The Effects of Boron Neutron Capture Therapy on the Lungs in Recurrent Breast Cancer Treatment.

Boron neutron capture therapy (BNCT) has predominantly been performed for brain tumors or head and neck cancers. Although BNCT is known to be applicable to breast cancer, it has only been performed in a few cases involving thoracic region irradiation with reactor-based BNCT systems. Thus, there are very few reports on the effects of BNCT on the thoracic region and no reports of BNCT for breast cancer with accelerator-based BNCT systems. This paper introduces the world's first clinical study employing an accelerator-based BNCT system targeting recurrent breast cancer after radiation therapy. We aim to assess the efficacy and safety of BNCT, focusing on the dose response in the thoracic region, especially concerning the potential for radiation pneumonitis. Preliminary findings from the first three cases indicate no evidence of radiation pneumonitis within three months post treatment. This study not only establishes a foundation for novel breast cancer treatment options but also contributes significantly to the field of BNCT in the thoracic region.

Kamebakaurin Suppresses Antigen-Induced Mast Cell Activation by Inhibition of FcεRI Signaling Pathway.

INTRODUCTION: Kamebakaurin is an active constituent of both Rabdosia japonica and Rabdosia excisa, which are utilized in Chinese traditional medicine for improving symptoms in patients with allergies. We investigated the molecular mechanisms of the anti-allergic effects of kamebakaurin using BMMCs. METHODS: The degranulation ratio, histamine release, and the interleukin (IL)-4, leukotriene B4 (LTB4), and cysteinyl leukotriene productions on antigen-triggered BMMC were investigated. Additionally, the effects of kamebakaurin on signal transduction proteins were examined by Western blot and binding to the Syk and Lyn kinase domain was calculated. The effects of kamebakaurin on antigen-induced hyperpermeability were investigated using mouse model. RESULTS: At 10 µm, kamebakaurin partially inhibited degranulation, histamine release, and IL-4 production. At 30 µm, kamebakaurin partially reduced LTB4 and cysteinyl leukotriene productions and suppressed degranulation, histamine release, and IL-4 production. Phosphorylation of both Syk Y519/520 and its downstream protein, Gab2, was reduced by kamebakaurin, and complete inhibition was observed with 30 µm kamebakaurin. In contrast, phosphorylation of Erk was only partially inhibited, even in the presence of 30 µm kamebakaurin. Syk Y519/520 is known to be auto-phosphorylated via intramolecular ATP present in its own ATP-binding site, and this auto-phosphorylation triggers degranulation, histamine release, and IL-4 production. Docking simulation study indicated kamebakaurin blocked ATP binding to the ATP-binding site in Syk. Therefore, inhibition of Syk auto-phosphorylation by kamebakaurin binding to the Syk ATP-binding site appeared to cause a reduction of histamine release and IL-4 production. Kamebakaurin inhibited antigen-induced vascular hyperpermeability in a dose-dependent fashion but did not reduce histamine-induced vascular hyperpermeability. CONCLUSION: Kamebakaurin ameliorates allergic symptoms via inhibition of Syk phosphorylation; thus, kamebakaurin could be a lead compound for the new anti-allergic drug.

Aqua-{µ-1,4-bis-[(1,4,7,10-tetra-aza-cyclo-dodecan-1-yl)meth-yl]benzene}(nitrato-κO)dicopper(II) tris-(nitrate) trihydrate.

In the title dinuclear CuII complex, [Cu2(NO3)(C24H46N8)(H2O)](NO3)3·3H2O, the two CuII mol-ecules both have a square-pyramidal geometry, but the ligands in the axial positions are different: a water mol-ecule and a nitrate ion. All nitrate ions, water mol-ecules, and N-H groups are involved in an inter-molecular hydrogen-bond network.

Tomotherapy: Comparison of Hi-ART, Tomo-HD, and Radixact.

Aim In this study, we compared three generations of tomotherapy (Hi-ART, Tomo-HD, and Radixact). This is to study the difference among tomotherapy systems in terms of dose distribution to planning target volume and organs at risk, and irradiation time.  Materials and methods The treatment planning CT and contour information used were seven cases of rectum cancer pre-operative irradiation. The contour information used was the planning target volume, and the organs at risk were set as the bladder and body. Optimization was conducted at each planning station using the parameters that were actually used in a clinical setting. The prescribed radiation dose was 25 Gy in five fractions and normalized at the isodose line, covering 95% of the planning target volume. Results There were no significant differences in planning target volume among the three models. Meanwhile, Hi-ART had a significantly higher dose than Tomo-HD and Radixact at body D50%. Radixact shortened the irradiation time by approximately 15% compared to Hi-ART/Tomo-HD. Conclusion Planning target volume dose distribution of tomotherapy devices was not different. Radixact required a significantly shorter time than Hi-ART and Tomo-HD.

Plan Quality Comparison Between Hippocampus-Sparing Whole-Brain Radiotherapy Treated With Halcyon and Tomotherapy Intensity-Modulated Radiotherapy.

Objective: Hippocampus-sparing whole-brain radiotherapy using Halcyon, an instrument dedicated to volumetric modulated arc therapy, has not been studied till date; hence, we aimed to examine whether it can meet the RTOG0933 criteria. Based on this, we compared Halcyon to Tomotherapy, which also uses an O-ring-type linear accelerator. Methods: This exploratory, experimental, and retrospective study used 5 sets of computed tomography images in the head area to investigate the planning target volume, hippocampal doses, and irradiation time. Calculations were performed from 1 to 4 arcs to determine the optimal number of arcs in the Halcyon plan, which were compared to those of Tomotherapy. Results: The Radiation Therapy Oncology Group 0933 criteria could not be satisfied in Halcyon with 1 arc. With 2 arcs, the condition Dmax<16 Gy was not satisfied for 1 case in the hippocampus. Since there were no significant differences between 3 and 4 arcs, including the irradiation time, 3 arcs were considered the best. We compared Halcyon at 3 arcs with tomotherapy and found that tomotherapy was inferior to Halcyon at D98%; however, it was superior to Halcyon in other dose parameters. In contrast, the irradiation time in Halcyon was overwhelmingly superior, with the irradiation time for Halcyon being 1/ninth the time for Tomotherapy. Conclusion: Halcyon was effective in handling hippocampus-sparing whole-brain radiotherapy. We believe that 3-arc radiation is best suited for this procedure. Although Halcyon was inferior to Tomotherapy in terms of dose distribution excluding D98%, it was overwhelmingly superior in terms of irradiation time.

Improvement of Metastatic Spinal Cord Compression After Decompression Surgery and Radiotherapy in a Patient Initially Treated for Rectal Cancer.

Many reports indicate that the prognosis of patients with rectal cancer who have thoracic spine metastases with spinal cord compression is poor. Here, we discuss a case of a patient who achieved an improvement of functional prognosis and long-term survival after undergoing surgery and radiotherapy. We report a case of a 64-year-old female who was found to have metastatic spinal cord compression (MSCC) in the second thoracic vertebra, 10 years after surgery for rectal cancer. She experienced numbness in both legs and had gait difficulties. She underwent posterior decompression surgery and radiotherapy. Her neurological symptoms improved after radiotherapy, and the patient could maintain a standing position without assistance within one week after irradiation. She has since received adjuvant chemotherapy and continues to survive five years six months since MSCC onset.

Influence of Modulation Factor on Treatment Plan Quality and Irradiation Time in Hippocampus-Sparing Whole-Brain Radiotherapy Using Tomotherapy.

Objectives: Hippocampus-sparing whole-brain radiotherapy (HS-WBRT) using tomotherapy is known to provide a better dose distribution than volumetric-modulated arc therapy but requires an extended irradiation time. The present study aimed to investigate whether irradiation time can be shortened by reducing the modulation factor (MF) without losing the target dose distribution. Methods: Using six tilted computed tomography images in the head area, the planning target volume (PTV) and hippocampal doses, and the irradiation time was investigated with a jaw width of 1 cm, a pitch of 0.200, and the MF changed from 3.0 to 2.6, 2.2, 1.8, and 1.4. Results: No significant changes in the PTV or hippocampus were found with MF in the range from 3.0 to 1.8, but marked deterioration was found with that of 1.4. The irradiation time showed a linear relationship with the MF within the range from 3.0 to 1.8, with 1334, 1158, 986, and 817 s at modulation factors of 3.0, 2.6, 2.2, and 1.8, respectively. However, when the MF was 1.4, the irradiation time was 808 s. Conclusions: When HS-WBRT is performed with a tilted body position and a jaw width of 1 cm, with a MF of 1.8, a favorable balance between dose parameters and irradiation time is achieved, whereas with a MF of 1.4, the quality of the radiotherapy plan deteriorates, and the irradiation time is approximately the same as that with a MF of 1.8.

Palliative radiation treatment used for multiple purposes in a single irradiation field.

In this case report, radiation therapy was performed for bilateral hydronephrosis developed during multiple bone metastases of breast cancer and ileus due to peritoneal dissemination. The patient's preirradiation creatinine level was 8.2 mg/dL, which decreased by the fourth day after starting irradiation therapy. Creatinine level ultimately decreased to 0.6 mg/dL. Pain due to lumbar spine metastasis alleviated and ileus was resolved, allowing the patient to live at home for approximately 5 weeks. The effect of radiotherapy for bilateral hydronephrosis and gastrointestinal obstruction was rapid and good. Palliative radiation treatment can be used for multiple purposes, and in the present patient, we were able to prolong the vital prognosis.

A Case of Suspected Radiation Recall Pneumonitis After a COVID-19 Infection.

We present the case of a 78-year-old woman who received definitive radiation therapy for small cell lung cancer three and a half years ago. She was asymptomatic when she tested positive for coronavirus disease 2019 (COVID-19). She then developed a rapid decline in respiratory status on day seven. Chest radiograph revealed a strong shadow at the prior irradiation site. Radiation recall reactions are usually caused by drug administration, but in this case, it was suspected to be caused by COVID-19.

Use of a Head-Tilting Baseplate During Tomotherapy to Shorten the Irradiation Time and Protect the Hippocampus and Lens in Hippocampal Sparing-Whole Brain Radiotherapy.

PURPOSE: The aim of this study is to comparatively examine the possibility of reducing the exposure dose to organs at risk, such as the hippocampus and lens, and improving the dose distribution of the planned target volume with and without the use of a head-tilting base plate in hippocampal-sparing whole-brain radiotherapy using tomotherapy. METHODS: Five paired images of planned head computed tomography without and with tilt were analyzed. The hippocampus and planning target volume were contoured according to the RTOG 0933 contouring atlas protocol. The hippocampal zone to be avoided was delineated using a 5-mm margin. The prescribed radiation dose was 30 Gy in 10 fractions. The absorbed dose to planning target volume dose, absorbed dose to the organ at risk, and irradiation time were evaluated. The paired t-test was used to analyze the differences between hippocampal-sparing whole-brain radiotherapy with head tilts and without head tilts. RESULTS: Hippocampal-sparing whole-brain radiotherapy with tilt was not superior in planning target volume doses using the homogeneity index than that without tilt; however, it showed better values, and for Dmean and D2%, the values were closer to 30 Gy. Regarding the hippocampus, dose reduction with tilt was significantly greater at Dmax, Dmean, and Dmin, whereas regarding the lens, it was significantly greater at Dmax and Dmin. The irradiation time was also predominantly shorter. CONCLUSION: In our study, a tilted hippocampal-sparing whole-brain radiotherapy reduced the irradiation time by >10%. Therefore, our study indicated that hippocampal-sparing whole-brain radiotherapy with tomotherapy should be performed with a tilt. The head-tilting technique might be useful during hippocampal-sparing whole-brain radiotherapy. This method could decrease the radiation exposure time, while sparing healthy organs, including the hippocampus and lens.

Pretreatment PSA levels affects the completion rate of Ra-223 treatment.

The aim of this study was to review our initial experience of using radium 223 (Ra-223) for metastatic castration-resistant prostate cancer (CRPC) and to evaluate whether pretreatment PSA levels correlate with completion of Ra-223 treatment. In addition, we examined change ratios of PSA, ALP and BAP after the third administration to evaluate the correlation of these change ratios with completion of the subsequent Ra-223 treatment. Forty patients were enrolled in this retrospective study. Ra-223 treatment was considered completed in patients who received five or six administrations. Patient backgrounds and changes in biomarkers were compared between patient groups (complete vs. incomplete Ra-223 treatment). PSA levels before treatment were significantly lower in the complete compared with the incomplete group (cutoff value; 21.7). ALP and BAP levels had decreased after the third administration in the complete group, compared with baseline levels, while levels in the incomplete group had increased. Significant difference was seen in ALP levels, while was not seen in BAP levels between the two groups. Ra-223 treatment should be considered for CRPC with low PSA levels. Changes in PSA and ALP during Ra-223 treatment might provide markers to identify patients likely to complete Ra-223 treatment, with implications for prognosis.

DNA-cleavage activity of the iron(II) complex with optically active ligands, meta- and para-xylyl-linked N',N'-dipyridylmethyl-cyclohexane-1,2-diamine.

DNA-cleavage agents such as bleomycin have potential anticancer applications. The development of a DNA-cleavage reagent that recognizes specific sequences allows the development of cancer therapy with reduced side effects. In this study, to develop novel compounds with specific DNA-cleavage activities, we synthesized optically active binuclear ligands, (1R,1'R,2R,2'R)-N1,N1'-(meta/para-phenylenebis(methylene))bis(N2,N2-bis(pyridin-2-ylmethyl)cyclohexane-1,2-diamine) and their enantiomers. The DNA-cleavage activities of these compounds were investigated in the presence of Fe(II)SO4 and sodium ascorbate. The obtained results indicated that the Fe(II) complexes of those compounds efficiently cleave DNA and that their cleavage was subtle sequence-selective. Therefore, we succeeded in developing compounds that can be used as small-molecule drugs for cancer chemotherapy.

Radiotherapy Planning System to Measure Tumor Doubling Time in Cervical Cancer.

Tumor doubling time is an important clinical parameter, but it is rarely reported in cervical cancer. We encountered a case in which the tumor doubling time could be measured using a radiotherapy planning device. A woman in her 40s was diagnosed with cervical cancer stage IB1 (squamous cell carcinoma) and refused treatment. One year and five months later, definitive radiation therapy was administered. Magnetic resonance imaging was performed five times before the start of treatment. When the tumor volume was measured using the radiotherapy planning system - RayStation🄬 (RaySearch Laboratories, Stockholm, Sweden) on the T2 sagittal image, the tumor doubling time was 76 days, and the tumor volume had increased exponentially.

Design and synthesis of an anthranyl bridged optically active dinuclear iron(II)-ligand and evaluation of DNA-cleaving activity.

It is necessary to design a ligand that is compatible with the target molecule to optimally use the DNA-cleaving ability of metal complexes. In this study, we synthesized an optically active dinuclear ligand, (1R,1'R,2R,2'R)-N1,N1'-(anthracene-1,8-diylbis(methylene))bis(N2,N2-bis(pyridin-2-ylmethyl)cyclohexane-1,2-diamine) (R-ABDC, 4a) and its enantiomer (S-ABDC, 4b). We then prepared their Fe(II) complexes by mixing the ligand with FeSO4·7H2O in situ and investigated DNA-cleaving activities using plasmid DNA in the presence of excess sodium ascorbate at atmospheric conditions. The Fe(II) complexes efficiently cleaved DNA and selectively recognized two consecutive A and/or T sequences.

Noncoplanar Radiation using Tomotherapy: A Phantom Study.

BACKGROUND: There are very few studies on noncoplanar radiation in tomotherapy because deformable image registration is not implemented in the TomoTherapy Planning Station, a treatment planning device used in tomotherapy. This study examined whether noncoplanar radiation can be performed on the head using a tilt-type head and neck fixture and deformable image registration. METHODS: Planning target volume spheres with diameters of 2, 3, and 4 cm were set on a head phantom, and computed tomography images were taken at 0° and 40° using a tilt-type head and neck fixture. Irradiation plans were created in the Tomotherapy Planning Station. Noncoplanar radiation was simulated, and the dose volume was evaluated by adding the 0° dose distribution and 40° dose distribution using the deformable image registration of the RayStation treatment planning system. RESULTS: The ratio of the phantom volume to the irradiation dose for 20% to 30% of the planning target volume in noncoplanar radiation was smaller than that for 40% to 90% of the planning target volume in single-section irradiation at 0° or 40°. CONCLUSIONS: Noncoplanar radiation on the head region using tomotherapy was possible by using a tilt-type head and neck fixture, and the dose distribution could be evaluated using deformable image registration. This method helps reduce the dose of the organ-at-risk region located slightly away from the planning target volume.

Activation of Ligand Reaction on an Iron Complex: H/D Exchange Reaction of a Low-Spin Bis[2-(Pyridylmethylidene)-1-(2-pyridyl)methylamine]iron(II) Complex.

With the aim of shedding some light on the still scarcely investigated mechanism of transformation of imines in metal complexes, this study describes the investigation of the hydrogen-deuterium (H/D) exchange reaction of a bis[2-(pyridylmethylidene)-1-(2-pyridylmethylamine]iron(II) complex ([Fe(PMAP)2]2+), following our previous work on a low-spin iron(II) complex bearing two molecules of S-2-pyridylmethylidene-1-(2-pyridyl)ethylamine. This complex has been proven to undergo successive transiminations in acetonitrile, yielding a bis[1-(2-pyridyl)ethylidene-2-pyridylmethylamine]iron(II) complex. In the analogous [Fe(PMAP)2]2+ complex, a 1,3-hydrogen rearrangement occurs in a 10% deuterium oxide-acetonitrile-d3 (D2O-CD3CN) solution. The H/D exchange reaction of [Fe(PMAP)2]2+ was examined in the presence of various concentrations of 2,6-dimethylpyridine as a base in a 10% D2O-CD3CN solution at 45 °C, and the reaction mechanism was investigated.

HSP70 induction by bleomycin metal core analogs.

Induction of heat shock protein 70 (HSP70) is known to be effective against various diseases. We are interested in HSP70 induction capability of an antitumor antibiotic bleomycin which produces oxidative stress by iron chelate formation and oxygen activation in a cell. The HSP70 induction activity of bleomycin and its six metal core analogs was examined, and a compound HPH-1Trt of 10 µM was found to induce this protein in a pheochromocytoma cell line and some T cell and monocytic cell lines. Its mechanism is increase of HSP70 mRNA, but higher concentration of this compound showed toxicity. Two new derivatives were then synthesized, and one of them named DHPH-1Trt was shown to have less toxicity and higher HSP70 induction activity. This study would lead to a clue for new HSP70 inducer clinically used in near future.

Significance of prostate-specific antigen kinetics after three-dimensional conformal radiotherapy with androgen deprivation therapy in patients with localized prostate cancer.

BACKGROUND: To evaluate the relationship between biochemical recurrence and post-radiation prostate-specific antigen (PSA) kinetics in patients with localized prostate cancer treated by radiotherapy with various durations of androgen deprivation therapy (ADT). METHODS: We reviewed our single-institution, retrospectively maintained data of 144 patients with T1c-T3N0M0 prostate cancer who underwent three-dimensional conformal radiotherapy (3D-CRT) between December 2005 and December 2015 and 113 patients were fulfilled the inclusion criteria. In this cohort, 3D-CRT was delivered with a dose in the range from 70.0 to 72.0 Gy with ADT. All patients received ADT as concurrent regimens. Biochemical recurrence was defined on the basis of the following: "PSA nadir + 2.0 ng/ml or the clinical judgement of attending physicians". Kaplan-Meier, log-rank, and Cox regression analyses were carried out. RESULTS: The median follow-up period was 54.0 months. The median duration of ADT was 17 months (interquartile range, 10-24 months). There was a trend toward statistical significant correlation between post-radiation PSA decline rate of ≥ 90% and PSA recurrence (p = 0.056). The same correlation could be observed in D'Amico high-risk patients (p = 0.036). However, it was not observed between PSA nadir and PSA recurrence (p = 0.40) in univariate analysis. Furthermore, multivariate analysis showed that post-radiation PSA decline rate of ≥ 90% was a significant predictor of biochemical recurrence in patients who received radiotherapy with various durations of ADT (p = 0.044). CONCLUSIONS: Post-radiation PSA decline rate of ≥ 90% was a prognostic factor for biochemical recurrence in localized prostate cancer patients received 3D-CRT with various durations of ADT.

Novel metal chelating molecules with anticancer activity. Striking effect of the imidazole substitution of the histidine-pyridine-histidine system.

Previously we have reported a metal chelating histidine-pyridine-histidine system possessing a trityl group on the histidine imidazole, namely HPH-2Trt, which induces apoptosis in human pancreatic adenocarcinoma AsPC-1 cells. Herein the influence of the imidazole substitution of HPH-2Trt was examined. Five related compounds, HPH-1Trt, HPH-2Bzl, HPH-1Bzl, HPH-2Me, and HPH-1Me were newly synthesized and screened for their activity against AsPC-1 and brain tumor cells U87 and U251. HPH-1Trt and HPH-2Trt were highly active among the tested HPH compounds. In vitro DNA cleavage assay showed both HPH-1Trt and HPH-2Trt completely disintegrate pUC19 DNA. The introduction of trityl group decisively potentiated the activity.