tbuckley/cabot-search huggingface dataset:
Abstract 3094: Estrogen receptor β agonist depletes ovarian cancer stem cells via repressing epithelial to mesenchymal transition
Authors: Ananya Banerjee, Shurui Cai, Na Li, Kousalya Lavudi, Tejinder Pal, Xuetao Bai, Qi-En Wang
Journal: Cancer Research (2021)

Abstract Ovarian cancer is considered a hormone sensitive tumor. A healthy ovary expresses both Estrogen Receptors alpha (ERα) and beta (ERβ). However, although expression of ERα fairly remains constant, the expression of ERβ gradually decreases as the cells undergo malignant transformation and furthers with the progression of cancer. ERα is thought to promote expression of genes associated with cell survival and proliferation enhancing tumor growth. In contrast, the ability of ERβ to suppress orthotropic ovarian xenograft development supported the role of ERβ as a ‘tumor suppressor' in EOC tumorigenesis. Thus, use of ERβ agonists might prove to be therapeutically beneficial in ovarian cancer. Our studies reveal that activation of ERβ by using a newly developed ERβ agonist, WT-IV-012, is able to suppress the subpopulation of ovarian cancer stem cells. Mechanistically, WT-IV-012 inhibits epithelial to mesenchymal transition (EMT)-mediated CSC expansion, probably by downregulating ERα, which is a key regulator in the maintenance of stemness of CSCs. Taken together, our data indicate that suppressed expression of ERβ is critical to maintaining stemness of ovarian cancer stem cells, in turn, contributing to cancer relapse and chemoresistance. ERβ agonist would be able to limit the CSC subpopulation and prevent tumor relapse and metastasis. Citation Format: Ananya Banerjee, Shurui Cai, Na Li, Kousalya Lavudi, Tejinder Pal, Xuetao Bai, Qi-En Wang. Estrogen receptor β agonist depletes ovarian cancer stem cells via repressing epithelial to mesenchymal transition [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 3094.
Neonatal Linear IgA Bullous Dermatosis Mediated by Breast Milk–Borne Maternal IgA
Authors: Shohei Egami, Chihiro Suzuki, Yuichi Kurihara, Jun Yamagami, Akiharu Kubo, Takeru Funakoshi, Wataru Nishie, Kazuya Matsumura, Takahiro Matsushima, Miho Kawaida, Michiie Sakamoto, Masayuki Amagai
Journal: JAMA Dermatology (2021)

Neonatal linear immunoglobulin A (IgA) bullous dermatosis (LABD) is a rare disease that can be fatal when associated with respiratory failure. All previously reported cases of neonatal LABD have been in newborns with healthy asymptomatic mothers, and the pathogenic IgA was of unknown origin.To clarify the origin of IgA associated with LABD in neonates born of healthy asymptomatic mothers.This case study analyzed the laboratory findings of a single breast-fed newborn male with neonatal LABD admitted to the Keio University Hospital in Tokyo and his healthy asymptomatic mother. The healthy newborn developed life-threatening blisters and erosions of the skin and mucous membranes on day 4 after birth. Blood serum, skin, and maternal breast milk were examined for IgA autoantibodies.Histopathologic and immunofluorescence analyses of specimens (serum, skin, and breast milk) from the patient and his mother.Histopathologic evaluation of the newborn's skin revealed subepidermal blisters with neutrophil infiltrates, and immunofluorescence testing showed linear IgA deposition along the basement membrane zone (BMZ), which lead to the diagnosis of neonatal LABD. Indirect immunofluorescence using normal human skin after treatment with 1-mol/L sodium chloride showed the patient to have circulating IgA binding to the dermal side of BMZ. Immunohistochemical staining proved the deposition of secretory IgA in the neonatal skin by demonstrating the presence of J chain-not been seen in other LABD cases-indicating that the autoantibodies producing the blisters were derived from the maternal breast milk. Although no circulating IgA against the skin was detected in mother's sera, the breast milk contained IgA that reacted with the dermal side of the BMZ. No new blister formation was observed after cessation of breastfeeding.The results of this case study suggest a passive transfer of pathogenic IgA to a newborn from an asymptomatic mother via breast milk. In prior reports, no serum from asymptomatic mothers of newborns with LABD had IgA autoantibodies binding to skin components; however, in this case, we found that the maternal breast milk contained IgA autoantibodies associated with neonatal LABD. In neonatal LABD, maternal breast milk should be examined for IgA autoantibodies and breast milk feeding should be discontinued as soon as neonatal LABD is suspected.
Abstract 303: Surface modification of paclitaxel-loaded nanoparticles based on polydopamine with pH sensitive property for targeted therapy in hepatocellular carcinoma
Authors: Mingfang Wu, Xinming Xia, Danna Sun, Chen Zhong
Journal: Cancer Research (2021)

Abstract Drug-loaded nanocarrier is a promising treatment for targeted therapy in hepatocellular carcinoma (HCC) due to their sustained release and outstanding tumor-targeting properties. Nevertheless, a limitation of current nanocarriers is the contradiction between multiple functions and favorable biocompatibility, owing to most of functional substances are non-biological. In this study, we introduced a targeting arginine-glycine-aspartic acid (RGD)-peptide on the surface of polydopamine (PDA)-ploy (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) to develop a novel nanoparticle, which were employed as a drug delivery system loaded with paclitaxel (PTX) for HCC therapy. Paclitaxel-loaded PHBV nanoparticles (PHBV-PTX-NPs) were prepared by emulsion solvent evaporation. As a gatekeeper, the pH-sensitive coating was formed by self-polymerization of dopamine. The RGD and PDA coated nanoparticles were combined through the Michael addition. The chemical structures and properties of these nanoparticles were characterized by dynamic light scattering-autosizer, transmission electron microscope, fourier transform infrared spectroscopy, differential scanning calorimetry, thermogravimetry and X-ray photoelectron spectroscopy. As expected, these RGD-PDA-PHBV-PTX-NPs achieved excellent targeting efficiency, which was revealed by the cellular uptake and cytotoxicity assay in HCC cells. Compared with that of free PTX, the RGD-PDA-PHBV-PTX-NPs showed more superior antitumor efficacy in the xenograft mouse model. Notably, in addition to efficient anticancer activities, RGD-PDA-PHBV-PTX-NPs exhibited lower toxicity than PTX to normal hepatocytes and mouse in vitro and in vivo, respectively. These studies suggest the potential beneficial use of RGD-PDA-PHBV-PTX-NPs in future HCC-targeted therapy with drug-loaded nanocarriers. Citation Format: Mingfang Wu, Xinming Xia, Danna Sun, Chen Zhong. Surface modification of paclitaxel-loaded nanoparticles based on polydopamine with pH sensitive property for targeted therapy in 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 303.
Abstract 2341: Metabolomic analysis reveals unique biochemical signatures associated with microbial dysbiosis, inflammation and energy metabolism in breast tissues of obese and nonobese black and white breast cancer patients
Authors: Athena Starlard-Davenport, Alana Smith, Elizabeth Tolley, Lu Lu
Journal: Cancer Research (2021)

Abstract Black women are more likely to be diagnosed with late-stage breast cancer than white women and have the lowest probability of cause-specific survival. Obesity is associated with increased breast cancer risk and deaths in black women. Insulin-resistant obesity features chronic systemic and local inflammation of fat, which has been linked to breast cancer outcomes. The breast also consists of a mucosal immune system that provides a complex mechanical barrier and an inherent defense against pathogens. Growing evidence shows that an imbalance in the microbiome due to inflammation may give rise to cancer development. However, there is a lack of data on the role of the microbiome in breast tumors from black women. Using a global metabolomics approach, we investigated normal (n= 24) and breast cancer (n=27) tissue from black and white women to identify microbial metabolites and metabolomic signatures that differ by breast tumor subtype and obesity status. Principal component analysis and hierarchical clustering of the global metabolite profiling data revealed separation between the metabolic signatures of normal and breast tumor tissue. Random forest analysis also revealed a unique biochemical signature in normal versus breast tumors by obesity status and breast tumor subtype, including triple negative breast tumors. Our data show that obesity associates with a unique set of metabolic pathways that facilitate the handling of inflammation, protein catabolism and tissue remodeling, and energy metabolism, which may be regulated by microbial processing in breast tumor tissue. Citation Format: Athena Starlard-Davenport, Alana Smith, Elizabeth Tolley, Lu Lu. Metabolomic analysis reveals unique biochemical signatures associated with microbial dysbiosis, inflammation and energy metabolism in breast tissues of obese and nonobese black and white breast cancer patients [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 2341.
Abstract 17215: Dietary Protein Activates Macrophage mTOR Signaling and Downstream Proatherogenic Effects in Both Mice and Humans
Authors: Divya Kapoor, Xiangyu Zhang, Brendan Caprio, Babak Razani
Journal: Circulation (2019)

High protein diets which are commonly utilized for weight loss have been reported to raise cardiovascular risk. However, the mechanisms underlying this risk are unknown. First using mouse models, w...
Abstract 2328: Interrogating the anti-cancer effects of co-enzyme Q10 (CoQ10) identifies metabolic and mitochondrial apoptotic responses as primary mechanisms in squamous cell carcinoma model
Authors: Niven R. Narain, Shiva Kazerounian, Shivani Khatu, Anne R. Diers, John McCook, Stephane Gesta, Robert S. Kirsner, Brian Berman, Rangaprasad Sarangarajan
Journal: Cancer Research (2021)

Abstract Targeting mitochondrial function as a therapeutic modality in cancer has been extensively investigated. BPM 31510 is a proprietary drug-lipid nanoconjugate formulation enabling delivery of supra-physiological concentrations of oxidized CoQ10 specifically into mitochondria. In this study, the anti-cancer properties of CoQ10 in squamous cell carcinoma (SCC) and its mechanism of action were investigated in in vivo xenograft and in vitro model systems. Nude mice were inoculated with a squamous carcinoma cell line isolated from tongue, SCC-25, and treated with a topical formulation containing 1.5% or 5% CoQ10. Treatment was associated with a dose-dependent delay in the detection of palatable tumors (14 ± 3 days vehicle control, 27 ± 7 days 1.5% cream, 39 ± 9 days 5% cream), (p&amp;lt;0.05). Histology and immunostaining analysis demonstrated a decrease in expression of VEGF in the treatment groups (p&amp;lt;0.05). The anti-cancer mechanism of action of CoQ10 was further investigated by interrogating the influence of CoQ10 exposure on molecular profiles using SCC-25 cells in vitro. Cell based assays, mRNA-based RT-PCR assays, and protein-based antibody chip microarrays confirmed an apoptotic response as a major anti-cancer effect in SCC-25 cells in response to CoQ10 exposure. The change in anti- and pro-apoptotic markers (Bcl-2 and caspase families) was independently confirmed by western blotting. In addition, global proteomic analysis revealed alterations in key metabolic proteins in the Pentose Phosphate Pathway (PPP). For example, expression of Transaldolase 1, an enzyme involved in the cellular protection against oxidative stress, resistance/susceptibility to apoptosis, and SCC tumor development and progression, was reduced 1.5 fold at both 6 and 24 hour time point in response to CoQ10 treatment. Together, the data suggests that CoQ10 influences cancer metabolism and redox pathway in activating apoptosis in SCC cancer model. Citation Format: Niven R. Narain, Shiva Kazerounian, Shivani Khatu, Anne R. Diers, John McCook, Stephane Gesta, Robert S. Kirsner, Brian Berman, Rangaprasad Sarangarajan. Interrogating the anti-cancer effects of co-enzyme Q10 (CoQ10) identifies metabolic and mitochondrial apoptotic responses as primary mechanisms in squamous cell carcinoma model [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 2328.
Abstract LB230: Inactivation of the CFTR gene in duodena of mice exposed to hexavalent chromium (Cr(VI)) in drinking water supports its tumor-suppressor status and implies its role in Cr(VI)-induced carcinogenesis of the small intestines
Authors: Roman Mezencev, Scott S. Auerbach
Journal: Cancer Research (2021)

Abstract Hexavalent chromium [Cr (VI)] compounds are used in metallurgical, chemical and refractory industries. Their carcinogenicity has been supported by a number of epidemiological and animal studies; however, their carcinogenic mode of action is still incompletely understood. To identify mechanisms involved in cancer development from toxicologically relevant exposures to Cr(VI), we analyzed gene expression data from duodena of mice exposed for 7 or 90 days to Cr(VI) in drinking water at concentrations 0.3-520 mg/L. This analysis included identification of upstream regulatory molecules that are likely responsible for the observed gene expression changes, and identification of annotated gene expression data from public repositories that correlate with gene expression changes in duodena of Cr(VI)-exposed mice. We identified the CFTR gene among top scoring upstream regulators, including at low exposure levels that, for the given timepoints, did not induce observable tissue damage. Furthermore, the expression data from duodena of Cr(VI)-exposed mice displayed a positive correlation with other datasets in public repositories associated with the inactive CFTR gene, of which the top scoring were datasets for ilea and duodena of Cftr-knockout mice. Our results support the tumor-suppressor role of the CFTR gene, which was previously suggested for intestinal carcinogenesis in humans and mice. Furthermore, our findings indicate, for the first time, the role of CFTR inactivation in chemical carcinogenesis and expand the range of plausible mechanisms that may be operative in Cr(VI)-mediated carcinogenesis of intestinal and possibly other tissues. Disclaimer: The views expressed are those of the authors and do not necessarily represent the views or policies of the US EPA. Citation Format: Roman Mezencev, Scott S. Auerbach. Inactivation of the CFTR gene in duodena of mice exposed to hexavalent chromium (Cr(VI)) in drinking water supports its tumor-suppressor status and implies its role in Cr(VI)-induced carcinogenesis of the small intestines [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 LB230.
Abstract 2102: Development and validation of Predicine methylation assay towards early cancer detection
Authors: Binggang Xiang, Chao Dai, Ming Wang, Zhixin Zhao, Amy Xiaohong Wang, Kemin Zhou, Shidong Jia, Shujun Luo, Pan Du
Journal: Cancer Research (2021)

Abstract DNA methylation is one of the earliest signatures during cancer development. DNA methylation patterns from different cancer types can provide distinct epigenetic signatures. Several methods are available for sequencing DNA methylation throughout the genome, including whole genome bisulfite sequencing (WGBS) and antibody-dependent DNA immunoprecipitation (MeDIP). As a non-invasive approach, plasma cfDNA and urinary cfDNA (ucfDNA) have been widely explored for clinical applications. More recently, in virtue of its cancer-specific methylation signatures, cfDNA has been adopted for early cancer detection and further identification of cancer tissue of origin. Predicine has developed a liquid biopsy methylation assay that can robustly detect methylation using genomic and circulating cell-free DNA in body fluids. Predicine's methylation assay has great improvement over WGBS in reducing DNA damage, GC bias and increasing NGS reads mapping rate, and mapping quality score. In this study, we report the clinical utility of Predicine's methylation assay, which efficiently distinguishing healthy donors from patients of various types of cancer. Combined with its genomics NGS counterpart, Predicine's methylation platform is a powerful tool for early cancer detection and real-time monitoring of cancer progression. Citation Format: Binggang Xiang, Chao Dai, Ming Wang, Zhixin Zhao, Amy Xiaohong Wang, Kemin Zhou, Shidong Jia, Shujun Luo, Pan Du. Development and validation of Predicine methylation assay towards early cancer detection [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 2102.
Abstract 15445: Beta-Adrenergic Receptor Stimulation Regulates Bcl-2 and Enhances Cardiomyocytes Sensitivity to Apoptosis
Authors: Brigitte R Gaume, Molly M Malone, Stephen Liggett
Journal: Circulation (2011)

Background: Loss of terminally differentiated cardiac myocytes contributes to the development of heart failure. Increased β-adrenergic receptors (βAR) stimulation regulates myocardial function in t...
Primary care takes the brunt of chronic NHS underfunding
Authors: Daniel K Goyal
Journal: BMJ (2021)

I read Salisbury’s article on remote consultations with interest.1 The value many patients place on their doctor’s ability to diagnose based on clinical examination is interesting. I have been on the other side of the consultation, hearing my relatives complain when “the doctor didn’t even examine me.” It is a lesson to all medical students: reassure after a clinical exam, not before. The exam itself might …
Enzyme-instructed and mitochondria-targeting peptide self-assembly to efficiently induce immunogenic cell death
Authors: Debin Zheng, Jingfei Liu, Limin Xie, Yuhan Wang, Yinghao Ding, Rong Peng, Min Cui, Ling Wang, Yongjie Zhang, Chunqiu Zhang, Zhimou Yang
Journal: Acta Pharmaceutica Sinica B (2021)

Immunogenic cell death (ICD) plays a major role in cancer immunotherapy by stimulating specific T cell responses and restoring the antitumor immune system. However, effective type II ICD inducers without biotoxicity are still very limited. Herein, a tentative drug- or photosensitizer-free strategy was developed by employing enzymatic self-assembly of the peptide F-pY-T to induce mitochondrial oxidative stress in cancer cells. Upon dephosphorylation catalyzed by alkaline phosphatase overexpressed on cancer cells, the peptide F-pY-T self-assembled to form nanoparticles, which were subsequently internalized. These affected the morphology of mitochondria and induced serious reactive oxygen species production, causing the ICD characterized by the release of danger-associated molecular patterns (DAMPs). DAMPs enhanced specific immune responses by promoting the maturation of DCs and the intratumoral infiltration of tumor-specific T cells to eradicate tumor cells. The dramatic immunotherapeutic capacity could be enhanced further by combination therapy of F-pY-T and anti-PD-L1 agents without visible biotoxicity in the main organs. Thus, our results revealed an alternative strategy to induce efficient ICD by physically promoting mitochondrial oxidative stress.
Abstract 3001: Multicellular structures of serous ovarian cancer nature isolated from pleural effusions are sufficient to recreate peritoneal carcinomatosis in immunosuppressed mice
Authors: Alicia A. Goyeneche, Ashwyna Sunassee, Sabrina J. Ritch, Michael Koch, Maria Bell, Zu-hua Gao, Carlos M. Telleria
Journal: Cancer Research (2021)

Abstract High-grade serous ovarian cancer (HGSOC) is a lethal disease often diagnosed in grade III International Federation of Gynecology and Obstetrics (FIGO) upon colonization of the peritoneal cavity, or in grade IV FIGO when it colonizes the pleural cavity. When in the pleural cavity, the disease often manifests with accumulation of pleural effusions containing multicellular structures (MCS). In this work, we studied whether MCS isolated from a pleural effusion of a patient that did not respond to chemotherapy are sufficient to cause peritoneal carcinomatosis in immunosuppressed mice when implanted orthotopically. Nude mice were injected intraperitoneally with MCS isolated from the pleural effusions of a heavily treated patient. We determined the time taken for the disease to develop, the tissues targeted, presence or absence of ascites, the macroscopic and microscopic disease appearance, and the expression of standard biomarkers of HGSOC. We contrasted the histopathology of the tumors recreated in mice against that of the original tumor taken during diagnostic surgery. MCS from pleural effusions were sufficient to recreate disease in the mice, which reached their humane-endpoint seven months following MCS injection (n=3). The animals developed abundant cellular peritoneal ascites. In addition, macro and microscopic discrete disease was observed in the fat surrounding the ovaries, the omental-pancreatic area, the peritoneal wall, a lymph node, the diaphragm, and the lung. The histopathology of the disease showed infiltrating papillary architecture, areas with cells arranged in a solid pattern, and tumor nests with slit-like lumens that stained positive for mutant p53, p16, and WT1. Our results provide proof of principle that MCS isolated from pleural effusions of a HGSOC patient are sufficient to recreate peritoneal carcinomatosis in nude mice, depicting most morphological features found at postoperative diagnosis. Citation Format: Alicia A. Goyeneche, Ashwyna Sunassee, Sabrina J. Ritch, Michael Koch, Maria Bell, Zu-hua Gao, Carlos M. Telleria. Multicellular structures of serous ovarian cancer nature isolated from pleural effusions are sufficient to recreate peritoneal carcinomatosis in immunosuppressed mice [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 3001.