PTK7 Expression in Triple-negative Breast Cancer

Background: Protein tyrosine kinase-7 (PTK7) plays an important role in cancer. Our aim was to evaluate PTK7 in triple-negative breast cancer (TNBC). Materials and Methods: PTK7 Expression was assessed by immunohistochemistry (IHC) in 133 patients with TNBC. Expression levels were correlated with clinicopathological features and survival, taking chemotherapy into account. Results: Positive PTK7 expression was detected in 28.6% of tumors. In the total population, no significant difference was detected in disease-free survival (DFS) or overall survival (OS) related to PTK7 status. However, in patients treated by chemotherapy, patients with PTK7-negative tumors seemed to have better DFS than those with PTK7-positive tumors, particularly for patients treated with only anthracycline-therapy drugs. In patients receiving other chemotherapy regimens, PTK7 status had no significant impact on DFS or OS. Conclusion: Our results support earlier findings that PTK7 may be associated with resistance to anthracycline-based chemotherapy

Dual-Acting Cholinesterase-Human Cannabinoid Receptor 2 Ligands Show Pronounced Neuroprotection in Vitro and Overadditive and Disease-Modifying Neuroprotective Effects in Vivo

We have designed and synthesized a series of 14 hybrid molecules out of the cholinesterase (ChE) inhibitor tacrine and a benzimidazole-based human cannabinoid receptor subtype 2 (hCB2R) agonist and investigated them in vitro and in vivo. The compounds are potent ChE inhibitors, and for the most promising hybrids, the mechanism of human acetylcholinesterase (hAChE) inhibition as well as their ability to interfere with AChE-induced aggregation of \u3b2-amyloid (A\u3b2), and A\u3b2 self-aggregation was assessed. All hybrids were evaluated for affinity and selectivity for hCB1R and hCB2R. To ensure that the hybrids retained their agonist character, the expression of cAMP-regulated genes was quantified, and potency and efficacy were determined. Additionally, the effects of the hybrids on microglia activation and neuroprotection on HT-22 cells were investigated. The most promising in vitro hybrids showed pronounced neuroprotection in an Alzheimer's mouse model at low dosage (0.1 mg/kg, i.p.), lacking hepatotoxicity even at high dose (3 mg/kg, i.p.)

Neoadjuvant Therapy Is Associated with Improved Chemotherapy Delivery and Overall Survival Compared to Upfront Resection in Pancreatic Cancer without Increasing Perioperative Complications.

The role of neoadjuvant chemoradiotherapy and/or chemotherapy (neoCHT) in patients with pancreatic ductal adenocarcinoma (PDAC) is poorly defined. We hypothesized that patients who underwent neoadjuvant therapy (NAT) would have improved systemic therapy delivery, as well as comparable perioperative complications, compared to patients undergoing upfront resection. This is an IRB-approved retrospective study of potentially resectable PDAC patients treated within an academic quaternary referral center between 2011 and 2018. Data were abstracted from the electronic medical record using an institutional cancer registry and the National Surgical Quality Improvement Program. Three hundred and fourteen patients were eligible for analysis and eighty-one patients received NAT. The median overall survival (OS) was significantly improved in patients who received NAT (28.6 vs. 20.1 months, p = 0.014). Patients receiving neoCHT had an overall increased mean duration of systemic therapy (p < 0.001), and the median OS improved with each month of chemotherapy delivered (HR = 0.81 per month CHT, 95% CI (0.76-0.86), p < 0.001). NAT was not associated with increases in early severe post-operative complications (p = 0.47), late leaks (p = 0.23), or 30-90 day readmissions (p = 0.084). Our results show improved OS in patients who received NAT, driven largely by improved chemotherapy delivery, without an apparent increase in early or late perioperative complications compared to patients undergoing upfront resection