tbuckley/cabot-search huggingface dataset:
Programmed Ventricular Stimulation for Risk Stratification in the Brugada Syndrome
Authors: Jakub Sroubek, Vincent Probst, Andrea Mazzanti, Pietro Delise, Jesus Castro Hevia, Kimie Ohkubo, Alessandro Zorzi, Jean Champagne, Anna Kostopoulou, Xiaoyan Yin, Carlo Napolitano, David J. Milan, Arthur Wilde, Frederic Sacher, Martin Borggrefe, Patrick T. Ellinor, George Theodorakis, Isabelle Nault, Domenico Corrado, Ichiro Watanabe, Charles Antzelevitch, Giuseppe Allocca, Silvia G. Priori, Steven A. Lubitz
Journal: Circulation (2016)

The role of programmed ventricular stimulation in identifying patients with Brugada syndrome at the highest risk for sudden death is uncertain.
Bone mass in patients with primary breast cancer: Measurements of the calcaneus by ultrasonometry
Authors: B. Kraemer, C. Mack, E. Kraemer, J. Huober, T. Fehm, D. Wallwiener, E. Solomayer
Journal: Journal of Clinical Oncology (2005)

827 Background Primary breast cancer patients are at higher risk of osteoporosis or further osseous complications such as metastases and consequent pain and pathological fractures. It is therefore necessary to easily screen bone mass of these patients. Detection of disseminated tumour cells in bone marrow (micrometastases) is a prognosis factor associated with poorer outcome. Immnunocytochemical detection is the standard Method: This study was undertaken to evaluate bone mass of pre- and postmenopausal breast cancer patients with heel ultrasonometry and its correlation to tumour size, grading, disseminated tumour cells in bone marrow, nodal state, marker Ki-67 and positive estrogen/progestagen receptors. Methods 188 women (age range, 31–84 years), (84 pre- and perimenopausal, 104 postmenopausal) with primary breast cancer underwent quantitative heel ultrasonometry heel before appropriate adjuvant chemotherapy when necessary. Speed of sound (SOS, m/s), broadband ultrasound attenuation (BUA, dB/MHz) and the stiffness index (combined parameter of BUA and SOS) were measured. According to Jamshidi technique 10 to 20 ml of bone marrow from each patient was aspirated intraoperatively from the anterior iliac crest and processed within 24 hours. Results Median T-score in the pre-/perimenopausal group was −0.37 (minimum −2.73 and maximum 2.70) and in the postmenopausal group −1.34 (min −5.19 and max 1.84). Median Z-scores were 0.42 and 0.38 respectively. No correlation was found between bone mass and tumour cell dissemination in the bone marrow, nodal state, marker Ki-67, and hormone receptors for both groups (P>0.05). Median T-score for patients with T1-tumours was −0.67, for T2-tumours −1.71 and for T3/4-tumours −1.77 in the whole group (P<0.05). Comparable results were also obtained for the postmenopausal group assessed alone (P<0.05). Mann Whitney and Kruskal-Wallis analysis were used. Conclusion We have demonstrated that bone mass is relatively high in primary breast cancer patients. A smaller tumour size is correlated to a higher bone mass both for pre-or peri- and for postmenopausal patients. No correlation was found for the other parameters investigated in this study. No significant financial relationships to disclose.
Spontaneous Tumors of Aging Wild House Mice, Incidence, Pathology, and C-Type Virus Expression2
Authors: Murray B. Gardner, Brian E. Henderson, Robert W. Rongey, John D. Estes, Robert J. Huebner
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Spontaneous Tumors of Aging Wild House Mice, Incidence, Pathology, and C-Type Virus Expression Get access Murray B. Gardner, Murray B. Gardner Department of Pathology, University of Southern California School of Medicine, Los Angeles, California 90033; Viral Carcinogenesis Branch, National Cancer Institute, Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Brian E. Henderson, Brian E. Henderson Department of Pathology, University of Southern California School of Medicine, Los Angeles, California 90033; Viral Carcinogenesis Branch, National Cancer Institute, Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert W. Rongey, Robert W. Rongey Department of Pathology, University of Southern California School of Medicine, Los Angeles, California 90033; Viral Carcinogenesis Branch, National Cancer Institute, Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar John D. Estes, John D. Estes Department of Pathology, University of Southern California School of Medicine, Los Angeles, California 90033; Viral Carcinogenesis Branch, National Cancer Institute, Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert J. Huebner Robert J. Huebner Department of Pathology, University of Southern California School of Medicine, Los Angeles, California 90033; Viral Carcinogenesis Branch, National Cancer Institute, Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 3, March 1973, Pages 719–734, https://doi.org/10.1093/jnci/50.3.719 Published: 01 March 1973 Article history Received: 04 August 1972 Accepted: 23 October 1972 Published: 01 March 1973
Evaluating genitourinary symptoms prior to therapy is essential when reporting on treatment related toxicities for newly diagnosed prostate cancer patients
Authors: E. A. Lyons, M. S. Wolf, S. J. Knight, C. L. Bennett
Journal: Journal of Clinical Oncology (2005)

6029 Background: Quality of life studies of prostate cancer patients such as the CAPSure and the Prostate Cancer Outcomes Study report high rates of abnormal genito-urinary and sexual function following radical prostatectomy or radiation therapy. However, these studies are limited by a paucity of information on symptoms prior to treatment. Chicago Cohort Study of Prostate Cancer investigators evaluated genito-urinary and sexual function prior to and following treatment for newly diagnosed prostate cancer. Methods: Newly diagnosed prostate cancer patients (n= 103) were approached at the time of diagnosis, immediately prior to choosing a treatment option, and 3 months later for providing answers to the EORTC-33. The instrument includes with 8 prostate specific symptoms, 4 urinary and 4 sexual function questions. Results: The mean age of the cohort was 66 years, 74% were African American, 60% were of lower socio-economic status (income <$20,000/year), and 83% had stage A/B prostate cancers. In comparison to 3-months post-treatment, pre-treatment symptoms were similar for frequent urination (43% vs 43%), urination difficulty (20% vs 23%), dysuria (10% vs 8%), nocturia (51% vs 52%), limited sexual interest (37% vs 59%), poor erections (49% vs 75%), absent sexual interest (55% vs 72%), and low sexual satisfaction (73% vs 78%). After adjustment for age and stage, urinary difficulties prior to diagnosis were the only significant predictor of urinary troubles post treatment (β=0.5, p<0.001). Baseline sexual function predicted post treatment dysfunction (β=0.6, p<0.001) though radical prostatectomy was also a significant predictor of sexual function (β=0.4, p=0.05). Conclusions: Our study is one of the first to include information from a prostate cancer cohort made up of predominantly minority and lower socioeconomic status individuals. Prostate cancer patients in our cohort reported high rates of genito-urinary and sexual dysfunction prior to as well as following therapy. Quality of life assessments of prostate cancer treatment related toxicities should take into consideration pretreatment measurements of genito-urinary and sexual function. No significant financial relationships to disclose.
Immunologic Studies With Mouse Mammary Tumor Viruses: Comparative Studies With Spontaneous Mammary Tumor Cell Vaccines From Five Inbred Mouse Strains&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A J Girardi, A S Dion, J A Holben
Journal: JNCI Journal of the National Cancer Institute (1985)

Vaccines were prepared from cells of primary spontaneous mammary tumors (MT) of RIII/Imr, GR/Imr, C3H/Imr, A/Imr, and C3HfC57BL/Imr mice. Each vaccine was used to immunize "murine mammary tumor virus (MuMTV)-free" BALB/c/Imr and C57BL/Imr mice before challenge with infectious RIII-MuMTV, GR-MuMTV, C3H-MuMTV, and A-MuMTV. RIII-MT and C3H-MT cells protected mice against tumorigenesis by all four MuMTV's; GR-MT cells protected against all but the RIII-MuMTV challenge; A-MT cells were ineffective against challenge by all four MuMTV's and significantly enhanced development of A-MuMTV-induced tumors. The activity of the C3H-MT cells was not seen when C3HfC57BL cells, free of the standard C3H-MuMTV, were used. The same cell vaccines were inoculated into the five donor strains of mice in attempts to prevent spontaneous MT in these high-incidence strains, which are naturally infected with MuMTV at birth. None of the vaccines prevented tumorigenesis in these mouse strains although delays in the appearance of tumors were observed in RIII and GR mice inoculated with either isologous MT cells or C3Hf-MT cells. The role of viral antigens acting alone or in concert with cellular antigens is discussed.
Mutation analysis of <i>PALB2</i> in high-risk and lower-risk patients negative for <i>BRCA1</i> and <i>BRCA2</i> mutations.
Authors: Shelly Cummings, Jenny Peterson, Elisha Hughes, Rajesh R. Kaldate, Sonia Chen, Jeffrey T. Trost, Christopher Arnell, Jennifer R. Saam, Benjamin Roa, Priscilla H. Fernandes
Journal: Journal of Clinical Oncology (2012)

30 Background: PALB2 has been identified as a breast cancer susceptibility gene conferring ~ 2-4 fold increased risk of breast cancer. A number of studies have estimated the PALB2 mutation prevalence to range from 0.5% - 2.9% in populations of breast cancer patients. We performed an analysis to determine the PALB2 mutation prevalence in a large U.S. referral testing population. Methods: DNA samples were anonymized from two subsets of patients: 955 early onset breast cancer patients with severe family history, and 524 patients with later onset of breast cancer and/or less severe family history. All patients were negative for deleterious sequence mutations or large rearrangements in BRCA1 and BRCA2. Results: We identified 10 disease associated PALB2 mutations in the high risk group of 955 patients and 2 deleterious PALB2 mutations in the lower risk group of 524 patients. Identified PALB2 mutations included 8 nonsense, 3 frameshift mutations and a splice site mutation. The mutation prevalence for the high risk population was 1.05% (95% C.I., 0.5 -1.92) whereas that for the lower risk population was 0.38% (95% C.I., 0.05-1.37). The observed rate of PALB2 variants of unknown significance (VUS) identified in this study was ~5% (78 VUS were in 75 of the 1479 patients that were tested). Our variant classification program which successfully decreased the VUS rate in BRCA1 and BRCA2 is similarly expected to enhance mutation classification on an on-going basis for PALB2 genetic testing. Conclusions: Genetic testing for PALB2 may be indicated as a reflex test for breast cancer patients who test negative for BRCA1 and BRCA2.
Phase I and DCE-MRI evaluation of CDP791, a di-Fab PEG conjugate that inhibits VEGFR2
Authors: G. C. Jayson, C. Ton, G. J. Parker, A. Jackson, S. Mullamitha, K. Zinkewich-Peotti, R. Felix, J. Soranson, L. Rolfe
Journal: Journal of Clinical Oncology (2007)

3523 Background: VEGF inhibitors are of proven clinical value. However, very few drugs specifically inhibit VEGFR2. CDP791 is a di-Fab PEG conjugate that binds VEGFR2 with a Kd of 49pM. Methods: We performed a single site, open label, dose-escalation study of CDP791. Cohorts of patients received between 0.3 and 30 mg/kg every 3 weeks until disease progression. DCE-MRI was performed at each dose level. Results: Thirty-one patients with colorectal, ovarian or renal cancer or other tumors were treated. There was no observed dose limiting toxicity or maximum tolerated dose. At doses of 10mg/kg or above, 7/16 patients developed cutaneous hemangiomata that regressed upon drug withdrawal. Biopsy of these confirmed that CDP791 was co-located with unphosphorylated VEGFR2. DCE-MRI revealed a dose- dependent inhibition of tumor growth over 20 days post-treatment, although there was no measurable change in K trans , an indicator of blood flow and capillary permeability. Fourteen patients received extended treatment and 5 (with renal (x2), colorectal, endometrial cancer and melanoma) had stable disease after 6 cycles. Plasma concentrations of CDP791 &gt;10mcg/mL were sustained across the 21-day cycle for doses 10mg/kg and above. Conclusions: CDP791 is a pure VEGFR2 antagonist that is well tolerated up to doses of 30mg/kg. The drug is mechanistically active, associated with hemangiomata and dose-level dependent inhibition of tumor growth but not with reduction in vascular permeability or blood flow on DCE-MRI. These data imply that the drug is active in patients but challenge our understanding of the regulation of tumor vascular permeability. In addition, they suggest that serial 3-dimensional measurements of short-term tumor growth patterns are a sensitive method to detect biological therapy-related tumor growth inhibition. [Table: see text]
Role of the Adrenal Glands in the Development of Lesions of the Liver in Rats Ingesting &lt;italic&gt;N&lt;/italic&gt;-2-Fluorenyldiacetamide&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Melvin D. Reuber
Journal: JNCI Journal of the National Cancer Institute (1965)

An experimental model with F1 hybrid rats from male A × C and female Sprague-Dawley rats fed 0.025 percent N-2-fluorenyldiacetamide in a semisynthetic diet was used to explore the role of the adrenal glands and adrenal hormones in the development of cirrhosis and cancer of the liver. The development of hepatocellular carcinomas or cirrhosis in the intact male rat was not prevented by adrenalectomy alone. In adrenal-ectomized males, hepatoma formation and cirrhosis were prevented by deoxycorticosterone, 9-α-fluorohydrocortisone, testosterone, or norethandrolone, and by castration plus cortisone administration. In intact male rats, the only hormone that decreased the incidence of hepatomas was adrenocorticotrophin. There was no change in incidence in intact males receiving deoxycorticosterone, 9-α-fluorohydrocortisone, or cortisone; or in either intact or adrenalectomized males given Medrol (6-methyl-Δ-1-hydrocortisone). Cirrhosis was decreased in intact males given deoxycorticosterone, adrenocorticotrophin, or Medrol. Intact or adrenalectomized females given cortisone or 9-α-fluorohydrocortisone, as well as those not given hormones, did not have hepatomas or cirrhosis.
Phase II trial of dose-escalated sorafenib in advanced solid tumors.
Authors: T. J. Semrad, C. Eddings, C. Pan, D. Lau, D. R. Gandara, L. Beckett, P. Lara
Journal: Journal of Clinical Oncology (2010)

3055 Background: Sorafenib is a multitargeted tyrosine-kinase inhibitor active in several tumor types. The dose-efficacy relationship of sorafenib has not been fully explored. A phase II trial in kidney cancer (Amato, ASCO 2007) reported a 52% CR/PR rate with acceptable toxicity above its recommended dose (400 mg PO BID). Here we report a phase II trial designed to explore sorafenib dose-escalation in (1) patients (pts) tolerating 400 mg BID for 28 days or (2) dose re-escalation in pts initially requiring a dose reduction but subsequently tolerating 400 mg QD. Methods: Pts started at 400 mg PO BID; doses were escalated to 600 mg BID for the second cycle and 800 mg BID for the third cycle if there were no grade 3+ adverse events (AEs) in the preceding cycle. If reduction to 400 mg QD was required in cycle 1 but tolerated for at least 28 days, sorafenib was re- escalated to 400 mg BID for cycle 3. Dose escalation was not allowed after cycle 3. The primary endpoint was the sum of the % tolerating a dose escalation to 600 mg BID for 28 days plus the % tolerating a re-escalation to 400 mg BID in cycle 3. With 90% power and 5% significance, 51 pts were needed to differentiate a dose escalation/re-escalation rate of 70% vs. the null rate of 50%. Results: Of 51 pts enrolled, 48 are evaluable with median age: 62 years; median prior regimens: 3; most common tumor types: non-small cell lung (32%) and colorectal (10%). Only 10 pts (21%) tolerated the primary endpoint of dose escalation or re-escalation and only 3 (6%) tolerated 2 successive dose escalations. Dose reduction in cycle 1 was required by 29 pts (62%) of which 4 attempted re-escalation and 3 tolerated it for 28+ days. Seven of 13 pts tolerated dose escalation to 600 mg BID for 28+ days. The most common reasons for escalation failure were AEs (34%) and progression (30%). Grade 3+ hand-foot, allergic reaction, hypophosphatemia, and abdominal pain were reasons for failure in 2+ pts. There were no RECIST responses but tumor necrosis was seen in 2 pts with head and neck cancer. Conclusions: In contrast to a prior report in kidney cancer pts, sorafenib dose escalation and/or re-escalation after a dose reduction were not feasible in this cohort of heavily pretreated solid tumor pts. Toxicities were substantial. Sorafenib dose escalation remains an investigational approach. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer
Nav1.5 N-terminal domain binding to α1-syntrophin increases membrane density of human Kir2.1, Kir2.2 and Nav1.5 channels
Authors: Marcos Matamoros, Marta Pérez-Hernández, Guadalupe Guerrero-Serna, Irene Amorós, Adriana Barana, Mercedes Núñez, Daniela Ponce-Balbuena, Sandra Sacristán, Ricardo Gómez, Juan Tamargo, Ricardo Caballero, José Jalife, Eva Delpón
Journal: Cardiovascular Research (2016)

Cardiac excitability and refractoriness are largely determined by the function and number of inward rectifier K+ channels (Kir2.1–2.3), which are differentially expressed in the atria and ventricles, and Nav1.5 channels. We have focused on how Nav1.5 and Kir2.x function within a macromolecular complex by elucidating the molecular determinants that govern Nav1.5/Kir2.x reciprocal modulation. The results demonstrate that there is an unexpected 'internal' PDZ-like binding domain located at the N-terminus of the Nav1.5 channel that mediates its binding to α1-syntrophin. Nav1.5 N-terminal domain, by itself (the 132 aa peptide) (Nter), exerts a 'chaperone-like' effect that increases sodium (INa) and inward rectifier potassium (IK1) currents by enhancing the expression of Nav1.5, Kir2.1, and Kir2.2 channels as demonstrated in Chinese hamster ovary (CHO) cells and in rat cardiomyocytes. Site-directed mutagenesis analysis demonstrates that the Nter chaperone-like effect is determined by Serine 20. Nav1.5–Kir2.x reciprocal positive interactions depend on a specific C-terminal PDZ-binding domain sequence (SEI), which is present in Kir2.1 and Kir2.2 channels but not in Kir2.3. Therefore, in human atrial myocytes, the presence of Kir2.3 isoforms precludes reciprocal IK1–INa density modulation. Moreover, results in rat and human atrial myocytes demonstrate that binding to α1-syntrophin is necessary for the Nav1.5–Kir2.x-positive reciprocal modulation. The results demonstrate the critical role of the N-terminal domain of Nav1.5 channels in Nav1.5–Kir2.x-reciprocal interactions and suggest that the molecular mechanisms controlling atrial and ventricular cellular excitability may be different.
CCGs told to delay signing £1.2bn deal on cancer and end of life services
Authors: Gareth Iacobucci
Journal: BMJ (2016)

A landmark £1.2bn (€1.6bn; $1.8bn) overhaul of services in Staffordshire for patients with cancer and for people at the end of life, dubbed by critics as “the biggest NHS privatisation yet,” has been put on hold until an inquiry into the collapse of a contract for older people’s care in Cambridgeshire has concluded.

The procurement of two contracts worth £700m for cancer care and £500m for end of life care in Staffordshire has proved controversial because of the sums of money involved and because it could lead to private firms directly running specialist services.1

The four clinical commissioning groups (CCGs) managing the procurement subsequently revealed that NHS and …
A predominance of self-identified Democrats is no evidence of a leftward bias
Authors: Benjamin E. Hilbig, Morten Moshagen
Journal: Behavioral and Brain Sciences (2015)

Abstract The reasoning of Duarte et al. hinges on the basic premise that a positive ratio of Democrats versus Republicans implies a political bias. However, when placed in a global and historical context, it is evident that U.S. Democrats currently represent a moderate position on the political left–right spectrum. Thus, Duarte et al. provide no evidence of a leftward bias in the scientific community.
Nasal septum perforations: A side effect of the association of bevacizumab and taxanes in patients with breast cancer?
Authors: A. Mailliez, C. Baldini, V. Servent, Y. Mallet, S. Dewas, J. Bonneterre
Journal: Journal of Clinical Oncology (2010)

671 Background: Bevacizumab in association with paclitaxel or docetaxel has been approved in patients with metastatic breast cancer. It is currently used in clinical studies in the adjuvant setting. We report our experience of the nasal septum perforation rate in patients receiving bevacizumab together with chemotherapy. Methods: 69 patients were treated with bevacizumab (15 mg/kg every 21 days) and chemotherapy between January 1 and December 31, 2009. An endonasal tract examination was performed in those experiencing epistaxis, mucosal crusting or nasal obstruction. Results: Sixty-two patients received bevacizumab in association with taxanes. Fifty-two (75%) had epistaxis and twenty-five had an ENT examination. Six cases of nasal septum perforation were diagnosed (8.7%); all of them had epistaxis and one had a nasal infection, some experienced turbulent airflow and whistling on inspiration. Four other patients had local symptomatic treatment and are followed by the head and neck surgeon. Four patients with nasal septum perforation had received docetaxel and two paclitaxel together with bevacizumab. Bevacizumab was discontinued in 3 patients after the diagnosis of nasal perforation. Conclusions: In our experience, the observed rate of nasal perforation is very high and might be underestimated since, up to now, a perforation has not been looked for in all the patients with nasal symptoms. We do not know whether this perforation can be cured and if bevacizumab treatment must be stopped. This side effect has been rarely reported in patients receiving bevacizumab: two cases in breast, one in ovarian and two in colon cancer. The reasons why the nasal perforation is observed is not clear: modification of the angiogenesis in the normal mucosa, the dose of bevacizumab, the combination of taxanes which induce mucositis of the nasal mucosa and possibly infection. No significant financial relationships to disclose.