bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-01-10: Optimal Sampling Number of Sentinel Lymph Nodes in Invasive Breast Cancer: Results of 1,026 Sentinel Lymph Node Biopsies by Radioisotope
Authors: Choi J-E , Park S-Y , Jeon M-H , Kang S-H , Lee S-J , Bae Y-K. 
Published: April 2011

Abstract
Backgrounds: For isotope mapping, many authors defined the sentinel lymph node (SLN) as one containing isotope counts higher than the axillary background. Some defined the SLN by using a node/background ratio. However no study has sought to define optimal guideline, and the number of SLNs needed for precise detection of metastatic SLNs is still on debate. So, we intended to determine the optimal sampling number of SLNs. Patients and Methods: From January 2005 to December 2008, 1,026 patients with primary invasive breast cancer who received sentinel lymph node biopsy (SLNB) using radioisotope at Yeungnam University hospital were enrolled. During SLNB, the ex vivo isotope counts were measured for each SLN. And the number and metastatic status of harvested SLNs were investigated. We defined SLNs as lymph nodes that show isotope count more than 10 times compared with that of axillary background. Each SLN was labeled as S1 (highest isotope count), S2 or S3 and so on, in descending isotope count order. If SLN was positive for metastasis, completion axillary lymph node dissection was performed. Pathologic report was reviewed for analysis.
Results: Mean age of patients was 48.9 years (ranges, 22∼83 years) and the mean number of removed SLNs was 2.8 (ranges, 1∼11). Among 311 (311/1026, 30.3%) patients who had SLN metastasis, S1 is positive (S1+) in 258 patients (82.9%), S2 (S1-, S2+) in 40 patients (12.3%), and S3 (S1-, S2-, S3+) in 13 patients (3.9%), respectively. There was no metastasis in SLN defined as S4, S5 and so on. So, the sampling of S1 was sufficient for a positive diagnosis in 82.9% of these cases, additional sampling of S2 and S3 increased metastatic detection rate to 95.2% and 100%, respectively. Average number of sampling SLNs until detecting metastasis in S1, S2 and S3 is 1.24 (1∼4), 2.45(2∼4) and 3.46(3∼5), respectively.
Metastatic status of SLN and the corresponding percentage of patients on the basis of the order of radioisotope count
SLN=sentinel lymph node
Conclusions: We concluded that during sentinel lymph node biopsy using radioisotope, for accurate axillary lymph node staging, at least 3rd isotope-count-order of sentinel lymph node should be removed. Therefore the average number of SLNs needed for detecting metastasis in S3 is four.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-10.
Abstract P1-01-14: Intraoperative Injection of Technetium-99m- Dextran 500 for the Identification of Sentinel Lymph Nodes in Breast Cancer
Authors: Graudenz MS , Delazeri GJ , Xavier NL , Menke CH , Spiro BL. 
Published: April 2011

Abstract
Background: The intraoperative injection of radiocolloid before a sentinel node biopsy (SLN) in breast cancer has been recently described.The advantages of this approach would be precluding the performance of a scintigram, cost reduction and elimination of pain and anxiety related to the preoperative procedure.
Objectives: To evaluate the efficacy of intraoperative injection of Dextran 500-99m-Tc and to analyze whether different radiocolloid doses, breast volume and Body Mass Index (BMI) influence the migration time to the axilla.
Material and Methods: This is a prospective study of 74 SLN biopsies of breast cancer patients, stages T1N0 and T2N0. After anesthesia induction, patients underwent subareolar dermal injection of 0.5 to 1.5 mCi (18 to 55 MBq) of filtered Dextran 500-99m-Tc (0.22µl) in a volume of 5 ml along with 2 ml of blue dye.
Results: The probe identification rate was 98% (73/74 cases) and the medium radiocolloid dose used was 0.97 mCi ± 0.22. The radiocolloid migration time to the axila was 10 min and 43 s (± 5:43 s). An average of 1.66 lymphnodes were identified through the use of radiocolloid and 1.53 through the use of bue dye. Different radiocolloid doses did not modify migration time to SLN (p=0.73). However, larger breast volumes were associated with longer migration time to the axilla (Pearson Correlation 0.393 p&lt; 0.01). The same correlation was observed with BMI (Pearson Correlation 0.469 p&lt; 0.01).
Discussion: The intraoperative injection of Dextran 500-99m-Tc is efficient in the identification of SLN in breast patients. Higher BMI and larger breasts determine longer migration time, however injection of larger doses of radiocolloid do not reduce transit time to the axilla.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-14.
Abstract P1-01-15: Intraoperative Imprint Cytology Examination of Sentinel Lymph Nodes after Neoadjuvant Chemotherapy in Breast Cancer Patients
Authors: Monrigal E , Dauplat M-M , Durando X , Abrial C , Le Bouedec G , Mouret-Reynier M-A , Cachin F , Kwiatkowski F , Tchirkov A , Dauplat J , Penault-Llorca F , Gimbergues P. 
Published: April 2011

Abstract
Background: Intraoperative imprint cytology (IC) is one of several accurate, proved methods to detect tumor cells in sentinel lymph nodes (SLN) from patients with operable breast cancer. In patients treated by neoadjuvant chemotherapy (NAC), studies have demonstrated the feasibility and accuracy of SLN biopsy procedure. The aim of this study was to evaluate the validity of tumor cell detection using IC in SLN from patients who underwent NAC.
Material and methods: Patients with infiltrating breast carcinoma receiving NAC (n= 132) were studied prospectively. At surgery, SLN biopsy followed by axillary lymph node dissection was performed. Intraoperative SLN evaluation using IC was performed in 80 out of 132 patients (60%). In the same period, IC has been evaluated at random for 100 chemonaïve patients in the same institution.
Results: Sentinel lymph node metastases were correctly identified using IC in 58 of 80 (72%) patients. False negative results were observed in 21 patients. The overall sensitivity and specificity of IC for the identification of lymph node metastases was respectively 38.2% and 97.8%. The positive predictive value was 92.9% and the negative predictive value was 68.2%. In univariate analysis and multivariate logistic regression analysis, patients with micrometastases or ITC in SLN have 2.3 times higher risk of a false negative IC result than patients with macrometastases of the SLN (P= 2.1.10-4; RR= 2.3; 95% confidence interval [1.37-3.85]). For chemonaïve patient, sensitivity, specificity, PPV and NPV were respectively 47.4%, 98.8%, 90% and 88.9%.
Conclusion: The accuracy of intraoperative IC observed in our study is similar to that reported previously in patients without NAC, indicating that IC is a clinically acceptable method for intraoperative pathological examination of SLN for patients after NAC. Variations in sensitivity are related to the proportion of cases with micrometastases and ITC, as it was also shown in chemonaive patients.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-15.
Abstract P1-01-31: Axillary Recurrence Rate Is Associated with Sentinel Lymph Node Pathology Protocol
Authors: Bolster MJ , Pepels MJ , Bult P , Wauters CA , Schapers RF , Meijer JW , Strobbe LJ , van Berlo CL , Klinkenbijl JH , Wobbes T , Voogd A , Tjan-Heijnen VC. 
Published: April 2011

Abstract
Background Internationally, there is no consensus on the pathology protocol to be used to examine the sentinel lymph node (SN). At present, therefore, various hospitals use different SN pathology protocols, leading to different SN findings and subsequent surgical treatment strategies. Previously, we reported in a prospective registry study of 4 hospitals in the Netherlands, that ultra-staging led to more axillary lymph node dissections (ALND) (Bolster et al. Ann Surg Oncol 2006). This present study reports follow-up data of the patients who had a negative SN, so patients who did not undergo an additional ALND. The question was, whether ultra-staging and thus fewer patients not undergoing an additional ALND, is effective in that it reduces the risk of relapse.
Patients and Methods Patients from 4 hospitals (A, B, C, and D) were prospectively registered when they underwent a SN biopsy because of a cytological or histological proven invasive breast cancer. In hospitals A, B, and C, 3 levels of the SN were examined pathologically, whereas in hospital D at least 7 additional levels were examined. In the absence of apparent metastases with H&E examination, immunohistochemical examination was performed in all 4 hospitals. Patients with a positive SN, including isolated tumor cells, underwent an ALND. This analysis focuses on the SN negative patients, who did not undergo a completion ALND. In all cases a follow-up period of at least 5 years was guaranteed. Primary endpoint was 5-year regional recurrence rate.
Results Of 541 patients who underwent a SN procedure, 341 (63%) patients had a negative SN, and did not undergo an ALND. In hospital D fewer patients had a negative SN when compared to patients in hospitals A, B, and C (34% versus 71%, P&lt;0.001). At 5 years follow-up, 9 (2.6%) patients showed a regional lymph node relapse. Five (1.5%) patients had an axillary lymph node recurrence and 4 (1.2%) patients a supraclavicular recurrence. In hospital D none of the patients had a regional recurrence, as compared to 9 (2.9%) cases of recurrence in hospitals A, B, and C. Conclusion We showed that patients who underwent a less intensified SN pathology protocol, with a reduced performance of ALND, had a slightly increased risk of recurrence. However, whether this justifies 37 additional lymph node dissections per every 100 patients can be questioned. Therefore, a SN pathology protocol as is used in most centers nowadays, with on average 3 levels per node, seems to be adequate.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-31.
Abstract P1-02-06: Tamoxifen, Flaxseed and the Lignan Enterolactone Increase Stroma and Cancer Cell Derived IL-1Ra, Decrease Tumor Growth and Angiogenesis in Estrogen Dependent Breast Cancer Explants
Authors: Dabrosin C , Lindahl G , Abrahamsson A , Saarinen N. 
Published: April 2011

Abstract
The proinflammatory cytokines IL-1α and IL-1β have been shown to promote tumor angiogenesis, which may be counteracted by the IL-1 receptor antagonist (IL-1Ra). A diet with high amounts of phytoestrogens such as flaxseed (Flax), genistein (GEN), and the mammalian lignan enterolactone (ENL) may affect breast cancer progression possibly in a similar fashion as the anti-estrogen tamoxifen. Both cancer cells and the tumor stroma may be targets for cancer therapy. Therefore, we set up a model with species-specific components of the microenvironment by establishing human breast cancers in nude mice and sampled released proteins by microdialysis. We show that tumors of mice treated with tamoxifen, fed Flax or ENL exhibited decreased in vivo release of IL-1β derived from the murine stroma and decreased microvessel density whereas dietary GEN had no effects compared to controls. Cancer cells released IL-1Ra were approximately five times higher compared with stroma derived and tamoxifen, Flax, and ENL increased these levels significantly whereas GEN did not. In vitro, estradiol decreased released IL-1Ra of breast cancer cells. ENL completely reversed this whereas tamoxifen further increased IL-1Ra levels. IL-1Ra had no effect on breast cancer cell proliferation in presence of E2 in vitro whereas endothelial cell proliferation was significantly decreased by IL-1Ra in a dose dependent manner. Finally, IL-1Ra therapy of tumor bearing mice opposed estrogen dependent breast cancer growth and decreased tumor angiogenesis. These data may provide insights into tumor-stroma mechanisms involved in estrogen effects on breast cancer progression and tamoxifen and dietary interventions against this disease.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-02-06.
Abstract P1-02-07: Real-Time Functional Imaging of Tumor Vascular Normalization by Anti-Angiogenic Agents
Authors: Xing HR , Zhang Q , Bindokas V , Shen J , Fan H , Hoffman RM. 
Published: April 2011

Abstract
Background: We describe here new technology that enables non-invasive imaging of normalization of tumor blood vessels by anti-angiogenic agents in real time.
Materials and Methods: Variable-magnification in vivo-fluorescence imaging as well as fluorescence tomography were used to visualize vessel normalization.
Results: Morphological changes in the same vessel prior to and after drug treatment were imaged with high resolution in real time. Differences in vascular responses to the mTOR inhibitor rapamycin and to an anti-VEGF antibody were functionally imaged. Tumor vessel normalization was demonstrated by significantly reduced leakiness and subsequent improved tumor delivery of Paclitaxel-BODPY as well as by normalized morphology. The tumor vascular pool agent, AngioSense750, was retained in tumors after both anti-VEGF antibody and rapamycin treatment as visualized by noninvasive fluorescence tomography. The anti-angiogenic therapy normalized vessels, which significantly enhanced the antitumor efficacy of Paclitaxel due to increased drug penetration throughout the tumor. Discussion: The optical imaging technology described here is thus a powerful real-tool imaging tool of functional and morphological tumor vessel normalization and its therapeutic consequences.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-02-07.
Abstract P1-03-07: Differential Effect of Specific p53 Mutations on Breast Cancer Growth and Response to Hsp90 Inhibition In Vivo
Authors: Appleyard VL , Murray KE , Coates PJ , Vojtesek B , Muller P , Hrstka R , Thompson AM. 
Published: April 2011

Abstract
Background p53 mutation influences breast cancer cell growth and patient prognosis. However, different p53 mutations impart specific functions to the mutant protein, including dominant negative or gain of function effects. Mutant p53 molecules R273H and R175H are commonly found in primary breast cancers and are present in the MDA-MB-468 and SKBR3 cell lines, respectively. To compare the direct effects of these two mutations in vivo in an identical cellular background, H1299 (p53-null) cells were constructed to express R273H or R175H p53 mutants. Methods
Thirty female SCID mice were injected subcutaneously with 106 H1299 (p53-null), H1299/R273H or H1299/R175H cells in DMEM + Matrigel (50:50) suspension. Some mice were treated with an Hsp90 inhibitor, which is required for correct folding of many oncogenic proteins. Results
Xenografts bearing R175H showed a mean lag phase (time between cell injection and tumors at exponential growth) of 21 days and a doubling time of 5 days, whereas tumors bearing H1299 (p53-null) or R273H mutation had a lag phase of 31 days with a doubling time of 7 days. Immunohistochemical examination demonstrated a highly heterogeneous pattern of p53 protein expression in the more aggressive R175H expressing cells compared with R273H expressing cells. Hsp90 inhibitor treatment reduced the growth of H1299 and R273H cells, but not R175H cells. Conclusions
The specific p53 mutations directly influence the rate of tumor growth and the p53 protein staining pattern on immunohistochemistry. The differential effects of specific p53 mutations should be considered when interpreting clinical data involving p53 mutation such as in the EORTC 10994 trial, with implications for prognostic determination of individual breast cancer patients.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-03-07.
Abstract P1-03-08: Targeting Neurotensinergic Receptors for Bone Cancer Pain Relief
Authors: Geneviève R , Lemire M , Belleville K , Beaudet N , Martinez J , Philippe S. 
Published: April 2011

Abstract
Metastatic breast cancer spreads principally to long bones like femur. The presence of breast cancer metastasis in bone microenvironment results in severe pain increasing with disease progression. Opioids, including morphine, are a standard for bone cancer pain management despite their adverse effects at high doses. Our aim here was to examine the effects of opioidergic-independent neurotensin (NT) receptor (NTS1, NTS2) activation in alleviating bone cancer pain in a new clinically relevant mouse model. To this end, neurotensinergic agonists (PD149163, JMV-2012 or JMV-431) were intrathecally administrated to C57BL/6 mice implanted with syngenic E0771 metastatic breast cancer cells in the femoral intramedullary canal. Compounds were analysed for touch-evoked (von Frey), forced movement-evoked (Rotarod) and ambulatory (dynamic weight bearing) pain 18 days following E0771 implantation. The intrathecal injection of PD149163, a NTS1-selective agonist, induced a marked decrease of touch-evoked pain reaching 64 ± 9%. On the Rotarod, PD149163 treatment failed to improve either time spent on the rotating cylinder or the visual pain score. The injection of a non-selective agonist, JMV-2012, reduced touch-evoked pain of 16 ± 5%, but was not efficient in reversing pain under a physical effort on the Rotarod. JMV-431, a NTS2-selective agonist, produced a significant reduction of touch-evoked pain of 70 ± 9% in cancer mice, which also spent more time (10 ± 13%) on the Rotarod and expressed less movement-evoked pain (97 ± 20%) than saline-treated cancer mice. However, acute spinal JMV-431 failed to restore ipsilateral weight bearing toward basal values. The analysis of spinal neuronal activity of mice injected with JMV-431 showed a significant reduction of 55 ± 6% of c-Fos expression in laminae V-VII of the ipsilateral horn 18 days post implantation. In conclusion, these results indicate that the NTS2 receptor represents a promising target for treating bone cancer pain. Further investigations of continuous delivery of NTS2-selective agonists at the central and peripheral levels are under way to evaluate the real potential of these compounds for prophylactic and curative treatments against cancer pain.
Supported by CIHR/Canadian Pain Society/AstraZeneca and Cancer Research Society grants.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-03-08.
Abstract P1-04-01: X-Linked Inhibitor of Apoptosis Protein (XIAP) Regulates TRAIL-Induced Apoptosis in Inflammatory Breast Cancer Cells
Authors: Allensworth JL , Aird KM , Murray MB , Devi GR. 
Published: April 2011

Abstract
TRAIL, a proapoptotic receptor agonist, is a promising tool for anticancer therapy due to its selective triggering of death receptor-mediated apoptosis in cancer cells while sparing the majority of normal cells. Overexpression of X-linked inhibitor of apoptosis protein (XIAP) has been identified as a major mechanism of TRAIL resistance as a result of its ability to inhibit caspase activity, the effector arm of apoptotic cell death. Previous studies in our laboratory in preclinical models of inflammatory breast cancer (IBC), a highly invasive and lethal subtype, have revealed that apoptotic dysregulation mediated by XIAP is a key factor in IBC pathogenesis and acquired therapeutic resistance to epidermal growth factor receptor (ErbB1/2) targeting agents. Characterization of TRAIL efficacy in IBC cell lines derived from primary tumors revealed that SUM149, a triple negative, EGFR activated cell line, is sensitive to TRAIL-induced apoptosis and exhibits a corresponding decrease in XIAP and an increase in caspase3 activation compared to TRAIL-resistant SUM190, ErbB2 overexpressing cells in which XIAP levels are unchanged by TRAIL treatment. Profile from an apoptotic proteomic array revealed that SUM190 cells have low basal levels of the TRAIL receptors DR4 and DR5 in comparison to SUM149 cells. Stable overexpression of XIAP in the TRAIL-sensitive SUM149 cells resulted in a two fold decrease in sensitivity to TRAIL with decreased caspase3 activation. Further, SUM149wtXIAP cells showed low levels of TRAIL receptor expression similar to the TRAIL-insensitive SUM190 line. Conversely, increased cell death was observed in SUM190 cells in which XIAP was knocked down using a lentiviral shRNA expression construct. In order to examine therapeutic strategies aimed at restoring function to the apoptotic pathways in IBC cells, we used the small molecule inhibitor Embelin to modulate XIAP action. Treatment of SUM149wtXIAP cells with Embelin in combination with TRAIL enhanced cell death compared to treatment with TRAIL or Embelin alone. Assessment of the interaction using a derivation of the Chou-Talalay method revealed a combination index of 0.054 in SUM149wtXIAP cells, which is indicative of strong synergism between the two agents. These results reveal that knockdown or antagonism of XIAP allows TRAIL to induce activation of effector caspases efficiently and establishes the feasibility of use of XIAP inhibitors to enhance therapeutic apoptosis in IBC therapy. Funded by American Cancer Society-RSG-08-290-01-CCE (GRD), predoctoral DOD BCRP award (KMA), and the Duke University Chancellor's Scholarship (JLA).
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-04-01.
Abstract P1-04-03: A Role for Cyclin D1 in Neoplastic Transformation in MCF-7 Breast Cancer Cells Post p14ARF-p53 Induced Senescence
Authors: McGowan E , Alling N , Shephard R , Yagoub D , Tran N , Xia P. 
Published: April 2011

Abstract
Many years of oncogenic insult and hormonal flux have important long-term implications for breast cancer emergence and progression. Premature-induced senescence is proposed to be a protective response against cancer development. We hypothesize that the senescence response can be subverted in some breast carcinomas, which exhibit latent hormone-dependent proliferative capacity.
The ARF-p53 pathway has long been known to play an important role in tumour surveillance halting cell cycle progression to transiently or permanently stop aberrant cells from proliferating. It is well documented that disruption of this pathway is involved in tumourigenesis, in part, through inactivation of cyclin D1. Cyclin D1 plays an important role in breast cancer progression as a regulator of CDK4/6. In addition cyclin D1 has been reported to stimulate estrogen receptor (ER) activity independent of CDK4/6.
Our initial observations showed that reactivation of ARF-p53-p21 is indeed a potent rapid inhibitor of cell proliferation in MCF-7 breast cancer cells with a senescent phenotype, however controversially cyclin D1 expression was increased and predominantly located in the nucleus. High expression of nuclear cyclin D1 and p14ARF inversely correlated with cell proliferation. Our studies showed that p14ARF regulated cyclin D1 at the post-transcriptional level. Furthermore, we have evidence from microRNA array analysis that microRNAs known to bind to the cyclin D1 3'UTR sequence were down regulated upon induction of p14ARF, contributing to cyclin D1 stability.
We found that long-term exposure to p14ARF was not a failsafe barrier to tumour progression, senescent-like cells re-entering the cell cycle correlated with reduction of nuclear cyclin D1. Conversely, continuous p14ARF expression resulted in chaotic multinucleation and preceded neoplasia. These aberrant nuclei co-stained with cyclin D1 and Ki-67, a well-known marker of cell proliferation.
These results suggest that induction of the p14ARF-p53 pathway does not entirely remove the threat of cancer resulting from hyperproliferative oncogenic signals and cyclin D1 plays a promiscuous role in prevention and progression. Arguably, in some breast cancers premature senescent cells may be precursor, or latent cancer cells.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-04-03.