tbuckley/cabot-search huggingface dataset:
Pattern of symptoms in head and neck cancer (HNC) survivors treated with radiation therapy (RT): Association with systemic therapy.
Authors: David Ira Rosenthal, Gary Brandon Gunn, Adam S. Garden, Charles Lu, Tito R. Mendoza, William H. Morrison, Steven J. Frank, Beth Michelle Beadle, Jack Phan, Clifton David Fuller, Ehab Y. Hanna, K. Kian Ang, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2012)

5589 Background: We sought, in a large, long-term follow-up cohort, to determine benchmark cross-sectional analysis of HNC patient (pt) symptom profiles as a function of chemotherapy (CT)/RT strategy. Methods: Pts treated with RT with or without CT in remission &gt; 18 mos. were surveyed with the MD Anderson Symptom Inventory–Head and Neck Module (MDASI-HN). Clinical data were extracted. Data were tabulated, and group comparison performed using non-parametric analyses. Results: 250 pts participated; 81% were male. Median age at RT was 54 years. 87% had oropharynx HNC. Most were T1/X (41%), 37% T2 and, 22% T3/4. For N-category, most were N2 (55%), &lt;5% N3, and 40% NX-1. 18% had induction CT, 26% concurrent, 5% both, and 50% had none. At a median follow-up time of 5.9 years (range 2-15), 11% of pts were entirely symptom free, 31% reported ≤mild symptom severity, 20% ≤moderate, and 38% reported ≥1 symptom as severe. 16% of pts receiving RT alone and 11% sequential CT followed by RT were symptom free, vs. 1% of those receiving concurrent CT (chi-square p&lt;0.01), and the symptom distribution profile was distinct (p&lt;0.03). The proportion of pts who received concurrent CT reporting any severe symptom item was 44%, vs. 36% of those not receiving concurrent CT (p=n.s.). No difference was seen in the moderate to severe (M/S) symptom report by treatment group. For all MDASI-HN items, most pts rated “0” or “not present”, except dry mouth and difficulty swallowing items, where mild symptoms were most likely (36% and 33%). The most common symptoms rated M/S were dry mouth, swallowing, choking, fatigue, and mouth and throat mucus reported by 42%, 23%, 18%, 16%, and 16%. MVA demonstrated T-stage and primary site, but not CT cohort correlated with M/S symptom report. Conclusions: Cumulatively, most pts had no more that mild symptom severity, but a substantial group of pts experience M/S levels. The symptom severity profile was highest with concurrent CT, though this effect appears mediated by disease specific factors. The addition of sequential CT to RT did not to appear to alter M/S symptom report substantially; however, concurrent pts were almost never symptom free, in contrast to induction and no CT cohorts.
Clinical predictive factors for mutations in epidermal growth factor receptor (EGFR) exon 19 and 21 in Japanese patients with lung cancer
Authors: K. Goto, Y. Kim, K. Yoh, S. Niho, H. Ohmatsu, K. Kubota, Y. Nishiwaki, N. Saijo
Journal: Journal of Clinical Oncology (2007)

18131 Background: It has been reported that lung cancer with activating mutations of EGFR are highly sensitive to gefitinib or erlotinib. Furthermore, the incidence of EGFR mutations is significantly higher in adenocarcinoma, female, never-smoker, Japanese patients. However, it is difficult to take sufficient amount of biopsy specimen of lung cancer with advanced disease for mutation analyses in clinical practice. Therefore, in this study, clinical predictive factors for EGFR mutations in Japanese patients with lung cancer were clarified. Methods: EGFR exon 19 and 21 mutation status was determined in 284 tumor samples using direct sequencing, polymerase chain reaction. To identify clinical independent predictive factors for EGFR mutation, the logistic regression analysis was performed. Results: 131 tumors of them could be analyzed for mutations in EGFR exon 19 and 21. EGFR mutations were detected in 38 tumors (29%). Median age of patients with EGFR mutations was 62 years (rage 43–84); 19 male and 19 female; 18 stage I, 15 stage II, and 5 stage III disease. Cigarette- smoking history of patients with EGFR mutations included non-smoker in 20 patients, light smoker (&lt; 10 pack-years smoker) in 4, and heavy smoker (&gt; 10 pack-years smoker) in 14. Multivariate analyses showed that non-smoker or light smoker (p=0.007) and adenocarcinoma (p=0.044) were the significant predictive factors contributing to EGFR mutations. Gender, serum CEA level, and clinical stage were not associated with EGFR mutations. Seventy patients treated with gefitinib and 25 PR were observed, and the overall response rate was 36%. The response rate to gefitinib in patients with and without EGFR mutations were 76% and 7%, respectively. In addition, EGFR mutations were detected in 51% (19/37) of patients with adenocarcinoma and light smoker, and the response rate to gefitinib of them was 49% (18/37). Conclusions: In Japanese patients with lung cancer, non-smoker or light smoker and adenocarcinoma were significant predictive factors for mutations in EGFR exon 19 and 21. No significant financial relationships to disclose.
Pharmacological Npt2a Inhibition Causes Phosphaturia and Reduces Plasma Phosphate in Mice with Normal and Reduced Kidney Function
Authors: Linto Thomas, Jianxiang Xue, Sathish Kumar Murali, Robert A. Fenton, Jessica A. Dominguez Rieg, Timo Rieg
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Hyperphosphatemia is common in the later stages of CKD and treatment options are limited to dietary phosphate restriction and oral phosphate binders. The sodium-phosphate cotransporter Npt2a, which mediates a large proportion of phosphate reabsorption in the kidney, might be a good therapeutic target for new medications for hyperphosphatemia. The authors show that pharmacologic inhibition of Npt2a in mice not only causes a dose-dependent phosphaturia, reductions in plasma phosphate levels, and suppression of parathyroid hormone, but also increases urinary excretion of sodium, chloride, and calcium. It does this without affecting urinary potassium excretion, flow rate, or pH. The results show for the first time that a novel Npt2a inhibitor has potential as a treatment for kidney disease-related hyperphosphatemia. Background The kidneys play an important role in phosphate homeostasis. Patients with CKD develop hyperphosphatemia in the later stages of the disease. Currently, treatment options are limited to dietary phosphate restriction and oral phosphate binders. The sodium-phosphate cotransporter Npt2a, which mediates a large proportion of phosphate reabsorption in the kidney, might be a good therapeutic target for new medications for hyperphosphatemia. Methods The authors assessed the effects of the first orally bioavailable Npt2a inhibitor (Npt2a-I) PF-06869206 in normal mice and mice that had undergone subtotal nephrectomy (5/6 Nx), a mouse model of CKD. Dose-response relationships of sodium, chloride, potassium, phosphate, and calcium excretion were assessed in response to the Npt2a inhibitor in both groups of mice. Expression and localization of Npt2a/c and levels of plasma phosphate, calcium, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) were studied up to 24-hours after Npt2a-I treatment. Results In normal mice, Npt2a inhibition caused a dose-dependent increase in urinary phosphate (ED 50 approximately 21 mg/kg), calcium, sodium and chloride excretion. In contrast, urinary potassium excretion, flow rate and urinary pH were not affected dose dependently. Plasma phosphate and PTH significantly decreased after 3 hours, with both returning to near baseline levels after 24 hours. Similar effects were observed in the mouse model of CKD but were reduced in magnitude. Conclusions Npt2a inhibition causes a dose-dependent increase in phosphate, sodium and chloride excretion associated with reductions in plasma phosphate and PTH levels in normal mice and in a CKD mouse model.
AAV8-vectored suprachoroidal gene transfer produces widespread ocular transgene expression
Authors: Kun Ding, Jikui Shen, Zibran Hafiz, Sean F. Hackett, Raquel Lima e Silva, Mahmood Khan, Valeria E. Lorenc, Daiqin Chen, Rishi Chadha, Minie Zhang, Sherri Van Everen, Nicholas Buss, Michele Fiscella, Olivier Danos, Peter A. Campochiaro
Journal: Journal of Clinical Investigation (2019)

There has been great progress in ocular gene therapy, but delivery of viral vectors to the retinal pigmented epithelium (RPE) and retina can be challenging. Subretinal injection, the preferred route of delivery for most applications, requires a surgical procedure that has risks. Herein we report a novel gene therapy delivery approach, suprachoroidal injection of AAV8 vectors, which is less invasive and could be done in an outpatient setting. Two weeks after suprachoroidal injection of AAV8.GFP in rats, GFP fluorescence covered 18.9% of RPE flat mounts and extended entirely around sagittal and transverse sections in RPE and photoreceptors. After 2 suprachoroidal injections of AAV8.GFP, GFP fluorescence covered 30.5% of RPE flat mounts. Similarly, widespread expression of GFP occurred in nonhuman primate and pig eyes after suprachoroidal injection of AAV8.GFP. Compared with subretinal injection in rats of RGX-314, an AAV8 vector expressing an anti-VEGF Fab, suprachoroidal injection of the same dose of RGX-314 resulted in similar expression of anti-VEGF Fab and similar suppression of VEGF-induced vascular leakage. Suprachoroidal AAV8 vector injection provides a noninvasive outpatient procedure to obtain widespread transgene expression in retina and RPE.
Abstract 20156: Rural-Urban Comparison of VAD-Related Hospitalization Risk and Survival in the 6 Months Following Device Implantation
Authors: Windy Alonso, Lisa Kitko, Jacqueline Mogle, Christopher Lee, Judith Hupcey
Journal: Circulation (2017)

Introduction: As the number of people living with Stage D HF rises, more patients are receiving ventricular assist devices (VADs). To date, over 15,000 patients have received a VAD. Due to the spec...
Live-attenuated Mycobacterium tuberculosis vaccine MTBVAC versus BCG in adults and neonates: a randomised controlled, double-blind dose-escalation trial
Authors: Michele Tameris, Helen Mearns, Adam Penn-Nicholson, Yolande Gregg, Nicole Bilek, Simbarashe Mabwe, Hennie Geldenhuys, Justin Shenje, Angelique Kany Kany Luabeya, Ingrid Murillo, Juana Doce, Nacho Aguilo, Dessislava Marinova, Eugenia Puentes, Esteban Rodríguez, Jesús Gonzalo-Asensio, Bernard Fritzell, Jelle Thole, Carlos Martin, Thomas J Scriba, Mark Hatherill, Hadn Africa, Denis Arendsen, Natasja Botes, Yolundi Cloete, Marwou De Kock, Margaret Erasmus, Lungisa Jack, Fazlin Kafaar, Xoliswa Kalepu, Nondumiso Gloria Khomba, Sandra Kruger, Thelma Leopeng, Lebohang Makhethe, Angelique Mouton, Humphrey Mulenga, Munyaradzi Musvosvi, Julia Noble, Fajwa Opperman, Tim Reid, Susan Rossouw, Constance Schreuder, Erica Smit, Marcia Steyn, Petrus Tyambethu, Elma Van Rooyen, Ashley Veldsman
Journal: The Lancet Respiratory Medicine (2019)
Depletion of mutant IDH1 impairs chondrosarcoma growth by downregulating integrins.
Authors: Luyuan Li, Xiaoyu Hu, Jonathan C. Trent
Journal: Journal of Clinical Oncology (2019)

11031 Background: chondrosarcomas are malignant bone tumors that produce cartilaginous matrix. Mutations in isocitrate dehydrogenase enzymes (IDH1/2) were recently described in several cancers, including chondrosarcomas. These mutations lead to the inability of IDH to convert isocitrate into α-ketoglutarate (α-KG). Instead, α-KG is reduced into 2-hydroxyglutarate (D-2HG), an oncometabolite. We sought to determine the role of IDH1 mutation in the tumorigenesis of human chondrosarcomas by inactivating mutant IDH1 (mIDH1) using genetic approaches. Methods: we employed two human chondrosarcoma cell lines, JJ012 and HT1080 that carry endogenous IDH1 mutations. D-2HG levels were measured by tandem mass spectrometry. mIDH1 was knocked out via the CRISPR/Cas9 technique. Colony-forming ability and cell migration were evaluated using soft agar assay and Transwell assay, respectively. The effect of mIDH1 on chondrosarcoma growth was analyzed in murine xenograft models. RNA-seq from total RNA was performed to identify differentially expressed genes (DEGs) between the parental and knockout cells. The biological functions of DEGs were identified through Ingenuity pathway analysis. Results: we found that mIDH1 knockout almost completely depleted D-2HG production, dramatically inhibited colony formation by 35% - 60% in JJ012 ( p &lt; 0.01) and by 40% - 80% in HT1080 ( p &lt; 0.01), and significantly reduced the migratory cell numbers by around 40% in both cell lines ( p &lt; 0.01). Moreover, we observed that loss of mIDH1 led to a marked attenuation of chondrosarcoma formation, whereby the mean volume of the tumors derived from mIDH1-knockout cells was approximately 30% of that of control tumors, in both cell lines (JJ012 and HT1080) ( p &lt; 0.01). Interestingly, RNA-seq data showed a significant downregulation of integrin genes such as ITGA10, ITGA5 and ITGB5 in response to mIDH1 knockout (adjusted p &lt; 0.001). These results were confirmed by qRT-PCR and Immunoblotting. Conclusions: our findings demonstrate that mutant IDH1 plays a vital role in chondrosarcoma tumor formation through aberrant activation of integrins.
SOX2 in development and cancer biology
Authors: Daniel Novak, Laura Hüser, Jonathan J. Elton, Viktor Umansky, Peter Altevogt, Jochen Utikal
Journal: Seminars in Cancer Biology (2019)

The transcription factor SOX2 is essential for embryonic development and plays a crucial role in maintaining the stemness of embryonic cells and various adult stem cell populations. On the other hand, dysregulation of SOX2 expression is associated with a multitude of cancer types and it has been shown that SOX2 positively affects cancer cell traits such as the capacity to proliferate, migrate, invade and metastasize. Moreover, there is growing evidence that SOX2 mediates resistance towards established cancer therapies and that it is expressed in cancer stem cells. These findings indicate that studying the role of SOX2 in the context of cancer progression could lead to the development of new therapeutic options. In this review, the current knowledge about the role of SOX2 in development, maintenance of stemness, cancer progression and the resistance towards cancer therapies is summarized.
Streptomycin in Tuberculosis
Authors: M Abdulla
Journal: BMJ (1947)

TJHE efTicacy of streptomycin in the treat- menit of tuberculosis is 11o longer open to doubt.The ever-incr.easingreports in the literature attest to its value, l)ut these reports are still tinge(l with eaution and at times hiint at disappointment.There is, at one and the same time, enthusiasmii for the effect of the drug oIn tuberculous lesioins aiid doubt and disap- pointmeint l)ecause the etfect is not sufficiently marked, or is complicated by somiie of the perverse actions of the drug.That streptomyciin will aftect tuberculosis beneficially is iiow an accepted fact; that it will of itself cure
Selective killing of human cancer cells by targeting a fusion mRNA between CYCLIN D1 and TROP2
Authors: S. Alberti, M. Trerotola, R. Dell’ Arciprete, G. Vacca, B. Veronica, R. Cosmo, L. Rossana, R. Lattanzio, M. Piantelli, E. Guerra
Journal: Journal of Clinical Oncology (2009)

e14569 Background: Trop-2 is a calcium signal transducer and a stem cell marker. Trop-2 is widely overexpressed by human cancers and stimulates their growth. A TROP2 mRNA was isolated as post-transcriptionally joined to CYCLIN D1 transcripts, suggesting this as one of the transforming mechanisms of TROP2. Methods: In vitro cell growth assays were utilized to assess the cell growth stimulatory capacity of the chimeric mRNA. Colony assays for growth in soft agarose and tumorigenicity assays in nude mice were utilized to assess for the transforming capacity of the fusion transcript. siRNA constructs were utilized for the stably shut-down of the expression of the CYCLIN D1-TROP2 mRNA. Results: The chimeric mRNA transforms primary cells in vitro and induces aggressive tumor growth in vivo in cooperation with activated RAS. The CYCLIN D1-TROP2 mRNA is expressed by a large fraction of human ovarian, endometrial and gastro-intestinal tumors. The chimera is coexpressed with activated RAS in a subset of tumors, consistent with a cooperative transforming activity. The chimeric mRNA is a bicistronic transcript that independently translates wild type Cyclin D1 and Trop-2 proteins, i.e. it does not generate chimeric, oncogenic proteins. On the other hand, joining to the stable TROP2 mRNA leads to a higher CYCLIN D1 mRNA stability, with inappropriate persistence during the cell cycle and acquisition of transforming capacity. As essentially no normal tissues express the chimeric mRNA, we targeted it for destruction in cancer cells with stably expressed siRNA constructs. Specific targeting led to essential annnihilation of the CYCLIN D1-TROP2 mRNA, in the absence of off-target effects. Silencing of the chimeric mRNA blocked the growth of expressing breast cancer cells. Conclusions: Our findings demonstrate a novel, widespread oncogenic mechanism in human cancers, and open novel avenues for mRNA-targeted anti-cancer therapies. Acknowledgments This work was supported by the the Fondazione of the Cassa di Risparmio della Provincia di Chieti, the Association for the Application of Biotechnology in Oncology (ABO and ABO Project S.p.A., grant no. VE01D0019) and the Marie Curie Transfer of Knowledge Fellowship, contract number 014541. No significant financial relationships to disclose.
Combined effects of radiation and endostatin gene therapy on leukocyte, erythrocyte, and thrombocyte populations in a lung carcinoma model
Authors: Xian Luo, Melba L. Andres, James M. Slater, Daila S. Gridley
Journal: Cancer Research (2005)

3354  The dose of radiation that can be safely administered to cancers residing in sensitive areas such as the lungs is limited by normal tissue tolerance. However, gene therapies have potential to enhance the efficacy of radiotherapy, as well as other forms of cancer treatment. We have constructed a unique plasmid, pXLG-mEndo, containing the mouse version of the endostatin gene. Anti-tumor efficacy of pXLG-mEndo in combination with radiation was tested in the syngeneic Lewis lung carcinoma (LLC) - C57BL/6 mouse model. In one series of experiments, intratumoral injections of plasmid at 100 micrograms followed by 10 gray (Gy) irradiation 16 hr later were each delivered twice over an 8-day period. As previously reported, pXLG-mEndo significantly enhanced radiation-mediated control of LLC growth; reductions up to 50% in tumor volume were obtained. Here we present results from analyses that were performed on a subset of these animals one day after the last treatment (n = 56 mice). The goals were to assess immunological changes and identify toxicities that may occur due to combination therapy. Highly significant leukocytosis occurred in untreated groups with tumor (P
Risk Prediction Model in Children With Hypertrophic Cardiomyopathy
Authors: Robert O. Bonow, Elizabeth M. McNally
Journal: JAMA Cardiology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
A role of endocytic proteins APPL1 and APPL2 in the regulation of cell growth.
Authors: Beata Pyrzynska, Jacek Jaworski, Marta Miaczynska
Journal: Cancer Research (2008)

3498  Recent discoveries have suggested that some endocytic proteins function as signal transmitters between the cytoplasm and the nucleus. Upon nuclear translocation they may participate in the regulation of chromatin modification and gene transcription. APPL1 and APPL2 are homologous adaptor proteins able to interact with activated Rab5 (a small GTPase). They participate in endocytosis of several transmembrane receptors and translocate to the nucleus. Upon nuclear translocation APPL proteins interact with the nucleosome-remodeling and histone deacetylase multiprotein complex called NuRD. This complex is an established regulator of chromatin structure and gene expression.  Beside the NuRD complex APPL proteins can also interact with, and increase the activity of AKT, which is one of the key kinases involved in the regulation of tumorigenesis.  In order to investigate a potential role of APPL proteins in regulation of cell growth we have engineered APPL1 and APPL2 genes containing additional nuclear-localization signal to ensure the constitutive localization of these proteins in the nucleus. To estimate their potential role in cancer progression we have overexpressed constitutively nuclear APPL proteins as well as silenced the expression of wild-type proteins in different cell lines. We have tested several cancer-related properties of these cells, such as: proliferation, migration, invasion and anchorage-independent growth. The preliminary results suggest a role of APPL proteins in the regulation of cell growth.
“Paid to Endure”: Paid Research Participation, Passivity, and the Goods of Work
Authors: Erik Malmqvist
Journal: The American Journal of Bioethics (2019)

A growing literature documents the existence of individuals who make a living by participating in phase I clinical trials for money. Several scholars have noted that the concerns about risks, consent, and exploitation raised by this phenomenon apply to many (other) jobs, too, and therefore proposed improving subject protections by regulating phase I trial participation as work. This article contributes to the debate over this proposal by exploring a largely neglected worry. Unlike most (other) workers, subjects are not paid to produce or achieve anything but to have things done to them. I argue that this passivity is problematic for reasons of distributive justice. Specifically, it fails to enable subjects to realize what Gheaus and Herzog call "the goods of work"-a failure not offset by adequate opportunities to realize these goods outside of the research context. I also consider whether granting subjects worker-type protections would accommodate this concern.