Identification of ephrinB2 positive vessels in non-Hodgkin lymphoma subtypes.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19542-e19542
Author(s):  
Kenneth Stuart Cohen ◽  
Mina Jamali ◽  
Elizabeth Hyjek
Keyword(s):  
Tumor Biology ◽  
Tyrosine Kinase Signaling ◽  
Eph Receptor ◽  
Follicular Hyperplasia ◽  
Reverse Signaling ◽  
Tissue Sections ◽  
Non Hodgkin Lymphoma ◽  
Clinical Models ◽  
Novel Target ◽  
The University

e19542 Background: Current anti-angiogenic therapies for tumors target signaling pathways such as VEGF. However, the role of alternative vascular pathways in tumor biology in general, and lymphoma biology specifically, are less well understood. Recently, the Eph receptor tyrosine kinase signaling pathway has emerged as a novel target for therapeutic inhibition. The EphB family member EphB4, and its reverse signaling ligand ephrinB2, are indispensible for developmental angiogenesis. Inhibition of ephrinB2 signaling results in impaired tumor growth in pre-clinical models. We therefore sought to determine if ephrinB2 is expressed in the microenvironment of human lymphomas and thereby represents a novel therapeutic target. Methods: We evaluated by immunohistochemistry on paraffin tissue sections expression of ephrinB2, CD34 (endothelial cells) and CD163 (macrophages) in LN biopsies from 12 cases of FL and 11 cases of DLBCL retrieved from the archives of the Department of Pathology at the University of Chicago (2000-2011). Eleven cases of follicular hyperplasia or quiescent LNs were used as controls (Cs). Slides were digitally scanned and examined both semi-quantitatively and by digital image analysis. Stained cells were quantified both in internal areas and at lymphoma-fat interfaces. Results: CD34+ microvessel densities were comparable between DLBCL and C groups but showed a significantly higher trend of interface angiogenic sprouts in FLs. Interface recruited CD163+ cell numbers were significantly higher in DLBCLs than in both FLs and Cs (p<0.0001). EphrinB2-expressing blood vessels were significantly increased in FLs but not in DLBCL. Conclusions: FLs demonstrate an increase in ephrinB2+/CD34+ vessels at the lymphoma-fat interface. In contrast, DLBCLs demonstrate no increase in ephrinB2+ vessels versus controls. However, DLBCLs were notable for increased recruitment of CD163+ macrophages at the tumor/host interface. These data represent the first analysis of ephrinB2 expression in human lymphomas and demonstrate heterogeneity between locations within a lymphoma and between histologic subtypes. Analysis of ephrinB2 in human lymphomas reveals marked heterogeneity in lymphoma microenvironmental domains.

scholarly journals Quantitative radioimmunohistochemical measurements of p185(erbB-2) in frozen tissue sections.

1996 ◽  
Vol 44 (11) ◽  
pp. 1251-1259 ◽  
Author(s):  
J R Reeves ◽  
J J Going ◽  
G Smith ◽  
T G Cooke ◽  
B W Ozanne ◽  
...  
Keyword(s):  
Tumor Biology ◽  
Breast Carcinomas ◽  
Tissue Sections ◽  
Biopsy Specimens ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Interstudy Variability ◽  
High Degree ◽  
The Relationship ◽  
Formalin Fixed

The relationship between expression of the c-erbB-2 proto-oncogene and the biology of breast cancer has been investigated widely, most studies using immunohistochemistry in formalin-fixed, paraffin-embedded tissues. This technique is at best semiquantitative and there is a high degree of interstudy variability because of its subjective nature and poor methodological standardization. The relationship between the levels of expression and biology can be examined thoroughly only with an accurately quantitative technique. We have developed a radioimmunohistochemical assay to measure p185(erbB-2) in tissue biopsy specimens. The method involves incubating frozen sections with 125I-labeled monoclonal antibody, microautoradiograpy, and grain counting with image analysis. Sections of cell pellets with known c-erbB-2 levels are processed with each batch of samples as internal calibration standards. We have quantified c-erbB-2 expression in 60 breast carcinomas and compared the results with conventional immunohistochemistry. Radioimmunohistochemistry measured receptor levels throughout the range of expression in breast carcinomas, whereas conventional immunohistochemistry detected the protein only in the highest expressing tumors. The quantitative, objective data produced by radioimmunohistochemistry allow a more thorough evaluation of the relationship between c-erbB-2 expression and tumor biology. This technique may have applications in other fields where quantitative data is required and relevant monoclonal antibodies are available.

scholarly journals Raman-Enhanced Spectroscopy (RESpect) Probe for Childhood Non-Hodgkin Lymphoma

2020 ◽  
Vol 2 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Melissa Agsalda-Garcia ◽  
Tiffany Shieh ◽  
Ryan Souza ◽  
Natalie Kamada ◽  
Nicholas Loi ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Hodgkin Lymphoma ◽  
Point Of Care ◽  
Principal Component ◽  
Initial Step ◽  
Follicular Hyperplasia ◽  
Raman Spectroscopic ◽  
Non Hodgkin Lymphoma ◽  
Cellular Pathogenesis ◽  
Ultimate Objective

Raman-enhanced spectroscopy (RESpect) probe, which enhances Raman spectroscopy technology through a portable fiber-optic device, characterizes tissues and cells by identifying molecular chemical composition showing distinct differences/similarities for potential tumor markers or diagnosis. In a feasibility study with the ultimate objective to translate the technology to the clinic, a panel of pediatric non-Hodgkin lymphoma tissues and non-malignant specimens had RS analyses compared between standard Raman spectroscopy microscope instrument and RESpect probe. Cryopreserved tissues were mounted on front-coated aluminum mirror slides and analyzed by standard Raman spectroscopy and RESpect probe. Principal Component Analysis revealed similarities between non-Hodgkin lymphoma subtypes but not follicular hyperplasia. Standard Raman spectroscopy and RESpect probe fingerprint comparisons demonstrated comparable primary peaks. Raman spectroscopic fingerprints and peaks of pediatric non-Hodgkin lymphoma subtypes and follicular hyperplasia provided novel avenues to pursue diagnostic approaches and identify potential new therapeutic targets. The information could inform new insights into molecular cellular pathogenesis. Translating Raman spectroscopy technology by using the RESpect probe as a potential point-of-care screening instrument has the potential to change the paradigm of screening for cancer as an initial step to determine when a definitive tissue biopsy would be necessary.

scholarly journals Microbiota alterations in proline metabolism impact on depression through GABA and ECM homeostasis

2021 ◽  
Author(s):  
Jordi Mayneris-Perxachs ◽  
María Arnoriaga-Rodríguez ◽  
Miquel Martín ◽  
Aurelijus Burokas ◽  
Gerard Blasco ◽  
...  
Keyword(s):  
Treatment Efficacy ◽  
Brain Dynamics ◽  
Depression Treatment ◽  
Confounding Factors ◽  
Proline Metabolism ◽  
Rich Club ◽  
Gaba Metabolism ◽  
Clinical Models ◽  
Network Disruptions ◽  
Novel Target

Abstract The microbiota-gut-brain axis has emerged as a novel target in depression, a disorder with low treatment efficacy. However, the field is dominated by underpowered studies focusing on major depression not addressing microbiome functionality, compositional nature, or confounding factors. We applied a multi-omics approach combining pre-clinical models with three human cohorts including mild-depressed patients. Microbial functions and metabolites converging into glutamate/GABA metabolism, particularly proline, were linked to depression. Whole-brain dynamics revealed rich club network disruptions associated with depression and circulating proline. Proline supplementation in mice exacerbated depression along with microbial translocation. Human microbiota transplantation induced an emotional-impaired phenotype in mice and alterations in GABA-, proline-, and extracellular matrix-related pre-frontal cortex genes. Targeting the microbiome and dietary proline may open new windows for an efficient depression treatment.

scholarly journals Application of mid-infrared (MIR) microscopy imaging for discrimination between follicular hyperplasia and follicular lymphoma in transgenic mice

The Analyst ◽  
2015 ◽  
Vol 140 (18) ◽  
pp. 6363-6372 ◽  
Author(s):  
C. Woess ◽  
M. Drach ◽  
A. Villunger ◽  
R. Tappert ◽  
R. Stalder ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Follicular Lymphoma ◽  
Infrared Radiation ◽  
Spectroscopic Technique ◽  
Microscopy Imaging ◽  
Mid Infrared ◽  
Follicular Hyperplasia ◽  
Tissue Sections

Mid-infrared (MIR) microscopy imaging is a vibrational spectroscopic technique that uses infrared radiation to image molecules of interest in thin tissue sections.

scholarly journals PROTON-INDUCED X-RAY ANALYSIS OF TRACE ELEMENTS IN TISSUE SECTIONS

1974 ◽  
Vol 22 (1) ◽  
pp. 1-6 ◽  
Author(s):  
F. C. JUNDT ◽  
K. H. PURSER ◽  
H. KUBO ◽  
E. A. SCHENK
Keyword(s):  
Trace Elements ◽  
X Rays ◽  
X Ray ◽  
Tissue Sections ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Tissue Homogenates ◽  
Autopsy Specimens ◽  
The University ◽  
Structure Research

A 3-meV proton beam from the MP Van de Graaff accelerator at the Nuclear Structure Research Laboratory of the University of Rochester has been used to induce characteristic x-rays of trace elements from a variety of biologic samples. The x-ray spectra have been measured with a high resolution Si(Li) detector which can detect and separate in energy x-rays from neighboring elements with Z > 13. Tissue homogenates, frozen sections and formalin-fixed, paraffin-embedded sections of various tissues obtained from surgical and autopsy specimens have been analyzed. Measurements have been made to check the sensitivity and reproducibility of the method. Data accumulated thus far indicate that this method is useful in evaluating absolute concentration of elements usually present in a given tissue and detecting environmental elements which may have accumulated in a given tissue.

scholarly journals Combination of Loncastuximab Tesirine and Polatuzumab Vedotin Shows Increased Anti-Tumor Activity in Pre-Clinical Models of Non-Hodgkin Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2273-2273
Author(s):  
Nikoleta Sachini ◽  
Asma Jabeen ◽  
Patrick H van Berkel ◽  
Francesca Zammarchi
Keyword(s):  
Monoclonal Antibody ◽  
Single Dose ◽  
Hodgkin Lymphoma ◽  
Annexin V ◽  
Publicly Traded ◽  
Non Hodgkin Lymphoma ◽  
Clinical Models ◽  
Anti Tumor Activity

Abstract Loncastuximab tesirine-lpyl (formerly ADCT-402) is an antibody-drug conjugate (ADC) comprising a humanised anti-CD19 monoclonal antibody conjugated to the pyrrolobenzodiazepine (PBD) dimer-based payload tesirine. Once bound to CD19 on the cell membrane, loncastuximab tesirine is rapidly internalised and the released PBD dimer warhead causes interstrand DNA crosslinks which ultimately trigger cell death. Pre-clinically, loncastuximab tesirine has shown potent and specific anti-tumor activity in lymphoma models both as single agent and in combination with other approved drugs, like venetoclax, idelalisib and bendamustine (Zammarchi, Corbett et al. 2018, Tarantelli, Spriano et al. 2019). Loncastuximab tesirine has been recently approved by the United States Food and Drug Administration (FDA) for the treatment of relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) and it is currently being tested in multiple clinical trials, either as monotherapy or in combination with other anti-lymphoma drugs. Polatuzumab vedotin is an ADC composed of a humanized anti-CD79b monoclonal antibody conjugated to monomethyl auristatin E (vcMMAE) and it is approved by the FDA for treatment of r/r DLBCL when used in combination with bendamustine and rituximab. Here, we investigated the in vitro and in vivo anti-tumor activity of loncastuximab tesirine combined with polatuzumab vedotin in pre-clinical models of non-Hodgkin lymphoma (NHL). In vitro, the combination of loncastuximab tesirine and polatuzumab vedotin was tested in three human-derived, CD19 and CD79b-positive NHL cell lines (WSU-DLCL2, TMD8 and Ramos) and it resulted in synergistic (TMD8 and Ramos) and additive (WSU-DLCL2) activity, as assessed by the Chou-Talalay method. Quantification of cell viability (propidium iodide [PI]-negative and Annexin V-negative) and early/late apoptosis (Annexin V-positive and PI-negative/ Annexin V-positive and-PI positive) on TMD8 and Ramos cells treated with loncastuximab tesirine, polatuzumab vedotin or the combination of the two agents showed a significant reduction of viable cells accompanied by an increase in apoptotic cells in the combination setting compared to the single agents. In vivo, loncastuximab tesirine was tested either alone (0.25 or 0.5 mg/kg, single dose) or in combination with polatuzumab vedotin (1 mg/kg, single dose) in the WSU-DLCL2 xenograft model. At the highest dose of loncastuximab tesirine, combination with polatuzumab vedotin resulted in improved anti-tumor activity and superior response rate compared to the 2 agents in monotherapy. All treatment regimens were well tolerated by the mice, as assessed by body weight measurements and frequent observation for signs of treatment-related side effects. In conclusion, the combination of loncastuximab tesirine and polatuzumab vedotin resulted in improved anti-tumor activity both in vitro and in vivo in lymphoma preclinical models and it was well tolerated. Altogether, these novel pre-clinical data warrant translation of the combination of loncastuximab tesirine and polatuzumab vedotin into the clinic for the treatment of NHL. Disclosures Sachini: ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company. Jabeen: ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company. van Berkel: ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Zammarchi: ADC Therapeutics: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties.

Same-day pegfilgrastim or pegfilgrastim-cbqv prophylaxis in miniCHOP chemotherapy based regimens for non-Hodgkin lymphoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19542-e19542
Author(s):  
Trace Bartels ◽  
Ali McBride ◽  
Neda AlRawashdh ◽  
Logan Moore ◽  
Daniel O Persky ◽  
...  
Keyword(s):  
B Cell Lymphoma ◽  
Study Groups ◽  
Primary Objective ◽  
Cancer Center ◽  
Safety And Efficacy ◽  
Non Hodgkin Lymphoma ◽  
University Of Arizona ◽  
Chemotherapy Dose ◽  
Grade 3 ◽  
The University

e19542 Background: Non-Hodgkin’s lymphoma, specifically, diffuse large B-cell lymphoma (DLBCL) is most frequently diagnosed among older patients. The utilization of a reduced dose of cyclophosphamide, doxorubicin, vincristine, and prednisone (miniCHOP) chemotherapy-based regimen has an improved tolerance and toxicity profile in select patient populations. Prophylaxis with pegfilgrastim or its biosimilar pegfilgrastim-cbqv is administration on the same day of chemotherapy in all patients with MiniCHOP at The University of Arizona Cancer Center (UACC). We report here on the first study to address the safety and efficacy of same day pegfilgrastim administration in lymphoma patients receiving MiniCHOP. Methods: A retrospective, single center, cohort study was conducted at UACC between October 1, 2013 and October 2020 to evaluate lymphoma patients who were treated with miniR-CHOP and given pegfilgrastim or its biosimilar (pegfilgrastim-cbqv) for FN prophylaxis. The primary objective was to compare the incidence of FN across all cycles of chemotherapy and after the first cycle of chemotherapy in DLBCL patients on miniR-CHOP and provided with next-day versus same-day pegfilgrastim administration. Our secondary outcomes of interests were incidence of chemotherapy-induced neutropenia (CIN) grade 3/4; hospitalization; anti-biotics administration; and chemotherapy dose-reduction or delays. Results: A total of 100 cycles of miniR-CHOP were received, of these pegfilgrastim was administered on same-day of chemotherapy in 95 cycles and five cycles on the next-day of chemotherapy. Among all cycles the incidence of FN was 5.3% vs. 0.0 ( P= 1.00); CIN 3/4 was 10.5% vs. 0.0 ( P= 1.00); hospitalization was 10.5% vs. 20.0% ( P= 0.45), anti-biotics administration was 6.3% vs. 40.0% ( P= 0.05) and the chemotherapy dose delays or reductions was 16.8% vs. 0.0% ( P= 0.99). In the first cycle of chemotherapy, the incidence of FN was 14.3% vs. 0.0% ( P= 1.00), CIN 3/4 was 21.4% vs. 0.0 ( P= 1.00), hospitalization 28.6% vs. 25.0% ( P= 0.99), and the anti-biotics administration was 21.4% vs. 50.0% ( P= 0.53) for same-day vs. next-day study groups. Conclusions: In our analysis, we have shown that same-day pegfilgrastim or pegfilgrastim-cbqv was safe and effective in lymphoma patients receiving miniR-CHOP. There was no significant increase in FN or delayed engraftment in either group. Future prospective studies are warranted to address the safety and efficacy profile of same day pegfilgrastim or a pegfilgrastim biosimilars in elderly lymphoma patients.

Signal transducer and activator of transcription 6 is frequently activated in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma

Blood ◽  
2002 ◽  
Vol 99 (2) ◽  
pp. 618-626 ◽  
Author(s):  
Brian F. Skinnider ◽  
Andrew J. Elia ◽  
Randy D. Gascoyne ◽  
Bruce Patterson ◽  
Lorenz Trumper ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Lines ◽  
Cellular Proliferation ◽  
Cytokine Signaling ◽  
Signal Transducer ◽  
Clinicopathologic Features ◽  
Stat Proteins ◽  
Tissue Sections ◽  
Non Hodgkin Lymphoma ◽  
Constitutive Phosphorylation

Abstract The unique clinicopathologic features of Hodgkin lymphoma (HL) are due to the multiple cytokines produced by its neoplastic cells, the Hodgkin and Reed-Sternberg (HRS) cells. Cytokine signaling is mediated through the signal transducer and activator of transcription (STAT) family of transcription factors. Immunoblotting and immunohistochemistry were used to examine cell lines and tissue sections derived from patients with HL and non-Hodgkin lymphoma (NHL) for expression of activated STAT proteins. Constitutive phosphorylation of STAT6 and STAT3 was common in HL. STAT6 was constitutively phosphorylated in 5 of 5 HL cell lines and in HRS cells from 25 of 32 (78%) classical HL cases. STAT3 was constitutively phosphorylated in 4 of 5 HL cell lines and in HRS cells from 27 of 31 (87%) classical HL cases. Only 4 of 24 NHL cases demonstrated constitutive STAT6 activation, whereas STAT3 activation was observed in 6 of 13 (46%) cases of B-cell NHL and 8 of 11 (73%) cases of T-cell NHL. Constitutive STAT5 phosphorylation was not a common feature of HL or NHL. STAT6 mediates signaling by interleukin 13 (IL-13), a cytokine frequently expressed by HRS cells. Antibody-mediated neutralization of IL-13 resulted in significant decreases in both cellular proliferation and levels of phosphorylated STAT6 of HL cell lines. In conclusion, constitutive STAT6 phosphorylation is a common and distinctive feature of HRS cells in classical HL, whereas STAT3 activation was regularly present in both HL and NHL. These results suggest that IL-13 signaling is largely responsible for the constitutive STAT6 activation observed in HRS cells and further implicate IL-13 as an important growth factor in classical HL.

scholarly journals Immunotherapy for T-Cell ALL and T-NHL: Highlights From SOHO 2020

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Allyson Price, MPAS, PA-C
Keyword(s):  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Cancer Center ◽  
University Of Texas ◽  
Keynote Presentation ◽  
Non Hodgkin Lymphoma ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Md Anderson ◽  
The University ◽  
Washington University

In his keynote presentation, John DiPersio, MD, PhD, of Washington University, recipient of the SOHO 2020 Distinguished Lecturer Award, discussed immunotherapy for T-cell acute lymphoblastic leukemia and T-cell non-Hodgkin lymphoma. Allyson Price, MPAS, PA-C, of The University of Texas MD Anderson Cancer Center, distills the seminal research by Dr. DiPersio and discusses implications for advanced practitioners.

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