The optimal tomotherapy treatment planning parameters for extremity soft tissue sarcomas

Background and purposeTo determine the optimum combination of treatment parameters between pitch, field width (FW) and modulation factor (MF) for extremity sarcomas in tomotherapy.Materials and methodsSix patients previously treated for extremity sarcomas (3 arms and 3 legs) with tomotherapy were included in this study. 288 treatment plans were recalculated, corresponding to all combinations between 2 FW (2.5 and 5 cm), 4 MF (1.5, 2, 2.5 and 3) and 6 pitches (0.215, 0.287, 0.43 and 3 off-axis pitches). The treatment parameters (MF, FW or pitch) are modified between each plan, and the calculation is relaunched for 400 iterations, without modifying the optimisation constraints of the plan under which the patient has been treated.ResultsWe suggest eliminating the 0.43 pitch and never combining a 0.215 pitch with an MF ≤ 2. We also do not recommend using an MF = 1.5 unless treatment time is an absolute priority over plan quality. We did not see any advantage in using Chen off-axis pitches, except for targets far from the axis (>15 cm) treated with a high pitch. A combination of MF = 2/FW = 5 cm/pitch = 0.287 gives plans of acceptable quality, combined with reduced treatment times. These conclusions are true only for extremity sarcomas treated in 2 Gy/fraction.ConclusionsWe have shown that the choice of pitch/MF/FW combination is crucial for the treatment of extremity sarcomas in tomotherapy: some produce good dosimetric quality with a reduced irradiation time, while others may increase the time without improving the quality.     

Analysis of embryonic proteome modulation by GA and ABA from germinating rice seeds

The phytohormones gibberellic acid (GA) and abscisic acid (ABA) play essential and often antagonistic roles in regulating plant growth, development, and stress responses. Using a proteomics-based approach, we examined the role of GA and ABA in the modulation of protein expression levels during seed germination. Rice seeds were treated with GA (200 microM), ABA (10 microM), ABA followed by GA, GA followed by ABA, and water as a control and then incubated for 3 days. The embryo was dissected from germinated seeds, and proteins were subjected to 2-DE. Approximately, 665 total protein spots were resolved in the 2-D gels. Among them, 16 proteins notably modulated by either GA or ABA were identified by MALDI-TOF MS. Northern analyses demonstrated that expression patterns of 13 of these 16 genes were consistent with those of the proteome analysis. Further examination of two proteins, rice isoflavone resuctase (OsIFR) and rice PR10 (OsPR10), using Western blot and immunolocalization, revealed that both are specifically expressed in the embryo but not in the endosperm and are dramatically downregulated by ABA.     

Defining targets of modulation of human tumor cell response to cisplatin

We previously observed that in yeast cisplatin activates different pathways accounting for stress response. Here, we investigated whether genes involved in yeast drug response were modulated by cisplatin in human tumor cell lines (A2780, IGROV-1, A431, U2-OS) including cisplatin-resistant sublines (A2780/BBR, IGROV-1/Pt1, A431/Pt and U2-OS/Pt). Factors and pathways involved in stress response (glutathione-S-transferase, proteasome, checkpoint control and recombinational repair) were increased by cisplatin in human tumor sensitive and resistant cells. Moreover, sensitization to cisplatin by pharmacologically targeting glutathione or proteasome was observed in sensitive and resistant cells. Interestingly, only in IGROV-1/Pt1 cells, in which cisplatin up-regulated HSP70 and HSP90, targeting of HSP90 resulted in sensitization of resistant cells, suggesting a protective role of stress response. In conclusion, the present findings support the potential relevance of interfering with heat shock protein response to increase cisplatin cytotoxicity in resistant cells. Overall, pathways activated by cisplatin in human tumor cells appear cell-type specific, at least in part reflecting the stress response observed in yeast.     

Bacterial resistance modifying agents from Lycopus europaeus

As part of an ongoing project to identify plant natural products which modulate bacterial multidrug resistance (MDR), bioassay-guided isolation of an extract of Lycopus europaeus yielded two new isopimarane diterpenes, namely methyl-1alpha-acetoxy-7alpha 14alpha-dihydroxy-8,15-isopimaradien-18-oate (1) and methyl-1alpha,14alpha-diacetoxy-7alpha-hydroxy-8,15-isopimaradien-18-oate (2). The structures were established by spectroscopic methods. These compounds and several known diterpenes were tested for in vitro antibacterial and resistance modifying activity against strains of Staphylococcus aureus possessing the Tet(K), Msr(A), and Nor(A) multidrug resistance efflux mechanisms. At 512 microg/ml none of the compounds displayed any antibacterial activity but individually in combination with tetracycline and erythromycin, a two-fold potentiation of the activities of these antibiotics was observed against two strains of S. aureus that were highly resistant to these agents due to the presence of the multidrug efflux mechanisms Tet(K) (tetracycline resistance) and Msr(A) (macrolide resistance).     

Comparative investigation of the detective quantum efficiency of direct and indirect conversion detector technologies in dedicated breast CT

PurposeTo investigate the dose saving potential of direct-converting CdTe photon-counting detector technology for dedicated breast CT.Materials and methodsWe analyzed the modulation transfer function (MTF), the noise power spectrum (NPS) and the detective quantum efficiency (DQE) of two detector technologies, suitable for breast CT (BCT): a flat-panel energy-integrating detector with a 70 μm and a 208 μm thick gadolinium oxysulfide (GOS) and a 150 μm thick cesium iodide (CsI) scintillator and a photon-counting detector with a 1000 μm thick CdTe sensor.ResultsThe measurements for GOS scintillator thicknesses of 70 μm and 208 μm delivered 10% pre-sampled MTF values of 6.6 mm⁻¹ and 3.2 mm⁻¹, and DQE(0) values of 23% and 61%. The 10% pre-sampled MTF value for the 150 μm thick CsI scintillator 6.9 mm⁻¹, and the DQE(0) value was 49%. The CdTe sensor reached a 10% pre-sampled MTF value of 8.5 mm⁻¹ and a DQE(0) value of 85%.ConclusionThe photon-counting CdTe detector technology allows for significant dose reduction compared to the energy-integrating scintillation detector technology used in BCT today. Our comparative evaluation indicates that a high potential dose saving may be possible for BCT by using CdTe detectors, without loss of spatial resolution.     

Synchronization modulation of Na/K pump molecules can hyperpolarize the membrane resting potential in intact fibers

Previously, we have theoretically studied the possibility of electrical rhythmic entrainment of carrier-mediated ion transporters, and experimentally realized synchronization and acceleration of the Na/K pumping rate in the cell membrane of skeletal muscle fibers by a specially designed synchronization modulation electric field. In these studies we either used cut fibers under a voltage clamp or intact fibers, but in the presence of ion channels blockers. A question remained as to whether the field-induced activation observed in the pump molecules could effectively increase the intracellular ionic concentration and the membrane potential at physiological conditions. In this paper, we studied the effects of the field on intact fibers without any channel blockers. We monitored the field-induced changes in the ionic concentration gradient across the cell membrane and the membrane potential non-invasively by using a fluorescent probe and confocal microscopic imaging techniques. The results clearly show that the entrainment of the pump molecules by the synchronization modulation electric field can effectively increase the ionic concentration gradient, and hence, hyperpolarize the membrane potential.     

Perceptual interaction between carrier periodicity and amplitude-modulation in the gerbil (<Emphasis Type="Italic">Meriones unguiculatus</Emphasis>)

Due to its extended low-frequency hearing, the Mongolian gerbil (Meriones unguiculatus) has become a well-established animal model for human auditory processing. Here, two experiments are presented which quantify the gerbil’s sensitivity to amplitude modulation (AM) and carrier periodicity (CP) in broad-band stimuli. Two additional experiments investigate a possible interaction of the two types of periodicity. The results show that overall sensitivity to AM and CP is considerably less than in humans (by at least 10 dB). The gerbil’s amplitude-modulation sensitivity is almost independent of modulation frequency up to a modulation frequency of 1 kHz. Above, amplitude-modulation sensitivity deteriorates dramatically. On the basis of individual animals, carrier-periodicity detection may improve with increasing fundamental frequency up to about 500 Hz or may be independent of fundamental frequency. Amplitude-modulation thresholds are consistent with the hypothesis that intensity difference limens in the gerbil may be considerably worse than in humans, leading to the relative insensitivity for low modulation frequencies. Unlike in humans, inner-ear filtering appears not to limit amplitude-modulation sensitivity in the gerbil. Carrier-periodicity sensitivity changes with fundamental frequency similar to humans. Unlike in humans, there is no systematic interaction between AM and CP in the gerbil. This points to a relatively independent processing of the perceptual cues associated with AM and CP.     

豌豆根瘤菌结瘤基因启动子内二级结构区与转录活性有关

用羟胺随机改变豌豆根瘤菌(Rhizobium leguminosarum)结瘤基因 nodD上游的调控区间的核苷酸顺序,将它们插入广谱转录质粒pMP220的LacZ基因前,启动LacZ基因的表达、突变表明与结瘤基因的转录活力有关.DNA序列分析发现,这些突变都在距nodD基因起始密码子约80bp的二级结构区内.     

Modulation of Cytarabine Induced Cytotoxicity Using Novel Deoxynucleoside Analogs in the HL60 Cell Line

In order to enhance the cytotoxicity of ara‐C in the HL60 cell line the following deoxynucleoside analogs were used: cladribine, fludarabine and gemcitabine. HL60 cells were co‐incubated with ara‐C and each of the modulators at the ratios of their respective IC50s. Cytotoxicity was determined with the MTT‐assay and drug interactions were evaluated with the combination index (CI) method (Calcusyn; Chou & Talalay). CI < 1, CI ± 1 and > 1 indicate synergism, additive effect and antagonism, respectively. We observed moderate synergism between ara‐C/cladribine and ara‐C/gemcitabine, with CIs of 0.76 ± 0.14 and 0.82 ± 0.04, respectively. The interaction between ara‐C/fludarabine resulted in moderate antagonism (CI = 1.29 ± 0.11). In conclusion, in this in vitro study we showed that the cytotoxicity of ara‐C can be succesfully modulated in the HL60 cell line by cladribine and gemcitabine.