tbuckley/cabot-search huggingface dataset:
Serum galactomannan (GM) assay for invasive aspergillosis (IA) in acute leukemia (AL) and hematopoietic stem cell transplantation (HSCT).
Authors: I. Ghosh, V. Raina, L. Kumar, A. Sharma, S. Bakhshi, S. Iqbal
Journal: Journal of Clinical Oncology (2011)

6538 Background: IA is a major cause of mortality in AL and HSCT. The objectives of this study were to determine the yield of GM assay for the diagnosis of probable IA, its temporal relationship with high-resolution computed tomographic scan (HRCT) scans and correlation with mortality in patients of AL and recipients of HSCT. Methods: Consecutive neutropenic episodes among inpatients aged ≥ 15 years with a diagnosis of AL and recipients of HSCT were prospectively evaluated over 1½ years. All patients received oral itraconazole or thrice weekly IV amphotericin B (AmB) as prophylaxis. Weekly serum GM assay was performed for all subjects. Optical density index (ODI) > 0.5 for two or more samples was defined as positive. Patients with persistent fever for ≥ 96 hours on intravenous antibiotics were evaluated with HRCT chest and received empiric AmB. IA was diagnosed according to EORTC 2008 guidelines and treated with therapeutic doses of voriconazole or AmB. Results: Of the 150 episodes enrolled, AL induction constituted 51.3% (AML 35.3%, ALL 16%), high-dose cytarabine 20%, autologous HSCT 24.7%, allogeneic HSCT 2.7% and cladribine for hairy cell leukemia 1.3% episodes. Forty-three episodes (28.7%) were diagnosed with IA: possible 25 (16.7%), probable 17 (11.3%) and proven 1 (0.7%). The yield of GM assay in diagnosing probable IA was 17/42 (39.5%). False-positivity of a single test was 54.2% but decreased to 11.2% with two results. Assessment of sensitivity was impaired due to the lack of proven cases. The lone proven case had 1/1 sample positive (ODI 2.17). In 88.2% of probable IA episodes GM was positive before HRCT at a median of 10 days (range, 1-16) earlier, while HRCT was positive before GM in the remaining 11.8% episodes at median of 3.5 days (range, 1-7) earlier. Of the 23 fatal episodes (15.3%), 17 had a diagnosis of IA. Considering only those episodes with ≥2 samples tested, fatality was 31.0% in those with at least 2 values positive for GM, compared to 13.2% in the episodes with < 2 GM samples positive (OR 2.96, 95% CI 1.09 – 8.00; p=0.04). Conclusions: In a population of high-risk patients, GM assay could identify patients with probable IA earlier than HRCT chest and also predicted a higher risk of death.
miRNAs in ancient tissue specimens of the Tyrolean Iceman
Authors: Andreas Keller, Stephanie Kreis, Petra Leidinger, Frank Maixner, Nicole Ludwig, Christina Backes, Valentina Galata, Gea Guerriero, Tobias Fehlmann, Andre Franke, Benjamin Meder, Albert Zink, Eckart Meese
Journal: Molecular Biology and Evolution (2016)

The analysis of nucleic acids in ancient samples is largely limited to DNA. Small noncoding RNAs (microRNAs) are known to be evolutionary conserved and stable. To gain knowledge on miRNAs measured from ancient samples, we profiled microRNAs in cryoconserved mummies. First, we established the approach on a World War One warrior, the "Kaiserjäger", which has been preserved for almost one century. Then, we profiled seven ancient tissue specimens including skeletal muscle, stomach mucosa, stomach content and two corpus organ tissues of the 5,300-year-old copper age mummy Iceman and compared these profiles to the presence of organ-specific miRNAs in modern tissues. Our analyses suggest the presence of specific miRNAs in the different Iceman's tissues. Of 1,066 analyzed human miRNAs, 31 were discovered across all biopsies and 87 miRNAs were detected only in a single sample. To check for potential microbiological contaminations, all miRNAs detected in Iceman samples and not present in ancient samples were mapped to 14,582 bacterial and viral genomes. We detected few hits (3.9% of miRNAs compared with 3.6% of miRNAs). Interestingly, the miRNAs with higher abundance across all ancient tissues were significantly enriched for Guanine (P value of 10-13) and Cytosine (P value of 10-7). The same pattern was observed for modern tissues. Comparing miRNAs measured from ancient organs to modern tissue patterns highlighted significant similarities, e.g., for miRNAs present in the muscle. Our first comprehensive analysis of microRNAs in ancient human tissues indicates that these stable molecules can be detected in tissue specimens after 5,300 years.
Abstract 2094: GSK-3 is a novel target of CREB and GSK-3-CREB signaling participates in cell survival in lung cancer
Authors: Sin-Aye Park, Jong Woo Lee, Roy S. Herbst, Jaseok Peter Koo
Journal: Cancer Research (2015)

Abstract The transcription factor cyclic AMP-response element-binding protein (CREB) regulates diverse cellular processes, including cell differentiation, proliferation, survival, glucose metabolism, immune regulation, and synaptic plasticity associated with memory. Previously, we showed that CREB is critical on the regulation of mucous differentiation of normal human tracheobronchial epithelial (NHTBE) cells. In addition, the overexpression of CREB is associated with negative prognosis of patients with non-small cell lung cancer (NSCLC). Further studies showed that the knockdown of CREB suppresses the growth of lung cancer cells. It has been demonstrated that genes regulated by CREB have been reported to be involved in the suppression of apoptosis, induce cell proliferation, inflammation and tumor metastasis. However, the critical target genes of CREB in lung cancer have not been well understood. In this study, we identified GSK-3 as one of the CREB target genes critical for the growth and survival of lung cancer cells. The CREB knockdown significantly reduced the expression of GSK-3 and the direct binding of CREB on the promoter of GSK-3 was identified. Kaplan-Meier analysis with a public database showed a prognostic significance of aberrant GSK-3 expression in lung cancer. Inhibition of GSK-3 suppressed cell proliferation, colony formation and tumor growth. Although GSK-3 has been studied as a tumor suppressor in certain types of cancer, there is increasing evidence that GSK-3 plays an oncogenic role in various human cancers. Here, for the first time, we demonstrated that GSK-3 is regulated by CREB in lung cancer and is required for the survival of lung cancer cells. These findings implicate CREB-GSK-3 axis as a novel therapeutic target for lung cancer treatment. Citation Format: Sin-Aye Park, Jong Woo Lee, Roy S. Herbst, Jaseok Peter Koo. GSK-3 is a novel target of CREB and GSK-3-CREB signaling participates in cell survival 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 2094. doi:10.1158/1538-7445.AM2015-2094
PO66THE DAILY NEURO-ONCOLOGY CNS WARD ROUND IMPROVES COMMUNICATION ACROSS THE MDT, REDUCES THE LENGTH OF STAY AND INCREASES THE OVERALL PATIENT EXPERIENCE AND QUALITY OF CARE
Authors: V. Hurwitz, L. Ford, L. Mullens, J. Maccoll, K. Ashkan, R. Bhangoo, R. Gullan, J. Day, H. Wren, S. Jones
Journal: Neuro-Oncology (2015)

INTRODUCTION: The Neuro-oncology Clinical Nurse Specialist team lead a daily ward round including all Neuro-oncology patients within the Trust. METHOD: The CNS team attend and lead the daily ward round of all Neuro-oncology inpatients. Twice weekly this is done in conjunction with the lead neurosciences pharmacist. This aids discharge planning leading to expedient discharge of patients. The pharmacist completes the drug list for the take home medications and the CNS completes the medical information and instructions to the GP. Once a week the CNS's lead the round with the Lead neuro-oncology therapists. This is day one post-operatively for most patients. RESULTS: Delays in getting Take home prescriptions completed are dramatically reduced. Patient satisfaction has increased by 75% with this element of their care. This can be directly related to the collaboration between CNS and pharmacist. The accuracy of information has also improved increasing GP's satisfaction. Collaborating with the Therapists has eliminated previous problems of blocked discharges due to unawareness of the patient's baseline function and prognosis. It has also led to greater access to rehab for high grade tumour patients. CONCLUSION: A daily ward round led by the Neuro-oncology patient's key worker has a direct positive impact on patient experience, a financial saving thus quantatively demonstrating to the Trust their investment in the CNS and improved communication across the MDT, a key aspect of the National cancer survey outcome.
Abstract 4942: Activation of Phosphatase toward the Retinoblastoma protein in breast and colorectal cancer cell spheroids
Authors: Jacklynn Egger, Lisa Antonucci, Maria Lane, Nancy A. Krucher
Journal: Cancer Research (2015)

Abstract Excessive phosphorylation of the Retinoblastoma protein is found in most cancer tumor types. Several cyclin dependent kinase (cdk) inhibitors are in development or in clinical trials at the present time. Our previous studies have focused on the regulation of Rb phosphorylation by the phosphatase, PP1. Specificity toward substrates is imparted onto PP1 by many different interacting proteins. In proliferating cells, PP1 is associated with a regulatory protein called PNUTS (Phosphatase Nuclear Targeting Subunit). Our previous experiments have shown that PNUTS inhibits PP1 activity toward specific Rb phosphorylation sites. Further we have demonstrated that siRNA mediated knockdown of PNUTS in several cancer cell types (colon, breast, ovarian) leads to an increase in Rb specific PP1 activity, Rb dephosphorylation on several sites, and a dramatic induction of apoptosis. Furthermore, the ability of PNUTS siRNA to induce apoptosis was shown to be dependent on Rb expression. Interestingly, further studies showed that PNUTS knockdown had no effect on non-transformed breast and colorectal cells, in which Rb is not hyperphosphorylated. Thus we have developed a method to activate the Rb phosphatase in cells by knockdown of the PP1 binding protein, PNUTS. The current study was undertaken to analyze the effect of PNUTS knockdown in cancer cells grown in three-dimensional spheroids grown by incubation of cells in hanging drop plates. The effect of PNUTS knockdown on Rb phosphorylation, cell proliferation and cell viability using this model system will be presented. Citation Format: Jacklynn Egger, Lisa Antonucci, Maria Lane, Nancy A. Krucher. Activation of Phosphatase toward the Retinoblastoma protein in breast and colorectal cancer cell spheroids. [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 4942. doi:10.1158/1538-7445.AM2015-4942
An Ongoing Phase 1 Study of ABT-263; Pharmacokinetics, Safety and Anti-Tumor Activity in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
Authors: Andrew W. Roberts, Jennifer Brown, John F. Seymour, William G. Wierda, Thomas J. Kipps, Hao Xiong, Yi-Lin Chiu, Todd Busman, Raymond A. Knight, Sari Enschede, Andrew Krivoshik, Rod Humerickhouse
Journal: Blood (2008)
Comparison of Gene Expression by Normal and Leukemic Progenitor Cells in Childhood B Cell Precursor ALL - Are There ALL Stem Cells? .
Authors: J. Anthony, A. George, S. Senadheera, L. Barsky, C. McCarthy, B. Schaub, T. Triche, D. Schofield, J. Franklin, R. Parkman, G. Crooks, P. Marjoram, K. Weinberg
Journal: Blood (2004)
403. Engineering Micro-Dystrophin AAV Vector for Clinical Translation
Authors: Chady H. Hakim, Yongping Yue, Yi Lai, Dongsheng Duan
Journal: Molecular Therapy (2015)

Duchenne muscular dystrophy (DMD) is the most severe muscular dystrophy affecting boys. It is caused by the loss of a cellular structural protein called dystrophin. Dystrophin preserves the integrity of the muscle cell membrane by providing a molecular link between the cytoskeleton and the extracellular matrix. The absence of dystrophin destabilizes the muscle membrane and promotes muscle death. AAV micro-dystrophin gene therapy has transformative potentials to significantly ameliorate DMD. Unfortunately, AAV therapy is challenged by destructive cellular immunity to newly expressed dystrophin. To overcome this obstacle, we engineered a double restrictive AAV microgene vector. Specifically, we limited off-target expression in non-muscle tissue with a muscle specific promoter and removed untoward expression in antigen-presenting cells using miR142-3p, a hematopoietic specific microRNA target sequence. Compared with the original AAV microgene vector, the newly engineered vector significantly reduced infiltration of CD4+ and CD8+ T cells in the canine DMD model. Our results suggest that the dual restriction strategy may greatly enhance clinical translation of AAV micro-dystrophin gene therapy.
Adjuvant analgesic therapy for cancer-related pain: Does the evidence support the practice?
Authors: C. R. Lewis
Journal: Journal of Clinical Oncology (2004)

8032 Background: Adjuvant analgesic treatments have primary indications for uses other than the treatment of pain but demonstrate analgesic activity in some conditions. Although there is high level evidence to support the use of adjuvant analgesics in the chronic pain setting (eg antidepressants and anticonvulsants for benign neuropathic pain) the evidence relevant to the cancer pain setting has never been reviewed. Methods: This study examined the literature assessing adjuvant analgesic treatments specifically for publications restricted to patients with cancer pain, where pain relief was the primary outcome. Relevant studies were identified following searches of MEDLINE, EMBASE and the Cochrane Library (including up to December 2003). An appropriate level of evidence (NHMRC Australia designation) was applied for each treatment. Results: Significant variation in the extent and quality of research was noted across treatments. Level I or II evidence existed to support analgesic efficacy for NSAIDs, intravenous bisphosphonates and radiation treatment for painful bone metastases. Treatments employed for relief of cancer-related neuropathic pain were associated with a low evidence for analgesic efficacy, including anticonvulsants (Level III), systemic local anaesthetics (Level III), ketamine (Level II) and antidepressants (no evidence). Conclusions: Recruitment of patients with cancer-related pain to studies assessing adjuvant analgesic treatments is difficult, but clearly there is an important need for further clinical trials in this area. No significant financial relationships to disclose.
Abstract 1623: Targeted therapy of Ewing's Sarcoma and childhood leukemia (ALL) by hybrid polymerized liposomal nanoparticles (HPLN)
Authors: Hyunggyoo Kang, Violette Shahbazian, Ryan Holly, Jon Nagy, Timothy Triche
Journal: Cancer Research (2015)

Abstract Poor selectivity of the current cancer therapies causes a variety of side effects such as secondary cancers, heart or lung damage, infertility or chronic hepatitis. Therefore a reliable tumor specific therapy is urgently needed to treat cancer patients. It has been widely recognized that the recent chemotherapy could be far more effective if higher doses could be specifically delivered to the tumor and not to normal tissues. Targeted nanoparticles have shown the potential to deliver anticancer drugs to cancer cells selectively and thus to overcome unexpected cytotoxicity and limited efficacy of the chemotherapy caused by the unselective delivery to normal cells. However in addition to the selectivity the efficacy of the targeted nanoparticles depends upon two more requirements: immune evasion and timely release of contents in target cells. In spite of a lot of effort still the optimal formulation of nanoparticle for the actual translational applications was not established yet. PLN (Polymerized Liposomal Nanoparticles) can be synthesized to a variety of physiochemical properties including a broad range of composition and size. By refining the early formulations and after extensive testing, recently we could invent HPLN (Hybrid Polymerized Liposomal Nanoparticles) and demonstrate that this new type of polymeric nanoparticle overcomes many, if not most, of the deficiencies noted and has tremendous potential as an effective delivery vehicle for treating many types of cancer. In our study it was shown that the targeted HPLN with antibodies (antiCD99 or antiCD19) can inhibit the growth of Ewing's sarcoma and childhood leukemia (ALL) in a murine model. The antitumor effects were diminished pretty much by the removal of antibody or drug (Doxorubicin), which proves efficacy of the targeted HPLNs is specifically dependent upon the targeting antibody and drug. In addition, no abnormalities in liver and kidney function tests, complete blood counts or pathology of major organs are observed from tail-vein administrations. These data provide strong evidence for the safety and efficacy of this targeted HPLN delivery system of anticancer drugs to Ewing's sarcoma and childhood leukemia (ALL). In conclusion, our result showed a potential of targeted HPLN as a selective delivery vehicle of cytotoxic drugs to cancers. Hopefully this technology will be applied to treat many other different types of tumor cells in the future. Citation Format: Hyunggyoo Kang, Violette Shahbazian, Ryan Holly, Jon Nagy, Timothy Triche. Targeted therapy of Ewing's Sarcoma and childhood leukemia (ALL) by hybrid polymerized liposomal nanoparticles (HPLN). [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 1623. doi:10.1158/1538-7445.AM2015-1623
Abstract 2116: HDAC9 and 11 contribute to UV resistance in melanoma cells
Authors: Elizabeth T. Chang, Palak R. Parekh, Qingyuan Yang, France Carrier
Journal: Cancer Research (2015)

Abstract We have previously shown that the Histone Deacetylase Inhibitor (HDACi) trichostatin A (TSA) can sensitize cancer cells to UV radiation by facilitating the formation of Cyclobutane pyrimidine dimers (CPD) without increasing the levels of HDAC1. Here we show that HDAC9 and HDAC11 are upregulated in response to UV radiation in a number of human melanoma cell lines. Both HDAC9 and HDAC11 have an hnRNP A18 signature motif in their 3′UTR. hnRNP A18 is a new regulator of protein translation that can confer growth advantages to tumor cells by specifically increasing the stability and translation of mRNA transcripts harboring its signature motif. Our data indicate that HDAC9 and 11 levels correspond to hnRNP A18 level in response to UV radiation in several melanoma cell lines while hnRNP A18 and HDAC 9 and 11 are not upregulated in response to UV radiation in the normal human fibroblasts Malme cells or the normal melanocytes HEMa-LP. Moreover, clonogenic colony survival assays indicate that melanoma cells expressing higher hnRNP A18 endogenous levels are more resistant to UV radiation than cells expressing lower hnRNP A18 levels. In addition, down regulation of hnRNP A18 prevents HDAC 9 and 11 upregulation in response to UV radiation. Furthermore, overexpression of hnRNP A18 increases further the levels of HDAC 9 and 11 in response to UV radiation. These data suggest that upregulation of HDAC9 and 11 in response to hnRNP A18 activation contribute to UV resistance and may increase sensitization to UV-induced cell killing by HDACi. Citation Format: Elizabeth T. Chang, Palak R. Parekh, Qingyuan Yang, France Carrier. HDAC9 and 11 contribute to UV resistance in melanoma cells. [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 2116. doi:10.1158/1538-7445.AM2015-2116
CrkL Mediates SDF-1-Induced Chemotaxis through Ras, Rac, and Erk Activation in Hematopoietic Cells.
Authors: Ayako Arai, Weihua Yan, Mae Aoki, Daisuke Mizuchi, Tetsuya Kurosu, Tohru Miki, Osamu Miura
Journal: Blood (2005)
Abstract LB-233: Blockade of TGF-beta1 and 2 without TGF-beta3 blockade is sufficient to facilitate tumor vaccine efficacy
Authors: Masaki Terabe, Faith Robertson, Shingo Kato, Emma De Ravin, Katharine Clark, Amer M. Mizra, Jay A. Berzofsky
Journal: Cancer Research (2015)

Abstract TGF-beta is one of the most potent immunosuppressive cytokines involved in the regulation of tumor immunity. TGF-beta has three isoforms, TGF-beta1, 2 and 3. It has been demonstrated in multiple mouse tumor models that blockade of all three isoforms of TGF-beta facilitates natural tumor immunosurveillance as well as tumor vaccine efficacy. Most studies on the roles of TGF-beta in immunology are on TGF-beta1, which has been demonstrated to induce Treg cells, IL-17-producing T cells and MDSCs. Although some studies reported immunosuppressive activities of TGF-beta2, the role of TGF-beta3 in immune regulation is not well understood. In this study we asked whether it is necessary to inhibit TGF-beta3 to enhance tumor immunity induced by a tumor vaccine in a syngeneic TC1 tumor model. When the tumor reached at least 5 mm in diameter, the mice were given a peptide-based vaccine targeting HPV16 E7, which is an oncogene expressed in TC1 cells. Although the vaccine alone had minimal effects on tumor growth, combination with an anti-TGF-beta antibody that neutralizes all three isoforms significantly delayed tumor growth. A similar effect was obtained with an antibody that neutralizes only TGF-beta1 and 2 but not TGF-beta3. Thus, it is not necessary to block TGF-beta3 to overcome immune suppression. Flow cytometric analysis of immune cells in tumor draining lymph nodes and tumors showed that there was no difference in the number of Treg and MDSCs between mice with/without treatment. The vaccine significantly increased the number of tumor antigen-specific CD8+ T cells and IFN-gamma producing T cells in both lymph nodes and tumors, but there was no further increase in combination with anti-TGF-beta. The vaccine also induced a significant number of T-bet-expressing T cells (both CD4 and CD8) in both tumor draining lymph nodes and tumors, and anti-TGF-beta, regardless of TGF-beta3 blockade, further increased the number of these cells. Together the results suggested that blockade of TGF-beta1 and 2 alone is sufficient to enhance therapeutic tumor vaccine efficacy by facilitating the induction of Th1 type T cells. With the notion that TGF-beta3 might be beneficial for patients in some cancers, developing TGF-beta antagonists that do not inhibit TGF-beta3 may be lead to better outcomes. Citation Format: Masaki Terabe, Faith Robertson, Shingo Kato, Emma De Ravin, Katharine Clark, Amer M. Mizra, Jay A. Berzofsky. Blockade of TGF-beta1 and 2 without TGF-beta3 blockade is sufficient to facilitate tumor vaccine efficacy. [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 LB-233. doi:10.1158/1538-7445.AM2015-LB-233
The DNA Methyltransferase Inhibitor Decitabine Induces DNA Damage, Cell Cycle Arrest and Apoptosis in Multiple Myeloma
Authors: Ken Maes, Miguel Lemaire, Jordan Gauthier, Hendrik De Raeve, Eline Menu, Els Van Valckenborgh, Helena Jernberg Wiklund, Karin Vanderkerken, Elke De Bruyne
Journal: Blood (2012)