Alterations in the Mineral Bone Metabolism of Living Kidney Donors After Uni-Nephrectomy: Prospective Observational Study.

We investigated the dynamic change of mineral bone metabolism and explored factors associated with the alteration of mineral bone metabolism in the living kidney donors (LKDs) after uni-nephrectomy. One-hundred forty-four prospective LKDs who underwent kidney donation between May 2016 and September 2018 were enrolled. Laboratory evaluation regarding mineral bone metabolism including intact parathyroid hormone (iPTH), renal fractional excretion of phosphate (FEPi), and technetium-99m diethylenetriaminepentaacetate (99mTc-DTPA) scan was performed predonation and 6 months after donation. We divided donors into two groups, the low ΔFEPi and high ΔFEPi groups, according to the change of FEPi after donation, and investigated significant risk factors associated with high ΔFEPi. At 6 months after uni-nephrectomy, estimated glomerular filtration rate (eGFR) significantly declined by 30.95 ml/min/1.73 m2 (p < 0.001), but the measured GFR (mGFR) of the remaining kidney by 99mTc-DTPA scan showed significant increase. Serum phosphorus decreased (p < 0.001), whereas FEPi (13.34-20.23%, p < 0.001) and serum iPTH (38.70-52.20 pg/ml, p < 0.001) showed significant increase. In the high ΔFEPi group, the proportion of preexisting hypertension (HTN) was higher, the baseline FEPi was lower, and the percent decline in eGFR was greater. Moreover, all of these factors were independently associated with high ΔFEPi upon multivariable logistic regression analysis. LKDs showed a significant change in mineral bone metabolism after uni-nephrectomy, especially when the donors had preexisting HTN, lower baseline FEPi, and showed greater loss of kidney function. Hence, strict monitoring of the mineral bone metabolism parameters and bone health may be required for these donors.

Inhibition of Carbonyl Reductase 1 Safely Improves the Efficacy of Doxorubicin in Breast Cancer Treatment.

AIMS: Doxorubicin (DOX) is a chemotherapeutic drug that is used to treat many cancers, but its use is limited by cardiotoxic side effect. Carbonyl reductase 1 (CBR1) is an NADPH-dependent oxidoreductase that reduces DOX to doxorubicinol (DOXOL), a less potent derivative that is responsible for DOX cardiotoxicity. Thus, we aimed to demonstrate that inhibition of CBR1 enhances the chemotherapeutic efficacy of DOX and attenuates cardiotoxicity. RESULTS: Pharmacological or genetic inhibition of CBR1 improved the anticancer effects of DOX in preclinical models of breast cancer. RNA interference or chemical inhibition of CBR1 improved the anticancer effect of DOX in breast cancer. Moreover, CBR1 overexpression enabled breast cancer cells to obtain chemotherapeutic resistance to DOX treatment. Intriguingly, inhibition of CBR1 decreased DOX-induced cardiotoxicity in animal model. Innovation and Conclusions: Inhibition of CBR1 increases chemotherapeutic efficacy of DOX and reduces cardiotoxicity by blocking DOX reduction to DOXOL. Therefore, we offer preclinical proof-of-concept for a combination strategy to safely leverage the efficacy of doxorubicin by blunting its cardiotoxic effects that limit use of this cytotoxic agent used widely in the oncology clinic. Antioxid. Redox Signal. 26, 70-83.

Eosinophils in Colorectal Neoplasms Associated with Expression of CCL11 and CCL24.

BACKGROUND: A decrease in the number of tissue eosinophils is known to reflect the malignancy potential of neoplastic lesions and even prognosis. Increased levels of the chemokines CCL11 and CCL24 in serum and tissue are also known to have diagnostic value as serum tumor markers or prognostic factors. The aim of this study was to evaluate the correlation between the degree of tissue eosinophilia and the expression of these chemokines in the glandular and stromal cells of colorectal neoplastic lesions ranging from benign to malignant tumors. METHODS: We counted the number of infiltrating eosinophils in neoplastic lesion tissue and we evaluated the expression of CCL11 and CCL24 in glandular cells and stromal cells by immunohistochemical staining. RESULTS: The results showed that the number of eosinophils decreased significantly and the expression of CCL11 and CCL24 in glandular cells decreased with tumor progression, whereas the stromal expression of CCL11 and CCL24 appeared to increase. CONCLUSIONS: The discrepancy in CCL11 and CCL24 expression between glandular cells and stromal cells might shed light on how colorectal cancer evades the immune system, which would enable further development of immunotherapies that target these chemokines. Further research on eosinophil biology and the expression pattern of chemokines in tumor cells is needed.

High DBC1 (CCAR2) expression in gallbladder carcinoma is associated with favorable clinicopathological factors.

There have been several studies on gallbladder carcinogenesis, and mutations of the KRAS, TP53, and CDKN2A genes have been reported in gallbladder carcinoma. The DBC1 gene (deleted in breast cancer 1) was initially cloned from region 8p21, which was homozygously deleted in breast cancer. DBC1 has been implicated in cancer cell proliferation and death. The functional role of DBC1 in normal cells and the role of DBC1 loss in cancer are not entirely clear. And DBC1 expression and its clinical implications in gallbladder carcinoma have yet to be thoroughly elucidated. Therefore, we evaluated DBC1 expression in 104 gallbladder carcinoma tissues in relation to survival and other prognostic factors via immunohistochemical analysis. DBC1 expression was divided into two categories: high DBC1 expression was observed in 32/104 cases (30.8%) and low expression in 72/104 cases (69.2%). High DBC1 expression correlated significantly with favorable clinicopathologic variables. Furthermore, in survival analysis, the high-DBC1 expression group showed a better survival rate compared to the low-DBC1 expression group. In conclusion, high DBC1 expression is associated with several favorable clinicopathologic factors in gallbladder carcinoma. These findings suggest that loss of DBC1 expression plays a role in tumorigenesis and tumor progression in gallbladder carcinoma.

Transverse mode instability induced by stimulated Brillouin scattering in a pulsed single-frequency large-core fiber amplifier.

We report the observation of transverse mode instability (TMI) in a pulsed single-frequency ytterbium-doped large-core fiber amplifier in which stimulated Brillouin scattering (SBS) is generated easily owing to the high peak power and narrow linewidth of the laser pulses. It was shown experimentally that the threshold of TMI is almost the same as that of SBS and that the suppression of SBS also increases the threshold of TMI, which indicates that the TMI originates from SBS in the fiber.

Changes in Nocturia and Lower Urinary Tract Symptoms after Radical Prostatectomy.

PURPOSE: The goal of this study was to evaluate changes in nocturia and other lower urinary tract symptoms (LUTS) after laparoscopic radical prostatectomy (LRP) and robot-assisted laparoscopic radical prostatectomy (RALP). MATERIALS AND METHODS: We reviewed the medical records of 96 patients who underwent LRP or RALP for clinically localized prostate cancer and completed the International Prostate Symptom Score (IPSS) questionnaire, which provided a basis for assessing their symptoms. We also evaluated maximal flow rate and post-void residual urine volume over a follow-up period of at least 24 months. We divided the patients into three groups according to postoperative changes in the frequency of nocturia. RESULTS: Voiding symptoms significantly improved over the course of 24 months in patients who underwent LRP or RALP. However, most patients showed persistent or increased nocturia after LRP or RALP. Moreover, more than one third of the patients (33/96) presented with exacerbated nocturia (1.0±0.9 episodes of preoperative nocturia vs. 3.0±1.3 episodes of postoperative nocturia). Multiple regression analysis showed that preoperative IPSS storage sub-score had negative association with the nocturia after radical prostatectomy (p=0.005). However, patients' age, body mass index, preoperative prostate specific antigen, Gleason score, T-stage, and prostate volume had no association. CONCLUSIONS: The present study showed that nocturia was influenced by a range of factors, including other storage LUTS and the relief of bladder outlet obstruction after radical prostatectomy. Moreover, the preoperative storage symptoms are regarded as an important factor which influences the changes of nocturia after radical prostatectomy.

Clinicopathologic correlation of autophagy-related Beclin-1 expression in gallbladder cancer.

BACKGROUND/AIMS: Autophagy plays critical roles in both cell survival and cell death. Beclin-1, a key modulator of autophagy function, is considered a haploinsufficient tumor suppressor. The role of Beclin-1 expression in cancer is still controversial. Some studies favor the idea that autophagy suppresses tumor development, whereas other researchers suggest that autophagy enhances tumorigenesis. The expression and function of Beclin-1 in gallbladder cancer (GBCA) remain largely unknown. METHODOLOGY: Methodology: We performed immunohistochemical staining for Beclin-1 in 119 GBCA cases, and investigated whether Beclin-1 expression correlated with clinicopathologic characteristics and prognosis of patients. RESULTS: Beclin-1 was expressed in the cytoplasm of cancer cells with occasional nuclear staining in 53 (44.5%) of the 119 cases of GBCA with no expression in adjacent normal epithelial cells. Increased expression of Beclin-1 was significantly associated with longer survival rate of patients with GBCA in univariate (p=0.006) and multivariate analyses (p=0.005). There is no association between Beclin-1 expression and clinicopathologic characteristics. CONCLUSIONS: Beclin-1 was highly expressed in GBCA, and positive expression in cancer cells was significantly related with favorable prognosis in GBCA patients. Our results suggest that the expression of Beclin-1 may be an independent predictive marker of favorable prognosis in GBCA.

Multifocal osteosarcoma of the skull: multiple primary or metastatic? A case report.

Osteosarcoma of the skull is a very rare condition. Moreover, it is extremely rare for osteosarcoma to present as multiple lesions confined to the skull. A 58-year-old woman was admitted with two masses in the parietal area of the skull, accompanied by mild headache and tenderness. Imaging revealed two masses with a heterogeneous consistency in the cranial bones. Excision craniectomy was performed and the pathology was consistent with osteoblastic osteosarcoma. Two nodules in the heart were found on routine follow-up imaging while the patient was undergoing chemotherapy. The nodules were biopsied and found to be metastatic osteosarcoma.

Effect of low-energy electron irradiation on DNA damage by Fe3+ ion.

We investigated the combined effects of low-energy electron irradiation and Fe(3+) ion on DNA damage. We used lyophilized pBR322 plasmid DNA films with various concentrations (0 ~ 7 mM) of Fe(3+) ions and irradiation with monochromatic, low-energy 3 or 5 eV electrons for these studies. DNA-Fe(3+) films were recovered and analyzed by agarose gel electrophoresis to identify and compare the effects of Fe(3+) ions and/or low-energy electrons alone or in combination on DNA damage. In nonirradiated DNA-Fe(3+) films, there was little DNA damage observed (less than 10% of the total DNA loaded on the gel appeared damaged) for Fe(3+) ion up to 7 mM concentration. In irradiated DNA films without Fe(3+) ions, there was also very little DNA damage observed (less than 3% of the total DNA loaded on the gel appeared damaged). However, when DNA-Fe(3+) films, were irradiated with low-energy electrons, DNA damage was significantly increased compared to the sum of the damage caused both by either Fe(3+) ion or low-energy electrons irradiation alone. We proposed that both DEA and/or electron transfer processes might play a role in the enhanced DNA damage when DNA-Fe(3+) films were irradiated by low-energy electrons.

Differential two-signal picosecond-pulse coherent anti-Stokes Raman scattering imaging microscopy by using a dual-mode optical parametric oscillator.

We propose and demonstrate a novel differential two-signal technique of coherent anti-Stokes Raman scattering (CARS) imaging microscopy using a picosecond (ps) optical parametric oscillator (OPO). By adjusting a Lyot filter inside the cavity, we operated the OPO oscillating in two stable modes separated by a few nanometers. The CARS images generated by the two modes are separated by a spectrograph behind the microscope setup, and their differential image is directly obtained by balanced lock-in detection. The feasibility of the technique is experimentally verified by imaging micrometer-sized polystyrene beads immersed in water.

Cross sections for electron trapping by DNA and its component subunits I: Condensed tetrahydrofuran deposited on Kr.

We report cross sections for electron capture processes occurring in condensed tetrahydrofuran (THF) for incident electron energies in the range of 0-9 eV. The charge trapping cross section for 6-9 eV electrons is very small, and an upper limit of 4 x 10(-19) cm2 is estimated from our results. This latter is thus also an upper bound for the cross section for dissociative electron attachment process that is known to occur at these energies for condensed THF. At energies close to zero eV electron trapping proceeds via intermolecular stabilization. The cross section for this process is strongly dependent on the quantity of deposited THF. Since THF may model the furyl ring found in deoxyribose, these measurements indicate that this ring likely plays little role in either initiating or enhancing strand break damage via the attachment of the low energy secondary electrons produced when DNA is exposed to ionizing radiation.