bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction and Preclinical Characterization of Fc-mGITRL for the Immunotherapy of Cancer
Authors: Hu Peisheng , Arias Robyn S. , Sadun Rebecca E. , Nien Yu-Chih , Zhang Nan , Sabzevari Helen , Lutsiak M.E. Christine , Khawli Leslie A. , Epstein Alan L. 
Published: January 2008

AbstractPurpose: To provide proper costimulation required for effective cancer T-cell immunity, Fc-GITRL fusion proteins were generated for use in immunotherapy protocols.Experimental Design: Soluble fusion proteins consisting of the Fc fragment of immunoglobulin and the murine glucocorticoid-induced tumor necrosis factor–related receptor ligand (mGITRL) connected with different linkers were genetically engineered and tested for their potency in two BALB/c solid tumor models.Results: In vivo, construct #178-14 (−5aa, −linker) showed the best activity (&gt;90% tumor reduction) at doses ranging from 5 to 25 μg and was found to be intact by gel electrophoresis. Similar doses used with construct #175-2 (-linker) produced good but not as high tumor regression. Construct #5-1 (+linker), which was found to be relatively unstable by SDS gel electrophoresis, produced &lt;60% tumor regression and required a higher dose (100 μg) to produce optimal results. Survival curves showed that Fc-mGITRL treatment extended the life of 80% of tumor-bearing mice to &gt;3 months compared with controls that died by day 40. T-cell depletion studies showed that CD8+ T cells play a major role in Fc-mGITRL immunotherapy, and tumors removed from Fc-mGITRL– and DTA-1–treated mice showed a significant influx of granzyme B+ lymphocytes compared with controls. Finally, T regulatory (Treg) cell assays showed that, unlike other Fc fusion proteins, all three Fc-mGITRL constructs profoundly suppressed Treg activity.Conclusions: These studies suggest that a stable, intact Fc-mGITRL fusion protein can provide missing costimulation for the immunotherapy of solid tumors. In addition, Fc-mGITRL may alter Treg activity to enhance its effectiveness for tumor immunotherapy.
A Novel Raji-Burkitt's Lymphoma Model for Preclinical and Mechanistic Evaluation of CD52-Targeted Immunotherapeutic Agents
Authors: Lapalombella Rosa , Zhao Xiaobin , Triantafillou Georgia , Yu Bo , Jin Yan , Lozanski Gerard , Cheney Carolyn , Heerema Nyla , Jarjoura David , Lehman Amy , Lee L. James , Marcucci Guido , Lee Robert J. , Caligiuri Michael A. , Muthusamy Natarajan , Byrd John C. 
Published: January 2008

AbstractPurpose: To date, efforts to study CD52-targeted therapies, such as alemtuzumab, have been limited due to the lack of stable CD52 expressing transformed B-cell lines and animal models. We describe generation and utilization of cell lines that stably express CD52 both in vitro and in vivo.Experimental Design: By limiting dilution, we have established several clones of Raji-Burkitt's lymphoma cell line that express surface CD52. Immunophenotype and cytogenetic characterization of these clones was done. In vivo usefulness of the CD52high cell line to evaluate the therapeutic efficacy of CD52-directed antibody was investigated using a SCID mouse xenograft model.Results: Stable expression of CD52 was confirmed in cells cultured in vitro up to 52 weeks of continuous growth. The functional integrity of the expressed CD52 molecule was shown using alemtuzumab, which induced cytotoxic effects in vitro in the CD52high but not the CD52low clone. Compared with control antibody, alemtuzumab treatment in CD52high inoculated mice resulted in significantly increased median survival. Comparable levels of CD52-targeted direct cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cytotoxicity and anti-CD52 immunoliposome-mediated delivery of synthetic oligodeoxyribo nucleotides in CD52high clone and primary B-chronic lymphocytic leukemia cells implicated potential in vivo application of this model for evaluation of CD52-targeted antibody and immunoliposomes encapsulating therapeutic agents.Conclusions: These results show the in vitro utility of the cloned Raji cell lines that stably express high levels CD52. The disseminated leukemia-lymphoma mouse model described herein using these stable cell lines can serve as an excellent system for in vivo therapeutic and mechanistic evaluation of existing and novel antibodies directed against CD52 molecule.
EMMPRIN Expression as a Prognostic Factor in Radiotherapy of Cervical Cancer
Authors: Ju Xing-Zhu , Yang Jin-Ming , Zhou Xiao-Yan , Li Zi-Ting , Wu Xiao-Hua 
Published: January 2008

Abstract
Purpose: Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN), a member of the immunoglobulin family and a glycoprotein enriched on the surface of many types of tumor cells, has been reported to be linked to invasion, metastasis, growth, and survival of malignant cells. Cervical cancer, the second most prevalent cancer in women worldwide and the fifth leading cause of cancer deaths, responds to radiotherapy variably, with 30% of cases recurring after therapy. The purpose of this study was to determine whether expression of EMMPRIN affects the response of cervical cancer to radiation therapy, and whether this membrane protein can be used as a prognostic marker for cervical cancer.
Experimental Design: The retrospective cohort study included 82 patients with invasive cervical cancer referred to the Department of Gynecologic Oncology at The Cancer Hospital of Fudan University (Shanghai) between 1991 and 2000. These patients were treated with brachytherapy at a dose of 15 Gy at point A before radical hysterectomy. Expression of EMMPRIN in cervical tumor specimens was examined by immunohistochemistry staining before and after brachytherapy and scored for both staining intensity and percentage of tumor cells stained. EMMPRIN immunoreactivity and clinicopathologic data were analyzed with respect to survival end points using univariate and multivariate approaches.
Results: The frequency of EMMPRIN overexpression was 52.4% in primary cervical cancer. After brachytherapy, EMMPRIN overexpression was significantly reduced (13.4%) compared with corresponding tumor before brachytherapy (P = 0.032). EMMPRIN expression was associated with pelvic lymph node metastasis (P = 0.026) and reduction in primary tumor volume following brachytherapy (P = 0.008). Although EMMPRIN expression before or after brachytherapy did not correlate with tumor-specific survival, but increased expression of EMMPRIN following brachytherapy tended to predict poor outcomes by univariate survival analysis (P = 0.0008). In addition, lymph vascular space invasion, deep stromal invasion, and lymph node metastasis were significantly associated with poor prognosis. In multivariate analysis, the independent prognostic factors for tumor-specific survival included the decreased expression of EMMPRIN after brachytherapy (P = 0.002; hazard ratio, 0.339; 95% confidence interval, 0.172-0.672) as well as lymph node metastasis (P = 0.044; hazard ratio, 2.053; 95% confidence interval, 1.020-4.133).
Conclusion: Expression of EMMPRIN was associated with a decrease in the reduction of cervical tumor following brachytherapy, and increased EMMPRIN expression after brachytherapy seemed to be an important predictor of poor survival in this patient cohort. Our study suggests that expression of EMMPRIN confers resistance to radiotherapy. Therefore, EMMPRIN expression in cervical cancer may be regarded both as a prognostic factor and a therapeutic target.
Effects of Plasmid-Based Stat3-Specific Short Hairpin RNA and GRIM-19 on PC-3M Tumor Cell Growth
Authors: Zhang Ling , Gao Lifang , Li Yang , Lin Guimiao , Shao Yueting , Ji Kun , Yu Hao , Hu Jiadi , Kalvakolanu Dhananjaya V. , Kopecko Dennis J. , Zhao Xuejian , Xu De-Qi 
Published: January 2008

AbstractPurpose: Persistent activation of signal transducers and activators of transcription 3 (Stat3) and its overexpression contribute to the progression and metastasis of several different tumor types. For this reason, Stat3 is a reasonable target for RNA interference–mediated growth inhibition. Blockade of Stat3 using specific short hairpin RNAs (shRNA) can significantly reduce prostate tumor growth in mice. However, RNA interference does not fully ablate target gene expression in vivo, owing to the idiosyncrasies associated with shRNAs and their targets. To enhance the therapeutic efficacy of Stat3-specific shRNA, we applied a combination treatment involving gene associated with retinoid-IFN–induced mortality 19 (GRIM-19), another inhibitor of STAT3, along with shRNA.Experimental Design: The coding sequences for GRIM-19, a cellular STAT3-specific inhibitor, and Stat3-specific shRNAs were used to create a dual expression plasmid vector and used for prostate cancer therapy in vitro and in mouse xenograft models in vivo.Results: The coexpressed Stat3-specific shRNA and GRIM-19 synergistically and more effectively suppressed prostate tumor growth and metastases when compared with treatment with either single agent alone.Conclusion: The simultaneous use of two specific, but mechanistically different, inhibitors of STAT3 activity exerts enhanced antitumor effects.
Rhabdoid Tumor Growth is Inhibited by Flavopiridol
Authors: Smith Melissa E. , Cimica Velasco , Chinni Srinivasa , Challagulla Kavitha , Mani Sridhar , Kalpana Ganjam V. 
Published: January 2008

Abstract
Purpose: Rhabdoid tumors are aggressive and incurable pediatric malignancies. INI1/hSNF5, a tumor suppressor biallelically deleted/inactivated in rhabdoid tumors, directly represses cyclin D1. Rhabdoid tumors and cells are exquisitely dependent on cyclin D1 for genesis and survival, suggesting that targeting the cyclin/cyclin-dependent kinase (cdk) axis may be an effective therapeutic strategy for these tumors. Because cdk inhibitors have not been used for preclinical or clinical testing on rhabdoid tumors, we investigated the effect of flavopiridol, a pan-cdk inhibitor with promising clinical activity, on rhabdoid tumors.
Experimental Design: The effect of flavopiridol on rhabdoid cells was tested in vitro using survival, cell cycle, and apoptosis assays. Its effect was assessed in vivo using xenografted rhabdoid tumor models. Immunoblot and immunohistochemical analysis was used to assess the effect of flavopiridol on cyclin D1 and p21 expression in vitro and in vivo, respectively.
Results: Nanomolar concentrations of flavopiridol inhibited rhabdoid cell growth (IC50 ∼200 nmol/L), induced G1 and G2 arrest, and apoptosis in vitro in a concentration-dependent manner. These effects were correlated with the down-modulation of cyclin D1, up-regulation of p21, and induction of caspase 3/7 activities. Flavopiridol (at 7.5 mg/kg) significantly inhibited the growth of xenografted rhabdoid tumors, and its effect was correlated with the induction of p21 and down-modulation of cyclin D1.
Conclusions: Flavopiridol is effective in inducing cell cycle arrest and cytotoxicity in rhabdoid tumors. Its effects are correlated with the down-regulation of cyclin D1 and the up-regulation of p21. Flavopiridol is potentially a novel chemotherapeutic agent for rhabdoid tumors.
Phase I Study of Alternate-Week Administration of Tipifarnib in Patients with Myelodysplastic Syndrome
Authors: Kurzrock Razelle , Kantarjian Hagop M. , Blascovich Michelle A. , Bucher Cindy , Verstovsek Srdan , Wright John J. , Pilat Susan R. , Cortes Jorge E. , Estey Elihu H. , Giles Francis J. , Beran Miloslav , Sebti Said M. 
Published: January 2008

Abstract
Purpose: To determine the safety and describe the antitumor activity of tipifarnib in patients with myelodysplastic syndrome (MDS) using an alternate-week schedule.
Experimental Design: Patients with MDS were given tipifarnib, escalating from 100 mg orally twice daily until the maximum tolerated dose for 8 weeks followed by maintenance therapy (same dose/schedule) for patients with stable disease or better.
Results: Sixty-three patients were treated. The most common toxicity was myelosuppression (60% of patients). Twenty percent of patients had no side effects. Nonhematologic toxicities included fatigue (20%), skin rash (9%), diarrhea (16%), increase in liver transaminases (14%) and bilirubin (11%), and nausea (11%). Dose-limiting toxicities of ataxia (n = 1), fatigue (n = 1), nausea (n = 1), and neutropenic fever (n = 2) occurred at tipifarnib doses above 1,200 mg/d. Sixteen of 61 (26%) evaluable patients responded (3 complete remissions and 13 hematologic improvements) with major platelet responses being most common (11 of 16 responders). There was no obvious dose-response relationship. Four of the 16 responders (25%; including a complete responder) were treated at the lowest dose level (100 mg twice daily). Only one responder had a Ras mutation. Giving tipifarnib resulted in potent inhibition of farnesyl transferase (usually more than 75%) in peripheral blood mononuclear cells regardless of dose. Partial farnesyl transferase inhibition persisted during the week off.
Conclusions: Alternate-week tipifarnib is active and well tolerated in patients with MDS at doses up to and including 600 mg orally twice daily. The biological activity of tipifarnib is not dependent on dose.
Herbal/Hormonal Dietary Supplement Possibly Associated with Prostate Cancer Progression
Authors: Shariat Shahrokh F. , Lamb Dolores J. , Iyengar Radha G. , Roehrborn Claus G. , Slawin Kevin M. 
Published: January 2008

Abstract
Background: Patients seek herbal/hormonal dietary supplements (HHDS) to prevent and/or solve health and aging issues. After two men developed an unusual course of clinically aggressive prostate cancer within months of starting daily consumption of the same HHDS product, we investigated the effect of this product on prostate cancer progression.
Methods: We evaluated serum levels of total testosterone, luteinizing hormone, and follicle-stimulating hormone and screened prostate biopsy and metastatic specimens for androgen receptor protein expression and mutations. We did hormone analyses and capillary electrophoresis. We tested the effect of the HHDS product on androgen receptor-negative (DU-145 and PC-3) and androgen receptor-positive (LNCaP) human prostate cancer cell lines.
Results: Both patients had low hormone levels. The androgen receptor was expressed in all primary and metastatic prostate cancer tissues and no mutations were identified. Hormone analysis revealed that the HHDS contained testosterone and estradiol. The HHDS product was a more potent dose-dependent stimulator of cancer cell growth than testosterone both in androgen receptor-negative and receptor-positive cell lines. Blocking experiments with increasing concentrations of bicalutamide did not prevent the HHDS product–stimulated growth. We filed an adverse event report with the Food and Drug Administration who issued a warning letter. The manufacturer responded by removing this HHDS product from the market.
Conclusions: The HHDS product contained one or more endocrinologically active tumor-promoting components that had cellular androgen receptor status–independent activity. The HHDS product exhibited potent prostate cancer growth stimulatory activity that was more powerful than that of testosterone, independent of the androgen-receptor status of prostate cancer cells, and resistant to antiandrogen blockade.
Development of a Real-time RT-PCR Assay for Detecting EGFRvIII in Glioblastoma Samples
Authors: Yoshimoto Koji , Dang Julie , Zhu Shaojun , Nathanson David , Huang Tiffany , Dumont Rebecca , Seligson David B. , Yong William H. , Xiong Zhenggang , Rao Nagesh , Winther Henrik , Chakravarti Arnab , Bigner Darell D. , Mellinghoff Ingo K. , Horvath Steve , Cavenee Webster K. , Cloughesy Timothy F. , Mischel Paul S. 
Published: January 2008

Abstract
Purpose: Epidermal growth factor receptor variant III (EGFRvIII) is an oncogenic, constitutively active mutant form of the EGFR that is commonly expressed in glioblastoma and is also detected in a number of epithelial cancers. EGFRvIII presents a unique antigenic target for anti-EGFRvIII vaccines and it has been shown to modulate response to EGFR kinase inhibitor therapy. Thus, detection in clinical samples may be warranted. Existing patents preclude the use of anti-EGFRvIII antibodies for clinical detection. Further, frozen tissue is not routinely available, particularly for patients treated in the community. Thus, detection of EGFRvIII in formalin-fixed paraffin-embedded (FFPE) clinical samples is a major challenge.
Experimental Design: We developed a real-time reverse transcription-PCR (RT-PCR) assay for detecting EGFRvIII in FFPE samples and analyzed 59 FFPE glioblastoma clinical samples with paired frozen tissue from the same surgical resection. We assessed EGFRvIII protein expression by immunohistochemistry using two distinct specific anti-EGFRvIII antibodies and examined EGFR gene amplification by fluorescence in situ hybridization.
Results: The FFPE RT-PCR assay detected EGFRvIII in 16 of 59 (27%) samples, exclusively in cases with EGFR amplification, consistent with the expected frequency of this alteration. The FFPE RT-PCR assay was more sensitive and specific for detecting EGFRvIII than either of the two antibodies alone, or in combination, with a sensitivity of 93% (95% confidence interval, 0.78-1.00) and a specificity of 98% (95% confidence interval, 0.93-1.00).
Conclusion: This assay will facilitate accurate assessment of EGFRvIII in clinical samples and may aid in the development of strategies for stratifying patients for EGFRvIII-directed therapies.
Survival and reproduction of Meloidogyne incognita on tomato as affected by humic acid
Authors: Al-Shalaby Mona , Kesba Hosny 
Published: January 2008

AbstractThe commercial products humic acid (Actosol®), humic acid (Actosol®) + NPK and humic acid (Actosol®) + micro-elements (Fe, Mn, Cu) were tested against the root-knot nematode, Meloidogyne incognita, in vitro and in vivo on tomato and compared with the nematicide, Vydate. In vitro, Vydate at 2 ml l–1 water was the best treatment for inhibiting hatch (30.8% inhibition) and was significantly more effective than all other treatments, except Vydate at 4 ml l–1. Humic acid + micro-elements (2 ml l–1 water) was the least effective treatment for inhibiting hatch. Humic acid supplemented with micro-elements was significantly better than other products in reducing the number of surviving juveniles and achieving the highest percentage of nematode inhibition (49.2%), followed by the two concentrations of Vydate, which were not significantly different from one another. In vivo, all treatments significantly reduced the numbers of galls, embedded stages in roots, final population and population build-up (Pf/Pi) in all types of soil as compared to the untreated control. Materials appeared to be more effective at preventing nematode penetration of roots in sandy loam soil than in the other two soil types (sandy and clay). The double application of humic acid + NPK gave the best plant growth (fresh and dry weights) in sandy loam soil. All treatments reduced plant content of NPK in sandy soil except for humic acid + micro-elements and the two doses of Vydate.
Stability of Heterodera glycines (Tylenchida: Heteroderidae) juvenile hatching from eggs obtained from different sources of soybean, Glycine max
Authors: Masler Edward , Sardanelli Sandra , Donald Patricia 
Published: January 2008

AbstractThe hatching behaviours of Heterodera glycines second-stage juveniles (J2) from eggs obtained from laboratory and glasshouse cultures, and from the field, were examined in vitro using large scale (Baermann funnel) and small-scale (depression slide) assay designs. Hatching of J2 from cultured eggs was robust, whereas J2 from field eggs hatched very poorly in vitro (<1% total cumulative percentage hatch). Qualitative aspects of hatch were stable as hatching of J2 from eggs from all sources was linear from 2 through to 8-10 days. By contrast, quantitative aspects were more variable. Total cumulative percentage hatch typically ranged from 45 to 70% but approached 90% depending upon the source of the cultured eggs. Egg density (eggs/cm2) affected hatch of J2 in the large scale in vitro system, with total cumulative percentage hatch significantly greater at 3100 eggs/cm2 than at 420 eggs/cm2. The poor hatch of J2 from field eggs was lost after two generations in culture and replaced by the typical hatch characteristics of J2 from eggs from an established culture. This included both qualitative and quantitative elements. Stability of H. glycines hatching behaviour and its reflection of dormancy and diapause of J2 are discussed.
Histological study of syncytia induced in cereals by the Mediterranean cereal cyst nematode Heterodera latipons
Authors: Oka Yuji , Mor Mishael , Spiegel Yitzhak 
Published: January 2008

AbstractFeeding sites of Heterodera latipons in wheat, barley and Lolium rigidum were studied and compared with those of Heterodera avenae in wheat. Juveniles of H. latipons penetrated mainly differentiated roots and chose a root cortical cell as their initial syncytium cell (ISC) in wheat and barley, whilst H. avenae chose a vascular parenchymal cell as an ISC. The cell associated with females in wheat root underwent hypertrophy, and incorporated endodermis, pericycle and parenchyma cells of the vascular cylinder by cell wall dissolution. Syncytia of H. latipons contained a high number of organelles, including endoplasmic reticulum, mitochondria, plastids and amoeboid nuclei, whilst those of H. avenae were highly vacuolated. The syncytium partly occupied both the cortex and the vascular cylinder in contrast to those of H. avenae, which occupied most of the space within the vascular cylinder near the infection site. The cortical cell associated with H. latipons males did not undergo hypertrophy, but had dense cytoplasm, and incorporation of other cells by cell wall dissolution was rare. A similar syncytium formation process was observed with barley, but a cortical cell, several cell layers away from the endodermis, was chosen for the ISC. In resistant L. rigidum, H. latipons juveniles chose an endodermal cell or its neighbouring cortical cell as an ISC. Partial dissolution of cell wall was observed in neighbouring parenchymal cells, although the nematode did not develop into adults.
Scavenging or infection? Possible host choosing by entomopathogenic nematodes
Authors: San-Blas Ernesto , Pembroke Barbara , Gowen Simon 
Published: January 2008

AbstractEntomopathogenic nematodes are able to survive by scavenging. We tested Steinernema feltiae, S. affine and Heterorhabditis megidis alone or in different combinations to evaluate the responses of these nematodes when dead or live Galleria mellonella larvae were offered. Steinernema feltiae and S. affine scavenged upon dead G. mellonella larvae and about 30% more dead larvae were penetrated than live ones. By contrast, H. megidis penetrated more live larvae than dead ones. When the nematode species were combined, the results varied among the combinations, but the dead larvae were always used as a host. The behaviour of natural field populations of S. feltiae and S. affine was also compared. Steinernema feltiae showed no difference between scavenging and performing 'normal infections', whereas S. affine scavenged to a reduced amount (around 60% less); this difference could be related to the particular foraging strategy of these nematodes.