tbuckley/cabot-search huggingface dataset:
Inhibition of human lung cancer cell growth by angiotensin II (Ang II) type 2 receptor (AT2) over-expression
Authors: Lara Pickel, Takaya Matsuzuka, Chiyo Doi, Rie Ayuzawa, Dharmendra Maurya, Sheng-Xue Xie, Cory Berkland, Masaaki Tamura
Journal: Cancer Research (2008)

1395  Lung cancer mortality is the highest among all cancer-associated deaths. Development of new therapeutic agents and effective treatment procedures are urgently needed. Endogenous Angiotensin II (Ang II) type 2 receptor (AT2), one of two isoforms of Ang II, has been shown to mediate apoptosis. Nanotechnology is a rapidly emerging drug-delivery system which makes possible the targeted drug delivery and the controlled release of therapeutic molecules and genes. Thus, the aim of this study was to determine the anti-cancer effect of over-expressed AT2 gene on lung adenocarcinoma cells in vitro using adenoviral vectors (Ad) and nanoparticles (NPs) conjugated with Ang II to specifically target lung tumor tissue. Here, we show that over-expression of Ad-AT2 induces cancer cell-specific apoptosis in several human lung adenocarcinoma cell lines with minimal effect on normal lung epithelial cells and fibroblasts. Ad-AT2 significantly attenuated multiple human lung cancer cell growth (A549, and H358) in vitro compared to the control viral vector, Ad-LacZ when cell viability was examined by direct cell count using trypan blue exclusion test. The growth attenuation effect was detected as early as 24h after Ad-AT2 transfection and lasted for 12 days. Western Blot analysis revealed the activation of the caspase pathway through caspases-9 and-3. Examination for Annexin V by flow cytometry also confirmed the activation of the apoptotic pathway via AT2 over-expression. Therefore, it is suggested that the mechanism by which AT2 over-expression attenuates lung cancer cell growth is due to intrinsic apoptosis. Similary, AT2 cDNA encapsulated poly(dl-lactide-co-glycolide) (PLGA) biodegradable nanoparticles (NPs) were shown to be effectively taken up into the lung cancer cell. The surface conjugation of angiotensin II peptide significantly stimulated uptake of the particles. This PLGA vector-dependent AT2 transfection was very effective in sustained gene expression. These results indicate that the AT2 over-expression effectively attenuated growth of lung adenocarcinoma cells through activation of apoptosis. Ang II conjugated PLGA nanoparticles can be used as lung adenocarcinoma targeted therapeutic gene delivery vehicles. This work was supported by KSU Terry C. Johnson Center for Basic Cancer Research, KSU CVM Dean’s fund, NIH P20 RR017686 and Joan’s Legacy Foundation Research Grant.
Ragweed SLIT-Tablets Induce Similar Patterns of Allergen-Specific IgE and IgG4 Responses in Children and Adults with Allergic Rhinoconjunctivitis
Authors: Peter Wurtzen, Hendrik Nolte, David Bernstein, Harold Nelson, Anne Ellis, Jorg Kleine - Tebbe, Peter Andersen
Journal: Journal of Allergy and Clinical Immunology (2020)
Randomized phase II study of sipuleucel-T (SipT) with or without radium-223 (Ra223) in men with asymptomatic bone-metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Catherine Handy Marshall, Jong Chul Park, Theodore L. DeWeese, Serina King, Michaella Afful, Julia Hurrelbrink, Charlotte Manogue, Patrick Cotogno, Nancy P. Moldawer, Pedro C. Barata, Charles G. Drake, Edwin M. Posadas, Andrew J. Armstrong, A. Oliver Sartor, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2020)

130 Background: SipT-induced antigen-specific immune responses in mCRPC patients correlate with survival. Due to the immunomodulatory effects of radiopharmaceutical agents (e.g. enhancing tumor-antigen display), we hypothesized that combined use of Ra223 and SipT would augment SipT-related immune response and improve outcomes compared to SipT alone. Methods: Patients with asymptomatic mCRPC and bone-predominant mets, without visceral mets &gt;1.0 cm, were randomized (1:1) to standard SipT alone or combined with 6 doses of Ra223 (NCT02463799). Men in the SipT+Ra223 arm received SipT between the 2nd and 3rd dose of Ra223. Clinical endpoints were radiographic/clinical PFS, PSA response (≥50% decline), AlkPhos response (≥30% decline), and safety. Immunologic endpoints were PA2024-specific T-cell proliferation 6 wks after the first SipT infusion, PA2024-specific ELISPOT response, PAP-specific proliferation and ELISPOT, humoral responses against both antigens, and antigen spread. Results: 32 men were randomized, 16 per arm. Baseline characteristics in SipT and SipT+Ra223 arms were matched with respect to age (median 70 vs 71 yrs), Gleason (8-10: 69% vs 69%), PSA (median 82 vs 72 ng/mL), AlkPhos (median 125 vs 125 U/L) and ECOG scores (≥1: 19% vs 31%). After median follow up of 5.3 (range 2.8–26.6) mo, median PFS was longer in the SipT+Ra223 arm (10.7 vs 3.1 mo; HR 0.35, 95% CI 0.15–0.81; P=0.02). Outcomes were also better in the SipT+Ra223 arm with respect to PSA responses (5/15=33% vs 0/14=0%; P=0.04) and AlkPhos responses (9/15=60% vs 1/15=7%; P=0.01). No safety concerns were observed with the combination (grade 3 AEs shown in the Table). Conclusions: SipT combined with Ra223 was associated with improved clinical outcomes compared to SipT alone. Since neither agent reliably induces PSA responses alone, these data suggest a synergistic effect of the combination. Immunologic endpoints will be presented at the meeting. Larger randomized studies of this combination are warranted. Clinical trial information: NCT02463799. [Table: see text]
Propensity score matched comparison of docetaxel and androgen receptor axis-targeted (ARAT) agents in castration-resistant prostate cancer patients with intraductal carcinoma of the prostate (IDC-P).
Authors: Akiyuki Yamamoto, Masashi Kato, Toyonori Tsuzuki, Momokazu Gotoh
Journal: Journal of Clinical Oncology (2020)

80 Background: Several studies have reported that intraductal carcinoma of the prostate (IDC-P) is a pathological adverse prognostic factor in patients with prostate cancer. However, the optimal treatment has not been established. The present study aimed to evaluate the efficacy of docetaxel and androgen receptor axis-targeted (ARAT) agents in patients with castration-resistant prostate cancer (CRPC) with IDC-P using a propensity score-matched analysis. Methods: We retrospectively identified 309 patients with CRPC from February 2007 to February 2016. They received initial androgen deprivation therapy (ADT) and after progression to CRPC, they received docetaxel or ARAT (abiraterone or enzalutamide) as the first-line life-prolonging therapy. The primary outcome of interest was OS from the time of CRPC diagnosis. We also investigated PFS from the time of docetaxel or ARAT initiation. Results: Propensity score-matching identified 85 patients in each group. There were no significant differences in patient characteristics between the groups. The median OS in the docetaxel group was 38.2 months versus 58.3 months in the ARAT group (HR 0.57; 95% CI 0.37–0.89; P =.01). Regarding patients with IDC-P, OS was significantly longer in the ARAT group than the docetaxel group (HR 0.48; 95% CI 0.26–0.86; P =.01), and there was no significant difference in each group, as in patients without IDC-P (HR 0.75; 95% CI 0.37–1.52; P =.43). The median PFS in the docetaxel group was 6.7 versus 7.8 months in the ARAT group (HR 0.65; 95% CI 0.45–0.94; P =.02). A multivariate analysis demonstrated that the presence of IDC-P, duration of primary ADT, visceral metastasis, and administration of ARAT as the first treatment for CRPC were independent prognostic factors for OS. Conclusions: Administration of ARAT as the first treatment for CRPC may prolong OS more than that of docetaxel, especially in patients with IDC-P.
Macrolide antibiotics in pregnancy are linked with birth defects, study suggests
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Children of mothers who took macrolide antibiotics during early pregnancy have shown an increased risk of major birth defects, particularly heart defects, than children of mothers who took penicillin, in a study published in The BMJ .1

Macrolide antibiotics (including erythromycin, clarithromycin, and azithromycin) are used to treat common bacterial infections and are considered alternatives for patients with penicillin allergy. Researchers from Great Ormond Street Institute of Child Health said that these antibiotics should be “used with caution during pregnancy and, if possible, feasible alternative antibiotics should be prescribed until further research is available.”

However, Pat O’Brien, vice president of the Royal College of Obstetricians and Gynaecologists, said …
Joseph Charles Stoddart
Authors: Anna Batchelor, Alan Craft
Journal: BMJ (2020)

Joseph Stoddart (“Joe”), who has died aged 87, was in the 1960s one of the pioneers of the specialty of intensive care. Today there are around 200 intensive care units across the UK, 3000 consultant intensivists and over 200  000 patients are admitted each year, with increasingly successful outcomes. The initial stimulus for this development came from patients who had respiratory failure and grew out of the major polio epidemic in Denmark in 1952, where iron lungs were developed to breathe for patients while they recovered. Successful immunisation against polio eradicated this cause of lung failure, but the experience gained with polio led on to the development of much more effective mechanisms of ventilator support. Iron lungs used an external negative pressure to inflate the lungs but they were not very effective. Positive pressure ventilation by inserting a tube into the windpipe and inflating the lungs, initially by hand but later by machine, revolutionised the outlook for those whose lungs had failed. Stoddart was at …
Endoscopic nasal biliary drainage-guided approach after endoscopic ultrasound-guided hepaticojejunostomy: safe stent exchange technique
Authors: Takeshi Ogura, Saori Ueno, Yasukichi Tanaka, Azusa Hara, Kazuhide Higuchi
Journal: Endoscopy (2020)

Endoscopic ultrasound (EUS)-guided biliary drainage is an alternative when endoscopic retrograde cholangiopancreatography (ERCP) has failed [1] [2]. Covered self-expandable metal stents (CSEMS) or dedicated plastic stents are usually deployed [3] [4]; however, especially when using a transhepatic approach, these stents have a risk of migrating into the abdominal cavity before fistula creation between the hepatic parenchyma and luminal wall. Plastic stents have a smaller diameter than CSEMS, so carry a greater risk of early stent occlusion if the bile is infected and viscous. If total gastrectomy is required, mucosa on the opposite side can become damaged when using CSEMSs. Therefore, an endoscopic nasobiliary drainage (ENBD) tube may be more effective, especially for EUS-guided hepaticojejunostomy (HJS). Because this is an external drainage technique, internal drainage using a plastic stent is however also required. Exchanging a stent from an ENBD tube to a plastic stent can be challenging because the lumen of the intestine is limited in size and the diameter of the fistula is small. We herein describe safe stent exchange using an ENB-guided approach.
Efficacy and Safety of Sequential Usage of Everolimus in Patients with Metastatic Renal Cell Carcinoma (MRCC) Previously Treated with Bevacizumab +/- Interferon (INF) Therapy. Results from the European Avator Retrospective Study
Authors: A. Vuillemin, C. Theodore, L. Jacobasch, J. Schmitz, A. Guillot, C. Papandreou, C. Emmanouilides, K. Slimane, M. Ktiouet, T. Nguyen
Journal: Annals of Oncology (2012)
Feasibility of finding circulating tumors cells and assigning PD-L1 receptor status using single-cell technology combined with Celsee Genesis system.
Authors: Shaheen Riadh Alanee, Vishal Sharma, William Chow, Bruce Kendrick Patterson
Journal: Journal of Clinical Oncology (2020)

567 Background: enumerating circulating tumor cells (CTC) may improve our ability to differentiate between localized and metastatic bladder cancer (BC) and predict response to systemic therapies. However, previously used CTC identification platforms had limited utility in managing patients diagnosed with this disease because they lacked the appropriate sensitivity level. Also, they did not report on the PD-L1 receptor status, which is becoming an essential component of modern immunotherapy of BC. Methods: We used a novel device to enrich and retrieve CTCs from blood samples of patients with high grade and low-grade BC, as well as benign conditions, treated with cystectomy by using a microfluidic chip. The Celsee Genesis (Celsee Inc) captures CTCs with high sensitivity and allows the captured CTCs to be retrieved for molecular analysis. It uses the microfluidic chip, which has approximately 56,320 capture chambers. Based on differences in cell size and deformability, each chamber ensures that small blood cells escape while larger CTCs of varying sizes are trapped and isolated in the chambers. PD-L1 expression on the isolated tumor cells was then evaluated using 4-color single-cell technology (IncellDX Inc.) directly on the chip. Results: Ten bladder cancer (5 low grade (LG) and 5 high grade (HG) disease) and two benign bladder pathology patients provided blood samples before their cystectomy. Circulating tumor cells were found in 3 patients (two LG and one HG disease). CTCs were four times higher in the HG sample than in the LG samples. PD-L1 expression was high on CTCs isolated from the HG patient’s blood sample and lower in the two LG blood samples. No CTCs were detected in patients with benign bladder pathology. Conclusions: Our results show the feasibility of using novel, high sensitivity CTC detection and PD-L1 single cell measuring technology in patients with BC. We also show that this technology has a potentially high sensitivity level for detecting CTC in patients with bladder malignancies by detecting low levels of CTCs in low-grade disease. More extensive studies are planned to validate our findings.
Development of peanut allergy is associated with coding SNPs in the C-terminus of the IL-33 receptor that impact signaling and TH2 effector function
Authors: Karen Cerosaletti, Janice Chen, Eleanor Johnson, Nahir Garabatos, Justine Calise, David Robinson, David Jeong, Mary Farrington, Alex Winters, Rasika Mathias, Noha Lim, Gerald Nepom, Marco Londei, Erik Wambre, Steven Ziegler
Journal: Journal of Allergy and Clinical Immunology (2020)
Notice of Retractions: “Association of Posttraumatic Stress Disorder With Reduced In Vivo Norepinephrine Transporter Availability in the Locus Coeruleus” and “Association of In Vivo κ-Opioid Receptor Availability and the Transdiagnostic Dimensional Expression of Trauma-Related Psychopathology” by Alexander Neumeister
Authors: Howard Bauchner, Dost Öngür
Journal: JAMA Psychiatry (2020)

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Prognostic factors in advanced seminoma: An analysis from the IGCCCG Update Consortium.
Authors: Joerg Beyer, Laurence Collette, Gedske Daugaard, Ronald De Wit, Alexey Tryakin, Costantine Albany, Olof Stahl, Karim Fizazi, Jourik A. Gietema, Ugo De Giorgi, Aaron Richard Hansen, Darren R. Feldman, Fay Cafferty, Torgrim Tandstad, Xavier Garcia del Muro, Robert A. Huddart, Christopher Sweeney, Andrea Necchi, Samson Assele, Silke Gillessen
Journal: Journal of Clinical Oncology (2020)

386 Background: Extrapulmonary visceral metastases were the only adverse prognostic factor among 660 advanced seminomas in the original classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) treated between 1975 and 1990 and published 1997. Outcomes may have improved with current era management and additional prognostic factors may exist. Methods: To update the original IGCCCG classification, an international consortium (30 centers/groups) provided data on 2458 advanced seminoma patients treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2015 in prospective cohorts or clinical trials. Progression-free (PFS) and overall survival (OS) probabilities were calculated. CART analysis was used to identify prognostic factors inside original IGCCCG good risk group to further refine the classification. Among eligible 2302 patients with full data, a training set of 1509 patients (1437 good risk and 72 intermediate risk) was used for model building. An independent set of 793 patients was set aside for validation. Primary endpoints were PFS and OS at 5 years. Results: Compared with the 1997 IGCCCG benchmarks, the 5-year PFS rates increased to 88.7% (87.2 - 89.9%) and 78.4% (69.6 - 84.9%) in good and intermediate IGCCCG patients. The corresponding 5-year OS rates were 95.4% (94.4 - 96.2%) and 87.2% (79.2 - 92.2%). CART analysis identified LDH with a cut-point of 2.5 x ULN as the single most significant prognostic factor in good risk patients with 5-y PFS rates of 92.1% (90.3 - 93.6%) and 79.2% (74.2 - 83.4%) in low and high LDH subgroups. (HR = 2.90, P &lt; .0001). Good risk patients with LDH above 2.5 x ULN (313 of 1411 patients) performed similarly to the intermediate IGCCCG patients; hCG was not independently prognostic. Conclusions: In this modern era series, the original IGCCCG still significantly discriminates between "good” and "intermediate" risk metastatic seminoma, but with significantly improved PFS and OS in both risk groups. LDH at a cut-off point of 2.5 x ULN further refines this classification and identifies men with intermediate risk seminoma in the absence of extrapulmonary visceral metastases. This refinement will be relevant to improve future seminoma care.
Affirming Transgender Youths’ Names and Pronouns in the Electronic Medical Record
Authors: Gina M. Sequeira, Kacie Kidd, Robert W. S. Coulter, Elizabeth Miller, Robert Garofalo, Kristin N. Ray
Journal: JAMA Pediatrics (2020)

This survey study assesses preferences concerning name and pronoun documentation in the electronic medical record and investigates how these preferences differ by demographic and gender-related characteristics among transgender youths seeking care at a specialty gender clinic.
Androgen receptor cfDNA longitudinal mutational analysis in metastatic castrate-resistant prostate cancer.
Authors: Elisa Marie Ledet, Patrick Cotogno, Whitley Hatton, Ellen Jaeger, Marcus W. Moses, Charlotte Manogue, Brian E. Lewis, Pedro C. Barata, A. Oliver Sartor, Jodi Lyn Layton
Journal: Journal of Clinical Oncology (2020)

197 Background: Androgen receptor (AR) mutations commonly occur in metastatic castrate resistant prostate cancer (mCRPC). Methods: Circulating tumor DNA (ctDNA) data were obtained from Guardant 360 assays throughout the clinical course of mCRPC patients (pts). Retrospective analysis for any pt with ≥ 3 Guardant assays at least 4 weeks apart were reviewed. Patients must have at least 1 AR mutation or amplification to qualify for inclusion. Statistical analyses, including chi-sq and longitudinal analyses, were conducted. Results: Of the 259 patients with Guardant testing, a total of 88 patients had at least 3 Guardant tests; of these, 59 (67%) had at least one AR alteration. Patients had a median of 4 Guardant assays (range 3-10). Patients with AR amplification, AR mutation or both were identified (23, 20, 16 respectively). The most common and clinically relevant AR mutations found alone or in combination with amplification were T878A (22%), L702H(19%), W742C (19%), and H875Y (10%). These particular functional AR mutations occurred alone in 16 patients. Only 3 patients had neither amplification nor common AR mutation. 17/59 patients were found to have at least one common AR mutation and amplification at some point (on same or different Guardant). One patient had seven different AR mutations with no amplification and two other patients had 3 AR mutations. Remainder of patients had either AR amplification or ≤ 2 alternative mutations. Patients with an AR amplification were 0.1138x (95% Cl 0.0289 - 0.4491) significantly less likely of having a common known functional mutation (p &lt;0.002) at any point. Conclusions: Patients with the most frequently identified known functional AR mutations are less likely to have AR amplification in pts with mCRPC; these common AR mutations have been shown to be associated with resistance to 2nd generation androgen deprivation. Further clinical correlation between treatment regimen and %cfDNA of these and other non-AR driver mutations is planned.
Multiregion expression profiling of prostate cancer from men randomized in the STAMPEDE trial: Stage I results of a multistage biomarker analysis.
Authors: Emily Grist, Marina Parry, Larissa Mendes, Sharanpreet Lall, Sakunthala C. Kudahetti, Sara Santos Vidal, Nafisah B. Atako, Mazna Anjum, Sofeya Ishaq, Tamara Todorovic, Huei-Chung Huang, David Waugh, Christopher Sweeney, Noel Clarke, Nicholas D. James, Daniel Berney, Mahesh K. B. Parmar, Elai Davicioni, Louise C. Brown, Gerhardt Attard
Journal: Journal of Clinical Oncology (2020)

153 Background: The PAM50 gene expression classifier stratifies localized prostate cancer into luminal A/B and basal subtypes: luminal A have superior prognosis compared to luminal B and basal. Drug response scores built using the NCI-60 cell lines predict luminal subtypes are more taxane sensitive compared to basal; luminal B is hypothesized to be the most proliferative and hormone responsive compared to the basal subtype. The STAMPEDE trial provides a framework to validate prognostic and predictive associations of the PAM50 test in tumors from men randomized to androgen deprivation therapy (ADT) alone or with docetaxel or abiraterone. We here present multi-region whole-transcriptome expression array data at completion of Stage I designed to confirm the feasibility of molecular subtyping STAMPEDE tumor blocks. Methods: In collaboration with Decipher Biosciences we generated clinical-grade whole-transcriptome expression array data (Human Exon 1.0 ST GeneChip) performed to CLIA standards on mRNA (from three 10 micron slides) from cancer-enriched areas and applied the PAM50 classifier. Results: As of January 2019, we retrieved blocks from 2012 men from an ITT population of 3879. For Stage I feasibility assessment, we sectioned diagnostic trans-rectal biopsies of the prostate from 50 randomly selected men treated with ADT. We extracted mRNA from 109 cores; &gt; 92% cores (101) from &gt; 94% patients (47/50) passed quality control. The prevalence of PAM50 subtypes was: 31 basal cases (62%), 18 luminal B (36%) and 1 luminal A (2%). 26 cases (52%) were identified as ETS-related gene (ERG) positive. More than one core was interrogated from 35/50 cases (range: 1-6 cores). ERG positive cores were homogeneous across cores from the same patient but PAM50 subtyping identified intra-patient variability across cores from the same case. Conclusions: We confirm the feasibility of expression profiling STAMPEDE tumor blocks and identify a low prevalence of luminal A subtype. Whereas ERG status is consistent across multiple cores, basal and luminal subtypes co-exist in the same prostate. Multi-region analysis will enable further refinement for individual patient classification.