scholarly journals Dielectric Characterization and Separation Optimization of Infiltrating Ductal Adenocarcinoma via Insulator-Dielectrophoresis

Micromachines ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 340 ◽  
Author(s):  
Ezekiel O. Adekanmbi ◽  
Anthony T. Giduthuri ◽  
Soumya K. Srivastava
Keyword(s):  
Breast Cancer ◽  
Effective Potential ◽  
Mononuclear Cells ◽  
Microfluidic Channel ◽  
Potential Difference ◽  
Ductal Adenocarcinoma ◽  
Confirmatory Test ◽  
Fluidic Channel ◽  
Peripheral Blood Mononuclear ◽  
Dielectric Characterization

The dielectrophoretic separation of infiltrating ductal adenocarcinoma cells (ADCs) from isolated peripheral blood mononuclear cells (PBMCs) in a ~1.4 mm long Y-shaped microfluidic channel with semi-circular insulating constrictions is numerically investigated. In this work, ADCs (breast cancer cells) and PBMCs’ electrophysiological properties were iteratively extracted through the fitting of a single-shell model with the frequency-conductivity data obtained from AC microwell experiments. In the numerical computation, the gradient of the electric field required to generate the necessary dielectrophoretic force within the constriction zone was provided through the application of electric potential across the whole fluidic channel. By adjusting the difference in potentials between the global inlet and outlet of the fluidic device, the minimum (effective) potential difference with the optimum particle transmission probability for ADCs was found. The radius of the semi-circular constrictions at which the effective potential difference was swept to obtain the optimum constriction size was also obtained. Independent particle discretization analysis was also conducted to underscore the accuracy of the numerical solution. The numerical results, which were obtained by the integration of fluid flow, electric current, and particle tracing module in COMSOL v5.3, reveal that PBMCs can be maximally separated from ADCs using a DC power source of 50 V. The article also discusses recirculation or wake formation behavior at high DC voltages (>100 V) even when sorting of cells are achieved. This result is the first step towards the production of a supplementary or confirmatory test device to detect early breast cancer non-invasively.

scholarly journals Alterations in regulatory T cells and immune checkpoint molecules in pancreatic cancer patients receiving FOLFIRINOX or gemcitabine plus nab-paclitaxel

2021 ◽  
Author(s):  
L. Sams ◽  
S. Kruger ◽  
V. Heinemann ◽  
D. Bararia ◽  
S. Haebe ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Immune Checkpoints ◽  
Prognostic Information ◽  
Peripheral Blood Mononuclear

Abstract Purpose This pilot study aimed on generating insight on alterations in circulating immune cells during the use of FOLFIRINOX and gemcitabine/nab-paclitaxel in pancreatic ductal adenocarcinoma (PDAC). Patients and methods Peripheral blood mononuclear cells were isolated before and 30 days after initiation of chemotherapy from 20 patients with advanced PDAC. Regulatory T cells (FoxP3+) and immune checkpoints (PD-1 and TIM-3) were analyzed by flow cytometry and immunological changes were correlated with clinical outcome. Results Heterogeneous changes during chemotherapy were observed in circulating T-cell subpopulations with a pronounced effect on PD-1+ CD4+/CD8+ T cells. An increase in FoxP3+ or PD-1+ T cells had no significant effect on survival. An increase in TIM3+/CD8+ (but not TIM3+/CD4+) T cells was associated with a significant inferior outcome: median progression-free survival in the subgroup with an increase of TIM-3+/CD8+ T cells was 6.0 compared to 14.0 months in patients with a decrease/no change (p = 0.026); corresponding median overall survival was 13.0 and 20.0 months (p = 0.011), respectively. Conclusions Chemotherapy with FOLFIRNOX or gemcitabine/nab-paclitaxel induces variable changes in circulating T-cell populations that may provide prognostic information in PDAC.

scholarly journals Phytochemicals from Ajwa dates pulp extract induce apoptosis in human triple-negative breast cancer by inhibiting AKT/mTOR pathway and modulating Bcl-2 family proteins

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohsin Ali Khan ◽  
Sahabjada Siddiqui ◽  
Imran Ahmad ◽  
Romila Singh ◽  
Durga Prasad Mishra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Mononuclear Cells ◽  
Apoptotic Cell ◽  
Human Peripheral Blood ◽  
Annexin V ◽  
Phoenix Dactylifera ◽  
Mtor Pathway ◽  
Peripheral Blood Mononuclear

AbstractAjwa dates (Phoenix dactylifera L.) have been described in traditional and alternative medicine to provide several health benefits, but their mechanism of apoptosis induction against human triple-negative breast cancer MDA-MB-231 cells remains to be investigated. In this study, we analyzed the phytoconstituents in ethanolic Ajwa Dates Pulp Extract (ADPE) by liquid chromatography-mass spectrometry (LC–MS) and investigated anticancer effects against MDA-MB-231 cells. LC–MS analysis revealed that ADPE contained phytocomponents belonging to classes such as carbohydrates, phenolics, flavonoids and terpenoids. MTT assay demonstrated statistically significant dose- and time-dependent inhibition of MDA-MB-231 cells with IC50 values of 17.45 and 16.67 mg/mL at 24 and 48 h, respectively. Hoechst 33342 dye and DNA fragmentation data showed apoptotic cell death while AO/PI and Annexin V-FITC data revealed cells in late apoptosis at higher doses of ADPE. More importantly, ADPE prompted reactive oxygen species (ROS) induced alterations in mitochondrial membrane potential (MMP) in ADPE treated MDA-MB-231 cells. Cell cycle analysis demonstrated that ADPE induced cell arrest in S and G2/M checkpoints. ADPE upregulated the p53, Bax and cleaved caspase-3, thereby leading to the downregulation of Bcl-2 and AKT/mTOR pathway. ADPE did not show any significant toxicity on normal human peripheral blood mononuclear cells which suggests its safe application to biological systems under study. Thus, ADPE has the potential to be used as an adjunct to the mainline of treatment against breast cancer.

scholarly journals Analysis of circulating breast cancer cell heterogeneity and interactions with peripheral blood mononuclear cells

2020 ◽  
Vol 59 (10) ◽  
pp. 1129-1139 ◽  
Author(s):  
Heather M. Brechbuhl ◽  
Kiran Vinod‐Paul ◽  
Austin E. Gillen ◽  
Etana G. Kopin ◽  
Kari Gibney ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Heterogeneity ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

scholarly journals Genome-Wide Methylation Profiling in Canine Mammary Tumor Reveals miRNA Candidates Associated with Human Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1466
Author(s):  
Su-Jin Jeong ◽  
Kang-Hoon Lee ◽  
A-Reum Nam ◽  
Je-Yoel Cho
Keyword(s):  
Breast Cancer ◽  
Mammary Tumor ◽  
Mononuclear Cells ◽  
Aberrant Methylation ◽  
Canine Mammary Tumor ◽  
Promoter Regions ◽  
Peripheral Blood Mononuclear ◽  
Genome Wide ◽  
Differentially Methylated Genes ◽  
Methylation Profiling

Genome-wide methylation profiling is used in breast cancer (BC) studies, because DNA methylation is a crucial epigenetic regulator of gene expression, involved in many diseases including BC. We investigated genome-wide methylation profiles in both canine mammary tumor (CMT) tissues and peripheral blood mononuclear cells (PBMCs) using reduced representation bisulfite sequencing (RRBS) and found unique CMT-enriched methylation signatures. A total of 2.2–4.2 million cytosine–phosphate–guanine (CpG) sites were analyzed in both CMT tissues and PBMCs, which included 40,000 and 28,000 differentially methylated regions (DMRs) associated with 341 and 247 promoters of differentially methylated genes (DMGs) in CMT tissues and PBMCs, respectively. Genes related to apoptosis and ion transmembrane transport were hypermethylated, but cell proliferation and oncogene were hypomethylated in tumor tissues. Gene ontology analysis using DMGs in PBMCs revealed significant methylation changes in the subset of immune cells and host defense system-related genes, especially chemokine signaling pathway-related genes. Moreover, a number of CMT tissue-enriched DMRs were identified from the promoter regions of various microRNAs (miRNAs), including cfa-mir-96 and cfa-mir-149, which were reported as cancer-associated miRNAs in humans. We also identified novel miRNAs associated with CMT which can be candidates for new miRNAs associated with human BC. This study may provide new insight for a better understanding of aberrant methylation associated with both human BC and CMT, as well as possible targets for methylation-based BC diagnostic markers.

A phase I-II and pharmacodynamic (PD) study of the combination of the proteasome inhibitor bortezomib (B) and paclitaxel (P) in patients with taxane-sensitive solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13029-13029
Author(s):  
E. Gallerani ◽  
S. Cresta ◽  
D. Tosi ◽  
C. Sessa ◽  
G. Capri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Ovarian Cancer ◽  
Antitumor Activity ◽  
Phase I ◽  
Anticancer Agents ◽  
Mononuclear Cells ◽  
Performance Status ◽  
Ecog Performance Status ◽  
Peripheral Blood Mononuclear

13029 Background: Proteasome inhibition blocks the chemotherapy-induced activation of NF-кB increasing chemosensitivity to anticancer agents due to increased apoptosis. NF-кB is frequently aberrantly activated in primary human carcinomas and over-expressed in aggressive breast cancer lines1 supporting the rationale for combining B with P. We designed a phase I-II and PD trial to determine the recommended dose (RD) of the B&P combination, to screen for antitumor activity in patients with potentially taxane-sensitive tumors, to search for drug-induced changes and to identify potential surrogate markers of drug activity and toxicity in peripheral blood mononuclear cells (PBMC). Methods: Eligibility included ECOG performance status < 2, neurotoxicity < 2 and adequate organ functions. Treatment was given Q21 days: B on days 1,4, 8 and 11 and P on days 1 and 8. PBMC for gene expression profiling have been collected on day 1 and 4 before and after therapy. RECIST for response was applied. Results: Twenty-nine patients (20 female, median age 60 yrs) were accrued and 25 are evaluable (breast cancer: 13, ovarian cancer: 7, prostate cancer 1, other 4) ; 16 pts were treated in 4 escalation levels and the RD defined respectively at 1.3 mg/m2/dose & 100 mg/m2/dose for B&P. Neurotoxicity was the main toxicity (G1 36%, G2 20% and 1 case G3) requiring treatment discontinuation in 2 pts at cy 6 & 7. Other toxicities (all grades) were nausea and vomiting (68%), diarrhea (56%, G3 12%), alopecia (52%), asthenia (36%, G2 4%), and myalgia (32%, G2 8%). Antitumor activity consisted of 3 PR in pts with ovarian cancer lasting respectively 14, 8+ and 16 wks; 2 PRs in pts with breast cancer (12+ wks,14+ wks) and 1 PR in a pt with prostate cancer. Conclusions: Thus far the regimen has acceptable toxicity with evidence of antitumor activity. The trial will continue until accrual of four additional patients as planned. Footnotes 1 Adams J Current Opin Oncol 2002, 14:628–634. [Table: see text]

Immunoglobulin G fragment C receptor polymorphisms and response to trastuzumab-based treatment in patients with HER-2/neu-positive metastatic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13090-13090 ◽  
Author(s):  
A. Musolino ◽  
N. Naldi ◽  
B. Bortesi ◽  
M. Capelletti ◽  
D. Pezzuolo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Immunoglobulin G ◽  
Mononuclear Cells ◽  
Metastatic Breast ◽  
Cancer Cell Line ◽  
Breast Cancer Patients ◽  
Peripheral Blood Mononuclear ◽  
Immune Effector ◽  
Her 2

13090 Background: A potential mechanism of action of the humanized anti-HER-2/neu monoclonal antibody Trastuzumab involves antibody-dependent cellular cytotoxicity (ADCC) with the activation of immune effector cells via their immunoglobulin G fragment C receptors (FcγRs). Trastuzumab has been shown to engage both activation (FcγRIIIa; FcγRIIa) and inhibitory (FcγRIIb) antibody receptors on myeloid cells and several FcγR polymorphisms have been identified that may affect the antibody-dependent cytotoxicity of natural killer cells and macrophages. Methods: Forty consecutive HER-2/neu-positive (FISH+) metastatic breast cancer patients receiving a trastuzumab-based treatment (combined with paclitaxel for the majority) were examined for the FcγRIIIa 158 valine (V)/phenylalanine (F), FcγRIIa 131 histidine (H)/arginine (R), and FcγRIIb 232 isoleucine (I)/threonine (T) polymorphisms. A PCR-RFLP based assay using genomic DNA was performed for FcγRIIIa and FcγRIIa genotyping, while PCR-SSCP methods using complementary DNA were utilized for FcγRIIb. Patients’ peripheral blood mononuclear cells were drawn before treatment initiation and their trastuzumab-mediated killing function was measured by 51Cr release using a HER-2/neu-expressing human breast cancer cell line as a target. The results were then correlated with clinical outcome of these patients. Results: Median age was 60 years (range 26–83 years). Thirty-six (90%) patients received a trastuzumab-based treatment as first-line therapy. The overall clinical benefit rate (CR+PR+SD) was 65% (95% Confidence Interval: 62–71%), including 8 (20%) complete and 11 (27.5%) partial responses. Median survival was 22.3 mo with a median PFS of 7 mo. Trastuzumab-based treatment was well tolerated and no changes in cardiac function were observed. Conclusions: This study evaluates for the first time the potential role of FcγR polymorphisms in predicting response to trastuzumab-based treatment. Results according to this study purpose will be presented at the meeting. No significant financial relationships to disclose.

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