tbuckley/cabot-search huggingface dataset:
CYP2D6 and ESR genotypes in adjuvant tamoxifen treatment for early breast cancer.
Authors: K. Kim, K. H. Jung, J. Ahn, S. Kim, H. J. Kim, B. Ko, J. W. Lee, B. H. Son, S. Ahn, G. Gong
Journal: Journal of Clinical Oncology (2011)

142 Background: The pharmacokinetics and pharmacodynamics of tamoxifen may influence the clinical outcome and tolerability of adjuvant treatment with tamoxifen in breast cancer. We investigated the effects of polymorphisms of CYP2D6, ESR1, and ESR2 for tamoxifen therapy in early stage breast cancer patients. Methods: Tissue DNA from 187 patients who received tamoxifen only as an adjuvant systemic therapy between 1997 and 2002 were extracted and genotyped for polymorphisms of CYP2D6 (*2A, *10, *14, *41) and estrogen receptor (ESR1, ESR2). While CYP2D6*10, *14 and *41 have been reported to be associated with decreased activation of tamoxifen, CYP2D6*2A, ESR1 PvuII CC and ESR2-02 GG have been associated with enhanced activity of tamoxifen. Statistical analyses include Fisher exact test, Chi-square and Kaplan-Meier analyses. Results: Median age was 43 years (range 25-49). Most of the patients (170/187) were stage I, while other patients were stage 0 (1/187) and stage II (17/187). None of the patients had nodal metastasis. Median follow-up was 100 months (7-166). Allele frequencies were as follows: CYP2D6*10, 0.69; *14, 0.02; *41, 0.01; *2A, 0.64; ESR1 PvuII C allele, 0.25; ESR2-02 G allele, 0.98. Each genotype group did not show significant differences in age, stage, pT, tumor size and follow up period. Twelve percent (24/187) had received tamoxifen therapy for less than 24 months. Of the 24 patients, 67% (16) discontinued tamoxifen therapy related to tolerability issues. Recurrence occurred in 12 patients (6.4%). There was no association between genotypes with either recurrence or tamoxifen duration &lt; 2 years. Although statistically nonsignificant, patients with either CYP2D6*2A homozygote, ESR1 PvuII CC genotype, ESR2-02 GG genotype tended to have a longer DFS when compared concomitantly to wild-type (p=0.445). Conclusions: Polymorphsims for CYP2D6*2A,*10, *14, *41, ESR1 PvuII, ESR2-02 did not show significant associations with either recurrence or tamoxifen duration &gt; 2 years. However, grouped analysis for CYP2D6*2A, ESR1 PvuII, ESR2-0210 genotypes need further evaluation regarding with tamoxifen outcome.
Impact of low estrogen- and progesterone-receptor expression on survival outcomes in breast cancers previously classified as triple-negative breast cancers.
Authors: K. P. S. Raghav, L. F. Hernandez-Aya, X. Lei, M. Chavez-Mac Gregor, F. Meric-Bernstam, T. A. Buchholz, A. A. Sahin, K. Do, G. N. Hortobagyi, A. M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2011)

1023 Background: Estrogen and progesterone receptor (ER/PR) expression is a fundamental prognostic and predictive marker for breast cancer. Conflicting thresholds for ER/PR positivity have resulted in uncertainty regarding endocrine therapy for low levels of ER/PR (1−10%). The purpose of our study was to evaluate the prognostic significance of low levels of ER/PR on survival outcomes in tumors previously defined as triple-negative breast cancers (TNBC). Methods: We reviewed records of 1257 patients with TNBC (defined as ER/PR < 10% and HER2 negative) followed between 1990 and 2009 at a single institution. Tumors were categorized according to ER/PR expression by immunohistochemistry into one of three groups: ER/PR <1% (Group A), ER/PR 1−5% (Group B) and ER/PR 6−10% (Group C). Kaplan-Meier product limit method was used to estimate recurrence-free survival (RFS) and overall survival (OS). Cox proportional hazards models were fit to determine the association between ER/PR expression and survival, after adjustment for other patient and disease characteristics. Results: Median age was 51 years (range 21 to 98 years). Groups A, B and C had 897 (71.4%), 241 (19.2%) and 119 (9.4%) patients, respectively. Group A had a larger proportion of grade III tumors (P = 0.001). At a median follow up of 44 months, there were 465 recurrences and 367 deaths. The 3-year RFS rates were 64%, 67% and 77% in groups A, B and C, respectively (P=0.34). Corresponding, 3-year OS rates in group A, B and C were 79%, 81% and 88% (P=0.33). ER/PR expression was not an independent predictor for RFS (Group B: HR: 1.11, 95% CI: 0.88−1.41, P=0.37 and Group C: HR: 0.92, 95% CI: 0.65−1.30, P=0.64) or OS (Group B: HR: 1.10, 95% CI: 0.84−1.44, P=0.47 and Group C: HR: 0.88, 95% CI: 0.60−1.31, P=0.54) when compared with Group A. A subset analysis among 118 patients within the three groups who received endocrine therapy showed no significant difference in RFS (P = 0.10) or OS (P = 0.45). Conclusions: In this cohort of TNBC patients, low levels of ER/PR (1−10%) expression appear to have no significant impact on survival outcomes. The benefit from endocrine therapy in tumors with ER/PR 1−10% is uncertain.
R-CHOP Modified with Pegilated Lyposomal Adriamycin in Elderly Diffuse Large B-Cell Non Hodgkin’s Lymphoma (DLBC-NHL) Therapy: An Attempt To Reduce Toxicity in Patients with Comorbidity.
Authors: Giulio Giordano, Matteo Dell’Olio, Silvia Piano, Giuliana Farina, Antonio La Sala, Daniele Colaprete, Nicola Cascavilla, Sergio Storti
Journal: Blood (2007)
ECG Challenge: October 8, 2013
Authors: Philip Podrid
Journal: Circulation (2013)

ECG Challenge 1686A 73-year-old man with a history of paroxysmal atrial fibrillation who was being treated with a β-blocker and digoxin presents to the emergency room after 2 days of nausea, vomiting, and abdominal pain.He is placed on telemetry because of a slightly irregular heart rate.It is thought that he has a viral gastroenteritis.Noted on telemetry are several pauses in the rhythm; hence, a 12-lead ECG is obtained.What is the diagnosis?To submit your diagnosis, go to http://circ.ahajournals.
Safety, Efficacy, and Pharmacokinetics of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously-Treated Children with Severe Hemophilia a (Kids-ALONG)
Authors: Guy Young, Johnny N. Mahlangu, Roshni Kulkarni, Beatrice Nolan, Raina Liesner, John Pasi, Christopher Barnes, Srividya Neelakantan, Giulia Gambino, Lynda M Cristiano, Christopher Barnowski, Glenn F Pierce, Geoffrey A. Allen
Journal: Blood (2014)
The Chemokine Receptor CX3CR1 Defines Three Antigen-Experienced CD8 T Cell Subsets with Distinct Roles in Immune Surveillance and Homeostasis
Authors: Carmen Gerlach, E. Ashley Moseman, Scott M. Loughhead, David Alvarez, Anthonie J. Zwijnenburg, Lisette Waanders, Rohit Garg, Juan C. de la Torre, Ulrich H. von Andrian
Journal: Immunity (2016)
Cryopreserved Allogeneic Peripheral Blood Stem Cells Result in Outcome Equivalent to Those of Fresh Infusions Enabling Rational Scheduling of Donations,
Authors: Bhuvan Kishore, John Davis, Katayoun Rezvani, David Marin, Richard M Szydlo, Loaiza Sandra, Giles Chrissy, Aristeidis Chaidos, Edward J Kanfer, Anastasios Karadimitris, Donald H MacDonald, Dragana Milojkovic, Amin Rahemtulla, John M Goldman, Jane F Apperley, Jiri Pavlu
Journal: Blood (2011)
Long-term therapy with sunitinib and sorafenib in patients with metastasizing renal cell carcinoma.
Authors: S. Richter, C. Piper, D. A. Pfister, B. Brehmer, A. Heidenreich
Journal: Journal of Clinical Oncology (2011)

407 Background: Multitargeted tyrosine kinase inhibitors (MTKIs) constitute the established therapy in patients with metastasizing renal cell carcinoma. There are only few data concerning efficiency and safety, the reasons for a longterm response with good tolerability under MTKIs is still unknown. Methods: We retrospectively analyzed the data of patients (pts.) under long-term therapy (&gt;1 year) with sorafenib or sunitinib. Localization of metastases, number of cycles, sequence of therapy, treatment-associated toxicities, and frequency of dose reductions were our main focus of interest. Results: 15 pts. (14 male, one female) with an mean age of 66,33 (44-81) years, were treated with 19,86 (12-35) cycles of sorafenib or sunitinib. 14/15 pts. underwent radical nephrectomy before the treatment. Localization of metastasis were as follows: pulmonary (9/15), hepatic (4/15), nodal (8/15), osseous (3/15), and pancreatic (2/15). In four pts. two or more organs were affected, in six pts. only one organ. As a first-line therapy nine pts. received sunitinib for 20.67 (12-35) cycles and one patient sorafenib for 44 cycles. For second line therapy two pts. were treated with sunitinib for 13 (12-14) cycles and three pts. with sorafenib for 23.33 (18-28) cycles. In five pts. a dose reduction of 25-50% was necessary due to significant treatment associated side effects, afterwards toxicities were tolerable under long term therapy (grade 1 in 10 pts.). Conclusions: The results show, that longterm therapy with sunitinib or sorafenib is tolerable and efficacious independent on previous treatment. Prognostic factors concerning longterm response and low toxicity profile at a molecular biological level are still unknown, further investigations are of importance and are currently performed at our institution. No significant financial relationships to disclose.
miR-483 Targeting of CTGF Suppresses Endothelial-to-Mesenchymal Transition
Authors: Ming He, Zhen Chen, Marcy Martin, Jin Zhang, Panjamaporn Sangwung, Brian Woo, Adriana H. Tremoulet, Chisato Shimizu, Mukesh K. Jain, Jane C. Burns, John Y.-J. Shyy
Journal: Circulation Research (2016)

Rationale: Endothelial–mesenchymal transition (EndoMT) is implicated in myofibroblast-like cell–mediated damage to the coronary arterial wall in acute Kawasaki disease (KD) patients, as evidenced by positive staining for connective tissue growth factor (CTGF) and EndoMT markers in KD autopsy tissues. However, little is known about the molecular basis of EndoMT involved in KD. Objective: We investigated the microRNA (miRNA) regulation of CTGF and the consequent EndoMT in KD pathogenesis. As well, the modulation of this process by statin therapy was studied. Methods and Results: Sera from healthy children and KD subjects were incubated with human umbilical vein endothelial cells. Cardiovascular disease–related miRNAs, CTGF, and EndoMT markers were quantified using reverse transcriptase quantitative polymerase chain reaction, ELISA, and Western blotting. Compared with healthy controls, human umbilical vein endothelial cell incubated with sera from acute KD patients had decreased miR-483, increased CTGF, and increased EndoMT markers. Bioinformatics analysis followed by functional validation demonstrated that Krüppel-like factor 4 (KLF4) transactivates miR-483, which in turn targets the 3′ untranslated region of CTGF mRNA. Overexpression of KLF4 or pre-miR-483 suppressed, whereas knockdown of KLF4 or anti-miR-483 enhanced, CTGF expression in endothelial cells in vitro and in vivo. Furthermore, atorvastatin, currently being tested in a phase I/IIa clinical trial in KD children, induced KLF4-miR-483, which suppressed CTGF and EndoMT in endothelial cells. Conclusions: KD sera suppress the KLF4-miR-483 axis in endothelial cells, leading to increased expression of CTGF and induction of EndoMT. This detrimental process in the endothelium may contribute to coronary artery abnormalities in KD patients. Statin therapy may benefit acute KD patients, in part, through the restoration of KLF4-miR-483 expression. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01431105.
Comparison of 5-Azacytidine Versus Allogeneic Hematopoietic Cell Transplantation In Elderly (≥ 60 years) Patients with De Novo High-Risk MDS - a Retrospective Matched Pair Analysis
Authors: Uwe Platzbecker, Johannes Schetelig, Juergen Finke, Rudolf Trenschel, Bart Lee Scott, Guido Kobbe, Kerstin Schaefer-Eckhart, Martin Bornhäuser, Raphael Itzykson, Ulrich Germing, Dietrich Beelen, Gerhard Ehninger, Pierre Fenaux, H. Joachim Deeg, Lionel Ades
Journal: Blood (2010)
Robotic radical cystectomy: Medium-term oncologic follow-up.
Authors: C. Mmeje, R. Nunez-Nateras, R. Pruthi, M. E. Nielsen, E. Wallen, M. Humphreys, E. P. Castle
Journal: Journal of Clinical Oncology (2011)

288 Background: We report our experience with robot assisted radical cystectomy (RARC) with regard to medium-term (at least 2 year) oncologic outcomes. Methods: A total of 275 patients have undergone RARC and urinary diversion at two institutions for invasive bladder cancer between 2005-present. We performed a retrospective analysis of the 139 patients who underwent RARC with a minimum of 2 years follow-up. Medium term oncologic outcomes including recurrence rates, time to recurrence, recurrence free survival (RFS), disease specific survival (DSS) were analyzed. Follow-up was measured from time of surgery to time of most recent clinical follow-up. Results: This cohort of patients consisted of 108 men (78%) and 31 women (22%) at a mean age of 67.3 years (range 45-86 years). Sixty-one (44%) patients had ≤ pT2 disease, 38 (27%) pT3/T4 disease, and 40 (29%) N+ disease. The mean number of lymph nodes removed was 18 (range 3-41). The average clinical follow up in this case series was nearly 3 years with a mean of 35.9 months (range 24-64 months). At this follow-up, 39 patients have recurred, 27 patients died of disease, and 5 patients died of other causes giving an overall RFS, DSS, and OS rates of 80%, 71%, and 68%, respectively. The mean (median) time to recurrence was 12.3 months (10 months). These findings are consistent with prior reports of the oncologic outcomes for open radical cystectomy. Conclusions: The oncologic follow-up of patients undergoing RARC appears to be favorable with acceptable outcomes in the medium-term (mean – 3 years). As our follow-up increases, we should expect to truly define the long-term clinical appropriateness and oncologic success of this procedure. No significant financial relationships to disclose.
The neoadjuvant management of bladder cancer in Canada: A survey of genitourinary medical oncologists.
Authors: T. Hsu, S. North, B. J. Eigl, K. N. Chi, C. M. Canil, L. Wood, A. Lau, T. Panzarella, S. S. Sridhar
Journal: Journal of Clinical Oncology (2011)

285 Background: The uptake of neoadjuvant chemotherapy (NC) for the treatment of stage II/III bladder cancer remains variable despite evidence supporting its use. The aim of this study is to better understand the use of NC in Canada to facilitate standardization of practice and develop a platform for clinical trials. Methods: The survey was initially tested on a subset of medical oncologists. It was then e-mailed to 30 medical oncologists across Canada who primarily treat bladder cancer. Results: In total, 25 (83%) surveys were completed. Respondents were 92% academic based, 100% full time, and 52% in practice for &gt;10 years. The majority of referrals for all stages came from urologists with 4 respondents (16%) seeing 5-10 cases/yr, 10 (40%) seeing 11-15/yr, 5 (20%) seeing 16- 20/yr and 6 (24%) seeing &gt;20/yr. Of these 8 reported having only 1-2 referrals for NC; 7 had 3-4 NC referrals; 7 had 5-6 NC referrals; and 2 reported seeing &gt;6 referrals/year. Patients referred for NC tended to be younger (50-65); Performance Status (PS) 0/1; T-stage T3a/T3b; or nodal status N1/N2. 96% indicated they do offer NC to selected patients as both standard of care and to downsize tumors. Key factors cited for not offering NC were: Age &gt;85, PS 3/4; T-stage T2a or T4a; Nodal status: N3; GFR &lt;40ml/min. Main baseline staging modalities included CT chest/abdomen/pelvis, bone scan and cystoscopy. Gemcitabine/cisplatin was most commonly used with 20% using high-dose MVAC. Six (27%) reported doing midway staging with CT abdomen/pelvis and cystoscopy; 36% report staging after completion of chemo. Average time from last chemotherapy to cystectomy was 4-6 wks, with no patients being offered adjuvant chemotherapy postoperatively. Conclusions: The majority of GU MO in Canada would offer NC. Stage, PS, renal function, and comorbidities were the biggest determinants of offering NC, while age played a lesser role. The number of overall referrals for NC, however, remains relatively low. We plan to survey urologists in Canada to determine if differences in attitudes about NC or barriers to referrals account for the low number of referrals. No significant financial relationships to disclose.
Features of recurrence of triple-negative (TN), non-metastatic breast cancer (NMBC) patients: A single institution study.
Authors: A. E. Alarcon-Rozas, M. R. Cueva, J. Galarreta, J. Torres, E. Gonzales, J. Ramirez
Journal: Journal of Clinical Oncology (2011)

180 Background: The TN BC is the most agressive subtype. Previous studies suggested that DFS of women with TN-BC is shorter than any other subtype and they demonstrated racial differences. The behaviour of these tumours are characterised by poor prognosis affecting mostly African American young obese women. Our goal is to determine the incidence of TN in non metastatic (NM) BC, the recurrence rate (RR), the patterns of recurrence by anatomic region and the DFS. Methods: We reviewed the medical records of patients with BC diagnosed between Jan/2000 to Dec/2005 at Almenara Hospital in Lima, Peru. There were a total of 1042 patients with BC; of them 215 were identified as TN NM BC according to IHC ER, PR, and Her2/neu negatives. We collected the clinical data including age, menopausal status, staging, hormone receptor status as well as Her2/neu status. The data were analized by statistic software SPSS v. 17.0. Results: The incidence of TN NM BC were 20.6% (215); of them 18.6% (40) patients had recurrences. The median age of recurrence were 52.5 years (31-93); the median DFS were 27 months, with a median follow-up of 64 months. According to inicial staging the recurrences were 7.5% (3); 32.5% (13); and 60% (24) respectively for patients with stages I, II and III. Almost one third (35%) of patients with recurrences were lymphatic node negative at diagnosis after mastectomy. The most frequent involved organs were visceral (lung=12, liver=3) 37.5% (15); bone 25% (10); skin 20% (8); CNS 12.5% (5) and contralateral breast 5% (2). There were four nuliparus women two of them had skin recurrence and the others two had bone metastasis. Conclusions: TN NM BC constitutes 20.6% of all BC in our institution; the majority of relapses were stage III (60%). The median DFS for recurrence were 27 months and the most frequent sites involved were visceral (37%) and bone (25%). 12.5% of recurrences were to CNS and one third of the patients were lymph node negatives. This is to our knowledge the first study of patterns of recurrence in TN nonmetastatic BC in a Latino population. The incidence of TN-BC which is close to African-American population (25%).
Breast cancer survivors’ motivation to perform preventive health behaviors: An application of the protection motivation theory.
Authors: I. Mohamed, T. Jordan, M. Coman
Journal: Journal of Clinical Oncology (2011)

251 Background: Little is known about what motivates breast cancer survivors to engage in preventive health behaviors to prevent recurrence of breast cancer. The primary objective was to assess how survivors’ fear of recurrence, spirituality, and perceptions of risk and coping appraisal were associated with their motivation to perform healthy lifestyle and cancer screening behaviors. Methods: A reliable and valid questionnaire was developed. An a priori power analysis indicated that a minimum of 386 completed surveys were needed for adequate statistical power. Based on an estimated 50% return rate, the investigators randomly selected a state-wide sample of 800 survivors from Ohio. A 3-wave mailing was used to increase response rate. Results: 559 surveys were completed (72%). Respondents with higher perceived risks of recurrence were more motivated to perform healthy lifestyle behaviors than those with lower perceived risks (t=2.51, df=521, p=.039). Most (&gt;70%) agreed that healthy lifestyle behaviors such as regular exercise reduce one’s risk of recurrence. Only 43% exercised regularly. Only 54% reported their doctor discussed how to reduce the risk of recurrence. Survivors who were satisfied with their physician’s communication exercised more regularly than those who were not satisfied (chi-square =13.09, p=.016, df=5). Cancer survivors with a high level of motivation and high level of behavioral intentions were more likely to be engaging in preventive health and cancer screening behaviors. Higher levels of spirituality were positively correlated with a higher level of motivation to engage in preventive health behaviors (r=.345, n=468, p&lt;0.001). Conclusions: This study provides strong evidence that the Protection-Motivation Theory (PMT) helps to explain certain factors that impact survivors’ motivation and behavioral intentions to engage in healthy lifestyle behaviors and follow up screening tests. When developing programs for breast cancer survivors, health professionals should consider incorporating spirituality, fear of recurrence, and the constructs of the PMT.
Radioembolization of breast hepatic metastasis with SIR spheres loaded with yttrium-90 (Y-90).
Authors: R. Cianni, G. Pelle, C. Urigo, A. Saltarelli, E. Notarianni, V. Pasqualini, P. Rabuffi, E. Cortesi
Journal: Journal of Clinical Oncology (2011)

e11577 Background: To evaluate the effectiveness, the toxicity and survival rates of radioembolization with yttrium-90 (Y90), in patients affected by advanced breast liver metastasis refractory to chemotherapy through our 5-year experience Methods: From February 2005 to January 2010, we treated 45 patients affected by breast cancer. All patients were preliminary evaluated by CT, PET. 32 patients underwent preliminary hepatic angiography with infusion of technetium macroaggregated (Tc-99 m) albumin (MAA) to evaluate hepatic vasculature and hepato-pulmonary shunts. Patients with a bilirubin level >1.8 mg/dl and pulmonary shunt >20% were excluded. All patient were treated, under fluoroscopic guidance, by implantation of Y90 microspheres; the correct dose was calculated on the basis of liver tumor involvement and the body surface area formula. All patients were discharged the day after treatment. Follow-up was scheduled in 8- and 12-week CT and PET controls Results: We observed, according to RECIST criteria, complete response/partial response (CR/PR) in 24 patients, stable disease (SD) in 17 patients, and progressive disease (PD) in 8 patients. Technical success rate andl effectiveness, estimated at 3 months were respectively of (98%?) and (80%). Side effects graded by Common Terminology Criteria on Adverse Events were represented by one grade 4 hepatic failure, one grade 2 gastritis, and one grade 2 cholecystitis. The median survival and the progression-free survival calculated were 354 and 279 days, respectively. Conclusions: Liver 90Y radioembolization is effective and well tolerated in patients with liver metastases from breast cancer. Response to therapy was supported by the decrease in tumor size and activity. Further investigation is warranted to prove survival benefit.
Single Center Experience of Lenalidomide/Dexamethasone Treatment in 40 Patients with Light Chain Amyloidosis: High Toxicity in Patients with Severe Impaired Renal and Cardiac Function.
Authors: Stefan O Schoenland, Tilmann Bochtler, Sascha Dietrich, Ulrike Klein, Hartmut Goldschmidt, Anthony Ho, Ute Hegenbart
Journal: Blood (2008)
Prevention of sudden cardiac death by the wearable cardioverter defibrillator in a young patient with cardiac sarcoidosis
Authors: René Andrié, Florian C Gaertner, Dirk Skowasch
Journal: Thorax (2016)

Patients with sarcoidosis with cardiac manifestation have a worse prognosis due to sudden cardiac death. The most important predictor of survival appears to be left ventricular function.1 A 25-year-old female patient was transferred to our hospital. Initial echocardiography demonstrated a reduced ejection fraction (EF) of 30%. Based on CT scan, a diagnosis of cardiac sarcoidosis was suspected. This was proven by transbronchial biopsy. As a novel method, macrophage-directed positron emission tomography (PET)/CT using the somatostatin receptor ligand 68Ga-DOTA-TOC was used to image active inflammation in the thorax. Potential advantages of 68Ga-DOTA-TOC over 18F-FDG are a lower radiation exposure and a simplified and …