Annotated highest variance abstracts citing {'original': '[Ii]mmunother'}

15931636

Establishing a platform for immunotherapy: clinical outcome and study of immune reconstitution after high-dose chemotherapy with progenitor cell support in breast cancer patients.
Claude Sportès, Nicole J McCarthy, Frances Hakim, Seth M Steinberg, David J Liewehr, David Weng, Shivaani Kummar, Juan Gea-Banacloche, Catherine K Chow, Robert M Dean, Kathleen M Castro, Donna Marchigiani, Michael R Bishop, Daniel H Fowler, Ronald E Gress
(Experimental Transplantation & Immunology Branch, Center for Cancer Research, National Cancer Institute, 10 Center Dr., CRC Room 43142, Bethesda, MD 20892-1203, USA. kastensc@mail.nih.gov)
Biol. Blood Marrow Transplant.

tumor vaccine after high-dose_chemotherapy hdc and autologous_stem cell_transplantation asct aims at directing immune recovery toward tumor responses after optimizing minimal_residual disease we have characterized t-cell recovery and tumor response after regimen devised as platform for such immunotherapy one_hundred patients with high-risk or metastatic breast cancer received to cycles of paclitaxel and cyclophosphamide overall response_rate and then hdc with melphalan and etoposide seventy-one patients received hdc and asct no mortality at days at months_after transplantation progression-free and overall_survival probabilities for patients with stage_iiia iiib and iv disease were and and and respectively the median_progression-free and overall_survivals from entry on study for stage_iv patients were and months respectively cd3_cd8 and cd4 cells were severely depleted after asct although total cd8_t-cell numbers approached the normal range by months most of these cells were cd28 naive cd45ra cd4 cells approached the normal range only months_after asct and only in younger patients the described observations provide the basis for devising strategy for cancer vaccine administration after asct incorporating immune_reconstitution enhancement after asct may_be advantageous

18041742

Distinct expression patterns of the immunogenic differentiation antigen NY-BR-1 in normal breast, testis and their malignant counterparts.
Jean-Philippe Theurillat, Ursina Zürrer-Härdi, Zsuzsanna Varga, André Barghorn, Elisabeth Saller, Claudia Frei, Martina Storz, Silvia Behnke, Burkhardt Seifert, Mathias Fehr, Daniel Fink, Christoph Rageth, Claudia Linsenmeier, Bernhard Pestalozzi, Yao-Tseng Chen, Alexander Knuth, Dirk Jäger, Holger Moch
(Institute of Surgical Pathology, Department Pathology, University Hospital of Zürich, Switzerland. jean-philippe.theurillat@cell.biol.ethz.ch)
Int. J. Cancer

ny-br-1 is differentiation antigen and potential target for cancer immunotherapy its mrna expression is restricted to breast testis prostate and breast cancer by rt-pcr in this_study we correlated ny-br-1 protein and mrna expression on tissue_microarrays of mammary prostatic and testicular malignancies using immunohistochemistry and in situ_hybridization with probes for exon 4-7 and 30-33 ny-br-1 mrna was confined to primary spermatocytes suggesting role in spermatogenesis exon 4-7 and 30-33 were equally expressed this cell type however ny-br-1 was absent in all germ cell tumours analyzed and present in one of prostate carcinomas in breast ny-br-1 mrna expression was detected in of primary carcinomas with strong_correlation to its protein expression mrna expression was significantly stronger and more_frequently detected by the exon 30-33 probe than by the exon 4-7 probe vs indicating the presence of alternative_splice variants that lack 5-prime sequences similar restricted mrna pattern was also observed in the normal breast epithelium ny-br-1 protein and mrna correlated significantly with estrogen_receptor alpha er_alpha protein expression with stronger association to ny-br-1 mrna than protein odds_ratio compared to we identified estrogen response_elements ere like sequences nearby the promoter_region suggesting_that ny-br-1 transcription might_be controlled by er_alpha accordingly analysis of matching pairs of primary tumors with their recurrences showed marked_decrease of ny-br-1 expression in recurrences after tamoxifen treatment

24466264

MAP1S controls breast cancer cell TLR5 signaling pathway and promotes TLR5 signaling-based tumor suppression.
Ming Shi, Yuanfei Yao, Fang Han, Yiqun Li, Yu Li
(School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.; School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.; School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.; School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.; School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.)
PLoS ONE

targeting tlr5_signaling in breast cancer represents_novel strategy in cancer immunotherapy however the underlying_mechanism by which tlr5_signaling inhibits cancer cell_proliferation and tumor growth has not been_elucidated in this_study we found tlr5 agonist flagellin inhibited the cell state of activation and induced autophagy and reported that autophagy protein map1s regulated the flagellin/tlr5 signaling_pathway in breast cancer cells through enhancement of nf-κb activity and cytokine_secretion remarkably map1s played critical_role in tumor suppression induced by flagellin and knockdown of map1s almost_completely abrogated the suppression of tumor growth and migration by flagellin treatment in addition elevated expression of map1s in response to flagellin feed-back regulated tumor inflammatory microenvironment in the late_stages of tlr5_signaling through degradation of myd88 in autophagy process these results_indicate mechanism of antitumor_activity that involves map1s-controlled tlr5_signaling in breast cancer

16908432

Comparison of multiplex ligation dependent probe amplification to immunohistochemistry for assessing HER-2/neu amplification in invasive breast cancer.
D Purnomosari, T Aryandono, K Setiaji, S B Nugraha, G Pals, P J van Diest
(Department of Histology and Cell Biology, Gadjah Mada University, Jogjakarta, Indonesia.)
Biotech Histochem

the her-2/neu transmembrane_tyrosine kinase receptor is both prognostic_marker and therapeutic_target for breast cancer accurate_determination of her-2/neu status is prerequisite_for selecting breast tumors for her-2/neu immunotherapy or for taxan based chemotherapy unfortunately there is no_consensus concerning how this determination should_be reached we compared assessment of her-2/neu status using multiplex_ligation-dependent probe_amplification mlpa and immunohistochemistry_ihc the patient group comprised indonesian breast cancers patients ihc was performed on paraffin_sections using the cb11_antibody from novocastra results were scored_according to the hercept test for mlpa dna was extracted_from frozen samples pcr amplified with probe set containing three hemi-primer sets for the her-2 locus and another nine control probes spread over chromosome and other chromosomes and analyzed on gene scanner ratio above two for at_least two her-2 locus probes compared to the control probes was regarded_as amplification ihc for her-2/neu was negative in cases and cases showed expression seven eight and nine of the latter cases were 1+_2+ and 3+ positive respectively forty-seven cases showed no amplification by mlpa and cases were amplified comparison of ihc and mpla showed that none of the ihc-negative or seven ihc 1+ cases was amplified five of the eight 2+ cases were amplified and eight of nine of the ihc_3+ tumors showed gene_amplification by mlpa_assay for her-2/neu there is good_correlation between gene_amplification detected by mlpa and overexpression by ihc in invasive breast cancer it_appears that mlpa can detect the her-2 amplified cases in the ihc_2+ class because mlpa is quick and inexpensive it is an_attractive method for detecting her-2/neu_amplification in daily laboratory practice

17620762

Breast cancer chemotherapy.
Heather L McArthur, Clifford A Hudis
(Breast Cancer Medicine Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. mcarthuh@mskcc.org)
Cancer J

chemotherapy can_be an_integral component of the adjuvant management strategy for women with early-stage breast cancer modern adjuvant strategies now comprises one or more chemotherapy agents hormonal maneuvers immunotherapy agents or experimental agents the use of adjuvant_chemotherapy is generally based_on estimates of an individual risk of recurrence and the expected benefit of therapy however risk-benefit calculations have recently become_increasingly sophisticated as result of advances in genetic_testing and molecular marker identification as_well as ongoing refinements in chemotherapy strategies in this_article we will review the role of important prognostic and predictive factors and the rationale_for adjuvant_systemic therapy and modern chemotherapy_regimens in the management of women with early-stage breast cancer

11956600

A summary of two clinical studies on tumor cell dissemination in primary and metastatic breast cancer: methods, prognostic significance and implication for alternative treatment protocols (Review).
S Kasimir-Bauer, C Oberhoff, A E Schindler, S Seeber
(Department of Internal Medicine (Cancer Research), West German Cancer Center, Essen. sabine.kasimir-bauer@uni-essen.de)
Int. J. Oncol.

although only less_than of women with primary breast cancer have clinicopathologic signs of overt_metastases metastatic relapse occurs in about_half of the cases with apparently localized tumors within five years after surgery in of the patients bone_marrow metastases are detectable at first relapse and this rate even increases in patients with metastatic breast cancer however hematogeneous or lymphatic_spread of occult tumor cells can arise before diagnosis at an early_stage of primary tumor growth and is regularly underestimated by currently_available clinical and pathologic staging_procedures we studied cytokeratin-positive_ck+ cells in the bone_marrow bm and tumor markers in the blood of patients with primary breast cancer in order to obtain an early diagnosis of residual_disease in second study we monitored cytokeratin_ck /17-1a positive cells in the bm and peripheral_blood stem_cells pbsc to evaluate whether dose intensive or high-dose_hd chemotherapy can eliminate micrometastases in high-risk breast cancer patients the overall ck+ rate was 44/128 patients 15/51 for patients with t1 tumors 28/84 for n0 patients and 26/82 for patients with g1-2 breast carcinoma interestingly of ck+ patients were only positive in one of the two bm_aspirates studied at_least one tumor marker including carcinoembryonic_antigen carbohydrate_antigen 15-3 and tissue_polypeptide antigen was increased in 58/128 patients 21/58 were ck+ in the bm surprisingly levels for the extracellular_domain of her-2/neu in serum_samples were within the normal range in every patient studied after 2-year_follow-up 7/128 patients relapsed 3/7 ck+/tm 2/7 ck-/tm+ 2/7 ck-/tm we concluded_that studying two bm_aspirates for ck+_cells by immunocytochemistry in combination with tumor marker determination is useful for identifying patients with higher risk for relapse tumor cell enrichment technique applied in patients prior to immunocytochemistry using dynabeads directly coupled to an antibody berep4 targeting the 17-1a_antigen did_not enhance the detection rate of disseminated_tumor cells in this patient group we monitored ck+/17-1a+ cells in the bm and pbsc and studied her-2/neu serum_levels of patients with locally_advanced group and metastatic breast cancer group ck+_cells were found in the bm of 3/13 group patients before but_not after chemotherapy resulting in an overall_survival os of after median_follow-up of months contamination of pbsc in 2/9 patients was not associated_with decreased survival in group patients the ck+ rate was 18/30 patients before and 4/10 patients after therapy with an os rate of after months pbsc samples were positive in 7/24 patients ck+ bm and pbsc led to rapid_progress and short os whereas tumor cell free bm and pbsc resulted in mean os of months the antigen 17-1a was detected on most ck+_cells in both patient groups before therapy on all ck+ pbsc and on ck+_cells in group patients after therapy increased her-2/neu levels were found in group patients before chemotherapy in conclusion micrometastatic cells are present in blood and pbsc grafts of high-risk breast cancer patients and can survive even hd-chemotherapy immunotherapeutic target antigens on the cell_surface of these cells support the idea that combined chemoimmunotherapy might_be successful in eliminating minimal_residual disease

20455858

CSPG4 in cancer: multiple roles.
X Wang, Y Wang, L Yu, K Sakakura, C Visus, J H Schwab, C R Ferrone, E Favoino, Y Koya, M R Campoli, J B McCarthy, A B DeLeo, S Ferrone
(University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA 15232, USA.)
Curr. Mol. Med.

chondroitin_sulfate proteoglycan cspg4 also known as high molecular weight-melanoma associated antigen is cell_surface proteoglycan which has_been recently shown to be expressed not only by melanoma cells but also by various_types of human carcinoma and sarcoma furthermore at_least in squamous_cell carcinoma of head and neck and in basal breast carcinoma cspg4 is expressed by cancer stem_cells cspg4 plays_an important_role in tumor cell growth and survival these cspg4-associated functional properties of tumor cells are inhibited by cspg4-specific monoclonal_antibodies mab in vitro moreover cspg4-specific mab can also inhibit tumor growth and metastasis in vivo the anti-tumor_effects of cspg4-specific mab are likely to reflect the blocking of important migratory mitogenic and survival signaling_pathways in tumor cells these results_indicate that cspg4 is promising_new target to implement mab-based immunotherapy of various_types of cancer

15583840

Tumor associated antigen recognition by autologous serum in patients with breast cancer.
Feng Qian, Kunle Odunsi, Lawrence M Blatt, Matthew J Scanlan, Manish Mannan, Nisha Shah, John Montgomery, Fadi Haddad, Milton Taylor
(Department of Biology, Indiana University, Bloomington, IN 47405, USA.)
Int. J. Mol. Med.

breast cancer accounts_for 30-40 of all deaths from cancers in females in an_effort to identify tumor associated antigens that may_be useful for immunotherapy we utilized serological_analysis of recombinant cdna expression libraries serex technique to identify breast cancer-associated_antigens serex screening of cdna expression libraries derived_from breast cancer patients identified total of positive clones bcg-1 to bcg-88 including hitherto_unknown sequences the cdna_sequences and mrna expression patterns were characterized seroreactivity of the serex clones were determined in sera_from breast cancer patients colon cancer patients and healthy_donors expression analysis on cdna panel from different normal_tissues by reverse_transcription-pcr rt-pcr revealed tissue restricted mrna expression of of the unknown antigens bcg-72 is expressed only in breast prostate and thymus while bcg-84 is expressed at moderate levels in testis spleen and breast the other unknown antigens were expressed in most other tissues serologic assay revealed that out of the clones showed reactivity to at_least one serum from either breast or colon cancer patients these clones did_not react with sera_from panel of healthy adult individuals our_results demonstrate the utility of the serex approach for the identification of potential tumor associated antigens in human breast cancer

25063873

Noncanonical NF-κB activation mediates STAT3-stimulated IDO upregulation in myeloid-derived suppressor cells in breast cancer.
Jinpu Yu, Yue Wang, Fang Yan, Peng Zhang, Hui Li, Hua Zhao, Cihui Yan, Fan Yan, Xiubao Ren
(Department of Immunology, Key Laboratory of Cancer Immunology and Biotherapy, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China; rwziyi@yahoo.com yujinpu@tjmuch.com.; Department of Immunology, Key Laboratory of Cancer Immunology and Biotherapy, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China;; Department of Immunology, Key Laboratory of Cancer Immunology and Biotherapy, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China; Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN 37232; and.; Department of Immunology, Key Laboratory of Cancer Immunology and Biotherapy, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China;; Department of Immunology, Key Laboratory of Cancer Immunology and Biotherapy, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China;; Department of Immunology, Key Laboratory of Cancer Immunology and Biotherapy, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China;; Department of Immunology, Key Laboratory of Cancer Immunology and Biotherapy, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China;; Department of Immunology, Key Laboratory of Cancer Immunology and Biotherapy, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China;; Department of Immunology, Key Laboratory of Cancer Immunology and Biotherapy, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China; Biotherapy Center, National Clinical Research Center of Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, People's Republic of China rwziyi@yahoo.com yujinpu@tjmuch.com.)
J. Immunol.

immunotherapy for cancer treatment is achieved through the activation of competent immune_effector cells and the inhibition of immunosuppressive cells such_as myeloid-derived_suppressor cells mdscs although mdscs have_been shown to contribute to breast cancer development the mechanism_underlying mdsc-mediated immunosuppression is unclear we have identified poorly_differentiated mdsc subset in breast cancer-suppressing cell function through stat3-dependent ido upregulation in this_study we_investigated the mechanisms_underlying aberrant expression of ido in mdscs mdscs were induced by coculturing human cd33 myeloid progenitors with mda-mb-231 breast cancer cells increased stat3_activation in mdscs was correlated with activation of the noncanonical nf-κb_pathway including increased nf-κb-inducing kinase nik protein level phosphorylation of cytoplasmic inhibitor of nf-κb kinase and p100 and relb-p52 nuclear_translocation blocking stat3_activation with the small_molecule inhibitor jsi-124 significantly_inhibited the accumulation of nik and ido expression in mdscs knockdown of nik in mdscs suppressed ido expression but_not stat3_activation relb-p52 dimers were found to directly_bind to the ido promoter leading to ido expression in mdscs il-6 was found to stimulate stat3-dependent nf-κb-mediated ido upregulation in mdscs furthermore significant positive_correlation between the numbers of pstat3 mdscs ido mdscs and nik mdscs was observed in human breast cancers these results_demonstrate stat3/nf-κb/ido pathway in breast cancer-derived mdscs which provides_insight into understanding immunosuppressive mechanisms of mdscs in breast cancer

11748637

EGFR family expression in breast carcinomas. c-erbB-2 and c-erbB-4 receptors have different effects on survival.
Zhenhe Suo, Bjørn Risberg, Mats G Kalsson, Kenneth Willman, Anne Tierens, Eva Skovlund, Jahn M Nesland
(Department of Pathology, The Norwegian Radium Hospital and Institute for Cancer Research, University of Oslo, Oslo, Norway. zhenhes@labmed.uio.no)
J. Pathol.

one_hundred patients with breast carcinoma followed for 7-11 years were included in the present_study of egfr family_members using immunohistochemistry and rt-pcr by immunohistochemistry and of the tumours were positive for egfr c-erbb-2_c-erbb-3 and c-erbb-4 all the immunoreactive tumours were confirmed positive by rt-pcr tumour_size histological_grade lymph_node status s-phase_fraction and stage were confirmed to be significantly associated_with both disease-free and cancer-specific_survival in the present_study methods of treatment histological_type and ploidy had no_significant effect on survival statistical_analysis of egfr family_members in these tumours showed significant_association between c-erbb-2 expression and reduced disease-free and cancer-specific_survival c-erbb-4 expression was associated_with more_favourable outcome co-expression of c-erbb-2 and egfr was associated_with worse_prognosis c-erbb-4 expression however showed an antagonistic_effect on the clinical influence of c-erbb-2 expression in conclusion c-erbb-2 expression in breast carcinomas is associated_with an unfavourable clinical_course and egfr expression has synergistic_effect however c-erbb-4 antagonizes the c-erbb-2 effect on clinical_course in breast carcinomas to achieve best results with immunotherapy against the c-erbb-2 receptor clarifying the status of c-erbb-4 expression may_be of significance