tbuckley/cabot-search huggingface dataset:
<sup>99m</sup>Tc-EC-DG: A novel tracer for tumor imaging
Authors: J. L. Bryant, D. J. Yang, N. R. Schechter, J. Y. Chang, S. Kohanim, A. Azhdarinia, D. Yu, R. Mendez, C. Oh, E. E. Kim
Journal: Journal of Clinical Oncology (2005)

2021 Background: The aims were to study 1) mechanisms of cellular uptake and 2) biodistribution of 99mTc-ethylenedicysteine-glucosamine (EC-DG) in animals and humans. Methods: To evaluate if 99mTc-EC-DG is involved in cell nuclei activity, in vitro thymidine incorporation and cell cycle assays of EC-DG were conducted using lung and breast cancer cells. Biodistribution of 99mTc-EC-DG in lung-tumor bearing mice (0.5–4 hrs, 1 μCi/mouse, iv) was used to estimate radiation absorbed dose. Autoradiograms of 99mTc-EC-DG and 18F-FDG were compared in nude mice bearing uterine sarcoma. Rabbits inoculated with VX-2 cells were imaged with 99mTc-EC-DG and 99mTc-EC. For therapeutic assessment studies, scintigraphic imaging studies with 99mTc-EC-DG in mammary tumor-bearing rats were conducted at various days after treatment with paclitaxel and cisplatin. The imaging findings were correlated immunohistochemical assays (mRNA expression, apoptosis and cell cycle changes in tumor) and flow cytometry analysis was performed. Biodistribution of 99mTc-EC-DG was performed in patients with non-small cell lung cancer. Radiation dosimetry was assessed using the MIRD method. Results: In vitro cellular uptake assays indicated that cell nuclei activity could be assessed by 99mTc-EC-DG. Scintigraphy and autoradiograms in animal models demonstrated the tumor could be clearly visualized by 99mTc-EC-DG. The efficacy of paclitaxel and cisplatin treatment in rodent models could be assessed using tumor/muscle ratios. Immunohistochemical staining indicated reduced expression of bFGF and increased apoptosis and cell cycle changes after paclitaxel and cisplatin treatment. The critical organ in human was the kidneys with an average radiation absorbed dose over all seven patients of 1.23E-02 mGy/MBq. The average total body absorbed dose was 2.35–03 mGy/MBq (2.61E-01 cGy/1110 MBq). Conclusions: 99mTc-EC-DG is involved in cell nuclei activity and could assess of therapeutic tumor response in animals. The novel 99mTc-EC-DG is safe and promising as a molecular imaging agent. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell Point LLC
Gleevec (imatinib mesylate): A potential new oral chemotherapeutic agent for the treatment of meningiomas
Authors: Vinay Gupta, Thomas C. Chen
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5978 

Meningiomas are the second most common CNS tumors, and are mostly benign in nature. However, as much as 20% cases show aggressive behavior and therefore, are not entirely curable by surgery or radiotherapy, leading to recurrences and increased morbidity. For such cases, chemotherapy in the form of hydroxyurea or RU486 has proven inadequate, and no clear benefit has been observed, especially in the recurrent cases. This prompted us to investigate new targets for chemotherapeutic intervention. There is a substantial body of work suggesting the role of aberrant platelet derived growth factor (PDGF) signaling pathway in the pathogenesis of meningiomas. We have performed immunohistochemical staining in a set of 18 meningioma cases, and found expression for both the PDGF-A and the PDGFR-α. Our hypothesis is that selective small molecule PDGF receptor tyrosine kinase inhibitors such as Gleevec may be used in the treatment of meningiomas. Primary cultures of meningiomas were established from surgical specimens, and stained for EMA, Vimentin and S-100 to confirm their origin. Gleevec was used to treat primary meningioma cultures in-vitro. MTT assay demonstrated dose dependent decreased proliferation rate of meningioma cells upon treatment with Gleevec over a period of 48 hours. Gleevec treatment also induced apoptosis, as demonstrated by TUNEL assay at doses of 12 μM at 36 hours duration, and increased the population of cells in the subG0 component to 35% as compared to 8% in the untreated cells. There were no changes in the cell cycle distribution. Our results indicate the need for further exploration for Gleevec as a potential treatment for meningiomas.
Kidney-specific Sonoporation-mediated Gene Transfer
Authors: Ryo Ishida, Daisuke Kami, Tetsuro Kusaba, Yuhei Kirita, Tsunao Kishida, Osam Mazda, Takaomi Adachi, Satoshi Gojo
Journal: Molecular Therapy (2015)

Sonoporation can deliver agents to target local organs by systemic administration, while decreasing the associated risk of adverse effects. Sonoporation has been used for a variety of materials and in a variety of organs. Herein, we demonstrated that local sonoporation to the kidney can offer highly efficient transfer of oligonucleotides, which were systemically administrated to the tubular epithelium with high specificity. Ultrasonic wave irradiation to the kidney collapsed the microbubbles and transiently affected the glomerular filtration barrier and increased glomerular permeability. Oligonucleotides were passed through the barrier all at once and were absorbed throughout the tubular epithelium. Tumor necrosis factor alpha (TNFα), which plays a central role in renal ischemia-reperfusion injury, was targeted using small interfering RNA (siRNA) with renal sonoporation in a murine model. The reduction of TNFα expression after single gene transfer significantly inhibited the expression of kidney injury markers, suggesting that systemic administration of siRNA under temporary and local sonoporation could be applicable in the clinical setting of ischemic acute kidney injury.
Treatment Patterns and Disease Burden of Stage Iiib/Iiic Melanoma in France, Germany and the Uk
Authors: P. Mohr, M. Harries, F. Grange, R. Ehness, L. Benjamin, O. Siakpere, L. McLeod, S. Wolowacz, J.A. Kaye, I. Kontoudis
Journal: Annals of Oncology (2014)
Low risk for symptomatic venous thromboembolic events (vte) during cytokine administration for peripheral blood stem cell mobilization
Authors: H. V. Naina, R. K. Pruthi, M. R. Litzow, S. M. Ansell, A. Dispenzieri, W. J. Hogan, M. A. Gertz, M. A. Elliott, D. A. Gastineau, S. K. Kumar
Journal: Journal of Clinical Oncology (2009)

7039 Background: Erythropoiesis-stimulating agents are known to increase the risk for VTE events, especially in patients with underlying malignancies. However, there is a paucity of information on other hematopoietic growth factors such as granulocyte colony-stimulating factor (GSCF) granulocyte-macrophage colony stimulating factor (GM-CSF) AMD 3001 and risk for VTE. Methods: Between January 2000 and October 2008, a total of 631 patients underwent peripheral blood stem cell mobilization (PBSCM) using either GCSF, GMCSF, cyclophosphamide, AMD 3100, or with any of the above combination. We included only patients with a diagnosis of AL amyloidosis (AL), multiple myeloma (MM) Hodgkin's lymphoma (HL) and non Hodgkin's lymphoma (NHL). Patients’ demographic details and diagnosis of VTE were collected from electronic medical records. Results: Of the 631 patients who underwent PBSCM the median age of the patients was 57 years (range 17–77). 448 patients (71%) received single agent GCSF, 82 (13%) received combination of GMCSF and cyclophosphamide, 52 (8%) received cyclophosphamide and GCSF, 30 patients received a combination of GMCSF and GCSF, 10 (1.5%) patients received GCSF and AMD 3100. Of the 631 patients, 278 (44%) MM, 209 (33%) NHL, 114 (18%) AL, and 20 (3%) had HL. We found 7 (1.1%) patients with symptomatic VTE occurring between administration of growth factors and stem cell transplant. The median duration from the administration of growth factors to detection of VTE was 5 days (range 1–30). Two AL,3 MM and 2 NHL. Of the 7 patients, 2 patients had pulmonary embolism and 1 patient developed deep vein thrombosis. Two patients with AL developed heparin induced thrombocytopenia (HIT). The remaining 4 patients developed symptomatic catheter related thrombosis. Only 1 patient had past history of VTE. Of the 7 patients, 5 received GCSF alone, 1 received GMCSF, and cyclophosphamide, 1 received GCSF and cyclophosphamide. Of the 4 patients who developed catheter related thrombosis, catheter was removed in 2 patients. None of the patients developed VTE related morality. Conclusions: The risk for symptomatic VTE during PBSCM is low. HIT should be considered as a possible cause for VTE in patients undergoing PBSCM. No significant financial relationships to disclose.
CD24 expression and breast cancer stem cell phenotype
Authors: G. Rappa, F. Anzanello, A. Lorico
Journal: Journal of Clinical Oncology (2009)

11106 Background: Several studies suggest the existence of breast cancer-initiating cells (BCIC), responsible for tumor development and progression. Initial reports that only the CD44 + CD24 −/low subpopulation contains BCIC have been challenged by subsequent studies. We examined the relationship between CD24 and biological properties of breast cancer cells. Methods: MA-11 breast carcinoma cells, originating from bone marrow micrometastases, are CD44 + and have an heterogeneous expression of CD24 (214,000/cell; range 0–1,120,000). We have previously reported that upon in vitro culture as mammospheres under stem cell-like conditions, MA-11 cells acquired increased tumorigenicity and a CD44 + CD24 −/low phenotype. We have now investigated the relationship between CD24 expression and tumorigenicity in the MA-11 model. Results: Upon passage of MA-11 mammospheres in adherent culture, cells rapidly re-expressed CD 24. The rapid increase in CD24 was consistent with antigen up-regulation, not selection of CD24 −/low cells. Exposure of adherent MA-11 cells to imatinib for 72h resulted in a reversible decrease in CD24 from 214,000 to 15,800/cell. CD44 + CD24 −/low cells, sorted by flow cytometry, generated CD44 + CD24 high , and CD44 + CD24 high generated CD44 + CD24 −/low . Immediately after sorting, &gt;90% CD44 + CD24 −/low cells were in G0/G1. After 24–48 h in culture, cell cycle distribution, growth rate and invasiveness of the sorted cell populations were equivalent. Upon injection and s.c. growth, CD24 expression of CD44 + CD24 −/low populations and clones increased from 10,000 to 220,000/cell. Similarly, CD44 + CD24 −/low clones derived from human MCF-7 breast carcinoma cells formed tumors containing &gt;99% CD44 + CD24 high cells. The average number of CD24 per cell was equivalent for tumors formed upon injection of CD44 + CD24 −/low , CD44 + CD24 + , mammosphere-derived cells or parental adherent MA-11 cells. The tumorigenic potentials of sorted CD44 + CD24 −/low , CD44 + CD24 −/low sub-populations and clones in nu/nu mice were equivalent. Conclusions: CD44 + CD24 −/low breast cancer cells are not associated with increased tumorigenicity; the high CD24 level of mouse xenografts derived from both CD44 + CD24 −/low and CD44 + CD24 hi breast cancer cells suggests an important role for CD24 in tumor growth. No significant financial relationships to disclose.
Abstract 200: Regional Difference in Emergency Medical Services Dispatcher Cardiopulmonary Resuscitation Prearrival Instructions for Patients with Out-of-Hospital Cardiac Arrest in Japan
Authors: Hiroyuki Hanada, Mamoru Hase, Naohiro Yonemoto, Hiroshi Nonogi, Ken Nagao, Takeshi Kimura
Journal: Circulation (2012)

[Background] The 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommend that dispatchers should recommend cardio-pulmonary resuscitation (CPR) for unresponsive patients who are not breathing normally. This guideline also recommended special education for dispatchers. Every regional medical control system (the organization which was specially designed for presenting protocols to regional emergency medical system (EMS) and evaluating EMS operation) created dispatcher protocols to recognize cardio-pulmonary arrest and to helping CPR by bystander from July 2009 in Japan. Unfortunately, dispatchers in every regional emergency EMS could not be always specially educated. [Goal] To evaluated regional difference in EMS dispatch prearrival CPR instruction for patients with out-of-hospital cardiac arrest (OHCA). [Methods and Results] From January 1, 2005, through December 31, 2010, we conducted a prospective, population-based, observational study involving the consecutive patients across Japan who had OHCA (n=670,314). Dispatcher recommended CPR increased year by year, 33.8% of OHCA during 2005, 37.7% during 2006, 41.7% during 2007, 44.3% during 2008, 45.3% during 2009 and 46.3% during 2010 across Japan. Regional differences were shown in the figure. [Conclusion] Although EMS dispatch CPR has been increased year by year, bystander CPR recommended by EMS dispatcher has been still less than 50% of all OHCA in Japan. There were regional differences in recommendation of CPR by dispatcher across Japan. Both EMS recommendation of CPR and CPR by bystander responding to EMS recommendation were lowest in Tokyo metropolitan area. Certain detailed protocols which can be done easily even after small amount of educational time for EMS dispatcher are needed.
Abstract 17905: Association of Microalbuminuria and Cystatin C for Mortality Among Nationally Representative Population with Normal Creatinine-based Estimated Glomerular Filtration Rate
Authors: Sandip K Zalawadiya, Vikas Veeranna, Chirag Bavishi, Luis Afonso
Journal: Circulation (2012)

Background: Limited information is available about the combined effect of higher Cystatin C (CysC) levels and presence of microalbuminuria (MA) for mortality prediction among nationally representat...
Abstract #5563: Superior in vivo antitumor activity of tubulin polymerization inhibitor IRC-083927 relative to anticancer drugs in a panel of human tumor xenografts
Authors: Philip Kasprzyk, Mark Carlson, Jeffrey Lauer, Ann Savola, Anne-Marie Liberatore, Sylvia Julien, Olivier Dutruel, Chantal Soulard, Florence Meyer-Losic, Caroline Touvay, Gregoire Prevost
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

The synthetic small molecule IRC-083927 inhibits tubulin polymerization by a direct binding to the colchicine binding site of tubulin. IRC-083927 inhibits in vitro cell growth of drug resistant cell lines in the very low nanomolar range ( Liberatore et al, MCT, 2008). Therefore, IRC-083927 was tested in animal models bearing human cancers where there are very high unmet medical needs. High potency and efficacy of IRC-083927 was shown using chronic oral treatment (2.5 or 5 mg/kg over a 28 day period) in all tested models. IRC-083927 is more efficient than: 1) Velcade against the human myeloma, RPMI-8226, 2) ABT-751 against androgen independent prostate cancer PC-3, 3) Gemcitabine against pancreatic cancer, MIA PaCa-2, and 4) Combretastatin CA4P or ABT-751 against human hormone-independent breast cancer, MDA-MB-231. No signs of toxicity have been observed in mice with this regimen. Chronic exposure of rats to IRC-083927 at the maximum tolerated dose induced significant reduction of the gastric emptying and a slight decrease of white blood cells. Together, the impressive in vivo antitumor effects induced by IRC-083927 on anticancer drug resistant tumor models associated with limited adverse side effects strongly support further investigations to evaluate its potential for the treatment of advanced cancers, particularly those resistant to current clinically available drugs.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5563.
UGT1A1 promoter genotype correlates with pharmacokinetics but not toxicity in patients receiving protracted irinotecan (IRN)
Authors: C. F. Stewart, J. C. Panetta, M. O’Shaughnessy, S. Throm, T. Liu, C. Billups, A. Gajjar, W. L. Furman, L. M. McGregor
Journal: Journal of Clinical Oncology (2006)

3078 Background: Recent USFDA recommendations include a dosage adjustment for patients who are homozygous for the UGT1A1*28 allele (i.e., 7 TA repeats in the promoter) due to an increase in neutropenia when those patients receive IRN. However, this recommendation was based upon data from adults treated with high IRN dosage (e.g., 350 mg/m 2 ). This study evaluates the relationship between UGT1A1 promoter genotype and phenotype (i.e., SN-38 glucuronidation and IRN toxicity) in patients treated with low-dose, protracted IRN. Methods: 31 children treated on 2 institutional protocols received low dosage (20 to 60 mg/m 2 ) i.v. IRN daily for 5 days of 2 consecutive weeks. PK sampling and UGT1A1 genotyping were performed during cycle 1. Patients were designated as 6/6, 6/7, or 7/7 depending on the number of TA repeats in the UGT1A1 promoter region. All patients were evaluable for gastrointestinal and hematological toxicity, primarily grades 3 and 4 neutropenia and diarrhea. Results: The frequencies of 6/6, 6/7, and 7/7 genotypes were 9/31 (29%), 15/31 (48%), and 7/31 (23%), respectively. Patients with 7/7 genotype had a statistically greater baseline bilirubin than patients with 6/6 or 6/7 genotype (p&lt;0.03), but the difference was not considered clinically significant. In females, the SN-38:IRN AUC ratio was greater in patients with 7/7 vs. 6/6 or 6/7 genotype (0.15 vs. 0.05 vs. 0.09;p&lt;0.005). Similarly the SN-38G:SN-38 ratio was less in females with 7/7 vs. 6/6 or 6/7 genotype (1.5 vs. 4.1 vs. 3.5;p&lt;0.03). Patients with 7/7 genotype did not have a greater incidence of diarrhea (0/7) or neutropenia (0/7) than patients with 6/6 (3/9 with diarrhea, 2/9 with neutropenia) or 6/7 (3/15 with diarrhea, 1/15 with neutropenia) genotype. Conclusions: Although female patients with a 7/7 genotype did have altered SN-38 disposition, toxicity was not increased in patients with the 7/7 genotype treated with a low dose protracted schedule of irinotecan. Therefore, no dosage adjustment for genotype is indicated with this IRN dosing schedule. No significant financial relationships to disclose.
Abstract 9412: Vasopressin V2 Receptor Antagonist Tolvaptan Prevents The Development of Chronic Heart Failure via Its Anti-inflammatory and Anti-fibrotic Actions
Authors: Takanori Yamazaki, Yasukatsu Izumi, Yasuhiro Nakamura, Takehiro Yamaguchi, Akihisa Hanatani, Kenei Shimada, Hiroshi Iwao, Minoru Yoshiyama
Journal: Circulation (2012)

Introduction: Arginine vasopressin (AVP), which promotes the reabsorption of renal water via the AVP V2 receptor, is overexpressed in chronic heart failure (CHF). A non-peptide V2 receptor antagonist, tolvaptan (TLV), induces aquaresis without affecting electrolyte. A recent clinical study indicates that the TLV-treated patients had significantly lower rates of mortality or hospitalization for worsening heart failure than those administered the placebo. Hypothesis: TLV has more beneficial effects than furosemide (FRS), a loop diuretic, on CHF after myocardial infarction (MI). Methods: Ten weeks after MI induction, rats were divided into 3 groups (n=9-10) adjusted to the infarct size as determined by echocardiography: a vehicle group (V), a group treated with 15 mg/kg/day of FRS (F), a group treated with 10 mg/kg/day of TLV (T). Control rats were subjected to a sham operation, and each treatment agent was administered for four weeks. After treatment, we compared the effects of TLV with FRS in hemodynamics, cardiac function, inflammation, and fibrosis. Results: Although no significant intergroup differences were noted in the blood pressure, heart rate and infarct size, echocardiographic study revealed that both end-diastolic and systolic volumes in the T group was lower levels than those in the V group (P&lt;0.01). The ejection fraction was also improved in the T group (p&lt;0.05) but not in the F group, compared with the V group. TLV treatment significantly attenuated MI-induced interstitial fibrosis and macrophage infiltration in the marginal area of the infarct by sirius red staining and and ED-1 immunostaining (p&lt;0.01, respectively), but FRS did not affect them. Compared with the V group, mRNA expressions of atrial natriuretic peptides, brain natriuretic peptides, monocyte chemotactic protein-1, and transforming growth factor-β1 were significantly attenuated in the marginal area of the T group (approximately 60%, 50%, 36%, and 35% decrease, p&lt;0.05, respectively). In contrast, FRS failed to decrease the expressions. Conclusions: Tolvaptan may prevent cardiac remodeling in CHF. This effect may be attributed to its volume-reducing effect as well as its anti-inflammatory and anti-fibrotic actions.
Constitutive Activation of mTORC1 in Endothelial Cells Leads to the Development and Progression of Lymphangiosarcoma through VEGF Autocrine Signaling
Authors: Shaogang Sun, Song Chen, Fei Liu, Haige Wu, Jonathan McHugh, Ingrid L. Bergin, Anita Gupta, Denise Adams, Jun-Lin Guan
Journal: Cancer Cell (2015)
The occurrence of hyponatriemia in SCLC and the influence on prognosis. A retrospective study of 468 patients treated in single institution in a 10-year period
Authors: O. Hansen, P. Sorensen, K. H. Hansen, E. Holtved
Journal: Journal of Clinical Oncology (2006)

7091 Background: Hyponatriemia is very often seen in SCLC due to the paraneoplastic syndrome SIADH. Hyponatriemia has been found to be associated with poorer outcome in some but not in the majority of published studies. This study was performed to investigate the prognostic value of hyponatriemia in SCLC. Methods: Data from the patient files from 468 patients diagnosed with SCLC and treated at Odense University Hospital 1995 to 2005. In the 444 cases data on the initial S-Na was available. A Cox multivariate analysis was performed including possible prognostic factors. Results: Stage: Extensive disease (ED) 283 (64%), limited disease (LD) 161 (36%). The standard chemotherapy was 6 cycles of carboplatin-etoposide. 70% of the patients with LD received thoracic radiotherapy, usually in a dose of 45 Gy/22–30 F and 49% received PCI usually as 25 Gy/11F. Median survival in ED 7.2 months with a 1 and 2-year survival rate of 21% and 6%. In LD the figures was 15.2 months, 65%, 31% and a 5-year survival rate of 16%. S-Na was &lt;125 mEq/L in 36 patients (8%), between 126–135 mEq/L in 158 (36%). 250 patients (56%) showed normal values of S-Na. In a Cox multivariate analysis, hyponatriemia was associated with poor prognosis. Other independent prognostic factors included LDH, gender, age, performance status and stage. Among non-significant factors were hemoglobin, WBC, and alkaline phosphatase. Conclusions: Hyponatriemia was a significant prognostic factor associated with poor prognosis with an odds ratio of 1.5 (p = 0.0013) if S-Na was 1.25–1.35 mEq/L and an odds ratio of 1.9 (p = 0.0008) if S-Na was &lt;1.25 mEq/L. [Table: see text] No significant financial relationships to disclose.