tbuckley/cabot-search huggingface dataset:
Disseminated tumor cells in bone marrow of patients with endometrial and cervical cancer.
Authors: Florin-Andrei Taran, Markus Wallwiener, Andreas D. Hartkopf, Christina Walter, Sara Brucker, Ralf Rothmund, Bernhard Kraemer, Diethelm Wallwiener, Tanja N. Fehm
Journal: Journal of Clinical Oncology (2013)

5598 Background: The presence of disseminated tumor cells (DTC) in the bone marrow (BM) of breast cancer patients is associated with poor prognosis. Several studies demonstrated that tumor cell dissemination may occur in gynecologic cancer and affect clinical outcome. The aim of our study was to evaluate the incidence of DTC and to assess their prognostic significance in patients with gynecologic malignancies. Methods: Bone marrow aspirates from 623 patients with primary endometrial (331), cervical (228), and vulvar cancer (64) undergoing surgery at the Department of Gynecology and Obstetrics, University Hospital, Tuebingen, Germany between November 2001 and May 2012, were included into the study. Disseminated tumor cells were identified by immunocytochemistry using the pancytokeratin antibody A45B/B3 and by cytomorphology. Results: Disseminated tumor cells were detected in 18% of BM aspirates from patients with gynecological malignancies. Incidences of DTC in endometrial, cervical, and vulvar cancer were 21%, 16% and 16%, respectively. The presence of DTC was associated with a lower tumor grade in endometrial cancer For patients with vulvar cancer, no correlation with established clinicopathological factors was observed. In case of cervical cancer, BM positivity was correlated with International Federation of Gynecology and Obstetrics stage, nodal involvement and the presence of lymphangiosis carcinomatosa. For all analyzed tumor entities, no association between BM status and clinical outcome could be observed. Conclusions: Disseminated tumor cells are a common phenomenon in solid tumors. However, only in cervical cancer DTC postivity was associated with advanced disease. The consequences for DTC positive patients have to be determined.
The potential benefit of trastuzumab-based therapy upon lapatinib progression in heavily preatreated patients with advanced HER2 positive breast cancer.
Authors: Anastasios L. Boutis, Sofia Chatzileontiadou, Nikolaos Diamantopoulos, Athanasios Pouptsis, Chariklia Fotiou
Journal: Journal of Clinical Oncology (2013)

e11576 Background: Overexpression of human epidermal growth factor receptor 2 (HER2) occurring in about 20% of breast cancers is associated with increased risk of disease recurrence and worse prognosis. Despite the advent of therapies that target HER2, particularly, trastuzumab and lapatinib, that have altered the natural course of HER2-positive advanced breast cancer, tumor progression remains inevitable. New agents are in clinical development, but up to date there are limited data to direct the treatment of patients after lapatinib progression. Methods: We retrospectively searched for HER2-positive advanced breast cancer patients treated at our clinic, who received both trastuzumab-based therapy and lapatinib upon trastuzumab-progression in the metastatic setting. Thirty patients, all female, suffering from HER2-positive advanced breast cancer were identified. HER-2 positivity was assessed by immunohistochemistry (IHC 3+) or chromogenic in situ hybridization (CISH+). Results: Of the 30 patients, 83.3% had invasive ductal carcinoma; 60% had positive hormone receptor status, and 80% grade 3 tumours. Half of the patients received adjuvant trastuzumab. Median age was 57 years, range 37-79 years. 36.6% were switched to lapatinib after a median of three (range 2-6 lines) trastuzumab-based treatment lines. In 8 pts (37.5%) trastuzumab was re-started after lapatinib progression. In 7 of these patients, trastuzumab was combined with chemotherapy. Median progression free survival and overall survival in these patients was 4.75 and 8.87 months respectively. 3 patients received bevacizumab-based therapy upon lapatinib failure. Conclusions: Trastuzumab rechallenge after lapatinib progression may be active in a subgroup of heavily pre-treated patients. Clinical benefit of this strategy has to be balanced especially in limited resource settings with unavailability of novel agents or early phase clinical trials. As of now, there is no uniform accepted standard to define the optimal treatment approach of patients upon lapatinib progression showing the real need for new therapies in this population.
AFRICAN AMERICANS PRESENT WITH LESS ATRIAL FIBRILLATION IN TRANSTHYRETIN CARDIAC AMYLOIDOSIS: A RETROSPECTIVE REVIEW
Authors: Lindsey Mitrani, Frederick L. Ruberg, Jeffeny De Los Santos, Stephen Helmke, Sergio Teruya, Samantha Guadalupe, Melissa Valarezo, Danillo Gamino, Mathew Maurer
Journal: Journal of the American College of Cardiology (2020)
Richter transformation in chronic lymphocytic leukemia (CLL)—a pooled analysis of German CLL Study Group (GCLLSG) front line treatment trials
Authors: O. Al-Sawaf, S. Robrecht, J. Bahlo, A. M. Fink, P. Cramer, J. v Tresckow, E. Lange, M. Kiehl, M. Dreyling, M. Ritgen, J. Dürig, E. Tausch, C. Schneider, S. Stilgenbauer, C. M. Wendtner, K. Fischer, None Goede, M. Hallek, B. Eichhorst
Journal: Leukemia (2020)
Decades After Diagnosis
Authors: Susan R. Strong
Journal: JACC CardioOncology (2020)

When I met Darryl in 2012, I was in the best shape of my life. Our first year together was joyful and active: we enjoyed mountain hikes and long talks, with the crunch of graveled trail underfoot and an expanse of azure sky overhead; summer concerts under a canopy of stars at the Red Rocks
ACUTE MANIA INDUCED TAKOTSUBO CARDIOMYOPATHY
Authors: Amr Idris, Jared Christensen, Mohanad Hamandi, Swathie Bayya, Sameh Sayfo, Chadi Dib, Srinivasa Potluri, Zuyue Wang, Molly Szerlip, Karim Al-Azizi
Journal: Journal of the American College of Cardiology (2020)
COST-EFFECTIVENESS COMPARISON OF RADIAL AND FEMORAL PERCUTANEOUS CORONARY INTERVENTION IN A LARGE MULTI-STATE HEALTH SYSTEM
Authors: Angela Winegar, Allison J. Ottenbacher, Thomas P. Erlinger, Joseph Wallace, Annie E. Cacchione, Ren-Huai Huang, Angelo Bufalino, Kevin Willmann, Edward T.A. Fry, Joseph G. Cacchione
Journal: Journal of the American College of Cardiology (2020)
Different <i>EGFR</i>/<i>KRAS</i> mutation spectrums in lung cancer between never smokers and heavy smokers.
Authors: Kazuya Takamochi, Shiaki Oh, Kenji Suzuki
Journal: Journal of Clinical Oncology (2012)

10548 Background: EGFR mutations are more commonly found in lung adenocarcinomas in never smokers, while KRAS mutations are more frequently present in those in heavy smokers. Although the incidence is low, EGFR mutations are also found in tumors in heavy smokers and KRAS mutations also occur in tumors in never smokers. Therefore, there may be different biological characteristics in EGFR/ KRAS mutated lung cancers according to the smoking status. Methods: This was a retrospective review of 382 patients with surgically resected lung cancers between February 2009 and March 2011. The clinicopathological factors (age, gender, histology, serum CEA level, pathological nodal status, lymphatic permeation, and blood vessel invasion) and EGFR/KRAS mutation spectrums were compared between never smokers (pack-year = 0, n = 161) and heavy smokers (pack-year &gt; 20, n = 167). Results: EGFR mutations were detected in 88 (55%) never smokers and in 33 (20%) heavy smokers. In contrast, K-ras mutations were detected in 7 (4%) never smokers and in 31 (19%) heavy smokers. Both EGFR and KRAS mutations were more frequently observed in female never smokers and in male heavy smokers. The spectrum of both EGFR and KRAS mutation differed according to the smoking status. Minor EGFR mutations other than exon 21 L858R and exon 19 deletions that are activating mutations indicating the efficacy of EGFR tyrosine kinase inhibitors (TKIs) were more frequently found in heavy smokers than in never smokers. G→A transitions were more common KRAS mutations in never smokers and G→T transversions that are thought to be related to exposure to the polycyclic aromatic hydrocarbons found in cigarette smoke were more common KRAS mutations in heavy smokers. Conclusions: The EGFR/KRAS mutation spectrums in lung cancer were quite different in never smokers and heavy smokers. Further study is needed to evaluate the relationship between the efficacy of such molecular targeting agents as EGFR TKIs and the EGFR/KRAS mutation spectrums.
OXYLIPINS PREDICT PRESENCE AND EXTENT OF OBSTRUCTIVE CORONARY ARTERY DISEASE
Authors: Elizabeth Le, Manuel García-Jaramillo, Armando Alcazar Magana, Diana Rinkevich, Yan Zhao, Igor V. Dykan, Donald B. Jump, Claudia S. Maier, Gerd Bobe, Timothy Simpson, Nabil J. Alkayed, Sanjiv Kaul
Journal: Journal of the American College of Cardiology (2020)
STRESS INDUCED CARDIOMYOPATHY ANY STRESSOR CAN ACTUATE, EVEN WHEN SIMPLY INTUBATE: A CASE OF TEE INDUCED TAKOTSUBO
Authors: Bader Abu Ghalyoun, Dhaval Shah, Rahul Vasudev, Rana Garris, Dema Shamoon, Hartaj Virk, Fayez Shamoon
Journal: Journal of the American College of Cardiology (2020)
Intra-lesional administrations of TG1042 (adenovirus expressing interferon-γ) combined with adoptive TIL transfer in patients with metastatic melanoma.
Authors: Amir Khammari, Jean-Marc Limacher, Jean-Michel NGuyen, Gaelle Quereux, Anabelle Brocard, Lucie Peuvrel, Anne-Chantal Knol, Soraya Saiagh, Vincent Bataille, Brigitte Dreno
Journal: Journal of Clinical Oncology (2012)

e19019 Background: Several tumour factors limit the efficacy of spontaneous immune responses. By changing the tumour environment through immune-stimulation, responses could be more efficient. Methods: This is a phase I/II open, monocentric study with a sample size of 12 patients. The main inclusion criteria were: age 18 to 75, melanoma stage IIIc/IV with cutaneous and visceral metastases except brain metastases. Patients received intra-lesional injections TG1042 combined with tumor infiltrating lymphocytes (TILs) infusions and interleukine-2 (IL2) sub-cutaneous injections. TILs were infused on days 1 and 29 followed by IL2 injections (6M UI daily) for 10 days. TG1042 was injected at the dose of 5x10 10 viral particles per lesion (in up to 6 lesions) every two weeks from day -15 to month 2 and then every month up to month 11 or progression. The main objectives were to evaluate the clinical response and safety. Results: Twelve patients stage IVa-c AJCC have been included. Three patients progressed rapidly before starting any treatment and for 2 others TILs were not obtained due to insufficient tumor tissue. Minor erythema at the TG1042 injection site as well as minor to moderate flu-like symptoms linked to IL2 injections was observed. No grade 3 or 4 treatment related adverse events were reported. Among the 7 patients evaluable for tumor response (RECIST rules), 2 partial and 2 complete responses were observed. Distant responses were also observed for 2 patients. Immunohistochemical analysis on biopsies from an injected lesion of 3 patients before and after 3 months of treatment showed an increase of CD8 T lymphocytes in 2 patients with clinical response associated with an increase of IFN-γ and STAT 1 expression. Conclusions: Results of this study demonstrate that TILs-based adoptive cell therapy combined with intra-lesional immunostimulation induced by TG1042 is feasible, safe and can induce a disease control in a majority of patients. Stimulation of innate immunity by adenovirus expressing interferon gamma seems able to reverse the tolerance state within the tumour environment, thus making TILs able to exercise their cytotoxic activity against melanoma.
The network of non-coding RNAs and their molecular targets in breast cancer
Authors: Francesca Crudele, Nicoletta Bianchi, Eva Reali, Marco Galasso, Chiara Agnoletto, Stefano Volinia
Journal: Molecular Cancer (2020)

Abstract Background Non-coding RNAs are now recognized as fundamental components of the cellular processes. Non-coding RNAs are composed of different classes, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Their detailed roles in breast cancer are still under scrutiny. Main body We systematically reviewed from recent literature the many functional and physical interactions of non-coding RNAs in breast cancer. We used a data driven approach to establish the network of direct, and indirect, interactions. Human curation was essential to de-convolute and critically assess the experimental approaches in the reviewed articles. To enrol the scientific papers in our article cohort, due to the short time span (shorter than 5 years) we considered the journal impact factor rather than the citation number. The outcome of our work is the formal establishment of different sub-networks composed by non-coding RNAs and coding genes with validated relations in human breast cancer. This review describes in a concise and unbiased fashion the core of our current knowledge on the role of lncRNAs, miRNAs and other non-coding RNAs in breast cancer. Conclusions A number of coding/non-coding gene interactions have been investigated in breast cancer during recent years and their full extent is still being established. Here, we have unveiled some of the most important networks embracing those interactions, and described their involvement in cancer development and in its malignant progression.
Analysis of health-related quality of life during neoadjuvant endocrine therapy with letrozole in postmenopausal breast cancer patients: N-SAS BC06 trial.
Authors: Shoichiro Ohtani, Naruto Taira, Kiyohiro Kihara, Yoshie Hasegawa, Takehiko Sakai, Takuji Iwase, Norikazu Masuda, Tomomi Fujisawa, Yasuhiro Yanagita, Shozo Ohsumi, Kenji Higaki, Takuhiro Yamaguchi, Hiroji Iwata
Journal: Journal of Clinical Oncology (2013)

6588 Background: The impact of neoadjuvant endocrine therapy (NET) on health-related QOL (HRQOL) has not been clarified yet. N-SAS BC 06 is a multicenter study in postmenopausal patients with hormone-sensitive primary breast cancer, two-staged (preoperative and postoperative) enrollment, and intervention. It includes a randomized controlled study of patients responding to NET, which is designed to compare chemotherapy followed by endocrine therapy, with endocrine therapy alone, as postoperative adjuvant therapy. The primary endpoint is DFS, and the secondary endpoints include adverse events, HRQOL and health economic evaluation. This report presents the planned analysis of HRQOL during 6 months of NET. Methods: The target sample size was 850 patients of whom the first 500 enrolled patients were included in HRQOL evaluation. Subjects were assessed at enrollment, and at 1 and 4 months after starting NET, using FACT-G (General), B (Breast), ES (Endocrine Symptoms) and HADS (Hospital Anxiety and Depression Scale). Results: Mean age was 63 years, mean BMI was 23.9. Results of clinical efficacy were as follows: CR: 2%; PR: 44.3%; SD: 48%; and PD: 5.7%. The questionnaire response rates at enrollment, and at 1 and 4 months were 93%, 90% and 82%, respectively, quite a high response rate. The mean scores at enrollment, and at 1 and 4 months were as follows: FACT-G: 82.9; 83.4; 82.7, FACT-B TOI (Trail outcome index): 68.3; 69.5; 68.9; ES subscale: 61.2; 60.1; 59.7 and HADS score: 10.4; 8.9; 8.8 respectively. There were no significant changes in the FACT-G or B-TOI over time, while the social domain score, ES subscale, decreased significantly (worse social well-being and ES). In the ES analysis by item, symptoms such as hot flash showed a greater decrease. HADS scores deceased significantly (improved anxiety and depression), and emotional domain scores increased significantly (better emotional well-being) at 1 month and 4 months after NET. Conclusions: NET had no impact on the overall HRQOL scores, but the anxiety and depression observed at enrollment had improved by 1 month after therapy. To our best knowledge, this is the first report of HRQOL during NET. Clinical trial information: 000001090.
UTILIZATION OF CORONARY INTERVENTIONS AND OUTCOMES IN WEEKEND VERSUS WEEKDAY ADMISSIONS FOR STEMI COMPLICATED BY CARDIOGENIC SHOCK
Authors: Brian Butera, Brian Butera, Alejandro Lemor, Lina Ya'qoub, Pouyan Daniel Arman, Michele Voeltz, Gerald Koenig, Khaldoon Alaswad, William W. O'Neill, Mir Basir
Journal: Journal of the American College of Cardiology (2020)
Early versus late treatment for smoldering (asymptomatic) multiple myeloma: A systematic review.
Authors: Mubarak Salem Alahamdi, Jason Tay
Journal: Journal of Clinical Oncology (2013)

8593 Background: Expectant management remains the current standard of care for patients with smoldering multiple myeloma (SMM). Recent appreciation of "high risk" smoldering myeloma and the advent of novel therapeutic agents may allow one to better tailor the timing of therapeutic interventions. Herein, we performed a systematic review of the literature, summarizing the available randomized controlled trial (RCT) evidence for treatment of SMM. Methods: Our systematic search strategy includes MEDLINE, EMBASE, Cochrane Database, and relevant bibliographies where the following search concepts were used: RCT, SMM as defined as per the IMW Criteria, and treatment. Two reviewers independently extracted data on study design, population, sample size, treatment, clinical outcomes, and trial quality, were any discrepancies were discussed and resolved. Results: We identified 7 RCTs (2 articles and 5 abstracts) representing 869 patients. Six articles compared early versus deferred treatment for SMM; 2 studies compared early Melphalan plus Prednisone (MP) versus deferred MP. 3 studies compared bisphosphonates versus abstention while one study compared lenalidomide with dexamethasone to therapeutic abstention. Further, one study compared thalidomide with zoledronate to zoledronate alone. The median age is 66. Four studies received a Jadad score of 3 while three studies received a score of 2. Allocation concealment was described in four studies. Risk of disease progression was lower in patients receiving therapy compared to abstention OR 0.5(0.38-0.68). The events that demonstrate disease progression were not clearly defined. Further, the use of combination therapy compared to a single intervention decreased the risk of progression OR 0.23(0.11-0.51). No difference in OS was noted in patients receiving therapy compared to abstention OR 0.95(0.57-1.57). Conclusions: Early treatment of SMM compared with abstention decreases the risk of disease progression. However, OS was not improved by earlier intervention. High risk SMM may benefit from early intervention. The optimal intervention(s) remains to be defined, and further studies are warranted in this understudied population.
Long-term trends in death and dependence after ischaemic strokes: A retrospective cohort study using the South London Stroke Register (SLSR)
Authors: Hatem A. Wafa, Charles D. A. Wolfe, Ajay Bhalla, Yanzhong Wang
Journal: PLoS Medicine (2020)

There have been reductions in stroke mortality over recent decades, but estimates by aetiological subtypes are limited. This study estimates time trends in mortality and functional dependence by ischaemic stroke (IS) aetiological subtype over a 16-year period.The study population was 357,308 in 2011; 50.4% were males, 56% were white, and 25% were of black ethnic backgrounds. Population-based case ascertainment of stroke was conducted, and all participants who had their first-ever IS between 2000 and 2015 were identified. Further classification was concluded according to the underlying mechanism into large-artery atherosclerosis (LAA), cardio-embolism (CE), small-vessel occlusion (SVO), other determined aetiologies (OTH), and undetermined aetiologies (UND). Temporal trends in survival rates were examined using proportional-hazards survival modelling, adjusted for demography, prestroke risk factors, case mix variables, and processes of care. We carried out additional regression analyses to explore patterns in case-fatality rates (CFRs) at 30 days and 1 year and to explore whether these trends occurred at the expense of greater functional dependence (Barthel Index [BI] < 15) among survivors. A total of 3,128 patients with first-ever ISs were registered. The median age was 70.7 years; 50.9% were males; and 66.2% were white, 25.5% were black, and 8.3% were of other ethnic groups. Between 2000-2003 and 2012-2015, the adjusted overall mortality decreased by 24% (hazard ratio [HR] per year 0.976; 95% confidence interval [CI] 0.959-0.993). Mortality reductions were equally noted in both sexes and in the white and black populations but were only significant in CE strokes (HR per year 0.972; 95% CI 0.945‒0.998) and in patients aged ≥55 years (HR per year 0.975; 95% CI 0.959‒0.992). CFRs within 30 days and 1 year after an IS declined by 38% (rate ratio [RR] per year 0.962; 95% CI 0.941‒0.984) and 37% (RR per year 0.963; 95% CI 0.949‒0.976), respectively. Recent IS was independently associated with a 23% reduced risk of functional dependence at 3 months after onset (RR per year 0.983; 95% CI 0.968-0.998; p = 0.002 for trend). The study is limited by small number of events in certain subgroups (e.g., LAA), which could have led to insufficient power to detect significant trends.Both mortality and 3-month functional dependence after IS decreased by an annual average of around 2.4% and 1.7%, respectively, during 2000‒2015. Such reductions were particularly evident in strokes of CE origins and in those aged ≥55 years.
Dissecting the link between nanoparticle lung effects and tumor markers with CD24 measurements.
Authors: Anwaar Mohammed Saeed, Ammar Ali Alkhazna, Agostino Molteni, Tim Quinn, Betty Herndon
Journal: Journal of Clinical Oncology (2012)

e21085 Background: It was postulated that carbon nanoparticles (CN) induced mesothelioma-like changes equal to asbestos in mice. We investigated CN added to human mesothelial cells in culture and reported that CN-induced cell damage to untransformed human mesothelial cells is rapidly followed by secretion of tumor markers like mesothelin and osteopontin. In vivo in animals, our group quantifies CN lung damage by HMGB1, an intranuclear protein released into alveolar lavage after CN exposure. Recent work suggests that the cell surface marker CD24 associates with HMGB1 to blunt lung responses to damage (like CN), but does not blunt cell response to pathogen-released HMGB1. Since CD24 is also a known cancer marker, elevated in many malignancies, we hypothesized that the cellular change elicited by CD24 when coupled with a damage marker would offer a mechanism through which CN could produce –repeated over time—malignant change in exposed human mesothelial cells. Such expression would support our previous research efforts. Methods: Untransformed human mesothelial cells were cultured and then stimulated or not with a CN dose giving 80% cell viability. At 24, 48 &amp; 72 hr cells were fixed and stained with anti-CD 24. Presence of positive stain was photographed and counted. CN exposed and control rat lungs were harvested and frozen at 0.5 hr, 3 hr, 24 hr and 4 weeks. Western blot and immunostaining (with Anti-CD24 antibody and mucin chemical stain) was used to measure CD24 levels. Results: In CN-exposed animals, CD24 was highest at 24 hr. Mucin presence confirms the CD24 staining. Homogenates by Western blot also showed highest CD24 reactivity at 24 hr. In CN-exposed cultured cells, at 48 hr, some anti-CD24 staining was seen and at 72 hr in clusters of hyperproliferating cells, strong CD24 stain was seen. Conclusions: Our data suggest, as shown by a second cellular marker CD24, that the mesothelin upregulation seen in our previous studies indicated a cellular change beyond necrosis. Nanoparticles at a dose producing 20% cell death induce this change in healthy human mesothelial cells in culture.