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Renal cell carcinoma - Top 30 Publications

Architectural Patterns are a Relevant Morphologic Grading System for Clear Cell Renal Cell Carcinoma Prognosis Assessment: Comparisons With WHO/ISUP Grade and Integrated Staging Systems.

We developed and validated an architecture-based grading for clear cell renal cell carcinoma (ccRCC) in an observational retrospective cohort study including 506 tumors (principal cohort, n=254; validation cohort, n=252). Study endpoints were disease-free survival (DFS) and cancer-specific survival (CSS). Relationships with outcome were analyzed using Harrell concordance index, time-dependent receiver operating characteristic curve, area under curve, and Cox regression model. An architecture-based grading was devised on positive likelihood ratio (LR+) for DFS at 50 months as follows: grade 1 (LR+<0.8), cystic, compact, acinar, clear cell papillary RCC-like, and/or regressive patterns; grade 2 (1.2≤LR+<5), large nest, alveolar, papillary, chromophobe/oncocytic cell-like, eosinophilic hyaline globule, and/or intratumoral inflammatory reaction patterns; grade 3 (5≤LR+<10), rhabdoid, tumor giant cell, enlarged vascular space, and/or hereditary leiomyomatosis renal cell carcinoma (HLRCC)-like patterns; grade 4 (LR+≥10), sarcomatoid, infiltrative growth patterns, and lymphatic invasion. In the principal cohort, 3-tier (grades 1-2, 3, and 4) and 4-tier architectural scores outperformed World Health Organization/International Society of Urological Pathology, and World Health Organization/ International Society of Urological Pathology+necrosis gradings for DFS and CSS, and constituted an independent predictor for DFS (hazard ratio [HR]=5.91; P<6.7E-10) and CSS (HR=4.49; P=2.2E-03), retained in the localized (pT1-3N0M0) ccRCC subgroup (HR=6.10; P=1.3E-07 for DFS, and HR=20.09; P=9.4E-05 for CSS). On comparing with integrated staging systems, architectural grade with 1 morphologic datum remained an independent predictor of CSS, as did University of California Los Angeles Integrated Staging System and SSIGN, and was associated with the highest HR (HR=2.60; P=9.1E-04 in all patients; HR=4.38; P=2.0E-05 in the localized ccRCC subgroup). Architecture-based score for ccRCC outperforms all other morphologic grading systems and constitutes an independent predictor for DFS and CSS. As the predictive values of 3-tier and 4-tier architecture-based scores were similar throughout the study, we proposed to keep the simplified version as the final score, and to define 3 risk groups as follows: low risk (grades 1 to 2), intermediate risk (grade 3), and high risk (grade 4).

Extensive Metastatic Sarcomatoid Renal Cell Carcinoma Evaluated by 18F-FDG PET/CT: a Case Report and Review of Literature.

Sarcomatoid renal cell carcinoma (sRCC) is a highly aggressive form of dedifferentiated renal cell carcinoma. We report a 62-year-old man who presented with respiratory symptoms and a lung mass on chest computed tomography (CT). The patient underwent positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (18F-FDG) and was found to have extensive metastatic disease. Based on the history and imaging findings, there were possible primary malignancies, including bronchogenic carcinoma, melanoma, or an aggressive lymphoma. An excisional biopsy surprisingly revealed a high-grade sarcomatoid carcinoma with no evidence of differentiation, and immunohistochemical (IHC) studies showed that the tumor cells were positive for markers of genitourinary origin (PAX-8 and vimentin). The histologic and IHC results, along with multiple FDG-avid exophytic lesions in both kidneys, were considered diagnostic of sRCC. Here we have highlighted the potential role of 18F-FDG-PET-CT in patients with sRCC, discussed the diagnostic challenges, and presented a brief review.

Gamma Knife Radiosurgery for Cancer Metastasized to the Ocular Choroid.

Choroidal metastases (CMs) are the most common intraocular tumor. Management is mainly radiation therapy with goals of pain control and visual improvement. However, many radiation-related complications are reported. Since gamma knife radiosurgery (GKS) for CM was first reported in 1995, few cases have been reported. We report 7 cases of CMs treated with GKS.

Function of miR-146a-5p in Tumor Cells As a Regulatory Switch between Cell Death and Angiogenesis: Macrophage Therapy Revisited.

Tumors survive and progress by evading killing mechanisms of the immune system, and by generating a tumor microenvironment (TME) that reprograms macrophages in situ to produce factors that support tumor growth, angiogenesis, and metastasis. We have previously shown that by blocking the translation of the enzyme inducible nitric oxide synthase (iNOS), miR-146a-5p inhibits nitric oxide (NO) production in a mouse renal carcinoma cell line (RENCA), thereby endowing RENCA cells with resistance to macrophage-induced cell death. Here, we expand these findings to the mouse colon carcinoma CT26 cell line and demonstrate that neutralizing miR-146a-5p's activity by transfecting both RENCA and CT26 cells with its antagomir restored iNOS expression and NO production and enhanced susceptibility to macrophage-induced cell death (by 48 and 25%, respectively, p < 0.001). Moreover, miR-146a-5p suppression simultaneously inhibited the expression of the pro-angiogenic protein EMMPRIN (threefolds, p < 0.001), leading to reduced MMP-9 and vascular endothelial growth factor secretion (twofolds and threefolds, respectively, p < 0.05), and reduced angiogenesis, as estimated by in vitro tube formation and scratch assays. When we injected tumors with pro-inflammatory-stimulated RAW 264.7 macrophages together with i.v. injection of the miR-146a-5p antagomir, we found inhibited tumor growth (sixfolds, p < 0.001) and angiogenesis (twofolds, p < 0.01), and increased apoptosis (twofolds, p < 0.01). This combination therapy increased nitrites and reduced TGFβ concentrations in tumor lysates, alleviated immune suppression, and allowed enhanced infiltration of cytotoxic CD8+ T cells. Thus, miR-146a-5p functions as a control switch between angiogenesis and cell death, and its neutralization can manipulate the crosstalk between tumor cells and macrophages and profoundly change the TME. This strategy can be therapeutically utilized in combination with the macrophage therapy approach to induce the immune system to successfully attack the tumor, and should be further explored as a new therapy for the treatment of cancer.

Safety of axitinib and sorafenib monotherapy for patients with renal cell carcinoma: a meta-analysis.

We sought to investigate safety of axitinib or sorafenib in renal cell carcinoma (RCC) patients and compare toxicity of these two vascular endothelial growth factor receptor inhibitors. Databases of PubMed and Embase were searched. We included phase II and III prospective trials, as well as retrospective studies, in which patients diagnosed with RCC were treated with axitinib or sorafenib monotherapy at a starting dose of 5 mg and 400 mg twice daily, respectively. The overall incidence of high grade hypertension, fatigue, gastrointestinal toxicity and hand-foot syndrome, along with their 95% confidence intervals (CI), were calculated using fixed- or random- effects model according to heterogeneity test results. A total of 26 trials, including 4790 patients, were included in our meta-analysis. Among them, 6 arms were related to axitinib and 22 were associated with sorafenib. The incidences of hypertension (24.9% vs. 7.9%), fatigue (8.2% vs. 6.6%), and gastrointestinal toxicity (17.6% vs. 11.3%) were higher in patients receiving axitinib versus those receiving sorafenib, while the incidence of hand-foot syndrome was lower in patients receiving axitinib versus those receiving sorafenib (9.5% vs. 13.3%). In conclusion, axitinib showed noticeably higher risks of toxicity versus sorafenib. Close monitoring and effective measures for adverse events are recommended during therapy.

Change in Neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma.

An elevated Neutrophil-to-lymphocyte ratio (NLR) is associated with worse outcomes in several malignancies. However, its role with contemporary immune checkpoint blockade (ICB) is unknown. We investigated the utility of NLR in metastatic renal cell carcinoma (mRCC) patients treated with PD-1/PD-L1 ICB.

Indications, complications, and outcomes following surgical management of locally advanced and metastatic renal cell carcinoma.

Surgery may set the basis for a potential cure or would provide the best achievable quality of life in locally advanced or metastatic renal cell carcinoma (mRCC). However, survival extension with this approach would be scarce and not exempt from adverse events, thus preventing its recommendation in an already frail patient. An evidence based analysis on the role of surgery in each of the possible clinical scenarios involved under this heading may provide a clear picture on this issue and would be of value in the decision making process. Areas covered: Current literature was queried in PubMed/Medline in a systematic fashion. Manuscripts included were selected according to the quality of the data provided. A narrative review strategy was adopted to summarize the evidence acquired. Expert commentary: A surgery-based multimodal treatment approach should be strongly considered after adequate counseling in locally advanced and mRCC, since it may provide for additional benefits in terms of survival. However, a critical reevaluation of its adequacy, optimal timing, and selection of ideal candidates is currently ongoing.

Case report: vertebral foreign body granuloma mimicking a skeletal metastasis.

Intraosseous foreign body granuloma formation related to migrated surgical material is a rarely reported condition with variable imaging appearance. In this case report, we describe a foreign body granuloma that occurred in a lumbar vertebral body one level above a prior surgical fusion. The lytic appearance mimicked a skeletal metastasis in a 65-year-old patient with recently diagnosed renal cell carcinoma. To the best of our knowledge, this is the first reported case of a lumbar vertebral foreign body granuloma occurring distant from the site of surgery, indistinguishable from skeletal metastasis on radiologic examination.

Next-generation sequencing to detect deletion of RB1 and ERBB4 genes in chromophobe renal cell carcinoma: A potential role in distinguishing chromophobe renal cell carcinoma from renal oncocytoma.

Overlapping morphological, immunohistochemical, and ultrastructural features make it difficult to diagnose chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO). Since ChRCC is a malignant tumor, whereas RO is a tumor with benign behavior, it is important to distinguish these two entities. We aimed to identify genetic markers that distinguish ChRCC from RO by using next-generation sequencing (NGS). NGS for hotspot mutations or gene copy number changes was performed on 12 renal neoplasms including seven ChRCC and five RO cases. Matched normal tissues from the same patients were used to exclude germline variants. Rare hotspot mutations were found in in cancer-critical genes (TP53, PIK3CA) in ChRCC but not RO. The NGS gene copy number analysis revealed multiple abnormalities. The two most common deletions were tumor suppressor genes RB1 and ERBB4 in ChRCC but not RO. Fluorescence in situ hybridization was performed on 65 cases (ChRCC, n=33; RO, n=32) to verify hemizygous deletion of RB1 (17/33, 52%) or ERBB4 (11/33, 33%) in ChRCC, but not in RO (0/32, 0%). In total, ChRCCs (23/33, 70%) carry either a hemizygous deletion of RB1 or ERBB4. The combined use of RB1 and ERBB4 fluorescence in situ hybridization to detect deletion of these genes may offer a highly sensitive and specific assay to distinguish ChRCC from RO.

Influence of Contrast Administration on Computed Tomography-Based Analysis of Visceral Adipose and Skeletal Muscle Tissue in Clear Cell Renal Cell Carcinoma.

Computed tomography (CT) scans are being utilized to examine the influence of skeletal muscle and visceral adipose quantity and quality on health-related outcomes in clinical populations. However, little is known about the influence of contrast administration on these parameters.

Overview of Current and Future Adjuvant Therapy for High-Risk Localized Renal Cell Carcinoma.

High-risk localized renal cell carcinoma represents a therapeutic challenge with high recurrence rates and poor survival with nephrectomy alone. Multiple agents targeting angiogenic and immunologic pathways have demonstrated remarkable efficacy in the metastatic setting but have failed to replicate similar successes in localized disease. Study results with adjuvant anti-angiogenic therapies may have been compromised by the high incidence of treatment discontinuations or dosage reductions secondary to intolerable side effects. Improving patient selection could play a major role in improving outcomes. Multiple models exist to predict survival but require improved accuracy in identifying recurrence to justify exposing patients to therapies that could significantly impair quality of life. Further understanding of pathological and molecular mechanisms of recurrence is required. Novel tools like gene recurrence scores are emerging to improve prognostication for patient selection. Immunotherapeutic approaches using check point inhibition have the potential to achieve sustained remissions with a significantly improved toxicity profile. Amplifying the immune response with a combination of neoadjuvant and adjuvant therapy to exploit the larger antigenic burden prior to nephrectomy has the biologic potential for making significant improvements in efficacy.

Mucin-Poor Mucinous Tubular and Spindle Cell Carcinoma of the Kidney Presented with Multiple Metastases Two Years after Nephrectomy: An Atypical Behaviour of a Rare, Indolent Tumour.

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of renal cell carcinoma, whose clinical behaviour and metastatic potential have not been fully elucidated to date. There are only a few metastatic cases in the literature, which all either featured sarcomatoid differentiation or were synchronously metastasised at diagnosis.

Cetuximab-Associated Crescentic Diffuse Proliferative Glomerulonephritis.

Cetuximab-induced nephrotoxicity is very rare, occurring in less than 1% of colorectal cancer patients and not defined in other populations. We report a rare case of crescentic diffuse proliferative glomerulonephritis (GN) that developed in close temporal association with cetuximab treatment. A 65-year-old female recently completed chemotherapy with cetuximab treatment for moderately differentiated oral squamous cell carcinoma. She was admitted with acute renal failure and nephrotic-range proteinuria. Laboratory data showed serum creatinine of 6.6 mg/dl and urinalysis showed proteinuria, moderate hemoglobinuria, hyaline casts (41/LPF), WBC (28/HPF), and RBC (81/HPF). Serologic studies were negative for ANA, anti-GBM, ANCA, hepatitis B, and hepatitis C. Serum C3 and C4 level were normal. Renal biopsy showed crescentic diffuse proliferative GN with focal features of thrombotic microangiopathy. Patient was started on cyclophosphamide and steroids. Her renal function did not improve on day 8 and she was started on hemodialysis. Previous reports suggest that EGFR-targeting medications can possibly trigger or exacerbate an IgA-mediated glomerular process leading to renal failure. This case suggests that cetuximab therapy may have triggered or exacerbated a severe glomerular injury with an unfavorable outcome. Treating physicians should maintain a high degree of caution and monitor renal function in patients on EGFR inhibitors.

Interferon-α adjuvant therapy decreases the recurrence of early clear cell renal cell carcinoma and improves the prognosis of Chinese patients.

The survival time of patients with early clear cell renal cell carcinoma (ccRCC) is fairly long, but 20% to 30% of patients with localized tumors experience relapse, and the effect of IFN-α on survival has not been well studied in patients with early ccRCC. In this study, 208 patients with early ccRCC were treated with surgery, and 54 of the patients received IFN-α as adjuvant therapy. The remaining 115 patients were treated with surgery but not with IFN-α therapy. The primary endpoint was the recurrence rate, 20.37% (11/54) and 33.04% (38/115) in the IFN-α and surgery-only group, respectively. The secondary endpoint was progression-free survival (PFS), which was 123.70 (95% CI: 107.18-140.22) months for the IFN-α group, and 95.80 (95% CI: 82.18-109.42) months for the non-IFN-α group; this difference was significant (P < 0.05). The main side effects were pyrexia (61.11%), muscle pain (24.07%), malaise (9.26%), anorexia (5.56%), hepatic dysfunction (3.70%) and renal dysfunction (1.85%). Moreover, a multivariate regression identified older age, higher BMI index and smoking as significant and independent predictors of decreased PFS (P < 0.05). Overall, IFN-α therapy significantly improved PFS in Chinese patients with early ccRCC and was an independent prognostic factor (P < 0.05). In conclusion, our study showed that adjuvant IFN-α therapy decreased the recurrence rate and prolonged PFS in patients with ccRCC. Thus, this treatment may help clinicians to select a better treatment modality and better predict survival in these patients.

Mutation Burden Predicts Anti-PD-1 Response.

A new study finds that objective response rates to anti-PD-1 therapies correlate with tumor mutation burden for most of the 27 cancer types studied. Objective response rates were higher than expected for Merkel cell carcinoma and renal cell carcinoma, which may be particularly immunogenic. The objective response rate was unexpectedly low for colorectal cancer with mismatch repair proficiency.

Activity and safety of afatinib in a window pre-operative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN).

To investigate the activity and safety of afatinib in the pre-operative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5:1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were performed at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other endpoints included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic enhanced contrast (DCE)-MRI, diffusion weighted (DW)-MRI, safety and translational research (TR).

p53β: a new prognostic marker for patients with clear-cell renal cell carcinoma from 5.3 years of median followup.

We previously reported six different p53 isoforms in renal cell carcinoma (RCC). In the present study, influences of p53β on recurrence-free survival (RFS) and overall survival (OS) were evaluated. Patients diagnosed with RCC in our center were into this study. mRNA expressions of p53 isoforms (p53α, p53β, p53γ) in tumors were determined by RT-PCR and real-time PCR. Functional yeast-based assay was performed to analyze p53 mutational status. p53β transfected 786-O and CAKi-1 cells were cultured to examine expressions of B-cell lymphoma 2-associated X protein (bax) and caspase-3, and ratios of apoptosis. After surgeries, all patients were followed up at programmed intervals. 266 patients were analyzed in this study. Median followup time was 5.3 years. RT-PCR (r = -0.72, P = 0.016) and real-time PCR (r = -0.65, P = 0.033) both showed only p53β expressed higher level in lower tumor stage versus higher stage. p53 wild-type and p53 mutation had comparable RFS (P = 0.361) and OS (P = 0.218), respectively. Kaplan-Meier analysis showed high p53β expression was associated with significantly improved RFS and OS, regardless of p53 mutational status. High p53β expression indicated better RFS (hazard ratio (HR) 2.599, 95% confidence interval (CI) 1.472-4.551, P = 0.038) and OS (HR 2.604, 95% Cl 1.453-4.824, P = 0.031). p53β transfected 786-O and CAKi-1 cells expressed significantly higher level of bax and caspase-3, and had higher ratios of apoptosis than untransfected cells. Taken together, higher level of p53β predict better prognosis in patients with RCC through enhancing apoptosis in tumors.

Present status and future perspective of peptide-based vaccine therapy for urological cancer.

The use of peptide-based vaccines as therapeutics aims to elicit immune responses through antigenic epitopes derived from tumor antigens. Peptide-based vaccines are easily synthesized and the lack of significant side effects when administered in-vivo. Peptide-based vaccine therapy against several cancers including urological cancers had made progress for several decades, but there is no approval peptide vaccine all over the world. Peptides vaccines were also shown to induce a high frequency of immune response in patients who were accompanied by clinical efficacy. These data are discussed at the light of recent progression of immunotherapy caused by the addition of immune check-point inhibitors thus providing a general picture of the potential therapeutic efficacy of the peptide-based vaccines and their combination with other biological agents. In this review, we discuss mechanism of anti-tumor effect by peptide-based vaccine therapy, development of our peptide vaccine, recent clinical trials using peptide vaccine for urological cancers, and perspective of peptide-based vaccine therapy. This article is protected by copyright. All rights reserved.

Clear cell carcinomas of the ovary and kidney: clarity through genomics.

Clear cell ovarian carcinoma (CCOC) and clear cell renal cell carcinoma (ccRCC) both feature clear cytoplasm due to the accumulation of cytoplasmic glycogen. Genomic studies have demonstrated several mutational similarities between these two diseases including frequent alterations in the chromatin remodeling SWI/SNF and cellular proliferation PI3K/mTOR pathways, as well as a shared hypoxia-like mRNA expression signature. Although many targeted treatment options have been approved for advance stage ccRCC, CCOC patients are still treated with conventional platinum and taxane chemotherapy, to which they are resistant. To determine the extent of similarity between these malignancies, we performed unsupervised clustering of mRNA expression data from these cancers. This review highlights the similarities and differences between these two clear cell carcinomas to facilitate knowledge translation within future research efforts.

MicroRNAs in Renal Diseases: A Potential Novel Therapeutic Target.

MicroRNAs (miRNAs) are a family of short noncoding RNAs that play important roles in posttranscriptional gene regulation. miRNAs inhibit target gene expression by blocking protein translation or by inducing mRNA degradation and therefore have the potential to modulate physiological and pathological processes.

Choroidal Melanoma Mimicker: A Case of Metastatic Clear-Cell Renal Cell Carcinoma.

Choroidal melanoma is the most common primary intraocular malignancy, yet metastatic disease remains the most common malignancy of the eye. Differentiating these entities is essential as treatment, systemic associations, and prognosis vary dramatically between the two. Established diagnostic criteria are accurate for the diagnosis of uveal melanoma. Yet, metastatic disease may be misdiagnosed as a uveal melanoma in rare cases. We report a case of metastatic clear-cell renal cell carcinoma masquerading as uveal melanoma. A 73-year-old Caucasian man with a history of renal cell carcinoma presented with a 15 × 12 × 7 mm homogenous, pigmented, and acoustically hollow mass without hemorrhage or exudation. The patient was initially treated with plaque radiotherapy with good tumor regression. However, the patient developed pain and vision loss due to total exudative retinal detachment. Subsequent enucleation allowed histopathologic confirmation of clear-cell renal cell carcinoma. Nine years following enucleation, the patient remains in complete remission without evidence of other systemic metastases. Renal cell carcinoma should be considered when evaluating patients with probable uveal melanoma. Delayed-onset ocular metastasis from renal cell carcinoma exhibits an atypical clinical course with the possibility of durable remission following enucleation.

Elevated serum levels of cardiovascular biomarkers are associated with progression of renal cancer.

Renal cell carcinoma (RCC) is a hypervascular tumour due to high constitutive production of vascular endothelial growth factor (VEGF), which is activated by hypoxia-inducible factor (HIF). Elevated levels of cardiovascular peptides, including brain natriuretic peptide (BNP), have been reported in patients with cancer, regardless of whether they have overt cardiovascular disease. Furthermore, it has been demonstrated that hypoxia stimulates BNP production by an HIF-dependent manner. However, the clinical implications of such cardiovascular peptides in patients with RCC have not been assessed.

WST11 Vascular Targeted Photodynamic Therapy Effect Monitoring by Multispectral Optoacoustic Tomography (MSOT) in Mice.

Objective: Monitoring emerging vascular-targeted photodynamic therapy (VTP) and understanding the time-dynamics of treatment effects remains challenging. We interrogated whether handheld multispectral optoacoustic tomography (MSOT) could noninvasively monitor the effect of VTP using WST11, a vascular-acting photosensitizer, on tumor tissues over time using a renal cell cancer mouse model. We also investigated whether MSOT illumination can induce VTP, to implement a single-modality theranostic approach. Materials and Methods: Eight BalB/c mice were subcutaneously implanted with murine renal adenocarcinoma cells (RENCA) on the flank. Three weeks later VTP was performed (10 min continuous illumination at 753 nm following intravenous infusion using WST11 or saline as control. Handheld MSOT images were collected prior to VTP administration and subsequently thereafter over the course of the first hour, at 24 and 48 h. Data collected were unmixed for blood oxygen saturation in tissue (SO2) based on the spectral signatures of deoxy- and oxygenated hemoglobin. Changes in oxygen saturation over time, relative to baseline, were examined by paired t-test for statistical significance (p < 0.05). In-vivo findings were corroborated by histological analyses of the tumor tissue. Results: MSOT is shown to prominently resolve changes in oxygen saturation in tumors within the first 20 min post WST11-VTP treatment. Within the first hour post-treatment, SO2 decreased by more than 60% over baseline (p < 0.05), whereas it remained unchanged (p > 0.1) in the sham-treated group. Moreover, unlike in the control group, SO2 in treated tumors further decreased over the course of 24 to 48 h post-treatment, concomitant with the propagation of profound central tumor necrosis present in histological analysis. We further show that pulsed MSOT illumination can activate WST11 as efficiently as the continuous wave irradiation employed for treatment. Conclusion: Handheld MSOT non-invasively monitored WST11-VTP effects based on the SO2 signal and detected blood saturation changes within the first 20 min post-treatment. MSOT may potentially serve as a means for both VTP induction and real-time VTP monitoring in a theranostic approach.

Overexpression of NEDD9 in renal cell carcinoma is associated with tumor migration and invasion.

Scaffold protein neural precursor cell expressed, developmentally downregulated 9 (NEDD9) is a member of the Crk-associated substrate protein family and is known to be a biomarker in multiple cancer types. It serves a critical function in regulating cell proliferation, migration, invasion and survival. The objective of this study was to evaluate the potential effects of NEDD9 in renal cell carcinoma (RCC). The expression of NEDD9 was analyzed by immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction. NEDD9 protein and mRNA levels were significantly upregulated in RCC tissues compared with normal tissues (P<0.001). Furthermore, the NEDD9 immunostaining level was significantly associated with primary tumor stage and tumor, node, metastasis stage (P<0.05). High NEDD9 expression resulted in significantly lower survival rates for patients compared with normal NEDD9 expression (P<0.01). In addition, wound healing and transwell assays indicated that NEDD9 depletion by small interfering RNA significantly attenuated the migration and invasion of RCC cells (P<0.001). The present data suggested that NEDD9 may be a novel target for prevention and treatment of RCC metastasis and recurrence.

MicroRNA-138 suppresses cell proliferation and invasion of renal cell carcinoma by directly targeting SOX9.

An accumulating number of studies have reported that the expression levels of microRNAs (miRNAs/miRs) are dysregulated in a variety of human cancer types, including renal cell carcinoma (RCC). miRNAs play essential functions in tumorigenesis and the progression of tumors by serving as oncogenes or tumor suppressors. Recently, the expression and functions of miR-138 have been studied in a number of human cancer types; however, its role in RCC remains poorly understood. In the present study, the results revealed that miR-138 was significantly downregulated in RCC cell lines and tissues, and that low expression levels of miR-138 were correlated with histological grade, tumor stage and lymph node metastasis. In functional studies, restoration of miR-138 expression inhibited cell proliferation and invasion of ACHN and A498 cells. In addition, SOX9 was validated as a direct target gene of miR-138 in RCC. SOX9 knockdown inhibited cell proliferation and invasion of RCC, with a similar effect to that induced by miR-138, rendering SOX9 a functional target of miR-138 in the disease. These findings indicate that miR-138 may present a novel target for therapeutic strategies in RCC.

Metachronous metastasis of renal cell carcinoma to the urinary bladder: a case report.

We report a case of intravesical metastasis of a clear cell renal cell carcinoma. In renal cell carcinoma 16% of patients present with metastatic disease. Renal cell carcinoma can metastasize to nearly every organ, although metastatic spread to the urinary bladder is rare, with fewer than 70 described cases. The route and pattern of metastatic spread is not yet fully understood and different pathways are suggested. Gross haematuria is the presenting symptom in the majority of cases. These intravesical metastases may be synchronous or metachronous and can be solitary or part of polymetastatic disease. No standard treatment can be suggested due to the rare nature of this phenomenon, and treatment varies from transurethral resection, partial or complete cystectomy to systemic therapy. Prognosis in patients with a solitary bladder lesion that developed metachronously is rather good, whereas poor prognosis can be expected in patients with synchronous and multiple metastases.

The correlation between gain of chromosome 8q and survival in patients with clear and papillary renal cell carcinoma.

The proto-oncogene c-MYC, located on chromosome 8q, can be upregulated through gain of 8q, causing alteration in biology of renal cell carcinoma (RCC). The aim of this study was to evaluate the prevalence of c-MYC through chromosome 8q gain and to correlate findings with cancer-specific mortality (CSM), and overall survival (OS).

The putative tumor suppressor, miR-199a, regulated by Snail, modulates clear cell renal cell carcinoma aggressiveness by repressing ROCK1.

Aberrant expression of miR-199a has been frequently reported in cancer studies; however, its role in renal cell carcinoma (RCC) has not been examined in detail.

Papillary renal cell carcinoma with abscess formation: A report of three cases.

We report three cases of renal cell carcinoma (RCC) associated with abscess formation. Such association has been reported uncommonly in literature. Our cases were unique in that final histopathological report was papillary RCC in all of the patients.

Painless Thyroiditis and Fulminant Type 1 Diabetes Mellitus in a Patient Treated with an Immune Checkpoint Inhibitor, Nivolumab.

The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. Nivolumab, an anti-PD-1 monoclonal antibody, blocks PD-1 and can restore anti-cancer immune responses by disrupting the signal that inhibits T-cell activation. Nivolumab may induce endocrine-related adverse events, including hypophysitis, autoimmune thyroiditis, and type 1 diabetes mellitus. Here we report a 68-year-old female patient with advanced renal cell carcinoma who was treated with nivolumab. She had positive anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies with slightly elevated thyroid-stimulating hormone (9.048 μU/mL), and was diagnosed as chronic thyroiditis with subclinical hypothyroidism before nivolumab therapy. She developed painless thyroiditis after the first cycle of the therapy (Day 14). At the 7th cycle of nivolumab therapy (Day 98), hyperglycemia (473 mg/dL) was noted, whereas glycated hemoglobin level was 6.9%. Islet-related autoantibodies were all negative. The glucagon tolerance test showed complete depletion of insulin. Human leukocyte antigen typing showed haplotype DRB1*09:01-DQB1*03:03, which was reported to be closely associated with type 1 diabetes mellitus in Japan. Fulminant type 1 diabetes mellitus was diagnosed, and she was immediately treated with multiple daily injections of insulin. Fulminant type 1 diabetes mellitus is characterized by rapid-onset diabetic ketoacidosis, and negative islet-related autoantibodies, and was proposed as a novel subtype of non-autoimmune diabetes. Preceding painless thyroiditis with positive thyroid autoantibodies observed in the present case, however, raises the possibility that autoimmune mechanisms are involved in the pathogenesis of nivolumab-induced fulminant type 1 diabetes mellitus.