ArticleNeuro-oncology2013
Clinical significance and novel mechanism of action of kallikrein 6 in glioblastoma.
Article in Neuro-oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- Cutaneous Melanoma: An Overview of Physiological and Therapeutic Aspects and Biotechnological Use of Serine Protease Inhibitors.Molecules (Basel, Switzerland) · 2024Review
- The peritumoral brain zone in glioblastoma: where we are and where we are going.Journal of neuroscience research · 2023Review
- Remodelling of the tumour microenvironment by the kallikrein-related peptidases.Nature reviews. Cancer · 2022Review
- KLK6 Functions as an Oncogene and Unfavorable Prognostic Factor in Bladder Urothelial Carcinoma.Disease markers · 2022Article
- Kallikrein-Related Peptidase 6 Is Associated with the Tumour Microenvironment of Pancreatic Ductal Adenocarcinoma.Cancers · 2021Article
- Transcriptome profiling reveals PDZ binding kinase as a novel biomarker in peritumoral brain zone of glioblastoma.Journal of neuro-oncology · 2019Article
- Kallikrein-related peptidase 6 orchestrates astrocyte form and function through proteinase activated receptor-dependent mechanisms.Biological chemistry · 2018Article
- The Thrombin Receptor Restricts Subventricular Zone Neural Stem Cell Expansion and Differentiation.Scientific reports · 2018Article
- Network-based analysis of oligodendrogliomas predicts novel cancer gene candidates within the region of the 1p/19q co-deletion.Acta neuropathologica communications · 2018Article
- Kallikrein-related peptidase 6 (KLK6) expression differentiates tumor subtypes and predicts clinical outcome in breast cancer patients.Clinical and experimental medicine · 2018Article
- Neuro-Immune Hemostasis: Homeostasis and Diseases in the Central Nervous System.Frontiers in cellular neuroscience · 2018Review
- Neuro-Coagulopathy: Blood Coagulation Factors in Central Nervous System Diseases.International journal of molecular sciences · 2017Review
- Expression of Kallikrein-Related Peptidase 6 in Primary Mucosal Malignant Melanoma of the Head and Neck.Head and neck pathology · 2017Article
- Specific microRNA-mRNA Regulatory Network of Colon Cancer Invasion Mediated by Tissue Kallikrein-Related Peptidase 6.Neoplasia (New York, N.Y.) · 2017Article
- Article
- Targeting the thrombin receptor modulates inflammation and astrogliosis to improve recovery after spinal cord injury.Neurobiology of disease · 2016Article
- The brain tissue response to surgical injury and its possible contribution to glioma recurrence.Journal of neuro-oncology · 2016Review
- Kallikreins - The melting pot of activity and function.Biochimie · 2016Review
- Article
- Thrombin Activity and Thrombin Receptor in Rat Glioblastoma Model: Possible Markers and Targets for Intervention?Journal of molecular neuroscience : MN · 2015Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundKallikreins have prognostic value in specific malignancies, but few studies have addressed their clinical significance to glioblastoma multiforme (GBM). Kallikrein 6 (KLK6) is of potential high relevance to GBM, since it is upregulated at sites of CNS pathology and linked to reactive astrogliosis. Here we examine the clinical value of KLK6 as a prognostic indicator of GBM patient survival and its activity in promoting resistance to cytotoxic agents.
methodsThe association between patient survival and levels of KLK6 immunoreactivity were investigated in 60 grade IV astrocytoma tumor specimens. Levels of KLK6 RNA were also evaluated in a separate set of GBM patient tumors (n = 23). Recombinant KLK6 or enforced KLK6 overexpression in GBM cell lines was used to evaluate effects on astrocytoma cell survival.
resultsA range of KLK6 expression was observed across grade IV tumors, with higher levels a poor prognostic indicator of patient survival (P = .02) even after adjusting for gender and Eastern Cooperative Oncology Group performance scores (P = .01). KLK6 reduced the sensitivity of GBM cell lines to cytotoxic agents, including staurosporine and cisplatin, and to the current standard of patient care: radiotherapy or temozolomide alone or in combination. The ability of KLK6 to promote resistance to apoptosis was dependent on activation of the thrombin receptor, protease activated receptor 1.
conclusionsTaken together, these results indicate that elevated levels of KLK6 in GBM are likely to promote the resistance of tumor cells to cytotoxic agents and are an indicator of reduced patient postsurgical survival times.
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