Radiolabelled PSMA PET/CT in breast cancer. A systematic review

BACKGROUND: Radiolabelled prostate-specific membrane antigen (PSMA)-based PET/CT is a whole-body imaging technique currently performed for the detection of prostate cancer lesions. PSMA has been also demonstrated to be expressed by the neovasculature of many other solid tumours. The aim of this review is to evaluate the possible diagnostic role of radiolabelled PSMA PET/CT in breast cancer. MATERIAL AND METHODS: A comprehensive literature search of the PubMed/MEDLINE, Scopus, Embase and Cochrane Library databases was conducted to find relevant published articles about the diagnostic performance of radiolabelled PSMA PET/CT in breast cancer. RESULTS: The comprehensive computer literature search revealed 652 articles. On reviewing the titles and abstracts, 640 articles were excluded because the reported data were not within the field of interest of this review. Twelve articles were selected and retrieved in full-text version; no additional study was found when screening the references of these articles. In total, 12 articles were included in the systematic review. CONCLUSIONS: Further studies enrolling a wider population are needed to clarify th

Stereotactic radiotherapy with simultaneous integrated protection planning technique for synovial sarcoma with stomach abutment: A case report of a complete response

Here, we report the clinical case of a 44-year-old lady, affected by synovial sarcoma (SS) of the mediastinum which was treated in 2014, and relapsed in the upper abdomen in 2020. SS is a relatively radioresistant disease, radiotherapy (RT) is routinely reserved for the neoadjuvant/adjuvant or palliative context. In our scenario, stereotactic RT consisting in 45Gy in 6 fractions was proposed to manage the upper abdominal relapse. Exploiting simultaneous integrated protection, a deliberated reduction in the dose prescription in area of planning target volume overlapped with stomach was achieved, obtaining reasonable dosimetric goals. Acute toxicity in the patient was acceptable, and she did not experience late toxicity and was still free from disease, as noted in last follow-up, 15 months after treatment

Stereotactic Radiotherapy and Androgen Deprivation Therapy for Localized Prostate Cancer: A Retrospective Mono-institutional Experience

Background/Aim: Stereotactic radiotherapy (SRT) is an effective treatment for localized prostate cancer. However, is it not clear whether the addition of androgen deprivation therapy (ADT) to SRT is beneficial. The aim of this study was to analyze the outcomes of a series of patients treated with SRT plus ADT for localized prostate cancer. Patients and Methods: Patients were treated with SRT with 42 Gy in 7 fractions with volumetric-modulated arc therapy plus Image Guided Radiotherapy (V-MAT IGRT) technique. ADT was administered to patients with intermediate unfavorable-and high-risk disease. Study endpoints were biochemical disease-free survival (bDFS), overall survival (OS), acute and late toxicity and patient-reported outcomes (PROs) using international prostate cancer symptoms scale (IPSS) and international index of erectile function (IIEF). Results: A total of 170 consecutive patients were identified, of which 49 (28.8%) with low-risk, 15 (8.8%) with favorable intermediate-risk 76 (44.7%) with unfavorable intermediate risk and 30 (17.6%) with high-risk class. All patients of unfavorable intermediate-and high-risk groups were for administered LHRH analogue concurrently to SRT and for at least 6 months. Patients with unfavorable intermediate and high-risk presented a 5-year bDFS of 81.7% and 76.9%, respectively. Conclusion: SRT consisting of 42 Gy in seven fractions with short-term ADT represents a safe and effective treatment for unfavorable intermediate and high risk prostate cancer. Our results support the need of high quality studies to test the efficacy of ADT combined with SRT for unfavorable intermediate-and high-risk localized prostate cancer

Unresectable stage III non-small cell lung cancer: could durvalumab be safe and effective in real-life clinical scenarios? Results of a single-center experience

IntroductionThe standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by consolidation durvalumab as shown in the PACIFIC trial. The purpose of this study is to evaluate clinical outcomes and toxicities regarding the use of durvalumab in a real clinical scenario. MethodsA single-center retrospective study was conducted on patients with a diagnosis of unresectable stage III NSCLC who underwent radical CRT followed or not by durvalumab. Tumor response after CRT, pattern of relapse, overall survival (OS) and progression-free survival (PFS), and toxicity profile were investigated. ResultsEighty-five patients met the inclusion criteria. The median age was 67 years (range 45-82 years). Fifty-two patients (61.2%) started sequential therapy with durvalumab. The main reason for excluding patients from the durvalumab treatment was the expression of PD-L1 < 1%. Only two patients presented a grade 4 or 5 pneumonitis. A median follow-up (FU) of 20 months has been reached. Forty-five patients (52.9%) had disease progression, and 21 (24.7%) had a distant progression. The addition of maintenance immunotherapy confirmed a clinical benefit in terms of OS and PFS. Two-year OS and PFS were respectively 69.4% and 54.4% in the durvalumab group and 47.9% and 24.2% in the no-durvalumab group (p = 0.015, p = 0.007). ConclusionIn this real-world study, patients treated with CRT plus durvalumab showed clinical outcomes and toxicities similar to the PACIFIC results. Maintenance immunotherapy after CRT has been shown to be safe and has increased the survival of patients in clinical practice

Hyperactive Akt1 Signaling Increases Tumor Progression and DNA Repair in Embryonal Rhabdomyosarcoma RD Line and Confers Susceptibility to Glycolysis and Mevalonate Pathway Inhibitors

In pediatric rhabdomyosarcoma (RMS), elevated Akt signaling is associated with increased malignancy. Here, we report that expression of a constitutively active, myristoylated form of Akt1 (myrAkt1) in human RMS RD cells led to hyperactivation of the mammalian target of rapamycin (mTOR)/70-kDa ribosomal protein S6 kinase (p70S6K) pathway, resulting in the loss of both MyoD and myogenic capacity, and an increase of Ki67 expression due to high cell mitosis. MyrAkt1 signaling increased migratory and invasive cell traits, as detected by wound healing, zymography, and xenograft zebrafish assays, and promoted repair of DNA damage after radiotherapy and doxorubicin treatments, as revealed by nuclear detection of phosphorylated H2A histone family member X (γH2AX) through activation of DNA-dependent protein kinase (DNA-PK). Treatment with synthetic inhibitors of phosphatidylinositol-3-kinase (PI3K) and Akt was sufficient to completely revert the aggressive cell phenotype, while the mTOR inhibitor rapamycin failed to block cell dissemination. Furthermore, we found that pronounced Akt1 signaling increased the susceptibility to cell apoptosis after treatments with 2-deoxy-D-glucose (2-DG) and lovastatin, enzymatic inhibitors of hexokinase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), especially in combination with radiotherapy and doxorubicin. In conclusion, these data suggest that restriction of glucose metabolism and the mevalonate pathway, in combination with standard therapy, may increase therapy success in RMS tumors characterized by a dysregulated Akt signaling

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Designing a Transparent and Fluorine Containing Hydrogel

Physical hydrogels are supramolecular materials obtained by self-assembly of small molecules called gelators. Aromatic amino acids and small peptides containing aromatic rings are good candidates as gelators due to their ability to form weak bonds as π-π interactions and hydrogen bonds between NH and CO of the peptide chain. In this paper we show our results in the preparation of a transparent hydrogel that was obtained by self-assembly of a fluorine-containing dipeptide that relies on the additional formation of halogen bonds due to the fluorine atoms contained in the dipeptide. We used Boc-D-F2Phe-L-Oxd-OH (F2Phe = 3,4-difluorophenylalainine; Oxd = 4-methyl-5-carboxy-oxazolidin-2-one) that formed a strong and transparent hydrogel in 0.5% w/w concentration at pH = 4.2. The formation of a hydrogel made of unnatural fluorinated amino acids may be of great interest in the evaluation of patients with parkinsonian syndromes and may be used for controlled release

Solar Wireless Sensor Nodes for Condition Monitoring of Freight Trains

The objective of this work is to present the design and testing of a Wireless Sensor Network, powered by solar energy, to be installed on freight trains with the purpose of performing on-board monitoring operations. A complete Wireless Sensor Network requires a certain number of Wireless Sensor Nodes, installed in significant points of a vehicle, provided with sensors and capable of elaborating raw data, transmitting them via wireless network as synthesis information to an on-board control unit. The on-board control unit periodically communicates the data gathered from different sensors to a ground central control unit through the Internet. Each Wireless Sensor Node needs to be powered independently. To achieve this purpose a small solar panel was used to provide the Wireless Sensor Node with the necessary amount of energy. Integrated circuits were designed for power management, acquisition, elaboration and wireless transmission of data and analyzed in terms of performances and energy consumption. The communication protocol between the Wireless Sensor Node and the control unit was first laboratory-tested and finally the whole system was installed on a real wagon, and on-field tests were conducted for a period of almost one year

18F-Fluciclovine (18F-FACBC) PET/CT or PET/MRI in gliomas/glioblastomas

18F-fluciclovine (18F-FACBC) is a radiotracer already studied for prostate cancer, and its potential role in brain tumors (such as glioma) is not yet well investigated despite promising results. The aim of this review is to evaluate the possible diagnostic role of 18F-FACBC PET/CT or PET/MRI in patients with gliomas and glioblastomas. A comprehensive literature search of the PubMed/MEDLINE, Scopus, Embase, and Cochrane library databases was conducted to find the relevant published articles about the diagnostic performance of FACBC PET/CT or PET/MRI in patients affected by glioma and/or glioblastoma. Seven papers were included in the systematic review. From the analyses of the selected studies, the following main findings were obtained: glioma and glioblastoma are FACBC-avid tumors with a detection rate of about 100%; FACBC PET has high-diagnostic accuracy in defining tumor extent, volumes, and satellite lesions better than MR; compared to methionine, FACBC has similar accuracy but better tumor-to-background contrast; FACBC uptake may help to discriminate between low-grade and high-grade glioma. Radiolabelled fluciclovine (18F-FACBC) imaging seems to be useful in analyzing glioma/glioblastoma. Further studies enrolling a wider population are needed to clarify the real clinical and diagnostic role of 18F-FACBC in this setting and its possible position in the diagnostic flowchart