tbuckley/cabot-search huggingface dataset:
Outcome following multiple lines of salvage chemotherapy prior to autologous stem cell transplant for relapsed or refractory diffuse large B-cell lymphoma (DLBCL)
Authors: J. Stakiw, J. Kuruvilla, K. Al-Farsi, S. Zadeh, T. Nagy, A. Keating, M. Crump
Journal: Journal of Clinical Oncology (2007)

8120 Background: The standard of care for chemosensitive relapsed or refractory DLBCL is autologous stem cell transplant (ASCT). There is no standard approach for patients (pts) whose disease fails to respond to platinum-based salvage chemotherapy (pSC) although pts who undergo further salvage chemotherapy to demonstrate chemosensitivity may benefit from ASCT (Chen, et al, BMT 2002). We analyzed the overall response rate (ORR) to each line of salvage therapy for pts with relapsed or refractory DLBCL and the impact of the number of salvage regimens necessary to demonstrate chemosensitivity on overall and progression-free survival (OS and PFS) post-ASCT. Methods: We retrospectively reviewed our computerized database and charts between Jan 1/99 - Dec 31/05 and identified 203 pts relapsed after or refractory to anthracycline-based chemo treated with pSC. Pts typically received 2–3 cycles of pSC to assess chemotherapy sensitivity. Responding patients received etoposide 60 mg/kg and melphalan 160 mg/m 2 supported by autologous PBSCs. Pts with stable or progressive disease following first line salvage chemotherapy (SC1) were offered alternate non-cross resistant second-line salvage chemotherapy (SC2) and proceeded to ASCT if chemosensitive. Results: Pt characteristics: Median age at time of salvage chemotherapy: 52 years (range 21–65); primary refractory: 48%; advanced stage disease at salvage: 50%; prior rituximab: 17%; prior radiation 26%. 119/203 pts did not respond to SC1, 81 pts received SC2 and 10 pts received 3 salvage regimens (SC3). ORRs to salvage were: SC1: 40%, SC2: 14%, SC3: 10%. Pts able to proceed to ASCT were: SC1: 37%, SC2: 14%, SC3: 0. With a median follow-up of 1.8 years, the 2-year OS post ASCT for the SC1 and SC2 groups was 69% and 56% respectively. The 2-year PFS post ASCT for the SC1 and SC2 groups were 58% and 40%. Conclusions: The ORR to platinum-based SC is low in this cohort of primary refractory/relapsed patients (40%), and only 14% of pts who received SC2 after pSC responded. Although some have prolonged PFS following SC2 and ASCT, additional strategies should be investigated in these patients. No significant financial relationships to disclose.
THU0002 Pathological Findings Using High END Ultrasonography in Primary SjÖGren's Syndrome
Authors: B. Hofauer, M. Bas, N. Mansour, A. Knopf
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> During the last years there have been numerous reports and discussions concerning the diagnostic value of ultrasonography of salivary glands for assessment of salivary gland involvement in patients suspected with primary Sjögren9s Syndrome (pSS). Modern ultrasound techniques, such as acoustic radiation force impulse (ARFI) imaging, real time tissue elastography (RTTE) and virtual touch tissue imaging (VTTI), could gain in importance lately and became part of the clinical routine in various specialties. <h3>Objectives</h3> Can modern ultrasound techniques provide further information in the assessment of salivary gland involvement in patients suspected with pSS in addition to B-mode ultrasonography (BMUS)? <h3>Methods</h3> The diagnostic value of modern ultrasound techniques was evaluated in 50 patients with pSS, diagnosed according to the AECG criteria. Patients underwent high-resolution ultrasonography (THI, 9-14 MHz) of the parotid and submandibular gland. Results of BMUS, RTTE, VTTI – each graded by using appropriate ultrsonographic scoring systems – and ARFI quantifications were compared to 50 patients with sicca symptoms but not fulfilling the AECG criteria. <h3>Results</h3> In BMUS, 41/50 parotid glands in patients with pSS and 20/50 in the control group had abnormal findings (p&lt;0.001). 42/50 patients with pSS showed abnormal findings in submandibular gland BMUS compared to 31/50 in patients without confirmed pSS (p&lt;0.001). Evaluation of parotid and submandibular RTTE did not show any difference (p=1.0 and p=0.06), nor did the evaluation of parotid and submandibular VTTI (p=0.251 and p=0.835). ARFI imaging of the parotid (mean: 2.99m/s<sup>2</sup>) and submandibular glands (mean: 2.54m/s<sup>2</sup>) showed significant higher values than parotid (mean: 2.16m/s<sup>2</sup>) and submandibular glands (mean: 2.04m/s<sup>2</sup>) in the control group (p&lt;0.001 and p=0,008). <h3>Conclusions</h3> In contrast to B-mode ultrasonography in patients suspected with primary Sjögren9s Syndrome, which is proved to be useful in visualization and subjective assessment of structural glandular alterations, ARFI imaging enables the objective measurement of glandular stiffness and might therefore be considered in the diagnostic algorithm of pSS. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5901
Abstract 2973: Poly(ADP)ribose inhibition forces the repair of topoisomerase I cleavage complexes through homologous recombination and non-homologous end joining
Authors: Yongwei Zhang, Marie Regairaz, Jennifer Seiler, Keli Agama, James Doroshow, Yves Pommier
Journal: Cancer Research (2010)

Abstract Poly(ADP-Ribose) polymerase (PARP) inhibitors represent a promising class of novel anticancer agents. In the present study, we explored the strategy of combining the classical topoisomerase I (Top1) inhibitor camptothecin (CPT) and the novel PARP inhibitor ABT-888 in human cancer cells. ABT-888 potentiated cell killing by CPT. By colony forming assay, the survival ratio of CPT-treated colon cancer HT-29 cells was 52%, while the survival fraction were decreased to 35% when HT-29 cells were co-treated with CPT and ABT-888. By measuring γH2AX, a DNA double-strand break marker, we found that ABT-888 enhanced the γH2AX level induced by CPT. The enhanced γH2AX response in the presence of ABT-888 affected both replication-related γH2AX but also transcription-related γH2AX. In osteosarcoma U2OS cells, ABT-888 also enhanced γH2AX in both EdU (5-ethynyl-2′- deoxyuridine) positive and negative cells. Even in non-replicating human primary lymphocytes, ABT-888 enhanced CPT-induced γH2AX foci (1.3 ± 1.2 vs. 5.1 ± 3.1 γH2AX foci/per cell in the absence and presence of co-treatment with ABT-888, respectively). Proteasome inhibition with MG-132 blocked the γH2AX induction by CPT, and PARP inhibition could not overcome the block, which demonstrates that PARP acts downstream from the proteasome. Neutral Comet assays showed that the enhanced γH2AX response was related to DNA breaks. Alkaline elution assays revealed that ABT-888 increased CPT-induced DNA single-strand breaks (SSBs) but without a corresponding increase in DNA protein crosslinks indicating that ABT-888 was inducing DNA breaks in addition to the Top1-DNA cleavage complexes trapped by CPT. These additional DNA breaks were dependent on XPF/ERCC1 endonuclease. Furthermore, after removing CPT, reversal of γH2AX in the absence or presence of ABT-888 showed the same reversal rate, although there was more γH2AX in the presence of ABT-888, suggesting that PARP inhibition did not affect the repair of double-strand breaks. Moreover, PARP inhibition enhanced DNA-PK and ATM activation with increased formation of Rad51 foci. Therefore, we propose that PARP inhibition forces the cells to activate alternative endonucleolytic and recombination pathways in response to Top1-mediated DNA damage. 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 2973.
PTU-047 Management of Polyp Cancers within the Bowel Cancer Screening Programme could be Improved!: Abstract PTU-047 Table 1
Authors: G Longcroft-Wheaton, P Bhandari
Journal: Gut (2013)

<h3>Introduction</h3> Endoscopic management of early colonic neoplasia or polyp cancer remains unclear. There are no national guidelines or good quality data to guide clinicians with these difficult lesions. The aim of this study is to identify the incidence of early cancer and variation in practise of managing these lesions <h3>Methods</h3> Data was prospectively collected in all patients undergoing screening within the Solent BCSP. The database was interrogated to identify all neoplasia. The endoscopists suspicion of cancer was noted from the reports. MDT outcome was recorded, along with final management of the cancer <h3>Results</h3> In total 3976 patients underwent screening colonoscopy between 2007 –2012. N = 5768 neoplastic polyps found giving a mean polyp detection rate of 1.5/patient. Cancer was found in 235/3976 (6%) patients. Mean age was 67yrs. 142/235 (60%) were male. 145/235 (62%) had advanced cancer, confirmed at surgery. 90/235 (38%) patients had polyp cancer. 83% of them in recto-sigmoid. (1) 13/90 were pedunculated polyps (mean size 23 mm, range 12–35 mm) (2) 77/90 were flat polyp cancers (mean size 24 mm, range 8–80 mm) See table 1 below 13/13 pedunculated polyp cancers were endoscopically resected. In 6/13 cases cancer was suspected prior to resection. Histology was reported accurately on 12/13 (92%) polyp cancers using Haggitt classification. 1/13 required surgery due to invasive features on histology. 30/77 (39%) of flat or sessile polyp cancers were endoscopically resected. Endoscopist suspected cancer in only 13/30 (43%) cases prior to resection. Histology was reported confidently by Kukuchi levels in 19/30 (63%) of lesions. 9/19 required surgery due to invasive features on histology. In 11/30 (37%) cases the histology report was inconclusive due to a poor quality EMR specimen. This led to surgery in all 11 patients but no residual disease or LN involvement was found. <h3>Conclusion</h3> The in-vivo endoscopic diagnosis of cancer prior to resection is suboptimal and can be improved Post EMR histology reporting is inconclusive in a large proportion of flat polyps leading to unnecessary surgery Clinical care could be improved by optimising in-vivo diagnostic skills and resecting large flat lesions in single piece by ESD. <h3>Disclosure of Interest</h3> None Declared
P130 Impact of left ventricular hypertrophy on mortality in COPD
Authors: PM Short, WJ Anderson, DH Elder, AD Struthers, BJ Lipworth
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Left ventricular hypertrophy (LVH) is a significant risk factor of cardiovascular disease and is associated with increased mortality. Previous studies have shown an increased prevalence of LVH in normoxaemic COPD patients. The impact of LVH on mortality in COPD is yet to be established. We evaluated the impact of LVH on mortality in COPD patients by measurement of left ventricular dimensions by echocardiography. <h3>Methods</h3> We performed a retrospective cohort study utilising a NHS database of COPD patients (TARDIS) in Tayside, Scotland between 2001 and 2010 that was linked with NHS Tayside databases regarding echocardiograms, pharmacy prescription and the General Register Office for Scotland death registry. Left ventricular internal diastolic diameter (LVIDd) and left ventricular mass index (LVMI) were measured. Increased LVIDd was defined as &gt; 5.3 cm (female) and &gt; 5.9 cm (male). LVMI was obtained by correcting the left ventricular mass to body surface area. LVH was defined as an LVMI of &gt;95 g/m<sup>2</sup> (female) and &gt; 115 g/m<sup>2</sup> (male). Patients with aortic valve disease were excluded from the analysis. The impact of increased LVIDd and LVMI on mortality were evaluated by Kaplan Meir testing and Cox Regression analyses after inclusion of covariates (age, FEV<sub>1</sub>%, SaO<sub>2</sub>%, history of diabetes and cardiovascular disease, medication (aspirin, ACE-inhibitor, statin, beta blocker). <h3>Results</h3> 617 patients were included for analysis. Mean (SD) age at diagnosis, 70 (9); mean FEV<sub>1</sub>% (SD), 60.6 (19.3); mean resting SaO<sub>2</sub>% (SD), 92.7 (10). Mean follow up 4.5 years. Increased LVIDd was not associated with increased mortality, X<sup>2</sup> = 0.767, p = 0.381. Increased LVMI was associated with a significant increased risk of mortality, X<sup>2</sup> = 5.447, p = 0.02. with an adjusted HR (95%CI) of 1.542 (1.068–2.228), p = 0.021. (see graph below). <h3>Conclusion</h3> The presence of left ventricular hypertrophy, demonstrated by elevated left ventricular mass index is associated with a significantly increased risk of mortality in COPD patients. Therapeutic interventions are required to address this important modifiable risk factor in COPD patients.
Characterization of Dystrophin in Muscle-Biopsy Specimens from Patients with Duchenne's or Becker's Muscular Dystrophy
Authors: Eric P. Hoffman, Kenneth H. Fischbeck, Robert H. Brown, Margaret Johnson, Rosella Medori, John D. Loire, John B. Harris, Robert Waterston, Michael Brooke, Linda Specht, William Kupsky, Jeffrey Chamberlain, C. Thomas Caskey, Frederic Shapiro, Louis M. Kunkel
Journal: New England Journal of Medicine (1988)

A deficiency of the protein dystrophin has recently been shown to be the probable cause of Duchenne's muscular dystrophy. We sought to determine the relation between the clinical phenotype and the status of dystrophin in muscle-biopsy specimens from 103 patients with various neuromuscular disorders. We found very low levels (<3 percent of normal levels) or no dystrophin in the severe Duchenne phenotype (35 of 38 patients), low concentrations of dystrophin in the intermediate (outlier) phenotype (4 of 7), and dystrophin of abnormal molecular weight in the mild Becker phenotype (12 of 18). Normal levels of dystrophin of normal molecular weight were found in nearly all the patients (38 of 40) with 20 other neuromuscular disorders we studied. These data show the clinical consequences of both quantitative alterations (in Duchenne's and intermediate dystrophy) and qualitative alterations (in Becker's dystrophy) in a single protein. The biochemical assay for dystrophin should prove helpful in delineating myopathies that overlap clinically with Duchenne's and Becker's dystrophies, and it shows promise as an accurate diagnostic tool. (N Engl J Med 1988; 318:1363–8.)
New prognostic factors for second-line targeted therapy (TT) in metastatic renal cell carcinoma (mRCC)
Authors: L. Derosa, A. Guida, L. Albiges, C. Massard, Y. Loriot, E. Biasco, A. Farnesi, R. Marconcini, L. Galli, A. Falcone, K. Fizazi, B. Escudier
Journal: Annals of Oncology (2015)
Abstract 5083: Nanoaerosol delivery of beclin1 combined with radiation suppressed tumor growth in the lungs of K-rasLA1 mice
Authors: Ji Young Shin, Myung Haing Cho
Journal: Cancer Research (2011)

Abstract As incidence and mortality due to lung cancer increase, great effort has been put into developing feasible therapeutics in medical field. Radiation, together with surgery and chemotherapy, is the must in treating lung cancer, however, side effects have to be taken into consideration. To minimize the side effect of radiotherapy, repeated exposures (5 times, 24 hours interval) with low dose (2Gy) of radiation to restricted area (thorax, 2cm) were attempted. After sensitizing lungs of K-rasLA1 mice with radiation, beclin1, known to be a tumor suppressor, involved in autophagy, complexed with nano-sized biodegradable poly(ester amine), was prepared and delivered into K-rasLA1 mice via aerosol 3 times for 4 weeks. Seventeen weeks old K-rasLA1 lung cancer model mice (n=20, 5 mice/group) were sacrificed and collected samples were analysed. K-rasLA1 mice treated with beclin1 and radiation showed significant tumor regression with low progression to adenocarcinoma and increment in number of autophagic vacuoles. Precedent event of beclin1-bcl2 dissociation stimulated synergistic anti-tumor effect via inhibition of protein translation and angiogenesis. Taken together, non-invasive treatment, radiation with PEA-beclin1 aerosol delivery, can be a feasible candidate for developing novel therapeutics in lung cancer treatment. This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (MEST) (NRF-2010-0000784). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5083. doi:10.1158/1538-7445.AM2011-5083
Efficacy of platinum-based chemotherapy after cranial irradiation in patients with brain metastasis from non-small cell lung cancer
Authors: D. Y. Kim, K. W. Lee, T. Yun, J. H. Kim, D. W. Kim, S. A. Im, T. Y. Kim, D. S. Heo, Y. J. Bang, N. K. Kim
Journal: Journal of Clinical Oncology (2004)

1575 Background: Although chemotherapy has not yet emerged as a standard therapy for patients with brain metastasis, evidences suggest that chemotherapy may have a role in the treatment of selected patients. Methods: We have evaluated 63 consecutive non-small cell lung cancer (NSCLC) patients with synchronous brain metastasis (BM) who had not been previously treated. After cranial radiation therapy (RT), all patients in ‘the chemotherapy arm’ (CTX) were treated with platinum-based combination chemotherapy, and best supportive care was selected for patients in ‘the no-chemotherapy arm’ (no-CTX). Results: The median age of all patients was 55 years. The performance status of all patients was ECOG grade 1–2. Thirty-one of the 63 patients received systemic chemotherapy. In the CTX arm, a paclitaxel + platinum (cisplatin or carboplatin) chemotherapy was administered in 38.7%, gemcitabine + platinum in 25.8%, and vinorelbine + platinum in 25.8% as the first-line chemotherapy. Seventeen patients were treated with a second-line chemotherapy, and 8 patients of them received paclitaxel + platinum followed by gemcitabine + platinum or vice versa. Extracranial overall responses were 36% in the first-line chemotherapy and 35% in the second-line, and the median response durations were 29.1 weeks and 30.4 weeks, respectively. The pattern of treatment failure revealed that ‘progression of the extracranial lesion’ (58.1%) was occurred more frequently than the ‘aggravation of neurologic status’ (19.4%) in the first-line chemotherapy. The causes of failure were identical in the second-line chemotherapy. The median overall survival of the CTX arm is significantly longer than that of the no-CTX arm (58.1 weeks vs. 19.0 weeks, p<0.001). Toxicity in the CTX arm was tolerable. Conclusions: The systemic chemotherapy was effective in increasing the overall survival of patients with BM from NSCLC, and extracranial progression was the main cause of chemotherapeutic failure. No significant financial relationships to disclose.
Abstract LB-306: Pre-treatment sera from NSCLC patients with different outcomes on EGFR-TKI therapy differentially affects sensitivity of lung cancer cell lines to EGFR-TKIs
Authors: Stephen W. Hunsucker, Julia Grigorieva, Barbara A. Helfrich, Jenna Allen, Paul A. Bunn, Heinrich Roder
Journal: Cancer Research (2011)

Abstract Background: VeriStrat (VS) is a pre-treatment mass spectrometry-based test that correlates with clinical outcome after 2nd line therapy with gefitinib or erlotinib in advanced NSCLC. The blinded validation showed that patients classified as “Good” had significantly better overall survival than those classified as “Poor” (HR = 0.47 P = 0.0094 in one cohort, HR = 0.33 P = 0.0007 in another).(1) Mass spectra from VS Poor patients have relatively high abundance of eight peaks (proteins) and we believe these reflect an elevated host response to the tumor. Based on our clinical data and our understanding of the VeriStrat signature, we hypothesized that serum from VS Poor patients would increase the resistance of tumor cells to gefitinib in vitro. Methods: The gefitinib sensitive line HCC4006 has an EGFR exon 19 deletion and the resistant line A549 is EGFR wild type. Human sera were from stage IIIB/IV NSCLC patients and characterized as VS Good or Poor. Pools were created by combining sera within each classification and used in growth inhibition assays. Cells were plated (10 replicates/drug concentration; 2,000 cells/well) using two media compositions; RPMI with 10% Good serum or RPMI with 10% Poor serum. After 24 hours, gefitinib was added and the plates were incubated for 6 days. The MTT assay was used to measure growth inhibition. Conclusion: There was a relative decrease in inhibition of sensitive cells when grown in VS Poor serum, but no significant change in resistant tumor cells. We demonstrate that VS Poor serum has a different biological effect on tumor cells than VS Good serum. These results shed light on the nature of the host-tumor interaction and the relative efficacy of targeted therapies in patient populations. We will have similar data from 6–8 additional cell lines with and without EGFR mutations. (1) Taguchi et al. J Natl Cancer Inst. 2007 99(11):838–46. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-306. doi:10.1158/1538-7445.AM2011-LB-306
Abstract 5155: BMP-2 inhibits the tumorigenicity of human osteosarcoma tumor-initiating cells
Authors: Lin Wang, Paul Park, Huina Zhang, Frank La Marca, Chia-Ying Lin
Journal: Cancer Research (2010)

Abstract Bone morphogenetic proteins (BMPs), members of the transforming growth factor (TGF)-β superfamily, were originally identified as molecules that induce bone and cartilage formation and are now considered as multifunctional cytokines. More recently, there have been a number of studies showing the inhibitory effects of BMP-2 on tumorigenesis in many cancers. However, very little has been investigated to date about the role of BMP-2 in human osteosarcoma. In the present study we show that BMP-2 inhibits the tumorigenicity of an aggressive human osteosarcoma cell line, OS99-1. Based on the stem cell theory of cancer, a subpopulation of cells showing characteristics of stem cells was identified using high aldehyde dehydrogenase (ALDH) activity (ALDHbr cells) from xenografts. These stem-like cells were found to be highly tumorigenic and were classified as tumor initiating cells. In vitro, the growth of the sorted tumorigenic ALDHbr cells was significantly inhibited by the addition of 300 ng/ml of BMP-2 in the presence of 0.5% fetal bovine serum (FBS) for 48h, as evaluated by cell proliferation assay. In addition, using RT-PCR analysis, we found BMP-2 down-regulated the expressions of embryonic stem cell markers Oct3/4, Nanog, and Sox-2. Conversely there was an increase in the transcription of osteogenic markers Runx-2 and Collagen Type I in the sorted tumorigenic ALDHbr cells treated with the same BMP-2 solution for 48h compared with the same volume of vehicle. In vivo, tumor formation in animals was compared to a control receiving ALDHbr cells maintained under identical conditions without BMP-2. All animals receiving untreated ALDHbr cells developed large tumor masses that showed characteristic osteosarcoma features, including nuclear atypia, extensive neovascularization, and high mitotic activity. Conversely, ALDHbr cells treated with 30μg/animal of BMP-2 did not form significant tumors. Further immunostaining confirmed most Ki-67 positive cells were shown in the tumor sections from mice injected with ALDHbr cells without BMP-2, whereas few Ki-67 positive cells were present in the sections of tumor from ALDHbr cells treated with BMP-2. Based on these results, it appears that BMP-2 may suppress tumor growth by inducing the differentiation of tumor -initiating cells. BMP-2 or BMP-2-mimetic drugs, if properly delivered to tumor and combined with traditional therapies, may therefore provide a new therapeutic option. 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 5155.