tbuckley/cabot-search huggingface dataset:
Thirteen miRNAs involved in the response of breast cancer cells to doxorubicin.
Authors: Eduardo Tormo, BegoÃƒÂ±a Pineda, Sandra Ballester, Octavio Burgues, Eva Serna, Ana Lluch, Pilar Eroles
Journal: Journal of Clinical Oncology (2013)

e12019 Background: Mature microRNAs (miRNAs) are a class of naturally occurring, small non-coding RNA molecules, about 21–25 nucleotides. Growing evidence shows that miRNAs exhibit a variety of regulatory functions related to cell growth, development, and differentiation, and are associated with a wide variety of human diseases. Several miRNAs have been linked to cancer; since expression analysis studies have revealed perturbed miRNA expression in tumors compared to normal tissues. As a consequence, human miRNAs are likely to be highly useful as biomarkers, especially for future cancer diagnostics, and are emerging as targets for disease intervention. Since doxorubicin (DOX) has been used for a long time in breast cancer treatment, and resistance mechanisms are not clear understood, the aim of this work was to find a miRNA expression profile that could explain the regulation in different breast cancer cell lines under DOX treatment. Methods: Three breast cancer cell lines (MDA-MB-231, MDA-MB-468, and MCF-7) were cultured in normal conditions and also treated with DOX. Total RNA containing small non-coding RNA was isolated and its expression profile was performed by using GeneChip miRNA 2.0 array. Real time PCR validation was carried out to confirm the results. Results: Principal Component Analysis (PCA) of the small non-coding RNA profiles showed different expression patterns between normal conditions and DOX treatment in each cell line separately. Taken together in a Heat Map, miRNA expression profiles of MDA-MB-231 and MDA-MB-468 cell lines were closer in both normal and DOX treatment conditions, while miRNA expression profile of MCF-7 cell line showed strong differences. Total of 13 common miRNAs between the three cell lines were found to be significantly affected by DOX treatment. PCR validation confirmed the results obtained. Conclusions: We conclude that 13 common miRNAs are responsables of changes compared to treatment with DOX in breast cancer cell lines MDA-MB-231, MDA-MB-468 and MCF-7. This miRNAs are mainly related with cellular processes such as cell differentiation, vascularisation, apoptosis and cell proliferation and also involved in other cellular processes, such as cell migration.
The efficacy and safety of first-line and salvage therapies with bevacizumab combination chemotherapy regimens in metastatic colorectal cancer: A retrospective ASMO experience.
Authors: Ramazan Yildiz, Suleyman Buyukberber, Dogan Koca, Lokman Koral, Aydin Ciltas, Olcun Umit Unal, Mahmut Gumus, Nuriye Ozdemir, Faysal Dane, Veli Berk, Mehmet Ali Kaplan, Tamer Elkiran, Melih Cem Boruban, Ugur Coskun, Dincer Aydin, Dogan Uncu, Metin Ozkan, Abdurrahman Isikdogan, Mustafa Benekli
Journal: Journal of Clinical Oncology (2013)

e14705 Background: The addition of bevacizumab to chemotherapy significantly shows survival advantage in metastatic colorectal cancer (mCRC), but with limited data about irinotecan combination in salvage therapy. Efficacy and toxicity of bevacizumab combination regimens were assessed in first-line and salvage therapies. Methods: Total of 1011 (659 in first-line and 352 in salvage) patients were retrospectively evaluated. Results: In first-line therapy, the ORR was 36.4%. Median PFS was 7 months for FOLFIRI, 6 months for IFL and 6 months for other chemotherapy regimens with a median overall PFS of 7 months. Median survival was 29 months for FOLFIRI, 28 months for IFL and 21 months for others with a median overall survival of 28 months. In salvage therapy, the ORR was 25.2%. Median PFS was 7 months for FOLFIRI, 7 months for IFL and 6 months for others with a median overall PFS of 7 months. Median survival was 19 months for FOLFIRI, 13 months for IFL and 21 months for others with a median overall survival of 19 months. The main toxicities in first-line and salvage therapy were neutropenia, febrile neutropenia, nausea and vomiting, diarrhea, mucositis, bleeding, hypertension, thromboembolism, fistulization and bowel perforation. Conclusions: Bevacizumab combination chemotherapy regimens are effective with a tolerable safety profile in mCRC patients in first-line and salvage therapy.
Lenalidomide, Adriamycin and Dexamethason (RAD) in Relapsed and Refractory Multiple Myeloma: Final Results from a Phase I/II Trial of “Deutsche Studiengruppe Multiples Myelom”
Authors: Christian Gerecke, Stefan Knop, Max S. Topp, Peter Liebisch, Christina Vollmuth, Uwe Platzbecker, Uwe Mäder, Hermann Einsele, Ralf C. Bargou
Journal: Blood (2008)
Pure Erythroid Leukemia Is Characterized By TP53mutations, a Complex Karyotype with Chromosome 17 Abnormalities, and Adverse Risk Independent of Therapy Type
Authors: Guillermo Montalban-Bravo, Christopher B. Benton, Sa A. Wang, Farhad Ravandi, Tapan M. Kadia, Jorge E. Cortes, Naval Daver, Koichi Takahashi, Courtney D DiNardo, Elias J. Jabbour, Gautam Borthakur, Marina Konopleva, Sherry Pierce, Keyur P. Patel, Steven M Kornblau, Hagop M. Kantarjian, Ken H. Young, Guillermo Garcia-Manero, Michael Andreeff
Journal: Blood (2016)
Clinical Features and Prognostic Relevance of Ovarian Involvement in Non-Hodgkin's Lymphoma: a Consortium for Improving Survival of Lymphoma (CISL) Report.
Authors: Jina Yoon, Seok Jin Kim, Jong Ho Won, Chul Won Choi, Hyeon-Seok Eom, Jin Seok Kim, Min Kyoung Kim, Jae-Yong Kwak, Won Seog Kim, Cheolwon Suh
Journal: Blood (2009)
Phase I study of TH-302, a hypoxia-activated cytotoxic prodrug, in subjects with advanced leukemias.
Authors: Marina Konopleva, Damian Handisides, Gustavo A. Lorente, Juliana M. Benito, Mary Ann Richie, Gautam Borthakur, Elias Jabbour, Stefan Faderl, Jorge E. Cortes, Stewart Kroll, Michael Andreeff, Hagop Kantarjian, Deborah A. Thomas
Journal: Journal of Clinical Oncology (2012)

6585 Background: TH-302 is a 2-nitroimidazole prodrug of the DNA alkylator, bromo-isophosphoramide mustard designed to be selectively activated in hypoxic conditions. Preclinical data in mice with ALL have demonstrated marked expansion of hypoxia in areas of marrow leukemia infiltrates (Benito et al., PlosOne, in press). TH-302 also exhibited specific hypoxia-dependent cytotoxicity when tested against primary ALL and AML samples in vitro. Based on these findings, a phase 1 study of TH-302 was designed for advanced leukemias. Methods: Eligibility: ECOG ≤ 3, relapsed/refractory leukemias for which no standard therapy options were available, and acceptable hepatorenal function. A standard 3+3 dose escalation design was used with 40% dose increments. TH-302 was administered IV over 30-60 minutes daily on Days 1-5 of a 21-day cycle. The objectives were to determine the MTD and PK profile of TH-302 with this schedule and to assess preliminary clinical activity of TH-302. Results: 34 subjects with previously treated AML (n=26), ALL (n=6) or CML in blast phase (n=1) received TH-302 at doses of 120 (n=4), 170 (n=4), 240 (n=3), 330 (n=3), 460 (n=16) or 550 (n=4) mg/m². No skin or mucosal toxicity was noted in participants treated with TH-302 doses ≤240 mg/m 2 . At 330 mg/m 2 , grade 2 dermatological toxicities included skin ulcer (n=1) and hand/foot syndrome (n=1). Grade 2 mucositis (n=3) and grade 2 skin toxicity (e.g. skin rash, skin ulcers; n=3) were reported at 460 mg/m 2 ; none were dose-limiting. Two of 3 evaluable subjects treated at the 550 mg/m 2 cohort experienced DLTs of grade 3 esophagitis. Eight subjects had stable disease or better after 1 cycle. One ALL subject (at 120 mg/m 2 ) cleared marrow blasts with persistent neutropenia. One AML subject (at 550 mg/m 2 ) achieved CRp after 1 cycle with resolution of leukemia cutis. Conclusions: TH-302 administered daily for 5 consecutive days every 3 weeks is well-tolerated with increased incidence of skin and mucosal toxicity at higher dose levels. Clinical activity has been noted with a few objective responses, but majority of cytoreductions in the AML subset were transient. Clinical trials combining TH-302 with various chemotherapeutics with established efficacy in AML and ALL are planned.
Burnout prevalence in medical and radiation oncologists at British Columbia Cancer Agency (BCCA).
Authors: Catherine A. Fitzgerald, Lyly H. Le, David W. Petrik, Kevin C. Murphy
Journal: Journal of Clinical Oncology (2012)

6071 Background: Burnout, reported to affect 30-60% of oncology workers, is a syndrome of psychological distress typically manifesting in three dimensions: Emotional Exhaustion (EE), Depersonalization (DP) and Low Personal Accomplishment (PA). Causal factors include workload, dealing with terminally ill patients and difficulties maintaining a balance between professional and personal life. As workload rises due to increased complexity of therapy and increasing prevalence of cancer patients, burnout may increase, especially in times of financial constraint. We sought to determine the prevalence of burnout in medical and radiation oncologists working at BCCA, which provides all radiation and the majority of medical oncology services to BC’s 4.5 million people. Methods: In March 2011, BCCA oncologists were invited to participate in a confidential online survey consisting of basic demographics and the 22 item MasLach Burnout Inventory (MBI) instrument, the latter a validated tool measuring distress in the three main dimensions of burnout. Normative data for physicians were used to interpret the results. Results: Response rate was 59%, female:male 40:60% with similar response rates for medical and radiation oncology (60 v 59%). Of the 73 who indicated their age range, 34 (47%) were between 35 and 44 years old. Respondents indicated that they had considered reducing their Full Time Equivalent (FTE) (67%) or leaving BC (46%). In those with at least 2 scores at a severe level, these rates were 76% and 71% respectively. Conclusions: Over 60% of responding BCCA oncologists report burnout in at least one domain of the MBI tool. Many have considered leaving the province or reducing their hours. These data are consistent with Grunfeld’s survey of Ontario oncologists (CMAJ 2000), although the rate of burnout is higher in this survey. Further research into ways to lessen burnout in oncology is urgently needed. [Table: see text]
Medical Community Gathers Steam to Tackle Climate’s Health Effects
Authors: M.J. Friedrich
Journal: JAMA (2017)

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Increasing risk of chronic health conditions in aging survivors of childhood cancer: A report from the Childhood Cancer Survivor Study.
Authors: Gregory T. Armstrong, Toana Kawashima, Wendy M. Leisenring, Marilyn Stovall, Charles A Sklar, Leslie L. Robison, Kevin C. Oeffinger
Journal: Journal of Clinical Oncology (2012)

9514 Background: Survivors of childhood cancer are at an increased risk for treatment-related chronic health conditions during early adulthood. However, the incidence, severity, and spectrum of chronic health conditions in the fourth and fifth decades of life have not been well studied. Methods: Analyses included 14,358 &gt; 5 yr survivors of childhood cancer (median age at last follow-up 32.3 yrs, range 8.0-58.0; 21.4% &gt; 40 years) and a sibling comparison group (n = 4,031). Self-reported health conditions were classified using NCI CTCAE 4.0 grading system. Analyses focused on two primary outcomes: severe/life-threatening/fatal conditions (grades 3-5), and multiple (≥ 2) conditions. Cumulative incidence of a new chronic health condition was calculated from age 26 yrs. Cox proportional hazards models adjusted for gender and race, were evaluated using age as the time scale. Results: Among survivors with no previous health conditions through age 25, the cumulative incidence for a new grade 3-5 condition by age 50 compared to siblings was 45.9% (95% CI 45.9-45.9) vs. 13.9%, (95% CI 13.9-14.0) and for new onset of ≥ 2 conditions 33.0% (95% CI 33.0-33.1) vs. 24.9% (95% CI 24.8-24.9) . Survivors ≥ 40 yrs of age had a 5.8-fold (95% CI 5.3 – 6.5) increased risk of a grade 3-5 condition compared to same age siblings, in contrast to those &lt; 40 years of age (HR 2.7, 95% CI 2.5-3.0). A similar magnitude of difference was present for risk of &gt;2 conditions (HR 2.7 vs. 1.2). In comparison to siblings, survivors &gt; 40 years of age had a significantly increased risk for: congestive heart failure (HR 15.7, 95% CI 9.2-26.7), myocardial infarction (HR 8.8, 95% CI 6.0-12.9), stroke (HR 8.6, 95% CI 5.6-13.2),joint replacement (HR 6.8, 95% CI 4.1-11.4), renal failure (HR 5.1, 95% CI 2.2-11.9) among other serious conditions. Conclusions: As they age, adult survivors of childhood cancer continue to develop new and serious health conditions at substantially higher rates than siblings. These data emphasize the importance of placing a greater focus on investigations of premature aging and organ senescence in this high risk population.
Magnesium oxide supplements for the treatment of post-chemotherapy sleep disturbance.
Authors: Cindy Alberts Carson
Journal: Journal of Clinical Oncology (2017)

175 Background: While every cancer patient suffers from anxiety and sleep disturbance during cancer treatment, many physicians do not recognize that these problems can continue long after treatment has ended. Many cancer patients feel increased anxiety immediately after treatment ends when they find themselves “on their own,” without the protection of the medical armamentarium. The fear of recurrence, uncertainty about the future, a sense of vulnerability, awareness of mortality, and grief for the loss of a disease-free life all contribute to anxiety and sleep disturbance long term. Magnesium has been used for sleep induction and relaxation for centuries. The primary mechanism by which sleep is enhanced is by muscle relaxation. Magnesium induces muscle relaxation by preventing calcium from binding to troponin, parvalbumin, myosin, and calmodulin, thereby blocking muscle contraction. High levels of free magnesium competitively bind these proteins, and the slow dissociation of bound magnesium provides prolonged relaxation. It is for this reason that magnesium has a long history of use as a tocolytic in labor, as an adjunct to asthma treatment, and as a powerful laxative. Methods: 23 patients in a primary care practice reported continued anxiety and difficulty with sleep initiation following chemotherapy and/or radiation for various forms of cancer. Rather than use SSRIs, benzodiazepines, or sleep medications, all patients were started on an over the counter 1,000 mg magnesium oxide supplement, taken 1 hour before bedtime for 2 weeks. Results: Four patients dropped out before the end of the study period due to magnesium-induced diarrhea. 19 patients completed the 2-week study. Of these, 14 reported a noticeable reduction of sleep latency and an improvement in sleep quality. 11 also reported a subjective sense of reduced anxiety overall. 5 reported an improvement in nocturnal leg cramps, which had been interfering with sleep quality. Conclusions: Overall, magnesium proved to be a well-tolerated treatment for sleep disturbance and anxiety in the majority of the patients studied.
A pilot study of insomnia and lung cancer symptoms in early stage lung cancer patients
Authors: J. Garst, M. Rumble, J. Edinger, L. Porter, P. Johnson, F. Keefe
Journal: Journal of Clinical Oncology (2004)

7269 Background: Sleep disturbances have been reported in up to 79% of pts with cancer. The purpose of this pilot study was to characterize the sleep patterns and possible cognitive/behavioral targets for intervention in early stage lung cancer (LC) pts with insomnia. Secondary endpoints included the evaluation of the relationship between sleep patterns and measures of sleep, mood and LC sxs. Methods: 33 patients with Stage I - IIIA lung cancer were enrolled with 20 pts reporting insomnia and 13 without insomnia. Participants completed a baseline series of questionnaires about their insomnia sxs, sleep habits, mood and LC sxs such as pain, cough, fatigue, and SOB. The following week, they completed sleep logs measuring total sleep time (TST), total wake time (TWT), time in bed (TIB) and sleep efficiency (SE) [(total sleep time/time in bed) x 100]. Results: Pts with insomnia reported significantly more insomnia sxs (p= 0.001), less TST (p=.003), more TWT (p=.003), and lower SE (p=0.0001). In addition, pts with insomnia reported significantly more dysfunctional beliefs and attitudes about beliefs (p-0.0262), and higher generalized anxiety (p = 0.0235) . Correlational analyses examining the relationship between the daily sleep log variables and the baseline measures of sleep, mood and LC sxs revealed that patients who reported lower levels of SE and higher levels of TWT also reported more insomnia sxs (p=.00002 and p=.0006), more negative sleep hygiene practices (p=.0199 and p=.0164), higher generalized anxiety (p=.0058 and p=.0045) more dyspnea (p=.0072 and p=.0035) and higher levels of pain in the chest Pts with insomnia reported a lower quality of life more fatigue and more diarrhea than those without insomnia. Conclusions:These preliminary findings suggest that early stage LC pts with insomnia sleep less efficiently, have more wake time during the sleep period, and experience more anxiety and chest pain than those without insomnia. A second study is on going using cognitive behavioral interventions toward identified targets such as dysfunctional beliefs and negative sleep hygiene practices toward the goal of affecting lung cancer symptomatology. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis NIH (PREP Grant) Aventis Aventis
Efficacy of mycobacterium phlei cell wall-nucleic acid complex (MCNA) in BCG-unresponsive patients.
Authors: Roger Li, John Amrhein, Zvi Cohen, Monique Champagne, Ashish M. Kamat
Journal: Journal of Clinical Oncology (2017)

342 Background: Previously, we reported the results of a single-armed, multi-institutional study on the efficacy of MCNA in patients who failed intravesical BCG treatment. Since that publication, a new standardized definition for BCG-unresponsiveness has been established. We re-analyzed the oncologic outcomes following intravesical MCNA in patients classified as BCG-unresponsive according to the new definition. Methods: Patients with recurring high grade NMIBC after intravesical BCG were enrolled. For this analysis, we focused on the patients satisfying the minimum criterion for adequate BCG treatment (5/6 induction and 2/3 maintenance). Treatment course included 6 weekly intravesical instillations of 8mg MCNA followed by 3 weekly instillations at months 3, 6, 12, 18, and 24. Followup assessments included cystoscopy, urine cytology and biopsy. Patients absent of high grade disease confirmed by central review of biopsy were deemed disease-free. Results: Of the 129 patients enrolled, 94 (68 CIS with/without papillary tumors, 26 papillary only tumors) fit the criteria for the new BCG-unresponsive definition. In the group with papillary tumors, DFS measured at months 6, 12, and 24 were 61.2%(38.2-77.8%), 61.2(38.2-77.8%), and 50.1%(27.5-69%). In the CIS-containing group, the corresponding DFS were 44.8%(32.3-56.4%), 26.5%(16.3-37.9%), and 16.6%(8.6-26.9%), respectively. Conclusions: Intravesical MCNA therapy has the potential to offer 26.5% of patients with CIS and 61.2% of patients with papillary tumors a chance to safely preserve their bladder for at least 1 year. The efficacy in BCG-unresponsive patients was higher than that reported with all-comers, suggesting that adequate priming with BCG might be required for further immune-based response.
Abstract 369: Isolation and Characterization of Developmentally and Functionally Discrete Subsets of Cardiac Fibroblasts
Authors: Reza Ardehali, Shah Ali, Irving Weissman
Journal: Circulation Research (2012)

Although cardiac fibroblasts (CF) are the most prominent cell types in the heart, little is known about their origin and development. Fibroblasts play a key role in regulating the normal myocardial function, as well as the adverse remodeling that occurs with injury. Fundamental to understanding cardiac development is the ability to determine when and where CFs are generated, their ancestry, and how they move to reside in their final position. We used novel transgenic mouse models to lineage trace the developmental origin of CFs and their contribution to fibrosis in response to injury. Here, we show that a subset of cardiac fibroblasts is derived from Mesp1-expressing cells (multipotent cardiac progenitor cells that contribute to precursors of both heart fields). Using Mesp1-Cre;mT/mG mice, in which cells derived from Mesp1-expressing cells are indelibly marked by the GFP reporter protein, we demonstrate that approximately 65% of CFs share an embryonic origin with cardiomyocytes, vascular smooth muscle, and endothelial cells. In addition, experimental myocardial fibrosis did change this proportion. In an attempt to identify the source of the fibroblasts that are non-MesP1-derived, we evaluated contribution from: (i) the bone marrow stromal cells and hematopoietic stem cells, (ii) endothelial-to-mesenchymal transition, (iii) circulating cells, and (iv) epicardial-derived cells. Transplantation of GFP-bone marrow into irradiated wildtype mice resulted in an insignificant contribution of stromal-derived fibroblasts in the heart in response to injury. Using Tie2-Cre;mT/mG mice, we did not observe cardiac fibroblasts originating from endothelial cells in injured hearts. Finally, using a parabiotic pair of GFP and wildtype mice where blood chimerism is established, no evidence for homing of circulating fibroblasts to the heart upon injury was noted. However, we provide unequivocal evidence that epicardial-derived cells migrate to myocardium as fibroblasts to contribute to fibrosis. In summary, using lineage-tracing systems, we provide evidence for two sources of fibroblasts in the heart, one that shares an embryonic origin with the cardiovascular lineages and the other from a non-cardiac origin, which is primarily derived from the epicardium.