A systematic review of exercise protocols applied to athymic mice in tumor-related experiments.

Athymic mice are unable to produce T-cells and are then characterized as immunodeficient. This characteristic makes these animals ideal for tumor biology and xenograft research. New non-pharmacological therapeutics are required owing to the exponential increase in global oncology costs over the last 10 years and the high cancer mortality rate. In this sense, physical exercise is regarded as a relevant component of cancer treatment. However, the scientific community lacks information regarding the effect of manipulating training variables on cancer in humans, and experiments with athymic mice. Therefore, this systematic review aimed to address the exercise protocols used in tumor-related experiments using athymic mice. The PubMed, Web of Science, and Scopus databases were searched without restrictions on published data. A combination of key terms such as athymic mice, nude mice, physical activity, physical exercise, and training was used. The database search retrieved 852 studies (PubMed, 245; Web of Science, 390; and Scopus, 217). After title, abstract, and full-text screening, 10 articles were eligible. Based on the included studies, this report highlights the considerable divergences in the training variables adopted for this animal model. No studies have reported the determination of a physiological marker for intensity individualization. Future studies are recommended to explore whether invasive procedures can result in pathogenic infections in athymic mice. Moreover, time-consuming tests cannot be applied to experiments with specific characteristics such as tumor implantation. In summary, non-invasive, low-cost, and time-saving approaches can suppress these limitations and improve the welfare of these animals during experiments.

Validity of the peak velocity to detect physical training improvements in athymic mice.

This study comprises two complementary experiments with athymic Balb/c (Nu/Nu) mice. In experiment 1, the aim was to verify the reproducibility of the peak velocity (VPeak) determined from the incremental test. The second experiment aimed to assess the VPeak sensitivity to prescribe and detect modulations of the physical training in athymic nude mice. Sixteen mice were submitted to two incremental treadmill tests separated by 48-h (Experiment 1). The test consisted of an initial warm-up of 5 minutes. Subsequently, animals initiated the tests at 8 m min-1 with increments of 2 m min-1 every 3 minutes. The VPeak was determined as the highest velocity attained during the protocol. In experiment 2, these animals were randomly allocated to an exercise group (EG) or a control group (CG). The training protocol consisted of 30-min of treadmill running at 70% of the VPeak five times a week for 4 weeks. High indexes of reproducibility were obtained for VPeak (Test = 19.7 ± 3.6 m min-1; Retest = 19.2 ± 3.4 m min-1; p = 0.171; effect size = 0.142; r = 0.90). Animals from the EG had a significant increase of VPeak (Before = 18.4 ± 2.7 m min-1; After = 24.2 ± 6.0 m min-1; p = 0.023). Conversely, a significant decrease was observed for the CG (Before = 21.1 ± 3.9 m min-1; After = 15.9 ± 2.7 m min-1; p = 0.038). The VPeak is a valid parameter for exercise prescription in studies involving athymic nude mice.

Ethical dilemmas for pediatricians administering palliative sedation to children in Brazil / Dilemas éticos de los pediatras al administrar sedación paliativa a niños en Brasil / Dilemas éticos de pediatras ao administrar sedação paliativa em crianças no Brasil

Abstract This study aims to analyze the use of pediatric palliative sedation and understand how it is connected to medical training and the doctor-patient relationship in Brazil. This is a cross-sectional exploratory study using an online survey targeted at pediatricians working in Brazil to evaluate concepts of palliative sedation and aggressive symptom management. The lack of specific training, protocols, and institutionalized guidelines can create uncertainties in palliative care. This also contributes to the increased end-of-life suffering those children and their families face. Improving education in pediatric palliative care is an urgent and pressing need in Brazil.

Resumen Este artículo tiene como objetivo analizar el uso de la sedación paliativa y comprender cómo esta se vincula con la formación médica y la relación médico-paciente en Brasil. Basándose en una encuesta en línea con pediatras que trabajan en Brasil, este estudio transversal y exploratorio pretendió evaluar los conceptos de sedación paliativa y tratamiento de síntomas agresivos. La falta de formación específica, de protocolos y guías institucionalizadas puede generar incertidumbres en los cuidados paliativos. Esto también contribuye al aumento del sufrimiento que enfrenta estos niños al final de la vida y sus familias. Es imprescindible y urgente mejorar la educación en cuidados paliativos pediátricos en Brasil.

Resumo Este artigo objetiva analisar o uso de sedação paliativa e entender como ela está ligada à formação médica e ao relacionamento médico-paciente no Brasil. Com base em pesquisa on-line focada em pediatras que trabalham no Brasil, este estudo transversal e exploratório buscou avaliar conceitos de sedação paliativa e tratamento de sintomas agressivos. A falta de treinamento específico, protocolos e diretrizes institucionalizadas pode gerar incertezas no cuidado paliativo. Isso também contribui para o aumento do sofrimento de fim da vida que essas crianças e suas famílias enfrentam. Melhorar a educação em cuidados paliativos pediátricos é uma necessidade urgente e imediata no Brasil.

A new therapeutic approach for bone metastasis in colorectal cancer: intratumoral melittin.

Background: Melittin has shown antiproliferative effects on tumor cells. Therefore, it comprises a valuable compound for studies on cancer treatment. To the best of our knowledge, no studies have reported melittin effects on bone metastasis. Herein, we propose an approach based on intrametastatic melittin injection to treat bone metastases in colorectal cancer. Methods: Following the characterization of melittin and antiproliferative tests in vitro, a single dose was injected through intrametastatic route into the mouse bone metastasis model. Following treatment, metastasis growth was evaluated. Results: A single dose of melittin was able to inhibit metastasis growth. Histological analysis showed necrosis and inflammatory processes in melittin-treated metastasis. Except by mild weight loss, no other systemic effects were observed. Conclusion: Our data suggest that melittin might be a promising agent for the future development of treatment strategies aiming to reduce the bone metastasis skeletal-related impact in colorectal cancer patients with bone metastasis.

Antitumor effect of isoquercetin on tissue vasohibin expression and colon cancer vasculature.

Tumor cells trigger angiogenesis through the expression of angiogenic factors. Vasohibins (VASHs) are a family of peptides that regulate angiogenesis. Flavonoids have antiproliferative antitumor properties; however, few studies have highlighted their antiangiogenic potential. This study evaluated the flavonoid isoquercetin (Q3G) as an antitumor compound related to colon cancer vascularization and regulation of VASH1 and 2. Mice bearing xenogeneic colon cancer (n = 15) were divided into 3 groups: Q3G-treated (gavage, daily over a week), bevacizumab-treated (intraperitoneal, single dose), or untreated animals. Tumor growth, histological characteristics, blood vessel volume, and VASH1 and 2 expressions were analyzed. Q3G impaired tumor growth and vascularization, upregulated VASH1, and downregulated VASH2 in comparison to untreated animals. Mice treated with Q3G showed approximately 65% fewer blood vessels than untreated animals and 50% fewer blood vessels than mice treated with bevacizumab. Thus, we show that Q3G has antitumor activity, impairs vascularization, and differentially modulates VASH1 and 2 expressions in colon cancer.

Home-based, supervised, and mixed exercise intervention on functional capacity and quality of life of colorectal cancer patients: a meta-analysis.

This systematic review and meta-analysis of randomized controlled trials tested the effects of home-based, supervised, or mixed exercise interventions on the functional capacity (FC) and quality of life (QoL) in colorectal cancer patients. A literature search was performed using the PubMed, Embase, Cochrane, and Medline databases. Two reviewers screened the literature through March 10, 2021 for studies related to exercise and colorectal cancer. Of the 1161 screened studies in the initial search, 13 studies met the eligibility criteria (home-based = 6 studies; supervised or mixed = 7 studies). Overall, 706 patients were enrolled in the trials, and 372 patients were submitted to home-based, supervised, or mixed exercise intervention. The overall results from the main meta-analysis showed a significant effect regarding supervised or mixed intervention (6 studies; p = 0.002; I2 = 43%; PI 0.41-1.39); however, no significant effect was observed for home-based intervention (5 studies; p = 0.05; I2 = 25%; PI - 0.34-0.76). A sensitivity analysis based on studies with intervention adherence ≥ 80% (home-based = 3 studies; supervised or mixed = 4 studies) revealed that home-based intervention or intervention entirely supervised or with some level of supervision (mixed) are effective in improving the QoL and FC of CRC patients. In summary, this meta-analysis verified that supervised and home-based exercise can modify QoL and FC when intervention adherence ≥ 80%. Regardless of the supervision characteristics, future RCTs are strongly encouraged to provide a detailed description of the exercise variables in physical interventions for CRC prescription. This perspective will allow a refined exercise prescription for patients with CRC, mainly according to their clinical status.

A new therapeutic approach for bone metastasis in colorectal cancer: intratumoral melittin

Background: Melittin has shown antiproliferative effects on tumor cells. Therefore, it comprises a valuable compound for studies on cancer treatment. To the best of our knowledge, no studies have reported melittin effects on bone metastasis. Herein, we propose an approach based on intrametastatic melittin injection to treat bone metastases in colorectal cancer. Methods: Following the characterization of melittin and antiproliferative tests in vitro, a single dose was injected through intrametastatic route into the mouse bone metastasis model. Following treatment, metastasis growth was evaluated. Results: A single dose of melittin was able to inhibit metastasis growth. Histological analysis showed necrosis and inflammatory processes in melittin-treated metastasis. Except by mild weight loss, no other systemic effects were observed. Conclusion: Our data suggest that melittin might be a promising agent for the future development of treatment strategies aiming to reduce the bone metastasis skeletal-related impact in colorectal cancer patients with bone metastasis.(AU)

A new therapeutic approach for bone metastasis in colorectal cancer: intratumoral melittin

Abstract Background: Melittin has shown antiproliferative effects on tumor cells. Therefore, it comprises a valuable compound for studies on cancer treatment. To the best of our knowledge, no studies have reported melittin effects on bone metastasis. Herein, we propose an approach based on intrametastatic melittin injection to treat bone metastases in colorectal cancer. Methods: Following the characterization of melittin and antiproliferative tests in vitro, a single dose was injected through intrametastatic route into the mouse bone metastasis model. Following treatment, metastasis growth was evaluated. Results: A single dose of melittin was able to inhibit metastasis growth. Histological analysis showed necrosis and inflammatory processes in melittin-treated metastasis. Except by mild weight loss, no other systemic effects were observed. Conclusion: Our data suggest that melittin might be a promising agent for the future development of treatment strategies aiming to reduce the bone metastasis skeletal-related impact in colorectal cancer patients with bone metastasis.

Effects of dipotassium glycyrrhizinate on wound healing

ABSTRACT Purpose: Dipotassium glycyrrhizinate (DPG) has anti-inflammatory properties, besides promoting the regeneration of skeletal muscle. However, it has not been reported on skin wound healing/regeneration. This research aimed to characterize the effects of DPG in the treatment of excisional wounds by second intention. Methods: Male adults (n=10) and elderly (n=10) Wistar rats were used. Two circular wounds were excised on the dorsal skin. The excised normal skins were considered adult (GAN) and elderly (GIN) naïve. For seven days, 2% DPG was applied on the proximal excision: treated adult (GADPG) and elderly (GIDPG), whereas distal excisions were untreated adult (GANT) and elderly (GINT). Wound healing areas were daily measured and removed for morphological analyses after the 14th and the 21st postoperative day. Slides were stained with hematoxylin-eosin, Masson's trichrome, and picrosirius red. Results: Histological analysis revealed intact (GAN/GIN) and regenerated(GANT/GINT/GADPG/GIDPG) skins. No differences of wounds' size were found among treated groups. Epidermis was thicker after 14 days and thinner after 21 days of DPG administration. Higher collagen I density was found in GIDPG (14th day) and GADPG (21st day). Conclusions: DPG induced woundhealing/skin regeneration, with collagen I, being more effective in the first 14 days after injury.

Prevalence of palliative sedation in the State of São Paulo: an emerging medical demand.

OBJECTIVE: To investigate the prevalence of palliative sedation use and related factors. METHODS: An observational study based on data collected via electronic questionnaire comprising 23 close-ended questions and sent to physicians living and working in the state of São Paulo. Demographic data, prevalence and frequency of palliative sedation use, participant's familiarity with the practice and related motivating factors were analyzed. In order to minimize memory bias, questions addressing use frequency and motivating factors were limited to the last year prior to survey completion date. Descriptive statistics were used to summarize data. RESULTS: In total, 20,168 e-mails were sent and 324 valid answers obtained, resulting in 2% adherence. The overall prevalence of palliative sedation use over the course of professional practice was 68%. However, only 48% of respondents reported having used palliative sedation during the last year, primarily to relieve pain (35%). The frequency of use ranged from one to six times (66%) during the study period and the main reason for not using was the lack of eligible patients (64%). Approximately 83% of physicians felt comfortable using palliative sedation but only 26% reported having specific academic training in this field. CONCLUSION: The prevalence of palliative sedation use is high, the primary indication being pain relief. However, frequency of use is low due to lack of eligible patients.

Multiplatform Investigation of Plasma and Tissue Lipid Signatures of Breast Cancer Using Mass Spectrometry Tools.

Plasma and tissue from breast cancer patients are valuable for diagnostic/prognostic purposes and are accessible by multiple mass spectrometry (MS) tools. Liquid chromatography-mass spectrometry (LC-MS) and ambient mass spectrometry imaging (MSI) were shown to be robust and reproducible technologies for breast cancer diagnosis. Here, we investigated whether there is a correspondence between lipid cancer features observed by desorption electrospray ionization (DESI)-MSI in tissue and those detected by LC-MS in plasma samples. The study included 28 tissues and 20 plasma samples from 24 women with ductal breast carcinomas of both special and no special type (NST) along with 22 plasma samples from healthy women. The comparison of plasma and tissue lipid signatures revealed that each one of the studied matrices (i.e., blood or tumor) has its own specific molecular signature and the full interposition of their discriminant ions is not possible. This comparison also revealed that the molecular indicators of tissue injury, characteristic of the breast cancer tissue profile obtained by DESI-MSI, do not persist as cancer discriminators in peripheral blood even though some of them could be found in plasma samples.

von Hippel-Lindau Syndrome: Genetic Study of Case With a Rare Pathogenic Variant With Optic Nerve Hemangioblastoma, a Rare Phenotypic Expression.

von Hippel-Lindau syndrome (VHLS) is a rare, autosomal dominant genetic disease with high penetrance and variable phenotypic expression caused by variants in the VHL gene. VHLS is associated with the presence of vascular tumors, often hemangioblastoma of the central nervous system, retina, or spinal cord and, less frequently, pancreatic cystic neoplasm, pancreatic neuroendocrine tumor, clear cell carcinoma of the kidney, endolymphatic sac tumor, pheochromocytoma, and paraganglioma. The authors report a case of a patient with VHLS with a rare pathogenic variant in the VHL gene and with an optic nerve hemangioblastoma, a rare phenotypic expression. Case report: A 49-year-old woman was diagnosed with cystic neoplasm of the pancreas, renal cell carcinoma of the right kidney, and hemangioblastoma of the left optic nerve. The patient's family history revealed siblings with VHLS manifestations. The index case was her mother who died at age 63 of clear cell renal carcinoma. The information was obtained by consulting the patient's medical register and by interviews with the patient and her relatives. The presence of left optic nerve hemangioblastoma was suggested by CT scan of the skull and orbit. The sequencing of the VHL gene was performed in the peripheral blood by the polymerase chain reaction (PCR) technique, and the duplication and deletion research was performed using the multiplex ligation-dependent probe amplification (MPLA) technique. The presence of a rare pathogenic variant c.263G> A (p.Trp88Ter) was observed in heterozygosity in the VHL gene that determined a premature stop codon. CT scan of the skull and orbits suggested the presence of HB in the optic nerve of the left eye. The results of the CT scan of the skull and orbits show thickening with tortuosity of the left optic nerve, with a small area of nodular enhancement. The right optic nerve had a conserved aspect. Conclusion: This is the fourth case described of this rare pathogenic variant of the VHL gene, according to the Human Gene Mutation Database and VHLdb database records and with an optic nerve hemangioblastoma of the optic nerve, a very rare phenotypic expression of the VHLS.

Prevalence of palliative sedation in the State of São Paulo: an emerging medical demand / Prevalência de sedação paliativa no Estado de São Paulo: uma demanda médica emergente

ABSTRACT Objective To investigate the prevalence of palliative sedation use and related factors. Methods An observational study based on data collected via electronic questionnaire comprising 23 close-ended questions and sent to physicians living and working in the state of São Paulo. Demographic data, prevalence and frequency of palliative sedation use, participant's familiarity with the practice and related motivating factors were analyzed. In order to minimize memory bias, questions addressing use frequency and motivating factors were limited to the last year prior to survey completion date. Descriptive statistics were used to summarize data. Results In total, 20,168 e-mails were sent and 324 valid answers obtained, resulting in 2% adherence. The overall prevalence of palliative sedation use over the course of professional practice was 68%. However, only 48% of respondents reported having used palliative sedation during the last year, primarily to relieve pain (35%). The frequency of use ranged from one to six times (66%) during the study period and the main reason for not using was the lack of eligible patients (64%). Approximately 83% of physicians felt comfortable using palliative sedation but only 26% reported having specific academic training in this field. Conclusion The prevalence of palliative sedation use is high, the primary indication being pain relief. However, frequency of use is low due to lack of eligible patients.

RESUMO Objetivo Verificar a prevalência e os fatores associados ao uso de sedação paliativa. Métodos Trata-se de estudo observacional realizado a partir do preenchimento de um questionário eletrônico com 23 questões objetivas enviado a médicos paulistas. Foram avaliados os dados demográficos, a prevalência e a frequência de uso da sedação paliativa; o nível de conhecimento a respeito da técnica; e as motivações para sua utilização. Visando minimizar o viés de recordação, questões sobre a frequência de uso e motivações para tal, as respostas deveriam se referir ao último ano em relação à data de preenchimento da pesquisa. Foi utilizada estatística descritiva para sumarizar os resultados. Resultados Foram enviados 20.168 e-mails e obtiveram-se 324 respostas válidas, resultando em 2% de adesão. A prevalência de utilização da sedação paliativa ao longo do histórico de atuação profissional foi de 68%, mas apenas 48% utilizaram a sedação paliativa no último ano, motivados, principalmente, pela presença de dor no paciente (35%). A frequência de uso foi de uma a seis vezes (66%), e a principal razão para não empregar a sedação paliativa foi a ausência de pacientes elegíveis (64%). Aproximadamente 83% dos médicos sentiam-se confortáveis quanto ao uso de sedação paliativa, mas apenas 26% possuíam formação teórica específica na área. Conclusão A prevalência de uso da sedação paliativa é alta, sendo utilizada, na maioria das vezes, para proporcionar o alívio da dor do paciente. Por outro lado, sua frequência de utilização é baixa, principalmente pela ausência de pacientes elegíveis.

Hydrolyzed Rutin Decreases Worsening of Anaplasia in Glioblastoma Relapse.

BACKGROUND: Gliomas are aggressive and resilient tumors. Progression to advanced stages of malignancy, characterized by cell anaplasia, necrosis, and reduced response to conventional surgery or therapeutic adjuvant, are critical challenges in glioma therapy. Relapse of the disease poses a considerable challenge for management. Hence, new compounds are required to improve therapeutic response. As hydrolyzed rutin (HR), a compound modified via rutin deglycosylation, as well as some flavonoids demonstrated antiproliferative effect for glioblastoma, these are considered potential epigenetic drugs. OBJECTIVE: The purpose of this study was to determine the antitumor activity and evaluate the potential for modifying tumor aggressivity of rutin hydrolysates for treating both primary and relapsed glioblastoma. METHODS: The glioblastoma cell line, U251, was used for analyzing cell cycle inhibition and apoptosis and for establishing the GBM mouse model. Mice with GBM were treated with HR to verify antitumor activity. Histological analysis was used to evaluate HR interference in aggressive behavior and glioma grade. Immunohistochemistry, comet assay, and thiobarbituric acid reactive substance (TBARS) values were used to evaluate the mechanism of HR action. RESULTS: HR is an antiproliferative and antitumoral compound that inhibits the cell cycle via a p53- independent pathway. HR reduces tumor growth and aggression, mainly by decreasing mitosis and necrosis rates without genotoxicity, which is suggestive of epigenetic modulation. CONCLUSION: HR possesses antitumor activity and decreases anaplasia in glioblastoma, inhibiting progression to malignant stages of the disease. HR can improve the effectiveness of response to conventional therapy, which has a crucial role in recurrent glioma.

Paradigma na Formação Médica: Atitudes e Conhecimentos de Acadêmicos sobre Morte e Cuidados Paliativos / End-of-Life Paradigm in Medical Training: Attitudes and Knowledge about Death and Palliative Care

RESUMO A Organização Mundial da Saúde (OMS) define Cuidados Paliativos como abordagem que aprimora a qualidade de vida dos pacientes e seus familiares que enfrentam problemas associados a doenças ameaçadoras de vida, por meio da prevenção e alívio do sofrimento. Recentemente no Brasil, promoveu-se a Medicina Paliativa a especialidade médica, obrigando a repensar os conceitos de educação em terminalidade da vida nas escolas brasileiras. O relacionamento pessoal com a morte parece influenciar diretamente a premissa do cuidar-mais-que-curar, sendo essencial na relação do cuidador com aquele que morre. Há estreita relação entre ansiedade e medo da morte e a atitude do estudante de Medicina perante situações de terminalidade de vida. A visão que o acadêmico tem sobre a morte poderá determinar a disponibilidade interna, valores, conceitos e preconceitos com relação à morte e ao morrer e determinar seu desempenho como profissional. Dessa forma, os programas de educação médica devem ressaltar não apenas os aspectos teóricos e técnicos em Cuidados Paliativos, mas também o clima emocional que envolve o ato médico e a finitude da vida. Objetivo: Comparar as atitudes de acadêmicos em curso de Medicina perante a morte e o processo de morrer segundo o contato teórico e/ou prático com a disciplina de Cuidados Paliativos ao longo de sua formação médica. Método: Estudo de coorte que avalia a modificação do perfil do acadêmico de Medicina com base nos questionários de Tanatofobia e Autoeficácia em Cuidados Paliativos. Resultados: A reflexão teórica diminui a ansiedade relacionada à atividade prática (p < 0,05). As habilidades em comunicação e multidisciplinaridade em Cuidados Paliativos são mais bem desempenhadas pelo grupo que recebe treinamento completo, teórico e prático, do que nos grupos que recebem apenas teoria ou nos que adquirem seus conhecimentos mediante aprendizado em serviço exclusivamente (p < 0,05). Conclusão: A disciplina Cuidados Paliativos auxilia na superação de medos relacionados à morte, reduzindo a ansiedade envolvida na prática dos cuidados de fim de vida, principalmente no quesito comunicação. Estudantes que recebem treinamento teórico e prático em Cuidados Paliativos mostram maior confiança diante de situações de terminalidade.

ABSTRACT Background: The World Health Organization (WHO) defines Palliative Care as an approach which, by preventing and alleviating suffering, improves the quality of life of patients and their families who face problems associated with life-threatening illnesses. In Brazil, Palliative Medicine has recently been promoted to the category of medical specialty, obliging Brazilian medical schools to review the educational concepts associated to end-of-life care. The personal relationship with death seems to directly influence the premise of care-more-than-healing, as an essential element of the caregiver's relationship with the terminal patient. There is a close relationship between anxiety and fear of death and the medical student's attitude in the face of end-of-life situations. The scholar's view of death may determine their inner disposition, values, concepts, and prejudices regarding death and dying and determine their performance as a professional. Thus, medical education programs must emphasize not only the theoretical-technical aspects in Palliative Care, but also the emotional climate that involves the medics' attitudes and actions in end-of-life situations. Objective: To compare the attitudes of medical students when faced with death and the process of dying according to their theoretical and/or practical training in Palliative Care. Method: A cohort study evaluating how the profile of medical students has changed based on questionnaires on Fear of Death and Self-Efficacy in Palliative Care. Results: Theoretical reflection reduces anxiety related to practical activity (p < 0.05). Communication and multidisciplinary skills in Palliative Care are performed far better by those who receive complete theoretical and practical training than those who are trained only in theoretical terms or those who rely exclusively on in-service learning (p < 0.05). Conclusion: The Palliative Care discipline helps students overcome fears related to death, thus reducing their anxiety when practicing end-of-life care, especially in terms of communication. Students who receive this theoretical and practical training. Students who receive theoretical and practical training in Palliative Care show greater confidence when faced with end-of-life situations.

Revisiting colorectal cancer animal model - An improved metastatic model for distal rectosigmoid colon carcinoma.

Colorectal cancer (CRC) is the second most frequent and fatal cancer in Western countries. Understanding its biology with different incidence along the colon and rectum, genetic profile and how these factors contribute to local/distant progression, has been hampered by the lack of a suitable CRC model. We report a reproducible model, using human CRC cell lines (CL) (WiDr, LS1034, C2BBe1) injected (1 × 107 cells/animal) in RNU rats (n = 55) which underwent cecostomy and descending colostomy with mucosal-cutaneous fistula of the sigmoid colon. CL were characterized by immunohistochemistry: CK20, CDX2, P53, vimentin, Ki67, CD44, CD133, E-cadherin, ß-catenin and CEA; cancer stem cells-immune system interaction was studied and tumor progression was assessed with nuclear medicine imaging (99mTc-MIBI). Animals developed locally invasive tumors and with WiDr neural invasion was registered. Cancer stem cells were detected in WiDr (CD44 positive). All the cell lines stimulated the immune system, being WiDr the most aggressive. Imaging studies demonstrated tumor uptake. With this CRC model we can study the microenvironment role and tumor-stroma interactions. All CL developed primary disease, but only the WiDR established neural invasion which may represent a metastatic pathway. This model can help unveiling the underlying metastatic mechanisms, and ultimately test better therapeutic approaches for CRC.

Plasmalogen lipids: functional mechanism and their involvement in gastrointestinal cancer.

The plasmalogens are a class of glycerophospholipids which contain a vinyl-ether and an ester bond at the sn-1 and sn-2 positions, respectively, in the glycerol backbone. They constitute 10 mol% of the total mass of phospholipids in humans, mainly as membrane structure components. Plasmalogens are important for the organization and stability of lipid raft microdomains and cholesterol-rich membrane regions involved in cellular signaling. In addition to their structural roles, a subset of ether lipids are thought to function as endogenous antioxidants and emerging studies suggest that they are involved in cell differentiation and signaling pathways. Although the clinical significance of plasmalogens is linked to peroxisomal disorders, the pathophysiological roles and their possible metabolic pathways are not fully understood since they present unique structural attributes for the different tissue types. Studies suggest that changes in plasmalogen metabolism may contribute to the development of various types of cancer. Here, we review the molecular characteristics of plasmalogens in order to significantly increase our understanding of the plasmalogen molecule and its involvement in gastrointestinal cancers as well as other types of cancers.

A new therapeutic proposal for inoperable osteosarcoma: Photodynamic therapy.

BACKGROUND: Osteosarcoma, a malignant tumor characterized by bone or osteoid formation, is the second most common primary bone neoplasm. Clinical symptoms include local and surrounding pain, unrelieved by rest or anesthesia. Osteosarcoma has a poor chemotherapeutic response with prognosis dependent on complete tumor excision. Therefore, for inoperable osteosarcoma new therapeutic strategies are needed. The present study aimed to develop murine models of cranial and vertebral osteosarcoma that facilitate simple clinical monitoring and real-time imaging to evaluate the outcome of photodynamic therapy based on a previously developed photosensitizer. METHODS: Balb/c nude mice were divided into two groups: the cranial and vertebral osteosarcoma groups. Each group was further subdivided into the photodynamic therapy-treated and untreated groups. Images were obtained by scintigraphy with 99mTc-MIBI and radiography. Tumor growth, necrotic area, osteoid matrix area, and inflammatory infiltration were analyzed. RESULTS: Cranial and vertebral tumors could be macroscopically observed and measured. Radiographic and scintigraphic images showed tumor cells present at the inoculation sites. After photodynamic therapy, scintigraphy showed lower tumoral radiopharmaceutical uptake, which correlated histologically with increased necrosis. Osteoid matrix volume increased, and tumor size decreased in all photodynamic therapy-treated animals. CONCLUSION: Cranial and vertebral osteosarcoma models in athymic mice are feasible and facilitate in vivo monitoring for the development of new therapies. Photodynamic therapy is a potential antitumoral treatment for surgically inoperable osteosarcoma.

Literature Evidence and ARRIVE Assessment on Neuroprotective Effects of Flavonols in Neurodegenerative Diseases' Models.

BACKGROUND AND OBJECTIVE: This paper was based on a literature search of PubMed and Scielo databases using the keywords "Flavonoids, Neuroprotection, Quercetin, Rutin, Isoquercitrin, Alzheimer, Parkinson, Huntington" and combinations of all the words. METHOD: We collected relevant publications, during the period of 2000 to 2016, emphasizing in vivo and in vitro studies with neurological assessment of flavonol's potentials, as well as classifying studies according to evidence levels, in order to elucidate evidence-based literature and its application on clinical research. In addition, we highlight the importance of flavonols in modern research fields, indicating their neuroprotective potential and use thereof as preventive and therapeutic treatment of numerous neurodegenerative disease. Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, represent worldwide a major health problem with great financial impact. They are multifactorial diseases, hallmarked by similar pathogenesis that covers conditions such as oxidative stress, formation of free radicals, abnormal protein dynamics (degradation and aggregation), mitochondrial dysfunction, lipid peroxidation and cellular death or senescence. Flavonols are polyphenolic compounds, widely distributed in the plant kingdom and found in high concentrations in vegetables, fruits and teas. Their neuroprotective effects are mainly related to their antioxidant, anti-proliferative and anti-inflammatory properties. CONCLUSION: It was this paper's intention to contribute with an evidence analysis of recent studies approaching neuroprotective effects of flavonols and the potential to conduct human clinical studies.

DNA Damage Is a Potential Marker for TP53 Mutation in Colorectal Carcinogenesis.

PURPOSE: The ability to measure oxidative DNA damage in a tissue allows establishment of the relationship between DNA damage and mutations in normal and neoplastic cells. It is well known that TP53 is a key inhibitor of tumor development and preserves the genome integrity in each cell. The aim of the present study was to investigate the relationship between DNA damage and TP53 mutation in colorectal adenoma and adenocarcinoma, and the value of DNA damage as potential marker of TP53 mutation in non-tumor tissues adjacent to colon malignant lesions. METHODS: Tissue samples were obtained by colonoscopy from patients with adenoma and/or adenocarcinoma and from healthy volunteers. Diagnosis was defined by histopathology. Immunohistochemistry with computer-assisted image analysis was performed to quantify TP53 mutation. Oxidative DNA damage was determined by comet assay. Statistical analyses were performed with 5 % of significance level. RESULTS: The TP53 level was higher in non-tumor tissues from tumor patients than in normal tissues from healthy volunteers (p = 0.01). Likewise, higher TP53 levels were observed in tumor tissues compared with the non-tumor tissues (p = 0.00). Oxidative DNA damage levels were higher in tumor tissues than in non-tumor tissues (p = 0.00). The amount of TP53 (p = 0.00) and oxidative DNA damage (p = 0.00) in normal and tumor tissue was related. The relationship between oxidative DNA damage and TP53 mutation was demonstrated in all samples (p = 0.00). CONCLUSION: Oxidative DNA damage is an intervening variable for TP53 mutation in colorectal adenoma-carcinoma. Our data suggests that oxidative DNA damage is a potential marker of TP53 mutation in colorectal carcinogenesis.