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1.
Pharmaceutics ; 15(12)2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38140114

RESUMO

Mucin-1 (MUC1) is a highly relevant antigen for cancer vaccination due to its overexpression and hypo-glycosylation in a high percentage of carcinomas. To enhance the immune response to MUC1, our group has developed C3-liposomes that encapsulate the MUC1 antigen along with immunostimulatory compounds for direct delivery to antigen-presenting cells (APCs). C3-liposomes bind complement C3, which interacts with C3-receptors on APCs, resulting in liposomal uptake and the delivery of tumor antigens to APCs in a manner that mimics pathogenic uptake. In this study, MUC1 and Toll-like receptor (TLR) agonists were encapsulated in C3-liposomes to provoke an immune response in transgenic mice tolerant to MUC1. The immune response to the C3-bound MUC1 liposomal vaccine was assessed by ELISA, ELISpot, and flow cytometry. Co-administering TLR 7/8 agonists with MUC1 encapsulated in C3-liposomes resulted in a significant antibody response compared to non-encapsulated MUC1. This antibody response was significantly higher in females than in males. The co-encapsulation of three TLR agonists with MUC1 in C3-liposomes significantly increased antibody responses and eliminated sex-based differences. Furthermore, this immunization strategy resulted in a significantly increased T cell-response compared to other treatment groups. In conclusion, the co-delivery of MUC1 and TLR agonists via C3-liposomes greatly enhances the immune response to MUC1, highlighting its potential for antigen-specific cancer immunotherapy.

2.
Nat Commun ; 14(1): 6624, 2023 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-37857640

RESUMO

Little is currently known about how climate modulates the relationship between plant diversity and soil organic carbon and the mechanisms involved. Yet, this knowledge is of crucial importance in times of climate change and biodiversity loss. Here, we show that plant diversity is positively correlated with soil carbon content and soil carbon-to-nitrogen ratio across 84 grasslands on six continents that span wide climate gradients. The relationships between plant diversity and soil carbon as well as plant diversity and soil organic matter quality (carbon-to-nitrogen ratio) are particularly strong in warm and arid climates. While plant biomass is positively correlated with soil carbon, plant biomass is not significantly correlated with plant diversity. Our results indicate that plant diversity influences soil carbon storage not via the quantity of organic matter (plant biomass) inputs to soil, but through the quality of organic matter. The study implies that ecosystem management that restores plant diversity likely enhances soil carbon sequestration, particularly in warm and arid climates.


Assuntos
Ecossistema , Solo , Carbono , Biodiversidade , Biomassa , Plantas , Nitrogênio
3.
Cancer Gene Ther ; 28(9): 924-934, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33664460

RESUMO

Gastric cancer (GC) is an aggressive malignancy that is the third leading cause of cancer mortality worldwide. Localized GC can be cured with surgery, but most patients present with more advanced non-operable disease. Until recently, treatment options for relapsed and refractory advanced GC have been limited to combination chemotherapy regimens, HER-2 directed therapy, and radiation, which lead to few durable responses. Over the past decade, there have been significant advances in our understanding of the molecular and immune pathogenesis of GC. The infectious agents Epstein-Barr virus and Helicobacter pylori perturb the gastric mucosa immune equilibrium, which creates a microenvironment that favors GC tumorigenesis and evasion of immune surveillance. Insights into immune mechanisms of GC have translated into novel therapeutics, including immune checkpoint inhibitors, which have become a treatment option for select patients with GC. Furthermore, chimeric antigen receptor T-cell therapies have emerged as a breakthrough treatment for many cancers, with recent studies showing this to be a potential therapy for GC. In this review, we summarize the current state of knowledge on immune mechanisms of GC and the status of emerging immunotherapies to treat this aggressive cancer, as well as outline current challenges and directions for future research.


Assuntos
Imunoterapia/métodos , Neoplasias Gástricas/tratamento farmacológico , Humanos , Microambiente Tumoral
4.
J Drug Target ; 29(7): 754-760, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33472457

RESUMO

Activation of antigen presenting cells (APCs) is necessary for immune recognition and elimination of cancer. Our lab has developed a liposome nanoparticle that binds to complement C3 proteins present in serum. These C3-liposomes are specifically internalised by APCs and other myeloid cells, which express complement C3-binding receptors. Known immune stimulating compounds, toll-like receptor (TLR) agonists, were encapsulated within the C3-liposomes, including monophosphoryl lipid A (MPLA), R848, and CpG 1826, specific for TLR4, TLR7/8, and TLR9 respectively. When recognised by their respective TLRs within the myeloid cells, these compounds trigger signal cascades that ultimately lead to increased expression of inflammatory cytokines and activation markers (CD80, CD83, CD86 and CD40). RT-PCR analysis of murine bone marrow cells treated with C3-liposomes revealed a significant increase in gene expression of pro-inflammatory cytokines and factors (IL-1ß, IL-6, IL-12, TNF-α, IRF7, and IP-10). Furthermore, treatment of 4T1 tumour-bearing mice with C3-liposomes containing TLR agonists resulted in reduced tumour growth, compared to PBS treated mice. Collectively, these results demonstrate that C3-liposome delivery of TLR agonists activates APCs and induces tumour-specific adaptive immune responses, leading to reduced tumour growth in a breast cancer model.


Assuntos
Células Apresentadoras de Antígenos/imunologia , Neoplasias da Mama/tratamento farmacológico , Nanopartículas , Receptores Toll-Like/agonistas , Animais , Células da Medula Óssea/imunologia , Neoplasias da Mama/imunologia , Linhagem Celular Tumoral , Complemento C3/imunologia , Citocinas/imunologia , Feminino , Lipossomos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Receptores Toll-Like/imunologia
5.
J Econ Entomol ; 113(4): 2016-2021, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32435807

RESUMO

Since the initial detection of the invasive Halyomorpha halys (Stål) in the United States in the late 1990s, this insect has emerged as a severe agricultural and nuisance pest. Nuisance problems are due to adult dispersal to overwintering sites in the fall at which time they alight onto and eventually settle within human-made structures in addition to natural harborage. This study examined how three factors, elevation, light, and moisture affected overwintering site selection by H. halys in the mid-Atlantic. Observational counts performed along elevational transects revealed elevation was significant predictor of H. halys abundance during both years of the study in 2014 and 2015 with more adults observed at higher elevations. Choice tests examining effects of moisture and light on settling behavior demonstrated H. halys settled within overwintering shelter boxes in significantly greater numbers when shelters were dry compared with those having moist conditions, and in darkened shelters compared with those augmented with LED lights. Our findings indicate that H. halys use cues at both landscape and very localized levels when seeking and selecting overwintering sites.


Assuntos
Heterópteros , Animais , Habitação , Estações do Ano , Estados Unidos
6.
Cancers (Basel) ; 12(1)2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31941061

RESUMO

Gastric cancer is an aggressive and heterogeneous malignancy that often varies in presentation and disease among racial and ethnic groups. The Alaska Native (AN) people have the highest incidence and mortality rates of gastric cancer in North America. This study examines molecular markers in solid tumor samples from eighty-five AN gastric adenocarcinoma patients using next-generation sequencing, immunohistochemistry, and in situ hybridization analysis. AN patients have a low mutation burden with fewer somatic gene mutations in their tumors compared to other populations, with the most common mutation being TP53. Epstein-Barr virus (EBV) was associated with 20% of AN gastric cancers, which is higher than the world average of 10%. The inflammation marker, cyclooxygenase-2 (COX-2), is highly expressed in patients with the lowest survival rates. Mismatch repair deficiency was present in 10% of AN patients and was associated with patients who were female, 50 years or older, gene mutations, and tumors in the distal stomach. Program death-ligand 1 (PD-L1) was expressed in 14% of AN patients who were more likely to have MMR deficiency, EBV-associated gastric cancers, and mutations in the PIK3CA gene, all of which have been linked to clinical response to PD-1 inhibitors. These studies suggest a portion of AN gastric cancer patients could be candidates for immunotherapy. Overall, this study highlights future avenues of investigation for clinical and translational studies, so that we can improve early detection and develop more effective treatments for AN patients.

7.
Pharm Front ; 12019.
Artigo em Inglês | MEDLINE | ID: mdl-31886474

RESUMO

In the tumor microenvironment, cytokines, growth factors, and oncogenes mediate constitutive activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway in both cancer cells and infiltrating immune cells. STAT3 activation in cancer cells drives tumorigenic changes that allow for increased survival, proliferation, and resistance to apoptosis. The modulation of immune cells is more complicated and conflicting. STAT3 signaling drives the myeloid cell phenotype towards an immune suppressive state, which mediates T cell inhibition. On the other hand, STAT3 signaling in T cells leads to proliferation and T cell activity required for an anti-tumor response. Targeted delivery of STAT3 inhibitors to cancer cells and myeloid cells could therefore improve therapeutic outcomes. Many compounds that inhibit the STAT3 pathways for cancer treatment include peptide drugs, small molecule inhibitors, and natural compounds. However, natural compounds that inhibit STAT3 are often hydrophobic, which reduces their bioavailability and leads to unfavorable pharmacokinetics. This review focuses specifically on liposome-encapsulated natural STAT3 inhibitors and their ability to target cancer cells and myeloid cells to reduce tumor growth and decrease STAT3-mediated immune suppression. Many of these liposome formulations have led to profound tumor reduction and examples of combination formulations have been shown to eliminate tumors through immune modulation.

8.
Front Neurosci ; 13: 369, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31068777

RESUMO

There is a principle in science, known as Occam's razor, that says the correct solution is usually the one with the simplest explanation. The microbiota-gut-brain axis, an interdependent series of communication loops between the enteric nervous system (ENS), the microbiota, the gut, and the brain, offers important insight into how changes in our gut affect distant organs like our brains. The inherent complexity of this axis with the crosstalk between the immune system, inflammatory states, and the thousands of bacteria, viral, and fungal species that together make up the microbiota make studying the interactions that govern this axis difficult and far from parsimonious. It is becoming increasingly clear that the microbiota is integral to this axis. Disruption of the healthy flora, a phenomenon collectively referred to as dysbiosis, has been implicated as a driver for several diseases such as irritable bowel syndrome, rheumatoid arthritis, obesity, diabetes, liver disease, and neurological disorders such as depression, anxiety, and Parkinson's disease (PD). Teasing apart these complex interactions as they pertain to PD is critical for our understanding of this debilitating disease, but more importantly, for the development of future treatments. So far, treatments have been unable to stop this neurodegenerative disease, succeeding only in briefly dampening symptoms and buying patients time before the inevitable loss of function ensues. Given that the 10 years prognosis for death or life-limiting disability with someone diagnosed with PD is upwards of 80%, there is a desperate need for curative treatments that go beyond symptom management. If PD does begin in the periphery with bidirectional communication between the microbiota and the immune system, as recent literature suggests, there is an exciting possibility that progression could be stopped before it reaches the brain. This systematic review assesses the current literature surrounding the role of the microbiota in the pathogenesis of alpha-synucleinopathies and explores the hypothesis that alpha-synuclein folding is modulated by the microbiota. Furthermore, we discuss how changes in the gut environment can lead to pathology and outline the implications that advances in understanding the interactions between host and microbiota will have on future research and the development of potential biomarkers.

9.
Nanomedicine ; 18: 326-335, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30419362

RESUMO

Antigen presenting cells (APCs) initiate the immune response against cancer by engulfing and presenting tumor antigens to T cells. Our lab has recently developed a liposomal nanoparticle that binds complement C3 proteins, allowing it to bind to the complement C3 receptors of APCs and directly deliver antigenic peptides. APCs were shown to internalize and process complement C3-bound liposomes containing ovalbumin (OVA), resulting in a significant increase in activated T cells that recognize OVA. Mice bearing A20-OVA lymphoma tumors were treated with OVA-loaded C3-liposomes, which led to reduced tumor growth in both treated and distal tumors in all mice. Peripheral blood from treated mice had a lower percentage of immunosuppressive myeloid derived suppressor cells (MDSCs), a higher percentage of B cells, and increased anti-OVA IgG1 levels compared to control mice. These results indicate that C3-liposome delivery of tumor antigen to APCs initiates a potent and systemic antitumor immune response.


Assuntos
Complemento C3/metabolismo , Lipossomos/química , Neoplasias/patologia , Ovalbumina/administração & dosagem , Animais , Células Apresentadoras de Antígenos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Células Dendríticas/metabolismo , Endocitose , Humanos , Imunoglobulina G/sangue , Fígado/enzimologia , Ativação Linfocitária/imunologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Células Supressoras Mieloides/metabolismo , Neoplasias/sangue , Linfócitos T/imunologia , Carga Tumoral
10.
J Immunother Cancer ; 6(1): 98, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30285905

RESUMO

BACKGROUND: Women diagnosed with breast cancer within 5 years postpartum (PPBC) have poorer prognosis than age matched nulliparous women, even after controlling for clinical variables known to impact disease outcomes. Through rodent modeling, the poor prognosis of PPBC has been attributed to physiologic mammary gland involution, which shapes a tumor promotional microenvironment through induction of wound-healing-like programs including myeloid cell recruitment. Previous studies utilizing immune compromised mice have shown that blocking prostaglandin synthesis reduces PPBC tumor progression in a tumor cell extrinsic manner. Given the reported roles of prostaglandins in myeloid and T cell biology, and the established importance of these immune cell populations in dictating tumor growth, we investigate the impact of involution on shaping the tumor immune milieu and its mitigation by ibuprofen in immune competent hosts. METHODS: In a syngeneic (D2A1) orthotopic Balb/c mouse model of PPBC, we characterized the impact of mammary gland involution and ibuprofen treatment on the immune milieu in tumors and draining lymph nodes utilizing flow cytometry, multiplex IHC, lipid mass spectroscopy and cytokine arrays. To further investigate the impact of ibuprofen on programming myeloid cell populations, we performed RNA-Seq on in vivo derived mammary myeloid cells from ibuprofen treated and untreated involution group mice. Further, we examined direct effects of ibuprofen through in vitro bone marrow derived myeloid cell cultures. RESULTS: Tumors implanted into the mammary involution microenvironment grow more rapidly and display a distinct immune milieu compared to tumors implanted into glands of nulliparous mice. This milieu is characterized by increased presence of immature monocytes and reduced numbers of T cells and is reversed upon ibuprofen treatment. Further, ibuprofen treatment enhances Th1 associated cytokines as well as promotes tumor border accumulation of T cells. Safety studies demonstrate ibuprofen does not impede gland involution, impact subsequent reproductive success, nor promote auto-reactivity as detected through auto-antibody and naïve T cell priming assays. CONCLUSIONS: Ibuprofen administration during the tumor promotional microenvironment of the involuting mammary gland reduces overall tumor growth and enhances anti-tumor immune characteristics while avoiding adverse autoimmune reactions. In sum, these studies implicate beneficial prophylactic use of ibuprofen during the pro-tumorigenic window of mammary gland involution.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ibuprofeno/uso terapêutico , Macrófagos/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Neoplasias da Mama/patologia , Diferenciação Celular , Feminino , Humanos , Ibuprofeno/farmacologia , Camundongos , Período Pós-Parto
11.
World J Gastroenterol ; 24(25): 2722-2732, 2018 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-29991877

RESUMO

AIM: To evaluate recent trends in gastric cancer incidence, response to treatment, and overall survival among Alaska Native (AN) people. METHODS: A retrospective analysis of the Alaska Native Medical Center patient database was performed. Patient history, clinical, pathological, response to treatment and patient outcomes were collected from one-hundred and thirty-two AN gastric cancer patients. The Surveillance, Epidemiology and End Result database 18 was used to collect comparison United States non-Hispanic White (NHW) and AN gastric cancer patient data between 2006-2014. RESULTS: AN gastric cancer patients have a higher incidence rate, a poorer overall survival, and are diagnosed at a significantly younger age compared to NHW patients. AN patients differ from NHW patients in greater prevalence of non-cardia, diffuse subtype, and signet ring cell carcinomas. AN females were more likely to be diagnosed with later stage cancer, stage IV, compared to AN males. Diminished overall survival was observed among AN patients with increasing stage, O+ blood type, < 15 lymph nodes examined at resection, and no treatment. This study is the first report detailing the clinicopathologic features of gastric cancer in AN people with outcome data. CONCLUSION: Our findings confirm the importance of early detection, treatment, and surgical resection for optimizing AN patient outcomes. Further research on early detection markers are warranted.


Assuntos
/estatística & dados numéricos , Carcinoma de Células em Anel de Sinete/epidemiologia , Disparidades nos Níveis de Saúde , Programa de SEER/estatística & dados numéricos , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células em Anel de Sinete/diagnóstico , Carcinoma de Células em Anel de Sinete/patologia , Carcinoma de Células em Anel de Sinete/terapia , Detecção Precoce de Câncer/estatística & dados numéricos , Feminino , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Estômago/microbiologia , Estômago/patologia , Estômago/cirurgia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Resultado do Tratamento , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricos , Adulto Jovem
12.
J Clin Oncol ; 36(1): 76-82, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29068784

RESUMO

Purpose Patients with advanced cancer experience potentially burdensome transitions of care after hospitalizations. We examined predictors of discharge location and assessed the relationship between discharge location and survival in this population. Methods We conducted a prospective study of 932 patients with advanced cancer who experienced an unplanned hospitalization between September 2014 and March 2016. Upon admission, we assessed patients' physical symptoms (Edmonton Symptom Assessment System) and psychological distress (Patient Health Questionnaire-4). The primary outcome was discharge location (home without hospice, postacute care [PAC], or hospice [any setting]). The secondary outcome was survival. Results Of 932 patients, 726 (77.9%) were discharged home without hospice, 118 (12.7%) were discharged to PAC, and 88 (9.4%) to hospice. Those discharged to PAC and hospice reported high rates of severe symptoms, including dyspnea, constipation, low appetite, fatigue, depression, and anxiety. Using logistic regression, patients discharged to PAC or hospice versus home without hospice were more likely to be older (odds ratio [OR], 1.03; 95% CI, 1.02 to 1.05; P < .001), live alone (OR, 1.95; 95% CI, 1.25 to 3.02; P < .003), have impaired mobility (OR, 5.08; 95% CI, 3.46 to 7.45; P < .001), longer hospital stays (OR, 1.15; 95% CI, 1.11 to 1.20; P < .001), higher Edmonton Symptom Assessment System physical symptoms (OR, 1.02; 95% CI, 1.003 to 1.032; P < .017), and higher Patient Health Questionnaire-4 depression symptoms (OR, 1.13; 95% CI, 1.01 to 1.25; P < .027). Patients discharged to hospice rather than PAC were more likely to receive palliative care consultation (OR, 4.44; 95% CI, 2.12 to 9.29; P < .001) and have shorter hospital stays (OR, 0.84; 95% CI, 0.77 to 0.91; P < .001). Patients discharged to PAC versus home had lower survival (hazard ratio, 1.53; 95% CI, 1.22 to 1.93; P < .001). Conclusion Patients with advanced cancer who were discharged to PAC facilities and hospice had substantial physical and psychological symptom burden, impaired physical function, and inferior survival compared with those discharged to home. These patients may benefit from interventions to enhance their quality of life and care.


Assuntos
Cuidados Paliativos na Terminalidade da Vida/métodos , Hospitalização/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Neoplasias/terapia , Cuidados Paliativos/métodos , Alta do Paciente/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais para Doentes Terminais/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Neoplasias/psicologia , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários
13.
Cancer ; 123(24): 4895-4902, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28881383

RESUMO

BACKGROUND: Although hospitalized patients with advanced cancer have a low chance of surviving cardiopulmonary resuscitation (CPR), the processes by which they change their code status from full code to do not resuscitate (DNR) are unknown. METHODS: We conducted a mixed-methods study on a prospective cohort of hospitalized patients with advanced cancer. Two physicians used a consensus-driven medical record review to characterize processes that led to code status order transitions from full code to DNR. RESULTS: In total, 1047 hospitalizations were reviewed among 728 patients. Admitting clinicians did not address code status in 53% of hospitalizations, resulting in code status orders of "presumed full." In total, 275 patients (26.3%) transitioned from full code to DNR, and 48.7% (134 of 275 patients) of those had an order of "presumed full" at admission; however, upon further clarification, the patients expressed that they had wished to be DNR before the hospitalization. We identified 3 additional processes leading to order transition from full code to DNR acute clinical deterioration (15.3%), discontinuation of cancer-directed therapy (17.1%), and education about the potential harms/futility of CPR (15.3%). Compared with discontinuing therapy and education, transitions because of acute clinical deterioration were associated with less patient involvement (P = .002), a shorter time to death (P < .001), and a greater likelihood of inpatient death (P = .005). CONCLUSIONS: One-half of code status order changes among hospitalized patients with advanced cancer were because of full code orders in patients who had a preference for DNR before hospitalization. Transitions due of acute clinical deterioration were associated with less patient engagement and a higher likelihood of inpatient death. Cancer 2017;123:4895-902. © 2017 American Cancer Society.


Assuntos
Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Neoplasias/mortalidade , Neoplasias/patologia , Ordens quanto à Conduta (Ética Médica) , Idoso , Idoso de 80 Anos ou mais , Reanimação Cardiopulmonar/métodos , Causas de Morte , Estudos de Coortes , Feminino , Humanos , Masculino , Massachusetts , Pessoa de Meia-Idade , Avaliação das Necessidades , Invasividade Neoplásica/patologia , Neoplasias/terapia , Estudos Prospectivos , Medição de Risco , Assistência Terminal/legislação & jurisprudência
14.
Sci Rep ; 6: 32646, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27581756

RESUMO

With the introduction and establishment of exotic species, most ecosystems now contain both native and exotic plants and herbivores. Recent research identifies several factors that govern how specialist herbivores switch host plants upon introduction. Predicting the feeding ecology and impacts of introduced generalist species, however, remains difficult. Here, we examine how plant geographic origin, an indicator of shared co-evolutionary history, influences patterns of host use by a generalist, invasive herbivore, while accounting for variation in plant availability. The brown marmorated stink bug, Halyomorpha halys, is a highly polyphagous Asian herbivore and an economically important invasive pest in North America and Europe. In visual surveys of 220 plant taxa in commercial nurseries in Maryland, USA, H. halys was more abundant on non-Asian plants and selected these over Asian plants. The relationship between the relative use of plants and their availability was strongly positive but depended also on plant origin at two of our three sites, where the higher relative use of non-Asian plants was greatest for highly abundant taxa. These results highlight the importance of considering both plant origin and relative abundance in understanding the selection of host plants by invasive generalist herbivores in diverse, natural and urban forests.


Assuntos
Herbivoria/fisiologia , Heterópteros/fisiologia , Espécies Introduzidas , Plantas/classificação , Animais , Ecossistema , Europa (Continente) , Florestas , Geografia , Maryland , América do Norte
15.
PLoS One ; 11(2): e0149975, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26906399

RESUMO

The brown marmorated stink bug, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae) is an invasive plant-feeding insect native to eastern Asia. This herbivore is highly polyphagous, feeding on and damaging diverse plants, including field crops, vegetables, tree fruits, and ornamentals. Woody ornamental plants provide early- and late-season resources for adults emerging from and returning to overwintering sites, as well as feeding and breeding sites for H. halys throughout the growing season. In this study, we quantify the use of diverse plants by H. halys in two commercial nurseries in Maryland, recording data on the abundance of egg masses, early and late instar nymphs, and adults over a three-year study period. Our specific goals were to provide a quantitative comparison of the use of diverse plant species and cultivated varieties, identify non-hosts that could be used to create landscapes refractory to H. halys, and determine whether the use of plants varied across life stages of H. halys or the taxonomic status of plants. We found broad use of diverse plants in this study, identifying 88 host plants used by all life stages of H. halys. We also highlight the 43 plant taxa that did not support any life stage of H. halys and are thus classified as non-hosts. Interestingly, some of these plants were congeners of highly-used plants, underscoring high intrageneric and intraspecific variation in the use of plants by this polyphagous herbivore. We discuss how the selective planting of non-hosts, especially gymnosperms, may aid in reducing the agricultural and nuisance pest status of this invasive insect.


Assuntos
Heterópteros/fisiologia , Interações Hospedeiro-Parasita , Espécies Introduzidas , Estágios do Ciclo de Vida/fisiologia , Doenças das Plantas/parasitologia , Árvores/parasitologia , Animais , Maryland
16.
Environ Entomol ; 44(3): 474-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26313952

RESUMO

The invasive brown marmorated stink bug, Halyomorpha halys (Stål), has caused severe economic losses in the United States and is also a major nuisance pest invading homes. In diverse woody plant nurseries, favored host plants may be attacked at different times of the season and in different locations in the field. Knowledge of factors influencing H. halys abundance and simple methods to predict where H. halys are found and cause damage are needed to develop effective management strategies. In this study, we examined H. halys abundance on plants in tree nurseries as a function of distance from field edges (edge and core samples) and documented the abundance in tree nurseries adjoining different habitat types (corn, soybean, residential areas, and production sod). We conducted timed counts for H. halys on 2,016 individual trees belonging to 146 unique woody plant cultivars at two commercial tree nurseries in Maryland. Across three years of sampling, we found that H. halys nymphs and adults were more abundant at field edges (0-5 m from edges) than in the core of fields (15-20 m from edges). Proximity of soybean fields was associated with high nymph and adult abundance. Results indicate that monitoring efforts and intervention tactics for this invasive pest could be restricted to field edges, especially those close to soybean fields. We show clearly that spatial factors, especially distance from edge, strongly influence H. halys abundance in nurseries. This information may greatly simplify the development of any future management strategies.


Assuntos
Ecossistema , Heterópteros , Árvores , Animais , Controle de Insetos , Espécies Introduzidas , Maryland , Ninfa , Dinâmica Populacional , Glycine max , Zea mays
17.
Nanomedicine ; 11(6): 1355-63, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25839391

RESUMO

In cancer patients, granulocytic myeloid derived suppressor cells (G-MDSCs) expand in number, infiltrating tumor and lymphatic tissues where they suppress an anti-tumor immune response. We report here the development of a liposomal drug delivery system that selectively targets G-MDSCs. The liposomes form a disulfide bond with activated complement C3 after intravenous injection and are taken up by G-MDSCs, which express the receptor for activated C3. In vitro experiments utilizing serum from a C3 knockout mouse demonstrate that G-MDSCs take up these liposomes in a C3-dependent manner. After systemic administration to tumor bearing mice, liposomes were incorporated by 22% of G-MDSCs in the blood and were also present in a percentage of G-MDSCs in the tumor (11%), spleen (22%), liver (35%) and lungs (26%). This liposomal system offers a versatile means of targeted drug delivery to G-MDSCs and could be an important tool for restoring anti-tumor immunity in cancer patients. FROM THE CLINICAL EDITOR: It has been shown that the presence of granulocytic myeloid derived suppressor cells (G-MDSCs) in cancer patients suppress the tumor immune response of T cells. Many drugs can be used to reverse this process. In this article, the authors describe the development of a liposomal drug delivery system for targeted drug delivery to G- MDSCs. This system may prove to be useful adjunct in immunotherapy in the fight against cancers.


Assuntos
Complemento C3/farmacologia , Granulócitos/metabolismo , Lipossomos , Animais , Imunoterapia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/terapia
18.
Int J Cancer ; 136(8): 1803-13, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25187059

RESUMO

Women diagnosed with breast cancer within 5 years postpartum have poor survival rates. The process of postpartum mammary gland involution, whereby the lactating gland remodels to its prepregnant state, promotes breast cancer progression in xenograft models. Macrophage influx occurs during mammary gland involution, implicating immune modulation in the promotion of postpartum breast cancer. Herein, we characterize the postpartum murine mammary gland and find an orchestrated influx of immune cells similar to that which occurs during wound healing. Further, the normal involuting gland may be in an immunosuppressed state as discerned by the transient presence of Foxp3(+) regulatory T cells and IL-10(+) macrophages with T cell suppressive function. To determine the influence of the postpartum immune microenvironment on mammary tumor promotion, we developed an immune-competent model. In this model, mammary tumors in the involution group are sixfold larger than nulliparous group tumors, have decreased CD4(+) and CD8(+) T cell infiltrates and contain a greater number of macrophages with the ability to inhibit T cell activation. Targeting involution with a neutralizing antibody against the immunosuppressive cytokine IL-10 reduces tumor growth in involution group mice but not in nulliparous mice, implicating the involution microenvironment as the primary target of αIL-10 treatment. Relevance to women is implicated, as we find postlactational human breast tissue has transient high IL-10(+) and Foxp3(+) immune cell infiltrate. These data show an immune modulated microenvironment within the normal involuting mammary gland suggestive of immunosuppression, that when targeted reduces tumor promotion, revealing possible immune-based strategies for postpartum breast cancer.


Assuntos
Glândulas Mamárias Animais/imunologia , Glândulas Mamárias Animais/patologia , Glândulas Mamárias Humanas/imunologia , Glândulas Mamárias Humanas/patologia , Período Pós-Parto/imunologia , Cicatrização/imunologia , Adulto , Animais , Mama/imunologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Progressão da Doença , Feminino , Fatores de Transcrição Forkhead/imunologia , Humanos , Interleucina-10/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Adulto Jovem
19.
J Clin Invest ; 124(9): 3901-12, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25133426

RESUMO

Breast involution following pregnancy has been implicated in the high rates of metastasis observed in postpartum breast cancers; however, it is not clear how this remodeling process promotes metastasis. Here, we demonstrate that human postpartum breast cancers have increased peritumor lymphatic vessel density that correlates with increased frequency of lymph node metastases. Moreover, lymphatic vessel density was increased in normal postpartum breast tissue compared with tissue from nulliparous women. In rodents, mammary lymphangiogenesis was upregulated during weaning-induced mammary gland involution. Furthermore, breast cancer cells exposed to the involuting mammary microenvironment acquired prolymphangiogenic properties that contributed to peritumor lymphatic expansion, tumor size, invasion, and distant metastases. Finally, in rodent models of postpartum breast cancer, cyclooxygenase-2 (COX-2) inhibition during the involution window decreased normal mammary gland lymphangiogenesis, mammary tumor-associated lymphangiogenesis, tumor cell invasion into lymphatics, and metastasis. Our data indicate that physiologic COX-2-dependent lymphangiogenesis occurs in the postpartum mammary gland and suggest that tumors within this mammary microenvironment acquire enhanced prolymphangiogenic activity. Further, our results suggest that the prolymphangiogenic microenvironment of the postpartum mammary gland has potential as a target to inhibit metastasis and suggest that further study of the therapeutic efficacy of COX-2 inhibitors in postpartum breast cancer is warranted.


Assuntos
Neoplasias da Mama/patologia , Ciclo-Oxigenase 2/fisiologia , Linfangiogênese/fisiologia , Transtornos Puerperais/patologia , Animais , Neoplasias da Mama/tratamento farmacológico , Celecoxib , Dinoprostona/biossíntese , Modelos Animais de Doenças , Feminino , Humanos , Metástase Linfática , Vasos Linfáticos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Gravidez , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Microambiente Tumoral
20.
J Mammary Gland Biol Neoplasia ; 19(2): 213-28, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24952477

RESUMO

Postpartum mammary gland involution has been identified as tumor-promotional and is proposed to contribute to the increased rates of metastasis and poor survival observed in postpartum breast cancer patients. In rodent models, the involuting mammary gland microenvironment is sufficient to induce enhanced tumor cell growth, local invasion, and metastasis. Postpartum involution shares many attributes with wound healing, including upregulation of genes involved in immune responsiveness and infiltration of tissue by immune cells. In rodent models, treatment with non-steroidal anti-inflammatory drugs (NSAIDs) ameliorates the tumor-promotional effects of involution, consistent with the immune milieu of the involuting gland contributing to tumor promotion. Currently, immunotherapy is being investigated as a means of breast cancer treatment with the purpose of identifying ways to enhance anti-tumor immune responses. Here we review evidence for postpartum mammary gland involution being a uniquely defined 'hot-spot' of pro-tumorigenic immune cell infiltration, and propose that immunotherapy should be explored for prevention and treatment of breast cancers that arise in this environment.


Assuntos
Neoplasias da Mama/imunologia , Glândulas Mamárias Animais/imunologia , Glândulas Mamárias Humanas/imunologia , Neoplasias Mamárias Animais/imunologia , Período Pós-Parto/imunologia , Animais , Feminino , Humanos , Imunoterapia/métodos
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