Heteropentanuclear Oxalato-Bridged nd-4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis, Crystal Structures, Aqueous Stability and Antiproliferative Activity

A series of heteropentanuclear oxalate-bridged Ru(NO)-Ln (4d-4f) metal complexes of the general formula (nBu(4)N)(5)[Ln{RuCl3(-ox)(NO)}(4)], where Ln=Y (2), Gd (3), Tb (4), Dy (5) and ox=oxalate anion, were obtained by treatment of (nBu(4)N)(2)[RuCl3(ox)(NO)] (1) with the respective lanthanide salt in 4:1 molar ratio. The compounds were characterized by elemental analysis, IR spectroscopy, electrospray ionization (ESI) mass spectrometry, while 1, 2, and 5 were in addition analyzed by X-ray crystallography, 1 by Ru K-edge XAS and 1 and 2 by (CNMR)-C-13 spectroscopy. X-ray diffraction showed that in 2 and 5 four complex anions [RuCl3(ox)(NO)](2-) are coordinated to Y-III and Dy-III, respectively, with formation of [Ln{RuCl3(-ox)(NO)}(4)](5-) (Ln=Y, Dy). While Y-III is eight-coordinate in 2, Dy-III is nine-coordinate in 5, with an additional coordination of an EtOH molecule. The negative charge is counterbalanced by five nBu(4)N(+) ions present in the crystal structure. The stability of complexes 2 and 5 in aqueous medium was monitored by UV/Vis spectroscopy. The antiproliferative activity of ruthenium-lanthanide complexes 2-5 were assayed in two human cancer cell lines (HeLa and A549) and in a noncancerous cell line (MRC-5) and compared with those obtained for the previously reported Os(NO)-Ln (5d-4f) analogues (nBu(4)N)(5)[Ln{OsCl3(ox)(NO)}(4)] (Ln=Y (6), Gd (7), Tb (8), Dy (9)). Complexes 2-5 were found to be slightly more active than 1 in inhibiting the proliferation of HeLa and A549 cells, and significantly more cytotoxic than 5d-4f metal complexes 6-9 in terms of IC50 values. The highest antiproliferative activity with IC50 values of 20.0 and 22.4M was found for 4 in HeLa and A549 cell lines, respectively. These cytotoxicity results are in accord with the presented ICP-MS data, indicating five- to eightfold greater accumulation of ruthenium versus osmium in human A549 cancer cells

European practice patterns and barriers to smoking cessation after a cancer diagnosis in the setting of curative versus palliative cancer treatment

Background: Smoking cessation after a cancer diagnosis is associated with improved overall survival. Few studies have reported oncologists' cessation practice patterns, but differences between the curative and palliative settings have not been described. We aimed to study the oncologist's perceptions on patients' tobacco use, current practices and barriers to providing smoking cessation support, while distinguishing between treatment with curative (C) and palliative (P) intent.Methods: In 2019, an online 34-item survey was sent to approximately 6235 oncologists from 16 European countries. Responses were descriptively reported and compared by treatment setting.Results: Responses from 544 oncologists were included. Oncologists appeared to favour addressing tobacco in the curative setting more than in the palliative setting. Oncologists believe that continued smoking impacts treatment outcomes (C: 94%, P: 74%) and that cessation support should be standard cancer care (C: 95%, P: 63%). Most routinely assess tobacco use (C: 93%, P: 78%) and advise patients to stop using tobacco (C: 88%, P: 54%), but only 24% (P) -39% (C) routinely discuss medication options, and only 18% (P)-31% (C) provide cessation support. Hesitation to remove a pleasurable habit (C: 13%, P: 43%) and disbelieve on smoking affecting outcomes (C: 3%, P: 14%) were disparate barriers between the curative and palliative settings (p Conclusion: Oncologists appear to favour addressing tobacco use more in the curative setting; however, they discuss medication options and/or provide cessation support in a minority of cases. All patients who report current smoking should have access to evidence-based smoking cessation support, also patients treated with palliative intent given their increasing survival. </div

Inhibition of growth of HT-29 human colon cancer xenografts in nude mice by treatment with bombesin/gastrin releasing peptide antagonist (RC-3095).

Abstract Nude mice bearing xenografts of HT-29 human colon cancer cell line were treated for 4 weeks with a [d-Trp6] agonist of luteinizing hormone releasing hormone (LH-RH), somatostatin analogue (RC-160), and bombesin/gastrin releasing peptide antagonist (RC-3095). Some inhibitory effect of [d-Trp6] LH-RH microcapsules releasing 25 µg/day on tumor growth was observed that could be due to sex steroid deprivation, but the inhibition was not statistically significant. Microcapsules of RC-160, releasing 50 µg/day, significantly reduced tumor volume after 21 and 24 days of treatment, but at the end of the experiment the inhibition in tumor volume and weight was not significant. Bombesin/gastrin releasing peptide antagonist RC-3095, at a dose of 20 µg/day administered by daily s.c. injections or by continuous infusion using Alzet osmotic minipumps, had the greatest inhibitory effect on tumor growth. Tumor volume, percentage change in tumor volume, and tumor weights were significantly decreased in both groups treated with RC-3095. This is the first report on inhibition of human colon cancer growth in vivo by bombesin antagonists

Inhibition of human epithelial ovarian cancer cell growth in vitro by agonistic and antagonistic analogues of luteinizing hormone-releasing hormone (cell proliferation/(3H)thymidine incorporation/luteinizing hormone-releasing hormone receptor/gynecologic cancer)

In this study, we investigated the effects of luteinizing hormone-releasing hormone (LH-RH) agonist (D-Trp6)LH-RH, LH-RH antagonist (Ac-D-Nal(2)1,D- Phe(pCI)2,D-Pal(3)3,D-Cit6,D-Ala'0)LH-RH (SB-75), and estra- diol on the growth of human epithelial ovarian cancer cell line OV-1063. Cells were cultured under estrogen-deprived condi- tions. Estradiol inhibited cell proliferation, as measured by cell number at 10-9-10-7 M and p3H)thymidine incorporation into DNA at 10-'3-10-9 M. Both LH-RH analogs inhibited cell growth dose dependently in the range 10-8_10-5 M, but SB-75 induced a greater growth inhibition than (D-Trp6)LH-RH. In OV-1063 cells, 1251-labeled (D-Trp6)LH-RH was bound to one class of specific, saturable binding sites with high affinity (Kd - 1.4 ? 0.3 nM) and low capacity (4000 binding sites per cell). I-51_labeled (D-Trp6)LH-RH could be displaced by unlabeled (D-Trp6)LH-RH and SB-75, suggesting that both analogs are bound to the same receptor on OV-1063 cells. Ligand binding was dependent on time and temperature. Receptor internal- ization assay showed that the ligand-receptor complex was internalized at 37?C, which indicates the presence of biologi- cally active LH-RH receptors on OV-1063 cells. These results suggest that estradiol and LH-RH analogs can suppress the growth of OV-1063 human epithelial ovarian cancer cells by a direct action and that the inhibitory effect of LH-RH analogs is mediated through the high-affinity LH-RH receptors