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| 1 | Tumor infiltrating lymphocytes in triple negative breast cancer receiving neoadjuvant chemotherapy显示文摘AIM To determine influence of neoadjuvant-chemotherapy(NAC) over tumor-infiltrating-lymphocytes(TIL) intriple-negative-breast-cancer(TNBC).METHODS TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de Enfermedades Neoplasicas from 2005 to 2010. Immunohistochemistry staining for CD3, CD4, CD8 and FOXP3 was performed in tissue microarrays(TMA) sections. Evaluation of H/E in full-face and immunohistochemistry in TMA sections was performed in pre and post-NAC samples. STATA software was used and P value < 0.05 was considered statistically significant. RESULTS Higher TIL evaluated in full-face sections from pre-NAC tumors was associated to pathologic-complete-response(pCR)(P = 0.0251) and outcome(P = 0.0334). TIL evaluated in TMA sections showed low level of agreement with full-face sections(ICC = 0.017-0.20) and was not associated to pCR or outcome. TIL in post-NAC samples were not associated to response or outcome. PostNAC lesions with pC R had similar TIL levels than those without pCR(P = 0.6331). NAC produced a TIL decrease in full-face sections(P < 0.0001). Percentage of TIL subpopulations was correlated with their absolute counts. Higher counts of CD3, CD4, CD8 and FOXP3 in pre-NAC samples had longer disease-free-survival(DFS). Higher counts of CD3 in pre-NAC samples had longer overallsurvival. Higher ratio of CD8/CD4 counts in pre-NAC was associated with pCR. Higher ratio of CD4/FOXP3 counts in pre-NAC was associated with longer DFS. Higher counts of CD4 in post-NAC samples were associated with pCR.CONCLUSION TIL in pre-NAC full-face sections in TNBC are correlated to longer survival. TIL in full-face differ from TMA sections, absolute count and percentage analysis of TIL subpopulation closely related. | Carlos A Castaneda Elizabeth Mittendorf Sandro Casavilca Yun Wu Miluska Castillo Patricia Arboleda Teresa Nunez Henry Guerra Carlos Barrionuevo Ketty Dolores-Cerna Carolina Belmar-Lopez Julio Abugattas Gabriela Calderon Miguel De La Cruz Manuel Cotrina Jorge Dunstan Henry L Gomez Tatiana Vidaurre | 2016 | World Journal of Clinical Oncology2016，7，5： | 6 |
| 2 | Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density显示文摘 | W.S Simonet D.L Lacey C.R Dunstan M Kelley M.-S Chang R Lüthy H.Q Nguyen S Wooden L Bennett T Boone G Shimamoto M DeRose R Elliott A Colombero H.-L Tan G Trail J Sullivan E Davy N Bucay L Renshaw-Gegg T.M Hughes D Hill W Pattison P Campbell S Sander G Van | 1997 | Cell1997，，2： | 6 |
| 3 | Clinicopathological predictors of long-term benefit in breast cancer treated with neoadjuvant chemotherapy显示文摘AIM To investigate the survival impact of clinicopathological factors, including pathological complete response(p CR) and tumor-infiltrating lymphocytes(s TIL) levels according to subtypes, in breast cancer(BC) patients who received neo-adjuvant chemotherapy(NAC).METHODS We evaluated 435 BC patients who presented and received NAC at the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. s TIL was analyzed as the proportion of tumor stroma occupied by lymphocytes, and was prospectively evaluated on hematoxylin and eosin-stained sections of the preN AC core biopsy. p CR was considered in the absence of infiltrating cancer cells in primary tumor and axillary lymph nodes. Analysis of statistical association between clinical pathological features, s TIL, p CR and survival were carried out using SPSSvs19.RESULTS Median age was 49 years(range 24-84 years) and the most frequent clinical stage was ⅢB(58.3%). Luminal A, Luminal B, HER2-enriched and(triple-negative) TN phenotype was found in 24.6%, 37.9%, 17.7% and 19.8%, respectively. p CR was observed in 11% and median percentage of s TIL was 40%(2%-95%) in the whole population. p CR was associated to Ct1-2(P = 0.045) and to high s TIL(P = 0.029) in the whole population. There was a slight trend towards significance for s TIL(P = 0.054) in Luminal A. s TIL was associated with grade Ⅲ(P < 0.001), no-Luminal A subtype(P < 0.001), RE-negative(P < 0.001), PgR-negative(P < 0.001), HER2-positive(P = 0.002) and p CR(P = 0.029) in the whole population. Longer disease-free survival was associated with grade Ⅰ-Ⅱ(P = 0.006), cN 0(P < 0.001), clinical stage Ⅱ(P = 0.004), ER-positive(P < 0.001), Pg R-positive(P < 0.001), luminal A(P < 0.001) and p CR(P = 0.002). Longer disease-free survival was associated with grade Ⅰ-Ⅱ in Luminal A(P < 0.001), N0-1 in Luminal A(P = 0.045) and TNBC(P = 0.01), clinical stage Ⅱ in Luminal A(P = 0.003) and TNBC(P = 0.038), and pC R in TNBC(P < 0.001). Longer overall survival was associated with grade Ⅰ-Ⅱ(P < 0.001), ER-positive(P < 0.001), PgR-positive(P < 0.001), Luminal A(P < 0.001), cN 0(P = 0.002) and p CR(P = 0.002) in the whole population. Overall survival was associated with clinical stage Ⅱ(P = 0.017) in Luminal A, older age(P = 0.042) in Luminal B, and pC R in TNBC(P = 0.005).CONCLUSION Predictive and prognostic values of clinicopathological features, like p CR and s TIL, differ depending on the evaluated molecular subtype. | Marco Galvez Carlos A Castaneda Joselyn Sanchez Miluska Castillo Lia Pamela Rebaza Gabriela Calderon Miguel De La Cruz Jose Manuel Cotrina Julio Abugattas Jorge Dunstan Henry Guerra Omar Mejia Henry L Gomez | 2018 | World Journal of Clinical Oncology2018，9，2： | 4 |
| 4 | Osteoprotegerin Ligand Is a Cytokine that Regulates Osteoclast Differentiation and Activation显示文摘 | D.L Lacey E Timms H.-L Tan M.J Kelley C.R Dunstan T Burgess R Elliott A Colombero G Elliott S Scully H Hsu J Sullivan N Hawkins E Davy C Capparelli A Eli Y.-X Qian S Kaufman I Sarosi V Shalhoub G Senaldi J Guo J Delaney W.J Boyle | 1998 | Cell1998，，2： | 4 |
| 5 | Loss of the vitamin D receptor in human breast and prostate cancers strongly induces cell apoptosis through downregulation of Wnt/β-catenin signaling显示文摘Vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers. The known anti-proliferative and pro-apoptotic actions of the active metabolite of vitamin D,1,25-dihydroxy-vitamin D [1,25(OH)2 D] are mediated through binding to the vitamin D receptor(VDR). Here,we report on the unexpected finding that stable knockdown of VDR expression in the human breast and prostate cancer cell lines, MDA-MB-231 and PC3, strongly induces cell apoptosis and inhibits cell proliferation in vitro. Implantation of these VDR knockdown cells into the mammary fat pad(MDA-MB-231),subcutaneously(PC3) or intra-tibially(both cell lines) in immune-incompetent nude mice resulted in reduced tumor growth associated with increased apoptosis and reduced cell proliferation compared with controls.These growth-retarding effects of VDR knockdown occur in the presence and absence of vitamin D and are independent of whether cells were grown in bone or soft tissues. Transcriptome analysis of VDR knockdown and non-target control cell lines demonstrated that loss of the VDR was associated with significant attenuation in the Wnt/β-catenin signaling pathway. In particular, cytoplasmic and nuclear β-catenin protein levels were reduced with a corresponding downregulation of downstream genes such as Axin2, Cyclin D1,interleukin-6(IL-6), and IL-8. Stabilization of β-catenin using the GSK-3β inhibitor BIO partly reversed the growth-retarding effects of VDR knockdown. Our results indicate that the unliganded VDR possesses hitherto unknown functions to promote breast and prostate cancer growth, which appear to be operational not only within but also outside the bone environment. These novel functions contrast with the known anti-proliferative nuclear actions of the liganded VDR and may represent targets for new diagnostic and therapeutic approaches in breast and prostate cancer. | Yu Zheng Trupti Trivedi Ruby CY Lin Colette Fong-Yee Rick Nolte Jeline Manibo Yunzhao Chen Musharraf Hossain Konstantin Horas Colin Dunstan Hong Zhou Markus J Seibel | 2017 | Bone Research2017，5，3： | 4 |
| 6 | Relevance of an in vitro osteoclastogenesis system to study receptor activator of NF-kB ligand and osteoprotegerin biological activities显示文摘 | Y Wittrant S Theoleyre S Couillaud C Dunstan D Heymann F Rédini | 2003 | Experimental Cell Research2003，，2： | 2 |
| 7 | Induced anisotropy in a sand显示文摘 | Arthur J R F Chua K S Dunstan T | 1977 | Geotechnique1977，27，1： | 2 |
| 8 | Osteoprotegerin:a novel secreted protein involved in the regulation of bone density显示文摘 | Lacey DL Dunstan CR | 1997 | Cell1997，89，2： | 1 |
| 9 | Beneficial associations of physical activity with 2-h but not fasting blood glucose in Australian adults:the AusDiab study显示文摘 | Healy G Dunstan D Shaw J | 2006 | Diabetes Care2006，29，： | 1 |
| 10 | The expression of osteoprotegerin and RANK ligand and the support of osteoclast by stromal osteoblast lineage cells is developmentally regulated显示文摘 | God F Hofbauer LC Dunstan CR | 2000 | Endocrinology2000，41，12： | 1 |
| 11 | The anti-malarial artesunate is also active against cancer显示文摘 | Efferth T Dunstan H Sauerbrey A | 2001 | int J Oucol2001，18，4： | 1 |
| 12 | The an- ti-malarial artesunate is also active against cancer 显示文摘 | EFFERTH T DUNSTAN H SAUERBREY A et ai | 2001 | Inerna- tional Journal of Oncology2001，18，4： | 1 |
| 13 | The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption显示文摘 | Hofbauer L.C Khosla S Dunstan C.R | | 0，，： | 1 |
| 14 | In- creased cardiometabolic risk is associated with increased TV viewing time显示文摘 | WIJNDAELE K HEALY G N DUNSTAN D W | 2010 | Med Sei Sports Exe2010，42，8： | 1 |
| 15 | Materials mechanical size effects: a review 显示文摘 | ZHU T T BUSHBY A J DUNSTAN D J | 2008 | Materials Technology2008，23，4： | 1 |
| 16 | Effects of harvest stage and light on the biochemical compositionof the diatom Thalassiosira pseudonana 显示文摘 | BROWN M R DUNSTAN G A NORWOOD S J | 1996 | Journal of Phycology1996，32，1： | 1 |
| 17 | The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption显示文摘 | Hofbauer L C Khosla S Dunstan C R | 2000 | J Bone Miner Res2000，，15： | 1 |
| 18 | Osteoprotegerin: a novel secreted protein involved in the regulation of bone density 显示文摘 | Simonet WS Lacey DL Dunstan CR | 1997 | Cell1997，89，： | 1 |
| 19 | Probiotic supplementation for the first 6 months of Iife fails to reduce the risk of atopic dermatitis and in- creases the risk of allergen sensitization in highrisk children:a randomized controlled显示文摘 | TAYLOR A L DUNSTAN J A PRESCOTT S L | 2007 | J Allergy Clin Immunol2007，119，： | 1 |
| 20 | Diabetes: exercise and T2DM-move muscles more often 显示文摘 | Dunstan D | 2011 | Nat RevEndocrlnol2011，7，4： | 1 |
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