tbuckley/cabot-search huggingface dataset:
RNAi against MDR1 but not MRP1 reverses multi-drug resistance in human small-cell lung carcinoma cells expressing both proteins
Authors: David Sadava, Wendy Hamman
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

601 

Clinical drug resistance is in part due to over-expression of drug efflux pumps at the plasma membrane. Clinical samples and cell lines from small-cell lung carcinoma (SCLC) patients can express two pumps, products of the MDR1 and MRP1 genes. The in vivo roles of these pumps are not clear. To investigate this, we used RNAi directed against the mRNA's of MDR1 and MRP1, which are both expressed in the multi-drug resistant H69VP line of SCLC, to block expression and test for reversal of drug resistance. A 21-nucleotide dsRNA yielding RNAi directed against positions 79-99 in the mRNA for MDR1 was transfected into H69 (drug-sensitive) and H69VP cells (6.6 x 104 cells/200 μl). After 24 h, RT-PCR showed down-regulation mRNA for MDR1 in transfected but not mock-transfected control cells. Then, appropriate drug was added in DMSO and the cells incubated for 3 days. Compared to mock-transfected controls, the IC50 for etoposide was unchanged in H69 cells (0.39 μM with RNAi compared to 0.52 μM, p>0.05). However, resistance in H69VP cells was reversed (0.72 μM with RNAi compared to 6.8 μM, p 0.05) as well as in H69VP cells (7.2 μM compared to 5.9 μM controls, p>0.05). Resistances to doxorubicin and vincristine were also unchanged in H69VP cells. Drug resistance was also measured by reduced accumulation of the fluorogenic dye, calcein acetomymethyl ester (calcein AM). Compared to H69 cells, accumulation after 15 min in H69VP cells was reduced by 80%. This was reversed by concurrent incubation in 2 μg/ml cyclosporin A. H69VP cells transfected with RNAi against MDR1 did not show a reduction of calcein AM accumulation. However, there was a 75% reduction in cells treated with RNAi against MRP1, indicating a functional drug efflux pump. These data indicate that the protein pump expressed by MDR1, but not MRP1, is important in drug resistance in these human SCLC cells.
Elastin-like hydrogel stimulates angiogenesis in a severe model of critical limb ischemia (CLI): An insight into the glyco-host response
Authors: Grazia Marsico, Chunseng Jin, Sunny A. Abbah, Eva M. Brauchle, Dilip Thomas, Ana Lúcia Rebelo, Doriana Orbanić, Sandrine Chantepie, Paolo Contessotto, Dulce Papy-Garcia, Carlos Rodriguez-Cabello, Michelle Kilcoyne, K. Schenke-Layland, N.G. Karlsson, Karl J.A. McCullagh, Abhay Pandit
Journal: Biomaterials (2021)

Critical limb ischemia (CLI) is characterized by the impairment of microcirculation, necrosis and inflammation of the muscular tissue. Although the role of glycans in mediating inflammation has been reported, changes in the glycosylation following muscle ischemia remains poorly understood. Here, a murine CLI model was used to show the increase of high mannose, α-(2, 6)-sialic acid and the decrease of hybrid and bisected N-glycans as glycosylation associated with the ischemic environment. Using this model, the efficacy of an elastin-like recombinamers (ELR) hydrogel was assessed. The hydrogel modulates key angiogenic signaling pathways, resulting in capillary formation, and ECM remodeling. Arterioles formation, reduction of fibrosis and anti-inflammatory macrophage polarization wa also induced by the hydrogel administration. Modulation of glycosylation was observed, suggesting, in particular, a role for mannosylation and sialylation in the mediation of tissue repair. Our study elucidates the angiogenic potential of the ELR hydrogel for CLI applications and identifies glycosylation alterations as potential new therapeutic targets.
Health-promoting behaviours and concussion history are associated with cognitive function, mood-related symptoms and emotional–behavioural dyscontrol in former NFL players: an NFL-LONG Study
Authors: Samuel R Walton, Zachary Y Kerr, Benjamin L Brett, Avinash Chandran, J D DeFreese, Abbie E Smith-Ryan, Lee Stoner, Ruben J Echemendia, Michael McCrea, William P Meehan, III, Kevin M Guskiewicz
Journal: British Journal of Sports Medicine (2021)

Objectives To examine the relationships among self-reported sport-related concussion (SRC) history and current health-promoting behaviours (exercise frequency, diet quality and sleep duration) with self-reported measures of brain health (cognitive function, symptoms of depression and anxiety and emotional–behavioural dyscontrol) in former NFL players. Methods In this cross-sectional study, a questionnaire was sent to former NFL players. Respondents reported SRC history (categorical: 0; 1–2; 3–5; 6–9; 10+ concussions), number of moderate-to-vigorous aerobic and resistance exercise sessions per week, diet quality (Rapid Eating Assessment for Participants—Shortened) and average nightly sleep duration. Outcomes were Patient-Reported Outcomes Measurement Information System Cognitive Function, Depression, and Anxiety, and Neuro-QoL Emotional-Behavioral Dyscontrol domain T-scores. Multivariable linear regression models were fit for each outcome with SRC history, exercise frequency, diet quality and sleep duration as explanatory variables alongside select covariates. Results Multivariable regression models (n=1784) explained approximately 33%–38% of the variance in each outcome. For all outcomes, SRC history (0.144≤|β|≤0.217) was associated with poorer functioning, while exercise frequency (0.064≤|β|≤0.088) and diet quality (0.057≤|β|≤0.086) were associated with better functioning. Sleeping under 6 hours per night (0.061≤|β|≤0.093) was associated with worse depressive symptoms, anxiety and emotional–behavioural dyscontrol. Conclusion Several variables appear to be associated with mood and perceived cognitive function in former NFL players. SRC history is non-modifiable in former athletes; however, the effects of increasing postplaying career exercise frequency, making dietary improvements, and obtaining adequate sleep represent important potential opportunities for preventative and therapeutic interventions.
ESMO recommendations on the standard methods to detect RET fusions and mutations in daily practice and clinical research
Authors: C. Belli, F. Penault-Llorca, M. Ladanyi, N. Normanno, J.-Y. Scoazec, L. Lacroix, J.S. Reis-Filho, V. Subbiah, J.F. Gainor, V. Endris, M. Repetto, A. Drilon, A. Scarpa, F. André, J.-Y. Douillard, G. Curigliano
Journal: Annals of Oncology (2021)
Distribution of <i>KRAS</i><sup>G12C</sup> Somatic Mutations across Race, Sex, and Cancer Type
Authors: Amin H. Nassar, Elio Adib, David J. Kwiatkowski
Journal: New England Journal of Medicine (2021)

To the Editor: Hong et al. (Sept.24 issue) 1 present results of an early-phase clinical trial of sotorasib, which showed promising clinical benefit.Patients had non-small-cell lung cancer (NSCLC; 46%) or colorectal cancer (33%), and White patients constituted 76% of the cohort.As drugs are being developed for the previously "undruggable" KRAS G12C mutation, it is imperative to study the distribution of this mutation across sex, race, 2 and all cancers.We extracted data from the registry of the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE), version 8.0 3 (see the Methods section in Supplementary Appendix 1).We studied the distribution of KRAS G12C mutations in 32,138 patients with cancer across race (Asian, Black, and White) and sex and in 10 cancer types (Table S1.1 in Supplementary Appendix 2).A total of 2045 patients (6.4%) were Asian, 2355 (7.3%) were Black, and 27,738 (86.3%) were White.KRAS G12C mutations were compared according to race and sex, and P values were corrected by the Benjamini-Hochberg method to determine false discovery rate-corrected Q values, which were considered significant when Q was less than 0.05.KRAS G12C mutations were identified in 1867 samples, most frequently in patients with NSCLC (1443 of 10,444 [13.8%]).KRAS G12C mutations were identified in 3.5% of patients (74 of 2105) with cancer of unknown primary site, 3.3% of patients (12 of 368) with appendiceal cancer, 3.2% of patients (234 of 7402) with colorectal cancer, and 3.1% of patients (7 of 223) with small-bowel cancer (Fig. 1A, and Table S1.2 in Supplementary Appendix 2).Among patients
MO01.40 Trilaciclib has Myelopreservation Benefits in Patients with Small Cell Lung Cancer Treated with Chemotherapy, Irrespective of Age
Authors: T. Beck, D.A. Richards, R. Agajanian, D. Berz, H. Chen, C. Ikpeazu, M.M. Tarruella, D. Verhoeven, Y. Pritchett, R.K. Malik, J.M. Antal, M. Hussein
Journal: Journal of Thoracic Oncology (2021)
Nanofibrous ε-polycaprolactone scaffolds containing Ag-doped magnetite nanoparticles: Physicochemical characterization and biological testing for wound dressing applications in vitro and in vivo
Authors: M.K. Ahmed, M.A. Zayed, S.I. El-dek, Mayssa Abdel Hady, Doaa H. El Sherbiny, Vuk Uskoković
Journal: Bioactive Materials (2021)

Skin wounds can lead to numerous complications with dangerous health consequences. In this work, magnetite nanoparticles were doped with different concentrations of antimicrobial silver (Ag) ions and incorporated into the electrospun nanofibrous ε-polycaprolactone (PCL) scaffolds. Nanoparticles and scaffolds with various Ag contents were characterized using a range of physicochemical techniques. Ag entered magnetite as cations and preferentially positioned at tetrahedral sites, introducing lattice distortions and topographic irregularities. Amorphization of the structure due to accommodation of Ag expanded the lattice in the bulk and contracted it on the surface, where broadened distribution of Fe–O coordinations was detected. Promoting spin canting and diminishing the double exchange interaction through altered distribution of ferric and ferrous ions, Ag softened the magnetism of magnetite. By making the nanoparticle structure more defective, Ag modified the interface with the polymer and promoted the protrusion of the nanoparticles from the surface of the polymeric nanofibers, thus increasing their roughness and hydrophilicity, with positive repercussions on cell adhesion and growth. Both the viability of human melanocytes and the antibacterial activity against E. coli and S. aureus increased with the concentration of Ag in the magnetite phase of the scaffolds. Skin wound healing rate in rats also increased in direct proportion with the concentration of Ag in the magnetite phase, and no abnormalities in the dermal and epidermal tissues were visible on day 10 in the treatment group. These results imply an excellent potential of these composite nanofibrous scaffolds for use as wound dressings and in other reconstructive skin therapies.
Approaches to treat pulmonary arterial hypertension by targeting BMPR2: from cell membrane to nucleus
Authors: Benjamin J Dunmore, Rowena J Jones, Mark R Toshner, Paul D Upton, Nicholas W Morrell
Journal: Cardiovascular Research (2020)

Abstract Pulmonary arterial hypertension (PAH) is estimated to affect between 10 and 50 people per million worldwide. The lack of cure and devastating nature of the disease means that treatment is crucial to arrest rapid clinical worsening. Current therapies are limited by their focus on inhibiting residual vasoconstriction rather than targeting key regulators of the cellular pathology. Potential disease-modifying therapies may come from research directed towards causal pathways involved in the cellular and molecular mechanisms of disease. It is widely acknowledged that targeting reduced expression of the critical bone morphogenetic protein type-2 receptor and its associated signalling pathways is a compelling therapeutic avenue to explore. In this review, we highlight the advances that have been made in understanding this pathway and the therapeutics that are being tested in clinical trials and the clinic to treat PAH.
68Ga-DOTA-FAPI-04 PET/CT in Erdheim-Chester Disease
Authors: Simin Wu, Yizhen Pang, Yangchun Chen, Huayu Sun, Haojun Chen
Journal: Clinical Nuclear Medicine (2021)

A 56-year-old woman presented with edema in the upper part of the body, enlarged axillary lymph nodes, and progressive bone pain for 1 year. Malignant disease was initially suspected. This patient underwent 68Ga-DOTA-FAPI-04 PET/CT for detection of the primary lesion and evaluation of disease extent. 68Ga-DOTA-FAPI-04 PET/CT revealed multiple abnormal foci at the skeleton, muscle, lymph nodes, and subcutaneous fat. The imaging findings, highly suggestive of Erdheim-Chester disease, have been later confirmed by histopathology. This case highlights that 68Ga-DOTA-FAPI-04 PET/CT would be useful for evaluating the disease extent, guiding biopsies, and gauging the treatment response in patients with Erdheim-Chester disease.
Abstract 9673: Sex-specific IKas Activation in Rabbit Ventricles With Drug-induced Qt Prolongation
Authors: Adonis Z Wu, Mu Chen, Shuai Guo, Dechun Yin, Zhenhui Chen, James N Weiss, Zhilin Qu, Thomas Everett, Peng-Sheng Chen
Journal: Circulation (2019)

Introduction: A previous study showed significant sex differences (females > males) in isoproterenol-induced apamin-sensitive small-conductance Ca2+-activated K+ (SK) current (IKAS) activation. IKA...
Abstract 17355: Anti-Inflammatory Nanotherapy Alters Immune Cell Composition and Reduces Lesion Area of Atherosclerotic Plaques in Ldlr-/- Mice
Authors: Sean D Allen, Yu-Gang Liu, Evan A Scott
Journal: Circulation (2018)

Introduction: Atherosclerosis is a multi-stage disorder with an inflammatory immune component. We hypothesized that the targeted delivery of an anti-inflammatory small molecule to macrophages could modulate immune cells in the plaque and potentially reduce plaque progression. We employed celastrol as an inhibitor of NF-kB and used poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-bl-PPS) polymeric micelles (MCs) for controlled delivery. Methods: PEG-bl-PPS polymer was formulated into nanocarriers at a concentration of 15 mg/mL in 1xPBS, with or without 100 ng of celastrol (Cel-MC or Blank MC). Ldlr-/- mice were fed a high fat diet for 3 months prior to the beginning of nanocarrier treatment. 100 μL of each MC formulation was administered to mice via tail vein injection once per week for 12 weeks. Results: Cel-MC inhibited NF-kB at lower concentrations compared to free celastrol (Fig. 1a) . In vivo , Cel-MCs significantly decreased neutrophils and NK cells in the aortas of atherosclerotic mice compared to blank MC controls (Fig. 1b) . Cel-MCs reduced the plaque lesion area, as determined by Oil Red O staining of aorta histology sections (Fig. 1c) . Figure 1. Cel-MC treatment of atherosclerosis. (a) NF-kB inhibition and cell viability using RAW Blue cells, error bars = S.D., n = 4. (b) Heatmap of percent change in cell populations based on flow analysis of ldlr-/- mice after 12 weeks of Cel-MC treatment, compared to blank MC treatment, n=6/4 respectively. (c) Oil Red O staining fluorescence area of aorta histology slides, n=4 mice, 3-4 sections per mouse. P-value determined using Welch’s t test. Conclusions: Cel-MC reduced NF-kB signaling in vitro and reduced immune cells in the aorta in vivo. The treatment course was well-tolerated by the mice and resulted in a significant reduction in plaque lesion area. These results demonstrate both the utility of targeted modulation of immune cells contributing to vascular inflammation.
B-Cell Lymphoma Patients Have a 10% Risk of Shingles, 7% in Cutaneous T-Cell Lymphoma
Authors: Syed Basir Hussaini, Jacqueline Chu, Nita Williams, Nidhi Sharma, Don M Benson, Ashley E Rosko, Yvonne A Efebera, Craig C Hofmeister
Journal: Blood (2017)
Vaginal Transmission of Cancer from Mothers with Cervical Cancer to Infants
Authors: Ayumu Arakawa, Hitoshi Ichikawa, Takashi Kubo, Noriko Motoi, Tadashi Kumamoto, Miho Nakajima, Kan Yonemori, Emi Noguchi, Kuniko Sunami, Kouya Shiraishi, Hiroki Kakishima, Hiroshi Yoshida, Tomoro Hishiki, Naonori Kawakubo, Takafumi Kuroda, Takako Kiyokawa, Kyosuke Yamada, Nozomu Yanaihara, Kazuaki Takahashi, Aikou Okamoto, Shinsuke Hirabayashi, Daisuke Hasegawa, Atsushi Manabe, Kentaro Ono, Masaki Matsuoka, Yasuhito Arai, Yosuke Togashi, Tatsuhiro Shibata, Hiroyoshi Nishikawa, Kazunori Aoki, Noboru Yamamoto, Takashi Kohno, Chitose Ogawa
Journal: New England Journal of Medicine (2021)

Two cases of pediatric lung cancer (in 23-month-old and 6-year-old boys) resulting from mother-to-infant transmission of uterine cervical tumors were incidentally detected during routine next-generation sequencing of paired samples of tumor and normal tissue. Spontaneous regression of some lesions in the first child and slow growth of the tumor mass in the second child suggested the existence of alloimmune responses against the transmitted tumors. Immune checkpoint inhibitor therapy with nivolumab led to a strong regression of all remaining tumors in the first child. (Funded by the Japan Agency for Medical Research and Development and others; TOP-GEAR UMIN Clinical Trials Registry number, UMIN000011141.).
尿中CD4 T細胞は増殖性ループス腎炎のSLE患者を同定し,治療反応のモニタリングに使用可能である
Authors: Enghard Philipp, Rieder Claudia, Kopetschke Katharina, Klocke J R, Undeutsch Reinmar, Biesen Robert, Dragun Duska, Gollasch Maik, Schneider Udo, Aupperle Karlfried, Humrich Jens Y, Hiepe Falk, Backhaus Marina, Radbruch A H, Burmester Gerd R, Riemekasten Gabriela
Journal: Annals of the Rheumatic Diseases (2014)
Association of Intensive Endoscopic Screening Burden With Gastric Cancer Detection
Authors: Choong-Kyun Noh, Eunyoung Lee, Gil Ho Lee, Joon Koo Kang, Sun Gyo Lim, Bumhee Park, Jae Bum Park, Sung Jae Shin, Jae Youn Cheong, Jin Hong Kim, Kee Myung Lee
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The rapidly increasing number of gastric cancer examinations performed over a short period might influence screening performance. Accessing the association between calendar month and gastric cancer detection rates might improve policy and guide institutional support. <h3>Objective</h3> To evaluate the association between the increased number of examinations over a certain period and gastric cancer detection rates among a large population included in the Korean National Cancer Screening Program (KNCSP). <h3>Design, Setting, and Participants</h3> This retrospective, population-based cohort study used data from the KNCSP comprising 26 765 665 men and women aged 40 years or older who participated in the screening program between January 1, 2013, and December 31, 2016. Data were analyzed from November 1, 2019, to March 31, 2020. <h3>Exposures</h3> Gastric cancer screening with endoscopy. <h3>Main Outcomes and Measures</h3> The primary outcome was monthly gastric cancer detection rates in the KNCSP. A negative binomial regression model was used to evaluate the association between the screening month and detection rates. <h3>Results</h3> In total, 21 535 222 individuals underwent endoscopy (mean [SD] age, 55.61 [10.61] years; 11 761 709 women [54.62%]). The quarterly number of participants was the highest in the last quarter of the study period (2013-2014: 4 094 951 [41.39%], 2015-2016: 4 911 629 [42.19%]); this proportion was 2.48 to 2.84 times greater than that of the first quarter. Cancer detection rates were the lowest in December (2013-2014: 0.22; 95% CI, 0.22-0.23; 2015-2016: 0.21; 95% CI, 0.21-0.22); this was approximately a 40.0% to 45.0% reduction compared with the rates in January. The age group was the significant factor for monthly detection rates. After adjustment for the age group and taking account of the number of screenings, the estimated coefficient range for the screening month was negative and the detection rate in December was significantly different than in January for both the consequent cycles (2013-2014: −0.05 to −0.18;<i>P</i> &lt; .001; and 2015-2016: −0.06 to −0.19;<i>P</i> &lt; .001). In the multivariable logistic model, the association of calendar month with detected cancer remained after adjusting for other confounding factors (December, 2013-2014: odds ratio, 0.82; 95% CI, 0.76-0.87;<i>P</i> &lt; .001; 2015-2016: odds ratio, 0.83; 95% CI, 0.79-0.89;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> The findings of this cohort study suggest that the workload of endoscopists increased with the increasing number of examinations toward the end of the year, as demonstrated by the decreased cancer detection rates. These findings may help to improve gastric cancer detection rates of screening programs by controlling the monthly screening number and policy modifications.
Structural airway imaging metrics are differentially associated with persistent chronic bronchitis
Authors: Surya P Bhatt, Sandeep Bodduluri, Abhilash S Kizhakke Puliyakote, Elizabeth C Oelsner, Arie Nakhmani, David A Lynch, Carla G Wilson, Spyridon Fortis, Victor Kim
Journal: Thorax (2021)

Background Chronic bronchitis (CB) is strongly associated with cigarette smoking, but not all smokers develop CB. We aimed to evaluate whether measures of structural airway disease on CT are differentially associated with CB. Methods In smokers between ages 45 and 80 years, and with Global Initiative for Obstructive Lung Disease stages 0–4, CB was defined by the classic definition. Airway disease on CT was quantified by (i) wall area percent (WA%) of segmental airways; (ii) Pi10, the square root of the wall area of a hypothetical airway with 10 mm internal perimeter; (iii) total airway count (TAC) and (iv) airway fractal dimension (AFD), a measure of the complex branching pattern and remodelling of airways. CB was also assessed at the 5-year follow-up visit. Measurements and main results Of 8917 participants, 1734 (19.4%) had CB at baseline. Airway measures were significantly worse in those with CB compared with those without CB: WA% 54.5 (8.8) versus 49.8 (8.3); Pi10 2.58 (0.67) versus 2.28 (0.59) mm; TAC 156.7 (81.6) versus 177.8 (91.1); AFD 1.477 (0.091) versus 1.497 (0.092) (all p&lt;0.001). On follow-up of 5517 participants at 5 years, 399 (7.2%) had persistent CB. With adjustment for between-visits changes in smoking status and lung function, greater WA% and Pi10 were associated with significantly associated with persistent CB, adjusted OR per SD change 1.75, 95% CI 1.56 to 1.97; p&lt;0.001 and 1.66, 95% CI 1.42 to 1.86; p&lt;0.001, respectively. Higher AFD and TAC were associated with significantly lower odds of persistent CB, adjusted OR per SD change 0.76, 95% CI 0.67 to 0.86; p&lt;0.001 and 0.69, 95% CI 0.60 to 0.80; p&lt;0.001, respectively. Conclusions Higher baseline AFD and TAC are associated with a lower risk of persistent CB, irrespective of changes in smoking status, suggesting preserved airway structure can confer a reserve against CB.
Race and Genetic Ancestry in Medicine — A Time for Reckoning with Racism
Authors: Luisa N. Borrell, Jennifer R. Elhawary, Elena Fuentes-Afflick, Jonathan Witonsky, Nirav Bhakta, Alan H.B. Wu, Kirsten Bibbins-Domingo, José R. Rodríguez-Santana, Michael A. Lenoir, James R. Gavin, Rick A. Kittles, Noah A. Zaitlen, David S. Wilkes, Neil R. Powe, Elad Ziv, Esteban G. Burchard
Journal: New England Journal of Medicine (2021)

Race and Genetic Ancestry in Medicine U.S. health inequities won’t be eliminated by abandoning the use of race and ethnicity in research and clinical practice, since these variables capture key epi...