tbuckley/cabot-search huggingface dataset:
A phase II study of nilotinib administered to imatinib resistant or intolerant patients with chronic myelogenous leukemia (CML) in blast crisis (BC) or relapsed/refractory Ph+ acute lymphoblastic leukemia (ALL)
Authors: R. Larson, O. Ottman, H. Kantarjian, P. le Coutre, M. Baccarani, A. Weitzman, F. Giles
Journal: Journal of Clinical Oncology (2007)

7040 Background: Nilotinib is a highly selective Bcr-Abl tyrosine kinase inhibitor that is 30-fold more potent than imatinib. In a phase I trial, nilotinib demonstrated efficacy and favorable tolerability in these pts. These results expand upon the phase I experience Methods: This phase II open-label study was designed to evaluate the safety and efficacy of nilotinib in adult imatinib-resistant or - intolerant BC pts or pts with relapsed/refractory Ph+ALL. Primary endpoint was investigator assessment of best hematologic response for BC and complete response for Ph+ALL pts. Nilotinib was started at 400mg BID with escalation to 600mg BID if no adequate response. Results: Safety and efficacy data are reported for 120 BC (27 lymphoid, 87 myeloid, 6 unknown) and 41 Ph+ALL pts (37 active disease, 4 residual disease, 38 relapsed, 3 refractory). 60% of pts had &gt;35% Ph+ metaphases for BC and 31% for Ph+ALL. Median ages was 54 yrs for BC and 46 yrs for Ph+ALL pts. Chromosomal abnormalities other than Ph+ were noted in 64 (53%) BC and 12 (29%) Ph+ALL pts. Extramedullary involvement was present in 44 (37%) BC and 3 (7%) Ph+ALL pts. Treatment is ongoing for 21 (18%) BC and 4 (10%) Ph+ALL pts. Majority of discontinuations were due to disease progression [61 (51%) in BC; 26 (63%) in Ph+ALL). Median treatment duration was 53 (1–441) and 72 (3–363) days for BC and Ph+ALL, respectively. Median dose intensity was 800mg/day for both pt groups. CHR was reported in 25 (21%) pts, marrow responses in 7 (6%) pts, and return to chronic phase in 10 (8%) pts. Complete response was reported in 10 (24%) Ph+ALL; of which, 1 patient had minimal residual disease. The most common Grade 3/4 AEs were thrombocytopenia (41%), neutropenia (28%), pneumonia (11%), and anemia (27%) in BC and thrombocytopenia (24%) in Ph+ALL pts. During study period death occurred in 9 (8%) BC and 3 (7%) Ph+ALL pts. No Ph+ALL pt developed CNS disease while on therapy. Conclusions: Nilotinib has significant clinical activity and is well tolerated in imatinib-resistant or -intolerant BC and relapsed/refractory Ph+ALL pts. Nilotinib represents an important new treatment option for these pts in which there remains a high unmet medical need. No significant financial relationships to disclose.
Abstract 13994: Masked Hypertension in Ischemic Stroke Patients
Authors: Sahrai Saeed, Ulrike Waje-Andreassen, Annette Fromm, Halvor øygarden, Eva Gerdts
Journal: Circulation (2014)

Background: Masked hypertension (MHT) is characterized by normal clinic blood pressure (BP), but elevated ambulatory BP (ABP) and associated with increased risk for target organ damage. We assessed clinical and metabolic characteristics of MHT in ischemic stroke patients. Methods: Clinic and ABP was recorded in 219 patients (aged 15-60 years) included in the prospective Norwegian Stroke in the Young Study (NORSYS) 3 ± 1 month after the acute stroke to identify normotension (NT), white-coat hypertension (WCHT), MHT and sustained hypertension (HT). Results: MHT was found in 10% of patients. In univariate analyses, patients with MHT had higher systolic ABP and serum triglycerides than those with HT, higher body mass index and waist circumference than those with NT and WTCH and lower serum HDL cholesterol than all other BP categories (all p<0.01) (Table). In multivariate logistic regression analysis, lower HDL cholesterol (OR 7.14[95% CI 1.61-33.33], p<0.01), lower fasting blood glucose (OR 2.44[95% CI 1.15-5...
Diagnostic accuracy of the gamma-glutamyl transpeptidase to platelet ratio (GPR) using transient elastography as a reference
Authors: Maud Lemoine, Mark Thursz, Vincent Mallet, Yusuke Shimakawa
Journal: Gut (2016)

We read with great interest the letter from Stockdale et al 1 in which they concluded that the gamma-glutamyl transpeptidase to platelet ratio (GPR) and aspartate transaminase (AST)-to-platelet ratio index (APRI) would not be ideal for the diagnosis of liver fibrosis in patients with HIV–HBV coinfection from West Africa. In a relatively small cohort of HIV–HBV coinfected subjects (n=100) from Ghana, the authors reported poor sensitivity (57%–67%) and specificity (63%–79%) of GRP and APRI in diagnosing advanced fibrosis (≥F3) and cirrhosis (F4). These findings are interesting, but should be interpreted with caution with regards to the internal validity of using transient elastography as the reference, the study population itself and the cut-offs generated as a result.

The GPR was originally developed for the assessment of liver fibrosis in HBV mono-infected individuals in a West African setting.2 It has been recently applied to patients predominately treated for HIV–HBV coinfection by a French team, reporting good diagnostic performance to diagnose cirrhosis (sensitivity 77%, specificity 87%).3 In both studies, the accuracy of GPR was assessed …
Abstract 12192: Association of HMGB1 With Atherosclerotic Plaque Composition and Burden in Stable Coronary Artery Disease
Authors: Grigorios Korosoglou, Christian Volz, Gitsios Gitsioudis, Nina Hofmann, Danai Laohachewin, Alexandra R Wienbrandt, Ziya Kaya, Angelika Bierhaus, Evangelos Giannitsis, Hugo A Katus, Martin Andrassy
Journal: Circulation (2012)

Objectives: The role of inflammation in atherosclerosis is widely appreciated. High mobility high group box 1 (HMGB1), an injury-associated molecular pattern molecule acting as a mediator of inflam...
Inhibition of cell proliferation by lenalidomide is associated with stimulation of Egr1 transcriptional activity in a chromosome 5 deleted Burkitt’s lymphoma and multiple myeloma cell line
Authors: A. K. Gandhi, J. Kang, D. Verhelle, D. I. Stirling, P. H. Schafer
Journal: Journal of Clinical Oncology (2007)

8110 Background: The mechanism by which lenalidomide exerts its anti-proliferative effects in deletion 5q MDS clones or MM cells is not yet fully elucidated. Early growth response (Egr1) gene is a tumor suppressor gene located on chromosome 5q31.1 that encodes a transcription factor involved in the regulation of cell proliferation and apoptosis. We hypothesized that lenalidomide may act by enhancing the expression or activity of Egr1 in sensitive hematopoietic tumor cells, especially those with only a single copy of the Egr1 gene. Methods: Transcriptional activity was measured using luciferase reporter plasmids. Gene knockdown and expression studies used siRNA technology and qRT-PCR, respectively. Cell proliferation was measured by 3 H-thymidine incorporation. Results: Lenalidomide stimulated the transcriptional activity of Egr1 in the lenalidomide-sensitive chromosome 5 deleted Burkitt's lymphoma Namalwa CSN.70 and in the MM cell line LP-1. Egr1 siRNA Namalwa cells proliferated more than mock controls, indicating that Egr1 functions as a tumor suppressor in Namalwa cells. Lenalidomide had no effect on expression of Egr1, but augmented Egr1 nuclear transport in a dose-dependent manner. Lenalidomide did not affect expression of the Egr1 downstream effector genes ATF3, fibronectin, p53, PTEN, and TGF-β1, while p21 levels increased. However, lenalidomide-induced p21 expression was not affected in Egr1 siRNA Namalwa cells. Interestingly, lenalidomide’s anti-proliferative potency was greater in Egr1 siRNA Namalwa but not in Egr1 siRNA LP-1 cells. Conclusions: Lenalidomide induces nuclear transport and transcriptional activation of the tumor suppressor Egr1, which may contribute to lenalidomide’s anti-proliferative activity in a non-p21 dependent manner. This activity may be related to the levels of Egr1 expression, explaining why del 5q31 myelodysplastic clones are especially sensitive to the cytotoxic effects of lenalidomide. No significant financial relationships to disclose.
Toxicity and prediction of survival benefit with metronomic chemotherapy in metastatic breast cancer.
Authors: Rabab Mohamed Gaafar, Marwa Mahmoud Hussein, Nasr Mohamed Ali Allahloubi, Ahmed Mohamed Abdel Warith, Wafaa Ahmed Abd Allah, Salem Eid Salem, Ebrahim Mohamed Abdel Salam
Journal: Journal of Clinical Oncology (2014)

1045 Background: Metronomic chemotherapy (MC) has shown efficacy in patients with metastatic breast cancer. We therefore tested the efficacy and toxicity of (MC) in pretreated metastatic breast cancer (MBC). Methods: This prospective phase II study was conducted in the period between July 2008 till July 2011. The study included 50 cases of heavily pretreated MBC who received (MC) (oral cyclophosphamide 50 mg/day & methotrexate 2.5 mg twice day1 and 2 every week). The primary end point was time to progression (TTP) while secondary end points were response rate, overall survival (OS), safety and impact of treatment on VEGF. Results: Forty eight patients were assessed. One case achieved complete response (CR) and 10 cases had partial response (PR) while 19 patients had stable disease with ORR of 22% while CBR was 45.5%. Median TTP was 5 months while median OS was 7 months with a median follow up period of 7 months (ranging from 1 to 33 months). Patients with negative progesterone receptors, ECOG PSI, achieving CR or PR and suffering from leucopenia, neutropenia and anemia due to treatment had significant prolonged TTP while patients with initial early stage at the time of diagnosis of breast cancer, receiving <5 previous treatment lines, achieving response and experienced anemia with (MC) had significant superior OS. In multivariate analysis, achieving response, PS I, time interval since initial diagnosis till starting (MC) and anemia were independent prognostic factors for longer TTP. Initial stage at presentation, number of previous treatment lines and response were independent prognostic factors for OS. No significant difference between the median level of VEGF at baseline and after 3 months. The median level of VEGF at baseline or after 3 months as well as the median percentage of reduction was not correlated with TTP or OS. Conclusions: MC is an attractive way of treatment being effective and less toxic. There is certain groups seem to benefit from this treatment especially those with good PS, achieved response and who experienced toxicity with treatment. Further trials are warranted to assess this approach early in the course of the disease and with other more active agents.
Comparison of Pediatric Anaphylaxis at Montreal Children's Hospital and British Columbia Children's Hospital: Rate, Clinical Characteristics, Triggers and Management
Authors: Alison YM. Lee, Paul Enarson, Ann Clarke, Sebastian La Vieille, Harley Eisman, Edmond S. Chan, Christopher Mill, Lawrence Joseph, Moshe Ben-Shoshan
Journal: Journal of Allergy and Clinical Immunology (2016)
Abstract 307: Fetal Deiodinase Increases in a Rodent Model of Myocardial Infarction
Authors: Kyle K Henderson, Rohit Vuppuluri, Robert Murphy
Journal: Circulation Research (2013)

Rationale: Thyroid hormone (T 3 ) has been shown to play a critical role in myocardial vascular homeostasis. Importantly, patients with congestive heart failure frequently have reduced serum T 3 concentrations which may induce vascular rarefaction and/or limit angiogenesis during left ventricular remodeling. One possible mechanism for reducing T 3 concentration is the reactivation of Type III deiodinase. Type III deiodinase (D3) is a fetal enzyme that inactivates thyroxine as well as T 3 . Objective: Determine whether enzymes regulating myocardial thyroid hormone concentration are altered after a myocardial infarction. Hypothesis: Myocardial D3 protein levels will increase in a rodent model of myocardial infarction, and immediate T 3 supplementation will augment angiogenesis and adaptive left ventricular remodeling. Methods and Results: The left anterior descending coronary artery was ligated in adult male Sprague Dawley rats with controls undergoing identical procedures without ligation. Osmotic mini-pumps were immediately implanted subcutaneously to deliver saline or T 3 (10ug/kg/day). One week post-surgery, hearts were removed and subdivided into ischemic, border-zone, and non-infarcted/posterior wall. Results show that Type II deiodinase (D2) protein levels were increased in the ischemic zone of infarcted hearts (D2 is normally expressed in the heart and converts thyroxine into T 3 ). D3 protein levels were also increased in the ischemic zone of MI-hearts. Importantly, the D2 to D3 ratio was reduced by ~60% suggesting T 3 concentrations could be reduced in the ischemic regions of the heart. Additionally, D3 dimers were only present in the ischemic region of the MI heart. Because dimerization is thought to be required for enzymatic activity, ischemic areas of the heart may have regional hypothyroidism. Overall, these findings support the hypothesis that myocardial D3 protein levels are increased 7-days after a myocardial infarction. Conclusion: The increase in dimerized D3 protein levels in the ischemic region of the heart may reduce local T 3 concentrations and contribute to mal-adaptive left ventricular remodeling.
Recalcitrant Condyloma Acuminatum
Authors: H S Yaffee
Journal: New England Journal of Medicine (1969)

Recently I have encountered a frustrating problem: recalcitrant condyloma acuminatum in young women.  Typically this involves unmarried females in their twenties frequently on oral contraceptives.  Three other cases involved young diabetic females  youngest 13 years of age.  Biopsy has confirmed  diagnosis.  Unlike usual cases which respond to applications of podophyllin and electrosurgery these have persisted.  Several have responded to treatment after discontinuance of the pill.  One severe case resisted all therapeutic attempts including administration of a vaccine made from  condyloma.  At present we find ourselves unclear in regard to  multiple factors involved in  transmission of wart virus and more importantly we do not understand  mechanism of natural and acquired resistance to infection by this agent.  Perhaps in diabetes and in  pseudopregnancy state  abundant vaginal mucosal glycogen favors  adaption and persistence of  offending viral microorganism.  More study will be needed in order to confirm  incidence and etiology of this condition before it can be established as a disturbance in physiological ecology which seems to be  case in intractable vaginal cadidiasis in women taking  the pill.(Full text)
Pathology of Intestinal Neoplasms and Other Lesions in Rats Exposed to Azoxymethane
Authors: Jerrold M. Ward, Richard S. Yamamoto, Carolyn A. Brown
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Pathology of Intestinal Neoplasms and Other Lesions in Rats Exposed to Azoxymethane Get access Jerrold M. Ward, Jerrold M. Ward Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard S. Yamamoto, Richard S. Yamamoto Search for other works by this author on: Oxford Academic PubMed Google Scholar Carolyn A. Brown Carolyn A. Brown Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 3, September 1973, Pages 1029–1039, https://doi.org/10.1093/jnci/51.3.1029 Published: 01 September 1973 Article history Received: 06 April 1973 Accepted: 03 May 1973 Published: 01 September 1973
BRCA1 germ-line mutation: Predictive of sensitivity to anthracyclin alkylating agents regimens but not to taxanes?
Authors: S. Delaloge, F. Bidard, Y. El Masmoudi, B. Bressac de Paillerets, O. Caron, C. Bourgier, J. Garbay, M. Spielmann, F. André
Journal: Journal of Clinical Oncology (2008)

574 Background: BRCA1-related breast cancers (BC) appear most of the time as aggressive, triple-negative tumors. BRCA1-related BC appear as a the perfect model of the such-described basal-like BC, a specific entity known to be partially chemoresistant. There have been preclinical descriptions of potential resistance of BRCA1-mutated BC to taxanes. We therefore aimed at assessing the in vivo sensitivity of BRCA1-related BC to both a FAC/FEC-type regimen and a more recent FEC-Taxane sequential regimen. Methods: We selected from our prospectively registered database all cases of localized BRCA1-related BC treated with primary CT and compared their rates of pathologic complete responses (PCR) with those of triple-negative sporadic cases receiving the same CT regimen. A logistic regression analysis was used to compare PCR rates among both treatment groups. Results: Pts and tumor characteristics, as well as PCR and pathologic nodal involvement rates after primary CT, are shown. (Table) BRCA1 BC pts were significantly younger than triple-negative controls (p<0.001). In the logistic regression model, BRCA1 mutation appeared as the only significant predictor of PCR in pts receiving FEC-type regimens (RR: 3.2 [1.1–9.2], p=0.03), while age, tumor size, cN or grade had no impact. However, there was no difference between BRCA1-carriers and controls with sequential FEC and taxanes (p=0.99). Conclusions: BRCA1-linked BC are more sensitive to FEC regimens than their sporadic counterparts. However, whereas the sequential addition of taxanes to anthracyclin alkylating agents-based neoadjuvant CT regimens increases PCR rates in triple-negative control BC pts, it does not add any benefit in BRCA1-carriers. This observation deserves further clinical assessment and biological exploration. BRCA1 mutated FEC regimen Controls FEC regimen BRCA1 mutated FEC-tax regimen Controls FEC-tax regimen N 19 73 7 15 Med age (yrs) 37 (25–48) 49 (29–66) 31 (27–38) 49 (42–66) Med T (mm) 55 (32–90) 50 (30–120) 40 (30–100) 45 (35–150) % ER- 84% 100% 100% 100% % grade 3 83% 86% 57% 73% Med nbr cycles 4 (3–6) 4 (3–6) 8 (3–8) 8 (8–8) PCR rate 47% 22% (p=0.03) 43% 47% (p= 0.99) pN+ 16% 40% 28% 48% No significant financial relationships to disclose.
Characteristics and survival of patients with lung cancer as secondary malignancy.
Authors: N. Reinmuth, P. Stumpf, A. Stumpf, T. Muley, H. Hoffmann, M. Thomas, H. Bischoff
Journal: Journal of Clinical Oncology (2010)

e18096 Background: Only sparse data are known to characterize lung cancer patients with previous malignancies. The aim of this study was to identify risk profiles for patient subgroups that could finally lead to adapted screening procedures. Methods: All patients with small cell lung cancer (SCLC) or non-SCLC (NSCLC) that were treated in our clinic between 2004 and 2006 were screened for further malignancies in their history. Data of identified patients were collected after obtaining an ethical approval. NSCLC patients without a previously treated malignancy (PrevMal) and updated follow-up served as a control group. Results: In a preliminary analysis, 436 lung cancer patients with a PrevMal were identified (Table). The previous tumors included the following: 69 breast cancers, 67 prostate cancers, 35 kidney cancers, 32 colorectal cancers, and 27 bladder cancers. 2,241 patients served as controls (con). Median age (67 vs. 64.6 years) and sex distribution (PrevMal 67% male, 33% female; Con 71% male, 29% female) were comparable (p>0.05). Interestingly, NSCLC patients with RevMals had a significantly better median overall survival (OS) compared to controls (p<0.001), which was only partly due to a lower stage at diagnosis (p<0.01). PrevMal patients with stage IV tumors had a better OS than stage IV controls (p<0.001). Moreover, PrevMal patients were diagnosed less frequently with SCLC (p<0.01), which had a similar OS compared to controls despite an earlier stage at diagnosis. Conclusions: In contrast to reported general incidence rates, lung cancer patients with PrevMals had experienced tumors that were rather often located in the genitourinary apparatus. Stage IV NSCLC shows a better survival when located in patients with PrevMal. Histology Total (%) OS (days) 95% CI (days) Stage IIIB/IV PrevMal NSCLC 383 (87.8) 1,052 800-1,304 48.3% SCLC 53 (12.2) 528 480-576 75.5% Con NSCLC 1,855 (82.8) 407 269-545 58.2% SCLC 386 (17.2) 363 314-412 83.7% No significant financial relationships to disclose.
Study's methods were inadequate
Authors: T. Esmonde
Journal: BMJ (1996)

9 4%) or surgical gastrostomy (19-9%).The success rate of radiological gastrostomy is 99-2%, compared with 95-7% for endoscopic placement.Radiological gastrostomy requires minimal sedation and is preferable to endoscopic gastrostomy, particularly in patients who are prone to aspiration (such as those with dysphagic stroke in Norton and colleagues' study), as the endoscopic method often requires heavy sedation if placement of the tube into the jejunum is considered.3The tube can be placed in the jejunum easily and rapidly when the radiological method is used, with no additional discomfort to the patient.Unlike with the endoscopic method, the colon can be routinely visualised during radiological gastro- stomy so that inadvertent perforation of the colon when it is interposed between the stomach and anterior abdominal wall is avoided.Infection at the site of the tube is less common with the radiological method as the tube is introduced through the surgically scrubbed anterior abdominal wall rather than the contaminated oral cavity.4Since radiological gastrostomy has been found to be the safest and most successful method of placing a gastrostomy tube it should be the method of choice in almost every circumstance.
Zoledronic acid in patients with adenocarcinoma of the prostate M1
Authors: F. M. Calais Da Silva, F. E. Calais Da Silva
Journal: Journal of Clinical Oncology (2006)

14623 Background: There is presently clinical evidence that confirms the value of bisphosphonates in metastatic bone disease. Studies have demonstrated that bisphosphonates may reduce bone morbidity and pain, thus increasing the quality of life of patients with multiple mieloma and bone metastases in breast cancer. In metastatic prostate cancer several oral and i.v. bisphosphonates have demonstrated a symptomatic improvement. Zoledronic acid is a bisphosphonate that has proved to diminish the skeletal related events (SRE) in metastatic prostate cancer. Methods: We have initiated a study with two types of patients: patients with bone metastases, With and Without pain, with the primary objective of measuring the efficacy of zoledronic acid in these patients, assessing the time to reduce the pain score or decrease the analgesic score in symptomatic patients and SRE in those non symptomatic, evaluating the time to bone pain and SRE. We started zoledronic acid 4 mg i.v. monthly. Results: We evaluated 87 patients, 16 were not evaluable and 71 evaluable, with at least 3 administrations. From these 70 patients, 11 had no pain with a median follow-up of 9.7 months (3–22 months) out of which 6 (54%) remain pain free (3–18 months). No SRE were registered. The remaining 60 patients had pain at initiation: 24 (40%) were not responsive and 36 (60%) were responsive and registered pain palliation, within an average follow-up of 9.2 months (3–22 months). The average time to response was 3.2 months (1–8 months) and average response duration was 4 months (1–11 months). Only 2 patients required administration of Samarium i.v.; no other SRE. Conclusions: Zoledronic acid is and I.V. bisphosphonate effective in the palliation of pain in patients with bone metastases, which produces decrease of pain and analgesic score with a fast response - in average 3.2 months - and a therapeutic efficacy maintained in average for 4 months. In high-risck patients with bone M1 but without pain, it was also verified that 54% kept pain free at the end of 9.2 months and 45% only started to feel pain again at 6 months. No significant financial relationships to disclose.