tbuckley/cabot-search huggingface dataset:
Comparison of Urinary and Plasma Hormone Levels in Daughters of Breast Cancer Patients and Controls2
Authors: M. C. Pike, John T. Casagrande, James B. Brown, Veeba Gerkins, Brian E. Henderson
Journal: JNCI Journal of the National Cancer Institute (1977)

Plasma and urinary levels of estrogens and progesterone were studied on days 11 and 22 of the menstrual cycle in 27 teenage daughters of breast cancer patients and 25 teenage daughters of controls. Plasma and urinary values correlated well, which implied that most previous findings based on urinary levels of these hormones were applicable to their plasma levels. The "estriol ratio" (urinary estriol:urinary estrone plus estradiol) hypothesis was not supported by this study, the ratio having been no lower in the daughters of breast cancer patients than in daughters of controls. The day-11 results showed elevated plasma prolactin-estrogen values in daughters of breast cancer patients; the day-22 results did not.
Proliferative Lesions in Cheek Pouch and Esophagus of Hamsters Treated With Plants From Curacao, Netherland Antilles
Authors: Lucia J. Dunham, Ray H. Sheets, Julia F. Morton, Julia F. Morton
Journal: JNCI Journal of the National Cancer Institute (1974)

Attempts were made to develop a reliable test for the presence or absence of carcinogens in the environment. Certain plant materials suspected of affecting the development of esophageal cancer in man were applied to hamsters' upper gastrointestinal tract, including cheek pouch, in several long-term experiments. The materials tested, often with calcium hydroxide added, were 9 plants from Curaçao used in native teas and remedies, a tobacco (in snuff), and an alkaloid (arecoline) present in betel quid. Lesions developing after treatment with the plants Annona muricata, He/iotropium ternatum, Krameria ixina, and Acacia villose, and with arecoline, were a superficial spreading carcinoma of pouch epithelium, papillomas of esophagus (4), and advanced atypias (1 in pouch, 3 in esophagus). These lesions developed in relation to the cheek pouch route of application only, while none resulted after ingestion of a concentrated tea (Acacia villosa), or when administered in the diet (Annona muricata, arecoline). The histologic types and distribution of the lesions in cheek pouch and esophagus suggested that they were caused by substances in the test materials tentatively presumed to be weaker or slower in action than the known chemical carcinogens.
Positive predictive factors for residual disease in re-excision specimens of early stage breast cancer
Authors: N. A. Haideri, J. Moormeier, N. Arora
Journal: Journal of Clinical Oncology (2006)

10604 Background: Breast conservation followed by radiation is the treatment in patients with Stage 0, 1, 2, breast cancer. Patients with positive, close or indeterminate margins on excisional biopsy typically undergo reexcision. Residual tumor is identified in 32% to 62% of reexcision specimens as reported in several studies. Such patients undergo subsequent surgery. This study analyzed the pathological specimens of patients undergoing reexcision, to identify characteristics that may predict residual disease. Methods: Patients with the AJCC Stage 0, 1, 2, were identified from Jan 95–Dec 02 with positive, close or indeterminate/unknown margins. All specimens were inked and patients undergoing reexcision were included. Pathological specimens with positive margins, undergoing reexcision were reviewed. Of the 211 patients studied, 159 were eligible. Age, stage, pathologic type, differentiation, microclacifications, extensive intraductal component, lymphovascular invasion, estrogen receptor status, progesterone receptor status, Her 2 neu, S phase and lymph node involvement were evaluated to predict residual disease. Univariate analysis was performed to evaluate the different variables independently. The P values obtained were 2 sided. Results: 131 (82.3%) specimens with positive margins underwent reexcision. Residual cancer was identified in 66 (41.5%) patients. Well differentiated tumors can be an independent predictor of residual disease based on the P value of 0.025 found in this study. Stage 2B, DCIS, microcalcifications and extensive intraductal component was frequent in re-excision specimens, but not significant. Conclusions: Incidence of residual carcinoma is significant in patients undergoing reexcision, making it difficult to identify a group with positive margins where a reexcision can be avoided. Therefore patients with positive margins should typically undergo reexcision, followed by radiation for comprehensive treatment of their early stage breast cancer. [Table: see text] No significant financial relationships to disclose.
Details of French trial must be released urgently, say UK experts
Authors: Nigel Hawkes
Journal: BMJ (2016)

British specialists have called for further information to be made available urgently about a drug trial in France that has claimed one life and left another five volunteers in hospital, three with serious brain damage.

Three separate inquiries have been launched into the disaster, by the French social affairs inspectorate, the national medical safety agency, and the gendarmerie, but details about the product under test and the trial’s protocol and dosing regimen have not been disclosed. Given that 90 people are reported to have been given the experimental treatment in various doses and that drugs with a similar mode of action have been tested by other manufacturers, Carl Heneghan of Oxford University said that an urgent need for transparency transcended any prosecution.

Munir Pirmohamed of the University of Liverpool said that it was possible that the adverse reactions were an off-target effect, in which the drug was interacting with a receptor other than that intended, but that without further information it was impossible to be sure. “It is therefore vitally important that as much information as possible is …
A pediatric phase I trial and pharmacokinetic study of MLN8237, an oral selective small molecule inhibitor of aurora a kinase: A Children's Oncology Group Phase I Consortium study.
Authors: Y. P. Mosse, E. G. Lipsitz, J. M. Maris, B. Weigel, P. C. Adamson, M. Ingle, C. H. Ahern, S. Blaney
Journal: Journal of Clinical Oncology (2010)

9529 Background: MLN8237, a selective small molecule inhibitor of Aurora A Kinase, has activity in a broad range of in vitro and in vivo preclinical models of pediatric cancer. We performed a phase I trial to determine the dose limiting toxicities (DLT), maximum tolerated dose (MTD), and pharmacokinetics (PK) of MLN8237 in children with refractory solid tumors. Methods: MLN8237 was administered orally either once daily (part A1) or divided twice daily (part A2) for 7 days, every 21 days. Using the rolling-six design, four dose levels (45, 60, 80, 100 mg/m2/d) were evaluated on the once daily regimen, and subsequently two dose levels (60 and 80 mg/m2/d) on the twice-daily regimen. Pharmacokinetic studies were performed with the initial dose, with trough drug concentrations also being obtained at steady-state. Results: 37 patients were enrolled, 32 were fully evaluable for toxicity [median (range) age 12.5 yrs (4.8 - 21.6)]: 21 on part A1 and 11 on part A2. In part A1, 1/6 pts developed DLT (grade 3 mucositis) at 45 mg/m2 and 1/6 developed DLT (grade 4 mood alteration) at 80 mg/m2. At 100 mg/m2, 3/4 patients developed DLT (neutropenia –thrombocytopenia), thus exceeding the MTD. In part A2, 2/6 patients developed dose limiting myelosuppression at 80 mg/m2; one of whom also experienced grade 3 mucositis. 1/5 patient experienced DLT (grade 3 alkaline phosphatase) at 60 mg/m2. Of note, 5/11 patients experienced hand-foot-skin syndrome (grade 1 - 3) on the bid schedule versus 1/21 (grade 2) on qd schedule. A high degree of inter- patient variability in systemic exposure was observed. Average trough concentrations exceeded 1 μ M, the efficacious concentration in preclinical studies. The mean (±SD) steady state MLN8237 trough concentrations at the 45, 60, 80 and 100 mg/m2/d dose levels were 5.1 ± 5.7, 4.9 ± 6.3, 3.7 ± 3.8, and 5.5 ± 4.9 μ M, respectively. Conclusions: Although the divided dose regimen appears to be well tolerated in adults, children experienced more myelosuppression and hand-foot-skin syndrome with divided versus once daily dosing. Therefore the recommended pediatric phase 2 dose and schedule of MLN8237 is 80 mg/m2/d administered once daily for 7 days. No significant financial relationships to disclose.
Film: 28 Days Later
Authors: A. Ellis
Journal: BMJ (2002)

Directed by Danny Boyle A film from Twentieth Century Fox UK release date: 1 November ——————— Rating: ![Graphic][1]</img>![Graphic][2]</img> Londoners have been subjected to a series of posters on underground escalators over the past 28 days. On day one the poster was titled “Exposure,” on day three “Infection,” and on day eight “Evacuation.” Given the current political climate, commuters gave each other sideways glances, wondering if this was some bizarre public health warning or even anti-war propaganda. The posters were actually a clever advertising campaign for a new film. I thought it was going to be about bioterrorism. In fact, 28 Days Later … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
Independent and Parallel Evolution of New Genes by Gene Duplication in Two Origins of C4 Photosynthesis Provides New Insight into the Mechanism of Phloem Loading in C4 Species
Authors: David M. Emms, Sarah Covshoff, Julian M. Hibberd, Steven Kelly
Journal: Molecular Biology and Evolution (2016)

C4 photosynthesis is considered one of the most remarkable examples of evolutionary convergence in eukaryotes. However, it is unknown whether the evolution of C4 photosynthesis required the evolution of new genes. Genome-wide gene-tree species-tree reconciliation of seven monocot species that span two origins of C4 photosynthesis revealed that there was significant parallelism in the duplication and retention of genes coincident with the evolution of C4 photosynthesis in these lineages. Specifically, 21 orthologous genes were duplicated and retained independently in parallel at both C4 origins. Analysis of this gene cohort revealed that the set of parallel duplicated and retained genes is enriched for genes that are preferentially expressed in bundle sheath cells, the cell type in which photosynthesis was activated during C4 evolution. Furthermore, functional analysis of the cohort of parallel duplicated genes identified SWEET-13 as a potential key transporter in the evolution of C4 photosynthesis in grasses, and provides new insight into the mechanism of phloem loading in these C4 species.
Value of Basophil Activation Test for Evaluating Immediate Reactions to Proton Pump Inhibitors
Authors: Maria Salas, Esther Barrionuevo, Inmaculada Doña, Oliver Muñoz-Daga, Francisca Gómez, Tahia D. Fernandez, Adriana Ariza, Maria Isabel Montañez, Cristobalina Mayorga, Miguel Blanca, María José Torres
Journal: Journal of Allergy and Clinical Immunology (2016)
Documentation of Fertility Preservation Discussions for Young Adults With Cancer: Examining Compliance With Treatment Guidelines
Authors: John M Salsman, Betina Yanez, Kristin N Smith, Jennifer L Beaumont, Mallory A Snyder, Khouri Barnes, Marla L Clayman
Journal: Journal of the National Comprehensive Cancer Network (2016)

Background: Professional guidelines have been developed to promote discussion between providers and newly diagnosed young adults with cancer about the possibility of cancer treatment–related infertility, but previous research suggests many young adults fail to receive this information. The aim of this study was to examine rates of and factors predictive of oncologists' compliance with national guidelines for discussing potential treatment-related infertility with newly diagnosed young adults with cancer seen at an NCI-designated comprehensive cancer center. Methods: We reviewed data from the electronic medical record for new clinic encounters between medical oncologists and young adults with cancer (ages 18–39 years) from 2010 to 2012. Data from oncologist discussions of fertility preservation were abstracted, as were patient (age, sex, race, ethnicity, cancer type) and oncologist (gender, graduation year from fellowship) characteristics. Results: A total of 1,018 cases were reviewed, with 454 patients (mean, 31.5 years; 67.8% women) meeting inclusion criteria. Overall, 83% of patients were informed about potential treatment-related infertility, with patients with breast cancer (85% informed), Hodgkin lymphoma (95% informed), non-Hodgkin's lymphoma (94% informed), leukemia (88% informed), or testicular cancer (100% informed) more likely to be informed than those with other cancer types (60%–74% informed). There was a significant effect for patient sex (odds ratio, 3.57; CI, 1.33, 9.60; P=.012), with women being more likely to be informed than men. Conclusions: Reported compliance with fertility preservation guidelines was greater than published rates. Higher compliance rates in female patients and in patients with cancers more common among young adults may reflect greater awareness of fertility-related concerns among these patients and their providers.
Epidermal filaggrin deficiency mediates increased systemic T-helper 17 immune response
Authors: C.M. Bonefeld, T.H. Petersen, J. Bandier, C. Agerbeck, A. Linneberg, K. Ross-Hansen, S. Stender, P.B. Szecsi, J.D. Johansen, C. Geisler, J.P. Thyssen
Journal: British Journal of Dermatology (2016)

Cellular T-helper (Th)17 infiltrates dominate skin inflammation in filaggrin-deficient flaky tail (ft/ft) mice, and Th17 cells are found in both the skin and blood of patients with acute atopic dermatitis. However, the potential role of loss-of-function mutations in the filaggrin gene (FLG) for increased peripheral Th17 cells is unclear.To study whether mutations in FLG influence the frequency of peripheral Th17 cells.We studied blood samples from six adults with mutations in FLG and five controls without mutations for frequencies of cytokine-producing CD4(+) T cells. We evaluated ft/ft mice and wild-type (WT) control mice for interleukin (IL)-17-producing CD4(+) T cells in naive mice and following 2,4-dinitrofluorobenzene (DNFB) challenge. In addition, the T-cell receptor (TCR) Vβ-chain repertoire was analysed by flow cytometry.Human studies showed increased frequency of peripheral Th17 cells in FLG mutation carriers when compared with WT individuals. Mouse studies showed increased frequency of peripheral Th17 cells in adult ft/ft mice but not in 2-week-old ft/ft mice. Moreover, altered TCR Vβ-chain repertoire was found in ft/ft mice when compared with WT mice. An increased frequency of CD4(+) Vβ10(+) T cells producing IL-17 was found in the spleen of adult ft/ft mice when compared with WT mice. Finally, DNFB challenge induced an increased number of Th17 cells in ft/ft mice compared with WT mice.Deficiency of filaggrin appeared to be a driver of increased peripheral levels of Th17 cells. This increase must be acquired as peripheral Th17 cells were found in adult ft/ft mice but not in 2-week-old ft/ft mice indicating involvement of exogenous factors.
Evaluation of early response to neoadjuvant chemotherapy in muscle-invasive bladder cancer using dynamic contrast-enhanced MRI and diffusion weighted MRI: MARBLE study.
Authors: Rachel Anne Pearson, Pete E Thelwall, Jim Snell, Jill McKenna, Piotr Pieniazek, Emily Louise Fitzgerald, Rakesh Heer, Rhona Margaret McMenemin, Ian D. Pedley, Ashraf S. Azzabi, Herbie Newell, Ross J. Maxwell, Elizabeth R. Plummer, John A. Frew
Journal: Journal of Clinical Oncology (2016)

403 Background: Functional imaging techniques which evaluate early treatment responses may identify non-responders who would benefit from a switch in therapy. This is a prospective feasibility study of serial diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI scanning in patients undergoing neoadjuvant chemotherapy for muscle-invasive bladder cancer. Methods: Scans were performed before and during chemotherapy (10-17 days after the first and second cycles). A repeatability DW-MRI scan was acquired on the first visit. Regions-of-interest (ROI) encompassing the entire tumour were defined. Analysis of MRI parameters was undertaken and related to findings from the routine restaging CT scan performed after 3 cycles of chemotherapy. Results: 10/16 patients were male, median age 59 years, 14/16 had T3/4 disease, and 5/16 were node positive. 10/16 have completed 3 or 4 cycles of chemotherapy to date and attended for the restaging CT scan. Radiological response was identified in all cases. In the DW-MRI analysis there was no significant difference in mean tumour ADC or tumour volume between baseline and repeatability scans (mean ADC 1.19 and 1.2 respectively, n=16). Visual assessment showed a fall in contrast agent uptake within the primary bladder tumour after treatment. Conclusions: The scanning protocols enabled visualisation of the bladder tumours and derivation of kinetic parameters. DW-MRI measurements were comparable between baseline and repeat scan, suggesting that a change in ADC was more likely to be attributable to treatment response or disease progression than measurement error or inherent variation. Statistically significant rises in mean ADC and decreases in tumour volume were observed early in the treatment pathway. No patients progressed on treatment in this study. Larger studies of DCE and DW-MRI as surrogate response imaging biomarkers in bladder cancer are recommended. Clinical trial information: Study ID 14489. [Table: see text]
Ovarian Cancers Harboring Inactivating Mutations in <i>CDK12</i> Display a Distinct Genomic Instability Pattern Characterized by Large Tandem Duplications
Authors: Tatiana Popova, Elodie Manié, Valentina Boeva, Aude Battistella, Oumou Goundiam, Nicholas K. Smith, Christopher R. Mueller, Virginie Raynal, Odette Mariani, Xavier Sastre-Garau, Marc-Henri Stern
Journal: Cancer Research (2016)

CDK12 is a recurrently mutated gene in serous ovarian carcinoma, whose downregulation is associated with impaired expression of DNA damage repair genes and subsequent hypersensitivity to DNA-damaging agents and PARP1/2 inhibitors. In this study, we investigated the genomic landscape associated with CDK12 inactivation in patients with serous ovarian carcinoma. We show that CDK12 loss was consistently associated with a particular genomic instability pattern characterized by hundreds of tandem duplications of up to 10 megabases (Mb) in size. Tandem duplications were characterized by a bimodal (∼0.3 and ∼3 Mb) size distribution and overlapping microhomology at the breakpoints. This genomic instability, denoted as the CDK12 TD-plus phenotype, is remarkably distinct from other alteration patterns described in breast and ovarian cancers. The CDK12 TD-plus phenotype was associated with a greater than 10% gain in genomic content and occurred at a 3% to 4% rate in The Cancer Genome Atlas-derived and in-house cohorts of patients with serous ovarian carcinoma. Moreover, CDK12-inactivating mutations together with the TD-plus phenotype were also observed in prostate cancers. Our finding provides new insight toward deciphering the function of CDK12 in genome maintenance and oncogenesis. Cancer Res; 76(7); 1882-91. ©2016 AACR.
Influence of Cimetidine on Cardiovascular Parameters in Man
Authors: I O Samuel, J W Dundee
Journal: Journal of the Royal Society of Medicine (1979)

Cardiac output was measured in 10 patients using the dye dilution method, before and after the intravenous injection of 400 mg cimetidine. The subjects were in the intensive care unit and required intermittent positive pressure ventilation. There was no change in the average blood pressure, heart rate and cardiac output during the 60 minutes following the cimetidine, although one patient showed a marked fall in cardiac output. The results suggest that cimetidine is without a marked depressant effect on cardiovascular system.
PWE-333 Rectal cancer resection specimen quality and pathological response at 6 vs. 12 weeks after long-course chemoradiotherapy: data from a pilot randomised controlled trial
Authors: J Foster, E Cooper, N West, N Francis
Journal: Gut (2015)

<h3>Introduction</h3> Long-course chemoradiotherapy (CRT) is often delivered to down-stage locally-advanced rectal cancer prior to surgical resection. Surgery is performed after an interval period to allow time for radiation-induced tumour shrinkage and to facilitate more accurate surgery. The optimal time interval remains unclear, with little high-quality evidence to guide clinical decisions about when to operate. <h3>Method</h3> This study explores pathological outcomes from a pilot Randomised Controlled Trial (RCT) comparing an interval of six weeks versus an interval of 12 weeks between CRT and rectal cancer resection surgery. Thirty one patients requiring CRT for locally-advanced rectal cancer were recruited from seven UK centres between June 2012 and May 2014 and randomised to an interval of either 6 or 12 weeks. Photographs were taken of the intact mesorectal surfaces, and of the serial slices of resected specimens. These were assessed by an, blinded histopathologist to describe the quality of mesorectal dissection using a three-point scale. Rates of complete response, down-staging, and circumferential resection margin (CRM) involvement were assessed according to Royal College of Pathology guidelines. For tumour cell density (TCD) assessment, slides from the resected specimen and baseline biopsy were scanned at x40 magnification. For each patient, the slide with the greatest amount of residual tumour was selected and between 285 and 315 data-points were analysed by a blinded expert to describe the percentage of different tissue components for the whole tumour area. <h3>Results</h3> Twenty three patients underwent tumour resection within the trial (10 patients from the 6-week arm and 13 patients from the 12-week arm). A mesorectal specimen score of 3/3 (mesorectal fascia plane) was assigned to seven specimens from the 6-week arm (70%) and eight from the 12-week arm (62%). Three patients at 6-weeks and two patients at 12-weeks had a complete pathological response to CRT. Only one patient (from the 12-week arm) had an involved CRM. TCD was 0.3% (IQR 0.7) for the 6-week arm and 4.3% (IQR 8) for the 12 week arm (p = 0.12) <h3>Conclusion</h3> In this small randomised study, rates of mesorectal specimen quality, complete pathological response, and TCD were broadly similar when rectal cancer was resected after either a 6 or 12 week interval following CRT. Further studies are needed to further clarify whether a longer interval actually does facilitate ongoing down-staging. <h3>Disclosure of interest</h3> None Declared.
Standards of Reporting Quality of Life in Clinical Trials
Authors: Richard Stephens, Penelope Hopwood
Journal: Journal of Clinical Oncology (2000)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.8.1801 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10764442 Standards of Reporting Quality of Life in Clinical Trials Richard StephensxRichard StephensSearch for articles by this author , Penelope HopwoodxPenelope HopwoodSearch for articles by this author Show More Medical Research Council Clinical Trials Unit LondonUnited KingdomChristie National Health Service Hospital Trust ManchesterUnited Kingdom https://doi.org/10.1200/JCO.2000.18.8.1801 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology