A5026098996- Cancer, Hypoxia, and Metabolism
- Angiogenesis and VEGF in Cancer
- Lung Cancer Treatments and Mutations
- Cancer Immunotherapy and Biomarkers
- Glioma Diagnosis and Treatment
- Cancer, Lipids, and Metabolism
- Ferroptosis and cancer prognosis
- Cancer Genomics and Diagnostics
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Retinal and Optic Conditions
- Colorectal Cancer Treatments and Studies
- Lung Cancer Research Studies
- Single-cell and spatial transcriptomics
- Retinal Diseases and Treatments
- HER2/EGFR in Cancer Research
- Radiomics and Machine Learning in Medical Imaging
- Spectroscopy Techniques in Biomedical and Chemical Research
- Immune Cell Function and Interaction
- Advanced Breast Cancer Therapies
- Neuroblastoma Research and Treatments
- Drug-Induced Adverse Reactions
- Retinal Imaging and Analysis
- Cancer, Stress, Anesthesia, and Immune Response
All India Institute of Medical Sciences
2025
Massachusetts General Hospital
2015-2024
Harvard University
1992-2024
Takeda (United States)
2022-2023
MGH Institute of Health Professions
2022
Boston University
2022
Paris Cardiovascular Research Center
2021
Université Paris Cité
2021
Inserm
2021
University of Cologne
2010-2020
Glioblastomas (GBMs) rapidly become refractory to anti-VEGF therapies. We previously demonstrated that ectopic overexpression of angiopoietin-2 (Ang-2) compromises the benefits receptor (VEGFR) treatment in murine GBM models and circulating Ang-2 levels patients rebound after an initial decrease following cediranib (a pan-VEGFR tyrosine kinase inhibitor) administration. Here we tested whether dual inhibition VEGFR/Ang-2 could improve survival two orthotopic GBM, Gl261 U87. Dual therapy using...
The molecular mechanisms that control the balance between antiangiogenic and proangiogenic factors initiate angiogenic switch in tumors remain poorly defined. By combining chemical genetics with multimodal imaging, we have identified an autocrine feed-forward loop tumor cells which tumor-derived VEGF stimulates production via VEGFR2-dependent activation of mTOR, substantially amplifying initial signal. Disruption this by perturbation or knockdown VEGFR2 dramatically inhibited vitro vivo....
ALK inhibitors induce complete tumor regression in a mouse model of ALK-driven neuroblastoma.
Liver metastasis is a major cause of mortality for patients with colorectal cancer (CRC). Mismatch repair-proficient (pMMR) CRCs make up about 95% metastatic CRCs, and are unresponsive to immune checkpoint blockade (ICB) therapy. Here we show that mouse models orthotopic pMMR CRC liver accurately recapitulate the inefficacy ICB therapy in patients, whereas same tumors sensitive when grown subcutaneously. To reveal local, nonmalignant components determine sensitivity treatment, compared...
Immune checkpoint blockers (ICBs) have failed in all phase III glioblastoma trials. Here, we found that ICBs induce cerebral edema some patients and mice with glioblastoma. Through single-cell RNA sequencing, intravital imaging, CD8 + T cell blocking studies mice, demonstrated this results from an inflammatory response following antiprogrammed death 1 (PD1) antibody treatment disrupts the blood–tumor barrier. Used lieu of immunosuppressive corticosteroids, angiotensin receptor blocker...
Tumor-draining lymph nodes (TDLNs) are important for tumor antigen–specific T cell generation and effective anticancer immune responses. However, TDLNs often the primary site of metastasis, causing suppression worse outcomes. Through cross-species single-cell RNA-Seq analysis, we identified features defining cancer heterogeneity, plasticity, evasion during breast progression node metastasis (LNM). A subset cells in exhibited elevated MHC class II (MHC-II) gene expression both mice humans....
Of 34 tyrosine residues in insulin receptor substrate 1 (IRS-1), 14 are adjacent to acidic residues, suggesting that they might be phosphorylation sites. Synthetic peptides corresponding sequences surrounding these tyrosines were used as substrates of the kinase. Surprisingly six these, each within YMXM motifs, phosphorylated with greatest efficiency (Km, 24-92 microM; kcat/Km, 0.6-2.1 x 10(4) M-1.sec-1). Substituted revealed a strong preference kinase for methionine at Y + and 3 positions....
NKG2D, an activating receptor expressed on NK cells and T cells, is critically involved in tumor immunosurveillance. In this study, we explored the potential therapeutic utility of NKG2D ligand ULBP2 for treatment colon carcinoma. To end designed a fusion protein consisting human antibody-derived single chain targeting carcinoembryonic antigen (CEA). The bispecific recombinant re-directed towards malignant by binding to both, triggered cell-mediated target cell killing vitro. Moreover,...
Malaria, caused by a protozoan parasite of the genus Plasmodium, is severe infectious disease with life-threatening consequences that has burdened mankind for centuries. Although Plasmodium falciparum (P. falciparum) malaria more prevalent globally than vivax vivax) malaria, India bears largest burden P. over 3.6 million cases accounting ∼48% global cases. Existing detection methods are costly or tedious have low accuracy. To address need specific diagnostic assay vivax, we generated...
Abstract Extensive oncologic experience argues that the most efficacious applications of antiangiogenic agents rely upon a combination with cytotoxic drugs. Yet there remains lack clarity about how to optimize scheduling for such drug combinations. Prudent therapy might transiently normalize blood vessels improve tumor oxygenation and exposure. Using [15O]H2O positron emission tomography imaging in preclinical mouse model non–small cell lung cancer, we observed short-term treatment vascular...
Anti-angiogenic treatment targeting vascular endothelial growth factor (VEGF)-VEGFR2 signaling has shown limited efficacy in lung cancer patients. Here, we demonstrate that inhibition of VEGFR2 tumor cells, expressed ∼20% non-squamous non-small cell (NSCLC) patients, leads to a pro-invasive phenotype. Drug-induced interferes with the formation EphA2/VEGFR2 heterocomplex, thereby allowing RSK interact Serine 897 EphA2. Inhibition decreases phosphorylation Selective genetic modeling EphA2 or...
// Jakob Schöttle 1,2,3 , Sampurna Chatterjee 1,2,10 Caroline Volz 1,2 Maike Siobal 2 Alexandra Florin 4 Dennis Rokitta 5 Yvonne Hinze 6 Felix Dietlein 3 Plenker Katharina König Kerstin Albus Johannes M. Heuckmann 7 Daniel Rauh 8 Thomas Franz Bernd Neumaier 2,9 Uwe Fuhr Lukas C. Heukamp 4,7 and Roland T. Ullrich 1 Department I of Internal Medicine, Center Integrated Oncology Köln-Bonn, University Cologne, Germany Molecular Medicine Cologne (ZMMK), Max-Planck-Institute for Metabolism, with...
Physical forces exerted by expanding brain tumors - specifically the compressive stresses propagated through solid tissue structures reduces perfusion and neurological function, but heretofore has not been directly measured in patients
Abstract Background: Mobocertinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that received FDA accelerated approval for non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations, based on data from a pivotal phase 1/2 study of mobocertinib (NCT02716116). In platinum-pretreated patients (pts) ex20ins NSCLC (N=114), the overall response rate (ORR) was 28%, median duration 17.5 months, and progression-free survival 7.3 months....
Abstract Background: Immune checkpoint blockers (ICBs) have revolutionized cancer treatment, but they are often associated with severe immune related adverse events (irAEs). These irAEs more seen in patients obesity or concomitantly treated cytotoxic therapies. Methods: We aimed to understand the mechanisms of ICB-induced irAEs, context and ICB/chemotherapy combinations. developed a mouse model cardiac which is most fatal type irAE ICB-treated patients, clinically relevant features: (i) an...
9108 Background: ctDNA is an important tool to diagnose and monitor mutations in pts with non–small cell lung cancer (NSCLC). We evaluated epidermal growth factor receptor gene ( EGFR) ex20ins tumor vs plasma samples, assessed changes EGFR variant allele frequency (VAF) mobocertinib treatment correlation response, identified potential emerging variants of acquired resistance. Methods: Tumor tissue samples were collected at baseline (BL) from ex20ins+ advanced NSCLC receiving 160 mg QD a...
<h3>Background</h3> Immune checkpoint blockers (ICBs) have revolutionized cancer treatment, but they are often associated with severe immune related adverse events (irAEs). These irAEs more seen in patients obesity or concomitantly treated cytotoxic therapies. <h3>Methods</h3> We aimed to understand the mechanisms of ICB-induced irAEs, context [FD1] and ICB/chemotherapy combinations. used a mouse model cardiac which is most fatal type irAE ICB-treated patients, clinically relevant features:...