that the ellagitannins and ellagic acid have good potential for the management of hyperglycemia and hypertension linked to type 2 diabetes. However, further studies with animal and human models are needed to advance the in vitro assay-based biochemical rationale from this study.

Determination of the Most Efficient Temperature for Radiofrequency Ablation of Renal Cells: A Prospective Study in Dogs

Background and Purpose: Radiofrequency (RF) ablation of renal tumors is a major technique for tumor cell destruction while preserving healthy renal parenchyma. There is no consensus in the literature regarding the optimal temperature, impedance, and time for RF application for effective cell destruction. This study investigated two variables while keeping time unchanged: Temperature for RF cell destruction and tissue impedance in dog kidneys. Materials and Methods: Sixteen dogs had renal punctures through videolaparoscopy for RF interstitial tissue ablation. A RF generator was applied for 10 minutes to the dog's kidney at different target temperatures: 80 degrees C, 90 degrees C, and 100 degrees C. On postoperative day14, the animals were sacrificed and nephrectomized. All lesions were macroscopically and microscopically examined. The bioelectrical impedance was evaluated at three different temperatures. Results: Renal injuries were wider and deeper at 90 degrees C (P < 0.001), and they were similar at 80 degrees C and 100 degrees C. The bioelectrical impedance was lower at 90 degrees C than at the temperatures of 80 degrees C and 100 degrees C (P < 0.001). Viable cells in the RF ablation tissue area were not found in the microscopic examination. Conclusion: The most effective cell destruction in terms of width and depth was achieved at 90 degrees C, which was also the optimal temperature for tissue impedance. RF ablation of renal cells eliminated all viable cells.

Novel Primate-Specific Genes, RMEL 1, 2 and 3, with Highly Restricted Expression in Melanoma, Assessed by New Data Mining Tool

Melanoma is a highly aggressive and therapy resistant tumor for which the identification of specific markers and therapeutic targets is highly desirable. We describe here the development and use of a bioinformatic pipeline tool, made publicly available under the name of EST2TSE, for the in silico detection of candidate genes with tissue-specific expression. Using this tool we mined the human EST (Expressed Sequence Tag) database for sequences derived exclusively from melanoma. We found 29 UniGene clusters of multiple ESTs with the potential to predict novel genes with melanoma-specific expression. Using a diverse panel of human tissues and cell lines, we validated the expression of a subset of three previously uncharacterized genes (clusters Hs.295012, Hs.518391, and Hs.559350) to be highly restricted to melanoma/melanocytes and named them RMEL1, 2 and 3, respectively. Expression analysis in nevi, primary melanomas, and metastatic melanomas revealed RMEL1 as a novel melanocytic lineage-specific gene up-regulated during melanoma development. RMEL2 expression was restricted to melanoma tissues and glioblastoma. RMEL3 showed strong up-regulation in nevi and was lost in metastatic tumors. Interestingly, we found correlations of RMEL2 and RMEL3 expression with improved patient outcome, suggesting tumor and/or metastasis suppressor functions for these genes. The three genes are composed of multiple exons and map to 2q12.2, 1q25.3, and 5q11.2, respectively. They are well conserved throughout primates, but not other genomes, and were predicted as having no coding potential, although primate-conserved and human-specific short ORFs could be found. Hairpin RNA secondary structures were also predicted. Concluding, this work offers new melanoma-specific genes for future validation as prognostic markers or as targets for the development of therapeutic strategies to treat melanoma.

Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease affecting the epithelium of the oral cavity, pharynx and larynx. Conditions of most patients are diagnosed at late stages of the disease, and no sensitive and specific predictors of aggressive behavior have been identified yet. Therefore, early detection and prognostic biomarkers are highly desirable for a more rational management of the disease. Hypermethylation of CpG islands is one of the most important epigenetic mechanisms that leads to gene silencing in tumors and has been extensively used for the identification of biomarkers. In this study, we combined rapid subtractive hybridization and microarray analysis in a hierarchical manner to select genes that are putatively reactivated by the demethylating agent 5-aza-2'-deoxycytidine (5Aza-dC) in HNSCC cell lines (FaDu, UM-SCC-14A, UM-SCC-17A, UM-SCC-38A). This combined analysis identified 78 genes, 35 of which were reactivated in at least 2 cell lines and harbored a CpG island at their 5' region. Reactivation of 3 of these 35 genes (CRABP2, MX1, and SLC15A3) was confirmed by quantitative real-time polymerase chain reaction (PCR; fold change, >= 3). Bisulfite sequencing of their CpG islands revealed that they are indeed differentially methylated in the HNSCC cell lines. Using methylation-specific PCR, we detected a higher frequency of CRABP2 (58.1% for region 1) and MX1 (46.3%) hypermethylation in primary HNSCC when compared with lymphocytes from healthy individuals. Finally, absence of the CRABP2 protein was associated with decreased disease-free survival rates, supporting a potential use of CRABP2 expression as a prognostic biomarker for HNSCC patients.

Associations between glutathione peroxidase-1 Pro198Leu polymorphism, selenium status, and DNA damage levels in obese women after consumption of Brazil nuts

Objective: Alterations in selenium (Se) status may result in suboptimal amounts of selenoproteins, which have been associated with increased oxidative stress levels. The Pro198Leu polymorphism at the glutathione peroxidase-1 (GPx1) gene is supposed to be functional. The response of Se status, GPx activity, and levels of DNA damage to a Se supplementation trial between the genotypes related to that polymorphism was investigated. Methods: A randomized trial was conducted with 37 morbidly obese women. Participants consumed one Brazil nut, which provided approximately 290 mu g of Se a day, for 8 wk. Blood Se concentrations, erythrocyte GPx activity, and DNA damage levels were measured at baseline and at 8 wk. The results were compared by genotypes. Results: The genotype frequencies were 0.487, 0.378, and 0.135 for Pro/Pro (the wild-type genotype), Pro/Leu, and Leu/Leu, respectively. At baseline, 100% of the subjects were Se deficient, and after the supplementation, there was an improvement in plasma Se (P < 0.001 for Pro/Pro and Pro/Leu, P < 0.05 for Leu/Leu), erythrocyte Se (P = 0.00 for Pro/Pro and Pro/Leu, P < 0.05 for Leu/Leu), and GPx activity (P = 0.00 for Pro/Pro, P < 0.00001 for Pro/Leu, P < 0.001 for Leu/Leu). In addition, the Pro/Pro group showed a decrease in DNA damage after Brazil nut consumption compared with baseline (P < 0.005), and those levels were higher in Leu/Leu subjects compared with those with the wild-type genotype (P < 0.05). Conclusion: Consumption of one unit of Brazil nuts daily effectively increases Se status and increases GPx activity in obese women, regardless of GPx1 Pro198Leu polymorphism. However, the evaluated biomarkers showed distinct results in response to the supplementation when the polymorphism was considered. (c) 2011 Elsevier Inc. All rights reserved.