tbuckley/cabot-search huggingface dataset:
77. Production and Purification of Measles Virus for Oncolytic Virotherapy Clinical Trials
Authors: Dhanalakshmi Chinnasamy, Michael Milsom, James Neuenfeldt, Geoffrey P. Margison, Leslie J. Fairbairn, Nachimuthu Chinnasamy
Journal: Molecular Therapy (2004)

Lentiviral vectors are emerging as a promising tool for efficient gene delivery into dividing and non-dividing cells. A number of gene therapy applications would benefit from vectors capable of expressing multiple genes. Previous strategies in constructing multigene lentiviral vectors by other groups included: splicing, multiple internal promoters, internal ribosome entry site (IRES) and fusion proteins. In this study we explored the feasibility of expressing two or three transgenes under the control of a single promoter with the use of IRES sequence of encephalomyocarditis virus (ECMV) and/or foot-and-mouth disease virus (FDMV) 2A cleavage factor. Single gene, bicistronic and tricistronic self-inactivating lentiviral vectors were constructed employing IRES and/or 2A cleavage factor under the control of human PGK promoter. We employed enhanced green fluorescent protein (EGFP), O6-methylguanine-DNA-methyltransferase (MGMT), luciferase and HOXB4 as model genes and their expressions were detected by appropriate methods including fluorescence microscopy, flow cytometry, immunocytochemistry, biochemical assay and western blotting. A three-plasmid expression system was used to generate vesicular stomatitis virus glycoprotein pseudotyped lentiviral vector particles and viral titers were measured by quantification of p24 gag by ELISA. All the multigene vectors produced high titer virus and were able to simultaneously express the two or three transgenes in transduced cells lines (K562 and HeLa). However, the expression of EGFP as measured by mean fluorescence intensity of the single gene construct was greater than that of bicistronic vectors and 5 to 10 times that of the three gene constructs. Expression of MGMT in two gene constructs were 4 to 20 times greater than three gene constructs. We noted that the FDMV 2A cleavage factor efficiently mediates the generation of the expected cleavage products from the artificial fusion protein in these cells. The small and efficient 2A sequence can be used in combination with IRES for the construction of tricistronic lentiviral vectors. In the case of bicistronic vectors the 2A system can be used as an alternative to IRES. These vectors can be used in a wide range of gene therapy applications including the expression of multiple subunits of a functional protein, tumor antigen and co-stimulatory molecule(s), multiple tumor antigens for immunotherapy applications and co-expression of selectable marker gene/s with therapeutic gene/s.
PROBLEM IN THE DIAGNOSIS OF LEUKEMIA
Authors: M J ROWEN
Journal: Annals of Internal Medicine (1957)

Article1 May 1957PROBLEM IN THE DIAGNOSIS OF LEUKEMIAMANUEL J. ROWEN, M.D., F.A.C.P.MANUEL J. ROWEN, M.D., F.A.C.P.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-46-5-907 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptINTRODUCTIONLeukemia as a clinical entity has been recognized for many years. It is identified by various combinations of adenopathy, hepatosplenomegaly, anemia and varied bleeding tendencies, as well as by other factors such as infection and necrosis. When the disease is full-blown clinically the bone marrow findings should be conclusive. Frequently they are not performed because of the obvious clinical picture and the appearance of the peripheral blood. According to Wintrobe,1"Hyperplasia is usually diffuse and widespread throughout the marrow spaces"; however, it is conceivable that it may not involve all of the marrow spaces at all stages of the...Bibliography1. Wintrobe MM: Clinical hematology, 3d Ed., 1952, Lea and Febiger, Philadelphia. Google Scholar2. BlockJacobsonBethard MLDWF: Preleukemic acute human leukemia, J. A. M. A. 152: 1018-1028, 1953. CrossrefMedlineGoogle Scholar3. AndreMartyRespeMorichman-Beuchant LJRJ: A case of acute leukemia preceded by neutropenia, of 18 months duration, Bull. et mém. Soc. méd. d. hôp. de Paris 69: 417-421, 1953. Google Scholar4. MeachamWeissberger GCAS: Early atypical manifestations of leukemia, J. Lab. and Clin. Med. 42: 923-924, 1953. Google Scholar5. BernardTubianaMathe JMG: Discrepancies between the state of the blood and that of the hematopoietic organs in the leukemias, Semaine d. hôp. Paris 28: 3726-3735, 1952. Google Scholar6. DanopoulosAngelopoulos EB: Der extramedulläre Beginn der akuten Leukämien; Beobachtungen und Schlüsse bei 3 eigenen Fällen, Med. Klin. 49: 1947-1950, 1954. MedlineGoogle Scholar7. DreyfusBessis BM: Acute leukemia preceded by myeloid aplasia, Sang 25: 787-797, 1954. MedlineGoogle Scholar8. BernardBoron JM: The preleucoblastic anemias of acute leukemias, Sang 25: 797-825, 1954. MedlineGoogle Scholar9. Erf LA: Leukemia—theory and therapy, Seminar 16: 2-6, 1945. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Elizabeth, New Jersey*Received for publication May 18, 1956.From the Department of Medicine, Alexian Brothers Hospital, St. Elizabeths Hospital, Elizabeth, New Jersey.Requests for reprints should be addressed to Manuel J. Rowen, M.D.133 West Jersey Street, Elizabeth, New Jersey. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHypoplastic Acute Myelogenous LeukaemiaPreleukemiaAcute myeloid leukemia following seven years of aplastic anemia induced by chloramphenicolSmoldering Acute Leukemia 1 May 1957Volume 46, Issue 5Page: 907-914KeywordsAnemiaBloodBone marrowHemorrhageHepatosplenomegalyHospital medicineNecrosis Issue Published: 1 May 1957 PDF downloadLoading ...
Abstract 3877: Evolution of cancer stem cells in glioma to promote their therapy-resistant phenotype
Authors: Ichiro Nakano
Journal: Cancer Research (2014)

Abstract High grade glioma (HGG) is a life-threatening brain tumor. Among heterogeneous tumor cells, glioma stem cells (GSCs) are defined as a subpopulation resistant to chemo- and radiotherapy with prominent tumorigenic ability. Identification of novel therapeutics designed to target the GSC population in HGGs is a challenge. The recent genome-wide transcriptome analysis identified 3 subtypes, proneural (PN), proliferative, and mesenchymal (MES), in HGGs. These HGG subtypes harbor distinct gene signatures and altered signaling pathways with some clinical relevance. During malignant transformation, HGGs appear to gain therapy resistance, at least in part, through their phenotypic drift into mesenchymal tumors. In addition, some of the current therapies, if not all, appear to induce mesenchymal transformation of HGGs resulting in more therapy-resistant tumors. Nonetheless, identification of subtype-specific GSCs remains elusive. My lab recently identified clinical HGG sample-derived two mutually-exclusive GSCs: PN and MES GSCs with striking phenotypic differences with clinical relevance (Mao et al., PNAS 2013). Transcritpome microarray analysis, miRNA profiling, and subsequent functional analysis demonstrated that distinct signaling pathways regulate tumorigenesis and propagation of the individual GSC subtypes. For example, PN GSCs are dependent on the oncogenic transcription factor c-Myb (Miyazaki et al., Clinical Cancer Res. 2012) and MES GSCs are dependent on the oncogene/mitotic kinase MELK and Survivin (Guvenc et al., Clinical Cancer Res. 2012; Gu et al., Stem Cells 2013; Joshi et al., Stem Cells 2013). Intriguingly, upon radiation treatment, PN GSCs gain the phenotypes of MES GSCs (PN-to-MES transformation; PMT), which are much more aggressive and radioresistant than original PN GSCs. Of note, targeting the MES-specific pathways partially blocks PMT of GSCs. These results may patially explain the molecular mechanisms underlying mesenchymal transformation of HGGs to promote therapy resistance. Here I summarize our latest data to elucidate the molecular mechanisms that drive GSC evolution to promote their therapy resistant phenotype. Citation Format: Ichiro Nakano. Evolution of cancer stem cells in glioma to promote their therapy-resistant phenotype. [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 3877. doi:10.1158/1538-7445.AM2014-3877
Elevated hyaluridase 1 expression in an in vivo tumor model predicts the metastatic phenotype.
Authors: Deirdre O'Sullivan, Brigid Maruszak, Brunhilde Felding-Habermann
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3101 

Hyaluronic Acid, a very high molecular weight glycosaminoglycan, is a major component of the extracellular matrix in both normal and tumor tissues. It is secreted by many cell types, including tumor cells and its concentration in the peri-cellular stroma is controlled by a balance of synthesis by Hyaluron Synthases and degradation by Hyaluronidase enzymes. Elevated levels of Hyaluronidase enzymes, particularly Hyaluronidase 1 have been reported in several cancers, most notably bladder and prostate tumors. It is thought that degradation of the stromal Hyaluronic Acid within the tumor mass may promote extravasation and subsequent seeding of distant metastases. It is also known that the degradation products of Hyaluronic Acid are strongly pro-angiogenic.

We used in vivo bioluminescent imaging to track the pattern of metastasis from implanted MDA MB-435 cells which formed a ‘primary’ tumor in the mammary fat pads of SCID mice. We identified lung, bone, brain and the adrenal glands as the major metastatic sites under these experimental conditions.

Microarray analysis of metastases to bone, brain and lung originating from individual ‘primary’ mammary fat pad tumors showed that the metastases and their ‘primary’ tumors shared an almost completely identical gene profile, despite the very different conditions which would prevail at their sites of growth. The only notable difference in gene expression was in the Hyaluronidase 1 gene, where the level in the cells originating from the ‘primary’ mammary fat pad tumor was significantly lower than the levels seen in all metastases deriving from it. This preferential expression of Hyaluronidase 1 in metastatic foci was noted in several independent experiments. Hyaluronic acid zymography confirmed that the elevated gene expression correlated with the secretion of high levels of biologically active enzyme by the metastatic cells.

Hyaluronidase 1 expression was also found to be elevated in the sera of mice which had metastatic lesions but was not observed in mice whose tumors had not yet metastasized from the orthotopic ‘primary’ site.

These data indicate that serum levels of Hyaluronidase 1 might be predictive of active metastatic disease and we are currently studying this hypothesis in both melanoma and breast cancer patients.
Dkk3, down-regulated gene by epigenetic alteration in cervical cancer could be therapeutic candidate targeting beta-catenin.
Authors: Eun-Ju Lee, Yae-Na Yoo, Kyoungsook Park, Heeseok Kang, Chul Jung Kim, Yoo-Young Lee, Chel Hun Choi, Tae-Joong Kim, Byoung-Gie Kim, Duk-Soo Bae, Je-Ho Lee
Journal: Clinical Cancer Research (2008)

B53   The Wnt/beta-catenin signaling pathway is inappropriately activated during the malignant transformation of keratinocytes that originate from the human uterine cervix. Dkk1, 2, and 4 have been shown to modulate the Wnt-induced stabilization of the beta-catenin signaling pathway. The function of Dkk3 is unknown, but since it is down-regulated in various cancer cell lines and cancer tissues. We hypothesized that Dkk3 down-regulation is responsible for the inappropriate activation of the Wnt/beta-catenin signaling pathway that contributes to the tumorigenesis. Comparison of the Dkk3 gene expression profiles in cervical cancer and normal cervical tissue shown by cDNA microarray and subsequent real-time PCR confirmed that the Dkk3 gene is frequently down-regulated in the cancer. Methylation studies showed that the promoter of Dkk3 was methylated in two of three cervical cancer cell lines and 22 (31.4%) of 70 cervical cancer tissue specimens. The reintroduction of Dkk3 into HeLa cells resulted in reduced colony formation and retarded cell growth. Consistent with the observation that Dkk proteins are involved in the regulation of the Wnt/beta-catenin signaling pathway, the forced expression of Dkk3 markedly attenuated beta-catenin-responsive luciferase activity in a dose-dependent manner and decreased beta-catenin levels. The stable expression of Dkk3 blocks the nuclear translocation of beta-catenin, resulting in down-regulation of its downstream targets (VEGF and cylcin D), while knockdown of Dkk3 abrogates this blocking. We conclude from our finding that Dkk3 is a negative regulator of beta-catenin and thus that Dkk3 could be exploited as a therapeutic gene targeting beta-catenin.
Diseases of Infection: An Illustrated Textbook
Authors: N. R. Grist, D. O. Ho-Yen, E. Walker, G. R. Williams
Journal: Annals of Internal Medicine (1988)

Introduction to infections infections of the respiratory tract, middle ear, and eyes localized skin and tissue infections infections of the gastrointestinal tract infections of abdominal organs infections of the nervous system infections with generalized rash septicaemia and shock fever, tuberculosis, brucellosis, and Q fever infections of the genital tract infection in pregnancy and neonates infections in the immunocompromised subject infection-related illnesses imported infections infection in the tropics prevention of infection - immunization and advice to travellers epidemiology in action specific drug treatment of pathogens infection and the laboratories.
Daylight-mediated photodynamic therapy of moderate to thick actinic keratoses of the face and scalp: a randomized multicentre study
Authors: S.R. Wiegell, S. Fabricius, M. Gniadecka, I.M. Stender, B. Berne, S. Kroon, B.L. Andersen, C. Mørk, C. Sandberg, K.S. Ibler, G.B.E. Jemec, K.M. Brocks, P.A. Philipsen, J. Heydenreich, M. Haedersdal, H.C. Wulf
Journal: British Journal of Dermatology (2012)

Summary Background Photodynamic therapy (PDT) is an attractive therapy for nonmelanoma skin cancers and actinic keratoses (AKs). Daylight‐mediated PDT is a simple and tolerable treatment procedure for PDT. Methyl aminolaevulinate (MAL)‐PDT is approved for the treatment of thin or nonhyperkeratotic AKs on the face and scalp. However, thick AK lesions are often treated as well when present in the field‐cancerized treatment area. Objectives In a randomized multicentre study to evaluate efficacy of daylight‐mediated PDT for different severity grades of AKs. Methods One hundred and forty‐five patients with a total of 2768 AKs (severity grades I–III) of the face and scalp were randomized to either 1½ or 2½ h exposure groups. After application of a sunscreen (sun protection factor 20) and gentle lesion preparation, MAL was applied to the entire treatment area. Patients left the clinic immediately after application and exposed themselves to daylight according to randomization. Daylight exposure was monitored with a wrist‐borne dosimeter. Results No difference in lesion response was found between the 1½ and 2½ h exposure group. The mean lesion response rate was significantly higher in grade I lesions (75·9%) than in grade II (61·2%) and grade III (49·1%) lesions (P <0·0001). Most grade II (86%) and III AKs (94%) were in complete response or reduced to a lower lesion grade at follow‐up. Large variations in response rate of grade II and III AKs were found between centres. No association was found between response rate and light dose in patients who received an effective light dose of > 3·5 J cm−2. Conclusions Daylight‐mediated PDT of moderate to thick AKs was less effective than daylight‐mediated PDT of thin AKs especially in some centres. However, nearly all thicker lesions (grades II and III) were reduced to a lower lesion grade at 3 months after a single treatment of daylight‐mediated PDT.
Breast Cancer in Mice as Influenced by Nursing&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: J J Bittner
Journal: JNCI Journal of the National Cancer Institute (1940)

Evidence suggests that maternal/extrachromosomal influence may be a factor in mammary carcinogenesis in mice.  There are 3 possible methods of transmission to the progeny:  1) by means of the cytoplasm or cytoplasmic inheritance 2) during intrauterine development and 3) by way of the mothers milk while nursing.  Various experiments in breast cancer etiology in mice have assumed a correlation between milk/hormonal/susceptibility factors and cancer development.  For stock A high-breast tumor breeding females this would suggest development of spontaneous mammary cancer in every female.  However this had not been the case.  If noncancerous animals of this stock are mated and their progeny continued the incidence of breast tumors among the offspring is very similar to that of the control stock suggesting that these mice are genetically cancerous and would probably develop the condition if they live longer.  Other experiments show that breast tumors can occur in a small percentage of animals where none were to be expected suggesting that there may be other contributing factors of unknown origin and/or there may be physiological upsets in the equilibrium or relationship of the known factors and changes characteristic of somatic mutation.  Experimental evidence also suggests that an excessive dose of estrogenic hormone may produce carcinoma more easily in males of a strain not susceptible to breast cancer but having the milk factor active than in males of a susceptible strain having the milk factor that is not active.
Abstract 16562: Peri-Aortic Leptin Augments the Aneurysmogenic Effect of Angiotensin II in Apolipoprotein E Deficient Mice
Authors: Binh Nguyen, Boaz Mizrahi, Naphtali Savion, Ming Tao, Galina K Sukhova, Frank Kolodgie, Renu Virmani, Keith C Ozaki, Jacob Schneiderman
Journal: Circulation (2011)

Background: Leptin functions as a proatherogenic hormone capable of inciting vessel wall remodeling mechanisms. We thus hypothesized that Ang II drives leptin generation by SMCs, and that leptin ac...
Statin Use During Hospitalization for Intracerebral Hemorrhage—Reply
Authors: Alexander C. Flint
Journal: JAMA Neurology (2015)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Neurology journal
Abstract P105: Sleep Disordered Breathing and Cardiac Autonomic Modulation in Adolescents - Penn State Child Cohort (PSCC) Study
Authors: Edward O Bixler, Fan He, Sol Rodriguez-Colon, Julio Fernandez-Mendoza, Alexandros Vgontzas, Susan Calhoun, Duanping Liao
Journal: Circulation (2014)

Objectives: To investigate the relationship between sleep disordered breathing (SDB) and cardiac autonomic modulation (CAM) in a population-based sample of adolescents. Methods: We used available data from 400 adolescents who completed the follow up examinations in the population-based PSCC study. 1-night polysomnography was used to assess apnea hypopnea index (AHI). AHI was used to define no-SDB (AHI&lt;1), mild SDB (1≤AHI&lt;5), and moderate SDB (AHI≥5). CAM was assessed by heart rate variability (HRV) analysis of beat-to-beat normal R-R intervals from a 39-hour high resolution Holter ECG. The HRV indices in frequency domain [high frequency power (HF), low frequency power (LF), and LF/HF ratio] and time domain [standard deviation of normal RR intervals (SDNN), and the square root of the mean squared difference of successive normal RR intervals (RMSSD), and heart rate (HR)] were calculated on a 30-minute basis (78 repeated measures). Mixed-effects models were used to assess the SDB and HRV relationship. Results: The mean age was 16.9 yrs (SD=2.19), with 54% male and 77% white. The mean (SD) AHI were 0.52 (0.26), 2.38 (1.03), and 12.27 (14.54) for no-, mild-, and moderate-SDB participants. The age, race, sex, and BMI percentile adjusted mean (SE) HRV indices across three SDB groups are presented in Table 1. In summary, sleep disordered breathing was associated with lower HRV and higher HR in this population-based adolescent sample, with a significant dose-response relationship. Conclusion: moderate SDB in adolescents is already associated with lower HRV, indicative of sympathetic activation and lower parasympathetic modulation, which has been associated with cardiac events in adults.
IMPAIRED MACROPHAGE MEDIATED ELASTIN TURNOVER LIMITS REVERSIBILITY OF LIVER CIRRHOSIS
Authors: Antonella Pellicoro, Rebecca Aucott, Prakash Ramachandran, Jonathan Fallowfield, Stephen N. Hartland, Luke G. Boulter, Madeleine A. Vernon, Jeremy S. Duffield, Stuart J. Forbes, John P. Iredale
Journal: Hepatology (2010)