2 research outputs found
Highly Effective and Hydrolytically Stable Vanadium(V) Amino Phenolato Antitumor Agents
VanadiumÂ(V) oxo complexes
with no labile ligands, including six
octahedral complexes with pentadentate diaminotrisÂ(phenolato) ligands
and one pentacoordinate complex with a tetradentate aminotrisÂ(phenolato)
ligand, were synthesized in high yields. All octahedral complexes
demonstrated high hydrolytic stability with no signs of decomposition
after days in the presence of water, whereas the pentacoordinate complex
decomposed within minutes to release the free ligand, demonstrating
the marked impact of coordination number and geometry on the complex
electrophilicity. All complexes showed marked cytotoxicity toward
human colon HT-29 and ovarian OVCAR-3 cells. In particular, the octahedral
complexes exhibited especially high activity, higher than that of
cisplatin by up to 200-fold. Selected complexes demonstrated similarly
high activity also toward the A2780 and the A2780cis cisplatin-resistant
line. High cytotoxicity was also recorded after prolonged incubation
in a DMSO solution at 4 and 37 °C temperatures and in biological
medium. <i>In vivo</i> studies pointed to high efficacy
in reducing tumor size, where no clinical signs of toxicity were detected
in the treated mice. These results overall indicate high potential
of the tested compounds as antitumor agents
Table_1_Association of Mouse Mammary Tumor Virus With Human Breast Cancer: Histology, Immunohistochemistry and Polymerase Chain Reaction Analyses.docx
Purpose<p>The purpose of this study is to determine whether mouse mammary tumor virus (MMTV)-associated human breast cancer has the same or similar histology to MMTV-associated mouse mammary tumors. Such associations may indicate a role for MMTV in human breast cancer.</p>Methods<p>Immunohistochemical techniques (using antibodies directed against the signal peptide p14 of the envelope precursor protein of MMTV) and polymerase chain reaction (PCR) analyses were used to identify MMTV proteins and MMTV-like envelope gene sequences in a series of breast cancers from Australian women. The histological characteristics of these human breast cancer specimens were compared with MMTV positive mouse mammary tumors. The same methods were used to study benign breast tissues which 1–11 years later developed into breast cancer.</p>Results<p>MMTV p14 proteins were identified in 27 (54%) of 50 human breast cancers. MMTV env gene sequences were identified by PCR in 12 (27%) of 45 human breast cancers. There was a significant correlation between the presence of MMTV (identified by p14 immunohistochemistry) in human breast cancers and histological characteristics similar to MMTV positive mouse mammary tumors (p = 0.001). There was a non-significant correlation between the presence of MMTV env gene sequences (identified by PCR) in human breast cancers and histological characteristics similar to MMTV positive mouse mammary tumors (p = 0.290). MMTV p14 proteins were identified in 7 (54%) of 13 benign breast specimens that later developed into human breast cancers. MMTV by PCR was identified in two benign specimens one of whom later developed MMTV positive breast cancer.</p>Discussion<p>These observations offer evidence that MMTV may be associated with characteristic human breast cancer histology. p14-based immunohistochemistry appears to be a more reliable technique than PCR for the identification of MMTV in human breast cancer. Identification of MMTV-associated p14 proteins in benign breast tissues confirms prior PCR-based studies that MMTV infection occurs before the development of MMTV positive breast cancer.</p>Conclusion<p>Many MMTV positive human breast cancers have similar histology to MMTV positive mouse mammary tumors. MMTV infection identified in benign breast tissues precedes development of MMTV positive human breast cancer. When considered in the context of prior studies, these observations indicate a likely role for MMTV in human breast cancer.</p