Inter-fractional error and intra-fractional motion of prostate and dosimetry comparisons of patient position registrations with versus without fiducial markers during treatment with carbon-ion radiotherapy.

A few reports have discussed the influence of inter-fractional position error and intra-fractional motion on dose distribution, particularly regarding a spread-out Bragg peak. We investigated inter-fractional and intra-fractional prostate position error by monitoring fiducial marker positions. In 2020, data from 15 patients with prostate cancer who received carbon-ion beam radiotherapy (CIRT) with gold markers were investigated. We checked marker positions before and during irradiation to calculate the inter-fractional positioning and intra-fractional movement and evaluated the CIRT dose distribution by adjusting the planning beam isocenter and clinical target volume (CTV) position. We compared the CTV dose coverages (CTV receiving 95% [V95%] or 98% [V98%] of the prescribed dose) between skeletal and fiducial matching irradiation on the treatment planning system. For inter-fractional error, the mean distance between the marker position in the planning images and that in a patient starting irradiation with skeletal matching was 1.49 ± 1.11 mm (95th percentile = 1.85 mm). The 95th percentile (maximum) values of the intra-fractional movement were 0.79 mm (2.31 mm), 1.17 mm (2.48 mm), 1.88 mm (4.01 mm), 1.23 mm (3.00 mm), and 2.09 mm (8.46 mm) along the lateral, inferior, superior, dorsal, and ventral axes, respectively. The mean V95% and V98% were 98.2% and 96.2% for the skeletal matching plan and 99.5% and 96.8% for the fiducial matching plan, respectively. Fiducial matching irradiation improved the CTV dose coverage compared with skeletal matching irradiation for CIRT for prostate cancer.

Spin dynamics phenomena of a cerium(III) double-decker complex induced by intramolecular electron transfer.

Switchable spin dynamic properties in single-molecule magnets (SMMs) via an applied stimulus have applications in single-molecule devices. Many SMMs containing heavy lanthanoid ions with strong uniaxial magnetic anisotropy have been reported to exhibit SMM characteristics in the absence of an external magnetic field. On the other hand, SMMs containing light lanthanoid cerium(III) (Ce3+) ions exhibit field-induced slow magnetic relaxation. We investigated the chemical conversion of a diamagnetic Ce4+ ion (4f0) to a paramagnetic Ce3+ ion (4f1) in Ce-phthalocyaninato double-decker complexes (TBA+[Ce(obPc)2]- (1) and TBA+[Ce(Pc)2]- (2)) which exhibit field-induced SMM behaviour due to a 4f1 system. The phthalocyaninato ligands with electron-donating substituents (obPc2- = 2,3,9,10,16,17,23,24-octabutoxyphthalocyaninato) in 1 have a significant effect on the valence state of the Ce ion, which is reflected in its magnetic properties due to the mixed valence state of the Ce ion. Given that Ce double-decker complexes with π-conjugated ligands undergo intramolecular electron transfer (IET) to the Ce ion mixed valence state, characterised by a mixture of 4f0 and 4f1 configurations, we examined the dynamic disorder inherent in IET influencing magnetic relaxation.

A Phase I Trial of Weekly Nab-paclitaxel Plus Carboplatin With Thoracic Radiotherapy for Non-small Cell Lung Cancer.

BACKGROUND/AIM: This study aimed to evaluate the safety and recommended dose of nab-paclitaxel in combination with carboplatin and thoracic radiotherapy for locally advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Nab-paclitaxel was administered weekly with escalating doses, combined with carboplatin area under the curve (AUC) 2 and concurrent standard thoracic radiotherapy. Escalating doses of nab-paclitaxel were as follows: level 0, 30 mg/m2; level 1, 35 mg/m2; level 2, 40 mg/m2; level 3, 45 mg/m2 Results: Twelve patients were enrolled and received the treatment according to the protocol; seven patients (58%) had squamous cell carcinoma and all cases had stage III disease. At level 1, none of the three patients experienced dose limiting toxicity (DLT). At level 2, one of the first three patients experienced a fatal DLT of bronchopulmonary hemorrhage. None of the three more additional patients experienced DLT. At level 3, two of the three patients experienced a DLT of grade 3 febrile neutropenia and grade 4 neutropenia, respectively. Consolidation chemotherapy was provided to 10 of 12 patients. Radiation pneumonitis developed in five of 12 patients (42%). Eight patients (66.7%) showed partial response, and four (33.3%) showed stable disease. For the above reasons, level 2 (40 mg/m2) was considered the recommended dose in this study. CONCLUSION: Concurrent chemoradiotherapy with weekly nab-paclitaxel (40 mg/m2) and carboplatin (AUC 2) is a feasible and well-tolerated regimen in patients with previously untreated locally advanced NSCLC. A phase II trial with this regimen is warranted.

Two cyclic electron flows around photosystem I differentially participate in C4 photosynthesis.

C4 plants assimilate CO2 more efficiently than C3 plants because of their C4 cycle that concentrates CO2. However, the C4 cycle requires additional ATP molecules, which may be supplied by cyclic electron flow (CEF) around photosystem I. One CEF route, which depends on a chloroplast NADH dehydrogenase-like (NDH) complex, is suggested to be crucial for C4 plants despite the low activity in C3 plants. The other route depends on proton gradient regulation 5 (PGR5) and PGR5-like photosynthetic phenotype 1 (PGRL1) and is considered a major CEF route to generate the proton gradient across the thylakoid membrane in C3 plants. However, its contribution to C4 photosynthesis is still unclear. In this study, we investigated the contribution of the two CEF routes to the NADP-malic enzyme subtype of C4 photosynthesis in Flaveria bidentis. We observed that suppressing the NDH-dependent route drastically delayed growth and decreased the CO2 assimilation rate to approximately 30% of the wild-type rate. On the other hand, suppressing the PGR5/PGRL1-dependent route did not affect plant growth and resulted in a CO2 assimilation rate that was approximately 80% of the wild-type rate. Our data indicate that the NDH-dependent CEF substantially contributes to the NADP-malic enzyme subtype of C4 photosynthesis and that the PGR5/PGRL1-dependent route cannot complement the NDH-dependent route in F. bidentis. These findings support the fact that during C4 evolution, photosynthetic electron flow may have been optimized to provide the energy required for C4 photosynthesis.

Archetype analysis of older adult immunization decision-making and implementation in 34 countries.

The global population of adults over 65 years of age is growing rapidly and is expected to double by 2050. Countries will face substantial health, economic and social burden deriving from vaccine-preventable diseases (VPDs) such as influenza, pneumonia and herpes zoster in older adults. It will be essential that countries utilize several public health strategies, including immunization. Understanding the different approaches countries have taken on adult immunization could help provide future learnings and technical support for adult vaccines within life-course immunization strategies. In this study, we describe the priorities and approaches that underlie adult immunization decision-making and implementation processes in 32 high-and-middle-income countries and two territories ("34 countries") who recommend adult vaccines in their national schedule. We conducted an archetype analysis based on a subset of two dozen indicators abstracted from a larger database. The analysis was based on a mixed-methods study, including results from 120 key informant interviews in six countries and a landscape review of secondary data from 34 countries. We found four distinct archetypes: disease prevention-focused; health security-focused; evolving adult focus; and, child-focused and cost-sensitive. The highest performing countries belonged to the disease prevention-focused and health security archetypes, although there was a range of performance within each archetype. Considering common barriers and facilitators of decision-making and implementation of adult vaccines within a primary archetype could help provide a framework for strategies to support countries with similar needs and approaches. It can also help in developing context-specific policies and guidance, including for countries prioritizing adult immunization programs in light of COVID-19. Further research may be beneficial to further refine archetypes and expand the understanding of what influences success within them. This can help advance policies and action that will improve vaccine access for older adults and build a stronger appreciation of the value of immunization amongst a variety of stakeholders.

[Recurrent High-grade Astroblastoma Treated with Stereotactic Radiotherapy:A Case Report].

INTRODUCTION: Astroblastoma is a rare, supratentorial glial tumor, occurring predominantly in children and young adults. However, treatment strategies have not yet been established for this rare disease. CASE PRESENTATION: A 6-year-old boy presented with headache and nausea. CT and MRI revealed a left frontal mass lesion with slight edema and macrocalcifications. Gross tumor resection was performed. Histological examination found neoplastic cells with astroblastic characteristics, and a striking perivascular array of pseudorosettes. The final diagnosis was high-grade astroblastoma. MRI 13 months after surgery suggested local recurrence, and an enlargement was found 3 months later. Stereotactic radiotherapy(SRT)was performed. MRI after SRT showed enhanced cyst formation around the tumor bed, suggesting tumor recurrence. However, 11C-methionine positron emission tomography(PET)revealed radiation necrosis. The last follow-up MRI 15 months after SRT showed no further recurrence. CONCLUSION: Astroblastoma is rare, therefore, no optimal management is known. SRT may be effective to treat recurrent astroblastomas. 11C-methionine PET/CT was useful to differentiate metastatic disease from radiation necrosis.

Involvement of an Oct4-related PouV gene, pou5f3/pou2, in neurogenesis in the early neural plate of zebrafish embryos.

In early vertebrate embryos, the dorsal ectoderm is induced by the axial mesendoderm to form the neural plate, which is given competence to form neural cells by soxB1 genes. Subsequently, neurogenesis proceeds in proneural clusters that are generated by a gene network involving proneural genes and Notch signaling. However, what occurs between early neural induction and the later initiation of neurogenesis has not been fully revealed. In the present study, we demonstrated that during gastrulation, the expression of the Oct4-related PouV gene pou5f3 (also called pou2), which is widely observed at earlier stages, was rapidly localized to an array of isolated spotted domains, each of which coincided with individual proneural clusters. Two-color in situ hybridization confirmed that each pou5f3-expressing domain included a proneural cluster. Further analysis demonstrated that anterior pou5f3 domains straddled the boundaries between rhombomere 1 (r1) and r2, whereas posterior domains were included in r4. The effects of forced expression of an inducible negative dominant-interfering pou5f3 gene suggested that pou5f3 activated early proneural genes, such as neurog1 and ebf2, and also soxB1, but repressed the late proneural genes atoh1a and ascl1b. Furthermore, pou5f3 was considered to repress her4.1, a Notch-dependent Hairy/E(spl) gene involved in lateral inhibition in proneural clusters. These results suggest that pou5f3 promotes early neurogenesis in proneural clusters, but negatively regulates later neurogenesis. Suppression of pou5f3 also altered the expression of other her genes, including her3, her5, and her9, further supporting a role for pou5f3 in neurogenesis. In vitro reporter assays in P19 cells showed that pou5f3 was repressed by neurog1, but activated by Notch signaling. These findings together demonstrate the importance of the pou5f3-mediated gene regulatory network in neural development in vertebrate embryos.

In vitro analysis of the transcriptional regulatory mechanism of zebrafish pou5f3.

Zebrafish pou5f3 (previously named pou2), a close homologue of mouse Oct4, encodes a PouV-family transcription factor. pou5f3 has been implicated in diverse aspects of developmental regulation during embryogenesis. In the present study, we addressed the molecular function of Pou5f3 as a transcriptional regulator and the mechanism by which pou5f3 expression is transcriptionally regulated. We examined the influence of effector genes on the expression of the luciferase gene under the control of the upstream 2.1-kb regulatory DNA of pou5f3 (Luc-2.2) in HEK293T and P19 cells. We first confirmed that Pou5f3 functions as a transcriptional activator both in cultured cells and embryos, which confirmed autoregulation of pou5f3 in embryos. It was further shown that Luc-2.2 was activated synergistically by pou5f3 and sox3, which is similar to the co-operative activity of Oct4 and Sox2 in mice, although synergy between pou5f3 and sox2 was less obvious in this zebrafish system. The effects of pou5f3 deletion constructs on the regulation of Luc-2.2 expression revealed different roles for the three subregions of the N-terminal region in Pou5f3 in terms of its regulatory functions and co-operativity with Sox3. Electrophoretic mobility shift assays confirmed that Pou5f3 and Sox3 proteins specifically bind to adjacent sites in the 2.1-kb DNA and that there is an interaction between the two proteins. The synergy with sox3 was unique to pou5f3-the other POU factor genes examined did not show such synergy in Luc-2.2 regulation. Finally, functional interaction was observed between pou5f3 and sox3 in embryos in terms of the regulation of dorsoventral patterning and convergent extension movement. These findings together demonstrate co-operative functions of pou5f3 and sox3, which are frequently coexpressed in early embryos, in the regulation of early development.

Development of a sandwich ELISA for the thrombin light chain identified by serum proteome analysis.

We previously identified novel biomarker candidates in biliary tract cancer (BTC) using serum proteome analysis. Among several candidates, we focused on thrombin light chain which is a 4204 Da peptide as the most promising biomarker for BTC. To move thrombin light chain toward potential diagnostic use, we developed an enzyme immunoassay that enables to measure serum thrombin light chain levels. Both one monoclonal antibody specific to the N-termini and one polyclonal antibody were used to develop a sandwich ELISA for thrombin light chain. The assay was evaluated by comparing the results with those obtained by the ClinProt™ system. Serum samples were obtained from 20 patients with BTC, 20 patients with BBTDs and 20 HVs using the ClinProt™ system and ELISA. The results of the established ELISA showed a positive correlation with the findings by ClinProt™ system (slope=0.3386, intercept=34.901, r2=0.9641). The performance of the ELISA was satisfactory in terms of recovery (97.9-102.5%) and within-run (1.5-4.8%) and between-day (1.9-6.7%) reproducibility. Serum thrombin light chain levels were significantly greater in BTC (176.5±47.2 ng/mL) than in BBTDs (128.6±17.4 ng/mL) and HVs (127.6±16.0 ng/mL) (p<0.001). The sandwich ELISA developed in this study will be useful for validation of the diagnostic significance of serum thrombin light chain levels in various cancers.

Therapeutic results of a novel enzyme-targeting radiosensitization treatment, Kochi oxydol-radiation therapy for unresectable carcinomas II, in patients with stage I primary breast cancer.

Linac-based stereotactic radiotherapy has little effect on the majority of advanced neoplasms. Therefore, the novel radiosensitizer Kochi oxydol-radiation therapy for unresectable carcinomas (KORTUC) II, which contains hydrogen peroxide and sodium hyaluronate, was developed. The effectiveness of KORTUC II for the treatment of chemotherapy-resistant supraclavicular lymph node metastases, recurrent breast cancer and stage IV primary breast cancer has previously been demonstrated. The present study evaluated the safety and efficacy of KORTUC II for patients with stage I primary breast cancer. A total of 15 patients (age range, 40-76 years) were enrolled. The injection of 3 ml of KORTUC II agent was initiated from the sixth radiotherapy fraction and was performed twice a week, under ultrasonographic guidance. The therapeutic effects were evaluated by PET-CT and/or MRI examinations prior to and following KORTUC II treatment. All patients exhibited complete responses and the overall survival rate was 100% after a follow-up period of five years. The mean duration of follow-up at the end of March 2015 was 53 months. Based on these results, KORTUC II treatment exhibited marked therapeutic effects with satisfactory treatment outcomes and an acceptable extent of adverse events.

[A Case of Stage IV Breast Cancer with Long-Term Survival by Chemotherapy Developing Pulmonary Tumor Thrombotic Microangiopathy during the Treatment Course].

Pulmonary tumor thrombotic microangiopathy(PTTM)caused by pulmonary artery microscopic tumor emboli and fibrocellular and/or fibromuscular proliferation leads to progressive pulmonary hypertension and respiratory failure.The prognosis is extremely poor and most patients die shortly after onset.We report a patient with Stage IV breast cancer and long-term survival who developed PTTM during chemotherapy treatment.A 63-year-old woman with multiple metastases in her cerebellum, bone, lung, and lymph node after left breast conserving surgery started to experience dyspnea and malaise 7 years after the surgery.Two months later, she was urgently admitted to hospital because of respiratory failure and was diagnosed with pulmonary hypertension.However, pulmonary thrombosis and tumor thrombus were not observed.We clinically diagnosed her with PTTM and administered chemotherapy in addition to treatment for pulmonary hypertension.Her medical condition improved gradually and she survived for the subsequent 2 years.When observing progressive hypoxia and pulmonary hypertension without obvious pulmonary embolism findings on imaging, PTTM should be considered.Early diagnosis and immediate induction of chemotherapy for primary disease can improve the survival of patients with PTTM.

Clinical Presentation of Tubulointerstitial Nephritis Caused by Amyloid Light-chain Amyloidosis in a Patient with Sjögren's Syndrome.

We report a 70-year-old woman with Sjögren's syndrome who had severe renal dysfunction with mild proteinuria and elevated urinary low-molecular-weight proteins. Based on these clinical presentations, interstitial nephritis due to Sjögren's syndrome was strongly suspected. Unexpectedly, renal pathology revealed amyloid light-chain (AL) lambda-type depositions predominantly in the vasculatures with severe tubulointerstitial damage. Concentrated urine immunofixation was positive for Bence Jones lambda-type monoclonal proteins. Given the involvement in other organs, systemic AL amyloidosis was diagnosed. The patient underwent chemotherapy, but hemodialysis was ultimately instituted. It should be remembered that renal amyloidosis occurs as a clinical presentation of interstitial nephritis.

Therapeutic response to a novel enzyme-targeting radiosensitization treatment (KORTUC II) for residual lesions in patients with stage IV primary breast cancer, following induction chemotherapy with epirubicin and cyclophosphamide or taxane.

Linac-based radiotherapy has a negligible effect on the majority of advanced neoplasms. Therefore, a novel radiosensitization treatment Kochi Oxydol Radiation Therapy for Unresectable Carcinomas II (KORTUC II), which utilizes hydrogen peroxide and sodium hyaluronate was developed. The effectiveness of KORTUC II for the treatment of chemotherapy-resistant supraclavicular lymph node metastases and recurrent breast cancers has previously been demonstrated. The present study evaluated the safety and efficacy of KORTUC II in patients with stage IV primary breast cancer. Seven patients (age range, 36-65 years) were enrolled. All patients received induction chemotherapy prior to KORTUC II treatment and underwent positron emission tomography-computed tomography (PET-CT) examinations prior to and 2-7 months following KORTUC II treatment, and every six months thereafter where possible. The radiotherapy regimen (x-ray irradiation) was 2.75 gray (Gy)/fraction, 5 fractions/week for 16-18 fractions with a total radiation dose of 44-49.5 Gy. Administration of the KORTUC II agent (3-6 ml: 3 ml for a lesion <3 cm in diameter and 6 ml for a lesion ≥3 cm) was initiated from the sixth radiotherapy fraction, and was conducted twice a week under ultrasonographic guidance. The therapeutic effects were evaluated by PET-CT examinations prior to and following KORTUC II treatment. Of the seven lesions from the seven patients, five exhibited complete responses, two exhibited partial responses and none exhibited stable disease or progressive disease. The overall survival rate was determined to be 100% at 1 and 86% at 2 years post-treatment. The mean duration of follow-up by December 2014 was 51 months. The results of the PET-CT studies indicated that KORTUC II treatment demonstrated marked therapeutic effects with satisfactory treatment outcomes and acceptable adverse effects.

Feasibility and early outcome of high-dose-rate Ir-192 brachytherapy as monotherapy in two fractions within 1 day for high-/very high-risk prostate cancer.

The aim of the present study was to evaluate the feasibility and preliminary outcomes of high-dose-rate (HDR)-brachytherapy as a monotherapy in two fractions within 1 day for localized prostate cancer, including high-/very high-risk cases. Among the 68 patients treated with HDR monotherapy between July 2011 and December 2014, 65 had a minimal follow-up of 12 months without adjuvant androgen deprivation therapy and were enrolled in the present study [42/65 (64.6%) exhibited high-/very high-risk diseases]. HDR monotherapy was performed in two fractions with a minimal interval of 6 h and the prescribed dose was 13.5 Gy (×2). Adverse events (AEs) were assessed using Common Terminology Criteria for Adverse Events (version 4; http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40), and biochemical failure was assessed by the Phoenix definition. The median follow-up time was 30.1 months. The majority of patients had Grade 0-1 acute AEs. Four patients (6.2%) exhibited urinary retention, requiring a Foley catheter. Grade 3 acute AEs occurred at a frequency of 3.1% and hematuria at 1.5%. The majority of patients also exhibited Grade 0-1 chronic AEs. Grade 3 chronic AEs occurred at a frequency of 1.5% and urethral stricture at 1.5%, for which endoscopic treatment was indicated. Acute and chronic gastrointestinal AEs were uncommon, and no Grade 3 or above AEs developed. Biochemical failure occurred in 4 patients who all exhibited high-/very high-risk diseases. Kaplan-Meier estimated that 3 year biochemical failure-free survival was 91.6% overall and 88.0% in high-/very high-risk cases. The present two-fraction 1 day HDR monotherapy is feasible with minimal AEs and achieved acceptable biochemical control of localized prostate cancer, including high-/very high-risk cases, although long-term follow-up is required.

A Truncated form of CD200 (CD200S) Expressed on Glioma Cells Prolonged Survival in a Rat Glioma Model by Induction of a Dendritic Cell-Like Phenotype in Tumor-Associated Macrophages.

CD200 induces immunosuppression in myeloid cells expressing its receptor CD200R, which may have consequences for tumor immunity. We found that human carcinoma tissues express not only full-length CD200 (CD200L) but also its truncated form, CD200S. Although CD200S is reported to antagonize the immunosuppressive actions of CD200L, the role of CD200S in tumor immunity has never been investigated. We established rat C6 glioma cell lines that expressed either CD200L or CD200S; the original C6 cell line did not express CD200 molecules. The cell lines showed no significant differences in growth. Upon transplantation into the neonatal Wistar rat forebrain parenchyma, rats transplanted with C6-CD200S cells survived for a significantly longer period than those transplanted with the original C6 and C6-CD200L cells. The C6-CD200S tumors were smaller than the C6-CD200L or C6-original tumors, and many apoptotic cells were found in the tumor cell aggregates. Tumor-associated macrophages (TAMs) in C6-CD200S tumors displayed dendritic cell (DC)-like morphology with multiple processes and CD86 expression. Furthermore, CD3(+), CD4(+) or CD8(+) cells were more frequently found in C6-CD200S tumors, and the expression of DC markers, granzyme, and perforin was increased in C6-CD200S tumors. Isolated TAMs from original C6 tumors were co-cultured with C6-CD200S cells and showed increased expression of DC markers. These results suggest that CD200S activates TAMs to become DC-like antigen presenting cells, leading to the activation of CD8(+) cytotoxic T lymphocytes, which induce apoptotic elimination of tumor cells. The findings on CD200S action may provide a novel therapeutic modality for the treatment of carcinomas.

Assessment of metabolic status in young Japanese females using postprandial glucose and insulin levels.

Lifestyle-related diseases develop through the accumulation of undesirable lifestyle habits both prior to the onset of disease as well as during normal healthy life. Accordingly, early detection of, and intervention in, metabolic disorders is desirable, but is hampered by the lack of an established evaluation index for young individuals. The purpose of this study was to investigate the utility of a biomarker of health in young female subjects. The subjects were young healthy Japanese females in whom energy expenditure was measured for a period of 210 min after a test meal. In addition, Δplasma glucose and Δserum insulin were calculated from the fasting and 30 min values. ΔPlasma glucose and Δserum insulin levels varied widely compared to fasting levels. Both the area under the curve of carbohydrate oxidation rate and serum free fatty acid levels were higher in individuals in the high Δplasma glucose group. Moreover, Δplasma glucose was higher in individuals in the high Δserum insulin group than in the low Δserum insulin group. We conclude that nutritional balanced liquid loading test using Δplasma glucose and Δserum insulin as the evaluation index is useful for the detection of primary metabolic disorders in young females.

Evaluation of influence of single nucleotide polymorphisms in cytochrome P450 2B6 on substrate recognition using computational docking and molecular dynamics simulation.

In this study, we investigated the influence of single nucleotide polymorphisms on the conformation of mutated cytochrome P450 (CYP) 2B6 proteins using molecular dynamics (MD) simulation. Some of these mutations influence drug metabolism activities, leading to individual variations in drug efficacy and pharmacokinetics. Using computational docking, we predicted the structure of the complex between the antimalarial agent artemether and CYP2B6 whose conformations were obtained by MD simulation. The simulation demonstrated that the entire structure of the protein changes even when a single residue is mutated. Moreover, the structural flexibility is affected by the mutations and it may influence the enzyme activity. The results suggest that some of the inactive mutants cannot recognize artemether due to structural changes caused by the mutation.

Outcome and toxicity of stereotactic body radiotherapy with helical tomotherapy for inoperable lung tumor: analysis of Grade 5 radiation pneumonitis.

To analyze outcomes and toxicities of stereotactic body radiotherapy with helical tomotherapy (HT-SBRT) for inoperable lung tumors, the medical records of 30 patients with 31 lung tumors treated with HT-SBRT were reviewed. The 3-year local control, cause-specific survival and overall survival rates (LC, CCS and OS, respectively) were analyzed using the Kaplan-Meier method. Toxicities were graded using Common Terminology Criteria for Adverse Events ver. 4. To investigate the factors associated with Grade 5 radiation pneumonitis (G5 RP), several parameters were analyzed: (i) patient-specific factors (age, gross tumor volume and PTV, and the interstitial pulmonary shadow on pretreatment CT); and (ii) dosimetry-specific factors (conformity index, homogeneity index, mean lung dose, and V5, V10, V15, V20 and V25 of the total lungs). The median duration of observation for all patients was 36.5 months (range, 4-67 months). The 3-year LC, CCS and OS were 82, 84 and 77%, respectively. Regarding Grade 3 or higher toxicities, two patients (6.7%) developed G5 RP. GTV was significantly associated with G5 RP (P = 0.025), and there were non-significant but slight associations with developing G5 RP for V5 (P = 0.067) and PTV (P = 0.096). HT-SBRT led to standard values of LC, CCS and OS, but also caused a markedly higher incidence of G5 RP. It is essential to optimize patient selection so as to avoid severe radiation pneumonitis in HT-SBRT.

Assessment of permanent brachytherapy combined with androgen deprivation therapy in an intermediate-risk prostate cancer group without a Gleason score of 4 + 3: a single Japanese institutional experience.

OBJECTIVES: To evaluate the outcome of low-dose-rate permanent brachytherapy combined with anti-androgen deprivation therapy for intermediate-risk prostate cancer excluding biopsy Gleason score 4 + 3. METHODS: Patients included in the intermediate-risk group were those presenting clinical stage T1c to T2c (by magnetic resonance imaging staging), Gleason score 3 + 4 or lower and/or prostate-specific antigen less than 20 ng/mL, whereas those with clinical stage T1c to T2a, Gleason score 3 + 3 and prostate-specific antigen less than 10 ng/mL represented the low-risk group, and were used as controls. In the intermediate-risk group, therapy with a luteinizing hormone-releasing hormone analog was continued for at least 6 months before and after permanent brachytherapy. RESULTS: A total of 147 low-risk group patients and 139 intermediate-risk group patients were included in the study. The median follow up was 51 and 52 months for the intermediate-risk group and low-risk group, respectively. The 5-year overall, cause-specific and distant-metastasis-free survival rates in the low-risk group and intermediate-risk group were 97.6/99.2, 100/100 and 100/100%, respectively. The 5-year biochemical disease-free survival in these groups were 95.9 and 92.5%, respectively (P = 0.18). There was no sexual activity and desire for erection before treatment in 50%, and in 46% of the patients in the low-risk group and intermediate-risk group, respectively. Overall satisfaction score at 2 years after permanent brachytherapy significantly improved, compared with pretreatment (P = 0.0399). CONCLUSIONS: In intermediate-risk prostate cancer, excluding biopsy Gleason score 4 + 3, permanent brachytherapy combined with androgen deprivation therapy for 6 months or more represents an effective treatment option in Japanese patients, based on a favorable prognosis, adverse event profile and quality of life analysis.

Uric acid transporter ABCG2 is increased in the intestine of the 5/6 nephrectomy rat model of chronic kidney disease.

BACKGROUND: Uric acid (UA) remains a risk factor of chronic kidney disease (CKD). Therefore, it is important to clarify the mechanism of UA excretion in CKD. The specific mechanisms of extrarenal excretion from the intestine are unknown. We evaluated the expression of the UA transporter in the intestinal tract--the ATP-binding cassette transporter G2 (ABCG2)--in a 5/6 nephrectomy rat model of CKD. METHODS: Male Wistar rats (6 weeks old) were randomly assigned to the 5/6 nephrectomized (Nx) group or the sham-operated control group. Urine and blood samples were collected every 4 weeks. All the rats were killed at 8 weeks to obtain liver, duodenum, jejunum, ileum, and transverse colon tissues. Uricase activity was measured in the liver. Expression of ABCG2 in intestinal mucosa was measured with real time polymerase chain reaction (PCR). RESULTS: The Nx group showed significantly decreased urine UA excretion/body weight and UA clearance compared to the control group at 4 and 8 weeks after nephrectomy. In contrast, serum UA and uricase activity were not significant. The expression of ABCG2 in the ileum of the Nx group showed significantly increased upregulation, while no changes were seen in the intestines of the control group. CONCLUSIONS: The Nx rats exhibited lower excretion of urine UA and over-expression of ABCG2 in the ileum. The fact that serum UA did not increase despite the decrease in UA excretion suggests that an excretory pathway other than the kidney, probably the intestine, may operate in a complementary role that corroborates the increase in ABCG2 expression in the ileum.