tbuckley/cabot-search huggingface dataset:
AR–PDEF pathway promotes tumour proliferation and upregulates MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative breast cancer
Authors: Lu Cao, Cong Xu, Guomin Xiang, Fang Liu, Xiaozhen Liu, Congying Li, Jing Liu, Qingxiang Meng, Jiao Jiao, Yun Niu
Journal: Molecular Cancer (2018)

Androgen receptor (AR) is expressed in 60%~ 70% oestrogen receptor (ER)-negative breast cancer (BC) cases and promotes the growth of this cancer subtype. Expression of prostate-derived Ets factor (PDEF), a transcription factor, is highly restricted to epithelial cells in hormone-regulated tissues. MYC and its negative regulator MAD1 play an important role in BC progression. Previously, we found that PDEF expression is strongly correlated with AR expression. However, the relationship between AR and PDEF and the function of PDEF in ER-negative BC proliferation are unclear. AR and PDEF expression in ER-negative BC tissues and cell lines was determined by performing immunohistochemistry or western blotting. Protein expression levels and location were analysed by performing western blotting, RT-qPCR and immunofluorescence staining. Co-immunoprecipitation and chromatin immunoprecipitation assays were performed to validate the regulation of AR–PDEF–MAD1–MYC axis. Moreover, the effect of AR and PDEF on BC progression was investigated both in vitro and in vivo. We found that PDEF was overexpressed in ER-negative BC tissues and cell lines and appeared to function as an oncogene. PDEF expression levels were strongly correlated with AR expression in ER-negative BC, and PDEF transcription was positively regulated by AR. PDEF upregulated MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative BC. Finally, we found that compared with the inhibition of AR expression alone, simultaneous inhibition of AR and PDEF expression further suppressed tumour proliferation both in vitro and in vivo. Our data highlight the role of the AR–PDEF–MAD1–MYC axis in BC progression and suggest that PDEF can be used as a new clinical therapeutic target for treating ER-negative BC.
Minimizing urinary toxicity in daily prostate stereotactic body radiotherapy with urethra dose constraints.
Authors: Hyun Kim, Alexandra L Hanlon, Walter E Knotts, Jodie A Noonan, Adam Raben
Journal: Journal of Clinical Oncology (2016)

e16614 Background: Stereotactic body radiotherapy (SBRT) is an evolving and promising treatment modality for prostate cancer but without mature data compared with other definitive therapies. There is currently no standard dose fractionation or timing for prostate SBRT. Prior preliminary data indicate that daily treatment is toxic and every other day (QOD) treatment is safer. However, some patients prefer daily treatments to decrease overall treatment time and travel expenses. We challenged the hypothesis that daily treatment is toxic and provide prospective data of daily SBRT treatment. Methods: 21 patients with localized prostate cancer were prospectively treated at our institution from 2009 to 2015 with SBRT using CyberKnife. Treatment consisted of 36.25 Gy in 5 daily fractions with prostatic and membranous urethra dose constraints (V47 < 20% and D50 < 37Gy, respectively) and daily dexamethasone. Patient reported bladder and rectal toxicity was graded on the Radiation Therapy Oncology Group scale. Baseline and post-treatment international prostate symptom score (IPSS), sexual health inventory for men (SHIM), urinary symptom quality of life (QOL) and PSA levels were compared using McNemar’s Chi’square and Bowker tests. Results: Median follow-up was 24 months. At last follow-up, 8, 5 and 4 patients had grade 1 and 2 urinary, and grade 1 rectal toxicity, respectively. No grade 3 toxicity was observed. There were no statistically significant differences in baseline and post-treatment IPSS, SHIM and urinary QOL scores. Median PSA at follow-up was 0.7 ± 1.1 ng/mL. No patients had biochemical recurrence by Phoenix criteria. Conclusions: The toxicity profile of QOD treatment compared favorably with historical data; grade 3 toxicity as reported in prior daily SBRT studies was not observed. Biochemical failure free survival compared favorably with other definitive treatment modalities. These data indicate that daily SBRT with urethra dose constraints for localized prostate cancer may result in a comparable toxicity profile to that of QOD treatment, decrease overall days of treatment duration and associated travel costs.
Circulating tumor cell status and benefit of radiotherapy in stage I breast cancer.
Authors: Chelain Rae Goodman, Brandon-Luke L Seagle, Eric Donald Donnelly, Jonathan Blake Strauss, Shohreh Shahabi
Journal: Journal of Clinical Oncology (2017)

11524 Background: Circulating tumor cell (CTC) status has been shown to be prognostic of decreased survival in non-metastatic breast cancer. While up to 20-30% of patients with early breast cancer have detectable CTCs, less is known regarding the role of CTC-status in guiding clinical management. Methods: An observational cohort study was performed on women with stage I breast cancer evaluated for CTCs from the 2004-2014 National Cancer Database. Logistic regression was used to explore clinicopathological associations with CTC-status. Kaplan-Meier and multivariable Cox proportional-hazards survival analyses were used to estimate associations of CTC-status with overall survival using a propensity score-adjusted and inverse probability-weighted matched cohort. Results: Of the stage I breast cancer women evaluated for CTCs, 23.1% (325/1,407) were CTC-positive. Age, histology, receptor status, and nodal stage were associated with CTC-status. CTC-status was an effect modifier of the radiotherapy-survival association: CTC-positive women who did not receive radiotherapy had an increased hazard of death compared to CTC-negative women who also did not receive radiotherapy (four-year survival: 85.7% vs. 93.3%, HR = 2.92, CI = 1.43-5.98, P = 0.003). CTC-positive patients treated with radiotherapy did not have decreased survival compared to CTC-negative patients not treated with radiotherapy (HR = 0.67, CI = 0.28-1.65, P = 0.40). From the matched cohort analysis, CTC-positive women who did not receive radiation had a 4.82-fold increased hazard of death compared to CTC-positive women treated with radiotherapy (four-year survival: 83.2% vs. 96.6%; CI = 2.62-8.85, P &lt; 0.001). Conclusions: Treatment with adjuvant radiotherapy was associated with improved survival in CTC-positive women with stage I breast cancer. If prospectively validated, CTC-status may be valuable as a predictor of benefit of radiotherapy in early stage breast cancer.
Use of medical simulation for cancer education in Nigeria.
Authors: Kelechi Ngozi Eguzo, Chinenye Okwuosa, Uwemedimbuk Smart Ekanem, Christie Divine Akwaowo, Enobong Divine Mkpang
Journal: Journal of Clinical Oncology (2018)

11011 Background: Among the many limitations of cancer control in Nigeria are lower awareness/competence and poorer training of healthcare professionals (HCP). These manifest as deficiencies in advocacy, screening /diagnostic practices, and patient management. Medical simulation (MS) using models is an effective approach for sustainably improving the competence of HCP, especially regarding clinical breast examination (CBE), pelvic examination (PE) and digital rectal examination (DRE). Study evaluates the effect of MS during a Nigerian training course focusing on CBE, PE and DRE. It answers the question: what are the perspectives of HCP on use of MS for cancer education? Methods: Participants included a convenience sample of Nigerian physicians and nurses who attended the ASCO-sponsored Multidisciplinary Cancer Management Course. Intervention was MS using high-fidelity models. The models demonstrated normal anatomic and common pathologic features of the breast, cervical and prostate. Participants cycled through MS stations (i.e. CBE, PE and DRE). Pre-and post-training surveys with comments evaluating self-reported comfort levels were basis for comparison. Data analysis included descriptive statistics, Wilcoxon signed rank test, chi-square and thematic analysis. Results: Of the 92 course participants (physicians-36, nurses-16), 51 completed the course evaluation forms (response rate = 55.4%; 51/92), and average number of years in practice was 8 (±5.2) years. Pre-training survey showed non-significant differences in practices patterns; 71% (22/35) of physicians rarely performed PE (p = 0.92), and 93% (14/16) of nurses rarely performed DRE (p = 0.07). According to some participants, “the use of simulation is quite commendable as it gives room for improvement before using a human; “it is the best method of learning I have ever enjoyed.” Conclusions: MS-based training significantly improved the comfort levels of participants regarding CBE and PE, as well as their likelihood to perform CBE, PE and DRE. Participants recommend widespread use of MS for continuing medical education and undergraduate training. Comfort levels Median IQR P-value CBE (Pre) 4 4-4 < 0.01 CBE (post) 5 4-5 PE (Pre) 4 2-5 < 0.01 PE (Post) 5 4-5 DRE (Pre) 3 1-5 0.01 DRE (Post) 3 1-4
TCT-329 Prospective Evaluation of Drug Eluting Self Apposing Stent for the Treatment of Unprotected Left Main Coronary Artery Disease: 1-Year Results of the TRUNC Study
Authors: Corrado Tamburino, Carlo Briguori, Gillian A. Jessurun, Krzysztof Reczuch, Bernardo Cortese, Luc Maillard, Andrzej Ochala, Floris Kauer, Marcus Siry, Gennaro Sardella, Adam Sukiennik, Alexander Ijsselmuiden, David Bouchez, Andreas Baumbach
Journal: Journal of the American College of Cardiology (2018)
TCT-348 Early Changes in Malapposition Assessed with Optical Coherence Tomography after Biolimus-coated BioFreedom Stent or Sirolimus Eluting Orsiro Stent in Patients with ST-segment Elevation Myocardial Infarction
Authors: None Christian Oliver Fallesen, Kirstine Hansen, Michael Maeng, Lisbeth Antonsen, Akiko Maehara, Lars Jakobsen, Julia Ellert, Christian Terkelsen, Ole Ahlehoff, Troels Thim, Steen Carstensen, Knud Nørregaard Hansen, Karsten Veien, Evald Christiansen, Lisette Okkels Jensen
Journal: Journal of the American College of Cardiology (2018)
Novel approach for unresectable salivary duct carcinoma: Targeting HER2 and androgen receptor.
Authors: Daisuke Kawakita, Yuichiro Tada, Chihiro Fushimi, Hideaki Takahashi, Tatsuo Masubuchi, Kouki Miura, Satoshi Kano, Kiyoaki Tsukahara, Hiroyuki Ozawa, Kenji Okami, Yuichiro Sato, Akira Shimizu, Yorihisa Imanishi, Toyoyuki Hanazawa, Mizuo Ando, Hideaki Hirai, Toshitaka Nagao
Journal: Journal of Clinical Oncology (2018)

6084 Background: Salivary duct carcinoma (SDC) is highly aggressive and rare cancer, often expressing androgen receptor (AR) and/or HER2. While chemotherapy has been failed to show significant efficacy on SDC, we have demonstrated efficacy and safety of AR- or HER2-targeted therapy in patients with unresectable locally advanced or recurrent/metastatic (LA/RM) SDC in a single-arm phase II trial. However, data regarding whether these targeted therapies prolong survival compared with conventional therapy is lacking. Methods: We conducted a multi-institutional retrospective cohort study of SDC patients in Japan. The survival impact of molecular-targeted therapy was compared with conventional therapy, including chemotherapy and/or cetuximab by multivariate proportional hazard models. Results: A total of 152 LA/RM patients were enrolled, of whom 65 received conventional therapy, 55 received HER2-targeted therapy, and 32 received AR-targeted therapy. Median follow-up time was 1.8 years (range: 0.1-9.5 years). The 2-year overall survival (OS) were 38.7% for conventional therapy, 69.3% for HER2-targeted therapy, and 57.9% for AR-targeted therapy. After adjustment by potential confounders, HER2-targeted therapy significantly improved OS compared with conventional therapy among HER2-positive patients (hazard ratio [HR]: 0.34; 95% confidence interval [CI], 0.16-0.71). AR-targeted therapy did not significantly improve OS compared with conventional therapy among AR-positive patients (HR: 0.63; 95% CI, 0.32-1.26). No other biomarker predicting efficacy of targeted therapies was found. Conclusions: Although this study was retrospective, this was the first study to demonstrate that novel therapy targeting HER2 prolonged OS compared with conventional therapy in patients with LA/RM SDC.
A phase II trial of stereotactic body radiation therapy for operable T1N0M0 non-small cell lung cancer: Japan Clinical Oncology Group (JCOG0403)—Long term follow-up results.
Authors: Yasushi Nagata, Masahiro Hiraoka, Taro Shibata, Hiroshi Onishi, Masaki Kokubo, Katsuyuki Karasawa, Yoshiyuki Shioyama, Rikiya Onimaru, Etsuo Kunieda, Satoshi Ishikura
Journal: Journal of Clinical Oncology (2018)

8512 Background: The purpose was to evaluate the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients (pts) with both operable and inoperable T1N0M0 non-small cell lung cancer (NSCLC) (UICC 6th ed., 2002). The 3 and 5 year follow-up results were published in 2015. This is the updated report with a 10-year follow-up for the operable population. Methods: The eligibility criteria included NSCLC, clinical T1N0M0, operable pts assessed by thoracic surgeons. Operability was recategorized by the study coordinator after registration and before the primary analysis. The prescription was 48 Gy at the isocenter in 4 fractions over 4-8 days. The primary endpoint was the 3-year overall survival (OS) and the secondary endpoints included progression-free survival (PFS), local-progression free survival (LPFS), event-free survival (EFS) and toxicity. Results: Between July 2004 and May 2007, 65 operable pts were registered and 64 eligible pts were included in efficacy analysis. The pts characteristics were: male 45, female 20; median age 79 (range 50-91). All pts completed the protocol treatment. At the last follow-up in February 2017 (median follow-up is 5.2 years), 20 died with disease, 24 died with other disease, 1 with treatment-related death, 2 died with unknown reason and 17 alive. The median survival was 5.6 year (95% CI: 4.1 – 7.1 year).The 3, 5, 10-year survival were 76.5% (95% CI: 64.0% - 85.1%), 54.0% (95% CI: 41.0% - 65.4%) and 23.8% (95% CI: 13.7% - 35.5%). The 10-year PFS, LPFS, and EFS were 19.1% (95% CI: 9.8% - 30.7%), 20.9% (95% CI: 11.1% - 32.8%), 13.7% (95% CI: 6.0% - 24.6%). A total of 27 failures were observed including 9 with local failure, 11 with regional nodal failure and 11 with distant metastases. Grade 3 toxicity occurred in 6 pts: chest pain 1 (1.5%), dyspnea 4 (6.2%), hypoxia 1 (1.5%), and pneumonitis 2 (3.1%). No grade 4 or 5 toxicity occurred. Conclusions: Long term results confirmed the efficacy and safety of the previous result. SBRT has a potential to be an alternative to surgery and deserves a further evaluation. To further improve the tumor control, a randomized phase III study investigating higher dose is underway (JCOG1408). Clinical trial information: NCT00238875.
Low-dose versus high dose radioactive iodine ablation differentiated thyroid carcinoma: a prospective randomized study.
Authors: Dina R. Ibrahim, Mohamed Reda Kelany, Maha M. Michael, Zeinab M. Elsayed
Journal: Journal of Clinical Oncology (2016)

6087 Background: Following total thyroidectomy of differentiated thyroid carcinoma (DTC), some patients are treated with adjuvant radioactive iodine I-131 (RAI). The present study compares the success of ablation with 30 millicurie (mci) versus 80 mci. Methods: From June 2013 to October 2015, we randomized the DTC patients to either 30 mci or 80 mci RAI after surgery. The study included patients with T1-T3, N0-N1, M0 tumors (The American Joint Cancer Committee AJCC 7th edition). For each patient baseline serum thyroglobulin (sTg), thyroglobulin antibody (Tg Ab) were performed. Six months post-ablation successful thyroid ablation was defined as a negative whole body scan and undetectable serum thyroglobulin. Results: Out of 50 patients with DTC, 45 patients fulfilled the eligibility criteria. Total thyroidectomy was performed in 27/45 (60%). 26/45 (57.8%) of these patients received 30 mci while19/45 (42.2%) patients received 80 mci. The median age was 37 and 36.5 in the arms 80 and 30 mci respectively. Females represented 35/45 (77.8%) of patients. Histopathology showed papillary carcinoma in 42/45 (93.3%) and follicular carcinoma in 3/45 (6.7%) of patients. T2 tumors predominated in 10/19 (52.6%), and 15/26 (57.7%) of the 80 and 30 mci arms respectively. According to the American Thyroid Association risk classification, all of the patients in both arms had low risk disease. Success of ablation was achieved in 15/19 (78.9%) of the am 80 mci, and in 15/26 (60%) of the arm 30 mci (p 0.13). No patients developed distant metastases in both arms. The 80 mci arm patients had longer hospital admission compared to the 30 mci arm (p 0.008). Only 6/26 (23.1%) patients in the 30 mci arm were isolated for 2-4 days, whereas all the 80 mci arm patients were isolated for 3-5 days. Conclusions: Both 80 mci and 30 mci of radioactive Iodine (I-131) have similar success rate in the ablation of thyroid remnant of low risk differentiated thyroid cancer patients. The 30 mci I-131 dose is associated with fewer side effects, shorter hospital admission duration, and less expensive in low risk DTC patients. Clinical trial information: 1578/2013.
Prevention of surgical site infection after oral cancer surgery by topical tetracycline: Results of a multicenter randomized control trial.
Authors: Madoka Funahara, Souichi Yanamoto, Michihiro Ueda, Takatsugu Suzuki, Yoshihide Ota, Fumihiro Nishimaki, Hiroshi Kurita, Nobuhiro Yamakawa, Tadaaki Kirita, Masaya Okura, Yasuaki Mekaru, Keiichi Arakaki, Masahiro Umeda
Journal: Journal of Clinical Oncology (2018)

6080 Background: In a pilot study, we showed that topical administration of a tetracycline could decrease oral bacteria levels for 6 hours in patients who underwent oral cancer surgery combined with tracheotomy and flap reconstruction. This multicenter, randomized control trial aimed to investigate the effectiveness of topical application of tetracycline ointment for prevention of surgical site infection (SSI) associated with major oral cancer surgery. Methods: One hundred and seventeen patients who underwent oral cancer resection combined with neck dissection, flap reconstruction, and tracheotomy were divided randomly into an intervention group (n = 56) and a control group (n = 61). The intervention consisted of topical administration of tetracycline ointment on the dorsum of the tongue every 6 hours for 48 hours postoperatively. Factors relating to the occurrence of SSI in both groups were subjected to logistic regression analysis. Results: SSI occurred in 11 patients (19.6%) in the intervention group and 22 patients (36.1%) in the control group. Multivariate analysis showed that a longer operating time and not receiving topical tetracycline were independent risk factors for development of SSI. Conclusions: Administration of topical tetracycline for 48 hours postoperatively is an effective way of preventing SSI after oral cancer surgery. Clinical trial information: 000018318.
Inherited BRCA2 mutations and tumor hemi/homozygosity of metastatic soft tissue sarcoma in up to one-third of the 55 patients with shorter survival time.
Authors: Katsuhito Takahashi, Atsushi Mizumoto, Jun Yashima, Keiko Kutsunai, Hiromasa Yamamoto, Junichi Sou, Shinichi Toyooka, Yu Oyama, Hiroaki Nomori, Hiroyuki Narahara, Junko Yotsumoto, Yasuo Ono, Makoto Tonsho, Satoshi Teraoka
Journal: Journal of Clinical Oncology (2018)

11571 Background: Soft tissue sarcoma (STS) is well-known rare cancer with few therapeutic options. Although recent comprehensive genomic analyses of adult STS revealed few somatic mutations and many copy number variations (CNVs), the pathogenesis, prognostic markers and drug sensitivity mechanisms remain to be understood. Methods: We recruited 55 patients (50 female and 5 male, mean age 49) with a confirmed metastasis, information on familial cancer burden and detailed sarcoma pathology under written informed consent approved by IRB. Whole-exome sequencing was performed on the illumina HiSeq 2500 with the mean coverage depth of 178x in tumor and 68x in germline samples. In order to find CNVs and germline contributions in tumor, we used Strelka and Virmid analysis software filtering all mutations with allele frequencies more than 80%. CNVs and specific mutations in the BRCA2 locus identified were validated by multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. Results: Among the somatic mutations, TP53, MED12, ATRX and RB1 are most frequently affected under mean total mutation numbers 1.26/Mb. All patients show MSS phenotype. Of the 72 genes with heritable cancer risk evaluated by Ballinger et al.(2016) in sarcoma germline, 25 have mutations with tumor bialletic loss of wild type sequence in 44/55 (80%) patients. Of these, six BRCA2 missense mutations recognized as variants of unknown significance (VUS) are most frequently found in 15/55 patients (27%, 12/37 LMS, 1/9 LPS, 1/1 MPNST, 1/1 AS) in both female and male. CNVs analysis by MLPA showed complete deletion of wild type BRCA2 locus, leading to hemizygosity of the VUS. Kaplan-Meier analysis revealed that patients with the BRCA2 mutations (N = 15) significantly reduced the 5-year survival rate as compared with patients with normal sequence or mutations in heterozygosity (N = 40) (48% vs 93%, P = 0.00272). Conclusions: Our results unveiled a different landscape of STS genomics from previous studies, indicating more germline and CNVs contributions in prognosis. Tumor loss of wild type allele and hemizygosity in BRCA2 implicates defective HRR as a potential therapeutic target in STS.
A Perspective on the Accuracy of Blood Glucose Meters During Pregnancy
Authors: Jincy Immanuel, David Simmons
Journal: Diabetes Care (2018)

Blood glucose monitoring is fundamental for hyperglycemia management during pregnancy, but are the devices up to the job? Studies assessing the accuracy of 10 commercially available glucose meters during pregnancy showed that although &amp;gt;98–99% of the meter values were in the acceptable zones of the error grid for the majority of the meters, the meter performance varied, with the majority showing positive bias and a few showing minimal negative bias. The mean difference between meter and laboratory plasma values varied between −0.33 and 0.73 mmol/L. Three meters showed deviations from laboratory results with a change in maternal hematocrit levels. No meters had a total analytical error &amp;lt;5%, and no studies evaluated meters using recent International Organization for Standardization 15197:2013 criteria. The Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) recently showed that an antenatal continuous glucose monitoring system (CGMS), as an adjunct to capillary monitoring, was associated with a lower incidence of large-for-gestational-age babies, fewer neonatal intensive care unit admissions (&amp;gt;24 h), and a lower incidence of neonatal hypoglycemia. The flash glucose monitoring system shows good accuracy in pregnant women but has not been marketed widely in the U.S. We suggest that meters cannot be assumed to be sufficiently accurate during pregnancy and that manufacturers should ensure a total error &amp;lt;5%, with bias and imprecision &amp;lt;2% during pregnancy. Large studies are needed to evaluate the usefulness of CGMS among pregnant women with type 2 diabetes and gestational diabetes mellitus.