tbuckley/cabot-search huggingface dataset:
Angiosarcoma after breast-conserving therapy for breast cancer.
Authors: E. Boelke, C. Matuschek, M. Peiper, D. Niederacher, W. Janni, W. Budach, P. A. Gerber, C. F. Eisenberger, W. T. Knoefel, G. Lammering, C. Nestle-Kraemling
Journal: Journal of Clinical Oncology (2011)

e20532 Background: Angiosarcoma is a rare tumor of endothelial origin which commonly arises in small blood or lymphatic vessels. Angiosarcoma of the breast represents a very rare disease. It occurs as secondary neoplasias with a latency of 5-10 years after primary treatment of breast cancer. It is associated with an unfavourable prognosis. A genetic predisposition is assumed. Radiation therapy, which is integrated within the concept of breast conserving therapy ranks as the main risk factor. Methods: 4 Caucasian women (mean 60.3 years, range 44-74 yrs) with angiosarcoma after breast sparing surgery and fractionated radiotherapy were included in this pilot study. Their molecular genetic pattern (BRCA1, BRCA2 and p53) as well as their clinical outcome were analysed and compared to the available literature. Results: In our patients angiosarcoma occurred 4.93 years (median value, range 4.25-6 yrs) after primary treatment of breast cancer with radiotherapy. Their median overall survival was 22.5 months (range: 3-48 months). The tumor suppressor genes BRCA1, BRCA2 and p53 tests were negative in our patients. Conclusions: Angiosarcoma occurs as a secondary neoplasm with a latency of 5 years after primary treatment of breast cancer and has an unfavourable prognosis. We could not find a significant role for tumor suppressor genes. Due to limited available data for these tumours, recommendations for therapy include radical tumour resection achieving wide free margins and inconsistent regimens of chemo- and/or immune-therapy modalities. In the majority these treatments are orientated on the systemic therapy regimens for other cutaneous sarcomas, such as Kaposi’s sarcoma. Efforts should be taken for a nationwide systematic registration of all cases of post-irradiation angiosarcomas.
A prospective study of cancer-related fatigue in women undergoing radiotherapy for breast cancer.
Authors: M. A. Torres, T. Liu, H. Chen, K. D. Godette, L. J. Stapleford, D. Mister, T. Pace, A. H. Miller
Journal: Journal of Clinical Oncology (2011)

110 Background: To investigate potential risk factors for cancer-related fatigue in women with breast cancer undergoing whole-breast radiotherapy (RT), we assessed the contribution of chemotherapy (CTX), RT-induced epidermal thickening, and inflammatory mediators to post RT fatigue. Methods: Following lumpectomy, 30 women received whole breast RT (50 Gy plus a 10 Gy boost). Prior to RT, at week 6 of RT, and 6 weeks post RT, subjects completed a validated questionnaire assessing fatigue (Multidimensional Fatigue Inventory [MFI-20]). At the above visits, patients underwent blood sampling for inflammatory mediators. In addition, breast epidermal thickness was measured using ultrasound tissue characterization. Results: Fatigue scores in the sample as a whole did not increase during RT. Independent multivariate analyses of clinical and demographic factors revealed that prior CTX (p&lt;.001) and age &lt;50 (p=.03) were significant predictors of higher post RT fatigue scores. Before, during, and after RT, CTX-treated patients had significantly higher mean fatigue scores than non-CTX-treated subjects. For example, mean MFI scores post RT in patients previously treated with CTX (n=15) were 28 points higher than patients not treated with CTX (mean 61 vs. 33, p&lt;.001), with a clinically meaningful difference being 10 points. Race, cancer stage, and epidermal thickening (defined as a 50% increase over baseline during or after RT, n=17) did not predict higher post RT fatigue scores. Of the inflammatory mediators, plasma IL-6 prior to RT was the strongest predictor of post RT fatigue (p=.02). In addition, plasma IL-6 concentrations prior to RT were significantly higher in patients who received CTX versus those who did not (mean 5.0 vs. 2.5, p=.01). IL-6 prior to RT was also significantly correlated with RT-induced epidermal thickening (p=.04). Conclusions: Our study suggests that CTX-induced inflammation, measured by plasma IL-6, is independently associated with the development of fatigue as well as epidermal thickening in women undergoing breast RT. Treatments targeting inflammation before RT may reduce both fatigue and epidermal thickening post RT, particularly in patients who have been previously been treated with CTX.
Lifetime ultraviolet radiation exposure and lentigo maligna melanoma
Authors: E. Linos, W.Q. Li, J. Han, T. Li, E. Cho, A.A. Qureshi
Journal: British Journal of Dermatology (2016)

Although ultraviolet light is considered a key factor in the etiology of malignant melanoma (MM), the relationship between sunlight and MM is complex. Intermittent exposure and sunburns are far more predictive of melanoma than chronic exposure, and melanoma can arise in non-sun exposed sites. Furthermore, retrospective studies have shown that outdoor workers exposed to sunlight chronically are not at higher risk of melanoma compared with indoor workers living at the same latitude.

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Action-based synthesis of parental brain consciousness
Authors: James E. Swain, Ilinca Caluser, Zainab Mahmood, Madalyn Meldrim, Diana Morelen
Journal: Behavioral and Brain Sciences (2016)

Abstract Parenting consciousness, in line with passive frame theory, may be considered inseparable from action. With combined brain-imaging and cognitive-behavioral analyses, we are in the early phases of understanding how parental brain circuits regulate parental thoughts and behavior. Furthermore, work on parental consciousness confirms the importance of motor outputs and outlines related circuits that inform consciousness across generations.
Abstract 12812: Leg Muscle Strength Independently Predicts Clinical Outcome In Patients With Acute Decompensated Heart Failure
Authors: Je-Wook Park, Jong-Chan Youn, Jaewon Oh, Sungha Park, Sang-Hak Lee, Donghoon Choi, Seok-Min Kang
Journal: Circulation (2015)

Introduction: Leg muscle strength (LMS) could be an index of frailty in patients with heart failure. However, its prognostic value in patients with acute decompensated heart failure (ADHF) is not well investigated. Hypothesis: We hypothesized that impaired LMS was independently associated with poor clinical outcome in patients with ADHF. Methods: We measured LMS in 110 prospectively and consecutively enrolled ADHF patients (75 male, mean age 60 ± 14 years, mean ejection fraction 29.9 ± 14.6%) at predischarge period. Primary endpoint was cardiovascular (CV) events defined as CV mortality, cardiac transplantation or rehospitalization due to HF aggravation. Results: The CV events occurred in 28 (25.5%) patients (5 cardiovascular deaths and 6 cardiac transplantations) during follow up period (median 246 days, 11-888 days). When the patients with ADHF were divided by LMS according to Contal and O’Quigley's method, impaired LMS was shown to be associated with poor clinical outcome (P&lt;0.001). Multivariate Cox regression analysis revealed that LMS was found to be an independent predictor of CV events (P=0.017) when controlled for age, gender, BMI, types of heart failure, hemoglobin, NT-proBNP and beta-blocker use. Conclusions: LMS independently predicts clinical outcome in patients with ADHF and might be used as a surrogate marker of frailty. Further studies are needed to evaluate the prognostic role of leg muscle strengthening exercise in these patients.
Rapidly-Generated EBV-Specific T Cells (EBVST-cells) to Treat Type 2 Latency Lymphoma
Authors: Rayne H. Rouce, Birju Mehta, Sandhya Sharma, Serena Kimi Perna, Benjamin Shin, Vicky Torrano, Fnu Spoorthi, Natalia Lapteva, Catherine M. Bollard, Adrian P. Gee, Carlos A. Ramos, Shannon Inman, Karen L. Hodgkin, Kurt C. Gunter, Malcolm K. Brenner, Helen E. Heslop, Cliona M. Rooney
Journal: Blood (2016)
Fibrin(ogen) drives repair after acetaminophen-induced liver injury via leukocyte αMβ2 integrin-dependent upregulation of Mmp12
Authors: Anna K. Kopec, Nikita Joshi, Holly Cline-Fedewa, Anna V. Wojcicki, Jessica L. Ray, Bradley P. Sullivan, John E. Froehlich, Brendan F. Johnson, Matthew J. Flick, James P. Luyendyk
Journal: Journal of Hepatology (2016)
Use of global histone modifications to predict response to gemcitabine in patients with pancreatic cancer.
Authors: Takuo Watanabe, Soichiro Morinaga, Makoto Akaike, Masakatsu Numata, Hiroshi Tamagawa, Naoto Yamamoto, Manabu Shiozawa, Shinichi Ohkawa, Kameda Yoichi, Yoshiyasu Nakamura, Munetaka Masuda, Yohei Miyagi
Journal: Journal of Clinical Oncology (2012)

232 Background: Epigenetic alternations such as DNA methylation and histone modification play important roles in carcinogenesis. It has been recently suggested that global histone modification pattern are independent predictors of cancer outcomes. We studied the prognostic and predictive value of five histone modifications in pancreatic cancer. Methods: Double 2-mm core tissue microarrays were made from 61 paraffin-embedded pancreatic cancer samples and examined by immunohistochemistry for histone H3 lysine 9 dimethylation (H3K9me2), and acetylation (H3K9ac), histone H3 lysine 4 dimethylation (H3K4me2), and trimethylation (H3K4me3), and histone H3 lysine 18 acetylation (H3K18ac). Positive tumor staining for each histone modification was used to classify patients into low- and high-staining groups, which were related to clinicopathologic features and clinical outcomes. Results: The high expression group of H3K4me3 was related to the well and moderately differentiated histological type (p=0.012) and the low expression of H3K4me2 was related to the presence of preineural invasion (p=0.007). The high expression of H3K9ac was related to the presence of lymph node metastasis (p=0.041). In the subgroup of patients receiving gemcitabine chemotheraphy, low levels of H3K4me2 were significantly associated with worse disease free survival (p=0.0239). Univariate and multivariate hazards models also indicated that low levels of H3K4me2 was significant independent predictor of disease-free survival (p=0.007). Conclusions: H3K4me2 is considered to be useful predictor of response to gemcitabine in patients with pancreatic cancer.
The effect of molecular subtype on survival in a racially diverse cohort of patients with high-risk breast cancer receiving trimodality therapy.
Authors: J. L. Wright, C. Takita, J. E. Panoff, I. M. Reis, W. Zhao, V. Sujoy, C. G. Fernandez, M. Jorda, D. Franceschi, J. Hurley
Journal: Journal of Clinical Oncology (2011)

156 Background: To understand the origins of racial disparities in breast cancer outcomes, the relative importance of race must be examined in the context of molecular subtype. We assessed racial differences in progression-free survival (PFS) and overall survival (OS) in relation to subtype in a cohort of uniformly treated stage II-III breast cancer patients. Methods: We reviewed records of 582 consecutive patients receiving post-mastectomy radiation (PMRT) between 1/1999 and 12/2009 and evaluated the effect of demographic, tumor, and treatment characteristics on PFS and OS. Results: Median follow-up 44.7 months. Patients: 24% black, 76% white, 55% pre/peri-menopausal. Disease: stage II 30%, stage III 70%. Treatment: all had mastectomy and PMRT; 98% had chemotherapy. All ER+ patients received endocrine therapy. Black and non-black patients were similar in age, menopause status, stage, and completion of trimodality therapy. Black patients were more likely to be ER- (56% vs 38%, p=0.0001), PR- (69% vs 54%, p=0.002), and triple negative (TN) (46% vs 24%, p&lt;.0001). Among ER+, there were no differences in menopause or PR status by race. Black patients had worse PFS (60.6% vs 78.3%, p=.001) and OS (72.8% vs 87.7%, p&lt;.0001). There was no racial difference in PFS (p=0.229 and 0.273 respectively) or OS (p=0.113 and 0.097 respectively) among ER- or TN. Among ER+, black patients had worse PFS (55% vs 81%, p&lt;.001) and OS (73% vs 91%, p&lt;.0001). The difference in PFS was seen in the ER+/PR+/HER2- (“luminal A”) subgroup (p=.002) but not ER+/PR-/HER2- (“luminal B”) (p=0.129), and in the post-menopausal ER+/HER2- subgroup (p=.004) but not pre/perimenopausal ER+/HER2- (p=.150). On multivariate analysis, racial differences in PFS (p=.055) and OS (p=.052) were maintained in the luminal A postmenopausal subgroup. Conclusions: In a cohort of breast cancer patients black women had worse survival. This disparity was driven by (1) a higher proportion of ER- and TN tumors in the black women and (2) worse outcome of similarly treated post-menopausal black women with luminal A breast cancer. The efficacy of various types of endocrine therapy must be examined in the setting of racial diversity.
Reply to Harry Herr's Letter to the Editor re: Marko Babjuk, Andreas Böhle, Maximilian Burger, et al. EAU Guidelines on Non–muscle-invasive Urothelial Carcinoma of the Bladder: Update 2016. Eur Urol 2017;71:447–61
Authors: Marko Babjuk, Maximilian Burger, Eva Compérat, Joan Palou, Morgan Rouprêt, Bas van Rhijn, Shahrokh Shariat, Richard Sylvester, Richard Zigeuner, Paolo Gontero, Hugh Mostafid
Journal: European Urology (2016)
Downregulation of Circadian Genes, PER1, PER2, and PER3, in Chronic Myeloid Leukemia.
Authors: Lin Sheng-Fung, Ming-Yu Yang, Jan-Gowth Chang, Hui-Hua Hsiao, Yi-Chang Liu, Shih-Bin Tseng, Hui-Jen Tsai, Ta-Chih Liu, Tyen-Po Chen
Journal: Blood (2004)
CD34 Expression On the Blasts of Bone Marrow Is a Novel Predictor of Poor Prognosis Independent of FlT3-ITD in Acute Myeloid Leukemia with NPM1-Mutation.
Authors: Hong-Hu Zhu, Yan-Rong Liu, Hao Jiang, Jin Lu, Yazhen Qin, Qian Jiang, Xiaojun Huang
Journal: Blood (2012)
Bone marrow stromal cells induce matrix metalloproteinase-12 and invasion in prostate cancer cells
Authors: Sanaa Nabha, R. Daniel Bonfil, Hamilto Yamamoto, Abdelfettah Belizi, Hong Meng, Zhong Dong, Emanuel Burck dos Santos, Michael Cher
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2797 

Bone is the most common site of distant metastasis in prostate cancer patients and the main cause of morbidity and mortality. The molecular mechanisms responsible for bone metastases are complex and involve bi-directional interactions between tumor and bone cells. Proteases are well known to regulate cell proliferation, cell death, tumor invasion, metastasis, and tumor angiogenesis. To evaluate the role of prostate cancer cell/bone stromal interaction in prostate cancer invasion through type I collagen, the main organic component in bone, PC3 prostate cancer cells and/or bone marrow stromal (BMS) cells were co-cultured for 24h using 24-well Transwell inserts pre-coated with type I collagen. The combination of PC3 and BMS cells revealed a higher invasive ability than each one of the cell types assayed individually. Cytokeratin immunohistochemistry showed that most of the cells which invaded through the filter were the cancer cells. The use of inhibitors for each of the protease families indicated that one or more metalloproteinases (MMP) were responsible for the enhanced invasion. To determine which MMPs were involved in the enhanced invasion due to tumor-stromal interaction, gene profiling of PC3 and BMS cells alone or in combination was performed. Several MMP genes showed an increased level in the combination of both cell types, as compared to each one of them when tested alone, results that were confirmed using semi-quantitative reverse transcription-PCR. However, only MMP-12 showed an increase in protein expression by Western blot analysis. To confirm a functional role for MMP-12 in the enhanced invasive ability demonstrated when PC3 and BMS cells interact, small interfering RNA (siRNA) for MMP-12 was used. Since MMP-12 was predominantly expressed at the protein level by PC3 cells, MMP-12 gene expression was downregulated in these cells. A dose response inhibitory effect on MMP-12 expression at the gene and protein levels was observed 48h after transient transfection of PC3 cells with different concentrations of siRNA molecules targeting MMP-12 . In vitro invasion assays were repeated as mentioned above, but now using PC3 cells transfected with MMP-12-siRNA or scrambled siRNA, alone or in combination with BMS cells. The results showed that blocking of MMP-12 expression in PC3 cells inhibited the enhanced invasion demonstrated by PC3-BMS cell interaction. Our data suggest that BMS cells induce MMP-12 expression/activity in prostate cancer cells, which results in enhanced degradation of bone type I collagen.
Phase I trial with carboplatin and RAD001 in metastatic breast cancer.
Authors: J. Eucker, S. Schwarzlose-Schwarck, P. Martus, A. C. Regierer, C. O. Schulz, H. Liu, C. W. Scholz, J. H. Schefe, K. Possinger
Journal: Journal of Clinical Oncology (2011)

e11554 Background: The mTOR inhibitor RAD001 is a promising drug in the treatment of solid tumors. Carboplatin experienced a kind of renaissance in the treatment of breast cancer. Preclinical studies suggested that combining RAD001 with carboplatin may produce higher activity than each drug alone. We present the final data of a phase I trial. The aims of this trial were to determine the maximum tolerated dose (MTD) of the carboplatin/RAD001 regimen and to assess its safety in pretreated patients (pts). Methods: In this study, pts with pretreated metastatic breast cancer received carboplatin AUC2 weekly and oral RAD001 at different dose level (level I: 2.5mg; II: 5mg; III: 7.5mg; IV: 10mg) daily of a 21-day cycle. Treatment was continued until progression or the occurrence of intolerable toxicity. 3 pts were assigned to dose level I-III, 6 to dose level IV. Dose levels were escalated strictly step by step. If no DLT occurred in 3 pts, following patients were assigned to the next dose level. Results: The study has enrolled 15 pts (median age 58). The median number of previous chemotherapies was 4 (range: 1-11). 12 pts had hormone receptor positive, 5 HER2 over-expressing disease. Dose level was escalated to level IV as no DLT occurred at level I-III. 6 pts were treated at level IV. Pts received a median of 4 cycles (range 1-13); 9 completed at least 4 cycles, 3 completed at least 8 cycles, and one patient 13 cycles. There were no DLTs at dose level I-IV during the first cycle. Based on the pre-determined definition of MTD, the maximum planned dose level IV was selected as the MTD. Overall, toxicities have been manageable. Most frequent G3/4 toxicities included thrombocytopenia in 5 pts, leukopenia in 4 pts, infection in 2 pts, dyspnea in 2 pts, and fatigue in 1 pts. Response rates in 14 pts evaluable for response were as follows: 14% PR, 43% SD, and 43% PD. In 9 pts who completed 4 cycles defined in the protocol for efficacy assessment, response rates were: 2/9 PR, 6/9 SD. Conclusions: Carboplatin/RAD001 is a well tolerated combination in heavily pretreated metastatic breast cancer. RAD001 (10 mg/d) / carboplatin (AUC 2 weekly) is defined as MTD. The 10mg dose of RAD001 is consistent with the doses recommended in other combinations. The dose is currently used in an ongoing phase II trial.
Effect of the simultaneous blockade of androgen and estrogen receptors on prostate cancer: Preliminary results.
Authors: R. Nunez-Nateras, E. P. Castle
Journal: Journal of Clinical Oncology (2011)

168 Background: Androgens and estrogens have been shown to play an important role in normal prostate development and function as well as carcinogenesis and development of the castration resistant phenotype of disease. The aim of this study was to evaluate the effect of a simultaneous administration of an androgen receptor antagonist (bicalutamide) and a selective estrogen receptor modulator (raloxifene) on both androgen sensitive and androgen insensitive prostate cancer cell lines. Methods: Experiments were performed on LNCaP, PC3 and DU145 cell lines. Western blot was utilized for the identification of androgen and estrogen receptors (a andb) in the cell lines. Drug concentrations required to achieve IC 50 were obtained using the MTT assay; such concentrations were identified for the drugs individually and when used in combination. The effect of the drugs on apoptosis was assessed using flow cytometry. Results: Results of the IC 50 for the drugs alone and in combination by each cell line are shown in the table. An enhanced effect was observed when the drugs were used in combination in all the cell lines. It was evident that the combination of the drugs decreased the total drug required to achieve the IC50 decreases considerably. Apoptosis rates were also affected by the simultaneous administration of bicalutamide and raloxifene. The synergistic effect of the combination was reflected in the increase of the apoptosis rate in all cell lines. Conclusions: The simultaneous administration of bicalutamide and raloxifene has a synergistic effect on cell death and apoptosis of DU145, PC3 and LNCaP cell lines. The pathway(s) responsible for this observation may be independent of the androgen receptor as both AR negative cell lines were still affected by the combination over the SERM alone. [Table: see text] No significant financial relationships to disclose.
The Value of Donor Lymphocyte Infusions In Unstable Mixed Chimerism In Patients with Beta Thalassemia.
Authors: Gülsün Tezcan Karasu, Akif Ye¸silipek, Sibel Karaüzüm, Vedat Uygun, Mediha Akcan, Esra Manguoğlu, Alphan Küpesiz, Volkan Hazar
Journal: Blood (2010)
Favorable Outcome of High-Risk Mediastinal Diffuse Large B-Cell Lymphoma (DLBCL) after Dose-Intensive Chemotherapy, Rituximab and Autologous Transplant (ASCT).
Authors: R. Pytlik, K. Kubackova, T. Kozak, D. Belada, J. Pirnos, M. Jankovska, J. Pukyova, T. Papajik, H. Siffnerova, P. Zak, I. Vasova, M. Hamouzova, M. Trneny
Journal: Blood (2004)