tbuckley/cabot-search huggingface dataset:
An Fc-optimized NKG2D-Ig fusion protein for induction of NK cell reactivity against breast cancer.
Authors: Julia Steinbacher, Stefanie Raab, Ludger Grosse-Hovest, Benjamin Joachim Schmiedel, Alexander Steinle, Lothar Kanz, Helmut Rainer Salih
Journal: Journal of Clinical Oncology (2013)

3054 Background: The anti-tumor activity and clinical success of the monoclonal antibody trastuzumab, approved for treatment of HER2/neu-overexpressing breast cancer, is at least partially mediated by induction of antibody dependent cellular cytotoxicity (ADCC). However, only about 20% of patients show HER2/neu overexpression, and trastuzumab treatment is associated with side effects. The ligands of the activating immunoreceptor NKG2D (NKG2DL) are widely expressed on malignant cells, but generally absent on healthy tissue. We aimed to take advantage of this tumor-restricted expression by using NKG2DL as target-antigens on breast cancer cells. To this end we generated NKG2D-Ig fusion proteins with modified Fc moieties and studied their ability to induce NK cell anti-tumor reactivity. Methods: The Fc parts within the constructs were modified by amino acid exchange as previously described (Lazar 2006; Armour 1999). Direct effects on tumor cell viability as well as induction of NK cell activation, degranulation, cytotoxicity and IFN-γ release in cultures with breast cancer cell lines expressing different HER2/neu levels were determined. Results: Compared to NKG2D-Fc containing a wildtype Fc part (NKG2D-Fc-WT) or trastuzumab, our mutants (S239D/I332E and E233P/L234V/L235A/ΔG236/A327G/A330S) displayed highly enhanced (NKG2D-Fc-ADCC) and abrogated (NKG2D-Fc-KO) affinity to the NK cell Fc receptor, respectively. In contrast to trastuzumab, no direct effect of the constructs on tumor cell viability was observed. In cultures of NK cells and breast cancer cells, NKG2D-Fc-KO significantly reduced NK reactivity due to blocking immunostimulatory NKG2D-NKG2DL interaction. NKG2D-Fc-WT substantially enhanced NK reactivity by induction of ADCC, while the effects of NKG2D-Fc-ADCC by far exceeded that of NKG2D-Fc-WT and, in case of HER2/neu-low targets also that of Herceptin. Conclusions: Fc-engineered NKG2D-Ig fusion protein effectively target breast cancer cells for NK anti-tumor reactivity. Due to the tumor-restricted expression of NKG2DL, NKG2D-Fc-ADCC may constitute an attractive means for immunotherapy especially of HER2/neu-low or -negative breast cancer.
Screening and Treatment Program to Eliminate Hepatitis C in Egypt
Authors: Imam Waked, Gamal Esmat, Aisha Elsharkawy, Magdy El-Serafy, Wael Abdel-Razek, Reham Ghalab, Galal Elshishiney, Aysam Salah, Soad Abdel Megid, Khaled Kabil, Manal H. El-Sayed, Hany Dabbous, Yehia El Shazly, Mohamed Abo Sliman, Khalid Abou Hashem, Sayed Abdel Gawad, Nevine El Nahas, Ahmed El Sobky, Sahar El Sonbaty, Hamdy El Tabakh, Ehab Emad, Hany Gemeah, Amal Hashem, Mohamed Hassany, Naseif Hefnawy, Abdel N. Hemida, Ayman Khadary, Kamal Labib, Faisal Mahmoud, Said Mamoun, Tamer Marei, Saad Mekky, Alsayeda Meshref, Alaa Othman, Omnia Ragab, Elhag Ramadan, Ahmed Rehan, Tarek Saad, Ramy Saeed, Mohamed Sharshar, Hesham Shawky, Mohamed Shawky, Wael Shehata, Hanaa Soror, Mohsen Taha, Mahmoud Talha, Adel Tealaab, Mohamed Zein, Alaa Hashish, Ahmed Cordie, Yasser Omar, Ehab Kamal, Islam Ammar, Mohamed AbdAlla, Wafaa El Akel, Wahid Doss, Hala Zaid
Journal: New England Journal of Medicine (2020)

Screening Program to Eliminate Hepatitis C in Egypt In 2018, the Egyptian government initiated a massive hepatitis C screening and treatment program. The Ministry of Health set the goal of screenin...
PREDICTORS OF MORTALITY IN ACUTE CORONARY SYNDROME-RELATED CARDIOGENIC SHOCK REQUIRING SHORT-TERM MECHANICAL CIRCULATORY SUPPORT
Authors: Qussay Marashly, Iosif Taleb, Elizabeth Dranow, Kimiya Nourian, Tyson Burnham, Anwar Tandar, Anu Abraham, Frederick Welt, Joseph Tonna, Sean Overton, Stephen McKellar, Antigone Koliopoulou, Line Kemeyou, James Fang, Josef Stehlik, Jose Nativi-Nicolau, Stavros Drakos
Journal: Journal of the American College of Cardiology (2020)
Clinical trials decision-making in African American patients with cancer: The role of cancer-coping religious beliefs.
Authors: Deliya Banda, Margaret Howard, Eshetu Tefera, Cheryl L Holt, Sandra M. Swain
Journal: Journal of Clinical Oncology (2012)

e16543 Background: Religious beliefs have been shown to play a significant role for African American patients coping with a cancer diagnosis. Less established is how these beliefs may relate to specific treatment decisions. The purpose of this study was to explore how patients used religious beliefs for coping and examine the relationship with specific attitudes towards and intention to enroll in a clinical trial (CT). Methods: Participants were 108 active treatment patients at a large urban cancer institute. The primary study outcome was self-reported likelihood to participate in a cancer therapeutic trial. Participant attitudes towards CTs were assessed using the Attitudes and Intention to Enroll in Therapeutic Clinical Trials instrument. The God as Healer construct was used to assess the perception of God as a healer, either directly or through the intervention of physicians and medicine. Kruskal-Wallis and Wilcoxon Mann-Whitney tests were used to examine the relationship between the sum scores of religious beliefs, attitude items and likelihood of patients to participate in CT. Results: The results of these analyses provided limited support for a direct relationship of belief in God as a healer and intention to enroll in a CT. Spearman’s correlation analysis revealed a statistically significant relationship between a belief in God as direct healer with ‘Distrust of doctors’ (r s = 0.26, p &lt; .01 ); and God as direct healer with ‘Fear of losing one’s rights after signing a CT consent form’ (r s = 0.24, p &lt; .05). While not statistically significant in this sample, those with a higher belief in ‘God as a healer through medicine and doctors’ had more negative attitudes of ‘fear of being treated unfairly on a CT due to being poor or a minority’, and of ‘losing their rights after signing a CT consent form’. Conclusions: These findings suggest providers should be aware of the culturally specific roles that religious/spiritual beliefs play in African American patients’ attitudes towards CTs and how they may align with CT decision-making.
Bilateral testicular cancer within two prospective, population-based SWENOTECA protocols in clinical stage I nonseminoma.
Authors: Torgrim Tandstad, Arne Solberg, Ulf Hakansson, Anders Angelsen, Hege Sagstuen Haugnes, Jan Oldenburg, Anders Kjellman, Olav Dahl, Gabriella Cohn-Cedermark
Journal: Journal of Clinical Oncology (2012)

4508 Background: Contralateral tumor (CLT) occurs in 3.5-5% in men diagnosed with testicular cancer. The precursor lesion, ITGCNU, transforms into invasive germ cell cancer in 50-100%. Although radiotherapy eradicates ITGCNU effectively, mandatory biopsy of the contralateral testis to detect ITGCNU is controversial. Whether, adjuvant chemotherapy (ACT) reduces the incidence of bilateral cancer is also uncertain. Methods: 988 patients with clinical stage 1 nonseminoma were included in two prospective, population-based SWENOTECA protocols. Thirteen patients were excluded due to previous contralateral biopsy, synchronous bilateral cancer or protocol violations. Treatment was either adjuvant chemotherapy (n=490), or surveillance (n=485). Contralateral testicular biopsy was recommended, but performed only in 283 patients. In case of ITGCNU radiotherapy to 16 Gy was recommended.The estimated cumulative incidence of CLT was calculated using the Kaplan-Meier method. Results: With a median follow-up of 6.3 years, twenty-nine (3.9%) patients developed CLT including five patients with synchronous cancer. Biopsies showed ITGCNU in 3.2%. The incidence of CLT was similar following ACT, 3.7 % (11/490), and surveillance, 3.1% (12/485), p=0.99. Biopsied patients had a risk of developing CLT of 4.3% (9/283), and seven patients treated for CIS never developed CLT. Unbiopsied patients had a risk of 3.0 % (14/668). The proportion of bilateral cancers was similar in biopsy negative patients 3.6% (7/274) and unbiopsied patients 3.0 % (14/668). Young age at orchiectomy was a significant risk factor for metachronous cancer, HR 0.94 (CI: 0.89-0.99), p=0.04. All patients with ITGCNU were offered RT. One irradiated patient developed CLT cancer, and one developed CLT before RT was given. Conclusions: In this selected population ACT did not reduce the incidence of CLT. There was a high proportion of false negative biopsies, which might explain why biopsy negative patients had the same risk of CLT as patients not undergoing biopsy. Young patients had the highest risk of developing contralateral cancer, the risk of CLT decreased by 6% yearly.
NoncoRNA: a database of experimentally supported non-coding RNAs and drug targets in cancer
Authors: Lulu Li, Pengfei Wu, Zhenyu Wang, Xiangqi Meng, Caijun Zha, Ziwei Li, Tengfei Qi, Yangong Zhang, Bo Han, Shupeng Li, Chuanlu Jiang, Zheng Zhao, Jinquan Cai
Journal: Journal of Hematology & Oncology (2020)

Abstract NoncoRNA ( http://www.ncdtcdb.cn:8080/NoncoRNA/ ) is a manually curated database of experimentally supported non-coding RNAs (ncRNAs) and drug target associations that aim to potentially provide a high-quality data resource for exploring drug sensitivity/resistance-related ncRNAs in various human cancers. ncRNA are RNA molecular that do not encode proteins, but are involved in gene regulation and cellular functions in variety of human diseases, including neurodegenerative diseases and cancers. Here, we developed NoncoRNA which contained 8233 entries between 5568 ncRNAs and 154 drugs in 134 cancers. Each entry in the NoncoRNA contains detailed information on the ncRNAs, drugs, and cancers, the ncRNA expression pattern and experimental detection techniques, drug response and other targets, literature references, and other information. NoncoRNA offers a user-friendly, open access web interface to easily browse, search, and download data. NoncoRNA also provides a submission page for researchers to submit newly validated ncRNA-drug-cancer associations. NoncoRNA might serve as an immeasurable resource for understanding the roles of ncRNAs in cancer therapy.
Compound kushen injection relieves tumor-associated macrophage-mediated immunosuppression through TNFR1 and sensitizes hepatocellular carcinoma to sorafenib
Authors: Yang Yang, Mayu Sun, Wenbo Yao, Feng Wang, Xiaoguang Li, Wei Wang, Jingquan Li, Zhihu Gao, Lin Qiu, Rongli You, Chenghua Yang, Qian Ba, Hui Wang
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background There is an urgent need for effective treatments for hepatocellular carcinoma (HCC). Immunotherapy is promising especially when combined with traditional therapies. This study aimed to investigate the immunomodulatory function of an approved Chinese medicine formula, compound kushen injection (CKI), and its anti-HCC efficiency in combination with low-dose sorafenib. Methods Growth of two murine HCC cells was evaluated in an orthotopic model, a subcutaneous model, two postsurgical recurrence model, and a tumor rechallenge model with CKI and low-dose sorafenib combination treatment. In vivo macrophage or CD8 + T cell depletion and in vitro primary cell coculture models were used to determine the regulation of CKI on macrophages and CD8 + T cells. Results CKI significantly enhanced the anticancer activity of sorafenib at a subclinical dose with no obvious side effects. CKI and sorafenib combination treatment prevented the postsurgical recurrence and rechallenged tumor growth. Further, we showed that CKI activated proinflammatory responses and relieved immunosuppression of tumor-associated macrophages in the HCC microenvironment by triggering tumor necrosis factor receptor superfamily member 1 (TNFR1)-mediated NF-κB and p38 MAPK signaling cascades. CKI-primed macrophages significantly promoted the proliferation and the cytotoxic ability of CD8 + T cells and decreased the exhaustion, which subsequently resulted in apoptosis of HCC cells. Conclusions CKI acts on macrophages and CD8 + T cells to reshape the immune microenvironment of HCC, which improves the therapeutic outcomes of low-dose sorafenib and avoids adverse chemotherapy effects. Our study shows that traditional Chinese medicines with immunomodulatory properties can potentiate chemotherapeutic drugs and provide a promising approach for HCC treatment.
THE EFFECTS OF CANAGLIFLOZIN ON HEART FAILURE AND CARDIOVASCULAR DEATH BY BASELINE PARTICIPANT CHARACTERISTICS: ANALYSIS OF THE CREDENCE TRIAL
Authors: Clare Arnott, Jing-Wei Li, Christopher P. Cannon, Brendon Neuen, Hiddo L. Heerspink, Bruce Neal, David M. Charytan, Rajiv Agarwal, George L. Bakris, Dick De Zeeuw, Tom Greene, Adeera Levin, Carol Pollock, Tara Chang, Norman Rosenthal, Hong Zhang, Bernard Zinman, Vlado Perkovic, Meg Jardine, Kenneth Mahaffey
Journal: Journal of the American College of Cardiology (2020)
CORONARY MICROVASCULAR DYSFUNCTION IS ASSOCIATED WITH SUBCLINICAL SYSTOLIC DYSFUNCTION AND HEART FAILURE ADMISSION IN HYPERTENSION
Authors: Wunan Zhou, Jenifer Brown, Alvin Chandra, Navkaranbir S. Bajaj, Sanjay Divakaran, Brittany Weber, Courtney Bibbo, Jon Hainer, Viviany R. Taqueti, Sharmila Dorbala, Ron Blankstein, Dale Adler, Patrick T. O’Gara, Marcelo Di Carli
Journal: Journal of the American College of Cardiology (2020)
Return on Investment From Co-locating Tax Assistance for Low-Income Persons at Clinical Sites
Authors: Shinelle Black, Sarah Sisco, Tatiana Williams, Makeela Brathwaite, Kalpana Bhandarkar, Dave A. Chokshi, Mitchell H. Katz
Journal: JAMA (2020)

This study characterizes net dollars low-income persons received from participation in tax preparation services co-located at clinical sites in New York City intended to maximize credits and reduce poverty.
VARIATION IN CARE PRACTICES FOR ACUTE MYOCARDIAL INFARCTION WITH MULTIVESSEL CORONARY ARTERY DISEASE PRESENTING WITH CARDIOGENIC SHOCK IN THE UNITED STATES, 2009-2018: A REPORT FROM THE NCDR RESEARCH TO PRACTICE (R2P) INITIATIVE
Authors: Rohan Khera, Eric Secemsky, Yongfei Wang, Nihar R. Desai, Thomas M. Maddox, Kendrick A. Shunk, Salim S. Virani, Deepak Bhatt, Jeptha P. Curtis, Robert W. Yeh
Journal: Journal of the American College of Cardiology (2020)
Intrinsic antiviral immunity drives neurodegeneration in Alzheimer disease
Authors: Stefano Pluchino, Cory Willis
Journal: Journal of Clinical Investigation (2020)

β-Amyloid aggregates found in brain plaques are viewed as triggers of cytotoxicity and neuroinflammation in Alzheimer disease (AD). However, the main β-amyloid (Aβ) species and what imbues the aggregates with such toxic potential are still not yet understood. In this issue of the JCI, Roy et al. show that Aβ complexed with nucleic acids triggers an antiviral type I interferon response in neuroglia, resulting in complement-mediated synapse elimination in AD models. These findings identify a putative endogenous immune signaling axis that drives neurodegeneration in AD and has strong implications for the development of precise therapeutic strategies.
APPLICATION OF ARTIFICIAL INTELLIGENCE-ENABLED ELECTROCARDIOGRAPHY IN FAMILIAL DILATED CARDIOMYOPATHY
Authors: Sanskriti Shrivastava, Michal Shelly, Zachi Itzhak Attia, Andrew Rosenbaum, Francisco Lopez-Jimenez, Kent Bailey, Suraj Kapa, Paul Friedman, Naveen Pereira
Journal: Journal of the American College of Cardiology (2020)
Serial hypoxia imaging with <sup>99m</sup>Tc-HL91 SPECT to predict radiotherapy response in non-small cell lung cancer
Authors: J. Li, L. Li, J. Yu, L. Xing, H. Guo, H. Zhu, X. Sun, G. Yang
Journal: Journal of Clinical Oncology (2006)

7143 Background: To evaluate the relationship between 99m Tc-HL91 ( 99m Tc labeled 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime) SPECT (single photon emission computed tomography) hypoxia imaging and the radiotherapy outcome and also to assess changes in tumor oxygenation during the course of treatment. Methods: 32 patients with pathologically proven non-small cell lung cancer received three-dimensional conformal radiotherapy were enrolled into the study. All patients were performed 99m Tc-HL91 SPECT scanning at one or two days before radiotherapy. 18 patients were also performed during radiotherapy (30–40 Gy) and one or two days after radiotherapy. Anterior, posterior and lateral planar images were collected at 2 hours, 4 hours and 6 hours respectively after intravenous injection approximately 740MBq 99m Tc-HL91. Regions of interest (ROIs) were drawn in the tumor and contralateral normal lung tissue and the radioactivity ratios of tumor to normal tissue (T/N) were calculated. Results: The relationship between T/N ratios at 4h images after injection which was shown as the best of three acquired images before radiotherapy and the response and over survival to radiotherapy were analyzed for all 32 patients. The results of 99m Tc-HL91 imaging of 32 patients correlate well with radiotherapy response (P = 0.049) and also patient survival (P = 0.043). The average T/N value of 18 patients who receiving serial scanning was 1.57 ± 0.18, 1.44 ± 0.19 and 1.30 ± 0.14 respectively. There was significant statistic difference between these three groups (P = 0.000). Conclusions: HL91 SPECT imaging identified the hypoxia status and changes during radiotherapy in lung cancer. It was confirmed that hypoxia imaging with HL91 SPECT before treatment may predict radiotherapy response and patient survival. The relationship between T/N ratio and radiotherapy outcome in NSCLC [Table: see text] No significant financial relationships to disclose.
Desmond Gareth Julian: cardiologist who revolutionised acute coronary care
Authors: Marika Davies
Journal: BMJ (2020)

As a junior doctor in 1956, Desmond Julian was advised against pursuing a career in cardiology. The main focus of the specialty at the time was on congenital and rheumatic heart disease, and he was warned that “all the mitrals have been operated on.” Fortunately, he did not follow this advice: he loved the specialty of cardiology, which he said “used all of the senses,” and his interest was further developed while he was working as a cardiology fellow in Boston, USA.

In the 1950s and early ’60s the practice of cardiology was very different. Patients who had had a myocardial infarction (MI) were admitted to general wards throughout the hospital—often in beds as far as possible from the busy nurses’ station—and were treated with morphine and rest. A cardiac arrest was treated using a defibrillator the size of a refrigerator, which had to be fetched from wherever it was in the hospital.

Working as a cardiology registrar at the Edinburgh Royal Infirmary, Julian was impressed by a film about treating cardiac arrest by an open chest …
COMPARISON OF ALTEPLASE DOSING STRATEGIES IN PATIENTS UNDERGOING CATHETER DIRECTED THROMBOLYSIS FOR ACUTE PULMONARY EMBOLISM
Authors: Shannon Kuhrau, Ibrahim Chowdhury, Dalila Masic, Jeremiah Haines, Stephen Morris, Lucas Chan, Katerina Porcaro, Sorcha Allen, Yevgeniy Brailovsky, Amir Darki
Journal: Journal of the American College of Cardiology (2020)
Abstract 13624: IL-19, a Novel Adipokine With Insulin Sensitizing Action
Authors: Christine Vrakas, Tatsuo Kawai, Sheri E Kelemen, Michael Autieri, Gavin Landesberg, Rosario G Scalia
Journal: Circulation (2019)

Background: Obesity causes a functional disorder of the white adipose tissue (WAT). Hypertrophic adipocytes, immune cells, and dysfunctional endothelium of the WAT microcirculation all contribute t...
Application of multiphoton/CARS tomography for detecting early stages of chemotherapeutically induced dermal side effects.
Authors: Juergen Lademann, Alexa Patzelt, Leonhard Zastrow, Radoslav Chekerov, Jalid Sehouli, Martin Weinigel, Karsten Koenig, Maxim E. Darvin
Journal: Journal of Clinical Oncology (2013)

e20688 Background: A wide variety of chemotherapeutics is available for systemic cancer therapy. Many of them are known to induce dermal side effects (DSE), although the pathomechanisms often remain unclear. Recently, it was found that pegylated liposomal doxorubicin (PLD) is delivered to the skin via the sweat. The palmar and plantar region provides the highest density of sweat glands and the thickest stratum corneum serving as reservoir, and thus seems to be the predestined area to develop a palmar plantar erythrodysethesia (PPE). Due to its specific fluorescent properties PLD is easily detectable. DSE can also be induced by other chemotherapeutics, however, as there are lacking fluorescence properties, the pathomechanism is difficult to verify. In the present study, a multiphoton/CARS (coherent anti-Stockes Raman scattering) tomograph was used to detect early stages of skin inflammation during therapy with various chemotherapeutics. Methods: The investigations involved 12 patients under chemotherapy with e.g., capecitabin, docetaxel and 5 FU. The patients had a history of 2 to 4 cycles of chemotherapy and were free from clinical signs of DSE at the time of investigation. An internationally unique system was used combining multiphoton tomography permitting cellular structures to be clearly imaged without contrast agents and CARS microscopy which detects lipids. Results: In the present study the lipid structure of patients under chemotherapy was compared to that of healthy volunteers determined in preliminary investigations. While no inflammation was visible on any patient’s skin surface, pathological changes were detected in deeper lipid structures revealing an early stage of DSE. Conclusions: Changes in the lipid structure are independent of the applied chemotherapeutic and imply an early stage of an inflammatory process. Thus, multiphoton/CARS tomography permits early DSE diagnostics before pathological changes manifest themselves on the skin surface. The method is suited to investigate the pathomechanism of DSE of various chemotherapeutics and can help to develop prevention measures such as the topical application of antioxidants during chemotherapy as proposed for PPE.