tbuckley/cabot-search huggingface dataset:
Abstract 2389: LINC00901 regulates glucose metabolism in pancreatic cancer
Authors: Wan-Xin Peng, Liu Yang, Yin-Yuan Mo
Journal: Cancer Research (2021)

Abstract Dysregulation of metabolism is one of the cancer hallmarks. However, little is known whether long coding RNAs (lncRNAs) play a role in the regulation of metabolism in pancreatic ductal adenocarcinoma (PDAC). In the present study, we focused on lncRNA LINC00901 because a high level of LINC00901 is associated with the poor outcome of PDAC patients. Functional studies showed that LINC00901 promotes PDAC cell proliferation and invasion, whereas knockout (KO) of LINC00901 impairs these abilities of PDAC cells. Furthermore, the xenograft animal model suggested that LINC00901 promotes tumorigenesis. To determine the underlying mechanism of LINC00901-mediated tumorigenesis, we performed RNA-seq analysis in LINC00901 overexpression or KO cells. Gene Set Enrichment Analysis (GSEA) analysis showed that gene sets involved in glucose biological processes such as ‘‘MYC targets”, “Glycolysis” and “Gluconeogenesis” are significantly enriched in the LINC00901 overexpression group, whereas these genes are down-regulated in the LINC00901 KO group. The top-scoring genes recurring in the three gene sets include key glycolysis-related genes, lactate dehydrogenase A (LDHA), hexokinase 2 (HK2), and enolase 1 (ENO1), all of which were validated by qRT-PCR and western blot. Moreover, we found that LINC00901 upregulates c-Myc by stabilizing c-Myc RNA. Together, these results suggest that LINC00901 is an oncogenic lncRNA capable of regulating glucose metabolism, leading to PDAC development. Experiments are underway to determine how LINC00901 regulates c-Myc RNA stability in pancreatic cancer cells. Citation Format: Wan-Xin Peng, Liu Yang, Yin-Yuan Mo. LINC00901 regulates glucose metabolism in pancreatic 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 2389.
Abstract 1930: 4-nitroquinoline-1-oxide enhances induction of apoptosis preferentially in HPV positive head and neck squamous cell carcinoma cells
Authors: Gauri Shishodia, Alice Lee, Rhodee Ric Toledo, Emily Zimmerman, Xiaohua Rong, Adam Xiao, Lynn Harrison, Cherie Ann Nathan
Journal: Cancer Research (2021)

Abstract Background: Tobacco use and human papillomavirus (HPV) infection are both strong contributors to the oncogenesis of head and neck squamous cell carcinoma (HNSCC). Despite HPV's causative role in HNSCC, it confers no statistically significant difference in mutational profile between HPV-associated HNSCC smokers and non-smokers. Our earlier preliminary data suggested that HPV positive (+) HNSCC cells have better activation of DNA repair proteins compared to HPV negative (-) HNSCC cells when treated with 4NQO, a mutagen and carcinogen which serves as a surrogate for tobacco exposure. This may partially explain HPV+ HNSCC's higher mutational resistance. In addition to increased DNA repair, HPV+ cells may also eliminate mutations through higher rates of apoptosis compared to HPV- cells. Hence, we wanted to test this hypothesis by analyzing the effects of 4NQO on apoptosis in HPV+ and HPV- HNSCC cells. Methods: NOK, NOK E6.E7, SCC40 (HPV-), SCC104 and UMSCC47 (HPV+) cells were treated with different concentrations of 4NQO (0, 0.1, and 0.2 ug/ml) for 24 and 48 hours. Untreated (control) and 4NQO treated cells were assessed for cell viability using MTT assay. Apoptotic cells were determined using Annexin-V FITC flow cytometry analysis, and Western blot was performed to check the apoptotic proteins for the afore-mentioned control and 4NQO treatments. Results: MTT assay showed decreased cell viability of NOK E6.E7, SCC47 and SCC104 cells in response to 4NQO treatment compared to relatively higher cell viability of SCC40 cells. Flow cytometry confirmed that HPV+ HNSCC cells are relatively more apoptotic compared to HPV- cells following 4NQO treatment at 24 and 48 hours. This is further supported by activation of pro-apoptotic proteins including p53, cleaved caspase 3, cleaved PARP, cleaved caspase 9, and p21 to a greater extent in HPV+ cells at different time points of 4NQO treatment using Western blot analysis. Conclusion: Our in-vitro data suggest HPV may stimulate a protective measure against smoking-induced mutations by increasing apoptosis before cells can contribute to the HNSCC mutational profile. Taken together, these data explain why HPV associated HNSCC have a better prognosis than HPV negative irrespective of smoking history. Citation Format: Gauri Shishodia, Alice Lee, Rhodee Ric Toledo, Emily Zimmerman, Xiaohua Rong, Adam Xiao, Lynn Harrison, Cherie Ann Nathan. 4-nitroquinoline-1-oxide enhances induction of apoptosis preferentially in HPV positive head and neck squamous cell carcinoma cells [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 1930.
Abstract 3112: Human melanocyte development and melanoma dedifferentiation at single cell resolution
Authors: Rachel L. Belote, Daniel Le, Ashley Maynard, Ursula E. Lang, Adriane Sinclair, Vincente Planells-Palop, Laurence S. Baskin, Aaron D. Tward, Spyros Darmanis, Robert L. Judson-Torres
Journal: Cancer Research (2021)

Abstract In humans, epidermal melanocytes are responsible for skin pigmentation, defense against ultraviolet radiation, and the deadliest common skin cancer, melanoma. While there is substantial overlap in melanocyte development pathways between different model organisms, species dependent differences are frequent and the conservation of these processes in human skin remains unresolved. Thus, the biology of developing and adult human melanocytes remains largely uncharacterized. Here, we used a single-cell enrichment and RNA-sequencing pipeline to study human epidermal melanocytes derived directly from skin, capturing transcriptomes across different anatomic sites, developmental age, sexes, and multiple skin tones. Using donor-matched skin from distinct volar and non-volar anatomic locations, we uncovered subpopulations of melanocytes exhibiting site-specific enrichment that occurs during gestation and persists through adulthood. In addition, we identified human melanocyte differentiation transcriptional programs that are distinct from gene signatures generated from model systems. Finally, we use these programs to define patterns of dedifferentiation that are predictive of melanoma prognosis. Overall, the characterization of human melanocytes fresh from skin revealed new subpopulations, human-specific transcriptional programs, and valuable insights into melanoma dedifferentiation. Citation Format: Rachel L. Belote, Daniel Le, Ashley Maynard, Ursula E. Lang, Adriane Sinclair, Vincente Planells-Palop, Laurence S. Baskin, Aaron D. Tward, Spyros Darmanis, Robert L. Judson-Torres. Human melanocyte development and melanoma dedifferentiation at single cell resolution [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 3112.
Post-COVID syndrome: Turning convalescence into illness? – Authors’ reply
Authors: Max Augustin, Clara Lehmann
Journal: The Lancet Regional Health - Europe (2021)

We have carefully read the reply letter by Doctores Cozzi, Amaddeo and Barbi [1Cozzi G Post-COVID syndrome: turning convalescence into illness?.Lancet Reg Health Eur. 2021; (doi: https://doi.org/10.1016/j.lanepe.2021.100163)Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar] to our research paper titled "Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study" [2Augustin M. Schommers P. Stecher M. et al.Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study.Lancet Reg Health Eur. 2021; 6 (doi: https://doi.org/10.1016/j.lanepe.2021.100122)100122Summary Full Text Full Text PDF PubMed Scopus (395) Google Scholar] and note that a disruptive event such as the pandemic can promote the development of somatoform symptoms in predisposed individuals. We agree that there is a danger in seeking health care that somatoform symptoms may instead be exacerbated, with the risk of convalescence becoming illness. Convalescence from COVID-19 can take a lengthy course over months resulting in great societal and economic consequences. We found anosmia, ageusia, shortness of breath and fatigue to be the most common persisting symptom up to 7 months after symptom onset. Here, specific symptoms face nonspecific symptoms, physical health faces mental health. Especially with regard to fatigue, a holistic approach is necessary to reduce bias. It is undisputed that the aggravating circumstances such as social distancing and frequently changing narratives pose a particular challenge in terms of mental health and coping strategies. This is precisely when it is important to perceive patient impressions, to put them into perspective and to examine them in a multidisciplinary manner, as we did with 958 SARS-CoV-2 convalescents. It is important to emphasize that all post-COVID symptoms reported were newly emerged and resulted in restrictions of everyday life. Thus, a differentiated and critical anamnesis is essential to assess the symptoms in order to finally make the clinical diagnosis of a post-COVID syndrome and furthermore to provide support and offer solutions with the aim of shortening time of convalescence. Taken together, we don't think critically evaluating and labelling health consequences after viral illness is about turning convalescence into illness but rather about labelling illness to accelerate convalescence. MA an CL contributed to all aspects of the Letter. MA and CL have nothing to disclose. Post-COVID syndrome: Turning convalescence into illness?We read the paper by Augustin and colleagues [1] and we have some concerns. Full-Text PDF Open Access
Free Heme Induces a Heme Importer, Heme Catabolism and an Angiogenic Factor in Multiple Organs in Mice: Implications for Organ-Specific Response to Intravascular Hemolysis
Authors: Oluwabukola Gbotosho, Maria G Kapetanaki, Yu Lin, Frances Weidert, Solomon Fiifi Ofori-Acquah, Gregory J. Kato
Journal: Blood (2017)
Abstract 3006: Melanoma cell lines derived from patient derived xenografts (PDX) can contain murine chromosomes resultant from cell fusions
Authors: Agustin Vega-Crespo, Ignacio Baselga-Carretero, Ivan Perez-Garcilaso, Sameeha Jilani, Kevin Chen, Vaneet Khullar, Egmidio Medina, Yaroslav Teper, Antoni Ribas, Begoña Comin-Anduix
Journal: Cancer Research (2021)

Abstract Introduction: Patient Derived Xenografts (PDX) provide a distinct platform to generate in vivo and ex vivo cell lines to investigate novel therapies. However, human-murine cell fusions may skew the models and is a poorly characterized phenomenon. Methods: Malignant melanoma IRB-consented biopsies [IRBs: 17-000548; 17-001685; 17-001351; 11-003254] were excised from various sites and implanted into gender-matched 4-6 weeks old NOD-scid IL2Rgammanull mice. Tumor-bearing mice were humanely euthanized and adherent cell lines were generated after Miltenyi gentleMACS™ dissociation of the PDXs. Briefly, adherent cells are allowed to proliferate and passaged when 70% confluent for approximately 4-8 weeks. PDX-derived cell products were processed for long term-cryostorage and an aliquot was sent for GenePrint 10 System-Promega®-LaragenTM cell line authentication paired with patient-matched peripheral blood mononuclear cells (PBMC) for specimen congruency. Mouse-genome contaminant resulting cultures were prepared and sent for cell line characterization by G-banded metaphase karyotyping-Cell Line GeneticsTM. Cultures containing murine karyotypes were processed according to manufacturer recommendations by Miltenyi Mouse Cell Depletion KitTM where the flow through (negative fraction) represents the human-cell fraction. Results: We implanted 86 patient-derived biopsies into mice over 3years, from which 39 [45%] resulted in progressively growing PDXs. From these PDXs we have generated 26 [37%]-patient-specific PDX-derived cell lines. G-banded metaphase karyotyping demonstrated that 6 [24%]- cell lines presented murine chromosome contamination. The immunoprofile of these 6 cellular materials appear to be murine as the totality of the cultures were sequestered in the column by mouse depletion cell cocktail. Separation assay was validated by bonafide human cell lines, utilized as human positive controls, M257 and MX210 both with human karyotypes and matched Cell ID profiling. The murine colon carcinoma cell line MC38, was utilized as a positive murine control, and performed identically as the 6 PDX-derived cellular materials with abnormal mouse genomes. Conclusion: Detection of murine-human fusion cells in cell lines derived from PDXs may limit the utility of these models. Citation Format: Agustin Vega-Crespo, Ignacio Baselga-Carretero, Ivan Perez-Garcilaso, Sameeha Jilani, Kevin Chen, Vaneet Khullar, Egmidio Medina, Yaroslav Teper, Antoni Ribas, Begoña Comin-Anduix. Melanoma cell lines derived from patient derived xenografts (PDX) can contain murine chromosomes resultant from cell fusions [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 3006.
Abstract 2298: A potent and selective EGFR/HER2 exon 20 mutations inhibitor NIP142 induced tumor regression
Authors: Huijun Yin, Xu Yan, Weixue Tian, Guobiao Chu, Zhuo Wang, Xin Zhao, lu zhang, Xile Liu, Charles Z. Ding, Lihong Hu, Chengyuan Li, Gang Bai, Yuanfeng Xia, Chi-Chung Chan, Shuhui Chen
Journal: Cancer Research (2021)

Abstract Objective: Approximately 1.6-3.4% and 2-4% of NSCLC patients harbor EGFR or HER2 exon20 insertion mutations, respectively. No targeted therapy has been approved for these patients yet. NIP142 is a novel EGFR/HER2 inhibitor with potent inhibitory activities against above mentioned mutations. Purpose of this study is to provide evidence to support NIP142 as a clinical candidate for treatment of NSCLC driven by EGFR or HER2 exon20 insertion mutations. Method: Enzymatic activities of NIP142 were evaluated in EGFR/HER2 exon20 insertion mutants, including EGFR (D770_N771insNPG) and HER2 (V777_G778ins&amp;gt;CG). Anti-proliferative activities of NIP142 were evaluated in Ba/F3 cell lines with exon20 mutants (such as EGFR(D770_N771insSVD), EGFR(H773_V774insNPH), EGFR(V769_D770insASV), HER2(A775_G776insYVMA)), LU0387(EGFR-H773_V774insNPH), NCI-H1975 (EGFRL858R/T790M) and A431 (EGFRWT) cell lines. In vivo efficacy was evaluated in genetically engineered Ba/F3 (EGFR-D770_N771insSVD) mouse model, and LU0387 (EGFR-H773_V774insNPH) PDX model. Result: NIP142 displayed potent enzymatic inhibition activities in exon20 mutants, such as EGFR (D770_N771insNPG) (IC50 = 0.5 nM), HER2 (V777_G778ins&amp;gt;CG) (IC50 = 0.67 nM) and potent anti-proliferative activities in Ba/F3 cell lines with exon20 mutants, EGFR-D770_N771insSVD (IC50 = 32 nM), EGFR-H773_V774insNPH (IC50 = 32 nM), EGFR-V769_D770insASV (IC50 = 22 nM), HER2 A775_G776insYVMA (IC50 = 30 nM) respectively. NIP142 also exhibited potent anti-proliferative activities in NCI-H1975 (EGFRT790M\L858R) (IC50 = 9.4 nM), LU0387 (EGFR-H773_V774insNPH) (IC50 = 25 nM), and moderate anti-proliferation activity in EGFRWT A431cell line (IC50 = 37 nM). NIP142 was investigated in various CDX models. In particular, NIP142 significantly inhibited tumor growth in the LU0387 (EGFR-H773_V774insNPH) PDX tumor model of NSCLC, and tumor regression was achieved at 15 mg/kg. Conclusion: NIP142 is a potent EGFR/HER2 exon20 insertions inhibitor and showed excellent activities in preclinical in vitro assays and relevant tumor models. These results together with its preclinical safety data (not shown) support NIP142 to enter the clinical research to explore its potential for treating NSCLC with EGFR/HER2 exon20 insertions. Citation Format: Huijun Yin, Xu Yan, Weixue Tian, Guobiao Chu, Zhuo Wang, Xin Zhao, lu zhang, Xile Liu, Charles Z. Ding, Lihong Hu, Chengyuan Li, Gang Bai, Yuanfeng Xia, Chi-Chung Chan, Shuhui Chen. A potent and selective EGFR/HER2 exon 20 mutations inhibitor NIP142 induced tumor regression [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 2298.
Prostate cancer in renal transplant recipients: Results from a large multicentre contemporary cohort
Authors: G. Marra, F. Peretti, G. Calleris, M. Oderda, L. Biancone, G. Lamanna, P. Todeschini, A. Secchi, C. Dariane, O. Timsit, J. Brancherau, O. Hedli, B. Mesnard, D. Tilki, J. Olsburgh, M. Kulkarni, V. Kasivisvanathan, C. Lebacle, J. Irani, A. Breda, O. Rodriguez-Faba, J.M. Gaya, G. Gandaglia, P. Gontero
Journal: European Urology (2021)
Abstract 2109: The bromodomain-containing protein ATAD2 promotes GR-mediated enzalutamide resistance in castration-resistant prostate cancer
Authors: Richard De La Rosa
Journal: Cancer Research (2021)

Abstract The purpose of this study is to investigate how the activity of the glucocorticoid receptor (GR) is orchestrated to drive the development of enzalutamide resistance in metastatic, castration resistant prostate cancer (mCRPC). Enzalutamide (Enz) is the second-generation antagonist of the androgen receptor, the fuel for the development and progression of prostate cancer. Even though enzalutamide is an effective and well-tolerated treatment in a broad spectrum of patients with castration-resistant prostate cancer, almost all the patients become resistant to the drug eventually. One of the plausible mechanisms to account for the development of enzalutamide resistance is the activation of GR signaling. Upon Enz treatment, GR is upregulated, binds to the cis-regulatory elements of some AR target genes, activates the transcription of these downstream genes and thus circumvents the inhibitory effect of the AR antagonist on prostate cancer cell growth. Unfortunately, it is still unknown how GR-mediated enzalutamide resistance is controlled. Recently, a group of epigenetic regulators, bromodomain (BRD)-containing proteins, have been indicated to promote prostate cancer progression. They function as AR cofactors and dictate the transcriptional activity of the nuclear receptor in response to different ligands. Our prior work found that one of the BRD family members, called ATAD2, plays an essential role in orchestration of GR signaling in the presence of enzalutamide. ATAD2 is significantly elevated upon GR activation and positively regulates GR expression in return. Coimmunoprecipitation demonstrated that ATAD2 binds to GR in enzalutamide-resistant CRPC cells, and it is required for the GR-dependent transcriptional reprogramming in the presence of Enz. Most importantly, we demonstrated that CRPC cells that are Enz-refractory due to the activation of GR signaling become Enz sensitive when ATAD2 is depleted All these findings suggest that ATAD2 acts as a cofactor for GR to induce a gene expression pattern that results in Enz-refractory phenotype in CRPC cells. Our work will not only provide an in-depth insight into the mechanisms underlying enzalutamide resistance, but also lay the foundation for the development of novel therapeutic strategies targeting glucocorticoid receptor (GR) signaling to treat this lethal disease. Citation Format: Richard De La Rosa. The bromodomain-containing protein ATAD2 promotes GR-mediated enzalutamide resistance in castration-resistant prostate 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 2109.
Abstract 1165: Complementary diagnostics for precision targeting of cellular pathways
Authors: Robert Siddaway, Liana Nobre, Monique Johnson, Scott Milos, Scott Ryall, Javal Sheth, Uri Tabori, Cynthia Hawkins
Journal: Cancer Research (2021)

Abstract Precision medicine aims to tailor treatment to an individual patient through understanding the molecular basis of their disease. Targeted therapies have the potential to optimize responses and minimize side effects, while also offering savings to the healthcare system through tailoring treatment and avoiding futile therapies. Regimes are usually designed through identifying DNA-level alterations in the tumour and selecting drugs tailored to that mutation. However, cancer is not a one-pathway disease: not all patients with a particular mutational profile will respond to the same treatment, and patients without a canonical pathway-activating alteration will be excluded from potentially life-saving treatment. To address this, we developed a NanoString assay that combines proteomic and transcriptomic profiling of 4 key cancer-related, actionable pathways (MAPK, PI3K, NF-κB and JAK/STAT). Using RNA-Seq data from gold standard cell lines with defined changes in each pathway we generated minimal sets of genes indicative of pathway activation, and integrated this with total and phospho protein measurements to show pathway activation levels. The combined panel was run on a series of isogenic cell lines and glioma samples with both known and unknown driving alterations. Overall, pathway activation is more variable than would be predicted based on DNA alterations alone, with alternate pathway activation emerging as a potential new target and implying that consideration of proteomic and/or transcriptomic-level information will be important for future therapeutic decision-making. Citation Format: Robert Siddaway, Liana Nobre, Monique Johnson, Scott Milos, Scott Ryall, Javal Sheth, Uri Tabori, Cynthia Hawkins. Complementary diagnostics for precision targeting of cellular pathways [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 1165.
Abstract 13145: Saphenous Vein Grafts Anastomosed on a Dacron Conduit Show Comparable One-Year Patency to Saphenous Grafts Anastomosed on the Native Aorta
Authors: Miriam Bass, Emilie Leroux, Pierre Voisine, Eric Dumont, Francois Dagenais
Journal: Circulation (2019)

Introduction: CABG is a well-accepted technique for coronary artery revascularization. Early saphenous vein graft (SVG) failure is reported between 10-20% at one year. However, patency of SVG anast...