Dynamic 2-Deoxy-2-[<Superscript>18</Superscript>F]Fluoro-D-Glucose Positron Emission Tomography for Chemotherapy Response Monitoring of Breast Cancer Xenografts

Purpose

Non-invasive response monitoring can potentially be used to guide therapy selection for breast cancer patients. We employed dynamic 2-deoxy-2-[¹⁸F]fluoro-D-glucose positron emission tomography ([¹⁸F]FDG PET) to evaluate changes in three breast cancer xenograft lines in mice following three chemotherapy regimens.

Procedures

Sixty-six athymic nude mice bearing bilateral breast cancer xenografts (two basal-like and one luminal-like subtype) underwent three 60 min [¹⁸F]FDG PET scans. Scans were performed prior to and 3 and 10 days after treatment with doxorubicin, paclitaxel, or carboplatin. Tumor growth was monitored in parallel. A pharmacokinetic compartmental model was fitted to the tumor uptake curves, providing estimates of transfer rates between the vascular, non-metabolized, and metabolized compartments. Early and late standardized uptake values (SUV_E and SUV_L, respectively); the rate constants k ₁, k ₂, and k ₃, and the intravascular fraction v _B were estimated. Changes in tumor volume were used as a response measure. Multivariate partial least-squares regression (PLSR) was used to assess if PET parameters could model tumor response and to identify PET parameters with the largest impact on response.

Results

Treatment responders had significantly larger perfusion-related parameters (k ₁ and k ₂) and lower metabolism-related parameter (k ₃) than non-responders 10 days after the start of treatment. These findings were further supported by the PLSR analysis, which showed that k ₁ and k ₂ at day 10 and changes in k ₃ explained most of the variability in response to therapy, whereas SUV_L and particularly SUV_E were of lesser importance.

Conclusions

Overall, rate parameters related to both tumor perfusion and metabolism were associated with tumor response. Conventional metrics of [¹⁸F]FDG uptake such as SUV_E and SUV_L apparently had little relation to tumor response, thus necessitating full dynamic scanning and pharmacokinetic analysis for optimal evaluation of chemotherapy-induced changes in breast cancers.

     

CustusX: an open-source research platform for image-guided therapy

Purpose

CustusX is an image-guided therapy (IGT) research platform dedicated to intraoperative navigation and ultrasound imaging. In this paper, we present CustusX as a robust, accurate, and extensible platform with full access to data and algorithms and show examples of application in technological and clinical IGT research.

Methods

CustusX has been developed continuously for more than 15 years based on requirements from clinical and technological researchers within the framework of a well-defined software quality process. The platform was designed as a layered architecture with plugins based on the CTK/OSGi framework, a superbuild that manages dependencies and features supporting the IGT workflow. We describe the use of the system in several different clinical settings and characterize major aspects of the system such as accuracy, frame rate, and latency.

Results

The validation experiments show a navigation system accuracy of \(<\)1.1 mm, a frame rate of 20 fps, and latency of 285 ms for a typical setup. The current platform is extensible, user-friendly and has a streamlined architecture and quality process. CustusX has successfully been used for IGT research in neurosurgery, laparoscopic surgery, vascular surgery, and bronchoscopy.

Conclusions

CustusX is now a mature research platform for intraoperative navigation and ultrasound imaging and is ready for use by the IGT research community. CustusX is open-source and freely available at http://www.custusx.org.

     

Exchange transfusion the hard way: massive hemolysis following transplantation of bone marrow with minor ABO incompatibility

BACKGROUND: Bone marrow transplantation using donors with minor ABO incompatibility may result in the rapid production of donor-derived red cell isohemagglutinins, causing hemolysis of recipient red cells. CASE REPORT: The transplant of sibling-donor marrow with minor ABO incompatibility (group O donor marrow to group A recipient), using FK- 506 as an immunosuppressant to prevent graft-versus-host disease, is reported. Following early myeloid engraftment, the recipient developed hemolysis of her entire A red cell population between Day 8 and Day 11. This brisk hemolytic anemia was due to rapid donor lymphoid engraftment that resulted in the explosive production of donor-derived anti-A. CONCLUSION: Patients undergoing the transplantation of marrow from donors with minor ABO incompatibility in which the donor cells can produce isohemagglutinins against the recipient's red cells must be kept under vigilant observation for the possible development of severe hemolysis, particularly in the setting of profound T-cell suppression without B-cell suppression.     

THE DURATION OF ACTION OF INHALED FORMOTEROL DRY POWDER

SUMMARY The duration of action of formoterol inhaled as a dry powder formulation is compared with placebo and a reference treatment of salbutamol dry powder in patients with bronchial asthma. This single-centre, double-blind, cross-over study recruited 23 outpatients with clinically stable asthma. These patients were treated with 12μg formoterol, 400μg salbutamol or placebo in a randomly allocated sequence, with at least 2 days between treatments. Forced expiratory volume in 1s of expiration (FEV₁) was measured at specified time points from 15 min to 15 hours post-treatment. Formoterol produced significantly higher values of FEV₁ at the primary endpoint of 12 hours compared with placebo and salbutamol. No differences between FEV₁ values were seen for the active treatments of formoterol and salbutamol for the first 5 hours post-inhalation. Formoterol was significantly superior to placebo at all time points, whereas salbutamol was significantly superior to placebo for the first 5 hours.This study demonstrates that formoterol, when given as a dry powder inhalation, has a significantly longer duration of acute bronchodilator action than 400μg salbutamol inhaled as a dry powder. The duration of action of formoterol of at least 12 hours seen in this study is at least as long as that reported following administration from a metered dose inhaler (MDI) at the same dose level. The study also demonstrates that 12μg formoterol dry powder is well tolerated by patients.     

人视网膜色素上皮细胞增殖与川芎嗪的影响

目的:观察糖基化终产物(advanced glycation end products,AGEs)对人视网膜色素上皮细胞增殖的影响,以及川芎嗪对AGEs诱导的人视网膜色素上皮细胞增殖的拮抗作用。方法:实验于2003-09/2004-07在中南大学湘雅二医院中心实验室完成。①实验分组:原代培养人视网膜色素上皮细胞,第3￣8代用于实验,设空白对照组,DMEM培养基中不加入任何药物;AGEs对照物组,培养液中含100mg/L的AGEs对照物;AGEs组,培养液中含10,50,100,200,400mg/L的AGEs,分别干预视网膜色素上皮细胞24h及48h。②实验操作:川芎嗪干预实验:也设空白对照组;AGEs对照物组;AGEs组,培养液中含100mg/L的AGEs;AGEs 川芎嗪组,培养液中加入10,20,40,80,160,320,640mg/L川芎嗪30min后加入100mg/L的AGEs,分别干预视网膜色素上皮细胞24h。③实验评估:MTT微量酶比色法检测视网膜色素上皮细胞增殖情况。结果:①视网膜色素上皮细胞增殖情况:不同浓度AGEs组细胞增殖率均高于对照物组(P<0.01),100mg/LAGEs组增殖率(24,48h分别为39.45%,31.97%)高于其他组(P<0.01),48h与24h结果一致。②川芎嗪的抑制效应:与AGEs组比较,10,20,40,80,160mg/L川芎嗪对AGEs诱导的视网膜色素上皮细胞增殖无抑制作用(P>0.05),320及640mg/L川芎嗪有抑制作用,其抑制率为8.96%,15.08%(P<0.01)。结论:①AGEs可诱导人视网膜色素上皮细胞增殖。②低浓度川芎嗪对AGEs诱导的人视网膜色素上皮细胞增殖无抑制作用,高浓度川芎嗪具有抑制作用。     

Molecular basis of intrahepatic cholestasis

Intrahepatic cholestasis, or impairment of bile flow, is an important manifestation of inherited and acquired liver disease. In recent years, human genetic and molecular studies have identified several genes, the disruption of which results in cholestasis. ATP8B1 (FIC1), ABCB11 (BSEP), and ABCB4 (MDR3) are disrupted in forms of progressive familial intrahepatic cholestasis (PFIC) and related disorders. Mutations in BAAT, TJP2 (ZO‐2), and EPHX1 have been identified in patients with hypercholanemia. A CLDN1 mutation was recently reported in patients with ichthyosis, leukocyte vacuoles, alopecia and sclerosing cholangitis (ILVASC), and North American Indian childhood cirrhosis (NAIC) is associated with a missense mutation in CIRH1A. Alagille syndrome patients carry mutations in JAG1, and mutations in VPS33B have been identified in patients with arthrogryposis, renal dysfunction and cholestasis syndrome (ARC). Identification of these genes, and characterization of the proteins they encode, is enhancing our understanding of the biology of the enterohepatic circulation in health and disease.     

Microbial Burden of Some Herbal Antimalarials Marketed at Elele, Rivers State

Herbal antimalarials still remain an alternative to our traditional communities who can not afford orthodox antimalarials. This study was aimed at investigating the microbial quality of six herbal antimalarials using standard microbiological methods. Of the six preparations analyzed, “schnapps”, palm wine and water were the media of preparation; the water base preparations recorded higher microbial load. The mean microbial load was 159.5×10⁵ cfu/ml and 217.4×10²cfu/ml in water and alcohol base preparations respectively. The microbial profile of the preparations showed that the schnapps base preparations were predominantly contaminated with Bacillus sp (Aerobic spore bearers) and Mucor spp. The palm wine preparation harboured Bacillus sp, yeasts and Mucor spp while the water base preparations had several isolates such as Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli 0157H7, Proteus mirabilis, Enterococcus feacalis, Serratia marcensces, Staph. aureus, Bacillus spp and Mucor spp. Conclusively, this study underlines the public health importance of these preparations given the high burden of such human pathogen as Ecoli O157H7, Ps aeruginosa, Stahp aureus, etc. in the preparations.