tbuckley/cabot-search huggingface dataset:
Abstract 421: Characteristics of melanoma diagnosed in patients with underlying HIV infection
Authors: Grace Wei, Sweta Sinha, Jane Messina, Anna E. Coghill
Journal: Cancer Research (2021)

Abstract Background: Melanoma is diagnosed more frequently in patients living with HIV (PLWH) compared to the general US population and HIV-infected melanoma patients also experience higher cancer-specific mortality. The mechanisms underlying these outcome disparities are poorly understood, and data describing tumor pathology and non-mortality outcomes for melanoma patients with HIV are lacking. Objective: To describe differences in tumor presentation and disease course among melanoma patients presenting with or without underlying HIV infection in the era of effective HIV therapy. Methods: We conducted an initial retrospective chart review of 29 HIV+ and 29 HIV- patients, matched as possible to HIV+ patients on age and disease stage, who presented to Moffitt Cancer Center between 2004 and 2019. Data abstracted included patient demographics, tumor pathology, treatment details, and clinical outcomes. Results: Certain melanoma pathology features differed by HIV status, with a higher prevalence of elevated mitotic rate (78.9% vs 41.2%, p=0.02) and vertical growth phase (90% vs 55%, p=0.02) in melanoma patients with HIV. Nearly all patients underwent lesion excision, but post-treatment complications were greater in PLWH (44.8% vs 24%, p=0.09). Among 16 patients who received systemic therapy after excision (HIV+ 6; HIV- 10), progressive disease was more frequent in PLWH (100% vs 30%, p=0.01), with further suggestion of higher severe side effect rates, defined as events interrupting systemic therapy (66.7% vs 30%; p=0.18). Despite these differences in progression, overall survival rate were similar in PLWH (79.3%) and uninfected patients (82.8%). Conclusions: These preliminary results suggest that PLWH and melanoma experience a unique disease course. Higher prevalence of post-excision complications and disease progression following systemic therapy in particular warrant further attention as age-related cancers, such as melanoma, are expected to grow in the US HIV population in coming years. Citation Format: Grace Wei, Sweta Sinha, Jane Messina, Anna E. Coghill. Characteristics of melanoma diagnosed in patients with underlying HIV infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 421.
Anticipatory effects of ADXBLADDER test results in the follow up of cystoscopy negative non muscle invasive bladder cancer patients in a large multicentric European cohort
Authors: M. Rouprêt, P. Gontero, E. Montanari, F. Longo, J.A. Witjes, T. Dudderidge, J. Stockley, A. Kennedy, F. Vanie, O. Rodriguez, M. Allasia, S. Mccracken, R. Sylvester, J. Palou
Journal: European Urology (2021)
Abstract LB210: MicroRNA function is malleable and can be governed by target gene expression levels
Authors: Alexander A. Svoronos, Stuart G. Campbell, Donald M. Engelman
Journal: Cancer Research (2021)

Abstract MicroRNAs are short, noncoding RNA molecules that reduce the expression of target genes by inhibiting messenger RNA translation and promoting messenger RNA degradation. They are highly dysregulated in cancer, with many microRNAs appearing to have potent oncogenic or tumor suppressive effects. As a result, there exists substantial interest in targeting microRNAs for cancer therapy. However, the literature is filled with conflicting accounts as to whether specific microRNAs are oncogenic or tumor suppressive, with many microRNAs appearing to exhibit entirely opposite functions when placed in different contexts. One explanation for this duality is that individual microRNAs can target tens to hundreds of different genes, many of which may possess opposing functions. Hence, it is likely that the expression levels of the target genes influence whether an individual microRNA will have a net oncogenic or net tumor suppressive effect. To examine this hypothesis, we developed a computational model of miR-125b's effect on the apoptosis pathway. This is an ideal system for examining the expression level hypothesis, as miR-125b is a microRNA that targets several closely interacting pro- and anti-apoptotic members of the pathway, which can be easily modeled as a system of differential equations. From the model, we elucidate a general trend that miR-125b is more pro-apoptotic when its anti-apoptotic targets are overexpressed and/or its pro-apoptotic targets are underexpressed, while it is more anti-apoptotic when its pro-apoptotic targets are overexpressed and/or its anti-apoptotic targets are underexpressed. To examine this experimentally, we switched miR-125b from being tumor suppressive to being oncogenic in cells by modifying the expression levels of one of miR-125b's anti-apoptotic targets. In addition, we observed that treating cells with anticancer drugs can also reverse miR-125b's status as a tumor suppressor. These results have important implications for the use of microRNAs as therapeutic targets in cancer. Citation Format: Alexander A. Svoronos, Stuart G. Campbell, Donald M. Engelman. MicroRNA function is malleable and can be governed by target gene expression levels [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB210.
Abstract 2227: Pan-cancer shedding patterns of tumor circulating cell free DNA
Authors: Fabio C. P. Navarro, Simo Zhang, Mengyao Tan, Charles Abbott, Josette Northcott, John Lyle, Gabor Bartha, Jason Harris, John West, Richard Chen, Sean Michael Boyle
Journal: Cancer Research (2021)

Abstract Introduction: Tumor circulating cell-free DNA (ctDNA) comprises DNA molecules cast from tumors that reach and survive in a patient's bloodstream. Given its non-invasive nature, the liquid biopsy of ctDNA has remarkable potential for diagnosis, prognosis, disease progression tracking, and treatment monitoring. Nonetheless, little is known about which tumor features yield higher representation of ctDNA in blood or even which regions in the tumor genome are more inclined to shed and thus be observed as ctDNA. Typically, studies of ctDNA have focused on a limited and well-established set of genes and recurrent variants. However, these limited gene panels may not capture the breadth of genetic alterations that reflect tumor biology. Their limited footprint hinders a comprehensive understanding of tumor heterogeneity, mechanisms of resistance, and DNA shedding patterns. To address these limitations, we developed a whole-exome scale cfDNA platform, NeXT Liquid Biopsy™, that enables sensitive detection and tracking of mutations in over twenty thousand genes from plasma samples. Results: Here we profile over 50 tumor, normal, and plasma matched samples using NeXT Liquid Biopsy to investigate pan-cancer patterns of DNA shedding. We observe varying levels of ctDNA shedding in plasma, suggesting that tracking tumors with an exome-scale set of variants, as opposed to with a targeted panel, can benefit greatly from the higher sensitivity and granularity of our enhanced exome sequencing. Next, we sought to investigate the patterns of somatic variants representation in plasma. For this, we integrate shedding ratios with transcriptome and epigenome data from healthy paired tissues and examine variant shedding biases associated with transcription rate and histone modifications in associated nucleosomes. Conclusion: We sequenced and analyzed one of the largest tumor, normal, and plasma cohorts to date with comprehensive coverage of somatic variants across all human genes. Our results suggest that tracking exome-scale somatic variants adds invaluable information to understand a tumor's biology. Moreover, our comprehensive coverage of the tumor genome can be used to unveil biases of tumor genome shedding patterns. We are able to investigate the shedding ratio across distinct genomic features deriving, to our knowledge, the first exome scale pan-cancer shedding resource of the human genome. Citation Format: Fabio C. P. Navarro, Simo Zhang, Mengyao Tan, Charles Abbott, Josette Northcott, John Lyle, Gabor Bartha, Jason Harris, John West, Richard Chen, Sean Michael Boyle. Pan-cancer shedding patterns of tumor circulating cell free DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2227.
Abstract 1634: Risk Factors for Venous Thromboembolism: Results From the Copenhagen City Heart Study
Authors: Anders G Holst, Eva Prescott
Journal: Circulation (2009)

Objectives Venous thromboembolism (VTE) (deep vein thrombosis and pulmonary embolism) and atherosclerotic disease (AD) have for many years been considered two different entities. Recent studies, th...
Clinicopathological features, oncological and functional outcomes in patients who underwent simultaneous radical cystectomy and nephroureterectomy in panurothelial carcinoma context
Authors: J.D. Subiela Henríquez, J. Huguet, J. Aumatell, A. Mercadé, J. Balañà, J. Calderón, I. Girón, A. Sánchez Puy, S. Fontanet, A. Bravo, E. Suquilanda, J. Robalino, I. Sanz, J.M. Gaya, O. Rodríguez-Faba, A. Territo, A. Breda, J. Palou
Journal: European Urology (2021)
Genetic Risk Score for Type 2 Diabetes and Traits Related to Glucose-Insulin Homeostasis in Youth: The Exploring Perinatal Outcomes Among Children (EPOCH) Study
Authors: Maggie A. Stanislawski, Elizabeth Litkowski, Sridharan Raghavan, Kylie K. Harrall, Jessica Shaw, Deborah H. Glueck, Ethan M. Lange, Dana Dabelea, Leslie A. Lange
Journal: Diabetes Care (2021)

OBJECTIVE The metabolic phenotype of youth-onset type 2 diabetes (T2D) differs from that of adult-onset T2D, but little is known about genetic contributions. We aimed to evaluate the association between a T2D genetic risk score (GRS) and traits related to glucose-insulin homeostasis among healthy youth. RESEARCH DESIGN AND METHODS We used data from 356 youth (mean age 16.7 years; 50% female) in the Exploring Perinatal Outcomes Among Children (EPOCH) cohort to calculate a standardized weighted GRS based on 271 single nucleotide polymorphisms associated with T2D in adults. We used linear regression to assess associations of the GRS with log-transformed fasting glucose, 2-h glucose, HOMA of insulin resistance (HOMA-IR), oral disposition index, and insulinogenic index adjusted for age, sex, BMI z score, in utero exposure to maternal diabetes, and genetic principal components. We also evaluated effect modification by BMI z score, in utero exposure to maternal diabetes, and ethnicity. RESULTS Higher weighted GRS was associated with lower oral disposition index (β = −0.11; 95% CI −0.19, −0.02) and insulinogenic index (β = −0.08; 95% CI −0.17, −0.001), but not with fasting glucose (β = 0.01; 95% CI −0.01, 0.02), 2-h glucose (β = 0.03; 95% CI −0.0004, 0.06), or HOMA-IR (β = 0.02; 95% CI −0.04, 0.07). BMI z score and in utero exposure to maternal diabetes increased the effect of the GRS on glucose levels. CONCLUSIONS Our results suggest that T2D genetic risk factors established in adults are relevant to glucose-insulin homeostasis in youth and that maintaining a healthy weight may be particularly important for youth with high genetic risk of T2D.
Abstract 1202: ERG344: A novel IRG1 inhibitor for the treatment of colon cancer
Authors: Adonia E. Papathanassiu, Francesca Lodi, Hong A. Vu, Diether Lambrechts
Journal: Cancer Research (2021)

Abstract Immune responsive gene 1 (Irg1) is an LPS-inducible gene within macrophages (MF) whose protein product is responsible for the synthesis of itaconate from aconitate through a break in the TCA cycle. Although primarily present in proinflammatory macrophages, IRG1 expression has been linked with certain cancers (glioblastoma, ovarian carcinoma) and its tumor-driven upregulation in peritoneal resident macrophages (pResMF) has been shown to contribute to peritoneal tumor growth. Here, we report Irg1 gene expression at the single cell level (scRNAseq) in samples obtained from colorectal cancer patients (n=7; ~11,000 single cells). Transcriptomic analysis showed that Irg1 was primarily expressed by cancer cells, although other tumoral cell types also showed substantial levels of the gene. To determine if IRG1 is a druggable target in cancer, we synthesized a series of small MW inhibitors and selected ERG344 for in vivo testing based on its ability to inhibit itaconate synthesis in a rat glioblastoma cell line (C6) engineered to stably express Irg1. The IC50 value of inhibition was ~150 μM. In vivo, ERG344 suppressed tumor growth and increased survival probability in a syngeneic colon cancer model (CT26). Drug administration was initiated when the tumors reached an average tumor volume of ~100 mm3 and involved daily ERG344 doses of 0.2 mg/kg ip or 0.3 mg/kg po. Complete tumor regressions (~17%) were observed in the same model when ERG344 was administered ip at 3 mg/kg. Immunophenotyping of CT26 tumors treated with either vehicle or 0.2 mg/kg ERG344 ip indicated that IRG1 inhibition renders the tumor microenvironment less immunosuppressive by decreasing the frequency of monocytic myeloid suppressor cells (m-MDSCs), increasing the frequency of cytotoxic CD8+ T cells, and decreasing the CD8+ expression of the negative co-stimulatory molecule PD-1. To determine if ERG344 is also able to reduce pResMF-driven peritoneal tumor growth, murine melanoma B16F15 cells were injected into the peritoneal cavity of C57BL/6 mice treated with vehicle or 1 mg/kg ERG344 (n=8/group). Seven days after tumor inoculation, mice treated with ERG344 showed reduced tumor growth in the peritoneal cavity, which led to increased survival probability of the animals. The studies collectively suggest that IRG1 is a novel target for the treatment of primary and metastatic tumor growth in colorectal cancer and highlight the therapeutic potential of ERG344. Citation Format: Adonia E. Papathanassiu, Francesca Lodi, Hong A. Vu, Diether Lambrechts. ERG344: A novel IRG1 inhibitor for the treatment of colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1202.
Reporting of Percutaneous Coronary Interventions Site-Specific Mortality—Reply
Authors: Ashwin S. Nathan, Jay Giri, Alexander Fanaroff
Journal: JAMA Cardiology (2021)

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Reconciling Asgardarchaeota Phylogenetic Proximity to Eukaryotes and Planctomycetes Cellular Features in the Evolution of Life
Authors: Damien P Devos
Journal: Molecular Biology and Evolution (2021)

The relationship between the three domains of life-Archaea, Bacteria, and Eukarya-is one of Biology's greatest mysteries. Current favored models imply two ancestral domains, Bacteria and Archaea, with eukaryotes originating within Archaea. This type of models has been supported by the recent description of the Asgardarchaeota, the closest prokaryotic relatives of eukaryotes. However, there are many problems associated with any scenarios implying that eukaryotes originated from within the Archaea, including genome mosaicism, phylogenies, the cellular organization of the Archaea, and their ancestral character. By contrast, all models of eukaryogenesis fail to consider two relevant discoveries: the detection of membrane coat proteins, and of phagocytosis-related processes in Planctomycetes, which are among the bacteria with the most developed endomembrane system. Consideration of these often overlooked features and others found in Planctomycetes and related bacteria suggest an evolutionary model based on a single ancestral domain. In this model, the proximity of Asgard and eukaryotes is not rejected but instead, Asgard are considered as diverging away from a common ancestor instead of on the way toward the eukaryotic ancestor. This model based on a single ancestral domain solves most of the ambiguities associated with the ones based on two ancestral domains. The single-domain model is better suited to explain the origin and evolution of all three domains of life, blurring the distinctions between them. Support for this model as well as the opportunities that it presents not only for reinterpreting previous results, but also for planning future experiments, are explored.
Abstract 2605: A natural history study of men with high-risk genetics for prostate cancer (PCa) using multiparametric MRI (mpMRI)
Authors: Fatima Karzai, Anna Couvillon, Yolanda McKinney, Katherine Lee-Wisdom, Peter L. Choyke, Veda N. Giri, Todd M. Morgan, Heather H. Cheng, Maria J. Merino, Peter A. Pinto, Baris Turkbey, William L. Dahut
Journal: Cancer Research (2021)

Abstract Introduction: The understanding of molecular genetics in PCa provides insight into disease progression and treatment. Less is known about PCa development in men with known high-risk germline pathogenic/likely pathogenic variants in PCa related genes, particularly DNA damage repair (DDR). mpMRI can localize and detect PCa lesions in this population. We are conducting a multicenter natural history study of male participants (prts) with documented germline variant(s) in BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, EPCAM, HOXB13, ATM, NBN, TP53, CHEK2, PALB2, RAD51D, BRIP1, or FANCA who do not have a PCa diagnosis using mpMRI (NCT03805919). Methods: Up to 500 men, 30-75 years old (y/o) will undergo mpMRI evaluation at baseline and every 2 years (yrs). Prts are followed at 12-mo intervals to determine PSA, PCa diagnosis, and/or disease/survival status until death. Indication for prostate biopsy includes PSA &amp;gt;2.0 for 30 - 49 y/o; &amp;gt;2.5 ng/mL for 50 - 75 y/o and/or PIRADS 3+ MRI lesion or clinical discretion. Tissue obtained will undergo full transcriptome analysis. Results: 100 prts have enrolled. Median age is 47 y/o. Median on-study PSA is 0.87 (0.16-10.05 ng/mL). Median PSA density is 0.029. Gene mutations are BRCA2 (40%), BRCA1 (33%), MSH2 (9%), and CHEK2 (4%). Mutations in ATM, HOXB13, MLH1, MSH6, PMS2, and EPCAM are ≤3%. No significant AEs have been observed. Of 96 prts, 25 (26%), had indication for biopsy [PIRADS 4 lesion: 16 (64%), PIRADS 3 lesion: 4 (16%), elevated PSA: 6 (24%), or clinical indication 1: (4%)]. 22 prostate biopsies were performed and 6 prts were diagnosed with PCa. One prt was upstaged on radical prostatectomy (RP). Conclusions: We found mpMRI-based PCa screening in men with high-risk gene mutations, especially DDR genes, is feasible and can be used to identify clinically significant PCa and monitor for disease progression. Future guidelines should consider age, mutation specificity and mpMRI. Accrual and correlative studies (biomarkers, PBMCs) are on-going. AgeMutationPSA (ng/mL)Biopsy Gleason ScoreTreatment65BRCA22.253+3RP52BRCA10.693+3Active Surveillance (AS)62CHEK22.493+3AS59PMS21.033+3AS59CHEK22.243+4Radiation55BRCA21.683+3RP: 4+4=8 Citation Format: Fatima Karzai, Anna Couvillon, Yolanda McKinney, Katherine Lee-Wisdom, Peter L. Choyke, Veda N. Giri, Todd M. Morgan, Heather H. Cheng, Maria J. Merino, Peter A. Pinto, Baris Turkbey, William L. Dahut. A natural history study of men with high-risk genetics for prostate cancer (PCa) using multiparametric MRI (mpMRI) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2605.
Abstract 2840: HK1 induces epithelial-mesenchymal transition and promotes metastasis of colorectal cancer
Authors: Xiaobin Zheng, Huashan Liu, Xiaoli Zhong, Xuanhui Liu, Zerong Cai, Yufeng Chen, Xiaosheng He, Ping Lan, Xiaojian Wu
Journal: Cancer Research (2021)

Abstract Hexokinase 1 (HK1) has been implicated in tumorigenesis. However, its role in tumor metastasis and progression has not been evaluated. The aim of this study is to evaluate the role of HK1 in the metastasis in CRC. Methods: The expression level of HK1 was detected using quantitative RT-PCR and western blot in 9 CRC cell lines and 1 human colon epithelial cell line NCM460 (Figure 1A). HK1 was overexpressed via lentiviral vector system and silenced using specific small interference RNA (si-HK1) in DLD1 and HCT8. Then wound-healing, migration assay and invasion assay were carried out to investigate the function of HK1 in CRC cells. RT-PCR and Western blot was performed to detect the change of Snail2 following the up-regulated expression of HK1. Results: HK1 expression was overexpressed by HK1-cDNA and was inhibited by si-HK1 in DLD1 and HCT8 (Figure 1B and 1C). Ectopic expression of HK1 promoted cell migration and invasion in CRC cells and promoted lung metastasis in mouse models (Figure 1D). Furthermore, HK1 induced migration and invasion in CRC cells was found to activate expression of Snail2 and in turn, induce epithelial-mesenchymal transition (EMT) and cancer progression (Figure 1E). Conclusions: High expression of HK1 could activate expression of Snail2 and in turn, induce EMT. Our findings suggest that HK1 may be a potential prognostic biomarker and therapeutic target for CRC invasion and metastasis. Keywords: Colorectal Cancer, HK1, Migration, Invasion Figure 1. A. The expression level of HK1 in 10 cell lines. B, C. HK1 expression was overexpressed by HK1-cDNA and was inhibited by si-HK1 in DLD1 and HCT8. *P&amp;lt; 0.05. D. Overexpression of HK1 in HCT8 increased the capacity of cell migration and invasion in vitro and in vivo. E. Expression levels of Snail2 and EMT were induced after HK1 overexpression. Citation Format: Xiaobin Zheng, Huashan Liu, Xiaoli Zhong, Xuanhui Liu, Zerong Cai, Yufeng Chen, Xiaosheng He, Ping Lan, Xiaojian Wu. HK1 induces epithelial-mesenchymal transition and promotes metastasis of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2840.
Prognostic Impact of Complete Response after First Line Therapy on Outcomes Following Initial Relapse in Newly Diagnosed Multiple Myeloma
Authors: Nidhi Tandon, Surbhi Sidana, S. Vincent Rajkumar, Wilson I Gonsalves, Prashant Kapoor, Angela Dispenzieri, Morie A. Gertz, Rahma Warsame, Taxiarchis Kourelis, Martha Q Lacy, David Dingli, Amie Fonder, Suzanne R. Hayman, Miriam Hobbs, Yi L. Hwa, Francis K Buadi, Robert A Kyle, Nelson Leung, Ronald S. Go, John A. Lust, Stephen J. Russell, Shaji K Kumar
Journal: Blood (2017)