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1.
Insects ; 15(3)2024 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-38535351

RESUMEN

The sand fly, Phlebotomus papatasi (Scopoli, 1786), is a major vector for Leishmania major in the Middle East, which has impacted human health and US military operations in the area, demonstrating the need to develop effective sand fly control and repellent options. Here, we report the results of spatial repellency and avoidance experiments in a static air olfactometer using the female P. papatasi testing essential oils of Lippia graveolens (Mexican oregano), Pimenta dioica (allspice), Amyris balsamifera (amyris), Nepeta cataria (catnip), Mentha piperita (peppermint), and Melaleuca alternifolia (tea tree); the 9-12 carbon saturated fatty acids (nonanoic acid, decanoic acid, undecanoic acid, and dodecanoic acid); and the synthetic repellents DEET and IR3535. The materials applied at 1% exhibited varying activity levels but were not significantly different in mean repellency and avoidance from DEET and IR3535, except in regards to nonanoic acid. Some materials, particularly nonanoic and undecanoic acids, produced sand fly mortality. The observed trends in mean repellency over exposure time included the following: (1) P. dioica oil, M. alternifolia oil, decanoic acid, undecanoic acid, DEET, and IR3535 exhibited increasing mean repellency over time; (2) oils of N. cataria, A. balsamifera, M. piperita, and dodecanoic acid exhibited relatively constant mean repellency over time; and (3) L. graveolens oil and nonanoic acid exhibited a general decrease in mean repellent activity over time. These studies identified the essential oils of N. cataria and A. balsamifera as effective spatial repellents at reduced concentrations compared to those of DEET. Additional research is required to elucidate the modes of action and potential synergism of repellents and essential oil components for enhanced repellency activity.

2.
Methods Mol Biol ; 2758: 401-423, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38549027

RESUMEN

Peptides have potential bioactive functions, and the peptidomics landscape has been broadly investigated for various diseases, including cancer. In this chapter, we reviewed the past four years of literature available and selected 16 peer-reviewed publications exploring peptidomics in diagnosis, prognosis, and treatment in cancer research. We highlighted their main aims, mass spectrometry-based peptidomics, multi-omics, data-driven and in silico strategies, functional assays, and clinical applications. Moreover, we underscored several levels of difficulties in translating the peptidomics findings to clinical practice, aiming to learn with the accumulated knowledge and guide upcoming studies. Finally, this review reinforces the peptidomics robustness in discovering potential candidates for monitoring the several stages of cancer disease and therapeutic treatment, leveraging the management of cancer patients in the future.


Asunto(s)
Neoplasias , Proteómica , Humanos , Péptidos/uso terapéutico , Espectrometría de Masas , Neoplasias/diagnóstico , Neoplasias/terapia
3.
Front Microbiol ; 14: 1207664, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37965564

RESUMEN

The consumption of non-steroidal anti-inflammatory drugs (NSAIDs) have increased significantly in the last years (2020-2022), especially for patients in COVID-19 treatment. NSAIDs such as diclofenac, ibuprofen, and paracetamol are often available without restrictions, being employed without medical supervision for basic symptoms of inflammatory processes. Furthermore, these compounds are increasingly present in nature constituting complex mixtures discarded at domestic and hospital sewage/wastewater. Therefore, this review emphasizes the biodegradation of diclofenac, ibuprofen, and paracetamol by pure cultures or consortia of fungi and bacteria at in vitro, in situ, and ex situ processes. Considering the influence of different factors (inoculum dose, pH, temperature, co-factors, reaction time, and microbial isolation medium) relevant for the identification of highly efficient alternatives for pharmaceuticals decontamination, since biologically active micropollutants became a worldwide issue that should be carefully addressed. In addition, we present a quantitative bibliometric survey, which reinforces that the consumption of these drugs and consequently their impact on the environment goes beyond the epidemiological control of COVID-19.

4.
Cureus ; 15(3): e35831, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37033547

RESUMEN

Eosinophilic cholecystitis (EC) is an uncommon cause of acute cholecystitis; the clinical presentation is indistinguishable from other types of cholecystitis, and the diagnosis is made by histopathology study. We present the case of a 73-year-old male patient with right hypochondrial abdominal pain suggestive of symptomatic cholelithiasis. There were no significant findings at the blood workup or physical examination; he underwent a cholecystectomy and was later diagnosed with eosinophilic cholecystitis by histopathology. EC may be associated with some other systemic conditions, such as eosinophilic granulomatosis, eosinophilic ascites, or parasitosis, which will require specific management.

5.
Cureus ; 15(2): e34845, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36919060

RESUMEN

Numerous pathologies can cause abdominal pain; thus, the surgeon's job is to precisely identify any pathologies that may require surgery and endanger the patient's life. Perforation of a gastric or duodenal ulcer associated with a clinical picture of acute appendicitis is known as Valentino syndrome (VS). To our knowledge, there are 22 cases of VS reported in the literature. We describe the clinical case of a 53-year-old female patient with abdominal pain in the right iliac fossa who came to the emergency room. A plain tomography was performed, which found free intraperitoneal fluid and free subdiaphragmatic air. Therefore, a laparotomy was performed, revealing a gastric perforation. VS is a rare pathology and when not recognized and managed properly, it can increase patients' mortality.

6.
J Anim Physiol Anim Nutr (Berl) ; 107(4): 1019-1027, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36524550

RESUMEN

This study was conducted to investigate if calves supplemented with rice bran in a creep feeding (CF) system associated with temporary weaning (TW) affects the performance of the cow-calf pair grazing natural grasslands during summer. Two experiments were performed using 275 cow-calf pairs of British breeds and their crosses of different parities (primiparous [n = 188] in Experiment 1 and multiparous [n = 87] in Experiment 2). In both experiments, the factors evaluated were: (1) supplementation of calves with rice bran using CF: yes (+CF) or no (-CF); (2) TW for 14 days using nose plates: yes (+TW) or no (-TW). Four experimental groups were formed in both experiments: -CF - TW, -CF + TW, +CF - TW and +CF + TW. TW decreased the average daily weight gain and live weight of calves independently of the age of their mothers. The use of CF decreased both of these parameters in calves born to primiparous cows, and there was no response in the case of calves born to multiparous cows. A greater proportion of primiparous cows that received +CF conceived in the first 21 days of mating (+CF - TW = 63.5% and +CF + TW = 50%) than the other groups. The final pregnancy rate was similar among groups in both experiments. In conclusion, TW decreased the average daily weight gain and weaning weight of calves. Supplementation of calves born to primiparous cows with rice bran decreased their daily weight gain during the period of TW and their weaning weight, but their dams were conceived earlier.


Asunto(s)
Oryza , Embarazo , Femenino , Animales , Bovinos , Destete , Fitomejoramiento , Suplementos Dietéticos , Aumento de Peso
7.
Foods ; 12(23)2023 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-38231670

RESUMEN

Cold brew coffee (CBC) has gained in popularity due to its distinct sensory experience. However, CBC can pose a risk for bacterial pathogens if not stored properly. High-Pressure Processing (HPP) is a nonthermal technology that can improve the safety of CBC while maintaining its quality. In this study, CBC made from ground roasted coffee grains was processed at 600 MPa for 3 min and stored at 4 or 23 °C for 90 days. The microbiological quality indicators remained stable throughout the study period. Physicochemical and quality parameters, such as pH, total dissolved solids, titratable acidity, color, total phenolic compounds and antioxidant activity, were not significantly affected by HPP. Both unprocessed and HPP CBC samples showed changes in pH, titratable acidity and color stability after 60 days at 23 °C. Unprocessed CBC samples spiked with Escherichia coli O157:H7, Listeria monocytogenes and Salmonella enterica showed decreased counts, but the pathogens were still detectable after 60 days at 4 °C and after 90 days at 23 °C. HPP achieved a >6-log10 reduction in the species tested, with non-detectable levels for at least 90 days at both storage temperatures. These findings suggest that HPP can effectively control vegetative pathogens and spoilage microorganisms in CBC while preserving its quality attributes.

9.
Rev. bras. oftalmol ; 82: e0003, 2023. tab
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1423621

RESUMEN

ABSTRACT Objective: To evaluate the effectiveness of text messaging in improving adherence to occlusion therapy for amblyopia. The secondary objective was to correlate the responses given in a self-reporting questionnaire with treatment outcome (improvement in visual acuity). Methods: This is a prospective, randomized, blinded clinical trial. The patients' parents or legal guardians in the intervention group received text messages reminding them of the importance of patching. The control group received no text messages. At final evaluation, after a period of three to six months, the patients' parents or legal guardians answered a self-reporting questionnaire to evaluate adherence to treatment. Results: The study included 34 patients with an average age of 5.35 years, 20 in the intervention group and 14 in the control group. According to the results of the self-reporting questionnaire, 50% of the study population was considered as having low adherence to treatment, 29% as having medium adherence, and 21% as having good adherence. There was no significant difference between trial groups. The comparison between an improvement in visual acuity and the mean value obtained in the self-reporting questionnaire showed a significant association between this improvement and adherence to treatment (p=0.03). Conclusion: The present study did not find a correlation between text messaging and an improvement in adherence to occlusion therapy, as shown by previous studies for different treatments. A statistically significant association was identified between an improvement in visual acuity and a good therapeutic adherence, as measured by the self-reporting questionnaire. This finding allows us to recommend using a self-reporting questionnaire as a simple method to measure adherence to treatment and help decisions about therapeutic strategies to be adopted in the patient's continuing treatment.


RESUMO Objetivo: Avaliar a eficácia do envio de mensagens de texto na melhora da adesão ao tratamento oclusivo da ambliopia. O objetivo secundário foi correlacionar as respostas dadas no questionário autorreportado e os resultados obtidos no tratamento (melhora da acuidade visual). Métodos: Ensaio clínico prospectivo, mascarado e randomizado. Os pais ou responsáveis legais dos pacientes no grupo intervenção receberam mensagens de texto para lembrar a importância dos oclusores. O grupo controle não recebeu mensagens. Na avaliação geral após 3 a 6 meses, os responsáveis responderam a um questionário autorreportado para avaliar a aderência ao tratamento. Resultados: Foram incluídos 34 pacientes com idade média de 5,35 anos; 20 eram do grupo intervenção. A população do estudo foi considerada 50% pouco aderente ao tratamento, 29% com aderência média e 21% com boa aderência, de acordo com resultado do questionário autorreportado. Não houve diferença significativa entre os grupos estudados. Quando comparada a relação entre a melhora da acuidade visual com o valor médio do questionário autorreportado, foi observada associação significativa da melhora com a adesão ao tratamento (p=0,03). Conclusão: Este estudo não mostrou melhora da aderência ao tratamento oclusivo com o envio de mensagens de texto, como tinha sido observado em estudos anteriores para outros tratamentos. Foi identificada uma relação estatisticamente significativa entre a melhora na acuidade visual e boa aderência terapêutica medida pelo questionário autorreportado. Isso permite recomendar o uso do questionário autorreportado como uma forma simples de mensurar aderência ao tratamento e auxiliar nas decisões sobre estratégias a serem adotadas na continuidade do seguimento do paciente.

10.
Molecules ; 27(23)2022 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-36500534

RESUMEN

Mosquitoes can be vectors of pathogens and transmit diseases to both animals and humans. Species of the genus Culex are part of the cycle of neglected diseases, especially Culex quinquefasciatus, which is an anthropophilic vector of lymphatic filariasis. Natural products can be an alternative to synthetic insecticides for vector control; however, the main issue is the poor water availability of some compounds from plant origin. In this context, nanoemulsions are kinetic stable delivery systems of great interest for lipophilic substances. The objective of this study was to investigate the larvicidal activity of the Hyptis suaveolens essential oil nanoemulsion on Cx. quinquefasciatus. The essential oil showed a predominance of monoterpenes with retention time (RT) lower than 15 min. The average size diameter of the emulsions (sorbitan monooleate/polysorbate 20) was ≤ 200 nm. The nanoemulsion showed high larvicidal activity in concentrations of 250 and 125 ppm. CL50 values were 102.41 (77.5253−149.14) ppm and 70.8105 (44.5282−109.811) ppm after 24 and 48 h, respectively. The mortality rate in the surfactant control was lower than 9%. Scanning micrograph images showed changes in the larvae's integument. This study achieved an active nanoemulsion on Cx. quinquefasciatus through a low-energy-input technique and without using potentially toxic organic solvents. Therefore, it expands the scope of possible applications of H. suaveolens essential oil in the production of high-added-value nanosystems for tropical disease vector control.


Asunto(s)
Aedes , Culex , Culicidae , Insecticidas , Lamiaceae , Aceites Volátiles , Humanos , Animales , Aceites Volátiles/farmacología , Aceites Volátiles/análisis , Larva , Mosquitos Vectores , Insecticidas/química , Extractos Vegetales/química , Hojas de la Planta/química
11.
Toxicol Rep ; 9: 1537-1547, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36518414

RESUMEN

Intestinal mucositis (IM) is a frequent adverse effect in anticancer therapy without standard treatment. The oil obtained from sucupira (Pterodon emarginatus) has anti-inflammatory properties, and the soybean lecithin reduces the intestinal toxicity of several xenobiotics. However, their water insolubility impairs the in vivo application. For this reason, we evaluated if the nanoencapsulation of sucupira oil (SO) in lecithin-based nanocapsules (SO-NC) could be a therapeutically effective system for the treatment of IM in murine cisplatin (CDDP)-induced intestinal mucositis model. SO was analyzed by LC-HRMS/MS and HPLC. SO-NC was prepared by nanoprecipitation and characterized using DLS, HPLC, and AFM. Mice body weight and food consumption were assessed daily during experimental mucositis induced by CDDP. The animals were euthanized, and intestinal permeability, inflammatory mediators, and intestinal histology were performed. SO-NC demonstrated adequate characteristics for oral administration as size under 300 nm, IP < 0.3, high EE, and spherical shape. In vitro cytotoxicity performed against RAW 264.7 cell lines resulted in cell viability above 80 % confirming the non-cytotoxic profile of SO (IC50 268 µg/mL) and SO-NC (IC50 118.5 µg/mL) up to 117.2 µg/mL. The untreated mice showed intestinal toxicity after i.p. of CDDP, principally weight loss, increased intestinal permeability, and MPO and TNF-α levels. Surprisingly, the administration of SO to CDDP-mucositis animals did not circumvent the CDDP effects and increased intestinal permeability. However, SO-NC proved efficient in mitigating the experimental intestinal mucositis by improving intestinal epithelium architecture, reducing intestinal permeability, and improving the MPO levels. In conclusion, SO-NC can positively impact intestinal mucositis by promoting mucosal recovery. This is a promising strategy for developing a new treatment for intestinal mucositis.

12.
Med Image Anal ; 82: 102576, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36126404

RESUMEN

Cortical thickness (CTh) is routinely used to quantify grey matter atrophy as it is a significant biomarker in studying neurodegenerative and neurological conditions. Clinical studies commonly employ one of several available CTh estimation software tools to estimate CTh from brain MRI scans. In recent years, machine learning-based methods emerged as a faster alternative to the main-stream CTh estimation methods (e.g. FreeSurfer). Evaluation and comparison of CTh estimation methods often include various metrics and downstream tasks, but none fully covers the sensitivity to sub-voxel atrophy characteristic of neurodegeneration. In addition, current evaluation methods do not provide a framework for the intra-method region-wise evaluation of CTh estimation methods. Therefore, we propose a method for brain MRI synthesis capable of generating a range of sub-voxel atrophy levels (global and local) with quantifiable changes from the baseline scan. We further create a synthetic test set and evaluate four different CTh estimation methods: FreeSurfer (cross-sectional), FreeSurfer (longitudinal), DL+DiReCT and HerstonNet. DL+DiReCT showed superior sensitivity to sub-voxel atrophy over other methods in our testing framework. The obtained results indicate that our synthetic test set is suitable for benchmarking CTh estimation methods on both global and local scales as well as regional inter-and intra-method performance comparison.


Asunto(s)
Benchmarking , Enfermedades Neurodegenerativas , Humanos , Estudios Transversales , Atrofia , Imagen por Resonancia Magnética/métodos , Encéfalo , Biomarcadores
13.
Licere (Online) ; 25(2): 233-260, set.2022. ilus
Artículo en Portugués | LILACS | ID: biblio-1399744

RESUMEN

Este artigo objetiva apresentar uma revisão das produções acadêmicas de algumas correntes teórico-metodológicas, denominadas de "escolas", que abordam o jogo na Educação Física brasileira. Trata-se de uma pesquisa de abordagem qualitativa, de cunho descritivo, do tipo bibliográfico. Os critérios de inclusão para definir as "escolas" foram: tradição de pesquisas produzidas por mais de uma década, formação profissional em grupos de pesquisa com orientações na graduação e pós-graduação e com contribuições didáticas e investigativas utilizadas como referências na área. A análise de conteúdo das obras principais (livros) deu-se a partir das unidades temáticas: educação escolar, esporte e lazer. O estudo identificou quatro escolas, assim denominadas: Jogo, entre a rua e a escola; Jogo Tradicional; Praxiologia Motriz do jogo e Escola Brincante. Neste artigo, está abordado o conceito de jogo e as contribuições das produções bibliográficas para a educação escolar, para o esporte e para o lazer, das duas primeiras escolas.


This article aims to present a review of the academic productions of some theoretical-methodological currents, called "schools", which approach the game in Brazilian Physical Education. This is a qualitative, descriptive, bibliographic research. The inclusion criteria to define the "schools" were: tradition of the researches produced for more than a decade, professional training in research groups with guidance at undergraduate and postgraduate levels and with didactic and investigative contributions used as references in the area. The content analysis of the main works (books) was based on the thematic units: school education, sport and leisure. The study identified four schools, named as follows: Game, between the street and the school; Traditional Game; Game Driving Praxiology and Playing School. In this article, the concept of game and the contributions of bibliographic productions for school education, for sport and for leisure, from the first two schools are discussed.


Asunto(s)
Educación
14.
Rev Chilena Infectol ; 39(2): 218-220, 2022 04.
Artículo en Español | MEDLINE | ID: mdl-35856997

RESUMEN

There are few cases reports of Enterobacter cancerogenus infections. Although it has been isolated in contaminated wounds associated with trauma, it has also been reported as an etiological agent in a wide variety of other infections, with the presence of bacteremia being infrequent. We present the first case reported in Chile of a bacteremia caused by this agent, in a 28-year-old patient with a stable pelvic fracture due a high-energy traffic accident. He had a good clinical response to treatment with ertapenem.


Asunto(s)
Bacteriemia , Infecciones por Enterobacteriaceae , Adulto , Bacteriemia/tratamiento farmacológico , Chile , Enterobacter , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Ertapenem , Humanos , Masculino
15.
Toxicol Res (Camb) ; 11(3): 520-528, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35782641

RESUMEN

Kefiran is a polysaccharide present in kefir grains that have been widely explored due to its potential health benefits. The objective of this work was to characterize and quantify the components present in the ethanolic extract of milk kefir grains; to study its pharmacokinetic and toxicological properties in silico and evaluate the acute toxicity of the kefiran in zebrafish. The prediction of pharmacokinetic properties was performed by QikProp software. In silico toxicity assessment was performed using the DEREK (deductive estimate of risk from existing knowledge) software. In the chromatographic, kefiran was identified as the major component. Results showed that the kefiran had low human oral absorption and intestinal absorption its due poor solubility profile; low logP value, indicating its lipophilicity and the low MDCK and Caco-2 cells permability, and unable to cross the blood-brain barrier. Kefiran did not present any structural warning for in silico toxicity. In zebrafish, the dose of 2,000 mg/kg of kefiran produced nonsignificant alterations in the analyzed organs. It can be said then that kefiran has an acceptable degree of safety for use in the development of drugs or functional foods. Further research such as in vivo testing to confirm its pharmacological potential is currently underway.

16.
Iran J Allergy Asthma Immunol ; 21(1): 98-100, 2022 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-35524384

RESUMEN

Cold-induced urticaria is considered as a subtype of physical urticaria and also the second most common type of chronic inducible urticaria. Contact with cold surfaces or the environment may cause systemic reactions, especially during aquatic activities. A 22-year-old female patient with a history of sulfa drug allergy began her condition 2 years before the presence of generalized pruritic erythema with hives as well as 2 episodes that had been characterized by facial angioedema and syncope 3-5 minutes after being in contact with cold air or surfaces.  On both events, she had just been outdoors on a cold, winter day. She was suspected to have cold-induced urticaria; thereby she had a positive reaction to the ice cube test. Due to the previous episodes of anaphylaxis, the patient was trained to administer intramuscular epinephrine. After 4 weeks of starting the treatment with antihistamines, no new events or injuries had occurred. Cold-induced urticaria may cause life-threatening reactions. The rate of anaphylaxis in these patients is low however, this case is presented to inform the importance of identifying this type of systemic reaction and preventing strategies.


Asunto(s)
Anafilaxia , Angioedema , Urticaria Crónica , Urticaria , Adulto , Anafilaxia/diagnóstico , Anafilaxia/etiología , Angioedema/diagnóstico , Angioedema/tratamiento farmacológico , Angioedema/etiología , Cara , Femenino , Humanos , Urticaria/diagnóstico , Urticaria/etiología , Adulto Joven
17.
Rev. chil. infectol ; 39(2): 218-220, abr. 2022. ilus
Artículo en Español | LILACS | ID: biblio-1388346

RESUMEN

Resumen Existen escasas comunicaciones de infecciones por Enterobacter cancerogenus. Aunque ha sido aislado en heridas contaminadas asociadas a traumas, también ha sido reportado como agente etiológico en una amplia variedad de otras infecciones, siendo infrecuente la presencia de bacteriemia. Presentamos el primer caso reportado en Chile de una bacteriemia causada por este microorganismo, en un varón de 28 años con una fractura de pelvis estable debido a un accidente de tránsito de alta energía. Tuvo una buena respuesta clínica al tratamiento con ertapenem.


Abstract There are few cases reports of Enterobacter cancerogenus infections. Although it has been isolated in contaminated wounds associated with trauma, it has also been reported as an etiological agent in a wide variety of other infections, with the presence of bacteremia being infrequent. We present the first case reported in Chile of a bacteremia caused by this agent, in a 28-year-old patient with a stable pelvic fracture due a high-energy traffic accident. He had a good clinical response to treatment with ertapenem.


Asunto(s)
Humanos , Masculino , Adulto , Bacteriemia/tratamiento farmacológico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Chile , Enterobacter , Ertapenem
18.
Cancers (Basel) ; 14(5)2022 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-35267611

RESUMEN

Breast ductal carcinoma in situ (DCIS) is clinically challenging, featuring high diagnosis rates and few targeted therapies. Expression/signaling from junctional adhesion molecule-A (JAM-A) has been linked to poor prognosis in invasive breast cancers, but its role in DCIS is unknown. Since progression from DCIS to invasive cancer has been linked with overexpression of the human epidermal growth factor receptor-2 (HER2), and JAM-A regulates HER2 expression, we evaluated JAM-A as a therapeutic target in DCIS. JAM-A expression was immunohistochemically assessed in patient DCIS tissues. A novel JAM-A antagonist (JBS2) was designed and tested alone/in combination with the HER2 kinase inhibitor lapatinib, using SUM-225 cells in vitro and in vivo as validated DCIS models. Murine tumors were proteomically analyzed. JAM-A expression was moderate/high in 96% of DCIS patient tissues, versus 23% of normal adjacent tissues. JBS2 bound to recombinant JAM-A, inhibiting cell viability in SUM-225 cells and a primary DCIS culture in vitro and in a chick embryo xenograft model. JBS2 reduced tumor progression in in vivo models of SUM-225 cells engrafted into mammary fat pads or directly injected into the mammary ducts of NOD-SCID mice. Preliminary proteomic analysis revealed alterations in angiogenic and apoptotic pathways. High JAM-A expression in aggressive DCIS lesions and their sensitivity to treatment by a novel JAM-A antagonist support the viability of testing JAM-A as a novel therapeutic target in DCIS.

19.
Cells ; 11(4)2022 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-35203384

RESUMEN

Overexpression of the human epidermal growth factor receptor-2 (HER2) is associated with aggressive disease in breast and certain other cancers. At a cellular level, the adhesion protein Junctional Adhesion Molecule-A (JAM-A) has been reported to regulate the expression of HER3 via a transcriptional pathway involving FOXA1. Since FOXA1 is also a suggested transcription factor for HER2, this study set out to determine if JAM-A regulates HER2 expression via a similar mechanism. An integrated tripartite approach was taken, involving cellular expression studies after targeted disruption of individual players in the putative pathway, in silico identification of relevant HER2 promoter regions and, finally, interrogation of cancer patient survival databases to deconstruct functionally important links between HER2, JAM-A and FOXA1 gene expression. The outcome of these investigations revealed a unidirectional pathway in which JAM-A expression transcriptionally regulates that of HER2 by influencing the binding of FOXA1 to a specific site in the HER2 gene promoter. Moreover, a correlation between JAM-A and HER2 gene expression was identified in 75% of a sample of 40 cancer types from The Cancer Genome Atlas, and coincident high mean mRNA expression of JAM-A, HER2 and FOXA1 was associated with poorer survival outcomes in HER2-positive (but not HER2-negative) patients with either breast or gastric tumors. These investigations provide the first evidence of a transcriptional pathway linking JAM-A, HER2 and FOXA1 in cancer settings, and support potential future pharmacological targeting of JAM-A as an upstream regulator of HER2.


Asunto(s)
Neoplasias de la Mama , Factor Nuclear 3-alfa del Hepatocito , Molécula A de Adhesión de Unión , Receptor ErbB-2 , Neoplasias de la Mama/patología , Moléculas de Adhesión Celular/genética , Línea Celular Tumoral , Femenino , Factor Nuclear 3-alfa del Hepatocito/genética , Humanos , Molécula A de Adhesión de Unión/genética , Receptor ErbB-2/genética , Receptores de Superficie Celular/genética
20.
J Oncol Pharm Pract ; 28(3): 598-604, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33847195

RESUMEN

BACKGROUND: Taxanes adjuvant therapy is recommended in certain high risk or metastatic tumors, particularly in lung and breast cancer, but also in other types of cancer like ovarian. The incidence of severe adverse drug reactions to paclitaxel is of approximately 10%. OBJECTIVES: Analyze type I hypersensitivity reactions to paclitaxel and their management in the Mexican population. METHOD: It is a retrospective, observational and descriptive study that included type I hypersensitivity reactions to paclitaxel reported from our database. Symptoms of hypersensitivity reactions to paclitaxel were classified and skin testing was performed with a 6 mg/mL paclitaxel concentration. The desensitization procedure consisted of a 12-steps, 3-bags of 250 mL protocol with a 6-7-hour duration. RESULTS: A total of 60 desensitization procedures were performed and were all completed successfully. All participants in our group were female, their median age was 44.5 years.All of our patients had hypersensitivity adverse drug reaction to paclitaxel during their first exposure and within the first 10 minutes of infusion. 63.6% of the patients had a moderate hypersensitivity reaction to paclitaxel and 36.4% had a severe reaction. CONCLUSIONS: Paclitaxel continues to be a common use drug and has a high rate of adverse drug reactions. This is the first study of hypersensitivity to paclitaxel in a Mexican population.


Asunto(s)
Neoplasias de la Mama , Hipersensibilidad a las Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Hipersensibilidad Inmediata , Adulto , Neoplasias de la Mama/complicaciones , Desensibilización Inmunológica/métodos , Hipersensibilidad a las Drogas/etiología , Hipersensibilidad a las Drogas/terapia , Femenino , Humanos , Hipersensibilidad Inmediata/inducido químicamente , Hipersensibilidad Inmediata/complicaciones , Masculino , Paclitaxel/efectos adversos , Estudios Retrospectivos
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