tbuckley/cabot-search huggingface dataset:
Effect of vorinostat (V)-loaded PLGA nanoparticles (NP) surface modified with a PSMA ligand on prostate cancer (PC) cells.
Authors: C. J. Hoimes, R. P. Murelli, W. K. Kelly, A. X. Zhang, C. J. Cheng, R. J. Fields, D. A. Spiegel, W. M. Saltzman
Journal: Journal of Clinical Oncology (2010)

e13629 Background: Polymeric NP can be tuned for controlled drug delivery and SM for cell-specific targeting. To overcome V concentration and time dependent reversible growth inhibition of PC cells, we designed a NP to deliver V to PC by polymeric NP that were SM with a ligand to prostate specific membrane antigen (PSMA). Methods: V was encapsulated in poly(lactic-co-glycolic acid) (PLGA) using oil in water emulsion. Pegylated (PEG) phospholipid was added to the aqueous phase for SM, electrostatic and steric stabilization, and longer circulation in vivo. For PSMA targeting, the lipid amino end was covalently modified to possess a glutamate urea with known pM Ki binding affinity to PSMA. Four NP designs were used in cytotoxicity assays : (1) V loaded PLGA NP (V-NP), (2) V loaded PLGA NP and PSMA functionalized (V-NP-PSMA), (3) no drug and PSMA functionalized NP (Bk-NP-PSMA), (4) V loaded and unmodified PEG phospholipid (V-NP-DSPE). LNCaP and PC-3 cells (104 /well) were cultured with V (0, 0.1, 0.5, 1, 5, 10, and 100 μM), or equivalent μM concentration of V-NP, V-NP-PSMA, Bk-NP-PSMA, V-NP-DSPE for up to 72hrs. Controlled release (CR) profiles were determined from incubation in PBS, cell proliferation was measured by MTT assay, and IC50 was calculated. Results: NP mean sizes were 110-130nm, and controlled release data show at least 50% release in 7 days and are ongoing. V loading of 9.5 μg V/mg PLGA was improved to over 150μg V/mg PLGA using the PEG phospholipid method. Nonlipid formulations yielded LNCaP IC50 of 8μM, whereas unencapsulated V and functionalized PEG phospholipid formulations yielded IC50 <1μM for LNCaP and PC-3. At 24hrs, V-NP-DSPE showed no cell kill in LNCaP (PSMA+) cells at concentrations of 10μM, whereas V-NP-PSMA did show suppression to less than 80% survival. By 48hrs, 10μM V-NP-PSMA induced complete cell kill compared to 40% survival in the V-NP-DSPE treated group. Conclusions: This novel SM NP design loads a high concentration of V and effective PC cell kill with non-inferior IC50 to unencapsulated drug. Ongoing studies involve characterizing the selective PSMA binding, controlled drug release properties, and optimizing these NP qualities by fraction of PEG phospholipid. No significant financial relationships to disclose.
Risk assessment and medical decision model for prophylaxis and treatment of hyperuricemia and tumor lysis syndrome (TLS): International expert panel analysis
Authors: M. S. Cairo, M. Cornelis, A. Baruchel, A. Bosly, B. Cheson, C. Pui, J. M. Ribera, S. Rule, A. Younes, B. Coiffier
Journal: Journal of Clinical Oncology (2007)

17006 Background: Hyperuricemia, a major component of TLS, has historically been prevented and treated using allopurinol and alkalinization, and recently managed effectively by rasburicase (recombinant urate oxidase) in children and adults at high risk of TLS. We sought to determine the risk factors associated with TLS and develop a risk adapted medical decision model for the prevention and treatment of hyperuricemia in TLS. Methods: TLS risk scoring was performed by an expert panel, based on an odds ratio evaluation of 68 patient characteristics and cancers with known TLS risk. The RAND Appropriateness Method (RAM) (1–3 inappropriate, 4–6 uncertain, 7–9 appropriate) was utilized to investigate the appropriateness of prevention and treatment in 92 different scenarios. All appropriateness ratios were validated using a set of 36 clinical cases. The strategies analyzed included no therapy, hydration (± diuretics [DI]), rasburicase, allopurinol, and allopurinol + alkalinization. Results: Risk factors (±SD) identified included age ≥ 60 years (1.6±0.5), decreased renal function (2.7±1.1), renal tumor infiltration (1.5±0.3), initial cytoreductive therapy (2.5±1.2), acute lymphoblastic leukemia with WBC ≥50x10 9 /L [Burkitt 8.6±5.3; pre-B 4.3±2.4; T-cell 4.6±2.8]; and non-Hodgkin lymphoma with LDH≥ 2x normal [Burkitt 6.6±3.0; lymphoblastic 3.2±2.8; diffuse large B-cell 2.4±1.9]. Hydration (± DI) was considered appropriate while no treatment and allopurinol + alkalinization were inappropriate in all scenarios. For prophylaxis, rasburicase was more appropriate than allopurinol (8.5±0.5 vs 4.9±2.1; p&lt;0.025) in patients with hyperuricemia and/or at high risk of TLS, whereas allopurinol was more appropriate than rasburicase (6.2±1.0 vs 4.9±1.9; p&lt;0.05) in those at low or moderate risk. In patients with TLS and normal urine output and uric acid, allopurinol and rasburicase were considered equally appropriate (5.0±0.9 vs 5.8±0.3). Conclusions: In summary, in addition to hydration (± DI), rasburicase is appropriate for patients at high risk of TLS and/or with hyperuricemia, and allopurinol for those with low risk of TLS and/or normal uric acid concentration. [Table: see text]
Evolutionary conservation of the chromosomal configuration and regulation of amylase genes among eight species of the Drosophila melanogaster species subgroup.
Authors: V Payant, S Abukashawa, M Sasseville, B F Benkel, D A Hickey, J David
Journal: Molecular Biology and Evolution (1988)

Nuclear DNA was extracted from each of the eight species comprising the Drosophila melanogaster species subgroup. Southern hybridization of this DNA by using a molecular probe specific for the alpha-amylase coding region showed that the duplicated structure of the amylase locus, first found in D. melanogaster, is conserved among all species of the melanogaster subgroup. Evidence is also presented for the concerted evolution of the duplicated genes within each species. In addition, it is shown that the glucose repression of amylase gene expression, which has been extensively studied in D. melanogaster, is not confined to this species but occurs in all eight members of the species subgroup. Thus, both the duplicated gene structure and the glucose repression of Drosophila amylase gene activity are stable over extended periods of evolutionary time.
A comparative study of cisplatin and vinblastine versus ifosfamide, cisplatin and vinblastine in non-operable non-small-cell lung cancer
Authors: P. Kosmidis, N. Mylonakis, D.V. Skarlos, E. Samantas, M. Beer, D. Theocharis, E. Zachariadis, A. Gioti, E. Papadakis, N. Poulakis, S. Parastatidis, G. Fountzilas
Journal: Annals of Oncology (1994)
Slow intravenous infusion of PV701, an oncolytic virus: Final results of a phase I study
Authors: S. J. Hotte, P. P. Major, H. W. Hirte, S. Polawski, M. K. Bamat, N. Rheaume, W. S. Groene, M. S. Roberts, J. A. Miller, R. M. Lorence
Journal: Journal of Clinical Oncology (2004)

3037 Background: PV701 is a non-recombinant, replication-competent Newcastle disease virus that targets tumor-specific defects in the interferon antiviral response. Methods: In the present phase I study of PV701 in advanced cancer patients (pts), the IV infusion rate of the 1st dose was decreased 18-fold, i.e., administration over 3 hrs compared to the 10 min bolus used previously [JCO 2002, 20:2251]. All other doses were given over 1 hr. A 3 wk cycle included 6 doses/2wks followed by 1wk rest. Dose 1 and doses 2–6 were escalated separately. Results: 18 pts (10M:8F) were enrolled and treated for a median of 6 cycles. The 1st dose was escalated from 12 billion plaque forming units (BPFU)/m2 up to the MTD of 24 BPFU/m2 with moderate fever and asymptomatic hypotension noted. Mild-to-moderate flu-like symptoms were the most common adverse events (AEs). These were attributed to elevated levels of plasma cytokines observed and were reduced in severity compared to the previous bolus dosing study. Doses 2–6 were escalated from 24 to 120 BPFU/m2 and were well tolerated. A reduced incidence and severity of AEs occurred with this repeat dosing, even when these doses were 5-fold higher than the first dose, indicating that the desensitization previously observed following bolus dosing was similarly induced following 3-hr infusion. All pts were seronegative at baseline and developed PV701 antibodies by 2 wks post dosing. In the 18 pts, there were 5 responses (PRs: 2 colorectal, 1 melanoma; minor responses: 2 carcinoid) with a median duration of 7 months. 61% of pts (11/18) had a time-to-progression of ≥4 months (range up to 14 months). These results correlate with preclinical findings that slowing the IV infusion rate 20-fold in mice completely abrogated the lethality at the previously determined LD-100, but did not negatively affect response rate. Conclusions: The results of this phase I trial indicate that slow IV infusion of PV701 over 3 hrs was well tolerated and preliminary evidence of efficacy was observed. These observations provide important dosing information for planned Phase II clinical studies and provide an example of the translation of preclinical testing into a successful clinical study. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Wellstat Biologics Corp. Wellstat Biologics Corp. Wellstat Biologics Corp.
A phase II trial of combination chemotherapy with topotecan and amrubicin in small cell lung cancer (SCLC).
Authors: N. Nogami, K. Kiura, N. Takigawa, S. Harita, K. Chikamori, T. Shibayama, M. Tabata, K. Hotta, T. Shinkai, M. Tanimoto
Journal: Journal of Clinical Oncology (2010)

7054 Background: We previously conducted a phase I trial of combination chemotherapy with topotecan and amrubicin for SCLC and found acceptable toxicity profiles with a favorable efficacy. The aim of this phase II trial was to further evaluate its efficacy and toxicity in this population. Methods: Primary endpoint was objective response. Thirty one chemo-naïve and 28 relapsed patients with SCLC were separately enrolled between 2004 and 2009. Topotecan and amrubicin were administered on days 1 to 5 and 3 to 5, every 3 weeks at doses of 0.75 and 35 mg/m2/day, respectively. Response and toxicity were assessed according to the RECIST guideline and NCI-CTCAE v3.0. Results: Demographics of the 59 pts were as follows: M/F:52/7, ECOG-PS 0/1/2:14/41/4, and smoker/non-smoker:54/5. A median numbers of courses administered were 4 and 3 in chemo-naïve and pretreated pts, respectively. Objective response was obtained in 23 (74%) of the 31 chemo-naïve and 12 (43%) of the 28 relapsed pts. Myelosuppresion was the principal toxixity with grade 4 leukopenia, neutropenia, thrombocytopenia and anemia of 46%, 80%, 25% and 7%, respectively. Grade 3-4 febrile neutropenia was observed in 41% of the pts, of whom one patient further developed Grade 5 septic shock. Other grade 3 or greater non-hematological toxicities included diarrhea, pneumonitis, vomiting, fatigue and hyponatremia in 2%, 3%, 5%, 9% and 2%, and one patient each developed fatal diarrhea and pneumonitis. At the time of data analysis with a median follow-up time of 43.2 months, MST and median PFS time were 14.9 and 5.3 months in the chemo-naïve pts and 10.2 and 5.1 months in the relapsed pts, respectively. Conclusions: This combination seemed effective for SCLC despite the moderate toxicity profiles. No significant financial relationships to disclose.
Kaposi's Sarcoma: A New Model in the Search for Viruses Associated With Human Malignancies2
Authors: G. Giraldo, E. Beth, P. Coeur, Ch. L. Vogel, D. S. Dhru
Journal: JNCI Journal of the National Cancer Institute (1972)

Tumor, lymph node, and skin biopsies of Kepesl's sercome (KS) patients were obtained from different high incidence areas of equatorial Africa and France. A total of 51 lines were established in tissue culture: 25 derived from tumor, 16 from lymph nodes, and 10 from skin biopsies. Long-term cultures had distinct, irregular growth patterns of cells, often noncontact-inhibited, with predominantly fibroblastoid or epithelioid characteristics. Cells were easily removed from the glass surface by trypsin and showed acid phosphatase and phagocytic activity to various degrees. Of 8 cultures (derived from cases of different regions) selected for study in greater detail, herpes-type viruses were observed in electron micrographs of 5. Comparative immunologic studies showed a common, precipitating, soluble antigen against human reference sera with high anti-cytomegalovirus (CMV) but low anti-Epstein-Barr virus (EBV) titers. In 4 cases, with high anti-EBV but low anti-CMV reactive sera from African Burkittts lymphoma patients, a common antigen was demonstrated. The possible implications of these results are discussed.
Abstract 13856: Plaque Echolucency of Carotid Artery is Useful for Assessment of Residual Cardiovascular Risk in Patients with Coronary Artery Disease after Achievement of LDL-C Goals on Statin Therapy
Authors: Manabu Uematsu, Takamitsu Nakamura, Mika Futamata, Tetsuji Mochida, Jun Nakamura, Wataru Sugamata, Juntarou Deyama, Daisuke Fujioka, Yukio Saitou, Yoshinobu Kitta, Ken-ichi Kawabata, Jun-ei Obata, Kiyotaka Kugiyama
Journal: Circulation (2012)

Ultrasound assessment of either intima-media thickness (IMT) or plaque echolucency of carotid artery is a surrogate for systemic atherosclerotic burden and provides prognostic information for coronary events. These parameters of the carotid artery change after lipid-lowering therapy using statin. This study examined hypothesis whether IMT and plaque echolucency of carotid artery may remain useful for prediction of coronary events in patients with coronary artery disease (CAD) after achievement of LDL- C goals (   Methods and Results:  Ultrasound assessment of carotid IMT and plaque echolucency with integrated backscatter (IBS) analysis was performed in 202 stable CAD patients with carotid plaques (IMT > 1.1 mm) and LDL-C levels    Conclusions:  Plaque echolucency but not plaque-IMTmax of the carotid artery had a predictive value and increased the predictability of coronary events in CAD patients with LDL-C
Cardiotoxicity of the experimental cytotoxic drug cyclopentenyl cytosine (CPEC) in rats
Authors: K. Schimmel, R. Bennink, A. Van Kuilenburg, N. Steinmetz, M. Van Den Hoff, M. Pfaffendorf, A. Verschuur, H.-J. Guchelaar
Journal: Journal of Clinical Oncology (2004)

2116 Background: Cyclopentenyl cytosine (CPEC) gave rise to unexpected severe cardiotoxicity leading to two toxic deaths in a phase I study (n=26). The aim of the present study was twofold; first we investigated whether the observed cardiotoxicity could be reproduced in in vitro and in vivo rat models. Secondly, we aimed at investigating the underlying mechanism. Methods: Effect on frequency and contractility was studied on isolated atria of 18 male Wistar rats upon incubation with CPEC (0.1 M; 1 M) and compared with controls (buffer solution). Effect on atrial blood pressure was studied in a pithed rat model (n=2) upon treatment with 1 and 10 mg/kg CPEC (bolus IV). The cardiac apoptosis inducing potential was studied in rats by 99mTc-Annexin V scintigraphy, followed by post mortem determination of radioactivity in tissues, histological confirmation with the TUNEL assay and immunohistochemical staining for cleaved caspase 3 and cytochrome C. Serum levels of the necrotic marker cardiac TroponinT were also determined. Results: No effect on heart frequency and arterial blood pressure was found in the isolated atria and pithed rat model. A trend towards a decrease of contraction force was observed. Cardiac uptake ratios with scintigraphy were not increased upon CPEC treatment. A few late apoptotic cells could only be identified by the TUNEL assay in the highest CPEC dose group. Staining for the early apoptosis markers caspase 3 and cytochrome C did not not show any significant difference in apoptotic cells. No cytochrome C positive cells were detected. Cardiac Troponin T levels were not increased after CPEC treatment. Conclusions: CPEC does not affect heart frequency, arterial blood pressure or contraction force in the studied rat models. Moreover, we did not find any indication of CPEC induced apoptosis in rat heart tissue. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Theseus Imaging Division NHF: Dutch Heart Foundation
<i>PIK3CA</i> mutation analysis in recurrent breast cancer
Authors: C. X. Ma, L. Lin, F. Gao, T. Giuntoli, Y. H. Chia, Z. Guo, R. McDowell, M. Naughton, M. Watson, M. Ellis
Journal: Journal of Clinical Oncology (2009)

11041 Background: Mutations in PIK3CA (encoding p110α catalytic subunit of phosphatidylinositol-3-kinase) are among the most common genetic events identified in breast cancer but the role of these mutations in determining the clinical course of the disease is uncertain. Furthermore the frequency of PIK3CA mutation in metastatic breast cancer samples has not been adequately studied but is an important concern in the design of studies with novel agents designed to inhibit mutant PIK3CA. Methods: We have established a tumor banking protocol for patients (pts) with metastatic breast cancer. In this study, we performed a mutational analysis of exons 9 (HD) and 20 (KD) of the PIK3CA using tumor DNA obtained from pts with recurrent disease and correlated mutational status with clinicopathological features and prognosis. Results: Biopsies were obtained from sites of recurrence in 51 pts with stage 4 disease. The median F/U was 44 (range: 0.9–239) months and death has occurred in 66%. Mutations in PIK3CA were identified in 24.5% (11.3% in HD and 13.2% in KD). PIK3CA mutation was significantly correlated with lower tumor grade (47% in grade 1/2 vs 8% in grade 3, p=0.004), positive ER (35% in ER+ vs 5% in ER-, p=0.017), and PR (37% in PR+ vs 5% in PR-, p=0.011). Overall survival (OS) was 139.5 and 53.7 months for mutation- and non-mutation- carriers respectively (p=0.014). Conclusions: About one quarter of pts with recurrent/advanced breast cancer carry PIK3CA mutations in samples of recurrent disease, which correlated with positive ER/PR status and a more indolent clinical course. These patients are good candidates for experimental protocols that combine endocrine agents with PI3 kinase inhibitors but the slower kinetics of disease progression in PIK3CA mutation carriers may have to be taken into account for statistical designs and power size calculations. No significant financial relationships to disclose.
腫瘍ワクチン接種を目的としたミュータノーム(Mutanome)の利用
Authors: C Castle John, Kreiter Sebastian, Diekmann Jan, Loewer Martin, Van De Roemer Niels, DE Graaf Jos, Selmi Abderraouf, Diken Mustafa, Boegel Sebastian, Paret Claudia, Koslowski Michael, N Kuhn Andreas, M Britten Cedrik, Huber Christoph, Tuereci Oezlem, Sahin Ugur
Journal: Cancer Research (2012)
The effect on survival of initial chemotherapy in advanced breast cancer: polychemotherapy versus single drug.
Authors: D L Ahmann, D J Schaid, H F Bisel, R G Hahn, J H Edmonson, J N Ingle
Journal: Journal of Clinical Oncology (1987)

Since current clinical trials assessing new agents occur in patients with advanced breast cancer having failed one and sometimes many polychemotherapy programs, these new agents may not be given a fair trial. In an effort to assess the possibility of using an alternative study design, we analyzed older clinical trials that used a controlled study design, randomizing between a single new drug and an established polychemotherapy program with a cross-over design upon failure. We were interested in noting that the pooled data did display a slight survival advantage (median 3.7 months) for the group receiving polychemotherapy as initial therapy. The survival distributions were clearly not significant using the log rank test, but did approach significance using the Smirnov. It is apparent that, while some slight advantage does occur for that group of patients receiving initial polychemotherapy, the magnitude of this effect is not great and is short in duration. Serious consideration should be given to the assessment of new agents as first-line therapy, particularly should they have a unique mode of action or lessened morbidities or toxicities.
Science, Language, Intuition, and the Many Meanings of Quality of Life
Authors: George P. Browman
Journal: Journal of Clinical Oncology (1999)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.6.1651 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10561200 Science, Language, Intuition, and the Many Meanings of Quality of Life George P. BrowmanxGeorge P. BrowmanSearch for articles by this author Show More McMaster University, The Program in Evidence-Based Care, Cancer Care Ontario, Hamilton, Ontario, Canada https://doi.org/10.1200/JCO.1999.17.6.1651 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
The role of surgery in high-risk gestational trophoblastic disease patients
Authors: S. N. Lewin, R. A. Soslow, M. J. Kim, F. A. Derosa, N. R. Abu-Rustum, Y. Sonoda, C. L. Brown, M. S. Baines, R. Flores, C. A. Aghajanian
Journal: Journal of Clinical Oncology (2007)

5541 Background: A survival rate of 81% has been reported in high-risk gestational trophoblastic disease (GTD) patients (pts) treated with multi-agent chemotherapy. We describe the surgical management in heavily treated pts with high-risk GTD. Methods: A retrospective chart review was performed of all pts receiving treatment for GTD at our institution from 1996–2006. High-risk pts who underwent surgery were selected. Results: Over the 10 year period, 32 pts with a median of two prior chemotherapy regimens (range 1–5) underwent 43 surgical procedures. 14 pts (44%) with undesired future fertility had hysterectomies to shorten their chemotherapy interval. 11 remain NED with median follow-up of 24 months (range 8–72). Surgeries to manage disease complications consisted of one craniotomy (for hemorrhage) and one laminectomy (for cord compression). Postoperatively the former received EMA/EP with interval hysterectomy followed by paclitaxel and carboplatin. She remains NED 75 months from diagnosis. The later died one month following laminectomy from pulmonary hemorrhage. Resection of solitary residual disease in chemotherapy refractory pts was attempted for cure in ten pts. Seven pts (70%) were cured following either thoracotomy with wedge resection or lobectomy (6) or radical abdominal trachelectomy (1) with median follow-up of 60 months (range 15 to 84). Of the remaining three, one developed brain metastasis following thoracotomy and was ultimately cured with EMA/EP. The other two with metastatic placental site trophoblastic tumor (PSTT) progressed and died, one and 60 months post-procedure. Planned hysterectomy due to non-metastatic PSTT was performed in two pts as their sole treatment. Both remain NED 19 and 26 months later. An additional seven PSTT pts had hysterectomies following EP/EMA treatment for metastatic disease. Three (43%) of the hysterectomy specimens had no residual disease. All required no further treatment and remain NED with median follow-up of 60 months (range 13 to 84 months). Conclusions: Surgical intervention during the management of high-risk GTD can be tailored to control disease complications, remove chemotherapy resistant disease or serve as therapy for PSTT. A multidisciplinary approach in specialized centers familiar with this disease entity is preferred. No significant financial relationships to disclose.