bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of 6-phosphofructo-2-kinase suppresses breast tumor growth in vivo.
Authors: Clem B , Telang S , Clem A , Goswami U , Chesney J 
Published: December 2010

Abstract
Abstract #3064
Phosphofructo-1-kinase, a rate-limiting enzyme of glycolysis, is activated in neoplastic cells by fructose-2,6-bisphosphate (Fru-2,6-BP), a product of four 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isozymes (PFKFB1-4). The inducible PFKFB3 isozyme is constitutively expressed by neoplastic cells and required for the high glycolytic rate and anchorage-independent growth of ras-transformed cells. We report that siRNA silencing or small molecule inhibition (3PO) of PFKFB3 causes a decrease in cell proliferation and metabolic flux in several breast cancer cell lines (MDA-MB-231, MDA-MB-468, BT-549, BT-474, SK-BR-3, ZR-75-1, MCF-7, and MCF-10A). Furthermore, 0.075mg/g 3PO administered via intraperitoneal injection suppresses tumor growth in two transgenic mouse models of breast cancer (MMTV-H-ras: 30% inhibition; MMTV-Erbb2(Her2/neu): 60% inhibition). Interestingly, the Her2 positive cell lines (SK-BR-3, BT-549) and the Her2 mouse transgenic model were more susceptible to PFKFB3 inhibition suggesting that the Her2 phenotype may be more sensitive to disruption of glycolytic flux. Taken together, these data support the clinical development of 3PO and other PFKFB3 inhibitors as chemotherapeutic agents against breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3064.
Adiponectin activates tumor suppressor LKB1 and AMP-activated protein kinase signaling to inhibit malignant properties of breast cancer cells.
Authors: Smith LT , Knight BB , Saxena NK , Sharma D 
Published: December 2010

Abstract
Abstract #3067
Introduction: The prevalence of obesity in the developed world has reached epidemic proportions in recent years. Obese breast cancer patients exhibit a higher risk for metastasis, larger tumor burden and poorer response to endocrine therapy. Therefore, it is very important to understand the adverse effects of obesity on breast cancer in order to devise appropriate new approaches to their treatment. Obesity is considered an endocrine disorder and serum levels of adiponectin, an adipocytokine proposed to have therapeutic potential, get significantly lowered with obesity. More recently, low serum adiponectin levels were associated with increased risk and more aggressive phenotype (larger tumor size and high histological grade) of breast cancer in women. Recently, anti-proliferative and pro-apoptotic response of adiponectin was shown in breast cancer cells but the molecular mechanisms governing the anti-cancer effects of adiponectin largely remain unknown. In the present study, we found a novel mechanism underlying adiponectin action involving upregulation of tumor suppressor LKB1 and activation of AMPK (AMP-activated protein kinase) signaling to inhibit malignant properties of breast cancer cells.&#x2028; Methods and Results: Adiponectin inhibited malignant properties such as invasion and migration of breast cancer cells in matrigel invasion, scratch migration and quantitative Electric Cell-Substrate Impedance Sensing (ECIS) invasion and migration assays. Interestingly, adiponectin induced phosphorylation of AMPK at Thr 172 in breast cancer cells. Adiponectin treatment also affected downstream targets of mTOR signaling pathway, including decreased phosphorylation of p70S6K showing the involvement of mTOR-S6K axis. Intriguingly, we found that adiponectin increased the expression of tumor suppressor LKB1 in breast cancer cells. Co-immunoprecipitation assays revealed that LKB1 co-immunoprecipitated with tumor suppressor TSC2. Increase in expression of upstream kinase LKB1 might directly regulate adiponectin induced activation of AMPK. We also found that breast cancer cells transfected with wild-type LKB1 plasmids increased phosphorylation of AMPK and decreased phosphorylation of p70S6K showing decrease in mTOR activity. In contrast, breast cancer cells transfected with kinase dead LKB1 decreased phosphorylation of AMPK and increased activation of p70S6K.&#x2028; Discussion: Taken together these data indicate a novel crosstalk between adiponectin and tumor suppressor LKB1 that modulates AMPK-S6K axis and inhibits metastatic properties, invasion and migration of breast cancer cells. The influence of adipocytokine, adiponectin on breast carcinogenesis is just beginning to be elucidated and our study is the first to show the direct involvement of tumor suppressor genes LKB1 and TSC2 in anti-cancer effects of adiponectin.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3067.
SATB1: a 'master genome organizer' in mammary carcinogenesis.
Authors: Worku D , Jiang WG , Mansel RE , Mokbel K 
Published: December 2010

Abstract
Abstract #3070
Background: SATB1 is a nuclear protein that has been recently reported to be a 'genome organizer' that delinates specific epigenetic modifications at target gene loci, directly up-regulating metastasis-associated genes while down-regulating tumor-suppressor genes. This study aimed to examine the level of mRNA expression of SATB1 gene in normal and malignant breast tissue and correlate the level to the clinico-pathological parameters.&#x2028; Material and Methods: One hundred and fifteen breast cancer tissue and 31 normal breast tissues were analyzed. Levels of transcription of SATB1 were determined using real-time quantitative PCR and were analyzed against TNM stage, nodal involvement, tumor grade and clinical outcome.&#x2028; Results: The levels of SATB1 mRNA were significantly higher in malignant compared with normal breast tissue (p=0.0167). The expression of SATB1 mRNA was demonstrated to increase with increasing TNM stage (TNM1 vs. TNM2, p=0.0264; TNM2 vs. TNM3, p=0.024) and increasing tumor grade (grade 1 vs. grade 3, p=0.017; grade 2 vs. grade 3, p=0.0437; grade 1 vs. grade 2&3, p=0.021). After a median follow up of 10 years, there was a trend for tumors with higher SATB1 expression levels to be associated with shorter overall survival times.&#x2028; Discussion: These results are consistent with the notion that SATB1 acts as the 'master genome organizer' in tumorigenesis of human breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3070.
The RNA binding protein HuR/ELAV1 regulates the estrogen receptor and epidermal growth factor receptor beta expression in BT 474 cells.
Authors: Licata LA , Hostetter C , Keen JC 
Published: December 2010

Abstract
Abstract #3076
The RNA binding protein HuR has been shown to increase the mRNA stability of the majority of transcripts to which in binds. Recent data has linked the cytoplasmic distribution of HuR to the tumorigenesis process in many cancer types. HuR levels were found to be higher in more metastatic, higher grade breast tumors, suggesting that it may play a role for stabilization of growth-promoting transcripts in breast cancer cells. Previously, our lab has shown that the DNA methyltransferase inhibitor 5-aza- 2'deoxycytidine (AZA) and histone deacetylase inhibitor Trichostatin A (TSA) decreased the cytoplasmic accumulation of HuR in MDA-MB-231 and MCF-7 cells. Therefore, to examine the role of HuR in the more tumorigenic, estrogen receptor (ER) positive, Tamoxifen resistant BT 474 cells were treated with AZA/TSA or siRNA probes specifically targeting HuR expression. The BT 474 cells had a baseline increase in the cytoplasmic distribution of HuR as compared to MCF-7 and MDA-MB-231 cells. The half-life of ER mRNA was also increased. Following AZA/TSA treatment for 24-96 hours, cytoplasmic HuR was noticeably lower after 48 hours of treatment. Subsequent mRNA levels of both ER and epidermal growth factor beta (erbB2/HER2) were also found to drop with treatment. siRNA inhibition of HuR had a similar effect on the mRNA levels. Biotin pulldown assays using probes specific for the ER 3' UTR showed HuR binding was decreased with AZA/TSA treatment. These were similar findings as previously reported in MCF7 cells. Since ER and erbB2 are central to hormonal therapy, Tamoxifen sensitivity was assessed using BT 474 cells transfected with siRNA probes specifically targeting HuR expression. Cellular viability following Tamoxifen treatment was significantly decreased when HuR expression was inhibited and Tamoxifen sensitivity was restored. Similar studies investigating the role of HuR in herceptin resistance are currently ongoing. Taken together, our data suggests that HuR plays a key role in both de novo and acquired Tamoxifen resistance.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3076.
Cytotoxic effects of crystal proteins from Bacillus thuringiensis against breast cancer cells.
Authors: Tharakan BD , Devaki G , Nair HB , Padikkala J 
Published: December 2010

Abstract
Abstract #3077
Insecticidal crystal proteins (ICPs) produced by the Gram-positive bacterium, Bacillus thuringiensis during sporulation, are widely used as bioinsecticides against lepidopteran larvae. The pro-protein, upon ingestion by larvae, is processed to an active form by proteases in midgut and binds to a specific receptor on the membrane surface of epithelial gut cells. This leads to permeable pore formation in the membrane surface and finally the death of the insects. The genes for crystal protein appear to reside on plasmids and shows high degree of diversity. Recent studies have shown that these potent toxins also exhibit selective cytotoxic activity against human breast cancer cells. In the present study, the cytotoxic effect of proteins extracted from three native strains of Bacillus thuringiensis from the Western Ghats of Kerala (India) was investigated. Crysal protein was harvested from 72h old cultures in sporulating medium, after confirming lysis of cells and release of crystal protein. The proteins were isolated and characterized through various chromatographic and electrophoretic procedures. The pro-protein isolated was activated and subjected in vitro cytotoxicity assay on various normal as well as breast cancer cell lines including MCF-7,MDA-MB-231, ZR-75 and SKBR3. The protein was found to have strong cytocidal activities against tumour cells and treated cells showed remarkable morphological alterations including cytoplasmic blebbing, cytoskeletal alterations etc. Considering these results, we suggest that the receptor mediated action of crystal proteins against tumour cells may have a new target in the therapeutic as well as diagnostic field of cancer therapy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3077.
Human papillomavirus in breast carcinomas of Korean women.
Authors: Choi J , Lee K , Kim W , Lee S , Lim H , Choi Y , Kim D , Lee J , Nam S , Yang J 
Published: December 2010

Abstract
Abstract #3086
Introduction&#x2028; The association between human papillomavirus (HPV) and cervical cancer is well documented. However, it remains unclear whether there is also a correlation between HPV infection and human breast cancer. The aim of this study was to investigate the status of HPV-DNA in breast carcinoma of Korean women and to examine the possible association between HPV and breast cancer development.&#x2028; Patients and Methods&#x2028; We examined the HPV-DNA of 154 patients including 123 cases of breast carcinoma, 31 cases of intraductal papilloma, and 27 cases of adequate nipple from cancer patients using DNA-chip method.&#x2028; Results&#x2028; The HPV-DNA was detected in 8 breast carcinomas (6.5%), but in none of the intraductal papillomas. All detected HPV was high-risk groups; the HPV-18 and HPV-70 were found in each two cases and each one cases HPV-16, 31, 56/58 and 59. In one case of nipple, both low-risk (HPV-62) and high-risk (HPV-18) group HPV-DNA was obtained. The papillary carcinomas and the invasive ductal carcinomas with adjacent intraductal papillomas showed slightly increased incidence (11% vs. 3-4%), however, there was no significant difference. No correlation between the presence of HPV-DNA and specific prognostic predictors for the disease outcome was observed.&#x2028; Conclusions&#x2028; Our results suggest that the presence of high-risk group HPV in the breast might be related to breast carcinogenesis, especially papillary phenotype. Further studies are warranted.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3086.
Mouse mammary tumor virus-related sequences in Mus musculus genome and human breast cancer tissues.
Authors: Lushnikova AA , Lyubchenko LN , Parokonnaya AA , Peredereeva EV , Polevaya EB 
Published: December 2010

Abstract
Abstract #3087
Background: Mouse mammary tumor virus is the causative agent for breast cancer (BC) in susceptible mouse lines. MMTV –homologous sequences were detected in breast carcinoma tissue DNA samples from 14-75% BC patients in Mexico, China, USA, Australia and Tunis. However, the sequences weren't found in Japanese, Austrian, English and some other human populations. Earlier, we have found the env MMTV –homologous sequences in BC tissues and peripheral blood lymphocyte DNA samples in 39-42% sporadic and 52% familial BC as well as in 64% of BC during pregnancy and/or lactation. These population differences in MMTV-related retrovirus frequencies might associated with geographic distribution of Mus musculus sp.domesticus – native MMTV reservoir. Material and methods: To demonstrate if wild commensal mice species are MMTV carriers we investigate 11 mice ( 3 males, 8 females) related to Mus musculus sp.domesticus from Moscow region (Russia) using specific PCR and RT-PCR followed by PCR products subcloning in pGEM-T vector and sequencing. A gp52 and ITAM-coding areas of the env MMTV gene, significant for MMTV infection and epithelial cells transformation , as well as a Sag-coding area of 3'LTR were analyzed. MMTV superantigen (Sag) – mediated amplification of MMTV in lymphoid cells is required for efficient viral transformation and dissemination in the mammary gland. Results: The sequences homologous to these functionally significant MMTV genome areas were detected in the DNA samples from mouse liver, timus and peripheral blood. In 63% (7/11) animals analyzed the sequences were expressed. The sequences homology with MMTV genome (C3H strain) according BLAST was 93-96%; homology with human MMTV- related provirus detected in BC patients was 86-95%. Recently MMTV-induced human epithelial cell transformation and important role of ITAM-coding area of the env MMTV gene was demonstrated in vitro. Conclusion: MMTV-related sequences were found in wild commensal mice, Mus musculus sp.domesticus, from Moscow region. In 60% cases these sequences, homologous to functionally significant env- and Sag-coding virus genome regions were expressed. Preliminary data support the possibility of the horizontal MMTV transmission from mice to humans, except of vertical one from mother to children.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3087.
Is there consensus in the definition of endpoints in metastatic breast cancer?.
Authors: Saad ED , Katz A 
Published: December 2010

Abstract
Abstract #3102
Objective: Progression-free survival (PFS) is defined as the time between treatment initiation and tumor progression or death from any cause, with censoring of patients who are lost to follow-up. Time to tumor progression (TTP) is theoretically different from PFS in that the event of interest is only disease progression. Both PFS and TTP have been considered as appropriate endpoints in drug development, but the extent to which investigators agree on their definition is unknown. We therefore assessed the recent literature regarding the consistence of the definition of PFS and TTP when used as primary endpoints in advanced breast cancer.&#x2028; Methods: We searched PubMed using the medical subject headings “breast neoplasms” and “drug therapy”, limiting the search to phase III trials on systemic antineoplastic therapies published between January 1, 2000, and December 31, 2007 in one of ten leading medical journals in the field (Annals of Oncology, Breast Cancer Research and Treatment, British Journal of Cancer, Cancer, European Journal of Cancer, Journal of Clinical Oncology, Journal of the National Cancer Institute, Lancet Oncology, The Lancet and The New England Journal of Medicine). We excluded randomized phase II trials, factorial trials, studies on high-dose chemotherapy, papers reporting combined analyses of two or more separate trials, and companion studies on correlative biology or prognostic factors.&#x2028; Results: The search yielded 59 trials enrolling a total of 23,371 evaluable patients in 122 treatment arms. PFS was the primary endpoint in 14 cases, and TTP in 21 when all treatment lines and modalities were considered (response rate was used in 20 cases, and overall survival in only one). For first-line chemotherapy trials (N=24), PFS and TTP were used as primary endpoints in 5 and 7 cases, respectively. In 5 of the 21 trials using TTP as the primary endpoint, no definition of this endpoint was reported in the article. Analysis of the other 16 cases showed that progressive disease was always considered an event in TTP analysis. However, in 13 of these cases, death (either from breast cancer or from any cause) was also counted as an event. The definition of PFS was reported in the article in 13 of the 14 trials using this primary endpoint. In all cases, the events of interest in Kaplan-Meier analyses included both progressive disease and death. In some cases, both terms (PFS and TTP) were even used to denote the same endpoint in the same paper.&#x2028; Conclusion: Our review suggests that investigators are frequently using PFS and TTP interchangeably in metastatic breast cancer. Such use of terms may lead to confusion when results of different trials are evaluated in perspective, and standardization of the definitions seems therefore in order.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3102.
Feasibility trial of electro-acupuncture for aromatase inhibitor related arthralgia in breast cancer survivors.
Authors: Mao JJ , Stricker CT , Farrar JT , Xie SX , Bowman MA , Bruner DW , Pucci D , Han X , DeMichele A 
Published: December 2010

Abstract
Abstract #3105
Background: Arthralgia affects postmenopausal women receiving aromatase inhibitors (AI) for breast cancer. Given the existing evidence for electro-acupuncture (EA) for treatment of osteoarthritis in the general population, this study aims to establish the feasibility of studying EA for treating AI-related arthralgia.&#x2028; Patients and Methods: Postmenopausal women with stage I-III breast cancer with joint pain related to AIs were enrolled in a pilot single arm trial of acupuncture. Acupuncture was provided twice a week for 2 weeks followed by 6 weekly treatments (total of 10 treatments over 8 weeks). Manualized protocol was based on Chinese medicine diagnosis of “Bi” syndrome with eletro-stimulation of needles around the painful joint(s). Pain severity of the modified Brief Pain Inventory was used as the primary outcome. Joint stiffness and Joint interference were secondary outcomes. Patient Global Impression of Change (PGIC) was used to assess clinical relevance. Fatigue and anxiety were also evaluated. Paired-t tests were used for analysis.&#x2028; Results: Twelve women were enrolled and all provided data for analysis. From baseline to the end of intervention, patients reported improvement in pain severity (5.3 to 1.9), stiffness (6.9 to 2.4), and joint symptom interference (4.7 to 0.8), all P&lt;0.001; 11/12 reported joint symptoms “very much improved” based on PGIC . Subjects also reported significant decrease in fatigue (4.4 to 1.9, p=0.005) and anxiety (7.1 to 4.8, p=0.01). One subject withdrew from interventions due to an adverse event (herpes zoster) thought to be unrelated to acupuncture. Two subjects reported grade 1 self-limiting pain associated with acupuncture. No infection or development or worsening of lymphedema was observed.&#x2028; Conclusion: EA is a potentially safe and effective treatment for AI-related arthralgia; thus, a randomized controlled trial is warranted to establish the short term and long term efficacy and safety of EA in breast cancer survivors.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3105.
Factors that influence seeking second opinions, patient satisfaction, and education in breast cancer care: an internet-based study.
Authors: Lund M , Bramley AM , Iyengar RG , Petersen J , Wood WC , Gabram SS 
Published: December 2010

Abstract
Abstract #3107
Purpose: To examine factors associated with seeking second opinions, patient satisfaction, and education among a recently diagnosed internet-based breast cancer population. Methods: In 2007, 6970 of the 90,426 internet-registered female breast cancer patients completed an internet-based survey, developed jointly by members of the Department of Surgical Oncology at Emory University and the educational staff at the Healthcare business of Thomson Reuters, formerly Nexcura. After excluding caregivers (n=205), those not within 5 years of diagnosis (n=962) or for whom treatment information was missing (n=40), we analyzed 5763 patients. Chi-square tests were used to assess system characteristics and patient demographics by their second opinion, satisfaction, and informed status. Patient satisfaction was collapsed as low (1-3), moderate (4-6), or high (7-10). How informed patients considered themselves was combined into 3 categories: well-informed (well or very well informed), somewhat informed and uninformed (somewhat or very uninformed). Results: The majority of the 5763 patients were between ages 40 and 59 when diagnosed (75.43%), Caucasian (92.96%), currently married (76.33%), had a household income ≥ $50,000 (60.92%) and at least a 4-year college education (55.78%). Stage I and II cancers comprised 36.61 and 35.71% respectively. Over one-third (n=2039) sought a second opinion. Factors significantly associated with seeking a second opinion were higher socioeconomic or education status, feeling informed, receiving the initial diagnosis from a primary care physician or private community hospital, close proximity to the biopsy location, and less satisfaction with the initial biopsy experience. Patients highly satisfied with their second opinion (87.35%) were more likely to refer others (96.52%), use the second opinion facility for the next treatment (63.90%), and to not seek additional opinions (75.29%). Facility options and initially being treated with surgery or systemic therapy predicted high satisfaction with initial treatment. Medical oncologists were the most frequently cited primary source of breast cancer education (37.81%), followed by surgeons (30.57%), and the internet (12.77%). About 20% who cited these sources considered themselves somewhat or very uninformed. Conclusions: Women who seek information via the internet rely primarily on medical professionals for their breast cancer education. Factors related to the initial biopsy affect the likelihood of patients seeking a second opinion, satisfaction with second opinions can influence choices regarding the ensuing treatment steps, and factors associated with initial treatment influence patient satisfaction. Probing the issues underlying these findings could improve care for all.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3107.