Integral membrane protease fibroblast activation protein sensitizes fibrosarcoma to chemotherapy and alters cell death mechanisms

Abstract Fibroblast activation protein (FAP), an integral membrane serine protease, is found on fibro- and osteo-sarcoma and on myofibroblasts in epithelial carcinoma, but rarely on other adult tissue. FAP has been demonstrated to be an excellent target for tumor imaging in clinical trials, and antibodies and other FAP-targeting drugs are in development. Here we have shown that FAP overexpression increased the growth of HT1080 fibrosarcoma cells in vitro and in vivo, and found that the expression of FAP affects response to chemotherapy. When treated with doxorubicin, expression of FAP increased susceptibility to the drug. In spite of this, FAP-HT1080 cells had fewer markers of classical apoptosis than HT1080 cells and neither necrosis nor necroptosis were enhanced. However, levels of early mitochondrial and lysosomal membrane permeability markers were increased, and autophagy switched from a protective function in HT1080 cells to part of the cell death mechanism with FAP expression. Therefore, FAP may affect how the tumor responds to chemotherapeutic drugs overall, which should be considered in targeted drug development. The overexpression of FAP also alters cell signaling and responses to the environment in this cell line. This includes cell death mechanisms, changing the response of HT1080 cells to doxorubicin from classical apoptosis to an organelle membrane permeability-dependent form of cell death.
Source: Apoptosis - Category: Molecular Biology Source Type: research

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AbstractThe conformation-dependent activity of azobenzene combretastatin A4 (Azo-CA4) provides a unique approach to reduce the side-effects of chemotherapy, due to the light-triggered conformation transition of its azobenzene moiety. Under hypoxic tumor microenvironment, however, the high expression of azoreductase can reduce azobenzene to aniline. It was postulated that the Azo-CA4 might be degraded under hypoxia, resulting in the decrease of its anti-tumor activity. The aim of this study was to verify such hypothesis in HeLa cellsin vitro. The quantitative drug concentration analysis shows the ratio-metric formation of d...
Source: European Journal of Applied Physiology - Category: Physiology Source Type: research
Effect of unsymmetrical oligo-phenylene-ethynylene OPE3 against multidrug-resistant bacteria in vitro and in vivo. J Chemother. 2020 May 28;:1-9 Authors: Yuan Q, Wang Y, Yao P, Lv J, Wang Q, Sun F, Feng W Abstract The rapid proliferation of multidrug-resistant (MDR) bacterial infections has posed the serious health threats. Photodynamic therapy is considered one of the most promising therapeutic strategies for combating bacterial resistance. In the present study, we synthesized an unsymmetrical oligo-p-phenylene ethynylene (OPE), namely OPE3, and investigated its antimicrobial activity agains...
Source: Journal of Chemotherapy - Category: Cancer & Oncology Tags: J Chemother Source Type: research
Noncutaneous melanomas are rare subtypes of melanoma with high rates of metastatic disease and poor overall survival. One-third to one-half of cases are amelanotic, which may contribute to a delay in diagnosis. Immunohistochemistry staining with typical melanoma markers helps confirm the diagnosis. There is no standard staging system across mucosal melanomas. Elective nodal dissection is not recommended and there is a paucity of data to support use of sentinel lymph node biopsy. Mutational analysis should be routinely performed. Systemic therapy options include targeted inhibitors, immunotherapy, and cytotoxic chemotherapy...
Source: Surgical Oncology Clinics of North America - Category: Surgery Authors: Source Type: research
This study investigated the impact of gross extrathyroidal extension into major neck structures on the prognosis of papillary thyroid carcinoma according to changes in the American Joint Committee on Cancer (AJCC)/Tumor-Node-Metastasis staging system. Overall, 183 patients with gross extrathyroidal extension into major neck structures were enrolled. The 10-year disease-specific survival (DSS) of patients in each stage showed appropriate correlation and stratification with the AJCC eighth edition. However, the 10-year DSS rate in stage III was better than the expected 10-year DSS rate, according to the AJCC eighth edition. ...
Source: Endocrine Journal - Category: Endocrinology Tags: Endocr J Source Type: research
Authors: Kuwabara-Ohmura Y, Iizuka K, Liu Y, Takao K, Nonomura K, Kato T, Mizuno M, Hosomichi K, Tajima A, Miyazaki T, Horikawa Y, Yabe D Abstract Pancreatic tail hypoplasia is a common manifestation of maturity onset diabetes of the young (MODY) 5 that can cause reno-genito-urinary malformations such as renal cysts and bicornuate uterus. A 69-year-old female was admitted to our hospital for consultation on her relatively high HbA1c value. At age 20, she was diagnosed with uterus bicornis. At age 68, she was diagnosed with pancreas tail hypoplasia, renal cysts and non-functioning pancreatic neuroendocrine tumor (NE...
Source: Endocrine Journal - Category: Endocrinology Tags: Endocr J Source Type: research
Publication date: Available online 28 May 2020Source: The LancetAuthor(s): Lennard Y W Lee, Jean Baptiste Cazier, T Starkey, C D Turnbull, UK Coronavirus Cancer Monitoring Project Team, Rachel Kerr, Gary Middleton
Source: The Lancet - Category: General Medicine Source Type: research
Authors: Li J, Liu X, Nan S, Xu C Abstract Aberrant expression of LINC00520 has been identified in head and neck squamous carcinoma (HNSCC). However, its function in the radiosensitivity of HNSCC remain unclear. Herein, we aimed to define the role LINC00520 in the radiosensitivity of HNSCC and identify the underlying mechanism. Tumour tissues and adjacent normal tissue were collected from HNSCC patients. Differentially expressed genes (DEGs) in HNSCC tumour were obtained from the cancer genome atlas (TCGA) database. Interactions between LINC00520 and miR-195, homeobox A10 (HOXA10) and miR-195 were evaluated by dual...
Source: Free Radical Research - Category: Research Tags: Free Radic Res Source Type: research
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Source: Indian Journal of Cancer - Category: Cancer & Oncology Authors: Source Type: research
We present a case where metastatic disease appeared in the lungs 35years after the initial diagnosis, representing the longest reported latency period to metastasis, which unfortunately led to the patient's demise.
Source: Human Pathology: Case Reports - Category: Pathology Source Type: research
This study was aimed at testing reproducibility and utility of this finding. Sixty‐eight SSs and 147 other tumours, in the form of various biopsies, were tested for IHC expression of INI1. Twenty‐six SSs were further confirmed with positive SS18 rearrangement. Forty monophasic spindle cell type (58.8%), 13 biphasic (19.1%), 12 poorly differentiated (17.6%) and three calcifying SSs (4.4%) were positive for epithelial membrane antigen (EMA) (46/62) (74.1%), pan cytokeratin (AE1/AE3) (31/47) (65.9%), cytokeratin (CK7) (20/31) (64.5%), BCL2 (62/66) (93.9%), MIC2 (61/63) (96.8%), transducin‐like enhancer of split 1 (TLE1)...
Source: APMIS - Category: Research Authors: Tags: Original Article Source Type: research
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