tbuckley/cabot-search huggingface dataset:
A phase I dose-escalation study of BI 811283, an Aurora B inhibitor, administered every three weeks in patients with advanced solid tumors.
Authors: K. B. Mross, M. E. Scheulen, A. Frost, D. Scharr, H. Richly, B. Nokay, K. Lee, J. Hilbert, F. Fleischer, O. Fietz
Journal: Journal of Clinical Oncology (2010)

3011 Background: The serine/threonine kinase Aurora B regulates several mitotic processes and is an attractive target for therapeutic intervention. BI 811283 has demonstrated potent antitumor activity in cancer models at well-tolerated doses, with hallmarks of Aurora B inhibition. Methods: Patients with advanced, nonresectable and/or metastatic solid tumors were randomized to two treatment schedules (q2w and q3w) in a bicentric phase I dose-escalation study. The primary outcome measure was to determine the MTD of each treatment schedule—results for the q2w schedule are reported separately. In the 3-week treatment schedule (q3w), patients received BI 811283 as a 24 h i.v. infusion on day 1 of each 21-day treatment cycle. To determine the MTD, a modified 3+3 trial design with de-escalation when DLT was reached was conducted. After determination of the MTD, up to nine additional patients could be treated. PK and determinations of the phosphorylation of histone H3 in skin biopsies as PD assessments were performed. Results: Until December 2009, 57 patients had been treated with 13.5-300 mg. After reaching DLT and de-escalation, the MTD was determined as 230 mg. Reversible hematotoxicity was the main AEs at the highest dose levels dose-limiting toxicities were neutropenia and febrile neutropenia. Neutrophil count was shown to be dose dependent. Other AEs with a frequency of ≥5% and CTCAE Grade ≥3 considered drug-related were neutropenia (n=24, 42.1%), leukopenia (n=21, 36.8%) and febrile neutropenia (n=5, 8.8%). The mean number of courses was 3.3 across all dose groups at this schedule. 16 or more courses of treatment at this schedule were administered in two patients without evidence of accumulating toxicity. Stable disease as best response was reported in 33.3% of patients. Conclusions: BI 811283 is a selective Aurora B inhibitor with a favorable safety profile. The MTD in the 3-week schedule was 230 mg. An expansion at this dose is ongoing for a full description of the PK and PD of BI 811283, as well as further safety data at this dose level. All data will be taken to consideration for recommendation of the phase II dosage. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Boehringer Ingelheim Boehringer Ingelheim
Detection rate and predictive factors of sessile serrated polyps in an organised colorectal cancer screening programme with immunochemical faecal occult blood test: the EQuIPE study (Evaluating Quality Indicators of the Performance of Endoscopy)
Authors: Manuel Zorzi, Carlo Senore, Filippo Da Re, Alessandra Barca, Luigina Ada Bonelli, Renato Cannizzaro, Giovanni de Pretis, Lucia Di Furia, Emilio Di Giulio, Paola Mantellini, Carlo Naldoni, Romano Sassatelli, Douglas K Rex, Marco Zappa, Cesare Hassan
Journal: Gut (2016)

Objectives To assess detection rate and predictive factors of sessile serrated polyps (SSPs) in organised colorectal cancer (CRC) screening programmes based on the faecal immunochemical test (FIT). Design Data from a case series of colonoscopies of FIT-positive subjects were provided by 44 Italian CRC screening programmes. Data on screening history, endoscopic procedure and histology results, and additional information on the endoscopy centre and the endoscopists were collected, including the age-standardised and sex-standardised adenoma detection rate (ADR) of the individual endoscopists. The SSP detection rate (SSP-DR) was assessed for the study population. To identify SSP-predictive factors, multilevel analyses were performed according to patient/centre/endoscopist characteristics. Results We analysed 72 021 colonoscopies, of which 1295 presented with at least one SSP (SSP-DR 1.8%; 95% CI 1.7% to 1.9%). At the per-patient level, SSP-DR was associated with males (OR 1.35; 95% CI 1.17 to 1.54) and caecal intubation (OR 3.75; 95% CI 2.22 to 6.34), but not with the FIT round. The presence of at least one advanced adenoma was more frequent among subjects with SSPs than those without (OR 2.08; 95% CI 1.86 to 2.33). At the per-endoscopist level, SSP-DR was associated with ADR (third vs first ADR quartile: OR 1.55; 95% CI 1.03 to 2.35; fourth vs first quartile: OR 1.89; 95% CI 1.24 to 2.90). Conclusion The low prevalence of SSPs and the lack of association with the FIT round argue against SSP as a suitable target for FIT-based organised programmes. Strict association of SSP-DR with the key colonoscopy quality indicators, namely caecal intubation rate and high ADR further marginalises the need for SSP-specific quality indicators in FIT-based programmes.
Abstract MP23: Urinary Magnesium Excretion and Risk of Incident Hypertension
Authors: Michel M Joosten, Ron T Gansevoort, Kenneth J Mukamal, Johanna M Geleijnse, Edith J Feskens, Gerjan Navis, Stephan J Bakker
Journal: Circulation (2013)

Background: Observational studies on dietary magnesium and risk of hypertension have reported mixed findings, but have lacked direct measures of magnesium uptake. Urinary excretion of magnesium, an indicator of dietary uptake, may clarify these discrepant findings. Methods: We examined 4,070 participants aged 28-75 years free of hypertension, kidney disease, and cardiovascular disease in the PREVEND Study, a prospective population-based cohort study. Urinary magnesium excretion was measured in two 24-hour urine collections at baseline. Incident hypertension was defined as blood pressure ≥140/90 mm Hg or initiation of antihypertensive medication. Results: During a median follow-up of 7.5 years (interquartile range: 5.5-9.2 years), 1,001 participants developed incident hypertension. Mean 24-hour urinary magnesium excretion was 4.35 ± 1.61 mmol for men and 3.65 ± 1.35 mmol for women. Urinary magnesium excretion was associated with risk of hypertension in a log-linear fashion (Figure) after adjustment for age, body mass index, sex, smoking status, alcohol intake, family history of hypertension, and urinary excretion of sodium, potassium, and calcium. Each 1-unit increment in ln-transformed urinary magnesium excretion was associated with a 26% lower risk of incident hypertension after multivariable adjustment (adjusted hazard ratio, 0.74; 95% confidence interval, 0.65-0.84). Conclusion: Urinary magnesium excretion is inversely and independently associated with risk of incident hypertension. Increasing dietary intake of magnesium could reduce the risk of hypertension. Figure legend: Natural log-transformed urinary magnesium concentrations and adjusted risk of hypertension. Magnesium levels were back-transformed to original values for ease of interpretation. Association estimated by Cox regression based on restricted splines with three knots. Dashed lines represent the 95% confidence interval. The spline curve is truncated at the 0.5 percentile and 99.5 percentile of the distribution curve.
Spontaneous Tumors and Common Diseases in Two Colonies of Syrian Hamsters. II. Respiratory Tract and Digestive System2
Authors: Parviz Pour, Ulrich Mohr, Antonio Cardesa, Jürgen Althoff, Norbert Kmoch
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Spontaneous Tumors and Common Diseases in Two Colonies of Syrian Hamsters. II. Respiratory Tract and Digestive System Get access Parviz Pour, Parviz Pour Search for other works by this author on: Oxford Academic PubMed Google Scholar Ulrich Mohr, Ulrich Mohr Search for other works by this author on: Oxford Academic PubMed Google Scholar Antonio Cardesa, Antonio Cardesa Search for other works by this author on: Oxford Academic PubMed Google Scholar Jürgen Althoff, Jürgen Althoff Search for other works by this author on: Oxford Academic PubMed Google Scholar Norbert Kmoch Norbert Kmoch Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 5, May 1976, Pages 937–948, https://doi.org/10.1093/jnci/56.5.937 Published: 01 May 1976 Article history Received: 12 May 1975 Revision received: 09 October 1975 Accepted: 21 November 1975 Published: 01 May 1976
Older Age, Use Of Myeloablative Regimens For Malignant Diseases and Chronic Graft-Versus-Host Disease Are Risk Factors For Avascular Necrosis Of Bone After Allogeneic Hematopoietic Cell Transplantation In Children and Adolescents
Authors: Xianxin Li, Ruta Brazauskas, Zhiwei Wang, Amal Al-Seraihy, K. Scott Baker, Jean-Yves Cahn, Haydar A. Frangoul, James L. Gajewski, Gregory A. Hale, Jack W. Hsu, Rammurti T. Kamble, Hillard M. Lazarus, Richard T. Maziarz, Bipin N. Savani, Ami J. Shah, Mohamed L. Sorror, William A. Wood, Navneet S. Majhail
Journal: Blood (2013)
Improvement in survival of breast cancer patients with synchronous metastases
Authors: A. Y. Salmon, B. Uziely, A. Meirowitz, N. Sharon, T. Peretz
Journal: Journal of Clinical Oncology (2007)

1063 Background: Less than 10% of breast cancer patients are diagnosed with metastatic disease upon initial diagnosis. Once metastases are detected, median survival ranges between 18 and 24 months. Many new chemotherapy agents, hormonal therapy, monoclonal antibodies and supportive care options were presented during the last decade. Although a few randomized trials have demonstrated improvement in survival for various agents, it has not been clear whether the overall survival of these patients has improved. In this study, we analyzed the survival of patients diagnosed with metastatic breast cancer in during the 1990’s Methods: We have analyzed 874 patients diagnosed with breast cancer at our Institute in the years 1991–1994 and 1102 patients in 1996–1999. Tumor characteristics, treatments, and the outcomes of these patients were compared. We used Kaplan-Meier, Wilcoxon test and Cox proportional hazard in order to investigate variants between the 2 groups. Results: After excluding all women with no evidence of metastatic disease at diagnosis, we analyzed 96 patients. No major difference in tumor characteristics was found between the group of patients diagnosed in the early 1990’s and the group diagnosed in the late 1990’s. We found a significant relationship between the period of diagnosis of metastatic breast cancer and survival: median survival was 19 months for the first group and 35 months for the second group (p=0.0398, 95% C.I), with 5-year overall survival rates 8% for patients diagnosed in the early 1990’s and 25% for patients diagnosed in the late 1990’s, p=0.0497. Two years survival was 25% and 60% respectively, although insignificant, p = 0.0941. Although there was no significant difference in number of chemotherapy courses given in the 2 groups, many more new generation treatments were used for the late 90 th group. The Hazard of death within 5 years for patients treated with at least one new generation protocol was 0.53, p= 0.004. Conclusions: This study suggests that there has been significant survival improvement in breast cancer patients diagnosed with synchronous metastasis during the second half of the 1990’s. This improvement can be explained by the introduction of new treatments agents and strategies during the last decade No significant financial relationships to disclose.
Abc-06: a Randomised Phase Iii, Multi-Centre, Open-Label Study of Active Symptom Control (Asc) Alone or Asc with Oxaliplatin / 5-Fu Chemotherapy for Patients with Locally Advanced / Metastatic Biliary Tract Cancers (Abc) Previously Treated with Cisplatin / Gemcitabine Chemotherapy.
Authors: A. Lamarca, D. Palmer, H. Wasan, W.D. Ryder, L. Davies, H. Flight, J. Rogan, R. Hubner, J.A. Bridgewater, J.W. Valle
Journal: Annals of Oncology (2014)
Pathologic complete response (pCR) following weekly (wkly) paclitaxel (cremophor or albumin-bound) and carboplatin (TC) ± trastuzumab (H), ± bevacizumab (B) in patients (pts) with doxorubicin/cyclophosphamide-resistant (AC-Res) and AC-sensitive (AC-S) large and inflammatory breast cancer
Authors: R. S. Mehta, T. Schubbert, K. Kong, D. Hsiang, J. Butler, C. Baick
Journal: Journal of Clinical Oncology (2007)

591 Introduction: Historically, pCR is rare in AC-Res in contrast to AC-S BC except following TCH in HER2+ BC in preliminary analysis (SABCS-2004, #1110). Moreover, robust predictors of pCR are needed. Methods: 106 consecutive BC pts on neoadjuvant studies were treated with GM/G-CSF supported dose-dense AC (except 7**- Table ), 2 cycles if AC-Res and 4 if AC-S. Pts then received 9–12 wkly TC (3 wks on, 1 off) ± 6–8 bi-wkly B if HER2- or +12–16 wkly H if HER2+, followed by surgery. Fisher’s exact test was performed to compare pCR percentages by various characteristics. Results: pCR in breast and lymph nodes in 38 of 84 assessable tumors in the first 82 pts were documented. 67% (56/84) tumors were reduced to ≤5 mm. Overall, no difference in pCR rates were found between AC-S and AC-Res BC, but pCR rates were 2- to 4-fold higher in HER2+, AC-S (79%) and AC-Res (65%) subsets compared to HER2-, AC-S (32%) and AC-Res (16%) subsets. Higher pCR rates were associated with HER2+/hormone receptor- (HR-) &gt; HER2+/HR+, HER2-/HR- (triple-) &gt; HER2-/HR+, and within the HER2+ subset-IHC 3+/FISH+ or unknown &gt; IHC 3+/FISH- or IHC 1–2+/FISH+, and ductal &gt; other histology. No patient had clinical cardiac dysfunction or EF &lt;50, except 1 on AC/TC. 13/106 (12%) progression or death at a median follow-up of 22 months (range 2–46) is mostly due to stage IV and CNS progression. Conclusion: Short course of TCH achieves a high rate of pCR in AC-Res and AC-S, HER2+ BC in contrast to TC ± B in AC-Res and AC-S, HER2- BC. This is the first demonstration of high rate of complete AC resistance reversal across stage II-IV, inflammatory and recurrent HER2+ BC. In vivo response adjusted 2–4 cycles of dose-dense AC limited clinical cardiac toxicity. HER2+ (IHC 3+/FISH+ or unknown), HR- and ductal histology are significant predictors of high pCR. HER2 and HR confer 4 predictive subtypes of BC. [Table: see text] No significant financial relationships to disclose.
Validation of screening tools for cancer related fatigue syndrome (CRFS)
Authors: S. B. Alexander, P. C. Stone, P. L. Andrews
Journal: Journal of Clinical Oncology (2008)

9601 Background: CRFS has been found in up to 30% of breast cancer survivors. The “gold standard” method of assessment involves patients undergoing the Diagnostic Interview for Cancer Related Fatigue (DICRF) and the Structured Clinical Interview for the Diagnostic and Statistical Manual 4th revision (SCID). These interviews require specialist training to administer and are time consuming. An effective screening questionnaire could facilitate the identification of CRFS and would reduce the number of patients required to undergo diagnostic interviewing. Methods: A prospective, cross sectional, prevalence and case-control study was undertaken in disease-free women (n = 208) who had completed primary treatment for breast cancer between 3 months and 2 years previously. Written informed consent was obtained. The study endpoints were to determine the sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of the Functional Assessment of Cancer Therapy Fatigue module (FACT-F) and the Bidimensional Fatigue Scale (BFS). Participants completed the FACT-F, the BFS, the SCID and the DICRF. A receiver operating characteristic curve (ROC) was produced and the best cut-offs for the questionnaires were determined. Results: 200/208 patients completed the study. A score of 36 on the FACT-F and a score of 11 on the BFS were identified as the optimal cut-offs. For the FACT-F; sensitivity = 80%, specificity = 71%, PPV = 55% and NPV = 89%. For the BFS; sensitivity = 91.7%, specificity = 52.9%, PPV = 45.5% and NPV = 93.6%. The Area under the ROC curve for FACT-F was 0.790 and for BFS was 0.787. Conclusions: Both the FACT-F and the BFS perform acceptably as screening instruments. If a woman has a sub-threshold score on either the FACT-F or the BFS then they are unlikely to be a true case of CRFS. However, a “positive” score on either questionnaire requires further evaluation with “gold standard” interviews in order to determine whether the woman is truly a case of CRFS. No significant financial relationships to disclose.
Feasibility and risks of pre-operative chemotherapy (CT) with Folfox 4 and surgery for resectable colorectal cancer liver metastases (LM). Interim results of the EORTC Intergroup randomized phase III study 40983
Authors: B. Nordlinger, H. Sorbye, M. Debois, M. Praet, B. Glimelius, G. J. Poston, P. M. Schlag, E. T. Walpole, W. Bechstein, T. Gruenberger
Journal: Journal of Clinical Oncology (2005)

3528 Background: After resection of LM, 5y survival is 30%, but cancer recurrence is frequent. The benefit of combining surgery and CT is not yet formally proven. Methods: This study evaluates pre- and postoperative CT. Between September 2000 and July 2004, 364 patients with potentially resectable liver metastases from colorectal cancer were randomized between peri-operative FOLFOX4 (oxaliplatin 85mg/m2 and LV5FU2), 6 cycles before and 6 cycles after surgery, and surgery alone. The primary endpoint was disease-free survival. Safety was a secondary end point. Results: We report the interim safety results of the first 346 patients with at least 3 months follow-up post surgery (174 patients in the CT arm and 172 in the surgery arm). Median follow up is 17 months. Baseline characteristics were similar in both arms. In the CT arm, 84.8% of the patients were documented to have completed CT (6 preoperative cycles). 28.2% of the patients who started CT required a dose reduction. Grade ≥3 diarrhea was reported in 6.7%, vomiting in 2.0% febrile neutropenia in 1.3% and grade 3 neurotoxicity in 4.7% of the patients. There was no toxic death. Surgery was performed within the timelines foreseen (median 114 days) in the CT arm. 92.5% and 96.7% of evaluated patients underwent surgery in the CT and surgery arm respectively. Surgical procedures were similar in both arms. Complete resection was achieved in 96.7% and 88.5% of operated patients in CT and surgery arms, respectively. Surgical complications (within 30 days of surgery) were observed in 24.5% and 13.3%, with 4.5% and 2.3% requiring reoperation, and deaths in 0.9% and 1.6% in the CT and surgery arms respectively. Most frequent surgical complications were: transient liver failure (6.4% and 1.6%), biliary fistula (5.5% and 1.6%), bleeding (2.7% and 2.3%), wound infection (2.7 and 3.1%), intra-abdominal infection (4.5% and 0.8%), and cardio-pulmonary failure (2.7% and 1.6%). Conclusions: Preoperative chemotherapy with FOLFOX4 was safely administered. Timing of surgery was respected. Surgical mortality and morbidity rates were low. Results on survival should be available in 2006. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi Sanofi
Lovastatin enhances the antiproliferative effect of trastuzumab in HER2 over expressing breast cancer cells
Authors: O. M. Halaweh, C. Lobocki, L. Dumasia, A. Drelichman
Journal: Journal of Clinical Oncology (2006)

2546 Background: Trastuzumab, a recombinant humanized anti-HER2 monoclonal antibody, has been found to have potent antiproliferative effects in HER2 overexpressing human breast tumors. Lovastatin, an HMG-CoA reductase inhibitor suppresses growth, and induces apoptosis in breast cancer cells. Both agents induce a G 0 /G 1 arrest of cell cycle progression. The purpose of this study was to evaluate the antiproliferative effect of the novel combination of lovastatin and trastuzumab in human breast cancer cell lines. Methods: Increasing doses of lovastatin (0.16-40 μM) and trastuzumab (0.039-1 μg/ml) were tested alone and in combination. Three breast carcinoma cell lines were studied: two HER2 overexpressing lines (BT474 and SKBR3) and one cell line that expresses low levels of the receptor (MCF7). Inhibition of growth was assessed after 7 days of treatment by the MTT colorimetric assay, while apoptosis was detected using an in situ DNA Fragmentation Detection kit. Results: A dose-dependent growth inhibition was demonstrated in all three cell lines tested with lovastatin, while trastuzumab was only effective in the HER2 overexpressing cells. Trastuzumab (0.06 μg/ml) inhibited cell growth by 29.3% and 40.1%, while lovastatin (2.5 μM) caused an inhibition of 19.1% and 43% in the BT474 and SKBR3 cell lines, respectively. The combination of trastuzumab and lovastatin, at these doses, significantly inhibited growth in BT474 and SKBR3 cells by 45.4% and 68.9% (P &lt; 0.001, oneway ANOVA) compared to either agent alone. Conclusions: Lovastatin plus trastuzumab treatment led to increased growth inhibition in HER2 positive breast cancer cell lines. Further studies in an animal model are warranted. This combination may also have important clinical therapeutic implications. No significant financial relationships to disclose.
Commentary
Authors: Steve Bird
Journal: British Journal of Sports Medicine (2000)

Objectives-(a)To assess the validity and reliability of producing and reproducing a given exercise intensity during cycle ergometry using a braille version of Borg's standard 6-20 rating of perceived exertion (RPE) scale, and (b) to determine whether the exercise responses of blind participants, at a given produced RPE, were similar to those reported in recognised guidelines for sighted subjects.Methods-Ten healthy registered blind volunteer participants (four women, six men; mean (SD) age 23.2 (9.0) years) performed an initial graded exercise cycle test to determine maximal heart rate (HRMAX) and maximal oxygen uptake (VO 2 MAX).Three trials of three exercise bouts at RPEs 9, 11, and 13 were then performed in random order on three separate days of the same week, with expired air and heart rate measured continuously.Each exercise bout was followed by 10 minutes of rest.The validity of the scale as a means of producing diVerent exercise intensities was assessed using a two factor (RPE × trial) repeated measures analysis of variance.Intertrial reliability was assessed using intraclass correlation coeYcients (ICC) and the bias ±95% limits of agreement (95%LoA) procedure.Results-Participants reported no diYculty in using the braille RPE scale.When asked to produce exercise intensities equating to RPE 9, 11, and 13, they elicited mean %VO 2 MAX values of 47%, 53%, and 63% respectively.Analysis of variance showed no significant diVerences in either %HRMAX or %VO 2 MAX between trials at each of the three RPEs, but there was a significant diVerence (p<0.001) in both %HRMAX and %VO 2 MAX between the three RPE levels.All pairwise comparisons of the three diVerent RPEs were significantly diVerent (p<0.016).The ICC between the second and third trial for %HRMAX was significant (p <0.05) for all three RPEs.Similarly for %VO 2 MAX, the ICC was significant for RPE 9 and 11 but not 13.The 95%LoA decreased for both %HRMAX and %VO 2 MAX with each successive trial.Conclusions-Blind participants were successful in using a braille RPE scale to diVerentiate exercise intensity on a cycle ergometer.In every trial at RPE 13, all participants achieved %HRMAX and %VO 2 MAX levels, which fell within the recommendedrangefordevelopingcardiorespiratory fitness.Using %HRMAX as a judge of intertrial reliability, the participants were able to repeat similar exercise intensities after two trials at each of the three RPEs (9, 11,13).The same was true for RPE 9 and 11, when %VO 2 MAX was used as a judge, but further trials were required to achieve similar reliability at RPE 13.A braille RPE scale can be used by healthy blind people during cycle ergometry, with similar eVect to the visual analogue scale recommended for use in healthy sighted people.