ACD can configure probes for the various manual and automated assays for INS for RNAscope Assay, or for Basescope Assay compatible for your species of interest.
JCI insight
2020 Feb 27
Tang N, Cheng C, Zhang X, Qiao M, Li N, Mu W, Wei XF, Han W, Wang H
PMID: 31999649 | DOI: 10.1172/jci.insight.133977
Free full text
Cancer Res.
2016 Aug 19
Sommer A, Kopitz C, Schatz CA, Nising CF, Mahlert C, Lerchen HG, Stelte-Ludwig B, Hammer S, Greven S, Schumacher J, Braun M, Zierz R, Wittemer-Rump S, Harrenga A, Dittmer F, Reetz F, Apeler H, Jautelat R, Huynh H, Ziegelbauer K, Kreft B.
PMID: 27543601 | DOI: 10.1158/0008-5472.CAN-16-0180
The fibroblast growth factor receptor FGFR2 is overexpressed in a variety of solid tumors, including breast, gastric and ovarian tumors, where it offers a potential therapeutic target. In this study, we present evidence of the preclinical efficacy of BAY 1187982, a novel antibody-drug conjugate (ADC). It consists of a fully human FGFR2 monoclonal antibody (mAb BAY 1179470), which is specific for the FGFR2 isoforms FGFR2-IIIb and FGFR2-IIIc, conjugated through a non-cleavable linker to a novel derivative of the microtubule-disrupting cytotoxic drug auristatin (FGFR2-ADC). In FGFR2-expressing cancer cell lines, this FGFR2-ADC exhibited potency in the low nM to sub-nM range and was more than 100-fold selective against FGFR2-negative cell lines. High expression levels of FGFR2 in cells correlated with efficient internalization, efficacy and cytotoxic effects in vitro. Pharmacokinetic analyses in mice bearing FGFR2-positive NCI-H716 tumors indicated that the toxophore metabolite of FGFR2-ADC was enriched more than 30-fold in tumors compared to healthy tissues. Efficacy studies demonstrated that FGFR2-ADC treatment leads to a significant tumor growth inhibition or tumor regression of cell line-based or patient-derived xenograft models of human gastric or breast cancer. Further, FGFR2 amplification or mRNA overexpression predicted high efficacy in both of these types of in vivo model systems. Taken together, our results strongly support the clinical evaluation of BAY 1187982 in cancer patients, and a Phase I study (NCT02368951) has been initiated.
Pathobiology.
2015 Oct 31
Han N, Kim MA, Lee HS, Kim WH.
PMID: 26516773 | DOI: -
Cancer immunology research
2022 Oct 04
Reschke, R;Shapiro, JW;Yu, J;Rouhani, SJ;Olson, DJ;Zha, Y;Gajewski, TF;
PMID: 35977003 | DOI: 10.1158/2326-6066.CIR-22-0362
Eur Urol Focus.
2017 Aug 27
Necchi A, Raggi D, Volpi CC, Giannatempo P, Colecchia M, Gloghini A.
PMID: 28855072 | DOI: 10.1016/j.euf.2017.08.002
Frontiers in endocrinology
2021 Aug 12
Adam, P;Kircher, S;Sbiera, I;Koehler, VF;Berg, E;Knösel, T;Sandner, B;Fenske, WK;Bläker, H;Smaxwil, C;Zielke, A;Sipos, B;Allelein, S;Schott, M;Dierks, C;Spitzweg, C;Fassnacht, M;Kroiss, M;
PMID: 34475850 | DOI: 10.3389/fendo.2021.712107
OncoImmunology
2018 Nov 05
Strasser K, Birnleitner H, Beer A, Pils D, Gerner MC, Schmetterer KG, Bachleitner-Hofmann T, Stift A, Bergmann M, Oehler R.
PMID: - | DOI: 10.1080/2162402X.2018.1537693
T cells in colorectal cancer (CRC) are associated with improved survival. However, checkpoint immunotherapies antagonizing the suppression of these cells are ineffective in the great majority of patients. To better understand the immune cell regulation in CRC, we compared tumor-associated T lymphocytes and macrophages to the immune cell infiltrate of normal mucosa. Human colorectal tumor specimen and tumor-distant normal mucosa tissues of the same patients were collected. Phenotypes and functionality of tissue-derived T cells and macrophages were characterized using immunohistochemistry, RNA in situ hybridization, and multiparameter flow cytometry. CRC contained significantly higher numbers of potentially immunosuppressive CD39 and Helios-expressing regulatory T cells in comparison to normal mucosa. Surprisingly, we found a concomitant increase of pro-inflammatory IFNγ -producing T cells. PD-L1+ stromal cells were decreased in the tumor tissue. Macrophages in the tumor compared to tumor-distant normal tissue appear to have an altered phenotype, identified by HLA-DR, CD14, CX3CR1, and CD64, and tolerogenic CD206+macrophages are quantitatively reduced. The prognostic effect of these observed differences between distant mucosa and tumor tissue on the overall survival was examined using gene expression data of 298 CRC patients. The combined gene expression of increased FOXP3, IFNγ, CD14, and decreased CD206 correlated with a poor prognosis in CRC patients. These data reveal that the CRC microenvironment promotes the coexistence of seemingly antagonistic suppressive and pro-inflammatory immune responses and might provide an explanation why a blockade of the PD1/PD-L1 axis is ineffective in CRC. This should be taken into account when designing novel treatment strategies.
Gastric Cancer
2017 Aug 29
Kuboki Y, Schatz CA, Koechert K, Schubert S, Feng J, Wittemer-Rump S, Ziegelbauer K, Krahn T, Kawano Nagatsuma A, Ochiai A.
PMID: - | DOI: 10.1007/s10120-017-0758-x
Abstract
Background
Fibroblast growth factor receptor (FGFR2) has been proposed as a target in gastric cancer. However, appropriate methods to select patients for anti-FGFR2 therapies have not yet been established.
Methods
We used in situ techniques to investigate FGFR2 mRNA expression and gene amplification in a large cohort of 1036 Japanese gastric cancer patients. FGFR2 mRNA expression was determined by RNAscope. FGFR2 gene amplification was determined by dual-color in situ hybridization (DISH).
Results
We successfully analyzed 578 and 718 samples by DISH and RNAscope, respectively; 2% (12/578) showed strong FGFR2 gene amplification (FGFR2:CEN10 >10); moderate FGFR2gene amplification (FGFR2:CEN10 <10; ≥2) was detected in 8% (47/578); and high FGFR2 mRNA expression of score 4 (>10 dots/cell and >10% of positive cells with dot clusters under a 20× objective) was seen in 4% (29/718). For 468 samples, both mRNA and DISH data were available. FGFR2 mRNA expression levels were associated with gene amplification; FGFR2 mRNA levels were highest in the highly amplified samples (n = 12). All highly amplified samples showed very strong FGFR2 mRNA expression (dense clusters of the signal visible under a 1× objective). Patients with very strong FGFR2 mRNA expression showed more homogeneous FGFR2 mRNA expression compared to patients with lower FGFGR2 mRNA expression. Gastric cancer patients with tumors that had an FGFR2 mRNA expression score of 4 had shorter RFS compared with score 0–3 patients.
Conclusion
RNAscope and DISH are suitable methods to evaluate FGFR2 status in gastric cancer. Formalin-fixed paraffin-embedded (FFPE) tissue slides allowed evaluation of the intratumor heterogeneity of these FGFR2 biomarkers.
J Immunol. 2018 Dec 10.
2018 Dec 10
Boxberg M, Leising L, Steiger K, Jesinghaus M, Alkhamas A, Mielke M, Pfarr N, Götz C, Wolff KD, Weichert W, Kolk A.
PMID: 30530592 | DOI: 10.4049/jimmunol.1800242
FEBS letters
2023 Apr 15
Sasaki, K;Hayamizu, Y;Murakami, R;Toi, M;Iwai, K;
PMID: 37060248 | DOI: 10.1002/1873-3468.14623
Tumor Biology
2021 Jul 01
Dikshit, A;Phatak, J;Hernandez, L;Doolittle, E;Murlidhar, V;Zhang, B;Ma, X;
| DOI: 10.1158/1538-7445.am2021-lb235
Oncotarget.
2018 Aug 14
Fromme JE, Schmitz K, Wachter A, Grzelinski M, Zielinski D, Koppel C, Conradi LC, Homayounfar K, Hugo T, Hugo S, Lukat L, Rüschoff J, Ströbel P, Ghadimi M, Beißbarth T, Reuter-Jessen K, Bleckmann A, Schildhaus HU.
PMID: 30181810 | DOI: 10.18632/oncotarget.25941
Abstract
OBJECTIVES:
Metastatic colorectal cancer (CRC) remains a leading cause of cancer related deaths. Patients with oligometastatic liver disease represent a clinical subgroup with heterogeneous course. Until now, biomarkers to characterize outcome and therapeutic options have not been fully established.
METHODS:
We investigated the prevalence of FGFR alterations in a total of 140 primary colorectal tumors and 63 liver metastases of 55 oligometastatic CRC patients. FGF receptors (FGFR1-4) and their ligands (FGF3, 4 and 19) were analyzed for gene amplifications and rearrangements as well as for RNA overexpression in situ. Results were correlated with clinico-pathologic data and molecular subtypes.
RESULTS:
Primary tumors showed FGFR1 (6.3%) and FGF3,4,19 (2.2%) amplifications as well as FGFR1 (10.1%), FGFR2 (5.5%) and FGFR3 (16.2%) overexpression. In metastases, we observed FGFR1 amplifications (4.8%) as well as FGFR1 (8.5%) and FGFR3 (14.9%) overexpression. Neither FGFR2-4 amplifications nor gene rearrangements were observed. FGFR3 overexpression was significantly associated with shorter overall survival in metastases (mOS 19.9 vs. 47.4 months, HR=3.14, p=0.0152), but not in primary CRC (HR=1.01, p=0.985). Although rare, also FGFR1 amplification was indicative of worse outcome (mOS 12.6 vs. 47.4 months, HR=8.83, p=0.00111).
CONCLUSIONS:
We provide the so far most comprehensive analysis of FGFR alterations in primary and metastatic CRC. We describe FGFR3 overexpression in 15% of CRC patients with oligometastatic liver disease as a prognosticator for poor outcome. Recently FGFR3 overexpression has been shown to be a potential therapeutic target. Therefore, we suggest focusing on this subgroup in upcoming clinical trials with FGFR-targeted therapies.
Description | ||
---|---|---|
sense Example: Hs-LAG3-sense | Standard probes for RNA detection are in antisense. Sense probe is reverse complent to the corresponding antisense probe. | |
Intron# Example: Mm-Htt-intron2 | Probe targets the indicated intron in the target gene, commonly used for pre-mRNA detection | |
Pool/Pan Example: Hs-CD3-pool (Hs-CD3D, Hs-CD3E, Hs-CD3G) | A mixture of multiple probe sets targeting multiple genes or transcripts | |
No-XSp Example: Hs-PDGFB-No-XMm | Does not cross detect with the species (Sp) | |
XSp Example: Rn-Pde9a-XMm | designed to cross detect with the species (Sp) | |
O# Example: Mm-Islr-O1 | Alternative design targeting different regions of the same transcript or isoforms | |
CDS Example: Hs-SLC31A-CDS | Probe targets the protein-coding sequence only | |
EnEm | Probe targets exons n and m | |
En-Em | Probe targets region from exon n to exon m | |
Retired Nomenclature | ||
tvn Example: Hs-LEPR-tv1 | Designed to target transcript variant n | |
ORF Example: Hs-ACVRL1-ORF | Probe targets open reading frame | |
UTR Example: Hs-HTT-UTR-C3 | Probe targets the untranslated region (non-protein-coding region) only | |
5UTR Example: Hs-GNRHR-5UTR | Probe targets the 5' untranslated region only | |
3UTR Example: Rn-Npy1r-3UTR | Probe targets the 3' untranslated region only | |
Pan Example: Pool | A mixture of multiple probe sets targeting multiple genes or transcripts |
Complete one of the three forms below and we will get back to you.
For Quote Requests, please provide more details in the Contact Sales form below
Our new headquarters office starting May 2016:
7707 Gateway Blvd.
Newark, CA 94560
Toll Free: 1 (877) 576-3636
Phone: (510) 576-8800
Fax: (510) 576-8798
19 Barton Lane
Abingdon Science Park
Abingdon
OX14 3NB
United Kingdom
Phone 2: +44 1235 529449
Fax: +44 1235 533420
20F, Tower 3,
Raffles City Changning Office,
1193 Changning Road, Shanghai 200051
021-52293200
info.cn@bio-techne.com
Web: www.acdbio.com/cn
For general information: Info.ACD@bio-techne.com
For place an order: order.ACD@bio-techne.com
For product support: support.ACD@bio-techne.com
For career opportunities: hr.ACD@bio-techne.com