Update on Poly-ADP-ribose polymerase inhibition for ovarian cancer treatment

Background: Despite standard treatment for epithelial ovarian cancer (EOC), that involves cytoreductive surgery followed by platinum-based chemotherapy, and initial high response rates to these, up to 80 % of patients experience relapses with a median progression-free survival of 12–18 months. There remains an urgent need for novel targeted therapies to improve clinical outcomes in ovarian cancer. Of the many targeted therapies currently under evaluation, the most promising strategies developed thus far are antiangiogenic agents and Poly(ADP-ribose) polymerase (PARP) inhibitors. Particularly, PARP inhibitors are active in cells that have impaired repair of DNA by the homologous recombination (HR) pathway. Cells with mutated breast related cancer antigens (BRCA) function have HR deficiency, which is also present in a significant proportion of non-BRCA-mutated ovarian cancer (“BRCAness” ovarian cancer). The prevalence of germline BRCA mutations in EOC has historically been estimated to be around 10–15 %. However, recent reports suggest that this may be a gross underestimate, especially in women with high-grade serous ovarian cancer (HGSOC). Main body of the abstract: The emergence of the DNA repair pathway as a rational target in various cancers led to the development of the PARP inhibitors. The concept of tumor-selective synthetic lethality heralded the beginning of an eventful decade, culminating in the approval by regulatory authorities both in Europe as a maintenance therapy and in the United States treatment for advanced recurrent disease of the first oral PARP inhibitor, olaparib, for the treatment of BRCA-mutated ovarian cancer patients. Other PARP inhibitors are clearly effective in this disease and, within the next years, the results of ongoing randomized trials will clarify their respective roles. Conclusion: This review will discuss the different PARP inhibitors in development and the potential use of this class of agents in the future. Moreover, combination strategies involving PARP inhibitors are likely to receive increasing attention. The utility of PARP inhibitors combined with cytotoxic chemotherapy is of doubtful value, because of enhanced toxicity of this combination; while, more promising strategies include the combination with antiangiogenic agents, or with inhibitors of the P13K/AKT pathway and new generation of immunotherapy

Niraparib in ovarian cancer. results to date and clinical potential

Ovarian cancer is the first cause of death from gynaecological malignancy. Germline mutation in BRCA1 and 2, two genes involved in the mechanisms of reparation of DNA damage, are showed to be related with the incidence of breast and ovarian cancer, both sporadic and familiar. PARP is a family of enzymes involved in the base excision repair (BER) system. The introduction of inhibitors of PARP in patients with BRCA-mutated ovarian cancer is correlated with the concept of synthetic lethality. Among the PARP inhibitors introduced in clinical practice, niraparib showed interesting results in a phase III trial in the setting of maintenance treatment in ovarian cancer, after platinum-based chemotherapy. Interestingly, was niraparib showed to be efficacious not only in BRCA-mutated patients, but also in patients with other alterations of the homologous recombination (HR) system and in patients with unknown alterations. These results position niraparib as the first PARP-inhibitor with clinically and statistically significant results also in patients with no alterations in BRCA 1/2 and other genes involved in the DNA repair system. Even if the results are potentially practice-changing, the action of niraparib must be further studied and deepened

Triple negative breast cancer: new perspectives for targeted therapies

Breast cancer is a heterogeneous disease, encompassing a large number of entities showing different morphological features and having clinical behaviors. It has became apparent that this diversity may be justified by distinct patterns of genetic, epigenetic, and transcriptomic aberrations. The identification of gene-expression microarray-based characteristics has led to the identification of at least five breast cancer subgroups: luminal A, luminal B, normal breast-like, human epidermal growth factor receptor 2, and basal-like. Triple-negative breast cancer is a complex disease diagnosed by immunohistochemistry, and it is characterized by malignant cells not expressing estrogen receptors or progesterone receptors at all, and human epidermal growth factor receptor 2. Along with this knowledge, recent data show that triple-negative breast cancer has specific molecular features that could be possible targets for new biological targeted drugs. The aim of this article is to explore the use of new drugs in this particular setting, which is still associated with poor prognosis and high risk of distant recurrence and death

Lean body weight-tailored Iodinated contrast Injection in obese patient. boer versus James Formula

Purpose. To prospectively compare the performance of James and Boer formula in contrast media (CM) administration, in terms of image quality and parenchymal enhancement in obese patients undergoing CT of the abdomen. Materials and Methods. Fifty-five patients with a body mass index (BMI) greater than 35 kg/m2were prospectively included in the study. All patients underwent 64-row CT examination and were randomly divided in two groups: 26 patients in Group A and 29 patients in Group B. The amount of injected CM was computed according to the patient's lean body weight (LBW), estimated using either Boer formula (Group A) or James formula (Group B). Patient's characteristics, CM volume, contrast-to-noise ratio (CNR) of liver, aorta and portal vein, and liver contrast enhancement index (CEI) were compared between the two groups. For subjective image analysis readers were asked to rate the enhancement of liver, kidneys, and pancreas based on a 5-point Likert scale. Results. Liver CNR, aortic CNR, and portal vein CNR showed no significant difference between Group A and Group B (all P ≥ 0.177). Group A provided significantly higher CEI compared to Group B (P = 0.007). Group A and Group B returned comparable overall subjective enhancement values (3.54 and vs 3.20, all P ≥ 0.199). Conclusions. Boer formula should be the method of choice for LBW estimation in obese patients, leading to an accurate CM amount calculation and an optimal liver contrast enhancement in CT

Primary prophylaxis of neutropenia in women affected by breast cancer undergoing adjuvant chemotherapy with fec 100+/- docetaxel. Comparison of efficacy and tolerability between lenograstim and pegfilgrastim

Objectives: evaluate safety and toxicity of a single injection of pegfilgrastim compared to daily administration of lenograstim in breast cancer patient undergoing adjuvant chemotherapy

Magmatic Signature in Submarine Hydrothermal Fluids Vented Offshore Ventotene and Zannone Islands (Pontine Archipelago, Central Italy)

Geochemical investigations carried out on submarine hydrothermal fluids vented offshore the Pontine Islands (Tyrrhenian Sea) revealed the existence of gas vents to the W of Zannone Island and SW of Ventotene Island. The geochemical features of the CO2-rich gas samples show a clear mantle-derived signature with3He/4He of 3.72-3.75 Ra and 1.33 Ra at Zannone and Ventotene, respectively. Gas geochemistry denotes how CO2-rich gases undergo fractionation processes due to CO2dissolution to a variable extent favoring enrichment in the less soluble gas species, i.e., CH4, N2, and He. The carbon isotope composition of CO2, expressed asδ13C vs. V-PDB, ranges from -0.71 and -6.16‰ at Zannone to 1.93‰ at Ventotene. Preliminary geothermometric and geobarometric estimations indicate equilibrium temperatures in the range of 150-200°C at Zannone and >200°C at Ventotene besides H2O pressures in the range of 5 bar and 20 bar at Zannone and Ventotene, respectively. Although the latest volcanic activity at the Pontine Archipelago is dated Middle Pleistocene, the combination of the new geochemical information along with geothermometric estimations indicates that cooling magmas are likely releasing enough thermal energy to form an efficient hydrothermal system

Innovative approach for the in vitro research on biomedical scaffolds designed and customized with CAD-CAM technology

Studies on biomaterials involve assays aimed to assess the interactions between the biomaterial and the cells seeded on its surface. However, the morphology of biomaterials is heterogeneous and it could be tricky to standardize the results among different biomaterials and the classic plastic plates. In this light, we decided to create, by means of computer-aided design (CAD) technology, a standardized sample model, with equal shape and sizes, able to fit into a classic shape of a 96-wells tissue culture plate (TCP)

Hazard Scenarios Related to Submarine Volcanic-Hydrothermal Activity and Advanced Monitoring Strategies: A Study Case from the Panarea Volcanic Group (Aeolian Islands, Italy)

Geohazards associated to submarine hydrothermal systems still represent a tricky enigma to face and solve for the scientific community. The poor knowledge of a submarine environment, the rare and scarce monitoring activities, and the expensive and sometimes complicated logistics are the main problems to deal with. The submarine low-energy explosion, which occurred last November 3, 2002, off the volcanic island of Panarea, highlighted the absence of any hazard scenario to be used to manage the volcanic crisis. The "unrest" of the volcanic activity was triggered by a sudden input of deep magmatic fluids, which caused boiling water at the sea surface with a massive CO2 release besides changes in the fluids' geochemistry. That event dramatically pushed scientists to develop new methods to monitor the seafloor venting activity. Coupling the information from geochemical investigations and data collected during the unrest of volcanic activity, we were able to (a) develop theoretical models to gain a better insight on the submarine hydrothermal system and its relationships with the local volcanic and tectonic structures and (b) to develop a preliminary submarine volcanic hazard assessment connected to the Panarea system (Aeolian Islands). In order to mitigate the potential submarine volcanic hazard, three different scenarios are described here: (1) ordinary hydrothermal venting, (2) gas burst, and (3) volcanic eruption. The experience carried out at Panarea demonstrates that the best way to face any submarine volcanic-hydrothermal hazard is to improve the collection of data in near real-time mode by multidisciplinary seafloor observatories and to combine it with periodical sampling activity

Pleomorphic Adenoma of the Parotid: Extracapsular Dissection Compared with Superficial Parotidectomy—A 10-Year Retrospective Cohort Study

The purpose of this study was to investigate the complication rates and effectiveness of extracapsular dissection compared with superficial parotidectomy for pleomorphic adenomas of the parotid gland from 2002 to 2012. The authors carried out a retrospective cohort study of 198 patients with pleomorphic adenomas of the parotid gland. Extracapsular dissection (ED) or superficial parotidectomy (SP) was performed. The recurrence rate and complications of the two surgical techniques were measured with a univariate analysis of each variable using the appropriate statistical analysis (chi-squared test or t-test). A total of 198 patients were enrolled between January 2003 and December 2012. The study included 97 females (48.99%) and 101 males (51.01%) whose mean age was 50.97 years (range 14–75). The type of surgery performed was ED in 153 patients (77.27%, 80 males and 73 females) and SP in 45 patients (22.73%, 21 males and 24 females). The mean follow-up time was 61.02 +/− 4.9 months for the patients treated with ED and 66.4 +/− 4.5 months for the patients treated with SP. Transient facial nerve injury and facial paralysis were significantly more frequent after SP than after ED (P=0.001 and P=0.065, resp.). No significant differences in capsular rupture, recurrence, and salivary fistula were observed after SP or ED: 2.2% versus 3.9%, 2.2% versus 3.3%, and 2.2% versus 0.65%, respectively. Extracapsular dissection may be considered the treatment of choice for pleomorphic adenomas located in the superficial portion of the parotid gland because this technique showed similar effectiveness and fewer side effects than superficial parotidectomy