Publications by authors named "Sunmin Lee"

160 Publications

Carfilzomib, Lenalidomide, and Dexamethasone Followed by Lenalidomide Maintenance for Prevention of Symptomatic Multiple Myeloma in Patients With High-risk Smoldering Myeloma: A Phase 2 Nonrandomized Controlled Trial.

JAMA Oncol 2021 Sep 16. Epub 2021 Sep 16.

Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Importance: High-risk smoldering myeloma has a 5-year risk of progression to symptomatic multiple myeloma of approximately 75%. Treatment with lenalidomide decreases the risk of progression; however, novel triplet regimens are superior, and earlier disease may be more treatment sensitive.

Objective: To evaluate the use of carfilzomib, lenalidomide, and dexamethasone (KRd) with lenalidomide maintenance therapy as early intervention in high-risk smoldering myeloma and to determine the rates of minimal residual disease (MRD)-negative complete response (CR).

Design, Setting, And Participants: In this single-arm, single-center, phase 2 nonrandomized controlled trial, responses were evaluated at every cycle during KRd treatment and every 3 cycles subsequently. Bone marrow biopsies and imaging were performed by cycle 8 and then annually. The study enrolled patients from May 29, 2012, to July 23, 2020, at the National Institutes of Health Clinical Center, a highly specialized tertiary cancer center. Patient key eligibility criteria included a diagnosis of high-risk smoldering myeloma based on the Mayo Clinic, Spanish, and/or Rajkumar, Mateos, and Landgren criteria.

Interventions: Patients received eight 4-week cycles of intravenous carfilzomib 36 mg/m2 (first 2 doses, 20 mg/m2), dexamethasone (20 mg, cycles 1-4; 10 mg, cycles 5-8 twice weekly), and lenalidomide 25 mg (days 1-21) followed by twenty-four 28-day cycles of maintenance lenalidomide 10 mg (days 1-21). Stem cell harvest and storage were optional.

Main Outcomes And Measures: The primary outcome was the MRD-negative CR rate. Key secondary outcomes included duration of MRD-negative CR and progression to multiple myeloma.

Results: A total of 54 patients (median age, 59 years [range, 40-79 years]; 30 men [55.6%]; and 2 Asian [3.7%], 15 Black [27.8%], 1 Hispanic [1.9%], and 36 White [66.7%] patients) were enrolled, with a median potential follow-up time of 31.9 months (range, 6.7-102.9 months). The MRD-negative CR rate was 70.4% (95% CI, 56.4%-82.0%), with a median sustained duration of 5.5 years (95% CI, 3.7 years to not estimable). The 8-year probability of being free from progression to multiple myeloma was 91.2% (95% CI, 67.4%-97.9%), and no deaths occurred. Nonhematologic grade 3 adverse events occurred in 21 patients (38.9%) and included thromboembolism, rash, and lung infection, with no grade 4 events.

Conclusions And Relevance: Results of this phase 2 nonrandomized controlled trial suggest that treatment of high-risk smoldering myeloma with novel triplet regimens, such as KRd and lenalidomide maintenance therapy, may alter the natural history of smoldering myeloma by significantly delaying development of end-organ disease. Randomized clinical trials are needed to confirm this favorable benefit-to-risk profile.

Trial Registration: ClinicalTrials.gov Identifier: NCT01572480.
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http://dx.doi.org/10.1001/jamaoncol.2021.3971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446896PMC
September 2021

Metabolite Profiling and Anti-Aging Activity of Rice Fermented with and : A Comparative Study.

Metabolites 2021 Aug 8;11(8). Epub 2021 Aug 8.

Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea.

Rice , used as a starter for maximizing fermentation benefits, produces versatile end products depending on the inoculum microbes used. Here, we performed metabolite profiling to compare rice fermented with two important filamentous fungus, and , during 8 days. The multivariate analyses showed distinct patterns of primary and secondary metabolites in the two s. The rice koji fermented with (RAO) showed increased -glucosidase activity and higher contents of sugar derivatives than the one fermented with (RAC). RAC showed enhanced -glucosidase activity and increased contents of flavonoids and lysophospholipids, compared to RAO. Overall, at the final fermentation stage (8 days), the antioxidant activities and anti-aging effects were higher in RAC than in RAO, corresponding to the increased metabolites such as flavonoids and auroglaucin derivatives in RAC. This comparative metabolomic approach can be applied in production optimization and quality control analyses of products.
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http://dx.doi.org/10.3390/metabo11080524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398186PMC
August 2021

Randomized phase II trial of a first-in-human cancer cell lysate vaccine in patients with thoracic malignancies.

Transl Lung Cancer Res 2021 Jul;10(7):3079-3092

Thoracic Epigenetics Section, Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.

Background: Although most malignancies express cancer-testis antigens (CTA), immune responses to these proteins are limited in thoracic oncology patients. This trial was undertaken to examine if a cancer cell lysate vaccine could induce immunity to CTA, and to ascertain if metronomic cyclophosphamide and celecoxib enhances vaccine-induced immune responses.

Methods: Eleven patients with primary thoracic malignancies and 10 patients with extrathoracic neoplasms metastatic to the chest rendered NED by conventional therapies were randomized to receive H1299 lung cancer cell lysates (10 mg protein/vaccine) with Iscomatrix™ adjuvant via deep intradermal injection q 4 weeks ×6 with or without daily oral metronomic cyclophosphamide/celecoxib. The primary endpoint was serologic response to purified CTA assessed 1 month after the 6 vaccination. Secondary endpoints included assessment of the effects of cyclophosphamide and celecoxib on frequency and magnitude of vaccine-induced immune responses to CTA. Exploratory endpoints included evaluation of the effects of the vaccine regimens on peripheral immune subsets. Standard of care imaging studies were obtained at baseline and 1 month after the 3 and 6 vaccinations.

Results: All patients exhibited local and systemic inflammatory responses lasting 72-96 hours following vaccinations. There were no dose limiting treatment related toxicities. Fourteen patients (67%) completed all six vaccinations. Eight of 14 patients (57%) exhibited serologic responses to NY-ESO-1. One patient developed antibodies to GAGE7; several patients exhibited reactivity to XAGE and MAGE-C2. Vaccine therapy decreased the percent of Tregs (P=0.0068), PD-1 expression on Tregs (P=0.0027), PD-L1 expression on CD14 monocytes (P=0.0089), PD-L1 expression on classical monocytes (P=0.016), and PD-L1 expression on intermediate monocytes (P=0.0031). Cyclophosphamide/celecoxib did not appear to increase immune responses or enhance vaccine-induced alterations in peripheral immune subsets.

Conclusions: H1299 lysate vaccines with Iscomatrix™ induce immune responses to CTA and modulate peripheral immune subsets in a manner that may enhance antitumor immunity in patients with thoracic malignancies.
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http://dx.doi.org/10.21037/tlcr-21-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350099PMC
July 2021

The central role of social support in the health of Chinese and Korean American immigrants.

Soc Sci Med 2021 09 14;284:114229. Epub 2021 Jul 14.

University of California, Irvine, School of Medicine, Department of Medicine, 1001 Health Sciences Rd., Irvine, CA 92617, USA. Electronic address:

Prior research contends that social support positively influences health by optimizing individuals' psychological processes such as appraisals, emotions, and sense of control-known as stress-buffering effects. This study tests this theoretical concept by examining whether the association between social support and health can be explained by the psychological processes of perceived stress and distress among Chinese and Korean American immigrants. Furthermore, we examine what predicts social support in this population, with a particular focus on factors related to immigration. Using a total sample of 400 Chinese and Korean American immigrants, we examine the association between social support and self-rated health (SRH), accounting for demographic factors, socioeconomic status, perceived stress, and perceived distress using multivariable logistic regression models. We conducted a mediation analysis using the Karlson, Holm, and Breen (KHB) method to determine whether perceived stress and distress partly explained the association between social support and SRH. Findings showed a strong total effect of higher social support on better SRH. Furthermore, mediation was detected, with perceived stress and distress explaining 42.98% of the total effect of social support on SRH. Multivariable linear regression models revealed that social support among Chinese and Korean American immigrants was associated with marital status, employment, ethnic identity, and acculturative stress. This study highlights the centrality of social support for Chinese and Korean American immigrants, which lowers perceived stress and distress, leading to better overall health. By confirming these stress-buffering effects, our findings suggest that bolstering social support among vulnerable Chinese and Korean American immigrant populations can have a positive effect on health by optimizing stress appraisals.
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http://dx.doi.org/10.1016/j.socscimed.2021.114229DOI Listing
September 2021

Anti-inflammatory effect of Ailanthus altissima (Mill.) Swingle leaves in lipopolysaccharide-stimulated astrocytes.

J Ethnopharmacol 2021 Jul 13:114258. Epub 2021 Jul 13.

Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul, 06974, Republic of Korea. Electronic address:

Ethnopharmacological Relevance: Activated astrocytes are involved in the progression of neurodegenerative diseases. Traditionally, Ailanthus altissima (Mill.) Swingle, widely distributed in East Asia, has been used as a medicine for the treatment of fever, gastric diseases, and inflammation. Although A. altissima has been reported to play an anti-inflammatory role in peripheral tissues or cells, its role in the central nervous system (CNS) remains unclear.

Aim Of The Study: In the present study, we investigated the anti-inflammatory effects and mechanism of action of A. altissima in primary astrocytes stimulated by lipopolysaccharide (LPS).

Materials And Methods: A nitrite assay was used to measure nitric oxide (NO) production, and the tetrazolium salt 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was performed to determine cytotoxicity. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and mitogen-activated protein kinase (MAPK) were determined with western blotting. Reverse-transcription PCR was used to assess the expression of inflammatory cytokines. The levels of reactive oxygen species were measured using 2,7-dichlorodihydrofluorescein diacetate. Luciferase assay and immunocytochemistry were used for assessing nuclear factor-kappa B (NF-κB) transcription and p65 localization, respectively. Memory and social interaction were analyzed using the Y-maze and three-chamber tests, respectively.

Results: The ethanol extract of A. altissima leaves (AAE) inhibited iNOS and COX-2 expression in LPS-stimulated astrocytes. Moreover, AAE reduced the transcription of various proinflammatory mediators, hindered NF-κB activation, and suppressed extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activation without p38 activation. Ultra-high performance liquid chromatography with mass spectrometry analysis revealed that AAE comprised ethyl gallate, quercetin, and kaempferol, along with luteolin, which has anti-inflammatory properties, and repressed LPS-induced nitrite levels and the nuclear translocation of p65. Finally, oral administration of AAE attenuated LPS-induced memory and social impairment in mice and repressed LPS-induced ERK and JNK activation in the cortices of mice.

Conclusion: AAE could have therapeutic uses in the treatment of neuroinflammatory diseases via suppression of astrocyte activation.
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http://dx.doi.org/10.1016/j.jep.2021.114258DOI Listing
July 2021

Metabolomic-Based Comparison of Traditional and Industrial Samples with Antioxidative Activities.

Foods 2021 Jun 15;10(6). Epub 2021 Jun 15.

Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea.

Numerous varieties of are manufactured by many food companies using different ingredients and fermentation processes, and thus, the qualities such as taste and flavor are very different. Therefore, in this study, we compared many products, specifically, 19 traditional (TD) and 17 industrial (ID). Subsequently, we performed non-targeted metabolite profiling, and multivariate statistical analysis to discover distinct metabolites in two types of . Amino acids, organic acids, isoflavone aglycones, non-DDMP (2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4- one) soyasaponins, hydroxyisoflavones, and biogenic amines were relatively abundant in TD. On the contrary, contents of dipeptides, lysophospholipids, isoflavone glucosides and DDMP-conjugated soyasaponin, precursors of the above-mentioned metabolites, were comparatively higher in ID. We also observed relatively higher antioxidant, protease, and -glucosidase activities in TD. Our results may provide valuable information on to consumers and manufacturers, which can be used while selecting and developing new products.
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http://dx.doi.org/10.3390/foods10061377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232091PMC
June 2021

Effects of the Addition of Herbs on the Properties of Doenjang.

Foods 2021 Jun 7;10(6). Epub 2021 Jun 7.

School of Culinary Arts, Youngsan University, Busan 48015, Korea.

Three types of doenjang, a fermented soybean paste, were prepared by adding coriander (CR), Korean mint (KM), and peppermint (PM) and compared to the control group (CN) by studying their metabolite profiles and antioxidant activities followed by different fermentation periods (1, 30, and 150 days, respectively). The primary metabolome was analyzed by GC-TOF-MS, and 36 of metabolites were identified in four types of doenjang samples (CN, CR, KM, and PM). Samples were clustered based on the herb type and fermentation period in PCA and PLS-DA analysis. For the secondary metabolome analysis, UHPLC-Q-orbitrap-MS was used, and 26 metabolites were identified. The statistical analysis showed that the samples were clustered by herb type rather than fermentation period, and the samples containing KM and PM were located in the same group. The DPPH assay showed that PM-containing doenjang had the highest antioxidant activity. Correlation analysis indicated that organic acids such as lactic acid, malonic acid, succinic acid, uracil, vanillic acid, and quinic acid showed positive correlation with the DPPH activity. Overall, our results demonstrated that incorporating herbs in doenjang during fermentation caused significant shifts (-value < 0.05) in the doenjang metabolites and antioxidant activity. Hence, herbs could be utilized for enhancing doenjang fermentation.
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http://dx.doi.org/10.3390/foods10061307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227189PMC
June 2021

The Influence of Asian Subgroup and Acculturation on Colorectal Cancer Screening Knowledge and Attitudes Among Chinese and Korean Americans.

J Cancer Educ 2021 Jun 9. Epub 2021 Jun 9.

Department of Medicine, School of Medicine, University of California Irvine, 1001 Health Sciences Rd., Irvine, CA, 92617, USA.

Understanding how knowledge and attitudes about colorectal cancer (CRC) screening differs among Asian immigrants is important for informing targeted health interventions aimed at preventing and treating CRC in this diverse population. This study examines how Asian subgroup and acculturation are associated with CRC knowledge and attitudes among Chinese and Korean immigrants in the United States (U.S.). Data come from the baseline survey of a randomized controlled trial to increase CRC screening among Chinese and Korean American immigrants living in the Baltimore-Washington DC Metropolitan Area (n = 400). We use linear regression to examine how Asian subgroup, time in the U.S., English-speaking proficiency, and ethnic identity are associated with CRC knowledge and screening attitudes, accounting for demographic variables, socioeconomic status, and health insurance status. Results show that greater socioeconomic status was associated with higher CRC knowledge, and socioeconomic status explained more of the variance in CRC knowledge than acculturation factors. Additionally, attitudes varied by Asian subgroup, with Chinese reporting lower CRC screening salience, worry, response efficacy, and social influence compared to Koreans. Findings suggest that in-language interventions aimed at increasing CRC knowledge and capitalizing on attitudes about screening can help to bridge disparities in CRC screening by socioeconomic status and country of origin. We discuss implications for future interventions to increase CRC screening uptake among Chinese and Korean immigrants in the U.S.
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http://dx.doi.org/10.1007/s13187-021-02042-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188737PMC
June 2021

Racial Discrimination and Health-Related Quality of Life: An Examination Among Asian American Immigrants.

J Racial Ethn Health Disparities 2021 Jun 4. Epub 2021 Jun 4.

Department of Medicine, School of Medicine, University of California, Irvine, 653 E Peltason Drive, Irvine, CA, 92697, USA.

Objectives: We aimed to examine the relationship between everyday and major racial discrimination with health-related quality of life (HRQOL), which consists of self-rated health, days of poor physical health, mental health, and activity limitation.

Design: In a cross-sectional analytic sample of 524 foreign-born Asian adults, aged 18 years and older, we conducted multivariable logistic regression and multivariable negative binomial regression to examine associations between discrimination and HRQOL. Furthermore, potential effect modification was tested by gender, ethnicity, and social support.

Results: Associations were found between everyday racial discrimination and days of poor physical health (incidence rate ratio, IRR = 1.05), mental health (IRR = 1.03), and activity limitation (IRR = 1.05). Stronger significant associations were observed between major racial discrimination and days of poor physical health (IRR = 1.21), mental health (IRR = 1.16), and activity limitation (IRR = 1.53), adjusting for all covariates. Racial discrimination was not associated with poor self-rated health. In addition, gender significantly modified the relationship between continuous racial discrimination and activity limitation days with associations of greater magnitude among men, while social support significantly modified the association between categorized major racial discrimination and physically unhealthy days. When stratified, the association was only significant among those with low social support (IRR = 3.04; 95% CI: 1.60, 5.79) as opposed to high social support.

Conclusions: This study supports the association between racial discrimination and worse HRQOL among Asian Americans, which can inform future interventions, especially among men and those with low social support, aimed at improving the quality of life in this population.
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http://dx.doi.org/10.1007/s40615-021-01067-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176876PMC
June 2021

Isolation of ssp. LRCC5306 and Optimization of Diacetyl Production Conditions for Manufacturing Sour Cream.

Food Sci Anim Resour 2021 May 1;41(3):373-385. Epub 2021 May 1.

Department of Food Bioscience and Technology, College of Life Science and Biotechnology, Korea University, Seoul 02841, Korea.

The sensory properties and flavor of sour cream are important factors that influence consumer acceptability. The present study aimed to isolate lactic acid bacteria with excellent diacetyl production ability and to optimize the fermentation conditions for sour cream manufacture. ssp. was isolated as a lactic acid bacterium derived from raw milk. This strain showed the greatest diacetyl production among other strains and was named LRCC5306. Various culture conditions were optimized to improve the diacetyl production of LRCC5306. The highest diacetyl production was found to be at 105.04±2.06 mg/L, when 0.2% citric acid and 0.001% Fe were added and cultured at 20°C for 15 h. Based on the optimal cultivation conditions, sour cream was manufactured using LRCC5306, with a viable count of 1.04×10 CFU/g and a diacetyl concentration of 106.56±1.53 mg/g. The electronic tongue system was used to compare the sensory properties of the sour cream; the fermented product exhibited sweetness and saltiness which was similar to that of an imported commercial product, but with slightly reduced bitterness and a significantly greater degree of sour taste. Therefore, our study shows that if cream is fermented using the LRCC5306, it is possible to produce sour cream with greatly improved sensory attractiveness, resulting in increased acceptance by consumers. Since this sour cream has a higher viable count of lactic acid bacteria, it is also anticipated that it will have a better probiotic effect.
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http://dx.doi.org/10.5851/kosfa.2021.e3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112315PMC
May 2021

Isolation of the Cholesterol-Assimilating Strain LRCC5307 and Production of Low-Cholesterol Butter.

Food Sci Anim Resour 2021 Mar 1;41(2):300-311. Epub 2021 Mar 1.

Department of Food Bioscience and Technology, College of Life Science and Biotechnology, Korea University, Seoul 02841, Korea.

The objective of the present study was to evaluate the cholesterol-assimilation ability of lactic acid bacteria (LAB), which were isolated from , a Korean traditional fermented cabbage. The isolated strain, using modified MRS medium, showed 30.5% cholesterol assimilation activity and was named LRCC5307. Types and concentrations of bile were investigated for their effects on increasing the cholesterol assimilation ability of the LRCC5307 strain, a 74.5% decrease in cholesterol was observed when 0.2% bile salts were added. In addition, the manufacture of low-cholesterol butter using LRCC5307 was examined. After fermentation, LRCC5307 with butter showed 8.74 Log CFU/g viable cells, pH 5.43, and a 11% decrease in cholesterol. These results suggest that LRCC5307 could help in the production of healthier butter by decreasing cholesterol and including living LAB.
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http://dx.doi.org/10.5851/kosfa.2020.e101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115011PMC
March 2021

Discrimination and Sleep among Asians and Pacific Islanders Adults.

Sleep 2021 Apr 29. Epub 2021 Apr 29.

Harvard T. H. Chan School of Public Health, Department of Social and Behavioral Sciences, USA.

Study Objectives: To examine the association between discrimination and sleep duration and difficulty among Asians and Pacific Islanders (APIs) in the United States, and to test nativity and ethnic identity (EI) as effect modifiers.

Methods: This cross-sectional study of 1,765 adults from the National Epidemiology Study of Alcohol and Related Conditions III, assessed discrimination using the Experiences of Discrimination scale. Discrimimation was classified as low, moderate, and high. Regression models were used to examine self-reported sleep duration and difficulty.

Results: In bivariate analyses, individuals with high discrimination had the shortest sleep and reported sleep difficulty most often. Using linear models adjusted for sociodemographic and health characteristics, moderate and high discrimination were associated with 9 minutes (standard error [SE]: 4.8, p <0.10) and 14.4 minutes (SE: 6.0, p <0.05) less sleep, respectively, relative to low discrimination. Individuals with moderate and high discrimination had higher prevalence of sleep difficulty compared to those with low discrimination (prevalence ratio [PR]: 1.51, 95% confidence interval [CI]: 1.14-1.99 and PR: 1.73, 95% CI: 1.33-2.24, respectively). Interaction effect was observed in sleep difficulty by nativity and EI, but not duration. The association between discrimination and sleep difficulty was stronger among US-born relative to foreign-born participants. Among participants with low EI, moderate and high discrimination were associated with sleep difficulty, whereas among those with high EI, only high discrimination displayed this association.

Conclusions: Discrimination is associated with sleep duration and difficulty, and varies by nativity and EI. Research is needed to improve sleep among APIs that experience discrimination.[.
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http://dx.doi.org/10.1093/sleep/zsab109DOI Listing
April 2021

Therapeutic targeting of ATR yields durable regressions in small cell lung cancers with high replication stress.

Cancer Cell 2021 Apr;39(4):566-579.e7

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Small cell neuroendocrine cancers (SCNCs) are recalcitrant cancers arising from diverse primary sites that lack effective treatments. Using chemical genetic screens, we identified inhibition of ataxia telangiectasia and rad3 related (ATR), the primary activator of the replication stress response, and topoisomerase I (TOP1), nuclear enzyme that suppresses genomic instability, as synergistically cytotoxic in small cell lung cancer (SCLC). In a proof-of-concept study, we combined M6620 (berzosertib), first-in-class ATR inhibitor, and TOP1 inhibitor topotecan in patients with relapsed SCNCs. Objective response rate among patients with SCLC was 36% (9/25), achieving the primary efficacy endpoint. Durable tumor regressions were observed in patients with platinum-resistant SCNCs, typically fatal within weeks of recurrence. SCNCs with high neuroendocrine differentiation, characterized by enhanced replication stress, were more likely to respond. These findings highlight replication stress as a potentially transformative vulnerability of SCNCs, paving the way for rational patient selection in these cancers, now treated as a single disease.
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http://dx.doi.org/10.1016/j.ccell.2021.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048383PMC
April 2021

Comprehensive Metabolite Profiling and Microbial Communities of (Fermented Soy Paste) and (Fermented Soy Sauce): A Comparative Study.

Foods 2021 Mar 18;10(3). Epub 2021 Mar 18.

Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea.

and are secondary fermented soybean products from (primary fermented product) following a complex fermentation process that separates the products into solid () and liquid () states. We performed a comparative study on gas chromatography mass spectrometry-(GC-MS) and liquid chromatography mass spectrometry-(LC-MS) based metabolite profiling with fungal and bacterial microbial community analysis of and during fermentation. Metabolite profiling and microbial community data showed distinct patterns, depending on the fermentation process. The relative levels of metabolic patterns were similar and most of the microorganisms produced halophilic or halotolerant microbes during the fermentation period in and . In the end products, isoflavones, soyasaponins, and amino acids were largely distributed and and were dominant, whereas the biogenic amine and phenylpropanoid contents were highly distributed in the end products, with higher levels of and . Our results demonstrate that the quality of and is predominantly influenced by the microbiome and by metabolite changes during fermentation. Moreover, the present study provides a platform for comparing samples in different states.
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http://dx.doi.org/10.3390/foods10030641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003076PMC
March 2021

In small cell lung cancer patients treated with RRx-001, a downregulator of CD47, decreased expression of PD-L1 on circulating tumor cells significantly correlates with clinical benefit.

Transl Lung Cancer Res 2021 Jan;10(1):274-278

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Background: Small cell lung cancer (SCLC) is the most aggressive lung tumor, characterized by a rapid doubling time and the development of widespread metastases, for which immune checkpoint inhibitors have been approved to overcome T cell anergy. In light of its dismal prognosis, and lack of curative options, new therapies for extensive-disease SCLC are desperately needed.

Methods: RRx-001 is a small molecule Myc inhibitor and down-regulates CD47 expression on tumor cells. We evaluated the programmed death-ligand 1 (PD-L1) status of circulating tumor cells (CTCs) pre and post RRx-001 treatment in a phase 2 clinical trial, called QUADRUPLE THREAT, where patients with previously treated SCLC received RRx-001 in combination with a platinum doublet. The trial was registered with ClinicalTrials.gov, number NCT02489903. Fourteen patients with SCLC were analyzed to investigate the association between clinical outcome and PD-L1 expression on CTCs pre and post RRx-001. The correlation between the binary clinical outcome (clinical benefit vs. progressive disease) and the change of PD-L1 expression on CTCs after RRx-001 was analyzed using a logistic regression adjusting for baseline PD-L1 expression.

Results: The logistic model McFadden goodness of fit score was 0.477. The logistic model analyzing the association between decreased PD-L1 expression on CTCs after RRx-001 and response to reintroduced platinum doublet had an approximate 92.8% accuracy in its prediction of clinical benefit. The estimated receiver operating characteristic (ROC) displayed a ROC area under the curve (AUC) of 0.93 (95% confidence interval, 0.78-0.99).

Conclusions: These results suggest that PD-L1 expression on CTCs decreased after RRx-001 was significantly correlated with response to reintroduced platinum-based doublet therapy. Monitoring PD-L1 expression on CTCs during RRx-001 treatment may serve as a biomarker to predict response to RRx-001-based cancer therapy.
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http://dx.doi.org/10.21037/tlcr-20-359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867783PMC
January 2021

Results from a biomarker study to accompany a phase II trial of RRx-001 with reintroduced platinum-based chemotherapy in relapsed small cell carcinoma.

Expert Opin Investig Drugs 2021 Feb 11;30(2):177-183. Epub 2021 Jan 11.

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH) , Bethesda, MD, USA.

: In a Phase II study RRx-001 was combined with Etoposide platinum (EP) in previously platinum treated SCLC. We correlated expression of the M2 marker, CD206, on HLA-DR monocytes, a phenotype that correlates with a poor prognosis, with response to RRx-001. : Patients received 4 mg RRx-001 once weekly until progression followed by the start of EP (etoposide 100 mg/m IV on days 1-3 of a 21-day cycle and either cisplatin 80 mg/m IV on day 1 or carboplatin AUC 5-6 IV on day 1). Treatment continued until progression or intolerable toxicity. Peripheral blood was collected in Cell Preparation Tubes with sodium citrate from 14 patients for exploratory studies during screening and after therapy on Days 1, 8, and 15. Peripheral blood mononuclear cells (PBMCs) were isolated from blood by centrifugation and multiparameter flow cytometric analysis was performed. : CD206 expression on HLA-DR monocytes was associated with response to chemotherapy and overall survival. : During treatment with RRx-001, reduced expression of the protumorigenic M2 marker CD206 on peripheral monocytes positively correlated with increased response and survival.
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http://dx.doi.org/10.1080/13543784.2021.1863947DOI Listing
February 2021

Use of Direct-Acting Antiviral Agents and Survival Among Medicare Beneficiaries with Dementia and Chronic Hepatitis C.

J Alzheimers Dis 2021 ;79(1):71-83

Division of Health Policy and Management, School of Public Health, University of Minnesota, MN, USA.

Background: Many patients with Alzheimer's disease and related dementia (ADRD) have chronic hepatitis C due to the high prevalence of both conditions among elderly populations. Direct-acting antivirals (DAAs) are effective in treating hepatitis C virus (HCV). However, the complexity of ADRD care may affect DAA use and outcomes among patients with HCV and ADRD. Little information exists on uptake of DAAs, factors associated with DAA use, and health benefits of DAAs among patients with HCV and ADRD.

Objective: To examine use and survival benefits of DAAs in Medicare patients with HCV and ADRD.

Methods: The study included Medicare patients with HCV between 2014 and 2017. We estimated Cox proportional hazards regressions to examine the association between having ADRD and DAA use, and the relation between DAA use and survival among patients with HCV and ADRD.

Results: The adjusted hazard of initiating a DAA was 50% lower in patients with ADRD than those without ADRD (adjusted HR = 0.50, 95% CI: 0.46-0.54). The hazard of DAA use among ADRD patients with behavioral disturbances was 68% lower than non-ADRD patients (adjusted HR = 0.32, 95% CI: 0.28-0.37). DAA treatment was associated with a significant reduction in mortality among ADRD patients (adjusted HR = 0.52, 95% CI: 0.44-0.61).

Conclusion: The rate of DAA treatment in patients with HCV and ADRD was low, particularly among those with behavioral disturbance. The survival benefits of DAA treatment for patients with ADRD were substantial.
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http://dx.doi.org/10.3233/JAD-200949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855832PMC
January 2021

Entinostat plus Pembrolizumab in Patients with Metastatic NSCLC Previously Treated with Anti-PD-(L)1 Therapy.

Clin Cancer Res 2021 02 17;27(4):1019-1028. Epub 2020 Nov 17.

Syndax Pharmaceuticals, Inc., Waltham, Massachusetts.

Purpose: New therapies are needed to treat immune checkpoint inhibitor-resistant non-small cell lung cancer (NSCLC) and identify biomarkers to personalize treatment. Epigenetic therapies, including histone deacetylase inhibitors, may synergize with programmed cell death-1 (PD-1) blockade to overcome resistance. We report outcomes in patients with anti-programmed cell death ligand-1 [PD-(L)1]-resistant/refractory NSCLC treated with pembrolizumab plus entinostat in ENCORE 601.

Patients And Methods: The expansion cohort of ENCORE 601 included patients with NSCLC who previously experienced disease progression with immune checkpoint inhibitors. The primary endpoint for the phase II expansion cohort is overall response rate (ORR); safety, tolerability, and exploratory endpoints are described.

Results: Of 76 treated patients, 71 were evaluable for efficacy. immune-regulated RECIST-assessed ORR was 9.2% [95% confidence interval (CI): 3.8-18.1], which did not meet the prespecified threshold for positivity. Median duration of response was 10.1 months (95% CI: 3.9-not estimable), progression-free survival (PFS) at 6 months was 22%, median PFS was 2.8 months (95% CI: 1.5-4.1), and median overall survival was 11.7 months (95% CI: 7.6-13.4). Benefit was enriched among patients with high levels of circulating classical monocytes at baseline. Baseline tumor PD-L1 expression and gene expression were not associated with benefit. Treatment-related grade ≥3 adverse events occurred in 41% of patients.

Conclusions: In anti-PD-(L)1-experienced patients with NSCLC, entinostat plus pembrolizumab did not achieve the primary response rate endpoint but provided a clinically meaningful benefit, with objective response in 9% of patients. No new toxicities, including immune-related adverse events, were seen for either drug. Future studies will continue to evaluate the association of monocyte levels and response.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-3305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887114PMC
February 2021

Cabozantinib plus docetaxel and prednisone in metastatic castration-resistant prostate cancer.

BJU Int 2021 04 23;127(4):435-444. Epub 2020 Oct 23.

Genitourinary Malignancies Branch, NCI, Bethesda, MD, USA.

Objective: To evaluate the safety and efficacy of cabozantinib combined with docetaxel.

Patients And Methods: This was a phase 1/2 multicentre study in patients with metastatic castration-resistant prostate cancer (mCRPC). Docetaxel (75 mg/m every 3 weeks with daily prednisone 10 mg) was combined with escalating doses of daily cabozantinib (20, 40 and 60 mg). Based on the results of the phase 1 study, the investigation was expanded into a randomized study of docetaxel with prednisone (hereafter 'docetaxel/prednisone') plus the maximum tolerated dose (MTD) of cabozantinib compared with docetaxel/prednisone alone.

Results: A total of 44 men with mCRPC were enrolled in this phase 1/2 trial. An MTD of 40 mg cabozantinib plus docetaxel/prednisone was determined. Dose-limiting toxicities were neutropenic fever and palmar-plantar erythrodysesthesia, and there was one death attributable to a thromboembolic event. In addition, grade 3 or 4 myelosuppression, hypophosphataemia and neuropathy were seen in three or more patients. In the phase 1 study, the median time to progression (TTP) and overall survival (OS) time were 13.6 and 16.3 months, respectively. In the phase 2 study, which was terminated early because of poor accrual, the median TTP and OS favoured the combination (n = 13) compared to docetaxel/prednisone alone (n = 12; 21.0 vs 6.6 months; P = 0.035 and 23.8 vs 15.6 months; P = 0.072, respectively).

Conclusion: Despite the limited number of patients in this study, preliminary data suggest that cabozantinib can be safely added to docetaxel/prednisone with possible enhanced efficacy.
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http://dx.doi.org/10.1111/bju.15227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265825PMC
April 2021

Spatial Distribution and Prognostic Implications of Tumor-Infiltrating FoxP3- CD4+ T Cells in Biliary Tract Cancer.

Cancer Res Treat 2021 Jan 31;53(1):162-171. Epub 2020 Aug 31.

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Purpose: The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated.

Materials And Methods: A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core.

Results: The density of CD8+ T cells, FoxP3- CD4+ helper T cells, and FoxP3+ CD4+ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8+ T cell and FoxP3- CD4+ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3- CD4+ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3- CD4+ helper T cells in the tumor margin was independently associated with favorable PFS and OS.

Conclusion: The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3- CD4+ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.
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http://dx.doi.org/10.4143/crt.2020.704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812013PMC
January 2021

Metabolite Profiling and Microbial Community of Traditional Meju Show Primary and Secondary Metabolite Differences Correlated with Antioxidant Activities.

J Microbiol Biotechnol 2020 Nov;30(11):1697-1705

Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Republic of Korea.

Meju, a type of fermented soybean paste, is used as a starter in the preparation of various Korean traditional soybean-based foods. In this study, we performed Illumina-MiSeq paired-end sequencing for microbial communities and mass spectrometry analysis for metabolite profiling to investigate the differences between 11 traditional meju products from different regions across Korea. Even though the bacterial and fungal communities showed remarkable variety, major genera including , and were detected in every sample of meju. The metabolite profile patterns of the 11 samples were clustered into two main groups: group I (M1-5) and group II (M6-11). The metabolite analysis indicated a relatively higher amino acid content in group I, while group II exhibited higher isoflavone, soyasaponin, and lysophospholipid contents. The bioactivity analysis proved that the ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)) radical-scavenging activity was higher in group II and the FRAP (ferric reducing antioxidant power) activity was higher in group I. The correlation analysis revealed that the ABTS activity was isoflavonoid, lipid, and soyasaponin related, whereas the FRAP activity was amino acid and flavonoid related. These results suggest that the antioxidant activities of meju are critically influenced by the microbiome and metabolite dynamics.
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http://dx.doi.org/10.4014/jmb.2007.07026DOI Listing
November 2020

Cabozantinib in patients with platinum-refractory metastatic urothelial carcinoma: an open-label, single-centre, phase 2 trial.

Lancet Oncol 2020 08 6;21(8):1099-1109. Epub 2020 Jul 6.

Developmental Therapeutics Branch, Magnuson Clinical Center, Bethesda, MD, USA.

Background: Cabozantinib is a multikinase inhibitor of MET, VEGFR, AXL, and RET, which also has an effect on the tumour immune microenvironment by decreasing regulatory T cells and myeloid-derived suppressor cells. In this study, we examined the activity of cabozantinib in patients with metastatic platinum-refractory urothelial carcinoma.

Methods: This study was an open-label, single-arm, three-cohort phase 2 trial done at the National Cancer Institute (Bethesda, MD, USA). Eligible patients were 18 years or older, had histologically confirmed urothelial carcinoma or rare genitourinary tract histologies, Karnofsky performance scale index of 60% or higher, and documented disease progression after at least one previous line of platinum-based chemotherapy (platinum-refractory). Cohort one included patients with metastatic urothelial carcinoma with measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Two additional cohorts that enrolled in parallel (patients with bone-only urothelial carcinoma metastases and patients with rare histologies of the genitourinary tract) were exploratory. Patients received cabozantinib 60 mg orally once daily in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate by RECIST in cohort one. Response was assessed in all patients who met the eligibility criteria and who received at least 8 weeks of therapy. All patients who received at least one dose of cabozantinib were included in the safety analysis. This completed study is registered with ClinicalTrials.gov, NCT01688999.

Findings: Between Sept 28, 2012, and Oct, 20, 2015, 68 patients were enrolled on the study (49 in cohort one, six in cohort two, and 13 in cohort three). All patients received at least one dose of cabozantinib. The median follow-up was 61·2 months (IQR 53·8-70·0) for the 57 patients evaluable for response. In the 42 evaluable patients in cohort one, there was one complete response and seven partial responses (objective response rate 19%, 95% CI 9-34). The most common grade 3-4 adverse events were fatigue (six [9%] patients), hypertension (five [7%]), proteinuria (four [6%]), and hypophosphataemia (four [6%]). There were no treatment-related deaths.

Interpretation: Cabozantinib has single-agent clinical activity in patients with heavily pretreated, platinum-refractory metastatic urothelial carcinoma with measurable disease and bone metastases and is generally well tolerated. Cabozantinib has innate and adaptive immunomodulatory properties providing a rationale for combining cabozantinib with immunotherapeutic strategies.

Funding: National Cancer Institute Intramural Program and the Cancer Therapy Evaluation Program.
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http://dx.doi.org/10.1016/S1470-2045(20)30202-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236112PMC
August 2020

Lung cancer screening decisional needs among African American smokers of lower socioeconomic status.

Ethn Health 2020 Jun 5:1-19. Epub 2020 Jun 5.

Department of Behavioral and Community Health, School of Public Health, University of Maryland, College Park, MD, USA.

Objectives: Adherence to most evidence-based cancer screenings is lower among African Americans due to system- and individual-level factors that contribute to persistent disparities. Given the recommendation for low-dose computed tomography (LDCT) screening among individuals at high risk for lung cancer, we sought to describe aspects of decision-making for LDCT among African Americans and to examine associations between select components of decision-making and screening-related intentions.

Design: African Americans ( = 119) with a long-term smoking history, aged 55-80 years, and without lung cancer were recruited to participate in a cross-sectional survey. We measured knowledge, awareness, decisional conflict, preferences, and values related to lung cancer screening.

Results: The majority of the study population was of lower socioeconomic status (67.2% had an annual income of ≤$20,000) and long-term current (79%) smokers. Participants had a median 20 pack-years smoking history. Most participants (65.8%) had not heard of LDCT and the total lung cancer screening knowledge score was  = 7.1/15.0 (SD = 1.8). Participants with higher scores on the importance of the pros and cons of screening expressed greater likelihood of talking with a doctor, family, and friends about screening (' < .10).

Conclusions: Findings have implications for addressing the decisional needs of lower socioeconomic African American current and former smokers to promote informed decision-making for LDCT.
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http://dx.doi.org/10.1080/13557858.2020.1771681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718398PMC
June 2020

Novel hybrid models between bivariate statistics, artificial neural networks and boosting algorithms for flood susceptibility assessment.

J Environ Manage 2020 Jul 20;265:110485. Epub 2020 Apr 20.

Center of Water Management and Climate Change, Institute for Environment and Resources, Vietnam National University - Ho Chi Minh City (VNU-HCM), Ho Chi Minh City, Viet Nam.

Across the world, the flood magnitude is expected to increase as well as the damage caused by their occurrence. In this case, the prediction of areas which are highly susceptible to these phenomena becomes very important for the authorities. The present study is focused on the evaluation of flood potential within Trotuș river basin in Romania using six ensemble models created by the combination of Analytical Hierarchy Process (AHP), Certainty Factor (CF) and Weights of Evidence (WOE) on one hand, and Gradient Boosting Trees (GBT) and Multilayer Perceptron (MLP) on the other hand. A number of 12 flood predictors, 172 flood locations and 172 non-flood locations were used. A percentage of 70% of flood and non-flood locations were used as input in models. From the input data, 70% were used as training sample and 30% as validating sample. The highest accuracy was obtained by the MLP-CF model in terms of both training (0.899) and testing (0.889) samples. A percentage between 21.88% and 36.33% of study area is covered with high and very high flood potential. The results validation, performed through the ROC Curve method, highlights that the MLP-CF model provided the most accurate results.
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http://dx.doi.org/10.1016/j.jenvman.2020.110485DOI Listing
July 2020

A Longitudinal Assessment of Parental Caregiving and Blood Pressure Trajectories: Findings from the China Health and Nutrition Survey for Women 2000-2011.

J Racial Ethn Health Disparities 2021 02 4;8(1):127-135. Epub 2020 May 4.

Department of Epidemiology and Biostatistics, University of Maryland School of Public Health, 2242 Valley Drive, College Park, MD, 20742, USA.

Background: Few studies have investigated the consequences of caregiving on the objectively measured physiological health outcomes in China. This study used population-based longitudinal data to examine the association between parental caregiving and blood pressure among Chinese women.

Method: This is a retrospective analysis of 2586 women using five waves of data from the Ever-Married Women Survey component of the China Health and Nutrition Survey (2000, 2004, 2006, 2009, and 2011). We applied growth curve models to examine trajectories of systolic blood pressure (SBP) and diastolic blood pressure (DBP) associated with parental caregiving among women in China.

Results: In multivariable analyses of blood pressure trajectories adjusting for potential confounders, parental caregivers had higher systolic (β-coefficient (β) = 1.16; p ≤ 0.01) and diastolic blood pressure (β = 0.75; p ≤ 0.01) compared with non-caregivers across multiple waves. Caregivers and non-caregivers had similar levels of systolic blood pressure at baseline, but caregivers exhibited relatively higher growth rate over time. Diastolic blood pressure was much higher among caregivers at the baseline measure, and across time relative to non-caregivers. Moreover, low-intensity but not high-intensity caregivers showed higher growth rate compared with non-caregivers for both SBP and DBP.

Discussion: Our results demonstrate the negative cardiovascular consequences of parental caregiving among Chinese women. Findings from the study can be used to develop future stress management interventions to decrease hypertension risk within women who provide care to their parents.
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http://dx.doi.org/10.1007/s40615-020-00764-0DOI Listing
February 2021

Exploring the metabolomic diversity of plant species across spatial (leaf and stem) components and phylogenic groups.

BMC Plant Biol 2020 Jan 28;20(1):39. Epub 2020 Jan 28.

Department of Bioscience and Biotechnology, Konkuk University, Seoul, 143-701, Korea.

Background: Plants have been used as an important source of indispensable bioactive compounds in various cosmetics, foods, and medicines. However, the subsequent functional annotation of these compounds seems arduous because of the largely uncharacterized, vast metabolic repertoire of plant species with known biological phenotypes. Hence, a rapid multi-parallel screening and characterization approach is needed for plant functional metabolites.

Results: Fifty-one species representing three plant families, namely Asteraceae, Fabaceae, and Rosaceae, were subjected to metabolite profiling using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and ultrahigh-performance liquid chromatography quadrupole orbitrap ion trap tandem mass spectrometry (UHPLC-Q-orbitrap-MS/MS) as well as multivariate analyses. Partial least squares discriminant analysis (PLS-DA) of the metabolite profiling datasets indicated a distinct clustered pattern for 51 species depending on plant parts (leaves and stems) and relative phylogeny. Examination of their relative metabolite contents showed that the extracts from Fabaceae plants were abundant in amino acids, fatty acids, and genistein compounds. However, the extracts from Rosaceae had higher levels of catechin and ellagic acid derivatives, whereas those from Asteraceae were higher in kaempferol derivatives and organic acids. Regardless of the different families, aromatic amino acids, branch chain amino acids, chlorogenic acid, flavonoids, and phenylpropanoids related to the shikimate pathway were abundant in leaves. Alternatively, certain amino acids (proline, lysine, and arginine) as well as fatty acids levels were higher in stem extracts. Further, we investigated the associated phenotypes, i.e., antioxidant activities, affected by the observed spatial (leaves and stem) and intra-family metabolomic disparity in the plant extracts. Pearson's correlation analysis indicated that ellagic acid, mannitol, catechin, epicatechin, and quercetin derivatives were positively correlated with antioxidant phenotypes, whereas eriodictyol was positively correlated with tyrosinase inhibition activity.

Conclusions: This work suggests that metabolite profiling, including multi-parallel approaches and integrated bioassays, may help the expeditious characterization of plant-derived metabolites while simultaneously unraveling their chemodiversity.
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http://dx.doi.org/10.1186/s12870-019-2231-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986006PMC
January 2020

Correction to: Development of Decisional Values Statements for Lung Cancer Screening among African American Smokers.

J Cancer Educ 2020 Apr;35(2):419-421

Department of Behavioral and Community Health, School of Public Health, University of Maryland, College Park, MD, USA.

The original version of this article unfortunately contained mistakes in Tables 1 and 3.
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http://dx.doi.org/10.1007/s13187-020-01693-6DOI Listing
April 2020

Decitabine and Vorinostat with Chemotherapy in Relapsed Pediatric Acute Lymphoblastic Leukemia: A TACL Pilot Study.

Clin Cancer Res 2020 05 22;26(10):2297-2307. Epub 2020 Jan 22.

Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, Missouri.

Purpose: Treatment failure from drug resistance is the primary reason for relapse in acute lymphoblastic leukemia (ALL). Improving outcomes by targeting mechanisms of drug resistance is a potential solution.

Patients And Methods: We report results investigating the epigenetic modulators decitabine and vorinostat with vincristine, dexamethasone, mitoxantrone, and PEG-asparaginase for pediatric patients with relapsed or refractory B-cell ALL (B-ALL). Twenty-three patients, median age 12 years (range, 1-21) were treated in this trial.

Results: The most common grade 3-4 toxicities included hypokalemia (65%), anemia (78%), febrile neutropenia (57%), hypophosphatemia (43%), leukopenia (61%), hyperbilirubinemia (39%), thrombocytopenia (87%), neutropenia (91%), and hypocalcemia (39%). Three subjects experienced dose-limiting toxicities, which included cholestasis, steatosis, and hyperbilirubinemia ( = 1); seizure, somnolence, and delirium ( = 1); and pneumonitis, hypoxia, and hyperbilirubinemia ( = 1). Infectious complications were common with 17 of 23 (74%) subjects experiencing grade ≥3 infections including invasive fungal infections in 35% (8/23). Nine subjects (39%) achieved a complete response (CR + CR without platelet recovery + CR without neutrophil recovery) and five had stable disease (22%). Nine (39%) subjects were not evaluable for response, primarily due to treatment-related toxicities. Correlative pharmacodynamics demonstrated potent modulation of epigenetic marks, and modulation of biologic pathways associated with functional antileukemic effects.

Conclusions: Despite encouraging response rates and pharmacodynamics, the combination of decitabine and vorinostat on this intensive chemotherapy backbone was determined not feasible in B-ALL due to the high incidence of significant infectious toxicities. This study is registered at http://www.clinicaltrials.gov as NCT01483690.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-1251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477726PMC
May 2020

Development of Decisional Values Statements for Lung Cancer Screening Among African American Smokers.

J Cancer Educ 2020 04;35(2):412-418

Department of Behavioral and Community Health, School of Public Health, University of Maryland, College Park, MD, USA.

Lung cancer screening via low-dose computed tomography (LDCT) has been underutilized by high-risk current and former smokers since its approval in 2013. Further, lower use of other evidence-based cancer screening tests (e.g., colorectal cancer, breast cancer) has been noted among African Americans when compared with other racial and ethnic groups. Reasons for low uptake are multilayered but include the need for consideration of patients' personal values about the screening decision. The goal of the present study was to (1) identify positive and negative factors specific to lung cancer screening via LDCT and (2) develop statements to capture values about the screening test for use in a new measure of decisional values. Key informant interviews (n = 9) identified several benefits and risks of lung cancer screening that may be important to African American smokers. Based on these interviews, a pool of items with the values statements was administered to a convenience sample of 119 African Americans [aged 55-80 years, current or former smokers (who quit < 15 years), and without lung cancer]. An exploratory factor analysis revealed two components explaining 64% of the variance: cons of screening (e.g., "make you feel badly about your smoking history") and pros of screening (e.g., "lowering your risk of dying from lung cancer"). The final 12-item measure had very good internal consistency (α = 0.89 overall; α = 0.86 and 0.88 for subscales, respectively). This tool provides a promising values measure for lung cancer screening among African Americans and could inform future values clarification tools promoting informed and shared decision-making.
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http://dx.doi.org/10.1007/s13187-020-01687-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333917PMC
April 2020

Occupational Differences in C-Reactive Protein Among Working-Age Adults in South Korea.

J Occup Environ Med 2020 03;62(3):194-201

Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health (Dr Kim, Dr Zaitsu, Dr Tsuno, Dr Li, Dr Jang, Dr Kawachi); Department of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo (Dr Zaitsu); School of Health Innovation, Kanagawa University of Human Services, Kanagawa (Dr Tsuno), Japan; Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital (Dr Li), Boston, Massachusetts; Department of Epidemiology and Biostatistics, University of Maryland School of Public Health, Maryland (Dr Lee); Red Cross College of Nursing, Chung-Ang University, Seoul, Republic of Korea (Dr Jang).

Objective: To examine the association between occupational class and high-sensitivity C-reactive protein (hsCRP) in Korean workers.

Methods: We used a nationally representative sample of Koreans (n = 2591) aged 19 to 65 years from the 2015 Korea National Health and Nutrition Examination Survey. The concentration of hsCRP (mg/L) was assessed by a high sensitivity immunoturbidimetric assay. Current occupation was categorized as: white-collar (managers/professionals), pink-collar (clerks/service/sales), blue-collar (craft/equipment/machine-assembling, agricultural/forestry/fishery, and elementary-level labor), or unemployed. Cross-sectional linear regression models adjusted for sociodemographic/work-related/health conditions and behaviors.

Results: Compared with blue-collar workers, white-collar workers showed significantly higher levels of hsCRP (β = 0.16, 95% CI: 0.02, 0.30) after adjusting for all covariates, whereby the pattern was more pronounced among professionals. However, the association was not significant for unemployed and pink-collar workers.

Conclusions: Findings suggest that Korean white-collar workers, particularly professionals, have elevated levels of inflammation.
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http://dx.doi.org/10.1097/JOM.0000000000001781DOI Listing
March 2020
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