tbuckley/cabot-search huggingface dataset:
Extended TME- and MRI-assisted pathology show high incidence of pt4 after neoadjuvant treatment
Authors: S. Aamdal, S. G. Larsen, K. H. Hole, K. K. Grøholt, S. Dueland, S. Aamdal, K. Giercksky
Journal: Journal of Clinical Oncology (2009)

e15033 Background: The clinical ability of pre- and post neoadjuvant MRI to predict the necessary extension of TME (ETME) in evaluation of the areas at risk in locally advanced rectal cancer (LARC). Evaluation of treatment response to chemo/ radiation in T4 tumours is difficult. MRI cannot discriminate between different tissue components within a voxel. Increasing rate of late local relapses are reported from different studies. Methods: Prospective registration of 92 MRI evaluated T4a cancers undergoing multimodal treatment for rectal cancer between 2002 and 2007 in a tertiary referral cancer centre. MRI was found to predict T- downstaging in 10% after neoadjuvant treatment. In 35% both MRI and histopathological examination staged the patients as T4 after treatment. 55% (n=51) of the patients were downstaged after the routine postoperative pathology work-up. A new technique with MRI- based sampling of areas of infiltration was introduced and dedicated histopathological evaluation of these threatened areas was performed. Results: ETME was performed in 95% of the patients, mostly as en-bloc resections. After MRI focused pathology 50% were reclassified and up scaled to have pT4. Accordingly, at least 2/3 of the MRI staged T4 tumours before treatment still were pT4 after multimodal treatment. Conclusions: The tumours were downsized, but to lesser amount downstaged. If cure is the goal of the treatment, extended TME as en-bloc resections has to be performed. It is necessary to remove tumour as shown in pre-treatment MRI, as well as tumour, fibrosis and mucus as shown in MRI after post neoadjuvant treatment. MRI assisted pathology is an important option for right T-stage classification and for planning the extent of surgical resection. No significant financial relationships to disclose.
Correlation of MMP-1 and PAR1 expression with epithelial ovarian cancer invasiveness
Authors: Feng-Qiang Wang, Jessica Fisher, David A. Fishman
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4361 

Objectives: Protease-activated receptor-1 (PAR1) is a unique G protein-coupled receptor that has been proposed to be involved in the invasive and metastatic processes of carcinomas. MMP-1 was recently found to be a new PAR1 agonist instead of thrombin in breast cancer cells and activation of PAR1 by MMP-1 promotes breast cancer invasion. However, the expression and function of PAR1 in epithelial ovarian cancer (EOC) remains unclear. In this study, we examined the expression of MMP-1 and PAR1 in carcinoma and normal ovarian cell lines and evaluated the correlation of their expression to EOC invasiveness. Additionally, we proposed to investigate a potential link between MMP1-PAR1 activation and lysphosphatidic acid (LPA), a naturally occurring phospholipid that promotes ovarian cancer invasion. Methods: The mRNA expression of PAR1 and MMP-1 were analyzed by real time RT-PCR in three EOC cell lines (DOV13, OVCA429, and R182), an immortalized normal ovarian epithelium (IOSE-29) and breast cancer cell line MCF-7. Total and active MMP-1 was measured by ELISA in conditioned medium. Cell invasiveness was determined by Matrigel invasion assay in vitro. Results: PAR1 expression is significantly higher in all ovarian cell lines tested than in MCF-7 cells; with R182, IOSE-29, OVCA429, and DOV13 cells showing a 23–, 86–, 95–, and 99–fold increase, respectively, in mRNA expression as compared to MCF-7. Even though the levels of PAR1 expression are similar in normal (IOSE-29) and malignant ovarian epithelium (DOV13 and OVCA429), the expression of MMP-1 in DOV13 cells is significantly higher than in IOSE-29 (38-fold) and OVCA429 (237-fold) cells ( P <0.05). With the lowest PAR1 expression among all ovarian cell lines tested, R182 has the highest levels of MMP-1 expression and activation as measured by RT-PCR and ELISA. Our results from the Matrigel invasion assay showed that not PAR1 expression alone, but MMP-1 and PAR1 expression combined correlated with the invasiveness of ovarian cell lines tested. DOV13 was the most invasive cell line, showing a 1-fold increase of invasion compared to IOSE-29, 40-fold to R182, and 112-fold to OVCA429 ( P <0.05). When used as a chemoattractant, MMP-1 (0.1 nM) significantly induced a 5.2 fold increase of invasion through matrigel in DOV13 cells as compared to vehicle control (P<0.001). In addition, LPA (20 μM) significantly induced the expression of MMP-1 by appoximate 2-fold in DOV13 cells. Conclusions: Our results suggest that the co-expression of MMP-1 and PAR1 correlated with ovarian epithelial invasiveness and PAR1 expression appeared to be a prerequisite for EOC cell invasion. The effect of LPA on MMP-1 expression in DOV13 cells suggests that LPA may induce EOC invasion directly or indirectly through the MMP-1-PAR1 axis activation.
Chimeric Antigen Receptor (CAR) T Cells Targeting the CD19 Antigen for the Treatment of Pediatric Relapsed B Cell ALL
Authors: Kevin J. Curran, Isabelle Riviere, Rachel Kobos, Nancy A. Kernan, Farid Boulad, Susan E. Prockop, Andromachi Scaradavou, Thomas M. Renaud, Neerav Shukla, Peter G Steinherz, Jae H Park, Craig S. Sauter, Richard J O'Reilly, Michel Sadelain, Renier J. Brentjens
Journal: Blood (2014)
The THRIL (thalidomide [T], rituximab [R], and lenalidomide [L]) regimen for chronic lymphocytic leukemia, small lymphocytic lymphoma, and mantle cell lymphoma: daily alternating IMiDs and rituximab maintenance
Authors: M. Coleman, P. Martin, J. Ruan, R. Niesvizky, J. P. Leonard, R. Elstrom, R. R. Furman
Journal: Journal of Clinical Oncology (2008)

7079 Background: The immunomodulatory drugs (IMiDs) thalidomide (T) and lenalidomide (L) have been reported to be effective agents in chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL). Marrow toxicity often limits the use of L when used as part of the 21 day on, 7 day off schedule, whereas neurologic toxicity prevents the long term use of T. In contrast, L produces minimal risk of neurologic toxicity and T results in no marrow toxicity. Preliminary data suggest that T and L may not be cross resistant and may possibly be synergistic in combination. Alternating T with L on a daily basis may ameliorate neurologic and marrow toxicities of each by reducing the total dose of either drug and result in an improved response. Methods: 11 pts with CLL/SLL and 3 with MCL, most with heavily pre-treated disease, were treated with a regimen of rituximab 375 mg/m2 weekly x 4 every 6 months, T 50 mg alternating with L 10 mg daily on a continuous basis, and 162 mg aspirin daily. Results: Of the 14 pts, 2 CLL pts achieved a CR by 4-color flow and 2 MCL pts by bone marrow/CT criteria. There were 3 PRs (2 CLL and 1 MCL), 3 SDs (all CLL), and four non- responders (all CLL). Median follow-up is 5 months (range 2–21, mean 6). There have been 4 instances of tumor flare, all in CLL pts, treated briefly with steroids and which heralded a response. Rash related to T or L occurred in 4 pts, prompting withdrawal of therapy in 2 pts, both of whom were responding. 7 pts are off treatment because of lack of response (4 pts), progression of disease after responding (1 pt), or rash (2 pts). No pts experienced significant neurologic toxicity or suffered thromboemoblic events, and in only two instances was L held briefly for cytopenias. Conclusions: These data suggest daily alternating T+L as part of the THRIL regimen may be an effective method of reducing toxicity while achieving responses in patients by enabling longer, continuous use of IMID therapy. Whether enhanced responsiveness results from the combined sequential use of T and L requires further investigation. This approach may also merit exploration in other IMiD responsive diseases, particularly myeloma and myelodysplasia. No significant financial relationships to disclose.
Muscle injury is the principal injury type and hamstring muscle injury is the first injury diagnosis during top-level international athletics championships between 2007 and 2015
Authors: Pascal Edouard, Pedro Branco, Juan-Manuel Alonso
Journal: British Journal of Sports Medicine (2016)

During top-level international athletics championships, muscle injuries are frequent.To analyse the incidence and characteristics of muscle injuries and hamstring muscle injuries (hamstring injuries) occurring during top-level international athletics championships.During 16 international championships held between 2007 and 2015, national medical team and local organising committee physicians reported daily all injuries on a standardised injury report form. Only muscle injuries (muscle tears and muscle cramps) and hamstring injuries have been analysed.40.9% of all recorded injuries (n=720) were muscle injuries, with 57.5% of them resulting in time loss. The overall incidence of muscle injuries was higher in male athletes than female athletes (51.9±6.0 vs 30.3±5.0 injuries per 1000 registered athletes, respectively; RR=1.71; 95% CI 1.45 to 2.01). Muscle injuries mainly affected the thigh (52.9%) and lower leg (20.1%), and were mostly caused by overuse with sudden onset (38.2%) and non-contact trauma (24.6%). Muscle injury risk varied according to the event groups. Hamstring injuries represented 17.1% of all injuries, with a higher risk in male compared to female athletes (22.4±3.4 vs 11.5±2.6 injuries per 1000 registered athletes, respectively; RR=1.94; 95% CI 1.42 to 2.66).During international athletics championships, muscle injury is the principal type of injury, and among those, the hamstring is the most commonly affected, with a two times higher risk in male than female athletes. Athletes in explosive power events, male athletes and older male athletes, in specific were more at risk of muscle injuries and hamstring injuries. Injury prevention strategies should be sex-specific.
Editorial
Authors: R. Coronel
Journal: Cardiovascular Research (1997)

CardioÕascular Research devotes its content to research papers dealing with studies on physiological and pathophysiological mechanisms in the entire cardiovascular sys-Ž .tem see Instructions to Authors .Clinical as well as experimental studies are allowed into the rapid peer review process.The topics of published papers cover the cardiac system, the vascular system, blood and their respective regulatory systems.Studies ranging from those employing subcellular techniques to those in a patient population are considered.In addition, spotlight issues on selected, specialized topics are published regularly.It is the present Editorial Team's policy to publish research papers from as wide a field as possible within the domain of the cardiovascular system allowing integration of the various disciplines.The organization of the contents of the issues reflects this policy.Rather than arranging the respective papers in separate sections dealing with subspecialities, the order of the original papers is as follows.The list of contents is headed by papers on cardiac research, followed by those on blood and those on vascular research.A subsequent order is made by arranging the manuscripts Ž .according to the experimental model employed: studies on humans lead those on animals, and are followed by those employing intact organisms, isolated organs, cells and studies on the subcellular level.The Instructions to Ž .Authors as from the July 1997 issue have been altered to facilitate this process and at the same time speed up the matching of manuscripts and reviewers.The present issue of CardioÕascular Research provides an example of the Editor's policy in the combination of the Monthly Mystery and the Mini-Review by Drs.Weber and Keating, respectively, on Williams syndrome, a congenital disorder with a wide range of clinical features but with a single cause, a deletion or mutation in the elastin gene and probably its neighboring genes.The Na-H exchanger in the cardiovascular system is revisited by Drs.Frohlich and Karmazyn as a follow-up of the February 1995 issue of CardioÕascular Research.Their review also covers the ground between the gene and the patients and contains
N-Terminal Pro-Brain Natriuretic Peptide and Heart Failure Risk Among Individuals With and Without Obesity
Authors: Chiadi E. Ndumele, Kunihiro Matsushita, Yingying Sang, Mariana Lazo, Sunil K. Agarwal, Vijay Nambi, Anita Deswal, Roger S. Blumenthal, Christie M. Ballantyne, Josef Coresh, Elizabeth Selvin
Journal: Circulation (2016)

Background— Obesity is a risk factor for heart failure (HF) but is associated with lower N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. It is unclear whether the prognostic value and implications of NT-proBNP levels for HF risk differ across body mass index (BMI) categories. Methods and Results— We followed up 12 230 ARIC participants free of prior HF at baseline (visit 2, 1990–1992) with BMI ≥18.5 kg/m 2 . We quantified and compared the relative and absolute risk associations of NT-proBNP with incident HF across BMI categories. There were 1861 HF events during a median 20.6 years of follow-up. Despite increased HF risk in obesity, a weak inverse association was seen between baseline BMI and NT-proBNP levels ( r =−0.10). Nevertheless, higher baseline NT-proBNP was associated with increased HF risk in all BMI categories. NT-proBNP improved HF risk prediction overall, even among those with severe obesity (BMI ≥35 kg/m 2 ; improvement in C statistic, 0.032; 95% confidence interval, 0.011–0.053). However, given the higher HF rates among those with obesity, at each NT-proBNP level, higher BMI was associated with greater absolute HF risk. Indeed, among those with NT-proBNP of 100 to &lt;200 pg/mL, the average 10-year HF risk was &lt;5% among normal-weight individuals but &gt;10% among the severely obese. Conclusions— Despite its inverse relationship with BMI, NT-proBNP provides significant prognostic information on the risk of developing HF even among individuals with obesity. Given the higher baseline HF risk among persons with obesity, even slight elevations in NT-proBNP may have implications for increased absolute HF risk in this population.
One-step encapsulation of siRNA between lipid-layers of multi-layer polycation liposomes by lipoplex freeze-thawing
Authors: Hiroyuki Koide, Ayaka Okamoto, Hiroki Tsuchida, Hidenori Ando, Saki Ariizumi, Chiaki Kiyokawa, Masahiro Hashimoto, Tomohiro Asai, Takehisa Dewa, Naoto Oku
Journal: Journal of Controlled Release (2016)
Analysis of Q-Banding Patterns in Human Cell Lines2
Authors: C.C. Lin, S. Goldstein
Journal: JNCI Journal of the National Cancer Institute (1974)

Chromosome analysis by Q-banding was done on 3 human cell lines, HeLa, KB, and Hep-2. Excess chromosome material and several marker chromosomes were found in cells from these 3 lines. The original source of all or part of a chromosome arm of several marker chromosomes could often be determined. The number of identifiable markers was 11, 10, and 9 in HeLa, KB, and Hep-2, respectively. Certain chromosomes (ie., #1, 7, 10, 12, 14, 15, and 21) were frequently present in triplicate or quadruplicate, which suggested that these chromosomes bore certain gene(s) controlling cell growth in vitro and that increased gene dosage created a selective growth advantage. The many identifiable chromosome variations in these cells suggested their use for somatic cell hybridization studies aimed at mapping human genes on regions within specific chromosomes. However, the observations that 3 markers appeared identical in the 3 cell lines, the nonrandom representation of certain chromosomes, and the presence in all lines of the glucose-6-phosphate dehydrogenase A electrophoretic variant and the normal phosphoglucomutase type 1 pattern substantiate the idea that these cell lines were derived as contaminants from HeLa cells.
Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney Transplant
Authors: Olivier Thaunat, Alice Koenig, Claire Leibler, Philippe Grimbert
Journal: Journal of the American Society of Nephrology (2016)

The negative effect of donor-specific antibodies on the success of solid transplant is now clearly established. However, the lack of effective treatment to prevent the development of antibody-mediated lesions deepens the need for clinicians to focus on primary prevention of de novo humoral allosensitization. Among the factors associated with the risk of developing de novo donor-specific antibodies, therapeutic immunosuppression is the most obvious parameter in which improvement is possible. Beyond compliance and the overall depth of immunosuppression, it is likely that the nature of the drugs is also crucial. Here, we provide an overview of the molecular effect of the various immunosuppressive drugs on B cell biology. Clinical data related to the effect of these drugs on de novo humoral allosensitization are also examined, providing a platform from which clinicians can optimize immunosuppression for prevention of de novo donor-specific antibody generation at the individual level.
An alternative schedule of oral vinorelbine tested as 2<sup>nd</sup>-line treatment on elderly patients with advanced non-small cell lung cancer (NSCLC): A phase I feasibility trial
Authors: L. de Petris, M. R. Migliorino, S. de Santis, A. Saponiero, S. Condò, R. Di Salvia, F. de Marinis
Journal: Journal of Clinical Oncology (2005)

7328 Background: Oral vinorelbine (O-VNR), administered weekly until PD, has shown good activity as 1st-line treatment in elderly pts (RR:11%, MST 8.2 mos), though G3–4 neutropenia and G1–2 diarrhea were reported in 50% and 33% of pts respectively (Gridelli, Eur J Cancer 2004). Therefore, in the attempt to reduce toxicity, we performed this phase I study to test an alternative schedule of O-VNR, administered 2 weeks out of 3, in 2nd-line setting of NSCLC elderly pts relapsed after front-line treatment. Methods: From Aug 2003 till Oct 2004, 18 consecutive elderly pts (>70y) with advanced NSCLC progressing after first-line therapy received O-VNR 60 mg/m2 dd 1,8 every 3 wks. Pts’ characteristics were as follows: median age 74 y (range 70–79), gender M/F 83%/17%, histology adeno/squamous/undiff. 33%/50%/17%, ECOG PS 0/1/2 5%/72%/22%. First-line chemotherapy: carboplatin-based doublets in fit pts (73%), single agent gemcitabine in frail pts (27%). Response was assessed after 3 cycles of therapy. Results: 47 cycles of O-VNR were administered (median 3 cycles). Grade 3–4 neutropenia was recorded in 1 pt (5%), G3 paresthesias in 1 pt (5%). Serious adverse events requiring hospitalization were reported in 2 pts (G3 diarrhea, arrhythmia). Other toxicities were mild (G1–2): anemia (16%), diarrhea (11%), constipation (5%). No PR was observed. SD was maintained in 33% of pts, while 66% of pts. underwent PD. Median TTP: 2.5 mos; actuarial median OS (events:61%): 4 mos. Evaluation of clinical benefit is ongoing. Conclusions: The weekly schedule of O-VNB is not convenient for elderly patients with advanced NSCLC. Tested in this 2nd-line setting, O-VNR administered 2 weeks out of 3, was a feasible treatment. If compared to other schedules toxicity is remarkably reduced, though activity is poor. An evaluation in 1st-line setting on advanced NSCLC elderly patients is thus required. No significant financial relationships to disclose.
Abstract 12400: Significant Association between Decreased Plasma Levels of Brain-derived Neurotrophic Factor in Heart Failure
Authors: Seiji Takashio, Seigo Sugiyama, Megumi Yamamuro, Tomoaki Uemura, Sunao Kojima, Osamu Yasuda, Hisao Ogawa
Journal: Circulation (2013)

Background: Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family, which regulates neuronal differentiation and functions. The decreased levels of BDNF are caused by the e...
Statistically adjusted estimates of geographic mortality profiles.
Authors: Manton Kg, Stallard E, Woodbury Ma, Riggan Wb, Creason Jp, Mason Tj
Journal: JNCI Journal of the National Cancer Institute (1987)

The spatial variation of site-specific cancer mortality rates at the county or state economic area level can provide a) insights into possible etiologic factors and b) the basis for more detailed epidemiologic studies. One difficulty with such studies especially for rare cancer types is that unstable local area rate estimates resulting from small population sizes can obscure the underlying spatial pattern of disease risk.  This paper presents a methodology for producing more stable rate estimates by statistically weighting the local area rate estimate toward the experience at the national level. The methodology is illustrated by the analysis of the spatial variation of two cancer types bladder and lung for U.S. white males over the three decades 1950-1979.  (EXCERPT)
Long term effect and allergic sensitization in newly employed workers in laboratory animal facilities
Authors: Britt-Marie Sundblad, Lena Palmberg, Maciek Kupczyk, Kjell Larsson
Journal: European Respiratory Journal (2011)

Background:  Allergic reactions are common in laboratory animal workers and one of four individuals working with laboratory animals report work-related allergic symptoms and may develop occupational asthma. Working in laboratory animal facilities also implies exposure to airborne dust, contaminated with microbial and other products, which may lead to health effects.   Objective:  The aim of this study was to identify targets that can predict sensitization to laboratory animals. Skin Prick Test change and sensitization to laboratory animals were used as an outcome variable.   Methods:  In a prospective longitudinal study newly employed personnel who were employed to work with laboratory animals at Karolinska Institutet (Sweden) were investigated before and 6, 12 and 24 month after employment. Lung function, bronchial challenges, exhaled NO and nasal lavage were performed and blood samples were taken at each visit.   Results:  Seventy subjects attended all four visits and 13 of those (19%) became sensitized to laboratory animals during the study. Lung function (VC and FEV 1 ) deteriorated (as compared with predicted values) and increased blood levels of eosinophils and IL-2 over time were observed.  An increased risk of developing laboratory animal allergy was significantly associated with female sex, atopy, symptoms, CD4 15.5 kUA/L, specific IgE to rat (e87>0.01 kUA/L) and mouse (e88>0.004 kUA/L).   Conclusions:  One of five subjects became sensitized to one or two laboratory animals in this study and atopic subjects before starting working with animals had a greater risk to develop laboratory animal allergy.