Otorhinolaryngological Toxicities of New Drugs in Oncology

<p><strong>Article full text</strong></p> <p><br> The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s12325-017-0512-0"><b>here</b>.</a><br> <br> <strong>Provide enhanced digital features for this article</strong><br> If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact <u>[email protected]</u>.<br> <br> The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.<br> <br> Other enhanced features include, but are not limited to:<br> • Slide decks<br> • Videos and animations<br> • Audio abstracts<br> • Audio slides<u></u></p

Antitumor Activity of 2,9-Di-<i>Sec</i>-Butyl-1,10-Phenanthroline

<div><p>The anti-tumor effect of a chelating phen-based ligand 2,9-di-<i>sec</i>-butyl-1,10-phenanthroline (dsBPT) and its combination with cisplatin were examined in both lung and head and neck cancer cell lines and xenograft animal models in this study. The effects of this agent on cell cycle and apoptosis were investigated. Protein markers relevant to these mechanisms were also assessed. We found that the inhibitory effect of dsBPT on lung and head and neck cancer cell growth (IC₅₀ ranged between 0.1–0.2 μM) was 10 times greater than that on normal epithelial cells. dsBPT alone induced autophagy, G1 cell cycle arrest, and apoptosis. Our <i>in vivo</i> studies indicated that dsBPT inhibited tumor growth in a dose-dependent manner in a head and neck cancer xenograft mouse model. The combination of dsBPT with cisplatin synergistically inhibited cancer cell growth with a combination index of 0.3. Moreover, the combination significantly reduced tumor volume as compared with the untreated control (p = 0.0017) in a head and neck cancer xenograft model. No organ related toxicities were observed in treated animals. Our data suggest that dsBPT is a novel and potent antitumor drug that warrants further preclinical and clinical development either as a single agent or in combination with known chemotherapy drugs such as cisplatin.</p></div

Liver and Kidney Function of Mice Treated with dsBPT.

<p>Liver and Kidney Function of Mice Treated with dsBPT.</p

dsBPT inhibits cancer cell growth more potently than cisplatin <i>in vitro</i>.

<p>(A) Chemical structure of dsBPT. (B) SRB cytotoxicity assays were performed to detect survival of lung tumor cell lines H1703 and A549 and two HNSCC cell lines Tu212 and Tu686 treated with increasing doses of dsBPT. The immortalized bronchial epithelial cell line BEAS-2B was included as a control. (C) The commonly used chemotherapeutic drug cisplatin was also tested in parallel as a reference. (D) IC₅₀ of dsBPT and cisplatin.</p

dsBPT alters cellular regulation pathways.

<p>Increased levels of caspase 3, and caspase 8 were seen in A549 and Tu212 tumor cell lines when treated with dsBPT for 24, 48 and 72 hours. DR5 expression levels were increased in both cancer cell lines upon treatment with dsBPT. p53 was induced in A549 cells, but not in Tu212 cells which have mutated p53. Expression levels of cyclin-dependent kinase inhibitors p21 and p27 were induced in both cancer cell lines by dsBPT compared to untreated control. Quantification is presented as percentage change of the expression level normalized to the control. Data represent 3 repeated experiments.</p

Toxicity study of dsBPT in mice.

<p>No organ toxicity was seen following treatment with different doses of dsBPT alone or in combination with 2mg/kg cisplatin in mice. Representative IHC images show 1 out of 6 mice.</p

Combination of dsBPT and cisplatin has a synergetic antitumor effect <i>in vitro</i> and <i>in vivo</i>.

<p>(A and B) Combination of dsBPT with cisplatin synergistically enhanced the inhibitory activity of both drugs <i>in vitro</i> in A549 cells (A) and in Tu212 cells (B). (C) Combination of dsBPT with cisplatin also more potently inhibited tumor growth in the Tu212 xenograft mouse model.</p

dsBPT alters cell cycle and induces apoptosis in cancer cells.

<p>Alteration of cell cycle was observed in A549 cells after 1 μM dsBPT treatment at 24 hours (A), 48 hours (C) and in Tu212 cells at 24 hours (B), 48 hours (D). dsBPT induced cell apoptosis at concentrations of 4 μM in a time-dependent manner in both A549 and Tu212 cell lines (E and F).</p

dsBPT inhibits Tu212 xenograft tumor growth in nude mice.

<p>(A) dsBPT significantly inhibited Tu212 xenograft tumor growth at doses of 5mg/kg and 10 mg/kg as compared with the control (both doses p<0.04). (B and C) IHC and TUNEL analyses of the xenograft tissues showed that dsBPT reduced levels of the proliferation marker Ki67 and induced apoptotic marker TUNEL signal.</p

The Impact of Histologic Phenotype in the Treatment of Sinonasal Cancer

<p><strong>Article full text</strong></p> <p><br> The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s12325-017-0605-9"><b>here</b>.</a><br> <br> <strong>Provide enhanced digital features for this article</strong><br> If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact <u>[email protected]</u>.<br> <br> The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.<br> <br> Other enhanced features include, but are not limited to:<br> • Slide decks<br> • Videos and animations<br> • Audio abstracts<br> • Audio slides<u></u></p