tbuckley/cabot-search huggingface dataset:
Type 3 Inositol 1,4,5‐Trisphosphate Receptor Is Increased and Enhances Malignant Properties in Cholangiocarcinoma
Authors: Pimwipa Ueasilamongkol, Tanaporn Khamphaya, Mateus T. Guerra, Michele A. Rodrigues, Dawidson A. Gomes, Yong Kong, Wei Wei, Dhanpat Jain, David C. Trampert, Meenakshisundaram Ananthanarayanan, Jesus M. Banales, Lewis R. Roberts, Farshad Farshidfar, Michael H. Nathanson, Jittima Weerachayaphorn
Journal: Hepatology (2019)

Cholangiocarcinoma (CCA) is the second most common malignancy arising in the liver. It carries a poor prognosis, in part because its pathogenesis is not well understood. The type 3 inositol 1,4,5‐trisphosphate receptor (ITPR3) is the principal intracellular calcium ion (Ca 2+ ) release channel in cholangiocytes, and its increased expression has been related to the pathogenesis of malignancies in other types of tissues, so we investigated its role in CCA. ITPR3 expression was increased in both hilar and intrahepatic CCA samples as well as in CCA cell lines. Deletion of ITPR3 from CCA cells impaired proliferation and cell migration. A bioinformatic analysis suggested that overexpression of ITPR3 in CCA would have a mitochondrial phenotype, so this was also examined. ITPR3 normally is concentrated in a subapical region of endoplasmic reticulum (ER) in cholangiocytes, but both immunogold electron microscopy and super‐resolution microscopy showed that ITPR3 in CCA cells was also in regions of ER in close association with mitochondria. Deletion of ITPR3 from these cells impaired mitochondrial Ca 2+ signaling and led to cell death. Conclusion: ITPR3 expression in cholangiocytes becomes enhanced in CCA. This contributes to malignant features, including cell proliferation and migration and enhanced mitochondrial Ca 2+ signaling.
Disclosure of Infant Unsafe Sleep Practices by African American Mothers in Primary Care Settings
Authors: Patricia Mahoney, Barry S. Solomon, Eileen M. McDonald, Wendy C. Shields, Andrea C. Gielen
Journal: JAMA Pediatrics (2019)

This study assesses the disclosure rates of African American new mothers regarding their infants’ unsafe sleep practices by analyzing the mothers’ responses during separate encounters with a research assistant, health educator, and pediatrician.
Abstract 2018: Cannabinoid receptor 2 agonist JWH-015 inhibits growth and metastasis of triple negative breast cancers through regulation of autophagy mechanism
Authors: Nabanita Chatterjee, Subhadip Das, Dinesh K. Ahirwar, Sanjay Mishra, Ramesh Ganju
Journal: Cancer Research (2019)

Abstract Metastasis to distant organs is the major cause of mortality associated with breast cancer. Triple-negative breast cancer (TNBC) subtype has been shown to be associated with worst patient survival due to high metastasis rate and lack of targeted therapies. Therefore, there is an utmost need to develop novel therapeutic strategies against TNBC growth and metastasis. Cannabinoids are known to possess anti-cancer activity. However, the associated psychotropic activity limits the therapeutic use of Cannabinoids in breast cancer patients. Here, we used synthetic cannabinoid JWH-015 which activates cannabinoid receptor 2 (CB2) and is devoid of psychotropic activity. In vitro molecular analysis revealed that JWH-015 induces TNBC cell death by activating autophagy associated apoptosis. In addition, we have further shown using in vivo tumor models, that JWH-015 potentially inhibits TNBC growth and metastasis through activation of autophagy mechanisms. Further analysis showed that JWH-015 treated tumors recruited the reduced number of macrophages compared to vehicle control treated tumors. In addition, there were more anti-tumor M1-type macrophages present in JWH-015 treated tumors. Conversely, vehicle control treated tumors possessed a higher number of pro-tumor M2-type macrophages. These observations have established the anti-metastatic potential of JWH-015 in different TNBC pre-clinical mouse models. The mechanistic studies have elaborated the role of JWH-015-induced autophagy in promoting tumor cell death to inhibit TNBC growth and metastasis. Citation Format: Nabanita Chatterjee, Subhadip Das, Dinesh K. Ahirwar, Sanjay Mishra, Ramesh Ganju. Cannabinoid receptor 2 agonist JWH-015 inhibits growth and metastasis of triple negative breast cancers through regulation of autophagy mechanism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2018.
Sarah Wollaston calls for doctors to “apply for my job” and represent NHS in parliament
Authors: Elisabeth Mahase
Journal: BMJ (2019)

More doctors should get involved in politics and run to be members of parliament, says Sarah Wollaston, MP and chair of the Health and Social Care Committee.

Speaking at the Royal College of Psychiatrists International Congress in London on 1 July, she urged doctors to “go further” into the political sphere and make their voices and the voices of their patients heard.

Wollaston used the speech to tell doctors to “apply for my job,” arguing that the NHS …
Abstract 12204: Effects of Percutaneous Transluminal Pulmonary Angioplasty on Respiratory Functions in Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Tatsuo Aoki, Koichiro Sugimura, Shunsuke Tatebe, Masanobu Miura, Saori Yamamoto, Nobuhiro Yaoita, Hideaki Suzuki, Haruka Sato, Kimio Satoh, Hiroaki Shimokawa
Journal: Circulation (2015)

Introduction: Percutaneous transluminal pulmonary angioplasty (PTPA) is an emerging therapeutic strategy to improve hemodynamics and prognosis of patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, it remains to be examined whether PTPA also improves respiratory functions in those patients. Methods and Results: From July 2011 to May 2015, 69 patients with inoperable CTEPH (median age 62 yrs., female 57/69 (83%)) underwent PTPA in our hospital. In 29 of them (36%), we examined respiratory functions, including %VC, FEV1.0%, %DLco, A-a DO 2 and intra-pulmonary shunt before and after PTPA procedure. Intra-pulmonary shunt was calculated using arterial and pulmonary arterial blood samples during administration of pure oxygen. A mean of 4.8 PTPA procedures were performed, and hemodynamics and respiratory functions were examined before and after the treatment. Mean pulmonary arterial pressure (41 ± 8 to 26 ± 7 mmHg, P&lt;0.01), pulmonary vascular resistance (9.4 ± 4.0 to 4.0 ± 1.7 Wood unit), 6-min walk distance (372±120 to 472±143 meters, P&lt;0.01) and brain natriuretic peptide (141±155 to 38±37 pg/ml, P&lt;0.01) were significantly improved after PTPA. Furthermore, saturation of oxygen measured in room air (SaO2, 87 ± 5 to 91 ± 5%, P&lt;0.01), A-a DO 2 (48 ± 10 to 35 ± 11 torr, P&lt;0.01) and intra-pulmonary shunt (24 ± 7 to 21 ± 5 %, P&lt;0.01) were also significantly ameliorated. SaO 2 and intra-pulmonary shunt before PTPA were significantly correlated ( r 2 =0.26, P&lt;0.01). Changes in SaO 2 after PTPA were also significantly correlated with those in intra-pulmonary shunt after the procedures ( r 2 =0.40, P&lt;0.01) (Figure). In contrast, PTPA had no significant effects on %VC, FEV1.0% or %DLco. Conclusions: These results indicate that PTPA improves not only pulmonary hemodynamics but also oxygenation capacity with a resultant decrease in intra-pulmonary shunt.
Abstract 1137: Unraveling spatially-dependent interactions of tumor-associated macrophage in the tumor microenvironment
Authors: Victor Wang, Jan Martinek, Hannah M. Brookes, Kyung In Kim, Karolina Palucka, Jeff Chuang
Journal: Cancer Research (2019)

Abstract Tumor-infiltrating lymphocytes (TIL) are a strong prognostic factor in cancer patient outcomes. This includes immune checkpoint blockade (ICB) of the PD-1/PD-L1 axis, where patients with a higher abundance of pre-treatment TILs respond more frequently. However, tumors often elaborate mechanisms to exclude TILs and/or suppress their function. Identifying negative regulators of TILs is thus of great importance to improve patient outcomes and increase the patient population that may benefit from ICB. Tumor-associated macrophages (TAM) are a known modulator of TIL activity but the interaction between the two cell types is typically characterized with in vitro experiments and spatially-agnostic sequencing, ignoring location-specific factors contributing to the interaction’s net effects. Interrogating the TAM-TIL interactions in an intact tumor microenvironment (TME) will uncover novel mechanisms responsible for TAM function and may be key to reversing TIL immunosuppression. Here we leverage bulk RNA-sequencing with histocytometry, a multiplex quantitative tissue imaging method, to spatially-resolve the TAM-TIL interactions in intact human metastatic melanoma microenvironments. Bulk sequencing distinguishes tumor samples by high and low enrichment of lymphocyte gene sets, with additional sub-stratification by macrophage enrichment. Modular repertoire analysis implicates an interferon response in the differential lymphocyte enrichment, but does not address macrophage-dependent effects. Drawing from physical chemistry concepts, our spatial analyses of cell-cell interactions from histocytometry reveals distinct TAM populations potentially regulating TIL activity. Phagocytic TAMs in the tumor and non-phagocytic TAMs in the stroma physically contact T-cells, with the former interaction strongly correlated with lymphocyte enrichment and T-cell infiltration. Local and regional TAM phagocytosis affinities estimated by the Langmuir adsorption model further detail the nature of this interaction within the tumor, as well as the role of macrophage phagocytosis in regulating TILs. We demonstrate linear models integrating bulk sequencing and spatial metrics to quantify the relationships between genetics, cell-cell interactions, and T-cell invasiveness. Our work unravels important TAM interactions that shape the TME which have not been previously appreciated, providing novel insight into the forces driving T-cell exclusion and revealing new TAM biology to explore further. Citation Format: Victor Wang, Jan Martinek, Hannah M. Brookes, Kyung In Kim, Karolina Palucka, Jeff Chuang. Unraveling spatially-dependent interactions of tumor-associated macrophage in the tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1137.
Abstract 16870: Myocardial Enhancement on 320 Detector-Row CT Acquired Immediately after PCI in Patients with Acute Myocardial Infarction: Comparison with Contrast Enhanced CMR in Acute and Chronic States
Authors: Hiroshi Nakajima, Kakuya Kitagawa, Katsuya Onishi, Hideki Miyagi, Shiro Nakamori, Shingo Kato, Motonori Nagata, Takashi Tanigawa, Mashio Nakamura, Hajime Sakuma, Masaaki Ito
Journal: Circulation (2011)

Background: Identification of irreversibly injured myocardium early after percutaneous coronary intervention (PCI) is important for optimizing management in patients with acute myocardial infarction (AMI). Myocardial CT acquired immediately after PCI is an emerging method that permits viability assessment without additional injection of iodine contrast medium in CT room. The purpose of this study was to determine the relation between CT late enhancement and contrast enhanced CMR findings in acute and chronic states. Methods: Fifteen consecutive patients with AMI (59±12 years, 13men) underwent 320 slice MDCT immediately after PCI (peak CK 2295±1309). All patients achieved TIMI flow grade 3 after PCI. CMR studies were performed in acute phase (6.5±3.9 days) and chronic phase(7.3±1.4 months) in all patients. Rest perfusion MRI, late gadolinium enhancement (LGE) MRI and displacement encoded (DENSE) MRI were performed by using a 1.5T MR imager with 32-ch coil. CT-LE, CMR microvascular obstruction (MO) in acute state, CMR-LGE and myocardial strain in acute and chronic states were determined by using a 16-segments model. Transmural lesion was defined as the segment with transmural extent of &gt;50% Results: CT-LE was observed in 77 (32.1%) of 240 segments (transmural extent 1-25%;n=9, 26-50%;n=36, 51-75%;n=5, 76-100%;n=27). On CMR obtained in acute state, CMR-LGE and CMR MO was observed in 137 (57.1%) and 31 (12.9%) segments, respectively. CMR LGE was found in 129 (53.8%) segments in chronic state. The area under the receiver operating characteristics curve (AUC) of transmural extent of CT-LE for predicting CMR-MO was 0.824. These values were 0.813 for transmural CMR-LGE in acute phase and 0.754 for transmural CMR-LGE in chronic phase (p&lt;0.001, respectively). In the segments with transmural CT-LE, myocardial radial strain determined by DENSE MRI was more severely impaired (p&lt;0.001) in comparison with other segments. Conclusion: CT-LE on MDCT acquired immediately after primary PCI was closely associated with MO and transmural LGE on CMR in acute state, and indicates poor functional recovery in chronic state. CT-LE can provide valuable information regarding regional myocardial damage and viability in AMI patients after PCI.
Abstract 1999: As4O6 suppresses triple-negative breast cancer via inhibiting EGFR/mTOR mediated EMT <i>in vitro</i> and <i>in vivo</i>
Authors: Illju Bae, Zenglin Lian, Ziyao Liu, Zhaoyan Wu
Journal: Cancer Research (2019)

Abstract Objective:The present study aimed to verify the anti-metastasis effects and its mechanisms of As4O6 on triple-negative breast cancer(TNBC)in vitro and in vivo. Methods:MTT assay was used to evaluate cell proliferation. Wound healing assay and the invasion assay were carried out to investigate cell migration and invasion. The xenograft zebrafish model and orthotopic xenograft nude mouse model derived from MDA-MB-231-Green fluorescent protein (GFP) cells was established to analysis the anti-metastasis effect of As4O6in vivo. Western blot and immunohistochemistry were performed to analysis the metastasis-related proteins expression. Result: MTT assay showed cell proliferation of TNBC cell MDA-MB-231 was inhibited in a dose-dependent manner by As4O6 treatment. Also, As4O6 suppressed cell migration and invasion by a Wound healing assay and the invasion assay, resulted in the reduction of MMP-2 and MMP-9 expression, especially for the inhibition of EGFR and mTOR phosphorylation. Meanwhile, As4O6 suppressed cancer metastasis in xenograft zebrafish model. The number of metastatic lesion in mouse lung was significantly reduced by the treatment of As4O6 in the orthotopic xenograft nude mouse model. The expression of p-mTOR, p-EGFR and EMT-related proteins such as Vimentin and E-cadherin were significantly reversed in As4O6 treated mouse lung tissues than that of non-treatment group. Furthermore, As4O6 treatment suppressed the expression of angiogenesis related proteins VEGF-a, VEGFR, CD34 and MMP2/9 in mouse lung tissues. Conclusion:Thus, the data suggests that As4O6suppresses triple-negative breast cancer metastasis via inhibiting EGFR/mTOR mediated EMT in vitro and in vivo. As4O6 might be served as a potential useful agent for TNBC metastasis in the future. Citation Format: Illju Bae, Zenglin Lian, Ziyao Liu, Zhaoyan Wu. As4O6 suppresses triple-negative breast cancer via inhibiting EGFR/mTOR mediated EMT in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1999.
WNT / β-catenin pathway in recovering IEC-6 intestinal cells after 5-FU induced injury and treatment with mimetic peptide APOE COG133
Authors: T. Pessoa, I. Carneiro, P. Aguiar, L. Vieira, M. Vitek, R. Guerrant, R. Oria, J. Abreu Junior
Journal: Annals of Oncology (2019)
Abstract 2847: Tenascin C expression in neural microenvironment enhances perineural invasion and is associated with locoregional recurrence-related poor prognosis in pancreatic ductal adenocarcinoma
Authors: Satoru Furuhashi, Takanori Sakaguchi, Tomohiro Murakami, Mayu Fukushima, Yoshifumi Morita, Koji Ikegami, Hirotoshi Kikuchi, Megumi Baba, Mitsutoshi Setou, Hiyoya Takeuchi
Journal: Cancer Research (2019)

Abstract Background: Perineural invasion (PNI) is commonly seen in pancreatic ductal adenocarcinoma (PDAC) and worsens the postoperative prognosis. However, the associated mechanisms in cancer progression remain unclear. Tenascin C (TNC), an extracellular matrix glycoprotein, is abundant in cancer stroma and modulates tumor progression. The aim of this study was to evaluate the functional roles of TNC in the neural microenvironment of PDAC. Methods: We immunohistochemically examined TNC expression in 78 resected PDAC specimens. TNC staining in perineural sites at the invasive front was classified as low or high intensity, by comparison with adjacent non-cancerous tissues in the same section. The relationships between TNC expression and clinicopathological features were retrospectively analyzed. Furthermore, interactions between cancer cells and nerves after supplementation with TNC were investigated when co-culturing a PDAC cell line with a mouse dorsal root ganglion (DRG) in vitro. Results: High perineural TNC expression at the invasive front, seen in 30 (38%) patients, was associated with PNI (p = 0.006), pathological T stage ≥ 3 (p = 0.01), and postoperative locoregional recurrence (p = 0.002). It was independently associated with postoperative, poor recurrence-free survival in multivariate analysis (p = 0.045). In the in vitro co-culture model, supplementation with TNC significantly enhanced both neurotropism of PDAC cells and tumor tropism of a DRG. On the other hand, when PDAC cells and a DRG were cultured separately, TNC did not affect cancer cell proliferation or neural outgrowth. Conclusions: Strong perineural TNC expression was a prognostic indicator of locoregional recurrence-related poor prognosis. The neurotropism of PDAC induced by TNC suggests that TNC could serve as a therapeutic target for PDAC. Citation Format: Satoru Furuhashi, Takanori Sakaguchi, Tomohiro Murakami, Mayu Fukushima, Yoshifumi Morita, Koji Ikegami, Hirotoshi Kikuchi, Megumi Baba, Mitsutoshi Setou, Hiyoya Takeuchi. Tenascin C expression in neural microenvironment enhances perineural invasion and is associated with locoregional recurrence-related poor prognosis in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2847.
Deregulated Expression of Long Non-Coding RNA AC092580.4 in Acute Myeloid Leukemia
Authors: Yachun Jia, Yuandong Feng, Ying Shen, Hongli Chen, Ru Zhang, Yue Peng, Yun Yang, Ju Bai, Jian-Li Wang, Baiyan Wang, Fang-Xia Wang, Aili He
Journal: Blood (2018)
Abstract 18370: Biventricular Strain as a New Marker of Severity of Neurocardiac Injury in Patients With Subarachnoid Hemorrhage
Authors: Nobuyuki Kagiyama, Masataka Sugahara, Nina E Hasselberg, Eliabeth A Crago, Theodore F Lagattuta, Khalil M Yousef, Marilyn Hravnak, John Gorcsan
Journal: Circulation (2017)

Introduction: Identifying neuro-cardiac injury in aneurysmal subarachnoid hemorrhage (SAH) is not fully understood. Strain imaging is a new sensitive method to quantify left ventricular (LV) and ri...
Diesel or soy:: which is the best solvent for cypermetrine in the profilaxis of dengue?
Authors: Maria L. Garcia, Ubiratan P. Santos, Milena Marques Pagliarelli Acencio, Fernanda D. Lopes, Giselli S. Matsumoto, Adenir Perini, Heloisa M. Guimarães, Beatriz M. Saraiva, Milton A. Martins, Paulo H. Saldiva
Journal: European Respiratory Journal (2003)
Mast cells as mediators of fibrosis and effector cell recruitment in dermal chronic graft-versus-host disease.
Authors: Ethan Strattan, Senthilnathan Palaniyandi, Reena Kumari, Jing Du, Timothy Huang, Melissa Kesler, Jamie Sturgill, Gerhard Hildebrandt
Journal: Journal of Clinical Oncology (2019)

7050 Background: Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative treatment for patients with malignant neoplasms or inborn defects of hematopoiesis. Benefits of allo-HSCT are hampered by graft-versus-host-disease (GVHD), which can be debilitating and potentially lethal. In chronic GVHD (cGVHD), inflammation and aberrant wound healing lead to pathological fibrosis across multiple organs, most frequently in the skin, yet the exact pathophysiology is not well-understood. Mast cells (MCs) are primarily known for their role in atopic disease. However, recent studies have demonstrated new roles for MCs, showing that they can be involved in wound healing and in the pathogenesis of fibrotic disease. Given these new paradigms and the MC tropism to skin, alongside their reported role in other fibrotic diseases, we investigated whether MCs may play a role in the pathogenesis of dermal cGVHD. Methods: Cells: MCs were grown ex vivo from murine bone marrow. Transplant: 8 Gy radiation, followed by injection of LP/J marrow and splenocytes into C57BL/6J (WT) or B6.Cg-Kit W-sh MC-deficient recipients. Results: Ex vivo, we show that MCs survive and are functional after lethal radiation, such as that used in conditioning prior to HCT. In a murine model of cGVHD WT mice had significantly more cGVHD symptoms than MC-deficient mice as measured by clinical scoring. This scoring correlated with a significant increase in skin pathology, collagen deposition, and expression of pro-fibrotic genes in WT as compared to B6.Cg-Kit W-sh mice. Dermal MC numbers were increased in WT mice, but were nearly undetectable in B6.Cg-Kit W-sh mice, implying that the MCs that are present were recipient-derived and had survived conditioning. Skin from WT but not B6.Cg-Kit W-sh mice was enriched in cGVHD effector cells and in inflammatory cytokines and chemokines. Murine MCs, upon stimulation were sources of many of these factors, production of which was blocked when treated with ibrutinib and ruxolitinib, drugs used in cGVHD treatment. Conclusions: In summary, we show here a previously unknown role for MCs in the pathogenesis of dermal cGVHD, suggesting that MCs may be targetable to prevent and treat this devastating complication of allo HCT.