bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3703: Nanoparticle-induced targeted pro-apoptotic peptide in glioblastoma
Authors: Agemy Lilach , Morvinski Dinorah Friedmann , Kotamraju Venkata Ramana , Sugahara Kazuki N. , Verma Inder M. , Ruoslahti, Erkki 
Published: February 2011

Abstract
Glioblastomas multiforme (GBM) are the most common and lethal form of intracranial tumors. They account for approximately 70% of the 22,500 new cases of malignant primary brain tumors that are diagnosed in adults in the United States each year. Although relatively uncommon, malignant gliomas are associated with disproportionately high morbidity and mortality (median survival is only 12 to 15 months). Malignant gliomas are among the most vascular of human tumors. Tumor vasculature has proven to be particularly well suited as a site for receptor-based targeting. It expresses a multitude of molecules that are not expressed in the vessels of normal tissues. Our laboratory screens phage-displayed peptide libraries in vivo and ex vivo to discover specific targets in tumor vessels. One of the peptides, CGKRK (1) binds to the blood vessels in various kinds of tumors. Initial experiments showed that intravenously injected CGKRK peptide effectively homes to lentiviral (H-RasV12-sip53)-induced glioma in mice. We coupled the CGKRK peptide to the alpha-helical amphipathic peptide D[KLAKLAK]2, which is toxic to eukaryotic cells if it internalized into the cells (2). The chimeric peptide, when added to actively growing HUVEC or U87 glioma cells colocalized with mitochondria, whereas D[KLAKLAK]2 did not. Iron oxide nanoworms (NW) coated with the chimeric D[KLAKLAK]2-CGKRK peptide were 100-200-fold more toxic to the HUVEC and U87 cells than the free peptide in vitro and specifically accumulated in the blood vessels of glioma. Treatment of lentiviral induced glioma in mice with the D[KLAKLAK]2-CGKRK-PEG-NW inhibited tumor growth and showed a significant survival increase compared to control-treated mice.
1. Hoffman, J.A., et al. Progressive vascular changes in a transgenic mouse model of squamous cell carcinoma. Cancer Cell 4, 383-391 (2003).
2. Ellerby, H.M., et al. Anti-cancer activity of targeted pro-apoptotic peptides. Nat Med 5, 1032-1038 (1999).
*These authors contributed equally to this work
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3703.
Abstract 3707: Design and characterization of a double packaged system for localized drug delivery for the treatment of cancers
Authors: Williams Eva C. , Toomey Ryan , Gordon Marcia , Williams Donald , Morgan Dave , Alcantar Norma 
Published: February 2011

Abstract
This research aims at developing a drug delivery system that will provide a plethora of benefits such as cost effectiveness, reduction of toxicity and a control over the release of chemotherapeutic drugs in brain and ovarian cancer patients. We have designed a model drug delivery system consisting of non-ionic surfactant vesicles (niosomes) packaged within a biodegradable, temperature and pH sensitive hydrogel (chitosan) network. Optimization of the release rates were accomplished by altering the condition of its two components, chitosan and niosomes. Two main cancer drugs, Paclitaxel and Carboplatin, were used for encapsulation. It was found that medium molecular weight chitosan with a crosslinker: chitosan ratio of 4:1, which corresponded to a pH of 7.4, resulted in the finest controlled release. Surface characteristics, such as the interaction between the niosomes and chitosan were determined using Surface Forces Apparatus. The system was also tested in-vivo in mice models, where the success of the drug delivery has been measured by measuring the drug concentrations of the mice blood with respect to time and by analyzing shrinking effects in induced cancer tumors in mice. Xenogen was used to visualize the release of drugs in-vivo. Release rates of this system have been compared with other delivery methods. Our results will help in the development of low cost and improved methods for drug delivery with applications to brain tumors and intracavitary ovarian cancer treatments.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3707.
Abstract 371: Expression and circulating level of VEGFR-3 in renal cell cancer: Implication for antiangiogenic treatments
Authors: Spano Jean-Philippe , Khaled Wassef , Mouawad Roger , De La Motte Rouge Tibault , Vignot Stephane , Conforti Rosa , Khayat David 
Published: February 2011

Abstract
Background: Regional lymph node metastasis is a common event in solid tumors and is considered a marker for dissemination, increased stage, and worse prognosis. In renal cell cancer (RCC) lymphatic tumor spread exists, but, despite impressive therapeutic advances in metastatic RCC, including targeting of VEGF induced angiogenesis, data on the role of vegfr-3 that's appears to be the signaling pathway for tumor-induced lymphangiogenesis in RCC are rare. In this study, we analyzed the expression and the presence of the soluble VEGFR-3 form in 30 RCC patients and results were correlated with clinicopathological parameters. Patients and Methods: Tumor and sera from 30 RCC patients (20 clear cell (ccRCC) and 10 papillary (pRCC) were included in this study. The expressions of VEGFR-3 on tumor were evaluated by immunohistochemestry. Using ELISA assays, sVEGFR–3 were measured in sera of RCC patients in comparison to 20 healthy controls. Results: A high expression of VEGFR-3 was observed in more than 55% of the patients as compared to the negative control. Regarding circulating VEGF R-3 the level were variable in all samples, but, the median sVEGF- R3 level was significantly higher (p=0.005) in RCC patients as compared to healthy donors. An inverse correlation between VEGFR-3 expression & its soluble form was noted (r=-0.33 p=0.040).. However, when patients were divided into subgroups, the expression as well as the circulating form of VEGFR-3 were significantly higher in pRCC than ccRCC (p= 0.035 and 0.022 respectively). No significant correlation with lymph node status was observed. Furthermore, there was no correlation with any clinicopathological variable in the two subgroups. Conclusions: we showed that in renal cell cancer, VEGFR-3 is expressed and present as soluble form, a different expression pattern in ccRCC and pRCC exist. Therefore, any clinical treatment strategy designed to target lymphangiogenesis in RCC should differentiate between ccRCC and pRCC
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 371.
Abstract 3711: New neocryptolepine derivatives: Mechanism of cytotoxicity and the best substituent
Authors: Masashi Okada , Mei Zhen-Wu , Odawara Tomohito , Tominaga Taihei , Kudoh Takayuki , El-Sayed Ibrahim , Inokuchi Tsutomu , Seno Masaharu 
Published: February 2011

Abstract
Since cancer is one of the major causes of death all over the world, discovery of effective anticancer agents has long been desired. Plant alkaloids are often considered to be potent candidates. Cryptolepsis sanguinolenta is a medicinal plant which habits in West Africa. In a traditional medicine, a decoction of the root of C. sanguinolenta is used to treat fevers. Neocryptolepine, one of the plant alkaloids extracted from the root of C. sanguinolenta, are reported to have several activities such as DNA intercalation, anti-malaria and Topoisomerase inhibition. Topoisomerase (Topo) is double helical DNA relaxation enzyme and responsible for DNA replication, transcription and recombination. Inhibition of Topoisomerase is one of the mechanisms of anti-cancer agent. In this research, we synthesized a number of neocryptolepine derivatives with several substituents added to the backbone and evaluated their inhibitory activities of cell growth and topoisomerase.
The derivatives were synthesized from indole carboxylic acid methyl ester and aniline derivatives through well-known procedure. DNA relaxation activity of the derivatives was assessed on plasmid pBR322 DNA in the presence of TopoI or TopoII. Cell growth inhibition was assessed on six cancer cell lines; K562, LNCaP, MDA-MB-453, SKOv3, A549, and WiDr. Those cell lines were exposed to the derivatives for 72 hours and their 50% survival rate IC50 was estimated by MTT colorimetric assay. Although no derivative inhibited TopoII activity, 12 derivatives inhibited TopoI activity. The inhibition of TopoI by neocryptolepine derivatives appears to be caused by their planar organic constitution, which enable derivatives to intercalate into double helix of DNA. Cell growth inhibitory effect has been improved in some derivatives that received modification at their substituent. Those derivatives also exhibited TopoI inhibition correlating with inhibition of cell growth.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3711.
Abstract 3715: Potent cytotoxins and their prodrugs
Authors: Bajjurri Krishna Mohan , Goswami Rajib K. , Erigala Venkata Reddy , Liu Yuan , Liu Cheng , Sinha Subhash C. 
Published: February 2011

Abstract
Epothilones, dolastatins (auristatins), tubulysins, duocarmycins, and enediynes are among the most potent anticancer agents, which inhibit cell growth of cancer cells with a low or subnanomolar activity. Epothilones inhibit tumor growth by stabilizing the microtubules in a manner similar to Taxol. There are hundreds of natural and synthetic epothilones known, and some of them are undergoing clinical trials. One semisynthetic analog, ixabepilone, has also been approved for the treatment of metastatic breat cancer. Similarly, there are numerous dolastatins, their synthetic analogs - auristatins, and tubulysins known, of which auristatins are currently being developed by Seattle Genetics, Inc. These compounds also inhibit microtubules, however unlike epothilones and Taxol, they function by destabilizing the microtubules. The other compounds, duocarmycins and enediynes, cause toxicity by interacting with DNA; duocarmycins alkylate DNA whereas enediynes cleave. At least one enediyne antibody conjugate, Mylotarg (or Gemtuzumab ozogamycin), prepared from calicheamicin and targeted to CD33, is an approved therapy for the treatment of acute myeloid leukemia.
Not surprisingly, most of these naturally occurring compounds or their synthetic analogs also cause nonselective toxicities to the rapidly dividing normal cells, including those from hair follicles, bone marrow, and gastrointestinal lining. To minimize such indiscriminate toxicity, these compounds can be conjugated to tumor-targeting antibodies, as the case is with auristatins and calicheamicin. While we are developing antibody conjugates, we have also been focusing on a prodrug approach, in that the prodrugs can be activated selectively in tumor and tumor microenvironments by the endogenous tumor-associated proteases. Alternatively, an exogenous enzyme, such as aldolase antibody, 38C2, that are directed using low molecular weight inhibitors of the cell surface receptors overexpressed in tumor cells and tumor microenvironments, can also catalyze the prodrug activation. In this presentation, we will be discussing our studies toward the synthesis and evaluation of many of these cytotoxins and/or their prodrugs, especially those belonging to the auristatins. The prodrugs are targeting to integrins and/or proteases, and activated by the aldolase antibody or the tumor-associated proteases.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3715.
Abstract 3716: Targeted therapy of high-grade gliomas using TGF-beta2 inhibitor trabedersen (AP 12009): Results of the Phase IIb study as basis for the Phase III SAPPHIRE Study
Authors: Jachimczak Piotr , Schlingensiepen Karl-Hermann , Heinrichs Hubert , Bogdahn Ulrich ,   AP 12009 study group
Published: February 2011

Abstract
Background: High-grade gliomas (HGG) strongly overexpress TGF-beta 2. Trabedersen, a phosphorothioate antisense oligonucleotide is a TGF-beta 2 inhibitor administrated intratumorally using convection-enhanced delivery (CED). So far, clinical studies in HGG have included three Phase I/II studies and one randomized, active-controlled, open-label, multinational dose-finding Phase IIb study.
Methods: Main objectives of the Phase IIb study were to compare response rate, survival, and safety of 2 doses of trabedersen (10 µM or 80 µM) vs. standard chemotherapy (TMZ or PCV). 145 patients with recurrent or refractory HGG (AA WHO grade III or GBM WHO grade IV) were randomized. Trabedersen was given intratumorally by convection-enhanced delivery via a single multi-hole catheter with up to 11 treatment cycles (7-d-on, 7-d-off / cycle).
Results: As in the previous Phase I/II studies, treatment with trabedersen led to long-lasting remissions in patients with recurrent or refractory AA or GBM. Trabedersen showed a good tolerability and safety profile. Overall, 10 µM was superior to 80 µM trabedersen in both efficacy and safety.
Overall, the highest efficacy was observed in AA patients treated with the lower dose of trabedersen. The 10 µM trabedersen group showed a consistently higher survival rate compared to 80 µM trabedersen and standard chemotherapy (at 24 months: 83.3%, 53.3% and 41.7%, respectively). Duration of response was about 3 times longer in the 10 µM trabedersen group (29.1 months) compared to the standard chemotherapy group (8.0 months). The median overall survival was higher in both trabedersen groups than in the chemotherapy control group, with a remarkable survival benefit of 10 µM trabedersen over chemotherapy of 17.4 months.
In GBM patients, trabedersen was as efficacious as standard chemotherapy. Furthermore, in a prespecified subgroup (age ≤55 years, KPS &gt;80%), trabedersen patients had a markedly higher 2-year survival rate compared to standard chemotherapy (40.0 vs. 13.3%).
Conclusion and Outlook: Trabedersen treatment is safe and has a clear clinical benefit in HGG. A randomized, multinational and active-controlled Phase III study (SAPPHIRE) with trabedersen as monotherapy in patients with recurrent or refractory AA (WHO grade III) has started and patient enrollment is ongoing. In this pivotal study, patients are randomized either to treatment with 10 µM trabedersen or to standard chemotherapy (TMZ or BCNU).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3716.
Abstract 372: Circulating endothelial progenitor cell levels predict survival benefit in metastatic renal cell cancer patients treated with antiangiogenic agents
Authors: Farace Françoise , Gross - Goupil Marine , Tournay Elodie , Taylor Melissa , Hill Catherine , Escudier Bernard 
Published: February 2011

Abstract
Background: There is no validated biomarker to predict the efficacy of antiangiogenic therapy in patients with metastatic renal cell carcinoma (MRCC). We tested the hypothesis that circulating endothelial cells (CEC) and circulating endothelial progenitor cell (CEP) could predict clinical outcome in MRCC patients undergoing treatment with tyrosine kinase inhibitors (TKI). Methods: Fifty five patients (pts) with MRCC were monitored both at baseline and day 14 after anti-angiogenic treatment (46 pts received sunitinib and 9, sorafenib). CECs were measured in 1ml erythocyte lysed whole blood by four color flow cytometry (FCM) and identified by a CD45−CD31+CD1467-amino-actinomycin (7AAD)− phenotype. CEPs were measured in 10ml blood after progenitor cell enrichment and were identified by FCM as extremely rare events with a CD45dimCD34+VEGFR2+7AAD− phenotype. Relation between CEC and CEP levels and both response to TKI determined by RECIST criteria after 2 cycles with the Wilcoxon-Mann Whitney test, and progression free survival (PFS) and overall survival (OS) with the Cox model (Log-rank test). Results: CEC and CEP levels at both baseline and day 14 were not correlated to response to TKI. No correlation was found between baseline or day 14 CEC values and PFS or OS. However, pre-treatment CEP levels were correlated to PFS (p=0.01) and OS (p=0.01). Patients with elevated pre-treatment levels of CEP (&gt; 2% of circulating CD34+ cells) had an increased risk of tumor progression and poor prognosis. Changes in CEP levels between day 1 and day 14 were also correlated with PFS (p=0.03). Conclusion: Our results indicate that pre-treatment CEP levels could accurately predict survival in MRCC patients treated with TKI. If these data are confirmed, measurement of CEP levels before TKI therapy in MRCC patients will allow to identify patients who will benefit most from treatment and those who will need to be rapidly switched to another treatment.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 372.
Abstract 3726: Sexual function following surgery with or without intracavitary vaginal brachytherapy for early stage endometrial carcinoma
Authors: Quick Allison M. , Seamon Leigh G. , Fernandez Soledad , Salani Ritu , Paskett Electra , Martin Douglas 
Published: February 2011

Abstract
Objective: The purpose of this research study is to describe the effects of intracavitary vaginal brachytherapy (IVB) on sexual function and quality of life of women with early stage endometrial cancer.
Methods: 156 women, ages 20-75, with FIGO stage I to II endometrial cancer from 2002-2007 treated with surgery alone or surgery and IVB were identified and mailed questionnaires. Quality of life and sexual function were measured using the previously validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, the Cervix Cancer module, and the Sexual function-Vaginal changes Questionnaire. Pertinent data from prior surgery and radiation treatments were abstracted. Fisher's exact tests were used to evaluate the association of the variables.
Results: In total, 87 surveys (56%) were returned. 70 patients completed the survey, 17 in the IVB arm and 53 in the surgery alone arm. In general, the overall quality of life was excellent in both treatment arms, with few patients reporting anxiety, depression, pain, or limitations of activities of daily living. However, 12% of patients treated with IVB (2/17) reported difficulty controlling their bowels compared to 8% of surgery alone patients (4/53) (p=0.037) and 30% (5/ 17) vs. 13% (7/ 53) reported edema in one or both legs (p=0.040). 55% of respondents had not been sexually active in the previous month (11/17, 65% IVB and 27/52, 52 % surgery) (p=0.6). Of sexually active patients (45%, N=31), 43% of IVB (3/7) and 42% (11/26) of surgery alone patients complained of vagina dryness during sexual activity (p=0.935) and 29% (2/7) vs. 20 % (5/25) felt their vagina was short (p=0.635). While 29% in both cohorts reported vaginal tightness, 14% of patients in both treatment groups described intercourse as painful. Sexual activity was enjoyable for only 43% (3/7) of the IVB patients and 60% (17/28) of the surgery alone patients (p=0.549).
Conclusions: Overall the quality of life of women with early stage endometrial cancer is excellent following surgery or IVB. Patients treated with IVB report more bowel toxicity and lower extremity edema. Patients in both treatment arms report similar vaginal changes that affect sexual function. It is anticipated that additional data from other institutions participating in the study will allow more definitive exploration of these issues.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3726.
Abstract 3747: Polymorphisms of ERCC1 C118T and ERCC2 Lys751Gln predict response and prognosis of platinum-treated gastroenterology cancer patients: A finding of pooled meta-analysis
Authors: Yin Ming , Yan Jingrong , Abad Albert , Graziano Francesco , Lenz Heinz-Josef , Kim Hyo-Jin , Robert Jacques , Im Seock-Ah , Wang Wei-Shu , Wei Qingyi 
Published: February 2011

Abstract
The nucleotide excision repair (NER) pathway modulates platinum-based chemotherapeutic efficacy by removal of drug-produced damage to DNA. To determine if NER genes (ERCC1 and ERCC2) influence responses to platinum-based chemotherapies, we performed a meta-analysis in gastric and colorectal cancer for polymorphisms of ERCC1 C118T and ERCC2 Lys751Gln. The analysis included 1413 (451 Asians and 962 Caucasians) cancer patients, who were treated with the platinum-based regimen. The primary outcomes included therapeutic response (TR) as evaluated by complete response + partial response vs. stable disease + progressive disease, progression-free survival (PFS) and overall survival (OS). We calculated odds ratio [OR] or hazard ratio [HR] with 95% confidence intervals [CI] to estimate the risk or hazard in the dominant model. We found consistent and clinically substantial risk or hazard estimates for TR, PFS and OS in the platinum-treated gastroenterology cancer patients. For ERCC1 C118T, we found an ethnical discrepancy in the prognostic values, favoring a pronounced effect in Asians (TR: OR, 0.53 and 95% CI, 0.35-0.81 for four studies of 378 patients; PFS: HR, 1.69 and 95% CI, 1.05-2.70 for five studies of 504 patients; and OS: HR, 1.85 and 95% CI, 1.37-2.48 for four studies of 405 patients, compared with Caucasians: TR: OR, 0.98 and 95% CI, 0.44-2.19 for five studies of 638 patients; PFS: HR, 1.15 and 95% CI, 0.72-1.86 for five studies of 609 patients; and OS: HR, 1.22 and 95% CI, 0.49-3.05 for three studies of 347 patients). For ERCC2 Lys751Gln, the prognostic effect was observed in colorectal cancer for both ethnicities (overall patients: TR: OR, 0.41 and 95% CI, 0.26-0.66 for four studies of 437 patients; PFS: HR, 1.63 and 95% CI, 1.19-2.22 for six studies of 741 patients; and OS: HR, 2.08 and 95% CI, 1.29-3.34 for four studies of 479 patients). This significance remained in Caucasians (TR: OR, 0.41 and 95% CI, 0.23-0.73 for three studies of 249 patients; PFS: HR, 1.55 and 95% CI, 1.08-2.21 for five studies of 553 patients; and OS: HR, 1.64 and 95% CI, 1.23-2.18 for three studies of 291 patients). Based on these results, we concluded that ERCC1 C118T and ERCC2 Lys751Gln polymorphisms might be useful prognostic factors in platinum-treated gastroenterology cancer patients. Further clinical trials are warranted to confirm these findings. (Supported by NIH grants R01CA131274 and R01ES011470)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3747.