A5002426578- Cancer-related Molecular Pathways
- Cancer Research and Treatments
- Click Chemistry and Applications
- Advanced Breast Cancer Therapies
- Monoclonal and Polyclonal Antibodies Research
- Heat shock proteins research
- Radiopharmaceutical Chemistry and Applications
- Cancer, Hypoxia, and Metabolism
- Cancer therapeutics and mechanisms
- Peptidase Inhibition and Analysis
- Cancer Cells and Metastasis
- Synthesis and Biological Evaluation
- Neuroendocrine Tumor Research Advances
- Toxin Mechanisms and Immunotoxins
- Neuroblastoma Research and Treatments
- Nanoplatforms for cancer theranostics
- CAR-T cell therapy research
- Medical Imaging Techniques and Applications
- Advanced Biosensing Techniques and Applications
- ATP Synthase and ATPases Research
- Glycosylation and Glycoproteins Research
- Immunotherapy and Immune Responses
- Thyroid Cancer Diagnosis and Treatment
- Lung Cancer Research Studies
- RNA Interference and Gene Delivery
Uppsala University
2015-2025
National Cancer Centre Singapore
2024
Institute of Molecular and Cell Biology
2024
Karolinska Institutet
2023
Cardio-Pulmonary Institute
2023
The cell surface proteins CD133, CD24 and CD44 are putative markers for cancer stem populations in colon cancer, associated with aggressive types poor prognosis. It is important to understand how these may predict treatment outcomes, determined by factors such as radioresistance. scope of this study was assess the connection between EGFR, CD24, (including isoforms) expression levels radiation sensitivity, furthermore analyze influence AKT isoforms on patterns markers, better underlying...
Although stapled α-helical peptides can address challenging targets, their advancement is impeded by poor understandings for making them cell permeable while avoiding off-target toxicities. By synthesizing >350 molecules, we present workflows identifying against Mdm2(X) with in vivo activity and no effects. Key insights include a clear correlation between lipophilicity permeability, removal of positive charge to avoid toxicities, judicious anionic residue placement enhance...
MDM2/MDMX inhibition by Sulanemadlin reduces cell growth dependent on p53 status activation leads to increased immunogenicity marker expression + anti-PD-1 immunotherapy increases lymphocyte infiltration synergizes with increasing overall survival
// Diana Spiegelberg 1 , Adrian Dascalu Anja C. Mortensen Andris Abramenkovs Gamze Kuku Marika Nestor 1, 2 Bo Stenerlöw Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden Unit Otolaryngology Head Neck Surgery, Surgical Sciences, Correspondence to: Spiegelberg, e-mail: Diana.spiegelberg@igp.uu.se Keywords: 17-AAG, synergy, DNA repair, EGFR, CD44v6 Received: May 31, 2015 Accepted: September 24, Published: October 06, ABSTRACT Overexpression heat shock protein...
Abstract Oncogenic client-proteins of the chaperone Heat shock protein 90 (HSP90) insure unlimited tumor growth and are involved in resistance to chemo- radiotherapy. The HSP90 inhibitor Onalespib initiates degradation oncoproteins, might also act as a radiosensitizer. aim this study was therefore evaluate efficacy combination with external beam radiotherapy an vitro vivo approach. downregulated client proteins, lead increased apoptosis caused DNA-double-strands. Monotherapy reduced colony...
Rational: Cisplatin based cancer therapy is an affordable and effective standard for several solid cancers, including lung, ovarian head neck cancers. However, the clinical use of cisplatin routinely limited by development drug resistance subsequent therapeutic failure. Therefore, methods circumventing have potential to increase efficiency dramatically overall survival. can be mediated alterations DNA damage response, where multiple components repair machinery been described client proteins...
Abstract About 50% of all cancers carry a mutation in p53 that impairs its tumor suppressor function. The missense R175H (p53 R172H mice) is hotspot various cancer types. Therefore, monoclonal antibodies selectively targeting clinically relevant mutations like could prove immensely value. We aimed to evaluate the vitro and vivo binding properties two novel anti-p53 assess their performance as agents for molecular imaging. In vitro, 125 I-4H5 I-7B9 demonstrated long shelf life...
Background Glioblastoma (GBM) is the deadliest form of brain cancer, impacting both adults and children, marked by exceptionally high morbidity mortality rates, even with current standard treatments such as surgery, radiation therapy, chemotherapy. Therefore, there a pressing need for new therapeutic strategies to improve survival reduce treatment side effects. In this study, we investigated effect HSP90 inhibition in combination radiotherapy established patient-derived glioblastoma cell...
Radiotherapy amplifies p53 expression in cancer cells with wild-type (wt) p53. Blocking the negative regulators MDM2 and MDMX stabilizes may therefore potentiate radiotherapy outcomes. In this study, we investigate efficacy of novel anti-MDM2/X stapled peptide PM2 alone combination external gamma radiation vitro vivo therapy combined elicited synergistic therapeutic effects compared monotherapy wt both assays, whereas these did not manifest -/- cells. Biodistribution autoradiography 125I-PM2...
The bone-seeking radiopharmaceutical Xofigo (Radium-223 dichloride) has demonstrated both extended survival and palliative effects in treatment of bone metastases prostate cancer. alpha-particle emitter Ra-223, targets regions undergoing active remodeling strongly binds to hydroxyapatite (HAp). However, the toxicity mechanism properties Ra-223 binding are not fully understood. By exposing 2D 3D (spheroid) cancer cell models free HAp-bound we here studied toxicity, apoptosis formation repair...
Abstract Purpose 177 Lu-DOTATATE targeting the somatostatin receptor (SSTR) is utilized for treatment of neuroendocrine tumors (NETs). Onalespib, a heat shock protein 90 (HSP90) inhibitor, has demonstrated radiosensitizing properties and may thus enhance effect Lu-DOTATATE. Consequently, aim this study was to assess potential Onalespib in combination with vivo examine toxicity profiles treatments. Methods selectivity distribution NET xenografts were studied using biodistribution...
CD44 is a complex family of molecules, associated with aggressive malignancies and cancer stem cells. However, the role variants in tumor progression treatment resistance not clear. In this study, expression its was assessed head neck squamous cell carcinomas (HNSCC). Furthermore, subpopulations cells expressing high amounts were identified characterized, for e.g., cycle phase radioresistance. Results revealed homogenous CD44v7 four lines CD44v4 CD44v6 three lines. CD44v3 highly expressed...
Heat shock protein 90 (HSP90) is essential for the activation and stabilization of numerous oncogenic client proteins. AT13387 a novel HSP90 inhibitor promoting degradation proteins upon binding, may also act as radiosensitizer. For optimal treatment there is, however, need identification biomarkers patient stratification therapeutic response monitoring, to find suitable targets combination treatments. The aim this study was assess surface antigens commonly expressed in squamous cell...
177Lu‑DOTATATE was recently approved for the treatment of somatostatin receptor (SSTR)‑positive neuroendocrine tumors (NETs). However, despite impressive response rates, complete responses are rare. Heat shock protein 90 (HSP90) inhibitors have been suggested as suitable therapeutic agents NETs, well a potential radiosensitizers. Consequently, aim this study to investigate whether HSP90‑inhibitor onalespib could reduce NET cell growth and act radiosensitizer when used in combination with...
The chimeric monoclonal antibody U36 (cMAb U36) recognizes the CD44v6 antigen. Its potential as a radioimmunotargeting agent, well its safety, has been shown in previous studies head and neck cancer patients. However, intact MAbs have long circulation time blood tumor targeting may also be hampered due to slow incomplete diffusion into solid tumors. In comparison, smaller monovalent Fab' divalent F(ab')2 fragments are expected exhibit shorter circulating half-lives, better penetration thus...
Medical imaging by use of immunotargeting generally relies on a labeled molecule binding to specific target the cell surface. It is important utilize both cell-based and time-resolved assays in order understand properties such molecular interactions relevant setting. In this report we describe detailed characterization interaction for AbD15179, promising CD44v6-targeting antibody fragment radio-immunotargeting. Influence labeling cell-line model protein kinetics was assessed using three...
Patients with squamous cell carcinoma in the head and neck region (HNSCC) offer a diagnostic challenge due to difficulties detect small tumours metastases. Imaging methods available are not sufficient, radio-immunodiagnostics could increase specificity sensitivity of diagnostics. The objective this study was evaluate, for first time, vivo properties radiolabelled CD44v6-targeting fragment AbD15179 assess its utility as targeting agent CD44v6-expressing tumours. fully human Fab labelled 111In...
We have developed the CD44v6-targeting human bivalent antibody fragment AbD19384, an engineered recombinant Fab formed via dimerization of dHLX (synthetic double helix loop motif) domains, for potential use in antibody-based molecular imaging squamous cell carcinoma head and neck region. This is a unique construct that has, to best our knowledge, never been assessed vivo before. The objective present study was evaluate first time vitro binding properties radio-iodinated assess its utility as...
The tumor suppressor protein p53 is mutated in close to 50% of human tumors and dysregulated many others, for instance by silencing or loss p14ARF. Under steady-state conditions, the two E3 ligases MDM2/MDM4 interact with inhibit transcriptional activity p53. Inhibition p53–MDM2/4 interaction reactivate wild-type (WT) has therefore been considered a therapeutic strategy. Moreover, studies indicate that reactivation may synergize radiation increase immunogenicity. In vivo most MDM2 inhibitors...
The tumor suppressor p53 is a key mediator of cellular stress and DNA damage response cascades activated after exposure to ionizing radiation. Amplifying wild-type expression by targeting negative regulators such as HDM2 in combination with external beam radiotherapy (EBRT) may result increased therapeutic effects. novel stapled peptide PM2 prevents from suppressing p53, thus promising agent for EBRT. Effects potential PM2-induced radiosensitivity were assessed panel cancer cell lines using...
Abstract Thyroid cancer is the most common endocrine malignancy, affecting nearly 600,000 new patients worldwide. Treatment with BRAF inhibitor sorafenib partially prolongs progression-free survival in thyroid patients, but fails to improve overall survival. This study examines enhancing efficacy by combination therapy novel HSP90 onalespib. In vitro of and onalespib monotherapy as well was assessed papillary (PTC) anaplastic (ATC) cells using cell viability colony formation assays....