Symptomatic radiation pneumonitis after stereotactic body radiotherapy for multiple pulmonary oligometastases or synchronous primary lung cancer

[Purpose] Stereotactic body radiation therapy (SBRT) can be easily used for patients with tumors in various organs and is a promising local therapy for eradicating tumors in cancer patients. There is a rising clinical need for increasing knowledge of oligometastases in the treatment of multiple pulmonary tumors. This study aimed to explore the predictive factors for symptomatic radiation pneumonitis (RP) after SBRT for multiple pulmonary oligometastases or synchronous primary lung cancer (SPLC). [Methods and Materials] A total of 38 consecutive patients who had 2 or more pulmonary oligometastases (n = 21) or SPLC (n = 17) and who were treated with SBRT were investigated. Patient characteristics, tumor characteristics, and details of radiation therapy were retrospectively collected from a clinical database. The association between RP of grade 2 or worse (grade 2+ RP) and clinical or dosimetric factors was assessed using logistic regression analyses. [Results] The tumors presented ipsilaterally in 24 patients and bilaterally in 14 patients. During the median follow-up period of 4.9 years, grade 2+ RP, grade 2 RP, and grade 3 RP were observed in 9 patients (23.7%), 7 patients (18.4%), and 2 patients (5.3%), respectively. The mean lung dose (MLD) and the volume of the normal lung receiving ≥5 Gy (lung V5Gy) were significantly associated with grade 2+ RP (P = .023 and P = .012, respectively). The logistic model showed that 20% and 50% of the predicted probability of grade 2+ RP were 6.1 Gy and 9.1 Gy for MLD and 31.6 % and 42.8% for lung V5Gy, respectively. [Conclusion] Although further investigation is required to validate the metrics and establish reliable dose constraints, the dose-volume metrics for the normal lung could be predictive of the development of grade 2+ RP after SBRT for multiple pulmonary oligometastases or SPLCs

Di-neutron correlation and soft dipole excitation in medium mass neutron-rich nuclei near drip-line

The neutron pairing correlation and the soft dipole excitation in medium-mass nuclei near drip-line are investigated from a viewpoint of the di-neutron correlation. Numerical analyses by means of the coordinate-space HFB and the continuum QRPA methods are performed for even-even $^{18-24}$O, $^{50-58}$Ca and $^{80-86}$Ni. A clear signature of the di-neutron correlation is found in the HFB ground state; two neutrons are correlated at short relative distances \lesim 2 fm with large probability $\sim 50$. The soft dipole excitation is influenced strongly by the neutron pairing correlation, and it accompanies a large transition density for pair motion of neutrons. This behavior originates from a coherent superposition of two-quasiparticle configurations $[l\times (l+1)]_{L=1}$ consisting of continuum states with high orbital angular momenta $l$ reaching an order of $l\sim 10$. It raises a picture that the soft dipole excitation under the influence of neutron pairing is characterized by motion of di-neutron in the nuclear exterior against the remaining $A-2$ subsystem. Sensitivity to the density dependence of effective pair force is discussed.Comment: 35 pages, 22 figure

RUNX1 transactivates BCR-ABL1 expression in Philadelphia chromosome positive acute lymphoblastic leukemia

The emergence of tyrosine kinase inhibitors as part of a front-line treatment has greatly improved the clinical outcome of the patients with Ph⁺ acute lymphoblastic leukemia (ALL). However, a portion of them still become refractory to the therapy mainly through acquiring mutations in the BCR-ABL1 gene, necessitating a novel strategy to treat tyrosine kinase inhibitor (TKI)-resistant Ph⁺ ALL cases. In this report, we show evidence that RUNX1 transcription factor stringently controls the expression of BCR-ABL1, which can strategically be targeted by our novel RUNX inhibitor, Chb-M'. Through a series of in vitro experiments, we identified that RUNX1 binds to the promoter of BCR and directly transactivates BCR-ABL1 expression in Ph⁺ ALL cell lines. These cells showed significantly reduced expression of BCR-ABL1 with suppressed proliferation upon RUNX1 knockdown. Moreover, treatment with Chb-M' consistently downregulated the expression of BCR-ABL1 in these cells and this drug was highly effective even in an imatinib-resistant Ph⁺ ALL cell line. In good agreement with these findings, forced expression of BCR-ABL1 in these cells conferred relative resistance to Chb-M'. In addition, in vivo experiments with the Ph⁺ ALL patient-derived xenograft cells showed similar results. In summary, targeting RUNX1 therapeutically in Ph⁺ ALL cells may lead to overcoming TKI resistance through the transcriptional regulation of BCR-ABL1. Chb-M' could be a novel drug for patients with TKI-resistant refractory Ph⁺ ALL

Gene flow from GM glyphosate-tolerant to conventional soybeans under field conditions in Japan

Natural out-crossing rates were evaluated for conventional soybeans (Glycine max (L.) Merr.) cultivated adjacent to genetically modified (GM) glyphosate-tolerant soybeans under field conditions during a four-year period in Japan. A total of 107 846 progeny of 2772 plants harvested from conventional varieties were screened for glyphosate herbicide tolerance. The highest out-crossing rates, 0.19% in 2001 and 0.16% in 2002, were observed in adjacent rows 0.7 m from the pollen source. The highest rate in 2004 was 0.052%, which was observed at 2.1 m. No out-crossing was observed in the rows 10.5 m from the pollen source over the four-year period. The farthest distances between receptor and pollen source at which out-crossing was observed were 7 m in 2001, 2.8 m in 2002, and 3.5 m in 2004. The greatest airborne pollen density during the flowering period, determined by Durham pollen samplers located between the rows of each variety, was 0.368 grains.cm-2.day-1, with the average value at 0.18 grains.cm-2.day-1, indicating that the possibility of out-crossing by wind is minimal. Thrips species and predatory Hemiptera visited the soybean flowers more frequently during the four-year period than any other common pollinators, such as bees