Establishment of the optimal follow-up schedule after radical prostatectomy

Purpose

Monitoring the serum level of prostate specific antigen (PSA) is indispensable for surveillance after radical therapy, and the aim of this study was to establish the optimal follow-up schedule.

Subclinical subretinal fluid detectable only by optical coherence tomography in choroidal naevi—the SON study

BackgroundSubretinal fluid is a risk factor for growth and malignant transformation of choroidal naevi, however it is unclear if this applies to subclinical fluid that is only detectable by optical coherence tomography (OCT). The objective of this study was to determine the prevalence and associations of subclinical but OCT-detectable subretinal fluid over choroidal naevi.MethodsCross-sectional study of 309 consecutive cases of choroidal naevi imaged by OCT between July 2017 to January 2019. Multicentre international study involving ten retinal specialist centres. All patients presenting to retinal specialists had routine clinical examination and OCT imaging. The prevalence of subclinical OCT-detectable subretinal fluid over choroidal naevi and its associations with other features known to predict growth and malignant transformation were noted and analysed.ResultsOf 309 identified consecutive cases, the mean patient age was 65 years, 89.3% of patients were Caucasian and 3.9% were Asian. The prevalence of subclinical but OCT-detectable subretinal fluid associated with choroidal naevi was 11.7% (36/309). Naevi with fluid were associated with larger basal diameters, greater thickness, presence of a halo, orange pigmentation, hyperautofluorescence, and hypodensity on B-scan ultrasonography.Conclusion and relevanceOf choroidal naevi where subretinal fluid is not visible on clinical examination, 11.7% demonstrate subretinal fluid on OCT scans. These naevi more commonly exhibit features known to be associated with growth and transformation to melanoma. The presence of subclinical OCT-detectable fluid over choroidal naevi may assist in their risk stratification.Subject terms: Risk factors, Uveal diseases, Eye manifestations     

Ribosomal proteins induce stem cell-like characteristics in glioma cells as an “extra-ribosomal function”

Brain Tumor Pathology - The characteristic features of plasticity and heterogeneity in glioblastoma (GB) cells cause therapeutic difficulties. GB cells are exposed to various stimuli from the tumor...     

Mesenchymal Stem Cells Display Tumor-Specific Tropism in an RCAS/Ntv-a Glioma Model

Bone marrow-derived mesenchymal stem cells (MSCs) have been shown to localize to gliomas and deliver therapeutic agents. However, the clinical translation of MSCs remains poorly defined because previous studies relied on glioma models with uncertain relevance to human disease, typically xenograft models in immunocompromised mice. To address this shortcoming, we used the RCAS/Ntv-a system, in which endogenous gliomas that recapitulate the tumor and stromal features of human gliomas develop in immunocompetent mice. MSCs were harvested from bonemarrowof Ntv-a mice and injected into the carotid artery of Ntv-a mice previously inoculated with RCAS-PDGF-B and RCAS-IGFBP2 to induce malignant gliomas (n = 9). MSCs were labeled with luciferase for in vivo bioluminescence imaging (BLI). After intra-arterial injection, BLI revealed MSCs in the right frontal lobe in seven of nine mice. At necropsy, gliomas were detected within the right frontal lobe in all these mice, correlating with the location of the MSCs. In the twomice without MSCs based on BLI, no tumor was found, indicating thatMSC localization was tumor specific. In another cohort of mice (n = 9), MSCs were labeled with SP-DiI, a fluorescent vital dye. After intra-arterial injection, fluorescence microscopy revealed SP-DiI-labeled MSCs throughout tumors 1 to 7 days after injection but not in nontumoral areas of the brain. MSCs injected intravenously did not localize to tumors (n = 12). We conclude that syngeneic MSCs are capable of homing to endogenous gliomas in immunocompetent mice. These findings support the use of MSCs as tumor-specific delivery vehicles for treating gliomas.     

Development of a novel interferon-α2b gene construct with a repetitive hypoxia-inducible factor binding site and its suppressive effects on human renal cell carcinoma cell lines in vitro

Background

Despite the advent of targeted therapies, interferon-alpha (IFN-α) remains a therapeutic option for advanced renal cell carcinoma (RCC), especially in Japan, with a treatment response rate of 15–20 %. To improve the efficacy of IFN-α-based therapies, we evaluated a novel treatment strategy for RCC using an IFN-α2b gene construct with a repetitive hypoxia-inducible factor binding site.

Methods

We constructed an expression plasmid designated 5HREp-IFN-α2b containing the coding region of the IFN-α2b gene. Five copies of the hypoxia-response element (HRE) sequences were inserted upstream of the IFN-α2b gene, and the construct was transfected into human RCC cell lines ACHN, 786-O and KU19-20. The concentrations of IFN-α2b in the conditioned media were measured by enzyme-linked immunosorbent assay. Cell viabilities were determined by MTS assays.

Results

Construct-induced IFN-α secretion was confirmed in all three cell lines. IFN-α production was significantly enhanced by the hypoxia-mimicking agent deferoxamine mesylate in cell lines expressing the wild-type von Hippel–Lindau (VHL) gene (KU19-20 and ACHN) compared with cells expressing the mutant VHL gene (786-O). The construct exerted significant suppressive effects on the viabilities of all RCC cell lines.

Conclusion

This is the first study to report on the construction of a cytokine gene with a repetitive hypoxia-inducible factor binding site and its application in the suppression of human cancer cells. Gene therapy using this IFN-α2b gene construct with HREs may represent a novel treatment modality for advanced RCC.     

Non-traumatic renal arteriopelvic fistula

PURPOSE: In the present paper, we report on a 34-year-old female with macroscopic hematuria due to a nontraumatic renal arteriopelvic fistula (APF). The patient initially presented at another hospital with asymptomatic macroscopic hematuria. Following abdominal ultrasonography, computed tomography (CT) and laboratory data, no abnormal findings were seen. Therefore, the patient was referred to Teine Keijinkai Hospital for a more precise evaluation of the urinary tract and vascular abnormality. METHODS/RESULTS: Endoscopically, there was bleeding from the right ureteral orifice, so the patient was admitted for further examination. No abnormal findings were seen on urinary cytology and following an intravenous pyelogram. A selective right lower polar renal arteriogram revealed arterial extravasation directly into the pelvis before the venous phase, so APF of the kidney was diagnosed. The patient had no history of urinary tract trauma, so the APF was thought to be idiopathic. After transcatheter arterial embolization (TAE) with a gelatine sponge, macroscopic and microscopic hematuria disappeared and a low-density area was seen in the middle pole of the right kidney in an abdominal CT scan 4 days after TAE. This was thought to be renal infarction due to TAE. CONCLUSIONS: After discharge, the patient had no further hematuria.     

Analysis of homozygous deletion of the p16 gene and correlation with survival in patients with glioblastoma multiforme

OBJECT: One of the most frequent genetic abnormalities found in patients with glioblastoma multiforme (GBM) is homozygous deletion of the p16 tumor suppressor gene. The authors investigated whether this deletion is associated with prognosis in patients with GBM. METHODS: In 46 adult patients with supratentorial GBM, homozygous deletion of the p16 gene in tumor DNA was examined using the multiplex polymerase chain reaction assay. The deletion was confirmed in 14 (30.4%) of 46 patients, eight (30.8%) of 26 men and six (30.0%) of 20 women. Cox proportional hazard regression analysis, adjusted for age at surgery, the Karnofsky Performance Scale score, extent of resection, and the MIB-1 labeling index. revealed that homozygous deletion of the p16 gene was significantly associated with overall survival and progression-free survival in men, but not in women. CONCLUSIONS: The results of this study suggest that p16 homozygous deletion is a significant unfavorable prognostic factor in male patients with GBM.     

Impact of baseline visceral fat accumulation on prognosis in patients with metastatic renal cell carcinoma treated with systemic therapy

Medical Oncology - Liver thermal ablation is an alternative treatment for hepatocellular carcinoma (HCC) and secondary liver malignancies. Microwave ablation (MWA) produces large ablation zones...     

Negative impact of neoadjuvant hormonal therapy on detecting biochemical recurrence after radical prostatectomy

International Journal of Clinical Oncology - Routine use of neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP) is not recommended, but it is sometimes performed to reduce the...