tbuckley/cabot-search huggingface dataset:
964. Infectivity Enhanced, hTERT Promoter-Based Conditionally Replicative Adenoviruses Are Useful for the Treatment of Small Cell Lung Cancer
Authors: Koichi Takayama, Junji Uchino, Akiko Harada, Yosuke Kawakami, David T. Curiel, Yoichi Nakanishi
Journal: Molecular Therapy (2004)

Treatment of advanced small cell lung cancer (SCLC) remains one of the major challenges in current medicine because of the high morbidity and mortality of the disease. Advanced stage lung cancer is refractory to conventional therapies and it also has an extremely poor prognosis. As a result, new therapeutic approaches are needed. Telomere maintenance to the regulation of replicative life span strongly implies that alterations in telomere biology play an important role during malignant transformation. Cancers that exhibit high levels of telomerase activity, such as all of the small-cell lung cancers were examined in a previous study. In this study, we turned the expression of hTERT by tumors to a therapeutic advantage using a conditionally replication-competent adenovirus (CRAd) in which the expression of E1 is controlled by the hTERT promoter. This virus achieved good levels of viral replication in SCLC cells and induced a substantial anti-cancer effect in vitro and in vivo. As a further enhancement the cancer cell killing effect was improved with a tropism modification of the virus to express the knob domain of Ad3, and this improved infectivity for cancer cells. Conversely, the hTERT promoter has low activity in normal tissues, and the CRAd caused no damage to normal lung fibroblast cells. Since the telomerase activity is common in many types of cancers, these CRAds may be applicable to a wide range of tumors. We concluded that the use of hTERT promoter-based CRAds may be a potentially effective strategy for cancer treatment.
A phenotypic assay to monitor therapeutic efficacy of signal transduction inhibitors
Authors: G. Huber, T. Roten, V. Brondani, F. Hamy, D. Heim, T. Klimkait, Vincent Vidal
Journal: Clinical Cancer Research (2006)

B69   Introduction: Cancer therapy has witnessed a paradigm shift with the introduction of the first gene-specific, targeted drugs. Major successes have been observed with signal transduction inhibitors (STI) such as Gleevec targeting the oncogenic activities of tyrosine kinases. However, it has also become clear that targeted therapy will have its limitations in the natural variability of the target gene itself. One of the consequences is that such variations can lead to different treatment response among patients. This necessitates sensitive diagnostic tools to identify the appearance of resistant variants and to predict therapy response to STI.Methods: The tyrosine kinase domain from the target gene isolated from clinical specimens is either sequenced or cloned into an expression system. Phenotypic susceptibility of the given tyrosine kinase to available STI was assessed in a cell-based reporter assay.Results: One drawback of available genotypic approaches is their requirement for prior knowledge of potential effects of mutations in the gene product on drug responsiveness. For overcoming these limitations we developed a sensitive phenotyping system. We recently validated one such phenotypic platform for inhibitors of Bcr/Abl. Genetic engineering of known therapy-resistant mutants confirmed in vitro differences in drug susceptibility. A main asset of our novel phenotyping system is its high sensitivity for therapy-relevant sub-populations typical for early phases of treatment failure: We measured resistance even if resistant variants only represented less than 1% of the total target cell population. For further validation, clinical samples from a phase II trial evaluating Dasatinib in CML were analyzed using both genotyping and phenotyping methods. In several instances resistant variants were only detected with the phenotypic assay. Yet subsequent sequencing of the Bcr/abl gene product in cells surviving drug pressure during in vitro exposure revealed the presence of relevant minority mutants in the authentic samples. At the same time, this assay identified and assigned new uncharacterized mutations in other samples. Reverse genetics confirmed that the latter variants conferred Gleevec resistance.Conclusions: Our pilot data highlight the power of the phenotyping system for functionally assessing susceptibility to STI of Bcr/Abl genes isolated from specimens. Moreover, it justifies extending this phenotypic platform to other targets such as EGFR, c-Kit, Flt3, which are currently in development. Furthermore, such test will be of utility for optimizing clinical drug development and for improving patient management as patients9 susceptibility at therapy onset and/or during treatment can be readily monitored.
Abstract 4391: Multi-modal nanomedicine for glioblastoma
Authors: Paula Ofek, Marcelo Calderon, Fatemeh Sheikhi-Mehrabadi, Shiran Ferber, Rainer Haag, Ronit Satchi-Fainaro
Journal: Cancer Research (2014)

Abstract Glioblastoma multiforme (GBM) is an aggressive primary neoplasm of the brain that exhibit notable refractivity to standard treatment regimens. Recent large-scale molecular profiling has revealed deregulated molecular networks as potential targets for therapeutic development. MicroRNAs (miRNAs) are noncoding RNA molecules which act as post-transcriptional regulators of specific messenger RNA transcripts. miRNAs play major roles in normal developmental processes, and their deregulation significantly contributes to various aspects of carcinogenesis. Nevertheless, in vivo delivery of small interfering RNA (siRNA) and miRNA remains a crucial challenge for their therapeutic success. siRNAs and miRNAs on their own are not taken-up by most mammalian cells in a way that preserves their activity. In order to circumvent these limitations, we developed a cationic carrier system, which can strongly improve its stability, intracellular trafficking and silencing efficacy. Polyglycerol (PG)-Amine, a water-soluble polyglycerol-based hyperbranched polymer accumulates in the tumor microenvironment due to the enhanced permeability and retention (EPR) effect, and therefore, represents an ideal nanocarrier for antitumor biological agents. Using our novel nanocarrier, we have studied the expression targets and functional effects of miR-34a in several human glioblastoma cell lines and human tissue samples. miR-34a levels inversely correlated to their target gene levels measured in the same cell lines or tissue. Transient transfection of PG-NH2-miR-34a polyplex into glioblastoma cells strongly inhibited cell proliferation, cell cycle progression, and cell migration. Consequently, we performed an in vivo experiment and achieved a significant tumor growth inhibition effect following treatment with PG-NH2-miR-34a polyplex in a human glioblastoma mouse model. We further characterized the synergistic effect of combining PG-NH2-miR-34a polyplex with chemotherapy and achieved promising results. Together, our findings show that PG-NH2 efficiently delivers anticancer miRNAs to glioblastoma cells and suppresses brain tumor growth. These results suggest that our polyplex could serve as a potential nanomedicine for glioblastoma. Citation Format: Paula Ofek, Marcelo Calderon, Fatemeh Sheikhi-Mehrabadi, Shiran Ferber, Rainer Haag, Ronit Satchi-Fainaro. Multi-modal nanomedicine for glioblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4391. doi:10.1158/1538-7445.AM2014-4391
A modified AIDA protocol with anthracycline-based consolidation results in high antileukemic efficacy and reduced toxicity in newly diagnosed PML/RARalpha-positive acute promyelocytic leukemia. PETHEMA group.
Authors: Miguel A. Sanz, Guillermo Martı́n, Consuelo Rayón, Jordi Esteve, Marcos González, Joaquı́n Dı́az-Mediavilla, Pascual Bolufer, Eva Barragán, Marı́a J. Terol, José D. González, Dolors Colomer, Carmen Chillón, Concha Rivas, Teresa Gómez, José M. Ribera, Rafael Bornstein, José Román, Marı́a J. Calasanz, Jesus Arias, Carmen Álvarez, Fernando Ramos, Guillermo Debén
Journal: Blood (1999)
Abstract 18697: “Forgotten” Cluster with Moderately-impaired LV Diastolic Function Determined by Doppler Echocardiography
Authors: Takuya Hasegawa, Masanori Asakura, Hideaki Kanzaki, Hiroshi Asanuma, Akira Funada, Takahiro Ohara, Yasuo Sugano, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai, Masafumi Kitakaze
Journal: Circulation (2014)

Background: Left ventricular (LV) diastolic function is mainly determined by the waves of transmitral flow and mitral annular velocity and classified as normal diastolic function, or mild, moderate, and severe diastolic dysfunction. However, it has been known that some subjects are not assigned to any group by the criteria. We investigated the prevalence and severity of the undetermined subjects in the general population. Methods: We studied 1559 community-dwelling subjects without obvious heart diseases or signs of heart failure (mean age, 61±12 years; 576 men, 983 women) who participated in the annual health checkup in a rural Japanese community, Arita-cho. LV diastolic dysfunction was determined with the waves of transmitral flow and mitral annular velocity, using established criteria (Redfield MM, JAMA2003). We investigated the plasma BNP levels in the predetermined and undetermined groups of LV diastolic dysfunction. Results: In this population, 769 subjects (49%) had normal LV diastolic function; 32...
Epithelial cell-derived antimicrobial peptides are multifunctional agents that bridge innate and adaptive immunity
Authors: Thomas S. McCormick, Aaron Weinberg
Journal: Periodontology 2000 (2010)

Mucosal barriers are not only physical; they are the source of potent antimicrobial peptides.These ancient compounds are important for the innate defense of an eukaryotic host.They function within a matter of hours, on a broad spectrum of bacteria, fungi, and encapsulated viruses (reviewed in (34, 94, 102)).The innate immune system works in conjunction with the adaptive immune system in mammals, by permitting the host to curb, delay, or avoid microbial growth shortly after an infection.For example, human β-defensins, specific epithelial cell-derived antimicrobial peptides (see below), have been shown to "cross-talk" with the adaptive immune system by interacting with specific chemokine and Toll-like receptors, resulting in modulation of immunocompetent cell responses of the host (6,27,29,98).It is theorized therefore, that surveillance through epithelial cell-derived antimicrobial peptides functions to keep the natural flora of microorganisms in a steady state in different niches such as the skin, the intestines, and the mouth.This review will highlight recent findings, by our group and others, demonstrating that antimicrobial peptides are not just antimicrobial; they play an added role of cross-talking with a number of cell types in functions as diverse as regulating epithelial cell proliferation, enhancing wound healing, inhibiting/inducing pro-inflammatory cytokines, promoting/inhibiting angiogenesis, stimulating chemokine production, promoting chemotaxis of various leukocytes, degranulating mast cells or modulating host cell gene expression.
Defective Expression of Granulocyte-Macrophage Colony-Stimulating Factor/Interleukin-3/Interleukin-5 Receptor Common β Chain in Children With Acute Myeloid Leukemia Associated With Respiratory Failure
Authors: Uta Dirksen, Uwe Hattenhorst, Peter Schneider, Horst Schroten, Ulrich Göbel, Alfred Böcking, Klaus-Michael Müller, Richard Murray, Stefan Burdach
Journal: Blood (1998)
Psychiatric considerations in the oncology setting
Authors: Reema D. Mehta, Andrew J. Roth
Journal: CA A Cancer Journal for Clinicians (2015)

Answer questions and earn CME/CNE An aging population and advances in diagnostics and treatment have resulted in a rapidly growing population of people impacted by cancer. People live longer after a cancer diagnosis and tolerate more aggressive treatments than in the past. Younger patients struggle with diversions from the normal developmental milestones in career and relationships, while older patients deal with the dual challenges of aging and cancer. Cancer's transition from likely death to survival has increased interest in its impact on psychosocial issues and quality of life, rather than just longevity. In this article, the authors review the psychiatric diagnosis and management of the mental health issues most often encountered in oncology. Oncology treatment teams, including oncologists, nurses, social workers, and other ancillary staff, are often on the front lines of addressing psychiatric distress and clinical syndromes when psychiatrists are not easily available. The purpose of this review article is to highlight opportunities for nonpsychiatrists to improve identification and treatment of psychosocial distress and psychiatric syndromes and to request formal psychiatric consultation in appropriate situations. Psychotherapeutic, psychopharmacologic, cognitive, and behavioral‐oriented interventions, as well as supportive interventions, are discussed for treating patients who are facing challenges during active cancer treatment, survivorship, and at the end of life. This review is not exhaustive but highlights the more common psychosomatic medicine and palliative care scenarios that impact cancer patient care. The importance of recognizing and addressing burnout and compassion fatigue in multidisciplinary professionals who care for those treated for cancer is also discussed given the secondary impact this can have on patient care. CA Cancer J Clin 2015;65:299–314. © 2015 American Cancer Society.
Identification of sensitive tumor types and predictive biomarkers to support the clinical development of small molecule inhibitors of insulin like growth factor-1 receptor (IGF-1R)
Authors: Junping Jing, Peter Sabbatini, Charity Atkins, Sridhar Rabindran, Rakesh Kumar, Kurtis Bachman, Barbara Weber, Richard Wooster
Journal: Clinical Cancer Research (2008)

B39   The insulin like growth factor-1 receptor (IGF-1R) signaling pathway is activated in many human cancers including those from colon, breast, prostate and soft tissue (sarcoma). To aid the clinical development of IGF-1R inhibitors, we generated tumor-type sensitivity and predictive biomarker data using a panel of >300 human cancer cell lines.  Cell lines from several pediatric sarcomas, including Ewing’s sarcoma (ES) and rhabdomyosarcoma (RMS), were among the most sensitive cell lines when compared to cell lines across multiple tumor types. These ES and RMS cell lines harbor distinct genetic translocations (EWS-FLI1, EWS-ERG, PAX-FKHR) resulting in fusion proteins that transactivate the IGF1R pathway. We also observed that all sensitive ES and RMS cell lines showed elevated expression of IGF-1R pathway components, IGF-1, IGF-2 and IGFBP-2, confirming the link between unique genetic events and activation of the IGF-1R pathway. These data also highlight the potential of IGF-1R inhibition as an effective therapy for pediatric tumors.  In summary, distinct genetic translocations, levels of IGF1, IGF-2 and IGFBP-2 are potential predictive biomarkers for identification of patient populations most likely to benefit from IGF-1R inhibitor treatment.
Poetry
Authors: Jay Liveson
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Four perfect quarters
Authors: Richard Donze
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 3909: Cisplatin resistant head and neck cancer cells are susceptible to growth inhibition by CDF curcumin
Authors: Saroj K. Basak, Alborz Zinabadi, Natarajan Venkatesan, Victor M. Duarte, Clifton L. Dalgard, Meera Srivastava, Marilene B. Wang, Fazlul H. Sarkar, Eri S. Srivatsan
Journal: Cancer Research (2014)

Abstract Head and neck (H&amp;N) cancer is the sixth most common type of cancer, with about 650,000 new cases in the world every year. Platinum-based agents (cisplatin/carboplatin) are the most common chemotherapeutic agents for H&amp;N cancer; however the five year survival rate is only 50% and development of drug resistance is one of the major challenges for effective therapy. Thus, development of new strategies to overcome drug resistance will help in H&amp;N cancer treatment. Our studies using H&amp;N cancer cisplatin resistant cell lines in vitro have indicated that Cancer Stem cell (CSC) specific markers such as CD44 and cytokines (IL-8, IL-10) are up-regulated during the development of drug resistance. Furthermore, our in vitro studies indicated that the treatment of drug resistant cell lines with a novel synthetic curcumin analog known as CDF in liposomal encapsulation (liposomal CDF) resulted in statistically significant growth inhibition (p&amp;lt;0.05). Similarly, our studies in a nude mouse xenograft drug resistant H&amp;N cancer tumor model showed that treatment with liposomal CDF (1 mg/100 µl in saline, i.v. injection 5 days a week for 3 weeks) resulted in greater than 50% tumor growth inhibition. The CDF treated cell lines and xenograft tumors showed a statistically significant reduction in the expression of CD44 (p&amp;lt;0.05), indicating an inhibitory effect of CDF on cancer stem cells, which is consistent with previously published data on other tumor models. These results demonstrate that CDF can be useful for the treatment of drug resistant H&amp;N cancer. Citation Format: Saroj K. Basak, Alborz Zinabadi, Natarajan Venkatesan, Victor M. Duarte, Clifton L. Dalgard, Meera Srivastava, Marilene B. Wang, Fazlul H. Sarkar, Eri S. Srivatsan. Cisplatin resistant head and neck cancer cells are susceptible to growth inhibition by CDF curcumin. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3909. doi:10.1158/1538-7445.AM2014-3909
Polymorphisms in melanoma differentiation‐associated gene 5 are not associated with clearance of hepatitis C virus in a European American population
Authors: Candelaria Vergara, Chloe L. Thio, David Thomas, Priya Duggal
Journal: Hepatology (2015)

Potential conflict of interest: Dr. Duggal received grants from Merck. Supported by R01013324, DA033541, DA12568, DA04334, U19AI088791, AI082630, UO1‐AI‐35004, UO1‐AI‐31834, UO1‐AI‐34994, UO1‐AI‐34989, UO1‐AI‐34993, UO1‐AI‐42590, UO1‐HD‐32632, R01HL076902, R01‐DA16159, R01‐DA21550, UL1‐RR024996. and R01‐HD41224. Author names in bold designate shared co‐first authorship. To the Editor: In a recent article in Hepatology, Hoffmann et al.1 used two different European‐ancestry cohorts to identify a haplotype in the melanoma differentiation‐associated gene 5 (mda5) that is associated with a 16‐fold increased likelihood for spontaneous hepatitis C virus (HCV) clearance. In this haplotype, H843/T946, the single‐nucleotide polymorphism (SNP) rs3747517 encoding the H843 variant was also associated with spontaneous HCV clearance, whereas the SNP (rs1990760) encoding T946 was not. As discussed in an accompanying editorial,2 if this finding is true, it broadens knowledge regarding the known innate immune response to HCV. Given these results and the potential implications, we used existing genotype data from our genome‐wide association study of 1708 European Americans previously characterized for HCV clearance (n = 689) and persistence (n = 1019) to interrogate the same variants.3 Unfortunately, our results demonstrated no association of either variant (rs3747517, allelic odds ratio = 1.01, P = 0.87; rs1990760, allelic odds ratio = 1.05) with HCV clearance. Furthermore, the implicated H843/T946 haplotype was absent in our population. The differences in these two studies may be reflective of the population compositions. The frequency of SNP rs3747517 varies widely across populations. Using 1000 Genomes Project data,4 the minor allele frequency (T) ranges from 25% in Europeans to 69% in Asians and 42% in Africans. In our study of individuals of European ancestry, the allele frequencies were consistent with those of Europeans in the 1000 Genomes Project (26%) in both the HCV spontaneous clearance and persistent individuals but differed from those reported by Hoffmann and colleagues (34%). Although their cohort is primarily German, 14% of the study population was from Ireland, Russia, and southern and eastern Europe; thus, population substructure may affect these association results, and no correction was employed. Moreover, the haplotype frequency (TT) was reported at 5%, yet this haplotype is completely absent from European populations in 1000 Genomes, reflective of the strong linkage disequilibrium (D′ = 1.0) between these two SNPs. Further studies are needed to explain the differences observed among populations and to make the results applicable to other European cohorts.