tbuckley/cabot-search huggingface dataset:
A novel human monoclonal antibody derived from tumor infiltrating lymphocytes in gastric cancer specific to cancer cells with cell growth inhibition
Authors: Rieko Nakamura, Yoshiro Saikawa, Saiko Hosokawa, Kazumasa Fukuda, Koichiro Kumai, Tetsuro Kubota, Masaki Kitajima
Journal: Cancer Research (2006)

645   [Background] The use of humanized or murine/human chimeric monoclonal antibodies (MoAbs) is applied to clinical use as anticancer therapy like HER-2-specific trastuzumab (Herceptin) against breast cancer, showing increased overall survival. These antibodies are characterized as humanized or murine/human chimeric MoAbs, which will cause adverse events with immune response recognizing these antibodies as foreign bodies in patients9 body. Fully human MoAb (HuMoAb) is ideal to prevent such immune response, and at the present, HuMoAb is not yet applied to clinical use. We have established a successful production of HuMoAbs, reacting specifically to cancer cells, not to normal cells, utilizing human hybridoma technique with tumor infiltrating lymphocytes (TILs) or lymphocytes derived from lymph nodes. In the present study, on the basis of reactivity to human cancer cell lines, we selected a novel clone of HuMoAb derived from lymphocytes in gastric cancer. [Materials and methods]Lymphocytes were collected from clinical specimen of a gastric carcinoma patient. Hybridomas were established using these lymphocytes and mouse myeloma cell, P3U1. After selecting hybridoma clones, which binds to cancer cells, fluorescence microscope and immunohistochemical staining were used to examine antibodies9 ability to attach on cell surface of various kinds of specimen. To evaluate inhibitory effect of each antibody on cancer cell growth, human lung cancer cell line HLC-1, the human stomach cancer cell line MKN-45, and the human pancreas cancer cell line PANC-1 were examined using MTT method. Cells were incubated with 100, 50, 25, 12.5, and 6.25μg/ml of each antibodies or non-specific human antibody as a control vehicle for 6 days, followed by calculating inhibition rate compared with the control. [Results] In established antibodies, we select a clone of HuMoAb derived from gastic cancer lymphocytes which showed growth inhibition rates by this antibody which was 94% in HLC-1, 64% in MKN-45 and 55% in PANC-1, while no growth inhibition occurred in normal HUVECs. This antibody showed specific and intense reactivity not only to the cell membrane, but also to the cell nucleus of HLC-1 and HSC-3 in immunohistochemical staining. Using xenografts forming from cancer cell lines in nude mice and surgically resected clinical specimen from patients, we could demonstrate a broad spectrum of reactivity of the antibody to 3 out of 4 xenografts (75%) and 4 out of 5 clinical specimen (80%), while no reactivity of the antibody was observed in normal sites, in fluorescence microscope. [Conclusion] we successfully produced a novel HuMoAb which reacted specifically to cancer cells, inhibiting cell growth. This HuMoAb will have a potential to be utilized as an anticancer agent without causing any immunological reaction in human.
Personalized Drug Sensitivity Screening for Bladder Cancer Using Conditionally Reprogrammed Patient-derived Cells
Authors: Kimmo Kettunen, Peter J. Boström, Tarja Lamminen, Taija Heinosalo, Gun West, Irena Saarinen, Katja Kaipio, Juha Rantala, Chris Albanese, Matti Poutanen, Pekka Taimen
Journal: European Urology (2019)

Many patients with muscle-invasive bladder cancer (BC) are either ineligible for or do not benefit from cisplatin-based chemotherapy, and there is an unmet need to estimate individuals' drug sensitivities. We investigated the suitability of conditionally reprogrammed (CR) cells for the characterization of BC properties and their feasibility for personalized drug sensitivity screening. The CR cultures were established from six BC tumors with varying histology and stage. Four cultures were successfully propagated for genomic, transcriptomic, and protein expression profiling and compared to the parental tumors. Two out of four CR cultures (urothelial carcinoma and small cell neuroendocrine carcinoma [SmCC]) corresponded well to their parental tumors and underwent drug sensitivity screening to identify novel drugs for the respective tumors. Both cultures were sensitive to standard BC chemotherapy agents (eg cisplatin and gemcitabine) and to conventional drugs such as taxanes and inhibitors of topoisomerase and proteasome. The SmCC cells were also sensitive to statins (eg, atorvastatin and pitavastatin). In summary, after confirming their representativeness and origin, we conclude that CR cells are a feasible platform for personalized drug sensitivity testing and might thus add to the approaches used to personalize BC treatment strategies. PATIENT SUMMARY: We investigated the conditional reprogramming method for generating patient-derived bladder cancer cell cultures and studied their feasibility for planning personalized treatment strategies.
Pattern and dynamics of metastatic sites during course of metastatic colorectal cancer (mCRC) trajectory in 1086 Finnish patients in the nationwide prospective RAXO study
Authors: P. Osterlund, A. Lamminmäki, L. Soveri, A. Ålgars, T. Salminen, R. Kallio, R. Ristamäki, P. Halonen, E. Osterlund, A. Rajanen, E. Lantto, A. Ovissi, A. Nordin, M. Murashev, L. Aroviita, A. Jekunen, R. Lindvall-Andersson, P. Nyandoto, J. Kononen, R. Kokko, A. Sjöstrand, H. Isoniemi, M. Kotkavaara, I. Kellokumpu, T. Tuomisto-Huttunen, A. Sainast, T. Hermanson, J. Tuominiemi, K. Möykkynen, O. Isokangas, T. Klaavuniemi, J. Kaleva-Kerola, E. Männistö, L. Sailas, R. Huuhtanen, A. Mansisto, T. Poussa
Journal: Annals of Oncology (2019)
Abstract 15438: A Massive Increase in Serum Levels of Fatty Acid Binding Protein 4 in Patients With Acute Myocardial Infarction Complicated by Out-of-Hospital Cardiac Arrest Due to Ventricular Fibrillation
Authors: Hiroaki Sunaga, Tatsuya Iso, Masaru Obokata, Yoshiaki Ohyama, Norimichi Koitabashi, Ryuichi Funada, Noriaki Takama, Hiroki Matsui, Tomoyuki Yokoyama, Masami Murakami, Masahiko Kurabayashi
Journal: Circulation (2016)

Introduction: Circulating fatty acid binding protein 4 (FABP4) is associated with obesity, insulin resistance and cardiovascular events. We recently showed that FABP4 is activity secreted from adip...
Donor outcomes in anonymous live liver donation
Authors: Nicolas Goldaracena, Judy Jung, Aloysious D. Aravinthan, Susan E. Abbey, Sandra Krause, Cheryl Pritlove, Joanna Lynch, Linda Wright, Nazia Selzner, Jennifer Stunguris, Paul Greig, Anand Ghanekar, Ian McGilvray, Gonzalo Sapisochin, Vicky Lee Ng, Gary Levy, Mark Cattral, David Grant
Journal: Journal of Hepatology (2019)
Abstract 2759: Chemoproteomic profiling of the oncometabolite fumarate
Authors: Sarah E. Bergholtz, Chloe A. Briney, Rhushikesh A. Kulkarni, David Wei, Daniel W. Bak, Jonathan H. Shrimp, Eranthie Weerapana, W. Marston Linehan, Jordan L. Meier
Journal: Cancer Research (2019)

Abstract Dysregulated metabolism is a feature of many diseases, including cancer. In addition to providing energy and building blocks to growing cells, altered metabolism can assist in tumor growth by producing “oncometabolites”. For example, in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) inactivating mutations in fumarate hydratase (FH) leads to accumulation of millimolar levels of an oncometabolite, fumarate. At such high concentrations, fumarate can spontaneously react with protein cysteine residues leading to a post-translational modification (PTM) called cysteine succination. This PTM can directly stimulate tumorigenic signaling, however, current methods to study this PTM are limited. Our lab has developed chemical proteomic methods to investigate proteome-wide targets of cysteine succination. Using these methods, we have identified hundreds of targets of fumarate in normal kidney cells as well as HLRCC cells. One interesting target identified that has implications in cancer progression is SMARCC1, a core subunit of a nucleosome remodeling complex known as the SWI/SNF complex. The SWI/SNF complex is a well-known tumor suppressor and mutation of this complex leads to cancer development. We have demonstrated that excess fumarate levels result in hyper-modification of SMARCC1 and decrease in SWI/SNF complex stability. This instability also results in an increase in EZH2 expression as well as activity, and an increase in H3K27Me3. Our current efforts are aimed at understanding how fumarate affects the function of this complex in vivo and exploring the potential of using EZH2 inhibitors in the treatment of HLRCC. Citation Format: Sarah E. Bergholtz, Chloe A. Briney, Rhushikesh A. Kulkarni, David Wei, Daniel W. Bak, Jonathan H. Shrimp, Eranthie Weerapana, W. Marston Linehan, Jordan L. Meier. Chemoproteomic profiling of the oncometabolite fumarate [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 2759.
Abstract 2063A: Glucolipotoxicity and altered oxidative stress responses in cancer cells
Authors: Arwa MT Al-Nahdi, Annie John, Haider Raza
Journal: Cancer Research (2019)

Abstract Alterations in energy metabolism, such as aerobic glycolysis and lactic acid production, and mitochondrial bioenergetics are the key metabolic changes associated with increased glucose uptake in cancer cells (Warburg effect). Metabolic adaptation, inflammatory responses and oxidative stress have been implicated in cancer etiology and pathology. Both experimental and epidemiological studies have suggested that caloric restriction is beneficial in reducing the complications of cancer cells. Studies have also suggested that increased availability of energy metabolites, such as glucose and fatty acids, as also seen in obesity and diabetes, which induces inflammatory and oxidative stress responses, may also be key factors in cancer development. In the present study, we have used human hepatoma, HepG2 and rodent pancreatic cancer derived Rin-5F cells to investigate the effects of high glucose (25mM) and high palmitic acid (up to 0.3mM) on cell survival and cell death along with the metabolic, inflammatory and oxidative stress associated alterations in these cells. Our results have shown that both increased glucose and fatty acids induce DNA damage and caspase-dependent apoptosis and mitochondrial respiratory dysfunction. Glucolipotoxicity in these cells, due to increased ROS production and oxidative stress has been suggested to be involved in altering the mitochondrial membrane potential and bioenergetics. Altered Nrf-2/NFk-B/AMPK/mTOR-dependent cell signaling and inflammatory (IL6/PGE2) responses have also been observed when cells were treated with high glucose and palmitic acid. Interestingly, pretreatment with N-acetyl cysteine (NAC, 10mM), a GSH precursor, resulted in partial recovery from the oxidative stress-induced glucolipotoxicity. Our results suggest that the presence of high energy metabolites enhance inflammatory and oxidative stress responses that may be responsible for alterations in cancer cell signaling and metabolism. Citation Format: Arwa MT Al-Nahdi, Annie John, Haider Raza. Glucolipotoxicity and altered oxidative stress responses in cancer cells [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 2063A.
Abstract 17789: Comprehensive Optical Imaging of Macrophages Associated With Intraplaque Hemorrhage Using the Integrated Dual Modal OCT-NIRF Structural-Molecular Imaging
Authors: Jae Joong Lee, Min Woo Lee, Tae Shik Kim, Joon Woo Song, Dong Joo Oh, Kyeongsoon Park, Wang-Yuhl Oh, Hongki Yoo, Jin Won Kim
Journal: Circulation (2015)

Introduction: Intraplaque hemorrhages (IPHs) are associated with rupture-prone plaques. Within IPHs, macrophages differentiate into a specific phenotype characterized by the expression of mannose receptors. The purpose of this study was to investigate the feasibility of intravascular optical coherence tomography (OCT)-near infrared fluorescence (NIRF) structural-molecular imaging combined with a NIRF probe targeting mannose receptors to estimate IPHs in vivo. Methods and Results: IPH was induced by injecting centrifuged autologous erythrocytes through a micro-infusion catheter into rabbit aortic plaques. Normal chow diet was continued for an additional 6 weeks for macrophage differentiation. 48 hours after intravenous injection of our newly synthesized NIRF labeled nanoprobe (ex/em 750/773 nm) targeting macrophage mannose receptors at a dose of 10 mg/kg, OCT-NIRF imaging demonstrated highly enhanced NIRF signals in IPH lesions characterized by black-dotted neovessels surrounded with heterogenous OCT signals (asterisk), suggesting the association of mannose receptor positive macrophages with intraplaque hemorrhagic transformation (Figure). FM and histologic findings from the corresponding sister sections corroborated the in vivo imagings, which demonstrated the co-localization of NIRF signals with macrophage mannose receptors and hemorrhagic compositions. Conclusions: OCT-NIRF imaging with a NIRF probe targeting mannose receptors could provide a promising novel strategy to estimate IPH-associated macrophages and detect high-risk plaques.
Project Switch: Lenalidomide and dexamethasone (Len-Dex) as a potential synthetic control arm (SCA) in relapsed or refractory multiple myeloma (rrMM).
Authors: Bindu Kanapuru, Yutao Gong, Pallavi Shruti Mishra-Kalyani, Michael E. Menefee, Rajeshwari Sridhara, Ann T. Farrell, Gideon Michael Blumenthal, Richard Pazdur
Journal: Journal of Clinical Oncology (2019)

8047 Background: Len-Dex is a common comparator arm to test novel therapies in rrMM trials. There is interest in evaluating if the control data from one clinical trial can be borrowed to another clinical trial, thus creating SCAs which could potentially improve accrual to trials, make better go/no-go decisions, and increase patients access to promising experimental therapies (ETs). We looked at legacy rrMM trials to assess the impact of switching and pooling Len-Dex control arms among different trials when evaluating ETs. Methods: We identified 4 contemporary rrMM trials that enrolled 2,729 patients testing ET + Len-Dex vs. Len-Dex alone. We calculated progression-free survival (PFS), Hazard Ratio (HR) and 95% Confidence Interval (CI) for ET compared to the original trial control, the switch Len-Dex controls, a pooled Len-Dex control, and a matched pooled control using bootstrapping sampling methods to match the experimental arm baseline demographics and prior lines with the pooled control. Results: See table. Conclusions: In this analysis, the switch and pooled controls matched the original control for Trials 1 and 2, but not for Trials 3 and 4. The bootstrapping methods did not substantially assist in replicating the original results. This could be due to several factors including heterogeneity of the enrolled populations including different lines of therapy, different pharmacologic classes of drugs studied in the ETs, and missing prognostic data including cytogenetics. Further investigations into propensity score matching will be explored to determine if SCAs can be improved.[Table: see text]
Abstract 1298: The anticancer effects of RX-5902 result from inhibition of phosphorylated p68-mediated β-catenin nuclear translocation
Authors: Young B. Lee, Christina George, Deog J. Kim
Journal: Cancer Research (2019)

Abstract Phosphorylated p68 (p-p68 or phospho-DDX5) has been shown to be associated with cell transformation, epithelial mesenchymal transition (EMT) and cell migration, and furthermore play a vital role in cell proliferation and tumor/cancer progression by promoting the nuclear translocation of β-catenin. RX-5902 is an oral, small molecule inhibitor of β-catenin nuclear translocation mediated by p-p68. Previous studies have shown that RX-5902 inhibits the growth of cancer cells at low nanomolar IC50 (10 to 24nM) and disrupts the p-p68-β-catenin signaling pathway through an interaction with p-p68 on Tyr 593. By interfering with the p-p68-β-catenin signaling pathway cancer cells undergo apoptosis. In this study, we expanded our investigation to study the effect of RX-5902 on nuclear β-catenin in several types of cancer cell lines that include colon, gastric, hepatic, head and neck, melanoma, breast, pancreatic, ovarian, and prostate. Western blot data, in the cell lines tested, showed a decrease of nuclear β-catenin protein as well as p-p68 and c-myc in a concentration-dependent manner. Furthermore, an in vivo study of the MDA-MD-231 xenograft model demonstrated the ability of RX-5902 to inhibit the tumor growth by decreasing p-p68, β-catenin, cyclin D1 and c-myc proteins. Collectively our findings in both in vitro and in vivo studies support the potential therapeutic effect of RX-5902 in multiple cancer indications through the disruption of the phospho-p68/nuclear β-catenin interaction and blocking the nuclear translocation of β-catenin. Citation Format: Young B. Lee, Christina George, Deog J. Kim. The anticancer effects of RX-5902 result from inhibition of phosphorylated p68-mediated β-catenin nuclear translocation [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 1298.
Circulating-free DNA analysis from long-term surviving metastatic colorectal cancer patients undergoing surgery for resectable disease
Authors: M. Ghidini, J. Hahne, C. Senti, A. Lampis, M. Ratti, C. Pizzo, A. Gobbi, G. Tomasello, R. Passalacqua, N. Valeri
Journal: Annals of Oncology (2019)
Abstract 98: Canonical TGF-β1 Signaling in Cardiomyocytes is Essential to Maintain Basal Cardiac Function
Authors: Prachi Umbarkar, Anand P Singh, Vipin K Verma, Manisha Gupte, Yuanjun Guo, Qinkun Zhang, Thomas L Force, Hind Lal
Journal: Circulation Research (2017)

The role of canonical transforming growth factor-β (TGF-β) pathway is well recognized in fibroblast biology and fibrosis in diseased hearts. However, its role in cardiomyocyte (CM) biology is not clear. SMAD4 is the central intracellular mediator of canonical TGF-β signaling. Herein, we investigate the role of SMAD4 in CM-biology and cardiac pathophysiology. SMAD4 homozygous floxed ( SMAD4 fl/fl ) and heterozygous floxed ( SMAD4 fl/- ) mice were crossed with α-myosin heavy chain (Mer-Cre-Mer) to create conditional CM-specific SMAD4-KO ( SMAD4 fl/fl Cre +/- ) and SMAD4 haploinsufficiency ( SMAD4 fl/- Cre +/- ), respectively. At 10 Wks of age, mice were subjected to well established tamoxifen diet protocol for 2 Wks. Echocardiographic analysis at 4 Wks post-tamoxifen treatment reveals that CM-specific loss of SMAD4 leads to dilatative ventricular remodeling as reflected by significantly increased LVIDs. This dilatative remodeling was associated with severe ventricular dysfunction as reflected by significantly reduced ejection fraction (EF) and fractional shortening (FS). Both HW/BW and LW/BW were significantly elevated in SMAD4 KO mice, suggesting pathological hypertrophy and heart failure in KOs. Analysis of Masson trichrome stained heart sections reveals a marked increase in fibrosis in the KO hearts. Q-PCR analysis showed the re-expression of fetal gene program (ANP, BNP), further confirming pathological remodeling in the KO hearts. As the heart functions of heterozygous mice and littermate controls were comparable at baseline, we stress them with TAC surgery. Consistent with KO findings, at 4 Wks post-TAC, heterozygous mice demonstrated characteristic heart failure phenotype. Taken together, these findings suggest that SMAD4 is required to maintain basal cardiac function and to prevent adverse ventricular remodeling in a pressure-overloaded heart.
Abstract 20323: Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) Infection and Risk of Adverse Outcomes After ST-Elevation Myocardial Infarction (STEMI) in a Low-Income Urban Population
Authors: Sanyog G Shitole, Mark H Kuniholm, Angel Y Peng, Cecilia Berardi, Tina Shah, Samuel Herzig, Anna E Bortnick, Panagiota Christia, James Scheuer, Jorge R Kizer
Journal: Circulation (2017)

Background: It is known that HIV-infected patients have an elevated risk of acute coronary syndromes, especially STEMI. The relationship between HCV infection and cardiovascular disease (CVD) risk ...
Avoiding General Anesthesia in Treating Port-Wine Stains in Infants to Avoid Neurotoxic Events
Authors: Bishr Haydar, Holly Gray, Ashlee Holman
Journal: JAMA Dermatology (2019)

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Endoscopic ultrasound-guided gallbladder drainage versus percutaneous cholecystostomy for high risk surgical patients with acute cholecystitis: a systematic review and meta-analysis
Authors: Sally Wai-Yin Luk, Shayan Irani, Rajesh Krishnamoorthi, James Yun Wong Lau, Enders Kwok Wai Ng, Anthony Yuen-Bum Teoh
Journal: Endoscopy (2019)

Abstract Background Recent evidence suggests that endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is an effective and safe alternative to percutaneous drainage (PT-GBD). We conducted a systematic review and meta-analysis to compare these two procedures in high risk surgical patients with acute cholecystitis. Methods A comprehensive electronic literature search was conducted for all articles published up to October 2017 to identify comparative studies between EUS-GBD and PT-GBD. A meta-analysis was performed on outcomes including technical success, clinical success, post-procedure adverse events, length of hospital stay, unplanned hospital readmission, need for reintervention, recurrent cholecystitis, and disease- or treatment-related mortality for these two procedures. Results Five comparative studies (206 patients in the EUS-GBD group vs. 289 patients in the PT-GBD group), were included in the final analysis. There were no statistically significant differences in technical success (odds ratio [OR] 0.43, 95 % confidence interval [CI] 0.12 to 1.58; P = 0.21; I 2 = 0 %) and clinical success (OR 1.07, 95 %CI 0.36 to 3.16; P = 0.90; I 2 = 44 %) between the two procedures. EUS-GBD had fewer adverse events than PT-GBD (OR 0.43, 95 %CI 0.18 to 1.00; P = 0.05; I 2 = 66 %). Moreover, patients undergoing EUS-GBD had shorter hospital stays, with pooled standard mean difference of – 2.53 (95 %CI – 4.28 to – 0.78; P = 0.005; I 2 = 98 %), and required significantly fewer reinterventions (OR 0.16, 95 %CI 0.04 to 0.042; P &lt; 0.001; I 2 = 32 %) resulting in significantly fewer unplanned readmissions (OR 0.16, 95 %CI 0.05 to 0.53; P = 0.003; I 2 = 79 %). Conclusions EUS-GBD was associated with lower rates of post-procedure adverse events, shorter hospital stays, and fewer reinterventions and readmissions compared with PT-GBD in patients with acute cholecystitis who were unfit for surgery.