Renal cell carcinoma: applicability of the apparent coefficient of the diffusion-weighted estimated by MRI for improving their differential diagnosis, histologic subtyping, and differentiation grade.

BACKGROUND: Renal cell carcinoma (RCC) represents the most common malignant epithelial neoplasm of the kidney. Accurate assessment of the renal masses, defining the histologic subtype and the grade of differentiation of the tumor, is vital to ensure an adequate case management as well as for staging and prognosis. Recently, diffusion-weighted imaging (DWI) magnetic resonance imaging (MRI) tends to be increasingly appealing for the clinicians as an imaging procedure of choice for the diagnosis and staging of the RCC, which is predetermined by several advantages over CT. The goal of the survey was to assess the applicability of the apparent diffusion coefficient (ADC) of the DWI MRI for the differential diagnostics, histologic subtyping, and defining the grade of differentiation of the RCC. METHODS: The study enrolled 288 adult patients with renal lesions: 188 patients with solid RCC-126 patients with clear cell subtype (ccRCC), 32 patients with papillary RCC (pRCC), 30 patients with chromophobe RCC (chRCC); 27 patient with cystic form or RCC (Bosniak cyst, category IV); 32 patients with renal angiomyolipoma (AML); 25 patients with renal oncocytoma (OC); and 16 patients with the renal abscess (AB). In total, 245 lesions were pathologically verified. As a reference, 19 healthy volunteers were included into the study. All patients underwent MRI of the kidneys, involving DWI with subsequent evaluation of the ADC. RESULTS: There was a reliable difference (p < 0.05) in mean ADC values between the normal renal parenchyma (NRP), solid RCC of different histologic subtypes and grades, cystic RCC, and benign renal lesions. The mean ADC values obtained in the result of the study were (×10-3 mm2/s): 2.47 ± 0.12 in NRP, 1.63 ± 0.29 in all solid RCCs, 1.82 ± 0.22 in solid ccRCC (1.92 ± 0.11-Fuhrman grade I, 1.84 ± 0.14-Fuhrman grade II, 1.79 ± 0.10-Fuhrman grade III, 1.72 ± 0.06-Fuhrman grade IV), 1.61 ± 0.07 in pRCC, 1.46 ± 0.09 in chRCC, 2.68 ± 0.11 in cystic RCC, 2.13 ± 0.08 in AML, 2.26 ± 0.06 in OC, and 3.30 ± 0.07 in AB. CONCLUSION: The data received in our study demonstrate a substantial restriction of diffusion of hydrogen molecules in tissues of ccRCC in comparison with the healthy renal parenchyma preconditioned by the greater density of tumor. A statistically significant difference in mean ADC values of ccRCC with different grades of nuclear pleomorphism by Fuhrman was observed: Low-grade tumors showed higher mean ADC values compared to high-grade tumors. The modality of the MRI DWI along with ADC measurement allows to reliably differentiate between the solid RCC of main histologic subtypes and grades, cystic RCC, and the benign renal lesions.

Is miR-34a a Well-equipped Swordsman to Conquer Temple of Molecular Oncology?

Overwhelmingly increasing advancements in miRNA biology have opened new avenues for pharmaceutical companies to initiate studies on designing effective, safe, and therapeutically active candidates using miRNA mimetics and miRNA inhibitors. In accordance with this approach, development of miravirsen and SPC3649, an LNA-based (locked nucleic acid) antisense molecule against miR-122, to treat hepatitis C has sparked interest in identifying most efficient microRNAs for journey from bench-top toward pharmaceutical industry and breakthroughs in delivery technology will pave the way to 'final frontier'. MRX34, a liposome-formulated mimic of miR-34 for treatment of metastatic cancer with liver involvement and unresectable primary liver cancer, has also entered in clinical trial. There is a successive increase in the research work related to miR-34 biology and miRNA regulation of modulators of intracellular signaling cascades. We partition this review into how miR-34a is regulated by different proteins and how Wnt- and TGF-induced intracellular signaling cascades are modulated by miR-34a. In this review, we bring to limelight how miR-34a regulates its target genes to induce apoptosis and inhibit cell proliferation as evidenced by in vitro and in vivo analysis. We also discuss miR-34 regulation of PDGFR and c-MET and recent advancements in nanotechnologically delivered miR-34a. Spotlight is also set on modulation of chemotherapeutic sensitivity by miR-34a in cancer cells using reconstruction studies. Clinical trial of miR-34 is indicative of its tremendous potential, and continuous cutting research will prove to be effective in efficiently translating laboratory findings into clinically effective therapeutics.

Rutin mediated targeting of signaling machinery in cancer cells.

Progress in our understanding of molecular oncology has started to shed light on dysregulation of spatio-temporally controlled signaling pathways, inactivation of tumor suppressor genes, tumour and normal stem cell quiescence, overexpression of oncogenes, extracellular and stromal microenvironments, epigenetics and autophagy. Sequentially and characteristically it has been shown that cancer cells acquire the ability to escape from apoptotic cell death, proliferate uncontrollably, sustain angiogenesis and tactfully reconstitute intracellular pathways to avoid immune surveillance. We have attempted to provide a recent snapshot of most recent progress with emphasis on how rutin modulates wide ranging intracellular signaling cascades as evidenced by in-vitro and in-vivo research. It is worth describing that 'single-cell proteomics' analysis has further improved our understanding regarding intracellular signaling pathways frequently activated in cancer cells resistant to therapeutics and can provide biomarkers for cancer diagnosis and prognosis. Data obtained from preclinical studies will prove to be helpful for scientists to bridge basic and translational studies.

Anticancer activity of essential oils: targeting of protein networks in cancer cells.

Cancer is a multifaceted and genomically complex disease and research over decades has gradually and sequentially shown that essential biological mechanisms including cell cycle arrest and apoptosis are deregulated. The benefits of essential oils from different plants have started to gain appreciation as evidenced by data obtained from cancer cell lines and xenografted mice. Encouraging results obtained from preclinical studies have attracted considerable attention and various phytochemicals have entered into clinical trials.

Value of the diffusion-weighted MRI in the differential diagnostics of malignant and benign kidney neoplasms - our clinical experience.

BACKGROUND: Diffusion-weighted imaging (DWI) is an MRI modality using strong bipolar gradients to create a sensitivity of the signal to the thermally-induced Brownian motions of water molecules and in vivo measurement of molecular diffusion. The apparent diffusion coefficient (ADC) is a quantitative parameter calculated from DWI images which is used as a measure of diffusion. DWI allows to obtain comprehensive information on morphological and functional state of the kidney during a single examination without contrast medium administration. The purpose of the study was to evaluate the value of DWI in differentiating benign and malignant solid kidney tumors based on the initial stage of the study. MATERIAL/METHODS: The study included 19 adult patients with pathologically verified renal tumors: 9 patients with clear cell subtype of the renal cell carcinoma, 5 patients with oncocytoma and 5 patients with angiomyolipoma (AML). In addition, 5 healthy volunteers with completely normal findings according to kidney ultrasound were included into this study and set as reference. All patients underwent renal MR imaging which included DWI with subsequent ADC measurement. MR imaging was performed with a 1.5 T body scanner using an eight-channel phased-array body coil. RESULTS: The mean ADC value of ccRCC was significantly lower than that of normal renal parenchyma (2.11±0.25×10(-3) mm(2)/s vs. 3.36±0.41×10(-3) mm(2)/s, p<0.01). There was a significant difference in ADC between the malignant and benign renal lesions: in patients with angiomyolipoma the ADC value was 2.36±0.32×10(-3) mm(2)/s vs. 2.11±0.25×10(-3) mm(2)/s; p<0.05 and in patients with oncocytoma - 2.75±0.27×10(-3) mm(2)/s vs. 2.11±0.25×10(-3) mm(2)/s; p<0.05. The difference in ADC values in patients with high and low ccRCC grades was observed. CONCLUSIONS: DWI can be used to characterize renal lesions; the ADC of a renal lesion can be potentially used as an additional parameter to help determine the appropriate clinical management.