tbuckley/cabot-search huggingface dataset:
Copy number amplification of 3q26-27 oncogenes in microdissected oral squamous cell carcinoma and oral brushed samples from areca chewers
Authors: Tzong-Ming Shieh
Journal: Cancer Research (2005)

4438  Oral squamous cell carcinoma (OSCC) is the 3rd leading malignancy in the male population of developing countries. In South Asians, OSCC is tightly linked to areca chewing. Since the prognosis for OSCC remains dismal, improvement of early diagnosis may benefit the survival of victims. Chromosome region 3q26-27 has been shown to carry several oncogenes and is a hot-spot region for genomic alterations in squamous cell carcinoma. By quantitative polymerase chain reaction (PCR), we have determined the gene copy number (CN) of TERC (3q26.2), PI3KCA (3q26.32), ZASC1 (3q26.33), and TP63 (3q27.2) from microdissected OSCC. Our results showed that CN amplifications of PI3KCA and ZASC1, a newly identified zinc finger transcription factor, were the most prominent alterations in primary and metastatic OSCC. Co-amplification of PI3KCA and ZASC1 in 50% of primary OSCC suggested that they are critical targets of 3q26.3 amplicon. In addition, OSCC carrying the higher PI3KCA and/or ZASC1 CN amplification conferred significantly higher propensity for lymph node metastasis than the counterparts. Quantitative-reverse transcription-PCR analysis also indicated that the great increase in ZASC1 mRNA expression in OSCC is associated with lymph node metastasis. We further detected the lower CN amplification of 3q26-27 oncogenes (2-5 folds CN increase) in brushed samples from oral leukoplakia, validating the sensitivity of this assay. In addition to OSCC, CN amplification of any of the four 3q26-27 oncogenes was also detected in the brushed samples from 20% areca chewers without visible lesion. The frequent CN amplification of TERC in oral leukoplakia and areca chewers suggested that it could be an early event in oral carcinogenesis. In summary, our data indicated the CN amplification and overexpression of ZASC1 in OSCC. The findings also suggested the potential on using the combination of quantitative-PCR on brush sampling to dissect OSCC risk population, and close follow-up has been performed to warrant the neoplastic formation. Key words: amplification, areca, quantitative-PCR, oncogene, oral carcinoma
SAT0290 HIGH SERUM MYOSTATIN LEVELS SUGGEST ACCELERATED MUSCLE SENESCENCE IN ACTIVE IDIOPATHIC INFLAMMATORY MYOSITIS
Authors: A. Anuja, M. Singh, M. K. Rai, H. Singh, V. Agarwal, L. Gupta
Journal: Annals of the Rheumatic Diseases (2020)

Background: Inflammation is the forerunner to fibrosis and premature ageing in various systemic diseases. Hence it seems plausible that idiopathic inflammatory myopathies (IIM) may exhibit accelerated senescence too. Objectives: Hence we investigated the Myostatin: Follistatin system in the serum as a reflection of early senescence in myositis as compared with healthy and diseased controls. Methods: Patients with inflammatory myositis (ACR/EULAR criteria) presenting to the wards and outpatient clinic between December 2017 to August 2019 were recruited. Those with active infection, pregnancy, renal dysfunction or chronic kidney disease were excluded. Apart from patient and disease variables, activity and damage were assessed using standard IMACS score set measures. Patients in inception cohort were additionally followed up at 1 and 6 months. Myostatin and Follistatin were estimated in sera using ELISA (R&amp;D systems, USA). Juvenile myositis and young adults (18-40 years) were subsequently analyzed separately. Non-parametric tests were used for paired and unpaired analysis. Results expressed as median. Results: 95 myositis (8 Juvenile myositis, 26 DM, 10 PM, 29 Overlap, 2 NAM 1 CAM and 19 ASS) patients (23 Male and 72 Female) with median age 38 (24.5-46.0) years and disease duration 0.9 (2.3-5.1) years were included. Serum Myostatin was lower in IIM than in healthy control (HC) (153.5 vs. 243.6 p&lt;0.0001, Fig 1A) but higher in IIM as compared with disease controls (153.5 vs 86.1 p=0.0174 Fig. 1B). Serum myostatin was comparable between juvenile and adult myositis and in the various subsets of adult myositis (Fig. 1 C and D). Myostatin levels were higher in active as compared with inactive myositis in young adults (211.7 vs. 158.9, p=0.0149, Figure 1E). Serum Myostatin correlated with height (r 0.3, p=0.003) and weight (r 0.2, p=0.047) but not MMT8 or muscle enzymes. Figure 1. Serum Myostatin levels in IIM as compared with healthy controls (A) and disease controls (B). Levels in juvenile myositis as compared with adult IIM (C) and in various subsets of IIM (D). Serum Myostatin levels in active and inactive disease (E). Although Follistatin was lower in IIM than HC (198.4 vs 243.6, p=&lt;0.0001), the neither Follistatin nor Myostatin: Follistatin ratios differ between subsets, and in active versus inactive disease Figure 2 A-D). On follow-up, the serial Myostatin estimation paralleled change in disease activity. Figure 2. Serum Follistatin levels in IIM as compared with healthy controls (A) and disease controls (C). Levels in juvenile and adult IIM (D) and in various subsets of IIM (D). Conclusion: Elevated serum Myostatin levels in active myositis raise the possibility of accelerated senescence in the inflamed muscle tissues which need further investigation. Acknowledgments: : Partly funded by APLAR and IRA research grants awarded to LG. Disclosure of Interests: None declared
Advances in Chronic Obstructive Pulmonary Disease
Authors: Michael C. Ferrera, Wassim W. Labaki, MeiLan K. Han
Journal: Annual Review of Medicine (2021)

Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder with significant morbidity and mortality. Despite its prevalence, COPD is underdiagnosed, and many patients do not receive a diagnosis until the disease is clinically advanced. Recent basic science and clinical research have focused on the early physiologic and pathobiologic changes in COPD with the hopes of improving diagnosis, providing targets for disease-modifying therapy, and identifying patients most likely to benefit from early intervention. Available treatments for COPD have grown substantially in the past 20 years with the introduction of new oral and inhaled medications as well as novel surgical and bronchoscopic procedures. This article summarizes some of the recent advances in our understanding of disease pathogenesis and treatment paradigms.
Comparison of first-line (1L) treatment (tx) patterns and overall survival by age at diagnosis among patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).
Authors: Rawad Elias, Paul Cockrum, Andy Surinach, Shu Wang, Bong Chul Chu
Journal: Journal of Clinical Oncology (2021)

388 Background: Pancreatic cancer is mostly diagnosed in patients (pts) aged ≥ 65 years and the mortality rate is the highest among older adults. As the population ages, it is expected that there will be a significant rise in the number of older pts with mPDAC but guidance regarding their management is limited as these pts are under-represented in clinical trials. The oncological care of older adults in daily practice is challenged by various age-related conditions. Therefore, a better understanding of the real-world population will help in the development of more effective tx strategies. This study describes the proportion of pts with mPDAC who were treated, the types of regimens received, and the associated survival outcomes by age at diagnosis. Methods: Data were extracted for pts diagnosed with mPDAC between Jan 2015 and Mar 2020 from the Flatiron Health database. Pts were stratified into three age groups at diagnosis: &lt;70y, 70-79y, and ≥ 80y. The proportion of pts was evaluated who received 1L tx and the types of regimens received in the metastatic setting. ECOG performance scores (PS) at tx initiation were described. Overall survival (OS) from the start of 1L was estimated using Kaplan-Meier methods. Results: Overall, of the 8,382 pts identified, 71.3% (n=5,973) received tx. Among pts who received tx, 55.5% (n=3,313) were aged &lt;70y at diagnosis, 33.0% (n=1,972) were 70-79y, and 11.5% (n=688) were 80y+. Among those with data available, ECOG PS ≥2 was observed in 15.9% (n=381) of pts &lt;70y, 21.0% (n=309) of pts 70-79y, and 29.9% (n=147) of pts 80y+(p &lt; 0.001). The proportion of pts who received tx decreased with increasing age at diagnosis: 74.9%, 70.9%, and 58.5% for pts aged &lt;70y, 70-79y, and 80y+, respectively. Gemcitabine monotherapy (gem-mono) and gemcitabine + nab-paclitaxel (GNP) accounted for &gt; 70% of regimens prescribed to pts aged 80y+. The median OS (mOS) for patients treated with GNP, gem-mono, FOLFIRINOX, and liposomal irinotecan-based regimens are presented in the table. Conclusions: This study of treatment patterns among pts with mPDAC found that older pts were more likely to have a decreased performance status and are less likely to receive treatment. However, older adults who received systemic therapy had comparable survival outcomes to younger pts treated with a similar regimen. The results of this large descriptive analysis suggest that the treatment strategy of mPDAC should not be based on age but rather on an overall assessment of the performance/functional status and geriatric profile of older pts. [Table: see text]
THU0209 Follow up observations of the patients with rheumatoid arthritis (ra) and reactive amyloidosis
Authors: E Stanislawska-Biernat, A Filipowicz-Sosnowska, T Wagner, M Prohorec-Sobieszek
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Secondary amyloidosis is a serious complication of rheumatoid arthritis and may result in significant morbidity and early death. The knowledge on standard and effective management of patients with secondary amyloidosis is limited. <h3>Objectives</h3> The objective of the study is follow up observation of RA patients with established reactive amyloidosis concerning the clinical aspects of the disease, acute phase reactants and the response to cytostatic treatment. <h3>Methods</h3> 43 patients with rheumatoid arthritis and histologically confirmed secondary amyloidosis were followed for 3 to 6 (mean 4,6) years. The patients were treated with cyclophosphamide or methotrexate combined with small doses of prednizone. Clinical symptoms, laboratory tests and general outcome were analysed after 3 to 6 years of development of amyloidosis. <h3>Results</h3> The time from the diagnosis of RA to the development of amyloidosis was 4 to 16 years, mean 8,7 years. In all patients advanced radiological changes were observed (radiological Steinbrocker stage III or IV). The most common symptoms of amyloidosis were: proteinuria-27(62,8%), nephrotic syndrom -12(27,9%), diarrhoea-4(9,3%). In most of the patients the course of RA was very severe since the onset and high activity parameters were observed despite treatment. Amyloidosis was histologically confirmed by subcutaneous fat tissue biopsy in 38(88,4%) cases. In 8 patients amyloid deposits were found in other organs (kidney, stomach, salivary gland). After the treatment with cyclophosphamide or methotrexate we observed decrease of some activity parameters (ESR, CRP) and decrease of proteinuria level. The treatment was well tolerated and we didn?t observe serious side effects. In the observed group 7(16,3%) patients died after 3 to 6 years of the diagnosis of amyloidosis. The most common cause of death were uremia (4/7) and infections (2/7). <h3>Conclusion</h3> Aggressive treatment with cytostatics influences the survival of patients with reactive amyloidosis in RA. The time of survival in 83,7% of the observed patients was longer than 4,6 years. The outcome of patients with RA and reactive amyloidosis is better when the diagnosis of amyloidosis is confirmed in the early stage of the disease.
Health Care Reform in Transition
Authors: Lawrence O Gostin, Elenora E Connors
Journal: JAMA (2010)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Screening for Lipoprotein(a) Levels in Persons at Low Risk for Cardiovascular Disease
Authors: Ludovico Furlan, Patrick Azcarate, Rita F. Redberg
Journal: JAMA Internal Medicine (2021)

This Teachable Moment assesses cardiac risk in a 64-year-old woman with a history of breast cancer and paroxysmal atrial fibrillation and considers whether referral to cardiology and statin therapy are advisable.
Impact of preoperative therapy for locally advanced thoracic esophageal cancer on the risk of perioperative complications: Results from multicenter phase III trial JCOG 1109.
Authors: Kazuo Koyanagi, Ken Kato, Yoshinori Ito, Hiroyuki Daiko, Soji Ozawa, Takashi Ogata, Hiroki Hara, Takashi Kojima, Tetsuya Abe, Takeo Bamba, Masaya Watanabe, Hirofumi Kawakubo, Yuichi Shibuya, Yasuhiro Tsubosa, Masahiro Tsuda, Isao Nozaki, Hideo Baba, Ryunosuke Machida, Haruhiko Fukuda, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2021)

162 Background: We have conducted randomized three-arm phase III trial comparing cisplatin plus 5-FU (CF) versus docetaxel plus CF (DCF) versus radiation with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer, which is on-follow-up for primary analysis planned in 2023 (JCOG 1109). This study aimed to evaluate the influence of preoperative therapies on perioperative complications and risk factors for perioperative complications after three-arm preoperative therapies. Methods: Patients with potentially resectable advanced thoracic esophageal cancer were randomly assigned to three preoperative therapies and followed by open or thoracoscopic esophagectomy with regional lymphadenectomy. Clinical data, surgical results, and perioperative complications in the patients received DCF and CF-RT were compared with those in the patients received CF. Univariate and multivariate analyses were performed to explore the risk factors of perioperative complications. Results: Between December 2012 and July 2018, 601 patients were randomized (CF/DCF/CF-RT; 199/202/200). Of 589 eligible patients, 546 patients underwent surgery (185/183/178). Patients` characteristics were not different between arms. Median number of harvested lymph node in patients received CF-RT was significantly lower than that in patients received CF (49 vs. 58; P &lt; 0.0001). Incidence of ≥ Grade 2 perioperative complications in patients received DCF was lower than that in patients received CF (44.8% vs. 56.2%; P = 0.036). Incidence of ≥ Grade 2 chylothorax in patients received CF-RT was higher than that in patients received CF (5.1% vs. 1.1%; P = 0.032). Incidence of reoperation and intra-hospital death in patients received DCF and CF-RT did not differ from that in patients received CF. Multivariate analysis showed that operation time (≥ median) and open esophagectomy were independently associated with an increase in ≥ Grade 2 perioperative complications. CF-RT was associated with an increase in occurrence of ≥ Grade 2 chylothorax (Relative Risk 4.84; P = 0.043). Conclusions: Preoperative DCF and CF-RT does not increase the risk of perioperative complications and mortality when compared with standard preoperative CF therapy, but CF-RT increases the risk of chylothorax after esophagectomy for advanced thoracic esophageal cancer.
Protecting the world’s finest athletes: periodic health evaluation practices of the top performing National Olympic Committees from the 2016 Rio or 2018 PyeongChang Olympic Games
Authors: Dustin Nabhan, David Taylor, Melie Lewis, Roald Bahr
Journal: British Journal of Sports Medicine (2021)

To describe the periodic health evaluation (PHE) practices of the top performing National Olympic Committees (NOCs).We sent a survey to NOCs finishing in the top 8 for medal count at the 2016 Rio Olympic Games or 2018 PyeongChang Olympic Games. The survey included four sections: (1) PHE staff composition and roles, (2) beliefs regarding the PHE, (3) a ranking of risk factors for future injury and (4) details on the elements of the PHE.All 14 NOCs with top 8 finishes at the 2016 Rio Olympic Games or 2018 PyeongChang Olympic Games completed the survey. NOCs included a median of seven staff specialties in the PHE, with physicians and physiotherapists having the highest level of involvement. There was agreement that PHEs are effective in identifying current health conditions (13/14) and that athletes should receive individualised action plans after their PHE (14/14), but less agreement (6/14) that PHEs can predict future injury. The practices of NOCs were diverse and often specific to the athlete population being tested, but always included the patient's health history, laboratory studies, cardiovascular screening and assessments of movement capacity. The top three risk factors for future injury were thought to be previous injury, age and training experience.Among the top performing NOCs, the PHE is a comprehensive, multidisciplinary process aimed to identify existing conditions and provide baseline health and performance profiles in the event of future injury. Research linking PHEs to injury prevention is needed.
TNIK Is a Therapeutic Target in Lung Squamous Cell Carcinoma and Regulates FAK Activation through Merlin
Authors: Pedro Torres-Ayuso, Elvira An, Katherine M. Nyswaner, Ryan C. Bensen, Daniel A. Ritt, Suzanne I. Specht, Sudipto Das, Thorkell Andresson, Raul E. Cachau, Roger J. Liang, Amy L. Ries, Christina M. Robinson, Simone Difilippantonio, Brad Gouker, Laura Bassel, Baktiar O. Karim, Chad J. Miller, Benjamin E. Turk, Deborah K. Morrison, John Brognard
Journal: Cancer Discovery (2021)

Lung squamous cell carcinoma (LSCC) is the second most prevalent type of lung cancer. Despite extensive genomic characterization, no targeted therapies are approved for the treatment of LSCC. Distal amplification of the 3q chromosome is the most frequent genomic alteration in LSCC, and there is an urgent need to identify efficacious druggable targets within this amplicon. We identify the protein kinase TNIK as a therapeutic target in LSCC. TNIK is amplified in approximately 50% of LSCC cases. TNIK genetic depletion or pharmacologic inhibition reduces the growth of LSCC cells in vitro and in vivo. In addition, TNIK inhibition showed antitumor activity and increased apoptosis in established LSCC patient-derived xenografts. Mechanistically, we identified the tumor suppressor Merlin/NF2 as a novel TNIK substrate and showed that TNIK and Merlin are required for the activation of focal adhesion kinase. In conclusion, our data identify targeting TNIK as a potential therapeutic strategy in LSCC. SIGNIFICANCE: Targeted therapies have not yet been approved for the treatment of LSCC, due to lack of identification of actionable cancer drivers. We define TNIK catalytic activity as essential for maintaining LSCC viability and validate the antitumor efficacy of TNIK inhibition in preclinical models of LSCC.This article is highlighted in the In This Issue feature, p. 1307.
FRI0147 Body mass density in patients with systemic lupus erythematosus
Authors: D Palic, R Stojanovic, G Susic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Physiological processes, as ageing and menopause, natural influence (diet, physical activity) and many other factors are important in development of osteopenia (OPE) or osteoporosis (OPO). The possible influence of some previous diseases and medications on bone density was investigated, too. <h3>Objectives</h3> To estimate bone density in patient with Systemic Lupus Erythematosus (SLE) and to investigate the influence of BMI, age at onset of SLE, duration of disease, age in time of study, duration of CS treatment as a possible risk factors for OPE/OPO. <h3>Methods</h3> In follow-up study we investigated 57 female patients with SLE, mean age 44,73 ± 11,34 years (min22 max68), mean age at the onset of SLE 35.83 ± 11.18 yr.(15–64). The duration of SLE was 9.03 ± 7.22 yrs (1–32). Menarha were started in 13.73 ± 1.47 yr. (11–18). 27 pts were in menopause in 44.03 ± 4.24 yr.(34–53). Corticosteroide therapy was used for 8.40 ± 6.85 yr.(1–32). Body mass density was measured on L2-L4 segment of vertebral spine. DEXA LUNAR osteodensitometer was used. According to T score patients were classified as: normal (N group) 21 patients (T &gt;-1.0), osteopenic (OPE group) 23 pts (-2,5 &lt;T &lt;-1.0), and ospeoporotic (OPO group) 13 pts (T &lt;-2.5). <h3>Results</h3> No difference were noted in: BMI and in duration of SLE in groups investigated. The borderline difference was existed between N and OPO group in duration of CS treatment (p = 0.049). The relation between particular data where statistical significance was obtained in groups investigated is presented in the Table 1. <h3>Conclusion</h3> Low body mass density was found in elder group of patients with SLE, where the disease started later in perimenopause. Duration of disease, and duration of corticosteroide treatment did not influence BMD. Further studies will consider other factors possibly significant in development of osteoporosis in SLE (subsets of disease, immunological disturbances, cumulative dose of CS and known risk factors for osteoporosis.