Effects of Low Carbohydrate High Protein (LCHP) diet on atherosclerotic plaque phenotype in ApoE/LDLR−/−ApoE/LDLR^{-/-} mice : FT-IR and Raman imaging

Low Carbohydrate High Protein (LCHP) diet displays pro-atherogenic effects, however, the exact mechanisms involved are still unclear. Here, with the use of vibrational imaging, such as Fourier transform infrared (FT-IR) and Raman (RS) spectroscopies, we characterize biochemical content of plaques in Brachiocephalic Arteries (BCA) from ApoE/LDLR−/− mice fed LCHP diet as compared to control, recomended by American Institute of Nutrition, AIN diet. FT-IR images were taken from 6–10 sections of BCA from each mice and were complemented with RS measurements with higher spatial resolution of chosen areas of plaque sections. In aortic plaques from LCHP fed ApoE/LDLR−/− mice, the content of cholesterol and cholesterol esters was increased, while that of proteins was decreased as evidenced by global FT-IR analysis. High resolution imaging by RS identified necrotic core/foam cells, lipids (including cholesterol crystals), calcium mineralization and fibrous cap. The decreased relative thickness of the outer fibrous cap and the presence of buried caps were prominent features of the plaques in ApoE/LDLR−/− mice fed LCHP diet. In conclusion, FT-IR and Raman-based imaging provided a complementary insight into the biochemical composition of the plaque suggesting that LCHP diet increased plaque cholesterol and cholesterol esters contents of atherosclerotic plaque, supporting the cholesterol-driven pathogenesis of LCHP–induced atherogenesis

Non-steroidal CYP17A1 Inhibitors: Discovery and Assessment.

CYP17A1 is an enzyme that plays a major role in steroidogenesis and is critically involved in the biosynthesis of steroid hormones. Therefore, it remains an attractive target in several serious hormone-dependent cancer diseases, such as prostate cancer and breast cancer. The medicinal chemistry community has been committed to the discovery and development of CYP17A1 inhibitors for many years, particularly for the treatment of castration-resistant prostate cancer. The current Perspective reflects upon the discovery and evaluation of non-steroidal CYP17A1 inhibitors from a medicinal chemistry angle. Emphasis is placed on the structural aspects of the target, key learnings from the presented chemotypes, and design guidelines for future inhibitors

Discovery of Novel Non-Steroidal Cytochrome P450 17A1 Inhibitors as Potential Prostate Cancer Agents

The current study presents the design, synthesis, and evaluation of novel cytochrome P450 17A1 (CYP17A1) ligands. CYP17A1 is a key enzyme in the steroidogenic pathway that produces androgens among other steroids, and it is implicated in prostate cancer. The obtained compounds are potent enzyme inhibitors (sub µM) with antiproliferative activity in prostate cancer cell lines. The binding mode of these compounds is also discussed

Synthesis and Structure-Activity Relationships of Novel Non-Steroidal CYP17A1 Inhibitors as Potential Prostate Cancer Agents.

Twenty new compounds, targeting CYP17A1, were synthesized, based on our previous work on a benzimidazole scaffold, and their biological activity evaluated. Inhibition of CYP17A1 is an important modality in the treatment of prostate cancer, which remains the most abundant cancer type in men. The biological assessment included CYP17A1 hydroxylase and lyase inhibition, CYP3A4 and P450 oxidoreductase (POR) inhibition, as well as antiproliferative activity in PC3 prostate cancer cells. The most potent compounds were selected for further analyses including in silico modeling. This combined effort resulted in a compound (comp 2, IC50 1.2 µM, in CYP17A1) with a potency comparable to abiraterone and selectivity towards the other targets tested. In addition, the data provided an understanding of the structure-activity relationship of this novel non-steroidal compound class

Origin of ferromagnetic response in diluted magnetic semiconductors and oxides

This paper reviews the present understanding of the origin of ferromagnetic response of diluted magnetic semiconductors and diluted magnetic oxides as well as in some nominally magnetically undoped materials. It is argued that these systems can be grouped into four classes. To the first belong composite materials in which precipitations of a known ferromagnetic, ferrimagnetic or antiferromagnetic compound account for magnetic characteristics at high temperatures. The second class forms alloys showing chemical nano-scale phase separation into the regions with small and large concentrations of the magnetic constituent. To the third class belong (Ga,Mn)As, heavily doped p-(Zn,Mn)Te, and related semiconductors. In these solid solutions the theory built on p-d Zener's model of hole-mediated ferromagnetism and on either the Kohn-Luttinger kp theory or the multi-orbital tight-binding approach describes qualitatively, and often quantitatively many relevant properties. Finally, in a number of carrier-doped DMS and DMO a competition between long-range ferromagnetic and short-range antiferromagnetic interactions and/or the proximity of the localisation boundary lead to an electronic nano-scale phase separation.Comment: review, 19 pages, 4 figure

Surgical treatment of rectal cancer in Poland — a report from a prospective, multi-centre observational study PSSO_01 conducted under the auspices of the Polish Society of Surgical Oncology

Introduction. Since 2016, as part of the PSSO_01 multi-centre research project conducted under the auspices of the Polish Society of Surgical Oncology, clinical data on rectal cancer treatment have been collected. The objective of the study was to illustrate the state of early results of surgical treatment. Material and methods. The research project is multi-centre in nature. Data shall be collected electronically. The study protocol does not impose or suggest any course of procedure. It only systematizes the way data are collected for scientific purposes. The analysis of early results of surgical treatment was compared with the results of population studies from other European countries (Netherlands, Belgium). Results. By the end of June 2018, 736 patients were registered in the study. In 399 (54.2%) an anterior resection was performed. More than half of patients undergoing subsequent surgical treatment (54.2%) receive neoadjuvant treatment, with the percentage of patients undergoing radiotherapy or radiochemical treatment for lower rectal cancer being about 70%. Most patients (96%) are operated in elective procedure. The percentage of laparoscopic surgeries is low (8.6%). Postoperative complications are observed in 21.1% of patients. Severe complications (grades III–V according to Clavien-Dindo classification) occur in 7.6% of patients undergoing surgery. Postoperative mortality is 1.1%. Discussion. Although the project does not have the character of a registry and does not allow for drawing wider conclusions concerning the compliance with the standards of qualification for neoadjuvant treatment, the important information is that more than half of rectal cancer patients receive preoperative treatment, and the percentage of severe postoperative complications does not exceed 10%. Conclusions. The results of the PSSO_01 project are representative and reflect the actual situation concerning surgical treatment of rectal cancer patients in Poland

The surgical treatment of rectal cancer in Poland. The findings of a multi-center observational study by the Polish Society of Surgical Oncology (PSSO-01)

Introduction. PSSO-01, a Polish prospective multi-center project on rectal cancer, started in 2016 with participation on a voluntary basis. This study evaluates the early outcome of the surgical treatment of rectal cancer in Poland according to hospital volume. Material and methods. The dataset derives from 17 clinical centers registered in the PSSO-01 study. From 2016 to 2020, the data of 1,607 patients were collected. Taking into account the number of patients enrolled in the study, the centers were divided into three categories: high volume, medium volume, and low volume. Nominal variables were compared between different categories of centers using the chi-square test. The STROBE guidelines were used to guarantee the reporting of this observational study. Results. More patients with metastatic disease were operated on in the low volume centers (p = 0.020). Neoadjuvant treatment was used in 35%, 52%, and 66% of patients operated on in low, medium, and high volume centers respectively (p < 0.001). Laparoscopic resection in medium volume centers was performed more often than in other centers (p < 0.001). The total rate of postoperative complications related to high, medium, and low centers was 22%, 26%, 18% (p = 0.044). One year following surgery, a stoma was present in 63% of patients. A defunctioning stoma following anterior resection was reversed in only 55% of patients. Anastomotic leakage was the main reason for a non-reversal diverting stoma. Conclusions. The representation of low volume centers in the PSSO-01 study was understated. However, the outcomes may show the actual situation of surgical treatment of rectal cancer in high and medium volume centers in Poland

Leczenie chirurgiczne raka odbytnicy w Polsce — raport z prospektywnego, wieloośrodkowego badania obserwacyjnego PSSO_01 prowadzonego pod auspicjami Polskiego Towarzystwa Chirurgii Onkologicznej

Wstęp. Od 2016 roku w ramach wieloośrodkowego projektu badawczego PSSO_01 prowadzonego pod auspicjami Polskiego Towarzystwa Chirurgii Onkologicznej, gromadzone są dane kliniczne dotyczące leczenia raka odbytnicy. Celem pracy było zobrazowanie stanu dotyczącego wczesnych wyników leczenia chirurgicznego. Materiał i metody. Projekt badawczy ma charakter wieloośrodkowy. Dane gromadzone są elektronicznie. Protokół badania nie narzuca ani nie sugeruje żadnego sposobu postępowania, systematyzuje jedynie sposób zbierania danych w celach naukowych. Analiza dotycząca wczesnych wyników leczenia chirurgicznego została porównana z rezultatami populacyjnych badań z innych krajów europejskich (Holandia, Belgia). Wyniki. Do końca czerwca 2018 roku w badaniu zarejestrowano 736 chorych. U 399 (54,2%) wykonano resekcję przednią. Leczenie neoadiuwantowe otrzymała ponad połowa chorych, poddanych następnie leczeniu operacyjne­mu (54,2%), przy czym odsetek pacjentów poddanych radio- bądź radiochemioterapii z powodu raka dolnej części odbytnicy wyniósł około 70%. Większość chorych (96%) operowana była w trybie planowym. Odsetek operacji wykonanych techniką laparoskopową jest niski (8,6%). Powikłania pooperacyjne zaobserwowano u 21,1% chorych. Ciężkie powikłania (III–V st. wg klasyfikacji Claviena-Dindo) sięgały 7,6% operowanych chorych. Śmiertelność po­operacyjna wyniosła 1,1%. Dyskusja. Chociaż projekt nie ma charakteru rejestru i nie pozwala na wyciągniecie szerszych wniosków dotyczących przestrzegania standardów kwalifikacji do leczenia neoadiuwantowego, istotną informacją jest to, że ponad połowa chorych na raka odbytnicy otrzymuje leczenie przedoperacyjne, a odsetek ciężkich powikłań pooperacyjnych nie przekracza 10%. Wnioski. Wyniki projektu PSSO_01 są reprezentatywne i odzwierciedlają faktyczną sytuację dotyczącą leczenia chirurgicznego chorych na raka odbytnicy w Polsce