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1.
Artigo em Inglês | MEDLINE | ID: mdl-34788530

RESUMO

Given the prominent success of the Ga gradient in CuIn1-xGaxSe2 (CIGSe) solar cells, Ge gradient implementation is a promising way to boost Cu2ZnSn(S,Se)4 (CZTSSe) solar cells. However, Ge-graded CZTSSe solar cells only possess a low efficiency of 9.2%, far from that of Ge-incorporated CZTSSe without a gradient (12.3%). Herein, we demonstrated a shallow Ge gradient CZTSe solar cell with an improved efficiency over 10%. The Ge gradient was achieved through a GeSe2-Se coselenization process, where GeSe2 acts as a low-temperature fluxing agent to assist crystallization and induce Ge transport toward the back interface. The relieved band tails and improved junction quality, leading to a better carrier separation, were found to take a primary responsibility for device improvement. These results highlight a remarkable breakthrough for Ge-graded CZTSe solar cells and offer a promising way to develop Ge-involved solar cells.

2.
ACS Appl Mater Interfaces ; 13(41): 49254-49265, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34633173

RESUMO

Membrane biofouling has long been a major obstacle to highly efficient water treatment. The modification of the membrane surface with hydrophilic materials can effectively enhance biofouling resistance. However, the water flux of the membranes is often compromised for the improvement of antifouling properties. In this work, a composite membrane composed of a zwitterionic hydrogel and electrospinning fibers was prepared by a spin-coating and UV cross-linking process. At the optimum conditions, the composite membrane could effectively resist the biofouling contaminations, as well as purify polluted water containing bacteria or diatoms with a high flux (1349.2 ± 85.5 L m-2 h-1 for 106 CFU mL-1 of an Escherichia coli solution). Moreover, compared with the commercial poly(ether sulfone) (PES) membrane, the membrane displayed an outstanding long-term filtration performance with a lower water flux decline. Therefore, findings in this work provide an effective antifouling modification strategy for microfiltration membranes and hold great potential for developing antifouling membranes for water treatment.

3.
PLoS Pathog ; 17(7): e1009764, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34297745

RESUMO

Both Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) establish the persistent, life-long infection primarily at the latent status, and associate with certain types of tumors, such as B cell lymphomas, especially in immuno-compromised individuals including people living with HIV (PLWH). Lytic reactivation of these viruses can be employed to kill tumor cells harboring latently infected viral episomes through the viral cytopathic effects and the subsequent antiviral immune responses. In this study, we identified that polo-like kinase 1 (PLK1) is induced by KSHV de novo infection as well as lytic switch from KSHV latency. We further demonstrated that PLK1 depletion or inhibition facilitates KSHV reactivation and promotes cell death of KSHV-infected lymphoma cells. Mechanistically, PLK1 regulates Myc that is critical to both maintenance of KSHV latency and support of cell survival, and preferentially affects the level of H3K27me3 inactive mark both globally and at certain loci of KSHV viral episomes. Furthremore, we recognized that PLK1 inhibition synergizes with STAT3 inhibition to efficiently induce KSHV reactivation. We also confirmed that PLK1 depletion or inhibition yields the similar effect on EBV lytic reactivation and cell death of EBV-infected lymphoma cells. Lastly, we noticed that PLK1 in B cells is elevated in the context of HIV infection and caused by HIV Nef protein to favor KSHV/EBV latency.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Infecções por Herpesviridae/metabolismo , Herpesvirus Humano 8/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Ativação Viral/fisiologia , Latência Viral/fisiologia , Linhagem Celular , Infecções por Vírus Epstein-Barr , Infecções por HIV , Humanos
4.
Artigo em Inglês | MEDLINE | ID: mdl-34250417

RESUMO

Hereditary cancer syndromes infer high cancer risks and require intensive surveillance. Identification of high-risk individuals among patients with colorectal cancer (CRC) needs improvement. METHODS: Three thousand three hundred ten unselected adults who underwent surgical resection for primary invasive CRC were prospectively accrued from 51 hospitals across Ohio between January 1, 2013, and December 31, 2016. Universal Tumor screening (UTS) for mismatch repair (MMR) deficiency was performed for all, and pathogenic germline variants (PGVs) were identified using multigene panel testing (MGPT) in those who met at least one inclusion criterion: MMR deficiency, diagnosed < 50 years, multiple primary tumors (CRC or endometrial cancer), or with a first-degree relative with CRC or endometrial cancer. RESULTS: Five hundred twenty-five patients (15.9%) had MMR deficiency. Two hundred thirty-four of 3,310 (7.1%; 16% of the 1,462 who received MGPT) had 248 PGVs in cancer susceptibility genes. One hundred forty-two (4.3%) had a PGV in an MMR gene, and 101 (3.1%) had a PGV in a non-MMR gene. Ten with Lynch syndrome (LS) also had a non-MMR PGV and were included in both groups. Two (0.06%) had constitutional MLH1 hypermethylation. Of unexplained MMR-deficient patients, 88.4% (76 of 86) had double somatic MMR mutations. Testing for only MMR genes in MMR-deficient patients would have missed 18 non-MMR gene PGVs (7.3% of total PGVs identified). Had UTS been the only method used to screen for hereditary cancer syndromes, 38.6% (91 of 236) would have been missed, including 6.3% (9 of 144) of those with LS. These results have treatment implications as 5.3% (175 of 3,310) had PGVs in genes with therapeutic targets. CONCLUSION: UTS alone is insufficient for identifying a large proportion of CRC patients with hereditary syndromes, including some with LS. At a minimum, 7.1% of individuals with CRC have a PGV and pan-cancer MGPT should be considered for all patients with CRC.

6.
Gynecol Oncol ; 160(1): 161-168, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33393477

RESUMO

OBJECTIVE: Lynch syndrome is the most common cause of inherited endometrial cancer, attributable to germline pathogenic variants (PV) in mismatch repair (MMR) genes. Tumor microsatellite instability (MSI-high) and MMR IHC abnormalities are characteristics of Lynch syndrome. Double somatic MMR gene PV also cause MSI-high endometrial cancers. The aim of this study was to determine the relative frequency of Lynch syndrome and double somatic MMR PV. METHODS: 341 endometrial cancer patients enrolled in the Ohio Colorectal Cancer Prevention Initiative at The Ohio State University Comprehensive Cancer Center from 1/1/13-12/31/16. All tumors underwent immunohistochemical (IHC) staining for the four MMR proteins, MSI testing, and MLH1 methylation testing if the tumor was MMR-deficient (dMMR). Germline genetic testing for Lynch syndrome was undertaken for all cases with dMMR tumors lacking MLH1 methylation. Tumor sequencing followed if a germline MMR gene PV was not identified. RESULTS: Twenty-seven percent (91/341) of tumors were either MSI-high or had abnormal IHC indicating dMMR. As expected, most dMMR tumors had MLH1 methylation; (69, 75.8% of the dMMR cases; 20.2% of total). Among the 22 (6.5%) cases with dMMR not explained by methylation, 10 (2.9% of total) were found to have Lynch syndrome (6 MSH6, 3 MSH2, 1 PMS2). Double somatic MMR PV accounted for the remaining 12 dMMR cases (3.5% of total). CONCLUSIONS: Since double somatic MMR gene PV are as common as Lynch syndrome among endometrial cancer patients, paired tumor and germline testing for patients with non-methylated dMMR tumor may be the most efficient approach for LS screening.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Reparo de Erro de Pareamento de DNA , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Metilação de DNA , Feminino , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/genética , Estadiamento de Neoplasias , Adulto Jovem
7.
Mod Pathol ; 34(2): 438-444, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32792597

RESUMO

Diagnostic testing of pancreatic cyst fluid obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has traditionally utilized elevated carcinoembryonic antigen (CEA) (≥192 ng/ml) and cytomorphologic examination to differentiate premalignant mucinous from benign pancreatic cystic lesions (PCLs). Molecular testing for KRAS/GNAS mutations has been shown to improve accuracy of detecting mucinous PCLs. Using a targeted next-generation sequencing (NGS) panel, we assess the status of PCL-associated mutations to improve understanding of the key diagnostic variables. Molecular analysis of cyst fluid was performed on 108 PCLs that had concurrent CEA and/or cytological analysis. A 48-gene NGS assay was utilized, which included genes commonly mutated in mucinous PCLs such as GNAS, KRAS, CDKN2A, and TP53. KRAS and/or GNAS mutations were seen in 59 of 68 (86.8%) cases with multimodality diagnosis of a mucinous PCL. Among 31 patients where surgical histopathology was available, the sensitivity, specificity, and diagnostic accuracy of NGS for the diagnosis of mucinous PCL was 88.5%, 100%, and 90.3%, respectively. Cytology with mucinous/atypical findings were found in only 29 of 62 cases (46.8%), with fluid CEA elevated in 33 of 58 cases (56.9%). Multiple KRAS mutations at different variant allele frequencies were seen in seven cases favoring multiclonal patterns, with six of them showing at least two separate PCLs by imaging. Among the 6 of 10 cases with GNAS + /KRAS- results, uncommon, non-V600E exon 11/15 hotspot BRAF mutations were identified. The expected high degree of accuracy of NGS detection of KRAS and/or GNAS mutations for mucinous-PCLs, as compared with CEA and cytological examination, was demonstrated. Multiple KRAS mutations correlated with multifocal cysts demonstrated by radiology. In IPMNs that lacked KRAS mutations, the concurring BRAF mutations with GNAS mutations supports an alternate mechanism of activation in the Ras pathway.

8.
Cancers (Basel) ; 12(11)2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33126432

RESUMO

Leukemia-associated alternative splicing of IKZF1 can result in proteins with loss of one to four copies of its N-terminal zinc finger domains (N-ZnF). The best characterized pathogenic splice isoforms, Ik-6 and Ik-8, have been commonly found in BCR-ABL1+ acute lymphoblastic leukemia (ALL) and a subset of BCR-ABL1-like ALL. Infantile and childhood ALL that express these pathogenic IKZF1 isoforms have shown inferior clinical outcomes and can be resistant to tyrosine kinase inhibitors. Using ALL cell lines, we designed and validated a method to detect abnormal IKZF1 transcripts. In the SUP-B15 leukemia cell line, we noted novel IKZF1 transcripts that include both an Ik-6 splice and a transcript with a 14 base pair insertion at the C-terminus. There was also increased IKZF2 protein in SUP-B15 as compared to other ALL lines. Expression of Ik-6 could be suppressed by treatment with the pro-apoptotic type II histone deacetylase inhibitor givinostat. In 17 adult ALL samples, we noted the Ik-6 isoforms in 6 of 15 BCR-ABL1-, and 1 of 2 BCR-ABL1+ cases, with Ik-8 also expressed in one case. Cases with Ik-6 expression showed inferior survival as well as older age at presentation, lower expression of CD10 and more commonly a diploid karyotype.

9.
Hum Pathol ; 103: 34-41, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32652087

RESUMO

It has been observed that some patients with colorectal cancer due to germline or double somatic pathogenic variants in the mismatch repair (MMR) genes may have intact protein expression in their tumors as assessed by immunohistochemistry (IHC). This has been speculated to occur more frequently in Lynch syndrome (LS) cases due to pathogenic missense mutations, leading to expression of a full-length but nonfunctional protein with retained antigenicity. Our goals were to study the frequency of unexpected MMR expression in colorectal cancers among LS cases with missense mutations, LS cases with truncating mutations, as well as cases with double somatic MMR mutations and evaluate if the unexpected MMR expression is more common in certain categories. IHC slides were available for 82 patients with MMR deficiency without methylation, which included 56 LS cases and 26 double somatic MMR mutation cases. Sixteen of 82 MMR-defective cases showed unexpected MMR expression, with 10 cases showing tumor staining weaker than the control and 6 cases (7%) showing intact staining. Unexpected MMR expression was most commonly seen with LS cases with missense mutations (4 of 9, 44%), followed by MMR double somatic mutation cases (7 of 26, 27%), and finally by LS cases with truncating mutations (5 of 47, 11%). Cautious interpretation of MMR IHC is advised when dealing with tumor staining that is weaker than the control regardless of the percentage of tumor staining as these cases may harbor pathogenic MMR gene mutations. Missense mutations may account for some LS cases that may be missed by IHC alone. Strict adherence to proper interpretation of IHC with attention to staining intensity and the status of heterodimer partner protein will prevent many potential misses.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Enzimas Reparadoras do DNA/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais Hereditárias sem Polipose/genética , Enzimas Reparadoras do DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Adulto Jovem
10.
ACS Omega ; 5(20): 11491-11506, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32478238

RESUMO

The purpose of this attempt is to present a new investigation approach to achieve the in situ observation of the microscopic structure and morphology of wax crystals under quiescent and shear conditions. The rheo-microscopy simultaneous measurement system of a rheometer is employed to ensure in situ observation. A multi-angle composite light source is created to obtain a high-quality image. It is demonstrated that the new approach can achieve a better identification and distinction of wax crystals, as well as the outstanding wax boundary delineation. Based on this, some new findings related to the microscopic structure and morphology of wax crystals are elaborated. Additionally, the in situ observations of wax crystals under dynamic cooling at different shear rates are performed. It is noticed from the obtained results that wax crystals and their aggregates exhibit significant stereoscopic structural characters, because of growth of wax crystals and their overlap in 3-D space. Shear can change the morphology of single wax crystals, but hardly destroy the structure or growth. The increase of the shear rate can induce the deformation propensity of wax crystals to flow field. The effect of shear on aggregation of wax crystals depends on the chemical composition and inherent structural properties. Normally, a low rate of shear can promote aggregation, and result in a complicated stereo-structure. Upon increasing the shear rate, two opposite effects simultaneously occur including promotion and inhibition of aggregation. As the shear rate further increases, the destructive effect increases and gradually plays a leading role, causing the wax crystal aggregates exhibit a smaller size and a weaker stereo structure.

11.
Langmuir ; 36(30): 8753-8763, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32551665

RESUMO

A metal-organic framework (MOF)-based antibiofouling hemoadsorbent (PCB-MIL101) was developed through a facile encapsulation of MIL-101(Cr) in zwitterionic poly carboxybetaine (PCB) hydrogel. PCB-MIL101 possessed strong mechanical strength and superior hemocompatibility, ensuring its safety in hemoperfusion applications. In addition, it showed efficient and effective adsorption toward bilirubin (BR), and its maximum adsorption capacity was ∼583 mg g-1. Moreover, due to the protection of antibiofouling PCB hydrogel, PCB-MIL101 showed ability to resist protein adsorption, thus working effectively to remove BR molecules from their binding albumin in biological solutions. The finding in this study provides a novel insight into developing MOF-based hemoadsorbents for the improvement of hemoperfusion therapies.


Assuntos
Estruturas Metalorgânicas , Adsorção , Bilirrubina , Hidrogéis
12.
ACS Appl Mater Interfaces ; 12(23): 25546-25556, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32393019

RESUMO

Adsorption-based hemoperfusion has been widely used to remove toxins from the blood of patients suffering acute liver failure (ALF). However, its detoxification effect has been severely hampered by the unsatisfactory adsorption performance of clinically used porous adsorbents, such as activated carbon (AC) and adsorption resin. Herein, two cage-based metal-organic frameworks (MOFs), PCN-333 (constructed from 4,4,4-s-triazine-2,4,6-triyl-tribenzoic acid (H3TATB) ligands and Al3 metal clusters) and MOF-808 (constructed from 1,3,5-benzenetricarboxylic acid (H3BTC) ligands and Zr6 metal clusters), are introduced for highly efficient hemoperfusion. They possess negligible hemolytic activity and can act as "bilirubin traps" to achieve outstanding adsorption performance toward bilirubin, a typical toxin related to ALF. Notably, PCN-333 shows a record-high adsorption capacity (∼1003.8 mg g-1) among various bilirubin adsorbents previously reported. More importantly, they can efficiently adsorb bilirubin in bovine serum albumin (BSA) solution or even in 100% fetal bovine serum (FBS) due to their high selectivity. Strikingly, the adsorption rate and capacity of PCN-333 in biological solutions are approximately four times faster and 69 times higher than those of clinical AC, respectively. Findings in this work pave a new avenue to overcome the challenge of low adsorption efficiency and capacity in hemoperfusion therapy.


Assuntos
Bilirrubina/isolamento & purificação , Hemoperfusão/métodos , Estruturas Metalorgânicas/química , Adsorção , Animais , Bilirrubina/química , Bovinos , Teoria da Densidade Funcional , Hemólise/efeitos dos fármacos , Estruturas Metalorgânicas/metabolismo , Modelos Químicos , Estudo de Prova de Conceito , Ligação Proteica , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo
13.
Nat Commun ; 11(1): 2037, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32341363

RESUMO

Developing autonomous self-healing materials for applications in harsh conditions is challenging because the reconstruction of interaction in material for self-healing will experience significant resistance and fail. Herein, a universally self-healing and highly stretchable supramolecular elastomer is designed by synergistically incorporating multi-strength H-bonds and disulfide metathesis in polydimethylsiloxane polymers. The resultant elastomer exhibits high stretchability for both unnotched (14000%) and notched (1300%) samples. It achieves fast autonomous self-healing under universal conditions, including at room temperature (10 min for healing), ultralow temperature (-40 °C), underwater (93% healing efficiency), supercooled high-concentrated saltwater (30% NaCl solution at -10 °C, 89% efficiency), and strong acid/alkali environment (pH = 0 or 14, 88% or 84% efficiency). These properties are attributable to synergistic interaction of the dynamic strong and weak H-bonds and stronger disulfide bonds. A self-healing and stretchable conducting device built with the developed elastomer is demonstrated, thereby providing a direction for future e-skin applications.

14.
Lung Cancer ; 143: 60-66, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32208298

RESUMO

OBJECTIVES: This study aimed to evaluate the prognostic and potential therapeutic value of expanded molecular testing of resected early-stage lung ACA. METHODS: We analyzed 324 patients who underwent lobectomy and lymphadenectomy for clinical Stage I&II lung ACA between 2011-2017. Molecular testing was routinely performed, first by PCR-based Sanger sequencing and FISH and then expanded to a 20 and then 50-gene next generation sequencing (NGS) panel. The frequency of mutations by testing method and their association with disease-free (DFS) and overall survival (OS) were tested. RESULTS: A total of 241 patients (74.4%) had at least one somatic mutation detected, with KRAS exon 2 (38.1%) and EGFR (17.9%) being the most common. TP53 was the most frequent co-existing mutation. Detection of at least one mutation increased from 49% with selective PCR/FISH testing to 82% with limited NGS/FISH, and 91% with extended NGS/FISH (p < 0.001). The rate of actionable mutations increased from 18% to 32% and 45% with expansion of molecular testing, respectively (p = 0.001). Using NGS, an additional 10 cases with EGFR mutations, and other rare mutations were found, including BRAF (5.9%), MET (5.6%), ERBB2 (4.1%), PIK3CA (2.3%), and DDR2 (2.1%). The expansion of FISH testing resulted in one additional detection of ROS1 and RET (1%) rearrangement. KRAS mutation was associated with worse DFS (HR 1.87; 95%CI 1.14-3.06) and OS (HR 2.09; 95%CI 1.11-3.92). BRAF mutation detected in NGS tested patients was also associated with decreased DFS (HR3.80; 95%CI 1.46-9.89) and OS (HR 7.37; 95%CI 2.36-22.99) on multivariate analysis. CONCLUSION: The expansion of molecular testing has resulted in a substantial increase in the detection of potentially therapeutically significant mutations in resected early-stage ACA. KRAS and BRAF mutation status by NGS was prognostic for relapse and survival. These data emphasize opportunities for clinical trials in a growing number surgical ACA patients with available targeted therapies.


Assuntos
Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Neoplasias Pulmonares/patologia , Técnicas de Diagnóstico Molecular/métodos , Mutação , Recidiva Local de Neoplasia/patologia , Procedimentos Cirúrgicos Pulmonares/mortalidade , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Idoso , Feminino , Seguimentos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
15.
Clin Cancer Res ; 26(15): 3918-3927, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32209572

RESUMO

PURPOSE: The safety and efficacy of ibrutinib, a once-daily Bruton's tyrosine kinase (BTK) inhibitor, in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was demonstrated in this phase Ib/II study. Extended follow-up up to 8 years is described, representing the longest follow-up for single-agent ibrutinib, or any BTK inhibitor, to date. PATIENTS AND METHODS: Phase Ib/II PCYC-1102 (NCT01105247) and extension study PCYC-1103 (NCT01109069) included patients receiving single-agent ibrutinib in first-line or relapsed/refractory CLL/SLL. RESULTS: Overall response rate was 89%, with similar rates in first-line (87%; complete response, 35%) and relapsed/refractory settings (89%; 10%). Estimated 7-year progression-free survival (PFS) rates were 83% in first-line and 34% in relapsed/refractory settings. Forty-one patients had CLL progression (n = 11 with Richter's transformation). Median PFS was not reached with first-line ibrutinib. In relapsed/refractory CLL/SLL, median PFS was 52 months overall, 26 months in patients with chromosome 17p deletion, 51 months with 11q deletion, not reached with trisomy 12 or 13q deletion, and 88 months in patients without these cytogenetic abnormalities. Estimated 7-year overall survival rates were 84% in first-line and 55% in relapsed/refractory settings. Grade ≥3 adverse events (AE) in >15% of patients were hypertension (28%), pneumonia (24%), and neutropenia (18%). These grade ≥3 AEs generally declined over time, except hypertension. AEs leading to discontinuation in ≥2 patients were observed only in the relapsed/refractory setting (sepsis, diarrhea, subdural hematoma, and Richter's transformation). CONCLUSIONS: With up to 8 years of follow-up, sustained responses and long-term tolerability of single-agent ibrutinib were observed with treatment of first-line or relapsed/refractory CLL/SLL, including high-risk CLL/SLL.

16.
Langmuir ; 36(9): 2396-2402, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32036655

RESUMO

The development of environmentally friendly and long-term marine antifouling coating remains a huge challenge in the maritime industry. For this purpose, we developed a novel and efficient antifouling coating based on a synergistic strategy, incorporating contact inhibition, fouling repelling, and antifouling properties. Results demonstrated that the coating could efficiently resist the adhesion of protein, bacteria, and Navicula diatoms. More importantly, marine field tests showed the coating could efficiently inhibit biofouling for at least 8 months. This approach paves a new way for the development of environmentally friendly and long-term antifouling coating.

17.
Blood Adv ; 4(4): 696-705, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32092139

RESUMO

Acute myeloid leukemia (AML) with either t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22) is referred to as core binding factor (CBF) AML. Although categorized as favorable risk, long-term survival for these patients is only ∼50% to 60%. Mutated (mut) or overexpressed KIT, a gene encoding a receptor tyrosine kinase, has been found almost exclusively in CBF AML and may increase the risk of disease relapse. We tested the safety and clinical activity of dasatinib, a multi-kinase inhibitor, in combination with chemotherapy. Sixty-one adult patients with AML and CBF fusion transcripts (RUNX1/RUNX1T1 or CBFB/MYH11) were enrolled on Cancer and Leukemia Group B (CALGB) 10801. Patients received cytarabine/daunorubicin induction on days 1 to 7 and oral dasatinib 100 mg/d on days 8 to 21. Upon achieving complete remission, patients received consolidation with high-dose cytarabine followed by dasatinib 100 mg/d on days 6 to 26 for 4 courses, followed by dasatinib 100 mg/d for 12 months. Fifteen (25%) patients were older (aged ≥60 years); 67% were CBFB/MYH11-positive, and 19% harbored KITmut. There were no unexpected or dose-limiting toxicities. Fifty-five (90%) patients achieved complete remission. With a median follow-up of 45 months, only 16% have relapsed. The 3-year disease-free survival and overall survival rates were 75% and 77% (79% and 85% for younger patients [aged <60 years], and 60% and 51% for older patients). Patients with KITmut had comparable outcome to those with wild-type KIT (3-year rates: disease-free survival, 67% vs 75%; overall survival, 73% vs 76%), thereby raising the question of whether dasatinib may overcome the negative impact of these genetic lesions. CALGB 10801 was registered at www.clinicaltrials.gov as #NCT01238211.


Assuntos
Leucemia Mieloide Aguda , Adulto , Idoso , Citarabina , Dasatinibe/uso terapêutico , Daunorrubicina , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Indução de Remissão
18.
J Geriatr Oncol ; 11(1): 107-113, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31668825

RESUMO

OBJECTIVE: To demonstrate feasibility of performing geriatric assessment (GA) in the National Clinical Trials Network (NCTN) and to explore the utility of GA to characterize treatment tolerance. MATERIALS AND METHODS: We conducted a multisite companion study (CALGB 361006) to CALGB 11001, a phase 2 trial of adults ≥60 years old with newly diagnosed FLT3- mutated AML, testing the efficacy of adding sorafenib to intensive chemotherapy. On 361006, a GA was administered prior to induction and prior to post-remission therapy. The GA is divided into items requiring administration by a health care professional (HCP) and patient self-administered questionnaires. Feasibility outcomes were recruitment rate, time to GA completion, difficulty with GA administration, percent of patients requiring assistance, and satisfaction. Change in GA measures pre- and post-induction were compared using Wilcoxon signed rank test and McNemar's tests. RESULTS: The recruitment rate was 80% (N = 43, median age 68 years). Median completion time of the GA was 30 min; (10 and 21 min for HCP and patients, respectively). HCP reported no difficulty completing assessments (100%). Most patients completed questionnaires without assistance (77%), and were satisfied with the length (89%). Self-reported physical function, mental health, social activity and nutritional parameters worsened after induction. CONCLUSION: GA is feasible to administer in the setting of intensive induction for older adults with AML in the NCTN and provides evidence of the impact of induction therapy on physical and emotional health.


Assuntos
Avaliação Geriátrica , Leucemia Mieloide Aguda , Atividades Cotidianas , Idoso , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Saúde Mental , Inquéritos e Questionários
19.
J Colloid Interface Sci ; 555: 145-156, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31377640

RESUMO

Resin hemoperfusion is a life-saving treatment for drug intoxication or hepatic failure of patients. However, current resin adsorbents exhibit a limited hemocompatibility or low adsorption efficiency, representing a major roadblock to successful clinical applications. In this work, we developed a hemocompatible and effective hemoadsorbent based on polystyrene resin (H103) microparticles encapsulated in anti-biofouling zwitterionic poly(carboxybetaine) (PCB) hydrogels. Apart from a strong mechanical stability, this PCB-based adsorbent (PCB-H103) exhibited excellent hemocompatibility (hemolysis ratio was ∼0.64%), which was attributed to the anti-biofouling property of PCB hydrogel. In addition, it can efficiently adsorb both small and middle molecular weight molecules in phosphate-buffered saline, and the efficiencies were significantly higher than poly(ethylene glycol) methacrylate-based and poly(2-hydroxyethyl methacrylate)-based adsorbent counterparts, indicating the favorable permeability of PCB hydrogel coating. More importantly, PCB-H103 could effectively remove protein-bound toxins including phenol red and bilirubin in bovine serum albumin solution or even in 100% fetal bovine serum (FBS). In 100% FBS, the adsorption capacity of PCB-H103 towards bilirubin was 8.3 times higher than that of pristine clinical-scale resin beads. Findings in this work may provide a new strategy for the development of modern resin hemoperfusion technology.


Assuntos
Bilirrubina/isolamento & purificação , Materiais Biocompatíveis/química , Fenolsulfonaftaleína/isolamento & purificação , Soroalbumina Bovina/isolamento & purificação , Adsorção , Animais , Bilirrubina/química , Humanos , Hidrogéis/química , Tamanho da Partícula , Fenolsulfonaftaleína/química , Soroalbumina Bovina/química , Propriedades de Superfície
20.
ACS Appl Mater Interfaces ; 11(37): 34330-34337, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31429271

RESUMO

The microdroplets in fog flow have been considered as an important resource for supplying fresh drinking water. Most of the reported works of fog collection focus on the water-collecting ability rather than the environmental reliability of selected materials. In this work, a beetle-inspired hierarchical fog-collecting interface based on the antibacterial needle-array (ABN) and hydrophilic/hydrophobic cooperative structure is displayed. The hydrophilic ABN is coated with zwitterionic carboxybetaine (CB) brushes that endow the fog collector with a long-term cleaning in harsh environment. Due to its strong affinity to water molecules, the tilted needles with a CB coating can facilitate the capture of fog and the rapid delivery of condensed water driven by gravity. After being transported to the connected hydrophobic sheet, the collected droplets can be rapidly detached and stored in the container, achieving a high fog-harvesting rate. Furthermore, CB-patterned channels are integrated on the hydrophobic sheet for the pathway-controlled water delivery. The CB coating is able to efficiently resist bacterial adhesion and contamination during fog harvesting, protecting the device from microbiological corrosion. The current design provides a promising method to incorporate antibacterial ability into fog collectors, which offer great opportunity to develop water harvesters for real-world applications.


Assuntos
Antibacterianos/química , Materiais Biomiméticos/química , Besouros , Agulhas , Animais , Antibacterianos/farmacologia , Materiais Biomiméticos/farmacologia
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