bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 534: Protein kinase c ≤ cooperates with Pten deficiency in prostate cancer progression
Authors: Garg Rachana , Blando Jorge , Perez Carlos J. , Benavides Fernando , Kazanietz Marcelo G. 
Published: August 2012

Abstract
Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related deaths among men. Protein kinase C epsilon (PKC∈), a member of the PKC family of phorbol ester/diacylglycerol receptors, has been shown to be up-regulated in human prostate cancer specimens. We recently demonstrated that mice that specifically overexpress PKC∈ in prostate under the control of the probasin promoter (PB-PKC∈) develop hyperplasia and PIN lesions. However, PKC∈ overexpression was insufficient to drive neoplastic changes in the mouse prostate. In the present study our goal was to determine whether PKC∈ overexpression can cooperate with Pten deficiency, one of the most common genetic alterations in human prostate cancer. We stably overexpressed PKC∈ in two pairs of isogenic mouse prostate epithelial lines that are either heterozygous (P2, P8) or homozygous (CaP2, CaP8) for Pten deletion. PKC∈ overexpression led to significant enhancement in cell proliferation compared to the respective control cells and this effect is more pronounced in CaP2 or CaP8 cells. Moreover, assays of colony formation in liquid medium revealed that anchorage-dependent growth was augmented in PKC∈-overexpressing cells relative to control cells. A significant elevation in phospho-Akt levels was observed in PKC∈ overexpressing cells relative to respective controls. To further elucidate the cooperativity between PKC∈ overexpression and Pten loss we intercrossed the PB-PKC∈ transgenic mice and Pten+/− mice. Strikingly, the resulting compound mutant mice overexpressing PKC∈ and haploinsufficient for Pten (PB-PKC∈; Pten+/−) developed fully invasive adenocarcinoma at 12 months of age. Very strong phospho-Akt, phospho-S6 and phospho mTOR staining could be detected in adenocarcinomas from PB-PKC∈; Pten+/− mice. Furthermore, we detected enhanced p-Erk, Cox-2, STAT3, NF-κB and cyclin D1 signaling in adenocarcinomas from PB-PKC∈;Pten+/− mice than in lesions from each monogenic model. These data thus suggest that PKC∈ overexpression cooperates with a defined oncogenic input to promote prostate tumorigenesis. These findings also suggest a crucial role of PKC∈ in survival.
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 534. doi:1538-7445.AM2012-534
Abstract 5343: Identification of brain tumor initiating cells using the stem cell marker aldehyde dehydrogenase 1
Authors: Choi Seung Ah , Lee Ji Yeoun , Phi Ji Hoon , Wang Kyu-Chang , Park Chul-Kee , Park Sung-Hye , Kim Seung-Ki 
Published: August 2012

Abstract
Aldehyde dehydrogenase 1 (ALDH1) has been identified in stem cells from both normal and cancerous tissue. This study aimed to evaluate the potential of ALDH1 as a universal brain tumor initiating cell (BTIC) marker applicable to primary brain tumors and their biological role in maintaining stem cell status. Cells from various primary brain tumors (24 pediatric and 6 adult brain tumors) were stained with Aldefluor and sorted by flow cytometry. We investigated the impact of ALDH1 expression on BTIC characteristics in vitro and on tumorigenic potential in vivo. Primary cultured brain tumor cells showed universal expression of ALDH1, with 0.3 to 28.9% of the cells in various tumors identified as ALDH1+. ALDH1+ cells generate neurospheres with high proliferative potential, express neural stem cell markers (nestin and musashi) and differentiate into multiple nervous system lineages. ALDH1+ cells are phenotypically distinct from CD133+ cells, and they show high expression of induced pluripotent stem cell-related genes. Notably, targeted knockdown of ALDH1 by shRNA interference in BTICs potently disturbed their self-renewing ability. After three months, ALDH1+ cells gave rise to tumors in 93% of mice whereas ALDH1- cells did not. The characteristic pathology of mice brain tumors from ALDH1+ cells was similar to that of human brain tumors, and these cells are highly proliferative in vivo. Our data suggest that primary brain tumors contain distinct subpopulations of cells that have high expression levels of ALDH1 and BTIC characteristics. ALDH1 might be a potential therapeutic target applicable to primary brain tumors.
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 5343. doi:1538-7445.AM2012-5343
Abstract 5346: Tumor cell heterogeneity and chromosomal abnormality in malignant pleural effusion (MPE) samples of lung cancer
Authors: Basak Saroj Kumar , Rao Nagesh P. , Oh Scott , Mysore Veena S. , Srivatsan Eri S. , Batra Raj K. 
Published: August 2012

Abstract
Tumor heterogeneity is a hallmark of cancer and different types and stages of cancer express various cell surface markers and gene expression profiles. To understand tumor cell heterogeneity in lung cancer, we have developed a model using primary cells from malignant plural effusion (MPE) from lung cancer patients. Using this system we have identified CD44high expressing primary tumor cells within the MPE that form colonies in soft agar in vitro, and tumors in SCID/NOD mice. RT-PCR analysis revealed higher expression of cancer stem cell markers, Bmi-1, hTERT, EZH2, and OCT-4 in CD44high cells than the CD44low cells. Thus, our results indicate that primary tumor cells of MPE derived from lung cancer patients show heterogeneity with respect to their tumorigenic potential. To determine whether we could detect cytogenetic abnormalities in these samples, we performed karyotypic analysis of the MPE samples. Fibroblast cell line GM 05399 served as a control for these studies. Hyperdiploidy was observed in all three MPE samples and in the control cell line H 2122. Abnormalities of chromosome 1p were observed seen in all the samples that led us to perform FISH (fluorescence in situ hybridization) studies using a dual color 1p36 and 1q25 probe (control). We found LOH (loss of heterozygosity) at 1p36 in two MPE samples and rearrangements of both 1p/1q regions in the third MPE sample. Cell line H 2122 contained one normal chromosome 1 and an unbalanced translocation of unknown origin at 1p36 consistent with deletion of 1p. Our studies therefore suggest that this 1p36 deletion could result in the inactivation of a tumor suppressor gene and other sequences that include miRNA 34a also mapped to this locus. Chromosomal rearrangements further indicate that cells with multiple phenotypes including those related to metastasis, and chemo-radiation resistance might be present in the MPE samples. These studies provide a good basis suggesting that MPE would serve as a useful model system for the identification of genes related to the progression of lung 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 5346. doi:1538-7445.AM2012-5346
Abstract 5347: Identification of differentially expressed proteins in breast cancer stem cells using proteomic profiling
Authors: Kanojia Deepak P. , Zhou Weidong , Zhang Jiajia , Lo Pang-Kuo , Zhou Jun , Chen Hexin 
Published: August 2012

Abstract
Cancer stem cells (CSCs) are now recognized as pivotal entity in the development and progression of breast cancer. The CSCs are believed to be responsible for recurrence/relapse of cancer because of their ability to resist chemotherapeutic drugs. The present drugs in the clinics predominantly target the highly proliferating cells sparing the slow dividing and resistant cells. If the drugs targeting the cancer stem cells evolve, there is a possibility of eradication of cancer. In this direction it is imperative to understand the fundamental difference between the cancer stem cells and the non cancer stem cells. Hence, a basic understanding of genes expressed in CSCs vs non-CSCs needs to be explored. A large number of high throughput and extensive Micro array studies have been carried out to understand the normal and various breast cancer subtypes however, the RNA profiles does not necessarily match the protein profile, Therefore determination of protein levels is the key to identify the novel targets for cancer stem cells. To address this issue and to identify meaningful targets for breast cancer we have characterized breast cancer stem cells from primary cultures of Her2/Neu transgenic mice. We identified the altered proteins through LC-MS/MS using an LTQ-orbitrap mass spectrometer and confirmed those results using quantitative RT-PCR. We further performed insilico analysis, using microarray datasets, for identification of group of genes, which in combination can provide prognostic importance. We identified PTMA, S100A4, S100A6, TNXRD1, COX-1, COX-2 and FTH1 as a group of genes, which in combination were significantly associated with poor clinical outcome of breast cancer patients. Among these genes FTH1 was identified as a novel protein associated with prognosis of breast cancer, which is overexpressed in enriched breast CSCs.
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 5347. doi:1538-7445.AM2012-5347
Abstract 5348: Transduction of tumors in vivo with choline kinase shRNA downregulates breast cancer stem cell markers
Authors: Krishnamachary Balaji , Penet Marie-France , Gadiya Mayur M. , Mori Noriko , Mironchik Yelena , Glunde Kristine , Bhujwalla Zaver M. 
Published: August 2012

Abstract
Increased phosphocholine is one of the metabolic signatures of cancer, and is closely associated with malignant transformation, invasion and metastasis. Increased phosphocholine is primarily due to increased expression of choline kinaseα, the enzyme that converts choline to the membrane precursor phosphocholine. Stem-like breast cancer cells (SBCCs) are drug resistant, invasive, and likely to lead to recurrence and repopulation. High CD44 adhesion molecule expression and high expression of the drug transporter ABCG2 are two markers associated with populations enriched with SBCCs [1]. Here we have examined the relationship between choline kinase and these two markers of SBCCs. We have determined the relationship between choline kinase downregulation and two markers of SBCCs, CD44 and ABCG2 in MDA-MB-231 breast cells in vitro and tumors in vivo upon lentiviral transduction of shRNA targeting choline kinase [2]. CD44 and its variant isoforms CD44v6 and CD44v8, together with ABCG2 showed a significant reduction in mRNA (30% for CD44 total; 80% for CDv6 and v8, and 45% for ABCG2) and protein expression levels following transduction of MDA-MB-231 cells with lentivirus expressing shRNA against choline kinase. Similar decreases were also observed following systemic intravenous injections of lentivirus expressing choline kinase shRNA delivered over four weeks. These studies provide insight into potential metabolic targeting of SBCCs. 1. Al-Hajj, M et al., Proc Natl Acad Sci U S A, 2003. 2. Krishnamachary, B et al., Cancer Research, 2009. This work was supported by NIH R01CA136576 and P50 CA103175.
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 5348. doi:1538-7445.AM2012-5348
Abstract 535: The role of high mobility group box 1 (HMGB1) in prostate carcinogenesis
Authors: Patel Purvi , Zheng Michelle , Bosland Maarten C. , Kajdacsy-Balla André , Munirathinam Gnanasekar 
Published: August 2012

Abstract
Prostate cancer is the most common cancer among older men and the second leading cancer-related cause of death in them. It is responsible for nearly 30,000 deaths per year in the United States. The causes for the development of prostate cancer are not clearly known although age and genetic factors play a key role in the etiology of this cancer. Epidemiological and experimental studies suggest that deregulated androgen levels and chronic inflammation also predispose to prostate cancer. However, the underlying molecular mechanisms which result in prostate cancer are not yet well known. Therefore, this study focuses on characterizing the role of High Mobility Group Box 1 protein (HMGB1), a co-activator of sex hormone receptors and a pro-inflammatory cytokine in the development of prostate carcinogenesis. In this study, we used an immortalized normal prostate cell (RWPE-1) to test if expression of HMGB1 in these cells will activate oncogenic signaling and transform them to a malignant phenotype. To achieve this, RWPE-1 cells were transfected with HMGB1 gene; stable lines were constructed and designated as RWPE-HMGB1. Cell cycle analysis by flow cytometry showed that majority (73%) of RWPE-1 cells over expressing HMGB1 was in the G2/M phase followed by polyploidy state (25%). Importantly, RWPE-HMGB1 cells when exposed to R1881 (synthetic androgen) treatment proliferated significantly in a time dependent manner compared to control RWPE-1 cells. Interestingly, the proliferative effects of HMGB1 in RWPE-1 cells was inhibited by anti-androgenic treatment (casodex) implicating HMGB1 to be a co-activator of androgen receptor in prostate cells. Further mechanistic studies revealed that expression of HMGB1 in RWPE-1 cells stimulated androgen receptor expression and PSA secretion in these cells. In addition, our studies also identified HMGB1 as an activator of two key extracellular (Extracellular signal-regulated kinase [Erk] and Toll-like receptor-4 [TLR-4]) pathways in RWPE-1 cells resulting in the inhibition of caspase-3 activation and prevention of PARP-1 cleavage suggesting HMGB1 is an inhibitor of apoptosis in prostate cancer cells. Overall, results of our study have identified a potential role of HMGB1 in prostate cancer which may help design drugs to target HMGB1 in preventing prostate 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 535. doi:1538-7445.AM2012-535
Abstract 5350: Aldehyde dehydrogenase 1 is useful for identifying some subtypes of non-basal triple negative breast cancer
Authors: Ishikawa Takashi , Ichikawa Yashushi , Shimizu Daisuke , Yamada Akimitsu , Tanabe Mikiko , Sasaki Takeshi , Kida Kumiko , Kimura Mariko , Ota Ikuko , Chishima Takashi , Endo Itaru 
Published: August 2012

Abstract
BACKGROUND Triple negative breast cancer (TNBC) is heterogeneous and consists of tumors associated with basal-type and cancer stem cell (CSC) phenotypes. Identifying these specific phenotypes is important for treating TNBC. The expression of aldehyde dehydrogenase 1 (ALDH-1), a biomarker of CSC phenotype, is observed more frequently in TNBC than non-TNBC and is associated with biologically aggressive features. AIM In order to categorize types of breast cancer, especially TNBC, ALDH-1 was examined in terms of 1) its association with pathological factors and 2) the genes significantly expressed in ALDH-1 positive cells. METHODS 1) The expression of ALDH-1 and its association with the other pathological factors of ER, PgR, HER2, p53, Ki-67, CK5/6, EGFR were examined immunohistochemically in 87 breast cancer samples. Histological grade was assigned to each of the samples.2) ALDH-1 positive and negative cells were collected by microdissection from formalin-fixed paraffin- embedded samples of 5 ALDH-1 positive breast cancer cases. mRNA was extracted and the expression profile of approximately 5,000 genes was assessed by cDNA microarray (Affymetrix GeneChip®, Human Genome U133 Plus 2.0 Array). By comparing gene expressions of ALDH-1 positive and negative cells in the same sample, characteristic genes related to CSC were identified. RESULTS 1) ALDH-1 was inversely correlated with ER (p=0.0006) and PgR (p=0.0054), while positively correlated with Ki67 (p=0.0023) and TopoII (p=0.0014). No association was found between ALDH-1 with CK5/6 or with EGFR. 2) Approximately 800 annotated genes were significantly up- or down- regulated. Several characteristic genes related to ALDH-1 have been presently confirmed by other methodologies. CONCLUSION CK5/6 and EGFR are currently used to identify basal-type TNBC. Because ALDH-1 was not associated with CK5/6 or EGFR, ALDH-1 and related genes may be helpful in identifying some non-basal types of TNBC.
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 5350. doi:1538-7445.AM2012-5350
Abstract 5352: Investigation of stem-cell markers in pleomorphic adenoma: Immunohistochemical and molecular study
Authors: Ianez Renata , Buim Marcilei , Coutinho-Camillo Cláudia , Soares Fernando , Lourenço Silvia 
Published: August 2012

Abstract
Background: Salivary gland neoplasms are originated from the various salivary gland compartments and are histologically related to these structures. Several protein and molecular markers are employed in research and diagnosis in order to classify and understand histogenesis and other aspects of salivary gland neoplastic lesions. Pleomorphic adenoma is a benign salivary gland neoplasm composed by epithelial and myoepithelial cells and a complex stroma. Its varied structural and architectural aspects suggest the participation of stem cells in its composition. Additionally, pleomorphic adenoma originates from intercalated duct of salivary glands, a region reputed to host the regenerative/ stem-cell compartment of these glands. The present work investigated stem-cell markers (CD24, CD44) in pleomorphic adenoma and in specimens of developing human salivary glands using immunohistochemistry and real-time RT-PCR. Material and Methods: 101 cases of pleomorphic adenomas were used - 55 cases were FFPE and 60 specimens were fresh frozen tissue. From the total, 14 were pared (FFPE and frozen tissue). Salivary gland specimens dissected from 20 human foetuses were also included. Results: All cases of pleomorphic adenomas were positive for the stem-cell markers studied. Neoplastic luminal structures were positive for CD24. Modified myoepithelial cells were positive for CD44. In foetal salivary glands, these markers were restricted to the intercalated duct region. Increased expression of CD44 stem-cell marker was observed in pleomorphic adenoma specimens using real-time RT-PCR technique when compared to normal salivary gland controls. An specific expression pattern was not observed for CD24 when compared to the normal salivary gland tissue - in some cases of pleomorphic adenoma there was an increased expression of the protein, whilst in other cases the expression was decreased or normal-like. Conclusion: Pleomorphic adenoma cells share similar markers with stem-cells; it is not possible to confirm that neoplastic cells bear the same characteristics of multipotency.
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 5352. doi:1538-7445.AM2012-5352
Abstract 5354: Nuclear spheres in developmental biology and diagnosis
Authors: Nieburgs Herbert E. 
Published: August 2012

Abstract
Introduction: The nuclear content of individual spheres with identical luminal diameters in buccal mucosa cells of patients with a malignant neoplasm at a distant site was first described by the author in 1962. Their biologic etiology remains unknown however. Recent studies revealed data on their correlation with nuclear spheres of cancer stem cells in asymmetric division. Materials and Methods: Observation of nuclear micro spheres was made by means of the highest magnification of the light microscope using a 100x objective and 10x ocular with a microscopic tube length of 1.25. The hematoxylin-eosin stain was applied for histological sections and cytological specimens. Buccal mucosa spreads of 145 cases were examined in correlation with cancer stem cells. Nuclear spheres in buccal mucosa cells were compared to those in self-renewal daughter cells of cancer stem cells in asymmetric division. Results: In asymmetric division of cancer stem cells the self-renewal daughter cell nucleus consisted entirely of spheres with identical luminal diameters of 0.33 to 0.5 µm. The other daughter cell was well differentiated with a nucleus devoid of spheres. In the buccal mucosa specimens with a distant malignant neoplasm, the nuclear content of spheres with luminal diameters of &lt; 0.5 µm were noted in 112 of 145 cases with a sensitivity of 77% and specificity of 86%. The primary tumors were diverse in type and location. Discussion: The scientific literature is silent as to the rationale for nuclear spheres that appear with their identical luminal diameters in the buccal mucosa cells distant from a primary malignant neoplasm and identical to those of self-renewal daughter cells in asymmetric stem cell division. Nuclear spheres in cells distant from the primary tumor may occur as a result of circulating blood DNA or through blood cell migration to the buccal mucosa. The systemic manifestation of nuclear spheres at distant sites from a primary tumor is in keeping with the systemic involvement of cancer described by numerous investigators including the teams led by M. Us-Krasovic and B. Palcic (2005) and D.S. Alberts and P.H. Bartels (2007). The identification of nuclear spheres as a result of an overt or occult cancer offers the potential of a non-invasive cancer test.
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 5354. doi:1538-7445.AM2012-5354