Radon Risk Analysis Through Geostatistical Tools Implemented in a WebGIS

Radon (Rn) is a colorless, odorless, tasteless, inert radioactive gas, and derives from the decay of uranium, which is a radioactive element that is found in small quantities in all sediments and rocks. The International Agency for Research on Cancer (IARC) and theWorld Health Organization (WHO) classify Rn pollution as the second leading cause of lung cancer after smoking. Since Rn is present, in the depths of the Earth, in gaseous phase, it reaches the surface because it interacts with other natural elements, such as uranium, thorium and radio (precursor elements); moreover other geo-lithological features, such as the mineralogical composition of the rocks, the underground permeability levels, the presence of faults, fractures and cavities, affect the transport of the Rn on the surface. In this paper, the spatial distribution of the Rn concentrations in soil gas over a survey area located in the South of Apulian Region (Italy) and its prediction at unsampled points have been discussed. In particular, Ordinary Kriging (OK), Log-Normal Kriging (LK), Cokriging with indicator variable (ICK) and Kriging with Varying Means (KVM) have been used to predict Rn concentrations over the study area. In this context, the integration of a Geographical Information System (GIS) and geostatistical tools can certainly support the evaluation of alternative scenarios, possible strategies for a sustainable development

Endometrial carcinoma: Past, present, and future

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TNPO3 protects HIV-1 replication from CPSF6-mediated capsid stabilization in the host cell cytoplasm

BACKGROUND: Despite intensive investigation the mechanism by which HIV-1 reaches the host cell nucleus is unknown. TNPO3, a karyopherin mediating nuclear entry of SR-proteins, was shown to be required for HIV-1 infectivity. Some investigators have reported that TNPO3 promotes HIV-1 nuclear import, as would be expected for a karyopherin. Yet, an equal number of investigators have failed to obtain evidence that supports this model. Here, a series of experiments were performed to better elucidate the mechanism by which TNPO3 promotes HIV-1 infectivity. RESULTS: To examine the role of TNPO3 in HIV-1 replication, the 2-LTR circles that are commonly used as a marker for HIV-1 nuclear entry were cloned after infection of TNPO3 knockdown cells. Potential explanation for the discrepancy in the literature concerning the effect of TNPO3 was provided by sequencing hundreds of these clones: a significant fraction resulted from autointegration into sites near the LTRs and therefore were not bona fide 2-LTR circles. In response to this finding, new techniques were developed to monitor HIV-1 cDNA, including qPCR reactions that distinguish 2-LTR circles from autointegrants, as well as massive parallel sequencing of HIV-1 cDNA. With these assays, TNPO3 knockdown was found to reduce the levels of 2-LTR circles. This finding was puzzling, though, since previous work has shown that the HIV-1 determinant for TNPO3-dependence is capsid (CA), an HIV-1 protein that forms a mega-dalton protein lattice in the cytoplasm. TNPO3 imports cellular splicing factors via their SR-domain. Attention was therefore directed towards CPSF6, an SR-protein that binds HIV-1 CA and inhibits HIV-1 nuclear import when the C-terminal SR-domain is deleted. The effect of 27 HIV-1 capsid mutants on sensitivity to TNPO3 knockdown was then found to correlate strongly with sensitivity to inhibition by a C-terminal deletion mutant of CPSF6 (R2 = 0.883, p \u3c 0.0001). TNPO3 knockdown was then shown to cause CPSF6 to accumulate in the cytoplasm. Mislocalization of CPSF6 to the cytoplasm, whether by TNPO3 knockdown, deletion of the CPSF6 nuclear localization signal, or by fusion of CPSF6 to a nuclear export signal, resulted in inhibition of HIV-1 replication. Additionally, targeting CPSF6 to the nucleus by fusion to a heterologous nuclear localization signal rescued HIV-1 from the inhibitory effects of TNPO3 knockdown. Finally, mislocalization of CPSF6 to the cytoplasm was associated with abnormal stabilization of the HIV-1 CA core. CONCLUSION: TNPO3 promotes HIV-1 infectivity indirectly, by shifting the CA-binding protein CPSF6 to the nucleus, thus preventing the excessive HIV-1 CA stability that would otherwise result from cytoplasmic accumulation of CPSF6

Clinical characteristics, treatment modalities, and potential contributing and prognostic factors in patients with bone metastases from gynecological cancers: A systematic review

The purpose of this study is to review the clinical characteristics, treatment modalities, and potential contributing and prognostic factors of bone metastases from gynecological cancers (GCs). A systematic literature search on PubMed, Scopus, Web of Science Core Collection and Cochrane Central Register of Controlled Trials databases was conducted. Thirty-one studies, all retrospective, were included in this review, for a total of 2880 patients with GC bone metastases. Primary tumors leading to bone metastases included endometrial cancer (EC), cervical cancer (CC), ovarian cancer (OC), uterine sarcoma (US) and vulvar cancer (VuC), mainly with an International Federation of Gynecology and Obstetrics (FIGO) Stage of III and IV. The main bone metastatic lesion site was the vertebral column, followed by the pelvic bone and lower extremity bones. The median survival rate after bone metastases diagnosis ranged from 3.0 to 45 months. The most frequent treatments were palliative and included radiotherapy and chemotherapy, followed by surgery. The findings of this review give a first dataset for a greater understanding of GC bone metastases that could help clinicians move toward a more “personalized” and thus more effective patient management

Can miRNAs be useful biomarkers in improving prognostic stratification in endometrial cancer patients? An update review

Endometrial cancer (EC) is the most common gynecological cancer, with annual incidence rates in Western countries ranging between 15 and 25 per 100 000 women. About 15% to 20% of patients with EC have high-risk disease and follow an aggressive clinical course. Unfortunately, the assessment of histologic parameters is poorly reproducible and conventional clinicopathological and molecular features do not reliably predict either the patient's response to the available treatments or the definition of personalized therapeutic approaches. In this context, the identification of novel diagnostic and prognostic biomarkers, which can be integrated in the current classification schemes, represents an unmet clinical need and an important challenge. miRNAs are key players in cancer by regulating the expression of specific target genes. Their role in EC, in association with clinical and prognostic tumor biomarkers, has been investigated but, so far, with little consensus among the studies. The present review aims to describe the recent advances in miRNAs research in EC taking into consideration the current classification schemes and to highlight the most promising miRNAs. Finally, a perspective point of view sheds light on the challenges ahead in the landscape of EC

Results of a phase I-II study on laser therapy for vaginal side effects after radiotherapy for cancer of uterine cervix or endometrium

Women who have previously received radiotherapy (RT) for gynecologic cancer often suffer from vaginal fibrosis and stenosis. The success of “non-ablative” laser therapy for postmenopausal vaginal atrophy has led to the idea of testing the laser in patients submitted to RT. In this prospective observational study, we selected patients who underwent pelvic RT followed by vaginal laser treatment. We scheduled three treatment sessions (at T0–T1–T2) and three controls (at T1–T2–T3) one month apart. The follow-up (at T4) was carried out six months after the last treatment. Vaginal Health Index (VHI) and vaginal length were evaluated. Sexual function was assessed through Female Sexual Function Index (FSFI). Overall, 43 patients with severe vaginal shortening, atrophy and stenosis was enrolled and treated with intravaginal non-ablative CO2 laser. We observed a progressive increase in vaginal length of 9% (p = 0.03) at T2 and 28% (p < 0.0001) at T3; effects were maintained at T4 (p < 0.0001). After the first application VHI showed a significant improvement of 57% at T3 (p < 0.0001). The results were maintained at T4 (p < 0.0001). No changes were found in FSFI. All procedures were well tolerated. In conclusion, laser therapy improved vaginal length and VHI in women undergoing pelvic RT; prospective studies are needed

Role of circulating mirnas in therapeutic response in epithelial ovarian cancer: A systematic revision

Epithelial ovarian cancer (EOC) is one of the most lethal cancers worldwide, mostly due to nonspecific symptoms and a lack of screening tests, which, taken together, contribute to delayed diagnosis and treatment. The current clinical biomarker is serum CA-125, which allows the identification of most advanced primary and relapsed disease and correlates with disease burden; however, as well highlighted in the literature, CA-125 often lacks sensitivity and specificity, and is not helpful in monitoring chemotherapeutic response or in predicting the risk of relapse. Given that, the identification of novel biomarkers able to foster more precise medical approaches and the personalization of patient management represents an unmet clinical requirement. In this context, circulating miRNAs may represent an interesting opportunity as they can be easily detected in all biological fluids. This is particularly relevant when looking for non-invasive approaches that can be repeated over time, with no pain and stress for the oncological patient. Given that, the present review aims to describe the circulating miRNAs currently identified as associated with therapeutic treatments in OC and presents a complete overview of the available evidence

Palliative Electrochemotherapy in Vulvar Carcinoma: Preliminary Results of the ELECHTRA (Electrochemotherapy Vulvar Cancer) Multicenter Study

Vulvar cancer (VC) is a rare disease of which recurrence poses management problems due to patients’ advanced age and comorbidities, and to the localization of the disease. Palliative treatments, allowing local disease control in patients previously treated with multimodal therapies or with comorbidities, are lacking. In this study we tested electrochemotherapy (ECT) on recurrent VC refractory to standard therapies to assess the tumor response and to define the selection criteria for patient’s candidate to ECT. This is a multicenter observational study carried out in five Italian centers. Data about patients and tumor characteristics, treatment, toxicity, and clinical response were recorded. In all procedures, intravenous bleomycin was administered according to European Standard Operative Procedure ECT (ESOPE) guidelines. Sixty-one patients, with a median age 79 years (range: 39–85) and mainly affected by squamous cellular carcinoma (91.8%), were treated with ECT. No serious adverse events were reported. Patients were discharged after three days (median, range: 0–8 days). Two months after ECT, the clinical response rate was 83.6% and was not related to age, body mass index, International Federation of Gynecology and Obstetrics (FIGO) stage, number of treated nodules, or previous treatments. ECT is a safe procedure with a favorable cost-effectiveness ratio and should be considered as a treatment option for local disease control in patients unsuitable for standard therapies

Electrochemotherapy of skin metastases from malignant melanoma: a PRISMA-compliant systematic review

The main treatment of MM metastases are systemic therapies, surgery, limb perfusion, and intralesional talimogene laherparepvec. Electrochemotherapy (ECT) is potentially useful also due to the high response rates recorded in cancers of any histology. No randomized studies comparing ECT with other local therapies have been published on this topic. We analyzed the available evidence on efficacy and toxicity of ECT in this setting. PubMed, Scopus, and Cochrane databases were screened for paper about ECT on MM skin metastases. Data about tumor response, mainly in terms of overall response rate (ORR), toxicity (both for ECT alone and in combination with systemic treatments), local control (LC), and overall survival (OS) were collected. The methodological quality was assessed using a 20-item validated quality appraisal tool for case series. Overall, 18 studies were included in our analysis. In studies reporting “per patient” tumor response the pooled complete response (CR) was 35.7% (95%CI 26.0–46.0%), and the pooled ORR was 80.6% (95%CI 68.7–90.1%). Regarding “per lesion” response, the pooled CR was 53.5% (95%CI 42.1–64.7%) and the pooled ORR was 77.0% (95%CI 56.0–92.6%). One-year LC rate was 80%, and 1-year OS was 67–86.2%. Pain (24.2–92.0%) and erythema (16.6–42.0%) were the most frequent toxicities. Two studies reported 29.2% and 41.6% incidence of necrosis. ECT is effective in terms of tumor response and tolerated in patients with skin metastases from MM, albeit with a wide variability of reported results. Therefore, prospective trials in this setting are warranted

Quality of life with vulvar carcinoma treated with palliative electrochemotherapy: The elechtra (electrochemotherapy vulvar cancer) study

The ELECHTRA (ELEctroChemoTherapy vulvaR cAncer) project was conceived to collect data on palliative electrochemotherapy (ECT) in vulvar cancer (VC) assessing patients’ outcomes (response and survival) and impact on quality of life (QoL). After reporting outcome data in 2019, here, we present the results on QoL. A multicenter prospective observational study was conducted on patients with VC refractory or not amenable to standard therapies undergoing palliative ECT as per clinical practice. The following questionnaires were administered before and after ECT (two and four months later, early and late follow-up): visual analog pain scale (VAS), EuroQol 5-Dimension 5-Level (EQ-5D-L5) and Functional Assessment of Cancer Therapy—Vulva cancer (FACT—V). Analyses were conducted on both the whole study population and by subgroups (clinical response after ECT and site, number and size of lesions). Questionnaires from 55 patients were evaluated. Compared to the baseline (6.1 ± 2.1), the VAS was significantly reduced at early (4.3 ± 2.5) and late follow-up (4.6 ± 2.8) (p < 0.0001). The FACT—V score improved significantly at early (9.6 ± 4.0) (p < 0.0001) and late follow-up (8.9 ± 4.1) (p < 0.0054) as compared to the baseline (7.1 ± 3.6). No EQ-5D-5L statistically significant changes were observed. Subgroup analyses showed worse QoL in patients with stable or progressive disease, posterior site and multiple or larger than 3 cm nodules. This is the first study reporting improved QoL in VC patients after palliative ECT. Based on these results, ECT in VC should be considered an effective option based on the favorable outcomes both in terms of response and QoL