LATS1 controls CTCF chromatin occupancy and hormonal response of 3D-grown breast cancer cells.

The cancer epigenome has been studied in cells cultured in two-dimensional (2D) monolayers, but recent studies highlight the impact of the extracellular matrix and the three-dimensional (3D) environment on multiple cellular functions. Here, we report the physical, biochemical, and genomic differences between T47D breast cancer cells cultured in 2D and as 3D spheroids. Cells within 3D spheroids exhibit a rounder nucleus with less accessible, more compacted chromatin, as well as altered expression of ~2000 genes, the majority of which become repressed. Hi-C analysis reveals that cells in 3D are enriched for regions belonging to the B compartment, have decreased chromatin-bound CTCF and increased fusion of topologically associating domains (TADs). Upregulation of the Hippo pathway in 3D spheroids results in the activation of the LATS1 kinase, which promotes phosphorylation and displacement of CTCF from DNA, thereby likely causing the observed TAD fusions. 3D cells show higher chromatin binding of progesterone receptor (PR), leading to an increase in the number of hormone-regulated genes. This effect is in part mediated by LATS1 activation, which favors cytoplasmic retention of YAP and CTCF removal.

Impact of preexisting autoimmune disease on myelodysplastic syndromes outcomes: a population analysis.

Preexisting autoimmune disease affects between 10% and 30% of patients with myelodysplastic syndromes (MDS). Studies comparing outcomes in patients with MDS with and without autoimmune disease show discordant results. Using the Surveillance, Epidemiology, and End Results Medicare database, we conducted a population analysis to define the impact of autoimmunity on MDS outcomes. Cases were ascertained between 2007 and 2017 and claim algorithms used to identify autoimmune disease, demographic characteristics, comorbidity scores, MDS histology, transfusion burden, treatment with hypomethylating agents, and hematopoietic stem cell transplantation. Cox regression models estimated the impact on survival, and competing-risk regression models defined the effect on leukemic transformation. We analyzed 15 277 patients with MDS, including 2442 (16%) with preexisting autoimmune disease. The epidemiologic profile was distinctive in cases with preexisting autoimmunity, who were younger, were predominantly female, and had higher transfusion burden without difference in MDS histologic distribution. Autoimmune disease was associated with 11% decreased risk of death (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.85-0.94; P < .001). The effect on risk of leukemic transformation differed based on MDS histology. In low-risk MDS histologies, autoimmunity was associated with a 1.9-fold increased risk of leukemia (HR, 1.87; 95% CI, 1.17-2.99; P = .008), whereas no significant effect was seen in other groups. These results suggest that autoimmune disease affects survival in MDS and is associated with decreased mortality. The survival effect was evident in low-risk histologies despite higher risk of progression to leukemia. This could represent inflammation-driven hematopoiesis, simultaneously favoring less aggressive phenotypes and clonal expansion, which warrants further investigation.

Expression and localization of vascular endothelial growth factor and its receptors in the pig uterus during peri-implantation and determination of the in vitro effect of the angiogenesis inhibitor SU5416 on VEGF system expression.

The aim of this work was to determine endometrial mRNA expression and uterine protein localization of vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2 during the estrous cycle and peri-implantation period in sows. Uterine tissues were collected from pregnant sows on days 12, 14, 16, and 18 after artificial insemination and from non-pregnant animals on days 2 and 12 of the estrous cycle (day 0 = day of estrus). Using immunohistochemistry, a positive signal for VEGF and its receptor VEGFR2 was found in uterine luminal epithelial cells, endometrial glands, stroma, blood vessels, and myometrium. A VEGFR1 signal was only found in endometrial and myometrial blood vessels and stroma. By day 18 of gestation, the mRNA expression levels of VEGF, VEGFR1, and VEGFR2 were higher than those observed on days 2 and 12 of the estrous cycle and on days 12, 14, and 16 of gestation. Then, a primary culture of sow endometrial epithelial cells was established to define the potential of the selective inhibition of VEGFR2 after treatment with inhibitor SU5416 and determine its effects on the expression pattern of the VEGF system. The endometrial epithelial cells treated with SU5416 showed a dose-dependent decrease in VEGFR1 and VEGFR2 mRNA expression. The present study provides additional evidence on the importance of the VEGF system during peri-implantation, as well as on the specific inhibitory activity of SU5416 in epithelial cells, which, as demonstrated, express the protein and mRNA of VEGF and its receptors VEGFR1 and VEGFR2.

The anti-immune dengue subgenomic flaviviral RNA is present in vesicles in mosquito saliva and is associated with increased infectivity.

Mosquito transmission of dengue viruses to humans starts with infection of skin resident cells at the biting site. There is great interest in identifying transmission-enhancing factors in mosquito saliva in order to counteract them. Here we report the discovery of high levels of the anti-immune subgenomic flaviviral RNA (sfRNA) in dengue virus 2-infected mosquito saliva. We established that sfRNA is present in saliva using three different methods: northern blot, RT-qPCR and RNA sequencing. We next show that salivary sfRNA is protected in detergent-sensitive compartments, likely extracellular vesicles. In support of this hypothesis, we visualized viral RNAs in vesicles in mosquito saliva and noted a marked enrichment of signal from 3'UTR sequences, which is consistent with the presence of sfRNA. Furthermore, we show that incubation with mosquito saliva containing higher sfRNA levels results in higher virus infectivity in a human hepatoma cell line and human primary dermal fibroblasts. Transfection of 3'UTR RNA prior to DENV2 infection inhibited type I and III interferon induction and signaling, and enhanced viral replication. Therefore, we posit that sfRNA present in salivary extracellular vesicles is delivered to cells at the biting site to inhibit innate immunity and enhance dengue virus transmission.

Microwave-enhanced synthesis of 26-amino-22-oxocholestanes and their cytotoxic activity.

The synthesis of a series of 26-amino-22-oxocholestanes derived from diosgenin was accomplished via the substitution of an iodine atom at C-26 by primary and secondary amines. The reactions were conducted in refluxing acetonitrile and through microwave-assisted heating. The latter shows significant improvements in terms of reaction times going from hours to a few minutes or even seconds for completion. Only one of the selected amines, 4-aminourazole, did not yield the substitution product and the imine formation pathway was investigated instead, achieving the 26-iminourazole-22-oxocholestane. All the final products have been characterized and the cytotoxic activity of three of them has been evaluated in SiHa, MCF-7 and MDA tumor cell lines by the sulforhodamine B assay.

Cytotoxic and antiproliferative activity of thiazole derivatives of Ochraceolide A.

A series of 15 novel 1,3-thiazole amide derivatives of the pentacyclic triterpene Ochraceolide A (1) was synthesized, characterized, and evaluated in vitro against three human cancer cell lines (MCF-7, MDA-MB-231 and SiHa) and a normal cell line (Vero). Synthetic derivatives were obtained by acylation of the 2-aminothiazole triterpene 2, previously reported. Remarkably, the 5-nitrofuramide derivative (2o) showed better cytotoxic and antiproliferative activity than compound 2 and the other derivatives against the three cancer cell lines with CC50 and IC50 values of 1.6-12.7 µM. Furthermore, butyramide derivative (2c) was approximately 25 times more selective than 2, as well as 3.4 times more selective than Docetaxel, against SiHa cells in the cytotoxic assay, while the phenyl amide derivatives were inactive against the three cancer cell lines.

The origin of the regiospecificity of acrolein dimerization.

Acrolein dimerization is a intriguing case since the reaction does not occur to form the electronically preferred regioisomeric adduct. Various explanations have been suggested to rationalize this experimental regioselectivity, however, none of these arguments had been convincing enough. In this work, the hetero Diels-Alder acrolein dimerization was theoretically investigated using DFT and MP2 methods. The influence of nucleophilic/electrophilic interactions and non-covalent interactions (NCI) in the regiospecificity of the reaction were analyzed. Our results show that the NCI at the transition state are the key factor controlling the regiospecificity in this reaction. Besides, we found that the choice of calculation method can have an effect on the prediction of the mechanism in the reaction, as all DFT methods forecast a one-step hetero Diels-Alder acrolein dimerization, while MP2 predicts a stepwise description for the lower energy reaction channel.

Increased Association between Previous Pregnancies and Use of Chemical Relaxers in 74 Women with Central Centrifugal Cicatricial Alopecia.

BACKGROUND: Central centrifugal cicatricial alopecia (CCCA) is a type of scarring alopecia exclusively seen in women of African descent. The etiology is unknown and epidemiologic studies including data on comorbidities in patients with CCCA are limited. Our primary objective was to identify possible etiologic and lifestyle associations in patients with CCCA. MATERIALS AND METHODS: A retrospective chart review was conducted for patients diagnosed with CCCA between January 1, 2013, and January 1, 2018, at a university dermatology outpatient clinic. Controls consisted of age-, sex-, and race-matched African-American women diagnosed with other hair loss conditions. Data from 74 cases and 96 controls were collected and analyzed via logistic regression. In addition, a phone survey was conducted in the CCCA cohort asking specific questions related to their condition and quality of life. RESULTS: A significant relationship was found between CCCA and previous pregnancies as well as the use of chemical relaxers: patients with CCCA were 11.71 times more likely to have had a previous pregnancy (P < 0.001) and 12.37 times more likely to have used chemical relaxers in the past (P < 0.001). Association with uterine fibroids was found not statistically significant (P > 0.05). CONCLUSION: We identified an association between previous pregnancies and use of chemical relaxers in patients diagnosed with CCCA when compared to controls. These findings may help to plan prospective studies aiming at establishing a more concrete link between hormones and CCCA.

Capsaicin in the Treatment of Refractory Neuropathic Pain after Mastectomy Surgery: A Case Report.

A 62-year-old female patient with a history of mastectomy surgery and sentinel lymphadenectomy in the context of breast cancer therapy was referred to our clinic for the treatment of refractory neuropathic pain. She reported a complex set of symptoms including burning and electrical-like sensations as well as profound hyperesthesia, hyperalgesia, and allodynia. The symptoms persisted chronically over months with a strong intensity and did not sufficiently respond to oral pain medication and co-analgetics, that is, tapentadol and pregabalin. As the patient could hardly move her right upper arm due to the pain, the quality of life was greatly reduced. In addition, the patient reported pain-related anxiety and depression. Therefore, a therapy with capsaicin 8% patch was initiated. Treatment with capsaicin 8% led to pain relief without tolerance development and improved flexibility in the affected body area. Despite significant pain relief, previous oral pain medications (tapentadol, pregabalin) as well as the anti-depressant amitriptyline were maintained to fully resolve pain symptoms, anxiety, and depression. In conclusion, capsaicin 8% may represent an effective therapeutic alternative for patients suffering from refractory neuropathic pain.

4D Genome Rewiring during Oncogene-Induced and Replicative Senescence.

To understand the role of the extensive senescence-associated 3D genome reorganization, we generated genome-wide chromatin interaction maps, epigenome, replication-timing, whole-genome bisulfite sequencing, and gene expression profiles from cells entering replicative senescence (RS) or upon oncogene-induced senescence (OIS). We identify senescence-associated heterochromatin domains (SAHDs). Differential intra- versus inter-SAHD interactions lead to the formation of senescence-associated heterochromatin foci (SAHFs) in OIS but not in RS. This OIS-specific configuration brings active genes located in genomic regions adjacent to SAHDs in close spatial proximity and favors their expression. We also identify DNMT1 as a factor that induces SAHFs by promoting HMGA2 expression. Upon DNMT1 depletion, OIS cells transition to a 3D genome conformation akin to that of cells in replicative senescence. These data show how multi-omics and imaging can identify critical features of RS and OIS and discover determinants of acute senescence and SAHF formation.

The Skin Cancer Index: quality-of-life outcomes of treatments for nonmelanoma skin cancer.

Introduction: Non-melanoma skin cancers (NMSCs) are the most common malignancies in humans. When treating NMSC, quality-of-life (QOL) is an important consideration. The purpose of this study was to measure and compare QOL outcomes of two common therapies for NMSC: Mohs micrographic surgery and excision, using a disease-specific QOL instrument, the Skin Cancer Index (SCI).Methods: The University of Miami Institutional Review Board approved this retrospective chart review of patients diagnosed with NMSC from 2016 through 2019 at a private dermatology clinic (Deerfield Beach, FL, USA). Disease-specific QOL before and after surgery was measured with the SCI.Results: Pre- and post-surgery surveys were completed by 208 patients undergoing Mohs surgery and 30 patients undergoing excisional surgery. All patients were similar in age, gender, and race, and most patients undergoing either procedure had a history of additional prior skin cancers. For the Mohs cohort, the total SCI scores and each of the subscales were significantly higher post-surgery when compared with the baseline scores. In contrast, in the excision cohort, the social subscale was significantly lower post-surgery when compared with the baseline scores.Conclusion: There is limited data in the literature describing the specific effects of Mohs or excision for NMSC on QOL using a disease-specific QOL instrument. Our data supports increased QOL at 2-week follow up for patients with NMSC treated with Mohs, but no improvement in QOL was noted for patients treated with excision. This data is limited by the fact there were far more patients that underwent Mohs as opposed to excision, which gave the Mohs cohort greater statistical power when analyzing the difference in SCI.

Síndrome de la espalda inclinada: Presentación de cuatro casos y revisión de la bibliografía / Bent spine syndrome. Presentation of four cases and literature review

El síndrome de la espalda inclinada o camptocormia es una causa de desequilibrio sagital del tronco no estructurada de difícil manejo médico y quirúrgico. Puede ser secundario a enfermedades del sistema nervioso central o periférico, o de origen primario muscular, como la atrofia aislada de la musculatura paravertebral espinal. El diagnóstico se basa en la evaluación clínica, los estudios por imágenes, la electromiografía y la biopsia muscular. El síndrome de la espalda inclinada, cualquiera fuera su causa, tiene un pronóstico pobre, los síntomas suelen progresar hasta afectar la bipedestación de manera irreversible. Presentamos un análisis retrospectivo de cuatro casos de síndrome de la espalda inclinada tratados en nuestro centro y una revisión de la bibliografía. Nivel de Evidencia: IV

Objectives: Bent spine syndrome (BSS) or camptocormia is a cause of unstructured sagittal imbalance of difficult medical and surgical management. The purpose of this paper is to describe the causes of BSS and how to approach its treatment. Materials and Methods: Retrospective analysis of 4 cases of BSS treated at our center and review of the literature. Results: The 4 patients were women between 60 and 82 years of age. In 3 of them, BSS was due to an isolated atrophy of the paravertebral erector spinae muscles, and in 1 of them, it was due to an inflammatory myopathy. Conclusions: The prognosis of BSS is poor in all cases, so symptoms usually progress to an irreversible difficulty to stand upright. Level of Evidence: IV

Coffee pulp supplementation prior to breeding improves oxidative status without affecting fertility of primiparous ewes / La suplementación con pulpa de café antes de la monta mejora el estado oxidativo sin afectar la fertilidad de ovejas primiparas / A suplementação de polpa de café antes da reprodução melhora o estado oxidativo sem afetar a fertilidade de ovelhas primíparas

Abstract Background: Coffee pulp has a high content of antioxidants capable of modifying the oxidative status in small ruminants. However, high amounts for a prolonged time can reduce fertility. Objective: To determine the effect of two inclusion levels of coffee pulp during estrous synchronization on reproductive variables and oxidative status of primiparous ewes. Methods: Sixty Suffolk x Dorset primiparous ewes were distributed into three treatments in a completely randomized design; T0: (n=20) 1.5 kg balanced diet, T1: (n=20) 1.5 kg balanced diet and 5% coffee pulp, T2: (n=20) 1.5 kg balanced diet and 10% coffee pulp. Supplementation was given for 16 days before estrus synchronization and until the beginning of the breeding season. A progestogen (CIDR®) was inserted for 11 days and a dose of PGF2α was applied two days prior to its withdrawal. Estrus detection started 12 hours after CIDR withdrawal. Blood samples were obtained during the supplementation period to measure oxidative status, antioxidant capacity, glucose and insulin, and up to 9 days after breeding to determine progesterone concentration. Pregnancy diagnosis was performed at 30 and 60 days post-breeding. An analysis of repeated measures of mixed effects and frequency analysis were carried out. Results: Inclusion of coffee pulp for a short period prior to breeding did not affect reproductive parameters, nor progesterone, glucose or insulin concentrations (p>0.05); however, antioxidant capacity increased, while lipid oxidation showed an opposite trend (p<0.05). Conclusion: Inclusion of up to 10% coffee pulp in the diet of ewe lambs for 16 days prior to breeding improves oxidative status without causing adverse effects on pregnancy, estrus or prolificacy.

Resumen Antecedentes: La pulpa de café tiene un alto contenido de antioxidantes capaces de modificar el estado oxidativo en pequeños rumiantes. Sin embargo, a dosis elevadas y por un tiempo prolongado puede reducir la fertilidad. Objetivo: Determinar el efecto de dos niveles de inclusión de pulpa de café durante la sincronización del estro en variables reproductivas y el estado oxidativo de ovejas primerizas. Métodos: Se utilizaron 60 ovejas primalas Suffolk x Dorset fueron distribuidas en tres tratamientos en un diseño completamente al azar; T0: (n=20) con 1,5 kg de dieta integral, T1: (n=20) con 1,5 kg de dieta integral y 5% de pulpa de café, T2: (n=20) con 1,5 kg de dieta integral y 10% de pulpa de café. La suplementación se realizó por 16 días, previo a la sincronización del estro y hasta el empadre. El progestágeno (CIDR®) se insertó en las ovejas por 11 días y se aplicó una dosis de PGF2α dos días antes de su retiro. La detección de estro comenzó a las 12 horas post-retiro del CIDR®. Se obtuvieron muestras sanguíneas durante el periodo de suplementación para medir estado oxidativo, capacidad antioxidante, glucosa e insulina, y hasta 9 días posteriores al empadre para determinar las concentraciones de progesterona. El diagnóstico de gestación se realizó a los 30 y 60 días post-monta. Se realizaron análisis de medidas repetidas utilizando un modelo de efectos mixtos, además de análisis de frecuencias. Resultados: La inclusión de pulpa por un periodo corto previo al empadre no afectó los parámetros reproductivos ni las concentraciones de progesterona, glucosa o insulina (p>0,05); sin embargo, la capacidad antioxidante se incrementó, mientras que la oxidación lipídica siguió una tendencia inversa (p<0,05). Conclusión: La inclusión hasta de 10% de pulpa de café en la dieta de ovejas por 16 días previo al empadre mejora el estado oxidativo sin ocasionar efectos adversos en el porcentaje de preñez, estro o prolificidad.

Resumo Antecedentes: A polpa de café tem alto conteúdo de antioxidantes capazes de modificar o estado oxidativo em pequenos ruminantes; no entanto, em doses elevadas e por um tempo prolongado reduz a fertilidade. Objetivo: Determinar o efeito de diferentes níveis de inclusão de polpa de café durante a sincronização do estro em diferentes variáveis reprodutivas e estado oxidativo das ovelhas primíparas. Métodos: Sessenta ovelhas primíparas dos cruzamentos Suffolk x Dorset foram distribuídas em três tratamentos em um design completamente aleatório; T0: (n=20) com 1,5 kg de dieta completa, T1: (n=20) com 1,5 kg de dieta completa contendo 5% de polpa de café, T2: (n=20) com 1,5 kg de dieta completa contendo 10% de polpa de café. A suplementação realizou-se por 16 dias, antes do início da sincronização de estros e até o momento do acasalamento. O progestogênio (CIDR) foi inserido nas ovelhas durante 11 dias e uma dose de PGF2α foi aplicada dois dias antes da sua retirada. Doze horas após a retirada do CIDR iniciou-se a detecção de estros. Foram obtidas amostras de sangue durante o período de suplementação, para medição do estado oxidativo, capacidade antioxidante, glicose e insulina e até 9 dias posteriores ao início da estação de monta para determinar as concentrações de progesterona. O diagnostico de gestação realizou-se aos 30 e 60 dias post-monta. Uma análise de medidas repetidas de efeitos mistos e análise de freqüência foi realizada. Resultados: A inclusão de polpa por um período curto antes da estação de monta não afetou os parâmetros reprodutivos nem as concentrações de progesterona, glicose e insulina (p>0,05); porém, a capacidade antioxidante nas ovelhas foi aumentada, enquanto a oxidação lipídica seguiu uma tendência inversa (p<0,05). Conclusão: Inclusão de polpa de café na dieta de ovelha até 10% durante 16 dias antes do acasalamento melhora o estado oxidativo, sem causar efeitos adversos na porcentagem de gravidez, estro e prolificidade.

Skin changes in the obese patient.

Obesity is a worldwide major public health problem with an alarmingly increasing prevalence over the past 2 decades. The consequences of obesity in the skin are underestimated. In this paper, we review the effect of obesity on the skin, including how increased body mass index affects skin physiology, skin barrier, collagen structure, and wound healing. Obesity also affects sebaceous and sweat glands and causes circulatory and lymphatic changes. Common skin manifestations related to obesity include acanthosis nigricans, acrochordons, keratosis pilaris, striae distensae, cellulite, and plantar hyperkeratosis. Obesity has metabolic effects, such as causing hyperandrogenism and gout, which in turn are associated with cutaneous manifestations. Furthermore, obesity is associated with an increased incidence of bacterial and Candida skin infections, as well as onychomycosis, inflammatory skin diseases, and chronic dermatoses like hidradenitis suppurativa, psoriasis, and rosacea. The association between atopic dermatitis and obesity and the increased risk of skin cancer among obese patients is debatable. Obesity is also related to rare skin conditions and to premature hair graying. As physicians, understanding these clinical signs and the underlying systemic disorders will facilitate earlier diagnoses for better treatment and avoidance of sequelae.

Crystal structure and Hirshfeld surface analysis of N-(5-iodo-4-phenyl-thia-zol-2-yl)acetamide.

Two crystallographically independent mol-ecules (A and B) are present in the asymmetric unit of the title compound, C11H9IN2OS, which differ mainly in the dihedral angle between the phenyl and thia-zole rings [38.94 (16) and 32.12 (15)°, respectively]. In the crystal, the mol-ecules form ⋯A⋯B⋯A⋯B⋯ chains along the [001] and [010] directions through moderate N-H⋯O hydrogen bonds and C-H⋯π inter-actions, respectively. The overall three-dimensional network is formed by I⋯I and I⋯S inter-actions. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H⋯C/C⋯H (26.2%), H⋯H (20.9%), H⋯I/I⋯H (19.4%) and H⋯O/O⋯H (6.8%) inter-actions.

Computational de-orphanization of the olive oil biophenol oleacein: Discovery of new metabolic and epigenetic targets.

The health promoting effects of extra virgin olive oil (EVOO) relate to its unique repertoire of phenolic compounds. Here, we used a chemoinformatics approach to computationally identify endogenous ligands and assign putative biomolecular targets to oleacein, one of the most abundant secoiridoids in EVOO. Using a structure-based virtual profiling software tool and reference databases containing more than 9000 binding sites protein cavities, we identified 996 putative oleacein targets involving more than 700 proteins. We subsequently identified the high-level functions of oleacein in terms of biomolecular interactions, signaling pathways, and protein-protein interaction (PPI) networks. Delineation of the oleacein target landscape revealed that the most significant modules affected by oleacein were associated with metabolic processes (e.g., glucose and lipid metabolism) and chromatin-modifying enzymatic activities (i.e., histone post-translational modifications). We experimentally confirmed that, in a low-micromolar physiological range (<20 µmol/l), oleacein was capable of inhibiting the catalytic activities of predicted metabolic and epigenetic targets including nicotinamide N-methyltransferase, ATP-citrate lyase, lysine-specific demethylase 6A, and N-methyltransferase 4. Our computational de-orphanization of oleacein provides new mechanisms through which EVOO biophenols might operate as chemical prototypes capable of modulating the biologic machinery of healthy aging.

New Chondrosarcoma Cell Lines with Preserved Stem Cell Properties to Study the Genomic Drift During In Vitro/In Vivo Growth.

For the cancer genomics era, there is a need for clinically annotated close-to-patient cell lines suitable to investigate altered pathways and serve as high-throughput drug-screening platforms. This is particularly important for drug-resistant tumors like chondrosarcoma which has few models available. Here we established and characterized new cell lines derived from two secondary (CDS06 and CDS11) and one dedifferentiated (CDS-17) chondrosarcomas as well as another line derived from a CDS-17-generated xenograft (T-CDS17). These lines displayed cancer stem cell-related and invasive features and were able to initiate subcutaneous and/or orthotopic animal models. Different mutations in Isocitrate Dehydrogenase-1 (IDH1), Isocitrate Dehydrogenase-2 (IDH2), and Tumor Supressor P53 (TP53) and deletion of Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) were detected both in cell lines and tumor samples. In addition, other mutations in TP53 and the amplification of Mouse Double Minute 2 homolog (MDM2) arose during cell culture in CDS17 cells. Whole exome sequencing analysis of CDS17, T-CDS17, and matched patient samples confirmed that cell lines kept the most relevant mutations of the tumor, uncovered new mutations and revealed structural variants that emerged during in vitro/in vivo growth. Altogether, this work expanded the panel of clinically and genetically-annotated chondrosarcoma lines amenable for in vivo studies and cancer stem cell (CSC) characterization. Moreover, it provided clues of the genetic drift of chondrosarcoma cells during the adaptation to grow conditions.

Adipose Infiltration of the Dermis, Involving the Arrector Pili Muscle, and Dermal Displacement of Eccrine Sweat Coils: New Histologic Observations in Frontal Fibrosing Alopecia.

BACKGROUND: Frontal fibrosing alopecia (FFA) is an irreversible scarring alopecia, and its incidence has reached epidemic size. Immune privilege collapse of the bulge and epithelial mesenchymal transition play a role in the pathogenesis. We have noted adipose tissue in the dermis in several specimens from FFA. OBJECTIVE: Our primary objective was to verify the presence of adipose tissue at the isthmus level in biopsies from FFA. Additional objectives included the presence of deep inflammation and position of the sweat coils. METHODS: Eighty-three histologic specimens of FFA diagnosed at the Dermatopathology Laboratory at the Department of Dermatology, University of Miami, within 3 years were evaluated retrospectively. All biopsies were bisected horizontally and assessed at several levels. Sixty biopsies from androgenetic alopecia served as controls. Statistical analysis was performed using the χ test. A P value of 0.05 or less was considered significant. RESULTS: Sixty specimens met the inclusion criteria for optimal quality and classic diagnostic features. Seventy percent demonstrated fat tissue infiltration at the isthmus level as clusters of cells or small globules versus 23% of the controls. The fat infiltration in the arrector pili muscle (APM) was present in 55% versus 15% of the controls, and the sweat coils were positioned in the reticular dermis in 43% versus 1.7% of the controls. All results were statistically significant (P < 0.0001). When accounting for the simultaneous presence of any of these 3 variables, 30% of the FFA cases had triple positivity, 61.7% had double positivity, and 75% had at least 1 positive variable versus 0%, 15%, and 10%, respectively, of the controls. CONCLUSION: New histologic findings in FFA involve the presence of adipose tissue in the dermis. We believe that the close interaction of the hair follicles and the APM with the adipose tissue may play a role in APM degeneration and in epithelial mesenchymal transition.

Chemical peels in the treatment of acne: patient selection and perspectives.

Acne vulgaris is the most common skin disorder in adolescents and young adults. It carries a significant psychological and economic burden to patients and society. A wide range of therapeutic options are available, including topicals and systemic therapies. Chemical peeling is a skin resurfacing procedure intended to regenerate normal skin from the application of exfoliative agents. It has been used for the treatment of acne vulgaris and other skin disorders for decades. There are several chemical agents with variable mechanisms of action, usually classified as superficial, medium, and deep peels. When selecting the patient and the appropriate peel, the dermatologist individualizes therapy, and performs an extensive interview, including past medical history and physical exam. Several host factors can affect the outcome of this procedure, including current psychological state, medications, history of surgery, and immune system, among others. The physician must also be confident that the peel is safe and effective for the target patient. The Fitzpatrick skin type scale is a useful tool to classify patients based on skin color and ability to tan, but also can be used to evaluate preoperative risk of postpeel response and complications. Dark-skinned patients (Fitzpatrick skin type IV-VI), including blacks, Asian, and Hispanic/Latino, are at higher risk of postinflammatory/postpeel hyperpigmentation. When treating these populations, deep chemical peels should be avoided, and preoperative preparation emphasized. There are many studies available in the literature supporting the use of superficial to medium depth peels as adjuvant therapy for acne vulgaris. This review article aims to present the most important factors when selecting a patient for a chemical peel, the evidence behind its safety and efficacy, and special considerations when choosing a specific agent.