tbuckley/cabot-search huggingface dataset:
Abstract 2146: RASSF1C modulation of Piwi-interacting RNAs (piRNAs) in lung cancer
Authors: Yousef G. Amaar, Matthew Firek, Mark E. Reeves, Mark E. Reeves
Journal: Cancer Research (2015)

Abstract Introduction: RASSF1C is emerging as an important oncoprotein in lung cancer cell growth. We have shown that RASSF1C promotes lung cancer cell proliferation and migration; and RASSF1C up-regulates important genes in lung cancer cell growth that include a stem cell self-renewal gene, piwi1 (hiwi). PIWI-like proteins are a subfamily of Argonaute proteins that interact with small PIWI-interacting RNA molecules (known as piRNAs that are 24-32 nucleotides long) to form complexes that regulate transcriptional and translational repression. This leads to inhibition of apoptosis, stimulation of cell division and proliferation, and down-regulation of cyclin inhibitors and tumor suppressors. Therefore, modulation of Piwil1-piRNA gene expression by RASSF1C suggests a potential role for RASSF1C in lung cancer stem cell development and progression. To further investigate our hypothesis, we carried out a global piRNA microarray screen to identify piRNAs that are modulated by RASSF1C in lung cancer cells. Method: A piRNA microarray screen was performed using the lung cancer cell line H1299 stably over-expressing RASSF1C (and controls). Total RNA was extracted from experimental and control cells and was submitted to Arraystar (Rockville, MD) for the piRNA microarray screen and data analysis. Results: The piRNA microarray screen identified several piRNAs that are regulated by RASSF1C and we have confirmed the expression of some of them in cell lines. The function of the piRNAs identified is yet to be determined. We have initiated studies to determine the function of some of the most up-regulated and down-regulated piRNA genes in lung cancer cells. We are also profiling the expression of these piRNAs in normal and lung tumor tissues. Conclusion: Several piRNAs are target genes of RASSF1C. Characterization of the function of these piRNAs may enhance our understanding of the role of RASSF1C in promoting lung cancer stem cell growth and progression. Linking a Rassf1c-Piwil1/piRNAs axis to lung cancer stem cell development and progression could possibly lead to discovery of new diagnostic and therapeutic targets for lung cancer. Citation Format: Yousef G. Amaar, Matthew Firek, Mark E. Reeves, Mark E. Reeves. RASSF1C modulation of Piwi-interacting RNAs (piRNAs) in lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2146. doi:10.1158/1538-7445.AM2015-2146
Methotrexate and/or Rituximab in a New Nude Rat Central Nervous System Lymphoma Model: Efficacy, Toxicity and Magnetic Resonance Imaging.
Authors: Kristoph Jahnke, Leslie L. Muldoon, Csanad G. Varallyay, Seth J. Lewin, Robert D. Brown, Dale F. Kraemer, Carole Soussain, Edward A. Neuwelt
Journal: Blood (2007)
Effect of GTx-024, a selective androgen receptor modulator (SARM), on physical function in patients with non-small cell lung cancer (NSCLC) with cancer cachexia.
Authors: M. S. Steiner, A. Dobs, M. L. Hancock, M. A. Johnston, G. Barnette, S. Dodson
Journal: Journal of Clinical Oncology (2011)

9022 Background: Cancer cachexia causes muscle wasting and leads to decline in physical function. NSCLC patients with weight loss at diagnosis are less able to tolerate chemotherapy, have worse outcomes and shorter survival. This wasting and decline in function may have detrimental consequences early in the course of a patient’s malignancy, underscoring the importance of diagnosing and treating this condition at an early stage. Published data has shown that a 10% improvement in physical function is a substantial clinically meaningful benefit. We conducted a randomized, double-blind, placebo-controlled multi center study to evaluate the effect of GTx-024 on muscle wasting and physical function in patients with cancer cachexia. Methods: Subjects (n=159) were randomized to oral GTx-024 (1 or 3 mg) or placebo (pbo) daily for 16 weeks. Subjects were males >45 y and postmenopausal females, with ≥2% weight loss in the 6 months prior to randomization and diagnosed with either NSCLC, colorectal cancer, non-Hodgkin lymphoma, chronic lymphocytic leukemia or breast cancer. The primary endpoint was change in lean body mass. Secondary endpoints included QOL and physical function with clinical benefit defined as 10% improvement in physical function assessed by stair climb power (responder analysis). Results: 103 subjects in the MITT population had stair climb power assessed at baseline and week 16. GTx-024 treated subjects demonstrated clinical benefit compared to pbo (P=0.03). Among NSCLC subjects, 28 were included in the physical function analysis. Seventy-eight percent treated with GTx-024 responded compared to 30% treated with pbo (P=0.02). Physical function was positively correlated with QOL as assessed by the FAACT questionnaire further substantiating clinical benefit (Spearman correlation coefficient = 0.60, P=0.001). Conclusions: GTx-024 was well tolerated and showed a statistically significant and clinically relevant improvement in physical function in NSCLC subjects. These data provide evidence that GTx-024 may play an important role in the management of patients with NSCLC. Further research is needed to assess the effect of GTx-024 on overall survival.
Abstract 2124: Analysis of the functional relevance of novel alternative splicing events in non-small cell lung cancer
Authors: Fernando J. de Miguel, Ravi D. Sharma, Pablo Reclusa, María J. Pajares, Angel Rubio, Ruben Pio, Luis M. Montuenga
Journal: Cancer Research (2015)

Abstract Lung cancer is the most common cause of death by cancer worldwide. Deregulation of alternative splicing (AS) is becoming increasingly relevant for the understanding of the molecular mechanisms of lung tumor progression. Genome-wide microarrays containing probes in exons and junctions can be used to identify differential AS events. We developed an algorithm, called ExonPointer, which was optimized to detect AS events using this kind of platforms. Using this technique, we successfully detected splicing events regulated by the oncogene serine/arginine-rich splicing factor 1 (SRSF1) in lung cancer cell lines. Moreover, four of these genes, ATP11C, IQCB1, TUBD1 and PRRC2C, showed a significantly different pattern of AS in primary non-small cell lung cancer (NSCLC) compared with normal lung tissue. In the case of PRRC2C, we also demonstrated that the deregulation of the splicing event was important for tumor progression. We next applied the same technique to target differential AS events in NSCLC primary tissues (13 lung squamous cell carcinomas and 9 lung adenocarcinomas). Their paired normal lung tissues were used as reference. The validation rate for the top 20 events identified by ExonPointer was 70%. Gene cluster analyses showed an enrichment of clusters implicated in cancer development such as Cellular Growth and Proliferation, or Cell Death and Survival. Among others, we observed accumulation of a tumor-specific splice variant in Mitogen-Activated Protein Kinase 9 (MAPK9 or JNK2). The tumor-specific variant for this gene contains an alternative exon 2 which causes a frame shift introducing a premature stop codon. Functional analyses using isoform-specific siRNAs showed that this variant did not affect tumor growth or progression. However, its expression significantly correlated with the expression of Regulator of Nonsense Transcripts 3A and B (UPF3A and UPF3B) in 42 lung cancer cell lines. These proteins belong to the Nonsense Mediated Decay (NMD) pathway, which eliminates aberrant mRNA transcripts, suggesting that the presence of some aberrant AS variants in lung cancer are caused by a malfunction of NMD. In conclusion, we have developed a reliable tool for the high throughput analysis of AS, and have identified new splicing events in lung cancer that can be studied as potential diagnostic markers and therapeutic targets. Citation Format: Fernando J. de Miguel, Ravi D. Sharma, Pablo Reclusa, María J. Pajares, Angel Rubio, Ruben Pio, Luis M. Montuenga. Analysis of the functional relevance of novel alternative splicing events in non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2124. doi:10.1158/1538-7445.AM2015-2124
Pre-Transplant Comorbidity as An Outcome Predictor in Hematopoietic Cell Transplantation for Severe Aplastic Anemia
Authors: Sung-Nam Lim, Je-Hwan Lee, Jung-Hee Lee, Dae-Young Kim, Se-Hyung Kim, Young-Shin Lee, Young-A Kang, Miee Seol, Sol-Ip Kang, Seong-Gil Ryu, Kyoo-Hyung Lee
Journal: Blood (2008)
Breast cancer in patients with HIV: A single-institution experience with a non-AIDS defining cancer.
Authors: S. N. Singh, M. R. Baer, K. H. Tkaczuk, S. Chumsri, T. Bao, D. Riedel
Journal: Journal of Clinical Oncology (2011)

e11108 Background:In the era of highly active antiretroviral therapy (HAART), HIV-infected individuals are at increased risk of developing malignancies, including non-AIDS-defining cancers. We sought to characterize breast cancer in HIV-infected patients. Methods:Charts of approximately 5000 HIV patients at the University of Maryland were reviewed to identify those diagnosed with breast cancer between 2000 and 2010. Data collected included gender, race, age at cancer diagnosis, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER-2) receptor status, histology, stage, CD4 count, use of HAART, family history, and presence of other malignancy. Results: Twenty cases were identified. Nineteen patients were female and one male; all were African-American. Median age at breast cancer diagnosis was 48.5 (range, 37-74) years; median age at diagnosis for all breast cancer cases at our institution was 54 (range, 23-93) years. 13 cases were ER-positive, 11 PR-positive, 8 Her-2-positive, and 3 were ER/PR/HER-2 negative. 14 cases were infiltrating ductal, 1 lobular, 1 mucinous, 3 DCIS and 1 LCIS. At diagnosis, 20% were in situ, 30% stage I, 30% stage II and 20% stage III. Median CD4 count at breast cancer diagnosis was 423 cells/mm3 (range, 43-748) and 70% of patients received HAART. One patient also had ovarian cancer; another had cervical and colon cancers and sarcoma. Family history of breast and/or ovarian cancer was documented in 10 patients. 10 patients are alive and progression-free (median follow up of 3.2 years, range 0.5-10 years), 1 died, 1 relapsed and 8 are lost to follow-up. Conclusions: Breast cancer in HIV-infected patients represented 0.7% of all breast cancer diagnoses at University of Maryland from 2000-2010. HIV-infected breast cancer patients presented with early stage breast cancer, contrary to what might be expected in an immunosuppressed group. They also presented at a young median age and had a high prevalence of family history of breast and/or ovarian cancer, suggesting possible differential penetrance of hereditary predisposition to breast cancer. There were no obvious differences in tolerance of therapy or outcome.
Modification of B-CLL Cells Via Infection with a Replication-Defective MVA Virus Encoding Three Costimulatory Molecules: A Potential Approach to Tumor Cell Immunotherapy of B-CLL.
Authors: Claudia Palena, Loni McIntosh, Jeffrey Schlom, Kenneth Foon, Dennis Panicali, Kwong Y. Tsang
Journal: Blood (2004)
No clinically important benefits of surgery over rehabilitation for lumbar spinal stenosis (PEDro synthesis)
Authors: Gustavo C Machado, Manuela L Ferreira
Journal: British Journal of Sports Medicine (2016)

▸  Zaina F , Tomkins-Lane C, Carragee E, et al . Surgical versus non-surgical treatment for lumbar spinal stenosis. Cochrane Database Syst Rev 2016; (1) :CD010264.

This section features a recent systematic review that is indexed on PEDro, the Physiotherapy Evidence Database (http://www.pedro.org.au). PEDro is a free, web-based database of evidence relevant to physiotherapy.

Lumbar spinal stenosis affects over 200 000 people in the USA and is the most common indication for spine surgery in older adults.1 Nearly 38 000 surgical procedures are performed every year, and decompression is often the surgical procedure of choice.2 Some surgeons, however, decide to perform fusion, though this procedure has been associated with an increased risk of complications and resource use.2 We currently lack placebo-controlled trials of surgery for lumbar spinal stenosis,3 thus the evidence to support surgery for this population comes largely from trials comparing surgery with non-surgical treatments.4

The aim of the review was to investigate the effects of surgery for lumbar spinal stenosis compared with non-surgical treatments. For this PEDro synthesis, we updated the pooled analyses by including data of a …
High-Throughput Genetic Profiling of Acute Myeloid Leukemias: Novel Mutations Detected in Signal Transduction Pathway Genes by a Strategy Utilizing Endonuclease-Based Heteroduplex Scanning and DNA Sequencing.
Authors: Stan L. Lilleberg, Jill Hempel, Jeff Durocher, Damien Foster, Christopher Hartman, Jason Stoddard, Brooke Walters, Michael L. Nickerson, Manika Koul
Journal: Blood (2006)
First Analysis of the Australasian Leukaemia and Lymphoma Group (ALLG) Trial of Thalidomide and Alternate Day Prednisolone Following Autologous Stem Cell Transplantation (ASCT) for Patients with Multiple Myeloma (ALLG MM6).
Authors: Andrew Spencer, Miles Prince, Andrew W. Roberts, Kenneth F. Bradstock, Ian W. Prosser
Journal: Blood (2006)
Phase II Trial of Oblimersen Sodium (G3139), Dexamethasone (Dex) and Thalidomide (Thal) in Relapsed Multiple Myeloma Patients (Pts).
Authors: Ashrof Z. Badros, Olga Goloubeva, Bashi Ratterree, Sabrina Natt, Aaron Rapoport, Javier Bolaños-Meade, Ben Zhang, Jerry Zeldis, Stanley Frankel, Barry Meisenberg, James Zwiebel, J. Flaws, D. Tomic, Robert Fenton
Journal: Blood (2004)
microRNA-221 Enhances MYCN via Targeting Nemo-like Kinase and Functions as an Oncogene Related to Poor Prognosis in Neuroblastoma
Authors: Xiao-yan He, Zheng-lan Tan, Qin Mou, Fang-jie Liu, Shan Liu, Chao-wen Yu, Jin Zhu, Lin-ya Lv, Jun Zhang, Shan Wang, Li-ming Bao, Bin Peng, Hui Zhao, Lin Zou
Journal: Clinical Cancer Research (2016)

Purpose:MYCN is one of the most well-characterized genetic markers of neuroblastoma. However, the mechanisms as to how MYCN mediate neuroblastoma tumorigenesis are not fully clear. Increasing evidence has confirmed that the dysregulation of miRNAs is involved in MYCN-mediated neuroblastoma tumorigenesis, supporting their potential as therapeutic targets for neuroblastoma. Although miR-221 has been reported as one of the upregulated miRNAs, the interplay between miR-221 and MYCN-mediated neuroblastoma progression remains largely elusive.Experimental Design: The expression of miR-221 in the formalin-fixed, paraffin-embedded tissues from 31 confirmed patients with neuroblastoma was detected by locked nucleic acid-in situ hybridization and qRT-PCR. The correlation between miR-221 expression and clinical features in patients with neuroblastoma was assessed. The mechanisms as to how miR-221 regulate MYCN in neuroblastoma were addressed. The effect of miR-221 on cellular proliferation in neuroblastoma was determined both in vitro and in vivoResults: miR-221 was significantly upregulated in neuroblastoma tumor cells and tissues that overexpress MYCN, and high expression of miR-221 was positively associated with poor survival in patients with neuroblastoma. Nemo-like kinase (NLK) as a direct target of miR-221 in neuroblastoma was verified. In addition, overexpression of miR-221 decreased LEF1 phosphorylation but increased the expression of MYCN via targeting of NLK and further regulated cell cycle, particularly in S-phase, promoting the growth of neuroblastoma cells.Conclusions: This study provides a novel insight for miR-221 in the control of neuroblastoma cell proliferation and tumorigenesis, suggesting potentials of miR-221 as a prognosis marker and therapeutic target for patients with MYCN overexpressing neuroblastoma. Clin Cancer Res; 23(11); 2905-18. ©2016 AACR.
A case-control study examining associations of germ-line oxidative DNA repair single-nucleotide polymorphisms (SNPs) with lethal prostate cancer (PCa) risk.
Authors: N. M. Hahn, J. Jung, J. Dantzer, S. Philips, Y. R. Patel, K. A. Carr, Y. Mohammadi, D. Magjuka, C. Camp, M. Bolden, E. F. Dropcho, J. A. Knight, M. L. Moore, A. D. Reed, M. J. Waddell, J. E. Klaunig, L. Li, C. Sweeney, T. C. Skaar
Journal: Journal of Clinical Oncology (2011)

4645 Background: PCa risk is multi-factorial with both genetic and environmental influences. Candidate SNPs identifying risk of lethal PCa have been poorly characterized. This case control study was conducted to identify oxidative DNA repair SNPs significantly associated with lethal PCa risk. Methods: Healthy Caucasian men with no history of malignancy (controls) and Caucasian men with metastatic PCa (cases) were consented through the IUSCC IRB-approved biorepository protocol. Controls were matched to cases according to age, body mass index (BMI), smoking history, alcohol history, family history of PCa, income level, and education level. All subjects provided a peripheral blood sample for SNP analysis. A 576-SNP Illumina Golden Gate custom array was constructed with previously reported PCa candidate risk SNPs (i.e chromosome 8q24 region) and SNPs with biologic roles in oxidative DNA repair, steroid synthesis/metabolism, and toxin elimination. 188 SNPs (with minor allele frequencies > 5%) were selected based on a pilot analysis of 40 cases and 40 controls. Genetic association study using a chi-square test was performed under the assumption of additive, dominant, and recessive models respectively. Results: A total of 100 cases and 191 controls were analyzed. Summary demographics (cases/controls) include median age (yrs) - (67/66), median BMI (kg/m2) - (29.2/28.9), prior smoking history (71%/60%), prior alcohol history (47% /42%), family history of PCa (27%/16%), median annual income > $50k (56%/40%), high school grad or some college (54%/56%). After a series of standard quality control procedures such as Hardy-Wienberg equilibrium test, 163 SNPs remained in the final analysis. 12 SNPs were statistically significant (p<0.01) across the three genetic models; the previously reported 8q24 SNP (rs6983267, p-value=0.004) was confirmed and SNPs with critical roles in oxidative DNA repair were identified: LIG1 (rs13436, p-value=0.0003), MTTR (rs2287780, p-value=0.008), and CYP24A1 (rs2296241, p-value=0.002). Conclusions: Common germ-line SNPs in genes critical to the repair of oxidative DNA damage may contribute to risk of lethal prostate cancer.
Association of Foxp3 expression with prognosis in resected non-small cell lung cancer (NSCLC).
Authors: M. Usó, E. Jantus-Lewintre, S. Gallach, E. Sanmartin, N. Martinez, A. Blasco, R. Guijarro, M. Martorell, R. Sirera, C. Camps
Journal: Journal of Clinical Oncology (2011)

e21114 Background: Regulatory T cells (Tregs) play a critical role in suppressing T-cell-mediated immunity in patients with cancer. A highly specific marker for Tregs is Foxp3, a transcription factor which appears to be a master control gene for their development and function. The aim of this study was to evaluate the role of Foxp3 as a prognostic marker in resectable NSCLC patients. Methods: Foxp3 expression was assessed by RT-PCR in frozen samples (tumor and normal lung) from 150 NSCLC patients. Foxp3 relative expression was normalized by an endogenous gene (GUSB) and compared with clinicopathological variables. Statistical analyses were considered significant at p<0.05. Results: RT-PCR analysis showed that Foxp3 was over-expressed (>2.0X) in 41/150 tumor lung tissues. No significant associations were found between Foxp3 expression and gender, ECOG-PS, stage or histology. Patients with Foxp3 > 1.48X (median value) showed a shorter TTP (median 22.1 vs 66.6 months, p= 0.017) and OS (median 26.8 vs 49.7 months, p= 0.036) than others. Conclusions: Foxp3 is a transcription factor necessary and sufficient for induction of the immunosuppressive functions in Tregs. In concordance, our results indicate that high expression of Foxp3 in tumor samples is a poor prognostic marker for TTP and OS in resectable NSCLC. It could be inferred that overcoming Treg activity, may be beneficial for the treatment of this type of cancer. Supported by grants PS09-01149 and RD06/0020/1024 from ISCIII.
Bone Marrow Cell Trafficking Analyzed by 89Zr-oxine Positron Emission Tomography in a Murine Transplantation Model
Authors: Kingsley O. Asiedu, Sho Koyasu, Lawrence P. Szajek, Peter L. Choyke, Noriko Sato
Journal: Clinical Cancer Research (2016)

Abstract Purpose: The success of hematopoietic stem cell transplantation (HSCT) depends on donor cell homing to the bone marrow. However, there is no reliable method of noninvasively monitoring the kinetics and distribution of transferred cells. Using zirconium-89 (89Zr)-oxine cell labeling combined with PET imaging, we sought to visualize and quantify donor cell homing in a mouse bone marrow transplantation model. Experimental Design: The effect of 89Zr-oxine labeling on bone marrow cell viability and differentiation was evaluated in vitro. 89Zr-labeled bone marrow cells (2 × 107 cells, 16.6 kBq/106 cells) were transferred intravenously, and serial microPET images were obtained (n = 5). The effect of a CXCR4 inhibitor, plerixafor (5 mg/kg) and G-CSF (2.5 μg) on bone marrow homing and mobilization were examined (n = 4). Engraftment of the transferred 89Zr-labeled cells was evaluated (n = 3). Results: 89Zr-oxine–labeled bone marrow cells showed delayed proliferation, but differentiated normally. Transferred bone marrow cells rapidly migrated to the bone marrow, spleen, and liver (n = 5). Approximately 36% of donor cells homed to the bone marrow within 4 hours, irrespective of prior bone marrow ablation. Inhibition of CXCR4 by plerixafor alone or with G-CSF significantly blocked the bone marrow homing (P &amp;lt; 0.0001, vs. nontreated, at 2 hours), confirming a crucial role of the CXCR4–CXCL12 system. Mobilization of approximately 0.64% of pretransplanted bone marrow cells induced a 3.8-fold increase of circulating bone marrow cells. 89Zr-labeled donor cells engrafted as well as nonlabeled cells. Conclusions: 89Zr-oxine PET imaging reveals rapid bone marrow homing of transferred bone marrow cells without impairment of their stem cell functions, and thus, could provide useful information for optimizing HSCT. Clin Cancer Res; 23(11); 2759–68. ©2016 AACR.