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  • 1
    Online Resource
    Online Resource
    The HIV Protease Inhibitors Saquinavir, Ritonavir, and Nelfinavir Induce Apoptosis and Decrease Barrier Function in Human Intestinal Epithelial Cells
    SAGE Publications ; 2005
    In:  Antiviral Therapy Vol. 10, No. 5 ( 2005-07), p. 645-655
    Details
    In: Antiviral Therapy, SAGE Publications, Vol. 10, No. 5 ( 2005-07), p. 645-655
    Abstract: Diarrhoea is a frequent adverse effect of HIV protease inhibitors (PIs) which may be due to intestinal barrier disruption. We investigated whether tight junction dysregulation, apoptosis or necrosis are responsible for this epithelial damage. Methods Saquinavir, nelfinavir, and ritonavir were added to the mucosal or serosal side of HT-29/B6 colon cell monolayers. Transepithelial resistance was monitored for 72 h to assess epithelial barrier function. Apoptosis and necrosis were investigated by light and electron microscopy and quantified by nucleosome ELISA and LDH measurement, respectively. Tight junction components were analysed by Western blots of occludin and zonula occludens. Apoptosis induction in normal human intestinal epithelium was examined by measurement of poly(ADP-ribose) polymerase (PARP) cleavage in Western blots of mucosal tissue explants cultured with PIs for 24 h. Results HIV PIs decreased transepithelial resistance by more than 44% in HT-29/B6 monolayers. Histology revealed massive apoptotic body formation but no evidence for necrosis after PI treatment. Correspondingly, LDH release was lower than 0.2%/h of total LDH, independent of PI treatment, and nucleosomes were increased up to 22-fold after drug treatment versus control. Occludin and zonula occludens-1 expression in the membrane were not diminished. PARP cleavage increased in normal human intestinal tissue treated with PIs. Conclusions PI-induced barrier disruption in intestinal epithelial cells is not due to necrosis or tight junction alterations, but to induction of massive apoptosis which may lead to leak-flux diarrhoea in vivo. Our findings suggest that induction of apoptosis by PIs could have potential for antitumour therapy.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    URL: Article
    DOI: 10.1177/135965350501000506
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2005
    detail.hit.zdb_id: 2118396-X
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  • 2
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    Assessment of the additional clinical potential of X-ray dark-field imaging for breast cancer in a preclinical setup
    SAGE Publications ; 2020
    In:  Therapeutic Advances in Medical Oncology Vol. 12 ( 2020-01), p. 175883592095793-
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    In: Therapeutic Advances in Medical Oncology, SAGE Publications, Vol. 12 ( 2020-01), p. 175883592095793-
    Abstract: Mammography can identify calcifications up to 50–100 μm in size as a surrogate parameter for breast cancer or ductal carcinoma in situ (DCIS). Microcalcifications measuring 〈 50 µm are also associated with breast cancer or DCIS and are frequently not detected on mammography, although they can be detected with dark-field imaging. This study examined whether additional breast examination using X-ray dark-field imaging can increase the detection rate of calcifications. Advances in knowledge:  (1) evaluation of additional modality of breast imaging;  (2) specific evaluation of breast calcifications. Implications for patient care: the addition of X-ray dark-field imaging to conventional mammography could detect additional calcifications. Methods: Talbot–Lau X-ray phase–contrast imaging and X-ray dark-field imaging were used to acquire images of breast specimens. The radiation dosage with the technique is comparable with conventional mammography. Three X-ray gratings with periods of 5–10 µm between the X-ray tube and the flat-panel detector provide three different images in a single sequence: the conventional attenuation image, differential phase image, and dark-field image. The images were read by radiologists. Radiological findings were marked and examined pathologically. The results were described in a descriptive manner. Results: A total of 81 breast specimens were investigated with the two methods; 199 significant structures were processed pathologically, consisting of 123 benign and 76 malignant lesions (DCIS or invasive breast cancer). X-ray dark-field imaging identified 15 additional histologically confirmed carcinoma lesions that were visible but not declared suspicious on digital mammography alone. Another four malignant lesions that were not visible on mammography were exclusively detected with X-ray dark-field imaging. Conclusions: Adding X-ray dark-field imaging to digital mammography increases the detection rate for breast cancer and DCIS associated lesions with micrometer-sized calcifications. The use of X-ray dark-field imaging may be able to provide more accurate and detailed radiological classification of suspicious breast lesions. Adding X-ray dark-field imaging to mammography may be able to increase the detection rate and improve preoperative planning in deciding between mastectomy or breast-conserving therapy, particularly in patients with invasive lobular breast cancer.
    Type of Medium: Online Resource
    ISSN: 1758-8359 , 1758-8359
    URL: Article
    DOI: 10.1177/1758835920957932
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
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