A5057399810- Receptor Mechanisms and Signaling
- Cancer, Stress, Anesthesia, and Immune Response
- Inflammatory mediators and NSAID effects
- Cancer, Hypoxia, and Metabolism
- Eicosanoids and Hypertension Pharmacology
- Growth Hormone and Insulin-like Growth Factors
- Estrogen and related hormone effects
- Cutaneous Melanoma Detection and Management
- Metabolism, Diabetes, and Cancer
- Computational Drug Discovery Methods
- Cancer-related Molecular Pathways
- Ubiquitin and proteasome pathways
- Ocular Oncology and Treatments
- Nonmelanoma Skin Cancer Studies
- Melanoma and MAPK Pathways
- Retinoids in leukemia and cellular processes
- Protein Degradation and Inhibitors
- Cutaneous lymphoproliferative disorders research
- Cancer Immunotherapy and Biomarkers
- Protein Kinase Regulation and GTPase Signaling
- Retinal Development and Disorders
- Advanced Breast Cancer Therapies
- Pituitary Gland Disorders and Treatments
- Fibroblast Growth Factor Research
- Colorectal Cancer Treatments and Studies
Karolinska University Hospital
2009-2024
Karolinska Institutet
2009-2024
Karolinska Development (Sweden)
2022
Skin Cancer Foundation
2022
Zhongnan Hospital of Wuhan University
2009
Wuhan University
2009
Abstract The insulin-like growth factor-1 receptor (IGF-1R) plays a pivotal role in transformation, growth, and survival of malignant cells, has emerged as general promising target for cancer treatment. However, no fully selective IGF-1R inhibitors have thus far been found. This is explained by the fact that highly homologous to insulin receptor, coinhibition which may cause diabetic response. receptors are both tyrosine kinases, their ATP binding sites identical, implying cannot...
The insulin-like growth factor (IGF-1) signalling is highly implicated in cancer. In this the IGF-1 receptor (IGF-1R) unquestionable, predominating single factor. IGF-1R crucial for tumour transformation and survival of malignant cell, but only partially involved normal cell growth. This part due to interactions with oncogenes. Recent findings suggest a close interplay p53/MDM2 pathway. Disturbances components p53/MDM2/IGF-1R network may cause upregulation advantage cancer cell. Targeting...
Recently, p53 was demonstrated to affect the expression of insulin-like growth factor 1 receptor (IGF-1R), a tyrosine kinase that plays crucial role in and survival cancer cells. However, underlying mechanisms for interaction between IGF-1R are still not fully understood. One challenging questions remaining be answered is why wild-type p53, which per se represses transcription gene, overexpressed form necessary high expression. In this study, we show inhibition causes ubiquitination...
The insulin-like growth factor-1 receptor (IGF-1R) plays important roles in physiological and aging as well promoting several crucial functions cancer cells. However, the molecular mechanisms involved expression down-regulation of IGF-1R are still poorly understood. Here we provide evidence that beta-arrestin, otherwise known to be regulation G protein-coupled receptors, serves an adaptor bring oncoprotein E3 ubiquitin ligase MDM2 IGF-1R. In this way, beta-arrestin acts a component...
Beta-arrestin1, which regulates many aspects of seven transmembrane receptor (7TMR) biology, has also been shown to serve as an adaptor, brings Mdm2, E3 ubiquitin ligase the insulin-like growth factor-1 (IGF-1R), leading its proteasome-dependent destruction. Here we demonstrate that IGF-1R stimulation leads ubiquitination beta-arrestin1, vesicular trafficking and activation ERK1/2. This beta-arrestin1-dependent ERK activity can occur even when classical tyrosine kinase signaling is impaired....
Abstract PURPOSE: Uveal melanoma has a high mortality rate due to incidence of metastasis (up 50%), which preferentially occurs in the liver. Conventional chemotherapy, being only therapeutic option today against metastatic uveal melanoma, not proved be effective. Therefore, new molecular targets important for malignant phenotype have found design efficient pharmacologic agents. EXPERIMENTAL DESIGN: We previously reported data indicating that insulin-like growth factor-1 receptor (IGF-IR) is...
β-Arrestins are multifunctional proteins that play central roles in G protein-coupled receptor (GPCR) trafficking and signaling. β-Arrestin1 is also recruited to the insulin-like growth factor-1 (IGF-1R), a tyrosine kinase (RTK), mediating degradation Because GPCR phosphorylation by GPCR-kinases (GRKs) governs interactions of receptors with β-arrestins, we investigated regulatory four widely expressed GRKs on IGF-1R signaling/degradation. By suppressing GRK expression siRNA, demonstrated...
Glioblastoma (GB) is the most common malignant brain tumor in adults. It has limited treatment opportunities and almost exclusively fatal. Owing to central role insulin-like growth factor-1 receptor (IGF-1R) plays cells, it been suggested as a target for anticancer therapy including GB. The cyclolignan picropodophyllin (PPP) inhibits IGF-1R without affecting highly homologous insulin receptor. Here, we show that PPP of human GB cell lines along with reduced phosphorylation AKT. In vivo,...
Owing to its essential role in cancer, insulin-like growth factor type 1 receptor (IGF-1R)–targeted therapy is an exciting approach for cancer treatment. However, when translated into clinical trials, IGF-1R–specific antibodies did not fulfill expectations. Despite promising responses Ewing’s sarcoma (ES) phase I/II III trials were discouraging, requiring bedside-to-bench translation and functional reevaluation of the drugs. The anti-IGF-1R antibody figitumumab (CP-751,871; CP) was designed...
The cancer burden in the Nordic European countries remains substantial, but new treatment approaches, such as targeted therapy, have increased survival of patients. During and following regimens, however, patients' quality life may be severely affected by sequelae, including cutaneous adverse events (cAEs). Overall, practical clinical tools for management cAEs patients survivors been lacking. Cutaneous Oncodermatology Management (NECOM) project addresses patients, aiming to identify specific...
Craniopharyngioma is a rare benign intracranial epithelial tumor that, however, often recurs and sometimes kills the affected patients, one-third of which are children. In many cases, patients acquire growth hormone deficiency postoperatively need substitution. Generally, promotes local release insulin-like factor I (IGF-I), in turn activates IGF-I receptor (IGF-IR) if present. Together, these circumstances raise question whether IGF-IR may be involved craniopharyngioma growth. To address...
The initial event upon binding of insulin-like growth factor 1 to the type-I receptor (IGF-1R) is auto-phosphorylation tyrosine residues within activation loop kinase domain followed by phosphorylation other and subsequent intracellular signaling cascades. We found recently that cyclolignan picropodophyllin (PPP) inhibits IGF-1R phosphatidyl-3 kinase/Akt (protein B) molecules without interfering with highly homologous insulin receptor. Furthermore, PPP causes regression tumor grafts...
Radiotherapy is often used to treat lentigo maligna. However, the long-term efficacy and safety of radiotherapy approaches have not been thoroughly evaluated. We aimed evaluate ultrasoft X-ray/Grenz ray treatment in those patients. A total 161 lesions from 159 patients received with Grenz between 2005 2007. Follow-up recurrence was performed 10 years after final treatment. In study setting, cure rates were 97% for primary therapy alone 100% when combined partial or radical excision. The well...
Abstract Background Metformin use has been associated with improved survival in patients different types of cancer, but research regarding the effect metformin on cutaneous melanoma (CM) is sparse and inconclusive. Objectives To investigate association between among CM diabetes. Methods All adult a primary invasive 2007 2014 were identified Swedish Melanoma Registry followed until death, or end follow-up 31 December 2017 this population-based cohort study. Patients both type 2 diabetes...
Although clinical guidelines exist, the management of patients with cutaneous melanoma (CM) is a complex process that may vary between different care providers potential dysfunctions ultimately mirrored in overall patient satisfaction. The aim present study was to investigate CM as related lead times, surgical quality and diagnosis communication hypothesis differ disparities impact Medical records 181 were retrospectively analyzed parallel satisfaction evaluation by telephone interviews....
Abstract Background The survival in metastatic melanoma has dramatically improved after the introduction of immune checkpoint‐ (ICIs) and MAPKinase inhibitors (MAPKis). Objective Our aim was to describe therapy response a real‐world population as well assess associations between clinical variables outcome for patients with receiving first‐line ICIs or MAPKis. Methods A total 252 (stage IV) were prospectively followed 1 January 2010 3 December 2017 follow‐up until 31 March 2019, at Karolinska...
Nevus-associated lentigo maligna and melanoma (NALMM) are rarely described in the literature considered an incidental finding. This study aimed to evaluate frequency of NALMM its clinicopathological features. A total 201 histopathology reports were reviewed among them 20% samples corresponded NALMM, with females overrepresented this group (p = 0.02). significant association was also observed between presence multiple nevi 0.01), dysplastic 0.04). Moreover, risk developing a second...
<p>Effect of β-arrestin isoform imbalance on survival patients with metastatic melanoma.</p>
<p>Table S2. Antibodies used in this study.</p>