Gemcitabine Plus Platinum versus Docetaxel Plus Platinum as First-Line Therapy for Metastatic Nasopharyngeal Carcinoma: A Randomized Clinical Study.

BACKGROUND: A well-established first-line chemotherapy standard for metastatic nasopharyngeal carcinoma is yet lacking. OBJECTIVES: To compare the efficacy and safety of gemcitabine plus platinum versus docetaxel plus platinum regimen as first-line therapies for distal metastatic nasopharyngeal carcinoma. STUDY DESIGN AND PARTICIPANTS: A single center, randomized, open-label, parallel-arm study. The study included 120 patients with metastatic nasopharyngeal carcinoma who met the study requirements. INTERVENTIONS: Participants were randomized in a 1:1 ratio through a sealed envelope selection. Gemcitabine 1000 mg/m2/d intravenously (IV) for >30 min (days 1 and 8) or docetaxel 75 mg/m2/d IV for 1 h (day 1) were administered to the respective group participants. Nedaplatin 75 mg/m2/d, IV (day 1), cisplatin 75 mg/m2/d IV (day 1) or carboplatin (area under the curve set as 5) IV (day 1) were used in both groups. One cycle duration was 21 days, with 4-6 cycles for all participants. OUTCOMES: The primary assessed outcomes were progression-free survival (PFS) and overall survival (OS), and the secondary outcomes were short-term efficacy [i.e., response rate (RR) and disease control rate (DCR)] and safety. RESULTS: Seven patients withdrew from the study, and efficacy and adverse reactions were obtained for 113 patients (gemcitabine: 56; docetaxel: 57). Compared with the docetaxel plus platinum group, the gemcitabine plus platinum group had significantly higher RR (71.4% vs. 52.6%, P < 0.05); mPFS (9.7 vs. 7.8 months, P < 0.05), and mOS (20.6 vs. 16.8 months, P < 0.01). The significance was not associated with increased adverse reactions, as both groups showed similar Grades 3 and 4 adverse reactions (P > 0.05). DCR was non-significantly higher in the gemcitabine group (85.7% vs. 75.4%, P > 0.05). Multivariable analysis revealed that time to disease progression, number of involved organs, liver metastasis, and grouping were associated with mPFS and mOS (all P < 0.05). CONCLUSION: The combination of gemcitabine with platinum is likely superior to that of docetaxel with platinum as first-line treatment for metastatic nasopharyngeal carcinoma.

MIF/CD74 axis is a target for metformin therapy in diabetic podocytopathy - real world evidence.

Introduction：To observe the effects of metformin on urinary excretion of MIF, CD74 and podocalyxin in type 2 diabetics and to explore its possible renoprotective mechanisms. METHODS: 202 uncontrolled type 2 diabetics, who were previously prescribed sulfonylurea monotherapy(n=100) or sulfonylurea in combination with metformin (n=102) were enrolled in the study. The amount of macrophage migration inhibitory factor(MIF) and CD74 in serum, urinary MIF to creatine ratio(UMCR), urinary CD74 to creatine ratio(UCCR), urinary albumin to creatine ratio(UACR) and urinary podocalyxin to creatine ratio (UPCR) were determined. RESULTS: Metabolic parameters including fasting blood glucose, postprandial 2 hours blood glucose, hemoglobin A1c, MIF and CD74 in serum were comparable between the two groups. Moreover, metformin add-on therapy showed significantly better efficacy in reducing UMCR, UCCR, UPCR and UACR in comparison with those in sulfonylurea monotherapy group, respectively. UPCR had positive correlation with UACR, UMCR and UCCR (r＝0.73, r=0.69, r=0.62, P < 0.01), respectively. CONCLUSIONS: Metformin could present its podocyte-protective capacity in type 2 diabetics and the underlying mechanisms may be partly attributed to its effects in suppressing MIF-CD74 axis mediated inflammatory cascade response. < p > < /p >.

Injury in Minipig Parotid Glands following Fractionated Exposure to 30 Gy of Ionizing Radiation.

OBJECTIVE: To explore the effects of 30 Gy of (60)Co γ-rays on apoptosis and reactive oxygen species (ROS) levels in minipig parotid cells as a possible mechanism for radiation-induced parotid injury. STUDY DESIGN: Experimental study. SETTING: Department of Radiotherapy, First Affiliated Hospital, Guangxi Medical University, Nanning, China. SUBJECTS AND METHODS: Forty male minipigs were divided into control and irradiated groups. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling was used for detecting apoptosis in the parotid cells, immunohistochemistry, and western blots were used to test expression of the B-cell lymphoma 2 (Bcl-2) and BCL2-associated X (Bax) proteins, and reverse transcription polymerase chain reaction was used to analyze the expression of Bcl-2, Bax, p53, and caspase-3 messenger ribonucleic acid. An enzyme-linked immunosorbent assay was used to detect ROS levels in the parotid tissue. RESULTS: At each time point, the apoptotic rates in the irradiated group were higher than those in the control group. Furthermore, the ROS and expression levels of Bax, p53, and caspase-3 messenger ribonucleic acid and proteins gradually increased and were higher than those in the control group. Conversely, the expression of Bcl-2 was decreased in the irradiated group (P < .05). CONCLUSIONS: Ionizing radiation induces the production of ROS and promotes changes in the expression of several apoptotic proteins, which increases apoptosis and likely contributes to the mechanism of radiation-induced parotid injury.