Obesity-Altered Adipose Stem Cells Promote Radiation Resistance of Estrogen Receptor Positive Breast Cancer through Paracrine Signaling.

Obesity is associated with poorer responses to chemo- and radiation therapy for breast cancer, which leads to higher mortality rates for obese women who develop breast cancer. Adipose stem cells (ASCs) are an integral stromal component of the tumor microenvironment (TME). In this study, the effects of obesity-altered ASCs (obASCs) on estrogen receptor positive breast cancer cell's (ER+BCCs) response to radiotherapy (RT) were evaluated. We determined that BCCs had a decreased apoptotic index and increased surviving fraction following RT when co-cultured with obASCs compared to lnASCs or non-co-cultured cells. Further, obASCs reduced oxidative stress and induced IL-6 expression in co-cultured BCCs after radiation. obASCs produce increased levels of leptin relative to ASCs from normal-weight individuals (lnASCs). obASCs upregulate the expression of IL-6 compared to non-co-cultured BCCs, but BCCs co-cultured with leptin knockdown obASCs did not upregulate IL-6. The impact of shLeptin obASCs on radiation resistance of ER+BCCs demonstrate a decreased radioprotective ability compared to shControl obASCs. Key NOTCH signaling players were enhanced in ER+BBCs following co-culture with shCtrl obASCs but not shLep obASCs. This work demonstrates that obesity-altered ASCs, via enhanced secretion of leptin, promote IL-6 and NOTCH signaling pathways in ER+BCCs leading to radiation resistance.

Sequential Imaging of a Rapidly Progressive Rheumatoid Vasculitis: A Unique Depiction.

Rheumatoid vasculitis is a clinically heterogenous complication of rheumatoid arthritis (RA), primarily affecting small- and medium-sized vessels.1 A 63-year-old man with long-standing seropositive erosive RA presented to our emergency department with abdominal pain and diarrhea.

Schwannoma quístico incidental del seno esfenoidal y cavernoso izquierdo en una mujer asintomática / Incidental cystic schwannoma of the left sphenoid and cavernous sinuses in an asymptomatic woman

CASO CLÍNICO: Mujer de 63 años, con antecedentes personales de hipertensión y sinusitis reciente, quien se presentó en el centro por un episodio de síncope. No describió presión o dolor de los senos paranasales o frontales, cambios en la visión, cefalea o pérdida de peso. La exploración física y la neurológica fueron normales, sin déficit evidente de los pares craneales. La tomografía computarizada de cráneo (Figura, a y b) descubrió incidentalmente un defecto óseo de dimensiones 3,8 × 3,6 × 2,4 cm causado por una masa expansiva con epicentro aparente en el hueso esfenoidal izquierdo, con remodelación adyacente del seno esfenoidal, el clivus, el ala mayor del hueso esfenoidal y la punta del hueso petroso izquierdo. No hubo evidencia obvia de extensión hacia el cerebro. La resonancia magnética de cabeza con y sin contraste (Figura c-f) demostró una masa parcialmente quística, expansiva, compleja, de dimensiones 4,8 × 3,4 × 2,1 cm, que surgía del seno esfenoidal/cavernoso lateral con extensión al aspecto medial de la fosa craneal izquierda medial, el espacio masticador y el seno cavernoso. La masa mostraba un realce heterogéneo en las imágenes con contraste. No se apreció un componente hemorrágico en la secuencia eco de gradiente. Se realizó una biopsia con la aparente impresión macroscópica de un gran mucocele, con resultados patológicos que demostraron atipia nuclear. La inmunohistoquímica reveló células fusiformes positivas para S-100 y vimentina. El informe final de patología concluyó que la ma­sa esfenoidal izquierda era un schwannoma. La paciente se sometió a cirugía sinusal endoscópica guiada por imagen para la reducción de la masa. Se concluyó que el episodio de síncope inicial era secundario a un reflejo vasovagal no relacionado con la masa en cuestión

CASE REPORT: A 63-year-old woman with a past medical history of hypertension and recent sinus infection presented to our institution due to an episode of syncope. She reported no sinus pressure or pain, changes in vision, headache, or weight loss. Physical and neurological examinations were both normal, including no cranial nerve deficits. As part of her workup she underwent a computed tomography scan of the head (Figure, a, b), which incidentally discovered a large 3.8 × 3.6 × 2.4 cm bone defect by an expansile mass with apparent epicenter in the left sphenoid sinus with adjacent remodeling of the sphenoid sinus, clivus, greater wing of the sphenoid bone, and tip of the left petrous bone. There was no obvious evidence of brain extension. Brain magnetic resonance imaging with and without contrast (Figure, c-f) demonstrated a 4.8 × 3.4 × 2.1 cm expansile, complex, partially cystic mass apparently arising from the lateral sphenoid/cavernous sinus with extension to the medial aspect of the left middle cranial fossa, masticator space, and cavernous sinus. The mass demonstrated hetero­genous enhancement on contrast images. No hemorrhagic component was seen on gradient-recalled echo. A biopsy was performed with the impression of a large mucocele, with frozen pathology showing nuclear atypia. Immunohistochemistry showed spindle cells that were positive for S-100 and vimentin. Final pathology report stated the left sphenoid mass was a schwannoma. Our patient underwent endoscopic sinus surgery with image guidance for debulking of her mass. Her original syncope was ultimately deemed to be of vasovagal etiology

Adaptation to climate change: trade-offs among responses to multiple stressors in an intertidal crustacean.

Trade-offs may influence both physiological and evolutionary responses to co-occurring stressors, but their effects on both plastic and adaptive responses to climate change are poorly understood. To test for genetic and physiological trade-offs incurred in tolerating multiple stressors, we hybridized two populations of the intertidal copepod Tigriopus californicus that were divergent for both heat and salinity tolerance. Starting in the F2 generation, we selected for increased tolerance of heat, low salinity, and high salinity in replicate lines. After five generations of selection, heat-selected lines had greater heat tolerance but lower fecundity, indicating an energetic cost to tolerance. Lines selected for increased salinity tolerance did not show evidence of adaptation to their respective environments; however, hypo-osmotic selection lines showed substantial loss of tolerance to hyperosmotic stress. Neither of the salinity selection regimes resulted in diminished heat tolerance at ambient salinity; however, simultaneous exposure to heat and hypo-osmotic stress led to decreased heat tolerance, implying a physiological trade-off in tolerance to the two stressors. When we quantified the transcriptomic response to heat and salinity stress via RNA sequencing, we observed little overlap in the stress responses, suggesting the observed synergistic effects of heat and salinity stress were driven by competing energetic demands, rather than shared stress response pathways.