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.

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.

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.

SummaryBackgroundDiffusion-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/MethodsThe 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.ResultsThe mean ADC value of ccRCC was significantly lower than that of normal renal parenchyma (2.11±0.25×10−3 mm2/s vs. 3.36±0.41×10−3 mm2/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 mm2/s vs. 2.11±0.25×10−3 mm2/s; p<0.05 and in patients with oncocytoma – 2.75±0.27×10−3 mm2/s vs. 2.11±0.25×10−3 mm2/s; p<0.05. The difference in ADC values in patients with high and low ccRCC grades was observed.ConclusionsDWI 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.

HRT with low-dosed L-thyroxine may improve left ventricular diastolic function in patients with SH.