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1.
Artigo em Inglês | MEDLINE | ID: mdl-38815111

RESUMO

Despite the popularity of electronic cigarettes (ECIGs), limited research has examined the role of sweeteners, independent of other flavors, in shaping ECIG human abuse potential (HAP). This study examined the effects of sucralose and nicotine in unflavored ECIG liquid solutions to provide a basic understanding of the effects of sweeteners on ECIG HAP compared to combustible cigarettes. Individuals who smoked cigarettes daily (N = 14) completed five within-subject, Latin-square ordered study sessions that differed by product used: (a) own-brand combustible cigarettes (OB), (b) 0 mg/mL nicotine, unsweetened liquid, (c) 0 mg/mL nicotine, sucralose-sweetened liquid, (d) 15 mg/mL nicotine, unsweetened liquid, and (e) 15 mg/mL nicotine, sucralose-sweetened liquid. Participants completed subjective questionnaires and behavioral tasks following a 10-puff directed use bout during which puff topography was measured, and blood was sampled for later measurement of plasma nicotine concentration. On average, the OB condition had a greater increase in plasma nicotine concentration and produced more pronounced subjective effects compared to the ECIG conditions. The 15 mg/mL nicotine ECIGs delivered significantly more nicotine and produced greater drug effects and reductions in tobacco abstinence symptoms than the 0 mg/mL nicotine ECIGs. Sucralose-containing solutions increased ECIG product appeal, puff duration, and puff volume during the 10-puff directed bout. Findings revealed greater HAP for OB cigarettes relative to all ECIGs tested and suggest that adding sucralose and nicotine elevates ECIG HAP via different mechanisms; sucralose appears to influence HAP through product appeal, while nicotine influences HAP through drug effects and tobacco/nicotine abstinence symptom suppression. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

2.
Psychol Addict Behav ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635200

RESUMO

OBJECTIVE: Co-use of tobacco and cannabis may be prevalent in pregnancy, potentially leading to additional adverse health outcomes. Utilizing a national sample of women followed prospectively before, during, and after pregnancy, this study tested whether prepregnancy co-use of tobacco and cannabis (vs. tobacco-only use and cannabis-only use) was associated with greater likelihood of continuing to use tobacco and/or cannabis during pregnancy and postpartum. METHOD: Data were drawn from Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health (PATH) Study. Prepregnancy, pregnancy, and postpartum data were captured and stacked over three intervals (Waves 1-3, 2-4, and 3-5). Participants were N = 686 U.S. women (72% White, 46% age 25-34) who were currently pregnant during the middle wave of an interval. Rates of tobacco-only use, cannabis-only use, and tobacco and cannabis co-use at all three time points were examined. RESULTS: Generalized estimating equation models demonstrated that pregnant women who reported prepregnancy tobacco and cannabis co-use (vs. tobacco-only or cannabis-only use) were more likely to continue to use tobacco and/or cannabis during pregnancy and relapse in postpartum (p < .05). Among women who endorsed prepregnancy co-use and continued to use tobacco and/or cannabis in pregnancy, about half transitioned to tobacco-only use (45.16%). CONCLUSIONS: Findings underscore the need for further clinical and empirical focus on dynamic patterns of use/co-use of tobacco and cannabis across the perinatal period, including cessation interventions to reduce tobacco and cannabis use in pregnancy and protect against relapse in postpartum. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

3.
Cancer Sci ; 115(5): 1446-1458, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38438247

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) patients have late presentation at the time of diagnosis and a poor prognosis. Metal dyshomeostasis is known to play a role in cancer progression. However, the blood and tissue metallome of PDAC patients has not been assessed. This study aimed to determine the levels of essential and toxic metals in the serum and pancreatic tissue from PDAC patients. Serum samples were obtained from PDAC patients before surgical resection. Tissue (tumor and adjacent normal pancreas) were obtained from the surgically resected specimen. Inductively coupled plasma-mass spectrometry (ICP-MS) analysis was performed to quantify the levels of 10 essential and 3 toxic metals in these samples. Statistical analysis was performed to identify dysregulated metals in PDAC and their role as potential diagnostic and prognostic biomarkers. Significantly decreased serum levels of magnesium, potassium, calcium, iron, zinc, selenium, arsenic, and mercury and increased levels of molybdenum were shown to be associated with PDAC. There were significantly decreased levels of zinc, manganese and molybdenum, and increased levels of calcium and selenium in the pancreatic tumor tissue compared with the adjacent normal pancreas. Notably, lower serum levels of calcium, iron, and selenium, and higher levels of manganese, were significantly associated with a poor prognosis (i.e., overall survival) in PDAC patients. In conclusion, this is the first study to comprehensively assess the serum and tissue metallome of PDAC patients. It identified the association of metals with PDAC diagnosis and prognosis.


Assuntos
Biomarcadores Tumorais , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Prognóstico , Metais/sangue , Metais/metabolismo , Metais/análise , Pâncreas/metabolismo , Pâncreas/patologia , Magnésio/sangue , Magnésio/metabolismo , Magnésio/análise , Adulto , Cálcio/sangue , Cálcio/metabolismo , Cálcio/análise , Selênio/sangue , Selênio/análise , Selênio/metabolismo , Ferro/metabolismo , Ferro/sangue , Zinco/sangue , Zinco/metabolismo , Zinco/análise , Molibdênio/sangue
4.
Cancer Med ; 12(17): 18050-18061, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37533202

RESUMO

AIM: Pancreatic ductal adenocarcinoma (PDAC) has the lowest survival rate of all major cancers. Chemotherapy is the mainstay systemic therapy for PDAC, and chemoresistance is a major clinical problem leading to therapeutic failure. This study aimed to identify key differences in gene expression profile in tumors from chemoresponsive and chemoresistant patients. METHODS: Archived formalin-fixed paraffin-embedded tumor tissue samples from patients treated with neoadjuvant chemotherapy were obtained during surgical resection. Specimens were macrodissected and gene expression analysis was performed. Multi- and univariate statistical analysis was performed to identify differential gene expression profile of tumors from good (0%-30% residual viable tumor [RVT]) and poor (>30% RVT) chemotherapy-responders. RESULTS: Initially, unsupervised multivariate modeling was performed by principal component analysis, which demonstrated a distinct gene expression profile between good- and poor-chemotherapy responders. There were 396 genes that were significantly (p < 0.05) downregulated (200 genes) or upregulated (196 genes) in tumors from good responders compared to poor responders. Further supervised multivariate analysis of significant genes by partial least square (PLS) demonstrated a highly distinct gene expression profile between good- and poor responders. A gene biomarker of panel (IL18, SPA17, CD58, PTTG1, MTBP, ABL1, SFRP1, CHRDL1, IGF1, and CFD) was selected based on PLS model, and univariate regression analysis of individual genes was performed. The identified biomarker panel demonstrated a very high ability to diagnose good-responding PDAC patients (AUROC: 0.977, sensitivity: 82.4%; specificity: 87.0%). CONCLUSION: A distinct tumor biological profile between PDAC patients who either respond or not respond to chemotherapy was identified.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Terapia Neoadjuvante , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Perfilação da Expressão Gênica , Biomarcadores , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Pancreáticas
5.
J Cancer Res Clin Oncol ; 149(14): 13437-13450, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37460806

RESUMO

Despite modern advances in cancer medicine, pancreatic cancer survival remains unchanged at just 12%. For the small proportion of patients diagnosed with 'early' (upfront or borderline resectable) disease, recurrences are common, and many recur soon after surgery. Whilst chemotherapy has been shown to increase survival in this cohort, the morbidity of surgery renders many candidates unsuitable for adjuvant treatment. Due to this, and the success of upfront chemotherapy in the advanced setting, use of neoadjuvant chemotherapy has been introduced in patients with upfront or borderline resectable disease. Randomized controlled trials have been conducted to compare upfront surgery to neoadjuvant chemotherapy in this patient cohort, opinions on the ideal upfront treatment approach are divided. This lack of consensus has highlighted the need for biomarkers to assist in clinical decision making. This review analyses the potential diagnostic, prognostic and predictive biomarkers that may assist in the diagnosis and management of early (upfront and borderline resectable) pancreatic cancer.

7.
Ann Surg Oncol ; 30(7): 4417-4428, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37020094

RESUMO

BACKGROUND: Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC. METHODS: We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based. RESULTS: A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC. CONCLUSIONS: In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.


Assuntos
Gencitabina , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Fluoruracila , Leucovorina/uso terapêutico , Terapia Neoadjuvante/efeitos adversos , Paclitaxel , Estudos Multicêntricos como Assunto
8.
J Clin Med ; 12(5)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36902776

RESUMO

Pancreatic cancer has poor survival despite modern-day advances in its management. At present, there are no available biomarkers that can predict chemotherapy response or help inform prognosis. In more recent years, there has been increased interest in potential inflammatory biomarkers, with studies revealing a worse prognosis of patients with a higher neutrophil-to-lymphocyte ratio in a range of tumour types. Our aim was to assess the role of three inflammatory biomarkers in peripheral blood in predicting chemotherapy response in patients with earlier disease treated with neoadjuvant chemotherapy and as a prognostic marker in all patients that underwent surgery for pancreatic cancer. Using retrospective records, we discovered that patients with a higher neutrophil-to-lymphocyte ratio (>5) at the time of diagnosis had worse median overall survival than those with ratios ≤5 at 13 and 32.4 months (p = 0.001, HR 2.43), respectively. We were able to appreciate a correlation between a higher platelet-to-lymphocyte ratio and increased residual tumour in the histopathological specimen in patients receiving neoadjuvant chemotherapy; however, the association was weak (p = 0.03, coefficient 0.21). Due to the dynamic relationship between the immune system and pancreatic cancer, it is unsurprising that immune markers may be useful as potential biomarkers; however, larger prospective studies are needed to validate these findings.

9.
Drug Alcohol Depend ; 229(Pt B): 109144, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34768140

RESUMO

BACKGROUND: The COVID-19 pandemic has had a significant global impact. As a respiratory illness, COVID-19 may pose unique risks to cigarette smokers. This study used concept mapping, a mixed-method participatory approach, to identify impacts of COVID-19 on cigarette smokers. METHODS: Cigarette smokers across the United States (U.S.) were recruited to complete this online, multi-step study. Of the 126 participants who were invited to participate in this study, 91 participants (mean age = 40.9; SD = 11.3) completed at least one of the three study tasks (i.e., brainstorming, sorting, and rating). Participants completed a brief demographic survey and brainstormed statements that completed a focus prompt: "A specific way that Coronavirus/COVID-19 has impacted/affected my cigarette use, smoking behaviors, tobacco purchasing behaviors, and/or other tobacco-related behaviors is." After duplicate statements were removed, participants sorted the final list of 87 statements by similarity of content and rated how true statements were from them (1-Definitely NOT true to 7-Definitely true). RESULTS: Nine thematic clusters were identified: Smoking More, Smoking to Cope/Reduce Stress, Change in Smoking Behaviors Due to COVID-19, Concerns about Smoking and COVID-19 Risk, Social Impacts, Maintaining and Rationing Cigarette Supply, Impacts on Obtaining Cigarettes, Use of Other Tobacco Products/Drugs, and Minimal/No Impacts/Concerns of COVID-19. The highest rated cluster (i.e., most true) was the Smoking More cluster followed by the Concerns about Smoking and COVID-19 Risk cluster. The highest rated statement in the study was the statement "Smoking keeps me calm". CONCLUSIONS: Cigarette smokers may endure additional impacts of COVID-19, such as increased COVID-19 health burdens, stressors related to risk of exposure, social stigma and isolation, financial burdens, and increased toxicant exposure from increased smoking frequency.


Assuntos
COVID-19 , Sistemas Eletrônicos de Liberação de Nicotina , Produtos do Tabaco , Vaping , Adulto , Humanos , Pandemias , SARS-CoV-2 , Fumar , Nicotiana
10.
J Clin Med ; 10(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207372

RESUMO

Pancreatic adenocarcinoma is a devastating disease with only 15-20% of patients resectable at diagnosis. Neoadjuvant chemotherapy for this cohort is becoming increasingly popular; however, there are no published randomized trials that support the use of neoadjuvant chemotherapy over upfront surgery in resectable disease. This retrospective cohort analysis was conducted to compare both treatment pathways and to identify any potential prognostic markers. Medical records from one large volume pancreatic cancer center from 2013-2019 were reviewed and 126 patients with upfront resectable disease were analyzed. Due to a change in practice in our center patients treated prior to December 2016 received upfront surgery and those treated after this date received neoadjuvant chemotherapy. Of these, 86 (68%) patients were treated with upfront surgery and 40 (32%) of patients were treated with neoadjuvant chemotherapy. Our results demonstrated that patients treated with upfront surgery with early-stage (1a) disease had a longer median OS compared to those treated with neoadjuvant chemotherapy (24 vs. 21 months, p = 0.028). This survival difference was not evident for all patients (regardless of stage). R0 resections were similar between groups (p = 0.605). We identified that both tumor viability (in neoadjuvant chemotherapy-treated patients) and tumor grade were useful prognostic markers. Upfront surgery for certain patients with low volume disease may be suitable despite the global trend towards neoadjuvant chemotherapy for all upfront resectable patients. A prospective clinical trial in this cohort incorporating biomarkers is needed to determine optimal therapy pathway.

12.
Eur J Surg Oncol ; 47(10): 2543-2550, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33952409

RESUMO

BACKGROUND: Pancreatic cancer is the 8th commonest cancer and the 5th commonest cause of cancer-related death in Australia, with a 9% average 5-year survival. This study aims to investigate the effects of neoadjuvant treatment on overall survival (OS) and recurrence-free survival (RFS) in borderline resectable (BRPC) and locally advanced (LAPC) pancreatic adenocarcinoma followed by curative resection. MATERIALS AND METHODS: Prospectively-collected demographic, medical, surgical and pathological data of patients with BRPC and LAPC treated with both neoadjuvant therapy (NAT) and surgery at a single tertiary referral centre in Australia were reviewed and analysed. RESULTS: Between 2012 and 2018, 60 patients, 34 with BRPC and 26 with LAPC, were treated with NAT followed by curative resection. The commonest neoadjuvant chemotherapy regimens were Gemcitabine + Abraxane (51.7%) and FOLFIRINOX (35.0%), with 48.3% of patients additionally receiving neoadjuvant radiotherapy. Median RFS was 30 months and median OS was 35 months. On multivariable analysis, inferior OS was predicted by enlarged loco-regional lymph nodes on initial computed tomography (p = 0.032), larger tumour size post-NAT (p = 0.006) and Common Terminology Criteria for Adverse Events post-NAT toxicity greater than grade 2 (p = 0.015). LAPC patients received more neoadjuvant chemotherapy (p = 0.008) and radiotherapy (p = 0.021) than BRPC and achieved a superior pathological response (p = 0.010). CONCLUSION: Patients who respond to NAT likely have a favourable disease biology and will progress well following resection. It is these patients who should be selected for more aggressive upfront management, and those with resistant disease should be spared from high-risk surgery.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Adulto , Idoso , Paclitaxel Ligado a Albumina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Pancreatectomia/efeitos adversos , Pancreaticoduodenectomia/efeitos adversos , Radioterapia Adjuvante , Radioterapia de Intensidade Modulada , Taxa de Sobrevida , Carga Tumoral , Gencitabina
13.
Int J Cancer ; 148(6): 1508-1518, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33128797

RESUMO

Our study aimed to identify a urinary metabolite panel for the detection/diagnosis of pancreatic ductal adenocarcinoma (PDAC). PDAC continues to have poor survival outcomes. One of the major reasons for poor prognosis is the advanced stage of the disease at diagnosis. Hence, identification of a novel and cost-effective biomarker signature for early detection/diagnosis of PDAC could lead to better survival outcomes. Untargeted metabolomics was employed to identify a novel metabolite-based biomarker signature for PDAC diagnosis. Urinary metabolites from 92 PDAC patients (56 discovery cohort and 36 validation cohort) were compared with 56 healthy volunteers using 1 H nuclear magnetic resonance spectroscopy. Multivariate (partial-least squares discriminate analysis) and univariate (Mann-Whitney's U-test) analyses were performed to identify a metabolite panel which can be used to detect PDAC. The selected metabolites were further validated for their diagnostic potential using the area under the receiver operating characteristic (AUROC) curve. Statistical analysis identified a six-metabolite panel (trigonelline, glycolate, hippurate, creatine, myoinositol and hydroxyacetone), which demonstrated high potential to diagnose PDAC, with AUROC of 0.933 and 0.864 in the discovery and validation cohort, respectively. Notably, the identified panel also demonstrated very high potential to diagnose early-stage (I and II) PDAC patients with AUROC of 0.897. These results demonstrate that the selected metabolite signature could be used to detect PDAC and will pave the way for the development of a urinary test for detection/diagnosis of PDAC.


Assuntos
Biomarcadores Tumorais/urina , Carcinoma Ductal Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Idoso , Carcinoma Ductal Pancreático/urina , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/urina , Urinálise/métodos
14.
Biochim Biophys Acta Gen Subj ; 1864(11): 129682, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32663515

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has the lowest survival rate of all major cancers. Surgery is the only curative intent therapy, but the majority of patients experience disease relapse. Thus, patients who do not benefit from highly morbid surgical resection needs to be identified and offered palliative chemotherapy instead. In this pilot study, we aimed to identify differentially regulated proteins in plasma and plasma derived microparticles from PDAC patients with poor and good prognosis. METHODS: Plasma and plasma derived microparticle samples were obtained before surgical resection from PDAC patients. Sequential Windowed Acquisition of all Theoretical fragment ion spectra - Mass Spectrometry (SWATH-MS) proteomic analysis was performed to identify and quantify proteins in these samples. Statistical analysis was performed to identify biomarkers for poor prognosis. RESULTS: A total of 482 and 1024 proteins were identified from plasma and microparticle samples, respectively, by SWATH-MS analysis. Statistical analysis of the data further identified nine and six differentially (log2ratio > 1, p < .05) expressed proteins in plasma and microparticles, respectively. Protein tyrosine phosphatases, PTPRM and PTPRB, were decreased in plasma of patients with poor PDAC prognosis, while proteasomal subunit PSMD11 was increased in microparticles of patients with poor prognosis. CONCLUSION AND GENERAL SIGNIFICANCE: A novel blood-based biomarker signature for PDAC prognosis was identified.


Assuntos
Carcinoma Ductal Pancreático/sangue , Neoplasias Pancreáticas/sangue , Complexo de Endopeptidases do Proteassoma/sangue , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/sangue , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/sangue , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático/diagnóstico , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Projetos Piloto , Prognóstico , Proteômica , Estudos Retrospectivos
15.
Front Oncol ; 10: 237, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32195182

RESUMO

Background: Neoadjuvant chemotherapy (NAC) has been of recent interest as an alternative to upfront surgery followed by adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma (PDAC). However, a subset of patients does not respond to NAC and may have been better managed by upfront surgery. Hence, there is an unmet need for accurate biomarkers for predicting NAC response in PDAC. We aimed to identify upregulated proteins in tumor tissue from poor- and good-NAC responders. Methods: Tumor and adjacent pancreas tissue samples were obtained following surgical resection from NAC-treated PDAC patients. SWATH-MS proteomic analysis was performed to identify and quantify proteins in tissue samples. Statistical analysis was performed to identify biomarkers for NAC response. Pathway analysis was performed to characterize affected canonical pathways in good- and poor-NAC responders. Results: A total of 3,156 proteins were identified, with 19 being were significantly upregulated in poor-responders compared to good-responders (log2 ratio > 2, p < 0.05). Those with the greatest ability to predict poor-NAC response were GRP78, CADM1, PGES2, and RUXF. Notably, canonical pathways that were significantly upregulated in good-responders included acute phase signaling and macrophage activation, indicating a heightened immune response in these patients. Conclusion: A novel biomarker signature for poor-NAC response in PDAC was identified.

16.
Tob Control ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041833

RESUMO

BACKGROUND: JUUL is an electronic cigarette that aerosolises a nicotine-containing liquid, while IQOS heats tobacco to produce an aerosol. Both are marketed to smokers, but their effects have seldom been examined in this population. METHODS: Eighteen cigarette smokers (13 men) with no JUUL or IQOS experience completed a within-subject, laboratory study assessing nicotine delivery and subjective effects after controlled (10 puffs, ~30 s interpuff interval) and ad libitum (90 min) use of JUUL, IQOS or own-brand (OB) cigarettes. RESULTS: JUUL increased mean plasma nicotine concentration significantly from 2.2 (SD=0.7) ng/mL to 9.8 (4.9) ng/mL after 10 puffs and to 11.5 (9.3) ng/mL after ad libitum use. IQOS increased mean plasma nicotine significantly from 2.1 (0.2) ng/mL to 12.7 (6.2) ng/mL after 10 puffs and to 11.3 (8.0) ng/mL after ad libitum use. OB increased mean plasma nicotine significantly from 2.1 (0.2) ng/mL to 20.4 (11.4) ng/mL after 10 puffs and to 21.0 (10.2) ng/mL after ad libitum use. Mean OB plasma nicotine concentration was significantly higher than JUUL and IQOS. OB increased expired carbon monoxide concentration, but IQOS and JUUL did not. 'Craving a cigarette/nicotine' and 'Urges to smoke' were reduced significantly for all products following the directed bout. CONCLUSIONS: Among smokers, JUUL and IQOS delivered less nicotine than cigarettes. Also, in this sample, IQOS and OB reduced abstinence symptoms more effectively than JUUL. Additional work with experienced JUUL and IQOS users is needed, as their nicotine delivery profiles and subjective experiences may differ.

17.
Tob Regul Sci ; 6(6): 416-422, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34423079

RESUMO

OBJECTIVE: This study's objective was to characterize the nicotine delivery profile of a variable voltage, tank-style electronic nicotine delivery system (ENDS). METHODS: Ten cigarette smokers (8 men, 2 women) completed this within-subject study assessing effects of 2 device power settings (15 W, 45 W) and 3 liquid nicotine concentrations (0, 3, and 6 mg/ml) using a tank-style ENDS. Participants completed one directed (10 puffs) and one ad libitum use period for each condition, with blood sampled throughout. RESULTS: Plasma nicotine concentration did not increase significantly at 15 W regardless of liquid nicotine concentration. At 45 W, mean plasma nicotine increased (not significantly compared to 0 mg/ml) from 2.24 ng/ml (SD=0.2) at baseline to 3.4 ng/ml (SD=0.6) in the 3 mg/ml condition. In the 6 mg/ml, 45 W condition, mean plasma nicotine increased significantly (compared to 0 mg/ml) from 2.0 ng/ml (SD=0) at baseline to 5.96 ng/ml (SD=1.3) after 10 puffs. In general, puff duration and volume decreased as device power and nicotine concentration increased. CONCLUSIONS: Despite using a variable wattage, tank-style device, nicotine delivery was minimal. These results, when combined with results from other studies using tank-style devices, highlight ENDS performance heterogeneity. Regulation may play a role in standardizing ENDS nicotine delivery.

18.
Exp Clin Psychopharmacol ; 28(5): 527-539, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31855003

RESUMO

Electronic cigarette (ECIG) nicotine delivery and other effects can be influenced by device and/or liquid characteristics and user puffing behavior. One class of ECIGs includes "sub-ohm" devices that incorporate heating coils with resistance less than 1 ohm (Ω), lower than that observed in conventional devices (e.g., ≥1.5 Ω). Relative to conventional ECIGs that operate at ≤10 W, low-resistance coils can be used to increase device power (e.g., 40-300 W). However, little is known about the individual and combined effects of ECIG power, manipulated by coil resistance, and liquid nicotine concentration on ECIG acute effects. Experienced ECIG users (N = 32) completed 4 sessions that differed by ECIG power and coil resistance (40.5 W, 0.5 Ω or 13.5 W, 1.5 Ω) and liquid nicotine concentration (3 or 8 mg/ml). In each session, participants used a 4.5-V Kanger SUBOX ECIG in a 10-puff directed and 60-min ad libitum bout. Nicotine delivery, heart rate, subjective effects, puff topography, and liquid consumption were measured. Nicotine delivery was greatest in the 8mg/ml+0.5Ω condition and lowest in the 3mg/ml+1.5Ω condition. The greatest reduction in abstinence symptoms were observed in the 8mg/ml+0.5Ω condition, although the highest ratings for satisfaction and liking were reported in the 3mg/ml+0.5Ω condition. Use of ECIGs containing 3 mg/ml nicotine liquid resulted in longer and larger puffs and increased puff frequency, though high-power/low-resistance ECIGs resulted in greater consumption of ECIG liquid. ECIG device and liquid characteristics and user puff topography should be considered simultaneously when making regulatory decisions aimed at protecting public health. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Frequência Cardíaca/efeitos dos fármacos , Temperatura Alta , Nicotina/administração & dosagem , Adolescente , Adulto , Feminino , Humanos , Masculino , Fumar/efeitos adversos , Síndrome de Abstinência a Substâncias , Adulto Jovem
19.
Exp Clin Psychopharmacol ; 28(2): 235-244, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31259592

RESUMO

Most electronic cigarettes (e-cigs) aerosolize a nicotine-containing liquid that users inhale. Few experimental studies have examined e-cig abuse liability (the extent to which use of these products may lead to persistent and/or problematic use). In this study, 24 experienced male e-cig users completed 4 sessions that differed byproduct used: own e-cig (OWN), an eGo e-cig filled with participants' own brand/flavor liquid in 0 mg/mL nicotine (e-cig0), an eGo e-cig filled with the highest nicotine concentration available in participants' own brand/flavor (e-cighighest), and a U.S. Food and Drug Administration-approved nicotine inhaler (IN). Outcome measures included crossover point on the multiple-choice procedure, plasma nicotine delivery, and subjective effect profile. After 10 puffs, a significantly higher mean crossover point was observed for OWN at $1.35 (SD = 0.90) compared to e-cighighest at $0.88 (SD = 0.89), e-cig0 at $0.83 (SD = 0.79), and IN at $0.72 (SD = 0.84). Significant increases in mean plasma nicotine concentration were observed for OWN at 7.94 ng/mL (SD = 6.19) and e-cighighest at 7.51 ng/mL (SD = 5.39). Significant reductions in abstinence symptom suppression and higher ratings of satisfaction were observed for OWN and e-cighighest, with significantly less suppression and lower ratings of satisfaction for e-cig0 and IN. These findings suggest that human laboratory methods can be used to assess e-cig abuse liability and that nicotine-containing e-cigs have greater abuse liability than nicotine-free e-cigs and the IN. Potential regulations intended to limit e-cig abuse liability should be tested using these or similar procedures. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Tabagismo/etiologia , Adulto , Estudos Cross-Over , Humanos , Masculino , Nicotina/sangue , Fumantes
20.
Exp Clin Psychopharmacol ; 27(5): 443-454, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30777773

RESUMO

Under certain conditions, electronic cigarettes (e-cigs) can deliver nicotine to and suppress tobacco abstinence symptoms in cigarette smokers. Growing popularity of e-cigs raises abuse liability concerns. This study's purpose was to compare the abuse liability of an e-cig (1.5 Ohm, 3.3 V) filled with 36 mg/mL or 0 mg/mL nicotine to an Food and Drug Administration (FDA)-approved nicotine inhaler (IN) and participants' own brand (OB) of cigarettes. Smokers (N = 24) completed four sessions in which they completed the multiple-choice procedure, and plasma nicotine concentration and subjective effects were measured. Mean (SD) multiple-choice procedure crossover point was $0.87 (1.0) for the 36-mg/mL nicotine e-cig and $0.96 (1.2) for the 0-mg/mL e-cig, significantly higher than the IN mean of $0.32 (0.6) but significantly lower than the OB cigarette mean of $1.42 (1.4). Ten puffs from an own-brand cigarette increased mean plasma nicotine concentration from 3.55 (2.8) to 13.64 (9.8) ng/mL, as compared to an increase from 3.16 (1.8) to 8.51 (5.4) ng/mL for the 36-mg/mL e-cig. The 36-mg/mL e-cig reduced nicotine abstinence symptoms more than the 0-mg/mL e-cig, and both e-cigs were rated as more reinforcing than the inhaler but less reinforcing than participants' OB cigarettes (ps < .05). Results suggest that the e-cig examined had higher abuse liability than the IN but lower than combustible cigarettes. These data and methods may be useful for policymakers by revealing how e-cig abuse liability compares to tobacco/nicotine products with abuse liability profiles that are well established. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Tabagismo/etiologia , Adulto , Estudos Cross-Over , Feminino , Humanos , Masculino , Nicotina/sangue , Fumantes , Síndrome de Abstinência a Substâncias/prevenção & controle
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