Expression of Soluble Form of Aurora A as a Predictive Factor for Neoadjuvant Therapy in Breast Cancer Patients: A Single-Center Pilot Study.

PURPOSE: To search for new predictive breast cancer biomarkers. We analyzed the serum concentrations of biomarkers involved in carcinogenesis, which can also be targeted by therapy. METHODS: In a single-center prospective study, the serum levels of Aurora A, thymidine kinase 1, and human epidermal growth factor receptor type 3 (HER3) were determined in 119 women with BC before neoadjuvant treatment using ELISA kits. RESULTS: The following clinical data were analyzed: age; TNM; the expression of ER, PGR, HER2, and Ki67; histological grade (G); and the response to neoadjuvant treatment (NAT) in the residual tumor burden classification (RCB). A complete pathological response (pCR) was achieved after NAT in 41 patients (34%). The highest proportion of the patients with a confirmed pCR was found for triple negative breast cancer (TNBC) (62.5%); non-luminal HER2-positive (52.6%) cancer subtypes (p = 0.0003); and in the G3 group (50%; p = 0.0078). The patients with higher levels of Aurora A were more likely to achieve pCR (p = 0.039). In the multivariate analysis, the serum Aurora A levels ≥ 4.75 ng/mL correlated with a higher rate of pCR (OR: 3.5; 95% CI: 1.2-10.1; p = 0.023). CONCLUSIONS: We showed that in a biologically heterogeneous group of BC patients, the pretreatment serum Aurora A levels were of significant value in predicting the response to NAT.

Immediate breast reconstruction in breast cancer patients with the use of Serasynth and SeragynBR synthetic meshes. Single-oncological center experience, analysis of complications.

<br><b>Introduction:</b> The use of meshes in mastectomies with immediate breast reconstruction (IBR) has become the gold standard.</br> <br><b>Aim:</b> The use of meshes in mastectomies with immediate breast reconstruction (IBR) has become a gold standard. The purpose of the study was to analyze the complications and own experience with the use of Serasynth fully absorbable and SeragynBR partially absorbable synthetic meshes.</br> <br><b>Material and methods:</b> In the period from December 2017 to July 2020, 118 IBR were performed in the Author's Department with the use of SeragynBR and Serasynth meshes in 93 patients operated for breast cancer. 78 Serasynth meshes (Group 1) and 40 SeragynBR meshes (Group 2) were implanted.</br> <br><b>Results:</b> The most common complication was persistent seroma collection, which was reported in 17.9% of cases in Group 1 and 25% in Group 2. Skin inflammation was reported in 7.6% and 17.5%, while infections in 2.5% and 5% of the operated breasts in Group 1 and Group 2. Reoperation was required in 5.1% and 5% of the patients in Group 1 and Group 2. The percentage of complications was lower when Serasynth rather than Seragyn BR meshes were implanted. The frequent incidence of the seroma collection did not contribute in any significant way to serious complications such as removal of mesh/implant or infection. The complications, which developed following the implantation of both mesh types, were similar to those presented in other publications concerning mastectomy with IBR with the use of synthetic meshes. The percentage of implant losses/explanations in the discussed groups was lower than that reported in the literature.</br> <br><b>Conclusion:</b> Despite the complications, both types of meshes can be considered as safe additions to reconstructive breast surgeries.</br> <br><b>Level of Evidence:</b> Level III.</br>.

Neoadjuvant Pertuzumab Plus Trastuzumab in Combination with Docetaxel and Carboplatin in Patients with HER2-Positive Breast Cancer: Real-World Data from the National Institute of Oncology in Poland.

Neoadjuvant systemic therapy has now become the standard in early breast cancer management. Chemotherapy in combination with trastuzumab +/- pertuzumab targeted therapy can improve the rates of pathologic complete response (pCR) in patients with HER2-positive breast cancer. Achieving a pCR is considered a good prognostic factor, in particular, in patients with more aggressive breast cancer subtypes such as TNBC or HER2-positive cancers. Furthermore, most studies demonstrate that chemotherapy in combination with trastuzumab and pertuzumab is well tolerated. The retrospective analysis presented here concentrates on neoadjuvant therapy with the TCbH-P regimen, with a particular emphasis on patients over 60 years of age. We analysed the factors affecting the achievement of pCR and present the adverse effects of the applied therapies, opening discussion about optimizing the therapy of older patients with HER-2 positive breast cancer.

Bounding volumes for proteins: a comparative study.

A chain tree is a data structure for representing changing protein conformations. It enables very fast detection of clashes and free potential energy calculations. The efficiency of chain trees is closely related to the bounding volumes associated with chain tree nodes. A protein subchain associated with a node of a chain tree will clash with another subchain only if their bounding volumes intersect. It is therefore essential that bounding volumes are as tight as possible while intersection tests can be carried out efficiently. We compare the performance of four different types of bounding volumes in connection with the rotation of protein bonds. It is observed that oriented bounding boxes are not as good as could be expected judging by their extensive use in various applications. Both rectangular- and line-swept spheres are shown to have very good tightness of fit but the line-swept, or even simple spheres, are shown to be significantly faster because of quick overlap checks. We also investigate how the performance of the recently introduced adjustable chain trees is affected by different bounding volume types.

Adjustable chain trees for proteins.

A chain tree is a data structure for changing protein conformations. It enables very fast detection of clashes and free energy potential calculations. A modified version of chain trees that adjust themselves to the changing conformations of folding proteins is introduced. This results in much tighter bounding volume hierarchies and therefore fewer intersection checks. Computational results indicate that the efficiency of the adjustable chain trees is significantly improved compared to the traditional chain trees.

Reconstructing protein structure from solvent exposure using tabu search.

BACKGROUND: A new, promising solvent exposure measure, called half-sphere-exposure (HSE), has recently been proposed. Here, we study the reconstruction of a protein's Calpha trace solely from structure-derived HSE information. This problem is of relevance for de novo structure prediction using predicted HSE measure. For comparison, we also consider the well-established contact number (CN) measure. We define energy functions based on the HSE- or CN-vectors and minimize them using two conformational search heuristics: Monte Carlo simulation (MCS) and tabu search (TS). While MCS has been the dominant conformational search heuristic in literature, TS has been applied only a few times. To discretize the conformational space, we use lattice models with various complexity. RESULTS: The proposed TS heuristic with a novel tabu definition generally performs better than MCS for this problem. Our experiments show that, at least for small proteins (up to 35 amino acids), it is possible to reconstruct the protein backbone solely from the HSE or CN information. In general, the HSE measure leads to better models than the CN measure, as judged by the RMSD and the angle correlation with the native structure. The angle correlation, a measure of structural similarity, evaluates whether equivalent residues in two structures have the same general orientation. Our results indicate that the HSE measure is potentially very useful to represent solvent exposure in protein structure prediction, design and simulation.