Fibroblast-Derived MMP-14 Regulates Collagen Homeostasis in Adult Skin.
Journal of Investigative Dermatology 136(8):1575 (2016)
Proteolytic activities in the extracellular matrix by the matrix metalloproteinase (MMP)-14 have been implicated in the remodeling of collagenous proteins during development. To analyze the function of fibroblast-derived MMP-14 in adult skin homeostasis, we generated mice with inducible deletion...
Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial.
The Lancet Oncology 17(6):757 (2016)
Complete lymph node dissection is recommended in patients with positive sentinel lymph node biopsy results. To date, the effect of complete lymph node dissection on prognosis is controversial. In the DeCOG-SLT trial, we assessed whether complete lymph node dissection resulted in increased surviv...
Oncogene and therapeutic target analyses in atypical fibroxanthomas and pleomorphic dermal sarcomas.
Oncotarget 7(16):21763 (2016)
Until now, almost nothing is known about the tumorigenesis of atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS). Our hypothesis is that AFX is the non-infiltrating precursor lesion of PDS.
We performed the world-wide most comprehensive immunohistochemical and mutational analysis ...
The impact of sequencing on diagnosis and treatment of malignant melanoma.
Expert Review of Molecular Diagnostics 16(4):423 (2016)
Melanoma is one of the clinically most important cancer types considering its high mortality rate and that it is commonly diagnosed in relatively young people. With the advent of targeted therapies and, more recently, immune checkpoint inhibitors, more treatment options are available resulting i...
Intermittent High-Dose Intravenous Interferon Alfa-2b for Adjuvant Treatment of Stage III Melanoma: Final Analysis of a Randomized Phase III Dermatologic Cooperative Oncology Group Trial.
Journal of Clinical Oncology 33(34):4077 (2015)
To evaluate the efficacy, safety, tolerability, and quality of life (QoL) in patients receiving intravenous, intermittent high-dose interferon alfa-2b (IFN-α-2b [iHDI]) compared with standard high-dose IFN-α-2b (HDI).
Patients with stage III resected lymph node or in-transit metastasis from cuta...
Nivolumab improved survival vs dacarbazine in patients with untreated advanced melanoma.
Journal of Translational Medicine 13(1):2063 (2015)
Identification and clinical relevance of PD-L1 expression in primary mucosal malignant melanoma of the head and neck.
Melanoma Research 25(6):503 (2015)
Mucosal melanoma of the head and neck is a rare and aggressive tumor entity with a poor prognosis. The standard treatment is radical tumor resection, with or without adjuvant radiation, where conventional chemotherapies in advanced stage or recurrent diseases have shown little benefit. Overexpre...
A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer
Cell 162(5):1169 (2015)
A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer.
Cell 162(1):146 (2015)
KRAS is one of the most frequently mutated oncogenes in human cancer. Despite substantial efforts, no clinically applicable strategy has yet been developed to effectively treat KRAS-mutant tumors. Here, we perform a cell-line-based screen and identify strong synergistic interactions between cell...
IAP antagonization promotes inflammatory destruction of vascular endothelium.
EMBO Reports 16(6):719 (2015)
In this study, we show for the first time that the therapeutic antagonization of inhibitor of apoptosis proteins (IAPs) inhibits B16 melanoma growth by disrupting tumor vasculature. Specifically, the treatment of mice bearing B16 melanoma with an IAP antagonist compound A (Comp A) inhibits tumor...
Enhanced FHL2 and TGF-β1 Expression Is Associated With Invasive Growth and Poor Survival in Malignant Melanomas.
American Journal of Clinical Pathology 143(2):248 (2015)
This study examines the expression and the role of four-and-a-half LIM domains protein 2 (FHL2) and transforming growth factor β1 (TGF-β1) in human malignant melanoma. It is determined whether both proteins influence melanoma survival time.
We analyzed the immunohistochemical staining intensitie...
TGF-β1-dependent induction and nuclear translocation of FHL2 promotes keratin expression in pilomatricoma.
Virchows Archiv. A. Pathological Anatomy and Hi... 466(2):199 (2015)
Pilomatricoma is a tumour derived from hair matrix cells, which shows progressive keratin expression. Tumorigenesis is frequently associated with activating mutations in β-catenin gene inducing nuclear expression of β-catenin protein. The present study analysed the role of transforming growth fa...
Nivolumab in previously untreated melanoma without BRAF mutation.
New England Journal of Medicine 372(4):320 (2015)
Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma. The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study....
Matrix metalloproteinase 14 is required for fibrous tissue expansion.
eLife 4:e09345 (2015)
Type I collagen-containing fibrils are major structural components of the extracellular matrix of vertebrate tissues, especially tendon, but how they are formed is not fully understood. MMP14 is a potent pericellular collagenase that can cleave type I collagen in vitro. In this study, we show th...
Host response to human breast Invasive Ductal Carcinoma (IDC) as observed by changes in the stromal proteome.
Journal of Proteome Research 13(11):4739 (2014)
Following initial transformation, tumorigenesis, growth, invasion, and metastasis involves a complex interaction between the transformed tissue and the host, particularly in the microenvironment adjacent to the developing tumor. The tumor microenvironment itself is a unique outcome of the host r...
Ocular diseases in metastatic cutaneous melanoma: review of 108 consecutive patients in two German tertiary centers.
Graefe's Archive for Clinical and Experimental ... 252(4):679 (2014)
To analyze the incidence and spectrum of ocular disease in patients with metastatic cutaneous melanoma.
One hundred and eight consecutive patients with metastatic cutaneous melanoma were screened for ocular diseases using standardized eye examination, including measurement of visual acuity and i...
Health-related quality of life, fatigue, and depression under low-dose IFN-α therapy in melanoma patients.
Journal of Immunotherapy 37(9):461 (2014)
Adjuvant melanoma treatment with interferon-α (IFN-α) has proven to be accompanied by several side effects and to decrease patients' health-related quality of life (HRQOL), fatigue and depression being essential factors at that. Although a large body of evidence exists for HRQOL under IFN-α ther...
Loss of epidermal Evi/Wls results in a phenotype resembling psoriasiform dermatitis.
Journal of Experimental Medicine 210(9):1761 (2013)
Cells of the epidermis renew constantly from germinal layer stem cells. Although epithelial cell differentiation has been studied in great detail and the role of Wnt signaling in this process is well described, the contribution of epidermal Wnt secretion in epithelial cell homeostasis remains po...
Enhanced deposition of cartilage oligomeric matrix protein is a common feature in fibrotic skin pathologies.
Matrix Biology 32(6):325 (2013)
Skin fibrosis is characterized by activated fibroblasts and an altered architecture of the extracellular matrix. Excessive deposition of extracellular matrix proteins and altered cytokine levels in the dermal collagen matrix are common to several pathological situations such as localized sclerod...
Proteomic anatomy of human skin.
Journal of Proteomics 84:190 (2013)
The extracellular matrix is composed of a variety of proteins which are essential for growth, wound healing, and fibrosis. It provides both structural support as well as contributing to the regulation of the local microenvironment. To further characterize the molecular composition of human skin ...