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  • 1
    In: SoftwareX, Elsevier BV, Vol. 13 ( 2021-01), p. 100658-
    Type of Medium: Online Resource
    ISSN: 2352-7110
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2819369-6
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  • 2
    In: The Lancet Global Health, Elsevier BV, Vol. 10, No. 11 ( 2022-11), p. e1575-e1581
    Type of Medium: Online Resource
    ISSN: 2214-109X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2723488-5
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  • 3
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 12037-12037
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 12037-12037
    Abstract: 12037 Background: Metastatic melanoma carries poor prognosis and traditional chemotherapy has limited efficacy. Immune checkpoint inhibitors (ICI) have drastically improved disease outcomes since first approved in 2011. Elderly patients were underrepresented in landmark early trials of ICI leading to limited clinical trial data on efficacy and treatment patterns in this population. We aimed to examine the real-world IO outcomes and demographics of elderly patients in the National Cancer Database. Methods: We queried the database for patients with stage IV melanoma diagnosed between 2011-2015 with survival data available. Patients were divided into receipt of immunotherapy (IO) or no receipt of IO; those without documentation were excluded. Cases were separated into 3 cohorts of age at diagnosis (60 years-old or younger, 61-74 years-old, and 75 years-old and greater). Descriptive variables were compared by Chi-squared analysis and survival analyses were performed by Kaplan-Meier method and log-rank test. Results: 11,265 cases met inclusion criteria: 4,117 aged 60 or less, 3,940 aged 61-74, and 3,208 aged 75 or older. Those receiving immuno-oncologic agents (IO) in all age groups showed a longer median OS (mOS) than those who did not receive IO (mOS overall 17.28 v 7.49; p 〈 0.01). Survival was longer in all age cohorts when IO was received compared to not received; ages less than 60 (mOS 20.3 v 9.2m; p 〈 0.01), ages 61-74 (mOS 15.5 v 7.8m; p 〈 0.01), and ages 75 or greater (mOS 14.4 v 5.8m; p 〈 0.01). A greater percentage of patients received IO in younger than older cohorts, 20.1% in ≥ 75, 37.6% in 61-74, and 42.3% in ≤ 60; p 〈 0.01. Additional descriptive variables shown in the table were compared between the cohorts include care at academic or integrated cancer network, uninsured, Charlson-Deyo Comorbidity Index (CDCI) of 2 or greater, and documented inclusion of palliative care treatment. Conclusions: Substantial survival benefit is realized with IO in all age cohorts although elderly cohorts did not receive IO as often as younger cohort. Elderly patients experienced lower rates of care at academic/network cancer programs, lower uninsured rate, and higher CDCI. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 3139-3139
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 3139-3139
    Abstract: 3139 Background: Breast cancer (BC) is a malignancy with a wide array of histopathological characteristics and tumor heterogeneity leading to major clinical implications for management. With the recent approval of antibody-drug conjugates (ADCs) for human epidermal growth factor receptor 2 (HER2)-low advanced BC, there is increased significance for characterizing the spectrum of HER2 expression in the curative setting. Methods: We conducted a single institution retrospective review of patients with BC who received neoadjuvant systemic therapy (NAST) followed by definitive surgical resection from 2008 to 2022. The initial tumor biopsies were tested for estrogen receptor (ER), progesterone receptor (PR), and HER2 status per ASCO/CAP guidelines and repeated on the residual tumor tissue after NAST. HER2 status was categorized into HER2-negative (IHC 0), HER2-low (IHC 1 or IHC 2/ Fluorescence in situ hybridization [FISH] negative), and HER2-positive (IHC 2/ FISH positive or IHC 3). Concordance and discordance with HER2 status in the pre and post NAST tumor samples were analyzed using descriptive statistics. Results: Of 340 patients with BC who received NAST, 55 patients with residual disease had pre and post treatment biomarker data available for analysis. Prevalence of HER2-low was 70.9 % (39/55) in the pretreatment tumors while it was 58.2% (32/55) in the post treatment tumors. 40% of tumors (22/55) had HER2 discordance while 60% (33/55) demonstrated concordance with HER2 expression after NAST. Among the changes in HER2 status, a shift from HER2-low to HER2-negative status occurred most frequently in 18.2% of tumors (10/55). In tumors with HER2 discordance, 36.4% (8/22) were also noted to have changes in ER or PR status while this was seen in 48.5% (16/33) of tumors with HER2 concordance. For rates of recurrence, 22.7% (5/22) of patients in the HER2 discordant group had relapsed compared to 18.2% (6/33) patients in the HER2 concordant group. Conclusions: Dynamics of HER2 expression is increasingly important in the rapidly changing therapeutic landscape of BC. Our study shows high prevalence of HER2-low expression in tumors with residual disease after NAST and frequent conversion of HER2-low to HER2-negative status with NAST. Further studies are warranted to determine the clinical and therapeutic relevance of biomarker evolution and tumor heterogeneity in the curative setting. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    SAGE Publications ; 2020
    In:  European Journal of Mass Spectrometry Vol. 26, No. 1 ( 2020-02), p. 36-45
    In: European Journal of Mass Spectrometry, SAGE Publications, Vol. 26, No. 1 ( 2020-02), p. 36-45
    Abstract: Sequence determination of peptides using mass spectrometry plays a crucial role in the bottom-up approaches for the identification of proteins. It is crucially important to minimise false detection and validate sequence of the peptides in order to correctly identify a protein. Chemical modification of peptides followed by mass spectrometry is an option for improving the spectral quality. In silico-derived tryptic peptides with different N-terminal amino acids were designed from human proteins and synthesized. The effect of acetylation on the fragmentation of peptides was studied. N-terminal acetylation of the tryptic peptides was shown to form b 1 -ions, improve the abundance and occurrence of b-ions. In some cases, the intensity and occurrence of some y-ions also varied. Thus, it is demonstrated that acetylation plays an important role in improving the de novo sequencing efficiency of the peptides. The acetylation method was extended to tryptic peptides generated from the proteome of an Antarctic bacterium Pseudomonas syringae Lz4W using the proteomics work flow and mass spectra of the peptides were analysed. Comparison of the MS/MS spectra of the acetylated and unacetylated peptides revealed that acetylation helped in improving the spectral quality and validated the peptide sequences. Using this method, 673 proteins of the 1070 proteins identified were validated.
    Type of Medium: Online Resource
    ISSN: 1469-0667 , 1751-6838
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
    detail.hit.zdb_id: 2021540-X
    detail.hit.zdb_id: 2021340-2
    SSG: 11
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    SAGE Publications ; 2018
    In:  European Journal of Mass Spectrometry Vol. 24, No. 2 ( 2018-04), p. 231-242
    In: European Journal of Mass Spectrometry, SAGE Publications, Vol. 24, No. 2 ( 2018-04), p. 231-242
    Abstract: A wide variety of post-translational modifications such as oxidation, phosphorylation, glycosylation, methylation, and acetylation play critical roles in cellular functions. Detection of post-translational modifications in proteins is important to understand their crucial roles in cellular functions. Identifying each modification requires special attention in mass spectral acquisition and analysis. Here, we report a mass spectral method for the detection of multiple phosphorylations in peptides by analyzing their products after fragmentation. Synthetic peptides were used to identify these modifications by matrix-assisted laser desorption/ionization (MALDI) TOF/TOF. Peptides with serine, threonine, and tyrosine were used with mono- to tetra-phosphorylation sites in different combinations to get insights into their fragmentation and identify the location of these sites. The y-ion series were observed without the loss of phosphate groups and were thus very useful in determining the localization and sequence of the phosphate residues. Acetylation of the peptides was found to be useful in detecting the b1-ion and helped in identifying the N-terminus. When a mixture of the phosphorylated peptides (from mouse protein sequences) were analyzed by LC-MS/MS on a Velos Orbitrap Mass Spectrometer and the data subjected to analysis by Sequest using the mouse database, the peptides were identified along with the parent proteins. A comparison of MALDI TOF/TOF spectra with ESI MS/MS helped in eliminating falsely discovered peptides using the database search.
    Type of Medium: Online Resource
    ISSN: 1469-0667 , 1751-6838
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
    detail.hit.zdb_id: 2021540-X
    detail.hit.zdb_id: 2021340-2
    SSG: 11
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 11013-11013
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 11013-11013
    Abstract: 11013 Background: There is continued uptake in the use of medical cannabis (MC) among patients with cancer. Our group previously conducted a national study that showed that while a majority of oncology fellows discussed MC with patients, very few feel well informed in doing so. We hypothesized that an evidence-based curriculum on the use of MC for oncology trainees is feasible to develop and would be effective in improving confidence to discuss MC with patients. Methods: A multidisciplinary expert team designed an evidence-based educational curriculum in 5 modules specifically for MC in oncology populations that included pharmacology/history, symptom management, cancer-directed effects, toxicities and practical/logistic concerns. The curriculum was piloted as a one-hour webinar at three US hematology oncology fellowship training programs in 2022-2023. Anonymous incentivized survey instruments that were designed to assess self-perceived knowledge, attitudes and behaviors pertaining to MC (on a 5-point Likert scale; strongly agree to strongly disagree) were distributed anonymously via email at the pilot (t = 0) and immediately after (t + 7 days); additional delayed surveys (t+90 days) are in progress. Results: Of 35 eligible trainees, 31 completed the pre-training surveys (88.6%), and 26 (74.3%) completed the post-training surveys. Most trainees indicated that the curriculum is helpful (88.5%, 95% CI: 69.8-97.6) and that they would recommend it to their colleagues (80.8%, 95% CI: 60.6-93.4). Following the webinar, there was significant improvement in self-reported comfort with discussing MC for symptom management (3.2% vs. 92.3%, P 〈 0.001), risks of MC (9.7% vs. 76.9%, P 〈 0.001) and modes of MC use (16.1 vs. 80.8%, P 〈 0.001). The majority of participants (80.0%, 95% CI: 59.3-93.2) reported that they were more likely to initiate conversations about MC with their patients after attending the webinar. Conclusions: In this multi-center study, we demonstrate that it is feasible to develop and deliver a fellow-focused, evidence-based curriculum for MC use in patients with cancer. The webinar was well received and demonstrated significant improvement in fellow-reported attitudes surrounding MC efficacy, risks, and modes of use. Further work to assess durability of the curriculum on knowledge, attitudes, and behaviors is ongoing.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Plant Nano Biology, Elsevier BV, Vol. 2 ( 2022-11), p. 100013-
    Type of Medium: Online Resource
    ISSN: 2773-1111
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 3168791-X
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  • 9
    In: Journal of Cellular Physiology, Wiley, Vol. 234, No. 1 ( 2019-01), p. 108-121
    Abstract: More than 40% of patients with luminal breast cancer treated with endocrine therapy agent tamoxifen demonstrate resistance. Emerging evidence suggests tumor initiating cells (TICs) and aberrant activation of Src and Akt signaling drive tamoxifen resistance and relapse. We previously demonstrated that aryl hydrocarbon receptor ligand aminoflavone (AF) inhibits the expression of TIC gene α6‐integrin and disrupts mammospheres derived from tamoxifen‐sensitive breast cancer cells. In the current study, we hypothesize that tamoxifen‐resistant (TamR) cells exhibit higher levels of α6‐integrin than tamoxifen‐sensitive cells and that AF inhibits the growth of TamR cells by suppressing α6‐integrin–Src–Akt signaling. In support of our hypothesis, TamR cells and associated mammospheres were found to exhibit elevated α6‐integrin expression compared with their tamoxifen‐sensitive counterparts. Furthermore, tumor sections from patients who relapsed on tamoxifen showed enhanced α6‐integrin expression. Gene expression profiling from the TCGA database further revealed that basal‐like breast cancer samples, known to be largely unresponsive to tamoxifen, demonstrated higher α6‐integrin levels than luminal breast cancer samples. Importantly, AF reduced TamR cell viability and disrupted TamR mammospheres while concomitantly reducing α6‐integrin messenger RNA and protein levels. In addition, AF and small interfering RNA against α6‐integrin blocked tamoxifen‐stimulated proliferation of TamR MCF‐7 cells and further sensitized these cells to tamoxifen. Moreover, AF reduced Src and Akt signaling activation in TamR MCF‐7 cells. Our findings suggest elevated α6‐integrin expression is associated with tamoxifen resistance and AF suppresses α6‐integrin–Src–Akt signaling activation to confer activity against TamR breast cancer.
    Type of Medium: Online Resource
    ISSN: 0021-9541 , 1097-4652
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1478143-8
    SSG: 12
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  • 10
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 1987-1987
    Abstract: Mortality rates after allogeneic hematopoietic cell transplantation for hematological malignancies remains high. Recently, a 50-point pretransplantation assessment of mortality (PAM) score was developed by clinical investigators at the Fred Hutchison Cancer Research Center utilizing eight pre-transplant clinical variables including age, donor type, disease risk, conditioning regimen, percentage of predicted FEV1, percentage of predicted DLCO, serum creatinine level and serum ALT level. The PAM score performed well to predict risk of death in the first two years after allogeneic hematopoietic cell transplantation. The objective of our study was to validate the PAM score in a retrospective cohort of patients that underwent allogeneic hematopoietic cell transplantation at Hahnemann University Hospital from 1986 until 2006. 400 patients underwent allogeneic hematopoietic cell transplantation from 1986 to 2006. 170 patients were found to be eligible for retrospective analysis since pre- transplant serum alanine aminotransferase (ALT) levels were not available for the remaining 230 patients. The PAM score was calculated for each patient using the scoring system outlined in the original article. The patients were categorized into four cohorts with scores ranging from 9 to 16 for category 1 (probability of death, 25%), from 17 to 23 for category 2 (probability of death, 25% to 50%), from 24 to 30 for category 3 (probability of death, 50% to 75%), and from 31 to 44 for category 4 (probability of death, 75%). Kaplan- Meier survival curves were generated for each of the four categories. Overall mortality was 62.9% at 2 years. PAM scores ranged from 11 to 36. 41 patients were grouped into category 1, 71 into category 2, 48 patients into category 3 and 10 patients into category 4. Mortality at 2 years was 39% in category 1, 56.3% in category 2, 85.4% in category 3 and 100% in the high-risk category. Compared to the low risk group, group 2 had a hazard ratio of 1.64 (p = 0.092, CI: 0.92 to 2.94); group 3 had a hazard ratio of 3.996 compared to the low risk group (p & lt; 0.001, CI: 2.23 to 7.16) and group 4 had a hazard ratio of 6.73 versus the low-risk group (p & lt; 0.001, 95% CI: 3.01 to 15.04). In conclusion, the PAM score successfully classified patients into distinct survival groups (p & lt; 0.001 for the comparison by log-rank test). Higher PAM scores were associated with progressively increased risk of death. Figure Figure
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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