Paclitaxel delivery using carrier made from curcumin derivative: Synergism between carrier and the loaded drug for effective cancer treatment

To fully make use of the synergism between paclitaxel and curcumin (CUR) in cancer treatment, carrier made from CUR derivative was synthesized and used to deliver paclitaxel into cancer cells. The methoxylpolyethylene oxide‐linked palmitate‐modified curcumin (mPEO–CUR–PA) was synthesized and the obtained amphiphilic mPEO–CUR–PA molecules were allowed to self‐assemble into microspheres. In vitro release of free CUR from mPEO–CUR–PA in the presence of lipase was proofed and the ability of cells to endocytose mPEO–CUR–PA microspheres was verified. Cytotoxic activity of the mPEO–CUR–PA microspheres toward cancer cell lines (S102 and A549) was evaluated and compared with that of the unmodified CUR. Paclitaxel was then loaded into the microspheres and the paclitaxel‐loaded mPEO–CUR–PA microspheres showed up to fivefold to 44‐fold increased in vitro cytotoxicity (in terms of % cell mortality) in susceptible (HCC‐S102 and A549) and paclitaxel‐resistant (A549RT‐eto) cancer cells, respectively, compared with that of free paclitaxel.     

Clinical outcomes of gastrointestinal stromal tumor in southern Thailand

AIM: To review a single institutional experience in clinical management of gastrointestinal stromal tumors (GIST) and analyze for factors determining treatment outcome. METHODS: Clinicopathological data of patients with a diagnosis of GIST who were treated at our institute during November 2004 to September 2009 were retrospectively reviewed. RESULTS: Ninety-nine cases were included in the analysis. Primary tumor sites were at the stomach in and small bowel in 44% and 33%, respectively. Thirty-one cases already had metastasis at presentation and the most common metastatic site was the liver. Sixty-four cases (65%) were in the high-risk category. Surgical treatment was performed in 77 cases (78%), 3 of whomreceived upfront targeted therapy. Complete resection was achieved in 56 cases (73% of operative cases) and of whom 27 developed local recurrence or distant metastasis at a median duration of 2 years. Imatinib was given as a primary therapy in unresectable cases (25 cases) and as an adjuvant in cases with residual tumor (21 cases). Targeted therapy gave partial response in 7 cases (15%), stable disease in 27 cases (57%) and progressive disease in 13 cases (28%). Four-year overall survival was 74% (95% CI: 61%-83%). Univariate survival analysis found that low-risk tumor, gastric site, complete resection and response to imatinib were associated with better survival. CONCLUSION: The overall outcomes of GIST can be predicted by risk-categorization. Surgery alone may not be a curative treatment for GIST. Response to targeted therapy is a crucial survival determinant in these patients.     

Transient adrenal insufficiency in diffuse large B cell lymphoma patients after chemotherapy with short-course,high-dose corticosteroids

Data on the rate of adrenal insufficiency (AI) in patients receiving short-course and high-dose corticosteroids are limited. In this study, we aimed to determine the incidence of AI in newly diagnosed, diffuse large B cell lymphoma (DLBCL) patients after receiving rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [or prednisolone] (R-CHOP/CHOP) regimen. We enrolled newly diagnosed DLBCL patients who were scheduled to receive 6–8 cycles of R-CHOP/CHOP regimen. One-microgram adrenocorticotropic hormone (ACTH) stimulation tests were performed at the study entry and 3 weeks after each cycle of chemotherapy (CMT). AI was defined by a peak-stimulated serum cortisol of less than 18 μg/dL. For patients who had AI after completing a course of CMT, 1-μg ACTH stimulation tests were carried out at 60 and 90 days after the last CMT cycle to assess the duration of hypothalamic-pituitary-adrenal (HPA) axis recovery. Ten DLBCL patients were included in this study, with a total of 84 1-μg ACTH stimulation tests. Their mean age was 52 years. AI occurred in 3 out of the 10 patients (30%). The first occurrence of AI was after the third CMT cycle, and the incidence was highest after the fifth cycle. Adrenal function recovered completely 3 to 5 weeks after completing the course of CMT, except for 1 patient, whose HPA axis suppression persisted 90 days after the last CMT cycle. Receiver operating characteristic (ROC) analysis revealed that a basal cortisol level of <?8.7 μg/dL was predictive of AI, with a sensitivity and specificity of 80% and 72.2%, respectively. Transient HPA axis suppression can occur in DLBCL patients receiving R-CHOP/CHOP regimen. We strongly encourage careful observation and examination for potential adrenal insufficiency in such patients, particularly after the fifth cycle of chemotherapy.