Search

This study introduces a novel multitargeting strategy that combines carbonic anhydrase (CA) activators and cholinesterase (ChE) inhibitors to enhance cognitive functions. A series of tacrine-based derivatives with amine/amino acid moieties were synthesized and evaluated for their dual activity on brain CA isoforms and ChEs (AChE and BChE). Several derivatives, notably compounds 26, 30, 34, and 40, demonstrated potent CA activation, particularly of hCA II and VII, and strong ChE inhibition with subnanomolar to low nanomolar IC50values. In vivostudies using a mouse model of social recognition memory showed that these derivatives significantly improved memory consolidation at doses 10–100 times lower than the reference compounds (either alone or in combination). Molecular modeling and ADMET predictions elucidated the compound binding modes and confirmed favorable pharmacokinetic and safety profiles. The findings suggest that dual modulation of CA and ChE activities is a promising strategy for treating cognitive deficits associated with neurodegenerative and psychiatric disorders.

Afatinib, a second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is effective as first-line treatment in patients with EGFR-mutated non-small cell lung cancer (NSCLC). We report 2 cases of EGFR-mutated locally advanced NSCLC treated in neoadjuvant setting with EGFR tyrosine kinase inhibitor at University of Florence/Careggi Hospital. In both cases, afatinib was used for up to 3 months, until 1 week before surgery. Both patients achieved significant reduction (downstaging) of the pulmonary mass and lymphadenopathies and after surgery, it was decided for both cases to restore afatinib treatment up to a further 4 months. Both patients experienced local and distant disease relapses after 9 and 10 months, respectively, and then we restored the afatinib treatment.

Somatostatine analogs (SSAs) are currently indicated in the treatment of acromegaly and neuroendocrine tumors (NETs). Actually, pregnancy in patients with acromegaly and NETs does not represent an exceptional event because reproductive behavior has changed in the last decades and patients with NETs show more frequently long-term survival. The safety profile of SSAs during pregnancy is still controversial. Concerning acromegaly, based on case reports and series, SSAs administration during pregnancy seems to be relatively well tolerated. Concerning patients with NETs, up to date only one patient with NET receiving SSA during pregnancy has been reported in literature. We report two cases of gastroenteropancreatic-NET patients receiving SSA lanreotide for the entire course of their pregnancy, with favorable outcomes for both mothers and babies. Our experience supports the possibility to continue safely SSA lanreotide during pregnancy in patients with NET.

Osteonecrosis of the jaw (ONJ) is a rare treatment related side effect that was firstly described in 2002 through a case report in metastatic bone cancer patient treated with bisphosphonates (BPs) therapy. ONJ is defined as an eight weeks or longer clinical finding of exposed bone in the oral cavity without response to appropriate therapy. The diagnosis is mainly clinical but often requires a radiological confirmation with an orthopantomography. So it must be made by a dental specialist with sufficient experience on ONJ and requires a detailed anamnestic exploration of comorbidities and treatments history. In particular, ONJ affects a wide number of oncologic patients treated with BPs for bone metastatic cancers and, more recently, with anti-angiogenic drugs. The aim of this this paper is to describe diagnosis and classification of this rare but serious side effect and its pathophysiology. In particular, we provide a detailed description of clinical evidences upon the relationship between anti-angiogenic drugs and ONJ. Considering the evolving of cancer epidemiology with a greater number of cancer surviving patients, this side effect always deserves more attention. We conclude that ONJ must be always carefully investigated and prevented with a multidisciplinary approach involving oncologist, radiation oncologist and skilled dental practitioner when a cancer patient must begin a BP or an antiangiogenic treatment.

Background:We aimed to explore the use of platinum plus bevacizumab in a real world NSCLC population.Patients and methods:We retrospectively collected data from patients affected by NS-NSCLC treated with platinum plus bevacizumab across Tuscany.Results:We evaluated 62 (median age: 63.5 [30–77] years) pts. All but one presented with adenocarcinoma and the majority had ECOG PS of 0/1. 17.7% presented with central lesion, 11.3% with brain metastasis, 38.7% with hypertension and 4.8% with mild haemoptysis. We observed a median time to progression (TTP) of 6.5 [2–37] and a median overall survival (OS) of 10.5 [2–39] months. Overall response rate (ORR) was 59.6% with a disease control rate (DCR) of 80.6%. Safety profile was acceptable. We observed five cardiovascular events and two major bleedings with no toxic deaths.Conclusion:Safety and efficacy real world data are consistent with those from clinical trials even in a less selected population.

Non-small-cell lung cancer is a term that encompasses a number of subtypes of lung cancer. In recent years, several intracellular pathways have been studied in order to discover a potential target for novel anticancer therapies such as anaplastic lymphoma kinase (ALK) and reactive oxygen species 1 (ROS1). Increased interest in oncologic treatment research has resulted from the observation that ALK- and ROS1-associated tyrosine kinases show molecular analogies in some of their domains. This discovery led to the hypothesis that target therapy against ALK translocation could have efficacy also in ROS1-positive tumors. Crizotinib is an oral tyrosine kinase inhibitor that binds the ALK tyrosine kinase domain, blocking its function. We report the case of a woman with heavily pretreated metastatic lung adenocarcinoma harboring ROS1 positivity who experienced a prolonged and dramatic clinical benefit from crizotinib therapy.

The purification of acidic synthetic peptides was achieved by using a linear gradient of ammonium acetate and methanol with reverse phase liquid chromatography.