The burden of Respiratory Tract Infections (RTIs) in children and adults is very high, especially... more The burden of Respiratory Tract Infections (RTIs) in children and adults is very high, especially in developing countries. At least 1.9 million children throughout the world died from acute RTIs in 2000, 70% of them in Africa and Southeast Asia. As causative therapies of these frequently recurring infections have substantial limits, preventive measures deserve priority. Among these, non-specific immunostimulation with bacterial extracts has been shown to prevent recurrent RTIs and to be very safe. The aim of this review is to focus on the immunostimulating agent OM-85, a biotechnology-derived lyophilised extract from eight bacteria frequently responsible for RTIs and formulated for oral administration. The topics will cover its pharmacological effects, its actions in clinical practice regarding both efficiency and safety, as well as pharmacoeconomic studies. A particular emphasis will be put on trials conducted in children, in adults suffering from chronic obstructive pulmonary diseases (COPD) and in special patient populations.
Exposure of tumor cells to ionizing radiation (IR) is widely known to induce a number of cellular... more Exposure of tumor cells to ionizing radiation (IR) is widely known to induce a number of cellular changes. One way that IR can affect tumor cells is through the development of neoantigens which are new molecules that tumor cells express at the cell membrane following some insult or change to the cell. There have been numerous reports in the literature of changes in both tumor and tumor vasculature cell surface molecule expression following treatment with IR. The usefulness of neoantigens for imaging and therapeutic applications lies in the fact that they are differentially expressed on the surface of irradiated tumor cells to a greater extent than on normal tissues. This differential expression provides a mechanism by which tumor cells can be "marked" by radiation for further targeting. Drug delivery vehicles or imaging agents conjugated to ligands that recognize and interact with the neoantigens can help to improve tumor-specific targeting and reduce systemic toxicity wit...
Vaginal cylinder high-dose-rate (HDR) brachytherapy is currently one of the most common procedure... more Vaginal cylinder high-dose-rate (HDR) brachytherapy is currently one of the most common procedures performed in the treatment of early-stage endometrial cancer. However, current recommendations by the American Brachytherapy Society regarding fractional re-imaging and dose calculation for organs at risk for HDR vaginal cuff brachytherapy are not well defined. In this study, we aim to compare a fractional re-imaging approach using computed tomographic (CT) scans prior to each fraction with a first fraction imaging-only approach with respect to bladder, rectal, and bowel dosimetry. Nineteen endometrial cancer patients undergoing vaginal cuff brachytherapy for endometrial cancer were imaged with CT scanning prior to every HDR fraction (fractional re-imaging [FRI]). Dose to the bowel, bladder, and rectum were calculated and compared with the estimated dose if imaging and planning were done only on the first fraction (first fraction imaging [FFI]). In the analysis of FFI versus FRI, we observed mean bladder doses of 8.34 Gy vs 8.33 Gy (P = .98), mean rectal doses of 12.19 Gy versus 12.14 Gy (P = .81), and mean bowel doses of 2.82 Gy versus 2.76 Gy (P = .81). The FFI approach underestimated the FRI doses to the bladder, rectum, and bowel by 20% or more in 11%, 5%, and 29% of patients, respectively. Cost analysis revealed an estimated $663.06, or a 35% savings per patient treated with FFI. There is no statistically significant difference in the mean dose to the bladder, rectum, or bowel in patients undergoing HDR vaginal cuff brachytherapy with a first fraction imaging scheme versus a fractional re-imaging scheme. These results indicate that fractional re-imaging is not necessary except in patients whose estimated dose to critical organs is near the maximum limit.
An early and reliable assessment of therapeutic efficacy during the treatment of cancer is essent... more An early and reliable assessment of therapeutic efficacy during the treatment of cancer is essential to achieve an optimal treatment regimen and patient outcome. The use of labeled peptides to monitor tumor response is associated with several advantages. For example, peptides are very stable, non-immunogenic, are easy to label for imaging, they undergo rapid clearance from the circulation, can penetrate tumor tissue, and are inexpensive to synthesize. In this review, studies using recombinant and non-recombinant peptides to monitor the response of glioblastoma multiforme, lung, breast, pancreas, colon, prostate, and skin carcinomas to radiation and/or chemotherapeutics such as camptothecin, doxorubicin, etoposide, 5-fluorouracil, paclitaxel, AG3340, sunitinib, and dasatinib, are presented. A consideration of the imaging techniques available to monitor peptide localization, including near-infrared (NIR) fluorescence, magnetic resonance imaging (MRI), positron emission tomography (PET), and ultrasonography, is also included. Peptides that have been successfully used to monitor various tumor types and therapies have been shown to target proteins that undergo changes in expression in response to treatment, endothelial cells that respond to radiation, or mediators of apoptosis. Peptides that are able to selectively bind responsive versus unresponsive tumors have also been identified. Therefore, the advantages associated with the use of peptides, combined with the capacity for selected peptides to assess tumor response as demonstrated in various studies, support the use of labeled peptides to evaluate the effectiveness of a given cancer therapy.
The burden of Respiratory Tract Infections (RTIs) in children and adults is very high, especially... more The burden of Respiratory Tract Infections (RTIs) in children and adults is very high, especially in developing countries. At least 1.9 million children throughout the world died from acute RTIs in 2000, 70% of them in Africa and Southeast Asia. As causative therapies of these frequently recurring infections have substantial limits, preventive measures deserve priority. Among these, non-specific immunostimulation with bacterial extracts has been shown to prevent recurrent RTIs and to be very safe. The aim of this review is to focus on the immunostimulating agent OM-85, a biotechnology-derived lyophilised extract from eight bacteria frequently responsible for RTIs and formulated for oral administration. The topics will cover its pharmacological effects, its actions in clinical practice regarding both efficiency and safety, as well as pharmacoeconomic studies. A particular emphasis will be put on trials conducted in children, in adults suffering from chronic obstructive pulmonary diseases (COPD) and in special patient populations.
Exposure of tumor cells to ionizing radiation (IR) is widely known to induce a number of cellular... more Exposure of tumor cells to ionizing radiation (IR) is widely known to induce a number of cellular changes. One way that IR can affect tumor cells is through the development of neoantigens which are new molecules that tumor cells express at the cell membrane following some insult or change to the cell. There have been numerous reports in the literature of changes in both tumor and tumor vasculature cell surface molecule expression following treatment with IR. The usefulness of neoantigens for imaging and therapeutic applications lies in the fact that they are differentially expressed on the surface of irradiated tumor cells to a greater extent than on normal tissues. This differential expression provides a mechanism by which tumor cells can be "marked" by radiation for further targeting. Drug delivery vehicles or imaging agents conjugated to ligands that recognize and interact with the neoantigens can help to improve tumor-specific targeting and reduce systemic toxicity wit...
Vaginal cylinder high-dose-rate (HDR) brachytherapy is currently one of the most common procedure... more Vaginal cylinder high-dose-rate (HDR) brachytherapy is currently one of the most common procedures performed in the treatment of early-stage endometrial cancer. However, current recommendations by the American Brachytherapy Society regarding fractional re-imaging and dose calculation for organs at risk for HDR vaginal cuff brachytherapy are not well defined. In this study, we aim to compare a fractional re-imaging approach using computed tomographic (CT) scans prior to each fraction with a first fraction imaging-only approach with respect to bladder, rectal, and bowel dosimetry. Nineteen endometrial cancer patients undergoing vaginal cuff brachytherapy for endometrial cancer were imaged with CT scanning prior to every HDR fraction (fractional re-imaging [FRI]). Dose to the bowel, bladder, and rectum were calculated and compared with the estimated dose if imaging and planning were done only on the first fraction (first fraction imaging [FFI]). In the analysis of FFI versus FRI, we observed mean bladder doses of 8.34 Gy vs 8.33 Gy (P = .98), mean rectal doses of 12.19 Gy versus 12.14 Gy (P = .81), and mean bowel doses of 2.82 Gy versus 2.76 Gy (P = .81). The FFI approach underestimated the FRI doses to the bladder, rectum, and bowel by 20% or more in 11%, 5%, and 29% of patients, respectively. Cost analysis revealed an estimated $663.06, or a 35% savings per patient treated with FFI. There is no statistically significant difference in the mean dose to the bladder, rectum, or bowel in patients undergoing HDR vaginal cuff brachytherapy with a first fraction imaging scheme versus a fractional re-imaging scheme. These results indicate that fractional re-imaging is not necessary except in patients whose estimated dose to critical organs is near the maximum limit.
An early and reliable assessment of therapeutic efficacy during the treatment of cancer is essent... more An early and reliable assessment of therapeutic efficacy during the treatment of cancer is essential to achieve an optimal treatment regimen and patient outcome. The use of labeled peptides to monitor tumor response is associated with several advantages. For example, peptides are very stable, non-immunogenic, are easy to label for imaging, they undergo rapid clearance from the circulation, can penetrate tumor tissue, and are inexpensive to synthesize. In this review, studies using recombinant and non-recombinant peptides to monitor the response of glioblastoma multiforme, lung, breast, pancreas, colon, prostate, and skin carcinomas to radiation and/or chemotherapeutics such as camptothecin, doxorubicin, etoposide, 5-fluorouracil, paclitaxel, AG3340, sunitinib, and dasatinib, are presented. A consideration of the imaging techniques available to monitor peptide localization, including near-infrared (NIR) fluorescence, magnetic resonance imaging (MRI), positron emission tomography (PET), and ultrasonography, is also included. Peptides that have been successfully used to monitor various tumor types and therapies have been shown to target proteins that undergo changes in expression in response to treatment, endothelial cells that respond to radiation, or mediators of apoptosis. Peptides that are able to selectively bind responsive versus unresponsive tumors have also been identified. Therefore, the advantages associated with the use of peptides, combined with the capacity for selected peptides to assess tumor response as demonstrated in various studies, support the use of labeled peptides to evaluate the effectiveness of a given cancer therapy.
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Papers by Roberto Diaz