Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) produced good tumor response in cases with lung squamous cell carcinoma, one of the most difficult cancers to treat. Secreted protein acidic and ...rich in cysteine (SPARC) binds to albumin, suggesting that SPARC plays an important role in tumor uptake of nab-paclitaxel. There is as yet no predictive marker for cytotoxic agents against non-small-cell lung cancer (NSCLC), and hence we believed that SPARC expression might be associated with tumor response to nab-paclitaxel.
We studied stromal SPARC reactivity and its association with clinicopathological characteristics in 200 cases of NSCLC using a custom tissue microarray fabricated in our laboratory by immunohistochemical staining. We also investigated the relationship between stromal SPARC reactivity and tumor response to nab-paclitaxel using biopsy or surgical specimens obtained from advanced or recurrent lung cancer patients.
High SPARC stromal reactivity (>50% of optical fields examined) was detected in 16.5% of cases and intermediate SPARC reactivity (10%-50%) in 56% of cases. High expression in cancer cells was rare (five cases). Stromal SPARC level was correlated with smoking index, squamous cell carcinoma, and vessel invasion. Furthermore, patients with high stromal SPARC reactivity in biopsy specimens such as transbronchial lung biopsy or surgical specimens tended to respond better to nab-paclitaxel.
Stromal SPARC was detected by immunohistochemical staining in ∼70% of NSCLC cases, and good tumor response to nab-paclitaxel was correlated with high stromal SPARC reactivity. SPARC may be a useful predictive marker for selecting patients likely to respond favorably to nab-paclitaxel treatment.
Abstract
Background
Dual antiplatelet therapy is recommended for patients (pts) with acute coronary syndromes (ACS). However, 10–15% of pts have indication of coronary artery bypass graft (CABG) for ...the index event and current guidelines recommend stopping clopidogrel at least 5 days prior to CABG. This waiting time could increase hospital length of stay, thus having negative impacts on costs and clinical complications.
Purpose
To evaluate if release to CABG based on platelet aggregability by Multiplate AnalyzerTM would be non-inferior in comparison with common practice (5 days) in terms of 24-hours post-CABG bleeding.
Methods
The PLAT-CABG (NCT 02516267) is a randomized, open label, non-inferiority trial (boundary 25%) testing a strategy of platelet aggregability-guided release to CABG versus standard-of-care on the primary endpoint of chest tube drainage in the first 24 hours post CABG. A total of 190 pts admitted with ACS, treated with aspirin + clopidogrel and with indication for CABG, were assigned to clopidogrel discontinued 5 days prior to CABG (control group) vs. daily measurements of platelet aggregability to ADP using Multiplate AnalyzerTM (intervention group) with CABG occurring after recovering from platelet inhibition (pre-defined as a threshold of 46 AU).
Results
The main results are depicted in the table
Main results of PLAT-CABG study
Variables
Control Group (n=95)
Intervention Group (n=95)
P-value for superiority
P-value for non-inferiority
Chest tube drainage (mL), Median (25th–75th)
350 (250–500)
350 (250–500)
0.680
0.001
Time symptom to CABG (hours), Median (25th–75th)
191 (150–281)
166 (119–225)
<0.001
NA
Time surgery indication to CABG (hours), Median (25th–75th)
136 (112–161)
112 (66–142)
<0.001
NA
CABG = coronary artery bypass graft.
Conclusion
Platelet-aggregability guided release to CABG is non-inferior to standard of care in ACS patients awaiting CABG in terms of peri-operative bleeding and significantly shortens the time to CABG.
Acknowledgement/Funding
Roche Diagnostica Brazil
Root rot of cocoyam (Xanthosoma sagittifolium L. Schott) caused by Pythium myriotylum Drechsler is a major disease of this crop in Africa (1,2) but is unreported from other regions of the world. ...During September 1999, commercially grown cocoyam (cv. Ratu-kiri-ala) in Gampaha (7°05'N, 80°00'E), Sri Lanka suffered from severe root rot. Initial symptoms were water-soaked lesions at the root tips that gradually enlarged to rot the entire root system and tuber. Wilting and yellowing of leaves were observed in advanced stages of disease. A Pythium sp. was regularly isolated from the affected roots and an isolate, SC5, was identified as P. myriotylum on the basis of morphology and the internal transcribed spacer (ITS) rDNA sequence. Characteristics of isolate SC5, grown on a grass-leaf water culture (3) were main hyphae up to 8.5 μm wide, oogonia terminal or intercalary (22.5 to 33.8 μm in diameter), antheridia diclinous occasionally monoclinous, one to eight per oogonium, stalks branched, often more or less loosely enveloping the oogonium, antheridium clavate or crook-necked, making apical contact with the oogonium, breadth of antheridium 2.5 to 7.0 μm, oospores aplerotic (17.0 to 22.5 μm in diameter), oospore wall 0.8 to 2.0 μm in thickness, sporangia terminal or intercalary, filamentous, inflated lobulate, and digitate, of variable length, breadth of sporangia 7.0 to 17.5 μm, formed in water; zoospores formed at 25°C, and diameter of encysted zoospores 10.0 to 12.5 μm. Cardinal temperatures on potato carrot agar 8°C minimum, 34°C optimum, and 37°C maximum with daily radial growth rate for 34°C at 32.8 mm. The ITS rDNA sequence of the isolate matched the sequences of P. myriotylum in GenBank (Accession Nos. AB095051 and AF452156) and isolate CBS254.70 used for the species description by van der Plaats-Niterink (3). The sequence of SC5 has been deposited in GenBank, Accession No. DQ102701. Pathogenicity tests used potted cocoyam plants (20 cm high), planted in an autoclaved potting mix. Four agar disks (8 mm in diameter) of isolate SC5 grown at 25°C for 48 h on potato dextrose agar was mashed and injected at a depth of 2 to 3 cm in the soil around the roots. Inoculated plants were placed in transparent plastic bags and kept for 7 days in a growth chamber maintained at 24 to 26°C with continuous light (52 to 98 μmol m
·s
). The experiment was carried out twice with three replications for each test. Dark brown rotting on roots and wilting of leaves were observed in 7 days after the inoculation. P. myriotylum was reisolated from diseased tissues and found to be morphologically identical to the original isolate SC5. Noninoculated control plants remained healthy. On the basis of the symptoms, morphological and molecular characteristics and confirmation of pathogenicity, P. myriotylum is the causal agent of root rot of cocoyam. To our knowledge, this is the first report of P. myriotylum causing root rot of cocoyam in Sri Lanka. References: (1) S. Nzietchueng. L'agronomie Tropicale 38:321, 1983. (2) R. P. Pacumbaba et al. J. Phytopathol. 135:265, 1992. (3) A. J. Van Der Plaats-Niterink. Stud. Mycol. 21:1, 1981.
Purpose:
To develop a measurement technique which suppresses the difference between profiles obtained with a multilayer ionization chamber (MLIC) and with a water phantom.
Methods:
The developed ...technique multiplies the raw MLIC data by a correction factor that depends on the initial beam range and water equivalent depth. The correction factor is derived based on a Bragg curve calculation formula considering range straggling and fluence loss caused by nuclear reactions. Furthermore, the correction factor is adjusted based on several integrated depth doses measured with a water phantom and the MLIC. The measured depth dose profiles along the central axis of the proton field with a nominal field size of 10 by 10 cm were compared between the MLIC using the new technique and the water phantom. The spread out Bragg peak was 20 cm for fields with a range of 30.6 cm and 6.9 cm. Raw MLIC data were obtained with each energy layer, and integrated after multiplying by the correction factor. The measurements were performed by a spot scanning nozzle at Nagoya Proton Therapy Center, Japan.
Results:
The profile measured with the MLIC using the new technique is consistent with that of the water phantom. Moreover, 97% of the points passed the 1% dose /1mm distance agreement criterion of the gamma index.
Conclusion:
We have demonstrated that the new technique suppresses the difference between profiles obtained with the MLIC and with the water phantom. It was concluded that this technique is useful for depth dose measurement in proton spot scanning method.
In a toroidal magnetic configuration, charged particles have long orbit lengths Kondoh and Yoshida (Nucl. Instr. and Meth. in Phys. Res. A 382 (1996) 561), and hence, a slow method of modulating the ...kinetic energy can be applied to confine the particles in the trapping region. Numerical simulation shows that a spatially inhomogeneous radio-frequency electric field induces effective diffusion of the particles toward the trapping region.
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