tbuckley/cabot-search huggingface dataset:
Patient selection in high-dose chemotherapy trials: relevance in high-risk breast cancer.
Authors: R García-Carbonero, M Hidalgo, L Paz-Ares, J Calzas, H Gómez, J A Guerra, R Hitt, J Hornedo, R Colomer, H Cortés-Funes
Journal: Journal of Clinical Oncology (1997)

To evaluate the impact of the selection criteria that are used in current high-dose consolidation chemotherapy (HDCT) trials on the outcome of high-risk breast cancer patients treated with conventional adjuvant chemotherapy.From 1975 to 1995, 265 breast cancer patients at our institution showed involvement of ten or more positive axillary lymph nodes. Of these, 171 received standard adjuvant combination chemotherapy, but not HDCT consolidation, and were the subjects of our study. One hundred twenty-eight patients met the standard selection criteria for HDCT with hematological support (< 60 years, no significant concomitant disease, and no progression during adjuvant treatment), whereas 43 did not. Clinical outcome was analyzed by using disease-free survival (DFS) and overall survival (OS) as endpoints. To provide an assessment of the short-term efficacy of HDCT, we also evaluated the outcome in a cohort of 39 patients from the last 4 years who met the criteria for, and were actually treated with, HDCT after adjuvant chemotherapy.With a median follow-up of 4.4 years (range, 0.7 to 17.2 years), 112 of the 171 patients have had a relapse, and 87 have died. The estimated 5-year DFS was 32.3%, and OS was 49.4%. DFS was significantly higher for patients who met the HDCT criteria (36.6% at 5 years) than for those who did not (15.8% at 5 years; P < .05). OS was also significantly more favorable in patients meeting HDCT criteria (55.4% at 5 years) than in patients not meeting HDCT criteria (22.7% at 5 years; P < .01). We performed a multivariate analysis to adjust for other potential prognostic factors and found that meeting the HDCT criteria and having undergone locoregional radiotherapy were the only significant independent predictors for DFS and OS. Finally, we compared the outcome of the 128 patients who met the HDCT criteria and were treated with conventional adjuvant chemotherapy only with that of the 39 patients who met the criteria and who actually underwent HDCT, and we did not observe significant differences in the DFS or OS between these groups.Meeting HDCT inclusion criteria is an independent indicator of favorable prognosis in high-risk breast cancer patients. The selection of patients by these criteria may explain, at least in part, the promising short-term results of nonrandomized adjuvant HDCT trials in high-risk breast cancer.
Abstract 12336: Non-invasive Screening for Pulmonary Hypertension in Idiopathic Pulmonary Fibrosis
Authors: Laith Alkukhun, Mostafa Ahmed, Manfred Baumgartner, Marie Budev, Raed Dweik, Adriano Tonelli
Journal: Circulation (2015)

Introduction: Pulmonaryhypertension (PH) is a common complication of idiopathic pulmonary fibrosis (IPF) that is associated with poor prognosis. Screening for PH in IPF patients proves to be challenging. Hypothesis: We hypothesized that combining several non-invasive studies can predict the presence of PH in IPF patients. Methods: We included 235 IPF patients who underwent right heart catheterization (RHC) as part of the lung transplant evaluation. We measured ECG and echocardiographic variables as well as the pulmonary artery (PA) diameter and ascending aorta (AA) diameters on chest CT. We recorded results of arterial blood gases (ABG), pulmonary function (PFT) and 6-min walk tests (6MWT). Results: Several variables were predictors of PH in IPF patients in univariate models including arterial oxygenation, 6MWT distance, worse right ventricular (RV) function, the QRS axis, FVC/DLCOc ratio, PA/AA diameter ratio and estimated RV systolic pressure. In multivariate analysis, RV function and PA/AA ratio remained predictors of PH (c-statistics 0.75 (0.65-0.84), accuracy 71.4%). Similarly, RV function, PA/AA ratio and QRS axis were independent predictors of precapillary PH (c-statistics 0.86 (0.76-0.92), accuracy 84.2%). A combination of PA/AA diameter ratio &lt;1.1, a QRS axis &lt;90° and normal RV function showed a negative predictive value of 85% for precapillary PH. Conclusions: There are significant differences in ECG, echocardiographic, chest CT, PFT and ABG parameters between IPF patients with and without PH. However, these noninvasive tests alone or combination are not accurate enough for PH screening in IPF.
Evidence that the Axis Comprised of TSP1-TGFβ-CTGF Plays a Major Role In the Pathophysiology of Diabetic Retinopathy:Regulatory Role Of IL-4 and IL-13
Authors: Jaime L Loyola, Melissa R Lester, Fabiola E Del Carpio-Cano, Mario C Rico, William Foster, Jeffrey Henderer, Raul A DeLa Cadena
Journal: Blood (2013)
Evolution of homologous domains of cytoplasmic intermediate filament proteins and lamins.
Authors: M Blumenberg
Journal: Molecular Biology and Evolution (1989)

The earliest gene duplications in the evolution of the intermediate filament proteins created the ancestors of acidic keratins, basic keratins, nonepithelial intermediate filament proteins, and lamins. Biochemistry and function of cytoplasmic intermediate filaments differ greatly from those of lamins. Cytoplasmic intermediate filament proteins have a different cellular location than lamins, form different types of supramolecular structures, and are missing a protein segment found in lamins; but the data presented here indicate that the cytoplasmic intermediate filaments do not have a common ancestor separate from the ancestor of lamins. In the non-epithelial intermediate filament branch, the ancestor of neurofilament proteins and the common ancestor of desmin, vimentin, and glial fibrillary acidic protein (GFAP) diverged first. By evolutionary criteria, the intermediate filament protein recently discovered in neuronal cells does not belong to the neurofilament family but is more closely related to desmin, vimentin, and GFAP. Sequences of different sub-domains yield different evolutionary trees, possibly indicating existence of sub-domain-specific functions.
Public health impact of PSA doubling time after radical prostatectomy on prostate cancer specific and overall survival
Authors: S. J. Freedland, E. B. Humphreys, L. A. Mangold, M. Eisenberger, D. J. George, A. W. Partin
Journal: Journal of Clinical Oncology (2006)

4568 Background: Among patients treated with radical prostatectomy (RP) with a PSA recurrence, we previously found men with a PSA doubling time (PSADT) &lt;3 months were at increased risk of prostate cancer death, though these men constituted a small subset of patients. We sought to determine the actual and predicted number of prostate cancer deaths stratified by PSADT. Methods: We retrospectively studied 379 men treated with RP between 1982 and 2000 with a PSA recurrence. We calculated the actual and 15-year actuarial number of prostate cancer deaths in each of the following PSADT categories: &lt;3, 3.0–8.9, 9.0–14.9, and ≥15.0 months. Results: Median follow-up after PSA recurrence was 7 years. During this time, there were 76 prostate cancer deaths; the majority (51%) were among men with a PSADT of 3.0–8.9 months. Though men with a PSADT &lt;3 months were at the greatest risk of death, this group accounted for only 20% (n=15) of all prostate cancer deaths. Using actuarial 15-year estimates of prostate cancer specific survival, 50% of all prostate cancer deaths were among men with a PSADT of 3.0–8.9 months while men with a PSADT &lt;3 months accounted for only 13% of prostate cancer deaths. Using actuarial 15-year estimates of all-cause and prostate cancer specific mortality, among men with a PSADT &lt;15 months, prostate cancer was estimated to be the cause of death in 94% (145/155). Only among men with a PSADT &gt;15 months was the risk of competing causes of mortality high enough such that the majority of deaths were not attributed to prostate cancer. Conclusions: Among a select cohort of men treated with RP who experienced a PSA recurrence, prostate cancer was estimated to account for 75% of all deaths. Though men with a PSADT &lt;3 months were at the greatest risk, the majority of deaths occurred among men with a PSADT of 3.0–8.9 months. Efforts to reduce prostate cancer mortality should focus on men with intermediate PSADT times (3.0–15.0 months) as they represent the greatest public health concern among men with PSA recurrence following RP. [Table: see text] No significant financial relationships to disclose.
Brief Communication : Marked Histoincompatibility Between and Within Sublines of AKR Mice Used in a Syngeneic Leukemia Model 2
Authors: Ralph J. Graff, Fred Valeriote, Gerald Medoff
Journal: JNCI Journal of the National Cancer Institute (1975)

Sublines of AKR mice differed significantly in their histoincompatibility to AKR/J mice, as indicated by their ability to reject AKR/J skin grafts and an AKR transplantable leukemia. Further, all sublines tested demonstrated some degree of heterogeneity, because isografts were rejected in 5-97% of the mice, depending on the subline. The presence of excessive heterogeneity among and within sublines poses a serious problem for experimental oncologists using these sublines in their tumor models.
Lead time bias in estimating survival outcomes
Authors: Antonio Facciorusso, Jose Ferrusquía, Nicola Muscatiello
Journal: Gut (2015)

We read with great interest the article by Govindarajan et al ,1 whose aim was to compare the survival outcomes among patients with postcolonoscopy colon rectal cancer (PCCRC), patients with colonoscopy-detected cancers and those diagnosed with CRC with no prior colonoscopy.

In this very well written paper, patients with PCCRC showed inferior survival time than colonoscopy-detected cancers, probably due to more advanced stages at diagnosis, while the worse outcomes were observed in those patients with no recent …
Text Messaging and Patient Engagement in an Increasingly Mobile World
Authors: Julie C. Lauffenburger, Niteesh K. Choudhry
Journal: Circulation (2016)

T he potential of short message system (SMS) text mes- saging and other mobile phone-based methods (collectively often called mHealth) to engage patients in their own health care has been met with great enthusiasm because of the relatively low cost, transportability, and widespread use of these technologies: More than 6 billion people worldwide have access to mobile phones. 1 By providing reminders and enhancing communication and interaction with healthcare professionals, there is compelling evidence for patients with HIV/AIDS that mHealth can improve adherence to medications and suppress viral loads.
Uptake of Methotrexate Linked to Polyclonal and Monoclonal Antimelanoma Antibodies by a Human Melanoma Cell Line&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: P Uadia, A H Blair, T Ghose, S Ferrone
Journal: JNCI Journal of the National Cancer Institute (1985)

[3H] Methotrexate [( 3H]MTX) was covalently linked to monoclonal antibody (MoAb) 225.28S against human melanoma, to a rabbit anti-human melanoma IgG absorbed either with human red blood cells (AHMGR) or with red blood cells and a variety of normal human tissues (AHMGR + T), or to normal rabbit IgG (NRG). Human melanoma M21 cells were incubated at 0 degrees C or 37 degrees C with 10 microM free MTX or 10 microM MTX linked to one of the above carriers. The order of net uptake of MTX during 6 hours was MTX-MoAb 225.28S greater than MTX-AHMGR greater than MTX-AHMGR + T greater than MTX-NRG greater than or equal to MTX. This order of uptake by the three antibody conjugates corresponded to the amount of conjugate bound at equilibrium at 0 degrees C and to the immunofluorescence titers. Binding sites for MoAb 225.28S were more efficient for internalization of MTX than were those for the two polyclonal antibody preparations. When M21 cells preloaded with MTX by incubation at a drug concentration of 1.0 or 10 microM were incubated in drug-free medium, the amount of cell-associated MTX rapidly declined to 1.8 pmol/mg protein, i.e., the level of intracellular dihydrofolate reductase (DHFR). However, when cells preloaded to a drug content of 112 pmol/mg protein by incubation with 10 microM MTX linked to AHMGR were transferred to conjugate-free medium, 65 pmol MTX/mg remained cell associated after 12 hours. The efflux was inhibited by chloroquine. Both the efflux medium and M21 cells after a 9.5-hour incubation period had MTX-containing catabolic fragments that inhibited DHFR.
Abstract 10295: A Novel Pathway of miR30c-Regulated Platelet-derived PAI-1 in Type 2 Diabetic Mellitus
Authors: Mao Luo, Qin Wan, Fei Liu, Rong Li, Jiyi Xia, Ni Chen, Xin Deng, Michael A Hill, Jianbo Wu
Journal: Circulation (2013)

Background: Type II diabetes mellitus is associated with higher rates of thrombotic complications in patients with coronary artery disease. High level of PAI-1 has been found in type II diabetes, however, the mechanisms by which platelets mediate thrombotic pathways are less well understood. Methods and Results: miR-30c was especially gradually down-expressed in leukocyte-depleted platelets (LDPs) from patients with pre-diabetic mellitus (pre-DM), non-complicated diabetic patients (NCDM) and diabetes mellitus type 2-coronary heart disease (DM-CHD). miR-30c level in DM-CHD was decreased 8-fold comparing to healthy individuals. Conversely, the expression of PAI-1 mRNA were up-expressed, and reached to peak in DM-CHD. Further analysis found that the total amount of PAI-1 protein in LDPs increased 4-fold~8-fold comparing to PPPs, and the amount of PAI-1 protein was high in NCDM and DM-CHD, but low in pre-DM and control. In luciferase reporter gene assay, miR-30c targets the 3’ untranslated region (3’ UTR) of ...
Relation of asthma and chronic daily headache
Authors: Young Seok Lee, Jae Seung Lee, Sang-Do Lee, Dong Soon Kim, Yeon-Mok Oh
Journal: European Respiratory Journal (2011)

Introduction: Asthma is one of most prevalent diseases worldwide. Asthma is reported to be related with diseases such as allergic rhinitis, depression, diabetes mellitus and others. Some studies with small sample size recently suggested a relation between asthma and headache. However, the relation needs to be confirmed by a study with larger sample size. The purpose of our study was to examine the relation between asthma and chronic daily headache using a large population-based database.

Method: Data of 8966 subjects were obtained from the Korean National Health and Nutrition Examination Survey II, a nationwide cross-sectional survey with a stratified random sampling. A multivariate logistic regression was performed to evaluate the relation of asthma and chronic daily headache with the adjustment of age, gender, education level, smoking, obesity, severity of stress, sleep disturbance, and divorce or bereavement.

Result: Among a total of 8966 subjects, 665 subjects had asthma and 91 subjects had chronic daily headache. 16 subjects (2.4%) in 665 subjects of asthma group and 75 subjects (0.9%) in 8301 subjects of non-asthma group suffered from chronic daily headache (P=0.001). In a subgroup analysis with only non-smokers, 12 (3.3%) in 367 subjects of asthma group and 52 (1.0%) in 5411 subjects of non-asthma group suffered from chronic daily headache (P=0.001). The multivariate logistic regression revealed that the odds ratios (OR) of chronic daily headache for asthma was 2.0 (95% CI 1.11-3.71). In the subgroup of non-smokers, the OR was 2.7 (95% CI 1.34-5.42).

Conclusion: Subjects with asthma had a higher risk of chronic daily headache than subjects without asthma in this population-based study. Asthma may be related to chronic daily headache.
Safety, efficacy, and time to clinical response with bevacizumab plus FOLFIRI regimen in metastatic colorectal cancer
Authors: S. Tomao, G. Spinelli, L. Rossi, G. Pasciuti, G. Arcangeli, M. D’Aprile, E. Veltri, G. Baiano
Journal: Journal of Clinical Oncology (2009)

e15138 Background: Bevacizumab (BEV) has shown clinical activity in metastatic colorectal cancer patients (mCRC)and randomised phase III trials have demonstrated that this agent significantly improves overall and/or progression-free survival when added to first-line irinotecan based chemotherapy (CT) regimens. We evaluated the efficacy and safety of BEV plus FOLFIRI (irinotecan, 5- fluorouracil, and leucovorin) as first line treatment in 27 consecutive metastatic colorectal cancer cases, with the primary end point to calculate the median time to clinical response with this chemotherapeutic schedule. Methods: Between October 2007 and January 2008 we collected the data on 27 patients with mCRC treated with first line chemotherapy with BEV plus FOLFIRI. Elegibility criteria had to be: mCRC; no prior CT for metastatic disease; ECOG PS 0/1, adequate organ function; no CNS metastases. The treatment consisted of a minimum of six cycles of irinotecan plus infusional 5-FU/LV according to the classical FOLFIRI schedule; BEV (5mg/kg) was given on day 1 with CT and then every 2 weeks until disease progression. Safety and response were assessed at the time of first CT and every 4 weeks thereafter. Results: 27 pts were evaluable (male 18; median age 61 years (range 45–77), ECOG PS 0: 52%, PS 1: 48%. The sites of metastases were: liver (15 pts), lung (5 pts), liver and lung (5 pts), peritoneal wall (2 pts).Median follow-up was 18 weeks. Two patients had complete response(CR) and 13 pts partial response (PR), with an overall response rate of 57.7%. Five patients had stable disease and 6 patients showed progressive disease. A clinical benefit was demonstrated in 77 % of pts. We observed a median time to clinical response of 11 weeks, evaluated with tumor markers and with CT/NMR/US examinations. A grade 3 or 4 neutropenia was detected in 39% of pts and grade 2 or 3 hypertension in 9%. We did’nt observe cases of thrombosis, bleeding and gastrointestinal perforation, sometimes related to the use of BEV. Conclusions: In this little experience the efficacy and safety of BEV associated with FOLFIRI schedule, a first line therapy in mCRC,is consistent with results from other previous studies, showing moreover a short time to clinical response with this association. No significant financial relationships to disclose.
A phase II study of sorafenib in metastatic thyroid carcinoma
Authors: M. S. Brose, A. Nellore, K. Paziana, K. Ransone, M. Redlinger, K. T. Flaherty, S. J. Mandel, A. B. Troxel, L. A. Loevner, V. Gupta-Abramson
Journal: Journal of Clinical Oncology (2008)

6026 Background: Sorafenib is a multi-tyrosine kinase inhibitor affecting Raf kinase, VEGFR, and PDGFR. We are conducting an open-label phase II study of sorafenib in patients with metastatic, iodine-refractory thyroid carcinoma to determine its efficacy and to identify biologic changes resulting from sorafenib therapy. Methods: Patients with metastatic, iodine-refractory, unresectable or locally-advanced thyroid cancer were administered sorafenib 400 mg orally BID. Responses were monitored by PET at four weeks and CT's every two to three months. The primary endpoints were response rate (RR) and time to progression (TTP) by RECIST criteria. BRAF mutation status is being determined by DNA sequencing. Pre-treatment and on-treatment tissue is being analyzed by immunohistochemistry and imaging analysis for markers of early biologic activity of sorafenib, including pERK and Ki-67, in a subset of patients in whom tissue is available. Results: To date, 36 patients have enrolled on study; median time on study is 19.5 weeks. Median age is 64 years (range 31 to 89), 18 pts (50%) are male. Histological subtypes include papillary: 22 pts (61%); follicular/Hurthle Cell: 10 pts (28%); medullary: 2 pts (5.5%), and poorly differentiated/anaplastic: 2 pts (5.5%). 34 patients are evaluable for response at this time. PR was achieved in 7 (21%) patients with a duration of response of 23.7+ to 82+ weeks. 20 (59%) had stable disease with a duration of response of 13.9+ to 87.9+ weeks. Among those who progressed, the median time to disease progression was 58.6 weeks. 21 patients remain on study. Sorafenib is well-tolerated; the most common treatment-related adverse events included fatigue, rash, diarrhea, palmer-plantar erythema (PPE), musculoskeletal pain, and weight loss. Grade 3 events included HTN: 3 pts (8%) and PPE: 3 pts (8%). One medullary thyroid cancer patient had grade 4 liver toxicity. 17 of 19 (95%) patients showed a marked response in thyroglobulin levels with a mean decrease of 70%. Correlative tissue studies, analysis of PET scans, and genotyping of all patients for BRAF mutation status are near completion. Conclusions: Sorafenib has significant anti-tumor activity in patients with advanced thyroid cancer with an overall clinical benefit rate (PR + SD) of 80%. No significant financial relationships to disclose.
Bortezomib in patients with relapsed or refractory mantle cell lymphoma (MCL): Preliminary results of the PINNACLE study
Authors: A. Goy, S. Bernstein, B. Kahl, E. Epner, J. P. Leonard, E. Stadtmauer, D. Morgan, R. Belt, S. Baidas, R. I. Fisher
Journal: Journal of Clinical Oncology (2005)

6563 Background: Bortezomib (VELCADE, Vc, Millennium Pharmaceuticals) is a novel proteasome inhibitor effective in relapsed multiple myeloma (MM) and is now being explored in MCL. Methods: Patients (pts) with relapsed or refractory MCL with a maximum of 2 prior therapies received Vc 1.3 mg/m2 IV bolus on days 1, 4, 8, and 11 of a 21-day cycle for 4 cycles beyond complete response (CR) or up to 1 year unless there was disease progression or toxicity. 102 patients have been enrolled (June 2003 through Nov 2004) in this 3-stage, phase 2 study at 29 sites (28 US, 1 UK). Response was assessed by the investigators using International Workshop criteria, while final results will be based on central radiology review. Results: 48 pts were evaluable for response at the second stage. Baseline characteristics included median age 66 y, 85% male, 88% International Prognostic Index ≥ 2, 40% lactic dehydrogenase > normal, 92% Karnofsky performance score ≥ 70%, 77% ≥ 1 extranodal site, and 57% with 2 prior lines of therapy. Median time from diagnosis was 2.3 y (range 0.2–9.0). A median of 4 cycles was administered. Median follow-up was 6.2 mo. Response rate (CR + unconfirmed CR [Cru] + partial response) was 40% (19/48) with CR + CRu 6% (3/48). Evaluation of time to progression, response duration, and survival is ongoing. Vc was well tolerated. 34% of 102 pt experienced a serious adverse event (SAE); however, only 21 of 46 events were considered related to Vc by the investigator. The most common Vc related SAEs included vomiting, abdominal pain, dehydration, and asthenia. Mean platelet (plt) counts followed a cyclical pattern, decreasing during treatment and recovering to baseline by the next cycle, as seen in MM. Only 9.3% of patients had a nadir plt count < 25,000 cells/μL. Conclusions: These data confirm the activity of Vc in MCL, and an update on the 152 pts scheduled for enrollment in this trial will be presented at the meeting. These results support the rapid development of Vc as a new treatment option for MCL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium Celgene, Cell Therapeutics, Millennium Millennium Millennium