• Hsp9β
• cancer
• chemical ligations
• drug repurposing
• geldanamycin
• molecular docking
• molecular dynamics
• ritonavir

• Lactams, Macrocyclic/pharmacology
• Lactams, Macrocyclic/chemistry
• Ritonavir/chemistry
• Ritonavir/pharmacology
• Benzoquinones/chemistry
• Benzoquinones/pharmacology
• Benzoquinones/metabolism
• HSP90 Heat-Shock Proteins/chemistry
• HSP90 Heat-Shock Proteins/metabolism
• HSP90 Heat-Shock Proteins/antagonists & inhibitors
• Humans
• Protein Binding
• Molecular Dynamics Simulation
• Molecular Docking Simulation
• Models, Molecular
• Binding Sites
• Adenosine Triphosphate/metabolism
• Adenosine Triphosphate/chemistry

• BEX Process 88887.319299/2019-00 Coordination for the Improvement of Higher Education Personnel - CAPES

• 3-bromopyruvate
• Raman spectroscopy
• Warburg effect
• cancer microenvironment
• glycolysis
• lipid metabolism
• pancreatic cancer

• Mice
• Animals
• Tumor Microenvironment
• Pancreatic Neoplasms/diagnostic imaging
• Pancreatic Neoplasms/drug therapy
• Microscopy, Fluorescence
• Biomarkers
• Multimodal Imaging
• Spectrum Analysis, Raman

• P30 DK072476 NIDDK NIH HHS
• R35 GM150564 NIGMS NIH HHS
• P20GM103528 NIH HHS
• P20GM135002 NIH HHS
• P20 GM135002 NIGMS NIH HHS
• R35GM150564 NIH HHS
• P20 GM103528 NIGMS NIH HHS
• P30DK072476 NIH HHS

• Ipomoea turpethum
• bioinformatics
• breast cancer
• nano LCMS/MS
• nanoparticles
• secretome analysis

• Council of Scientific and Industrial Research, India

• Natural Science Foundation of Shandong Province

• MALDI
• biomarkers
• biomedical research
• proteomics
• tandem mass spectrometry (MS/MS)

• Biomedical Research
• Peptides/chemistry
• Proteins/chemistry
• Proteomics/methods
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods
• Tandem Mass Spectrometry

• R15 CA260126 NCI NIH HHS
• R15CA260126 NIH HHS

• Alpha fetal protein
• Aptamer
• Gold microelectrode
• One-step detection
• Square wave voltammetry
• Tumor markers

Rapid and highly sensitive detection of carcinoembryonic antigen (CEA) in blood could effectively improve the diagnostic sensitivity of colorectal cancer. In this work, a platinum microelectrode (PtμE) modified with gold nanoparticles was developed as a microsensor for the detection of CEA. As the recognition element, a CEA aptamer modified with sulfhydryl could be conjugated onto the surface of the PtμEs/Au. The quantitative analysis of the concentration of CEA [CEA] by the prepared PtμEs/Au aptasensor was carried out through square wave voltammetry. Under the optimized conditions, the PtμEs/Au aptasensor exhibits a linear response toward [CEA] in the range of 1.0 × 10^–11—1.0 × 10^–7 g/ml (S = 5.5 nA/dec, R² = 0.999), and the detection limit is 7.7 × 10^–12 g/ml. The PtμEs/Au aptasensor also has good selectivity against other types of proteins existing in blood. The availability of the developed assay toward [CEA] in blood samples was investigated, and the results agreed well with those obtained through electrochemiluminescence provided by the hospital, and the volume of the blood sample for detection is only 20 μl. Herein, the proposed detection system could be used for the quantitative analysis of CEA in blood, with the advantages of high sensitivity, short time, and low cost. Moreover, the PtμEs/Au aptasensor has a potential application in clinical diagnosis.

• computational biology and bioinformatics
• systems biology

• Breast Neoplasms/genetics
• Breast Neoplasms/mortality
• Breast Neoplasms/pathology
• Datasets as Topic
• Female
• Gene Regulatory Networks
• Genome-Wide Association Study/methods
• Humans
• Kaplan-Meier Estimate
• Neoplasm Recurrence, Local/genetics
• Neoplasm Staging/methods
• Protein Interaction Maps/genetics
• Survival Rate
• Systems Biology/methods
• Transcriptome

• Cancer drug resistance
• CyTOF
• PTMs
• biomarker discovery
• comparative proteomics
• mass spectrometry
• personalized medicine

• cancer therapy
• network-based strategy
• siRNA therapy
• triple-negative breast cancer (TNBC)

Proteomic analyses are rapid and powerful tools that are used to increase the understanding of cancer pathogenesis, discover cancer biomarkers and predictive markers, and select and monitor novel targets for cancer therapy. Feline injection-site sarcomas (FISS) are aggressive skin tumours with high recurrence rates, despite treatment with surgery, radiotherapy, and chemotherapy. Doxorubicin is a drug of choice for soft tissue sarcomas, including FISS. However, multidrug resistance is one of the major causes of chemotherapy failure. The main aim of the present study was to identify proteins that differentiate doxorubicin-resistant from doxorubicin-sensitive FISS using two-dimensional gel electrophoresis (2DE), followed by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) analysis. Using the three-dimensional (3D) preclinical in ovo model, which resembles features of spontaneous fibrosarcomas, three significantly (p ≤ 0.05) differentially expressed proteins were identified in tumours grown from doxorubicin-resistant fibrosarcoma cell lines (FFS1 and FFS3) in comparison to the doxorubicin-sensitive one (FFS5): Annexin A5 (ANXA5), Annexin A3 (ANXA3), and meiosis-specific nuclear structural protein 1 (MNS1). Moreover, nine other proteins were significantly differentially expressed in tumours grown from the high doxorubicin-resistant cell line (FFS1) in comparison to sensitive one (FFS5). This study may be the first proteomic fingerprinting of FISS reported, identifying potential candidates for specific predictive biomarkers and research targets for doxorubicin-resistant FISS.

• MALDI-TOF MS
• chemotherapy resistance
• doxorubicin
• feline injection-site sarcoma
• in ovo assay
• proteomic analysis
• two-dimensional electrophoresis

• 14-3-3 Zeta/delta
• ALDH2
• Biomarkers
• Intravesical BCG
• Monitoring
• Rab-GDIβ

• Administration, Intravesical
• Animals
• BCG Vaccine/immunology
• Cancer Vaccines/immunology
• Disease Models, Animal
• Female
• Guanine Nucleotide Dissociation Inhibitors/genetics
• Guanine Nucleotide Dissociation Inhibitors/metabolism
• Humans
• Immunotherapy/methods
• Precancerous Conditions
• Proteome
• Rats
• Rats, Wistar
• Urologic Neoplasms/immunology
• Urologic Neoplasms/therapy
• Urothelium/metabolism
• Urothelium/pathology

• 2015/035 Kocaeli Üniversitesi

• Pharmacodynamics
• Pharmacokinetics
• Pharmacometrics
• Population analysis
• Quantitative systems pharmacology
• Tumor priming

• 14-3-3ζ
• Breast cancer recurrence
• Predictive marker
• Prognostic marker
• Tamoxifen

• 14-3-3 Proteins/genetics
• 14-3-3 Proteins/metabolism
• Adult
• Aged
• Antineoplastic Agents, Hormonal/pharmacology
• Antineoplastic Agents, Hormonal/therapeutic use
• Biomarkers, Tumor
• Breast Neoplasms/drug therapy
• Breast Neoplasms/epidemiology
• Breast Neoplasms/genetics
• Breast Neoplasms/pathology
• Case-Control Studies
• Denmark/epidemiology
• Drug Resistance, Neoplasm/genetics
• Female
• Gene Expression
• Humans
• Immunohistochemistry
• Middle Aged
• Neoplasm Recurrence, Local
• Neoplasm Staging
• Odds Ratio
• Population Surveillance
• Tamoxifen/pharmacology
• Tamoxifen/therapeutic use

• R01 CA118708 NCI NIH HHS
• R01 CA166825 NCI NIH HHS

• breast cancer
• epithelial
• estrogen related receptor alpha
• kinesin
• transcription

This paper presents a three-dimensional dynamic model for the chemotherapy design based on a multiphysics and multiscale approach. The model incorporates cancer cells, matrix degrading enzymes (MDEs) secreted by cancer cells, degrading extracellular matrix (ECM), and chemotherapeutic drug. Multiple mechanisms related to each component possible in chemotherapy are systematically integrated for high reliability of computational analysis of chemotherapy. Moreover, the fidelity of the estimated efficacy of chemotherapy is enhanced by atomic information associated with the diffusion characteristics of chemotherapeutic drug, which is obtained from atomic simulations. With the developed model, the invasion process of cancer cells in chemotherapy treatment is quantitatively investigated. The performed simulations suggest a substantial potential of the presented model for a reliable design technology of chemotherapy treatment.

• Clear cell carcinoma
• Endometrium
• MALDI IMS
• Mass spectrometry
• Ovary

• apoptosis
• biochemistry
• signal transduction
• small molecules
• sphingosine

• 14-3-3 Proteins/genetics
• 14-3-3 Proteins/metabolism
• Animals
• Apoptosis
• Humans
• Jurkat Cells
• Lung Neoplasms/genetics
• Lung Neoplasms/pathology
• Mice
• Phosphorylation
• Signal Transduction
• Sphingosine/pharmacology

The degree and the origins of quantitative variability of most human plasma proteins are largely unknown. Because the twin study design provides a natural opportunity to estimate the relative contribution of heritability and environment to different traits in human population, we applied here the highly accurate and reproducible SWATH mass spectrometry technique to quantify 1,904 peptides defining 342 unique plasma proteins in 232 plasma samples collected longitudinally from pairs of monozygotic and dizygotic twins at intervals of 2–7 years, and proportioned the observed total quantitative variability to its root causes, genes, and environmental and longitudinal factors. The data indicate that different proteins show vastly different patterns of abundance variability among humans and that genetic control and longitudinal variation affect protein levels and biological processes to different degrees. The data further strongly suggest that the plasma concentrations of clinical biomarkers need to be calibrated against genetic and temporal factors. Moreover, we identified 13 cis-SNPs significantly influencing the level of specific plasma proteins. These results therefore have immediate implications for the effective design of blood-based biomarker studies.

• SWATH‐MS
• heritability
• longitudinal variability
• plasma biomarkers
• twin study

Estrogen receptors [ERs (subtypes α and β)], classified as a nuclear receptor super family, are intracellular proteins with an important biological role as the transcription factors for estrogen target genes. For ER-induced transcription, an interaction must exist between ligand and coregulators. Coregulators may stimulate (coactivators) or inhibit (corepressors) transcription, following binding with a specific region of the gene, called the estrogen response element. Misbalanced activity of coregulators or higher ligand concentrations may cause increased cell proliferation, resulting in specific types of cancer. These are exhibited as overexpression of ER proteins. Breast cancer currently ranks first in the incidence and second in the mortality of cancer in females worldwide. In addition, 70% of breast tumors are ERα positive and the importance of these proteins for diagnostic use is indisputable. Early diagnosis of the tumor and its classification has a large influence on the selection of appropriate therapy, as ER-positive tumors demonstrate a positive response to hormonal therapy. Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI TOF MS) has been hypothesized to have great potential, as it offers reliable, robust and efficient analysis methods for biomarker monitoring and identification. The present review discusses ER protein analysis by MALDI TOF MS, including the crucial step of protein separation.

• cancer
• estrogen receptor
• estrogen response element
• matrix-assisted laser desorption/ionization time of flight

Beyond its possible correlation with stemness of tumor cells, CD133/prominin1 is considered an important marker in breast cancer, since it correlates with tumor size, metastasis and clinical stage of triple-negative breast cancers (TNBC), to date the highest risk breast neoplasia.

To study the correlation between the levels of CD133 expression and the biology of breast-derived cells, CD133^low and CD133^high cell subpopulations isolated from triple negative MDA-MB-231 cells were compared in terms of malignant properties and protein expression.

High expression of CD133 characterizes cells with larger adhesion area, lower proliferation rate and reduced migration speed, indicative of a less undifferentiated phenotype. Conversely, when compared with CD133^low cells, CD133^high cells show higher invasive capability and increased expression of proteins involved in metastasis and drug-resistance of breast tumors. Among the signalling proteins examined, PLC-β2 expression inversely correlates with the levels of CD133 and has a role in inducing the CD133^high cells to CD133^low cells conversion, suggesting that, in TNBC cells, the de-regulation of this PLC isoform is responsible of the switch from an early to a mature tumoral phenotype also by reducing the expression of CD133.

Since CD133 plays a role in determining the invasiveness of CD133^high cells, it may constitute an attractive target to reduce the metastatic potential of TNBC. In addition, our data showing that the forced up-regulation of PLC-β2 counteracts the invasiveness of CD133-positive MDA-MB-231 cells might contribute to identify unexplored key steps responsible for the TNBC high malignancy, to be considered for potential therapeutic strategies.

• Annexin-V
• Apoptosis
• Hep-2
• Proteomics
• Red propolis
• TUNEL

• Biomarkers
• Breast cancer
• Molecular subtypes
• Proteomics
• Review

Post-surgery therapies are given to early-stage breast cancer patients due to the possibility of residual micrometastasis, and optimized by clincopathological parameters such as tumor stage, and hormone receptor/lymph node status. However, current efficacy of post-surgery therapies is unsatisfactory, and may be varied according to unidentified patient genetic factors. Increases of breast cancer occurrence and recurrence have been associated with dyslipidemia, which can attribute to other known risk factors of breast cancer including obesity, diabetes and metabolic syndrome. Thus we reasoned that dyslipidemia-associated nucleotide polymorphisms (SNPs) on the APOA1/C3/A5 gene cluster may predict breast cancer risk and tumor progression.

We analyzed the distribution of 5 selected APOA1/C3/A5 SNPs in recruited Taiwanese breast cancer patients (n=223) and healthy controls (n=162). The association of SNP (APOA1 rs670) showing correlation with breast cancer with baseline and follow-up parameters was further examined.

APOA1 rs670 A allele carriage was higher in breast cancer patients than controls (59.64% vs. 48.77%, p=0.038). The rs670 A allele carrying patients showed less favorable baseline phenotype with positive lymph nodes (G/A: OR=3.32, 95% CI=1.77-6.20, p<0.001; A/A: OR=2.58, 95% CI=1.05-6.32, p=0.039) and negative hormone receptor expression (A/A: OR=4.85, 95%CI=1.83-12.83, p=0.001) in comparison to G/G carriers. Moreover, rs670 A/A carrying patients had higher risks in both tumor recurrence (HR=3.12, 95% CI=1.29-7.56, p=0.012) and mortality (HR=4.36, 95% CI=1.52-12.47, p=0.006) than patients with no A alleles after adjustments for associated baseline parameters. Furthermore, the prognostic effect of rs670 A/A carriage was most evident in lymph node-negative patients, conferring to the highest risks of recurrence (HR=4.98, 95% CI=1.40-17.70, p=0.013) and mortality (HR=9.87, 95%CI=1.60-60.81, p=0.014) than patients with no A alleles.

APOA1 rs670 A/A carriage showed poor post-surgery prognosis in Taiwanese lymph node-negative breast cancer patients, whose prognosis were considered better and adjuvant treatment might be less stringent according to currently available assessment protocols. Our findings suggest that APOA1 rs670 indicate a post-surgery risk of breast cancer disease progression, and that carriers of this SNP may benefit from more advanced disease monitoring and therapy regimens than the current regular standards. Furthermore, control of lipid homeostasis might protect APOA1 rs670 minor allele carriers from breast cancer occurrence and progression.

Breast cancer is a multifactorial disease. A spectrum of internal and external factors contributes to the disease promotion such as a genetic predisposition, chronic inflammatory processes, exposure to toxic compounds, abundant stress factors, a shift-worker job, etc. The cumulative effects lead to high incidence of breast cancer in populations worldwide. Breast cancer in the USA is currently registered with the highest incidence rates amongst all cancer related patient cohorts. Currently applied diagnostic approaches are frequently unable to recognise early stages in tumour development that impairs individual outcomes. Early diagnosis has been demonstrated to be highly beneficial for significantly enhanced therapy efficacy and possibly full recovery. Actual paper shows that the elaboration of an integrative diagnostic approach combining several levels of examinations creates a robust platform for the reliable risk assessment, targeted preventive measures and more effective treatments tailored to the person in the overall task of breast cancer management. The levels of examinations are proposed, and innovative technological approaches are described in the paper. The absolute necessity to create individual patient profiles and extended medical records is justified for the utilising by routine medical services. Expert recommendations are provided to promote further developments in the field.

Breast cancer is a healthcare concern of women worldwide. Despite procedures being available for diagnosis, prognosis and treatment of breast cancer, researchers are working intensively on the disease in order to improve the life quality of breast cancer patients. At present, there is no single treatment known to bring a definite cure for breast cancer. One of the possible solutions for combating breast cancer is through identification of reliable protein biomarkers that can be effectively used for early detection, prognosis and treatments of the cancer. Therefore, the task of identification of biomarkers for breast cancer has become the focus of many researchers worldwide.

• Breast cancer
• Protein
• Biomarkers
• Proteomics