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Treatment strategies for locally advanced and metastatic urothelial carcinoma based on molecular profiles: A Review
No full textUrothelial carcinoma (UC), which includes
bladder carcinoma (accounting for 90-95% of cases) and
upper urinary tract carcinoma (comprising 5-10%), is
one of the most prevalent malignancies worldwide. For
several decades, platinum-based chemotherapy has been
the primary treatment modality for this disease.
However, recent advancements have significantly
transformed the therapeutic landscape for patients with
UC. This transformation has been facilitated by the
introduction of various treatment options, including
immune checkpoint inhibitors targeting PD-L1 or PD-1,
antibody-drug conjugates that target nectin-4 or
trophoblast cell surface antigen 2 expressed on cancer
cells, and fibroblast growth factor receptor (FGFR)
inhibitors specifically indicated for Patients with UC
with FGFR3 mutations. Although these novel therapies
have demonstrated marked survival benefits for patients
with locally advanced or metastatic UC, their efficacy
can vary depending on the specific molecular profile
present on cancer cells. In this review, we summarize the
molecular classifications of UC and the corresponding
treatment landscape associated with these classifications
Discordance of intrinsic subtype between primary tumor and lymph node metastasis in breast cancer patients
No full textThe heterogeneity of cancer cells between
primary breast tumors and lymph node (LN) metastases
at the initial therapy remains unclear. This study aimed
to determine whether intrinsic subtypes of LN metastasis
differ from those of primary breast tumors and how
much additional information is obtained.
Ninety-three breast cancer cases with LN metastasis
were enrolled in the study. Immunohistochemistry for
ER, PgR, HER2, and Ki-67 was performed for primary
breast tumors and the largest LN metastases. The
intrinsic subtype was determined as luminal A (ER+,
PgR+, HER2-, Ki-67 index ≤20%), luminal B (ER+,
HER2-, PgR- or PgR+, and Ki-67 index >20%), luminal
B HER2 rich (ER+, HER2+), HER2 (ER-, HER2+), and
triple-negative (ER-, PgR-, HER2-). The discordance
ratios for intrinsic subtypes between the primary tumor
and LN metastasis were analyzed.
The discordance ratios for ER, PgR, HER2, and Ki
67 were 0/93 (0%), 7/93 (7.5%), 2/93 (2.2%), and 10/93
(10.8%), respectively. The discordance ratio for the
intrinsic subtype was 9/93 (9.7%). Considering the
intrinsic subtype of LN metastasis, the effects of
additional chemotherapy and anti-HER2 therapy could
be expected in 4/93 (4.3%) and 1/93 (1.1%) patients,
respectively.
The discordance ratio for the intrinsic subtype
between the primary breast tumor and LN metastasis
was 9.7%. Considering the intrinsic subtype of LN
metastasis, additional medical therapy could be expected
to be effective in 5/93 (5.4%) breast cancer cases with
LN metastasis. Immunohistochemistry of metastatic LNs
may be useful for planning adjuvant therapy when the
analysis of the primary site is inconclusive
SLMO2 inhibits apoptosis in ovarian cancer cells by modulating mitochondrial function via TRIAP1
No full textObjective. This study aimed to investigate
the role of SLMO2 in regulating mitochondrial function
and its interaction with TRIAP1, which inhibited
apoptosis in ovarian cancer cells. The findings provided
valuable insights into potential therapeutic targets for
ovarian cancer.
Methods. Lentiviral infection models were
developed using SKOV3 and OVCAR3 ovarian cancer
cell lines. Techniques such as flow cytometry, western
blotting, immunofluorescence, and transmission electron
microscopy were employed to systematically assess the
regulatory effects of SLMO2 and TRIAP1 on cell
proliferation, apoptosis, mitochondrial function, and
autophagy. Additionally, a subcutaneous mouse tumor
xenograft model was utilized to further investigate the
combined effects of SLMO2 and TRIAP1 on ovarian
cancer cells, with the aim of elucidating the specific
mechanisms underlying tumor growth and apoptosis.
Results. SLMO2 enhanced mitochondrial function
by increasing membrane potential and reducing reactive
oxygen species (ROS) levels. Furthermore, through its
interaction with TRIAP1, SLMO2 inhibited autophagy,
which further suppressed apoptosis in ovarian cancer
cells and regulated mitochondrial function. In vivo
experiments showed decreased ROS levels and reduced
expression of autophagy-related proteins, further
supporting the roles of SLMO2 and TRIAP1 in the
regulation of mitochondrial function.
Conclusions. SLMO2 regulated mitochondrial
function and inhibited apoptosis in ovarian cancer cells
by interacting with TRIAP1. The combination of
SLMO2 and TRIAP1 promoted tumor cell growth and
induced oxidative stress, suggesting potential therapeutic
targets for ovarian cancer
Drum therapy in early intervention
No full textOver time, music has evolved from being an element of daily activity to an art that demands sensitivity and emotion. Their association with developmental difficulties has enabled them to improve the emotional well-being of individuals by promoting their social, personal and academic functioning. The purpose of this article is to explore the possibilities of intervention in early care with a proposal that incorporates listening and playing the drum to comprehend the advantages that this can provide for children between 0 and 6 years experiencing developmental difficulties with this information we will include suggestions on how to use the drum during stimulation sessions. It is concluded that the union of the rhythmic patterns of the drum in the early attention sessions optimizes the quality of life of the children.A lo largo de los años, la música ha mostrado una evolución que ha pasado de ser un elemento de la actividad diaria a ser un arte que implica sensibilidad y emoción. Es por ello por lo que, su unión con las dificultades del desarrollo ha permitido beneficiar el bienestar emocional de las personas, fomentando su funcionamiento social, personal y académico. Este artículo se enfoca en conocer las posibilidades de intervención en atención temprana con una propuesta que implique la escucha y el toque del tambor, para conocer así los beneficios que este puede proporcionar ante las dificultades del desarrollo en niños de entre 0 y 6 años, por lo que se añadirán propuestas de actuación con el tambor en las sesiones de estimulación. Con base en las investigaciones consultadas que relacionan la música y las dificultades del desarrollo, a través de la musicoterapia, se concluye que la unión de los patrones rítmicos del tambor en las sesiones de atención temprana optimiza la calidad de vida de los niños
Lactancia materna y calidad de vida relacionada con la salud en la población escolar
No full textIntroducción
La lactancia materna es un proceso fisiológico cuyos beneficios a corto, medio y largo plazo en la infancia se siguen investigando. Estos hallazgos refuerzan la importancia de iniciar y mantener la lactancia el mayor tiempo posible, tanto para madres como para profesionales sanitarios, aunque existen desafíos relacionados con los estilos de vida y la conciliación laboral. Sin embargo, aún faltan estudios que analicen la asociación entre lactancia materna y la calidad de vida relacionada con la salud (CVRS) en niños en edad escolar.
Objetivos
El objetivo principal fue analizar si haber recibido lactancia materna de cualquier tipo, lactancia exclusiva o lactancia materna durante al menos 6 meses desde el nacimiento se asocia a mejores puntuaciones en las dimensiones y subdimensiones de CVRS, así como a un menor riesgo de presentar síntomas compatibles con el diagnóstico de TDAH o sus subtipos.
Metodología
Se realizó un estudio de cohortes retrospectivas con escolares de 3º de Educación Infantil y 1º y 2º de Educación Primaria de Jumilla y Yecla (Área V de Salud), con una población total de 2.112 niños. Los progenitores completaron el cuestionario LACVA5, que incluía el instrumento CHIP-CE/PRF para medir CVRS en cinco dimensiones (Satisfacción Global, Bienestar Global, Resiliencia, Prevención de riesgos y Logros) y doce subdimensiones (como Autoestima, Bienestar físico, Rendimiento académico, entre otras). También se utilizó la escala ADHD-RS-IV.es para evaluar sintomatología de TDAH y se recogieron datos sobre lactancia materna, características sociodemográficas, antecedentes familiares y exposición al humo del tabaco.
Resultados
La tasa de respuesta fue del 58,4% (n=1234), con una distribución equilibrada entre niños y niñas. La participación fue mayor en Jumilla(74%) que en Yecla(48%). Se observaron diferencias estadísticamente significativas entre localidades en las dimensiones Satisfacción Global (mejor en Jumilla) y Bienestar Global (mejor en Yecla). En cuatro de las doce subdimensiones también hubo diferencias: Jumilla destacó en Autoestima y Prevención del riesgo individual, mientras que Yecla lo hizo en Bienestar físico y Restricción de la actividad.
Respecto a la sintomatología de TDAH, se identificaron 34 casos de TDAH inatento(2,8%), 34 de TDAH hiperactivo-impulsivo(2,8%) y 35 de TDAH combinado(2,9%), siendo más frecuentes en Jumilla. La exposición a lactancia materna de cualquier tipo fue del 82,9%, a lactancia exclusiva del 47% (duración media de 3,2 meses) y a lactancia materna posparto de al menos 6 meses del 41,8%. El 80,3% de las madres estuvieron expuestas a lactancia artificial y el 75% la recibió más de 12 meses. El 93,3% de las madres tenía expectativas prenatales de amamantar y el 86,5% mantenía la lactancia al alta hospitalaria. El 47,6% cumplió o superó el tiempo previsto de lactancia.
Se encontró una relación significativa entre haber recibido lactancia materna de cualquier tipo y mejores resultados en la dimensión Logros (OR ajustada 1,599; IC95%: 1,131-2,261;p=0,008). No se observó asociación entre lactancia exclusiva y CVRS. También se confirmó la asociación entre lactancia materna de al menos 6 meses y mejores resultados en Logros (OR ajustada 1,398; IC95%:1,058-1,848; p=0,019) y en Rendimiento académico (OR ajustada 1,619; IC95%:1,185-2,212; p=0,002).
No se halló relación entre lactancia materna y la presencia de sintomatología de TDAH global, inatento o hiperactivo-impulsivo.
Conclusiones
Este estudio, uno de los pocos que analiza la relación entre lactancia materna y CVRS usando instrumentos validados, confirma que la exposición a lactancia materna de cualquier tipo y mantenida al menos 6 meses se asocia a mejores resultados en salud en la dimensión Logros y en el Rendimiento académico. No se encontró asociación entre lactancia y sintomatología de TDAH o sus subtiposIntroduction
Breastfeeding is a physiological process whhose short-, medium-, and long-term benefits in childhood continue to be investigated. These findings reinforce the importance of initiating and maintaining breastfeeding for as long as possible, both for mothers and health care professionals, although there are challenges related to lifestyle and work-life balance. However, studies analyzing the association between breastfeeding and healthrelated quality of life (HRQoL) in school-aged children are still lacking.
Objectives
The main objective was to analyze whether having received any type of breastfeeding, exclusive breastfeeding, or breastfeeding for at least 6 months from birth is associated with better scores on the dimensions and subdimensions of HRQoL, as well as a lower risk of presenting symptoms compatible with a diagnosis of ADHD or its subtypes.
Methodology
A retrospective cohort study was conducted with 2,112 children in the third year of Early Childhood Education and First and Second years of Primary Education in Jumilla and Yecla (Health Area V). Parents completed the LACVA5 questionnaire, which included the CHIP-CE/PRF instrument to measure HRQoL in five dimensions (Global Satisfaction, Global Well-being, Resilience, Risk Revention, an Achievement) and twelve subdimensions (such as Self-Esteem, Physical Well-being, Academic Performance, among others). The ADHD-RS-IV.es scale was also used to assess ADHD symptons, and data were collected on breastfeeding, sociodemographic characteristics, family history, and tobacco smoke exposure.
Results
The response rate was 58.4% (n=1234), with a balanced distribution between boys and girls. Participation was higher in Jumilla (74%) than in Yecla (48%). Statistically significant differences were observed between localities in the dimensions of Global Satisfaction (best in Jumilla) and Global Well-being (best in Yecla). Differences also occurred in four of the twelve subdimensions: Jumilla excelled in Self-Esteem and Individual Risk Prevention, while Yecla excelled in Physical Well-being and Activity Restriction.
Regarding ADHD symptoms, 34 cases of Inattentive ADHD (2.8%), 34 of Hyperactive-Impulsive ADHD (2.8%), and 35 of Combined ADHD (2.9%) were identified, with the latter being more frequent in Jumilla. Exposure to any type of breastfeeding was 82.9% to exclusive breastfeeding 47% (average duration of 3.2 months), and to postpartum breastfeeding of al least 6 months 41.8%. 80.3% of mothers were exposed to bottle feeding, and 75% received it for more than 12 months. Ninety-three point three percent of mothers had prenatal expectations of breastfeeding, and 86.5% were breastfeeding at hospital discharge. 47.6% met or exceeded their expected breastfeeding duration.
A significant relationship was found between haing received any type of breastfeeding and better outcomes in the Achievement dimension (adjusted OR 1.599;95% CI: 1.131-2.261; p=0,008). No association was observed between exclusive breastfeeding and HRQoL. An association was also confirmed between breastfeeding for at least 6 months and better outcomes in Achievement (adjusted OR 1.398; 95% CI: 1.058-1.848; p=0,019) and Academic Performance (adjusted OR 1.619;95% CI: 1.185-2.212;p=0,002).
No relationship was found between breastfeeding and the presence of ADHD symptonms overall, inattentive, or hyperactive-impulsive.
Conclusions
This study, one of the few to analyze the relationshio between breastfeeding and HRQoL using validated instruments, confirms that exposure to breastfeeding of any type and maintained for at least 6 months is associated with better health outcomes in the Achievement and Academic Performance dimensions. No association was found between breastfeeding and ADHD symptoms or its subtypes
Brazilin attenuates kidney ischemia- reperfusion injury by regulating inflammation, oxidative stress, and mitochondrial dysfunction
No full textBrazilin, a natural homoisoflavonoid, is the
primary bioactive ingredient derived from the bark and
heartwood of Caesalpinia sappan L. It has been proven
to exhibit multiple biological activities and therapeutic
potential in chronic degenerative diseases, fibrotic
disorders, inflammatory diseases, and cancers. However,
whether it is involved in regulating the pathological
process of acute kidney injury (AKI) is not fully
understood. This study aimed to elucidate the role and
key pharmacological molecular mechanisms of brazilin
in AKI. Our data demonstrated that pretreatment with
brazilin can significantly reduce the high expression of
serum creatinine (Scr), blood urea nitrogen (BUN), and
lipocalin-2 (LCN2) in mice exposed to ischemia/
reperfusion (I/R) and alleviate kidney histopathological
damage. Meanwhile, pretreatment with brazilin can
alleviate apoptosis, inflammation, and oxidative stress
injury in the kidney tissue cells by partially inhibiting
the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B
(NF-κB)/NOD-like receptor family pyrin domain
containing 3 (NLRP3) inflammatory pathway or
activating the nuclear factor erythroid 2-related factor 2
(Nrf2)/heme oxygenase‐1 (HO-1) antioxidant pathway.
In vitro, pretreatment with brazilin significantly
downregulated pro-apoptotic Bax and upregulated anti
apoptotic Bcl-2 expression in human renal proximal
tubular cells (HK-2) subjected to oxygen-glucose
deprivation/reoxygenation (OGD/R). Besides, it
ameliorated mitochondrial dysfunction by enhancing
mitochondrial biogenesis and restoring mitochondrial membrane potential. These effects collectively
suppressed oxidative stress injury and NLRP3
inflammasome signaling pathway activation. In
summary, brazilin exhibits significant protective effects
against I/R-induced AKI by attenuating inflammation,
oxidative stress and cell apoptosis, and mitochondrial
damage. These findings suggest that brazilin holds
promise as a potential therapeutic agent for AKI
The evolution of mast cells across all vertebrate classes: The mystery continues
No full textThe paper examines what the mast cell, a cell that arose in urochordates and reached humans with the same morphological profile, is used for. Activated mast cells contribute to the regulation of the local immune response and major inflammation and healing processes with the help of a broad range of mediators. Located primarily at the interface between the host and the external environment, mast cells are widely distributed. The local microenvironment directly affects mast cell development, phenotype, and function, which in turn affects the cells' capacity to identify and react to different stimuli by releasing a variety of physiologically active mediators. By interacting with a range of other cells involved in physiological and immunological responses, mast cells can react to changes in their surroundings and serve as first responders in dangerous situations. Consequently, the mast cell’s crucial function in innate and adaptive immunity, including immuno-logical tolerance, has come to light more frequently. On the other hand, mast cell malfunction has identified these cells as the primary culprits in a number of autoimmune illnesses, cancer, and chronic allergic/inflammatory conditions
HMMR inhibition by 4-methylumbelliferone is effective in preclinical hepatocellular carcinoma models
No full textThe poor prognosis of hepatocellular carcinoma (HCC), especially in advanced stages, underscores the need for new therapeutic strategies. In this study, we show that hyaluronan-mediated motility receptor (HMMR) is highly expressed in HCC tumors compared with normal liver tissues. Knockdown of HMMR using siRNA significantly reduced cell proliferation and migration in both parental and doxorubicin-resistant HCC cell lines without inducing apoptosis. Similarly, treatment with 4-Methyl-umbelliferone (4-MU), a pharmacological HMMR inhibitor, led to dose-dependent decreases in proliferation and migration in vitro. In vivo, 4-MU treatment significantly inhibited tumor growth in a HepG2 xenograft model, resulting in a 44% reduction in tumor volume by day 20 and an 80% decrease in HMMR expression in tumor tissues. These results demonstrate that HMMR promotes growth and migration in HCC, and targeting HMMR effectively inhibits both parental and drug-resistant HCC cells. Additionally, our findings suggest that 4-MU, an approved drug for biliary tract disorders, holds promise as a repurposed therapeutic candidate for HCC treatment
José Luis Bellón Aguilera. Animismo y literatura. Una investigación histórica (de Platón al tecno-animismo). Berlín: De Gruyter, 2025, 227 pp. [Reseña bibliográfica]
No full textEs reseña del libro Animismo y literatura. Una investigación histórica (de Platón al tecno-animismo)/ José Luís Bellón Aguilera. Berlín: De Gruyter, 202
Bureaucratic malaise, violence, and adaptation within the neoliberal university
No full textThis article aims to highlight some of the effects of bureaucratic transfor-mations within academia, particularly on academic subjectivity. To this end, it analyses the ways in which administrative innovations have not only al-tered academic institutions butalso the behaviours, attitudes, expectations, and self-perception of individuals connected to academic life in one way or another. Bureaucratic malaise is described as one of these effects, and the ar-ticle examines how these changes respond to a logic of exploitation of bodies, disciplined through a repertoire of practices that, like software applications, require active participation. Rather than providing a description of the cur-rent state of university bureaucracy, this work offers a reflection on the bu-reaucratic nature of universities today –its significance for the definition of the academic profession, its modes of productivity and violence, its multiple ambivalences, and the forms of adaptation it generates. Among these, bu-reaucratism deserves special attention.Este artículo tiene como objetivo señalar algunos de los efectos de las trans-formaciones de la burocracia en el mundo académico y, más en particular, sobre la subjetividad académica. Para ello, se analizan los modos en que las innovaciones de índole administrativa han alterado no sólo sus instituciones, sino también los comportamientos y actitudes como las expectativas y auto-comprensión de las personas de un modo u otro vinculadas a la vida académi-ca. Se describe el malestar burocrático como uno de estos efectos y se exami-na la inserción de estos cambios en una lógica de explotación de los cuerpos a los que se disciplina mediante un repertorio de prácticas que, como en el caso de las aplicaciones, demandan la propia participación de quienes las sufren. Antesque una descripción de la burocracia universitaria actual, se trata más bien de una reflexión sobre lo burocrático de lo universitario hoy, su signifi-cado para la definición de la profesión académica, sus modos de productivi-dad y violencia, sus múltiples ambivalencias y las formas de adaptación que genera. Entre éstas, se concede especial atención al burocratismo