tbuckley/cabot-search huggingface dataset:
Five-year longitudinal mammographic follow-up after breast cancer.
Authors: Laura Bruce, Jessica Kerns, W. Bradford Carter, Thomas G. Frazier
Journal: Journal of Clinical Oncology (2019)

37 Background: Breast Cancer recurrences following radiation are seen in the first three to five years after treatment. As part of our Survivorship Program, annual screening mammography is a guideline following treatment with the exception of those patients who undergo bilateral mastectomy. To evaluate compliance with this guideline, we followed patients treated in 2012 for breast cancer at our institution, over the five-year period through 2017. Methods: A retrospective chart review of patients diagnosed with breast cancer in 2012 was conducted and annual mammography was assessed for compliance for a period of five-years. Compliance was defined as having annual mammography screening for five years, until recurrence or until death. Results: 252 patients were treated for Breast Cancer in 2012. Of these, 15 patients had follow-up elsewhere. 4 patients had metastatic disease at the time of diagnosis and were not included. 3 patients with male breast cancer had no mammographic follow-up. 5 patients had bilateral mastectomies and were excluded leaving 225 patients followed for compliance. Of the 225 evaluable patients, 134 (59.5%) were compliant with mammography. 126 (56.0%) had a full five years of follow-up and had no recurrent breast cancer. 158 (70.2%) had four years of follow-up. 168 patients (74.7%) had three years of follow-up. 178 (79.1%) had two years of follow-up. 190 (84.4%) had at least one year of follow-up. 14 (6.2%) died before the five year follow-up of causes not related to breast cancer. 7 (3.1%) developed metastatic disease during follow-up and no additional mammography was carried out. 7 had ipsilateral recurrence, 3 had contralateral recurrence (4.4%). Conclusions: In an upper-middle class population that is well insured and should be compliant, only 59.5% of eligible patients were compliant with mammography for five-years, until recurrence or death. Since almost 5% of patients in this cohort recurred in the breast, follow-up with annual mammography is critical. The Survivorship Care Plan (SCP) discussion with the patient is a strategy to address compliance with annual follow-up. Future studies are planned to re-evaluate compliance with annual mammography.
Utility Of 9-Color, 11-Parameter Flow Cytometry For Detection Of Plasma Cell Neoplasms: A Comparison With Bone Marrow Morphologic Findings and Concurrent M-Protein Studies In Serum and Urine
Authors: Amir Behdad, Charles Warren Ross, Joshua Jacques, Usha Kota, Noah A. Brown, David Keren, Lloyd Stoolman
Journal: Blood (2013)
Risk Factors of Thromboembolic Disease in Men with Prostate Cancer: Report from a Hispanic Population
Authors: Rodrigo Luna-Santiago, Maria T Bourlon, Ariel Jasqui-Bucay, Alan Jasqui-Bucay, Oscar Manuel Fierro-Angulo, Jesus A Garcia-Ramos, Guillermo Rosales-Sotomayor, Silvia Martiñon-Gutierrez, Hugo E Velazquez, Carlos A Castro, Christianne Bourlon
Journal: Blood (2018)
Vaccination with WT1 mRNA-Electroporated Dendritic Cells: Report of Clinical Outcome in 66 Cancer Patients
Authors: Zwi N. Berneman, Ann L. Van de Velde, Yannick Willemen, Sébastien Anguille, Kirsten Saevels, Paul Germonpré, Manon T. Huizing, Marc Peeters, Annemie Snoeckx, Paul Parizel, Viggo F Van Tendeloo, Eva Lion, Griet Nijs, Barbara Stein, Katrien Vermeulen, Marie-Berthe Maes, Ronald Malfait, Inge Vrelust, Anke Verlinden, Alain P. Gadisseur, Wilfried A Schroyens, Martin Lammens, Evelien L. Smits
Journal: Blood (2014)
Abstract 152: Tip60 Depletion Promotes Cardiomyocyte Proliferation and Attenuates Ischemic Injury in the Adult Heart
Authors: Xinrui Wang, Tina C Wan, Carri Lupton, Mitchell Harrison, John Lough, John A Auchampach
Journal: Circulation Research (2019)

The pathogenesis of myocardial infarction (MI) is largely attributed to the loss of cardiomyocytes (CMs) and their insufficient regeneration. Inducing the proliferation of pre-existing CMs has emerged as a potential therapeutic strategy for cardiac repair. Results in our laboratory indicate that Tip60 (Tat-interactive protein 60 kD), a pan-acetylase protein encoded by the Kat5 gene, inhibits CM proliferation consequent to its induction of the DNA damage response (DDR) at neonatal stages, which has recently been shown to cause CM replicative senescence. To determine whether Tip60 depletion permits re-entry of adult CMs into the cell-cycle and confers protection from MI, we are employing a line of Kat5 flox/flox mice wherein Tip60 is conditionally and specifically depleted in CMs via tamoxifen-induced activation of a Myh6 -driven merCremer transgene. In uninjured hearts, Tip60 depletion results in transient thickening of the left ventricular walls, accompanied by markedly increased expression of G 2 /M-phase cell cycle regulators (cyclins A2 &amp; B1, Cdk1) and de-differentiation markers (Myh7, Osm, OsmR, Runx1), diminished CM size, decreased expression of cell-cycle inhibitors (p27, Meis1), and remarkable increases in Ki67 and pH3-positive CMs as well as non-CMs. In hearts infarcted by permanent ligation, tamoxifen administration increases fractional shortening, ejection fraction, and anterior wall thickening within 7 days, conditions that are sustained for at least 18 additional days, when reduced scarring is indicated by trichrome staining. Taken together, these results indicate that Tip60 depletion in adult heart may preserve cardiac performance after MI by inducing CM regeneration. These findings should help advance our understanding of the molecular mechanisms that keep CMs in replicative senescence, establishing a possible therapeutic target for maintaining and restoring cardiac muscle after MI.
Recurrent Venous Thromboembolism (VTE), Major Bleeding (MB), and Associated Cost of Treatment with Low Molecular Weight Heparin (LMWH) or Direct Oral Anticoagulant (DOAC) in High Risk Patients with Gastrointestinal (GI) Malignancies: Retrospective Real-World Analysis at a Comprehensive Cancer Center
Authors: Alejandro Recio Boiles, Ali McBride, Hani M. Babiker, Nimer Alsaid, Ivo Abraham, Emad Elquza
Journal: Blood (2018)
Abstract 108: Reactivation of Myc Transcription in the Heart Unlocks its Proliferative Capacity
Authors: Catherine H Wilson, Megan J Bywater, Deborah L Burkhart, Arianna Sabò, Jasmin Straube, Vera Pendino, James E Hudson, Gregory A Quaife-Ryan, Enzo R Porrello, Theresia R Kress, Bruno Amati, Trevor D Littlewood, Gerard I Evan
Journal: Circulation Research (2019)

It is unclear why some tissues are refractory to the mitogenic effects of the pleiotropic transcription factor Myc, even when its expression is deregulated. We have developed an in vivo model permitting determination of the early transcriptional consequences of Myc activation across all tissues of an adult mouse. Myc activation induces rapid transcriptional responses, followed by cell proliferation in some, but not all, organs. Despite such disparities in proliferative response, Myc bound DNA at open promotor and enhancer elements, in representative responsive (liver) and non-responsive (heart) tissues, but failed to induce a robust transcriptional and proliferative response in the heart. Therefore, the determinants of transcriptional responsiveness are distinct from chromatin state and DNA binding by Myc. Using heart as an exemplar of a non-responsive tissue, we show that Myc-driven transcription may be re-engaged in mature cardiomyocytes by elevating levels of the P-TEFb, instating a profound proliferative response to Myc. These data indicate that the cardiac epigenomic architecture does not preclude Myc binding to E-boxes; rather, it is the inability of Myc to drive transcriptional output from Myc target genes that thwarts cardiomyocyte proliferation. Hence, P-TEFb activity is a key limiting determinant of whether or not an individual tissue is permissive for Myc transcriptional activation and mitogenesis. These data provide not only a greater understanding of how Myc transcriptional activity is determined in cellular contexts, they also indicate that modification of the expression levels of the transcriptional co-factor P-TEFb could be a means through which adult cardiomyocytes could be regenerated for the treatment of heart conditions.
A New Therapeutic Hypothesis: Nonsense-Mediated Decay Is an Exploitable Target in Multiple Myeloma
Authors: Alexander Leeksma, Ingrid A.M. Derks, Brett Garrick, Torsten Trowe, Aldo Jongejan, Perry Moerland, Arnon P. Kater, Eric Eldering, Ellen Filvaroff
Journal: Blood (2018)
Feasibility of High Doses Peg-Asparaginase Administration in a Cohort of Adult Acute Lymphoblastic Leukemia Patients
Authors: Paola Minetto, Nadia Bisso, Fabio Guolo, Marino Clavio, Riccardo Marcolin, Filippo Ballerini, Maurizio Miglino, Marco Gobbi, Roberto Massimo Lemoli
Journal: Blood (2018)
Abstract 519: Desmin Protects Cardiomyocyte Nuclei From Microtubule-dependent Collapse
Authors: Julie Heffler, Parisha P Shah, Patrick Robison, Sai Phyo, Kimberly Veliz, Alexey Bogush, Joshua Rhoades, Rajan Jain, Benjamin L Prosser
Journal: Circulation Research (2019)

Alterations to mechanical forces have been long-appreciated to be sufficient to drive cardiac pathophysiological remodeling; however, the mechanism by which cardiomyocytes sense and transduce mechanical stressors remains poorly understood. In part, mechanical forces can be transduced to transcriptional responses by direct strain transmission to the nucleus via the Linkers of the Nucleo- and Cytoskeleton (LINC) complex, which couples the cytoskeleton to the nuclear lamina and DNA. While LINC complex mutations are known to cause cardiomyopathy, cytoskeletal-LINC interactions are understudied in the cardiomyocyte. To probe these interactions, we acutely disrupted the LINC complex as well as microtubules, actin, and intermediate filaments and assessed the consequences on baseline nuclear homeostasis in the cardiomyocyte. Our result show that a balance of microtubules and desmin intermediate filaments is required to maintain nuclear shape and the fidelity of the nuclear envelope and lamina. Upon acute depletion of desmin (or Nesprin-3, its binding partner in the LINC complex), microtubules drive infolding of the nuclear membrane. This results in DNA damage, a loss of genome organization, and broad transcriptional changes. Desmin knockdown also causes compromised excitation-contraction coupling and contractile function. Together, our data suggest that a balance of forces imposed by intermediate filaments and microtubules is required to maintain nuclear structure and genome organization in the cardiomyocyte, and that this process is important for maintaining proper myocyte health and function.
A systematic approach for high-quality care in complex malignant hematology.
Authors: C. Tom Kouroukis, Christopher Bredeson, Aaron Pollett, Elaine Meertens, Julia Monakova, Jonathan Wang, Jennifer Hart, Hasmik Beglaryan, Lesley Moody, Sherrie Hertz
Journal: Journal of Clinical Oncology (2019)

57 Background: Capacity limits in Ontario, Canada, resulted in long waits and out-of-country care for hematopoietic cell therapy (HCT) and inconsistent access for acute leukemia (AL) patients. A multi-pronged system improvement approach was implemented to ensure high quality care as close to home as possible. Methods: Robust forecasting models and physician workload benchmarks were developed to quantify needs and drive health human resource and capital planning. Clinical and organizational guidelines were developed for new models of care, pathology and laboratory medicine services, and networks of care. Funding models were introduced to support care needs and service models. A comprehensive measurement strategy, including patient reported experience measures, was developed. Results: Six services sites providing HCT and AL care are networked with four AL sites and three supporting sites. Capital expansion projects have been completed and others continue. Two biomarker reference centers were established to serve as quality leads and ensure timely testing. Average turnaround time is 12 days for cytogenetic testing. 19 additional physician specialists and 5 additional fellowships were approved for allocation across Ontario. Three nurse practitioners participated in mentorship programs. Access has improved and wait times are monitored. In 2018 there were 736 autologous and 357 allogeneic transplants done vs 396 and 159 respectively in 2014. 43 patients were referred out of country in 2016 compared with two in 2018, with a median wait of 70 days from AL remission to transplant in 2018. Nine (of 14) regional cancer centers offer outpatient AL consolidation. Patient experience was highest in treatment planning, physical comfort and patient preferences. Conclusions: A multi-pronged approach to planning, funding and quality assurance resulted in measureable increased capacity and high quality care closer to home.
Genetic Alterations of the MHC Class II Transactivator CIITA Are Frequent in Primary Mediastinal Large B-Cell Lymphoma and Associated with Diminished MHC Class II Expression
Authors: Anja Mottok, Bruce W. Woolcock, Fong Chun Chan, Adele Telenius, Elizabeth A. Chavez, Merrill Boyle, Susana Ben-Neriah, Lisa M. Rimsza, Reiner Siebert, Randy D. Gascoyne, Christian Steidl
Journal: Blood (2014)
P14.47 Tissue immune markers for central nervous system germinoma
Authors: A K CHAN, Z F Shi, K W Lo, H K Ng, C C Lau
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Germinoma is the commonest CNS germ cell tumor. An important histological feature is prominent immune cell infiltrates. The composition of such immune cell infiltrates remains under-investigated in the literature. MATERIAL AND METHODS We collected a cohort of 40 cases of intra-cranial germinomas and examined the clinical and histopathological features. The tumor infiltrating immune cells were characterized by immunohistochemistry and image analysis. RESULTS Across the cohort, the mean positivity ± SE of CD3-positive T cell and CD20-positive B cells was 31.2% ± 3.1% and 15.2% ± 2.2%, respectively (p&lt;0.001). The mean positivity of CD4-positive T helper cell and CD8-positive cytotoxic T cell was 19% ± 2.3% and 14.3% ± 1.7%, respectively (p&lt;0.001). PD-L1 expression was detected in 50% of the cases and was observed exclusively in immune cells but not in neoplastic cells. Germinomas with positive PD-L1 expression had significantly more abundant CD3-positive T cells (p=0.001), CD4-positive T helper cells (p&lt;0.001) and CD8-positive cytotoxic T cells (p=0.004) as compared with those lacking PD-L1 expression. Immunostain for HLA-A and HLA-B revealed loss of HLA class I expression occurring in 92.5% of the germinomas. Loss of HLA class I expression was associated with less abundant CD3-positive T cells (p=0.04). CONCLUSION Taken together, the predominant T cells infiltrate and PD-L1 expression suggest anti-PD-L1 therapeutic agents as potential novel treatment option for germinoma patients. The loss of HLA class I may represent one of the mechanisms for tumor immune escape in germinoma.
Longitudinal Analyses of CXCR4dimCD5brCD19+ Fractions of Chronic Lymphocytic Leukemia Clones Reveal Features Consistent with a Source of Clonal Heterogeneity
Authors: Rajendra N Damle, Carlo Calissano, Sonal Temburni, Ryon M. Andersen, Steven L. Allen, Jonathan E. Kolitz, Kanti R. Rai, Nicholas Chiorazzi
Journal: Blood (2011)
Sequential VAD (Vincristine, Adriamycin, Dexamethasone) and VTD (Bortezomib, Thalidomide, Dexamethasone) Induction Followed by High-Dose Therapy with Autologous Stem Cell Transplantation and Maintenance Treatment with Bortezomib for Newly Diagnosed Multiple Myeloma: Final Analysis of Phase II Trial.
Authors: Sung-Soo Yoon, Hye Jin Kim, Joo Seop Chung, HyeonSeok Eom, Jun-Ho Jang, Hye Jin Kang, Cheol Soo Kim, Kihyun Kim, Dongsoon Lee, Jae Hoon Lee, Junglim Lee, Sang Jae Lee, Yoo Hong Min, Chu-Myong Seong, Sang-Kyun Sohn, Cheolwon Suh, Jong-Ho Won
Journal: Blood (2008)
Image Gallery: White piedra
Authors: E.A. Kumetz, S.C. Rivard
Journal: British Journal of Dermatology (2019)

DEAR EDITOR, A 25-year-old woman presented with white, soft casts adherent to her hair that developed during humanitarian work on the island of Tinian, western Pacific Ocean (a).She reported a perceived 'heaviness' of her hair, but was otherwise asymptomatic.Multiple hypopigmented bead-like nodules were observed on the distal hair shafts of the scalp (b).Hair clipping analysis confirmed the presence of periodic acid-Schiff positive hyphae and microscopic nodules comprised hyaline consistent with white piedra.A trial of topical benzoyl peroxide 5% wash, clindamycin 1% solution and ketoconazole 2% shampoo successfully treated the condition.For refractory cases, daily itraconazole treatment has been demonstrated to result in increased cure rates.
Prognostic factors associated with long-term mortality in 1445 patients with nontuberculous mycobacterial pulmonary disease: a 15-year follow-up study
Authors: Byung Woo Jhun, Seong Mi Moon, Kyeongman Jeon, O Jung Kwon, Heejin Yoo, Keumhee C. Carriere, Hee Jae Huh, Nam Yong Lee, Sung Jae Shin, Charles L. Daley, Won-Jung Koh
Journal: European Respiratory Journal (2019)

Limited data are available regarding the prognostic factors for patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the prognostic factors associated with long-term mortality in NTM-PD patients after adjusting for individual confounders, including aetiological organism and radiological form. A total of 1445 patients with treatment-naïve NTM-PD who were newly diagnosed between July 1997 and December 2013 were included. The aetiological organisms were as follows: Mycobacterium avium (n=655), M. intracellulare (n=487), M. abscessus (n=129) and M. massiliense (n=174). The factors associated with mortality in NTM-PD patients were analysed using a multivariable Cox model after adjusting for demographic, radiological and aetiological data. The overall 5-, 10- and 15-year cumulative mortality rates for the NTM-PD patients were 12.4%, 24.0% and 36.4%, respectively. On multivariable analysis, the following factors were significantly associated with mortality in NTM-PD patients: old age, male sex, low body mass index, chronic pulmonary aspergillosis, pulmonary or extrapulmonary malignancy, chronic heart or liver disease and erythrocyte sedimentation rate. The aetiological organism was also significantly associated with mortality: M. intracellulare had an adjusted hazard ratio (aHR) of 1.40, 95% CI 1.03–1.91; M. abscessus had an aHR of 2.19, 95% CI 1.36–3.51; and M. massiliense had an aHR of 0.99, 95% CI 0.61–1.64, compared to M. avium . Mortality was also significantly associated with the radiological form of NTM-PD for the cavitary nodular bronchiectatic form (aHR 1.70, 95% CI 1.12–2.59) and the fibrocavitary form (aHR 2.12, 95% CI 1.57–3.08), compared to the non-cavitary nodular bronchiectatic form. Long-term mortality in patients with NTM-PD was significantly associated with the aetiological NTM organism, cavitary disease and certain demographic characteristics.
Monalizumab: inhibiting the novel immune checkpoint NKG2A
Authors: Thorbald van Hall, Pascale André, Amir Horowitz, Dan Fu Ruan, Linda Borst, Robert Zerbib, Emilie Narni-Mancinelli, Sjoerd H. van der Burg, Eric Vivier
Journal: Journal for ImmunoTherapy of Cancer (2019)

The implementation of immune checkpoint inhibitors to the oncology clinic signified a new era in cancer treatment. After the first indication of melanoma, an increasing list of additional cancer types are now treated with immune system targeting antibodies to PD-1, PD-L1 and CTLA-4, alleviating inhibition signals on T cells. Recently, we published proof-of-concept results on a novel checkpoint inhibitor, NKG2A. This receptor is expressed on cytotoxic lymphocytes, including NK cells and subsets of activated CD8<sup>+</sup> T cells. Blocking antibodies to NKG2A unleashed the reactivity of these effector cells resulting in tumor control in multiple mouse models and an early clinical trial. Monalizumab is inhibiting this checkpoint in human beings and future clinical trials will have to reveal its potency in combination with other cancer treatment options.
Transcriptomic Profile Identified a Specific Signature in Children with Acute Myeloid Leukemia (AML) and Primary Induction Failure (PIF): Preliminary Data and Future Perspectives
Authors: Luca Lo Nigro, Vincenza Barresi, Nellina Andriano, Giulio Pulvirenti, Giorgia Spampinato, Paola Bonaccorso, Valeria Iachelli, Manuela La Rosa, Emanuela Cannata, Andrea Di Cataldo, Giovanna Russo, Daniele Condorelli
Journal: Blood (2018)
Sex Hormones and Prostate Cancer
Authors: Richard J. Auchus, Nima Sharifi
Journal: Annual Review of Medicine (2019)

The prostate is an androgen-dependent organ that develops only in male mammals. Prostate cancer is the most common nonskin malignancy in men and the second leading cause of cancer deaths. Metastatic prostate cancer initially retains its androgen dependence, and androgen-deprivation therapy often leads to disease control; however, the cancer inevitably progresses despite treatment as castration-resistant prostate cancer, the lethal form of the disease. Although it was assumed that the cancer became androgen independent during this transition, studies over the last two decades have shown that these tumors evade treatment via mechanisms that augment acquisition of androgens from circulating precursors, increase sensitivity to androgens and androgen precursors, bypass the androgen receptor, or a combination of these mechanisms. This review summarizes the history of prostate cancer research leading to the contemporary view of androgen dependence for prostate cancers and the current treatment approaches based on this modern paradigm.
Using HSP90 Inhibitors to Target DNA Repair Proteins in AML
Authors: Janani Ravikrishnan, Tzung-Huei Lai, Shaneice Renee Mitchell, Pei-Jung Wu, Shelley Orwick, Chaomei Liu, Jennifer A. Woyach, Alice S. Mims, William Plunkett, Vinay K Puduvalli, John C. Byrd, Rosa Lapalombella, Deepa Sampath
Journal: Blood (2018)
CP-CML Seems Related to Specific HLA Subtypes and the HLA DRB1 07 Allele Might Identify a Subgroup of Newly Diagnosed CP-CML Patients on Imatinib First-Line of Better Prognosis
Authors: Franck-Emmanuel Nicolini, Stéphanie Désilets, Sandrine Hayette, Isabelle Tigaud, Liliana Vila, Stephane Morisset, Mohamad Sobh, Mauricette Michallet, Valerie Dubois
Journal: Blood (2018)
Overexpression of HIF1 Alpha Predicts Worse Overall and Event-Free Survival in Patients with Philadelphia Chromosome-Negative Precursor B-Lymphoblastic Leukemia
Authors: S. Konoplev, S.M. Kornblau, E. Schlette, H Lu, D. A Thomas, N Zhang, Y.H. Qiu, K Coombes, S. Neeley, Hagop M Kantarjian, L.J. Medeiros, M. Andreeff, M. Konopleva
Journal: Blood (2008)
Clinical Significance of Clonal Cytogenetic Heterogeneity (CCH) at Diagnosis in Adult Patients with Acute Lymphoblastic Leukemia (ALL)
Authors: Hiroaki Shimizu, Nahoko Hatsumi, Satoru Takada, Takuma Ishizaki, Akihiko Yokohama, Takayuki Saitoh, Toru Sakura, Hiroshi Handa
Journal: Blood (2018)