Dideriksenvestergaard1623

Focal therapies such as high-intensity focused ultrasound (HiFU) are an emerging therapeutic option for prostate cancer (PCA). Thermal or mechanical effects mediate most therapies. Moreover, locally administered drugs such as bicalutamide or docetaxel are new focal therapeutic options. We assessed the impact of such focal medical treatments on cell viability and heat sensitivity by pre-treating PCA cell lines and then gradually exposing them to heat. The individual heat response of the cell lines tested differed largely. Vertebral-Cancer of the Prostate (VCaP) cells showed an increase in metabolic activity at 40-50 °C. Androgen receptor (AR)-negative PC3 cells showed an increase at 51.3 °C and were overall more resistant to higher temperatures. Pre-treatment of VCaP cells with testosterone (VCaPrev) leads to a more PC3-like kinetic of the heat response. Pre-treatment with finasteride and bicalutamide did not cause changes in heat sensitivity in any cell line. Mitoxantrone treatment, however, shifted heat-induced proliferation loss to lower temperature in VCaP cells. Further analysis via RNAseq identified a possible correlation of heat resistance with H3K27me3-dependent gene regulation, which could be related to an increase in the histone methyltransferase EZH2 and a possible neuroendocrine differentiation. Pre-treatment with mitoxantrone might be a perspective for HiFU treatment. Further studies are needed to evaluate possible combinations with Hsp90 or EZH2 inhibitors.Mites are arthropods and some of them infest dry meat cured products and produce allergic reactions. Some mites, such as Tyrolichus casei, Tyrophagus putrescentiae, or Tyrophagus longior feed on filamentous fungi that grow during the meat curing process. Removal of mite infestation of meat products is extremely difficult and there are no adequate miticidal compounds. The filamentous fungus Eurotium rubrum growing on the surface of ham is able to exert a biocontrol of the population of mites due to the production of miticidal compound(s). We have purified two compounds by silica gel chromatography, gel filtration, semipreparative and analytical HPLC and determined their miticidal activity against T. Fluoxetine casei using a mite feeding assay. Mass spectrometry and NMR analysis showed that these two compounds are prenylated salicilyl aldehydes with a C-7 alkyl chain differing in a double bond in the C-7 alkyl chain. Structures correspond to those of flavoglaucin and aspergin. Pure flavoglaucin has a miticidal activity resulting in more than 90% mite mortality whereas aspergin does not affect the mites. Both compounds were formed simultaneously by E. rubrum C47 cultures in different media suggesting that they are synthesized by the same pathway. Production of both compounds was higher in solid culture media and the products were associated with abundant formation of cleistothecia. In liquid cultures both compounds remained mainly cell-associated and only about 10% of the total compounds was released to the culture broth. This miticidal compound may be used to combat efficiently mite infestation in different habitats. These results, will promote further advances on the utilization of flavoglaucin in food preservation and in human health since this compound has antitumor activity.Kalmegh (Andrographis paniculata (Burm. F.) Nees) is one of the most important medicinal plants and has been widely explored as traditional medicine. To exploit its natural genetic diversity and initiations of molecular breeding to develop novel cultivars or varieties, developments of genomic resources are essential. Four microsatellite-enriched genomic libraries-(CT)14, (GT)12, (AG)15 and (AAC)8-were constructed using the genomic DNA of A. paniculata. Initially, 183 recombinant colonies were screened for the presence of CT, GT, AG, and AAC microsatellite repeats, out of which 47 clones found positive for the desired simple sequence repeats (SSRs). It was found that few colonies had more than one desirable SSR. Thus, a sum of 67 SSRs were designed and synthesized for their validation among 42 A. paniculata accessions. Out of the 67 SSRs used for genotyping, only 41 were found to be polymorphic. The developed set of g-SSR markers showed substantial genetic variability among the selected A. paniculata accessions, with an average polymorphic information content (PIC) value of 0.32. Neighbor-joining tree analysis, population structure analysis, analysis of molecular variance (AMOVA), and principal coordinate analysis (PCoA) illustrated the considerable genetic diversity among them. The novel g-SSR markers developed in the present study could be important genomic resources for future applications in A. paniculata.DNA repair deficiency (DRD) is an important driver of carcinogenesis and an efficient target for anti-tumor therapies to improve patient survival. Thus, detection of DRD in tumors is paramount. Currently, determination of DRD in tumors is dependent on wet-lab assays. Here we describe an efficient machine learning algorithm which can predict DRD from histopathological images. The utility of this algorithm is demonstrated with data obtained from 1445 cancer patients. Our method performs rather well when trained on breast cancer specimens with homologous recombination deficiency (HRD), AUC (area under curve) = 0.80. Results for an independent breast cancer cohort achieved an AUC = 0.70. The utility of our method was further shown by considering the detection of mismatch repair deficiency (MMRD) in gastric cancer, yielding an AUC = 0.81. Our results demonstrate the capacity of our learning-base system as a low-cost tool for DRD detection.Breast cancer (BC) is one of the most important cancers worldwide, and usually, chemotherapy can be used in an integrative approach. Usually, chemotherapy treatment is performed in association with surgery, radiation or hormone therapy, providing an increased outcome to patients. However, tumors can develop resistance to different drugs, progressing for a more aggressive phenotype. In this scenario, the use of nanocarriers could help to defeat tumor cell resistance, providing a new therapeutic perspective for patients. Thus, this systematic review aims to bring the molecular mechanisms involved in BC chemoresistance and extract from the previous literature information regarding the use of nanoparticles as potential treatment for chemoresistant breast cancer.