tbuckley/cabot-search huggingface dataset:
Adipose tissue biomarkers and type 2 diabetes incidence in normoglycemic participants in the MESArthritis Ancillary Study: A cohort study
Authors: Farhad Pishgar, Mahsima Shabani, Thiago Quinaglia A. C. Silva, David A. Bluemke, Matthew Budoff, R Graham Barr, Matthew A. Allison, Alain G. Bertoni, Wendy S. Post, João A. C. Lima, Shadpour Demehri
Journal: PLoS Medicine (2021)

Given the central role of skeletal muscles in glucose homeostasis, deposition of adipose depots beneath the fascia of muscles (versus subcutaneous adipose tissue [SAT]) may precede insulin resistance and type 2 diabetes (T2D) incidence. This study was aimed to investigate the associations between computed tomography (CT)-derived biomarkers for adipose tissue and T2D incidence in normoglycemic adults.
Reproducibility of m7-FLIPI Risk Scores in Follicular Lymphoma Using Tumor Biopsies and Blood Specimens
Authors: Joanne Soo, Florian Scherer, David M. Kurtz, Joseph G Schroers-Martin, Michael Jin, Alexander Craig, Henning Stehr, Chih Long Liu, Michael R Green, Oliver Weigert, Maximilian Diehn, Ash A. Alizadeh
Journal: Blood (2017)
Magnetothermal regulation of in vivo protein corona formation on magnetic nanoparticles for improved cancer nanotherapy
Authors: Tingbin Zhang, Galong Li, Yuqing Miao, Junjie Lu, Ningqiang Gong, Yifan Zhang, Yuantai Sun, Yuan He, Mingli Peng, Xiaoli Liu, Xing-Jie Liang, Haiming Fan
Journal: Biomaterials (2021)
Abstract 1327: Role of intra-tumoral bacteria in EGFR-tyrosine kinase inhibitor resistance
Authors: Wendong Li, Aviva Rotter-Maskowitz, Ting Sun, Keqiang Zhang, Ravid Straussman, Dan Raz
Journal: Cancer Research (2021)

Abstract Mutations of the epidermal growth factor receptor (EGFR) are the most common group of actionable mutations in lung cancer, and they predict response to EGFR-tyrosine kinase inhibitos (EGFR-TKIs). The third-generation EGFR-TKI osimertinib is the standard of care for first-line treatment of patients with advanced EGFR-mutated lung cancer. Although most lung cancers with EGFR-mutation respond to osimertinib, resistance is eventually observed in all patients, and there are no approved targeted therapies once resistance to osimertinib occurs. Mechanisms of resistance to osimertinib are poorly understood and involve both EGFR and non-EGFR related pathways. Intra-tumoral bacteria are emerging as a cause of therapy resistance in cancer.Intra-tumoral bacteria have been reported in many cancers and emerging evidence suggests that the tumor microbiome plays an important role in drug resistance in a variety of cancers. But the link between intra-tumoral bacteria and therapy resistance in lung cancer remains elusive. We previously described the tumor microbiome identified within a cohort of non-small cell lung cancers. In order to determine if intra-tumoral bacteria within lung adenocarcinoma patient with EGFR mutation could play role on the resistance to EGFR-TKIs, such as osimertinib and erlotinib, we used a bacterial pre-conditioned medium (PCM) screening system which utilized various bacteria identified in lung cancer specimens. We used a cell viability evaluation method in GFP-labeled PC9 cells (EGFR Ex19del) to identify the bacterial PCM that may lead to resistance to EGFR-TKIs. We found that PCM from Chryseobacterium indologenes (C-PCM) markedly rescued PC9 cells from osimertinib or erlotinib treatment. We also found that proteinase K treatment eliminated the rescue of C-PCM on EGFR-TKI treatment, suggesting that a proteins within C-PCM are responsible for its effect of EGFR-TKI treatment. Mass spectrometry (MS) analysis showed that C-PCM does not degrade osimertinib or erlotinib, suggesting that C-PCM mediated resistance does not occur through drug degradation. Western blot analysis showed that C-PCM does not affect EGFR, phospho-EGFR, or AKT expression level but C-PCM significantly increased AKT phosphorylation level. Our current studies indicated that intra-tumoral bacteria within lung adenocarcinoma patient may leads to resistance to osimertinib and erlotinib. Further mechanistic studies of C-PCM mediated resistance are under way and may lead to new therapies to overcome osimertinib-resistance. Citation Format: Wendong Li, Aviva Rotter-Maskowitz, Ting Sun, Keqiang Zhang, Ravid Straussman, Dan Raz. Role of intra-tumoral bacteria in EGFR-tyrosine kinase inhibitor resistance [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 1327.
3D virtual renal modeling to improve the learning curve of percutaneous nephrolithotripsy
Authors: M.G. Giampaoli, C.V. Pultrone, L. Bianchi, E. Molinaroli, A. Angiolini, L. Cercenelli, B. Bortolani, A. Mottaran, D. Recenti, F. Chessa, C. Gaudiano, R. Golfieri, E. Marcelli, R. Schiavina, E. Brunocilla
Journal: European Urology (2021)
Are patients really willing to undergo surgery for Peyronie’s disease?
Authors: P. Capogrosso, L. Candela, W. Cazzaniga, A. Costa, G. Fallara, L. Boeri, E. Pozzi, F. Belladelli, N. Schifano, D. Cignoli, C. Abbate, F. Montorsi, A. Salonia
Journal: European Urology (2021)
Abstract 1402: HNRNPA2B1 increases the serine synthesis pathway in endocrine-resistant breast cancer cells
Authors: Carolyn M. Klinge, Belinda J. Petri, Kellianne M. Piell, Brian C. Clem
Journal: Cancer Research (2021)

Abstract Despite the limited success of new combination therapies with fulvestrant improving survival of breast cancer patients with metastatic disease after initial response to endocrine therapies based on primary estrogen receptor alpha (ER+) tumors, mechanisms for acquired endocrine resistance remain to be fully elucidated. The RNA binding protein HNRNPA2B1, a reader of epitranscriptomic N(6)-methyladenosine (m6A) in transcribed RNA, is upregulated in endocrine-resistant, ER+ LCC9 and LY2 cells compared to parental MCF-7 endocrine-sensitive luminal A breast cancer cells. HNRNPA2B1 regulates pri- to pre- miRNA processing as well as splicing and transcript stability, depending on interacting proteins and cellular context. The miRNA-seq transcriptome of MCF-7 cells transiently overexpressing HNRNPA2B1 identified gene ontology (GO) pathways including cellular response to steroid hormone signaling and serine family amino acid metabolic processes, i.e., the serine synthesis pathway (SSP). Stable, modest (4.5-fold) overexpression of HNRNPA2B1 in MCF-7 cells (MCF-7-A2B1 cells) phenocopies the endocrine-resistance of LCC9 and LY2 cells including ablation of growth inhibition by 4-hydroxytamoxifen (4-OHT) and fulvestrant. This was not the result of decreased ER alpha; rather, ER alpha, and androgen receptor (AR), were increased. Conversely, transient knockdown of HNRNPA2B1 in LCC9 and LY2 cells sensitized the cells to growth inhibition by 4-OHT and fulvestrant. MCF-7-A2B1 cells, like LCC9 and LY2 cells, have higher expression of phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase (PSAT1) transcripts and proteins compared to MCF-7 cells. We identified two miRNAs, miR-424-5p and miR-145-5p downregulated in MCF-7-A2B1 cells that directly target the PSAT1 3'UTR in dual luciferase assays. Lower miR-424-5p and miR-145-5p in endocrine-resistant LCC9 and LY2 correlate with increased PSAT1 and higher PSAT1 is associated with reduced overall and metastasis-free survival in breast cancer patients. The correlation of HNRNPA2B1 and PSAT1 expression was examined by IHC in a breast tumor/tissue microarray. Overall, our data suggest a role for increased HNRNPA2B1 in endocrine-resistance and upregulation of the SSP to promote tumor progression in ER+ breast cancer. Citation Format: Carolyn M. Klinge, Belinda J. Petri, Kellianne M. Piell, Brian C. Clem. HNRNPA2B1 increases the serine synthesis pathway in endocrine-resistant breast cancer 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 1402.
Abstract 2090: TP73 expression may be influenced by DNA methylation in human tumorigenesis
Authors: Zhixing Yao, David R. Yao, William Yu, Ahmed Malki, Zaki A. Sherif
Journal: Cancer Research (2021)

Abstract Epigenetic events that cause alterations in gene expression are common in human cancers. The connection between TP73 expression and its epigenetic functionality in tumorigenesis has scarcely been explored. As a transcription factor, TP73 (aka, p73) like its cousin, p53, is activated in response to DNA damage and regulates the expression of downstream genes involved in cell cycle arrest and apoptosis. However, there are other compounding functions of this gene that reflect its non-tumor-related characteristics, thus making it very difficult to assess its specific role in tumorigenesis. Our previous work showed that DNA methylation activates TP73 expression in hepatocellular carcinoma (HCC) and gastrointestinal cancer. In this study, we determined TP73 expression in normal human mammary epithelial cells (HMECs), human non-cancerous Li-Fraumeni Syndrome (LFS) skin fibroblast cells, human breast cancer cell lines (MCF7, MDA-MB-231 &amp; MDA-MB-468), prostate cancer cell lines (LNCaP &amp; MDA-PCa2b), lung cancer cell lines (A549 &amp; NCI-H596), neuroblastoma cell lines (IMR32 &amp; SK-N-SH) and normal human skin fibroblast cell line (HS27). The results show that TP73 was expressed solely in cancer cells. Subsequent immunohistochemical analyses of TP73 expression in cancerous and adjacent non-cancerous liver tissues of HCC patients clearly showed that TP73 expression was exclusively evident in cancerous tissues but not in the adjacent normal liver tissues. Mechanistically, methylation-specific PCR and bisulfite sequencing studies revealed that TP73 promoter is activated only in cancer cells and this activation occurs via DNA methylation. Moreover, ChIP assays demonstrated that a CTCF (a chromosomal networking protein CCCTC binding factor) and tumor protein p53 (TP53) bind to TP73 promoter and regulate TP73 expression. Our observations demonstrate that a positive correlation in tumorigenesis exists between TP73 expression and DNA methylation in promoter regions of TP73. These findings suggest that TP73's role in carcinogenesis may prove to be pivotal for the development of future diagnostic and therapeutic applications. Citation Format: Zhixing Yao, David R. Yao, William Yu, Ahmed Malki, Zaki A. Sherif. TP73 expression may be influenced by DNA methylation in human tumorigenesis [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 2090.
Abstract 1017: Arsenic trioxide reduces the expression of E2F1, cyclin E, and phosphorylation of PI3K signaling molecules in acute leukemia cells
Authors: Paul B. Tchounwou, Sanjay Kumar
Journal: Cancer Research (2021)

Abstract Arsenic trioxide (ATO) has been used for the treatment of acute promyelocytic leukemia (APL). Although ATO modulates cell cycle progression and apoptosis in APL cells, its exact mechanism of action remains elusive. In this research, we investigated its effects on E2F1, cyclin E, p53, pRb and PI3K signaling molecules by western blotting, immunocytochemistry and/or confocal imaging. We found that ATO inhibited the proliferation of APL cells through down-regulation of E2F1 and cyclin E expression, and stimulation of pRb. It also reduced the interaction of pRb and E2F1with binding to the E2F1 promoter, by stimulating pRb association. ATO also effected the phosphorylation of pRb at S608 and T373 residues and association of E2F1, pRb, and p53, simultaneously. However, in p53-knockdown NB4 cells, ATO did not significantly reduce E2F1 and cyclin E expression. Our findings demonstrate that ATO inhibits APL cell growth through reduced expression of E2F1, cyclin E, and stimulation of pRb. It also effected both interaction and association of E2F1, pRb and p53 by phosphorylation of pRb at T373 and S608 residues and reduced phosphorylation of PI3K signaling molecules. This novel mode of action of ATO in APL cells may be useful for designing new APL drugs. Citation Format: Paul B. Tchounwou, Sanjay Kumar. Arsenic trioxide reduces the expression of E2F1, cyclin E, and phosphorylation of PI3K signaling molecules in acute leukemia 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 1017.
NF-κB–dependent IRF1 activation programs cDC1 dendritic cells to drive antitumor immunity
Authors: Ghita Ghislat, Ammar S. Cheema, Elodie Baudoin, Christophe Verthuy, Pedro J. Ballester, Karine Crozat, Noudjoud Attaf, Chuang Dong, Pierre Milpied, Bernard Malissen, Nathalie Auphan-Anezin, Thien P. Vu Manh, Marc Dalod, Toby Lawrence
Journal: Science Immunology (2021)

Conventional type 1 dendritic cells (cDC1s) are critical for antitumor immunity. They acquire antigens from dying tumor cells and cross-present them to CD8+ T cells, promoting the expansion of tumor-specific cytotoxic T cells. However, the signaling pathways that govern the antitumor functions of cDC1s in immunogenic tumors are poorly understood. Using single-cell transcriptomics to examine the molecular pathways regulating intratumoral cDC1 maturation, we found nuclear factor κB (NF-κB) and interferon (IFN) pathways to be highly enriched in a subset of functionally mature cDC1s. We identified an NF-κB-dependent and IFN-γ-regulated gene network in cDC1s, including cytokines and chemokines specialized in the recruitment and activation of cytotoxic T cells. By mapping the trajectory of intratumoral cDC1 maturation, we demonstrated the dynamic reprogramming of tumor-infiltrating cDC1s by NF-κB and IFN signaling pathways. This maturation process was perturbed by specific inactivation of either NF-κB or IFN regulatory factor 1 (IRF1) in cDC1s, resulting in impaired expression of IFN-γ-responsive genes and consequently a failure to efficiently recruit and activate antitumoral CD8+ T cells. Last, we demonstrate the relevance of these findings to patients with melanoma, showing that activation of the NF-κB/IRF1 axis in association with cDC1s is linked with improved clinical outcome. The NF-κB/IRF1 axis in cDC1s may therefore represent an important focal point for the development of new diagnostic and therapeutic approaches to improve cancer immunotherapy.
進行性胆管腺癌での初回化学療法としてのゲムシタビンおよびカペシタビン(GEMCAP) : 第二相臨床試験結果
Authors: Rozzi A, Corona M, Nardoni C, Restuccia M, Falbo T, Lanzetta G
Journal: Annals of Oncology (2010)
Disease characteristics, prognosis, and response to therapy in patients with large-cell transformed mycosis fungoides: A single-center retrospective study
Authors: Megan O'Donnell, Romsin Zaya, Emily Correia, Shalini Krishnasamy, Joya Sahu, Wenyin Shi, Jisun Cha, Seyfettin Onder Alpdogan, Pierluigi Porcu, Neda Nikbakht
Journal: Journal of the American Academy of Dermatology (2021)
Utility of ex vivo confocal fluorescence microscopy for renal mass biopsy optimization
Authors: A.S. Valiquette, M. Marchioni, J. Rubio-Briones, A. Wong, A. Gomez-Ferrer, A. Collado Serra, J.L. Marenco, J. Casanova Ramon-Borja, M. Ramirez Backhaus, J.L. Dominguez, E. Sanchez Aparisi, A. Calatrava, M.C. Mir
Journal: European Urology (2021)
Relationship between the clinical profile of women with recurrent urinary tract infections and the prophylactic treatment chosen
Authors: J.E. Hernández-Sánchez, T. Hernández-Sánchez, F. García-Gómez, S. Valverde-Martínez, B.Y. Padilla Fernandez, M.T. Márquez-Sánchez, G. Márquez-Sánchez, M.C. Flores-Fraile, M.B. García-Cenador, C. González-Enguita, M.F. Lorenzo Gomez
Journal: European Urology (2021)
Abstract 2379: microRNA-7 replacement therapy: a promising approach for hepatocellular carcinoma
Authors: Dianne J. Beveridge, Tasnuva Kabir, Andrew J. Woo, Kirsty L. Richardson, Lisa M. Stuart, Peter J. Leedman
Journal: Cancer Research (2021)

Abstract Hepatocellular carcinoma (HCC) is increasing in incidence, has a very poor prognosis and presents massive global unmet clinical need. Current treatment of advanced HCC with sorafenib and other targeted therapies offers short-term relief with little significant clinical advantage. New approaches to the treatment of HCC are urgently needed. Non-coding RNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs), are gaining prominence in clinical medicine as potential diagnostics and therapeutics. The introduction of 2nd generation synthetic chemistry has led to dramatic stabilization of siRNAs and miRNAs producing prolonged effects on target gene expression. This has led the FDA to approve multiple RNA-mediated drugs starting in 2018, the first being a siRNA drug, Patisiran. A second major advance in the RNA-therapeutics field is the specific targeting of the liver by conjugating a galactose moiety (GalNAc) to the passenger RNA strand. This enables the dsRNA to be selectively and efficiently taken up by the asialoglycoprotein receptor (ASGPR) on the hepatocyte. The recent FDA approval of Givosiran, based on its clinical success in patients with porphyria using an ALAS-1 siRNA-GalNAc, illustrates the clinical utility of this system. We have shown that miRNA-7 (miR-7), a tumor suppressor miRNA, is a powerful inhibitor of HCC cell viability, via marked inhibition of EGFR, TYRO3, P-Akt and caveolin-1 signaling pathways. In vivo, miR-7 is a potent inhibitor of HCC tumor growth. In addition, miR-7 readily overcomes sorafenib resistance in multiple HCC cell lines. We utilized 2nd generation synthetic chemistry to develop a novel mimic of miR-7, mRx-7, for the treatment of HCC. mRx-7 is a significant inhibitor of HCC in vitro and is also substantially more stable than commercially available miR-7. In addition, we have engineered a liver-specific version of mRx-7 (mRx-7-GalNAc), which is a conjugate of mRx-7 plus GalNAc, and is a potent inhibitor of multiple signaling pathways, including P-Akt. Taken together, these data suggest that mRx-7 and mRx-7-GalNAc hold promise as novel HCC therapeutics. Citation Format: Dianne J. Beveridge, Tasnuva Kabir, Andrew J. Woo, Kirsty L. Richardson, Lisa M. Stuart, Peter J. Leedman. microRNA-7 replacement therapy: a promising approach for hepatocellular carcinoma [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 2379.
Two Hematopoietic Transcription Factors, RUNX1 and FUBP1, Control the Expression of KIT Oncogene in Pre-B Lymphoblasts
Authors: Lydie Debaize, Hélène Jakobczyk, Anne-Gaëlle Rio, Stéphane Avner, Aurélien Serandour, Frédéric Chalmel, Gilles Salbert, Marie-Dominique Galibert, Virginie Gandemer, Marie-Berengere Troadec
Journal: Blood (2017)
Longitudinal Changes in Cognitive Function in a Nationwide Cohort Study of Patients With Lymphoma Treated With Chemotherapy
Authors: Michelle C Janelsins, Mostafa Mohamed, Luke J Peppone, Allison Magnuson, Elizabeth K Belcher, Marianne Melnik, Shaker Dakhil, Jodi Geer, Charles Kamen, Lori Minasian, Patrick M Reagan, Supriya G Mohile, Gary R Morrow, Tim A Ahles, Charles E Heckler
Journal: JNCI Journal of the National Cancer Institute (2021)

Cancer-related cognitive decline (CRCD) is an important clinical problem, but limited research exists on assessment of cognitive function in patients with lymphoma.The overall objective of this nationwide, prospective, observational study conducted in the National Cancer Institute Community Clinical Oncology Research Program (NCORP) was to assess changes in memory, attention, and executive function in patients with lymphoma from pre- (A1) to postchemotherapy (A2) and to 6 months postchemotherapy (A3). Individuals without cancer served as noncancer controls, paired to patients by age and sex, and assessed at the same time-equivalent points. Longitudinal linear mixed models (LMM) including A1, A2, and A3 and adjusting for age, education, race, sex, cognitive reserve score, baseline anxiety, and depressive symptoms were fit. We assessed changes in patients compared with control participants without cancer and assessed differences in cognitive function in those patients with Hodgkin vs non-Hodgkin disease and by disease subtype. All statistical tests were 2-sided.Patients with lymphoma (n = 248) and participants without cancer serving as controls (n = 212) were recruited from 19 NCORP sites. From pre- to postchemotherapy and from prechemotherapy to 6 months follow-up, patients reported more cognitive problems over time compared with controls (Functional Assessment of Cancer-Therapy-Cognitive Function [FACT-Cog] perceived cognitive impairment effect size (ES) = 0.83 and 0.84 for A1 to A2 and A1 to A3, respectively; P < .001; single-item cognitive symptoms ES range = 0.55 to 0.70 inclusive of A1 to A2 and A1 to A3; P < .001); the complaints were more pronounced in women with lymphoma compared with men with lymphoma (FACT-Cog Perceived Cognitive Impairment (PCI) score group-by-time-by-sex interaction, P = .007). Patients with lymphoma also performed statistically significantly less well on tests of verbal memory and delayed recall, attention and executive function, and telephone-based category fluency.Patients with lymphoma experience worse patient-reported and objectively assessed cognitive function from prechemotherapy to 6-month follow-up compared with age- and sex-paired controls without cancer assessed at similar time intervals.
Recent advances and prospects of hyaluronan as a multifunctional therapeutic system
Authors: Niranjan G. Kotla, Srinivasa Reddy Bonam, Swetha Rasala, Jitendra Wankar, Raghvendra A. Bohara, Jagadeesh Bayry, Yury Rochev, Abhay Pandit
Journal: Journal of Controlled Release (2021)

Hyaluronan (HA) is a naturally occurring non-sulfated glycosaminoglycan (GAG), cell-surface-associated biopolymer and is the key component of tissue extracellular matrix (ECM). Along with remarkable physicochemical properties, HA also has multifaceted biological effects that include but not limited to ECM organization, immunomodulation, and various cellular processes. Environmental cues such as tissue injury, infection or cancer change downstream signaling functionalities of HA. Unlike native HA, the fragments of HA have diversified effects on inflammation, cancer, fibrosis, angiogenesis and autoimmune response. In this review, we aim to discuss HA as a therapeutic delivery system development process, source, biophysical-chemical properties, and associated biological pathways (especially via cell surface receptors) of native and fragmented HA. We also tried to address an overview of the potential role of HA (native HA vs fragments) in the modulation of inflammation, immune response and various cancer targeting delivery applications. This review will also highlight the HA based therapeutic systems, medical devices and future perspectives of various biomedical applications were discussed in detail.