Atypical fibroxanthoma is a malignant skin tumor with histologic features similar to those of undifferentiated pleomorphic sarcoma, but lacking its more aggressive behavior. The tumor is composed of pleomorphic cells with hyperchromatic nuclei and abundant cytoplasm, commonly arranged in a spindle cell pattern. Recent genetic studies have identified similarities between atypical fibroxanthoma and undifferentiated pleomorphic sarcoma, such as the presence of 9p and 13q deletions in both tumors, favoring a common histogenesis. However, the lack of K-ras and H-ras mutations in atypical fibroxanthoma compared with undifferentiated pleomorphic sarcoma could explain the difference in aggressiveness and continued separation of these entities. Exclusion of other neoplasms by histology and immunohistochemistry followed by complete surgical removal remains the standard of care.
In this study, electrochemical impedance spectroscopy was used for the first time to study the adsorption of dopamine in carbon fiber microelectrodes. In order to show a proof-of-concept, static and dynamic measurements were taken at potentials ranging from -0.4 to 0.8 V versus Ag|AgCl to demonstrate the versatility of this technique to study dopamine without the need of its oxidation. We used electrochemical impedance spectroscopy and single frequency electrochemical impedance to measure different concentrations of dopamine as low as 1 nM. Moreover, the capacitance of the microelectrodes surface was found to decrease due to dopamine adsorption, which is dependent on its concentration. The effect of dissolved oxygen and electrochemical oxidation of the surface in the detection of dopamine was also studied. Nonoxidized and oxidized carbon fiber microelectrodes were prepared and characterized by optical microscopy, scanning electron microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. Optimum working parameters of the electrodes, such as frequency and voltage, were obtained for better measurement. Electrochemical impedance of dopamine was determined at different concentration, voltages, and frequencies. Finally, dynamic experiments were conducted using a flow cell and single frequency impedance in order to study continuous and real-time measurements of dopamine.
Changes in mitochondrial DNA (mtDNA) integrity have been reported in many cancers, however, the contribution of mtDNA integrity to tumorigenesis is not well understood. We used a transgenic mouse model that is haploinsufficient for the apurinic/apyrimidinic endonuclease 1 (Apex1+/-) gene, which encodes the base excision repair (BER) enzyme APE1, to determine its role in protecting mtDNA from the effects of azoxymethane (AOM), a carcinogen used to induce colorectal cancer (CRC). Repair kinetics of AOM-induced mtDNA damage was evaluated using quantitative PCR after a single AOM dose and a significant induction in mtDNA lesions in colonic crypts from both wild type (WT) and Apex1+/-animals were observed. However, Apex1+/- mice had slower repair kinetics in addition to decreased mtDNA abundance. Tumors were also induced using multiple AOM doses and both WT and Apex1+/-animals exhibited significant loss in mtDNA abundance. Surprisingly, no major differences in mtDNA lesions were observed in tumors from WT and Apex1+/-animals, whereas a significant increase in nuclear DNA lesions was detected in tumors from Apex1+/- mice. Finally, tumors from Apex1+/-mice displayed an increased proliferative index and histological abnormalities. Taken together, these results demonstrate that APE1 is important for preventing changes in mtDNA integrity during AOM-induced CRC.
Implications: Azoxymethane, a colorectal cancer carcinogen, generates damage to the mitochondrial genome and the BER enzyme APE1 is required to maintain its integrity.
Stereotactic radiosurgery (SRS) poses a minimal but important risk for tumour transformation, typically occurring 8–10 years after the treatment. Malignant peripheral nerve sheath tumour (MPNST) is the most common tumour arising from a vestibular schwannoma treated with SRS, with only 14 cases previously reported. We present the fifteenth case and describe its evolution and clinical course. A 56-year-old man without a history of neurofibromatosis was diagnosed 9 years prior with a vestibular schwannoma. SRS to the residual tumour was given 3 months later. During the current hospitalisation, he was reoperated where histology confirmed a MPNST. All 15 MPNST cases were analysed, showing a 77% female predominance presenting a malignant transformation at a mean age of 51. The diagnosis was made at a mean time of 74 months after SRS. The mean survival time after diagnosis was 16 months. MPNST arising from benign vestibular schwannoma after SRS treatment is an uncommon but devastating complication.
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