tbuckley/cabot-search huggingface dataset:
Lung cancer in HIV versus non-HIV population: Nationwide analysis of mortality, morbidity, demographics, and healthcare utilization.
Authors: Muhammad Junaid Tariq, Shweta Gupta
Journal: Journal of Clinical Oncology (2021)

9125 Background: Lung cancer (LC) is the most common non-AIDS defining cancer with a high cancer-related mortality in patients with HIV. With improving survival in HIV patients, the incidence of LC is increasing. We attempted to evaluate the characteristics and outcomes, including healthcare utilization in patients with HIV-LC compared to non-HIV-LC using a national sample. Methods: Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) was queried to identify HIV and non-HIV-LC admissions between 2016-2018. We studied socio-demographic differences, medical comorbidities (including hypertension (HTN), diabetes (DM), Coronary artery disease (CAD), Chronic kidney disease (CKD), Heart failure (HF), dialysis (HD), COPD), all-cause mortality, mean length of stay (LOS), mean total hospital charges (THC). Secondary outcomes included sepsis, septic shock, acute kidney injury (AKI), influenza, pneumonia, respiratory failure, lung collapse, ICU care, hemoptysis, anemia, pain, and protein energy malnutrition (PEM). Statistics were performed using the t-test, univariate and multinomial logistic regression. Results: A total 4,105 HIV-LC and 1,204,365 non-HIV-LC admissions were identified. HIV-LC were younger (mean age 48.7 vs 53.4 p&lt;0.05), male (67% vs 51%, p&lt;0.01), African American (52% vs 12% p&lt;0.01), on Medicaid (35% vs 10% p&lt;0.01), from lowest quartile income zip codes (51% vs 30% p&lt;0.01). HIV-LC had significantly high rates of CKD and HD (p&lt;0.05) while non-HIV-LC had significantly higher rates of HTN, DM, Dyslipidemia, CAD, COPD, obesity, HF and smoking (all p&lt;0.05). Odds of adjusted all-cause mortality were significantly lower in HIV-LC (aOR 0.47 CI 0.36-0.63 p&lt;0.001). HIV-LC had higher LOS (8.1 vs 6 days p&lt;0.001) and higher THC ($83,328 vs $65,642 p&lt;0.001), amounting to over $72 million over 3 years. Significantly different secondary outcomes between the two groups are shown in Table, the rest were similar between the groups. Conclusions: HIV-LC patients were younger, minority with a significantly lower all-cause mortality despite higher rates of complications and significantly higher LOS and THC compared to non-HIV-LC cohort. A higher comorbidity burden may be responsible for higher mortality in the non-HIV group while higher rates of secondary complications, CKD, HD may be driving up healthcare utilization in HIV-LC. More studies are needed to clarify these findings.[Table: see text]
IL-17A and CCL2 in blood serum and circulating neutrophils in patients with ovarian tumors.
Authors: Snezhanna Gening, Tatyana Abakumova, Tatyana Gening
Journal: Journal of Clinical Oncology (2021)

e17536 Background: During the ovarian carcinogenesis, circulating neutrophils (Nph) phenotype switches to the pro-tumor, with an increase in the Nph C-C motif ligand 2 (CCL2) expression. Proinflammatory interleukin-17A (IL-17A) is able to induce the CCL2 expression in Nph. The study aimed to evaluate the IL-17A and CCL2 levels in serum and circulating Nph in patients with ovarian tumors. Methods: The study included 97 ovarian cancer (OC) patients, 30 patients with benign ovarian tumors (BT) and the control (n=22). The levels of IL-17A (LLC "Cytokine", Russia) and CCL2 (Vector-Best-Volga, Russia) in serum and Nph lysate were assessed by ELISA. The systemic inflammation was assessed by neutrophil to lymphocyte ratio (NLR). Informed voluntary consent was obtained from all women. Statistical processing was performed using one-way ANOVA, Spearman correlations (Statistica 13.0 (TIBCO, USA)). Results: We found an increase in NLR in BT (4.3 ± 1.0) compared with the control (2.2 ± 0.1) (p = 0.020), a decrease in stage I-II OC (2.4 ± 0.2) compared with BT (p = 0.053), and an increase in stage III (4.5 ± 0.9) and IV (4.6 ± 0.5) compared with stage I-II OC (p = 0.054 and p = 0.046, respectively). The cytokines levels are presented in Table. The serum level of IL-17A in BT was higher than in the control (p = 0.010). In stage I-II OC, the serum IL-17A level was decreased in comparison with the BT (p = 0.004). In stage IV OC, the serum IL-17A was higher than in stage I-II (p = 0.015) and the control (p = 0.017). The level of IL-17A in Nph in BT did not differ from the control. In all stages of the OC, the IL-17A Nph level was lower than in the control (p 1, 2, 3 = 0.0001). In stage IV OC, the expression of IL-17A in Nph was lower compared with stage III (p = 0.031). The serum and Nph levels of IL-17A were correlated only in stage I-II OC (r = 0.679, p = 0.011). The CCL2 serum levels in BT (p = 0.0002) and OC stage I-II, III, IV were higher compared with the control (p 1 = 0.031, p 2 = 0.001, p 3 = 0.0005, respectively). The Nph CCL2 level was higher in BT than in the control (p = 0.001). In stage I-II OC, the expression of CCL2 in Nph was higher than in the control (p = 0.034), but lower than in the BT (p = 0.003). In OC stages III and IV, the Nph CCL2 level was higher than in the control, but did not differ from that in BT and stages I-II. In stage III OC, the CCL2 level in Nph negatively correlated with the serum IL-17A level (r = -0.405, p = 0.049). Conclusions: The pro-tumor polarization of circulating Nph is not IL-17A-dependent in patients with ovarian tumors. The patterns of the systemic immune response differ in benign ovarian tumors, early, and advanced ovarian cancer.[Table: see text]
TMOD-05. GENOME-WIDE DNA METHYLATION PROFILE: A POWERFUL STRATEGY TO RECAPITULATE HETEROGENEITY OF PEDIATRIC BRAIN TUMORS IN PRIMARY CELL LINES
Authors: Lucia Pedace, Simone Pizzi, Maria Vinci, Giulia Pericoli, Giuseppina Catanzaro, Luana Abballe, Agnese Po, Francesca Del Bufalo, Sabrina Rossi, Francesca Diomedi Camassei, Felice Giangaspero, Luca Tiberi, Angela Mastronuzzi, Elisabetta Ferretti, Marco Tartaglia, Franco Locatelli, Andrea Ciolfi, Evelina Miele
Journal: Neuro-Oncology (2021)

Abstract Background Development of in vitro models of pediatric brain tumors (pBT) is instrumental for both understanding the contributing oncogenic molecular mechanisms and identifying and testing new therapeutic strategies. Primary cell lines should be established and managed to prevent epigenetic and genetic alterations and thus recapitulating the original tumor. DNA methylation (DM) is a stable epigenetic modification, altered in cancer and recently used to classify tumors. We aim to apply DM and Copy Number Variation (CNV) profiling to characterize pBT primary cell lines and tumors. Methods We investigated 34 pBT tissues from different histology paired to 52 their derived primary cultures in both 2D and 3D conditions, as stem-cells or in serum-supplemented medium, and both short and long-terms in culture. We studied 18 additional pBT-derived cell-lines, 9 organoids, 5 commercial cell-lines, and 122 pBT tissues from the same histological categories, as controls, for a total of 240 genome-wide DM profiles. We analyzed DM and CNV profiles by using Illumina EPIC-arrays. By means of a bump hunting strategy, we identified differentially methylated regions in faithful vs unfaithful cell lines, and performed a functional characterization using over-representation analysis. Results The 69% (25/36) of cells at early passages retained genetic alteration and the same DM patterns of the original tumors, with no differences related to 2D/3D methods or the presence of serum in media. The 70% (24/34) of primary cell lines analyzed at later passages (&amp;gt;5 or &amp;gt;14 days in culture) diverged from the primary tumor, the totality of those cultured with serum. All divergent cells clustered together acquiring common deregulated epigenetic signature induced by serum culture media, 2D methods and longer time in culture. Conclusions We have shown that global DM profiles, along with CNV analysis are useful tools to detect the recapitulation of pBT-derived primary cell-lines from the original tumor. Whatever subgroups tested, our results suggest that in vitro models should be passaged as little as possible to retain the epigenetic and genetic alterations of the tumors and thus to be considered relevant for basic and translational biology.
SGK1 regulated apoptosis in invasive breast carcinoma.
Authors: Yuxin Song, Lei Li, YinJiao Fei, Wenquan Chen, Guan qun Wo, Jinhai Tang
Journal: Journal of Clinical Oncology (2021)

e13061 Background: Worldwide, breast cancer is the most common type of cancers and the presentation of drug resistance is often associated with poor prognosis. Previous studies have shown the mechanism of drug resistance was affected by apoptosis at different levels in the signaling cascades. This article is aimed to explore the relationship between the serum and glucocorticoid-regulated kinase 1 (SGK1) and apoptosis in invasive breast cancer (IBC). Methods: We evaluated the expression of SGK1 in IBC using publicly available data from The Cancer Genome Atlas (TCGA) and Curtis Breast program. TaqMan probe-based qRT-PCR assay and Western Blot analysis were performed to quantitatively detect the expression of SGK1 at RNA and protein levels in the IBC specimens. Clinicopathologic characteristics associated with overall survival were tested by Cox regression. Gene Set Enrichment Analysis (GSEA) was performed to mine the biological pathways involved in IBC pathogenesis related SGK1 regulatory network using MSigDB database. Immunohistochemistry staining (IHC) was used to detect apoptotic markers Fas, Bcl2 and SGK1 in the IBC specimens. Results: Totally 1109 IBC samples with SGK1 expression data were downloaded from TCGA databases for analyzed. SGK1 expression was elevated in normal breast tissues compared with both invasive ductal carcinoma and invasive lobular carcinoma (p &lt; 0.0001). Among them, SKG expression in 112 tumor tissues was significantly lower than that in paracancerous tissues, especially in advanced patients with TNM stage IV. Western Blot and qRT-PCR assay confirmed that SGK1 expression in IBC was distinctly lower than normal. The Kaplan-Meier survival analysis showed that decreased expression of SGK1 was significantly correlated with the clinical stage (p = 0.036). In Curtis Breast program, we further verified SGK1 gene expression was reduced in stage IV than stage I. The univariate analysis demonstrated that clinicopathologic variables associated with poor survival include age, advanced stage, lymph nodes, distant metastasis and deep myometrial invasion. GSEA revealed that apoptosis was differentially enriched when SGK1 was highly expressed. Similarly, TCGA data indicated that the positive rate of SGK1 was higher in Fas positive IBCs, and the same result was also obtained by IHC in the IBC specimens. Conclusions: Expression of SGK1 regulated apoptosis in invasive breast carcinoma, which might be a potential therapeutic target to overcome refractory and drug-resistant breast cancer.
Immune Thrombocytopenia: Recent Advances in Pathogenesis and Treatments
Authors: Sylvain Audia, Matthieu Mahévas, Martin Nivet, Sethi Ouandji, Marion Ciudad, Bernard Bonnotte
Journal: HemaSphere (2021)

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to both a peripheral destruction of platelets and an inappropriate bone marrow production. Although the primary triggering factors of ITP remain unknown, a loss of immune tolerance—mostly represented by a regulatory T-cell defect—allows T follicular helper cells to stimulate autoreactive splenic B cells that differentiate into antiplatelet antibody-producing plasma cells. Glycoprotein IIb/IIIa is the main target of antiplatelet antibodies leading to platelet phagocytosis by splenic macrophages, through interactions with Fc gamma receptors (FcγRs) and complement receptors. This allows macrophages to activate autoreactive T cells by their antigen-presenting functions. Moreover, the activation of the classical complement pathway participates to platelet opsonization and also to their destruction by complement-dependent cytotoxicity. Platelet destruction is also mediated by a FcγR-independent pathway, involving platelet desialylation that favors their binding to the Ashwell-Morell receptor and their clearance in the liver. Cytotoxic T cells also contribute to ITP pathogenesis by mediating cytotoxicity against megakaryocytes and peripheral platelets. The deficient megakaryopoiesis resulting from both the humoral and the cytotoxic immune responses is sustained by inappropriate levels of thrombopoietin, the major growth factor of megakaryocytes. The better understanding of ITP pathogenesis has provided important therapeutic advances. B cell-targeting therapies and thrombopoietin-receptor agonists (TPO-RAs) have been used for years. New emerging therapeutic strategies that inhibit FcγR signaling, the neonatal Fc receptor or the classical complement pathway, will deeply modify the management of ITP in the near future.
Use of Lipid-Lowering Therapies Over 2 Years in GOULD, a Registry of Patients With Atherosclerotic Cardiovascular Disease in the US
Authors: Christopher P. Cannon, James A. de Lemos, Robert S. Rosenson, Christie M. Ballantyne, Yuyin Liu, Qi Gao, Tamara Palagashvilli, Shushama Alam, Katherine E. Mues, Deepak L. Bhatt, Mikhail N. Kosiborod, Thomas Knickelbine, Charles Augenbraun, James Talano, Faisal Wahid, David Suh, Ranchhod Khant, Shamaila Aslam, Scott Merryman, David Herrington, Philip Patel, Kenneth Fox, Sumant Lamba, Steven Brodie, Neil Sheth, Kahlid Sheikh, Allen Geltzer, Michael Lillestol, Kamlesh Dave, Stanley Koch, Steven Lupovitch, Carlos Piniella, Lawrence Allen, Rakesh Vohra, Steven Geller, Rohit Amin, Charles Michieli, Philip Levin, Nicolas Shammas, Andrew Potler, Vladimir Santos, Madaiah Revana, Ellis Lader, David Strobl, Megan Supple, Denes Korpas, Donna DeSantis, Debra Fuchs-Ertman, Wael Eid, Linda Calhoun, Narendra Upadhyaya, Ryan Cotter, James Maciejko, Paul Ziajka, William Smith, Eduardo Antezano, Philip O Donnell, Lance Sloan, Vance Wilson, Denise Janosik, James Kmetzo, Sumana Gangi, Chrisette Dharma, Darshan Godkar, Philip Nicol, Micheal Hong, Catherine Popkin, Rajesh Patel, Abelardo Vargas, Minesh Patel, Vikas Desai, Yunsheng Ma, Robert Block, Louis Hiotis, Colby Grossman, Ahmed Arif, Seth Baum, Carlos Sotolongo, Rebecca Jordan, Paul Thompson, Mark Napoli, Robert Davidson, Hugh Durrence, Karen Aspry, Randall Miller, David Headley, Richard Rothschild, Raymond Little, Carl Meisner, Richard Powell, Eliot Moon, Kul Aggarwal, Mark Turner, Idalia Acosta, Martin Schear, Robert Harris, Robert Lending, Abraham Salacata, Vicki Kalen, C David Bird, Caroline Mbogua, Yamirka Duardo-Guerra, Deirdre McMullen, Hessam Aazami, Charles Lovell, Robert Busch, Marek Janout, Lawrence Alwine, Kim Barbel Johnson, Svjetlana Dziko, John Larry, Joseph Cherian, Gregory Allen, Faye Vargas, Stuart Zarich, Armando Ropero-Cartier, Milroy Samuel, Sandeep Khurana, Lilia Rodriguez Ables, Marisela Gonzalez, Gregston Nelson, Lester de Leon, Luis Martinez, Francisco Badar, Thomas Phiambolis, Naseem Jaffrani, John Eck, Brett Nowlan, Trever Martin
Journal: JAMA Cardiology (2021)

Guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) recommend intensive statin therapy and adding nonstatin therapy if low-density lipoprotein cholesterol (LDL-C) levels are 70 mg/dL or more. Compliance with guidelines is often low.
Contribution of family history of melanoma to associated risk factors: Analysis of an Internet-based risk assessment tool.
Authors: Ryan M O'Keefe, Michael Joseph LaRiviere, Carolyn Vachani, Margaret K. Hampshire, Christina Bach, Karen Arnold-Korzeniowski, Marisa Healy, James M. Metz, Christine E. Hill-Kayser
Journal: Journal of Clinical Oncology (2021)

10546 Background: Risk factors for melanoma (ML) include UV exposure, sunburns, multiple nevi, and fair skin. Smoking and alcohol use may also play a role. Demographics associated with increased UV exposure include male gender, white race, age 18-29, and high-income. Those with family history (FH) of ML have increased risk of developing ML themselves yet are often unaware or do not engage in preventive behaviors. We sought to understand the association between FH of ML and other personal risk factors for cancer. Methods: Since 2009, voluntary participants could receive personalized information regarding their cancer risk via the OncoLink.org Reduce My Risk tool. Survey data was collected on demographics, FH, risk-factors, and risk-associated behaviors. Use of data was IRB approved. Differences between respondents with v. without FH of ML were analyzed using chi-square test and adjusted via logistic regression. Results: 25255 responses were analyzed; 1928 (7.6%) had FH of ML. Of these, median age was 26 (range 18-75), 73.1% were female, 88.6% from North America, 91.4% White, 78.2% had at least some college, and 62.0% household income &gt; $45,000. Comparing those with FH of ML to those without, no significant differences were observed in education, income, or home setting. Those with a FH of ML were less likely to be “light” smokers ( &lt; 1 pack per day) but were more likely to be both “light” drinkers and “heavy” drinkers (Table). There were no significant differences in BMI or exercise habits. Those with FH of ML were more likely to sunbathe, to have had “blistering” sunburns, have 50+ moles, show signs of sun damage on their skin, and have dysplastic nevi (Table). There were no differences in use of indoor tanning beds (Table). Conclusions: Those with a FH of ML were more likely to sunbathe and to report skin damage and history of blistering sunburns; they were more likely to use tanning beds, though not statistically significant. These behaviors are modifiable and may suggest parental influence on sun-protective behaviors. Those with FH also reported increased non-modifiable risks. Future work should continue to explore targeted intervention for those with a FH of ML to educate on risk and promote sun-protective behaviors.[Table: see text]
Elucidating Prostate Cancer Behaviour During Treatment via Low-pass Whole-genome Sequencing of Circulating Tumour DNA
Authors: Semini Sumanasuriya, George Seed, Harry Parr, Rossitza Christova, Lorna Pope, Claudia Bertan, Diletta Bianchini, Pasquale Rescigno, Ines Figueiredo, Jane Goodall, Gemma Fowler, Penelope Flohr, Niven Mehra, Antje Neeb, Jan Rekowski, Mario Eisenberger, Oliver Sartor, Stéphane Oudard, Christine Geffriaud-Ricouard, Ayse Ozatilgan, Mustapha Chadjaa, Sandrine Macé, Chris Lord, Joe Baxter, Stephen Pettitt, Maryou Lambros, Adam Sharp, Joaquin Mateo, Suzanne Carreira, Wei Yuan, Johann S. de Bono
Journal: European Urology (2021)

Better blood tests to elucidate the behaviour of metastatic castration-resistant prostate cancer (mCRPC) are urgently needed to drive therapeutic decisions. Plasma cell-free DNA (cfDNA) comprises normal and circulating tumour DNA (ctDNA). Low-pass whole-genome sequencing (lpWGS) of ctDNA can provide information on mCRPC behaviour. To validate and clinically qualify plasma lpWGS for mCRPC. Plasma lpWGS data were obtained for mCRPC patients consenting to optional substudies of two prospective phase 3 trials (FIRSTANA and PROSELICA). In FIRSTANA, chemotherapy-naïve patients were randomised to treatment with docetaxel (75 mg/m2) or cabazitaxel (20 or 25 mg/m2). In PROSELICA, patients previously treated with docetaxel were randomised to 20 or 25 mg/m2 cabazitaxel. lpWGS data were generated from 540 samples from 188 mCRPC patients acquired at four different time points (screening, cycle 1, cycle 4, and end of study). lpWGS data for ctDNA were evaluated for prognostic, response, and tumour genomic measures. Associations with response and survival data were determined for tumour fraction. Genomic biomarkers including large-scale transition (LST) scores were explored in the context of prior treatments. Plasma tumour fraction was prognostic for overall survival in univariable and stratified multivariable analyses (hazard ratio 1.75, 95% confidence interval 1.08–2.85; p = 0.024) and offered added value compared to existing biomarkers (C index 0.722 vs 0.709; p = 0.021). Longitudinal changes were associated with drug response. PROSELICA samples were enriched for LSTs (p = 0.029) indicating genomic instability, and this enrichment was associated with prior abiraterone and enzalutamide treatment but not taxane or radiation therapy. Higher LSTs were correlated with losses of RB1/RNASEH2B, independent of BRCA2 loss. Plasma lpWGS of ctDNA describes CRPC behaviour, providing prognostic and response data of clinical relevance. The added prognostic value of the ctDNA fraction over established biomarkers should be studied further. We studied tumour DNA in blood samples from patients with prostate cancer. We found that levels of tumour DNA in blood were indicative of disease prognosis, and that changes after treatment could be detected. We also observed a "genetic scar" in the results that was associated with certain previous treatments. This test allows an assessment of tumour activity that can complement existing tests, offer insights into drug response, and detect clinically relevant genetic changes.
Awareness, perceptions, and usage of whole person integrative oncology practices: Similarities and differences between breast cancer patients and oncologists.
Authors: Terri Crudup, Linna Li, Elizabeth Lawson, Jennifer Wright Dorr, Rachel Stout, Pedram Vazifeh Niknam, Judi Jones, Robert Steen, Lynn L Lu, Susan Casner, Yi Wang, James Scott, Shelby Zanine, Stacey Robertshaw, Gabriella Broderick, Vaishali Palommella, Tye Harris, Michael Hanamirian, Mula Shivani Reddy, Wayne Jonas
Journal: Journal of Clinical Oncology (2021)

e24123 Background: The use of Complementary and Lifestyle (C&amp;L) approaches in conjunction with medical treatments is known as Integrative Oncology. While Integrative Oncology practices have been steadily rising in the past few decades, there are still awareness and education gaps that medical professionals can help address for their patients. Methods: Survey-based data collection and analysis was used to assess awareness, perceptions, and usage of Integrative Oncology. Patients were randomly sampled among breast cancer patients diagnosed within 2 years and included all stages (0-IV) and all US regions (NE, South, Midwest, West). Physicians were sampled from a panel of community and academic practices across the US, with the requirement they treat at least 10 breast cancer patients in a typical 3-month period and have been in practice for at least 6 years since residency or fellowship. Results: Survey invitations were sent to 1,901 patients and 2,758 Oncologists; 164 breast cancer patients and 115 Oncologists completed the surveys. Approximately two-thirds of Oncologists and patients agree that C&amp;L approaches contribute to improved quality of life and well-being for patients (table row 1, 2). However, significantly more patients than Oncologists believe that Integrative Oncology also leads to better treatment outcome and survival (row 3). In addition, Oncologists are significantly more aware of C&amp;L practices than are patients (row 4). When asked what percent of breast cancer patients they discuss C&amp;L methods with, Oncologists report 55% average (CI: 50-60%). However, when asked how they became aware of C&amp;L, only 28% of patients (CI: 21-35%) mention their Oncologist/cancer care team or the institution where they were treated (not in table). Ideally, patients desire information about C&amp;L to come directly from Oncologists, but that is not the predominant model (row 5). Conclusions: Many breast cancer patients believe an Integrative approach will improve their treatment outcomes and prefer their providers to discuss this with them.[Table: see text]