bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4412: Combining cytokine gene therapy with conventional cancer chemotherapyfor treatment of metastatic renal cell carcinoma
Authors: Yao Qian , Li Jianfeng , Liu Dexi 
Published: August 2012

Abstract
Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 85-90% of kidney cancer. Treatment was generally aggressive involving nephrectomy and excision of the metastatic lesion. The current study was designed to evaluate a new strategy for treatment of RCC, using combination of cytokine gene therapy with conventional cancer chemotherapy. The study established tumor metastasis in Balb/c mice using Renca cells as a model1. Treatment was performed on tumor bearing mice with hydrodynamic gene delivery of plasmids containing either mIL-2 or mIL-12 gene, separately, or in combination with or without two weekly injection of 5-flououracil (5-FU) (20 mg/kg, ip). The results showed that the lung, liver and kidney were the primary sites of tumor growth. 5-FU is capable of inhibiting tumor growth in the liver and kidney and effective in slowing down tumor growth in the lung when treatment started early and with high frequency. mIL-2 gene therapy inhibited tumor growth in the liver and kidney. The effect became more obvious if treatment started early. However, IL-2 alone is unable to eliminate all liver tumors. mIL-2 gene therapy had almost no effect on tumor growth in lung. mIL-12 gene therapy significantly blocked cancer-induced weight loss. mIL-12 inhibited tumor growth in the liver and kidney, but IL-12 alone is unable to eliminate all liver and kidney tumors. In addition, IL-12 inhibited lung swelling induced by tumor, especially when treatment was started early. Cytokine gene therapy combined with chemotherapy is effective in blocking tumor-induced weight loss, and tumor growth in the liver, lung and kidney. These results provide direct evidence in support that combined therapy of cytokine gene therapy with traditional chemotherapy is effective in treating RCC. Key words: Renal cell carcinoma, gene therapy, IL-12, IL-2, 5- flououracil 1 Jianfeng Li, Qian Yao and Dexi Liu (2011) Hydrodynamic cell delivery for simultaneous establishment of tumor growth in mouse lung, liver and kidney. Cancer Biol Ther 12:737-741.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4412. doi:1538-7445.AM2012-4412
Abstract 4416: The pre-neoplastic lesion, mucin-depleted foci, reveals as de novo high-grade dysplasia in rat colon carcinogenesis
Authors: Cui Changxu , Takamatsu Reika , Doguchi Hiroshi , Matsuzaki Akiko , Saio Masanao , Yoshimi Naoki 
Published: August 2012

Abstract
Aberrant crypt foci (ACF) and mucin-depleted foci (MDF) have recently been recognized as the pre-neoplastic lesions in the colon of carcinogen-treated rodents. In the present study, we analyzed the sequential development of ACF and MDF histopathologically in the colon of rats from 5 to 40 weeks after DMH treatment. The number of ACF per colon increased over time during the experiment, and was much more than the numbers of tumor, while the number of MDF per colon remained unchanged from the early stage (the 5th week after carcinogen exposure), and approximate to that of tumor. The incidence of ACF, which was much higher than that of tumor, also increased gradually in a time-dependent way. The incidence of MDF, however, was similar to that of tumor and did not have significant change during the whole experiment. No the lesion as dysplasia with high-grade (DHG) or adenocarcinoma (AC) was found in any large ACF from the 5th to 40th week histopathologically, whereas all of the large MDF showed DHG or AC. Even at 5 weeks, MDF shows the appearance as DHG. We classified to two forms of MDF, a flat and a protruded MDF. At the 40 weeks, the number of a flat MDF per colon decreased significantly compared with that in the 20 weeks (p&lt;0.05), but number of a protruded MDF per colon increased (p&lt;0.01), and the percentage of DHG in a protruded MDF decreased but that of AC increased remarkably. In conclusion, MDF might develop into cancer through the so-called “de novo cancer” pathway.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4416. doi:1538-7445.AM2012-4416
Abstract 4419: The role of ABC transporters in PhIP-induced colon carcinogenesis
Authors: Durmus Selvi , van der Valk M.A. , Teunissen S.F. , Wagenaar Els , Beijnen Jos , Schinkel Alfred H. 
Published: August 2012

Abstract
ABC transporters such as BCRP, P-gp, Mrp2 and Mrp3 are thought to protect organisms from xenobiotics, including dietary carcinogens and anticancer drugs. These multidrug transporters reduce the oral uptake, systemic availability and tissue or cellular accumulation of transported substrates by mediating their extrusion from cells and the body in general. Therefore, they could have very important roles in the distribution of carcinogens to certain tissues and cell types, and carcinogen susceptibility. In this study, we aimed to investigate the role of ABC transporters in the tumorigenicity of a dietary carcinogen, PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine), which is produced during high-temperature cooking of meat. We have performed a pharmacokinetic experiment in wild-type FVB and ABC transporter knockout strains (Bcrp;Mrp2;Mrp3-/- and Bcrp;Mdr1a/1b;Mrp2-/-) with 200 mg/kg orally administered PhIP and observed that ABC transporters have an impact on the distribution of PhIP metabolites to several organs. There was an accumulation of N-OH-PhIP, a potentially carcinogenic metabolite, in the liver of Bcrp;Mrp2;Mrp3-/- mice and a decrease in the levels of PhIP-5-sulfate, a surrogate marker for DNA exposure to reactive compound, in small intestine of Bcrp;Mrp2;Mrp3-/- and Bcrp;Mdr1a/1b;Mrp2-/- mice compared to wild-type FVB. For carcinogenesis experiments, we used a chemically-induced colon carcinogenesis model where wild-type FVB and ABC transporter compound knock-out mice received a single, oral administration of 200 mg/kg PhIP for initiation and seven days administration of Dextran Sodium Sulfate (DSS) in drinking water for promotion of the tumorigenesis process via colonic inflammation. During the whole experiment, mice were closely checked for their body weight loss, diarrhea and rectal bleeding. Our results showed that PhIP and DSS treatment together induced colonic tumors in all strains over 180 days. No tumor formation could be found in only PhIP-treated, only DSS-treated and negative control groups that received vehicle. Tumor incidence was lower in both knock-outs compared to the wild-type FVB when inflammation levels between the groups were corrected. Our results suggest that these ABC transporters are not protecting the intestinal tract from PhIP-induced carcinogenesis upon oral ingestion in mice, and perhaps even partially enhance PhIP-induced carcinogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4419. doi:1538-7445.AM2012-4419
Abstract 442: Increased miR-let7c level indicates transition from localized bladder cancer to metastasis
Authors: Meng Wei , Chakravarti Arnab , Lautenschlaeger Tim 
Published: August 2012

Abstract
Purpose/Objective(s): MicorRNAs are a group of short ribonucleic acid molecules with an average of 22 nucleotides and play an important role in regulation of gene expression. Because the microRNA profiles of tumor are related to cancer development and prognostication, it becomes a new frontier of cancer research. The current tools for studying microRNA like microarray have limited dynamic range and poor sensitivity, and Taqman microRNA assay has higher sensitivity but limited number of microRNAs. The SOLiD system provides a sensitive and robust assay for discovery and profiling of novel microRNAs using sequencing by ligation. The aim of this study is to find key miRNA which can provide insights into the cancer cell invasion and metastasis. Materials/Methods: 12 bladder cancer FFPE samples were used in this study, including 6 cases of stage N0, 3 cases of stage N1 and 3 cases of stage N2. Total RNA from FFPE blocks was isolated by Ambion RecoverAll Total Nucleic Acid Isolation kit according to manufacturer's instructions. The concentration and quality of total RNA were examined by Nanodrop 1000 spectrophotometer. The small RNA was enriched by flashPAGE fractionation and the microRNA library was built using Ambion SOLiD Small RNA Expression Kit with the barcode system (Life Technologies, CA, US). 35 bp long reads were generated on the SOLiD (version 3.0) sequencing system (Life Technologies) and were analyzed by using the SOLiD System Small RNA Analysis Tool (Life Technologies). Results: Analyzed samples were from male caucasian patients with a median age of 63.5 years. Tumors were all grade 3 urothelial carcinomas. Patients had T1-4 and M0-1 disease. We examined global miRNA expression in bladder cancer FFPE samples, and SOLiD results revealed that the expression of 10 microRNAs significantly differed between N0 stage and N1/2 stage. miR-let7c precursor and mature miR-let7c were upregulated in samples from patients with lymphnode metastasis. A previous study from Leite et al. showed that miR-let7c expression was similar in matched FFPE and frozen prostate cancer tissue with a Pearson's correlation coefficient of 0.927. Conclusion: miR-let7c expression is associated with the presence of lymphnode metastasis in high-grade urothelial bladder cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 442. doi:1538-7445.AM2012-442
Abstract 4421: PDE5 inhibitors suppress proliferation and augment the epithelial barrier by activating PKG2 in the colon
Authors: Wang Rui , Kwon In-Kiu , Subbaramia Sridhar , Browning Darren D. 
Published: August 2012

Abstract
Increasing cGMP levels has emerged as a potentially important suppressor of tumorigenesis in the colon, but the downstream signaling is poorly defined and a viable therapeutic strategy remains to be established. The present study has tested whether type 2 cGMP-dependent protein kinase (PKG2) mediates the homeostatic effects of cGMP in the colon. In addition, the feasibility of using phosphodiesterase 5 (PDE5) inhibitors therapeutically to increase cGMP levels in the colon mucosa has been examined. PKG2 is a central effector of cGMP in enterocytes, and consistent with a growth-inhibitory and differentiation-promoting role, knockout animals showed crypt hyperplasia and reduced mature goblet cells in the colonic mucosa. This phenotype is similar to guanylyl-cyclase C (GCC) knockout animals, which have also been reported to exhibit increased susceptibility to colon tumorigenesis. The possibility that PKG2 signaling might be activated pharmacologically, was examined using PDE5 inhibitors to regulate colonic proliferation and differentiation. These experiments demonstrated that intraperitoneal administration of clinically relevant PDE5 inhibitors provoked a rapid increase cGMP levels in the colon mucosa of mice. Moreover, prolonged treatment with PDE5 inhibitors led to reduced proliferation in the colonic crypts and a dramatic increase in mature goblet cells. Consistent with the importance of PKG2 in this process, the PDE5 inhibitors did not inhibit proliferation or increase goblet cell numbers in PKG2 knockout animals. The increase in goblet cell density in PDE5 inhibitor-treated animals was striking (50%, 85%, and 44% relative to controls in the ascending, transverse and descending colon respectively). Reduced basal epithelial apoptosis measured in PDE5 inhibitor treated animals suggested the the increased goblet cells could have a barrier-protective effect. To test this possibility further, the effect of PDE5 inhibitor treatment on epithelial damage by dextran sulfate sodium was measured. These studies demonstrated a significant attenuation of disease activity by PDE5 inhibitor treatment in this colitis model. In summary, our results demonstrate a central role for PKG2 in the regulation of proliferation and differentiation in the colon mucosa. In addition, this pathway can be exploited using PDE5 inhibitors, suggesting that these agents could be part of a novel therapeutic strategy for colon cancer prevention.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4421. doi:1538-7445.AM2012-4421
Abstract 4423: Transgenic liver expression of human arylamine N-acetyltransferase NAT2 restores sensitivity of male Nat1/2 null mice to 4-aminobiphenyl-induced liver tumorigenesis
Authors: Grant Denis M. , Brenneman Debbie , Sugamori Kim S. 
Published: August 2012

Abstract
We recently observed that male Nat1/2(-/-) mice, which are deficient in the arylamine N-acetyltransferases Nat1 and Nat2, have a significantly lower incidence and multiplicity of liver tumors than wild-type C57BL/6 mice after their neonatal exposure to the aromatic amine carcinogen 4-aminobiphenyl (ABP). Female mice showed low or no liver tumors from ABP exposure regardless of Nat1/2 status. The goal of the present study was to determine the effect of liver-selective transgenic expression of human NAT2 on ABP-induced liver tumorigenicity in male and female Nat1/2(-/-) mice. We generated a hNAT2tgNat1/2(-/-) strain of mice that express human NAT2 selectively in liver on a Nat1/2 null background, exposed male and female mice to either DMSO vehicle, a low dose (600 nmoles) or a high dose (1200 nmoles) of ABP during the second postnatal week, and assessed mice for tumor growth at one year of age. Male hNAT2tgNat1/2(-/-) mice had liver tumor incidences of 29% (low dose) and 61% (high dose), which more closely resembled those of C57BL/6 mice (60% and 69%, respectively) than those of Nat1/2(-/-) mice (0% and 35%, respectively). This suggests that human NAT2 is capable of substantially restoring the sensitivity of mice to ABP-induced liver tumorigenicity that is lost by the absence of mouse Nat1 and Nat2. On the other hand, female hNAT2tgNat1/2(-/-) mice were still as resistant to liver tumors as C57BL/6 or Nat1/2(-/-) mice. No tumors were observed in any other organs. These results suggest that the human and mouse NAT enzymes play similar roles in enhancing liver tumor growth, and that the mechanism of female protection against ABP-induced tumor growth is unrelated to NAT status. However, neither the sex nor the NAT status of the mice appear to be correlated with the ability of ABP to produce acute DNA-damaging or mutation-inducing effects in liver. This suggests that the role of the human and mouse NAT enzymes in promoting liver tumor growth in mice may be due to a mechanism that is independent of their ability to influence the process of ABP metabolic activation and subsequent DNA damage leading to tumor initiation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4423. doi:1538-7445.AM2012-4423
Abstract 4473: Urinary biomarkers of exposure to 1,3-Butadiene and its bioactivation to DNA-reactive metabolites
Authors: Kotapati Srikanth , Sangaraju Dewakar , Walker Vernon E. , Swenberg James A. , Tretyakova Natalia Y. 
Published: August 2012

Abstract
1,3-butadiene (BD) is one of the most potent and abundant carcinogens present in cigarette smoke. BD is metabolically activated to 3,4-epoxy-1-butene (EB), 1,2,3,4-diepoxy butane (DEB), hydroxymethylvinylketone (HMVK), and 3,4-epoxy-1,2-butanediol (EBD), which can react with DNA nucleobases and proteins to form promutagenic adducts. Alternatively, these electrophilic metabolites can be detoxified via hydrolysis or conjugation with glutathione. The glutathione conjugates of these metabolites are ultimately excreted in urine as 1-hydroxy 2-(N-acetylcysteinyl)-3-butene (MHBMA), 1,4-bis-(N-acetylcysteinyl)butane-2,3-diol (bis-BDMA), 1,2-dihydroxy-4-(N-acetylcysteinyl)-butane (DHBMA), and 1,2,3-trihydroxy-4-(N-acetylcysteinyl)-butane (THBMA), respectively. Since epoxide metabolites of BD are thought to be responsible for its adverse health effects, it is important to develop specific biomarkers of their formation in vivo to be used in molecular epidemiology studies. While MHBMA, DHBMA, THBMA have been previously detected in smoker's urine, bis-BDMA has not been reported. In the present study, novel stable isotope dilution HPLC-ESI-MS/MS methods for accurate and precise quantification of MHBMA, DHBMA, THBMA, and bis-BDMA in urine have been developed. Dose dependent formation of all BD-mercapturic acids including bis-BDMA was observed in urine samples from male and female F344 rats exposed to 0, 62.5 and 200 ppm of BD for 2 weeks by inhalation. The relative amounts of MHBMA, DHBMA, THBMA, and bis-BDMA in rat urine were 20:50:50:1. Furthermore, MHBMA, DHBMA, and THBMA were detected in urine samples from known smokers and non-smokers, with significantly higher concentrations observed in smokers. The mean levels of these BD-mercapturic acids in smokers were 3, 340, and 27 ng/mg creatinine, respectively. In contrast, bis-BDMA could not be detected in human urine samples, probably a result of the inefficient DEB formation in humans. These methods are now being applied to a multi-ethnic cohort study to identify any differences in metabolism that contribute to ethnic and inter-individual differences in lung cancer incidence.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4473. doi:1538-7445.AM2012-4473
Abstract 4474: Occupational exposure to benzene and leukocyte telomere length
Authors: Bassig Bryan , Zhang Luoping , Cawthon Richard , Yin Songnian , Li Guilan , Rappaport Stephen , Hu Wei , Smith Martyn T. , Rothman Nathaniel , Vermeulen Roel , Lan Qing 
Published: August 2012

Abstract
Benzene is an important industrial solvent and a ubiquitous environmental contaminant. IARC has classified benzene as a human leukemogen (Group 1) and a possible lymphomagen. We have previously demonstrated that exposure to benzene results in hematotoxic effects in a cross-sectional study, and that longer telomere length may be associated with non-Hodgkin lymphoma (NHL) in a prospective study conducted in the general population. To further explore the biologic plausibility that benzene may be a lymphomagen, we tested if leukocyte telomere length was altered in a cross-sectional biomarker study of workers occupationally exposed to benzene in Shanghai, China. Forty-four benzene-exposed workers were enrolled from factories that used benzene, along with 44 age and gender-matched controls from two workplaces in the same geographic area that did not use benzene or other chemicals associated with bone marrow toxicity. Personal exposure measurements were obtained for each exposed worker using passive 3M organic vapor monitoring badges. Blood samples were collected from each worker, and leukocyte telomere length was measured using a quantitative PCR procedure. Linear regression using the natural logarithm of telomere length and adjusting for potential confounders was used to test for differences in telomere length between exposed workers and controls. The median benzene personal air level was 31 ppm in the exposed workers. Compared to unexposed workers, the mean leukocyte telomere length was increased by about 8% in all benzene-exposed workers (p=0.05). There was a 4% increase in workers exposed to &lt; 31 ppm and a 12% increase in workers exposed to &gt; 31 ppm and a statistically significant dose-dependent increase in telomere length with increasing levels of benzene exposure in air (ptrend = 0.01). Some preliminary evidence has suggested that benzene exposure may stimulate telomerase expression in lymphocytes and other cell lines. Given that longer telomere length has been associated with risk of NHL, our findings provide some support for the biologic plausibility that benzene is a lymphomagen but require replication in larger studies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4474. doi:1538-7445.AM2012-4474
Abstract 4477: Progesterone (P4) and testosterone (T) concentrations in random fine needle aspirates of the breast in pre- and postmenopausal women
Authors: Heinz Richard E. , Kenney Kara , Lee Oukseub , Iyer Sivaraman , Khan Seema A. , Chatterton Robert T. 
Published: August 2012

Abstract
Background: The availability of steroid hormones in the breast may be an important measure of the potential for proliferation of hormone-dependent breast cancer, and because retention of hormones may be influenced by serum levels, in situ formation, and the presence of binding proteins and lipids in the tissue, measurements of tissue concentrations are more informative than serum concentrations alone. Methods: Subjects were normal women, aged 36-65 yr, without breast cancer and not taking hormones. Tissue was obtained by fine needle aspiration of the breast. The cellular pellet was saved for analysis of DNA, and lipids were extracted from the supernatant including the fatty layer. Previous work had shown the cellular pellet contained a very little of the total steroids of the sample. Triglycerides were precipitated from 90% methanol at –20 °C and the remaining lipids were applied to a C18 HPLC column for purification in a gradient of methanol and acetonitrile in phosphate buffer. Fractions containing P4 and T were analyzed by immunoassays. The total DNA in the cellular pellet was isolated and quantified by UV absorbance. The steroid content was expressed as either per mg of purified lipid or per microgram of DNA. The data, when expressed as the natural log of the concentrations, followed a normal distribution. Differences in pre- and postmenopausal concentrations were analyzed by group t-tests. Results: The geometric means of the hormone concentrations are shown in the table. Comment: Despite the almost complete loss of progesterone in serum of postmenopausal women, the concentrations in the tissue are reduced but remain, on average, at more than 25% of the premenopausal level, somewhat more than the previously reported percentage in NAF of 5%. Relationships within individual women to other risk factors will be explored. Testosterone is also maintained at a relatively high level in the tissue of postmenopausal women, and may serve as a substrate for aromatase.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4477. doi:1538-7445.AM2012-4477