Role of surgical treatment in endometriosis.

Endometriosis can take one of three forms depending on its clinical presentation and management: endometriotic ovarian cyst (ovarian endometrioma), superficial or peritoneal endometriosis and deep infiltrating endometriosis (DIE).1Among them, DIE is considered the most aggressive, and the patient is often affected by more than one type together. The therapeutic methodology should not be influenced by a combination of different types of endometriotic lesion. According to the clinical context and the patient's needs, the treatment of this pathology can be medical or surgical. Although medical therapy could improve endometriosis-associated symptoms, it never offers a definite treatment for symptomatic patients, who often require surgical treatment. The rationale behind endometriosis surgical treatment is to achieve the complete removal of all lesions through a one-step surgical procedure; to obtain promising long-term results for pelvic pain, recurrence rate, and fertility; and to protect the functionality of the involved organs. Achieving these results depends on the total removal of the pathology from the pelvis, in an attempt to preserve, as much as possible, the healthy tissues surrounding the site of the disease. The choice of a surgical approach rather than medical therapy is subject to the patient's expectations, such as pregnancy desire, the effectiveness of treatment compared to possible complications, the type of pain and its intensity, and the location and severity of the disease. In this context, surgical management using a multidisciplinary endometriosis team is an important factor for achieving good outcomes.

Nabiximols plus robotic assisted gait training in improving motor performances in people with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, affecting ambulation even in people with only mild neurological signs. Patients with MS frequently experience spasticity, which contributes significantly to impair their motor functions, including ambulation, owing to muscle stiffness, spasms, and pain. OBJECTIVES: To clarify the role of delta-9-tetrahydrocannabinol(THC):cannabidiol(CBD) oromucosal spray, coupled to robot-aided gait training (RAGT) using the Lokomat©Pro to improve functional ambulation in patients with MS. METHODS: We compared 20 patients with MS, who were treated with THC:CBD oromucosal spray in add-on to the ongoing oral antispastic therapy (OAT) (group A), with 20 individuals with MS (matched for clinical-demographic characteristics) who were treated only with OAT (group B). Both the groups underwent RAGT using the Lokomat-Pro (three 45-minute sessions per week). Our primary outcome measures were the Functional Independence Measure (FIM) and the 10 meters walking test (10MWT). As secondary outcome measures we evaluated the brain cortical excitability by using Transcranial Magnetic Stimulation. Both parameters were taken before and after the end of the RAGT. RESULTS: FIM improved in group A more than in group B (p<0.001). Moreover, 10MWT decreased in group A more than in group B (p<0.001). These clinical findings were paralleled by a more evident reshape of intracortical excitability in both upper and lower limbs, as suggested by motor evoked potential amplitude increase (p<0.001), intracortical inhibition strengthening (p<0.001), and intracortical facilitation decrease (p=0.01) in group A as compared to group B. CONCLUSIONS: Our results suggest that the combined THC:CBD-RAGT approach could be useful in improving gait performance in patients with MS.

Comparative Study of NGS Platform Ion Torrent Personal Genome Machine and Therascreen Rotor-Gene Q for the Detection of Somatic Variants in Cancer.

Molecular profiling of a tumor allows the opportunity to design specific therapies which are able to interact only with cancer cells characterized by the accumulation of several genomic aberrations. This study investigates the usefulness of next-generation sequencing (NGS) and mutation-specific analysis methods for the detection of target genes for current therapies in non-small-cell lung cancer (NSCLC), metastatic colorectal cancer (mCRC), and melanoma patients. We focused our attention on EGFR, BRAF, KRAS, and BRAF genes for NSCLC, melanoma, and mCRC samples, respectively. Our study demonstrated that in about 2% of analyzed cases, the two techniques did not show the same or overlapping results. Two patients affected by mCRC resulted in wild-type (WT) for BRAF and two cases with NSCLC were WT for EGFR according to PGM analysis. In contrast, these samples were mutated for the evaluated genes using the therascreen test on Rotor-Gene Q. In conclusion, our experience suggests that it would be appropriate to confirm the WT status of the genes of interest with a more sensitive analysis method to avoid the presence of a small neoplastic clone and drive the clinician to correct patient monitoring.

Future directions and management of liquid biopsy in non-small cell lung cancer.

Lung cancer represents the world's most common cause of cancer death. In recent years, we moved from a generic therapeutic strategy to a personalized approach, based on the molecular characterization of the tumor. In this view, liquid biopsy is becoming an important tool for assessing the progress or onset of lung disease. Liquid biopsy is a non-invasive procedure able to isolate circulating tumor cells, tumor educated platelets, exosomes and free circulating tumor DNA from body fluids. The characterization of these liquid biomarkers can help to choose the therapeutic strategy for each different case. In this review, the authors will analyze the main aspects of lung cancer and the applications currently in use focusing on the benefits associated with this approach for predicting the prognosis and monitoring the clinical conditions of lung cancer disease.

miR-125b Upregulates miR-34a and Sequentially Activates Stress Adaption and Cell Death Mechanisms in Multiple Myeloma.

miR-125b, ubiquitously expressed and frequently dysregulated in several tumors, has gained special interest in the field of cancer research, displaying either oncogenic or oncosuppressor potential based on tumor type. We have previously demonstrated its tumor-suppressive role in multiple myeloma (MM), but the analysis of molecular mechanisms needs additional investigation. The purpose of this study was to explore the effects of miR-125b and its chemically modified analogs in modulating cell viability and cancer-associated molecular pathways, also focusing on the functional aspects of stress adaptation (autophagy and senescence), as well as programmed cell death (apoptosis). Based on the well-known low microRNA (miRNA) stability in therapeutic application, we designed chemically modified miR-125b mimics, laying the bases for their subsequent investigation in in vivo models. Our study clearly confirmed an oncosuppressive function depending on the repression of multiple targets, and it allowed the identification, for the first time, of miR-125b-dependent miR-34a stimulation as a possible consequence of the inhibitory role on the interleukin-6 receptor (IL-6R)/signal transducer and activator of transcription 3 (STAT3)/miR-34a feedback loop. Moreover, we identified a pattern of miR-125b-co-regulated miRNAs, shedding light on possible new players of anti-MM activity. Finally, functional studies also revealed a sequential activation of senescence, autophagy, and apoptosis, thus indicating, for the first two processes, an early cytoprotective and inhibitory role from apoptosis activation.

Evidence of novel miR-34a-based therapeutic approaches for multiple myeloma treatment.

MiR-34a acts as tumor suppressor microRNA (miRNA) in several cancers, including multiple myeloma (MM), by controlling the expression of target proteins involved in cell cycle, differentiation and apoptosis. Here, we have investigated the combination between miR-34a and γ-secretase inhibitor (γSI), Sirtinol or zoledronic acid (ZOL) in order to enhance the inhibitory action of this miRNA on its canonical targets such as Notch1 and SIRT1, and on Ras/MAPK-dependent pathways. Our data demonstrate that miR-34a synthetic mimics significantly enhance the anti-tumor activity of all the above-mentioned anti-cancer agents in RPMI 8226 MM cells. We found that γSI enhanced miR-34a-dependent anti-tumor effects by activating the extrinsic apoptotic pathway which could overcome the cytoprotective autophagic mechanism. Moreover, the combination between miR-34a and γSI increased the cell surface calreticulin (CRT) expression, that is well known for triggering anti-tumor immunological response. The combination between miR-34a and Sirtinol induced the activation of an intrinsic apoptotic pathway along with increased surface expression of CRT. Regarding ZOL, we found a powerful growth inhibition after enforced miR-34a expression, which was not likely attributable to neither apoptosis nor autophagy modulation. Based on our data, the combination of miR-34a with other anti-cancer agents appears a promising anti-MM strategy deserving further investigation.

Detection of olfactory dysfunction using olfactory event related potentials in young patients with multiple sclerosis.

BACKGROUND: Several studies reported olfactory dysfunction in patients with multiple sclerosis. The estimate of the incidence of olfactory deficits in multiple sclerosis is uncertain; this may arise from different testing methods that may be influenced by patients' response bias and clinical, demographic and cognitive features. AIMS: To evaluate objectively the olfactory function using Olfactory Event Related Potentials. MATERIALS AND METHODS: We tested the olfactory function of 30 patients with relapsing remitting multiple sclerosis (mean age of 36.03±6.96 years) and of 30 age, sex and smoking-habit matched healthy controls by using olfactory potentials. A selective and controlled stimulation of the olfactory system to elicit the olfactory event related potentials was achieved by a computer-controlled olfactometer linked directly with electroencephalograph. Relationships between olfactory potential results and patients' clinical characteristics, such as gender, disability status score, disease-modifying therapy, and disease duration, were evaluated. RESULTS: Seven of 30 patients did not show olfactory event related potentials. Sixteen of remaining 23 patients had a mean value of amplitude significantly lower than control group (p<0.01). The presence/absence of olfactory event related potentials was associated with dichotomous expanded disability status scale (p = 0.0433), as well as inversely correlated with the disease duration (r = -0.3641, p = 0.0479). CONCLUSION: Unbiased olfactory dysfunction of different severity found in multiple sclerosis patients suggests an organic impairment which could be related to neuroinflammatory and/or neurodegenerative processes of olfactory networks, supporting the recent findings on neurophysiopathology of disease.