Is there a rationale for aggressive breast cancer liver metastases resections in Polish female patients? Analysis of overall survival following hepatic resection at a single centre in Poland

Introduction Breast cancer (BC) makes up nearly 26% of malignant tumours worldwide and is the leading cause of cancer-related deaths in European women. With approximately 18,000 new cases of BC diagnosed in Polish women annually, breast cancer liver metastasis (BCLM) is respectively an increasing issue. Recent data found in literature indicates improved survival following liver resection with systemic therapy. Objective The aim of study was to evaluate surgical treatment in patients with isolated BCLM. Material and Methods During 2009–2013, a retrospective study was undertaken and 30 cases analysed. From nearly 2,000 liver resections performed, 11 female patients at the mean age of 59.18 years with BCLM were qualified for surgery. Results The median time between primary and secondary treatment was 3.5 years (1–7). One patient (9.1%) presented an extrahepatic lesion – bone metastasis. The left lobe, right lobe and both lobes of the liver were affected, respectively, in 3 (27.3%), 4 (36.4%) and 4 (36.4%) patients. 5 patients (45.5%) presented single hepatic lesion, in contrast to the maximum number of lesions which equalled 6 in the right lobe. Average hospitalisation period was 13.27 days and discharge on the 11.3 postoperative day. One-year survival was 72.7% (8 patients); therefore, three-year survival was 36.4% (4 patients). Conclusions Oncological centres should assess BCLM patients more openly and qualify them for hepatic resection along with adjuvant systemic treatment in order to improve overall survival. This, however, needs to be studied in a multicentre randomized trial

Is there a rationale for aggressive breast cancer liver metastases resections in Polish female patients? Analysis of overall survival following hepatic resection at a single centre in Poland

Introduction Breast cancer (BC) makes up nearly 26% of malignant tumours worldwide and is the leading cause of cancer-related deaths in European women. With approximately 18,000 new cases of BC diagnosed in Polish women annually, breast cancer liver metastasis (BCLM) is respectively an increasing issue. Recent data found in literature indicates improved survival following liver resection with systemic therapy. Objective The aim of study was to evaluate surgical treatment in patients with isolated BCLM. Material and Methods During 2009–2013, a retrospective study was undertaken and 30 cases analysed. From nearly 2,000 liver resections performed, 11 female patients at the mean age of 59.18 years with BCLM were qualified for surgery. Results The median time between primary and secondary treatment was 3.5 years (1–7). One patient (9.1%) presented an extrahepatic lesion – bone metastasis. The left lobe, right lobe and both lobes of the liver were affected, respectively, in 3 (27.3%), 4 (36.4%) and 4 (36.4%) patients. 5 patients (45.5%) presented single hepatic lesion, in contrast to the maximum number of lesions which equalled 6 in the right lobe. Average hospitalisation period was 13.27 days and discharge on the 11.3 postoperative day. One-year survival was 72.7% (8 patients); therefore, three-year survival was 36.4% (4 patients). Conclusions Oncological centres should assess BCLM patients more openly and qualify them for hepatic resection along with adjuvant systemic treatment in order to improve overall survival. This, however, needs to be studied in a multicentre randomized trial

Design, Synthesis, and Evaluation of Novel 3-Carboranyl-1,8-Naphthalimide Derivatives as Potential Anticancer Agents

We synthesized a series of novel 3-carboranyl-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, using click chemistry, reductive amination and amidation reactions and investigated their in vitro effects on cytotoxicity, cell death, cell cycle, and the production of reactive oxygen species in a HepG2 cancer cell line. The analyses showed that modified naphthalic anhydrides and naphthalimides bearing ortho- or meta-carboranes exhibited diversified activity. Naphthalimides were more cytotoxic than naphthalic anhydrides, with the highest IC50 value determined for compound 9 (3.10 µM). These compounds were capable of inducing cell cycle arrest at G0/G1 or G2M phase and promoting apoptosis, autophagy or ferroptosis. The most promising conjugate 35 caused strong apoptosis and induced ROS production, which was proven by the increased level of 2′-deoxy-8-oxoguanosine in DNA. The tested conjugates were found to be weak topoisomerase II inhibitors and classical DNA intercalators. Compounds 33, 34, and 36 fluorescently stained lysosomes in HepG2 cells. Additionally, we performed a similarity-based assessment of the property profile of the conjugates using the principal component analysis. The creation of an inhibitory profile and descriptor-based plane allowed forming a structure–activity landscape. Finally, a ligand-based comparative molecular field analysis was carried out to specify the (un)favorable structural modifications (pharmacophoric pattern) that are potentially important for the quantitative structure–activity relationship modeling of the carborane–naphthalimide conjugates

Design, Synthesis, and Evaluation of Novel 3-Carboranyl-1,8-Naphthalimide Derivatives as Potential Anticancer Agents

We synthesized a series of novel 3-carboranyl-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, using click chemistry, reductive amination and amidation reactions and investigated their in vitro effects on cytotoxicity, cell death, cell cycle, and the production of reactive oxygen species in a HepG2 cancer cell line. The analyses showed that modified naphthalic anhydrides and naphthalimides bearing ortho- or meta-carboranes exhibited diversified activity. Naphthalimides were more cytotoxic than naphthalic anhydrides, with the highest IC50 value determined for compound 9 (3.10 µM). These compounds were capable of inducing cell cycle arrest at G0/G1 or G2M phase and promoting apoptosis, autophagy or ferroptosis. The most promising conjugate 35 caused strong apoptosis and induced ROS production, which was proven by the increased level of 2′-deoxy-8-oxoguanosine in DNA. The tested conjugates were found to be weak topoisomerase II inhibitors and classical DNA intercalators. Compounds 33, 34, and 36 fluorescently stained lysosomes in HepG2 cells. Additionally, we performed a similarity-based assessment of the property profile of the conjugates using the principal component analysis. The creation of an inhibitory profile and descriptor-based plane allowed forming a structure–activity landscape. Finally, a ligand-based comparative molecular field analysis was carried out to specify the (un)favorable structural modifications (pharmacophoric pattern) that are potentially important for the quantitative structure–activity relationship modeling of the carborane–naphthalimide conjugates

Carboranyl-1,8-naphthalimide intercalators induce lysosomal membrane permeabilization and ferroptosis in cancer cell lines

The synthesis of carborane-1,8-naphthalimide conjugates and evaluation of their DNA-binding ability and anticancer activity were performed. A series of 4-carboranyl-3-nitro-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, were synthesised via amidation and reductive amination reactions, and their calf thymus DNA (ct-DNA)-binding properties were investigated using circular dichroism, UV–vis spectroscopy, and thermal denaturation. Results showed that conjugates 34–37 interacted very strongly with ct-DNA (ΔTm = 10.00–13.00 °C), indicating their ability to intercalate with DNA, but did not inhibit the activity of topoisomerase II. The conjugates inhibited the cell growth of the HepG2 cancer cell line in vitro. The same compounds caused the G2M phase arrest. Cell lines treated with these conjugates showed an increase in reactive oxygen species, glutathione, and Fe2+ levels, lipid peroxidation, and mitochondrial membrane potential relative to controls, indicating the involvement of ferroptosis. Furthermore, these conjugates caused lysosomal membrane permeabilization in HepG2 cells but not in MRC-5 cells.</p