In Vivo Tumor Growth Rate Measured by US in Preoperative Period and Long Term Disease Outcome in Breast Cancer Patients

Objective

The aim of our study was to evaluate the effect of tumor growth rate, calculated from tumor size measurements by US, on breast cancer patients’ outcome.

Patients and Methods

Breast cancer patients who received at least two serial breast ultrasonographies (US) in our institution during preoperative period and were surgically treated between 2002 and 2010 were reviewed. Tumor growth rate was determined by specific growth rate (SGR) using the two time point tumor sizes by US.

Results

A total of 957 patients were analyzed. The median duration between initial and second US was 28 days (range, 8–140). The median initial tumor size was 1.7cm (range, 0.4–7.0) and median second size was 1.9cm (range, 0.3–7.2). 523(54.6%) cases had increase in size. The median SGR(x10^-2) was 0.59 (range, -11.90~31.49) and mean tumor doubling time was 14.51 days. Tumor growth rate was higher when initial tumor size was smaller. Lymphovascular invasion, axillary lymph node metastasis, and higher histologic grade were significantly associated with higher SGR. SGR was significantly associated with disease-free survival (DFS) in a univariate analysis (p = 0.04), but not in a multivariate Cox analysis (p>0.05). High SGR was significantly associated with worse DFS in a subgroup of initial tumor size >2cm (p = 0.018), but not in those with tumor size <2cm (p>0.05).

Conclusion

Our results showed that tumor growth rate measured by US in a relatively short time interval was associated with other worse prognostic factors and DFS, but it was not an independent prognostic factor in breast cancer patients.     

Photo-induced DNA scission by Cu(ii)-meso-tetrakis(n-N-methylpyridiniumyl)porphyrins (n = 2, 3, 4) and their binding modes to supercoiled DNA

The photo-induced cleavage of pGEM-7zf-NIS super-coiled DNA by Cu(ii)-meso-tetrakis(n-N-methylpyridiniumyl)porphyrins (n = 2, 3, 4 referred to as o-, m- and p-CuTMPyP, respectively) and their binding mode were investigated in this study. m-CuTMPyP was most efficient in cleavage than o- and p-CuTMPyP isomers. Cleavage was suppressed by N(2) bubbling, suggesting that the cleavage occurred by an oxidative cleavage mechanism. Sodium azide, an (1)O(2) quencher, and DMSO, a hydroxyl radical scavenger, inhibited cleavage, indicating that hydroxyl radicals and singlet oxygen were likely reactive species responsible for the cleavage. Reduced linear dichroism spectroscopy showed angles of o-CuTMPyP's electric transition moments, in which the periphery pyridinium ring was prevented from free rotation, of 59° and 61° with respect to the local DNA helix axis. The spectra of m- and p-CuTMPyP complexed with pGEM-7zf-NIS DNA were characterized by large signals in the Soret band, coincident with those of known intercalated porphyrins.     

Monoclonal antibody K312-based depletion of pluripotent cells from differentiated stem cell progeny prevents teratoma formation

Human pluripotent stem cells (PSCs) have been utilized as a promising source in regenerative medicine. However, the risk of teratoma formation that comes with residual undifferentiated PSCs in differentiated cell populations is most concerning in the clinical use of PSC derivatives. Here, we report that a monoclonal antibody (mAb) targeting PSCs could distinguish undifferentiated PSCs, with potential teratoma-forming activity, from differentiated PSC progeny. A panel of hybridomas generated from mouse immunization with H9 human embryonic stem cells (hESCs) was screened for ESC-specific binding using flow cytometry. A novel mAb, K312, was selected considering its high stem cell-binding activity, and this mAb could bind to several human induced pluripotent stem cells and PSC lines. Cell-binding activity of K312 was markedly decreased as hESCs were differentiated into embryoid bodies or by retinoic acid treatment. In addition, a cell population negatively isolated from undifferentiated or differentiated H9 hESCs via K312 targeting showed a significantly reduced expression of pluripotency markers, including Oct4 and Nanog. Furthermore, K312-based depletion of pluripotent cells from differentiated PSC progeny completely prevented teratoma formation. Therefore, our findings suggest that K312 is utilizable in improving stem cell transplantation safety by specifically distinguishing residual undifferentiated PSCs.     

High-throughput single-molecule imaging system using nanofabricated trenches and fluorescent DNA-binding proteins

DNA curtain is a high-throughput system, integrating a lipid bilayer, fluorescence imaging, and microfluidics to probe protein–DNA interactions in real-time and has provided in-depth understanding of DNA metabolism. Especially, the microfluidic platform of a DNA curtain is highly suitable for a biochip. In the DNA curtain, DNA molecules are aligned along chromium nanobarriers, which are fabricated on a slide surface, and visualized using an intercalating dye, YOYO-1. Although the chromium barriers confer precise geometric alignment of DNA, reuse of the slides is limited by wear of the barriers during cleaning. YOYO-1 is rapidly photobleached and causes photocleavage of DNA under continuous laser illumination, restricting DNA observation to a brief time window. To address these challenges, we developed a new nanopatterned slide, upon which carved nanotrenches serve as diffusion barriers. The nanotrenches were robust under harsh cleaning conditions, facilitating the maintenance of surface cleanliness that is essential to slide reuse. We also stained DNA with a fluorescent protein with a DNA-binding motif, fluorescent protein–DNA binding peptide (FP–DBP). FP–DBP was slowly photobleached and did not cause DNA photocleavage. This new DNA curtain system enables a more stable and repeatable investigation of real-time protein–DNA interactions and will serve as a good platform for lab-on-a-chip.     

The bacterial population of a blanket peat

The number of aerobic bacteria in a blanket peat decreased with depth from 26 times 10⁶/g dry peat in the surface layers to 0.5 times 10⁶/g dry peat at 30–40 cm down the profile, thereafter remaining roughly constant. Obligate psychrophiles comprised <2.5% of this population. Anaerobes were most numerous, 9 times 10⁶/g dry peat at 6–10 cm depth, decreasing to 0.5 times 10⁶/g at 20–30 cm. Calculations indicated that these counts, 10³–10⁴-fold lower than the direct counts, substantially underestimated the active microbial population. Gram negative rods, the predominant aerobes in the surface layers, were replaced by unidentified Bacillus strains at 10–20 cm depth but became increasingly more numerous further down the profile. The Gram negative rods were the most numerous organisms/m² but the Bacillus strains, one third of which were present as spores, made the largest contribution to the biomass/m². Gram positive cocci, Arthrobacter and, infrequently, Nocardia were also isolated. Actinomyces -like forms were the predominant obligate anaerobes and were approximately three times more numerous than clostridia and a curved Gram negative rod.     

Design of user-centric semantic rights model for validation of user-generated content

In these days, the creative user really enjoys creating digital items and sharing their works with other people on the Web. Most users, who create digital contents, want to make secured packages of their works and distribute them with the attachment of valid licenses. Current digital rights management (DRM) systems, however, do not provide the functionality that supports the requirement of the creative users who are considered as just consumers by the current available DRM systems. To make the user-centric DRM functionality possible, we found that license management should be more intelligent to enable users make appropriate licenses for the secured distribution of their created works. In this paper, we define the semantic-based rights expression and management model for the user generated content. Each user created content can have one or more licenses with different types, reproduction, distribution, and usage. Based on our semantic license model and big data analytics, we can support a new business model in which users can sell and buy their created digital items in a secure environment.     

Myxomycetes from Thailand

Thirty–four species of mycomycetes are reported, mostly from northern Thailand, of which sixteen are new records for Thailand. Cribraria rufa is reported from tropical latitudes for the first time.     

DNA-free genome editing with preassembled CRISPR/Cas9 ribonucleoproteins in plants

Transgenic Research - Processes of traditional trait development in plants depend on genetic variations derived from spontaneous mutation or artificial random mutagenesis. Limited availability of...