tbuckley/cabot-search huggingface dataset:
Multicentric, open-label, single-arm phase II study with oral lapatinib in combination with oral capecitabine plus intrathecally administered liposomal cytarabine for the treatment of meningeal metastases (NM) in HER2-positive breast cancer patients.
Authors: J. Bischoff
Journal: Journal of Clinical Oncology (2010)

TPS123 Background: Rationale: BC with meningeal involvement is associated with a poor prognosis. At present there is a need for a multimodal therapy. Up to date little is known about the role of tyrosine-kinase-inhibitors (TKIs), which cross the blood-brain barrier. On the other hand lapatinib has proven to be active against systemic disease and brain metastases from HER2-positive breast cancer in combination with capecitabine. Several case reports provide anecdotal evidence of efficacy of EGF-directed TKIs in lung cancer associated NM. Goals:To evaluate the advantage of adding HER1/2 TKI (lapatinib) plus capecitabine to intrathecal application of liposomal cytarabin in the treatment of HER2-positive breast cancer and NM. Methods: A maximum of 34 patients with histological proven HER2-positive BC and meningeal and/or brain mets, assessed by MRI scan and/or positive liquor cytology and/or clinical symptoms of NM. Study Medication: 1,250 mg of lapatinib daily, 2,000 mg capecitabine d 1-14 q3w, 50 mg liposomal cytarabine d 15 q3w. Objectives: The primary objective: CNS response rate, secondary objective: time to neurological progression (TNP), time to systemic progression (TSP), clinical benefit rate (CBR) and overall survival (OS). In addition an assessment of the toxicities. Conclusions: Two-stage Design: A run in phase with 9 patients is planned to evaluate the preliminary efficacy and feasibility of this experimental triplet. At least 2 patients should present a response to the treatment administered within 3 months. If 9 or more patients show a positive response to the drugs administered we concider a positive outcome and the study will be finished. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline, Mundipharma
Flexible Electronics: Theoretical and Experimental Studies of Epidermal Heat Flux Sensors for Measurements of Core Body Temperature (Adv. Healthcare Mater. 1/2016)
Authors: Yihui Zhang, Richard Chad Webb, Hongying Luo, Yeguang Xue, Jonas Kurniawan, Nam Heon Cho, Siddharth Krishnan, Yuhang Li, Yonggang Huang, John A. Rogers
Journal: Advanced Healthcare Materials (2016)

On page 119, J. A. Rogers and co-workers present theoretical approaches, modeling algorithms, materials, and device designs for the noninvasive measurement of core body temperature by using multiple differential temperature sensors that attach softly and intimately onto the surface of the skin. The image shows the construction of differential temperature sensors using thermally insulating foam as the separation material.
A phase I study of docetaxel as a radiosensitizer for locally advanced squamous cell cervical cancer
Authors: E. A. Alvarez, A. H. Wolfson, J. M. Pearson, M. Crisp, N. C. Lambrou, F. Auguste, J. A. Lucci
Journal: Journal of Clinical Oncology (2006)

5053 Background: Concomitant radiotherapy with cisplatin chemotherapy is the standard of care for locally advanced squamous cell cervical cancer (LASCCC). Alternatives to cisplatin are needed due to patient intolerance or toxicity. Taxanes have demonstrated clinical cytotoxic activity to SCCC and in-vitro radio-sensitization. This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel with concurrent radiotherapy for the primary treatment of LASCCC. Methods: Twenty-three patients with FIGO stage IIB-IVA LASCCC without para-aortic lymph node involvement were screened and 13 enrolled in a dose-escalating phase I study. Docetaxel dose levels were 20 mg/m 2 , 30 mg/m 2 and 40 mg/m 2 given intravenously every 7 days for 6 cycles. Three patients were treated at each dose level and six patients received the MTD. Radiation therapy (RT) delivered a total dose of approximately 85 Gy to Point “A”. RT was administered with megavoltage external beam irradiation (EBI) at 1.8 Gy/fraction (fx) for 30 fxs to the pelvis over 6 weeks using a 4-field “box” technique for the first 25 fxs. A midline shield was applied for the last 5 fxs. Following EBI, patients underwent low-dose-rate brachytherapy. Results: Thirteen patients completed 4 - 6 cycles of chemotherapy. The other patients withdrew consent or needed alternative treatment before initiating the study. Reasons for completing less than 6 cycles were: noncompliance (5), adverse event (2), progression (1). One patient was lost to follow-up after 4 cycles. DLT’s were not observed at the 20 mg/m 2 dose level. At the 30 mg/m 2 dose level, 1/4 patient had a treatment-unrelated pelvic abscess and celiotomy. Another had progression 4 months after treatment. At the 40 mg/m 2 dose level, 1/6 patients had progression and experienced grade 2 pneumonia, not treatment related. DLT was not observed in 6 patients at the 40 mg/m 2 level. Overall, 5/13 (38%) experienced grade 2 diarrhea, 5 had grade 2 hematologic toxicity, and 2 had grade 2 hypersensitivity. Seven of 9 patients (78%) had no evidence of disease with follow-up ranging from 10–21 months. Conclusions: The recommended phase II dose of docetaxel administered weekly with concurrent radiotherapy for LASCCC is 40 mg/m 2 . The phase II trial is underway. No significant financial relationships to disclose.
Synergistic effect of human tubal mesenchymal stem cell (htMSCs) and low level laser (LLL) therapy significantly reduces experimental COPD in mice
Authors: Flavia Greiffo, Aurileia Brito, Elaine Silveira, Gabriel Moraes, Felipe Cipriani, Vinicius Neves, Carlos Czeresnia, Paulo Perin, Marcelo Nisenbaum, Mariangela Maluf, Flavio Aimbire, Jean Pierre Peron, Rodolfo Vieira, Ana Paula Oliveira
Journal: European Respiratory Journal (2014)

Currently the Chronic Obstructive Pulmonary Disease (COPD) has a high prevalence and a high economic and social cost. In this context, several experimental models have been proposed, aiming at the discovery of new therapeutic approaches. Accordingly, the use of mesenchymal stem cells (MSC) is an innovative and accessible treatment of pulmonary acute and chronic disease. Therapy with low level laser (LLL) is a relatively new effective therapy, with very low cost and no side effects. In this project we aim to study some parameters in animals with COPD undergoing therapies with LLL (15 days before the experiment) and MSC obtained from human fallopian tube (htMSC, administered 2 times: 15 days and 7 days before the experiment). The protocol used for the induction of COPD consists in submitting C57BL/6 mice for 75 days (2 times / day) to inhaled cigarette smoke. On day 76th the animals were sacrified and structural and functional parameters of lungs were evaluated. Our results indicate that the treatment with LLL and htMSC greatly reduces lung inflammation (as demonstrated through BAL cell counting and histomorphometric analysis in lung parenchyma), BAL pro-inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-alpha and KC) and the lung expression of NF-KB, NFAT and IL-10. Furthermore, these therapies also reduced airway mucus secretion and collagen deposition, beyond to promote re-alveolization of lung parenchyma. Thus, the association of both therapies improves the main features of COPD, becoming a potential therapeutic strategy for lung disease treatment. Support Financial: UNINOVE, FAPESP e CNPq.
Abstract 199: Automated External Defibrillator Awareness and Knowledge Among the Lay Public in a Busy Urban Transportation System
Authors: Mariana R Gonzalez, Marisa J Cinousis, Michael A Ward, Kathryn DiPuppo Tucker, Lance B Becker, Marion Leary, Benjamin S Abella
Journal: Circulation (2012)

Background: The prompt utilization of automatic external defibrillators (AEDs) by bystanders can greatly improve survival from sudden cardiac arrest occurring in public locations. A recent study of laypersons in a European transportation hub has suggested public knowledge and surrounding AED use is lacking; we sought to confirm and extend these findings in similar settings in the US. We hypothesized that awareness of AEDs and who can use them will be low among the general public. Objectives: To characterize layperson knowledge about AED use and emergency response in a major US metropolitan area transportation system. Methods: A survey instrument was adapted from a prior investigation performed in Europe. Trained survey personnel administered this oral survey (approx. five minute duration) to adult laypersons at two public transportation centers in a large US city during May 2012. The participants were asked questions relating to their knowledge of AEDs and who is permitted to use them, as well as their willingness to utilize an AED in an emergency. Results: Surveys were completed by 222 individuals. Mean age of respondents was 49.4±17.1 y, 44% were female and 25% reported prior CPR training within the past 5 years. When presented with a hypothetical cardiac arrest scenario, 63% said they would call for help and/or dial 911, but only 8% of respondents spontaneously suggested using an AED when prompted for other actions. When an AED was described, 59% of participants were aware that AEDs are available in public places, but only 38% were aware that AEDs can be used by laypersons. When informed regarding the availability for layperson use, 60% of respondents said that they would be willing to use an AED in an emergency situation. Conclusions: Though the majority of layperson respondents were willing to use an AED in an emergency when educated, few respondents considered an AED in their immediate response and the minority were aware that AEDs could be accessed by the general public. Additional broad efforts to educate the US public about AED availability and use should be prioritized.
Sunitinib for unselected Korean patients with advanced renal cell carcinoma: A comparable efficacy with different toxicity profiles.
Authors: H. Kim, M. Hong, S. J. Shin, J. Ahn, H. C. Chung, K. Kim, Y. Koh, S. Lee, Y. Bang, S. Y. Rha
Journal: Journal of Clinical Oncology (2010)

e15107 Background: Sunitinib demonstrated favorable efficacy with manageable toxicities, both for selected and unselected patients. However, there is little experience for sunitinib in Asian population. Therefore, we performed this study to describe the efficacy and safety of sunitinib treatment in unselected Korean advanced RCC patients. Methods: From November 2005 to August 2008, 132 patients with histologically confirmed advanced RCC (100 in global EAP and 32 in general oncology practice) were enrolled. Response and toxicity evaluation were assessed regularly according to the protocol. Results: This population includes 82.6% of clear cell histology, 87.9% of ECOG status 0-1, and 28.8% of treatment naïve patients. The PFS and OS were 8.2 months and 23.1 months, respectively. Patients received a median 5 cycles of sunitinib. With the 130 evaluable patients, the ORR was 34.1% (n=45), and 44.7% (n=59) exhibited SD. Reasons for discontinuation were disease progression (n=99) and treatment related toxicity (n=10). The mean relative dose intensity (RDI) was 82.0% (SD+14.20). The most frequent adverse events were thrombocytopenia (75.0%), neutropenia (70.5%), anemia (69.7%), and stomatitis/mucositis (66.7%). Grade 3-4 adverse events were also very high, being thrombocytopenia (37.8%), neutropenia (29.5%), anemia (21.9%), and hand-foot syndrome (15.2%). Proportion of patients experienced grade 3-4 or all grades thrombocytopenia was peaked during week 1 through 4 (about 15-23.1%), and gradually reduced in accordance with the decreasing RDI. Low body surface area (Odd ratio [OR] 4.2, P=0.02), and previously treated status (OR=3.1, p=0.01) were highly predictable for grade 3-4 toxicities. Based on these results, a nomogram predicting 12 month-PFS probability was constructed with the 0.675 of concordance index. Conclusions: For unselected Korean advanced RCC patients, sunitinib demonstrates favorable efficacy and manageable toxicities. Based on these different toxicity profiles, further studies to optimize the dose/schedule of sunitinib are warranted with the reliable pharmacokinetic/pharmacodynamic markers. No significant financial relationships to disclose.
Outcome after combined modality treatment for uterine papillary serous carcinoma (UPSC): A Rare Cancer Network (RCN) Multicenter Study
Authors: H. Goldberg, R. Abdah-Bortniak, M. Shteiner, Y. Gilboa, S. Villa Freixa, S. Marin, A. Mendez, D. Azria, P. Poortmans, A. Kuten
Journal: Journal of Clinical Oncology (2005)

5078 Background: There are no established guidelines for treatment of UPSC, either in the adjuvant setting or in advanced disease. The aim of this retrospective, multi-center study was to analyze the outcome of pts.with UPSC treated with combined modalities. Methods: This was a cooperative study within the framework of the RCN. Charts of patients with UPSC diagnosed between 1980 - 2003 were reviewed. Pts were followed for 3–294 months (Median 35). Treatment included surgery, chemotherapy, and/or radiation therapy (RT) according to discretion of treating physician. Results: Sixty-eight pts, 37–85 yrs (median 67) were included. Histology features: mixed histology (containing UPSC elements and typical adenocarcinoma)and pure UPSC were found in 18 pts (26%), and in 50 pts (74%) respectiviely. Stage distribution: stage I 26 pts (38%), II 12 pts (18%), III 16 pts (24%), IV 13 pts (19%), no data 1 pt. Sixty-five pts had surgery, 3 pts biopsy only, 30 pts (44%) treated with RT in an adjuvant setting. Five pts irradiated for palliation, and 2 for pelvic recurrence. 29 pts (43%) received platinum-based adjuvant chemotherapy (CT). In 28 pts CT was given for persisting disease, resulting in 54% response rate (5 complete and 10 partial responders). 20 pts (29%) are alive and NED, 3 alive with disease, 35 died of disease, 9 (13%) died of other causes, and one died of toxicity. Five-year Disease specific survival (DSS) rates as follows: All pts (N=68) 46%, mixed type pathology 84%, pure UPSC 35% (p<0.0001), stage 1&2 72%, stage 3&4 13% (p<10-6), pts receiving CT 50%, no CT 56% (NS), pts receiving RT 55%, no RT 51% (NS). 5 yr disease free survival rates as follows: all pts 40%, mixed type 82%, pure UPSC 27% (p<10-6), stages 1&2 62%, stages 3&4 6% (p<10-6), pts receiving CT 39%, no CT 51% (NS), pts receiving RT 58%, no RT 34% (p<0.021). In a Cox regression analysis for DSS, stages (HR 4.7) and pathology subtype (HR 4.6) were found highly significant. CT and RT not significant. RT did not make any difference in pelvic recurrence rate. Conclusions: 1.Stage of disease and pathology subtype are significant prognostic factors. 2. Results do not support any benefit from either chemotherapy or radiotherapy in the adjuvant setting. No significant financial relationships to disclose.
Inhibitory Effect of the Transcription Factor Encoded by themi Mutant Allele in Cultured Mast Cells of Mice
Authors: Akihiko Ito, Eiichi Morii, Dae-Ki Kim, Tatsuki R. Kataoka, Tomoko Jippo, Kazutaka Maeyama, Hiroshi Nojima, Yukihiko Kitamura
Journal: Blood (1999)
Abstract 12912: Model of End-Stage Liver Disease Excluding INR (MELD-XI) Scoring System Predicts Mode of Death in Patients Admitted With Acute Decompensated Heart Failure
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Tsutomu Kawai, Satoshi Takahashi, Masashi Ishimi, Hideyuki Hakui, Tatsuhisa Ozaki, Yoshihiro Satoh, Masahiro Seo, Masatake Fukunami
Journal: Circulation (2014)

Backgrounds: Cardiohepatic interactions have been a focus of attention among heart failure. A model of end-stage liver disease excluding INR (MELD-XI) is a robust scoring system of liver dysfunction, and a high score has been shown to be associated with poor prognosis in patients with heart failure. Prediction of mode of death (sudden cardiac death (SCD) and pump failure death (PFD)) in patients with heart failure may facilitate decisions about specific medications or devices. However, there is no information available on the prognostic significance of MELD-XI in patients admitted with acute decompensated heart failure (ADHF), from the viewpoint of mode of death. Methods and Results: We studied 303 consecutive patients admitted with ADHF and discharged with survival. MELD-XI score was calculated by the following formula: 5.11[[Unable to Display Character: &amp;#65381;]]ln(bilirubin)+11.79[[Unable to Display Character: &amp;#65381;]]ln(creatinine)+9.44. During a follow-up period of 5.0±4.3 yrs, 37 patients had SCD and 27 patients had PFD. At multivariate Cox analysis, MELD-XI score was significantly independently associated with SCD (p=0.002) and PFD (p=0.003). Receiver-operator curve analysis revealed that MELD-XI of 11 and 13 was fair discriminators for SCD (AUC 0.667(95%CI 0.575-0.758), p=0.001; sensitivity 78% and specificity 48%) and PFD (AUC 0.764(95%CI 0.683-0.845; sensitivity 74% and specificity 69%), p&lt;0.0001), respectively. Patients with higher MELD-XI score had significantly a higher risk of not only SCD (17% vs 6%, p=0.0005, adjusted HR: 3.19 (95%CI 1.44-7.08) but also PFD (20% vs 3%, p&lt;0.0001, adjusted HR: 4.53 (95%CI 1.72-12.07)), compared to those with lower MELD-XI score. Conclusion: A MELD-XI scoring system might predict not only sudden cardiac death but also pump failure death in patients admitted with ADHF.
Net benefit approaches to the evaluation of prediction models, molecular markers, and diagnostic tests
Authors: Andrew J Vickers, Ben Van Calster, Ewout W Steyerberg
Journal: BMJ (2016)

Many decisions in medicine involve trade-offs, such as between diagnosing patients with disease versus unnecessary additional testing for those who are healthy. Net benefit is an increasingly reported decision analytic measure that puts benefits and harms on the same scale. This is achieved by specifying an exchange rate, a clinical judgment of the relative value of benefits (such as detecting a cancer) and harms (such as unnecessary biopsy) associated with models, markers, and tests. The exchange rate can be derived by asking simple questions, such as the maximum number of patients a doctor would recommend for biopsy to find one cancer. As the answers to these sorts of questions are subjective, it is possible to plot net benefit for a range of reasonable exchange rates in a “decision curve.” For clinical prediction models, the exchange rate is related to the probability threshold to determine whether a patient is classified as being positive or negative for a disease. Net benefit is useful for determining whether basing clinical decisions on a model, marker, or test would do more good than harm. This is in contrast to traditional measures such as sensitivity, specificity, or area under the curve, which are statistical abstractions not directly informative about clinical value. Recent years have seen an increase in practical applications of net benefit analysis to research data. This is a welcome development, since decision analytic techniques are of particular value when the purpose of a model, marker, or test is to help doctors make better clinical decisions.
Elevated Coexpression of KITENIN and the ErbB4 CYT-2 Isoform Promotes the Transition from Colon Adenoma to Carcinoma Following <i>APC</i> loss
Authors: Jeong A Bae, Dhong Hyo Kho, Eun Gene Sun, Yoo-Seung Ko, Somy Yoon, Kyung Hwa Lee, Kyu Youn Ahn, Jae Hyuk Lee, Young Eun Joo, Ik Joo Chung, Sug Hyung Lee, Hangun Kim, Kyung Keun Kim
Journal: Clinical Cancer Research (2015)

The molecular events in the malignant progression of colon adenoma after loss of adenomatous polyposis coli (APC) are not fully understood. KITENIN (KAI1 C-terminal interacting tetraspanin) increases the invasiveness of colorectal cancer cells, and we identified a novel EGFR-independent oncogenic signal of EGF that works under coexpressed KITENIN and ErbB4. Here we tested whether elevated KITENIN and ErbB4 contribute to further progression of intestinal adenoma following APC loss.The intestinal tissues of villin-KITENIN transgenic mice in which villin-driven KITENIN expression induces increased c-Jun expression exhibit mild epithelial cell proliferation but no epithelial lineage changes compared with those of nontransgenic mice. Among the four ErbB4 isoforms, JM-a/CYT-2 and JM-b/CYT-2 exhibited the highest AP-1 activity when cells coexpressing KITENIN and each isoform were stimulated by EGF. Interestingly, predominant overexpression of the ErB4-CYT-2 mRNA as well as increased EGFR expression were observed in intestinal adenoma of APC(min/+) mice, which makes the microenvironment of activated EGF signaling. When we crossed villin-KITENIN mice with APC(min/+) mice, intestinal tumor tissues in the crossed mice showed the characteristics of early-stage invading adenocarcinoma. In patients with colorectal cancer, ErbB4-CYT-2 mRNA expression was significantly greater in tumor tissues than in normal adjacent tissues, but no significant differences in tumor tissue expression were found between different colorectal cancer stages. Furthermore, the mRNA expression of KITENIN and that of ErbB4-CYT-2 were positively correlated in human colorectal cancer tissue.Elevated coexpression of KITENIN and ErbB4-CYT-2 promotes the transition of colon adenoma to adenocarcinoma within an APC loss-associated tumor microenvironment.
Functional pathways analyses to identify candidate therapeutic targets in triple-negative breast cancer
Authors: F. Andre, P. Dessen, B. Job, S. Delaloge, L. Pusztai, V. Lazar
Journal: Journal of Clinical Oncology (2009)

569 Background: In the present study, we have analyzed dysregulated pathways in triple-negative breast cancers. Methods: Two datasets of cDNA arrays were used to identify differentially expressed genes between triple negative breast cancer and either normal/benign breast tissue or other molecular classes. The first dataset (I) was included 165 samples. The second data set (II) included 148 samples. Pathway analyses (gene set) were done based using BRB array tool and a software developed in house (SBIME). Results: Fifteen and 27 patients presented a triple negative breast cancer in the dataset I and II respectively. Ten and eleven pathways were significantly different between triple negative and other molecular classes in dataset I and II respectively (LS permutation p value&lt;0.01). Six pathways were common between the two datasets (p53, cyclin E, E2F1, p27 phosphorylation, Ran, cycle regulation). We then focused the analyses on differential pathways between triple negative and normal/benign tissue. In the dataset I, targetable pathways were identified (hotelling t-test &lt;10–7) including VEGF signalling pathway, proteasome, Hedgehog and Notch pathway. In addition, an enrichment of histone overexpression was observed in triple negative breast cancer (3% of overexpressed genes, ratio expression &gt;2). In the dataset II, histone (p = 2x10–6), chromosome organization (p = 2x10–4) gene sets were enriched in triple negative breast cancer. We then assessed whether such pathway dysregulations could be linked to genomic aberration enriched in triple negative breast cancer. Using high resolution CGH arrays (Agilent, 4*44K) on 53 triple negative breast cancers, we detected that 31% of triple negative tumors presented a gene gain in 6p21 and 6p22, two regions that contain VEGFA gene (6p21) and a cluster of histones (6p22). Conclusions: Triple negative breast cancers present dysregulation of targetable pathways, including VEGF signaling and chromosome organization. Dysregulation of these two pathways could be related to gene gains in 6p21–22 regions observed in 30% of triple negative breast cancer. No significant financial relationships to disclose.