tbuckley/cabot-search huggingface dataset:
Lupeol, a dietary triterpene, inhibits the proliferation of human prostate cancer cells: modulation of microtubule assembly and inhibition of proteosome
Authors: Imtiyaz Murtaza, Mohammad Saleem, Bilal Hafeez, Price Sonkarley, Vaqar Adhami, Imtiaz Siddiqui, Hasan Mukhtar
Journal: Cancer Research (2008)

3270  Recent studies from our laboratory showed that Lupeol induces apoptosis and inhibits the tumorigenicity of androgen-sensitive human prostate cancer (PCa) cells in animal models. Current study was aimed to understand the mechanism which precedes the apoptotic process induced by Lupeol in PCa cells. We observed that Lupeol (5-50 μM) treatment significantly was equally effective in decreasing the viability of androgen-sensitive (LNCaP) as well as androgen-insensitive (DU145 and PC-3) cells. Further, Lupeol treatment inhibited the proliferative and clonogenic potential of all PCa cells when observed for 21 days. Since Lupeol was observed to inhibit the proliferation of PCa cells, we asked if Lupeol interferes in the cell cycle process of PCa cells. We observed that Lupeol induces G2/M cell cycle arrest of PCa cells. The phenomenon of G2/M cell cycle arrest is a microtubule regulated process. The importance of microtubules in cell division makes them an important target for anticancer drugs. Since we observed that Lupeol induces G2/M cell cycle arrest we next investigated its effect on microtubule assembly in PCa cells. Interestingly, Lupeol treatment was observed to decrease the expression level of α and β-tubulin. The critical balance between mitotic arrest and exit is maintained by CDKp34/Cyclin B1 complex. We observed that Lupeol treatment causes a reduction in the expression level of Cyclin B1, modulation in Cyclin/Cdk complex and an increase in p21 protein. Mitotic spindle checkpoint is reported to be regulated by Survivin protein which exhibits an aberrant expression level in PCa patients. Lupeol was found to significantly reduce the expression level of Survivin in PCa cells. Stathmin protein (also known as oncoprotein 18) is known to regulate microtubule dynamics and its expression level is known to be highly increased in various malignancies. Lupeol treatment caused a significant reduction in the expression level of Stathmin in PCa cells. The involvement of proteosome in the regulation of cell cycle and microtubule dynamics is well known. MG132, a well known proteosome inhibitor was observed to significantly decrease the expression level of β-tubulin, and Cyclin D1 in PCa cells. Interestingly, MG132-mediated effects were observed to increase several fold in PCa cells treated with Lupeol suggesting a synergistic effect of Lupeol and MG132. However, Lupeol did not change the expression level of Survivin in the presence of proteosome inhibitor MG132 suggesting that Lupeol-induced modulation in microtubule assembly is at least in part dependent on proteosome. We suggest that Lupeol could be used alone or as an adjuvant to known microtubule and proteosome targeting agents for the treatment of PCa.
Clinical experience with atypical spitzoid tumors in patients younger than age 18: Does fluorescence in situ hybridization predict lymph node metastasis?
Authors: Eric J. Stanelle, Klaus J. Busam, Barrie S. Rich, Daniel G. Coit, Michael P. La Quaglia
Journal: Journal of Clinical Oncology (2012)

8586 Background: Determining the malignant potential of atypical spitzoid melanocytic proliferations can be diagnostically challenging, and many patients are therefore managed as if they had melanoma. However, few studies focus specifically on atypical spitzoid tumors (AST). Further, cytogenetic analysis using fluorescence in situ hybridization (FISH) has been used to determine malignant potential. We reviewed our institutional experience to determine staging and clinical outcomes, and the correlation between FISH findings and regional nodal positivity in patients with AST. Methods: With IRB approval, we retrospectively reviewed all patients aged &lt;18 years treated for AST from 1981-2011 to determine staging variables, outcome, and the results of 4-probe FISH assay. A total of 44 patients with a median age of 11.5 years were identified. All pathology was re-reviewed by a single dermatopathologist. Staging was based on 2010 AJCC criteria. Correlations were determined using either the Pearson or Spearman correlation coefficient. Results: Median lesion thickness was 2.8 mm (range: 0.55-12) and eight (18%) lesions met spitzoid melanoma criteria. Median followup was 4.1 years for all patients (5.5 years for spitzoid melanomas). Thirty-nine patients (89%) underwent sentinel lymph node biopsies (SLNB) and 15 (38%) were positive. Lymph node (LN) positivity correlated with tumor thickness (p=0.002), stage (p=0.001), and mitotic rate (p=0.05). FISH was available for 17/39 patients who had SLNB; sensitivity and specificity for LN metastases were 50% and 54%, respectively. Of 15 patients with a positive SLNB, 12 underwent completion LN dissection, three of which were positive for 1, 2, and 3 additional nodes, respectively. There were no recurrences or disease-related deaths. Conclusions: Traditional indicators of thickness and stage predicted nodal involvement in pediatric patients with AST. However, FISH results did not predict nodal status and should not be used to guide management. With 100% disease specific survival and no recurrences, AST should be considered a separate entity from melanoma and complete excision may be sufficient therapy.
HOLODIASTOLIC RETROGRADE FLOW BY CARDIAC MAGNETIC RESONANCE ASSOCIATES WITH WORSE REMODELING AND OUTCOMES IN PATIENTS WITH SIGNIFICANT AORTIC REGURGITATION
Authors: Go Hashimoto, Felix Oh, Matthew Wang, Keith Acosta, Miho Fukui, John R. Lesser, Paul Sorajja, Santiago Garcia, Mario Gossl, Scott W. Sharkey, Joao L. Cavalcante
Journal: Journal of the American College of Cardiology (2020)
PREVALENCE AND PREDICTORS OF HEALTH APPS OWNERSHIP AMONG US ADULTS WITH HEART DISEASE
Authors: Setri Fugar, Henry Onyeaka, Kesiena Onoriode, Chinoso Asinugo, Patrick Berchie, Obafemi Sanni, Adole Moevi, Stephen Wemakor, Alexis Okoh
Journal: Journal of the American College of Cardiology (2020)
Regional variation in Medicare spending and survival among older adults with advanced cancer.
Authors: Gabriel Brooks, Ling Li, Dhruv B Sharma, Deborah Schrag
Journal: Journal of Clinical Oncology (2012)

6003 Background: There is substantial regional variation in medical spending in the United States. Whether this variation extends to spending for cancer care and is associated with cancer survival outcomes is unknown. Methods: Patients aged 65 and older with incident advanced cancer were identified from the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database. Advanced cancers included lung (stage IIIB/IV), pancreas (stage III/IV) colorectal, breast and prostate (stage IV). Medicare spending from 2 months pre-diagnosis until death or 12 months post-diagnosis was totaled in 2010 USD for Medicare-enrolled advanced cancer patients from 80 hospital referral regions (HRR’s). HRRs were then ranked by mean composite 14-month spending and grouped into quintiles. The hazard ratio for death was assessed in each disease cohort for the comparison between the quintiles with lowest (Q1, referent) and highest (Q5) composite spending. Results: Mean composite 14-month spending ranged from $143,870 to $303,902 in HRR’s with the lowest and highest spending (Mason City, IA and Los Angeles, CA). As shown in the table, increased spending was associated with decreased risk of death for lung, colorectal and pancreas cancer but not for prostate or breast cancer. Conclusions: There is substantial regional variation in Medicare spending for patients with advanced cancer. This variation is associated with modest differences in risk of death between the lowest and highest quintiles of spending for lung, colorectal and pancreas cancer. [Table: see text]
Lenalidomide and dexamethasone in overtreated multiple myeloma patients: A single center update.
Authors: Alessandro Moscetti, Daniela De Benedittis, Federica Resci, Giusy Antolino, Maria Paola Bianchi, Virginia Naso, Giacinto La Verde
Journal: Journal of Clinical Oncology (2013)

e19527 Background: Lenalidomide (Len - Revlimid) is a therapeutic option for relapsed and refractory multiple myeloma, especially in association with steroids. Methods: Oraldaily lenalidomide (10-25 mg) for 21 days every month (median courses 9.7) and weekly dexamethasone (Dex) were administered until progression in 41 pretreated patients (median age 66.2 yrs) observed between June 2008 and January 2013 at Hematology Department of Sant’Andrea Hospital in Rome. Past treatment included alkylants, anthracyclines, IFN-α, thalidomide, bortezomib and single or double autograft. Twenty five patients were evaluated after 6 courses of therapy, administered as second to fifth line, and prospectively followed-up; two patients weren’t considered because of early death. Treatment response was assessed according to IMWG uniform response criteria. Results: The overall response rate was 56% (14/25 pts) with a median duration of response of 13 months: 1 patient reached CR, 1 VGPR, 12 patients reached a partial response (PR), 10 showed a stable disease (SD) and 1 progressive disease (PD). The median progression free survival was 14.8 months. Among responder patients, 4 died due to progression disease after a median of 16.5 courses, while 9 are in continuous treatment (3 with over 33 courses each) and 1 in salvage therapy; among non responder ones, 7 died for PD, while 3 are in continuous treatment and 1 in salvage therapy. The reported side effects included pneumonia, neutropenia, diarrhea, peripheral sensitive polyneuropathy, transient liver failure, lower urinary tract infection, skin rash, transient aphasia, conjunctival hemorrhage and deep vein thrombosis, all resolved with brief discontinuance and specific support therapy without hospitalization. Conclusions: This study shows that Len-Dex combination is an effective oral salvage therapy with good response rate and manageable side effects for relapsed and refractory multiple myeloma patients.
Lysyl Oxidase (LOX) Family Members: Rationale and Their Potential as Therapeutic Targets for Liver Fibrosis
Authors: Wei Chen, Aiting Yang, Jidong Jia, Yury V. Popov, Detlef Schuppan, Hong You
Journal: Hepatology (2020)

The cross‐linking of structural extracellular matrix (ECM) components, especially fibrillar collagens and elastin, is strongly implicated in fibrosis progression and resistance to fibrosis reversal. Lysyl oxidase family members (LOX and LOXL1 [lysyl oxidase‐like 1], LOXL2 [lysyl oxidase‐like 2], LOXL3 [lysyl oxidase‐like 3], and LOXL4 [lysyl oxidase like 4]) are extracellular copper‐dependent enzymes that play a key role in ECM cross‐linking, but have also other intracellular functions relevant to fibrosis and carcinogenesis. Although the expression of most LOX family members is elevated in experimental liver fibrosis of diverse etiologies, their individual contribution to fibrosis is incompletely understood. Inhibition of the LOX family as a whole and of LOX, LOXL1, and LOXL2 specifically has been shown to suppress fibrosis progression and accelerate its reversal in rodent models of cardiac, renal, pulmonary, and liver fibrosis. Recent disappointing clinical trials with a monoclonal antibody against LOXL2 (simtuzumab) in patients with pulmonary and liver fibrosis dampened enthusiasm for LOX family member inhibition. However, this unexpected negative outcome may be related to the inefficient antibody, rather than to LOXL2, not qualifying as a relevant antifibrotic target. Moreover, LOX family members other than LOXL2 may prove to be attractive therapeutic targets. In this review, we summarize the structural hallmarks, expression patterns, covalent cross‐linking activities, and modes of regulation of LOX family members and discuss the clinical potential of their inhibition to treat fibrosis in general and liver fibrosis in particular.
Risk of Ipsilateral Reamputation Following an Incident Toe Amputation Among U.S. Military Veterans With Diabetes, 2005–2016
Authors: Alyson J. Littman, Chin-Lin Tseng, Andrew Timmons, Kathryn Moore, Gregory Landry, Joseph M. Czerniecki, Jeffrey Robbins, Edward J. Boyko
Journal: Diabetes Care (2020)

To assess whether the risk of subsequent lower-limb amputations and death following an initial toe amputation among individuals with diabetes has changed over time and varies by demographic characteristics and geographic region.Using Veterans Health Administration (VHA) electronic medical records from 1 October 2004 to 30 September 2016, we determined risk of subsequent ipsilateral minor and major amputation within 1 year after an initial toe/ray amputation among veterans with diabetes. To assess changes in the annual rate of subsequent amputation over time, we estimated age-adjusted incidence of minor and major subsequent ipsilateral amputation for each year, separately for African Americans (AAs) and whites. Geographic variation was assessed across VHA markets (n = 89) using log-linear Poisson regression models adjusting for age and ethnoracial category.Among 17,786 individuals who had an initial toe amputation, 34% had another amputation on the same limb within 1 year, including 10% who had a major ipsilateral amputation. Median time to subsequent ipsilateral amputation (minor or major) was 36 days. One-year risk of subsequent major amputation decreased over time, but risk of subsequent minor amputation did not. Risk of subsequent major ipsilateral amputation was higher in AAs than whites. After adjusting for age and ethnoracial category, 1-year risk of major subsequent amputation varied fivefold across VHA markets.Nearly one-third of individuals require reamputation following an initial toe amputation, although risks of subsequent major ipsilateral amputation have decreased over time. Nevertheless, risks remain particularly high for AAs and vary substantially geographically.
Targeted sequencing in DLBCL, molecular subtypes, and outcomes: a Haematological Malignancy Research Network report
Authors: Stuart E. Lacy, Sharon L. Barrans, Philip A. Beer, Daniel Painter, Alexandra G. Smith, Eve Roman, Susanna L. Cooke, Camilo Ruiz, Paul Glover, Suzan J. L. Van Hoppe, Nichola Webster, Peter J. Campbell, Reuben M. Tooze, Russell Patmore, Cathy Burton, Simon Crouch, Daniel J. Hodson
Journal: Blood (2020)
Definitive image guided (IGRT) intensity-modulated arc radiotherapy (arctherapy) for locally advanced squamous cell carcinoma of the vulva.
Authors: Marie Louise Vorndran Coeln Banner-Voigt, Hanne From Mathiesen, Soeren Lassen, Mansoor Raza Mirza
Journal: Journal of Clinical Oncology (2013)

e16540 Background: To determine early clinical outcome of PET-CT image guided intensity modulated arc radiotherapy with concomitant weekly cisplatin as definitive treatment of locally advanced or loco-regional unresectable relapsed vulvar cancer. Methods: Primary or relapsed (after surgery) patients (pts) with locally or loco-regionally advanced vulvar cancer not amenable to surgery were treated with radiation (RT) plus weekly cisplatin. All pts were planed by PET-CT scan. The decision to irradiate vulva and/or unilateral/bilateral nodes was made independently. Vulva was irradiated if macroscopic tumor was present (64Gy) or free-margins were less than 8mm (50Gy). Radiotherapy was applied to the unilateral or bilateral nodal regions according to nodal involvement/sentinal node/central or lateral vulvar tumor statuses. Principal of one-plus nodal region was applied. Target volumes were delineated together with onc-radiologist. Arctherapy was used. Results: 24 consecutive pts (median age 68 years) were treated during 01.09.2008-30.09.2012. In the initial period IMRT was used (9 pts). Vulva was treated in 20 pts; unilateral nodal RT in 7 pts and bilateral nodal RT in 17 pts. Grade ≥2 skin toxicity was registered in 20 pts, diarrhea in 3 pts., bladder related toxicity in 4 pts. Median follow-up is 15.7 months. 18 pts had complete clinical &amp; radiological remission. 6 pts had treatment failure (residual tumor at 3 months follow-up) and another 6 pts relapsed. Conclusions: Image guided arctherapy is well tolerated and is effective in unresectable locally advanced vulvar cancer pts. Further experience and long-term data with this technique is to be attained.
Immune Profiling of Human Gut-Associated Lymphoid Tissue Identifies a Role for Isolated Lymphoid Follicles in Priming of Region-Specific Immunity
Authors: Thomas M. Fenton, Peter B. Jørgensen, Kristoffer Niss, Samuel J.S. Rubin, Urs M. Mörbe, Lene B. Riis, Clément Da Silva, Adam Plumb, Julien Vandamme, Henrik L. Jakobsen, Søren Brunak, Aida Habtezion, Ole H. Nielsen, Bengt Johansson-Lindbom, William W. Agace
Journal: Immunity (2020)
THE ASSOCIATION OF CHRONIC LUNG DISEASE WITH 1-YEAR SURVIVAL AFTER MITRAL VALVE SURGERY
Authors: Mohanad Hamandi, Robert Smith, Paul A. Grayburn, Kelley Hutcheson, Karim Al-Azizi, Molly Szerlip, Sameh Sayfo, Xuan Wang, Seth Woolbert, Michael William, Zoheb Khan, William Ryan, Michael Mack, J. Michael DiMaio, Timothy J. George
Journal: Journal of the American College of Cardiology (2020)
RELATIONSHIP BETWEEN ATRIAL FIBRILLATION AND ANGIOPOIETIN-2 ELEVATION REMAINS SIGNIFICANT FOLLOWING 1-YEAR INTERVAL
Authors: Jack S. Bontekoe, Dimpi Patel, Justin Lee, Vinod Bansal, Mushabbar A. Syed, Debra A. Hoppensteadt, Paula Maia, Amanda Walborn, Jeffrey Liles, Yevgeniy Brailovsky, Jawed Fareed
Journal: Journal of the American College of Cardiology (2020)
Tracheal squamous cell papilloma with an aberrant artery in the stalk
Authors: Yahua Li, Kewei Ren, Liqun Ye, Jianzhuang Ren, Xinwei Han
Journal: Thorax (2020)

An 81-year-old woman presented with a 1-year history of chronic cough and progressive breath shortness. Physical examination was notable for wheezing. Her laboratory test results were normal. The chest contrast-enhanced CT scan revealed a cauliflower-like lesion in the upper third dorsolateral trachea, and an artery in the stalk of the tumour was observed (figure 1A,B). Considering the potential of massive bleeding during bronchoscopic resection, artery embolisation …
m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in gastric cancer
Authors: Bo Zhang, Qiong Wu, Ben Li, Defeng Wang, Lei Wang, You Lang Zhou
Journal: Molecular Cancer (2020)

The epigenetic regulation of immune response has been demonstrated in recent studies. Nonetheless, potential roles of RNA N6-methyladenosine (m6A) modification in tumor microenvironment (TME) cell infiltration remain unknown.We comprehensively evaluated the m6A modification patterns of 1938 gastric cancer samples based on 21 m6A regulators, and systematically correlated these modification patterns with TME cell-infiltrating characteristics. The m6Ascore was constructed to quantify m6A modification patterns of individual tumors using principal component analysis algorithms.Three distinct m6A modification patterns were determined. The TME cell-infiltrating characteristics under these three patterns were highly consistent with the three immune phenotypes of tumors including immune-excluded, immune-inflamed and immune-desert phenotypes. We demonstrated the evaluation of m6A modification patterns within individual tumors could predict stages of tumor inflammation, subtypes, TME stromal activity, genetic variation, and patient prognosis. Low m6Ascore, characterized by increased mutation burden and activation of immunity, indicated an inflamed TME phenotype, with 69.4% 5-year survival. Activation of stroma and lack of effective immune infiltration were observed in the high m6Ascore subtype, indicating a non-inflamed and immune-exclusion TME phenotype, with poorer survival. Low m6Ascore was also linked to increased neoantigen load and enhanced response to anti-PD-1/L1 immunotherapy. Two immunotherapy cohorts confirmed patients with lower m6Ascore demonstrated significant therapeutic advantages and clinical benefits.This work revealed the m6A modification played a nonnegligible role in formation of TME diversity and complexity. Evaluating the m6A modification pattern of individual tumor will contribute to enhancing our cognition of TME infiltration characterization and guiding more effective immunotherapy strategies.
PROGNOSTIC UTILITY OF TRIGLYCERIDE RICH LIPOPROTEINS RELATED MARKERS IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE ON STATIN THERAPY
Authors: Ye-Xuan Cao, Hui-Wen Zhang, Jing-Lu Jin, Hui-Hui Liu, Yan Zhang, Rui-Xia Xu, Ying Gao, Yuan-Lin Guo, Na-Qiong Wu, Cheng-Gang Zhu, Chuan-Que Cui, Geng Liu, Qian Dong, Jing Sun, Qi Hua, Yan-Fang Li, Jian-Jun Li
Journal: Journal of the American College of Cardiology (2020)
DIGOXIN INITIATION IS NOT ASSOCIATED WITH ALL-CAUSE MORTALITY IN PATIENTS WITH HEART FAILURE AND ATRIAL FIBRILLATION: INSIGHTS FROM THE MEDICARE-LINKED OPTIMIZE-HF REGISTRY
Authors: Samuel Wopperer, Markus Anker, Lakshmi Suma Tummala, Phillip Hong Lam, Lowell Safren, Gregg C. Fonarow, Steven Singh, Ali Ahmed
Journal: Journal of the American College of Cardiology (2020)
Rare discrepancy in driving gene mutations between histologically heterogeneous primary lung cancer.
Authors: Wenzhao Zhong, Zhi-yong Chen, Fangping Xu, Xue-Ning Yang, Jian Su, Zhihong Chen, Xuchao Zhang, Shejuan An, Qing Zhou, Jinji Yang, Yi Long Wu
Journal: Journal of Clinical Oncology (2013)

e18547 Background: The mixed subtype adenocarcinomas account for nearly 90%. The driving gene mutations are found with different frequency in various histological subtypes. The role of the intra-tumoral heterogeneity is still controversial. Methods: In order to compare the gene status of the area of different growth patterns, the representative morphologically different tumor areas within the same surgical resected primary tumour were extracted from tissue sections. Driver genes were detected by sequencing, ARMS and FISH methods. Results: During routine clinical genotyping, 79 consecutive surgical resected cases with mixed subtype adenocarcinoma harboring driving gene mutation were selected. The gene statuses of different growth patterns within the same primary tumor were compared. The discrepancies of EGFR mutation were 10 in 65 with direct sequencing, and 1 in 65 with ARMS, among which consistent EGFR mutations were found in all the 5 cases adenosquamous cell carcinoma. The discrepancy of KRAS mutation in direct sequencing was 2 in 10. No discrepancy of EML4-ALK rearrangement in FISH was found in 4 cases. Conclusions: Rare discrepancy of driving gene mutations within histologically heterogeneous primary lung adenocarcinoma was found. It indicated that the different components of the primary lung cancer may have originated from a common ancestor.
12 MONTH EFFICACY, SAFETY, SYMPTOMS AND IMPROVED QUALITY OF LIFE POST ARCTIC FRONT ADVANCE CRYOBALLOON ABLATION IN PERSISTENT AF PATIENTS: RESULTS FROM THE GLOBAL PROSPECTIVE MULTICENTER STOP PERSISTENT AF STUDY
Authors: Hugh Calkins, Wilber Su, Kabir Bhasin, Jean Champagne, Robert Sangrigoli, Paul Novak, Sanjaya Gupta, Teiichi Yamane, Vivek Reddy
Journal: Journal of the American College of Cardiology (2020)