618 Background: Trastuzumab, a humanized recombinant monoclonal antibody, targets HER2 and is approved for treatment of HER2-overexpressing breast and gastric cancers. PF-05280014 is being developed as a potential biosimilar to trastuzumab. Similarity of PF-05280014 to trastuzumab sourced from the EU and US (trastuzumab-EU and -US) was assessed using structural and functional, nonclinical pharmacokinetic (PK) and tolerability, and clinical studies; the toxicity of PF-05280014 was also assessed. Methods: Structural similarity was determined by peptide mapping. Functional similarity was measured using an in vitro tumor cell growth inhibition assay. Comparative PK, tolerability, and anti-drug antibody (ADA) responses were evaluated in male CD-1 mice following a single dose; PK and toxicity of PF-05280014 alone were evaluated in CD-1 mice (both sexes) after 5 doses. In a phase I study, 105 healthy male volunteers received a single 6 mg/kg IV dose of PF-05280014, trastuzumab-EU, or trastuzumab-US. Drug concentration-time data were analysed by noncompartmental methods. PK similarity was considered demonstrated for a given test-to-reference comparison if the 90% CI was within 80.00%-125.00%. Results: Peptide mapping showed PF-05280014 was similar to trastuzumab-EU and trastuzumab-US. Dose response curves in the in vitro cell growth inhibition assay were superimposable. In vivo PK profiles were similar in mice and there were no toxicity findings for PF-05280014. In the phase I study, PK similarity was shown between PF-05280014 and trastuzumab-EU and trastuzumab-US, with 90% CI of Cmax, AUCT, and AUC0-∞ within 80.00%–125.00% for each pair-wise comparison. Adverse events were similar across groups; only 1 subject (trastuzumab-EU group) was ADA positive postdose. Conclusions: Evaluation of PF-05280014 thus far supports its development as a potential biosimilar to trastuzumab. An ongoing, phase III, randomized, double-blind clinical trial is comparing PF-05280014 + paclitaxel with trastuzumab-EU + paclitaxel for first-line treatment of patients with HER2+ metastatic breast cancer. A second phase III, randomized, double-blind trial evaluating PF-05280014 in the neoadjuvant setting for breast cancer is ongoing. Clinical trial information: NCT01603264, NCT02187744, and NCT01989676.
In order to study the anti-inflammatory function of “Prostate-Calming Formula I () and observe influence of its high and low dose by perfusion into the stomach on auricular tumefaction caused by dimethylbenzene in mice, foot tumefaction caused by carrageenin in rats and granulation proliferation caused by cotton ball in rats, in comparison with prednisone control group. The results showed that two different doses were all effective to the above-mentioned three indexes, with a certain dose-effect relationship. In resisting auricular tumefaction in mice and foot tumefaction in rats, the function of high dose of “Prostate-Calming Formula I was similar to prednisone. The findings indicate that “Prostate-Calming Formula I has a stronger anti-inflammatory function.
The techniques of cutting propagation and high quality and yield for planting Stevia rebaudiana were introduced and applied in the southwest Shandong province.
AIM:To investigate the effects of tetramethylpyrazine combined with aminoguanidine on the renal functions of neonatal-0 streptozotocin-induced(n0-STZ) rats.METHODS: Neonatal Wistar rats were intraperitoneally injected with a single dose of streptozotocin(STZ) to establish the n0-STZ rat model.The n0-STZ rats were divided into 4 groups: normal control group,insulin resistance group,metformin treatment group and tetramethylpyrazine+aminoguanidine treatment group.Fasting plasm glucose,fasting insulin,insulin resistance index,blood urea nitrogen,serum creatinine,urine albumin and glomerular filtration rate were measured at the 32nd week.The mRNA content of inducible nitric oxide synthase(iNOS) in peripheral blood leukocytes was detected by the technique of in situ hybridization.Nitric oxide(NO) concentration,iNOS activity,the protein expression of iNOS and 3-nitrotyrosine(3-NT) were also assessed in the renal tissues.RESULTS: At the 8th week after the administration of STZ,82.5% of Wistar rats showed that the fasting plasm glucose level was ≥7.0 mmol/L and the renal functions were seriously damaged.Although both metformin and the combined treatment reduced fasting plasm glucose,fasting insulin and insulin resistance index,the combined treatment was superior in improving the insulin resistance.The damaged renal functions were improved by the combined treatment as reducing blood urea nitrogen and creatinine,increasing glomerular filtration rate were observed.Furthermore,the combined treatment reduced NO concentration,decreased iNOS activity and diminished mRNA content of iNOS,resulting in depressing the generation of 3-NT and iNOS,which surpassed the treatment of metformin.CONCLUSION: Tetramethylpyrazine combined with aminoguanidine improves the renal functions of n0-STZ rats by depressing nitrative stress and enhancing the effect of metformin.
Background Decellularized allograft tendons are highly regarded for their accessibility and the reduced risk of immune rejection, making them a promising choice for grafting due to their favorable characteristics. However, effectively integrating reconstructed tendons with host bone remains a significant clinical challenge. Purpose This study aims to investigate the relationship between the duration of tendon exposure to trypsin and its impact on tendon biomechanical properties and healing capacity. Methods Morphological assessments and biochemical quantifications were conducted. Allograft tendons underwent heterotopic transplantation into the anterior cruciate ligament (ACL) in a rabbit model, with specimens harvested 6 weeks post-surgery for a comparative analysis of cell adhesion strength and mechanical performance. Duration-response curves were constructed using maximum stress and cell adhesion quantity as primary indicators. Results The trypsin treatment enhanced cell adhesion on the tendon surface. Adhesion rates in the control group vs. the experimental groups were as follows: 3.10 ± 0.56% vs. 4.59 ± 1.51%, 5.36 ± 1.24%, 6.12 ± 1.98%, and 8.27 ± 2.34% ( F = 6.755, p = 0.001). However, increasing treatment duration led to a decline in mechanical properties, with the ultimate load (N) in the control vs. experimental groups reported as 103.30 ± 10.51 vs. 99.59 ± 4.37, 93.15 ± 12.38, 90.42 ± 7.87, and 82.68 ± 6.89, F = 4.125 ( p = 0.013). Conclusion The findings reveal an increasing trend in adhesion effectiveness with prolonged exposure duration, while mechanical strength declines. The selection of the optimal processing duration should involve careful consideration of the benefits derived from both outcomes.
One of the key concerns of the clinician is to identify and manage risk factors for major adverse cardiovascular events (MACEs) in nondiabetic and diabetic patients with acute coronary syndrome (ACS) undergoing stent implantation. Mean corpuscular volume (MCV) is a marker of erythrocyte size and activity and is associated with prognosis of cardiovascular disease. However, the role of admission MCV in predicting MACEs following stent implantation in diabetes mellitus (DM), non-DM, or whole patients with ACS remains largely unknown.A total of 437 ACS patients undergoing stent implantation, including 294 non-DM (59.08 ± 10.24 years) and 143 DM (63.02 ± 9.92 years), were analyzed. Admission MCV was higher in non-DM than DM patients. During a median of 31.93 months follow-up, Kaplan-Meier curve demonstrated that higher admission MCV level was significantly associated with increased MACEs in whole and non-DM, but not in DM patients. In Cox regression analysis, the highest MCV tertile was associated with higher MACEs in whole ([HR] 1.870, 95% CI 1.113-3.144, P = 0.018), especially those non-DM ([HR] 2.089, 95% CI 1.077-4.501, P = 0.029) patients after adjustment of several cardiovascular risk factors. MCV did not predict MACEs in DM patients. During landmark analysis, admission MCV showed better predictive value for MACEs in the first 32 months of follow-up than in the subsequent period. Finally, the receiver operating characteristic (ROC) curve was conducted to confirmed the value of admission MCV within 32 months.In patients with ACS, elevated admission MCV is an important and independent predictor for MACEs following stent implantation, especially amongst those without DM even after adjusting for lifestyle and clinical risk factors. However, as the follow-up period increased, the admission MCV lost its ability to predict MACEs.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)