tbuckley/cabot-search huggingface dataset:
Treatment-emergent adverse events (TEAEs) in lenalidomide (LEN)-treated Low-/Int-1-risk myelodysplastic syndromes (MDS) patients (pts) without del(5q) ineligible for or refractory to erythropoiesis-stimulating agents (ESAs).
Authors: Antonio Medina Almeida, Pierre Fenaux, Guillermo Garcia-Manero, Aristoteles Giagounidis, Stuart Goldberg, Stefanie Gröpper, Anna Jonasova, Ghulam J. Mufti, Guillermo F. Sanz, Norbert Vey, Carmen Castaneda, Jianhua Zhong, C L. Beach, Valeria Santini
Journal: Journal of Clinical Oncology (2016)

7061 Background: In the phase 3 MDS-005 study of LEN in RBC transfusion-dependent lower-risk non-del(5q) MDS pts ineligible for or refractory to ESAs, a significantly higher proportion of LEN-treated pts achieved RBC transfusion independence ≥ 8 weeks vs placebo (P< 0.001). Here, we describe frequency, timing, and management of TEAEs in pts from MDS-005. Methods: AEs of all 160 pts randomized to LEN who received ≥ 1 dose were reported per NCI-CTCAE v3.0. Results: Median duration of LEN treatment was 164 days (range 7–1,158). Grade (G)1/2 and G3/4 TEAEs were reported in 96.9% and 86.3% of pts, respectively. The most common G3/4 TEAEs were neutropenia (61.9%), thrombocytopenia (35.6%), anemia (5.6%), pneumonia (5.6%); G3/4 deep vein thrombosis (DVT) occurred in 1.9%. G3/4 neutropenia and thrombocytopenia generally occurred in cycles 1–4. The most common G1/2 TEAEs were diarrhea (42.5%), constipation (22.5%), asthenia (21.9%), rash (21.3%), fatigue (20.6%), peripheral edema (20.6%). TEAEs led to 54.4% dose interruptions, 6.3% dose reductions, and 42.5% dose interruptions with subsequent reduction. Median time to first dose interruption or reduction was 57 days (range 6–504). The most common reasons for dose reduction following interruption were neutropenia (25.0%) and thrombocytopenia (16.3%); 1.9% of pts due to rash. TEAEs led to LEN discontinuation in 31.9% of pts; the most common reasons were thrombocytopenia (8.8%), neutropenia (4.4%), DVT (1.9%). In this short follow-up period, no increased incidence of AML or secondary primary malignancies was seen. Conclusions: LEN has a predictable and manageable TEAE profile in this pt population. Diarrhea was the most common G1/2 TEAE; G1/2 TEAEs generally did not require dose reduction or discontinuation. The most common G3/4 TEAEs were neutropenia and thrombocytopenia; these occurred early and, in the majority of pts, reverted with dose reductions or interruptions, avoiding the need for discontinuation. The timing and characterization of TEAEs highlights the importance of frequent monitoring at the start of therapy. Clinical trial information: NCT01029262.
New insights suggesting a possible role of a heat shock protein 70-kD family-related protein in antigen processing/presentation phenomenon in humans
Authors: GC Manara, P Sansoni, L Badiali-De Giorgi, G Gallinella, C Ferrari, V Brianti, FF Fagnoni, CL Ruegg, G De Panfilis, G Pasquinelli
Journal: Blood (1993)
EGFR signal activated HIF-1α/survivin pathway is important for the progression of breast cancer
Authors: Prasanthi Karna, Zehong Cao, Lily Yang
Journal: Clinical Cancer Research (2007)

B43  To identify cellular factors that are critical for breast cancer development from premalignant to malignant, we have examined the MCF10 series of cell lines as model systems for the in vitro and in vivo studies. Our previous study found that epidermal growth factor (EGF) stimulation increased the level of expression of the inhibitor of apoptosis protein survivin in breast cancer cells but not in normal mammary epithelial cells. Activation of survivin gene expression is mediated by oxygen-independent hypoxia-inducible factor (HIF)-1α upregulation in EGF-treated cancer cells. As the cells transform to premalignant, DCIS and invasive breast carcinoma, the survivin expression was increased. However, the highest levels of EGFR and HIF-1α were detected in premalignant MCF10 AT1 and MCF10 DCIS, suggesting that EGFR and HIF-1α signal may be critical for the early stage of breast cancer development. Our in vivo and in vitro studies using tyrosin kinase inhibitor Erlotinib that blocks the EGFR signal showed that the levels of HIF-1α/survivin and growth of DCIS xenografts was significantly inhibited. Recent experimental and clinical evidence shows that CD44 is upregulated in breast cancer and is involved in cancer cell proliferation, migration and invasion, as well as tumor associated angiogenesis and are correlated with patient survival. In breast cancer, CD44+ progenitor cells were found to be more tumorogenic compared to CD44- cells. In our study we found that the percentage of cells showing coexpression of CD44 and survivin were increased according to the stages of cell transformation. Targeting tumors of individual patients expressing high CD44 and active EGFR induced HIF-1/survivin pathway will create an opportunity for improved personalized treatment.
Dysregulation of Membrane-Bound Tumor Necrosis Factor-α and Tumor Necrosis Factor Receptors on Mononuclear Cells in Human Immunodeficiency Virus Type 1 Infection: Low Percentage of p75-Tumor Necrosis Factor Receptor Positive Cells in Patients With Advanced Disease and High Viral Load
Authors: Kjetil Hestdal, Pål Aukrust, Fredrik Müller, Egil Lien, Vigdis Bjerkeli, Terje Espevik, Stig S. Frøland
Journal: Blood (1997)
Abstract 344: Finding the Achilles’ heel of Muscle Giant---TALEN-mediated Gene-editing in Zebrafish Titin
Authors: Yu-Huan Shih, Xiaolei Xu
Journal: Circulation Research (2015)

Background: TITIN (TTN) has more than 300 exons and encodes a gigantic protein that is crucial for heart and muscle development. Mutations in TTN caused a variety of human diseases including cardiomyopathy and muscular dystrophy. Recently, dilated cardiomyopathy-associated mutations on TTN have been found more frequently in exons encoding A-band domains but less in exons encoding the N-terminal Z-disc domains, suggesting that mutations in different exons of TTN cause distinct consequences. To elucidate the underlying mechanisms, we leveraged the Transcription Activator-Like Effects Nuclease (TALEN) technology in zebrafish to introduce truncating mutations in different exons of ttn, and then study their effects on heart and somites. Results: We generated truncational mutations in different exons of zebrafish titins encoding Z-disc, N2B, Novex-3, and A domains, respectively. Because zebrafish contains two titin homologues, ttna and ttnb, we introduced mutations in both genes at the corresponding loci. While both Z-disc and A band mutations on ttna disrupted sarcomere assembly in heart and somites, Z-disc or A band mutations on ttnb only affect somites without affecting the heart. Interestingly, a Z-disc mutation on ttna resulted in milder phenotypes than an A-band mutation, while a Z-disc mutation on ttnb generated severer phenotypes than an A-band mutation. No phenotype was observed in the homozygous fish in either ttna-novex-3 or ttnb-N2B mutant fish. Conclusions: A spectrum of truncational mutations in ttna and ttnb has been generated in zebrafish using the TALEN technology. Mutations in different exons result in different phenotypes. Detailed characterization of these mutants and double mutants will be presented, which shall elicit distinct contribution of alternative splicing and exon skipping as two candidate mechanisms during pathogenesis of Titinopathies.
Losing Weight During the Postpartum Period
Authors: Adam Gilden Tsai, Wanda K. Nicholson
Journal: JAMA (2017)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Evaluation of mutation in BRCA1 gene with clinico-pathological features among the breast cancer patients of eastern India.
Authors: Abhijit Chakraborty, Jayasri Basak, Ashis Mukhopadhyay
Journal: Journal of Clinical Oncology (2016)

e13114 Background: BRCA1 gene mutations immensely increase the risk of developing breast cancer (BC) among women. The motivation behind this study was to focus on the pathological aspects of BC patients with and without a BRCA1 mutation, and to study in detail the clinical diversities in Eastern Indian population. Methods: The clinical characteristics of 231 BC patients along with tumor size, grade, lympho-vascular invasion LVI, estrogen receptor (ER) and progesterone receptor (PR) expression and Her2/neu status were studied. BRCA1 mutation was detected by multiplex PCR, AS-PCR and direct sequencing. Functional effects of mutations were confirmed by in-silico analysis and m-RNA folding. Results: Out of 231 patients (age range: 26–77 years) with family history (FH) (130 individuals) and without FH (101 individuals) were screened. Average age of 231 patients was 48.40±11.32 years. We found 58.44% patients experienced early onset of disease ( < 45yrs). The two founder mutations 185delAG in BRCA1 and 6174delT in BRCA2 were not found in any of the subjects. In total, 18 (7.79%) genetic alterations were identified: 5382insC (n = 7); c.5237A > C (n = 1); c.5210 G > A (n = 1); UTR-17ins g (n = 3); UTR -17ins g and UTR-13g > c (n = 2), UTR-13g > c (n = 1), c.75C > A (n = 1) and c.4675+1G > A (n = 1). The mutations, c.5237A > C and c.5210G > A are novel missense mutation as these have not yet been reported. One novel frameshift mutation (c.4495GC > C) was also identified. We also found that tumor histology; grade, size and Her2/Neu over expression were significantly associated with ER/PR status. FH and laterality of BC identiﬁed in BRCA1 carriers was signiﬁcantly higher than in non-carriers. There was a signiﬁcant increase in the patients with menarche before 13 years of age (p < 0.01, OR: 2.39; CI: 1.26-4.29) Conclusions: Our data confirm a noticeable contribution of BRCA1 mutation in BC development and establishes a correlation between the BRCA1 mutations with clinical characteristics. It also shown that genetic and clinical factors are mainly responsible for systematic progression. The data may be used to tailor the management of patients with BC with the aim of minimizing as much as possible diagnostic and therapeutic procedures.
Risk of Primary Tumor Sidedness as a Criterion for Screening, Diagnostic Colonoscopy, and Surveillance Intervals—Reply
Authors: Gianluca Tomasello, Fausto Petrelli, Sandro Barni
Journal: JAMA Oncology (2017)

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 Oncology 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 Oncology journal
Geographic variation in the adoption rate of partial nephrectomy over radical nephrectomy for the treatment of malignant renal neoplasm.
Authors: Khawaja Hassan Bilal, Mark Finkelstein, Michael Palese
Journal: Journal of Clinical Oncology (2016)

e13066 Background: Studies have shown that an increasingly greater proportion of renal malignancy cases are now being treated by partial nephrectomy (PN) rather than radical nephrectomy (RN). This study observed the adoption rate of PN over RN in different health service areas (HSAs) for the treatment of malignant neoplasm of the kidney, over the past 31 years in New York State (NYS). Methods: The study was a retrospective cohort study of 50,953 cases between 1982-2012, from the Statewide Planning And Research Cooperative System database. Patient records matching the diagnosis of malignant renal neoplasm (ICD9:18.90) were extracted and separated by surgical procedure, RN (ICD9 55.5, N = 39,318) and PN (ICD9 55.4, N = 11,365). The records were organized based on the facility zip code and grouped into 8 individual HSAs. The compound annual growth rate (CAGR) was calculated for the number of PN and RN procedures occurring in each of the HSAs between 1982-2012. The total ancillary charges were compared for all patients. Results: The frequency of both PN and RN increased over the past three decades however, the CAGR of PN (13.76% per year) was significantly higher than the CAGR of RN (1.68% per year). Moreover, HSAs were not equal in their adoption of PN over RN. NYC (HSA-7) had the fastest growth rate in the state and thus in 2007, the number of renal malignancy cases treated by PN, surpassed the number of RN procedures. In all other areas of NYS, the number of cases treated by PN remained relatively equal to the number of cases treated by RN. Also of note was the fact that in 2012 the average ancillary fees of PNs ($34,610) was $4,839 greater than the average ancillary fee of RNs ($29,770), in NYC (N = 2,289, p = < 0.001). Conclusions: Our results show that there is geographical variation in the adoption rates of PN over RN. Facilities in NYC have been at the fore-front of adopting PN for the treatment of malignant renal neoplasm, and since 2007 it has replaced RN as the primary treatment choice. Significantly greater ancillary charges were observed for patients who underwent PN compared to RN, in NYC. As more and more RN procedures are replaced by PN, the implications for the health care costs will have to be studied further.
Do lung cancer screening age criteria represent a missed opportunity for early detection in Kentucky?
Authors: Raymond Elsoueidi, Jaclyn Nee, Agnes Caudill, Mark Dignan
Journal: Journal of Clinical Oncology (2016)

e13073 Background: Recent data support using low-dose computed tomography scan of the chest to screen patients who are at high risk for lung cancer. Most recommendations rely on National Lung Screening Trial risk criteria for selecting individuals for screening. However, it has been shown that selecting individuals for screening based on accurate lung cancer risk prediction models is significantly more sensitive in detecting individuals who will be diagnosed with lung cancer. Kentucky has the highest incidence of lung cancer in the United States. In order to see the number of patients who would benefit from current lung cancer screening we reviewed the lung cancer population characteristics in Kentucky. Methods: Data of patients diagnosed with lung cancer in the state of Kentucky between 2009 and 2013 were obtained from Kentucky cancer registry. Age, sex, stage, medical insurance, smoking history, family history and residence were reviewed and data was analyzed using Z-test. Results: Between the years of 2009 and 2013 a total of 17469 patients were diagnosed with lung cancer. Among these 2428 (13.9%) patients were younger than 55 years. 10431 (59.71%) patients were 55-74 years of age and 4610 (26.3%) patients were older than 75 years. The Surveillance Epidemiology and End Results (SEER) incidence of lung cancer in patients younger than 55 was 9.9%. Between 55 and 74 years it was 53.3% and 36.7% for age 75 and older. The Kentucky rates were higher than SEER for patients younger than 55 and those 55-74 years and lower for patients 75 and older and this was statistically significant for all age groups (p < .0001). When comparing stage, among 2428 patients younger than 55 years, a higher proportion (76.7%) were stage III and IV at diagnosis compared to (68.3%) of patients older than 55 which is also statistically significant (p < .0001). Conclusions: These results indicate a higher rates of lung cancer in patients younger than 55 years in Kentucky. Currently, patients younger than 55 years are not eligible for lung cancer screening; however some of them may benefit from screening. Further studies using different criteria to include this younger group would be helpful in the selection of appropriate individuals and saving more lives.
Piece of string can assess cardiovascular risk, study finds
Authors: J. Wise
Journal: BMJ (2015)

Measuring a person’s waist with a piece of string is a better predictor of cardiovascular risk than using body mass index (BMI) alone, researchers have said.

A study published at the European Congress on Obesity in Prague this week supported the finding that a person was at lower cardiovascular risk if they kept their waist measurement to less than half their height measurement.1 This could be done by personnel with minimal training and resources by …
Industrial Fluorosis: A Study of the Hazard to Man and Animals Near Fort William, Scotland.
Authors: J. N. Agate, G. H. Bell, G. F. Boddie, R. G. Bowler, M. Buckell, E. A. Cheeseman, T. H. J. Douglas, H. A. Druett, J. Garrad, D. Hunter, K. M. A. Perry, J. D. Richardson, J. B. De V. Weir
Journal: Annals of Internal Medicine (1949)
Abexinostat (ABX) as a means to reverse pazopanib (PAZ) resistance: A phase 1 study in advanced solid tumor malignancies.
Authors: Rahul Raj Aggarwal, Scott Thomas, Jennifer A. Grabowsky, Armand Harb, Jim Leng, Anne Reinert, Ilaria Mastroserio, Thach-Giao Truong, Pamela N. Munster
Journal: Journal of Clinical Oncology (2016)

2519 Background: PAZ is a tyrosine kinase inhibitor of VEGFR approved for use in renal cell carcinoma (RCC). ABX is a potent pan-HDAC inhibitor (HDACi). Pre-clinical models suggest that HDACi-mediated epigenetic modulation of VEGF expression prevents PAZ resistance and potentiates efficacy. We therefore designed a Phase I clinical trial combining ABX with PAZ in pts with advanced solid tumors with an expansion cohort in RCC. Methods: The primary endpoint was the maximal tolerated dose (MTD) of PAZ plus ABX. Secondary endpoints included pharmacokinetics (PK) and efficacy. PAZ was dosed days 1-28 and ABX days 1-5, 8-12, and 15-19 of 28-day cycle (schedule A) with at a starting dose of 400 mg/day and 45 mg/m2orally twice daily respectively. An alternate ABX dosing schedule days 1-4, 8-11, and 15-18 was investigated (schedule B) due to toxicity of Schedule A. Results: 52 patients (pts) (RCC; N = 23) with advanced solid tumors were enrolled (N = 22 schedule A; N = 30 schedule B). There were six dose-limiting toxicities including fatigue (N = 2), thrombocytopenia (N = 2), and elevated AST/ALT (N = 2). The most common grade ≥ 3 related adverse events observed were fatigue (13%), thrombocytopenia (12%), and diarrhea (10%). The MTD was PAZ 800 mg/day + ABX 45 mg/m2 BID on schedule B. 8 evaluable pts (19%) (N = 6 RCC; 2 thyroid) achieved partial tumor response (PR), with median duration of response of 9.2 months (1-33.2+). 7/9 (78%) of pts with prior disease progression on PAZ monotherapy had reduction in tumor burden on study. 15 out of 48 evaluable pts (31%) experienced stable disease or better for ≥ 6 months, and two previously PAZ-refractory pts with PRs remain on study for > 20 and 37 mos respectively. PK analyses did not reveal drug-drug interaction. Analyses of histone acetylation, circulating tumor DNA, and plasma metabolomic profile are ongoing. Conclusions: The combination of PAZ + ABX was well tolerated and durable tumor control ( > 3 yrs) was observed in RCC and thyroid cancer. Tumor regressions observed in majority of PAZ-refractory tumors preliminarily support the potential of ABX to reverse therapeutic resistance. A randomized phase 2 study with cross-over design is planned to further evaluate the combination of PAZ + HDACi. Clinical trial information: NCT01543763.
Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT
Authors: Eolia Brissot, Myriam Labopin, Matthias Stelljes, Gerhard Ehninger, Rainer Schwerdtfeger, Jürgen Finke, Hans-Jochem Kolb, Arnold Ganser, Kerstin Schäfer-Eckart, Axel R. Zander, Donald Bunjes, Stephan Mielke, Wolfgang A. Bethge, Noël Milpied, Peter Kalhs, Igor-Woflgang Blau, Nicolaus Kröger, Antonin Vitek, Martin Gramatzki, Ernst Holler, Christoph Schmid, Jordi Esteve, Mohamad Mohty, Arnon Nagler
Journal: Journal of Hematology & Oncology (2017)

Primary refractory acute myeloid leukemia (PRF-AML) is associated with a dismal prognosis. Allogeneic stem cell transplantation (HSCT) in active disease is an alternative therapeutic strategy. The increased availability of unrelated donors together with the significant reduction in transplant-related mortality in recent years have opened the possibility for transplantation to a larger number of patients with PRF-AML. Moreover, transplant from unrelated donors may be associated with stronger graft-mediated anti-leukemic effect in comparison to transplantations from HLA-matched sibling donor, which may be of importance in the setting of PRF-AML. The current study aimed to address the issue of HSCT for PRF-AML and to compare the outcomes of HSCT from matched sibling donors (n = 660) versus unrelated donors (n = 381), for patients with PRF-AML between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. HSCT provide patients with PRF-AML a 2-year leukemia-free survival and overall survival of about 25 and 30%, respectively. In multivariate analysis, two predictive factors, cytogenetics and time from diagnosis to transplant, were associated with lower leukemia-free survival, whereas Karnofsky performance status at transplant ≥90% was associated with better leukemia-free survival (LFS). Concerning relapse incidence, cytogenetics and time from diagnosis to transplant were associated with increased relapse. Reduced intensity conditioning regimen was the only factor associated with lower non-relapse mortality. HSCT was able to rescue about one quarter of the patients with PRF-AML. The donor type did not have any impact on PRF patients’ outcomes. In contrast, time to transplant was a major prognostic factor for LFS. For patients with PRF-AML who do not have a matched sibling donor, HSCT from an unrelated donor is a suitable option, and therefore, initiation of an early search for allocating a suitable donor is indicated.