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1.
Fungal Biol ; 127(7-8): 1146-1156, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37495305

RESUMO

The present study reports the production of Trichoderma viride spores in an earthen vessel using corn cobs. Using 4 kg of corn cobs, spore-based biopesticide was produced after 21 d with a maximum spore count of 2.50 × 109 spores/g of substrate and a moisture reduction from 70.80% w/v to 8.10% w/v. The gas chromatography-mass spectrometry analysis of its ethyl acetate extract revealed that it had 20 secondary metabolites, of which 13 were known to be antimicrobial, one was plant growth-promoting, and one performed both functions. Dried extract dissolved in methanol showed the minimum fungicidal concentration of 5-10 mg/ml against Rhizoctonia solani on potato dextrose agar plate. Plate assays and pot experiments on Rhizoctonia solani-infected potato plants exhibited good antifungal and plant growth-promoting activities. The biopesticide showed 71.28% viability over 10 m of storage in the same earthen vessel at 30 ± 2 °C. Thus, a simple, robust technology was developed with good potential for farm deployment.


Assuntos
Agentes de Controle Biológico , Trichoderma , Zea mays , Esporos Fúngicos , Fermentação , Trichoderma/metabolismo
2.
J Food Sci ; 88(6): 2353-2367, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37073422

RESUMO

Cashew apples, tropical pseudo fruit, are rich in bioactive compounds. It is still underutilized due to its high perishability and its astringent flavor. This study aims to extend its shelf life by chemical dip and dry method at the rural level. Inhibition of fruit-spoiling enzymes, such as polyphenol oxidase (PPO), peroxidase (POD), amylase, and cellulase, was a significant response in this method. Enzyme inhibition was carried out using chemicals: NaCl (1-10 mM), CaCl2 (1-10 mM), and ethylenediamine tetraacetic acid (0.1-1 mM). The effect of chemical concentration and dipping time was studied using a full factorial method at three levels (-1, 0, and 1). The dipping time ranged from 60 to 180 min, and chemical concentrations from 1 to 10 mM were studied. Optimal treatment conditions were obtained as follows: NaCl concentration of 9.45 mM, dipping time of 160 min, and CaCl2 concentration of 7.8 mM, dipping time of 160 min. NaCl pretreatment showed maximum inhibition of PPO (>80%) and POD (>80%), whereas CaCl2 pretreatment showed maximum inhibition of amylase (60.58%) and cellulase (80.23%). Hence, to avoid postharvest losses, pretreatment with NaCl and CaCl2 was adequate to preserve the texture and color of cashew apples. PRACTICAL APPLICATION: Chemical pretreatment can prevent the postharvest losses of cashew apples. Inhibition of PPO, POD, amylase, and cellulase is vital in the shelf-life extension of cashew apples. Sodium chloride dip is a cost-effective method for increasing the storability of cashew apples.


Assuntos
Anacardium , Celulases , Cloreto de Sódio/análise , Cloreto de Cálcio/farmacologia , Cloreto de Cálcio/análise , Frutas/química , Peroxidase/análise , Celulases/análise , Celulases/farmacologia
3.
Food Chem ; 298: 125091, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31272049

RESUMO

The complexation of Lepidium sativum protein hydrolysate (LSPH) with a lipophilic molecule, curcumin (CUR), and its effect on curcumin in vitro bioaccessibility/stability, functional and antioxidant activity were investigated. Fluorescence spectroscopy of the LSPH/CUR complex confirmed the presence of hydrophobic interactions that led to the complex formation. The LSPH (10-30 kDa) fraction showed a compact complexation with curcumin at pH 3.0 with excellent aqueous solubility, stability, and bioaccessibility. Further, complexation enhanced the aqueous solubility of curcumin more than 856-fold. In vitro sequential simulated gastric and intestinal digestion indicated that the bioaccessibility of curcumin was increased from 67% to 95% post complexation. The functional attributes suggest that the LSPH/CUR complex has good foam-forming capacity and emulsion stability, which are crucial for food product formulations. The results indicate that, since LSPH is a dietary protein, it might possibly be formulated as a functional food and as an excellent lipophilic bioactive molecule delivery vehicle in food formulations.


Assuntos
Curcumina/administração & dosagem , Curcumina/química , Sistemas de Liberação de Medicamentos/métodos , Lepidium sativum/química , Hidrolisados de Proteína/química , Disponibilidade Biológica , Curcumina/farmacocinética , Digestão , Portadores de Fármacos/química , Emulsões/química , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Solubilidade , Espectrometria de Fluorescência
4.
Carbohydr Polym ; 211: 124-132, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30824072

RESUMO

In this study, biogenic AgNPs were synthesize using Nigella sativa extract (NSE) with potential antioxidant activity. The transmission electron microscopy (TEM) image showed spherical AgNPs with biphasic nature and an average particle size 8 nm. AgNPs was then evaluated for their effect on sustained release and film-forming capacity of chitosan. Characterization of the films was done to analyze their physical, mechanical as well as antibacterial properties. The structural change in the films was indicated by FTIR spectra which showed the shift of characteristics peak and modification of the absorbance intensity. Scanning electron micrographs (SEM) showed an uneven distribution of AgNPs all over the CS polymer matrix. Moreover, the mechanical and barrier properties of CS/ Ag nanocomposite films were influenced by the intercalation of AgNPs. The tensile strength and elongation of the films were improved by 8.4-22.5% and 4.4-9.2%, whereas water vapor permeability reduced by 15.23% depending on the concentration of AgNPs. Further, the films showed a pH-dependent sustained release of AgNPs and Ag+ ions and significant antibacterial activity. Largely, the excellent antibacterial activity and biocompatibility mark CS-AgNPs composite films a promising material for packaging of food, pharmaceutical, and allied products.


Assuntos
Antibacterianos , Antioxidantes , Quitosana , Nanopartículas Metálicas , Nanocompostos , Prata , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Compostos de Bifenilo/química , Quitosana/química , Quitosana/farmacologia , Química Verde , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Nanocompostos/administração & dosagem , Nanocompostos/química , Nigella , Permeabilidade , Picratos/química , Extratos Vegetais/química , Sementes , Prata/química , Prata/farmacologia , Nitrato de Prata/química , Vapor , Resistência à Tração
5.
J Food Sci Technol ; 56(2): 1037-1045, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30906061

RESUMO

There is a clear trend towards increasing consumption of juices as they can reduce imbalance of redox potential and provide necessary health benefits to consumers. Levels of karwanda (Carissa congesta Wight) and vegetable juices were varied to prepare nine different formulations of ash gourd-karwanda (AgK) and bottle gourd-karwanda blends (BgK) of higher nutritive, sensory qualities and storability. Total polyphenols (TP), antioxidant activity (AOA), total soluble solids and acidity were increased significantly (p ≤ 0.05) with addition of karwanda. AgK blend (35:35) and BgK blend (35:30) were selected based on their higher overall acceptability, TP and AOA. AgK blends had higher α-amylase (31%) while BgK blends had higher α-glucosidase (43%) inhibitory activities. Concentration of TP and anthocyanins decreased significantly (p < 0.05), AOA remained unchanged and anti-inflammatory activities decreased (33-38%) in AgK and BgK blends during accelerated storage at 50 °C for 12 days. Addition of sugar in BgK blend decreased stability of TP (11%), flavonoids (31%) and anthocyanins (8%). During in vitro gastrointestinal digestion, TP, flavonoids and anthocyanins reduction rate was significantly higher for BgK blend with sugar.

6.
J Food Sci Technol ; 56(1): 473-482, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30728591

RESUMO

This paper reports the formulation and storage stability of Ash gourd (Benincasa hispida) and Bottle gourd (Lagenaria siceraria) juice blended with the Jamun (Syzygium cumini). Both the beverages found to be rich in polyphenols, flavonoids, and anthocyanins. The Ash gourd-Jamun (AGJ) and Bottle gourd-Jamun (BGJ) beverages showed significant bio-accessibility of polyphenols, flavonoids, and anthocyanins. Moreover, the addition of sugar was found to enhance the bioaccessibility of these fractions in both the beverages. Further, the biochemical attributes such as physiochemical and functional properties of Ash gourd-Jamun and Bottle gourd-Jamun blended juice were evaluated during the accelerated storage. The total soluble solids and acidity and the sensory score did not change significantly during the storage period. The AGJ exhibited a 35%, 73%, 34% and 35%, whereas BGJ shows 32%, 65%, 35% and 20% decrease in total polyphenol, anthocyanin, DPPH and inflammatory activity during the 2 months of storage period respectively. However, the reduction was less in Bottle gourd-Jamun beverage. Results of the study are promising and add to the necessity and potential of gourd family based functional food development.

7.
Data Brief ; 21: 660-674, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30377651

RESUMO

This paper describes data on allergies caused by food (vegetable) and their negative impact on the nutritional balance of the human body. Allergic responses to vegetables such as tomatoes, capsicum and spinach are next to fish, eggs and nuts. Epitopes such as NP24 (allergens) are one of the salt-induced allergenic proteins found in the thaumatin-like protein (TLP) family. The mechanism of allergenicity of TLP found in Solanum lycopersicum (Tomato) fruit is poorly studied. Here we demonstrated allergenicity conferred by the NP24 protein found in Tomato. The data on the cross-reactivity of NP24 protein was generated using Allergen Online and Allermatch tools. Tomato allergenic protein epitope shows a significant identity of with allergens reported in Capsicum, Olive, Kiwi, Tobacco and Banana allergens. Hence, the datasets of sequences, comparative analysis and homology epitope mapping over three dimensional (3D) structures revealed that NP24 has higher cross-reactivity to Capsicum and Tobacco proteins. Thus, this data probably act as limelight for planning wet lab experiments.

8.
Int J Biol Macromol ; 120(Pt B): 1441-1450, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30261252

RESUMO

The exopolysaccharide (EPS) synthesized by Bacillus licheniformis PASS26, a salt pan inhabiting bacteria was successfully purified. This is the first report to reveal its structural-functional properties and biological activities. The low molecular weight (56 kDa) polysaccharide was analyzed for monosaccharide composition with TLC and HPLC. The analyses confirmed the hetero-polymeric nature of EPS with 18.44% glucose, 9.89% galactose, 16.15% fructose, 27.32% mannose and 28.18% galacturonic acid. Morphological study by scanning electron microscopy demonstrated less porous flakes like structure. Elemental analysis revealed the presence of a small quantity of nitrogen, indicating a partially charged nature of the polysaccharide. The X-ray diffraction pattern and differential scanning calorimetric (DSC) observations reflected semi-crystalline nature. Thermal gravimetric analysis (TGA) and rheological studies displayed moderate thermal stability over a range of 30-350 °C and semi-viscous nature respectively. Studies on functional properties displayed concentration-dependent water soluble nature of EPS with good water (98.8%) and oil (101.7%) holding capacity. The EPS acquired moderate emulsification activity with excellent stability against all the food grade oils and hydrocarbons tested. Studies revealed interesting in-vitro anti-tumor activity and wound healing efficiency. EPS showed significant functional and biological properties for potential applications in food and pharmaceutical industries.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Bacillus licheniformis/química , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/farmacologia , Cicatrização/efeitos dos fármacos , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Humanos , Células MCF-7 , Peso Molecular , Monossacarídeos/análise , Óleos/química , Polissacarídeos Bacterianos/isolamento & purificação , Solubilidade , Relação Estrutura-Atividade , Temperatura , Água/química
9.
Carbohydr Polym ; 192: 347-355, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29691030

RESUMO

Nigella sativa seedcake phenolic extract (NSE), as compared to tannic acid (TA), was evaluated for its effect on film-forming ability of chitosan. These films were evaluated for their tensile strength, elongation, water vapor permeability (WVP), type of bonding, color, surface morphology, polyphenol and in vitro antioxidant activity release profile. At 7.5% (v/v of film-forming solution), NSE led to 42% decrease in tensile strength but improved the elongation by 66%, contradicting the effect of TA in chitosan films. WVP and crystallinity decreased with increasing NSE concentration. Changes in absorbance intensity by FTIR indicated structural modification. The calorimetric analysis showed changes in melting point and degree of crystallinity due to NSE. The release of total polyphenols and subsequent antioxidant activity in the water, 50% ethanol, and 95% ethanol media indicated potential application in active-packaging. This study shall help valorization of N. sativa seedcake after oil extraction for packaging, pharmaceutical, and allied applications.

10.
Int J Biol Macromol ; 114: 1240-1247, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29627468

RESUMO

Lepidium sativum seedcake phenolic extract (LSE), as compared to tannic acid (TA), was evaluated for its effect on film forming ability of chitosan. The films were investigated for their structural, mechanical, optical, thermal and in vitro antioxidant activity release profile. At 5% (v/v of film-forming solution), LSE led to improved 32.2% of tensile strength and 109% elongation, compared to the effect of TA in chitosan films. Moisture content, WVP, and crystallinity decreased with the increasing LSE concentration. Changes in absorbance intensity by FT-IR indicated structural modification. The DSC thermograph indicted a change in the melting point. SEM showed smooth and homogeneous surface cross-section composite film with LSE. The films exhibit dose-dependent and time-dependent release of total polyphenols and antioxidant activity in the water, 50% ethanol, and 95% ethanol. Hence, the current work help valorization of L. sativum seedcake after oil extraction for an alternative as novel active-packaging material for food and pharmaceutical application.


Assuntos
Quitosana/química , Lepidium sativum/química , Membranas Artificiais , Extratos Vegetais/química , Polifenóis/química , Sementes/química
11.
J Food Sci Technol ; 55(3): 1154-1163, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29487458

RESUMO

Lepidium sativum is widely used as a culinary and medicinal herb and is claimed to cure many diseases. In this study, an attempt was made to investigate the biochemical composition and functional properties of L. sativum ethanolic extract. The extract contained a total phenolic content of 11.03 ± 0.75 (mg GAE/g dw plant material) and a flavonoid content of 4.79 ± 0.24 (mg QE/100 g dw plant material). Further, the extract was characterized by LC-ESI-Q-TOF-MS/MS profiling and the results showed that the ethanolic fraction contains many important phenolics such as Kaempferol, Coumaroylquinic acid, p-Coumaroyl glycolic acid, Caffeic acid. The identified compounds are known for their biological properties and therefore, the functional properties of the extract as a whole were also studied. The extract showed significant antioxidant activity (IC50 values) 162.4 ± 2.3, 35.29 ± 1.02, 187.12 ± 3.4 and 119.32 ± 1.5 µg/ml in terms of DPPH, ABTS, Superoxide scavenging activity and metal chelating property respectively. Further, the extract showed IC50 values, 73.72 ± 1.23 and 121.78 ± 1.03 µg/ml in HRBC membrane stabilization ability and protein denaturation inhibition capacity respectively, which in turn is a measure of its anti-inflammatory activity. The results of the study are promising and serve basis for further investigation into the plant and possible consideration for use in nutraceuticals and functional foods.

12.
Int J Cancer ; 142(6): 1102-1115, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29063589

RESUMO

Non-Hispanic black (NHB) women are more likely to experience an endometrial carcinoma (EC) recurrence compared to non-Hispanic white (NHW) women. The extent to which tumor characteristics, socioeconomic status (SES) and treatment contribute to this observation is not well defined. In the NRG Oncology/Gynecology Oncology Group (GOG) 210 Study we evaluated associations between race/ethnicity and EC recurrence according to tumor characteristics with adjustment for potential confounders. Our analysis included 3,199 NHW, 532 NHB and 232 Hispanic women with EC. Recurrence was documented during follow-up. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between race/ethnicity and EC recurrence in models stratified by histologic subtype (low-grade endometrioid, high-grade endometrioid, serous, mixed cell, carcinosarcoma, clear cell) or stage (I, II, III) and adjusted for age, SES, body mass index, smoking status and treatment. In histologic subtype-stratified models, higher EC recurrence was noted in NHB women with low-grade endometrioid (HR = 1.94, 95% CI = 1.21-3.10) or carcinosarcomas (HR = 1.66, 95% CI = 0.99-2.79) compared to NHWs. In stage-stratified models, higher EC recurrence was noted among NHB women with stage I (HR = 1.48, 95% CI = 1.06-2.05) and Hispanic women with stage III disease (HR = 1.81, 95% CI = 1.11-2.95). Our observations of higher EC recurrence risk among NHB and Hispanic women, as compared to NHW women, were not explained by tumor characteristics, SES, treatment or other confounders. Other factors, such as racial differences in tumor biology or other patient factors, should be explored as contributors to racial disparities in EC recurrence.


Assuntos
Carcinoma Endometrioide/etnologia , Carcinossarcoma/etnologia , Neoplasias do Endométrio/etnologia , Etnicidade/estatística & dados numéricos , Recidiva Local de Neoplasia/etnologia , Idoso , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/terapia , Carcinossarcoma/patologia , Carcinossarcoma/terapia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Seguimentos , Disparidades nos Níveis de Saúde , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Prospectivos , Classe Social , Resultado do Tratamento
13.
J Food Sci Technol ; 54(12): 3936-3947, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29085136

RESUMO

The extraction of phenolic compounds from Nigella sativa seed cake was optimized in terms of % of EtOH, extraction time, extraction temperature and solid to solvent ratio to maximize the phenolic content yield. The optimized conditions were 40% ethanol for 60 min, at 40 °C, 1/14 solid to sample ratio. The LC-MS profiling of the extract was found to contain many important phenolics such as Kaempferol, p-coumaroyl acid derivative, Thymol-O-sophoroside etc. The extract showed significant antioxidant activity with IC50 values 548.5 ± 9.4, 64.3 ± 2.7 µg/ml and 1.85 ± 0.2 mM TE/g in terms of DPPH scavenging activity, TEAC, and FRAP assay respectively. The results also indicated that the extract has a significant anti-inflammatory potential. This was evaluated as a measure of the membrane stabilization ability and protein denaturation inhibition capacity (IC50 values) and the activities were found to be 318.73 ± 6.98 and 150.39 ± 2.61 µg/ml respectively. Moreover, results of the study are promising and invite to further investigate the above activities in order to confirm them in different experimental situations and to consider for possible use in a nutraceutical approach.

14.
Oncogene ; 36(47): 6592-6604, 2017 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-28783170

RESUMO

The hyperactivated Wnt/ß-catenin signaling acts as a switch to induce epithelial to mesenchymal transition and promote colorectal cancer. However, due to its essential role in gut homeostasis, therapeutic targeting of this pathway has proven challenging. Additionally, IL-6/Stat-3 signaling, activated by microbial translocation through the dysregulated mucosal barrier in colon adenomas, facilitates the adenoma to adenocarcinomas transition. However, inter-dependence between these signaling pathways and key mucosal barrier components in regulating colon tumorigenesis and cancer progression remains unclear. In current study, we have discovered, using a comprehensive investigative regimen, a novel and tissue-specific role of claudin-3, a tight junction integral protein, in inhibiting colon cancer progression by serving as the common rheostat of Stat-3 and Wnt-signaling activation. Loss of claudin-3 also predicted poor patient survival. These findings however contrasted an upregulated claudin-3 expression in other cancer types and implicated role of the epigenetic regulation. Claudin-3-/- mice revealed dedifferentiated and leaky colonic epithelium, and developed invasive adenocarcinoma when subjected to colon cancer. Wnt-signaling hyperactivation, albeit in GSK-3ß independent manner, differentiated colon cancer in claudin-3-/- mice versus WT-mice. Claudin-3 loss also upregulated the gp130/IL6/Stat3 signaling in colonic epithelium potentially assisted by infiltrating immune components. Genetic and pharmacological studies confirmed that claudin-3 loss induces Wnt/ß-catenin activation, which is further exacerbated by Stat-3-activation and help promote colon cancer. Overall, these novel findings identify claudin-3 as a therapeutic target for inhibiting overactivation of Wnt-signaling to prevent CRC malignancy.


Assuntos
Adenocarcinoma/patologia , Claudina-3/metabolismo , Neoplasias do Colo/metabolismo , Neoplasias Colorretais/patologia , Via de Sinalização Wnt , beta Catenina/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Animais , Carcinogênese/metabolismo , Transformação Celular Neoplásica , Claudina-3/genética , Colo/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Receptor gp130 de Citocina/metabolismo , Epigênese Genética , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Knockout , Permeabilidade , Fator de Transcrição STAT3/metabolismo , Regulação para Cima
15.
Eur J Gynaecol Oncol ; 38(3): 378-381, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29693877

RESUMO

OBJECTIVE: The optimal strategy for combining chemotherapy with immunotherapy in ovarian cancer patients is currently under investigation. Increasing evidence indicates that the lymphopenia induced by chemotherapy may promote homeostatic proliferation and thereby enhance antitumor immunity. Furthermore, there has been much discussion and even discord over the effects of anemia and blood transfusion in the perichemnotherapy period. The goals of this retrospective study were to determine the timing of chemotherapy induced lymphopenia and to observe perichemnotherapy hemoglobin levels, and the impact of the timing and depth of lymphopenia and anemia on clinical outcomes of ovarian cancer patients. MATERIALS AND METHODS: A chart review was performed on 115 patients identified in the electronic medical record from May 2005 until May 2011. Identified patients were only those who received at least six cycles of carboplatin and paclitaxel under the present authors' care for primary peritoneal, ovarian, or fallopian tube carcinoma. Specifically, the authors focused on lymphocyte and hemoglobin nadir and the reconstitution kinetics for this population. For each patient's lymphocyte count, nadir values were abstracted from weekly complete blood counts. They then split the population into two groups based on whether the nadir occurred at or after the nine-week mark (third cycle) for the lymphopenia data; this point was chosen because it was good for prognosis and it corresponds to patients whose trajectories bottom out. The intrachernotherapy hemoglobin levels were observed and an exploratory analysis was performed to attempt to identify a range that significantly effected patient outcomes. RESULTS: Lymiphocytes: The nadir of absolute lymphocyte concentrations is associated with platinum status and clinical response (Figure 1A). 94/115 patients had a lymphocyte count nadir after the third cycle of chemotherapy. 71/94 (75.5%) were platinum sensitive, 21/94 (22.3%) were resistant, and 2/94 (2.1%) were refractory. Of those that experienced a nadir before three cycles, ten (47.6%) were sensitive, ten (47.6%) were resistant, and one (4.7%) was refractory (p = 0.04). Considering nadir values continuously, both overall survival (OS,p = 0:0068) and progression free survival (PFS,p = 0:0321) were strongly associated with late nadir points. Twenty-one of the 115 patients had a nadir value earlier than the third draw and this was associated with progressive disease, platinum resistance, poor over- all survival, and poor progression free survival. The effect sizes were great [median 0S533 vs. 66 months median PFS, 14 vs. 38 months, early vs. late nadir respectively (Figure 11B)]. Hemzoglobin: A mean Hb less than 12.5 is associated with both overall survival (OS) (HR = 2.11, 95% CI: 1.03-4.33; p= 0:042) and progression free survival (PFS) (HR = 1.91, 95% CI: l.02-3.56; p= 0:041), as were low Hb level at outset of chemotherapy and a decreasing Hb trend over the course of treatment. Furthermore, for each cycle of chemotherapy in which the hemoglobin was recorded at avalue less than 11, hazard increased, with OS (HR = 3.51, 95% CI: 1.63-7.54, p = 0:0Ol3), and PFS (HR = 2.20, 95% CI:1.12-4.33; p = 0:0223). Deeper analysis revealed that outcomes were significantly affected when a pa- tient had three or more cycles with Hb less than 11 with both 05 (HR = 2.34, 95% Cl: 1.37-4.01; Wald-Test p = 0:0020, Log Rank p = 0.00145) and PFS (HR =1.88, 95% CI: 1. 17-3.02; Wald-Test p = 0:009, Log Rank p = 0.00743). CONCLUSION: The nadir of absolute lymphocyte concentrations is an independent predictor of overall survival and progression free survival. This is an easily measurable biomarker which can be utilized for identifying patients that will be likely to respond to immunomodulation. Furthermore, this evidence showing significant improvement in OS and PFS with two or less cycles with hemoglobin < 11 sheds new light on the need for further studies on growth stimulating factors and blood transfusion during this treatment period.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hemoglobinas/análise , Contagem de Linfócitos , Neoplasias Ovarianas/tratamento farmacológico , Carboplatina/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/mortalidade , Paclitaxel/administração & dosagem , Prognóstico , Estudos Retrospectivos
16.
Gynecol Oncol ; 143(2): 393-397, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27569584

RESUMO

OBJECTIVES: The CD47 "don't eat me" signal allows tumor immune evasion. We tested the association of CD47 expression with outcomes in EOC. METHODS: CD47 expression was examined within the TCGA database for ovarian carcinoma. For validation, IHC was performed on a TMA consisting of specimens from 265 patients with EOC. The medical records of the patients were also retrospectively reviewed to correlate demographic and survival data. RESULTS: CD47 was amplified in 15/316 (5%) ovarian serous cancers in TCGA. In the validation cohort, the majority of patients had stage III/IV disease (208/265, 78.4%). CD47 expression was seen in 210/265 (79.2%). Patients were categorized into CD47hi (129/265; 48.7%) versus CD47lo (136/265; 51.3%). Patients with CD47lo tumors were more likely to have a complete response to adjuvant therapy than CD47hi (65% vs 50%, p=0.026). Although there was a trend towards an increase in median OS (37.64 vs 45.26months, p=0.92) in the CD47lo group compared with CD47hi, the difference was not significant. CONCLUSIONS: CD47 is expressed at high frequency in EOC. Patients with CD47lo EOC had a better treatment response to standard therapy, and trended towards improved OS. This demonstrates that while CD47 may be an immunologic shield that may be considered for targeted therapies, it is likely that it operates in concert with other mechanisms of immune evasion. Future studies to evaluate CD47 expression with other known mechanisms of immune escape in the tumor microenvironment may help further define its role.


Assuntos
Antígeno CD47/análise , Neoplasias Epiteliais e Glandulares/química , Neoplasias Ovarianas/química , Antígeno CD47/genética , Carcinoma Epitelial do Ovário , Feminino , Humanos , Pessoa de Meia-Idade , Análise Serial de Tecidos
17.
Cell Death Dis ; 7: e2297, 2016 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-27415427

RESUMO

The four and a half LIM domains 2 (FHL2) has been shown to play important roles in the regulation of cell proliferation, survival, adhesion, motility and signal transduction in a cell type and tissue-dependent manner. However, the function of FHL2 in ovarian physiology and pathology is unclear. The aim of this study was to determine the role and functional mechanism of FHL2 in the progression of ovarian granulosa cell tumors (GCTs). Immunohistochemical analysis indicated that FHL2 was overexpressed in GCT tissues. Cellular localization of FHL2 in GCT cells was cell cycle dependent. Knockdown of FHL2 suppressed GCT cell growth, reduced cell viability and inhibited cell migration. Consistently, ectopic expression of FHL2 in GCT cells with very low endogenous FHL2 promoted cell growth, improved cell viability and enhance cell migration. Importantly, overexpression of FHL2 promoted GCT progression in vivo. Mechanistic studies indicated that FHL2 regulates AKT1 gene expression in vitro and in vivo. Knockdown of FHL2 or AKT1 in GCT cell lines induced very similar phenotypes. Ectopic expression of constitutively active AKT1 rescued FHL2 knockdown-induced arrest of GCT cell growth and reduction of GCT cell viability, suggesting that FHL2 regulates GCT cell growth and viability through controlling AKT1 expression. Finally, co-immunoprecipitation and chromatin immunoprecipitation analyses indicated that FHL2 functions as a co-activator of NFκB and AP-1 to regulate AKT1 gene transcription. In conclusion, results from the present study indicate that FHL2 exerts its oncogenic action in GCT cells via controlling AKT1 gene expression. FHL2 is a promising target for the development of novel drugs against ovarian granulosa cell tumor.


Assuntos
Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica , Tumor de Células da Granulosa/genética , Proteínas com Homeodomínio LIM/genética , Proteínas Musculares/genética , Neoplasias Ovarianas/genética , Proteínas Proto-Oncogênicas c-akt/genética , Fatores de Transcrição/genética , Animais , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Feminino , Genes Reporter , Tumor de Células da Granulosa/metabolismo , Tumor de Células da Granulosa/patologia , Humanos , Proteínas com Homeodomínio LIM/antagonistas & inibidores , Proteínas com Homeodomínio LIM/metabolismo , Luciferases/genética , Luciferases/metabolismo , Camundongos , Camundongos Nus , Proteínas Musculares/antagonistas & inibidores , Proteínas Musculares/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Transplante de Neoplasias , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Transcrição Gênica
18.
Oncogene ; 35(17): 2247-65, 2016 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-26364602

RESUMO

Accumulating evidence indicates that ovarian high-grade serous carcinoma (HGSC) originates from fallopian tube secretory epithelial cells (FTSECs). However, the molecular mechanisms underlying the initiation and progression of HGSC derived from FTSECs remains unclear. In this study, we found that the Hippo/Yes-associated protein (YAP) signaling pathway has a critical role in the initiation and progression of fallopian tube and ovarian HGSC. Importantly, YAP was overexpressed in inflammatory and cancerous fallopian tube tissues. Further, overexpression of wild-type YAP, or constitutively active YAP in immortalized FTSECs, induced cell proliferation, migration, colony formation and tumorigenesis. Moreover, the Hippo/YAP and the fibroblast growth factor (FGF) signaling pathways formed an autocrine/paracrine-positive feedback loop to drive the progression of the FTSEC-derived HGSC. Evidence in this study strongly suggests that combined therapy with inhibitors of YAP (such as verteporfin) and FGF receptors (such as BGJ398) can provide a novel therapeutic strategy to treat fallopian tube and ovarian HGSC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carcinogênese/genética , Cistadenocarcinoma Seroso/genética , Neoplasias das Tubas Uterinas/genética , Neoplasias Ovarianas/genética , Fosfoproteínas/genética , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Movimento Celular/genética , Proliferação de Células/genética , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/patologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias das Tubas Uterinas/patologia , Tubas Uterinas/metabolismo , Tubas Uterinas/patologia , Feminino , Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Fatores de Crescimento de Fibroblastos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Gradação de Tumores , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Compostos de Fenilureia/administração & dosagem , Fosfoproteínas/antagonistas & inibidores , Porfirinas/administração & dosagem , Pirimidinas/administração & dosagem , Transdução de Sinais/genética , Fatores de Transcrição , Verteporfina , Proteínas de Sinalização YAP
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