PD-L1 quantification across tumor types using the reverse phase protein microarray: implications for precision medicine

PD-L1 quantification across tumor types using the reverse phase protein microarray: implications for precision medicine post thumbnail image
Background: Anti-programmed cell dying protein 1 and programmed cell dying ligand 1 (PD-L1) brokers are broadly utilized in first-line and second-line therapy throughout completely different tumor sorts. Whereas immunohistochemistry-based assays are routinely used to evaluate PD-L1 expression, their medical utility stays controversial as a result of partial predictive worth and lack of standardized cut-offs throughout antibody clones. Utilizing a excessive throughput immunoassay, the reverse section protein microarray (RPPA), coupled with a fluorescence-based detection system, this research in contrast the efficiency of six anti-PD-L1 antibody clones on 666 tumor samples.
Strategies: PD-L1 expression was measured utilizing 5 antibody clones (22C3, 28-8, CAL10, E1L3N and SP142) and the therapeutic antibody atezolizumab on 222 lung, 71 ovarian, 52 prostate and 267 breast cancers, and 54 metastatic lesions. To seize clinically related variables, our cohort included frozen and formalin-fixed paraffin-embedded samples, surgical specimens and core needle biopsies. Pure tumor epithelia had been remoted utilizing laser seize microdissection from 602 samples.
Correlation coefficients had been calculated to evaluate concordance between antibody clones. For 2 impartial cohorts of sufferers with lung most cancers handled with nivolumab, RPPA-based PD-L1 measurements had been examined together with response to therapy.
Outcomes: Median-center PD-L1 dynamic ranged from 0.01 to 39.37 throughout antibody clones. Correlation coefficients between the six antibody clones had been heterogeneous (vary: -0.48 to 0.95) and beneath 0.50 in 61% of the comparisons. In nivolumab-treated sufferers, RPPA-based measurement recognized a subgroup of tumors, the place low PD-L1 expression equated to lack of response.
Conclusions: Steady RPPA-based measurements seize a broad dynamic vary of PD-L1 expression in human specimens and heterogeneous concordance ranges between antibody clones. This excessive throughput immunoassay can probably determine subgroups of tumors wherein low expression of PD-L1 equates to lack of response to therapy.

Profiling Autoantibody Responses to Devise Novel Diagnostic and Prognostic Markers Utilizing Excessive-Density Protein Microarrays

 

Protein microarrays are a various and high-throughput platform for screening biomolecular interactions, autoantigens, and protein expression profiles throughout tissues, and many others. Autoantibodies produced towards aberrant protein expression are sometimes noticed in malignancies which makes protein microarrays a robust platform to elucidate biomarkers of translational curiosity.

Early analysis of malignancies is a permanent medical downside that has a direct affect on illness prognosis. Right here, we offer an summary of a technique employed to display screen autoantibodies utilizing affected person sera in mind tumors. In case of mind malignancies, early analysis is notably difficult and infrequently requires extremely invasive mind biopsies as a confirmatory check. This chapter summarizes the assorted concerns for making use of a serum-based autoantibody biomarker discovery pipeline that would present a minimally invasive preliminary diagnostic display screen, potentiating classical diagnostic approaches.

Protein Microarray-Primarily based Proteomics for Illness Evaluation

 As we strategy the 20th anniversary of finishing the worldwide Human Genome Mission, the following (and arguably most important) frontier in biology consists of functionally understanding the proteins, that are encoded by the genome and play an important function in all of biology and medication. To perform this problem, completely different proteomics methods should be devised to look at the actions of gene merchandise (proteins) at scale.

Amongst them, protein microarrays have been used to perform all kinds of investigations similar to analyzing the binding of proteins and proteoforms to DNA, small molecules, and different proteins; characterizing humoral immune responses in well being and illness; evaluating allergenic proteins; and profiling protein patterns as candidate disease-specific biomarkers. In Protein Microarray for Illness Evaluation: Strategies and Protocols, knowledgeable researchers concerned within the area of protein microarrays present concise descriptions of the methodologies that they presently use to manufacture microarrays and the way they apply them to investigate protein interactions and responses of proteins to dissect human illness.

 

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Evaluation of Protein-Protein Interactions by Protein Microarrays

 

The evaluation of the proteome and the interactome can be helpful for a greater understanding of the pathophysiology of a number of issues, permitting the identification of potential particular markers for early analysis and prognosis, as properly as potential targets of intervention. Amongst completely different proteomic approaches, high-density protein microarrays have turn out to be an attention-grabbing software for the screening of protein-protein interactions and the interactome definition of disease-associated dysregulated proteins. This info may contribute to the identification of altered signaling pathways and protein features concerned within the pathogenesis of a illness.

Remarkably, protein microarrays have been already satisfactorily employed for the research of protein-protein interactions in most cancers, allergy, or neurodegenerative ailments. Right here, we describe the utilization of recombinant protein microarrays for the identification of protein-protein interactions to assist in the definition of disease-specific dysregulated interactomes.

Phage Microarrays for Screening of Humoral Immune Responses

 

Continual ailments are the main explanation for incapacity and accountable for about 63% of deaths worldwide. Among the many noninfectious persistent ailments with the very best incidence are most cancers and neurodegenerative ailments. Though they’ve been extensively studied within the final years, there may be nonetheless an pressing want to seek out and elucidate the molecular mechanisms underlying their formation and development to get an early analysis and discover new therapeutic targets of intervention.

Past different microarray-based proteomic strategies extra extensively used due to their industrial availability, similar to protein and antibody microarrays, phage microarrays are one other type of protein microarrays helpful for the identification and characterization of disease-specific humoral immune responses and to get additional insights into these devastating ailments. Right here, we describe the mixing and utilization of phage microarrays, which supply such a mixture of sensitivity and cost-effective multiplexing capabilities that makes them an reasonably priced technique for the characterization of humoral immune responses in a number of ailments.

Massive-scale investigation of single cell actions and response dynamics in a microarray chip with a microfluidics-fabricated microporous membrane

 

Microengineering expertise involving microfabrication, micropatterning and microfluidics allows promising advances in single cell manipulation and evaluation. Herein, we describe a parallel, large-scale, and temporal investigation of various single cell actions and response dynamics utilizing a facile-assembled microwell array chip with a microfluidics-molded microporous membrane. We demonstrated that the flexibility with respect to geometrical homogeneity and variety of microporous membrane fabrication, in addition to the soundness, repeatability, and reproducibility depend on the well-improved molding. Serial and sensible operations together with controllable single cell trapping, array-like tradition or chemical stimulation, and temporal monitoring will be easily accomplished in the chip.

We confirmed that the microwell array chip allowed an environment friendly building of a single cell array. Utilizing the cell array, on-chip detection of single cell behaviours beneath varied tradition and drug remedy circumstances to discover phenotypic heterogeneity was achieved in large and dynamic manners.

These achievements present a facile and dependable methodology for fabricating microporous membranes with exact management and for creating common microplatforms to carry out strong manipulation and versatile evaluation of single cells. This work additionally presents an perception into the event of straightforward to manufacture/use and market-oriented microsystems for single cell analysis, pharmaceutical growth, and high-throughput screening.

 

Frozen Tissue Section Panel - Mouse Normal Tissue, Multi-tissue II

T6334608 5 slides
EUR 504

Frozen Tissue Section Panel - Mouse Normal Tissue, Multi-tissue III

T6334423 5 slides
EUR 504

Skin cancer and normal tissue high density (69 cases/208 core) tissue microarray

SK208 each
EUR 546
Description: Skin cancer and normal tissue high density (69 cases/208 core) tissue microarray

Frozen Tissue Section Panel - Rat Normal Tissue, Multi-tissue I

T6434448 5 slides
EUR 504

Frozen Tissue Section Panel - Rat Normal Tissue, Multi-tissue III

T6434423 5 slides
EUR 504

Frozen Tissue Section Panel - Human Adult Normal Tissue, Multi-tissue I

T6234431 5 slides
EUR 507

Frozen Tissue Section Panel - Human Adult Normal Tissue, Multi-tissue II

T6234432 5 slides
EUR 507

Frozen Tissue Section Panel - Human Adult Normal Tissue, Multi-tissue III

T6234433 5 slides
EUR 507

Frozen Tissue Section Panel - Monkey (Rhesus) Normal Tissue, Multi-tissue I

T6534448 5 slides
EUR 504

Brain primary tumor high density (69 cases/208 cores) tissue microarray of astrocytoma

GL208 each
EUR 546
Description: Brain primary tumor high density (69 cases/208 cores) tissue microarray of astrocytoma, glioblastoma, glioblastoma multiforme (GBM) and normal tissue

Frozen Tissue Section Panel - Monkey (Rhesus) Normal Tissue, Multi-tissue III

T6534423 5 slides
EUR 504

Frozen Tissue Section Panel - Monkey (Cynomolgus) Normal Tissue, Multi-tissue I

T6534448-Cy 5 slides
EUR 504

Frozen Tissue Section Panel - Monkey (Cynomolgus) Normal Tissue, Multi-tissue III

T6534423-Cy 5 slides
EUR 504

Frozen Tissue Section Panel - Human Disease Tissue, Alzheimer's Disease, Multi-tissue I, 7 different tissues

T6236444Alz 5 slides
EUR 1135

Frozen Tissue Section Panel - Human Disease Tissue, Alzheimer's Disease, Multi-tissue II, 7 different tissues

T6236445Alz 5 slides
EUR 1135

Frozen Tissue Section Panel - Human Disease Tissue, Alzheimer's Disease, Multi-tissue III, 8 different tissues

T6236446Alz 5 slides
EUR 1135

Frozen Tissue Section Panel - Human Disease Tissue, Alzheimer's Disease, Multi-tissue IV, 7 different tissues

T6236564Alz 5 slides
EUR 1135

384 Well Storage Microarray Plates, V-Shaped Wells

GP712 50 Plates
EUR 602.4

384 Well Storage Microarray Plates, Cylindrical Wells

GP711 50 Plates
EUR 602.4

Frozen Tissue Section - Lupus: Pancreas

T1236188Lup 5 slides
EUR 515

FDA Standard Frozen Tissue Array - Mouse Normal

T6334701-1 2 slides
EUR 629

FDA Standard Frozen Tissue Array - Mouse Normal

T6334701-2 4 slides
EUR 1135

Frozen Tissue Section - Human Diabetic Diseased Tissue: Pancreas

T1236188Dia 5 slides
EUR 475

Frozen Tissue Section - Human Tumor: Pancreas

T1235188 5 slides
EUR 330

Rabbit MUSCLE TISSUE MT FROZEN 1kg

41325-2 1 kg
EUR 337.69

Frozen Tissue Section - Asthma: Lung

T1236152Ld-1 5 slides
EUR 475

Frozen Tissue Section - Lupus: Ovary

T1236183Lup 5 slides
EUR 682

Frozen Tissue Section - Lupus: Kidney

T1236142Lup 5 slides
EUR 587

Frozen Tissue Section - Lupus: Spleen

T1236246Lup 5 slides
EUR 515

Frozen Tissue Section - Lupus: Adrenal

T1236004Lup 5 slides
EUR 515

Frozen Tissue Section - Emphysema: Lung

T1236152Ld-3 5 slides
EUR 475

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