tbuckley/cabot-search huggingface dataset:
Abstract OT1-01-06: A pilot study utilizing a HER2 directed dendritic cell vaccine during neoadjuvant therapy of HER2+ breast cancer
Authors: Hatem Soliman, Deanna Hogue, Hyo Han, Hung Khong, Ricardo Costa, Avan Armaghani, Axia Soyano Muller, Nazanin Khakpour, Marie C Lee, John Kiluk, Brian Czerniecki
Journal: Cancer Research (2020)

Abstract Background: During the natural progression of early breast cancer, it has been demonstrated that the protective host immune response against HER2 is lost early on. Using a type 1 dendritic cell (DC1) vaccine loaded with HER2 peptides has been shown to be effective in restoring anti HER2 immune responsiveness and can lead to regression of very early non-invasive breast cancers. Prior investigations conducted by our group has suggested DC vaccines may sensitize cancers to subsequent systemic chemotherapy, and the Geparnuevo trial also suggested a prechemotherapy dosing with checkpoint therapy may improve pathologic complete response (pCR) rates in TNBC. We launched a pilot study to demonstrate safety, feasibility, and preliminary efficacy of administering the DC1 HER2 vaccine for 3 weeks prior to the initiation of neoadjuvant systemic therapy for stage II-III ER-HER2+ breast cancer. Methods: This single site study is a pilot design with a safety run in phase (n = 12) followed by an expansion cohort of 18 patients. Patients with stage II-III ER-HER2+ breast cancer who are eligible to receive neoadjuvant HER2 based chemotherapy (TCHP) can enroll. The safety run in evaluates two schedules of DC1 vaccination (ARM A = once weekly x 3 weeks and ARM B = twice weekly x 3 weeks) and will enroll six patients in each arm. After the first 3 weeks of DC1 neoadjuvant chemotherapy will be administered using standard docetaxel, carboplatin, trastuzumab, and pertuzumab given intravenously once every 3 weeks for 6 cycles. Booster vaccines will be given at weeks 25, 56, 80, and 104 and immune monitoring will be performed at these timepoints. The safety run in will evaluate safety using CTCAE 4.03 criteria along with the immunogenicity of each arm measured by ELISPOT. The arm with the best immune response at 3 weeks will be selected to proceed forward during the expansion cohort using an endpoint of pCR. Secondary endpoints will be recurrence free survival rate at 3 years and immune response. The pilot design is hypothesis generating but is likely able to detect a significant difference in pCR if the true rate is 75% assuming a historical rate of 55%. Accrual to the safety run in phase is complete and the expansion phase is underway using the twice weekly vaccination schedule. Citation Format: Hatem Soliman, Deanna Hogue, Hyo Han, Hung Khong, Ricardo Costa, Avan Armaghani, Axia Soyano Muller, Nazanin Khakpour, Marie C Lee, John Kiluk, Brian Czerniecki. A pilot study utilizing a HER2 directed dendritic cell vaccine during neoadjuvant therapy of HER2+ breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-01-06.
Phenotypic profiling of high-throughput transfections of anti- and pre-miRNA libraries into breast and prostate cancer cells using protein lysate microarray technology
Authors: Rami Makela, Suvi-Katri Leivonen, Paivi Ostling, Pekka Kohonen, Kirsi Hellstrom, Tao He, Saija Haapa-Paananen, Petri Saviranta, Merja Perala, Olli Kallioniemi
Journal: Cancer Research (2008)

5018  We developed protein lysate microarray technology for the analysis of multiple endpoints from a single high-throughput screening (HTS) experiment and applied this to functional miRNA studies in cancer cells. Following 384-well cell-based screens, protein lysates are prepared directly in the assay plates and printed on nitrocellulose slides. at densities of up to 10,000 spots/slide. Over 100 replicate slides could be generated from a single HTS experiment and exposed to different antibody stains in order to profile phenotypic markers or specific signalling pathways. We use a 3-color detection of total protein (counterstain) and two target-specific antibodies detected with infra-red dyes quantified with an IR scanner. Replicate spot CVs within array were
Characterization of human cancer xenografts in humanized mice
Authors: Jonathan Rios-Doria, Christina Stevens, Christopher Maddage, Kerri Lasky, Holly K Koblish
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Preclinical evaluation of drugs targeting the human immune system has posed challenges for oncology researchers. Since the commercial introduction of humanized mice, antitumor efficacy and pharmacodynamic studies can now be performed with human cancer cells within mice bearing components of a human immune system. However, development and characterization of these models is necessary to understand which model may be best suited for different agents. Methods We characterized A375, A549, Caki-1, H1299, H1975, HCC827, HCT116, KU-19–19, MDA-MB-231, and RKO human cancer cell xenografts in CD34 + humanized non-obese diabetic-scid gamma mice for tumor growth rate, immune cell profiling, programmed death ligand 1 (PD-L1) expression and response to anti-PD-L1 therapy. Immune cell profiling was performed using flow cytometry and immunohistochemistry. Antitumor response of humanized xenograft models to PD-L1 therapy was performed using atezolizumab. Results We found that CD4 + and CD8 + T-cell composition in both the spleen and tumor varied among models, with A375, Caki-1, MDA-MB-231, and HCC827 containing higher intratumoral frequencies of CD4 + and CD8 + T cells of CD45 + cells compared with other models. We demonstrate that levels of immune cell infiltrate within each model are strongly influenced by the tumor and not the stem cell donor. Many of the tumor models showed an abundance of myeloid cells, B cells and dendritic cells. RKO and MDA-MB-231 tumors contained the highest expression of PD-L1 + tumor cells. The antitumor response of the models to atezolizumab was positively associated with the level of CD4 + and CD8 + tumor-infiltrating lymphocytes (TILs). Conclusions These data demonstrate that there are tumor-intrinsic factors that influence the immune cell repertoire within tumors and spleen, and that TIL frequencies are a key factor in determining response to anti-PD-L1 in tumor xenografts in humanized mice. These data may also aid in the selection of tumor models to test antitumor activity of novel immuno-oncology or tumor-directed agents.
Volixibat in adults with non-alcoholic steatohepatitis: 24-week interim analysis from a randomized, phase II study
Authors: Philip N. Newsome, Melissa Palmer, Bradley Freilich, Muhammad Y. Sheikh, Aasim Sheikh, Harry Sarles, Robert Herring, Parvez Mantry, Zeid Kayali, Tarek Hassanein, Hak-Myung Lee, Guruprasad P. Aithal
Journal: Journal of Hepatology (2020)

Volixibat is an inhibitor of the apical sodium-dependent bile acid transporter (ASBT) that has been hypothesized to improve non-alcoholic steatohepatitis (NASH) by blocking bile acid reuptake and stimulating hepatic bile acid production. We studied the safety, tolerability and efficacy of volixibat in patients with NASH.In this double-blind, phase II dose-finding study, adults with ≥5% steatosis and NASH without cirrhosis (N = 197) were randomized to receive volixibat (5, 10 or 20 mg) or placebo once daily for 48 weeks. The endpoints of a predefined interim analysis (n = 80), at week 24, were: ≥5% reduction in MRI-proton density fat fraction and ≥20% reduction in serum alanine aminotransferase levels. The primary endpoint was a ≥2-point reduction in non-alcoholic fatty liver disease activity score without worsening fibrosis at week 48.Volixibat did not meet either interim endpoint; the study was terminated owing to lack of efficacy. In participants receiving any volixibat dose, mean serum 7-alpha-hydroxy-4-cholesten-3-one (C4; a biomarker of bile acid synthesis) increased from baseline to week 24 (+38.5 ng/ml [SD 53.18]), with concomitant decreases in serum total cholesterol (-14.5 mg/dl [SD 28.32]) and low-density lipoprotein cholesterol (-16.1 mg/dl [SD 25.31]). These changes were generally dose-dependent. On histological analysis, a greater proportion of participants receiving placebo (38.5%, n = 5/13) than volixibat (30.0%, n = 9/30) met the primary endpoint. Treatment-emergent adverse events (TEAEs) were mainly mild or moderate. No serious TEAEs were related to volixibat. Diarrhoea was the most common TEAE overall and the most common TEAE leading to discontinuation.Increased serum C4 and decreased serum cholesterol levels provide evidence of target engagement. However, inhibition of ASBT by volixibat did not elicit a liver-related therapeutic benefit in adults with NASH.A medicine called volixibat has previously been shown to reduce cholesterol levels in the blood. This study investigated whether volixibat could reduce the amount of fat in the liver and reduce liver injury in adults with an advanced form of non-alcoholic fatty liver disease. Volixibat did not reduce the amount of fat in the liver, nor did it have any other beneficial effect on liver injury. Participants in the study generally tolerated the side effects of volixibat and, as in previous studies, the main side effect was diarrhoea. These results show that volixibat is not an effective treatment for people with fatty liver disease.NCT02787304.
Paraneoplastic neutrophilic leukaemoid reaction in a patient with melanoma: association between tumour volume and leucocytosis
Authors: L. Fredeau, G. Bohelay, J. Shourick, D. Piver, A. Guyot, M.‐H. Schlageter, F. Caux, E. Maubec
Journal: British Journal of Dermatology (2020)
Oncolytic vaccinia virus delivering tethered IL-12 enhances antitumor effects with improved safety
Authors: Yan Ge, Haiyan Wang, Jinghua Ren, Weilin Liu, Lingjuan Chen, Hongqi Chen, Junjie Ye, Enyong Dai, Congrong Ma, Songguang Ju, Zong Sheng Guo, Zuqiang Liu, David L Bartlett
Journal: Journal for ImmunoTherapy of Cancer (2020)

Immune checkpoint blockade is arguably the most effective current cancer therapy approach; however, its efficacy is limited to patients with “hot” tumors, warranting an effective approach to transform “cold” tumors. Oncolytic viruses (especially properly armed ones) have positive effects on almost every aspect of the cancer–immunity cycle and can change the cancer–immune set point of a tumor. Here, we tested whether oncolytic vaccinia virus delivering tethered interleukin 12 (IL-12) could turn a “cold” tumor into a “hot” tumor while avoiding IL-12’s systemic toxicity. Our data demonstrated that tethered IL-12 could be maintained in the tumor without treatment-induced toxic side effects. Moreover, the treatment facilitated tumor infiltration of more activated CD4 + and CD8 + T cells and less Tregs, granulocytic myeloid-derivedsuppressor cells, and exhausted CD8 + T cells, with increased interferon γ and decreased transforming growth factor β, cyclooxygenase-2, and vascular endothelial growth factor expression, leading to transformed, immunogenic tumors and improved survival. Combined with programmed cell death 1 blockade, vaccinia virus expressing tethered IL-12 cured all mice with late-stage colon cancer, suggesting immediate translatability to the clinic.
Chemical Alteration of Polysaccharide from &lt;italic&gt;Serratia Marcescens&lt;/italic&gt;. II. Effects of Iodopolysaccharide in Patients with Malignant Tumors&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/xref&gt;
Authors: T SACK, A M SELIGMAN
Journal: JNCI Journal of the National Cancer Institute (1948)

Journal Article Chemical Alteration of Polysaccharide from Serratia Marcescens. II. Effects of Iodopolysaccharide in Patients with Malignant Tumors Get access Theodore Sack, Theodore Sack Search for other works by this author on: Oxford Academic PubMed Google Scholar Arnold M. Seligman Arnold M. Seligman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 9, Issue 1, August 1948, Pages 19–34, https://doi.org/10.1093/jnci/9.1.19 Published: 01 August 1948 Article history Received: 31 March 1948 Published: 01 August 1948
Reactive arthritis, a missing link: comment on the recent article from Sepriano<i>et al</i>
Authors: Henning Zeidler, Alan P Hudson
Journal: Annals of the Rheumatic Diseases (2020)

The recent paper from Sepriano et al provides an extremely important new insight on the concept of axial spondyloarthritis (axSpA).1 Clearly, the Gestalt of axSpA is heterogeneous, with three recognisable clinical entities labelled as: ‘pure axial SpA’, ‘axial SpA with peripheral signs’ and ‘axial SpA at risk’. The finding given in the paper suggests a larger overlap between axSpA and pSpA than anticipated at the time when the Assessment of SpondyloArthritis international Society (ASAS) criteria were developed. Thus, the question arises as to how accurately the three recognisable clinical entities of the ASAS classification criteria represent the diseases entities originally lumped together in the historical concept of SpA.

The unifying historical concept of SpA lumps together an inter-related yet heterogeneous group of disorders which includes ankylosing spondylitis …
Comparison of commonly used solid tumor targeted gene sequencing panels for estimating tumor mutation burden shows analytical and prognostic concordance within the cancer genome atlas cohort
Authors: Nicholas Bevins, Shulei Sun, Zied Gaieb, John A Thorson, Sarah S Murray
Journal: Journal for ImmunoTherapy of Cancer (2020)

Tumor mutation burden (TMB) is a biomarker frequently reported by clinical laboratories, which is derived by quantifying of the number of single nucleotide or indel variants (mutations) identified by next-generation sequencing of tumors. TMB values can inform prognosis or predict the response of a patient's tumor to immune checkpoint inhibitor therapy. Methods for the calculation of TMB are not standardized between laboratories, with significant variables being the gene content of the panels sequenced and the inclusion or exclusion of synonymous variants in the calculations. The impact of these methodological differences has not been investigated and the concordance of reported TMB values between laboratories is unknown.Sequence variant lists from more than 9000 tumors of various types were downloaded from The Cancer Genome Atlas. Variant lists were filtered to include only appropriate variant types (ie, non-synonymous only or synonymous and non-synonymous variants) within the genes found in five commonly used targeted solid tumor gene panels as well as an in-house gene panel. Calculated TMB was paired with corresponding overall survival (OS) data of each patient.Regression analysis indicates high concordance of TMB as derived from the examined panels. TMB derived from panels was consistently and significantly lower than that derived from a whole exome. TMB, as derived from whole exome or the examined panels, showed a significant correlation with OS in the examined data.TMB derived from the examined gene panels was analytically equivalent between panels, but not between panels and whole-exome sequencing. Correlation between TMB and OS is significant if TMB method-specific cut-offs are used. These results suggest that TMB values, as derived from the gene panels examined, are analytically and prognostically equivalent.
Overcoming hepatic artery thrombosis after living donor liver transplantations; An experience from the Asan Medical Center
Authors: Gil Chun Park, Deok Bog Moon, Sang Hyun Kang, Chul Soo Ahn, Shin Hwang, Ki Hun Kim, Gi Won Song, Dong Hwan Jung, Young In Yoon, Sung Gyu Lee
Journal: International Journal of Surgery (2020)
Whole genome and phylogenetic analysis of two SARS-CoV-2 strains isolated in Italy in January and February 2020: additional clues on multiple introductions and further circulation in Europe
Authors: Paola Stefanelli, Giovanni Faggioni, Alessandra Lo Presti, Stefano Fiore, Antonella Marchi, Eleonora Benedetti, Concetta Fabiani, Anna Anselmo, Andrea Ciammaruconi, Antonella Fortunato, Riccardo De Santis, Silvia Fillo, Maria Rosaria Capobianchi, Maria Rita Gismondo, Alessandra Ciervo, Giovanni Rezza, Maria Rita Castrucci, Florigio Lista
Journal: Eurosurveillance (2020)

Whole genome sequences of SARS-CoV-2 obtained from two patients, a Chinese tourist visiting Rome and an Italian, were compared with sequences from Europe and elsewhere. In a phylogenetic tree, the Italian patient's sequence clustered with sequences from Germany while the tourist's sequence clustered with other European sequences. Some additional European sequences in the tree segregated outside the two clusters containing the patients' sequences. This suggests multiple SARS-CoV-2 introductions in Europe or virus evolution during circulation.
COVID-19 Does Not Lead to a “Typical” Acute Respiratory Distress Syndrome
Authors: Luciano Gattinoni, Silvia Coppola, Massimo Cressoni, Mattia Busana, Sandra Rossi, Davide Chiumello
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

ARDS with COVID-19.An intermediate VT (7-8 ml/kg PBW) ventilation strategy was applied to the first four patients to increase pulmonary efficiency to eliminate CO 2 , and this was used in the next four patients.Gas exchange consists of oxygenation and ventilation.Oxygenation is quantified by the Pa O 2 /FI O 2 ratio, and this method has gained wide acceptance, particularly since publication of the Berlin definition of ARDS (7).However, the Berlin definition does not include additional pathophysiological information about ARDS, such as alveolar ventilation, as measured by pulmonary dead space, which is an important predictor of outcome (8).Increased pulmonary dead space reflects the inefficiency of the lungs to eliminate CO 2 , which may lead to hypercapnia.In our patients with ARDS with COVID-19, hypercapnia was common at ICU admission with low VT ventilation.Assuming the anatomic portion of dead space is constant, increasing VT with constant respiratory rate would effectively increase alveolar ventilation.Any such increase in VT would decrease Pa CO 2 , which would be captured by VR (6).VR, a novel method to monitor ventilatory adequacy at the bedside (4-6), was very high in our patients, reflecting increased pulmonary dead space and inadequacy of ventilation.With an acceptable plateau pressure and driving pressure, titration of VT was performed.Pa CO 2 and VR were significantly decreased when an intermediate VT (7-8 ml/kg PBW) was applied.We suggest that intermediate VT (7-8 ml/kg PBW) is recommended for such patients.Therefore, low VT may not be the best approach for all patients with ARDS, particularly those with a less severe decrease in respiratory system compliance and inadequacy of ventilation.In summary, we found that hypercapnia was common in patients with COVID-19-associated ARDS while using low VT ventilation.VR was increased in these patients, which reflected increased pulmonary dead space and inadequacy of ventilation.An intermediate VT was used to correct hypercapnia efficiently, while not excessively increasing driving pressure.Clinicians must have a high index of suspicion for increased pulmonary dead space when patients with COVID-19-related ARDS present with hypercapnia.
Evaluation of RAPNO criteria in medulloblastoma and other leptomeningeal seeding tumors using MRI and clinical data
Authors: Jian Peng, Hao Zhou, Oliver Tang, Ken Chang, Panpan Wang, Xiaowei Zeng, Qin Shen, Jing Wu, Yanhe Xiao, Sohil H Patel, Chongyu Hu, Ke Jin, Bo Xiao, Jerrold Boxerman, Xiaoping Gao, Patrick Y Wen, Harrison X Bai, Raymond Y Huang, Li Yang
Journal: Neuro-Oncology (2020)

Although the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group has made recommendations for response assessment in patients with medulloblastoma (MBL) and leptomeningeal seeding tumors, these criteria have yet to be evaluated. We examined MR imaging and clinical data in a multicenter retrospective cohort of 269 patients with MBL diagnoses, high grade glioma, embryonal tumor, germ cell tumor, or choroid plexus papilloma. Interobserver agreement, objective response (OR) rates, and progression-free survival (PFS) were calculated. Landmark analyses were performed for OR and progression status at 0.5, 1.0, and 1.5 years after treatment initiation. Cox proportional hazards models were used to determine the associations between OR and progression with overall survival (OS). Subgroup analyses based on tumor subgroup and treatment modality were performed. The median follow-up time was 4.0 years. In all patients, the OR rate was .0.565 (95% CI: 0.505-0.625) by RAPNO. The interobserver agreement of OR determination between 2 raters (a neuroradiologist and a neuro-oncologist) for the RAPNO criteria in all patients was 83.8% (k statistic = 0.815; P < 0.001). At 0.5-, 1.0-, and 1.5-year landmarks, both OR status and PFS determined by RAPNO were predictive of OS (hazard ratios [HRs] for 1-year landmark: OR HR = 0.079, P < 0.001; PFS HR = 10.192, P < 0.001). In subgroup analysis, OR status and PFS were predictive of OS for all tumor subtypes and treatment modalities. RAPNO criteria showed excellent consistency in the treatment response evaluation of MBL and other leptomeningeal seeding tumors. OR and PFS determined by RAPNO criteria correlated with OS.
Rare diseases 2030: how augmented AI will support diagnosis and treatment of rare diseases in the future
Authors: Martin Christian Hirsch, Simon Ronicke, Martin Krusche, Annette Doris Wagner
Journal: Annals of the Rheumatic Diseases (2020)

WHaT Will THe fuTure of rare diseases look like?We picture an 18-year-old young man from a village somewhere in Europe.His name is Omer.Omer has been suffering from disease episodes since his early childhood: bursts of fever, fatigue and abdominal pain.He visited many doctors, but none of them was able to establish a satisfactory treatment.He went through a diagnostic and therapeutic odyssey typical for rare disease patients.Fatigue has led him into social isolation.He is perceived as a malingerer.
Successful remission with tofacitinib in a patient with refractory Takayasu arteritis complicated by ulcerative colitis
Authors: Saki Kuwabara, Shun Tanimura, Shogo Matsumoto, Hiroyuki Nakamura, Tetsuya Horita
Journal: Annals of the Rheumatic Diseases (2020)

Takayasu arteritis (TAK) is a form of large vessel vasculitis resulting in thickening and stenosis of the large-sized arteries, particularly the aorta and its main branches. Ulcerative colitis (UC) is a major complication of TAK, sharing some genetic background and pathogenesis.1 Serum levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), are potential biomarkers to reflect disease activity of TAK. Thus, IL-6 or TNF-α inhibitors have been used for treating refractory TAK. A randomised controlled trial suggested clinical efficacy and safety of tocilizumab in patients with refractory TAK, although the trial failed to achieve its primary endpoint.2 We here present a patient in whom tofacitinib (TOF), a Janus kinase (JAK) inhibitor, successfully induced a remission of TAK and UC resistant to both TNF-α and IL-6 inhibitors.

A 32-year-old Japanese female with a medical history of TAK and UC visited our hospital complaining of chest pain, abdominal …
Blood pressure changes correlate with short-chain fatty acid production potential shifts under a synbiotic intervention
Authors: Hendrik Bartolomaeus, Ellen G Avery, Theda U P Bartolomaeus, Samat Kozhakhmetov, Zhaxybay Zhumadilov, Dominik N Müller, Nicola Wilck, Almagul Kushugulova, Sofia K Forslund
Journal: Cardiovascular Research (2020)