Acacia senegal gum exudate offers protection against cyclophosphamide-induced urinary bladder cytotoxicity

Cylophosphamide (CYCL) is a strong anticancer and immunosuppressive agent but its urotoxicity presents one of the major toxic effects that limit its wide usage particularly in high dose regimens. Therefore, this study aimed to investigate Acacia Senegal gum exudate, Gum Arabic (GA), for its possible role as a natural, nontoxic agent against CYCL-induced urotoxicity. Male Swiss albino rats were exposed to CYCL (150 mg/kg BW, once i.p) with or without GA oral supplementation (7.5 g/kg/day for 6 days) through drinking water. Glutathione (GSH), Malondialdehyde (MDA) and Nitric oxide (NO) bladder contents were assessed. Responsiveness of the bladder rings to acetylcholine (ACh) in vitro, microscopic and macroscopic features are also investigated. CYCL produced pronounced harmful effects on bladder urothelial lining with significant increases in (MDA) and NO levels in the tissue homogenates. Bladder-GSH content is dropped by over 60% following CYCL injection. Bladder contractility, as measured by its responsiveness to ACh, recorded a marked reduction. The isolated bladders exhibited such macroscopic changes as severe edema, inflammation and extravasation. The bladder weight increased as well. Histological changes were evident in the form of severe congestion, petechial hemorrhage and chronic inflammatory reaction in the lamina propria accompanied with desquamated epithelia. GA, a potential protective agent, produced an almost complete reversal of NO induction, lipid peroxidation or cellular GSH bladder contents in the GA + CYCL-treated group. Likewise, bladder inflammation and edema were reduced. Bladder rings showed a remarkable recovery in their responsiveness to ACh. Bladder histological examination showed a near normal configuration and structural integrity, with a significant reduction in inflammation and disappearance of focal erosions. These remarkable effects of GA may be attributed to its ability to neutralize acrolein, the reactive metabolite of CYCL and/or the resultant reactive oxygen metabolites, through a scavenging action. GA may limit the cascading events of CYCL-induced damage, initiating a cytoprotective effect leading to structural and functional recovery of the bladder tissues

Volumetric-modulated arc therapy (VMAT) versus 3D-conformal radiation therapy in supra-diaphragmatic Hodgkin’s Lymphoma with mediastinal involvement: A dosimetric comparison

Purpose: To compare volumetric-modulated arc therapy (VMAT) with 3D-conformal radiation therapy (3D-CRT) mediastinal irradiation for stage I–II supra-diaphragmatic Hodgkin’s Lymphoma (HL). Patients and methods: Eleven patients were planned for RT after 4–6 cycles of ABVD chemotherapy: conventional 3D-CRT (AP/PA) and VMAT plans were conformed to the same PTV. Objective was to choose the best PTV coverage plan with the least OAR dose. The 2 plans were compared for: PTV coverage, mean dose and V5,V20lung, mean dose and V30heart, V5, V10, V15breast (female patients), and the integral body dose. Results: Both techniques achieved adequate PTV coverage. Mean lung and heart dose was consistently lower in VMAT plans. The lung V20 dose was acceptable for VMAT, but exceeded the tolerance threshold in 6 cases with 3DCRT plans. A mean difference of 15.9% for both lungs V20 favored VMAT plans; average MLD difference was 2.3 Gy less for VMAT plans. Similarly, lower maximum and mean heart doses with a 3.3 Gy dose reduction and a 9.4% difference in V30 favored VMAT plans. Mean V5lung/female breast and integral dose were invariably higher in VMAT plans because of the low-dose spread. Conclusions: VMAT is a valuable technique for treatment of large mediastinal HL. VMAT spares the lung and heart compared to 3DCRT using ISRT in select HL cases. VMAT allows dose escalation for post-chemotherapy residual disease with minimal dose to OARs. VMAT low radiation dose (V5) to the normal tissues, and the increased integral dose should be considered

Impact of Pathologic Complete Response following Neoadjuvant Chemotherapy ± Trastuzumab in Locally Advanced Breast Cancer

Purpose. This study was designed to examine the relationship between breast cancer molecular subtypes and pathological response to neoadjuvant chemotherapy (NAC) ± trastuzumab, in locally advanced breast cancer (LABC). Methods. Female patients with LABC (T2–T4, N0–N2, and M0) who received neoadjuvant chemotherapy + trastuzumab if HER2+ subtype, followed by surgery and radiotherapy ± hormonal therapy, were identified. The primary endpoint was pathologic complete response (pCR) in the breast and axilla (ypT0/ypN0), with final analysis on disease-free survival (DFS) and overall survival (OS). Results. Six hundred eighty-one patients with a median age of 44 years, premenopausal: 70%, median tumour size: 7.0 cm (range 4–11 cm), stage II B: 27% and III A/III B: 73%, ER+/HER2−: 40.8%, ER−/HER2−: 23%, ER+/HER2+: 17.7%, and ER−/HER2+: 18.5%. Overall pCR (ypT0/ypN0) was 23%. The pCR rates based on molecular subtypes were ER+/HER2−: 9%; ER+/HER2+: 29%; ER−/HER2−: 31%; and ER−/HER2+: 37%. At median follow-up of 61 months, ER+/HER2+ and ER+/HER2− subtypes had the best 5-year DFS and OS; meanwhile, ER−/HER2+ and ER−/HER2− subtypes had the worst. Conclusion. Women with ER+/HER2− disease are the least likely to achieve pCR, with the highest rates in HER2+ and triple-negative subgroups. Degree of response is associated with OS; despite the comparatively higher likelihood of achieving pCR in ER−/HER2+ and triple-negative, these subgroups experience a survival detriment. We are consistent with the published data that patients who attain the pathological complete response defined as ypT0/ypN0 have improved outcomes