tbuckley/cabot-search huggingface dataset:
Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With Previously Treated Advanced Lung Adenocarcinoma: WJOG 5108L
Authors: Yoshiko Urata, Nobuyuki Katakami, Satoshi Morita, Reiko Kaji, Hiroshige Yoshioka, Takashi Seto, Miyako Satouchi, Yasuo Iwamoto, Masashi Kanehara, Daichi Fujimoto, Norihiko Ikeda, Haruyasu Murakami, Haruko Daga, Tetsuya Oguri, Isao Goto, Fumio Imamura, Shunichi Sugawara, Hideo Saka, Naoyuki Nogami, Shunichi Negoro, Kazuhiko Nakagawa, Yoichi Nakanishi
Journal: Journal of Clinical Oncology (2016)

The epidermal growth factor receptor (EGFR) tyrosine kinase has been an important target for non-small-cell lung cancer. Several EGFR tyrosine kinase inhibitors (TKIs) are currently approved, and both gefitinib and erlotinib are the most well-known first-generation EGFR-TKIs. This randomized phase III study was conducted to investigate the difference between these two EGFR-TKIs.Previously treated patients with lung adenocarcinoma were randomly assigned to receive gefitinib or erlotinib. This study aimed to investigate the noninferiority of gefitinib compared with erlotinib. The primary end point was progression-free survival (PFS).Five hundred sixty-one patients were randomly assigned, including 401 patients (71.7%) with EGFR mutation. All baseline factors (except performance status) were balanced between the arms. Median PFS and overall survival times for gefitinib and erlotinib were 6.5 and 7.5 months (hazard ratio [HR], 1.125; 95% CI, 0.940 to 1.347; P = .257) and 22.8 and 24.5 months (HR, 1.038; 95% CI, 0.833 to 1.294; P = .768), respectively. The response rates for gefitinib and erlotinib were 45.9% and 44.1%, respectively. Median PFS times in EGFR mutation-positive patients receiving gefitinib versus erlotinib were 8.3 and 10.0 months, respectively (HR, 1.093; 95% CI, 0.879 to 1.358; P = .424). The primary grade 3 or 4 toxicities were rash (2.2% for gefitinib v 18.1% for erlotinib) and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation (6.1%/13.0% for gefitinib v 2.2%/3.3% for erlotinib).The study did not demonstrate noninferiority of gefitinib compared with erlotinib in terms of PFS in patients with lung adenocarcinoma according to the predefined criteria.
Abstract C36: Using the <i>Rb/E2f3</i> mutant mouse model to reveal markers for the progression to metastasis
Authors: Kirsten Vormbrock, Caroline Schreiber, Christoph Loddenkemper, Ulrike Ziebold
Journal: Cancer Research (2009)

Abstract The retinoblastoma tumor suppressor protein (pRb) was the first tumor suppressor to be identified. The E2F family of transcription factors is considered the best-studied class of interaction partners of pRB. Specifically, E2F1-3 are all capable to control re-entry and progression through the S-phase of the cell cycle. The simplified view is that hypo-phosphorylated pRb is bound by E2F and recruits chromatin remodeling complexes to represses the transcription of E2F target genes. Upon cell cycle progression pRb is phosphorylated leading to a release of E2Fs and the subsequent progression through the G1/S-transition. In order to understand the consequences of deregulation of the pRb/E2F-pathway, a number of groups have established mouse knock-out models of various members of this pathway. Using a combined knockout mouse model it was demonstrated that E2F3 contributes to both the inappropriate proliferation and p53-dependent apoptosis that arises in pRb-deficient embryos. Furthermore, it was shown that absence of E2F3 results on one hand in the attenuation of the growth of pituitary adenomas, on the other hand it promotes the development of medullary thyroid carcinomas (MTCs) yielding metastases at an increased frequency. Since this is one of the few existing mouse models to study metastasis, we wished to use this model to identify novel markers and mechanisms that regulate this process. We established the whole genomic transcriptional profile of mouse MTCs harvested from Rb/E2f3 mutant mice. The comparison of metastatic MTCs with non-metastatic tumors defined a data set of 123 putative metastatic markers. Among this data set, we identified a cluster of 22 genes that are directly involved in the formation of the kinetochore, establishment of the centromere or play a distinct role in the spindle assembly checkpoint. We validated the expression of these novel metastatic markers using mouse RNA, as well as material from human metastatic MTC biopsies. Importantly, we were able to establish that the same genes were only upregulated in metastatic tumors utilizing immunhistochemistry on sections of human metastatic MTCs but not in non-metastatic counterparts. Moreover, chromatin immunoprecipitation assays support that these genes are direct targets of the pRB/E2F-pathway. In summary we identified novel markers of metastasis. Moreover, these markers are also putative E2F target genes, the fact of which emphasizes the important contribution of E2Fs to tumor progression. Citation Information: Cancer Res 2009;69(23 Suppl):C36.
Expression of Androgen Receptor in Breast Cancer.
Authors: S. Park, H. Park, S. Choi, J. Lee, B. Park, K. Lee
Journal: Cancer Research (2009)

Abstract Background: Androgen receptor (AR) is one of biomarkers and its role in breast cancer is still unclear. The aim of this study was to investigate the relationship between AR expression and clinicopathological factors in breast cancer patients.Patients and Methods: AR was consecutively evaluated in 413 primary breast cancers from whole sections of surgically resected specimens using immunohistochemical staining from January 2008 to March 2009. The associations between AR expression and clinicopathological parameters were analyzed. Tumors with 10% or more nuclear stained cells were considered as positive for AR expression. The differences between variables were calculated by chi-square test and Fisher's exact test was used when appropriate.Results: The median age at diagnosis was 49 years (range, 26-84). AR was found in 72.7% (48/66) of in-situ carcinoma and in 72.9% (253/347) of invasive carcinoma. Overall expression rates of AR were 72.9%, which were higher than those of ER and PR expression, 68.5% and 62.0%, respectively. AR was significantly expressed in patients with no elevated preoperative serum cancer antigen 15-3 (CA 15-3) levels (p = .042), smaller tumor size (p = .035), lower histologic grade (p &amp;lt; .001), ER-positive (p &amp;lt; .001), progesterone receptor-positive (p &amp;lt; .001), and non-triple-negative breast cancer (p &amp;lt; .001). Metaplastic, medullary, and mucinous types carcinomas showed less AR expression (p = .030). Although it was statistically not significant, patients with younger age (≤ 35 years), axillary lymph node involvements, and higher stage showed higher rates of AR negativity. In ER-negative tumors, AR expression was significantly correlated with HER-2 over-expression (p &amp;lt; .001). In ER-positive tumors, however, there was no relationship between AR expression and HER-2 over-expression (p &amp;gt; .05).Conclusions: AR is expressed in a significant number of breast cancers and is associated with favorable tumor differentiation and smaller tumor size. These results might suggest that AR may be an independent prognostic factor in breast cancer. AR may also be associated with growth factor signaling and be useful therapeutic target in ER-negative tumors. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4156.
124I-Anti-CD52 Dosimetry Before Radioimmunotherapy as Part of Conditioning for Stem Cell Transplantation in Acute Leukemia
Authors: Daniel Putzer, Georg Dobrozemsky, Roland Haubner, Johannes Clausen, David Nachbaur, Irene Virgolini
Journal: Clinical Nuclear Medicine (2012)

We report bone marrow ablation in a 21-year-old patient with recurrent refractory CD52-positive acute lymphoblastic leukemia, using murine 131I-anti-CD52 monoclonal antibody (mAb) in the conditioning regimen for allogeneic hematopoietic stem cell transplantation. 124I-labeled anti-CD52-mAb PET evaluated radioimmunotherapy (RIT) dosimetry. After myeloablative conditioning, hematopoietic stem cell transplantation from a human leukocyte antigen (HLA)-1-antigen–mismatched, haploidentical family donor was performed. Recurrence 3 months after transplantation led to repeat 124I-alemtuzumab dosimetry, followed by 131I–labeled anti-CD52-mAb RIT (76.8 mCi; effective dose, 0.59 Sv). RIT was well tolerated without toxicity or graft-versus-host disease. Marrow ablation and donor cell engraftment was achieved with conditioning and immunosuppression. Leukemia control was transient. The patient succumbed 2 months after transplantation.
Alternative splicing in wild-type AF10 and CALM cDNAs and in AF10-CALM and CALM-AF10 fusion cDNAs produced by the t(10;11)(p13–14;q14–q21) suggests a potential role for truncated AF10 polypeptides
Authors: CC Silliman, L McGavran, Q Wei, LA Miller, S Li, SP Hunger
Journal: Leukemia (1998)
Intravitreal Triamcinolone for Diabetic Macular Edema
Authors: GianPaolo Giuliari
Journal: New England Journal of Medicine (2010)

A 55-year-old man with diabetic retinopathy and diabetic macular edema refractory to laser photocoagulation treatment underwent intravitreal injection of 4 mg (0.1 ml) of triamcinolone. On fundus photography performed after the procedure, the triamcinolone crystals are clearly visible as small specks within the vitreous cavity of the left eye (Panel A). Optical coherence tomography performed before the procedure (Panel B) and 4 weeks after the procedure (Panel C) reveals a decrease in central retinal thickness and resolution of cystic spaces after triamcinolone administration. The patient's visual acuity improved from 20/400 to 20/40.
Abstract 3148: Mapping mobile DNAs in human cancer cell lines.
Authors: John G. Zampella, Wan Rho Yang, Nemanja Rodric, Cheng Ran Lisa Huang, Jane Welch, Veena P. Gnanakkan, Toby C. Cornish, Jef D. Boeke, Kathleen H. Burns
Journal: Cancer Research (2013)

Abstract Genomic instability represented by genetic and epigenetic changes is a hallmark of oncogenesis and tumor progression. The study of genomic instability using conventional methods has necessarily been restricted to regions of unique DNA and excludes repetitive DNA sequences. Repeat elements derived from mobile DNAs comprise a large portion of the human genome and are known sources of genetic variation in humans. Active transposable elements (TE) have recently been shown to cause genetic heterogeneity in tumors through somatic insertions. The functional impact of inherited and somatically acquired TE in cancer development and progression remains unproven. To begin to understand the roles of these mobile DNA elements in transformed cells, we used a novel genomic method to map TEs in a panel of well-characterized human cancer cell lines. Using transposon insertion profiling (TIP)-chip we discover transposition competent families of L1 and Alu TEs. This technique recovered many known reference and polymorphic insertions, novel polymorphisms shared by unrelated tumor cell lines, as well as unique, potentially tumor-specific insertions. Insertions were discovered in several important oncogenes such as KRAS, ALK and BRAF. Most insertions discovered were intronic or intergenic, however 16 TEs were putative exonic. Analysis of the novel and polymorphic insertions revealed a relative enrichment of L1 and Alu insertions in cancer gene loci that are mutated in human cancers or implicated in tumor development in forward genetic screens (p=7.74e-10). We also report associations of individual insertion sites with cellular phenotypes, including DNA methylation status, RNA and protein expression, and drug sensitivities. Epigenetic, gene expression and gene pathway associations were evaluated to delineate local (cis) from pathway (trans) effects. We identified several examples of cis effects of TEs on gene structure as well as nearly 250 curated proliferation pathways affected by a TE insertion. These data suggest that TE insertions may function locally to alter genomic structure or act more globally in concert with other genetic mechanisms to promote the development and progression of several common tumor types. Citation Format: John G. Zampella, Wan Rho Yang, Nemanja Rodric, Cheng Ran Lisa Huang, Jane Welch, Veena P. Gnanakkan, Toby C. Cornish, Jef D. Boeke, Kathleen H. Burns. Mapping mobile DNAs in human cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3148. doi:10.1158/1538-7445.AM2013-3148
P79 Comparison of CF and Non CF LCI results using the Exhalyzer D and InnocorTM devices
Authors: KJ Bayfield, C Saunders, EWFW Alton, JC Davies
Journal: Thorax (2015)

<h3>Background</h3> Multiple breath washout (MBW) is a pulmonary function test that allows measurement of lung clearance index (LCI), a marker of ventilation heterogeneity. LCI is increasingly being considered as a clinical trial outcome measure. The Exhalyzer D N<sub>2</sub> washout (N<sub>2</sub>/ExD, Ecomedics AG, Switzerland) is the recommended technique by the ECFS CTN. Mostly our group’s experience with LCI uses the Innocor<sup>TM</sup> gas analyser (Innovision, Denmark), SF<sub>6</sub> as a tracer gas (SF<sub>6</sub>/Inn). To understand the N<sub>2</sub>/ExD technique, the aims of this study were to compare a) intra-test variability; b) LCI values c) LCI and FEV<sub>1</sub> for the two techniques. <h3>Methods</h3> 21 CF (14F, mean 20 ± 12 yrs) and 10 non-CF (8F, mean 28 ± 10 yrs) have completed MBW trials with the 2 techniques in random order on the same visit; methods previously described (Horsley <i>et al</i>. 2009, Jensen <i>et al</i>. 2013). <h3>Results</h3> Intra-test CoV (2–3 repeats) was similar for SF<sub>6</sub>/Inn and N<sub>2</sub>/ExD (3.57 vs 3.78 CF, ns). LCI was significantly higher with N<sub>2</sub>/ExD than with SF<sub>6</sub>/Inn in both CF (14.05 vs 9.33; p = &lt;0.0001) and non-CF (7.08 vs 6.64, p = 0.04). Both techniques show a significant correlation for LCI and FEV<sub>1</sub>%, although the regression slopes were significantly different (p = 0.005); much steeper for N<sub>2</sub>/ExD. <h3>Conclusions</h3> LCI values cannot be used interchangeably between the Innocor<sup>TM</sup> and Exhalyzer D. In non CF, there was a statistically significant difference, with higher values in the N<sub>2</sub>/ExD. The difference was much greater in CF and increased as LCI did. In the context of similar intra-test variability, the hypothesis that this may translate into improved power in future clinical trials needs to be tested. Sponsored by a non-restricted grant from Novartis. <h3>References</h3> 1 Horsley AR, Gustafsson PM, Macleod KA. <i>et al. </i>Lung clearance index is a sensitive, repeatable and practical measure of airways disease in adults with cystic fibrosis.<i> Thorax</i>. 2008;<b>63</b>:135–40 2 Jensen R, Stanojevic S, Gibney K, <i>et al.</i> Multiple breath nitrogen washout: a feasible alternative to mass spectrometry.<i> PLoS One</i>. 2013;<b>8</b>:e56868
Abstract 4066: Benzyl isothiocyanate causes degradation of the aryl hydrocarbon receptor in hepa1c1c7 cells
Authors: Stephen M. Kioko, Ward G. Kirlin
Journal: Cancer Research (2010)

Abstract The biotransformation and detoxification of many carcinogens, including 2,3,7,8-tetrachlorodibenzodioxin, benzo [a] pyrene and 3-methylchloranthrene is dependent upon the activity of phase I and II enzymes, particularly CYP1A1 and NQO1. The transcriptional activation of these enzymes is regulated by the aryl hydrocarbon receptor (AhR) and Nuclear Factor-Erythroid 2-Related Factor. These transcription factors reside in the cytoplasm and when activated, shed their respective chaperones and translocate into the nucleus where they interact with nuclear proteins involved with transcription of genes possessing xenobiotic (XRE) and antioxidant (ARE) response elements. We have previously observed that the phytochemical benzyl isothiocyanate (BITC) induces nuclear translocation of the AhR independently of traditional ligands in Hepa1c1c7 cells and also induces AhR heterodimerization with ARNT. These observations suggest that BITC might bind the AhR and affect activity of these enzymes as well as the transcriptional regulation of XRE-responsive genes. In the current study we investigated whether BITC causes degradation of the AhR. This is important because it provides insight into potential mechanisms by which BITC affects AhR transcriptional regulation and the activity of phase I and II enzymes. Hepa1c1c7 cells were treated for 4 hours with DMSO alone, 10 μM BITC, 10 μM BNF or a combination of both 10 μM BITC and 10 μM BNF. Whole cell lysates were prepared and AhR immunoprecipitated and analyzed by western blot. Results showed that AhR was rapidly degraded in cells treated with BITC alone compared to controls. Furthermore, BITC enhanced degradation of the receptor in cells treated with a combination of both BITC and BNF compared to cells treated with BNF alone. In other experiments, Hepa1 cells were treated for 16 hours with BNF alone or a combination of 1, 2, 5, 10 and 20 μM BITC. Isolated proteins analyzed by western blot indicated that BITC enhanced degradation of the AhR in a dose dependent manner in cells treated with both BITC and BNF compared to BNF-only treated cells. Cumulatively, these data show that BITC degrades the AhR, which might decrease its function in transcription of XRE responsive genes. The results also suggest that increased degradation of the AhR might affect the activity of CYP1A1 and NQO1 thus affecting biotransformation and detoxification of carcinogens. They also provide preliminary evidence into one of the potential mechanisms by which BITC is chemopreventive. (Support: NIH MBRS/GM028248; RCMI RR033032). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4066.
Abstract 2292: Tumor suppressive <i>miR-124</i> targets androgen receptor and inhibits proliferation of prostate cancer cells
Authors: Xu-Bao Shi, Lingru Xue, Clifford G. Tepper, Ralph W. deVere White
Journal: Cancer Research (2012)

Abstract Recent studies have revealed that miR-124 functions as a tumor suppressor and is downregulated in several types of human cancer. Until now, however, whether miR-124 is involved in prostate cancer (CaP) is totally unknown. In order to explore the role of miR-124 in CaP, we detected the expression level of miR-124 in prostate cell lines and clinical prostatic tissues using qPCR, and observed a reduced expression of miR-124 in all malignant cell lines tested and in a majority of clinical CaP samples examined, compared to that in the benign cell lines and in benign prostatic hyperplasia (BPH), suggesting that miR-124 is a putative tumor suppressor gene. Since the 3′UTR of androgen receptor (AR) mRNA contains a broadly conserved miR-124-binding site, experiments were performed to validate miR-124-mediated regulation of AR. We found that transfection of synthetic miR-124 mimic (miR-124m) downregulated the AR protein level and its downsteam effectors PSA and miR-125b. To verify that the miR-124 binding site is responsible for regulation by miR-124, the AR 3β UTR was cloned into the pRIM Reporter-luciferase vector, and cotransfected with miR-124m into CaP cells. We observed that transfection of miR-124m resulted in 40% reduction of luciferase activity, indicating a direct interaction between miR-124 and AR mRNA. We then examined whether clinical CaP samples having low level of miR-124 overexpress the AR using IHC analysis, and found a reverse correlation between miR-124 and AR expression levels in 7 of 8 CaP samples. These data suggest that miR-124 targets the AR and down-regulation of miR-124 results in increased expression of the AR in CaP cells. In addition, we tested whether miR-124 inhibits the growth of CaP cells, and found that treatment with miR-124m induced significant inhibition of cell proliferation compared to treatment with miR-NC control. We also evaluated the effect of miR-124 on tumorigenesis of 22Rv1 CaP cells that were transiently transfected with miR-124m. We observed that tumors derived from miR-124-transfected 22Rv1 cells grew substantially slowly, when compared to miR-NC tumors. Taken together, our data suggest that miR-124 is a potential tumor suppressor gene in CaP, and restoration of miR-124 expression may represent a novel therapeutic strategy in CaP therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2292. doi:1538-7445.AM2012-2292
The Vitamin D Content of Fortified Milk and Infant Formula
Authors: Michael F. Holick, Qing Shao, Wen Wei Liu, Tai C. Chen
Journal: New England Journal of Medicine (1992)

The fortification of milk and infant formula with vitamin D has had an important role in eliminating rickets in children and osteomalacia in adults. A recent outbreak of vitamin D intoxication caused by drinking milk fortified with excess vitamin D has led to questions about the level of vitamin D in milk from other producers.
Evaluation of Abnormal Liver-Enzyme Results in Asymptomatic Patients
Authors: Daniel S. Pratt, Marshall M. Kaplan
Journal: New England Journal of Medicine (2000)

Now that routine laboratory testing is automated and is frequently part of an annual checkup, physicians are often faced with the problem of a patient with one abnormal result on measurement of serum aminotransferases or alkaline phosphatase but no symptoms. Many batteries of screening tests now include measurement of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyltransferase. Although these enzymes are present in tissues throughout the body, they are most often elevated in patients with liver disease and may reflect liver injury.The first step in the evaluation of a patient with elevated liver-enzyme levels but no symptoms is . . .
Hepatic infarction caused by vascular migration of fiducial marker previously placed under endosonographic guidance to assist radiotherapy
Authors: Dongwook Oh, Do Park, Young Cho, Tae Song, Sang Lee, Dong Seo, Sung Lee, Myung-Hwan Kim
Journal: Endoscopy (2014)

A 39-year-old woman attended our hospital with jaundice. A computed tomography (CT) scan revealed a low attenuation 3.3 × 2.0 cm mass in the caudate lobe of the liver with left hepatic artery and left portal vein invasion, and bile duct obstruction ([Fig. 1]). Endoscopic biliary drainage and endoscopic ultrasound fine-needle aspiration (EUS-FNA) were performed. A biopsy taken from the mass contained adenocarcinoma cells. Because of the unresectability of this cholangiocarcinoma, three fiducial markers were inserted into the tumor under EUS guidance ([Fig. 2]). Image-guided radiation therapy was then performed with a 26-Gy dosage delivered in four fractions. The patient also received systemic chemotherapy and photodynamic therapy. After 5 months, a follow-up CT scan showed that the tumor mass in the caudate lobe was markedly smaller. However, thrombosis of left and right (P7) branches of the portal vein was detected. No definite migration of any fiducial marker was seen.