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1.
J Palliat Med ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008413

RESUMEN

Many seriously ill patients undergo surgical interventions. Palliative care clinicians may not be familiar with the nuances involved in perioperative care, however they can play a valuable role in enabling the delivery of patient-centered and goal-concordant perioperative care. The interval of time surrounding a surgical intervention is fraught with medical, psychosocial, and relational risks, many of which palliative care clinicians may be well-positioned to navigate. A perioperative palliative care consult may involve exploring gaps between clinician and patient expectations, facilitating continuity of symptom management or helping patients to designate a surrogate decision-maker before undergoing anesthesia. Palliative care clinicians may also be called upon to direct discussions around perioperative management of modified code status orders and to engage around the goal-concordance of proposed interventions. This article, written by a team of surgeons and anesthesiologists, many with subspecialty training in palliative medicine and/or ethics, offers ten tips to support palliative care clinicians and facilitate comprehensive discussion as they engage with patients and clinicians considering surgical interventions.

2.
Am J Hosp Palliat Care ; : 10499091241259034, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38830349

RESUMEN

BACKGROUND: Patients with cancer-related pain are at high risk for aberrant drug use behaviors (ADB), including self-escalation, diversion and concurrent illicit substance or opioid misuse; however, limited evidence is available to guide opioid prescribing for patients with life-limiting illness and concurrent or suspected ADB. We sought to characterize how specialists evaluate for and manage these high-risk behaviors in patients with cancer-related pain. METHODS: We conducted telephonic semi-structured interviews with palliative care and pain medicine providers. Participants discussed their own comfort and experience level with identifying and managing ADB in patients with life-limiting illness. They were subsequently presented with a series of standardized scenarios and asked to describe their concerns and management strategies. RESULTS: 95 interdisciplinary pain and palliative care specialists were contacted; 37 agreed to participate (38.9%). Analysis of interview contents revealed several central themes: (1) widespread discomfort and anxiety regarding safe and compassionate opioid prescribing for high-risk patients, (2) belief that widely used risk-mitigation tools such as opioid contracts and urine drug screens provided inadequate support for decision-making, and (3) lack of institutional and organizational support and guidance for safe prescribing strategies. Most clinicians reported self-education regarding addiction and alternative prescribing/pain management strategies. Providers varied widely in their willingness to discontinue opioid prescribing in a patient with aberrant behavior and pain associated with life-limiting illness. CONCLUSION: Providers caring for patients demonstrating ADB and cancer-related pain struggle to balance safe prescribing with symptom management. Increased guidance is needed regarding opioid prescribing, monitoring, and discontinuation in high-risk patients.

4.
Environ Manage ; 72(1): 135-146, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-34341866

RESUMEN

Globally, Indigenous Knowledge Systems (IKSs), which have evolved through rigorously tested methods and practices, are a testimony of human intelligence and endurance. The diversity of goods such as food, beverages, herbs, etc., and its associated systems, which form an integral part of modern cuisine and healthcare systems, are deeply rooted in IKS and immensely contributing to overall well-being of mankind. The present study is an attempt to document and understand the contribution of indigenous and local knowledge to biodiversity conservation and management. Appreciation to the value of traditional and indigenous knowledge is globally recognized for their principles of coexistence and sustainable use practices. Past studies indicate a strong relationship between indigenous knowledge and sustainable development goals. This knowledge is valuable not only to dependent communities, but also to the modern world for ensuring food security and human well-being. The documentation of such valuable knowledge is therefore fundamentally essential for mainstreaming and strengthening the discourses on sustainable ecosystem management, and to address the preponderance of poverty among indigenous communities. Amid the changing scenario of consumption and the trend of revisiting nature-based solutions, the IKS hold a tremendous scope of engaging the community people in sustainable harvest and utilization of natural resources.


Asunto(s)
Biodiversidad , Ecosistema , Humanos , Pobreza , Conocimiento , Conservación de los Recursos Naturales
5.
Bioinformation ; 18(3): 170-179, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36518123

RESUMEN

It is of interest to document the Molecular Dynamics Simulation and docking analysis of NF-κB target with sulindac sodium in combating COVID-19 for further consideration. Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) of the arylalkanoic acid class that is marketed by Merck under the brand name Clinoril. We show the binding features of sulindac sodium with NF-κB that can be useful in drug repurposing in COVID-19 therapy.

6.
J Med Econ ; 25(1): 755-761, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35611840

RESUMEN

AIM: Gaucher disease (GD) is a rare autosomal recessive condition. Type 1 GD (GD1) is the most prevalent form of GD in Western countries; enzyme replacement therapy (ERT) is a treatment option for patients with GD1. To understand the economic value of the GD1 ERT velaglucerase alfa, a budget impact model (BIM) was developed from a United States (US) payer perspective. METHODS: We estimated the budget impact of velaglucerase alfa for a 10-million-member US health plan by comparing the annual total costs of therapy between a scenario using current velaglucerase alfa uptake to a projected scenario with increased velaglucerase alfa uptake. Total drug costs for both scenarios were estimated as the sum of the product of the number of eligible patients on each treatment and the annual per-patient cost of each medication. Average per-patient costs for ERTs were calculated by adding the yearly drug acquisition, drug administration, and site-of-care markup costs. The budget impact was measured over years 1-3. RESULTS: An estimated 65 patients would receive velaglucerase alfa treatment in year 1, increasing to 90 patients by year 3. Across analyses, cost savings were realized with velaglucerase alfa compared with imiglucerase ($115,909) and taliglucerase alfa ($80,401). An annual total budget savings of $8.67 million could be realized for a hypothetical 10-million-member US health plan with increased velaglucerase alfa uptake. The per-member per-month costs decreased by $0.0241 across years 1-3. CONCLUSIONS: BIM results show that increased velaglucerase alfa uptake for GD1 treatment is cost-saving for US health plans.


Type 1 Gaucher disease (GD1) is a rare inherited condition. Long-term enzyme replacement therapy (ERT) can reverse and prevent complications. Imiglucerase, taliglucerase alfa, and velaglucerase alfa are 3 ERTs used to treat GD1. In this study, we estimated how increasing uptake of velaglucerase alfa vs. the other ERTs would impact the budget of a hypothetical US healthcare plan. The results show that increased uptake of velaglucerase alfa is cost-saving for US health plans.


Asunto(s)
Enfermedad de Gaucher , Presupuestos , Ahorro de Costo , Costos de los Medicamentos , Terapia de Reemplazo Enzimático/métodos , Enfermedad de Gaucher/tratamiento farmacológico , Humanos , Estados Unidos
7.
Mol Genet Metab ; 136(1): 4-21, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35367141

RESUMEN

Gaucher disease (GD) is an autosomal recessive inherited lysosomal storage disease that often presents in early childhood and is associated with damage to multiple organ systems. Many challenges associated with GD diagnosis and management arise from the considerable heterogeneity of disease presentations and natural history. Phenotypic classification has traditionally been based on the absence (in type 1 GD) or presence (in types 2 and 3 GD) of neurological involvement of varying severity. However, patient management and prediction of prognosis may be best served by a dynamic, evolving definition of individual phenotype rather than by a rigid system of classification. Patients may experience considerable delays in diagnosis, which can potentially be reduced by effective screening programs; however, program implementation can involve ethical and practical challenges. Variation in the clinical course of GD and an uncertain prognosis also complicate decisions concerning treatment initiation, with differing stakeholder perspectives around efficacy and acceptable cost/benefit ratio. We review the challenges faced by physicians in the diagnosis and management of GD in pediatric patients. We also consider future directions and goals, including acceleration of accurate diagnosis, improvements in the understanding of disease heterogeneity (natural history, response to treatment, and prognosis), the need for new treatments to address unmet needs for all forms of GD, and refinement of the tools for monitoring disease progression and treatment efficacy, such as specific biomarkers.


Asunto(s)
Enfermedad de Gaucher , Biomarcadores , Niño , Preescolar , Progresión de la Enfermedad , Enfermedad de Gaucher/diagnóstico , Enfermedad de Gaucher/genética , Enfermedad de Gaucher/terapia , Humanos , Lisosomas , Fenotipo
8.
Environ Chall (Amst) ; 7: 100497, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37519306

RESUMEN

More than just a health crisis, COVID-19 pandemic has stressed across social, economical and emotional dimensions of human well being and health. The sudden enforcement although willful and honest, perpetuated a sense of insecurity and uncertainty as a result of livelihood loss, especially for the people employed in unorganized and private sectors across different urban centers of the country. The unexpected scenario not only caused widespread joblessness but also created varied conditions of psychological stresses foreseeing the less likelihood of returning of pre-COVID conditions. As an outcome of the pandemic, the involuntarily return of youth was seen as a boon for reversing the undesirable and unprecedented trends impacting the traditional rural dynamics. Present study is an attempt to highlights impacts, challenges and opportunities under and after COVID-19 on rural populace of Kailash Sacred Landscape (KSL) amid the sudden halt of remittances and jobless aspiring youth. A systematic approach was followed, where 16 villages in eight Blocks of KSL were assessed and migrants (n=815) were interviewed for compiling the information. Results revealed that COVID-19 has impacted (both positively and negatively) various sectors such as agriculture, tourism, overall family income, etc., as perceived by the respondents. Sectors like restaurants/shops, tourism, and agriculture emerged as potential cash generating avenues, with 30 %, 21 %, and 20 % respondent's perception, respectively. It is also revealed that in the absence of immediate alternatives, and policy intervention, villagers engaged themselves in the time tested traditional sectors of livelihoods or created their own niche by integrating traditional wisdom and acquired skills.

9.
Heliyon ; 8(12): e12570, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36643309

RESUMEN

Background: Non-metastatic muscle invasive urothelial bladder cancer (MIBC) has a poor prognosis and standard of care (SOC) includes neoadjuvant cisplatin-based chemotherapy (NAC) combined with cystectomy. Patients receiving NAC have at best <10% improvement in five-year overall survival compared to cystectomy alone. This major clinical problem underscores gaps in our understanding of resistance mechanisms and a need for reliable pre-clinical models. The chicken embryo chorioallantoic membrane (CAM) represents a rapid, scalable, and cost-effective alternative to immunocompromised mice for establishing patient-derived xenografts (PDX) in vivo. CAM-PDX leverages an easily accessible engraftment scaffold and vascular-rich, immunosuppressed environment for the engraftment of PDX tumors and subsequent functional studies. Methods: We optimized engraftment conditions for primary MIBC tumors using the CAM-PDX model and tested concordance between cisplatin-based chemotherapy response of patients to matching PDX tumors using tumor growth coupled with immunohistochemistry markers of proliferation and apoptosis. We also tested select kinase inhibitor response on chemotherapy-resistant bladder cancers on the CAM-PDX using tumor growth measurements and immuno-detection of proliferation marker, Ki-67. Results: Our results show primary, NAC-resistant, MIBC tumors grown on the CAM share histological characteristics along with cisplatin-based chemotherapy resistance observed in the clinic for matched parent human tumor specimens. Patient tumor specimens acquired after chemotherapy treatment (post-NAC) and exhibiting NAC resistance were engrafted successfully on the CAM and displayed decreased tumor growth size and proliferation in response to treatment with a dual EGFR and HER2 inhibitor, but had no significant response to either CDK4/6 or FGFR inhibition. Conclusions: Our data suggests concordance between cisplatin-based chemotherapy resistance phenotypes in primary patient tumors and CAM-PDX models. Further, proteogenomic informed kinase inhibitor use on MIBC CAM-PDX models suggests a benefit from integration of rapid in vivo testing of novel therapeutics to inform more complex, pre-clinical mouse PDX experiments for more effective clinical trial design aimed at achieving optimal precision medicine for patients with limited treatment options.

10.
Sci Rep ; 11(1): 2323, 2021 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-33504880

RESUMEN

G-proteins are implicated in plant productivity, but their genome-wide roles in regulating agronomically important traits remain uncharacterized. Transcriptomic analyses of rice G-protein alpha subunit mutant (rga1) revealed 2270 differentially expressed genes (DEGs) including those involved in C/N and lipid metabolism, cell wall, hormones and stress. Many DEGs were associated with root, leaf, culm, inflorescence, panicle, grain yield and heading date. The mutant performed better in total weight of filled grains, ratio of filled to unfilled grains and tillers per plant. Protein-protein interaction (PPI) network analysis using experimentally validated interactors revealed many RGA1-responsive genes involved in tiller development. qPCR validated the differential expression of genes involved in strigolactone-mediated tiller formation and grain development. Further, the mutant growth and biomass were unaffected by submergence indicating its role in submergence response. Transcription factor network analysis revealed the importance of RGA1 in nitrogen signaling with DEGs such as Nin-like, WRKY, NAC, bHLH families, nitrite reductase, glutamine synthetase, OsCIPK23 and urea transporter. Sub-clustering of DEGs-associated PPI network revealed that RGA1 regulates metabolism, stress and gene regulation among others. Predicted rice G-protein networks mapped DEGs and revealed potential effectors. Thus, this study expands the roles of RGA1 to agronomically important traits and reveals their underlying processes.


Asunto(s)
Oryza/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Unión al GTP/genética , Proteínas de Unión al GTP/metabolismo , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica de las Plantas/genética , Regulación de la Expresión Génica de las Plantas/fisiología , Glutamato-Amoníaco Ligasa/genética , Glutamato-Amoníaco Ligasa/metabolismo , Metabolismo de los Lípidos/genética , Metabolismo de los Lípidos/fisiología , Nitrito Reductasas/genética , Nitrito Reductasas/metabolismo , Nitrógeno/metabolismo , Oryza/genética , Proteínas de Plantas/genética , Análisis de Secuencia de ARN/métodos , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
11.
Laryngoscope ; 131(3): 610-617, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-32603507

RESUMEN

OBJECTIVES/HYPOTHESIS: Characterization of the localized adaptive immune response in the airway scar of patients with idiopathic subglottic stenosis (iSGS). STUDY DESIGN: Basic Science. METHODS: Utilizing 36 patients with subglottic stenosis (25 idiopathic subglottic stenosis [iSGS], 10 iatrogenic post-intubation stenosis [iLTS], and one granulomatosis with polyangiitis [GPA]) we applied immunohistochemical and immunologic techniques coupled with RNA sequencing. RESULTS: iSGS, iLTS, and GPA demonstrate a significant immune infiltrate in the subglottic scar consisting of adaptive cell subsets (T cells along with dendritic cells). Interrogation of T cell subtypes showed significantly more CD69+ CD103+ CD8+ tissue resident memory T cells (TRM ) in the iSGS airway scar than iLTS specimens (iSGS vs. iLTS; 50% vs. 28%, P = .0065). Additionally, subglottic CD8+ clones possessed T-cell receptor (TCR) sequences with known antigen specificity for viral and intracellular pathogens. CONCLUSIONS: The human subglottis is significantly enriched for CD8+ tissue resident memory T cells in iSGS, which possess TCR sequences proven to recognize viral and intracellular pathogens. These results inform our understanding of iSGS, provide a direction for future discovery, and demonstrate immunologic function in the human proximal airway. Laryngoscope, 131:610-617, 2021.


Asunto(s)
Obstrucción de las Vías Aéreas/inmunología , Cicatriz/inmunología , Memoria Inmunológica/inmunología , Laringoestenosis/inmunología , Subgrupos de Linfocitos T/inmunología , Adulto , Anciano , Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos T/inmunología , Antígenos CD8/inmunología , Constricción Patológica , Femenino , Glotis/inmunología , Glotis/patología , Humanos , Inmunohistoquímica , Cadenas alfa de Integrinas/inmunología , Lectinas Tipo C/inmunología , Masculino , Persona de Mediana Edad
12.
Sci Rep ; 10(1): 12228, 2020 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-32699267

RESUMEN

Nitrate (N) response is modulated by light, but not understood from a genome-wide perspective. Comparative transcriptomic analyses of nitrate response in light-grown and etiolated rice leaves revealed 303 and 249 differentially expressed genes (DEGs) respectively. A majority of them were exclusive to light (270) or dark (216) condition, whereas 33 DEGs were common. The latter may constitute response to N signaling regardless of light. Functional annotation and pathway enrichment analyses of the DEGs showed that nitrate primarily modulates conserved N signaling and metabolism in light, whereas oxidation-reduction processes, pentose-phosphate shunt, starch-, sucrose- and glycerolipid-metabolisms in the dark. Differential N-regulation of these pathways by light could be attributed to the involvement of distinctive sets of transporters, transcription factors, enriched cis-acting motifs in the promoters of DEGs as well as differential modulation of N-responsive transcriptional regulatory networks in light and dark. Sub-clustering of DEGs-associated protein-protein interaction network constructed using experimentally validated interactors revealed that nitrate regulates a molecular complex consisting of nitrite reductase, ferredoxin-NADP reductase and ferredoxin. This complex is associated with flowering time, revealing a meeting point for N-regulation of N-response and N-use efficiency. Together, our results provide novel insights into distinct pathways of N-signaling in light and dark conditions.


Asunto(s)
Nitratos/metabolismo , Oryza/genética , Oryza/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Transcriptoma/genética , Oscuridad , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica de las Plantas/genética , Redes Reguladoras de Genes/genética , Luz , Oxidación-Reducción , Proteínas de Plantas/genética , Transducción de Señal/genética
13.
Oncoimmunology ; 7(10): e1490853, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30288358

RESUMEN

Cancer-induced myeloid-derived suppressor cells (MDSC) play an important role in tumor immune evasion. MDSC programming or polarization has been proposed as a strategy for leveraging the developmental plasticity of myeloid cells to reverse MDSC immune suppressive functions, or cause them to acquire anti-tumor activity. While MDSC derived ex vivo from murine bone marrow precursor cells with tumor-conditioned medium efficiently suppressed T cell proliferation, MDSC derived from conditioned medium in presence of TGF-ß1 (TGFß-MDSC) acquired a novel immune-stimulatory phenotype, losing the ability to inhibit T cell proliferation and acquiring enhanced antigen-presenting capability. Altered immune function was associated with SMAD-2 dependent upregulation of maturation and costimulatory molecules, and downregulation of inducible nitric oxide synthase (iNOS), an effector mechanism of immunosuppression. TGFß-MDSC also upregulated FAS-ligand expression, leading to FAS-dependent killing of murine human papillomavirus (HPV)-associated head and neck cancer cells and tumor spheroids in vitro and anti-tumor activity in vivo. Radiation upregulated FAS expression on tumor cells, and the combination of radiotherapy and intratumoral injection of TGFß-MDSC strongly enhanced class I expression on tumor cells and induction of HPV E7 tetramer-positive CD8 + T cells, leading to clearance of established tumors and long-term survival. TGFß-MDSC derived from human PBMC with tumor conditioned medium also lost immunosuppressive function and acquired tumor-killing activity. Thus, TGFß1 mediated programming of nascent MDSC leads to a potent anti-tumor phenotype potentially suitable for adoptive immunotherapy.

14.
J Environ Sci (China) ; 73: 69-77, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30290873

RESUMEN

Particle density is an important physical property of atmospheric particles. The information on high time-resolution size-resolved particle density is essential for understanding the atmospheric physical and chemical aging processes of aerosols particles. In the present study, a centrifugal particle mass analyzer (CPMA) combined with a differential mobility analyzer (DMA) was deployed to determine the size-resolved effective density of 50 to 350nm particles at a rural site of Beijing during summer 2016. The measured particle effective densities decreased with increasing particle sizes and ranged from 1.43 to 1.55g/cm3, on average. The effective particle density distributions were dominated by a mode peaked at around 1.5g/cm3 for 50 to 350nm particles. Extra modes with peaks at 1.0, 0.8, and 0.6g/cm3 for 150, 240, and 350nm particles, which might be freshly emitted soot particles, were observed during intensive primary emissions episodes. The particle effective densities showed a diurnal variation pattern, with higher values during daytime. A case study showed that the effective density of Aitken mode particles during the new particle formation (NPF) event decreased considerably, indicating the significant contribution of organics to new particle growth.


Asunto(s)
Contaminantes Atmosféricos/análisis , Atmósfera/química , Monitoreo del Ambiente , Material Particulado/análisis , Aerosoles/análisis , Beijing
15.
Am J Cancer Res ; 8(8): 1642-1660, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30210932

RESUMEN

Patient-derived xenografts (PDX) are an increasingly valuable tool in oncology, providing biologically faithful models of many different cancer types, and potential platforms for the development of precision oncology approaches. However, PDX have primarily been established in immunodeficient rodent models, with accompanying cost and efficiency constraints that pose barriers to more widespread adoption. The chicken egg chorioallantoic membrane (CAM) is an alternative in vivo PDX model. We provide here a comprehensive review of studies that grafted primary human tissue, as opposed to cell lines, onto the CAM. Twenty publications met our criteria of having inoculated patient-derived tumor tissue onto the CAM. Successful engraftment has been reported for over a dozen tumor subtypes, supporting the appropriateness of the CAM as a PDX platform. Resemblance of xenografts to the original patient tumor, increased vascularity of the CAM following engraftment, and micrometastasis into the chick mesenchyme were frequently reported. Application of standard or experimental cancer therapies to xenografts has also been undertaken, with the discovery of both synergistic drug effects and positive associations between the assay and clinical outcome. The CAM provides opportunities for RNA and DNA based sequencing of patient tumors, and the ability to efficiently (in 5-10 days) test multiple targeted therapies on fragments derived from the same tumor. While routine use of the CAM-based PDX model would benefit from a more-complete understanding of the stromal environment of CAM xenografts and interaction with the developing avian immune system, current literature supports the model's potential as an efficient, scalable precision medicine platform.

16.
Sci Rep ; 8(1): 11799, 2018 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-30087388

RESUMEN

Fabrication of heterojunction between 2D molybdenum disulfide (MoS2) and gallium nitride (GaN) and its photodetection properties have been reported in the present work. Surface potential mapping at the MoS2/GaN heterojunction is done using Kelvin Probe Force Microscopy to measure the conduction band offset. Current-voltage measurements show a diode like behavior of the heterojunction. The origin of diode like behavior is attributed to unique type II band alignment of the heterojunction. The photocurrent, photoresponsivity and detectivity of the heterojunction are found to be dependent on power density of the light. Photoresponse investigations reveal that the heterojunction is highly sensitive to 405 nm laser with very high responsivity up to 105 A/W. The heterojunction also shows very high detectivity of the order of 1014 Jones. Moreover, the device shows photoresponse in UV region also. These observations suggest that MoS2/GaN heterojunction can have great potential for photodetection applications.

17.
Biomaterials ; 177: 125-138, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29886385

RESUMEN

Autologous cell transplantation holds enormous promise to restore organ and tissue functions in the treatment of various pathologies including endocrine, cardiovascular, and neurological diseases among others. Even though immune rejection is circumvented with autologous transplantation, clinical adoption remains limited due to poor cell retention and survival. Cell transplant success requires homing to vascularized environment, cell engraftment and importantly, maintenance of inherent cell function. To address this need, we developed a three dimensional (3D) printed cell encapsulation device created with polylactic acid (PLA), termed neovascularized implantable cell homing and encapsulation (NICHE). In this paper, we present the development and systematic evaluation of the NICHE in vitro, and the in vivo validation with encapsulated testosterone-secreting Leydig cells in Rag1-/- castrated mice. Enhanced subcutaneous vascularization of NICHE via platelet-rich plasma (PRP) hydrogel coating and filling was demonstrated in vivo via a chorioallantoic membrane (CAM) assay as well as in mice. After establishment of a pre-vascularized bed within the NICHE, transcutaneously transplanted Leydig cells, maintained viability and robust testosterone secretion for the duration of the study. Immunohistochemical analysis revealed extensive Leydig cell colonization in the NICHE. Furthermore, transplanted cells achieved physiologic testosterone levels in castrated mice. The promising results provide a proof of concept for the NICHE as a viable platform technology for autologous cell transplantation for the treatment of a variety of diseases.


Asunto(s)
Materiales Biocompatibles/química , Células Intersticiales del Testículo/trasplante , Poliésteres/química , Andamios del Tejido/química , Animales , Supervivencia Celular , Células Cultivadas , Células Inmovilizadas/citología , Células Inmovilizadas/trasplante , Células Endoteliales de la Vena Umbilical Humana , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Islotes Pancreáticos/citología , Células Intersticiales del Testículo/citología , Masculino , Ratones , Neovascularización Fisiológica , Impresión Tridimensional , Ingeniería de Tejidos
18.
Am J Pathol ; 188(1): 72-83, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29107073

RESUMEN

Tumor immune microenvironment and tumor metabolism are major determinants of chemoradiotherapy response. The interdependency and prognostic significance of specific immune and metabolic phenotypes in head and neck squamous cell carcinoma (HNSCC) were assessed and changes in reactive oxygen species were evaluated as a mechanism of treatment response in tumor spheroid/immunocyte co-cultures. Pretreatment tumor biopsies were immunohistochemically characterized in 73 HNSCC patients treated by definitive chemoradiotherapy and correlated with survival. The prognostic significance of CD8A, GLUT1, and COX5B gene expression was analyzed within The Cancer Genome Atlas database. HNSCC spheroids were co-cultured in vitro with peripheral blood mononuclear cells (PBMCs) in the presence of the glycolysis inhibitor 2-deoxyglucose and radiation treatment followed by PBMC chemotaxis determination via fluorescence microscopy. In the chemoradiotherapy-treated HNSCC cohort, mitochondrial-rich (COX5B) metabolism correlated with increased and glucose-dependent (GLUT1) metabolism with decreased intratumoral CD8/CD4 ratios. High CD8/CD4, together with mitochondrial-rich or glucose-independent metabolism, was associated with improved short-term survival. The Cancer Genome Atlas analysis confirmed that patients with a favorable immune and metabolic gene signature (high CD8A, high COX5B, low GLUT1) had improved short- and long-term survival. In vitro, 2-deoxyglucose and radiation synergistically up-regulated reactive oxygen species-dependent PBMC chemotaxis to HNSCC spheroids. These results suggest that glucose-independent tumor metabolism is associated with CD8-dominant antitumor immune infiltrate, and together, these contribute to improved chemoradiotherapy response in HNSCC.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Neoplasias de Cabeza y Cuello/terapia , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Antígenos CD8/genética , Antígenos CD8/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidad , Línea Celular Tumoral , Grupo Citocromo c/genética , Grupo Citocromo c/metabolismo , Bases de Datos Genéticas , Complejo IV de Transporte de Electrones , Femenino , Transportador de Glucosa de Tipo 1/genética , Transportador de Glucosa de Tipo 1/metabolismo , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Especies Reactivas de Oxígeno/metabolismo , Tasa de Supervivencia
19.
Cancer Res ; 77(21): 5977-5988, 2017 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-28916657

RESUMEN

Deposition of the extracellular matrix protein tenascin-C is part of the reactive stroma response, which has a critical role in prostate cancer progression. Here, we report that tenascin C is expressed in the bone endosteum and is associated with formation of prostate bone metastases. Metastatic cells cultured on osteo-mimetic surfaces coated with tenascin C exhibited enhanced adhesion and colony formation as mediated by integrin α9ß1. In addition, metastatic cells preferentially migrated and colonized tenascin-C-coated trabecular bone xenografts in a novel system that employed chorioallantoic membranes of fertilized chicken eggs as host. Overall, our studies deepen knowledge about reactive stroma responses in the bone endosteum that accompany prostate cancer metastasis to trabecular bone, with potential implications to therapeutically target this process in patients. Cancer Res; 77(21); 5977-88. ©2017 AACR.


Asunto(s)
Huesos/metabolismo , Integrinas/metabolismo , Neoplasias de la Próstata/metabolismo , Tenascina/metabolismo , Animales , Neoplasias Óseas/metabolismo , Neoplasias Óseas/secundario , Huesos/patología , Adhesión Celular , Línea Celular Tumoral , Movimiento Celular , Embrión de Pollo , Membrana Corioalantoides/metabolismo , Integrinas/genética , Masculino , Organoides/metabolismo , Organoides/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Unión Proteica , Interferencia de ARN
20.
Data Brief ; 10: 315-324, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28004021

RESUMEN

We present data on the evolution of intrinsically disordered regions (IDRs) taking into account the entire human protein kinome. The evolutionary data of the IDRs with respect to the kinase domains (KDs) and kinases as a whole protein (WP) are reported. Further, we have reported its post translational modifications of FAK1 IDRs and their contribution to the cytoskeletal remodeling. We also report the data to build a protein-protein interaction (PPI) network of primary and secondary FAK1-interacting hybrid proteins. Detailed analysis of the data and its effect on FAK1-related functions have been described in "Structural pliability adjacent to the kinase domain highlights contribution of FAK1 IDRs to cytoskeletal remodeling" (Kathiriya et. al., 2016) [1].

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