tbuckley/cabot-search huggingface dataset:
Mental mood of gynecologic cancer patients assessed by distress and impact thermometer (DIT; a two-item, self-report questionnaire) and hospital anxiety and depression scale (HADS; a 14-item, self-report questionnaire) during the initial treatment in the first 6 months: KCOG-G1103 study.
Authors: Yoshio Itani, Atsushi Arakawa, Hiroshi Tsubamoto, Kimihiko Ito, Ryutaro Nishikawa, Kayo Inoue, Tsunekazu Kita, Atsushi Shugiura, Shinji Toyoda, Keiko Kuritani, Shizuka Shichido Yamamoto, Yasunari Miyagi, Naoto Furukawa
Journal: Journal of Clinical Oncology (2014)

9568 Background: Thirty percent of cancer patients are reported to suffer from psychological distress which detracts from treatment adherence, but that is often underestimated in clinical settings. HADS is one of the validated scales for screening emotional distress in cancer patients. However, it is not used widely because it is cumbersome to score. DIT is a 2-item (the Distress and the Impact) self-report questionnaire, but is not well verified. Methods: One hundred and seventeen patients were enrolled between 2011.5.1 and 2012.3.31 and 95 were eligible. Median age was 54 years (range 31–77). The numbers of completed questionnaires (HADS & DIT) at (a) pretreatment, (b) 3 months, and (c) 6 months were 95, 80, and 70, respectively. No patients relapsed during the investigated period. Results: 1) Areas under the curve of receiver operating characteristic curves for Distress and Impact with respect to HADS positivity were 0.855 and 0.875 respectively. At Distress ≥4 and Impact ≥2, sensitivity, specificity, positive predictive value, and negative predictive value were 0.818 (95% confidence interval (CI): 0.707–0.898), 0.875 (95%CI: 0.739–0.945), 0.9 (95%CI: 0.786–0.957), and 0.778 (95%CI: 0.637–0.875), respectively. 2) In each patient, the mean scales of (b) were significantly reduced in HADS (mean 3.2; p<0.0002) and in Distress (mean 1.7; p<0.0001), but not in Impact (mean 0.66; p=0.072) compared with (a). Those of (c) were significantly reduced in HADS (mean 4.5; p<0.0001), in Distress (mean 2.3; p<0.0001), and in Impact (mean 1.09; p=0.031) compared with (a) (Student’s paired t-test). Conclusions: 1) DIT is a reliable tool for ruling out clinical psychiatric distress. 2) For the first 6 months of treatment, mental mood would have a tendency to be improved, but not completely. Therefore, gynecologic oncologists should screen psychiatrically distressed patients by DIT and introduce them to psychiatric treatment early in the initial treatment. Clinical trial information: 000005727.
Acquired <i>MET</i>D1228V Mutation and Resistance to MET Inhibition in Lung Cancer
Authors: Magda Bahcall, Taebo Sim, Cloud P. Paweletz, Jyoti D. Patel, Ryan S. Alden, Yanan Kuang, Adrian G. Sacher, Nam Doo Kim, Christine A. Lydon, Mark M. Awad, Michael T. Jaklitsch, Lynette M. Sholl, Pasi A. Jänne, Geoffrey R. Oxnard
Journal: Cancer Discovery (2016)

Amplified and/or mutated MET can act as both a primary oncogenic driver and as a promoter of tyrosine kinase inhibitor (TKI) resistance in non-small cell lung cancer (NSCLC). However, the landscape of MET-specific targeting agents remains underdeveloped, and understanding of mechanisms of resistance to MET TKIs is limited. Here, we present a case of a patient with lung adenocarcinoma harboring both a mutation in EGFR and an amplification of MET, who after progression on erlotinib responded dramatically to combined MET and EGFR inhibition with savolitinib and osimertinib. When resistance developed to this combination, a new MET kinase domain mutation, D1228V, was detected. Our in vitro findings demonstrate that MET
A Novel Compound ARN-3236 Inhibits Salt-Inducible Kinase 2 and Sensitizes Ovarian Cancer Cell Lines and Xenografts to Paclitaxel
Authors: Jinhua Zhou, Albandri Alfraidi, Shu Zhang, Janice M. Santiago-O'Farrill, Venkata Krishna Yerramreddy Reddy, Abdulkhaliq Alsaadi, Ahmed A. Ahmed, Hailing Yang, Jinsong Liu, Weiqun Mao, Yan Wang, Hiroshi Takemori, Hariprasad Vankayalapati, Zhen Lu, Robert C. Bast
Journal: Clinical Cancer Research (2016)

Purpose: Salt-inducible kinase 2 (SIK2) is a centrosome kinase required for mitotic spindle formation and a potential target for ovarian cancer therapy. Here, we examine the effects of a novel small-molecule SIK2 inhibitor, ARN-3236, on sensitivity to paclitaxel in ovarian cancer.Experimental Design: SIK2 expression was determined in ovarian cancer tissue samples and cell lines. ARN-3236 was tested for its efficiency to inhibit growth and enhance paclitaxel sensitivity in cultures and xenografts of ovarian cancer cell lines. SIK2 siRNA and ARN-3236 were compared for their ability to produce nuclear-centrosome dissociation, inhibit centrosome splitting, block mitotic progression, induce tetraploidy, trigger apoptotic cell death, and reduce AKT/survivin signaling.Results: SIK2 is overexpressed in approximately 30% of high-grade serous ovarian cancers. ARN-3236 inhibited the growth of 10 ovarian cancer cell lines at an IC50 of 0.8 to 2.6 μmol/L, where the IC50 of ARN-3236 was inversely correlated with endogenous SIK2 expression (Pearson r = -0.642, P = 0.03). ARN-3236 enhanced sensitivity to paclitaxel in 8 of 10 cell lines, as well as in SKOv3ip (P = 0.028) and OVCAR8 xenografts. In at least three cell lines, a synergistic interaction was observed. ARN-3236 uncoupled the centrosome from the nucleus in interphase, blocked centrosome separation in mitosis, caused prometaphase arrest, and induced apoptotic cell death and tetraploidy. ARN-3236 also inhibited AKT phosphorylation and attenuated survivin expression.Conclusions: ARN-3236 is the first orally available inhibitor of SIK2 to be evaluated against ovarian cancer in preclinical models and shows promise in inhibiting ovarian cancer growth and enhancing paclitaxel chemosensitivity. Clin Cancer Res; 23(8); 1945-54. ©2016 AACR.
Translating translation into patient benefit for atopic eczema
Authors: N.J. Reynolds, A. Sinha, M.S. Elias, S.J. Meggitt
Journal: British Journal of Dermatology (2016)

This review considers, in the context of British Skin Foundation (BSF)‐funded translational research into atopic eczema conducted in Newcastle, the complex interactions between clinical and non‐clinical scientists in both academia and industry and how this may have impacted on clinical care. However, research in individual centres does not occur in isolation and clinically relevant outcomes from collaborative research are increasingly supported through regional and national networks. This is illustrated by our trial of azathioprine in adults with atopic eczema conducted across centres in the North East of England that employed pharmacogenetic dosimetry. Correspondingly the formation of a UK Translational Network for Translational Research in Dermatology (UK TREND) has facilitated the development of a UK‐wide network to support atopic eczema projects based on an e‐Delphi prioritisation exercise.
Effect of 1-year intravenous ibandronate treatment on time to serum creatinine increase in patients with skeletal metastases from breast cancer
Authors: I. J. Diel, D. Tripathy, J.-J. Body, B. Bergström
Journal: Journal of Clinical Oncology (2004)

733 Background: In a 2-year, phase III clinical trial, intravenous ibandronate, a newly-approved aminobisphosphonate for the prevention of skeletal events in patients with breast cancer and bone metastases, was shown to have a renal adverse event profile comparable to placebo (Body JJ, et al. Ann Oncol 2003;14:1399–405). This abstract reports the results of an analysis of time to renal function deterioration from this trial, over the first year of treatment. Methods: Women with a confirmed diagnosis of metastatic breast cancer were included in this multicenter, randomized, double-blind study, and received placebo or 6mg ibandronate infused over 1–2 hours every 3–4 weeks. A post-hoc Kaplan-Meier analysis assessed time to serum creatinine increase, defined by an increase of 0.5mg/dL from baseline (if <1.4mg/dL); 1.0mg/dL from baseline (if ≥1.4mg/dL), or twice the baseline value. Results: 309 patients were randomized to treatment and included in this safety analysis (placebo n=157, ibandronate 6mg n=152). The Kaplan-Meier estimate of the time to first deterioration of renal function over 1 year of treatment was comparable between the placebo and ibandronate groups. The proportion of patients without defined serum creatinine increases after 48 weeks was 96% with placebo and 98% with ibandronate 6mg (ns, p>0.05 versus placebo). Conclusions: There was no clinically-relevant increase in serum creatinine levels with intravenous ibandronate over 1 year of treatment. Considered alongside previously-reported 2-year renal adverse event data from the same trial, these results demonstrate that a 6mg dose infused every 3–4 weeks does not affect renal functioning. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Pharmaceuticals Roche Pharmaceuticals Roche Pharmaceuticals Roche Pharmaceuticals F. Hoffmann-La Roche
Clinical benefit of liver hanging maneuver for right-side major hepatectomy
Authors: H. Hayashi, T. Beppu, J. Nasu, T. Masuda, T. Mizumoto, T. Ishiko, H. Takamori, K. Kanemitsu, M. Hirota, H. Baba
Journal: Journal of Clinical Oncology (2007)

15171 Background: Liver hanging maneuver is a new technique in anterior approach of major hepatectomy. However, the impact of the maneuver has never been fully investigated in patients with liver tumors. To evaluate the surgical benefits of liver hanging maneuver, we set up a comparative study in right-side major hepatectomy. Methods: From 2000 to 2006, 326 hepatectomy were performed in our institution. Fifty-eight patients with liver tumor (hepatocellularcarcinoma in 36, metastatic liver tumor in 13, and the others in 9) considered for right-side major hepatectomy were prospectively analyzed. Right-side hepatectomy included 26 right hepatectomy, 24 extended right hepatectomy, and 8 tri-segmentectomy. The patients were devided into a group with conventional approach (n = 21), a group with anterior approach without hanging maneuver (n = 19), and a group with approach with liver hanging maneuver (n = 18). In the three groups, age, body mass index, child-pugh classification, type of liver tumor, staging in hepatocellularcarcinoma, tumor size, resected liver weights, intraoperative blood loss, frequency of transfusion and surgical time were analyzed. Results: In conventional approach, anterior approach without hanging maneuver, and approach with liver hanging maneuver, mean age was 55, 59, and 65 years, and mean tumor size was 65, 75, and 108mm, respectively. Patients with liver hanging maneuver were significantly elder (p&lt;0.05) and have larger tumor size (p&lt;0.01). There were no significant differences in body mass index, child-pugh classification, type of liver tumor, staging in hepatocellularcarcinoma, and resected liver weights. Mean intraoperative blood loss was 1771, 805, and 704g, and mean surgical time was 562, 483, and 435minutes, and the frequency of red blood cell transfusion was 33, 21, and 17%, respectively. Patients with liver hanging maneuver had significantly less intraoperative blood loss (P=0.0001) and surgical time (P=0.002). The frequency of red blood cell transfusion in the liver hanging maneuver group was significantly lower than that of the conventional group (p&lt;0.05). Postoperative morbidity rate were 33.3, 15.8, and 16.7%, respectively. Conclusions: Liver hanging maneuver is less invasive and a quite useful method for right-side major hepatectomy. No significant financial relationships to disclose.
A Genetic Screen In Zebrafish Identified Dlst As a Potential Therapeutic Target For Human Acute T-Lymphoblastic Leukemia
Authors: Nicole M Anderson, Hongling Peng, Daniel Helman, Itrat Harrold, Takaomi Sanda, Trevor Grant, Nicholas Nagykery, Yasmina Samaha, Meng Le, Adam Amsterdam, Donna Neuberg, Marc R. Mansour, Travis Denton, John Kanki, Anurag Singh, A. Thomas Look, Hui Feng
Journal: Blood (2013)
Treatment of Older Patients, 40 to 70 Years of Age, with Acute Lymphoblastic Leukemia According to a Chemotherapy Regimen That Includes a Novel Pre-Phase for Rapid Tumor Load Reduction. Results of the Dutch-Belgian HOVON-71 Study.
Authors: Simon M. G. J. Daenen, Bronno van der Holt, Adriaan W. Dekker, Roelof Willemze, Anita Rijneveld, Bart J. Biemond, Petra Muus, Arjan A van de Loosdrecht, Harry Schouten, M. van Marwijk Kooy, Dimitri Breems, Johan Maertens, Hilde Demuynck, Pierre W Wijermans, Shulamiet Wittebol, Ellen W. de Klerk, Jan J. Cornelissen
Journal: Blood (2009)
Clinical Relevance of Cardiac Iron Overload Estimated by MRI T2* in Regularly Transfused Low Risk MDS.
Authors: C. Ferte, O. Ernst, O. Beyne-Rauzy, M.P. Chaury, S. Brechignac, M. Brauner, T. Mirault, K. Kanaan, E. Bourgeois, N. Cambier, Bruno Quesnel, Pierre Fenaux, Christian Rose
Journal: Blood (2006)
Abstract B24: Targeting hyaluronan sensitizes breast cancer-associated fibroblasts to lapatinib and overcomes stromal resistance
Authors: Andriy Marusyk, Doris Tabassum, Jennifer Guerriero, Andrew Place, Andrii Rozhok, Antony Letai, Kornelia Polyak
Journal: Cancer Research (2016)

Abstract Tumors represent abnormal organs comprised not only of neoplastic cells, but also of normal cells and extracellular matrix (ECM). Therefore, clinical progression as well as response to therapies depends not only on properties of neoplastic cells, but also on the interactions between different types of cells within tumors. Cancer-associated fibroblasts (CAFs) are the major non-nenoplastic cell component of tumors and major the producers of ECM. Despite extensive research, mechanisms and consequences of interactions between breast carcinoma cells and CAFs remain insufficiently understood. Using organotypic 3d co-cultures between breast carcinoma cell lines representing different sub-types of the disease and CAFs, we interrogated changes in gene expression and metabolism that result from the interaction. We found that while contact with fibroblats induces robust changes in expression and metabolism, the majority of changes are subtype and cell line specific. Furthermore, we found that fibroblasts can provide a dramatic protection against dual EGFR/HER2 inhibitor lapatinib. Protective effect requires close contact between the two cell types in context of 3d culture, and is mediated by both reduced accumulation of the drug within carcinoma cells and elevated apoptotic threshold. Using synthetic lethality screens, we have identified several signaling pathways whose inhibition enhances cytotoxic effects of lapatinib. Interrogation of functional relevance of ECM has revealed that the stromal protection can be reversed by targeting hyaluronan, a major ECM component produced by fibroblasts. Rather than simply enhancing cytotoxic activity of lapatinib against carcinoma cells, hyaluronidase treatment sensitized CAFs to lapatinib, thereby removing the protective niche. Our studies shed light on molecular changes induced by the interaction with CAFs and offer novel approaches for overcoming microenvironmental protection by therapeutically targeting CAFs. Citation Format: Andriy Marusyk, Doris Tabassum, Jennifer Guerriero, Andrew Place, Andrii Rozhok, Antony Letai, Kornelia Polyak. Targeting hyaluronan sensitizes breast cancer-associated fibroblasts to lapatinib and overcomes stromal resistance. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B24.
Detective leptin signaling improves regulatory T cell immune response and protects mice from atherosclerosis
Authors: Soraya Taleb, Olivier Herbin, Hafid Ait-Oufella, Wirn Verreth, Pierre Gourdy, Veromque Barateau, Regine Merval, Bruno Esposito, Karine Clement, Paul Holvoet, Alain Tedgui, Ziad Mallat
Journal: Circulation (2007)
Bilateral breast cancer
Authors: J. Oh, B. Park
Journal: Journal of Clinical Oncology (2007)

17073 Background: The clinical significance of bilateral breast cancer is unclear and its influence on prognosis is controversial. The aim of this study is to assess the impact of bilateral breast cancer on the prognosis compared with unilateral breast cancer and examine clinicopathologic characteristics of Bilateral and Unilateral breast cancer. Methods: 108 patients included in this study from Jan 1980 to Dec 2005 and all information regarding medical and family history of breast cancer came from medical records and questionnaires. Results: There were 108 patients with bilateral breast cancer and its incidence was 2.3% of total breast cancer. The incidence of bilateral breast cancer after 1998 was 3.5% (90/2548) compare with the incidence before 1998 (0.9%). The mean age of patients with bilateral and unilateral breast cancer was 45.34 and 47.54 years, respectively. (p=0.032) Compared to unilateral breast cancer, bilateral group did not differ in gravida, marital status, use of HRT, but the number of case which was diagnosed with breast cancer among close relatives was more frequent (7 cases/6.5% vs 126 cases/2.8%, p=0.024). Although the most frequent histopathologic subtype was ductal carcinoma in both groups, the distribution of the histopathologic subtypes was different between the groups as invasive lobular carcinoma was present in a higher percentage of patients with bilateral breast cancer than in patients with unilateral breast cancer (6.5% vs 2.1%, p=0.002). It suggested that risk factors of developing bilateral breast cancer were family history, lobular tumor, use of hormonal therapy based on the result of multivariate regression analysis. There were no statistically significant difference in 5-year disease free survival and overall survival in both groups (bilateral: 83.25%, 89.52% vs unilateral: 82.74%, 88.79%), (p=0.3934, p=0.3114). Conclusion: In lobular carcinoma patients with family history of breast cancer during follow-up, the possibility of contralateral breast cancer should be considered more carefully and the therapeutic strategy for secondary tumor should resemble the treatment procedure for the primary tumor. No significant financial relationships to disclose.
An examination of oncology drug purchasing compared to average sales price
Authors: U. B. Favret, W. M. Jordan, M. S. Kirchof, M. E. Neltner, D. A. Chudzik
Journal: Journal of Clinical Oncology (2008)

20500 Background: Drug costs make up approximately 70–85% of expenses for community oncology practices. This study examines the buying power effectiveness of community oncology practices relative to Average Sales Price (ASP) and ASP+6% reimbursement. Methods: During the 2nd & 3rd qtrs of 2007, data was independently collected from 20 oncology practices ranging in size from 1–18 physicians on 12 key oncology products and compared to CMS published ASP data for the 2nd qtr 2007. Results: The average of pricing data submitted for 11/12 practices and the median pricing data submitted for 12/12 practices were higher than ASP. The minimum price for 5/12 practices was higher than ASP and the maximum price for 8/12 was higher than ASP+6%. The average product difference in price between practices was $84.41. The 20 practices reported multiple different prices for individual products ranging from 14 up to 19 unique prices for a given product. Conclusions: Effective systems and methods are not being used to negotiate pricing at many community oncology practices. Few practices in our data negotiated prices below ASP and many practices pay prices above ASP+6% reimbursement for key products. This economic strain combined with inadequate reimbursement limits patient access to care when practices are forced to turn away patients or go out of business. A wide variance of pricing occurs in community oncology. This variation is a signal of a highly fragmented market in need of unity to gain buying power and visibility to pricing. Practice Pricing Analysis (Cost/Billing Unit) Drug Name/Billing Unit Darbepoetin Alfa/Epoetin Alfa 1 mcg/1,000 u Pegfilgrastim/Bevacizumab 6 mg/10 mg Cetuximab/Docetaxel 10 mg/20 mg Gemcitabine/Irinotecan 200 mg/20 mg Oxaliplatin/Paclitaxel 0.5 mg/30 mg Rituximab/Trastuzumab 100 mg/10 mg JCODE J0881/J0885 J2505/J9035 J9055/J9170 J9201/J9206 J9263/J9265 J9310/J9355 MIN PRICE $2.66/$8.58 $1797.76/$44.21 $46.02/$281.21 $119.85/$119.02 $8.68/$11.30 $469.10/$54.69 ASP $2.97/$8.92 $2040.88/$54.27 $46.99/$289.45 $118.08/$118.87 $8.47/$11.88 $468.13/$54.60 AVG PRICE $3.64/$9.70 $2360.71/$54.63 $47.55/$297.89 $124.51/$127.05 $9.41/$12.63 $488.01/$56.66 MEDIAN $3.82/$8.99 $2465.34/$55.00 $47.52/$296.45 $125.15/$120.84 $8.92/$12.18 $485.60/$56.52 ASP+6% $3.14/$9.45 $2163.33/$57.53 $49.81/$306.81 $125.16/$126.00 $8.97/$12.59 $496.22/$57.87 MAX PRICE $4.12/$12.27 $2546.00/$57.47 $49.84/$341.35 $127.69/$240.51 $18.09/$18.46 $502.72/$58.26 MAX-MIN DIFFERENCE $1.46/$3.69 $748.24/$13.26 $3.82/$60.14 $7.84/$121.49 $9.41/$7.16 $33.62/$3.57 UNIQUE PRICES 16/18-14/17 19/20-16/19 15/19-18/19 19/20-18/20 17/20-15/19 18/20-19/20 Due to formatting limitations, products should be viewed from top to bottom, not making comparisons. No significant financial relationships to disclose.
Workload pressures are leading to unsafe hospital discharges, say MPs
Authors: Adrian O’Dowd
Journal: BMJ (2016)

Workload pressures and a lack of resources in hospitals are forcing staff to make potentially dangerous decisions and discharge patients before it is safe, MPs have said.

Worrying practices around discharging patients were becoming common rather than isolated incidents, said MPs on the parliamentary public administration and constitutional affairs committee in a report on the issue of unsafe discharge from hospital.1

The report, which is a follow-up to a similar inquiry2 carried out by the predecessor committee last year, said that the incidence of unsafe discharge from NHS hospitals was “unacceptably high.”

For their inquiry, MPs followed up on a …