Clinical and treatment features associated with improved 5-year survival rate in ALK-positive lung cancer treated with ALK-TKIs

n/

Correlation among different KRAS alterations, genetic co-mutations and PD-L1 expression in patients treated with immunotherapy in metastatic NSCLC

n/

Neuroprotection induced by delta-9-THC in a model of transient global cerebral ischemia

There is increasing experimental evidence of a neuroprotective effect of cannabinoids in experimental models including ischemia (Nagayama et al. 1999; Braida et al. 2000, 2003; van der Stelt et al., 2001a, 2001b; Veldhuis et al., 2003; Marsicano et al., 2003) and head trauma (Panikashvli et al., 2001). D9-THC, the major and psychoactive constituent of marijuana, is known to exert protective actions either in vitro, in rat cortical neurons (Hampson et al., 1998), or in vivo, in a model of rat forebrain ischemia (Louw et al., 2000) and neurotoxicity (van der Stelt et al., 2001; El-Remessy et al., 2003). However the role of CB1 cannabinoid receptor on D9-THC -induced neuroprotection is still controversial since partial (El-Remessy et al., 2003) or any (Hampson et al., 1998; van der Stelt et al., 2001) antagonism was found. The aim of the present work was to further investigate in vivo the effect of post-ischemic treatment with D9-THC on transient global cerebral ischemia in gerbils using a wide range of doses (0.05 \u2013 2 mg/kg) and to evaluate the role of CB1 cannabinoid receptor using the selective CB1 cannabinoid antagonist SR 141716. Gerbils, previously submitted to bilateral carotid occlusion for 10 min, were treated with D9-THC 5 min after recirculation and monitored for 7 days. Electroencephalographic (EEG) mean total spectral power (on Day 7), spontaneous motor activity (on Day 1) and cognitive function (on Day 3), were evaluated as parameters known to be hardly influenced by cerebral ischemia. D9-THC protected against ischemia-induced EEG flattening and hyperlocomotion, evaluated in an activity cage, with a dose-dependent bell-shaped curve, the maximal active dose being 1 mg/kg. Ischemia-induced memory impairment, evaluated through the passive avoidance test was blocked by D9-THC from 0.5 to 2 mg/kg. Preliminary results indicate that the neuroprotection by D9-THC is in part mediated by the cannabinoid receptor CB1

Effect of the anandamide transporter inhibitor,AM404, on anxiety response in rats

There are many and contradictory reports on the interaction between cannabinoids and anxiety. Both cannabinoid agonists and antagonists have been shown to have anxiolytic- and anxiogenic-like behavioural reactions in rodents depending on the dose and the context (Onaivi et al. 1990; Crawley et al. 1993; Onaivi et al. 1995; Rodriguez de Fonseca, 1996; Navarro et al., 1997; Akinshola et al. 1999; Haller et al., 2002; Berrendero and Maldonado 2002;Valjent et al.. 2002; Haller et al. 2004). The aim of the present work was to further elucidate the role of endocannabinoid system in anxiety response. For this purpose, the anandamide transport inhibitor, AM 404 (2.5-10 mg/kg), and D9\u2013THC (0.015-1.5 mg/kg), previously evaluated in our laboratory for its reinforcing properties in a Conditioned Place Preference test (Braida et al., 2005), were studied in a plus-maze apparatus according to Pellow et al. (1985) The test length was 5 min and the total time spent in each arm and the number of arm entries were scored by trained observers in male Sprague-Dawley rats, 30 min after treatment. The role of the CB1 cannabinoid and opioid receptor was investigated pre-treating rats with SR 141716 (0.25-1 mg/kg) and naloxone (0.5-2 mg/kg), 10 min before D9\u2013THC or AM 404. Both D9\u2013THC (0.75 mg/kg) and AM 404 (10 mg/kg) significantly elevated the percentage of open arm entries and the time spent in the open arms, showing an anxiolytic activity. This effect was reversed by pre-treatment with SR 141716. An interaction with opioid system was also found. These findings further support a key role of endocannabinoid system in the regulation of emotional states

Complex Differential Diagnosis between Primary Breast Cancer and Breast Metastasis from EGFR-Mutated Lung Adenocarcinoma: Case Report and Literature Review

We present a case of a woman with epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma who received gefitinib for 2 years and obtained a partial response. The patient then developed liver metastasis and a breast lesion, displaying high estrogen receptor (ER) expression and harboring the same EGFR mutation. From the radiological studies, it was not possible to make a differential diagnosis between primary breast cancer and breast metastasis from lung cancer. After the removal of the breast nodule, thanks to the clinical history, radiology, and above all, molecular and immunohistochemical investigations, a diagnosis of breast metastasis from lung adenocarcinoma was made. This case emphasizes the importance of a comprehensive clinical, pathological, and molecular analysis in the differential diagnosis between primary breast cancer and metastases from extramammary tumor to guide adequate treatment decision making

Efficacy of Anti-PD1/PD-L1 Therapy (IO) in KRAS mutant non-small cell lung cancer patients. a retrospective analysis

BACKGROUND/AIM: The role of anti-PD1/PD-L1 therapy (IO) in NSCLC harboring driver mutations is questionable. This study aimed to examine the efficacy of IO in patients with non-small cell lung cancer (NSCLC) with a KRAS mutation (KRAS+). PATIENTS AND METHODS: We retrospectively identified NSCLC patients harboring KRAS mutation treated with IO in our Institution. We analyzed the results in comparison to non-KRAS patients. RESULTS: Among 328 consecutive KRAS+ NSCLC patients, 43 (13.1%) received IO in our Institution. In parallel 117 non-KRAS NSCLC patients treated with IO were selected for comparison. The baseline characteristics were similar between the two groups. No significant difference was observed between KRAS+ and non-KRAS patients in terms of mPFS (4.6 vs. 3.3 months, p=0.58) or OS (8.1 vs. 13.0 months, p=0.38). CONCLUSION: KRAS mutations seem to be irrelevant for selecting patients for IO that could be therefore considered an effective therapy for NSCLC patients, independently of KRAS status

The molecular landscape of breast mucoepidermoid carcinoma

: Mucoepidermoid carcinoma (MEC) of the breast is an extremely rare salivary gland-type tumor characterized by epidermoid, basaloid, intermediate, and/or mucinous cells arranged in solid and cystic patterns. Despite their triple-negative phenotype, breast MECs are generally considered low-risk malignancies but their biology is largely unexplored; therefore, guidelines for clinical management are lacking. Here, we sought to characterize the molecular landscape of breast MECs. Thirteen cases were histologically reviewed, characterized for tumor-infiltrating lymphocytes (TILs), and were subjected to immunohistochemistry for programmed death-ligand 1 (PD-L1, clone 22C3), EGFR, and amphiregulin (AREG). Rearrangements in MAML2 and EWSR1 were investigated by fluorescent in situ hybridization. Targeted next-generation sequencing of 161 genes was performed on eight cases. Most MECs had low histological grade (n = 10, 77%), with the presence of TILs (n = 9/12; 75%) and PD-L1 combined positive score ranging from 10 to 20 (n = 4/6; 67%). All cases showed EGFR and AREG overexpression and were fusion negative. Enrichment of genetic alterations was observed in PI3K/AKT/mTOR and cell cycle regulation pathways, while only one case harbored TP53 mutations. This is the first study providing extensive molecular data on breast MECs and the largest collection of cases available to date in the literature. Breast MECs lack TP53 mutations found in high-grade forms of triple-negative breast cancers and MAML2 or EWSR1 rearrangements pathognomonic of salivary MECs. Triple-negativity and PD-L1 positivity suggest a window of opportunity for immunotherapy in these patients. The EGFR/AREG axis activation, coupled with the mutational patterns in PI3K/AKT/mTOR and cell cycle pathways warrants caution in considering MECs as low-risk neoplasms