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1.
Food Chem ; 371: 131123, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34555706

RESUMO

The anabolism of aroma volatiles in response to non-biological factors during the drying process of shiitake mushrooms was analyzed. Temperatures (40 °C, 50 °C, and 60 °C) had secondary activation effects on the synthetase activity. The enzymatic reaction time could last 4-5 h under medium-temperature drying process (40 °C and 50 °C), and 1.5-2 h under a high-temperature drying process (60 °C and 70 °C). The aroma synthesis dominated by non-enzymatic reactions were chemical reactions between amino acids and reducing sugars. The hot-air drying process of shiitake mushroom was consistent with the cubic model and the key control points influencing the enzymatic reaction parameters were in the order of moisture rate > temperature > drying time > drying rate. The non-enzymatic reaction parameters were in the order of temperature > drying time > drying rate > moisture rate. The total sulfur volatiles produced in the optimized process were significantly higher, and the drying time of the process could be completed within 6 h.


Assuntos
Cogumelos Shiitake , Dessecação , Conservação de Alimentos , Odorantes/análise , Enxofre
2.
Int J Biol Macromol ; 191: 996-1005, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34597698

RESUMO

In the present study, effects of maturity stage on structural characteristics and biosynthesis/hydrolysis-associated genes expression of glucans from Volvariella volvacea fruit body were well investigated. Elongation and pileus expansion stages decreased total soluble carbohydrate and protein contents to 17.09 mg/g and 8.33 mg/g, and significantly accumulated the total amino acids contents to 32.37 mg/g. Yields of crude polysaccharides significantly increased to 8.12% at egg stage and decreased to 3.72% at pileus expansion stage. Purified VVP I-a and VVP I-b were proved to be α-glucans. The maturity process affected the monosaccharide compositions, decreased the molecular weights of VVP I-a and VVP I-b with decreased transcription levels of glucan biosynthesis-associated enzyme genes vvugp and vvgls and increased glucan hydrolysis-associated glucanase gene vvexg2 expression with no significant effects on backbone structures including glycosidic linkages and configurations. The findings would benefit for understanding change patterns of V. volvacea glucan structures and their biosynthesis/hydrolysis-associated genes expression at maturity stages.

3.
J Phys Chem A ; 125(40): 8882-8890, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34607427

RESUMO

Photodissociation dynamics of the jet-cooled vinoxy radical (CH2CHO) via the B̃2A″ state was studied in the near-ultraviolet (near-UV) region of 308-328 nm using high-n Rydberg H atom time-of-flight (HRTOF) and resonance-enhanced multiphoton ionization (REMPI) techniques. The vinoxy radical beam was produced by 193 nm photolysis of ethyl vinyl ether followed by supersonic expansion. The H + CH2CO product channel was observed directly in the H atom TOF spectra. The H atom photofragment yield (PFY) spectra were obtained by integrating the H atom TOF spectra and measuring the H atom REMPI signals, and showed several vibronic bands of the B̃2A″ state. The translational energy distributions of the H + CH2CO products, P(ET)'s, were obtained at several vibronic transitions. The P(ET) distributions were broad, peaking at a low energy of ∼3500 cm-1. The product translational energy release was moderate; the average translational energy release in the maximum available energy, ⟨fT⟩, was in the range of 0.24-0.27. The product angular distributions in this wavelength region were slightly anisotropic, with the ß parameter in the range of 0.10-0.24. The near-UV photodissociation mechanism of the H + CH2CO product channel of the vinoxy radical is consistent with unimolecular dissociation on the electronic ground state (X̃2A″) following internal conversion from the B̃2A″ state to the Ã2A' state and then to the X̃2A″ state (although unimolecular dissociation from the first excited Ã2A' may also contribute).

4.
Clin Cancer Res ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598946

RESUMO

PURPOSE: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic BRCA1 or BRCA2 (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA+), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in patients with BRCA+ mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2. PATIENTS AND METHODS: Patients had progressed after next-generation androgen receptor-directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized. RESULTS: TRITON2 enrolled 115 patients with BRCA+ identified by central plasma (n = 34), central tissue (n = 37), or local (n = 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the 3 assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different from patients identified as BRCA+ by tissue testing. CONCLUSIONS: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA+ mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.

5.
Urol Oncol ; 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34426068

RESUMO

BACKGROUND: Clinical trials have not shown a significant overall survival (OS) difference between chemotherapy and immunotherapy as first-line agents in metastatic urothelial carcinoma (UC). However, the generalizability of these findings in a real-world setting has not yet been evaluated in comparative effectiveness studies. OBJECTIVE: To assess the effectiveness of first-line immunotherapy compared with chemotherapy regimens on OS in patients with metastatic UC of the bladder. DESIGN, SETTING, AND PARTICIPANTS: This retrospective propensity-matched study identified metastatic bladder UC patients in the National Cancer Database from 2014 to 2017 who received either first-line immunotherapy-monotherapy or multi-agent chemotherapy, and who were not treated on a clinical trial protocol. OUTCOME MEASURES AND ANALYSIS: The primary outcome was OS from the date of diagnosis to date of death or censoring at last follow-up. Patients were stratified into first-line immunotherapy and chemotherapy treatment groups. After 1:1 nearest-neighbor caliper-matching of propensity scores, the survival analysis was conducted using Cox regression modeling and Kaplan-Meier estimates. RESULTS AND LIMITATIONS: A total of 2,796 patients were included in the final study population, and 960 in the matched cohort (480 per treatment group). Utilization of immunotherapy increased over the time period studied as chemotherapy decreased (Immunotherapy: 3%-37%; Chemotherapy: 97%-63%; P < 0.001). In the overall cohort, patients who received first-line immunotherapy were older and more comorbid than those who received first-line chemotherapy (Age: 73 v. 67, respectively, P < 0.001; Charlson-Deyo score ≥2: 17% v. 11.5%, respectively, P < 0.001). In the matched cohort, patients who were treated with first-line immunotherapy had similar OS to those who were treated with first-line chemotherapy (HR: 0.91, 95CI 0.72-1.15). Due to the retrospective nature of the study, interpretation is limited by potential selection bias from unmeasured confounding. CONCLUSIONS AND RELEVANCE: Metastatic bladder UC patients who received first-line immunotherapy had similar OS to those who received first-line chemotherapy.

6.
J Refract Surg ; 37(8): 538-544, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34388073

RESUMO

PURPOSE: To analyze the results of new intraocular lens (IOL) formulas (Emmetropia Verifying Optical [EVO], Kane, Olsen, and Barrett Universal II), traditional formulas (Haigis and SRK/T), and modified Wang-Koch axial length adjustment formulas with the SRK/T and Holladay 1 (SRK/Tmodified-W/K and H1modified-W/K) in Chinese patients with long eyes. METHODS: In this retrospective case series, patients with an axial length of 26 mm or greater having uneventful femtosecond laser-assisted cataract surgery with one trifocal IOL model were enrolled. The actual postoperative spherical equivalent of the manifest refraction was compared with the formula-predicted refraction based on the implanted IOL power. A subgroup analysis was performed based on the axial length. RESULTS: A total of 113 eyes was enrolled. Using User Group for Laser Interference Biometry constants, the modified Wang-Koch formulas had the lowest percentage of eyes with hyperopic outcomes. The Barrett Universal II, Olsen, Kane, and EVO 2.0 formulas produced a statistically lower median absolute error than the SRK/Tmodified-W/K and SRK/T formulas (P < .05). The Barrett Universal II formula produced higher percentages of eyes within ±0.50 diopters (D) of the prediction error than the SRK/T formula (P < .05). In eyes with axial lengths of less than 28 mm, there were no significant differences in the prediction accuracy of the eight formulas. In eyes with axial lengths of 28 mm or greater, the new IOL formulas yielded the lowest median absolute error, followed by the H1modified-W/K and Haigis formulas. The SRK/Tmodified-W/K formula had the highest mean absolute error and the lowest percentages of eyes within ±0.25 and ±0.50 D of endpoint. The traditional formulas yielded the highest risk of refractive surprise. CONCLUSIONS: All formulas achieved good results in eyes with axial lengths of less than 28 mm with trifocal IOL implanted. The newer formulas tend to produce better outcomes for eyes with high myopia. The SRK/Tmodified-W/K formula provided improved accuracy only in eyes with axial lengths of 30 mm or greater. [J Refract Surg. 2021;37(8):538-544.].


Assuntos
Lentes Intraoculares , Miopia , Facoemulsificação , Comprimento Axial do Olho , Biometria , Humanos , Implante de Lente Intraocular , Miopia/cirurgia , Óptica e Fotônica , Refração Ocular , Estudos Retrospectivos , Acuidade Visual
7.
ACS Appl Mater Interfaces ; 13(33): 39446-39457, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34387085

RESUMO

Step-scheme (S-scheme) photocatalysts have been proposed for highly efficient charge separation and strong redox activity in the photocatalysis field. Here, we reported a facile strategy to obtain the S-scheme heterojunction composite TiO2/chlorophyll (Chl). The S-scheme heterojunction enables the significant improvement of electron transfer efficiency at the interfacial heterojunction of TiO2/Chl. Also, the lifted conduction band and valence band of TiO2/Chl resulted in more than 1.61 times generation of reactive oxidizing species, compared to that of bare TiO2. In addition, TiO2/Chl was applied as a photocatalytic bactericidal material to fabricate commercial masks for prolonged life span of the mask. The TiO2/Chl-coated mask filter exhibited excellent bactericidal effect on Escherichia coli under light illumination (2.94 × 107 cfu E. coli were killed by 1 cm-2 coated mask filters within illumination of 3 h), while commercial mask filters showed no bactericidal effect. After three circulation-sterilization tests, the TiO2/Chl-made mask filter maintained the initial bactericidal effect, which greatly extended the life span of the mask that presents a promising strategy to alleviate the supply stress of masks.


Assuntos
Antibacterianos/química , Clorofila/química , Nanocompostos/química , Titânio/química , Antibacterianos/farmacologia , Catálise , Escherichia coli/efeitos dos fármacos , Humanos , Luz , Máscaras , Oxirredução , Processos Fotoquímicos , Esterilização/métodos , Nanomedicina Teranóstica
8.
Cardiovasc Intervent Radiol ; 44(11): 1755-1762, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34312688

RESUMO

PURPOSE: The management of Renal cell carcinoma (RCC) patients with liver metastases is challenging. Liver-directed therapy, such as Transarterial radioembolization (TARE), is a reasonable option for these patients; however, its safety and efficacy are not well characterized. This study evaluated the safety and efficacy of TARE in patients with liver-dominant metastatic RCC. MATERIALS AND METHODS: This is a retrospective, single-center study. Thirty-eight patients' medical records were reviewed who underwent TARE between January 1, 2009, and December 31, 2019, in a tertiary cancer center. Two were excluded from further analysis. Thirty-six patients received 51 TARE treatments. Median follow-up time was 18.2 months. Imaging data were evaluated using mRECIST or RECIST 1.1 criteria. Toxicities, treatment responses, liver progression-free survival (LPFS), and median overall survival (OS) were calculated. Univariate and multivariate analyses were conducted to reveal predictors of OS. RESULTS: Median OS from TARE was 19.3 months (95% CI, 22.6-47.4) and from diagnosis of liver metastases was 36.5 months (95% CI: 26.4-49.8). Mild, grade 1 or 2, biochemical toxicity developed in 27 patients (75%). Grade 3-4 toxicity was noted in two patients (5.5%). The objective response rate was 89%; the disease control rate was 94% (21 complete response, 11 partial response, two stable disease, and two progressive disease). Univariate and multivariate analyses showed longer survival in patients who had objective response, lower lung shunt fraction, and better baseline liver function. CONCLUSIONS: TARE is safe and effective and led to promising overall survival in patients with liver-dominant metastatic RCC. LEVEL OF EVIDENCE: Level 3, retrospective cohort study.


Assuntos
Carcinoma Hepatocelular , Carcinoma de Células Renais , Embolização Terapêutica , Neoplasias Renais , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/radioterapia , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/terapia , Fígado , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Estudos Retrospectivos , Resultado do Tratamento , Radioisótopos de Ítrio/uso terapêutico
9.
J Phys Chem Lett ; 12(28): 6582-6588, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34242507

RESUMO

By examining the product-state distribution of a prototypical nonadiabatic predissociation system, HCO(Ã2A″-X̃2A'), we demonstrate that the dissociation dynamics is strongly modulated by parent rotational quantum numbers. The predissociation of the nominal (νC-H = 0, νbend, νC-O = 1) vibronic levels of the Ã2A″ state surprisingly gives rise to both vibrational ground and excited states of the CO product, despite the assumed spectator nature of the CO moiety. This anomaly is attributed to the dependence of the lifetime of the vibronic resonance facilitated by the Renner-Teller interaction on the parent rotational angular momentum quantum numbers coupled with transient intensity borrowing from nearby vibronic resonances with νC-O = 0. This unique phenomenon is a purely quantum mechanical behavior that has no classical analogue.

10.
Neoplasia ; 23(9): 851-858, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34298234

RESUMO

Abiraterone acetate (AA) has been proven effective for metastatic castration-resistant prostate cancer (mCRPC), and it has been proposed that adaptive AA may reduce toxicity and prolong time to progression, when compared to continuous AA. We developed a simple quantitative model of prostate-specific antigen (PSA) dynamics to evaluate prostate cancer (PCa) stem cell enrichment as a plausible driver of AA treatment resistance. The model incorporated PCa stem cells, non-stem PCa cells and PSA dynamics during adaptive therapy. A leave-one-out analysis was used to calibrate and validate the model against longitudinal PSA data from 16 mCRPC patients receiving adaptive AA in a pilot clinical study. Early PSA treatment response dynamics were used to predict patient response to subsequent treatment. We extended the model to incorporate metastatic burden and also investigated the survival benefit of adding concurrent chemotherapy for patients predicted to become resistant. Model simulations demonstrated PCa stem cell self-renewal as a plausible driver of resistance to adaptive therapy. Evolutionary dynamics from individual treatment cycles combined with metastatic burden measurements predicted patient response with 81% accuracy (specificity=92%, sensitivity=50%). In those patients predicted to progress, simulations of the addition of concurrent chemotherapy suggest a benefit between 1% and 11% reduction in probability of progression when compared to adaptive AA alone. This study developed the first mCRPC patient-specific mathematical model to use early PSA treatment response dynamics to predict subsequent responses to adaptive AA, demonstrating the putative value of integrating mathematical modeling into clinical decision making.

11.
Cell Discov ; 7(1): 44, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34127650

RESUMO

The presence of SARS-CoV-2 mutants, including the emerging variant B.1.1.7, has raised great concerns in terms of pathogenesis, transmission, and immune escape. Characterizing SARS-CoV-2 mutations, evolution, and effects on infectivity and pathogenicity is crucial to the design of antibody therapies and surveillance strategies. Here, we analyzed 454,443 SARS-CoV-2 spike genes/proteins and 14,427 whole-genome sequences. We demonstrated that the early variant B.1.1.7 may not have evolved spontaneously in the United Kingdom or within human populations. Our extensive analyses suggested that Canidae, Mustelidae or Felidae, especially the Canidae family (for example, dog) could be a possible host of the direct progenitor of variant B.1.1.7. An alternative hypothesis is that the variant was simply yet to be sampled. Notably, the SARS-CoV-2 whole-genome represents a large number of potential co-mutations. In addition, we used an experimental SARS-CoV-2 reporter replicon system to introduce the dominant co-mutations NSP12_c14408t, 5'UTR_c241t, and NSP3_c3037t into the viral genome, and to monitor the effect of the mutations on viral replication. Our experimental results demonstrated that the co-mutations significantly attenuated the viral replication. The study provides valuable clues for discovering the transmission chains of variant B.1.1.7 and understanding the evolutionary process of SARS-CoV-2.

12.
Nat Rev Urol ; 18(9): 543-555, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34183833

RESUMO

The advent of immune checkpoint inhibition (ICI) has transformed the treatment paradigm for bladder cancer. However, despite the success of ICI in other tumour types, the majority of ICI-treated patients with bladder cancer failed to respond. The lack of efficacy in some patients could be attributed to a paucity of pre-existing immune reactive cells within the tumour immune microenvironment, which limits the beneficial effects of ICI. In this setting, strategies to attract lymphocytes before implementation of ICI could be helpful. Oncolytic virotherapy is thought to induce the release of damage-associated molecular patterns, eliciting a pro-inflammatory cytokine cascade and stimulating the activation of the innate immune system. Concurrently, oncolytic virotherapy-induced oncolysis leads to further release of neoantigens and subsequent epitope spreading, culminating in a robust, tumour-specific adaptive immune response. Combination therapy using oncolytic virotherapy with ICI has proven successful in a number of preclinical studies and is beginning to enter clinical trials for the treatment of both non-muscle-invasive and muscle-invasive bladder cancer. In this context, understanding of the mechanisms underpinning oncolytic virotherapy and its potential synergism with ICI will enable clinicians to effectively deploy oncolytic virotherapy, either as monotherapy or as combination therapy in the different clinical stages of bladder cancer.

13.
Toxicol Res (Camb) ; 10(3): 531-541, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34141167

RESUMO

The use of natural substances derived from traditional Chinese medicine and natural plants as safe radiosensitizing adjuvants is a new trend for cancer radiotherapy. Ganoderma lucidum has been used as a traditional Chinese medicine with a history of more than 2000 years. Ganoderic acid T (GAT) is a typical triterpene of G. lucidum, which has strong cytotoxicity to cancer cells, but whether it has radiation sensitization effect has not been explored. In this work, we treated the HeLa cells with different concentrations of GAT before exposure to gamma-ray radiation and investigated its influence on the radiosensitivity. The cell viability, apoptosis rate, necoptosis rate, intracellular ATP level, cell cycle, the amount of H2AX and 53BP1, reactive oxygen species, and mitochondrial membrane potential were examined. Apoptotic, necroptotic, and autophagic biomarker proteins, including caspase 8, cytochrome c, caspase 3, RIPK, MLKL, P62, and LC3, were analyzed. As a result, we confirmed that with treatment of GAT, the gamma-ray radiation induced both apoptosis and necroptosis in HeLa cells, and with increase of GAT, the percentage ratio of necroptosis was increased. The involved pathways and mechanisms were also explored and discussed.

14.
J Phys Chem A ; 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34133143

RESUMO

The ultraviolet (UV) photodissociation dynamics of the jet-cooled cyclohexyl (c-C6H11) radical is studied using the high-n Rydberg atom time-of-flight (HRTOF) technique. The cyclohexyl radical is produced by the 193 nm photodissociation of chlorocyclohexane and bromocyclohexane and is examined in the photolysis wavelength region of 232-262 nm. The H-atom photofragment yield (PFY) spectrum contains a broad peak centered at 250 nm, which is in good agreement with the UV absorption spectrum of the cyclohexyl radical and assigned to the 3p Rydberg states. The translational energy distributions of the H-atom loss product channel, P(ET)'s, are bimodal, with a slow (low ET) component peaking at ∼6 to 7 kcal/mol and a fast (high ET) component peaking at ∼44-48 kcal/mol. The fraction of the average translational energy in the total excess energy, ⟨fT⟩, is in the range of 0.16-0.25 in the photolysis wavelength region of 232-262 nm. The H-atom product angular distribution of the slow component is isotropic, while that of the fast component is anisotropic with an anisotropy parameter of ß ≈ 0.5-0.7. The bimodal product translational energy and angular distributions indicate two dissociation pathways to the H + C6H10 products in cyclohexyl. The high-ET anisotropic component is from a repulsive, prompt dissociation on a repulsive potential energy surface coupling with the Rydberg excited states to produce H + cyclohexene. The low-ET isotropic component is consistent with the unimolecular dissociation of hot radical on the ground electronic state after internal conversion from the Rydberg states. The similarity of the photodissociation dynamics of the cyclohexyl radical to the previously studied small linear and branched alkyls expands on the understanding of the dissociation dynamics of alkyl radicals to include larger cyclic alkyl radicals.

15.
JAMA Netw Open ; 4(5): e2111329, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-34032854

RESUMO

Importance: Clinical trials have shown an overall survival (OS) benefit associated with first-line immunotherapy (IT) and combination targeted therapy (TT) and IT regimens compared with TT among patients with metastatic clear cell renal cell carcinoma (RCC). Generalizability of these findings in a real-world cohort outside of a clinical trial setting is unclear. Objective: To assess the association of first-line TT, IT, and combination TT and IT regimens with OS in a real-world cohort of patients with metastatic clear cell RCC. Design, Setting, and Participants: This retrospective propensity-matched cohort study identified 5872 patients with metastatic clear cell RCC in the National Cancer Database from January 1, 2015, to December 31, 2017, who received first-line TT, IT, or combination TT and IT and were not treated on a clinical trial protocol. Patients were stratified by first-line systemic treatment. Statistical analysis was conducted from October 1 to December 1, 2020. Main Outcomes and Measures: The primary outcome was OS from the date of diagnosis to death or censoring at last follow-up. After 1:1:1 nearest-neighbor caliper matching of propensity scores, survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates. Results: The final study population included 5872 patients (TT group: n = 4755 [81%]; 3332 men [70%]; median age, 64 years [interquartile range, 57-71 years]; IT group: n = 638 [11%]; 475 men [74%]; median age, 61 years [interquartile range, 54-69 years]; and combination TT and IT group: n = 479 [8%]; 321 men [67%]; median age, 62 years [interquartile range, 55-69 years]), and the matched cohort included 1437 patients (479 per treatment group). Patients in the IT and combination TT and IT groups were younger than those in the TT group, had fewer comorbid conditions (Charlson-Deyo score of 0, 480 of 638 [75%] in the TT group, 356 of 479 [74%] in the IT group, and 3273 of 4755 [69%] in the combination TT and IT group), and were more often treated at academic centers (315 of 638 [49%], 216 of 479 [45%], and 1935 of 4755 [41%], respectively). Both first-line IT and combination TT and IT were associated with improved OS compared with first-line TT for patients with metastatic clear cell RCC (IT group: hazard ratio [HR], 0.60 [95% CI, 0.48-0.75]; P < .001; combination TT and IT group: HR, 0.74 [95% CI, 0.60-0.91]; P = .005). No survival difference was seen between the IT and combination TT and IT groups (combination TT and IT: HR, 1.24 [95% CI, 0.98-1.56]; P = .08). Conclusions and Relevance: This study suggests that both first-line IT and combination TT and IT were associated with improved OS compared with first-line TT for patients with metastatic clear cell RCC. These findings are similar to those identified in recently reported clinical trials, lending confidence to the broader applicability of these findings outside of a clinical trial setting.

16.
J Urol ; 206(4): 924-932, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34032503

RESUMO

PURPOSE: Patients with muscle invasive bladder cancer (MIBC) of variant histology have a poor prognosis. It is unclear if neoadjuvant chemotherapy prior to radical cystectomy is associated with pathological downstaging or improved overall survival (OS) for patients with variant histology. Our objective was to assess for associations between receipt of neoadjuvant chemotherapy, pathological downstaging and OS for patients with variant histology MIBC. MATERIALS AND METHODS: Patients were identified in the National Cancer Database from 2004 to 2017 with MIBC, without metastases, who underwent radical cystectomy. Patients were stratified by histological subgroup, and receipt or nonreceipt of neoadjuvant chemotherapy. Pathological downstaging was defined as pT0N0 or pT ≤1N0, and OS from the time of diagnosis to date of death or censoring at last followup. Multivariable logistic regression analysis determined associations between neoadjuvant chemotherapy and pathological downstaging. Multivariable Cox regression analysis determined associations between neoadjuvant chemotherapy and OS. RESULTS: A total of 31,218 patients were included in the final study population (urothelial carcinoma [UC]: 27,779; sarcomatoid UC: 501; micropapillary UC: 418; squamous cell carcinoma: 1,141; neuroendocrine carcinoma: 629; adenocarcinoma: 750). Neoadjuvant chemotherapy was associated with pathological downstaging to pT0N0 in all histological subgroups (UC: OR 5.1 [4.6-5.6]; sarcomatoid UC: OR 13.8 [5.5-39.0]; micropapillary UC: OR 9.7 [2.8-46.8]; squamous cell carcinoma: OR 7.4 [2.1-24.5]; neuroendocrine: OR 4.7 [2.6-9.2]; adenocarcinoma: OR 23.3 [8.0-74.2]). Neoadjuvant chemotherapy was associated with improved OS for UC (HR 0.8 [0.77-0.84]), sarcomatoid UC (HR 0.64 [0.44-0.91]) and neuroendocrine carcinoma (HR 0.55 [0.43-0.70]). CONCLUSIONS: Neoadjuvant chemotherapy was associated with pathological downstaging for all MIBC histological variants, with improved OS for patients with UC, sarcomatoid variant UC and neuroendocrine carcinoma.


Assuntos
Cistectomia , Músculos/efeitos dos fármacos , Terapia Neoadjuvante/estatística & dados numéricos , Neoplasias da Bexiga Urinária/terapia , Bexiga Urinária/patologia , Idoso , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Terapia Neoadjuvante/métodos , Invasividade Neoplásica/diagnóstico , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento , Bexiga Urinária/efeitos dos fármacos , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
17.
Int J Med Mushrooms ; 23(3): 43-53, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33822498

RESUMO

Ganoderma lucidum mycelia are rich in active substances such as triterpenoids and sterols. However, reports on the development of effective submerged fermentation processes are lacking and the resulting total triterpene and sterol yield is still quite low. In this study, a new G. lucidum strain G0017 mycelium isolated by screening was studied in a 3-L fermenter to investigate the effect of aeration rate in liquid submerged fermentation production of triterpenoids and sterols. By fitting the specific mycelial growth rate and the specific production rate of the triterpenoid and sterol model, an effective multistage aeration rate control process for triterpenoid and sterol fermentation production was developed. This process was validated and proven in 3-L and 50-L fermenters. The resulting yields of triterpenoids and sterols were 3.34 and 3.46 g/L, respectively, which were 69.54% and 75.63% higher than the fixed aeration rate of 1.50 volume of air per volume of liquid per minute. This optimized fermentation production process conceivably could be applied to larger-scale industrial production and perhaps also to improve liquid submerged fermentation processes with relevant edible and medicinal mushrooms.


Assuntos
Agaricales/química , Reishi , Esteróis/metabolismo , Triterpenos/metabolismo , Fermentação , Micélio/crescimento & desenvolvimento
18.
Am Health Drug Benefits ; 14(1): 15-20, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33841621

RESUMO

Background: The use of a novel strategy known as adaptive abiraterone therapy based on mathematical modeling of evolutionary dynamics of tumor subpopulations was shown in a clinical trial to extend the time to disease progression in patients with metastatic castration-resistant prostate cancer (CRPC) and reduced the use of abiraterone therapy. Although the clinical impact of adaptive abiraterone treatment is clear, the economic impact of this strategy has not been investigated. Objective: To compare the cost of care with adaptive abiraterone therapy versus standard continuous abiraterone therapy in patients with metastatic CRPC, using patient billing data. Methods: We performed a retrospective review of billing data for patients with metastatic CRPC who received abiraterone treatment at a large cancer center between June 1, 2012, and August 31, 2018. Patients were divided into 2 groups based on whether they received adaptive abiraterone therapy (N = 15) or continuous abiraterone therapy (N = 21). All patients with refractory, metastatic prostate cancer after castration that was indicated for abiraterone therapy were eligible for this study. Each patient in the adaptive abiraterone therapy cohort received abiraterone plus prednisone treatment until the patient reached a target threshold of 50% or more reduction in prostate-specific antigen (PSA) level compared with his PSA level before abiraterone therapy; treatment was then suspended until the PSA level rose above the 50% of PSA before abiraterone therapy target threshold. The continuous therapy cohort received abiraterone plus prednisone daily until radiographic progression. The primary outcomes were the mean annual cost of care per patient, including and excluding the cost of abiraterone, and the cost of care, by clinical category. Results: The median time to disease progression was 25.8 months for patients who received adaptive abiraterone therapy compared with 12.1 months for patients who received continuous abiraterone therapy. Overall, the mean total, including the cost of drug, annual cost per patient who received adaptive abiraterone therapy was $79,093 compared with $146,782 for patients who received continuous abiraterone therapy (P <.0001). The annual cost of care per patient, excluding the cost of abiraterone, was $13,883 for those who received adaptive therapy versus $22,322 for those who received continuous abiraterone therapy (P = .2757), which was not statistically significant. Conclusion: Practical precision medicine strategies, such as adaptive abiraterone treatment or pharmacogenomics-targeted dosing, can use known biomarkers, such as PSA, to tailor therapy, generate improved outcomes, and reduce costs without the need for novel drug and diagnostic discovery and development. The results of this study suggest that a large clinical study of adaptive abiraterone therapy is warranted to validate the potential of this strategy to extend the time to disease progression and reduce costs of treatment of metastatic CRPC.

19.
Food Sci Nutr ; 9(4): 2247-2256, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33841840

RESUMO

Aroma is an important factor affecting mushroom character and quality. According to the different reaction pathway, the key aroma metabolites (sulfur and eight-carbon volatiles) formation can be classified into enzymatic reactions and nonenzymatic reactions. Aroma volatiles are generated from precursors via the biocatalytic activities of various synthases during the growth stages of shiitake mushrooms. Understanding the specific relationships between the key aroma metabolites and their synthases is key to improving shiitake mushroom quality. At the same time, to reduce forest logging and burning of agricultural by-products in farmland, agricultural by-products have been applied to shiitake mushroom cultivation. Nevertheless, how to further improve the production of aroma volatiles in mushroom cultivated with agricultural waste is still a challenge. In order to understand the biosynthesis of volatiles via enzymatic reactions and screen the agricultural by-products that can improve the production of aroma volatiles in mushroom cultivation, the mechanism of producing aroma volatiles needs to be further elucidated. In this study, the activities and gene expression levels of the key synthases involved in volatile metabolism, the contents of key aroma volatiles, and the correlations between related synthetase, volatiles, and cultivation substrate (CS) were investigated. Network models for visualizing the links between synthetase, volatiles, and CSs were built through partial least squares (PLS) regression analysis. The correlation coefficients among three related synthetase and enzymatic gene expression were high, and the combined effects of multiple synthetase promoted the production of volatiles. PLS analysis showed that the corncob and corn meal were more related to the production of volatiles and synthetase gene expression, and they can be added to the CSs as flavor promoting substances. The enrichment of key aroma volatiles in shiitake mushroom cultivated by the gradient of 20% corn meal combination CS was noticeable.

20.
Phys Chem Chem Phys ; 23(16): 9804-9813, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33908508

RESUMO

Thermal decomposition of cyclohexane at temperatures up to 1310 K was performed using flash pyrolysis coupled with vacuum ultraviolet (118.2 nm) photoionization time-of-flight mass spectrometry. The experimental results revealed that the major initiation reaction of cyclohexane decomposition was C-C bond fission leading to the formation of 1,6-hexyl diradical. The 1,6-hexyl diradical could isomerize to 1-hexene and decompose into ˙C3H7 + ˙C3H5 and ˙C4H7 + ˙C2H5. The 1,6-hexyl diradical could also undergo direct dissociation; the C4H8 fragment via the 1,4-butyl diradical intermediate was observed, serving as evidence of the 1,6-hexyl diradical mechanism. Quantum chemistry calculations at UCCSD(T)/cc-pVDZ level of theory on the initial reaction pathways of cyclohexane were performed and found to be consistent with the experimental conclusions. Cyclohexyl radical was not observed as an initial intermediate in the pyrolysis. Benzene was produced from sequential H2 eliminations of cyclohexane at high temperatures.

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