bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth Inhibition of HeLa Cells Is a Conserved Feature of High-Risk Human Papillomavirus E8^E2C Proteins and Can Also Be Achieved by an Artificial Repressor Protein
Authors: Fertey Jasmin , Hurst José , Straub Elke , Schenker Astrid , Iftner Thomas , Stubenrauch Frank 
Published: December 2010

ABSTRACT

Infections with certain human papillomaviruses (HPV), such as type 16 (HPV16), 18, or 31, are a necessary risk factor for the development of cervical cancer. Transcript analyses of several HPV revealed that the viral E2 gene encodes both the E2 regulator protein and the E8∧E2C protein, which differ in their amino termini. Up to now, functional studies have focused on HPV31 E8∧E2C and demonstrated that it is a potent repressor of viral transcription and replication. However, recent analyses of HPV16 genomes have suggested that E8∧E2C proteins may differ in their activities. Therefore, we performed a comparative analysis of E8∧E2C proteins of HPV16, -18, and -31. All E8∧E2C proteins potently inhibited HPV E6/E7 oncogene promoters, and also displayed long-distance transcriptional-repression activities. Furthermore, the expression of all E8∧E2C proteins inhibited the growth of HeLa cells. Expression of E8∧E2C proteins rapidly increased the protein levels of the E6 and E7 targets p53 and p21, consistent with the repression of the endogenous HPV18 E6/E7 promoter. All E8∧E2C proteins induced G
1
arrest more efficiently than E2 proteins and activated senescence markers. Furthermore, we demonstrate that the 31E8 domain can be functionally replaced by the KRAB repression domain derived from KOX1. The KRAB-E2C fusion protein possesses long-distance transcriptional-repression activity and inhibits the growth of HeLa cells comparably to E8∧E2C. Taken together, our results suggest that the E8∧E2C proteins of HPV16, -18, and -31 are highly conserved transcriptional repressors that inhibit the growth of HeLa cells by repression of E6/E7 transcription but do not have proapoptotic activities.
Multiple Interactions between the ESCRT Machinery and Arrestin-Related Proteins: Implications for PPXY-Dependent Budding
Authors: Rauch Susanne , Martin-Serrano Juan 
Published: December 2010

ABSTRACT

Late domains are short peptide sequences encoded by enveloped viruses to promote the final separation of the nascent virus from the infected cell. These amino acid motifs facilitate viral egress by interacting with components of the ESCRT (endosomal sorting complex required for transport) machinery, ultimately leading to membrane scission by recruiting ESCRT-III to the site of viral budding. PPXY late (L) domains present in viruses such as murine leukemia virus (MLV) or human T-cell leukemia virus type 1 (HTLV-1) access the ESCRT pathway via interaction with HECT ubiquitin ligases (WWP1, WWP2, and Itch). However, the mechanism of ESCRT-III recruitment in this context remains elusive. In this study, we tested the
a
rrestin-
r
elated
t
rafficking (ART) proteins, namely, ARRDC1 (arrestin domain-containing protein 1) to ARRDC4 and TXNIP (thioredoxin-interacting protein), for their ability to function as adaptors between HECT ubiquitin ligases and the core ESCRT machinery in PPXY-dependent budding. We present several lines of evidence in support of such a role: ARTs interact with HECT ubiquitin ligases, and they also exhibit multiple interactions with components of the ESCRT pathway, namely, ALIX and Tsg101, and perhaps with an as yet unidentified factor. Additionally, the ARTs can be recruited to the site of viral budding, and their overexpression results in a PPXY-specific inhibition of MLV budding. Lastly, we show that WWP1 changes the ubiquitination status of ARRDC1, suggesting that the ARTs may provide a platform for ubiquitination in PPXY-dependent budding. Taken together, our results support a model whereby ARTs are involved in PPXY-mediated budding by interacting with HECT ubiquitin ligases and providing several alternative routes for ESCRT-III recruitment.
System of General Variational Inequalities Involving Different Nonlinear Operators Related to Fixed Point Problems and Its Applications
Authors: Inchan Issara , Petrot Narin 
Published: December 2010

AbstractBy using the projection methods, we suggest and analyze the iterative schemes for finding the approximation solvability of a system of general variational inequalities involving different nonlinear operators in the framework of Hilbert spaces. Moreover, such solutions are also fixed points of a Lipschitz mapping. Some interesting cases and examples of applying the main results are discussed and showed. The results presented in this paper are more general and include many previously known results as special cases.
Iterative Methods for Family of Strictly Pseudocontractive Mappings and System of Generalized Mixed Equilibrium Problems and Variational Inequality Problems
Authors: Shehu Yekini 
Published: December 2010

AbstractWe introduce a new iterative scheme by hybrid method for finding a common element of the set of common fixed points of infinite family of "Equation missing"-strictly pseudocontractive mappings and the set of common solutions to a system of generalized mixed equilibrium problems and the set of solutions to a variational inequality problem in a real Hilbert space. We then prove strong convergence of the scheme to a common element of the three above described sets. We give an application of our results. Our results extend important recent results from the current literature.
Feasibility and Accuracy of Sentinel Lymph Node Biopsy in Clinically Node Negative Patients after Neoadjuvant Chemotherapy for Breast Cancer – A Systematic Review and Metaanalysis.
Authors: Tan V. , Lee S. , Goh B. , Chung A. , Sebastian M. , Yong W. , Wong W. 
Published: December 2010

Abstract
BackgroundThe sentinel lymph node biopsy (SLNB) has become an accepted alternative to the axillary lymph node dissection (ALND) for pathologic evaluation of the axillary lymph node status in patients with early breast cancer and a clinically negative axilla. Patients with a negative sentinel lymph node are spared the ALND and its associated morbidities.Currently, there is insufficient evidence to recommend the use of SLNB in patients who have received neoadjuvant chemotherapy (NAC), and treatment of the axilla after neoadjuvant chemotherapy is an ALND.The use of neoadjuvant chemotherapy is increasing, and NAC has been shown to downstage both the primary tumour and axillary lymph nodes. Potentially, an additional proportion of patients who are node negative after NAC may be spared a full ALND and its attendant morbidities.AimsTo determine the feasibility and accuracy of SLNB in patients who have a clinically negative axilla after neoadjuvant chemotherapy for breast cancer.MethodsA systematic review of the English literature of SLNB in patients who have had neoadjuvant chemotherapy (NAC) was conducted and meta analyses performed. Studies selected had an identifiable group of patients with breast cancer who received neoadjuvant chemotherapy and were clinically node negative. These patients had a SLNB prior to the standard ALND regardless of outcome of the SLNB.ResultsTen studies that met the eligibility criteria were identified. A total of 449 patients were studied. Pooled analysis using the fixed effects model was used to calculate successful identification rate and accuracy parameters. The summary rate of identification of SLN was 94% [95% CI: 91.6% – 96.7%]. The pooled sensitivity of SLNB after NAC was 93% [95% CI: 88.5% – 96.8%] and the false negative rate 7.0% [95% CI: 3.2% – 11.5%].ConclusionSLNB in patients with a clinically node negative axilla after neoadjuvant chemotherapy is feasible and accurate.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1013.
Level III Lymph Node Involvement Cannot Be Predicted Following Positive Sentinel Node Biopsy.
Authors: Romano E. , Absar M. , Kirwan C. , Wilson M. , Pritchard S. , Barr L. , Baildam A. , Bundred N. 
Published: December 2010

Abstract
Background: Radiotherapy is a treatment alternative to axillary node clearance following a positive sentinel node biopsy. However level III lymph nodes are not usually treated with current axillary radiotherapy protocols, raising the concern of inadequate treatment.Methods: A retrospective review of 636 patients undergoing sentinel node biopsy for breast cancer, following normal axillary ultrasound, to identify factors predicting for level III involvement.Results:In total 115 (18% of 636 women undergoing sentinel node biopsy had node involvement. Subsequent axillary node clearance in these patients identified 50% with further axillary node involvement. Further lymph node involvement was not predicted by standard pathological factors (oestrogen/progesterone/Her 2 neu receptor status/tumour size/grade). The Memorial Sloane Kettering Cancer Center (MSKCC) breast nomogram for additional node metastases had limited clinical utility. The mean (range) score to predict node involvement in node positive patients was 22% (4-95%) and node negative patients was 13% (5-33%) (p=0.01). 11% of patients had metastatic disease in level III nodes at surgery. Level III involvement was not predicted by routine clinicopathological factors, and although the MSKCC breast nomogram gave higher scores for the prediction of patients with subsequent level III involvement (level III positive: 32% (6-95%); negative: 14% (4-69%)), it was not discriminatory.Conclusion: Neither the MSKCC breast nomogram or standard clinicopathological factors predict for level III node involvement following positive sentinel node biopsy. Level III axillary node clearance must therefore be recommended as the gold standard for positive axillary disease to avoid the risk of undertreating 11% of patients.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1015.
Can Axillary Lymphadenectomy Be Avoided in any Case of Sentinel Node Metastasis?
Authors: Giménez-Climent M. , Merck B. , Martínez- Alzamora N. , Fliquete Peris M. , Martínez-Carsí C. , Almenar-Medina S. , Bayón A. , Llopis-Martínez F. , Sancho M. , Ruíz A. , Vázquez-Albadalejo C. 
Published: December 2010

Abstract
INTRODUCTION: Axillary lymphadenectomy is the gold standard for sentinel node metastasis (SN). Metastasis rate of non – sentinel node (NSN) is related to tumor and SN metastasis sizes. In over 50% of cases of SN metastasis, the SN is the only node with neoplasm involvement. We have studied the variables that are known to influence most on SN metastasis (tumor size) and on NSN metastasis (size of the SN metastasis) with the aim to find out a subgroup of patients in whom axillary lymphadenectomy could be avoided despite of SN involvement.OBJECTIVE: To determine if lymphadenectomy is necessary in all patients with SN metastasis.MATERIAL AND METHOD: A sequential and prospectively maintained database was retrospectively searched, for patients staged with SN biopsy for breast carcinoma. We have reviewed 1285 consecutive breast cancer patients treated between December 1998 and April 2009, average age: 55 ± 12.5 years. SN localization was performed with isotopic (34%) or combined technique (66%). SN biopsy was associated to breast conserving technique in 79.8% of cases. The histopathologic study of SN consisted of serial sectioning, H&E and immunohistochemical (IHC) staining.Statistical analyses were performed using SPSS version 15.0 (SPSS Inc, Chicago, Ill). Comparisons of NSN tumoral infiltration among groups (negative SN, isolated tumoral cells (ITC) and SN micrometastasis) related to tumoral size were assessed by univariate analysis with contingency tables and χ2 test. Multivariate analysis was performed using a binary logistic regression model.RESULTS: Identification rate was of 95.8%. SN metastasis was detected in 418 patients, axillary lymphadenectomy was the treatment in 384 cases. The SN was the only metastatic lymph node in 276 patients (71.9%), whereas more involved nodes were found in 108 patients (28.1%). On multivariate analysis, the variables independently associated to SN metastasis were: age (p=0.005), tumor size (p&lt;0.005) and lymphovascular infiltration (LVI) (p=0,005) and the size of the SN metastasis was an independent factor (p=0.005) related to NSN metastasis.In all the 150 cases where the tumor size was ≤ 10 mm, there was no significant difference in NSN involvement between the three forms of SN (negative, micrometastasis, ITC) (p=0,132).CONCLUSIONS: SN metastasis was associated to younger age, large tumor size and LVI. NSN metastasis, in case of SN involvement, is related to the extent of the SN metastasis. In tumors ≤ 10mm where a micrometastasis is found in the SN, axillary lymphadenectomy could be omitted, due to the insignificant difference related to NSN involvement.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1027.
The Influence of Mammaplasty in Axillary Lymphatic Drainage Patterns and Sentinel Lymph Node Detection.
Authors: Soler C. , Bouteille C. , Mignotte H. , Steiner A. , Gremillet E. , Geissler B. 
Published: December 2010

Abstract
Introduction: Controlateral mammaplasty is often necessary during the procedure of breast reconstruction after mastectomy.However the impact of this kind of surgery on axillary lymphatic drainage and sentinel node (SN) detection remains controversial. The American Society of Clinical Oncology (ASCO) as published a guideline in 2005 and recommended that SN biopsy should not be performed in patients with previous mammplasty or axillary surgery.However, because of insufficient evidence and lack of scientific studies, mammaplasty cannot be considered as an absolute contraindication for SN biopsy procedure. Therefore, the same panellists of the ASCO guideline suggested that a preliminary lymphoscintigraphy (LSG) could be done when considering a SN biopsy in patients with previous mammaplasty, with the objective of verifying the integrity of the mammary gland and axillary nodes.The aim of our study was to evaluate the lymphatic patterns and SN detection rates after mammaplasty by using lymphoSPECT-CT (LS).Methods: ten patients who underwent mammaplasty were evaluated by LSG immediately after intradermal periareolar injections of 99mTc -labelled sulphur colloid (NanoCIS*) at two time points: before mammaplasty (Pre-LS) and between 40 to 60 days after mammaplasty (Post- LS).Results: all breasts drained primarily to the axillary SN. The binomial test did not show statistical difference in lymphatic drainage patterns between Pre-LSG and Post-LSG.The average number of hot SN was 1.28 in Pre-LS, 1.14 in Post-LS.The localisation of hot SN was evaluated by:- antero-posterior distance was estimated in centimeter from SN region to dorsal vertebrae spine center-SN's coronal position was compared to grill rib.The preservation of axillary lymphatic drainage after mammaplasty was allowed for SN detection in all studied breasts and the localisation of the sentinel node was the same after surgery than before.Conclusion: after evaluating the impact of the previous mammaplasty surgery on the accuracy of SLN biopsy, we observed that this kind of surgery did not significantly affects the accuracy of lymphatic mapping and that it may be possible to propose sentinel node biopsy after mammaplasty.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1028.
Multiple Breast Cancer Risk Factors Do Not Improve Patient Acceptance of Chemoprevention.
Authors: Lo S. , Henry E. , Rychlik K. , Mumby P. , Bowling L. , Robinson P. , Albain K. 
Published: December 2010

Abstract
Background: Patients may be at increased risk of developing breast cancer due to hereditary or familial risk or a pathological diagnosis of breast atypia or lobular carcinoma in situ (LCIS). Although tamoxifen and raloxifene are effective and approved chemopreventive agents to reduce risk of developing breast cancer in high risk individuals, acceptance of chemoprevention as a risk reduction strategy is low. Our objective was to assess whether chemoprevention is more readily accepted by those at genetic or familial risk versus pathologic risk, and if the presence of multiple breast cancer risk factors improves chemoprevention acceptance.Methods: All patients seen at the Loyola University Cancer Risk Assessment and Prevention clinic completed information including demographics, health, family and social history. Patients with a family history of either a first or second degree family member with breast cancer (FH) were compared to those who presented due to atypia or LCIS on breast biopsy as well as those with an elevated Gail score. Acceptance of risk reducing strategies between these groups was compared.Results: The initial 115 patients presenting to the clinic were analyzed. Thirty-six (31%) women had FH only, 26 (23%) had a biopsy with atypia or LCIS only, 10 (9%) had an elevated Gail score, 17 (15%) had a biopsy indicating atypia or LCIS plus FH, and 26 (23%) had an elevated Gail plus FH. Seventy-three patients were candidates for chemoprevention; 16 (22%) accepted chemoprevention. Patients with a FH plus atypia/LCIS did not accept chemoprevention more than patients with FH alone (p=1.00). Patients with a FH plus atypia/LCIS did not accept chemoprevention more than than patients with atypia/LCIS alone (p=0.451). Pts with elevated Gail plus FH did not accept chemoprevention more than patients with elevated Gail alone (p=0.144). Four women in the FH group were known BRCA mutation carriers; all elected to proceed with risk reducing surgery, none accepted chemoprevention.Conclusions: Acceptance of chemoprevention is low in women at genetic or familial risk, those at risk due to atypia/LCIS, and those with an elevated Gail score. Having both familial and pathologic risk factors for breast cancer development did not increase acceptance of chemoprevention. Better understanding of women's comprehension of breast cancer risk, and barriers to patient acceptance of chemoprevention are needed.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1039.
Use of MMTV-Neu/P53 KO Transgenic Mice To Screen for Potential Chemopreventive Agents.
Authors: Grubbs C. , Juliana M. , Bode A. , Iwata K. , Ruppert M. , Lubet R. 
Published: December 2010

Abstract
The MMTV-Neu transgenic model of mammary cancer was developed almost 20 years ago in which the mice develop Neu over-expressing ER- mammary cancers. Since human ER- Neu over-expressing mammary cancers often also have mutations in P53, a heterozygous KO of P53 was incorporated into the model. We used this model to examine a wide variety of potential chemopreventive agents. The agents were administered to virgin female MMTV-Neu/P53 KO mice beginning when they were 60 days of age. Initiation of treatment with the agents was later than that typically employed by other investigators (e.g., 35 days of age). Mice were monitored until 360 days of age. In agreement with Brown and colleagues (e.g., Cancer Research 62, 6376-6380, 2002), it was found that both RXR agonists (Targretin, UAB-30) and EGFR 1 and/or 2 inhibitors (Tarceva, Lapatinib) were highly effective in preventing the development of these cancers. We also observed that a wide variety of agents were ineffective; including Atorvastatin, rosiglitazone (a PPAR gamma agonist), SAHA (an HDAC inhibitor), and a soy isoflavones mixture. In separate studies, mice bearing small palpable mammary tumors were treated for five days with these various agents, and examined for alterations in potential biomarkers; including proliferation. As previously shown by our lab in an ER+ rat model of mammary cancer, effective agents (e.g., Iressa and Targretin) strongly inhibited cancer cell proliferation, whereas ineffective agents failed to significantly inhibit proliferation. Thus, such a short-term assay might be employed to predict potential chemopreventive compounds. Short-term treatment with the EGFR inhibitors also decreased levels of expression of phosphorylated EGFR and downstream proteins; e.g., AKT/ERK. Thus, this model is useful in identifying agents that will prevent the development of human breast cancers that over-express Neu. This is important since Neu over-expressing ER- cancers have a relatively poor prognosis, and Neu over-expressing ER+ tumors are relatively unresponsive to standard hormonal therapies (e.g., tamoxifen and aromatase inhibitors). Supported by NCI contract HHSN261200433001C.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1042.
Surgical/Pathologic Breast Cancer Indicators: Adherence by the Florida Initiative for Quality Cancer Care (FIQCC) Consortium.
Authors: Laronga C. , Gray J. , Siegel E. , Ji-Hyun L. , Fulp W. , Jacobsen P. 
Published: December 2010

Abstract
Background: The FIQCC is comprised of 11 practice sites across the state that participate in a comprehensive review of quality of care specific to cancer patients across many disease sites. Quality indicators were scripted based on the accepted QOPI, NCCN, ACOS, and site-specific PI panel consensus indicators for breast cancer patients. An evaluation was done to assess adherence to performance indicators among the sites.Methods: Comprehensive chart reviews were conducted for all patients with breast cancer first seen in 2006 by a medical oncologist at one of the 11 FIQCC sites (3 academic/8 community). Quality measures included: 1) presence and completeness of the pathology report (tumor size, grade, specimen orientation, margins inked, margin status, receptor status); 2) documentation of surgery type (breast conserving vs. mastectomy); 3) documentation of sentinel lymph node biopsy (SLNB) and if SLNB positive for metastatic disease documentation of a complete axillary node dissection; 4) mammogram usage post surgery; and 5) referral to radiation. Statistical comparisons were performed using chi-square test.Results: Charts of 622 patients (99% female) with a median age of 60 years (range 22-95) were reviewed. With respect to pathologic reporting, there was strong compliance (&gt;90%) for documentation of a pathology report, AJCC or TMN staging, tumor size and grade, status of margins, and receptor status. However, only 370 of 537 (69%) reports documented that the specimen was oriented and 474 of 537 (88%) stated the margins were inked. Breast conserving surgery was performed in 294 of 539 patients (55%). In clinical N0 patients, SLNB was performed in 447 of 543 (82%). Of the patients with a metastatic SLNB, 123 of 156 (79%) went on to have a complete axillary node dissection. Compliance was highly variable with obtaining a mammogram within 14 months of surgery (77%; range 26-98%). However, referral to radiation within 1 year was highly consistent (97%; range 80-100%). Significant variances across practice sites were noted for the reporting of margin orientation (p&lt;0.001), inking of the margins (p&lt;0.001), performance of SLNB (p&lt;0.001), and obtaining a mammogram within 14 months of surgery (p&lt;0.001).Discussion: The FIQCC allows for identification of the need for quality improvement in multiple aspects of breast cancer care. Findings based on 2006 cases identified a need for improvements in margin orientation and inking, use of SLNB and obtaining mammograms in follow-up after breast conserving surgery. These findings are now being used at the participating sites to guide quality improvement efforts.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1079.