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https://www.readbyqxmd.com/read/28222068/inhibition-of-cdk5-induces-cell-death-of-tumor-initiating-cells
#1
Melanie M Mandl, Siwei Zhang, Melanie Ulrich, Elisa Schmoeckel, Doris Mayr, Angelika M Vollmar, Johanna Liebl
BACKGROUND: Tumour-initiating cells (TICs) account for chemoresistance, tumour recurrence and metastasis, and therefore represent a major problem in tumour therapy. However, strategies to address TICs are limited. Recent studies indicate Cdk5 as a promising target for anti-cancer therapy and Cdk5 has recently been associated with epithelial-mesenchymal transition (EMT). However, a role of Cdk5 in TICs has not been described yet. METHODS: Expression of Cdk5 in human cancer tissue was analysed by staining of a human tissue microarray (TMA)...
February 21, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28219700/inhibition-of-ros-production-autophagy-or-apoptosis-signaling-reversed-the-anticancer-properties-of-antrodia-salmonea-in-triple-negative-breast-cancer-mda-mb-231-cells
#2
Chia-Ting Chang, Mallikarjuna Korivi, Hui-Chi Huang, Varadharajan Thiyagarajan, Kai-Yuan Lin, Pei-Jane Huang, Jer-Yuh Liu, You-Cheng Hseu, Hsin-Ling Yang
We investigated the in vitro and in vivo anticancer properties of Antrodia salmonea (AS), a well-known edible/medicinal mushroom in Taiwan, on human triple-negative breast cancer (MDA-MB-231) cells and xenografted nude mice; and revealed the underlying molecular mechanisms involved in autophagic- and apoptotic-cell death. Treatment of MDA-MB-231 cells with fermented culture broth of AS (0-200 μg/mL) inhibited cell viability/growth. AS-induced autophagy was evidenced via increased LC3-II accumulation, GFP-LC3 puncta and AVOs formation in MDA-MB-231 cells...
February 17, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28219246/dna-generated-electric-current-biosensor
#3
Lanshuang Hu, Shengqiang Hu, Linyan Guo, Congcong Shen, Minghui Yang, Avraham Rasooly
In addition to its primary function as a genetic material, deoxyribonucleic acid (DNA) is also a potential biologic energy source for molecular electronics. For the first time, we demonstrate that DNA can generate a redox electric current. As an example of this new functionality, DNA generated redox current was used for electrochemical detection of human epidermal growth factor receptor 2 (HER2), a clinically important breast cancer biomarker. To induce redox current, the phosphate of the single stranded DNA aptamer backbone was reacted with molybdate to form redox molybdophosphate precipitate and generate an electrochemical current of ∼16...
February 21, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28218905/phosphorylation-mediated-activation-of-ldha-promotes-cancer-cell-invasion-and-tumour-metastasis
#4
L Jin, J Chun, C Pan, G N Alesi, D Li, K R Magliocca, Y Kang, Z G Chen, D M Shin, F R Khuri, J Fan, S Kang
Metastases remain the major cause of death from cancer. Recent molecular advances have highlighted the importance of metabolic alterations in cancer cells, including the Warburg effect that describes an increased glycolysis in cancer cells. However, how this altered metabolism contributes to tumour metastasis remains elusive. Here, we report that phosphorylation-induced activation of lactate dehydrogenase A (LDHA), an enzyme that catalyses the interconversion of pyruvate and lactate, promotes cancer cell invasion, anoikis resistance and tumour metastasis...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28218902/retinoic-acid-directs-breast-cancer-cell-state-changes-through-regulation-of-tet2-pkc%C3%AE-pathway
#5
M-J Wu, M R Kim, Y-S Chen, J-Y Yang, C-J Chang
The key molecular mechanism governing the cancer cell state (stem cell-like state vs differentiation state) to control the cancer stem cell (CSC) pool remains elusive. This study provides the first evidence showing that all-trans retinoic acid (ATRA) induces the interaction and chromatin recruitment of a novel RARβ-TET2 complex to epigenetically activate a specific cohort of gene targets, including MiR-200c. TET2-activated miR-200c further targets and suppresses PKCζ, a cell polarity protein that has a pivotal role in directing asymmetric division of mammalian stem cells to sustain the stem cell pool...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28218347/breast-cancer-early-diagnosis-and-effective-treatment-by-drug-delivery-tracing
#6
Mahdiyeh Shamsi, Jalil Pirayesh Islamian
Breast cancer is the most frequent cancer in women and it is the main reason of cancer-related deaths of women worldwide. Different types of breast cancer diagnostic examinations are also available, such as mammography, MRI, biopsy, ultrasound and molecular imaging. Radionuclide-based imaging methods including SPECT and PET are useful in early diagnosis and treatment of the cancer. The radiolabeling of chemo drugs with nanoparticles should be recommended from the standpoint of an early diagnosis and effective treatment of breast cancer...
2017: Nuclear Medicine Review. Central & Eastern Europe
https://www.readbyqxmd.com/read/28218039/demethylation-and-alterations-in-the-expression-level-of-the-cell-cycle-related-genes-as-possible-mechanisms-in-arsenic-trioxide-induced-cell-cycle-arrest-in-human-breast-cancer-cells
#7
Farima Moghaddaskho, Haniyeh Eyvani, Mohsen Ghadami, Javad Tavakkoly-Bazzaz, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Arsenic trioxide (As2O3) has been used clinically as an anti-tumor agent. Its mechanisms are mostly considered to be the induction of apoptosis and cell cycle arrest. However, the detailed molecular mechanisms of its anti-cancer action through cell cycle arrest are poorly known. Furthermore, As2O3 has been shown to be a potential DNA methylation inhibitor, inducing DNA hypomethylation. We hypothesize that As2O3 may affect the expression of cell cycle regulatory genes by interfering with DNA methylation patterns...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28216417/expression-profiling-of-clinical-specimens-supports-the-existence-of-neural-progenitor-like-stem-cells-in-basal-breast-cancers
#8
Alex Panaccione, Yan Guo, Wendell G Yarbrough, Sergey V Ivanov
BACKGROUND: We previously characterized in salivary adenoid cystic carcinoma (ACC) a novel population of cancer stem cells (CSCs) marked by coexpression of 2 stemness genes, sex-determining region Y (SRY)-related HMG box-containing factor 10 (SOX10) and CD133. We also reported that in ACC and basal-like breast carcinoma (BBC), a triple-negative breast cancer subtype, expression of SOX10 similarly demarcates a highly conserved gene signature enriched with neural stem cell genes. On the basis of these findings, we hypothesized that BBC might be likewise driven by SOX10-positive (SOX10(+))/CD133(+) cells with neural stem cell properties...
January 27, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/28216224/targeted-proteomics-driven-verification-of-biomarker-candidates-associated-with-breast-cancer-aggressiveness
#9
Iva Procházková, Juraj Lenčo, Alena Fučíková, Jiří Dresler, Lenka Čápková, Roman Hrstka, Rudolf Nenutil, Pavel Bouchal
Breast cancer is the most common and molecularly relatively well characterized malignant disease in women, however, its progression to metastatic cancer remains lethal for 78% of patients 5years after diagnosis. Novel markers could identify the high risk patients and their verification using quantitative methods is essential to overcome genetic, inter-tumor and intra-tumor variability and translate novel findings into cancer diagnosis and treatment. We recently identified 13 proteins associated with estrogen receptor, tumor grade and lymph node status, the key factors of breast cancer aggressiveness, using untargeted proteomics...
February 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28215732/targeted-therapy-in-older-women-with-breast-cancer-what-s-the-target
#10
M Kiderlen, C J H van de Velde, G-J Liefers
In this review, the results of the FOCUS (Female breast cancer in the elderly: Optimizing Clinical guidelines USing clinico-pathological and molecular data) program are summarized. This study was originally designed with the aim to define guidelines for the treatment of older women with breast cancer. With data from several studies within FOCUS, a prediction model can be constructed. Such a model helps to define individualized treatment for older patients with breast cancer, taking into account tumour characteristics and patient-related factors...
February 3, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28215644/from-molecular-insight-to-therapeutic-strategy-the-holistic-approach-for-treating-triple-negative-breast-cancer
#11
REVIEW
Rittwika Bhattacharya, Koyel Banerjee, Nupur Mukherjee, Minakshi Sen, Ashis Mukhopadhyay
Aim of the present study was to analyze the molecular pathogenesis of TNBC, therapeutic practice, challenges, and future goals in treatment strategies. Based on the alterations of distinct pathways, Lehmann's subgroups of TNBCs were further categorized. Those with defective DNA damage repair and replication pathways, viz. Basal Like 1 & 2 (BL1, BL2) were found susceptible to DNA intercalating drugs while those with upregulated cell signalling & motility (mesenchymal (M), mesemchymal stem like (MSL)), cell survival (BL2, M, MSL), angiogenesis (BL2, MSL), T cell signalling (Immunomodulatory/IM) pathways required targeted therapies...
January 19, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28214331/pomc-maintains-tumor-initiating-properties-of-tumor-tissue-derived-long-term-cultured-breast-cancer-stem-cells
#12
Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P Zhou, Mien-Chie Hung, Xiaoming Xie
The identification and understanding of the molecular network of cancer stem cells (CSCs) have had a profound impact on our view of carcinogenesis and treatment strategy. Unfortunately, a major problem is that serial passages of CSCs from clinical solid tumor specimens currently are not available in any lab, and thus, reported data are difficult to confirm and intensively interrogated. Here, we have generated two tumor tissue-derived breast CSC (BCSC) lines that showed prolonged maintenance over 20 serial passages in vitro, while retaining their tumor-initiating biological properties...
February 18, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28214016/melk-expression-in-ovarian-cancer-correlates-with-poor-outcome-and-its-inhibition-by-otssp167-abrogates-proliferation-and-viability-of-ovarian-cancer-cells
#13
Reto S Kohler, Henriette Kettelhack, Alexandra M Knipprath-Mészaros, André Fedier, Andreas Schoetzau, Francis Jacob, Viola Heinzelmann-Schwarz
OBJECTIVE: Maternal embryonic leucine-zipper kinase (MELK) shows oncogenic properties in basal-like breast cancer, a cancer subtype sharing common molecular features with high-grade serous ovarian cancer. We examined the potential of MELK as a molecular and pharmacological target for treatment of epithelial ovarian cancer (EOC). METHODS/MATERIALS: Bioinformatic analysis was performed on nine OC transcriptomic data sets totaling 1241 patients. Effects of MELK depletion by shRNA or inhibition by OTSSP167 in cell lines were assessed by colony formation and MTT (proliferation) assays, Western blotting (apoptosis), and flow cytometry (cell cycle analysis)...
February 14, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28213333/hmba-is-a-putative-hsp70-activator-stimulating-hexim1-expression-that-is-down-regulated-by-estrogen
#14
Rati Lama, Chunfang Gan, Nethrie Idippily, Viharika Bobba, David Danielpour, Monica Montano, Bin Su
Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) is identified as a novel inhibitor of estrogen stimulated breast cell growth, and it suppresses estrogen receptor-α transcriptional activity. HEXIM1 protein level has been found to be downregulated by estrogens. Recently, HEXIM1 has been found to inhibit androgen receptor transcriptional activity as well. Researchers have used Hexamethylene bis-acetamide (HMBA) for decades to stimulate HEXIM1 expression, which also inhibit estrogen stimulated breast cancer cell gene activation and androgen stimulated prostate cancer gene activation...
February 14, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28212608/transcriptomic-dynamics-of-breast-cancer-progression-in-the-mmtv-pymt-mouse-model
#15
Ying Cai, Ruben Nogales-Cadenas, Quanwei Zhang, Jhih-Rong Lin, Wen Zhang, Kelly O'Brien, Cristina Montagna, Zhengdong D Zhang
BACKGROUND: Malignant breast cancer with complex molecular mechanisms of progression and metastasis remains a leading cause of death in women. To improve diagnosis and drug development, it is critical to identify panels of genes and molecular pathways involved in tumor progression and malignant transition. Using the PyMT mouse, a genetically engineered mouse model that has been widely used to study human breast cancer, we profiled and analyzed gene expression from four distinct stages of tumor progression (hyperplasia, adenoma/MIN, early carcinoma and late carcinoma) during which malignant transition occurs...
February 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28212580/network-pharmacology-based-and-clinically-relevant-prediction-of-the-active-ingredients-and-potential-targets-of-chinese-herbs-in-metastatic-breast-cancer-patients
#16
Yu Mao, Jian Hao, Zi-Qi Jin, Yang-Yang Niu, Xue Yang, Dan Liu, Rui Cao, Xiong-Zhi Wu
Chinese Herbal Medicine (CHM) plays a significant role in breast cancer treatment. We conduct the study to ascertain the relative molecular targets of effective Chinese herbs in treating stage IV breast cancer.Survival benefit of CHM was verified by Kaplan-Meier method and Cox regression analysis. A bivariate correlation analysis was used to find and establish the effect of herbs in complex CHM formulas. A network pharmacological approach was adopted to explore the potential mechanisms of CHM.Patients in the CHM group had a median survival time of 55 months, which was longer than the 23 months of patients in the non-CHM group...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212337/synthesis-anti-breast-cancer-activity-and-molecular-docking-study-of-a-new-group-of-acetylenic-quinolinesulfonamide-derivatives
#17
Krzysztof Marciniec, Bartosz Pawełczak, Małgorzata Latocha, Leszek Skrzypek, Małgorzata Maciążek-Jurczyk, Stanisław Boryczka
In this study, a series of regioisomeric acetylenic sulfamoylquinolines are designed, synthesized, and tested in vitro for their antiproliferative activity against three human breast cacer cell lines (T47D, MCF-7, and MDA-MB-231) and a human normal fibroblast (HFF-1) by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay. The antiproliferative activity of the tested acetylenic quinolinesulfonamides is comparable to that of cisplatin. The bioassay results demonstrate that most of the tested compounds show potent antitumor activities, and that some compounds exhibit better effects than the positive control cisplatin against various cancer cell lines...
February 16, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28211079/gata3-expression-in-triple-negative-breast-cancers
#18
David J Byrne, Siddhartha Deb, Elena A Takano, Stephen B Fox
AIMS: GATA-binding protein 3 (GATA3) is a well-studied transcription factor found to be essential in the development of luminal breast epithelium and has been identified in a variety of tumour types including breast and urotheilial carcinomas making it a useful immunohistochemistry marker in the diagnosis of both primary and metastatic disease. METHODS AND RESULTS: We investigated GATA3 protein expression in a 106 primary triple negative breast carcinomas (100 basal-like, 6 non-basal-like) using Cell Marque mouse monoclonal anti-GATA3 (L50-823)...
February 17, 2017: Histopathology
https://www.readbyqxmd.com/read/28210973/renal-drug-transporters-and-drug-interactions
#19
REVIEW
Anton Ivanyuk, Françoise Livio, Jérôme Biollaz, Thierry Buclin
Transporters in proximal renal tubules contribute to the disposition of numerous drugs. Furthermore, the molecular mechanisms of tubular secretion have been progressively elucidated during the past decades. Organic anions tend to be secreted by the transport proteins OAT1, OAT3 and OATP4C1 on the basolateral side of tubular cells, and multidrug resistance protein (MRP) 2, MRP4, OATP1A2 and breast cancer resistance protein (BCRP) on the apical side. Organic cations are secreted by organic cation transporter (OCT) 2 on the basolateral side, and multidrug and toxic compound extrusion (MATE) proteins MATE1, MATE2/2-K, P-glycoprotein, organic cation and carnitine transporter (OCTN) 1 and OCTN2 on the apical side...
February 16, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28210903/role-of-exchange-protein-directly-activated-by-camp-epac1-in-breast-cancer-cell-migration-and-apoptosis
#20
Naveen Kumar, Sonal Gupta, Surbhi Dabral, Shailja Singh, Seema Sehrawat
Despite the current progress in cancer research and therapy, breast cancer remains the leading cause of mortality among half a million women worldwide. Migration and invasion of cancer cells are associated with prevalent tumor metastasis as well as high mortality. Extensive studies have powerfully established the role of prototypic second messenger cAMP and its two ubiquitously expressed intracellular cAMP receptors namely the classic protein kinaseA/cAMP-dependent protein kinase (PKA) and the more recently discovered exchange protein directly activated by cAMP/cAMP-regulated guanine nucleotide exchange factor (EPAC/cAMP-GEF) in cell migration, cell cycle regulation, and cell death...
February 16, 2017: Molecular and Cellular Biochemistry
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