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https://www.readbyqxmd.com/read/29145561/clinical-significance-of-cd73-in-triple-negative-breast-cancer-multiplex-analysis-of-a-phase-iii-clinical-trial
#1
L Buisseret, S Pommey, B Allard, S Garaud, M Bergeron, I Cousineau, L Ameye, Y Bareche, M Paesmans, J P A Crown, A Di Leo, S Loi, M Piccart-Gebhart, K Willard-Gallo, C Sotiriou, J Stagg
Background: CD73 is an ecto-enzyme that promotes tumor immune escape through the production of immunosuppressive extracellular adenosine in the tumor microenvironment. Several CD73 inhibitors and adenosine receptor antagonists are being evaluated in phase I clinical trials. Patients and methods: Full-face sections from formalin-fixed paraffin-embedded primary breast tumors from 122 samples of triple-negative breast cancer from the BIG 02-98 adjuvant phase III clinical trial were included in our analysis...
November 14, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29145336/expression-of-hormone-receptors-in-low-grade-adenosquamous-carcinoma-of-the-breast-a-case-report
#2
Hai-Bo Wu, An-Li Zhang, Wei Wang, Heng Li
RATIONALE: Low-grade adenosquamous carcinoma (LGASC) is a rare subtype of metaplastic breast carcinoma which is generally recognized as a characteristic subgroup of triple-negative breast cancers previously. However, in this study, we reported for the first time a case of LGASC with hormone receptors expression. PATIENT CONCERNS: Pathological analysis of breast tumor specimen obtained by a 42-year-old female patient was performed. Morphologically, it composed of glandular structures with scattered squamous differentiation accompanied by haphazard arrangement of spindle cell stroma...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29144746/oxyprenylated-phenylpropanoids-bind-to-mt1-melatonin-receptors-and-inhibit-breast-cancer-cell-proliferation-and-migration
#3
Mahmud Hasan, Salvatore Genovese, Serena Fiorito, Francesco Epifano, Paula A Witt-Enderby
Oxyprenylated compounds (i.e., ferulic acid and coumarin derivatives) demonstrate neuroprotection and anticancer properties as reported in previous studies. We have tested the affinity of oxyprenylated ferulic acid (1-4) and umbelliferone derivatives (5-11) to melatonin receptors as well as their antiproliferation and antimigratory properties against breast cancer (BC) cell lines. All the compounds except for ferulic acid, boropinic acid, and umbelliferone had binding affinities to melatonin receptors in the nM to μM range, and both auraptene and umbellinprenin reduced BC cell proliferation and migration in phenotypically diverse BC including triple negative...
November 16, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/29144137/design-of-novel-3-pyrimidinylazaindole-based-cdk2-9-inhibitors-with-potent-in-vitro-and-in-vivo-antitumor-efficacy-in-a-triple-negative-breast-cancer-model
#4
Umed Singh, Gousia Chashoo, Sameer U Khan, Priya Mahajan, Amit Nargotra, Girish Mahajan, Amarinder Singh, Anjna Sharma, Mubashir Javeed Mintoo, Santosh Kumar Guru, Hariprasad Aruri, Thanusha Thatikonda, Promod Sahu, Pankaj Chibber, Vikas Kumar, Sameer A Mir, Sonali S Bharate, Sreedhar Madishetti, Utpal Nandi, Gurdarshan Singh, Dilip Manikrao Mondhe, Shashi Bhushan, Fayaz Malik, Serge Mignani, Ram A Vishwakarma, Parvinder Pal Singh
In the present study, novel series of 3-pyrimidinylazaindoles were designed and synthesized using bioinformatics strategy as cyclin-dependent kinases CDK2 and CDK9 inhibitors, which play critical roles in cell-cycle control and regulation of cell transcription. The present approach has given new dimensions to existing SAR and opens the new opportunity for lead optimization from comparatively inexpensive starting materials. The study led to the identification of alternative lead candidate 4ab with nanomolar potency against CDK2 and CDK9 and potent anti-proliferative activities against a panel of tested tumor cell lines along better safety ratio of ~30 in comparison to reported leads...
November 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29142600/co-activation-of-hedgehog-and-wnt-signaling-pathways-is-associated-with-poor-outcomes-in-triple-negative-breast-cancer
#5
Kimberly M Arnold, Ryan T Pohlig, Jennifer Sims-Mourtada
Hedgehog (HH) and Wnt pathway activation have been implicated in poor prognosis of breast cancer. Crosstalk between these two pathways has been demonstrated to be important in breast cancer progression, however the association between these two pathways and breast cancer survival rate is unknown. The present study comprised a cohort of 36 patients with triple negative breast cancer (TNBC) to investigate co-activation of HH and canonical Wnt pathway in association to patient outcome. All patients had varying degrees of cytoplasmic sonic HH and glioma-associated oncogene homolog (Gli)-1 staining, which positively correlated with tumor stage...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29142588/characterization-of-hormonal-receptors-and-human-epidermal-growth-factor-receptor-2-in-tissues-of-women-with-breast-cancer-at-muhimbili-national-hospital-dar-es-salaam-tanzania
#6
Amos Rodger Mwakigonja, Nyanda Elias Lushina, Ally Mwanga
Background: Breast cancer is a leading cause of morbidity and deaths among women worldwide. In Tanzania there is no published data on human epidermal growth receptor-2 (HER2/neu) expression in breast carcinoma. Hormonal receptors and HER2/neu status reportedly influence post-mastectomy adjuvant therapy and predict treatment outcome and prognosis. Here we evaluate hormonal receptors and HER-2 status in biopsies of women with breast cancer at Muhimbili National Hospital (MNH). Methods: A cross-sectional study of female breast post-modified radical mastectomy (MRM)/incisional biopsies confirmed to be carcinoma at the Histopathology Unit (January-December 2013)...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/29142367/case-of-carcinoma-breast-with-unusually-large-tumor-thrombus-in-superior-vena-cava-detected-on-18-f-fluorodeoxyglucose-positron-emission-tomography-computed-tomography-scan
#7
Arun Sasikumar, Anto Baby, Mathews Jose, Retcy Mary Paul
A 60-year-old female with triple negative breast cancer, postsurgery, neoadjuvant chemotherapy and radiotherapy, on follow-up had facial puffiness and giddiness. (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) done for suspected recurrence evaluation revealed a large tumor thrombus (TT) in superior vena cava (SVC) with radiological evidence of SVC obstruction. (18)F-FDG PET/CT also showed evidence of FDG avid brain metastases, lymph nodal metastases, and metastatic soft tissue deposits...
October 2017: Indian Journal of Nuclear Medicine: IJNM: the Official Journal of the Society of Nuclear Medicine, India
https://www.readbyqxmd.com/read/29142206/egfr-conjunct-fscn1-as-a-novel-therapeutic-strategy-in-triple-negative-breast-cancer
#8
Chao-Qun Wang, Yang Li, Bi-Fei Huang, Yong-Ming Zhao, Hui Yuan, Dongfang Guo, Chen-Ming Su, Gui-Nv Hu, Qian Wang, Tengyun Long, Yan Wang, Chih-Hsin Tang, Xiaoni Li
Emerging evidence indicates that Fascin-1 (FSCN1) may possess a causal role in the development of several types of cancers and serves as a novel biomarker of aggressiveness in certain carcinomas. However, the regulatory mechanism of FSCN1 in triple-negative breast cancer (TNBC) cell invasion and migration is still largely unknown. In our study, we observed that the FSCN1 expression rates were significantly higher in invasive ductal carcinoma, compared with both usual ductal hyperplasia and ductal carcinoma in situ...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29140689/tissue-inhibitor-of-metalloprotease-2-timp-2-bioprocess-development-physicochemical-biochemical-and-biological-characterization-of-highly-expressed-recombinant-protein
#9
Ananda Chowdhury, Robert G Brinson, Beiyang Wei, William G Stetler-Stevenson
Tissue Inhibitor of Metalloprotease -2 (TIMP-2) is a secreted 21 kDa multifunctional protein first described as an endogenous inhibitor of matrix metalloproteinases (MMPs) that prevents breakdown of the extracellular matrix often observed in chronic diseases. TIMP-2 diminishes growth factor-mediated cell proliferation in vitro, as well as neoangiogenesis and tumor growth in vivo independent of its MMP-inhibitory activity, . These physiological properties make TIMP-2 an excellent candidate for further pre-clinical development as a biologic therapy of cancer...
November 15, 2017: Biochemistry
https://www.readbyqxmd.com/read/29138806/effect-of-bis-hydroxymethyl-alkanoate-curcuminoid-derivative-mth-3-on-cell-cycle-arrest-apoptotic-and-autophagic-pathway-in-triple-negative-breast-adenocarcinoma-mda-mb-231-cells-an-in-vitro-study
#10
Ling-Chu Chang, Min-Tsang Hsieh, Jai-Sing Yang, Chi-Cheng Lu, Fuu-Jen Tsai, Je-Wei Tsao, Yu-Jen Chiu, Sheng-Chu Kuo, Kuo-Hsiung Lee
Curcumin has been shown to exert potential antitumor activity in vitro and in vivo involved in multiple signaling pathways. However, the application of curcumin is still limited because of its poor hydrophilicity and low bio-availability. In the present study, we investigated the therapeutic effects of a novel and water soluble bis(hydroxymethyl) alkanoate curcuminoid derivative, MTH-3, on human breast adenocarcinoma MDA-MB-231 cells. This study investigated the effect of MTH-3 on cell viability, cell cycle and induction of autophagy and apoptosis in MDA-MB-231 cells...
November 14, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29138761/a-metastasis-biomarker-metasite-breast%C3%A2-score-is-associated-with-distant-recurrence-in-hormone-receptor-positive-her2-negative-early-stage-breast-cancer
#11
Joseph A Sparano, Robert Gray, Maja H Oktay, David Entenberg, Thomas Rohan, Xiaonan Xue, Michael Donovan, Michael Peterson, Anthony Shuber, Douglas A Hamilton, Timothy D'Alfonso, Lori J Goldstein, Frank Gertler, Nancy E Davidson, John Condeelis, Joan Jones
Metastasis is the primary cause of death in early-stage breast cancer. We evaluated the association between a metastasis biomarker, which we call "Tumor Microenviroment of Metastasis" (TMEM), and risk of recurrence. TMEM are microanatomic structures where invasive tumor cells are in direct contact with endothelial cells and macrophages, and which serve as intravasation sites for tumor cells into the circulation. We evaluated primary tumors from 600 patients with Stage I-III breast cancer treated with adjuvant chemotherapy in trial E2197 (NCT00003519), plus endocrine therapy for hormone receptor (HR)+ disease...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29138558/%C3%AE-v%C3%AE-3-integrin-targeted-micellar-mertansine-prodrug-effectively-inhibits-triple-negative-breast-cancer-in-vivo
#12
Ping Zhong, Xiaolei Gu, Ru Cheng, Chao Deng, Fenghua Meng, Zhiyuan Zhong
Antibody-mertansine (DM1) conjugates (AMCs) are among the very few active targeting therapeutics that are approved or clinically investigated for treating various cancers including metastatic breast cancer. However, none of the AMCs are effective for the treatment of triple-negative breast cancers (TNBCs). Here, we show that cRGD-decorated, redox-activatable micellar mertansine prodrug (cRGD-MMP) can effectively target and deliver DM1 to αvβ3 integrin overexpressing MDA-MB-231 TNBC xenografts in nude mice, resulting in potent tumor growth inhibition...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29138528/the-predictive-value-of-pitx2-dna-methylation-for-high-risk-breast-cancer-therapy-current-guidelines-medical-needs-and-challenges
#13
REVIEW
Michaela Aubele, Manfred Schmitt, Rudolf Napieralski, Stefan Paepke, Johannes Ettl, Magdalena Absmaier, Viktor Magdolen, John Martens, John A Foekens, Olaf G Wilhelm, Marion Kiechle
High-risk breast cancer comprises distinct tumor entities such as triple-negative breast cancer (TNBC) which is characterized by lack of estrogen (ER) and progesterone (PR) and the HER2 receptor and breast malignancies which have spread to more than three lymph nodes. For such patients, current (inter)national guidelines recommend anthracycline-based chemotherapy as the standard of care, but not all patients do equally benefit from such a chemotherapy. To further improve therapy decision-making, predictive biomarkers are of high, so far unmet, medical need...
2017: Disease Markers
https://www.readbyqxmd.com/read/29138278/a-cytoplasmic-compass-is-necessary-for-cell-survival-and-triple-negative-breast-cancer-pathogenesis-by-regulating-metabolism
#14
Lu Wang, Clayton K Collings, Zibo Zhao, Kira Alia Cozzolino, Quanhong Ma, Kaiwei Liang, Stacy A Marshall, Christie C Sze, Rintaro Hashizume, Jeffrey Nicholas Savas, Ali Shilatifard
Mutations and translocations within the COMPASS (complex of proteins associated with Set1) family of histone lysine methyltransferases are associated with a large number of human diseases, including cancer. Here we report that SET1B/COMPASS, which is essential for cell survival, surprisingly has a cytoplasmic variant. SET1B, but not its SET domain, is critical for maintaining cell viability, indicating a novel catalytic-independent role of SET1B/COMPASS. Loss of SET1B or its unique cytoplasmic-interacting protein, BOD1, leads to up-regulation of expression of numerous genes modulating fatty acid metabolism, including ADIPOR1 (adiponectin receptor 1), COX7C, SDC4, and COQ7 Our detailed molecular studies identify ADIPOR1 signaling, which is inactivated in both obesity and human cancers, as a key target of SET1B/COMPASS...
November 14, 2017: Genes & Development
https://www.readbyqxmd.com/read/29138235/brip1-overexpression-is-correlated-with-clinical-features-and-survival-outcome-of-luminal-breast-cancer-subtypes
#15
Ishita Gupta, Allal Ouhtit, Adil Al-Ajmi, Syed Gauhar A Rizvi, Hamad Al-Riyami, Marwa Al-Riyami, Yahya Tamimi
In Oman, breast cancer is most common, representing approximately more than 25% of all cancers in women. Relatively younger populations of patients (25 to 40 years) present surprisingly with an aggressive phenotype and advanced tumor stages. In this study, we investigated differential gene expressions in Luminal-A, Luminal-B, Triple negative and Her2+ breast cancer subtypes and compared data to benign tumor samples. We identified a potential candidate gene BRIP1, showing differential expression in the four breast cancer subtypes examined, suggesting that BRIP1 has the profile of a useful diagnostic marker, suitable for targeted therapeutic intervention...
November 14, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29138205/long-term-prognosis-of-young-breast-cancer-patients-%C3%A2-40-years-who-did-not-receive-adjuvant-systemic-treatment-protocol-for-the-paradigm-initiative-cohort-study
#16
Gwen Mhe Dackus, Natalie D Ter Hoeve, Mark Opdam, Willem Vreuls, Zsuzsanna Varga, Esther Koop, Stefan M Willems, Carolien Hm Van Deurzen, Emilie J Groen, Alicia Cordoba, Jos Bart, Antien L Mooyaart, Jan G van den Tweel, Vicky Zolota, Jelle Wesseling, Anna Sapino, Ewa Chmielik, Ales Ryska, Frederic Amant, Annegien Broeks, Ron Kerkhoven, Nikolas Stathonikos, Mitko Veta, Adri Voogd, Katarzyna Jozwiak, Michael Hauptmann, Marlous Hoogstraat, Marjanka K Schmidt, Gabe Sonke, Elsken van der Wall, Sabine Siesling, Paul J van Diest, Sabine C Linn
INTRODUCTION: Currently used tools for breast cancer prognostication and prediction may not adequately reflect a young patient's prognosis or likely treatment benefit because they were not adequately validated in young patients. Since breast cancers diagnosed at a young age are considered prognostically unfavourable, many treatment guidelines recommend adjuvant systemic treatment for all young patients. Patients cured by locoregional treatment alone are, therefore, overtreated. Lack of prognosticators for young breast cancer patients represents an unmet medical need and has led to the initiation of the PAtients with bReAst cancer DIaGnosed preMenopausally (PARADIGM) initiative...
November 14, 2017: BMJ Open
https://www.readbyqxmd.com/read/29137951/triple-negative-breast-cancer-stem-cells-and-african-ancestry
#17
REVIEW
Evelyn Jiagge, Dhananjay Chitale, Lisa A Newman
Triple-negative breast cancers (TNBC) are more common among African ancestry populations, such as African Americans and western, sub-Saharan Africans, compared to European ancestry populations. This phenotype prevalence contributes to breast cancer outcome disparities between African Americans and Caucasian Americans. Breast cancer stem cells represent the tumor subpopulation responsible for metastatic virulence and ongoing research seeks to characterize the extent to which TNBC versus non-TNBC stem cells may differ...
November 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29137420/anti-angiogenic-and-anti-tumor-effects-of-metronomic-use-of-novel-liposomal-zoledronic-acid-depletes-tumor-associated-macrophages-in-triple-negative-breast-cancer
#18
Xin-Jun Cai, Zeng Wang, Jia-Wei Cao, Jian-Jun Ni, Ying-Ying Xu, Jun Yao, Hong Xu, Fang Liu, Gao-Yi Yang
Zoledronic acid (ZOL) has been used as an adjuvant therapy for breast cancer. It is suggested that ZOL might be associated with inhibition of macrophages, which in turn reduces tumor growth, metastasis and tumor angiogenesis. Moreover, metronomic therapy can inhibit tumor angiogenesis and tumor immune cells. Previously we developed ZOL based cationic liposomes that allowed a higher intratumor delivery of drug compared with free ZOL in vivo. Therefore, in this study, Asn-Gly-Arg (NGR) and PEG2000 were used as ligands to modify the surface of liposomes (NGR-PEG-LP-ZOL) in metronomic therapy to clear the tumor-associated macrophages (TAMs) and inhibit the formation of tumor angiogenesis, achieving the purpose of anti-tumor growth...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137393/synergistic-effect-of-eribulin-and-cdk-inhibition-for-the-treatment-of-triple-negative-breast-cancer
#19
Shreyas S Rao, Jenna Stoehr, Danijela Dokic, Lei Wan, Joseph T Decker, Kristine Konopka, Alexandra L Thomas, Jia Wu, Virginia G Kaklamani, Lonnie D Shea, Jacqueline S Jeruss
Activation of CDK2 in triple negative breast cancer (TNBC) can contribute to non-canonical phosphorylation of a TGFβ signaling component, Smad3, promoting cell proliferation and migration. Inhibition of CDK2 was shown to decrease breast cancer oncogenesis. Eribulin chemotherapy was used effectively in the treatment of TNBC. To this end, we tested therapeutic efficacy of a novel CDK2/9 inhibitor, CYC065, eribulin, and the combination of CYC065 and eribulin in 3 different TNBC cell lines, and an in vivo xenograft model...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137356/disruption-of-stat3-dnmt1-interaction-by-sh-i-14-induces-re-expression-of-tumor-suppressor-genes-and-inhibits-growth-of-triple-negative-breast-tumor
#20
Hyo Jin Kang, Yong Weon Yi, Shu-Jie Hou, Hee Jeong Kim, Yali Kong, Insoo Bae, Milton L Brown
Epigenetic regulation of gene expression is an emerging target to treat several human diseases including cancers. In cancers, expressions of many tumor suppressor genes are suppressed by hyper-methylation in their regulatory regions. Herein, we describe a novel carbazole SH-I-14 that decreased the level of the acetyl-STAT3 at the K685 residue. Mutation analysis revealed that SH-I-14 disrupted STAT3-DNMT1 interaction by removing acetyl group from K685 of STAT3. Finally, the inhibition of STAT3-DNMT1 interaction by SH-I-14 resulted in re-expression of tumor suppressor genes such as VHL and PDLIM4 through de-methylation of their promoter regions...
October 13, 2017: Oncotarget
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