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Site-specific postoperative risk models for localized upper tract urothelial carcinoma (UTUC) are unavailable.To create specific risk models for renal pelvic urothelial carcinoma (RPUC) and ureteral urothelial carcinoma (UUC), and to compare the predictive accuracy with the overall UTUC risk model.A multi-institutional database retrospective study of 1917 UTUC patients who underwent radical nephroureterectomy (RNU) between 2000 and 2018 was conducted.A multivariate hazard model was used to identify the prognostic factors for extraurinary tract recurrence (EUTR), cancer-specific death (CSD), and intravesical recurrence (IVR) after RNU. Patients were stratified into low-, intermediate-, high-, and highest-risk groups. External validation was performed to estimate a concordance index of the created risk models. We investigated whether our risk models could aid decision-making regarding adjuvant chemotherapy (AC) after RNU.The UTUC risk models could stratify the risk of cumulative incidence of three endpoints. The RPUC- and UUC-specific risk models showed better stratification than the overall UTUC risk model for all the three endpoints, EUTR, CSD, and IVR (RPUC: concordance index, 0.719 vs 0.770, 0.714 vs 0.794, and 0.538 vs 0.569, respectively; UUC: 0.716 vs 0.767, 0.766 vs 0.809, and 0.553 vs 0.594, respectively). The UUC-specific risk model can identify the high- and highest-risk patients likely to benefit from AC after RNU. A major limitation was the potential selection bias owing to the retrospective nature of this study.We recommend using site-specific risk models instead of the overall UTUC risk model for better risk stratification and decision-making for AC after RNU.Upper tract urothelial carcinoma comprises renal pelvic and ureteral carcinomas. We recommend using site-specific risk models instead of the overall upper tract urothelial carcinoma risk model in risk prediction and decision-making for adjuvant therapy after radical surgery.

Background Photodynamic therapy (PDT) and diagnosis (PDD) using 5-aminolevulinic acid (ALA) to control the production of an intracellular photosensitizer, protoporphyrin IX (PpIX), are in common clinical use. Although various studies have been published regarding cell death analysis after photoirradiation by ALA-PDT, the changes in gene expressions induced by it are yet unclear. Here, we focused on studying gene expression and cell proliferation changes in cancer cells that survive photoirradiation. Methods HEK293 human embryonic kidney cells, MKN45 human gastric cells, and PC-3 human prostate cancer cells were selected for this research. Cell viability was measured using trypan blue and MTT assays. ALA-PDT experiments were performed using a calibrated LED irradiation module. Furthermore, mRNA and protein gene expression analysis were performed using our previously reported methods. Results mRNAs of PAI-1, HO-1, and p21 were upregulated after photoirradiation of HEK293, which was suppressed by N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger. Primer array results in PC-3 cells and p21 and Ki-67 expression results in both PC-3 and MKN45 cells suggested that photoirradiation suppressed cell proliferation. Cell numbers post-photoirradiation revealed that the proliferation of surviving cells was suppressed in PC-3 and MKN45 cells. Conclusion ALA-PDD or ALA-PDT can result in rapid ROS-induced cell death and may decrease long-term recurrence rates through several pathways including the HO-1/p21 pathway.

Purpose To evaluate the influence of percutaneous cryoablation for renal cell carcinoma on function of the affected kidney. Materials and Methods Between June 2016 and September 2017 at our institution, 12 inoperable patients underwent 15 cryoablation sessions for 17 small renal tumors. Of these, 9 patients who underwent 11 sessions of cryoablation were the focus of this study. For those patients, time-dependent changes in postoperative renal function were investigated by a retrospective review of clinical records. Evaluated were the estimated glomerular filtration rate (eGFR) and scintigraphy using 99m technetium-mercaptoacetyltriglycine (99mTc-MAG3) before and 1 week, 1–2 months, and more than 6 months after cryoablation. Results Mean baseline eGFR was 76.88 ± 29.82 mL/min/1.73 m2 (mean ± standard deviation; range, 23.4–112.5). Mean eGFR 1 week, 1–2 months, and more than 6 months after cryoablation were 74.56 ± 26.68 mL/min/1.73 m2 (21.0–101.1), 69.5 ± 25.28 mL/min/1.73 m2 (24.1–105.6), and 75.08 ± 26.25 mL/min/1.73 m2 (29.0–107.3), respectively. Changes were statistically insignificant (P = .6044, P = .6699, and P = .9038, respectively). Regarding split renal function, the mean baseline contribution of the affected kidney determined by 99mTc-MAG3 was 47.27% ± 6.14 (38.8%–57.0%). Mean contributions of the affected kidney 1 week after, 1–2 months after, and more than 6 months after cryoablation were 44.40% ± 5.37 (38.3%–53.6%), 44.57% ± 6.52 (34.35%–55.0%), and 45.41% ± 7.77 (34.4%–56.5%), respectively. Differences from baseline were significant for the earliest 2 periods (P = .0473 and P = .0334, respectively) but not the later period (P = .2532). Conclusions Results suggested that total renal function does not worsen after cryoablation; however, function of the affected kidney worsened after cryoablation but later partially recovered.

Photodynamic diagnosis (PDD) with administration of oral aminolevulinic acid (ALA) prior to transurethral resection of bladder tumor (TURBT) can now be used for non-muscle invasive bladder cancer (NMIBC) in clinical settings in Japan. Since ALA was first marketed, a limited number of reports have described PDD-TURBT outcomes, and the effects of resecting false-positive tissue on outcomes have not been clarified.This study compared tumor recurrence among NMIBC patients who underwent TURBT under either white light cystoscopy (WL) or PDD. In addition, the frequency of recurrence was compared between patients with or without false-positive lesions at the time of PDD-TURBT.The frequency of recurrence in NMIBC patients (cumulative number of recurrences/cumulative number of follow-up days, number of recurrences/10,000 days), including progression to muscle-invasive bladder cancer (MIBC), was 12.80 in the WL-TURBT group and 5.82 in the PDD-TURBT group (p 0.05). Tumor recurrence after TURBT was seen in 29 of 88 patients (33.0%) in the WL-TURBT group and 21 of 105 patients (20.0%) in the PDD-TURBT group (p 0.05). Mean (± standard deviation) time to first recurrence was 249 ± 140 days in the WL-TURBT group and 419 ± 219 days in the PDD-TURBT group (p 0.05). The frequency of recurrence in PDD-TURBT-group NMIBC patients was significantly lower in patients with resection of false-positive tissue (4.19/10,000 days) than in those without (9.00/10,000 days, p 0.05).The frequency of recurrence was lower and the time to recurrence was longer in the PDD-TURBT group than in the WL-TURBT group. The frequency of recurrence decreased with resection of false-positive resection.

A 73-year-old man had multiple coronary aneurysms that resulted in acute myocardial infarction on the day before surgery for cerebral aneurysms. Emergent coronary angiography revealed that the lesion that caused the myocardial infarction was a distal left circumflex artery, and two huge coronary aneurysms were also found in the left circumflex artery. A two-stage treatment strategy was planned, including coronary aneurysm surgery, followed by cerebral aneurysm surgery. He underwent coronary artery aneurysmorrhaphy with closure of the ostia of the afferent and efferent arteries, and coronary artery bypass grafting with a saphenous vein graft applied to the left circumflex artery. The pathological findings suggested chronic thromboangiitis, as the inflammatory cells were observed to have infiltrated the coronary artery wall. The tissue remodeling of the aneurysmal wall indicated a positive response to tenascin C. We report a case of multiple coronary aneurysms, focusing on the pathological findings.

Aims Our previous study revealed that cyclic hindlimb ischaemia–reperfusion (IR) activates cardiac acetylcholine (ACh) synthesis through the cholinergic nervous system and cell-derived ACh accelerates glucose uptake. However, the mechanisms regulating glucose metabolism in vivo remain unknown. We investigated the effects and mechanisms of IR in mice under pathophysiological conditions. Methods Using IR-subjected male C57BL/6J mice, the effects of IR on blood sugar (BS), glucose uptake, central parasympathetic nervous system (PNS) activity, hepatic gluconeogenic enzyme expression and those of ACh on hepatocellular glucose uptake were assessed. Results IR decreased BS levels by 20% and increased c-fos immunoreactivity in the center of the PNS (the solitary tract and the dorsal motor vagal nucleus). IR specifically downregulated hepatic gluconeogenic enzyme expression and activities (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase) and accelerated hepatic glucose uptake. Transection of a hepatic vagus nerve branch decreased this uptake and reversed BS decrease. Suppressed gluconeogenic enzyme expression was reversed by intra-cerebroventricular administration of a choline acetyltransferase inhibitor. Moreover, IR significantly attenuated hyperglycaemia in murine model of type I and II diabetes mellitus. Conclusions IR provides another insight into a therapeutic modality for diabetes mellitus due to regulating gluconeogenesis and glucose-uptake and advocates an adjunctive mode rectifying disturbed glucose metabolism.

Background Photodynamic therapy is a clinically approved, minimally invasive , therapeutic procedure used for the treatment of several cancers. In recent years, sunitinib, one of the tyrosine kinase inhibitors, has also attracted attention as a novel photosensitizer. However, there is currently no data available on the combined cytotoxic effects of sunitinib and photoirradiation on renal cell carcinoma including how the treatment induced cellular toxicity. Methods In the present study, we used sunitinib as a photosensitizer and evaluated the effects of sunitinib and photodynamic therapy treatment on renal cancer cell lines, including the induction of cell death. Results Our study showed that treatment with sunitinib and photoirradiation at 8 mW/cm2 for 30 min resulted in the production intracellular reactive oxygen species (ROS), which is indicated by the increase in mRNA expression levels of PAI-1, NF-κβ, and Caspase-3. An increase in rate of apoptotic reaction and increase in the expression level of apoptotic marker were also observed when cells undergo treatment with sunitinib and photoirradiation. Conclusions Our findings suggest that combining photodynamic therapy with sunitinib represents a minimally invasive therapeutic procedure with cancer selectivity for renal cell carcinoma.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) has been incorporated into the recent international histological classification of renal tumors. However, to date, there are limited studies describing the clinicopathological features of fumarate hydratase (FH)-deficient RCC, including the hereditary (HLRCC) and sporadic forms. Herein, we present a clinicopathological study of seven cases with FH-deficient RCC. The age of patients ranged from 26 to 70 years with mean and median age of 51.7 and 57 years, respectively. The follow-up data of all patients were available. One patient was alive without the disease and five patients were alive with active disease. One patient died of the disease. Family history of RCC, or skin or uterine smooth muscle tumor within second degree of kinship was present in four of seven patients. Metastasis was observed in all tumors. Metastatic sites included bone, lungs, liver, peritoneum, ovaries, tonsils, or lymph nodes. Grossly, the cut surface of the tumor usually showed light brown, brown, or whitish color. Microscopically, the cytoplasm of the tumor cells was predominantly eosinophilic and all tumors displayed various architectural patterns such as papillary, tubular, solid, or microcystic patterns. Furthermore, two tumors demonstrated a tubulocystic pattern. Sarcomatoid change and rhabdoid features were seen in five tumors and two tumors, respectively. Large cytomegaloviral (CMV) inclusion-like eosinophilic nucleoli surrounded by a clear halo were identified in all tumors. All tumors showed negative immunohistochemical reaction for FH protein. False positive results of TFE3 protein were observed in three tumors. Furthermore, a germline mutation of FH gene was identified in one patient with family history of the disease. In conclusion, FH-deficient RCC includes hereditary and sporadic forms. Grossly, this tumor is solitary and occurs unilaterally. Histologically, the tumor is characterized by various patterns such as papillary, tubular, solid, tubulocystic, or microcystic, has eosinophilic cytoplasm and CMV-like high-grade nuclei. FH-deficient RCCs frequently metastasize to other anatomic sites. TFE immunoreactivity may occur in some FH-deficient RCCs, and immunohistochemistry can accurately diagnose these tumors and mutational analysis of FH gene.

Objective To examine the utility and safety of photodynamic diagnosis (PDD) after oral administration of 5-aminolevulinic acid (5-ALA) (ALA-PDD) of non-muscle-invasive bladder cancer (NMIBC) using fluorescent-light (FL)-cystoscopy. Methods The study was a single-arm, open-label, multi-center prospective study on ALA-PDD of NMIBC, with safety as the primary endpoint and efficacy as the secondary endpoint. Diagnostic potential was evaluated through comparisons with the conventional diagnostic method using a white-light (WL)-source. Clinically recommended doses were also examined. Oral administration of 5-ALA (1.0 g/50 mL) was performed 180–240 min before FL-cystoscopy, and positive or negative results were judged using a WL-source and based on presence or absence of red fluorescence on exposure to a blue FL-source. Results Regarding safety, the adverse drug reactions were observed as grade 1 pruritus in 1 patient (0.6%). As for efficacy, specificity and positive predictability were lower than those of a WL-source, but sensitivity was higher with a FL-source than with a WL-source. The proportion of patients with tumors detected only by FL-cystoscopy was greater than the proportion of patients with tumors detected only by conventional WL-cystoscopy. Moreover, not only sensitivity, but also the proportion of patients with tumors detected only by FL-cystoscopy, was highest among patients who received 5-ALA at ≧20 mg/kg/body. Conclusions ALA-PDD was shown to be safe and effective. Furthermore, diagnostic accuracy of PDD increased with increased dose of 5-ALA, and the recommended dose was determined as ≧20 mg/kg/body in the present study.

Background Photodynamic therapy (PDT) and diagnosis (PDD) using 5-aminolevulinic acid (ALA) to control the production of the intracellular photosensitizer protoporphyrin IX (PpIX) are commonly used clinically. Previously, we demonstrated that dormant and drug-induced dormancy-like cancer cells accumulated high PpIX levels, making them sensitive to ALA-PDT. Because EAU Guidelines awarded a level of evidence of 1a to mitomycin C, the drug is widely used to treat bladder cancer. In this study, we investigated that the effect of mitomycin C-induced cell cycle arrest on porphyrin metabolism, including that induced by ALA-PDT. Methods T24 human urinary bladder carcinoma cells were selected for this research. T24 cells were irradiated using a light-emitting diode emitting red light for the ALA-PDT assay. Cell cycle analysis was conducted by flow cytometry using bromodeoxyuridine. Cell viability was confirmed using the MTT or colony formation assay. Furthermore, mRNA gene expression analysis was performed using our previously reported methods. Results The cell cycle of T24 cells was arrested at G2/M phase by mitomycin C. PpIX accumulation was dramatically increased by mitomycin C treatment. Cell viability after ALA-PDT was remarkably decreased by mitomycin C pretreatment. The gene expression of porphyrin transporters was consistent with the metabolic and morphological results. Finally, we confirmed that ALA-PDT combined with mitomycin C treatment exerted a long-term inhibitory effect on cell proliferation. Conclusion This study demonstrated a new approach to enhance the effects of ALA-PDT using drugs that induce a dormancy-like status and upregulate porphyrin metabolism.

To investigate the diagnostic accuracy of 5- aminolevulinic acid-mediated photodynamic diagnosis (ALA-PDD) for upper urinary tract tumor (UTUC) including carcinoma in situ (CIS) lesions using flexible fluorescence ureterorenoscopy.A solution of ALA was orally administrated at 20 mg/kg body weight at 3 h prior to surgery. Fluorescence observation was carried out with IMAGE1S OPAL1 PDD system. Positive lesions that were identified as abnormal changes under white light and/or blue light were biopsied, followed by cold-cup biopsy of negative lesions that were normal-looking mucosa under white light and/or blue light. Diagnostic accuracy was analysed by comparing ureterorenoscopic observations under white light or blue light with pathological analysis results.A total of 31 biopsy specimens were obtained from 10 patients. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for PDD to detect UTUC was 100 %, 50 %, 52.4 % and 100 %, respectively. The sensitivity of PDD ureterorenoscopy was significantly higher than that of white light ureterorenoscopy by statistics (p 0.05). Especially, 5 CIS lesions were detected only by ALA-PDD ureterorenoscopy (p 0.05). Of 10 patients, one patient (10 %) experienced hypotension during the ALA-PDD.ALA-PDD for UTUC is a feasible and safe techniques with acceptable adverse events. Additional advantage of ALA-PDD for UTUC is the high sensitivity to detect CIS lesions with blue light mode.

Background Photodynamic diagnosis (PDD) of non-muscle-invasive bladder cancer (NMIBC) following transurethral administration of a hexalated form of 5-aminolevulinic acid (5-ALA), 5-ALA hexyl ester, is widely performed in Western countries. In this study, effectiveness and safety of the oral administration of 5-ALA is assessed in a phase II/III study of PDD for NMIBC in comparison to those of conventional white-light endoscopic diagnosis. Methods Patients with NMIBC were allocated to two groups that were orally administered 10 and 20 mg/kg of 5-ALA under the double-blind condition. Effectiveness was evaluated by setting the primary endpoint to sensitivity. Safety was also analyzed. Moreover, clinically recommended doses of 5-ALA was also investigated as an investigator-initiated multicenter cooperative clinical trial in which five medical institutions participated. Results All 62 enrolled patients completed the clinical trial. The sensitivities of PDD were higher (84.4 and 75.8% in the 10 and 20 mg/kg-groups, respectively) than those of conventional endoscopic diagnosis (67.5 and 47.6%, respectively) (p = 0.014 and p

A challenge in cancer therapy is the destruction of tumours, where there is the potential issue of cancer cells residing within hypoxic tissue. The concept of hypoxic regions within tumours dates back to 1909 and it has long been suspected that under low oxygen tension, cells are “afforded” radiation protection. It has been shown many decades ago, that raising the concentration of oxygen in tissues can significantly improve the outcomes in radiotherapy. For example, in 1953, a meta-analysis of 83 randomised trials showed a clear benefit from raising tissue oxygen tension during radiation therapy, with the clearest benefits seen in cancers of neck and head [1]. However, there are only a limited number of ways to raise oxygen tension in tissues, which include breathing pure oxygen at or above standard temperature and pressure, or hypoxic modification by the means of an administered drug (e.g. nimorazole) [2, 3, 4]. Recently, we (and other research groups) have shown that cold atmospheric plasma jets not only readily deliver reactive oxygen and nitrogen species (RONS) into tissue, but concomitantly raise the oxygen tension in tissue. Combined RONS and oxygen delivery, may significantly elevate oxidative stress in cancer cells, resulting in destruction of these cells within hypoxic tumours. In this presentation, I will provide a brief historical overview of research on the modification of hypoxia in cancers; I will then discuss results that have shown how plasma jets can be used to treat hypoxia in tumours (through delivery of RONS and oxygen into tissues). I will also discuss the potential opportunities, challenges and limitations of the plasma technology for treatment of hypoxic cancer tumours.

Summary Background The aim of this study was to clarify the mechanism of accumulation of 5-aminolevulinic acid (ALA)-dependent protoporphyrin IX (PpIX), ALA-photodynamic therapy (PDT)-induced cell death and enhanced efficiency by a ferrochelatase inhibitor in prostate cancer PC-3 cells. Methods The accumulation of ALA-induced PpIX in PC-3 cells was observed by fluorescence microscopy and measured by flow cytometry analysis. The efficiency of ALA-PDT was analyzed by flow cytometry and assessed by cell death, caspase-3 activity and mitochondrial membrane potential. The ALA-PDT-promoting effects of ferrochelatase inhibitors, such as deferoxamine and NOC-18, were also analyzed. We confirmed the results obtained in vivo with an animal model using nude mice. Results ALA-induced PpIX accumulation increased in time- and ALA concentration-dependent manners. ALA-PDT decreased the levels of mitochondrial membrane potential, and induced cell death occurred by both apoptosis and necrosis. Inhibition of ferrochelatase by deferoxamine and NOC-18 led to increase of PpIX accumulation and enhanced effect of ALA-PDT in PC-3 cells. In vivo, the degeneration of tumor tissue by ALA-PDT was observed within a broader range and led to apoptosis and necrosis. Conclusion This study demonstrated ALA-PDT induced PC-3 cell death by the mechanisms of both necrosis and apoptosis through a caspase-independent mitochondrial pathway. Inhibition of ferrochelatase enhanced these effects, suggesting that ferrochelatase played an important role in ALA-PDT. ALA-PDT could be a new modality for focal therapy of prostate cancer.

Summary Background Tumor biomarkers are commonly used for cancer screening and as indicators of treatment effects. We recently reported that urine porphyrin levels from tumor-bearing mice were elevated compared with those from normal mice after administration of 5-aminolevulinic acid (ALA). In the present study, we evaluated the use of urine samples from bladder cancer patients as tumor biomarkers. Methods ALA, 1.0 g, was orally administered to 66 bladder cancer patients and 20 healthy adults. The urine concentrations of uroporphyrin I (UPI), uroporphyrin III (UPIII), coproporphyrin I (CPI), coproporphyrin III (CPIII), and total porphyrins were measured using High Performance Liquid Chromatography (HPLC) system. Results Almost all of the urinary porphyrin concentrations from the patients with bladder cancer were higher than those from healthy adults. Moreover, 8 h after ALA administration, urinary UPI and CPI showed high sensitivity (100 for UPI and CPI) and specificity (96.4 for UPI and 91.4 for CPI). Conclusion These results indicate that the presence of urinary porphyrins after administration of ALA may function as tumor biomarkers. This method represents a possible new tumor screening method called photodynamic screening (PDS) using ALA-induced porphyrins.

SummaryA 44-year-old woman was referred to our hospital with pathological nipple discharge from her left breast. Ultrasonography revealed a solid tumor beneath her left areola that measured 17 mm in diameter with a dilated mammary duct. Contrast-enhanced magnetic resonance imaging showed an early-enhanced cystic tumor and a dilated mammary duct. We performed a duct-lobular segmentectomy using near-infrared indocyanine green (ICG)-fluorescence imaging. Under general anesthesia, a silicone tube was inserted into an orifice of a fluid-discharging mammary duct, and 1 mL dye-fluorescence liquid containing ICG and indigo carmine was injected into the mammary duct. A periareolar incision was made, and the fluorescence image of the demarcated mammary duct segment was obtained. The mammary duct segment was dissected, along with the demarcation line. The cystic lesion and dilated mammary duct were fully resected, and the pathological diagnosis was intraductal papilloma of the breast. We report that near-infrared ICG fluorescence could be applied for imaging of the mammary duct segment, and the fluorescence image allowed for easier duct-lobular segmentectomy for nipple discharge.

SummaryThe patient was a 74-year-old woman with angina pectoris, who had undergone percutaneous coronary intervention with stent placement in the right coronary artery on October 2, 2007. On November 12 of the same year, she suffered from paroxysmal atrial fibrillation. She was treated with pilsicainide hydrochloride administered by intravenous injection, which was followed by a sudden sinus standstill, with marked bradycardia and a shock state. The patient was then treated with a catecholamine, however, the shock state persisted for about an hour. An electrocardiogram revealed persistent ST depression in leads V4–6 along with elevation of the serum creatinine kinase. A coronary angiography performed on the admission day revealed no abnormality. On the third hospital day, a dual-isotope myocardial SPECT using 201Tl and 99mTc-pyrophosphate demonstrated an annular accumulation of 99mTc-pyrophosphate concordant with the endocardium from apex to the mid-portion of the left ventricle, suggestive of subendocardial infarction. The case is reported here, as there are few reports of subendocardial infarction developing due to ischemia arising from a shock state.

[3H]Spermidine (SPD) was accumulated in subcellular fractions enriched of the nucleus in a temperature-dependent manner with a saturable profile in murine brain. The accumulation reached a plateau within 30 min at 2 degrees C and 30 degrees C, while excess unlabeled SPD significantly inhibited the accumulation at 2 degrees C without markedly affecting that at 30 degrees C when added after equilibrium. The temperature-dependent accumulation of [3H]SPD was significantly inhibited by the triamine SPD and the tetraamine spermine, but not by the diamine putrescine. Phospholipases were invariably effective in significantly inhibiting the accumulation at 30 degrees C in a concentration-dependent manner. Amongst different discrete murine central structures examined, the temperature-dependent [3H]SPD accumulation was highest in neocortex with progressively lower activities in striatum, hypothalamus, spinal cord, medulla-pons, hippocampus, midbrain and cerebellum. These results suggest the possible presence of a hitherto unidentified nuclear transport system for particular polyamines in murine brain.

CD9 is a glycoprotein that is abundant in hematopoietic cells. Recently, it has been reported that CD9 is also present in the human kidney. In this article, we investigated the expression of CD9 using an immunohistochemical technique. We also studied the expression of CD9 protein and messenger RNA (mRNA) in tissue samples of some renal tumors using immunoblotting and reverse-transcription polymerase chain reaction (RT-PCR) analysis. Immunohistochemically, all tumors of papillary and chromophobe renal cell carcinomas (RCCs) and oncocytomas expressed CD9. In addition, CD9 was expressed in 31 of 66 conventional RCCs and 1 of 4 collecting duct carcinomas. On immunoelectron microscopy, CD9 was identified on the plasma membrane of a conventional RCC. The presence of CD9 protein in normal kidneys and various renal tumors, except for a collecting duct carcinoma and an oncocytoma, was confirmed by immunoblotting. On RT-PCR analysis, the expression of CD9 mRNA was observed in 1 normal kidney, 2 conventional RCCs, and 1 oncocytoma. The frequency of immunohistochemical CD9 positivity was significantly higher in papillary and chromophobe RCCs than in collecting duct carcinomas and conventional RCCs, respectively. These results suggest that CD9 may be a beneficial marker in the differential diagnosis between papillary RCCs and collecting duct carcinomas and also between chromophobe and conventional RCCs.

We examined the expression levels of a number of metastasis-related genes to determine the relationship of these levels to the development of metastasis in renal cell carcinoma. Gene expression was examined in 46 formalin-fixed, paraffin-embedded, archival specimens of primary organ-confined, clear-cell, renal cell carcinoma from patients who had undergone radical nephrectomy. Twenty samples were from patients who did not have metastasis after a median of 48 months; 26 were from patients with either synchronous or metachronous metastases. Microvessel density was assessed by anti-CD-34 immunohistochemical analysis. The expression levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), matrix metalloproteinases (MMP)-2 and -9, and E-cadherin were examined at the periphery of the tumor by a colorimetric in situ mRNA. The expression levels of bFGF, VEGF, IL-8, MMP-2, and MMP-9 were significantly higher in primary renal tumors from patients with either synchronous or metachronous metastases than those who were disease-free at a median of 48 months of follow-up. Multivariate analysis of disease-free survival showed that the ratio of MMP-9 to E-cadherin (P = 0.012) and the expression level of bFGF expression (P = 0.045), were independent predictors for the development of metastases. The expression levels of bFGF, VEGF, and IL-8 did not correlate with microvessel density, which in itself was not a significant predictor of progression (P = 0.21). In summary, expression levels of genes that regulate metastasis angiogenesis can predict the metastatic potential in individual patients with organ-confined clear-cell renal carcinoma.

Protein biosynthesis is mainly under the control at the level of gene transcription in eukaryotes. Transcription factors are nuclear proteins with abilities to modulate the activity of RNA polymerase II which is responsible for the formation of messenger RNA from double stranded DNA in the cell nuclei. Binding of a radiolabeled oligonucleotide probe for the transcription factor activator protein-1 (AP1) was transiently potentiated 1 to 6 h after the recirculation of blood supply in the thalamus and striatum, but not in the entorhinal cortex, olfactory bulb, frontal cortex, cerebellar cortex and medulla-pons, in gerbils with transient global forebrain ischemia for 5 min, in addition to the hippocampal subregions. The ischemic insult not only increased the immunoreactivity with an antibody against cyclic AMP response element binding protein (CREB) phosphorylated at serine133, but also induced the expression of both c-Jun and c-Fos family proteins 3 h after the recirculation in the thalamus. Limited proteolysis by Staphylococcus aureus (S. aureus) V8 protease revealed the expression of different partner proteins of AP1 in response to ischemic signals in the thalamus. Moreover, ischemia for 2 min led to more prolonged elevation of AP1 binding in the thalamus at least up to 12 h after the reperfusion than that seen with ischemia for 5 min. These results suggest that potentiation of AP1 DNA binding may at least in part involve mechanisms associated with the expression of c-Fos protein through phosphorylation of CREB at serine133 in the thalamus of gerbils with ischemia.

Binding of radiolabeled double stranded oligonucleotide probes for nuclear transcription factors with leucine-zipper motifs, such as activator protein-1 (AP1), cyclic AMP response element binding protein (CREB) and Myc, was unevenly distributed in gerbil brain in a manner peculiar to each factor. Among 3 different hippocampal subfields examined, the dentate gyrus had the highest basal DNA binding activities of AP1 with progressively less potent binding in the CA3 and CA1 subfields. Similarly, the dentate gyrus was highest in the basal binding of probes for both CREB and Myc among the 3 distinct hippocampal subregions. However, transient forebrain ischemia for 5 min induced more potent enhancement of the AP1 binding in the CA1 subfield 4 h after the insult than in the CA3 subfield and dentate gyrus. In contrast, the ischemic injury similarly tripled DNA binding activities of CREB without markedly affecting those of Myc in hippocampal CA1 and CA3 subfields. Binding of the probe for AP1 was also markedly potentiated following ischemia in the thalamus, caudate putamen, frontal cortex and cerebellar cortex in a rank order of decreasing magnitude, while the ischemia insult induced slight but statistically significant potentiation of both CREB and Myc binding in the thalamus without affecting that in other discrete brain regions. These results suggest that expression of AP1 may be a determinant of unique vulnerability and/or resistance to an ischemic insult in the gerbil hippocampus.

The crystal formation of huntite borates LnAl3(BO3)4, where Ln is Yb or a combination of (Yb,Tm,Er) doped by Bi3+, Li+, Ti4+, V5+, Mo6+ and Ge4+, was observed in stoichiometric systems after heating to 1340–1370°C and cooling to room temperature. All crystals grown by spontaneous crystallization were studied by X-ray diffraction powder analysis and only the huntite-borate phase was detected. The dependence of stability of the huntite-borate structure on crystal composition is discussed.

Using the Bi2O3-B2O3 solvent, single crystals of (Ho,Bi)(Al,Ga)3(BO3)4, (Yb,Bi)Al3(BO3)4:Nd3+, (Er,Bi)Al3(BO3)4:Cr3+ and (Er,Bi)Ga3(BO3)4:Cr3+ with the huntite structure have been grown by spontaneous crystallization from a flux. The achieved productivity of the melt (crystal/melt weight ratio) was 38 wt%. The crystal composition and distribution coefficients for different cation positions were studied and the dependence of the probability of congruent melting on crystal composition was discussed. X-ray powder diffraction analysis data for grown crystals are presented.

Aim: Nanoparticle albumin-bound paclitaxel (nab-PTX) has become a key drug used in chemotherapy for breast cancer, but it often causes adverse effects such as peripheral neuropathy (PN). No effective prophylactic management has so far been established. We have applied a “3S” approach to prevent and treat PN based on two concepts: compression therapy using stockings and sleeves, and medication therapy using selected prophylactic medications. We previously reported better CTCAE v4.0 grades and notably superior nab-PTX dose maintenance in a 3S group compared to a control group with no prophylactic treatment. However, little is known about the effects of compression therapy on the relationship between PN and the skin blood perfusion. Methods: The skin perfusion of the lower limbs was measured before and after stocking use in a 3S prophylactic treatment group for nab-PTX therapy (n = 50), and in a control group of healthy volunteers (n = 50). The 3S group was subdivided by PN grade for a subsequent analysis (n = 18 for Grade 0, n = 22 for Grade 1 and n = 10 for Grades 2 and 3 combined). The skin perfusion was measured using a laser Doppler blood flow meter with an integrated probe (NL-101 Nahri Nexis Japan). Results: In the control group of healthy volunteers, stocking use tended to increase the median skin perfusion level (mL/min/100g) from 10.9 ± 3.8 to 11.8 ± 4.3. Interestingly, the median skin perfusion level for the 3S group as a whole significantly increased from 8.7 ± 3.3 before stocking use to 11.3 ± 3.8 after stocking use (p Conclusions: This study demonstrated that the skin perfusion of the lower limbs is decreased following nab-PTX chemotherapy, and also that compression therapy can successfully restore the skin perfusion levels in nab-PTX patients across every grade of peripheral neuropathy. This apparent restoration in skin perfusion may increase the drug clearance, which could potentially alleviate peripheral neuropathy. Disclosure: All authors have declared no conflicts of interest.