Potent and conditional redirected T cell killing of tumor cells using Half DVD-Ig

Novel biologics that redirect cytotoxic T lymphocytes (CTLs) to kill tumor cells bearing a tumor associated antigen hold great promise in the clinic. However, the ability to safely and potently target CD3 on CTL toward tumor associated antigens (TAA) expressed on tumor cells remains a challenge of both technology and biology. Herein we describe the use of a Half DVD-Ig format that can redirect CTL to kill tumor cells. Notably, Half DVD-Ig molecules that are monovalent for each specificity demonstrated reduced non-specific CTL activation and conditional CTL activation upon binding to TAA compared to intact tetravalent DVD-Ig molecules that are bivalent for each specificity, while maintaining good drug like properties and appropriate PK properties.

Quantitative study of nine main components in Yueju Tablets by HPLC coupled with wavelength switching and gradient elution method / 中草药

Objective: To establish HPLC coupled with wavelength switching and gradient elution method (HPLC-DVD) for simultaneous determination of nine main components (α-cyperone, genipin-1-β-D-gentiobioside, geniposide, crocin I, senkyunolide H, senkyunolide I, senkyunolide A, ligustilide, and atractylodin) in Yueju Tablets. Methods: The chromatographic separation was achieved on Zorbax Eclipse Plus C18 (250 mm × 4.6 mm, 5 μm) column with methanol-acetonitrile (2∶1) (A)-0.2% glacial acetic acid solution (B) as mobile phases for gradient elution, at the flow rate of 0.9 mL/min; The detection wavelength was set at 240 nm for α-cyperone, genipin-1-β-D-gentiobioside and geniposide, 440 nm for crocin I, 280 nm for senkyunolide H, senkyunolide I, senkyunolide A and ligustilide, and 340 nm for atractylodin. The volume of sample injection was 10 μL. Results: The nine active components were well separated and showed good linearity, such as α-cyperone 2.58—51.60 μg/mL (r = 0.999 4), genipin-1-β-D- gentiobioside 11.99—239.80 μg/mL (r = 0.999 9), geniposide 17.96—359.20 μg/mL (r = 0.999 6), crocin-I 3.98—79.60 μg/mL (r = 0.999 7), senkyunolide H 2.82—56.40 μg/mL (r = 0.999 9), senkyunolide I 2.38—47.60 μg/mL (r = 0.999 9), senkyunolide A 6.04—120.80 μg/mL(r = 0.999 5), ligustilide 7.98—159.60 μg/mL (r = 0.999 3), and atractylodin 6.51—130.20 μg/mL (r = 0.999 2). The precision was good, and RSD was not more than 1.22%. The repeatability was good, and RSD was not more than 1.75%. The stability was good in 18 h, and RSD was not more than 1.37%. The average recoveries and corresponding RSD values were 97.64% (0.98%), 99.09% (1.46%), 100.11% (1.03%), 97.87% (0.80%), 98.59% (1.19%), 96.89% (1.34%), 99.38% (0.58%), 98.50% (1.22%), and 99.71% (0.85%), respectively. The contents of 10 batches of α-cyperone, genipin-1-β-D-gentiobioside, geniposide, crocin I, senkyunolide, H, senkyunolide I, senkyunolide A, ligustilide and atractylodin were 0.282—0.344, 2.099—2.445, 3.628—4.225, 0.758—0.913, 0.241—0.286, 0.217—0.266, 1.077—1.291, 1.386—1.623, and 1.137—1.434 mg/tablet. Conclusion: HPLC coupled with wavelength switching and gradient elution method has been established for simultaneous determination of nine components in Yueju Tablets. The method is simple, quick, accurate, and it can be used for content determination and quality control of Yueju Tablets.

Determination of six kinds of index components in Dieda Zhitong San by HPLC-DVD variable wavelength method / 中草药

Objective: To develop an HPLC-DVD wavelength switching combined with gradient elution method for the determination of the contents of hydroxysafflor yellow A, protodioscin, dioscin, methylprotodioscin, pseudoprotodioscin, and gracillin in Dieda Zhitong San (DZS) simultaneously. Methods: The chromatographic separation was achieved on a Diamonsil C18 (250 mm × 4.6 mm, 5 μm) with acetonitrile (A)-0.4% formic acid solution (B) as mobile phase at the flow rate of 0.9 mL/min for gradient elution; Hydroxysafflor yellow A was detected at 403 nm; Protodioscin, dioscin, methylprotodioscin, pseudoprotodioscin, and gracillin were detected at 203 nm; Sample quantity was 20 μL. Results: The six active components were well separated and showed good linearity, such as hydroxysafflor yellow A 3.46-69.20 μg/mL (r = 0.999 4), protodioscin 9.52-190.40 μg/mL (r = 0.999 7), dioscin 8.74-174.80 μg/mL (r = 0.999 6), methylprotodioscin 4.45-89.00 μg/mL (r = 0.999 9), pseudoprotodioscin 2.64-52.80 μg/mL (r = 0.999 5), and gracillin 3.28-65.60 μg/mL (r = 0.999 8). The precision and repeatability were good, and RSD values were less than 2.0%. The stability was good in 12 h. The average recoveries and the corresponding RSD values were 98.57% (1.59%), 97.64% (1.28%), 99.43% (1.07%), 97.98% (1.64%), 98.57% (1.16%), and 97.17% (1.37%), respectively. Conclusion: An HPLC wavelength switching combined with gradient elution method has been successfully established for simultaneous determination of six components in DZS. The method is simple, quick, accurate, and helpful for the quality control of DZS.

Eye Fixation in Patients with Dissociated Vertical Diviation

PURPOSE: To clinically determine the proportion of people with a fixed dissociating eye in patients with dissociated vertical deviation (DVD). METHODS: Medical records of 86 patients diagnosed with DVD in our department of ophthalmology from 2001 to November 2011 were retrospectively analyzed. RESULTS: Of the 71 patients, 25 (35.21%) showed a higher degree of dissociation in the fixating eye, 26 (36.62%) had higher dissociation in the non-fixating eye; 20 of 25 patients with a higher level of dissociation in the fixating eye and 22 of 26 patients with a higher level of dissociation in the non-fixating eye received surgical correction for DVD, such as superior rectus muscle recession or inferior oblique muscle anterior transposition. CONCLUSIONS: In DVD, the proportion of patients showing a higher level of dissociation in the fixating eye was significant. Patients with DVD require thorough evaluation; measurement of the level of dissociation and determination of the fixating eye is beneficial for management and surgical intervention.

Consecutive Exotropia After Bilateral Medial Rectus Recession for Infantile Esotropia

PURPOSE: To evaluate associated factors by comparing the patients with consecutive exotropia to the patients with orthophoria after undergoing surgery for infantile esotropia. METHODS: The study consisted of 50 patients who underwent bilateral medial rectus recession and attended follow-ups until eight years of age. The authors retrospectively investigated the clinical characteristics ofage at operation, duration between diagnosis and operation, the spherical equivalent of both eyes, the deviated angle at the first visit and immediately before the operation, the recession amount, and the total follow-up period. RESULTS: During the mean follow-up period of 78.51+/-54.70 months, 13 patients (26%) had consecutive exotropia, 27 patients (54%) had orthophoria and 10 patients (20%) had remnant esotropia. As the result of comparing orthophoric patients to consecutive exotropic patients, there were no significant differences in the birth weights, the deviated angles at the first visit and immediately before the operation, the spherical equivalents of both eyes, the ages at operation, the recession amounts, and the durations between diagnosis and operation. However, in consecutive exotropia, inferior oblique muscle overaction was 46.5%, dissociated vertical deviation was 46.5% in orthophoric patients, inferior oblique muscle overaction was 19.24%, and dissociated vertical deviation was 8.7%. CONCLUSIONS: A thorough follow-up is necessary when inferior oblique muscle overaction and dissociated vertical deviation occur after undergoing a bilateral medial rectus operation.

Comparison of DVd and VAdM in the treatment of newly diagnosed multiple myeloma / 白血病·淋巴瘤

Objective To compare effects and toxicities of DVd and VAdM regimen for newly diagnosed multiple myeloma.nethods 17 newly diagnosed active multiple myeloma received DVd treatment,dexamethasone(20 mg/d)on days 1～4 as an intravenous infusion.16 newly diagnosed active multiple myeloma on days 1～4 plus melphalan(12 mg/d)as an intravenous infusion.Results Objective response rates(DVd,76.5%;VAd,81.3%,P=0.737)were similar between the two treatment groups.In the DVd group,the mean time to max response was shorter than the VAdM group[(3.2±1.7)months vs.(4.6±1.0)months,P=0.039].DVd was associated with low Grade 3/4 neutropenia(23.5% vs.68.8%,P=0.015),less use of G-CSF(11.8% vs.62.5%,P=0.004),less use antibiotic(11.8% vs.37.5%,P=0.118),lower incidence of hospitalization for adverse events(37.5% vs.17.6%,P=0.259),but more hand-foot syndrome.Coilcinsion The DVd regimen demonstrated similar efficacy compared with VAdM,while with less toxicity and supportive care,which might be used as a modified VAd regimen for newly diagnosed myeloma.

The Vertical Effect of Anterior Transposition of the Inferior Oblique Muscle for DVD with IOOA

Anterior transposition(AT) of inferior oblique muscle is an effective method to treat dissociated vertical deviation(DVD) with inferior oblique overaction(IOOA). We evaulated the clinical results of the AT and the correlation between preoperative conditions(DVD, IOOA) and postoperative vertical correction. The results was that the amount of anterior transposition was related with that of postoperative vertical correction, which was determined by the amount of preoperative DVD.

Amblyopia in Infantile Esotropia

Sixty-eight children who had undergone surgery for infantile esotropia were analysed. The mean follow-up time was 2.7 years. Thirty-two patients without amblyopia prior to surgery remained as such postoperatively except one child(3.1%). There were twenty-seven children that received treatment for amblyopia prior to strabismus surgery. Out of these, twenty children(20/27, 74%) developed recurrent amblyopia in postoperative follow-up period. Dissociated vertical deviation and/or inferior oblique overaction occurred in 21 children(21/39, 54%) in the group free of amblyopia, while those occurred in 16 children(16/29, 55%) in amblyopic group, postoperatively. In conclusion, children without amblyopia before surgery remained as such postoperatively. The development of postoperative vertical deviation such as DVD and IOOA is not related to the existence of amblyopia in postoperative periods.

The Effect of Recession of Superior Rectus Muscle Combined with Anterior Transposition of the Inferior Oblique Muscle for Dissociated Vertical Deviation

The authors studied the effect of recession of superior rectus muscle combined with anterior transposition of the inferior oblique muscle for DVD. Superior rectus muscle was tecessed by 4.0-4.5mm combined with antetior transposition of IOM on 26 eyes in 16 patients with 15 +/- 25 delta DVD from March 1991 to September 1995. In all cases we have done transposition of the IOM to just temporal insertion of IRM. The eyes, which have the amount of DVD were less than 20 delta, received 4.0mm recession of SRM, the ones and which have the amount of DVD were more than 20 delta, received 4.5mm recession of SRM. Averaged reduction of DVD in 4.0mm group was 14.5 delta, and in 4.5mm group was 17.6 delta. As for post operative complication, only mild upgaze limitation was abserved in all cases. Recession of SRM combined with anterior transposition of IOM can correct moderate degree of dissociated vertical deviation and this method is relatively simple than other procedure.

The Effect of Superior Rectus Recession for Dissociated Vertical Deviation(DVD)

Dissociated vertical deviation(DVD) is a peculiar clinical entity consisting of an upward and extortional drift of a nonfixating eye. Many different surgical procedures have been advocated for its treatment, but the best approach is still debated. The authors performed superior rectus recession for treatment of DVD in 13 eyes of 8 patients. All patients were followed up for average 15 months after operation. In the vast majority cases, unilateral or bilateral superior rectus recession of graded amounts(7-8 mm) was performed. The amount of preoperative DVD was ranged from 10 to 25 delta and the mean effect of surgery was 11 delta After operation, 46% of the eyes were aligned within good to excellent categories(0-9 prism diopters), and 12 of 13 eyes within fair to excellent results(0-14 prism diopters).

The Effect of Superior Rectus Recession for Dissociated Vertical Deviation (DVD)

Dissociated vertical deviation (DVD) is a peculiar clinical entity consisting of an upward and extortional drift of a nonfixating eye. Many different surgical procedures have been advocated for its treatment, but the best approach is still debated. The authors performed superior rectus recession for treatment of DVD in 13 eyes of 8 patients. All patients were followed up for average 15 months after operation. In the vast majority cases, unilateral or bilateral superior rectus recession of graded amounts (7-8mm) was performed. The amount of preoperative DVD was ranged from 10 to 25.6. and the mean effect of surgery was 11 delta. After operation, 46% of the eyes were aligned within good to excellent categories (0-9 prism diopters), and 12 of 13 eyes within fair to excellent results (0-14 prism diopters).