tbuckley/cabot-search huggingface dataset:
Development of Multifunctional Magnetic Nanoparticles for Genetic Engineering and Tracking of Neural Stem Cells
Authors: Christopher Adams, Liron Limor Israel, Stella Ostrovsky, Arthur Taylor, Harish Poptani, Jean‐Paul Lellouche, Divya Chari
Journal: Advanced Healthcare Materials (2016)

Genetic modification of cell transplant populations and cell tracking ability are key underpinnings for effective cell therapies. Current strategies to achieve these goals utilize methods which are unsuitable for clinical translation because of related safety issues, and multiple protocol steps adding to cost and complexity. Multifunctional magnetic nanoparticles (MNPs) offering dual mode gene delivery and imaging contrast capacity offer a valuable tool in this context. Despite their key benefits, there is a critical lack of neurocompatible and multifunctional particles described for use with transplant populations for neurological applications. Here, a systematic screen of MNPs (using a core shown to cause contrast in magnetic resonance imaging (MRI)) bearing various surface chemistries (polyethylenimine (PEI) and oxidized PEI and hybrids of oxidized PEI/alginic acid, PEI/chitosan and PEI/polyamidoamine) is performed to test their ability to genetically engineer neural stem cells (NSCs; a cell population of high clinical relevance for central nervous system disorders). It is demonstrated that gene delivery to NSCs can be safely achieved using two of the developed formulations (PEI and oxPEI/alginic acid) when used in conjunction with oscillating magnetofection technology. After transfection, intracellular particles can be detected by histological procedures with labeled cells displaying contrast in MRI (for real time cell tracking).
Gallium scans in patients with mediastinal Hodgkin's disease treated with chemotherapy.
Authors: D L Cooper, V J Caride, M Zloty, J Germino, L R Farber, P B Hoffer
Journal: Journal of Clinical Oncology (1993)

To determine the predictive value of gallium scans in patients with mediastinal Hodgkin's disease treated with chemotherapy or combined modality treatment.A retrospective study was performed of 48 patients with mediastinal Hodgkin's disease treated with chemotherapy or combined modality therapy. Patients were monitored with whole-body planar scans (34 patients) or chest single-photon-emission computed tomography (SPECT) plus planar abdominal imaging studies (14 patients). Scans were performed at diagnosis, following three to eight cycles of chemotherapy, and after the end of treatment. The value of gallium scans in modifying treatment and predicting outcome was assessed.All patients studied at the time of diagnosis had abnormal gallium accumulation in the mediastinum. After chemotherapy, four patients had residual mediastinal activity; two patients with persistent activity on planar scans failed to enter remission and died of disease; two other patients with abnormal activity only seen on SPECT had therapy modified and remain in remission. After chemotherapy, 44 patients had a normal gallium scan. Twelve patients with negative scans relapsed, including nine patients with recurrence above the diaphragm.The use of gallium scans after several courses of chemotherapy resulted in a modification of treatment in four patients, including two patients who are apparently cured. However, after negative scans, 20% of patients relapsed above the diaphragm. These results suggest that gallium imaging, including SPECT, is of limited value in predicting disease sterilization, although the number of patients studied with SPECT was small. At present, the major value of gallium scans is to identify patients who may benefit from a modification of treatment.
Carboplatin dose optimization.
Authors: C R Pinkerton, J R Hardy
Journal: Journal of Clinical Oncology (1990)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1990.8.7.1283 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 1694237 Carboplatin dose optimization. C R PinkertonxC R PinkertonSearch for articles by this author , J R HardyxJ R HardySearch for articles by this author https://doi.org/10.1200/JCO.1990.8.7.1283 First Page PDF © 1990 by American Society of Clinical Oncology
Novel method for the estimation of PCWP using CINE cardiac MRI in patients with pulmonary hypertension
Authors: Andrew Swift, Smitha Rajaram, Robin Condliffe, Helen Marshall, Dave Capener, Judith Hurdman, Charlie Elliot, Jim Wild, David Kiely
Journal: European Respiratory Journal (2011)

Introduction: Several studies question the reliability of pulmonary capillary wedge pressure (PCWP) for accurate assessment of left ventricular end-diastolic pressure (LVEDP). Developing markers that can aid the separation of pre and post capillary pulmonary hypertension (PH) is desirable. Due to the elevated ventricular pressure differential in patients with PH the left ventricle becomes deformed. We hypothesise patients with PH owing to left heart disease (PH-LHD) have proportionately less left ventricular (LV) deformation than patients with IPAH due to raised left sided pressures.

Methods: 92 patients underwent MRI and RHC within 48 hours; IPAH (n=34), PH-LHD (n=24) and “no PH” (n=34). Short axis CINE images were acquired on a 1.5T whole body MR scanner using a cardiac gated balanced SSFP sequence. LV deformation was defined in all patients using the measured left ventricular systolic eccentricity index (sEIm). Linear regression was used to assess the relationship between sEI and mPAP in patients with PCWP ≤15, thus predicted sEI was derived (sEIp) and was calculated for all patients.

Results: sEIp values were significantly higher than sEIm in patients with PH-LHD. No significant difference was demonstrated between sEIp and sEIm in patients with IPAH. Patients with PH-LHD demonstrated higher sEIp/sEIm values than those with IPAH, p<0.0001. A significant correlation was found between sEIp/sEIm and PCWP r=0.64, p<0.0001. Good interobserver agreement was demonstrated, k=0.80.

Conclusion: Patients with PH-LHD have proportionately less LV deformation than patients with pre-capillary PH. sEIp/sEIm may be a useful marker for differentiating pre from post capillary PH.
Phase II trial of postoperative adjuvant intraperitoneal cisplatin and fluorouracil and systemic fluorouracil chemotherapy in patients with resected gastric cancer.
Authors: O T Atiq, D P Kelsen, M H Shiu, L Saltz, W Tong, D Niedzwiecki, B Trochanowski, S Lin, F Toomasi, M Brennan
Journal: Journal of Clinical Oncology (1993)

PURPOSE This study was performed to assess the short- and long-term toxicities and the impact on relapse pattern and survival of postoperative intraperitoneal (IP) cisplatin and fluorouracil (FU) plus systemic intravenous (IV) FU as adjuvant therapy for gastric cancer patients who are at high risk for recurrence after potentially curative resection (T2N1-2M0 or T3-4N(any)M0). PATIENTS AND METHODS Starting 14 to 28 days after potentially curative resection of primary gastric cancers, 35 patients were given IP cisplatin 25 mg/m2 and FU 750 mg daily for 4 days; FU 750 mg/m2 was concurrently given as a continuous 24-hour i.v. infusion. Five cycles of therapy delivered at 1-month intervals were used. RESULTS After a median follow-up of 24 months, 51% of patients remain alive and free of disease. Sixteen patients have recurred; 13 of 16 had an intraabdominal component, whereas three had extraabdominal failure only. Two major treatment-related toxicities were noted: neutropenia and a late toxicity of peritoneal fibrosis (sclerosing encapsulating peritonitis [SEP]). There was one postoperative death. Eleven patients underwent second laparotomy: five patients had SEP, two patients had bowel obstruction from adhesions unrelated to SEP, and four patients had recurrent cancer. Potential causes of SEP included an alkaline pH of infused FU and cisplatin that possibly led to activation of cisplatin before infusion. CONCLUSION IP cisplatin and FU and concurrent systemic FU is a tolerable adjuvant therapy in the postoperative setting for patients with resected gastric cancer. The recommended dosage schedule with this technique is cisplatin 25 mg/m2 and FU 750 mg total dose IP with FU 500 mg/m2 as a continuous 24-hour infusion daily for days 1 to 4. SEP as a late toxicity, which was observed in 15% of patients, is treatable by surgical lysis of adhesions.
Quality of life, depression and anxiety in chronic lymphocytic leukemia during phases of “watchful waiting” and active treatment
Authors: T. Levin
Journal: Journal of Clinical Oncology (2006)

6603 Background: Although chronic lymphocytic leukemia (CLL) accounts for 25–30% of leukemia cases in the USA, little is known about its quality of life (QOL) and psychosocial burden. The purpose of this study was to compare QOL, anxiety and depression in watch and wait versus actively treated CLL. Methods: Using a cross-sectional design, 105 patients were recruited from a CLL research database. 57 were classified as watch and wait and 48 as receiving or having received chemotherapy for CLL. The patients completed a battery of QOL measures including the SF-36, FACT-Lym, Beck Depression Inventory (BDI-II), Beck Anxiety Inventory (BAI) and the Patient Health Questionnaire. Results: No differences were found between the treatment groups on the main QOL outcome measures - Mental Component Score, Physical Component Score, FACT-G, FACT-lymphoma (15 item), BDI-II and BAI. There was a clear age effect: younger patients (&lt;60 years old) have worse Mental Component (p=0.0001), FACT-G (p=0.060), depression (p=0.014), Role Emotional (p=0.042), Mental Health (p=0.001), FACT-Emotional (p=0.0001) and FACT-Social (p=0.002) scores. Younger watch and wait patients seem to be particularly vulnerable to anxiety (p=0.052). Social and emotional QOL are statistically similar in both newly diagnosed and patients diagnosed six or more years ago, although patients do carry a greater physical QOL burden with time (p=0.05). Conclusions: Overall QOL, depression and anxiety are remarkably similar in watch and wait versus actively treated CLL, despite the latter group having, by definition, later stage disease. Younger patients (&lt;60 years old) seem particularly vulnerable to having a reduced emotional and social QOL and having more depression. Younger watch and wait patients stood out as suffering from more anxiety. Patients diagnosed for more than 6 years carry a greater physical QOL burden, but social and emotional QOL are similar to newly diagnosed patients. Implications of these findings are considered. [Table: see text] No significant financial relationships to disclose.
Multiple nuclear-gene phylogenies: application to pinnipeds and comparison with a mitochondrial DNA gene phylogeny.
Authors: R W Slade, C Moritz, A Heideman
Journal: Molecular Biology and Evolution (1994)

Phylogenetic analyses of closely related species should use information from multiple, independent genes with relatively high rates of sequence evolution. To investigate species for which there are few prior sequence data for single-copy nuclear (scnDNA) genes, primers for gene amplification can be designed to highly conserved regions of exons in order to amplify both coding (exons) and noncoding (introns) sequences. We have explored this approach in a phylogenetic analysis of six species of pinnipeds that, together with terrestrial carnivore outgroups, encompass divergence times < or = 40-50 Mya. We sequenced one intron from each of the aldolase A (ALD-A), aldolase C (ALD-C), and histone H2AF genes; one exon from the major-histocompatibility-complex DQA gene; a H2AF processed pseudogene (psi H2AF); and, for comparison with the nuclear genes, the 5' portion of the mitochondrial DNA (mtDNA) control region. The pinniped psi H2AF genes were found to be of limited use because they were paralogous with the gene in the outgroup. The rate of silent substitution in scnDNA (primarily introns) was 5-10-fold lower than that for mtDNA control region I, and scnDNA sequence divergence increased linearly with time < or = 40-50 Mya. Alleles at three polymorphic scnDNA loci (ALD-A, H2AF, and DQA) in the southern elephant seal were paraphyletic with respect to the allele from the closely related northern elephant seal, while the more numerous mtDNA alleles were monophyletic. This we attribute to the consequences of a higher mutation rate rather than to a lower effective population size of mtDNA compared with scnDNA. Within the short (i.e., < 500-bp) sequences of individual scnDNA sequences, phylogenetically informative variation was insufficient to obtain robust phylogenies. However, the combined scnDNA sequences produced a well-supported phylogeny congruent with that derived from mtDNA. This analysis illustrates the high resolution of mtDNA sequences compared with a similar length of scnDNA sequence, but it also demonstrates the utility of combining information from multiple short scnDNA sequences obtained using broadly applicable primers.
Intranasal buserelin in the treatment of advanced prostatic cancer: a phase II trial.
Authors: G Falkson, D A Vorobiof
Journal: Journal of Clinical Oncology (1987)

Thirty-five patients with advanced prostatic cancer were entered in a trial of nasally administered gonadotropin-releasing hormone analogue agonist (GnRHA) buserelin. Four patients were unevaluable for response and toxicity. Twenty-five patients responded to treatment, two with complete remissions, 12 with partial remissions, and 11 who improved. The median baseline value for testosterone was 14.4 nmol/L. After 1 week of treatment, the median value was 10.8 nmol/L, while after 1 month the median value had decreased to 1.1 nmol/L (normal, 10.0 to 34.7). It is concluded that intranasal buserelin is an effective, simple, and safe method to achieve androgen deprivation in the treatment of advanced prostate cancer and is an alternative to orchiectomy and more acceptable than daily subcutaneous injections.
Differences in Activity of &lt;italic&gt;N&lt;/italic&gt;&lt;sup&gt;2&lt;/sup&gt; -Guanine tRNA Methyltransferase II Among Several Inbred Strains of Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M Dizik, E Wainfan
Journal: JNCI Journal of the National Cancer Institute (1985)

The tRNA methyltransferase activities of C57BL/6J, C57L/J, C58/J, AKR/J, and C3H/HeJ inbred mice were studied with the use of various amino acid-specific Escherichia coli tRNA's as substrates. Mice from two strains with high incidence of spontaneous leukemia (AKR/J and C58/J) exhibited levels of liver N2-guanine tRNA methyltransferase II (N2-MeGII) activity that were double those of two strains of mice with low incidence of spontaneous leukemia (C57BL/6J and C57L/J). Activities of liver and kidney N2-MeGII of the high spontaneous hepatoma strain C3H/HeJ were also found to be twice as high as those of C57BL/6J mice. The activities of other tRNA base-specific liver tRNA methyltransferases were very similar in all strains studied. The N2-MeGII activity of the F1 progeny of a cross between C57BL/6J and C3H/HeJ showed levels of activity intermediate to those of the parental strains. Activities of liver N2-MeGII of two inbred strains of mice that differ in their H-2 haplotype (C57BL/10SnJ and the congenic strain B10.BR/SgSnJ) were also compared. Both C57BL/10SnJ and B10.BR/SgSnJ strains exhibited low levels of liver N2-MeGII activity, indicating that H-2 does not directly control the activity of this enzyme.
Consent Is the Cornerstone of Ethically Valid Research: Ethical Issues in Recontacting Subjects Who Enrolled in Research as a Minor
Authors: Erin Talati Paquette, Lainie Friedman Ross
Journal: The American Journal of Bioethics (2015)

Informed consent is fundamental to the conduct of ethical research (Belmont Report 1979; Nuremberg Code 1949). Consent requires disclosure regarding the methods, risks, benefits, and alternatives, ...
Association of single-nucleotide polymorphisms in DNA repair genes with progression and survival of primary cutaneous melanoma patients
Authors: D. Schadendorf, A. Figl, A. Sucker, A. Gast, R. Kumar
Journal: Journal of Clinical Oncology (2008)

9018 Background: Host genetics has so far not been appreciated as an important factor in adjuvant and palliative study design in melanoma. Single nucleotide polymorphisms (SNPs) in DNA repair genes may affect not only cancer predisposition, but also progression and survival of primary cutaneous melanoma patients. We evaluated the association of SNPs in DNA repair genes with overall survival (OS), metastasis-free survival (MFS) and survival following the first metastasis (SFM) in patients with primarily unmetastasized melanoma. Methods: 13 SNPs in 8 DNA repair genes were evaluated in 400 primary melanoma patients (any T,N0,M0) using genotyping assays and associated with follow-up data of these patients. Deviation of Hardy-Weinberg equilibrium using the Pearson-x2 test, censored survivorship function Kaplan-Meier, log-rank test were used. Cox Hazards regression modeling and multivariate analysis models including age, gender and Breslow were employed. Results: Of the evaluated SNPs 4 showed significant associations with overall survival. Two of each were correlated with MFS but not with SFM and viceversa. For XRCC1 R399Q AA, the hazard ratio (HR) for MFS was 0.4 (95% CI, 0.21 to 0.78) and the HR for OS was 0.3 (95% CI, 0.11 to 0.90), while SFM was unchanged. Similarly, for ERCC2 K751Q CC the HR for MFS was 0.6 (95% CI, 0.35 to 0.94) and the HR for OS was 0.4 (0.21 to 0.93), while SFM was unchanged. MFS was unchanged for ERCC2 D312N AA, while the HR for SFM was 0.3 (95% CI, 0.10 to 0.78) and the HR for OS was 0.2 (95% CI, 0.09 to 0.66). For the -1843 XRCC3 promoter variant genotypes the HR for SFM was 1.9 (95% CI, 1.25 to 3.02) and the HR for OS was 1.6 (1.02 to 2.41), and MFS was also unaffected. Conclusions: SNPs in DNA repair genes may be differentially predictive of metastatic capacity and survival following metastasis in primary cutaneous melanoma patients. Impact of host genetics on clinical trial outcome needs to be systematically addressed. No significant financial relationships to disclose.
Abstract 19434: Early Ischemic Preconditioning Requires Akt- and PKA-Mediated Activation of eNOS via Serine1176 Phosphorylation
Authors: Changjun Yang, M.A. Hassan Talukder, Saradhadevi Varadharaj, Murugesan Velayutham, Jay L Zweier
Journal: Circulation (2012)
Inhibition of Bovine Leukemia Virus Release 2
Authors: M. Onuma, C. Olson, L. E. Baumgartener
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Inhibition of Bovine Leukemia Virus Release Get access M. Onuma, M. Onuma Search for other works by this author on: Oxford Academic PubMed Google Scholar C. Olson, C. Olson Search for other works by this author on: Oxford Academic PubMed Google Scholar L. E. Baumgartener L. E. Baumgartener Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 54, Issue 5, May 1975, Pages 1199–1202, https://doi.org/10.1093/jnci/54.5.1199 Published: 01 May 1975 Article history Received: 29 October 1974 Accepted: 14 January 1975 Published: 01 May 1975
Sessile Serrated Polyps: An Important Route to Colorectal Cancer
Authors: Matthew F. Kalady
Journal: Journal of the National Comprehensive Cancer Network (2013)

The serrated neoplastic pathway accounts for approximately 30% of colorectal cancers. Characterized by mutations in the oncogene BRAF, DNA promoter hypermethylation, and microsatellite instability, cancers arising in this pathway develop via serrated polyp intermediates. Serrated polyps represent a heterogeneous group of lesions with distinct genetic, molecular, and clinical features. Sessile serrated polyps (also called sessile serrated adenomas) have emerged as the key intermediates in this pathway. These lesions have malignant potential and are often difficult to detect endoscopically, thus contributing to the development of interval cancers. Recent advances in the understanding of sessile serrated polyps have led to new histologic classifications, increased endoscopic recognition, and changes in clinical management recommendations. This article focuses on sessile serrated polyps as a unique and important route to colorectal cancer.
Predicting recurrence following post-chemotherapy retroperitoneal lymph node dissection for residual fibrosis or teratoma
Authors: B. S. Carver, B. Shayegan, R. J. Motzer, D. Bajorin, G. V. Kondagunta, G. J. Bosl, J. Sheinfeld
Journal: Journal of Clinical Oncology (2006)

4551 Background: The current recommendation for the management of patients with the histologic finding of fibrosis or teratoma at PC-RPLND is surveillance. We evaluated men at our institution who underwent PC-RPLND for metastatic non-seminomatous germ cell tumor (NSGCT) to determine predictors of disease recurrence. Methods: From 1989 through 2003, a total of 532 men underwent PC-RPLND for metastatic NSGCT at our institution. Of these, 473 (89%) had either fibrosis or teratoma present in the RPLND specimen. Following IRB approval, clinical and pathologic data were obtained from our prospective surgical database. A Cox regression model was constructed to evaluate variables that may predict for recurrence of viable NSGCT following PC-RPLND and a prognostic index was developed. Freedom from disease recurrence was analyzed using the Kaplan Meier method. Results: Of the 473 patients with fibrosis or teratoma, all patients underwent complete resection of all residual retroperitoneal masses, however 35 (7%) did not undergo a full PC-RPLND. With a median follow-up of 41 months, 47 (10%) patients relapsed with viable NSGCT. The 2- and 5- year probability of freedom from recurrent viable GCT for the entire cohort was 90% and 89%, respectively. In our multivariable model only post-chemotherapy nodal size &gt; 5cm (p = 0.008), clinical stage III (p = 0.002), and absence of a full PC-RPLND (p = 0.002) were independent predictors for recurrence with viable NSGCT. Based on these three adverse predictors, a prognostic index was developed with favorable patients having no risk factors, intermediate prognosis patients with one risk factor, and poor prognosis patients having 2 or more risk factors. Favorable, intermediate, and poor prognosis patients had a 2-year progression free probability of 97% (95% CI 95–99%), 90% (95% CI 85–95%), and 66% (95% CI 54–78%), respectively (p &lt; 0.001). Conclusions: This data suggests that patients who have a high risk of reucrrence with viable GCT should undergo more frequent follow-up during the first 2-years with serum tumor markers and imaging. Additionally, this data suggests that an incomlete RPLND is not sufficient surgery for men with metastatic NSGCT. These men should undergo a bilateral RPLND. No significant financial relationships to disclose.