Lung most cancers is the primary explanation for cancer-related deaths on the earth. Sufferers handled with present chemotherapies for non-small-cell lung cancers (NSCLCs) have a survival fee of roughly 15% after 5 years. Novel approaches are wanted to deal with this illness. We present elevated NAD(P)H:quinone oxidoreductase-1 (NQO1) ranges in tumors from NSCLC sufferers. beta-Lapachone, an efficient chemotherapeutic and radiosensitizing agent, selectively killed NSCLC cells that expressed excessive ranges of NQO1. Isogenic H596 NSCLC cells that lacked or expressed NQO1 together with A549 NSCLC cells handled with or with out dicoumarol, had been used to elucidate the mechanism of motion and optimum therapeutic window of beta-lapachone.
Kinetically, beta-lapachone-induced cell demise was characterised by the next: (i) dramatic reactive oxygen species (ROS) formation, eliciting in depth DNA injury; (ii) hyperactivation of poly(ADP-ribose)polymerase-1 (PARP-1); (iii) depletion of NAD+/ATP ranges; and (iv) proteolytic cleavage of p53/PARP-1, indicating mu-calpain activation and apoptosis. Beta-lapachone-induced PARP-1 hyperactivation, nucleotide depletion, and apoptosis had been blocked by 3-aminobenzamide, a PARP-1 inhibitor, and 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid acetoxymethyl ester (BAPTA-AM), a Ca2+ chelator. NQO1- cells (H596, IMR-90) or dicoumarol-exposed NQO1+ A549 cells had been resistant (LD50, >40 microM) to ROS formation and all cytotoxic results of beta-lapachone.
Our knowledge point out that probably the most efficacious technique utilizing beta-lapachone in chemotherapy was to ship the drug in brief pulses, drastically lowering cytotoxicity to NQO1- “regular” cells. beta-Lapachone killed cells in a tumorselective method and is indicated to be used in opposition to NQO1+ NSCLC cancers. Poly(ADP-ribose) polymerase (PARP-1) binds to DNA breaks to facilitate DNA restore. Nevertheless, the function of PARP-1 in DNA restore seems to not be vital since PARP-1 knockout mice are viable, fertile and don’t develop early onset tumors. Cells remoted from these mice present an elevated stage of homologous recombination.
Though PARP-1 seems to not be required for homologous recombination itself, it regulates the method via its involvement within the restore of DNA single-strand breaks (SSBs). SSBs persisting into the S part of the cell cycle collapse replication forks, triggering homologous recombination for replication restart. We focus on the current discoveries on the usage of PARP-1 inhibitors as a focused most cancers remedy for recombination poor cancers, equivalent to BRCA2 tumors. There may be an intricate hyperlink between homologous recombination and PARP-1 and a doable function for PARP-1 in DNA double-strand break restore.
PARP inhibitors within the administration of breast most cancers: present knowledge and future prospects.
Poly(ADP-ribose) polymerases (PARP) are enzymes concerned in DNA-damage restore. Inhibition of PARPs is a promising technique for concentrating on cancers with faulty DNA-damage restore, together with BRCA1 and BRCA2 mutation-associated breast and ovarian cancers. A number of PARP inhibitors are at the moment in trials within the adjuvant, neoadjuvant, and metastatic settings for the remedy of ovarian, BRCA-mutated breast, and different cancers. NSCLC cells had been killed in an NQO1-dependent method by beta-lapachone (LD50, roughly four microM) with a minimal 2-h publicity.
We herein evaluation the event of PARP inhibitors and the idea for the joy surrounding these brokers, their use as single brokers and in combos, in addition to their toxicities, mechanisms of acquired resistance, and companion diagnostics. Small cell lung carcinoma (SCLC) is an aggressive malignancy affecting almost 30,000 individuals yearly in the USA. We now have beforehand recognized elevated PARP1 ranges in SCLC and demonstrated in vitro sensitivity to the PARP inhibitors AZD 2281 and AG014699. Right here, we consider exercise of a novel, potent PARP inhibitor,
BMN 673, and determine markers of response as a foundation for growing predictive markers for medical utility. Inhibition of SCLC proliferation by BMN 673 was assayed in vitro and results on tumor progress had been measured in SCLC xenograft fashions. Protein expression and pathway activation was assessed by reverse part protein array and western blot evaluation. PARP inhibition was confirmed utilizing a PAR ELISA. We show placing, single agent exercise of BMN 673 in SCLC cell strains and xenografts, with single agent BMN 673 exhibiting in vivo exercise much like cisplatin.
Sensitivity to BMN 673 was related to elevated baseline expression ranges of a number of DNA restore proteins, whereas larger drug resistance was noticed in SCLC fashions with baseline activation of the PI3K/mTOR pathway. Moreover, we developed and confirmed these knowledge with a novel “DNA restore rating” consisting of a gaggle of 17 DNA restore proteins. Elevated expression of a number of DNA restore proteins, in addition to a corresponding “DNA restore protein rating,” predict response to BMN 673 in in vitro SCLC fashions. These observations complement current work by which PI3K inhibition sensitizes breast most cancers fashions to PARP inhibition, suggesting cooperation between DNA restore and PI3K pathways.
PARP Inhibitor Upregulates PD-L1 Expression and Enhances Most cancers-Related Immunosuppression.
To discover whether or not a cross-talk exists between PARP inhibition and PD-L1/PD-1 immune checkpoint axis, and decide whether or not blockade of PD-L1/PD-1 potentiates PARP inhibitor (PARPi) in tumor suppression.Experimental Design: Breast most cancers cell strains, xenograft tumors, and syngeneic tumors handled with PARPi had been assessed for PD-L1 expression by immunoblotting, IHC, and FACS analyses. The phospho-kinase antibody array display screen was used to discover the underlying mechanism of PARPi-induced PD-L1 upregulation.
 CancerSeq™ Paraffin Tissue Tumor Block: Skin Melanoma |
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T2235218A-SB |
Biochain |
1 Block |
EUR 4215 |
 CancerSeq™ Paraffin Tissue Tumor Slides: Lung |
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T2235152-ST |
Biochain |
5 Slides |
EUR 601 |
 CancerSeq™ Paraffin Tissue Tumor Slides: Breast |
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T2235086-ST |
Biochain |
5 Slides |
EUR 601 |
 CancerSeq™ Paraffin Tissue Tumor Slides: Skin Melanoma |
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T2235218A-ST |
Biochain |
5 Slides |
EUR 601 |
 CancerSeq™ Plus Paraffin Tissue Tumor Section: Lung |
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T2235152-SC |
Biochain |
5 curls |
EUR 818 |
 CancerSeq™ Plus Paraffin Tissue Tumor Sections: Breast |
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T2235086-SC |
Biochain |
5 curls |
EUR 818 |
 CancerSeq™ Plus Paraffin Tissue Tumor Sections: Stomach |
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T2235248-SC |
Biochain |
5 curls |
EUR 818 |
 CancerSeq™ Plus Paraffin Tissue Tumor Sections: Thyroid |
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T2235265-SC |
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5 curls |
EUR 818 |
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T2235090 |
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5 slides |
EUR 262 |
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T2235090-1 |
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5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Colon Tumor: Adenocarcinoma, MSH |
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T2235090MSH |
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5 slides |
EUR 771 |
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T2235090MSS |
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5 slides |
EUR 550 |
) Paraffin Tissue Section - Human Colon Tumor: Adenocarcinoma (Ulcer) |
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T2235090-3 |
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5 slides |
EUR 262 |
) Paraffin Tissue Section - Human Colon Tumor: Adenocarcinoma (Mucoid) |
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T2235090-2 |
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5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Colon Tumor: Non-hodgkin's lymphoma |
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T2235090-9 |
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5 slides |
EUR 262 |
 Paraffin Tissue Section – Human Colon Tumor, EGFR/Kras Characterized |
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T2235090EK |
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5 slides |
EUR 550 |
 Colon Cancer Tissue Slides, Human Paraffin Sections, 5 slides/pk |
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TS-H5106 |
IHC World |
- |
EUR 145 |
 Section (5 slides/pack)) Paired Cancer and Normal Colon Paraffin Tissue (FFPE) Section (5 slides/pack) |
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NCT061 |
TissueArray |
5 slides |
EUR 300 |
 Cerebellar paraffin Tissue block |
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87 |
BioCoreUSA |
1 unit |
EUR 425 |
 Paraffin Tissue Section - Human Colon Tumor: Diffuse Type Non-Hodgkin's Lymphoma |
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T2235090-8 |
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5 slides |
EUR 262 |
: Colon) Matched Pair - Paraffin Tissue Section - Human Primary Tumor and Normal (PP): Colon |
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T8235090-PP |
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5 slides x2 |
EUR 383 |
 Colon Cancer Tissue block |
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40 |
BioCoreUSA |
1 unit |
Ask for price |
: Colon) Matched Pair - Paraffin Tissue Section - Human Primary and Matched Metastatic Tumor (PM): Colon |
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T8235090-PM |
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5 slides x2 |
EUR 639 |
 Paraffin Tissue Section - Human Diabetic Diseased Tissue: Colon |
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T2236090Dia |
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5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Adult Normal: Colon |
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T2234090 |
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5 slides |
EUR 204 |
: Colon, 10x Visium-Characterized) Matched Pair - Paraffin Tissue Section - Human Primary Tumor and Normal (PP): Colon, 10x Visium-Characterized |
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T8235090-PP-SV |
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1 slide x2 |
EUR 1212 |
 Paraffin Tissue Section - Human Bone Tumor |
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T2235023 |
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5 slides |
EUR 262 |
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T2235152 |
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5 slides |
EUR 262 |
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T2235218 |
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EUR 262 |
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T2235035 |
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EUR 262 |
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T2235149 |
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5 slides |
EUR 262 |
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T2235142-7 |
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5 slides |
EUR 262 |
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EUR 262 |
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T2235142 |
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EUR 262 |
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T2235260 |
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5 slides |
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EUR 262 |
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EUR 262 |
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EUR 262 |
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T2235201 |
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5 slides |
EUR 262 |
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T2235001 |
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5 slides |
EUR 262 |
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T2235189 |
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5 slides |
EUR 262 |
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T2235118 |
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5 slides |
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5 slides |
EUR 262 |
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5 slides |
EUR 262 |
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EUR 262 |
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T2235260-3 |
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T2235035-7 |
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T2235218-2 |
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EUR 262 |
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EUR 262 |
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EUR 262 |
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5 slides |
EUR 262 |
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T2255830 |
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5 slides |
EUR 262 |
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T2235006-1 |
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T2235188-1 |
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5 slides |
EUR 262 |
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T2235201-1 |
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5 slides |
EUR 262 |
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T2235023-8 |
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5 slides |
EUR 262 |
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T2235023-6 |
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5 slides |
EUR 262 |
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T2235035-5 |
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5 slides |
EUR 262 |
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T2235001-7 |
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5 slides |
EUR 262 |
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T2235218-3 |
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5 slides |
EUR 262 |
) Paraffin Tissue Section Panel - Human Tumor Same Tumor Type, Different Donors (5 tissues) |
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T8235086 |
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5 slides |
EUR 416 |
) Paraffin Tissue Section Panel - Human Tumor, Same Tumor Type, Different Donors (5 tissues) |
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T8235090 |
Biochain |
5 slides |
EUR 446 |
Paraffin Tissue Section Panel - Human Tumor, Same Tumor Type, Different Donors (5 tissues) |
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T8235106 |
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5 slides |
EUR 446 |
Paraffin Tissue Section Panel - Human Tumor, Same Tumor Type, Different Donors (5 tissues) |
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T8235142 |
Biochain |
5 slides |
EUR 446 |
Paraffin Tissue Section Panel - Human Tumor, Same Tumor Type, Different Donors (5 tissues) |
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T8235149 |
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5 slides |
EUR 446 |
Paraffin Tissue Section Panel - Human Tumor, Same Tumor Type, Different Donors (5 tissues) |
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T8235152 |
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5 slides |
EUR 446 |
Paraffin Tissue Section Panel - Human Tumor, Same Tumor Type, Different Donors (5 tissues) |
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T8235183 |
Biochain |
5 slides |
EUR 446 |
Paraffin Tissue Section Panel - Human Tumor, Same Tumor Type, Different Donors (5 tissues) |
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T8235206 |
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5 slides |
EUR 446 |
Paraffin Tissue Section Panel - Human Tumor, Same Tumor Type, Different Donors (5 tissues) |
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T8235248 |
Biochain |
5 slides |
EUR 446 |
Paraffin Tissue Section Panel - Human Tumor, Same Tumor Type, Different Donors (5 tissues) |
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T8235274 |
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5 slides |
EUR 446 |
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T2235023-7 |
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5 slides |
EUR 262 |
) Paraffin Tissue Section - Human Brain Tumor: Meningioma (Fibrous) |
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T2235035-10 |
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5 slides |
EUR 262 |
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T2235086-3 |
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5 slides |
EUR 262 |
) Paraffin Tissue Section - Human Brain Tumor: Meningioma (Necrotic) |
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T2235035-11 |
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5 slides |
EUR 262 |
 Paraffin Tissue Section – Human Breast Tumor, BRCA Characterized |
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T2235086BRCA |
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5 slides |
EUR 550 |
 Paraffin Tissue Section - Human Rectum Tumor: Adenocarcinoma, MSS |
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T2235206MSS |
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5 slides |
EUR 550 |
 Paraffin Tissue Section - Human Uterus Tumor: Adenocarcinoma, MSS |
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T2235274MSS |
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5 slides |
EUR 550 |
 Paraffin Tissue Section - Human Stomach Tumor: Adenocarcinoma, MSS |
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T2235248MSS |
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5 slides |
EUR 550 |
 Paraffin Tissue Section - Human Parotid Tumor: Pleomorphic Adenoma |
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T2235190-5 |
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5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Brain Tumor: Pilocytic Astrocytoma |
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T2235035-13 |
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5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Breast Tumor: Mucous Adenocarcinoma |
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T2235086-6 |
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5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Lung Tumor: Large Cell Carcinoma |
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T2235152-6 |
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5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Lung Tumor: Small Cell Carcinoma |
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T2235152-9 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Tonsil Tumor: Lymphoma of Tonsil |
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T2235268-1 |
Biochain |
5 slides |
EUR 262 |
 Colon Tissue Slides, Normal Human Paraffin Sections, 5 slides/pack |
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TS-H5007 |
IHC World |
- |
EUR 145 |
 Paraffin Tissue Section - Human Brain Tumor: Astrocytoma Grade I |
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T2235035-1 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Brain Tumor: Astrocytoma Grade II |
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T2235035-2 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Uterus Cervix Tumor, HPV positive |
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T2235275HPV |
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5 slides |
EUR 550 |
Paraffin Tissue Section - Human Uterus Cervix Tumor, HPV positive |
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T2235275HPV+ |
Biochain |
5 slides |
EUR 646.8 |
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Description: Our tissue products are produced by strictly following the IRB ethical standards and procedures and from highest quality tissues. Immediately after collection the tissues are placed in liquid nitrogen and examined by certified pathologists. The thickness of each individual section is ~5um. They are Hematoxylin and Eosin stained and quality tested by immunostaining with anti-beta-actin antibodies. Our tissue products are suitable for various studies on cellular level (RNA localization, Protein expression, etc.) on both normal and pathological cases. It is also an excellent control and educational tool. |
 Paraffin Tissue Section - Human Uterus Cervix Tumor, HPV negative |
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T2235275HPV- |
Biochain |
5 slides |
EUR 550 |
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Description: Our tissue products are produced by strictly following the IRB ethical standards and procedures and from highest quality tissues. Immediately after collection the tissues are placed in liquid nitrogen and examined by certified pathologists. The thickness of each individual section is ~5um. They are Hematoxylin and Eosin stained and quality tested by immunostaining with anti-beta-actin antibodies. Our tissue products are suitable for various studies on cellular level (RNA localization, Protein expression, etc.) on both normal and pathological cases. It is also an excellent control and educational tool. |
Paraffin Tissue Section - Human Uterus Cervix Tumor, HPV negative |
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T2235275HPV-negative |
Biochain |
5 slides |
EUR 524 |
Paraffin Tissue Section - Human Uterus Cervix Tumor, HPV positive |
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T2235275HPV-positive |
Biochain |
5 slides |
EUR 524 |
 Paraffin Tissue Section Panel - Human Tumor, Different Tumor Type, Different Donors, Panel I, 5 tissue spots |
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T8235417 |
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5 slides |
EUR 399 |
 Paraffin Tissue Section Panel - Human Tumor, Different Tumor Type, Different Donors, Panel II, 5 tissue spots |
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T8235418 |
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5 slides |
EUR 399 |
 Paraffin Tissue Section Panel - Human Tumor, Different Tumor Type, Different Donors, Panel III, 5 tissue spots |
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T8235419 |
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5 slides |
EUR 399 |
 Paraffin Tissue Section Panel - Human Tumor, Different Tumor Type, Different Donors, Panel IV, 5 tissue spots |
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T8235420 |
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5 slides |
EUR 399 |
 Paraffin Tissue Section Panel - Human Tumor, Different Tumor Type, Different Donors, Panel V, 5 tissue spots |
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T8235421 |
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5 slides |
EUR 399 |
 Paraffin Tissue Section Panel - Human Tumor, Different Tumor Type, Different Donors, Panel VI, 5 tissue spots |
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T8235422 |
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5 slides |
EUR 399 |
 Paraffin Tissue Section Panel - Human Tumor, Different Tumor Type, Different Donors, Panel I, 8 tissue spots |
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T8235437 |
Biochain |
5 slides |
EUR 622 |
 Paraffin Tissue Section Panel - Human Tumor, Different Tumor Type, Different Donors, Panel II, 8 tissue spots |
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T8235438 |
Biochain |
5 slides |
EUR 622 |
 Paraffin Tissue Section Panel - Human Tumor, Different Tumor Type, Different Donors, Panel III, 8 tissue spots |
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T8235439 |
Biochain |
5 slides |
EUR 622 |
 Paraffin Tissue Section Panel - Human Tumor, Different Tumor Type, Different Donors, Panel IV, 8 tissue spots |
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T8235440 |
Biochain |
5 slides |
EUR 622 |
 Paraffin Tissue Section Panel - Human Tumor, Different Tumor Type, Different Donors, Panel V, 8 tissue spots |
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T8235441 |
Biochain |
5 slides |
EUR 622 |
 Paraffin Tissue Section Panel - Human Tumor, Different Tumor Type, Different Donors, Panel VI, 8 tissue spots |
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T8235442 |
Biochain |
5 slides |
EUR 622 |
 Paraffin Tissue Section Panel - Human Tumor, Different Tumor Type, Different Donors, Panel VII, 8 tissue spots |
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T8235443 |
Biochain |
5 slides |
EUR 622 |
 Paraffin Tissue Section - Human Liver Tumor: Hepatocellular Carcinoma |
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T2235149-4 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Pelvic Tumor: Malignant Mesothelioma |
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T2235193-2 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Brain Tumor: Astrocytoma Grade III |
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T2235035-3 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Kidney Tumor: Clear cell carcinoma |
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T2235142-2 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Kidney Tumor: Renal Cell Carcinoma |
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T2235142-5 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Lung Tumor: Squamous Cell Carcinoma |
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T2235152-10 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section – Human Lung Tumor, EGFR/Kras Characterized |
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T2235152EK |
Biochain |
5 slides |
EUR 550 |
 Paraffin Tissue Section - Human Skin Tumor: Squamous Cell Carcinoma |
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T2235218-7 |
Biochain |
5 slides |
EUR 262 |
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T2235001-1 |
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5 slides |
EUR 262 |
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T2235001-6 |
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5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Adrenal Tumor: Adrenal Pheochromocytoma |
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T2235004-2 |
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5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Bone Tumor: Chondroblastic Osteosarcoma |
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T2235023-1 |
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5 slides |
EUR 262 |
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T2235265-7 |
Biochain |
5 slides |
EUR 262 |
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T2235086-4 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Tumor: Lung, 10x Visium-Characterized |
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T2235152-SV |
Biochain |
1 slide |
EUR 550 |
 Paraffin Tissue Section - Human Prostate Tumor: Neoplasia of Prostate |
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T2235201-2 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Stomach Tumor: Squamous Cell Carcinoma |
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T2235248-10 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Brain Tumor: Malignant Oligodendroglioma |
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T2235035-8 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Liver Tumor: Cholangiocellular Carcinoma |
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T2235149-2 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Uterus Tumor: Endometrium Adenocarcinoma |
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T2235274-3 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Breast Tumor: Invasive ductal carcinoma |
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T2235086-2 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Tumor: Breast, 10x Visium-Characterized |
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T2235086-SV |
Biochain |
1 slide |
EUR 550 |
) Paraffin Tissue Section - Human Skin Tumor: Basal Cell Carcinoma (Face) |
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T2235218-1 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Bone Tumor: Chondrosarcoma, Grade I - II |
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T2235023-4 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Breast Tumor: Medullarycarcinoma of Breast |
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T2235086-5 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Head & Neck Tumor: Squamouse Cell Carcinoma |
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T2235121 |
Biochain |
5 slides |
EUR 256 |
 Paraffin Tissue Section - Human Lymph Nodes Tumor: Non-Hodgkin's Lymphoma |
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T2235161-1 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Thyroid Tumor: Nodular Goiter of Thyroid |
|
T2235265-5 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Stomach Tumor: Signet-Ring Cell Carcinoma |
|
T2235248-9 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Bone Tumor: Chondrosarcoma, Well Differentiated |
|
T2235023-5 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Liver Tumor: Nodulous Hepatocellular Carcinoma |
|
T2235149-5 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Small Intestine Tumor: Duodenum Adenocarcinoma |
|
T2235226-1 |
Biochain |
5 slides |
EUR 262 |
 Paraffin Tissue Section - Human Kidney Tumor: Papillary Renal Cell Carcinoma |
|
T2235142-4 |
Biochain |
5 slides |
EUR 262 |
 Section (5 slides/pack)) Paired Cancer and Normal eye Paraffin Tissue (FFPE) Section (5 slides/pack) |
|
NCT251 |
TissueArray |
5 slides |
EUR 300 |
 Section (5 slides/pack)) Paired Cancer and Normal Lung Paraffin Tissue (FFPE) Section (5 slides/pack) |
|
NCT076 |
TissueArray |
5 slides |
EUR 300 |
The therapeutic efficacy of PARPi alone, PD-L1 blockade alone, or their mixture was examined in a syngeneic tumor mannequin. The tumor-infiltrating lymphocytes and tumor cells remoted from syngeneic tumors had been analyzed by CyTOF and FACS to judge the exercise of antitumor immunity within the tumor microenvironment. PARPi upregulated PD-L1 expression in breast most cancers cell strains and animal fashions. Mechanistically, PARPi inactivated GSK3β, which in flip enhanced PARPi-mediated PD-L1 upregulation. PARPi attenuated anticancer immunity through upregulation of PD-L1, and blockade of PD-L1 resensitized PARPi-treated most cancers cells to T-cell killing.
