Simulating the Selection of Resistant Cells with Bystander Killing and Antibody Coadministration in Heterogeneous HER2 Positive Tumors

2021 ◽  
pp. DMD-AR-2021-000503
Author(s):  
Bruna Menezes ◽  
Jennifer J. Linderman ◽  
Greg M. Thurber
Keyword(s):  
Her2 Positive ◽  
Bystander Killing ◽  
Selection Of ◽  
Resistant Cells

scholarly journals A microfluidic device enabling drug resistance analysis of leukemia cells via coupled dielectrophoretic detection and impedimetric counting

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yağmur Demircan Yalçın ◽  
Taylan Berkin Töral ◽  
Sertan Sukas ◽  
Ender Yıldırım ◽  
Özge Zorlu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
K562 Cells ◽  
Leukemia Cells ◽  
Drug Resistant ◽  
Wild Type ◽  
Gene Expressions ◽  
Before And After ◽  
The Difference ◽  
Selection Of ◽  
Resistant Cells

AbstractWe report the development of a lab-on-a-chip system, that facilitates coupled dielectrophoretic detection (DEP-D) and impedimetric counting (IM-C), for investigating drug resistance in K562 and CCRF-CEM leukemia cells without (immuno) labeling. Two IM-C units were placed upstream and downstream of the DEP-D unit for enumeration, respectively, before and after the cells were treated in DEP-D unit, where the difference in cell count gave the total number of trapped cells based on their DEP characteristics. Conductivity of the running buffer was matched the conductivity of cytoplasm of wild type K562 and CCRF-CEM cells. Results showed that DEP responses of drug resistant and wild type K562 cells were statistically discriminative (at p = 0.05 level) at 200 mS/m buffer conductivity and at 8.6 MHz working frequency of DEP-D unit. For CCRF-CEM cells, conductivity and frequency values were 160 mS/m and 6.2 MHz, respectively. Our approach enabled discrimination of resistant cells in a group by setting up a threshold provided by the conductivity of running buffer. Subsequent selection of drug resistant cells can be applied to investigate variations in gene expressions and occurrence of mutations related to drug resistance.

scholarly journals Rotavirus Persistence in Cell Cultures: Selection of Resistant Cells in the Presence of Foetal Calf Serum

1983 ◽  
Vol 64 (5) ◽  
pp. 1101-1110 ◽  
Author(s):  
A. Chiarini ◽  
S. Arista ◽  
A. Giammanco ◽  
A. Sinatra
Keyword(s):  
Cell Cultures ◽  
Calf Serum ◽  
Foetal Calf Serum ◽  
Selection Of ◽  
Resistant Cells

scholarly journals Hypoxia Selection of Death-resistant Cells

2003 ◽  
Vol 279 (10) ◽  
pp. 9215-9221 ◽  
Author(s):  
Zheng Dong ◽  
Jinzhao Wang
Keyword(s):  
Selection Of ◽  
Resistant Cells

scholarly journals Positive Selection of Apoptosis-resistant Cells Correlates with Activation of Dominant-Negative STAT5

1998 ◽  
Vol 273 (33) ◽  
pp. 20779-20784 ◽  
Author(s):  
Chiara Bovolenta ◽  
Lucia Testolin ◽  
Luisa Benussi ◽  
Patricia M.-J. Lievens ◽  
Elio Liboi
Keyword(s):  
Positive Selection ◽  
Dominant Negative ◽  
Selection Of ◽  
Resistant Cells

Selection of Optimal Adjuvant Chemotherapy Regimens for Human Epidermal Growth Factor Receptor 2 (HER2) –Negative and Adjuvant Targeted Therapy for HER2-Positive Breast Cancers: An American Society of Clinical Oncology Guideline Adaptation of the Cancer Care Ontario Clinical Practice Guideline

2016 ◽  
Vol 34 (20) ◽  
pp. 2416-2427 ◽  
Author(s):  
Neelima Denduluri ◽  
Mark R. Somerfield ◽  
Andrea Eisen ◽  
Jamie N. Holloway ◽  
Arti Hurria ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Clinical Practice ◽  
Targeted Therapy ◽  
Adjuvant Chemotherapy ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Epidermal Growth ◽  
American Society ◽  
Selection Of

Purpose A Cancer Care Ontario (CCO) guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer including adjuvant targeted therapy for human epidermal growth factor receptor 2 (HER2)–positive breast cancers was identified for adaptation. Methods The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for adapting clinical practice guidelines developed by other organizations. The CCO guideline was reviewed for developmental rigor and content applicability. Results On the basis of the content review of the CCO guideline, the ASCO Panel agreed that, in general, the recommendations were clear and thorough and were based on the most relevant scientific evidence, and they presented options that will be acceptable to patients. However, for some topics addressed in the CCO guideline, the ASCO Panel formulated a set of adapted recommendations on the basis of local context and practice beliefs of the Panel members. Recommendations Decisions regarding adjuvant chemotherapy regimens should take into account baseline recurrence risk, toxicities, likelihood of benefit, and host factors such as comorbidities. In high-risk HER2-negative populations with excellent performance status, anthracycline- and taxane-containing regimens are the standard of care. Docetaxel and cyclophosphamide for four cycles is an acceptable non-anthracycline regimen. In high-risk HER2-positive disease, sequential anthracycline and taxanes administered concurrently with trastuzumab or docetaxel, carboplatin, and trastuzumab for six cycles are recommended. An alternative regimen in a lower-risk, node-negative, HER2-positive population is paclitaxel and trastuzumab once per week for 12 cycles. Trastuzumab should be given for 1 year. Platinum salts should not be routinely administered in the adjuvant triple-negative population until survival efficacy data become available.

scholarly journals A Companion Diagnostic With Significant Clinical Impact in Treatment of Breast and Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jan Trøst Jørgensen ◽  
Henrik Winther ◽  
Jon Askaa ◽  
Lena Andresen ◽  
Dana Olsen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Predictive Biomarker ◽  
Clinical Impact ◽  
Phase Iii ◽  
Cancer Drug ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Metastatic Setting ◽  
Companion Diagnostic ◽  
Selection Of

The development of trastuzumab (Herceptin®) was one of the most significant cancer drug development projects of the 20th century. Not only was it a scientific and medical achievement but it also paved the way for the drug-diagnostic codevelopment model, where a predictive biomarker assay is developed in parallel to the drug. One of the challenges in the development of trastuzumab was to select the right patient population likely to respond and here, it was critical to have access to an accurate, robust and reliable assay for detection of HER2 overexpression in tumors. In the clinical development of trastuzumab, a clinical trial assay (CTA), developed by Genentech, was used for selection of HER2 positive patients. However, during the phase III trial with trastuzumab, a new optimized IHC assay, HercepTest™ was designed and developed by Dako. In the final stage of its development, a comparative study with the CTA was conducted in order to show concordance between the two assays. In September 1998, the Food and Drug Administration (FDA) simultaneously granted approval to trastuzumab and HercepTest™. The assay has been used for patient selection in a number of significant breast cancer clinical trials such as the HERA, CLEOPATRA, EMILIA and more. In these trials, HercepTest™ demonstrated its clinical utility in the neoadjuvant, adjuvant, and metastatic setting as well as in relation to different types of HER2 targeted therapies. Likewise, the assay was used for selection of HER2 positive gastric cancer patients in the important ToGA trail. HercepTest™ was the first companion diagnostic ever approved by the FDA, and more than 20 years of use has documented its clinical impact.

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