tbuckley/cabot-search huggingface dataset:
Abstract 3260: Training for cancer surgery in Sub Saharan Africa
Authors: Mohamed Jalloh, Serigne Magueye Gueye
Journal: Cancer Research (2017)

Abstract BACKGROUND: Low- and middle-income countries (LMICs) face both training and infrastructural challenges for surgical care, particularly for cancer. Practitioners charged with caring for these patients have few options for basic or advanced training. OBJECTIVES: To describe the training options for cancer surgery in Sub Saharan Africa METHODS: The different methods of training are described and the advantages and limits of each methods is highlighted. RESULTS: Training during residency and onsite fellowship are a good option but requires an appropriate number and capacity of training programme. International fellowships have the limitation of readjustment back home for the trained fellow. Onsite International training missions like IVUmed’s missions have the advantage of “Teach One, Reach Many” outcome where a whole team in trained in accordance of local needs and the participation of all stakeholders. CONCLUSIONS: Long-term program commitments; effective communication; and a shared vision among the program site, the coordinating nongovernmental organization, and supporting organizations facilitate the development of thriving surgical teaching programs capable of serving local communities and conducting outreach training. Citation Format: Mohamed Jalloh, Serigne Magueye Gueye. Training for cancer surgery in Sub Saharan Africa [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3260. doi:10.1158/1538-7445.AM2017-3260
Abstract 3985: NCoR2 regulates glioblastoma progression and treatment resistance
Authors: Shelly Kaushik, Joanna J. Phillips, Valerie M. Weaver
Journal: Cancer Research (2017)

Abstract Glioblastoma Multiforme (GBM, WHO Grade IV glioma) is one of the deadliest adult CNS tumors with a median survival of less than two years. It is largely resistant to aggressive therapeutic regimes, which combine radiation, chemotherapy and surgery. Thus, it is imperative to identify the molecular players and pathways that facilitate GBM resistance and recurrence. Nuclear co-repressor protein NCoR2 is upregulated in GBM and its increased expression correlates with poor prognosis in GBM patients (Alrfaei. Plos one. 2013). NCoR2, through its binding to the histone deacetylase protein HDAC3, mediates transcriptional repression (Zhu et al. Brain Res. 2013). NCoR2 is also involved in maintenance of neural stem cells (Jepson et al. Nature. 2007), which contribute to treatment resistance. Our study employs two distinct lineages of glioma - the less aggressive proneural and the highly aggressive mesenchymal subtypes. We show that NCoR2 is differentially expressed across these subtypes, suggesting a role for NCoR2-mediated transcriptional reprogramming in GBM progression. Moreover, knockdown of NCoR2 leads to phenotypic changes both in vitro and in vivo - including effects on neurosphere formation and proliferation, differential expression of stem-like markers as well as regulation of tumor growth and progression in mice. We also demonstrate that NCoR2 expression is increased upon treatment with temozolomide (used for GBM therapy), indicating a protective pro-tumor role for NCoR2. Finally, we explore the contribution of the GBM microenvironment to GBM progression by varying the three-dimensional properties as well as the rigidity of the extracellular matrix and investigating changes in NCoR2 expression and its regulation of tumor progression. We conclude that NCoR2 regulates GBM progression and resistance to therapy potentially via inducing a stem-like phenotype as well as responding to the tumor-promoting mechanical cues within the GBM microenvironment. Citation Format: Shelly Kaushik, Joanna J. Phillips, Valerie M. Weaver. NCoR2 regulates glioblastoma progression and treatment resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3985. doi:10.1158/1538-7445.AM2017-3985
Abstract 218: Functional proteomic analysis of TβRI immunocomplex in TGF-β signaling
Authors: Liuya Tang, Zhaojing Meng, Mary Heller, Ming Zhou, Ying Zhang
Journal: Cancer Research (2017)

Abstract Transforming growth factor-beta (TGF-β) regulates a wide array of biological responses ranging from proliferation to apoptosis, and alterations in its signaling pathway are associated with a variety of human diseases, including cancer. During the activation of TGF-β signaling, TGF-β receptor I (TβRI) plays an important role in transducing signals to downstream effectors. To identify TβRI interacting proteins which are responsible for Smad-dependent pathways as well as Smad-independent pathways, we employed a large-scale quantitative proteomic analysis of TβRI immunocomplex. AML12 cells were labeled with L-Lysine and L-Arginine (K0R0, light) or L-Lysine-13C6-15N2 and L-Arginine-U-13C6-15N4 (K8R10, heavy). The cells cultured in K8R10 medium (H: Heavy) were transfected with Flag-TβRI, while the cells cultured in K0R0 medium (L: Light) were transfected with Flag vector. The cell lysates were combined at equal protein amount, and TβRI immunocomplex were purified using FLAG M2 agarose. The resulting peptides from eluted TβRI immunocomplex were subjected to mass spectrometry quantitation. If a protein whose ratio of H/L was not smaller than 1.3, it was categorized as a constitutively interacting protein of TβRI. A total of 687 proteins were quantitated and 325 proteins were defined as constitutively interacting proteins. Pathway enrichment analysis found these proteins are involved in a number of signaling pathways, which indicates the cross-talks between TGF-β signaling and other signaling. Future work will include validation of interaction between TβRI and candidate proteins, and understand functional significance of candidate proteins in TGF-β signaling or signaling cross-talks by a series of molecular biological approaches. Citation Format: Liuya Tang, Zhaojing Meng, Mary Heller, Ming Zhou, Ying Zhang. Functional proteomic analysis of TβRI immunocomplex in TGF-β signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 218. doi:10.1158/1538-7445.AM2017-218
Abstract 1191: The dopamine (DA) D3receptor antagonists (PG01037, NGB2904, SB-277011A, and U99194) significantly attenuate ABCG2-mediated multidrug resistance
Authors: Noor Hussein, Haneen Amawi, Charles R. Ashby, Karthikeyan Chandrabose, Roopali Mittal, Ryann Christman, Piyush Trivedi, Amit Tiwari
Journal: Cancer Research (2017)

Abstract ATP-binding family G2 (ABCG2) transporters are known to produce multidrug resistance (MDR) and limit successful cancer chemotherapy. Using molecular modeling, we obtained data indicating that highly potent and selective dopamine (DA) D3 receptor antagonists had significant docking scores for the active site of the ABCG2 transporter. In this in vitro study, we determined the effect of the D3 receptor antagonists (PG01037, NGB2904, SB-277011A, and U99194) on MDR resulting from the overexpression of ABCG2 transporters. The D3 receptor antagonists alone did not significantly affect the viability of HEK293/ABCG2, H460/MX-20, S1-M1-80 or A549-MX-10 cells, which overexpress ABCG2 transporters. However, the D3 receptor antagonists (PG01037, NGB2904, SB-277011A, and U99194) significantly increased the efficacy of the anticancer drugs mitoxantrone and doxorubicin in the above mentioned cell lines. Efflux studies indicated that both PG01037 and NGB2904 significantly decreased the efflux of rhodamine 123 from H460-MX20 cells. Interestingly, PG01037 and NGB2904 significantly decreased the expression levels of the ABCG2 protein levels as shown by immunocytochemical and Western blot analysis. This suggests that D3 antagonists inhibit both function and expression of ABCG2 transporters at relevant non-toxic concentrations. In conclusion, our in vitro results indicate that PG01037, NGB2904, SB-277011A, and U99194 reverse resistance to mitoxantrone and doxorubicin mediated by overexpression of ABCG2 transporters. Further mechanistic and animal studies are warranted to establish the clinical use of D3 receptor antagonists in reversing ABCG2-mediated MDR. Citation Format: Noor Hussein, Haneen Amawi, Charles R. Ashby, Karthikeyan Chandrabose, Roopali Mittal, Ryann Christman, Piyush Trivedi, Amit Tiwari. The dopamine (DA) D3 receptor antagonists (PG01037, NGB2904, SB-277011A, and U99194) significantly attenuate ABCG2-mediated multidrug resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1191. doi:10.1158/1538-7445.AM2017-1191
Abstract 3978: B7-H1/PD-L1 soluble expression in multiple cancer subtypes: High sensitivity measurement by immunoassay
Authors: Justin Haworth, Rainer Grant, Samuel Thayer, Melissa Floren, Nathan Steere, Isabel O'Brien, Paul Younge, Michael Anderson, Greta Wegner, Kathryn Brumbaugh
Journal: Cancer Research (2017)

Abstract Aberrant expression of the B7-H1/PD-L1 immunomodulatory molecule is evident in many forms of cancer. The evidence for increased protein levels of B7-H1/PD-L1 comes largely from immunohistochemistry analysis of surgical and biopsy specimens. While several studies attempt to correlate B7-H1/PD-L1 expression with poor prognosis, there are studies that conclude no correlation based on technical difficulties associated with detecting B7-H1/PD-L1 protein expression on the cell surface. We were able to quantifiably measure soluble B7-H1/PD-L1 in conditioned medium from tumor cell cultures using two new immunoassays, a Quantikine® ELISA and a Simple Plex™ Assay. We show that breast, prostate, glioma, and non-Hodgkin’s lymphoma cells express various levels of B7-H1/PD-L1 which correlate to their PTEN or proliferation status. This is in agreement with previous findings showing that increases in B7-H1/PD-L1 expression levels are frequently coincident with loss of the PTEN tumor suppressor or increased activation of the phosphoinositide 3-kinase (PI 3-K) pathway. The androgen-responsive LNCaP prostate cancer cell line does not exhibit measurable B7-H1/PD-L1 in any instance, while the androgen-independent prostate cancer cell line PC-3 expresses measurable B7-H1/PD-L1 that is further inducible with PMA treatment. In all cell lines included in our study, incubation with PMA increases the level of B7-H1/PD-L1 released into the culture media, while pretreatment with the PI 3-K inhibitor, LY294002, abrogates this increase. Importantly, the Simple Plex platform is able to quantify very low levels of B7-H1/PD-L1 that are below detection by ELISA. Our data suggest that combining the Quantikine ELISA and Simple Plex platforms is a powerful strategy for reliably and quantitatively assessing soluble B7-H1/PD-L1 levels. Citation Format: Justin Haworth, Rainer Grant, Samuel Thayer, Melissa Floren, Nathan Steere, Isabel O'Brien, Paul Younge, Michael Anderson, Greta Wegner, Kathryn Brumbaugh. B7-H1/PD-L1 soluble expression in multiple cancer subtypes: High sensitivity measurement by immunoassay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3978. doi:10.1158/1538-7445.AM2017-3978
Abstract LB-189: Blockade of stearoyl CoA desaturase 1 promotes immunogenic clearance of tumors
Authors: Christina Anna Elizabeth Von Roemeling, Thomas Caulfield, Yaqing Qie, Derek C. Radisky, Xiujie Liu, Yuanxin Chen, Joshua Knight, John Copland, Betty Kim
Journal: Cancer Research (2017)

Abstract Metabolic reprogramming plays a critical role in carcinogenesis, in part due its ability to promote immune suppressive properties within tumors. Agents that specifically target crucial metabolic enzymes utilized by cancer are been actively investigated. However, it is unclear whether inhibition of fatty acid metabolism in tumors affects their immunogenicity. Here, we show for the first time that inhibition of stearoyl-CoA desaturase 1 (SCD1), a key enzyme involved in fatty-acid synthesis and a potential prognostic marker for human cancers, increases the immunogenicity of poorly immunogenic tumors. The enhanced immune activation is accompanied by upregulated endoplasmic reticulum (ER) stress and is dependent on the translocation of ER protein calreticulin to the tumor cell surface. Inhibition of SCD1 increased both recruitment and activation of immune cells in vivo, which when combined with PD-1 blockade resulted in potent and durable anti-tumor T cell responses. Together, our results indicate that inhibition of tumorigenic de novo lipogenesis represents a novel approach to enhance T cell based cancer immunotherapy. Citation Format: Christina Anna Elizabeth Von Roemeling, Thomas Caulfield, Yaqing Qie, Derek C. Radisky, Xiujie Liu, Yuanxin Chen, Joshua Knight, John Copland, Betty Kim. Blockade of stearoyl CoA desaturase 1 promotes immunogenic clearance of tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-189. doi:10.1158/1538-7445.AM2017-LB-189
Endoscopic treatment of Zenker’s diverticulum using a stag beetle knife
Authors: Juan Martín-Guerrero, Alba Belda-Cuesta, Adan Lamilla-Fernández
Journal: Endoscopy (2017)

Zenker’s diverticulum can be treated successfully using flexible endoscopy [1]. Several methods have been used to cut the septum of the diverticulum, such as LigaSure (Medtronic, Minneapolis, Minnesota, USA), needle-knife, and other submucosal dissection devices. Recently, isolated cases using the stag beetle (SB) knife dissector, SB jr 3.5 mm, have been reported [2] [3] [4]. We present the case of a patient with a Zenker’s diverticulum who was treated using an SB jr (Sumitomo Bakelite Co., Ltd, Japan) – an unusual device for this procedure.
What exactly distinguishes aggressive from chronic periodontitis: is it mainly a difference in the degree of bacterial invasiveness?
Authors: Ubele Van der Velden
Journal: Periodontology 2000 (2017)

Abstract At the International Workshop for Classification of Periodontal Diseases and Conditions in 1999, the classification of aggressive and chronic periodontitis that is presently used was introduced. A literature review of papers published in 2015 and having aggressive periodontitis in the title revealed that most studies use this terminology but it is questionable whether all established criteria were really applied correctly. Review of the literature showed no qualitative differences between aggressive and chronic periodontitis regarding bacterial and viral aspects. It is also unlikely that that there are major immunologic differences between aggressive and chronic periodontitis. Neutrophil function can be compromised in both conditions but may be more genetically related in aggressive periodontitis and be associated more with lifestyle factors in chronic periodontitis. In general, genetics plays a more important role in aggressive periodontitis than in chronic periodontitis. It is likely that periodontitis progresses by recurrent acute episodes during which invasion of bacteria into the connective tissue may occur. Two cases are presented for which invasive periodontitis is treated with systemic antibiotics, showing remarkable periodontal healing in terms of probing attachment gain, as well as radiographic bone gain. Periodontitis in an active state with bacterial invasion is probably accompanied with a significant increase in subgingival temperature. It is hypothesized that elevated subgingival temperature may help to distinguish between invasive and non‐invasive periodontitis. Scaling and root planing during a burst of disease activity may result in removal of connective tissue fiber attachment and down‐growth of epithelium, thereby preventing the reattachment of connective tissue. Because the burst of disease is accompanied by an increase of temperature, assessment of the temperature may help in deciding whether or not to prescribe systemic antibiotics. When the use of systemic antibiotics is indicated, the antibiotic therapy may help to maintain the connective tissue attachment at the most possible coronal level. The above implies that the ability to diagnose bacterial invasive periodontitis is quite important, and future research is needed to determine if assessment of subgingival temperature may help in diagnosing invasive periodontitis. In addition, it is suggested that future classification systems of periodontitis include the item of bacterial invasive periodontitis.
Abstract 191: Double blockade of interacting CK2 and EGFR pathways by tumor-targeting nanobioconjugates increases therapeutic efficacy against glioblastoma multiforme
Authors: Julia Y. Ljubimova
Journal: Cancer Research (2017)

Abstract Introduction: Glioblastoma multiforme (GBM) remains the deadliest brain tumor in adults, and is notorious for drug and radiation resistance. To inhibit GBMs more effectively, polymalic acid-based blood-brain barrier crossing nanobioconjugates were synthesized that are delivered to the cytoplasm of cancer cells and specifically inhibit the master regulator serine/threonine protein kinase CK2 and the wild-type/mutated epidermal growth factor receptor (EGFR/EGFRvIII), which are overexpressed in gliomas according to The Cancer Genome Atlas (TCGA) GBM database. Methods and Results: The used nanobioconjugates are novel nanotherapeutics where all moieties are covalently connected to poly(β-L-malic acid) (PMLA). Our biodegradable and non-toxic nanodrugs bind to the receptors enriched on tumor vasculature and cross the BBB by transcytosis. They specifically bind to cancer cells and after internalization exit to the tumor cell cytoplasm using pH-sensitive endosomal disruption unit. Two xenogeneic mouse models bearing intracranial human GBMs from cell lines LN229 and U87MG that expressed both CK2 and EGFR were used. The knockdown of CK2α and EGFR/EGFRvIII suppressed their downstream prosurvival signaling. Treatment also markedly reduced the expression of programmed death-ligand 1 (PD-L1), a negative regulator of cytotoxic lymphocytes. Downregulation of CK2 and EGFR also caused suppression of heat shock protein 90 (Hsp90) co-chaperone Cdc37, which may inhibit the activity of key cellular kinases. Inhibition of either target was associated with downregulation of the other target as well, which may underlie efficacy of the dual nanobioconjugate that is directed against both CK2 and EGFR. Importantly, the single nanodrugs, and especially the dual nanodrug, markedly suppressed the expression of cancer stem cell markers c-Myc, CD133, and nestin, which could contribute to the efficacy of these nanodrugs. In both tumor models, the dually targeting nanobioconjugate significantly increased (up to 2-fold) animal survival compared with the control group. Conclusion: The versatile nanobioconjugates developed in this study, with the ability of anti-cancer drug delivery across biobarriers and inhibition of key tumor regulators, offer a promising nanotherapeutic approach to treat GBMs and to potentially prevent drug resistance and retard the brain tumor recurrence. Support: NIH grants U01 CA151815, R01 CA136841, R01 CA188743, R01 CA209921, R01 EY013431 Citation Format: Julia Y. Ljubimova. Double blockade of interacting CK2 and EGFR pathways by tumor-targeting nanobioconjugates increases therapeutic efficacy against glioblastoma multiforme [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 191. doi:10.1158/1538-7445.AM2017-191
Abstract 4451: Elevated USP22 is a potential therapeutic target for human non-small cell lung cancer
Authors: Keqiang Zhang, Tommy R Tong, Xinwei Yun, Rebecca Nelson, Nardi Isaac, Ravi Salgia, Dan Raz
Journal: Cancer Research (2017)

Abstract Elevated ubiquitin-specific protease 22 (USP22) is associated with enhanced malignancy, therapeutic resistance, and poor prognosis of various human cancers. In this study, the clinicopathological significance of USP22, therapeutic implication of targeting USP22, and underlying molecules of USP22 knockdown were investigated in human non-small cell lung cancer (NSCLC). Immunohistochemistry analysis revealed that USP22 protein was dramatically elevated in ~ 67% of 197 NSCLC tissues compared with adjacent normal lung tissues. Importantly, statistical analysis demonstrated that elevated USP22 was positively associated with advanced cancer stage and a trend to poor prognosis of NSCLC patients. Moreover, siRNA-mediated knockdown of USP22 induced a cell cycle arrest in G1/S phase and significantly suppressed cell proliferation and soft agar colony formations in NSCLC cell lines. In addition, knockdown of USP22 significantly enhanced cisplatin-induced genotoxic effects in NSCLC cell lines. Furthermore, USP22 silencing substantially down-regulated SIRT1 and upregulated p53 tumor suppressor in NSCLC cells, indicating downregulation of USP22 may boost p53-mediated tumor suppression and DNA damage response in NSCLC cells. Knockdown of USP22 also increased global histone H2B monoubiquitylation, H3K4 and H3K79 trimethylation leading to global gene expression profile changes in these NSCLC cells. These results suggest that targeting USP22 will have broad anti-cancer effects via altering multiple cancer signaling pathways. Taken together, data of this study further indicate that the elevated USP22 may potentially represent a prognostic factor and therapeutic target for NSCLC patients. Note: This abstract was not presented at the meeting. Citation Format: Keqiang Zhang, Tommy R Tong, Xinwei Yun, Rebecca Nelson, Nardi Isaac, Ravi Salgia, Dan Raz. Elevated USP22 is a potential therapeutic target for human non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4451. doi:10.1158/1538-7445.AM2017-4451