bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1473: Fra-2 and JunB are overexpressed in precancerous bile ducts and primary/transplanted hamster cholangiocarcinomas with a strong positive correlation
Authors: Jeon Byung-Suk , Lee Byung-Woo , Yoon Byung-Il 
Published: February 2011

Abstract
The transciption factor complex AP-1 plays important roles in cell proliferation, differentiation and apoptosis of which dysregulation is closely associated with cancer development. Fra-2 and JunB, components of AP-1 family proteins, had been found overexpressed in certain of tumors, suggesting their possible implication in carcinogenesis. In the present study, we investigated differential expression patterns of those two AP-1family proteins during hamster cholangiocarcinogenesis and aggressive transplanted cholangiocarcinomas (ChCs). First, we prepared appropriate liver tissue samples with precancerous lesions and ChCs from hamster ChC model as well as normal liver. The transplanted ChCs were produced by syngenic transplantation of the primary ChCs. We then performed immunohistochemistry (IHC) for Fra-2 and JunB using ABC methods. The typical nuclear staining for Fra-2 and JunB was determined as positive immunoreactivity and the ratio of positive cells was evaluated by counting 800-3000 cells, followed by statistical analysis. The correlation of Fra-2 and JunB expression was analyzed by scattergram. Our IHC indicated significantly increased frequency of Fra-2 and JunB positive cells according to the tumor progression, i.e., respectively in the early dysplatic bile ducts (10∼20%) and late dysplastic bile ducts (40∼50%), primary ChC (40∼60%) and transplanted ChC (higher than 70% positivity), while normal and simple hyperplastic bile duct epithelia were negative or indicated very low labeling index for both Fra-2 and JunB (under 1% positivity). The expression of Fra-2 and JunB showed a strong correlation (r=0.93) and the immunoreactive cells for Fra-2 and JunB were mainly localized in the invading areas adjacent to normal surrounding tissue. In summary, we found in the present study the followings 1) Expression of Fra-2 and JunB progressively increased as bile duct cells become carcinogenic, 2) Fra-2 and JunB have a high correlation in the expression patterns in the biliary cell populations including cancers, 3) In the transplanted biliary cancers, overexpression of Fra-2 and JunB (especially JunB) were localized in the neoplastic cells which are very aggressive to invade into adjacent normal tissue. Based on our results, Fra-2 and JunB could play significant roles in cholangiocarcinogenesis, possibly by collaboratively participating in dysplastic changes and acquisition of tumorigenicity of candidate bile duct cells for ChC. Also, those two AP-1 family proteins could contribute to invasiveness of biliary cancer cells.
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 1473.
Abstract 1488: Role of human leukocyte antigen-G (HLA-G) in cancer progression and susceptibility
Authors: Abbas Ata , Hussain Syed R. , Naqvi Hena , Fatima Rabab , Hasan Sikandar , Mahdi Farzana 
Published: February 2011

Abstract
Human Leukocyte antigen -G is an immunosuppressive protein with multiple functions. The 14bp insertion / deletion in exon-8 of HLA-G gene have been shown to play an important role in HLA-G mRNA stability as well as expression level; and can be correlated with its immunosuppressive function. The role of HLA-G in various cancers has already been demonstrated. Cancerous cells start expressing HLA-G which in turn provides a shield for various immune responses. In the present study we have tested the possibility of the role of 14bp insertion / deletion polymorphism of HLA-G in cancer progression and susceptibility. We have genotyped 59 cancer samples (26 benign and 33 malignant) and 79 matched controls for 14bp polymorphism of HLA-G. Data showed increase of +14bp/-14bp and −14bp/-14bp genotype with both benign and malignant cancer. We observed significantly higher frequency of +14bp/+14bp genotype in control (p=0.01). This is consistent with both benign and malignant tumors as well as cancer types showing possibility of protective effect of +14bp/+14bp genotype in various cancers. However, further studies will be required with large sample size to test this hypothesis. The +14bp/-14bp and −14bp/-14bp genotypes have already been shown to be associated with higher expression of HLA-G and its mRNA stability and might be providing favorable micro-environment for cancer progression. There is no published work till date showing the role of HLA-G 14bp polymorphism in various cancers. These preliminary data showed that HLA-G 14bp genotypes might be playing an important role in pathogenesis of various cancers.
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 1488.
Abstract 1489: Basal cell carcinomas express functional indoleamine 2,3-dioxygenase (IDO) which may confer immunoprotection
Authors: Lo Blanche K. , Jalili Reza B. , Zloty David , Ghahary Aziz , Cowen Bryce , Shapiro Jerry , McElwee Kevin J. 
Published: February 2011

Abstract
Basal cell carcinoma (BCC) is the most common malignancy in humans worldwide. Besides genetic alterations, abrogation of host immune defense has been suggested to enable tumor growth. Cancer cells may express factors that confer resistance to inflammatory cell mediated activity and may actively suppress immune targeting mechanisms. BCCs can derive from hair follicle bulge region keratinocytes; a structure which exhibits elements of immune privilege (IP). As such, BCCs may also exhibit immunoprotective characteristics during tumorigenesis.
Indoleamine 2,3-dioxygenase (IDO) suppresses T lymphocyte proliferation via tryptophan catabolism in the kynurenine pathway. IDO is used as an immune subversion strategy by several types of cancer such as ovarian carcinomas. Expression of IDO has also been identified in hair follicle keratinocytes. Taken together, we hypothesized that IDO might have an impact on the putative IP of BCCs.
In a preliminary study, we identified increased expression of mRNA in BCCs for several IP related factors. In this study, real-time RT-PCR identified significant upregulation of IDO-1 and IDO-2 (12.5- and 19.1-fold change respectively) in human nodular BCCs (n=10) as compared to non-lesional skin epithelium tissues (n=10). Dual label immunohistochemistry revealed co-localization of IDO and keratin 17 (K17), which is a BCC keratinocyte marker, in human BCC tissues (n=5). Western blot detected IDO (42kDa) and a 30kDa IDO isoform in BCC tissues (n = 6). Activity of IDO was shown by significantly increased production of L-kynurenine in the conditioned medium from cell cultures. CXCL11 has recently been shown to be a supplement required for the survival and growth of primary human BCC cells in culture. Addition of CXCL11 to primary BCC cell cultures in increased concentrations promoted increased L-kynurenine in a dose dependent manner. However, there was no significant increase in L-kynurenine production by normal primary human keratinocytes under CXCL11 treatment.
In conclusion, of several differentially expressed genes associated with IP, mRNA for IDO was identified with significantly increased expression. The co-expression of the peptide with K17, as well as the IDO-mediated L-kynurenine production in human BCC cell cultures, provides further evidence of functional IDO synthesis by BCCs during their growth. The results suggest that BCCs may exhibit IP characteristics through IDO production and induction of a local collapse of such IP systems in BCC tumors may be a novel strategy for promoting BCC regression.
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 1489.
Abstract 1490: Overexpression of a calcium channel protein TRPM8 in prostate cancer cells enhances their anchorage-independent growth and resistance to paclitaxel-induced apoptosis
Authors: Yu Shan , Xu Zhenyu , Chan Franky L. 
Published: February 2011

Abstract
The non-voltaged-gated transient receptor potential protein melastatin member 8 (TRPM8) has been characterized to function as a cold- and menthol-activated calcium-permeable channel protein, which it was originally cloned in a prostate-specific substracted cDNA library and shown to be up-regulated in benign prostatic hyperplasia and prostate cancer as compared to normal prostatic epithelial cells. Recent studies in cultured prostate cancer cells and clinical prostate cancer tissues show that TRPM8 is an androgen receptor-regulated calcium channel which is required for the survival and androgen-dependent growth of prostate cancer cells. Based on this evidence, it is believed that TRPM8 may play an important role in the advanced growth of prostate cancer. However, the prostate-specific function of TRPM8 and the role of TRPM8-regulated calcium-influx in prostate function and its carcinogenesis remain unclear. Our preliminary studies showed that TRPM8 was significantly over-expressed in an androgen-independent and metastatic prostate cancer cell line C4-2B as compared to its parental line LNCaP and also in two animal models of metastatic prostate cancers (a transgenic mouse model of prostate cancer-TGMAP and xenograft model of C4-2B). In order to elucidate the functional significance of TRPM8 in prostate cancer cell growth, we over-expressed TRPM8 in an androgen-sensitive prostate cancer cell line LNCaP by lentiviral transduction and generated stable TRPM8 clones for phenotypic growth studies. Our findings showed that stable ectopic TRPM8 expression induced morphological changes in LNCaP cells with reduction of filopodial processes and also suppressed their in vitro cell proliferation as shown by MTT assay. However, stable LNCaP-TRPM8 clones demonstrated significantly enhanced colony formation efficiencies in soft agar assay. Moreover, stable TRPM8 expression also enhanced the in vivo tumor growth of LNCaP cells in immunodeficient SCID mice and resistance to paclitaxel-induced apoptosis, as compared to their parental line. The results of our present study suggest that altered calcium-homeostasis as disturbed by TRPM8 overexpression in prostate cancer cells could enhance their in vitro anchorage-independent and in vivo tumor growth, and also resistance to paclitaxel-induced apoptosis, while the involved calcium-dependent signaling pathways still remain to be elucidated. (Study supported by a RGC Competitive Earmarked Research Grant project code 461007)
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 1490.
Abstract 1494: Characterization of a novel pro-tumorigenic TGF-β RII mutation from oral squamous cell carcinoma
Authors: Son Hwakyung , Park Iha , Che Z.M. , Kim J 
Published: February 2011

Abstract
TGF-β signaling plays various roles in tumor progression. Tumor suppressive TGF- β signaling is involved in early steps of carcinogenesis through loss of function which leads to deregulated proliferation. On the contrary, TGF- β signaling could be pro-tumorigenic in later stages of carcinogenesis by promoting epithelial-mesenchymal transition (EMT). Most of the reported TGF- β receptor-II mutations were loss of tumor suppressor function mutations and no pro-tumorigenic TGF- β receptor-II mutation has been identified in human tumors. This study aimed to analyze a novel mutation of TGF- β receptor-II found in metastatic lymph node of oral squamous cell carcinoma. This mutant converts amino acid 227 from I to T and amino acid 236 from N to D of TGF- β receptor-II. Promoter assay using 3TP-lux reporter showed that 227/236 double mutation significantly increased both basal and TGF- β-induced luciferase activity as compared to wild type in DR-26, TGF- β receptor-II-defective mink lung epithelial cells. Stable expression of 227/236 mutant enhanced migration and invasion as well as cell growth of HSC-2 cells, human oral squamous cancer cell line whose TGF- β signaling is not growth inhibitory. In 227/236 mutant transfectant, E-cadherin expression is reduced whereas snail expression has not been changed significantly. In orthotopic xenograft model to monitor the tumor growth, 227/236 mutant transfectant formed significantly larger tumors as compared to wild type transfectant. But, unexpectedly, there was no difference in the expression pattern of involucrin and E-cadherin in these tumor tissues, suggesting that this mutation did not affect EMT in vivo model system. In the study we present a novel gain-of-function mutation of TGF- β receptor II, which increased TGF- β signaling and thereby induced tumor growth without affecting EMT in HSC-2 oral squamous cancer cells.
This work was supported by a grant from the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic research promotion fund KRF-2005-005-J05901).
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 1494.
Abstract 1496: Oxidatively induced DNA base damage in colorectal carcinoma
Authors: Kirkali Guldal , Keles Didem , Canda Aras Emre , Terzi Cem , Jaruga Pawel , Dizdaroglu Miral , Oktay Gulgun 
Published: February 2011

Abstract
Molecular pathways that play a role in the development of colorectal cancer involve multiple genetic changes in cancer-related genes that may be caused by overproduction of reactive oxygen species (ROS) including free radicals. Various types of ROS are capable of damaging DNA and other biomolecules. Increased formation of ROS can contribute to genetic instability and promote the development of malignancy. These facts led us to hypothesize that oxidatively induced DNA damage may accumulate in colorectal cancer patients. To test this hypothesis, we investigated oxidatively induced DNA damage in colon and rectum tissues of cancer patients in comparison with their normal paired tissues. DNA was isolated from 51 colorectal cancer tissues. The levels of oxidatively induced DNA lesions such as 4,6-diamino-5-formamidopyrimidine (FapyAde), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua), 8-hydroxyguanine (8-OH-Gua) and (5′S)-8,5′-cyclo-2′-deoxyadenosine (S-cdA) were measured by gas chromatography/isotope-dilution mass spectrometry and liquid chromatography/isotope-dilution mass spectrometry. We found that the level of 8-OH-Gua, FapyAde and FapyGua were significantly lower in cancer tissues than those in paired normal tissues (p=0.002, p=0.019 and p=0.005, respectively), whereas the S-cdA levels showed no significant difference between both tissues. These DNA base damages correlated with clinical and pathological data such as tumor location, tumor stage, gender and perineural invasion. The low levels of DNA base damage in tumor tissues when compared to their normal counterparts suggest an increase in DNA repair capacity in malignant tumors that may contribute to the resistance to therapeutic agents. This finding may lead to development of new therapeutic approaches.
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 1496.
Abstract 150: HPV and aberrant DNA methylation status in paired saliva and tumor samples in HNSCC
Authors: Havard Shaleta , Chen Kang Mei , Stephen Josena K. , Worsham Maria J. 
Published: February 2011

Abstract
To examine the utility of non-invasive detection of high risk HPV and aberrant DNA methylation in matched saliva and tumor DNA in squamous head and neck cancer (HNSCC). In a cohort of 35 primary HNSCC with matched tumor (cases) and saliva specimens, HPV status was initially determined using the Linear Array HPV Genotyping kit and confirmed by PCR for HPV subtypes 16, 31, 33 and 45. Aberrant methylation of 24 tumor suppressor genes was interrogated using the methylation specific multiplex ligation probe amplification (MS-MLPA) assay. Of the 35 cases, 20 were negative for HPV in the saliva and tumor, 9 were positive for HPV in both and in 6 cases HPV was positive in the tumor specimen but not detected in the corresponding saliva. In the 9 cases that were positive for HPV in the tumor and matched saliva, 6 were HPV 16 positive and 1 case each was positive for HPV 31, 33 and 45. The sensitivity and specificity for HPV in this cohort were 100% and 60%, respectively. Promoter hypermethylation frequency in tumor samples was 60% (21/35) as compared to 14% (5/35) in saliva. The most frequently methylated genes in tumors included RARB-10/21, APC- 9/21, TIMP3 and CDKN2B- 7/21, CDKN2A and IGSF4- 5/21 tumor samples. The most frequently methylated genes in saliva samples included TIMP3, ESR1 and IGSF4 (3/5 saliva samples), followed by APC, CDKN2B and DAPK1 (2/3). Two of the 35 tumor and saliva pairs had commonly methylated genes, APC in one pair, and TIMP3, CDKN2B, ESR1 and IGSF4 in the other. There was no association between HPV and methylation. PCR analysis of HPV DNA in salivary rinses allows for detection of HPV and promoter methylation status in HNSCC and is a feasible noninvasive alternative to more invasive procedures.
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 150.
Abstract 1501: Tumor cells engineered to codisplay on their surface 4-1BBL and LIGHT costimulatory proteins as a novel vaccine approach for cancer immunotherapy
Authors: Sharma Rajesh K. , Yolcu Esma S. , Elpek Kutlu G. , Shirwan Haval 
Published: February 2011

Abstract
Therapeutic vaccines based on whole tumor cells genetically modified to express various immunomodulatory molecules represent an important modality for the treatment of cancer. However, generation of genetically modified tumor cells as vaccine is not only cost, labor, and time intensive, but also has safety repercussions. As an alternative, we have recently developed the ProtEx™ technology that involves modification of the cell membrane with biotin and engineering of biotinylated cells with proteins of interest chimeric with core streptavidin. We herein tested if tumor cells can be engineered efficiently to simultaneously display on their surface two SA-chimeric costimulatory ligands, SA-4-1BBL and SA-LIGHT, and if vaccination with such engineered cells has better therapeutic efficacy than cells displaying single molecule in the TC-1 cervical cancer mouse model. The choice of 4-1BBL is due to pleiotropic immune activity of 4-1BBL to stimulate innate, adaptive immune responses as well as overcome various immune evasion mechanisms. The choice of LIGHT is due to its stimulatory effects on tumor stroma, which pose a physical barrier to the entry of effector immune cells to tumor site. Biotinylated TC-1 tumor cells codisplayed both chimeric costimulatory ligands on their surface with equal efficiency after incubation with equal molar of SA-4-1BBL and SA-LIGHT proteins. Vaccination with irradiated TC-1 tumor cells codisplaying both chimeric costimulatory ligands resulted in the generation of antigen specific T cell proliferative and killing responses, resulting in 100% efficacy in prophylactic and &gt; 57% efficacy in therapeutic settings. In marked contrast, vaccination with TC-1 tumor cells displaying on their surface either of these molecules singly only delayed the tumor growth in the prophylactic setting. Vaccine efficacy was associated with effective generation of primary and memory T cell and Ab responses, enhanced CD8+ T cell infiltration into the tumor, IFN-γ production, and tumor-specific killing. In conclusion, engineering tumor cells in a rapid and effective manner to simultaneously display on their surface a collection of immunostimulatory molecules with distinct immune functions presents a novel approach with considerable potential for cancer immunotherapy.
Funded in parts by NIH 2R44 AI071618-02, R43 AI074176, R41 CA121665, KLCP, the W.M. Keck Foundation, and the Commonwealth of Kentucky Research Challenge Trust Fund.
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 1501.
Abstract 1503: PSMA Aptamer-targeted siRNAs selectively Eehance prostate cancer radiation sensitivity
Authors: Ni Xiaohua , Zhang Yonggang , Ribas Judit , DeWeese Theodore L. , Lupold Shawn E. 
Published: February 2011

Abstract
The application of dose escalated radiation therapy for localized prostate cancer has a clear therapeutic benefit; however, its clinical use is hampered by the increased risk of damage to surrounding normal tissues. One attractive alternative to elevated doses is radiation sensitizing agents. Prostate cancer cells can be made radiosensitive by targeted reductions of DNA repair proteins via RNA interference. However, without tissue-selective targeting, these agents will also sensitize surrounding tissue, leading to increased adverse effects. Here we describe a strategy where prostate-targeted RNA interference is used to selectively radio-sensitize prostate cancer cells. A high throughput siRNA screen was completed to identify DNA-repair pathway targets for prostate cancer radio-sensitization. Candidate siRNAs were then conjugated to PSMA-targeted RNA aptamers for selective delivery of siRNAs to Prostate cancer cells. In vitro and in vivo data support PSMA and aptamer-specific targeting and gene knock-down. These studies support continued development of this technology as a path to enhance radiotherapeutic outcomes for men with Prostate cancer and it is the first report of targeted, prostate-specific siRNAs for radio-sensitization.
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 1503.