MR breast imaging: A comparative analysis of conventional and parallel imaging acquisition [RM delle mammelle: Confronto tra tecnica convenzionale ed imaging parallelo]

Purpose. The objective of this study was to compare conventional breast magnetic resonance imaging (MRI) with breast MRI acquired with the sensitivity-encoding (SENSE) technique on a 1.5-T MRI scanner in the same patient, on the basis of image quality and kinetics analysis. Materials and methods. Thirty-one patients with suspicious mammography and US findings were included in the study. Conventional breast MRI consisted of the following sequences: T1 (matrix, 288x512); T2 (matrix 225x512); short tau inversion recovery (STIR) (matrix 320x224) and dynamic T1 [2D fast-field echo (FFE)] (matrix 256x512; temporal resolution =80 s). The SENSE technique included the following sequences: T1 (matrix 512x512); T2 (matrix 512x512); short-tau inversion recovery (STIR) (matrix 320x224); dynamic T1 (3D FFE) (matrix 512x512, with a temporal resolution ≤70 s). Image quality was graded on a four-point scale, and the mean scores given to each sequence were compared between the two protocols. The relative enhancement rates and the qualitative features of the signal intensity (SI)/time curves were also compared between the two protocols. Results. The readers found 64 contrast-enhanced lesions in 31 patients. Nineteen patients had a total of 27 malignant lesions. In the remaining 12 patients, 37 benign lesions were found. No significant differences between the two protocols were observed with regard to the mean relative enhancement rates and the qualitative features of the SI/time curves. In detail, the mean image quality scores were higher for SENSE imaging (p<0.05). The mean image quality score for the T1 and T2 morphological sequences were comparable. In contrast, the quality scores for the STIR images differed significantly between the two protocols (p<0.001), and a significant difference was also observed when comparing the T1 postcontrast images (p<0.001). Conclusions. Our data suggest that the SENSE imaging protocol applied in our study is superior to conventional imaging with regard to image quality, especially for T1 postcontrast and STIR images. SENSE imaging protocols may provide an alternative to conventional sequences for contrast-enhanced MRI of the breast using 1.5-T MR scanners. © 2008 Springer-Verlag

The Use of Artificial Intelligence (AI) in the Radiology Field: What Is the State of Doctor–Patient Communication in Cancer Diagnosis?

Simple Summary Artificial Intelligence (AI) has been increasingly used in radiology to improve diagnostic procedures over the past decades. The application of AI at the time of cancer diagnosis also creates challenges in the way doctors should communicate the use of AI to patients. The present systematic review deals with the patient's psycho-cognitive perspective on AI and the interpersonal skills between patients and physicians when AI is implemented in cancer diagnosis communication. Evidence from the retrieved studies pointed out that the use of AI in radiology is negatively associated with patient trust in AI and patient-centered communication in cancer disease. Background: In the past decade, interest in applying Artificial Intelligence (AI) in radiology to improve diagnostic procedures increased. AI has potential benefits spanning all steps of the imaging chain, from the prescription of diagnostic tests to the communication of test reports. The use of AI in the field of radiology also poses challenges in doctor-patient communication at the time of the diagnosis. This systematic review focuses on the patient role and the interpersonal skills between patients and physicians when AI is implemented in cancer diagnosis communication. Methods: A systematic search was conducted on PubMed, Embase, Medline, Scopus, and PsycNet from 1990 to 2021. The search terms were: ("artificial intelligence" or "intelligence machine") and "communication" "radiology" and "oncology diagnosis". The PRISMA guidelines were followed. Results: 517 records were identified, and 5 papers met the inclusion criteria and were analyzed. Most of the articles emphasized the success of the technological support of AI in radiology at the expense of patient trust in AI and patient-centered communication in cancer disease. Practical implications and future guidelines were discussed according to the results. Conclusions: AI has proven to be beneficial in helping clinicians with diagnosis. Future research may improve patients' trust through adequate information about the advantageous use of AI and an increase in medical compliance with adequate training on doctor-patient diagnosis communication

RIP1-HAT1-SirT complex identification and targeting in treatment and prevention of cancer

Purpose: Alteration in cell death is a hallmark of cancer. A functional role regulating survival, apoptosis, and necroptosis has been attributed to RIP1/3 complexes.Experimental Design: We have investigated the role of RIP1 and the effects of MC2494 in cell death induction, using different methods as flow cytometry, transcriptome analysis, immunoprecipitation, enzymatic assays, transfections, mutagenesis, and in vivo studies with different mice models.Results: Here, we show that RIP1 is highly expressed in cancer, and we define a novel RIP1/3-SIRT1/2-HAT1/4 complex. Mass spectrometry identified five acetylations in the kinase and death domain of RIP1. The novel characterized pan-SIRT inhibitor, MC2494, increases RIP1 acetylation at two additional sites in the death domain. Mutagenesis of the acetylated lysine decreases RIP1-dependent cell death, suggesting a role for acetylation of the RIP1 complex in cell death modulation. Accordingly, MC2494 displays tumor-selective potential in vitro, in leukemic blasts ex vivo, and in vivo in both xenograft and allograft cancer models. Mechanistically, MC2494 induces bona fide tumor-restricted acetylated RIP1/caspase-8-mediated apoptosis. Excitingly, MC2494 displays tumor-preventive activity by blocking 7,12-dimethylbenz(α)anthracene-induced mammary gland hyperproliferation in vivoConclusions: These preventive features might prove useful in patients who may benefit from a recurrence-preventive approach with low toxicity during follow-up phases and in cases of established cancer predisposition. Thus, targeting the newly identified RIP1 complex may represent an attractive novel paradigm in cancer treatment and prevention

Regulatory Interplay between miR-181a-5p and Estrogen Receptor Signaling Cascade in Breast Cancer

he efficacy and side effects of endocrine therapy in breast cancer (BC) depend largely on estrogen receptor alpha (ERα) expression, the specific drug administered, and treatment scheduling. Although the benefits of endocrine therapy outweigh any adverse effects in the initial stages of BC, later- or advanced-stage tumors acquire resistance to treatments. The mechanisms underlying tumor resistance to therapy are still not well understood, posing a major challenge for BC patient care. Epigenetic regulation and miRNA expression may be involved in the switch from a treatment-sensitive to a treatment-resistant state and could provide a valid therapeutic strategy for ERα negative BC. Here, a hybrid lysine-specific histone demethylase inhibitor, MC3324, displaying selective estrogen receptor down-regulator-like activities in BC, was used to highlight the interplay between epigenetic and ERα signaling. MC3324 anticancer action is mediated by microRNA (miRNA) expression regulation, indicating an innovative function for this molecule. Integrated analysis suggests a crosstalk between estrogen signaling, ERα interactors, miRNAs, and their putative targets. Specifically, miR-181a-5p expression is regulated by MC3324 and has an impact on cellular levels of ERα. A comparison of breast tumor versus healthy mammary tissues confirmed the important role of miR-181a-5p in ERα regulation and points to its putative predictive function in BC therapy

Complete removal of the lesion as a guidance in the management of patients with breast ductal carcinoma in Situ

Background: Considering highly selected patients with ductal carcinoma in situ (DCIS), active surveillance is a valid alternative to surgery. Our study aimed to show the reliability of post-biopsy complete lesion removal, documented by mammogram, as additional criterion to select these patients. Methods: A total of 2173 vacuum‐assisted breast biopsies (VABBs) documented as DCIS were reviewed. Surgery was performed in all cases. We retrospectively collected the reports of post‐ VABB complete lesion removal and the histological results of the biopsy and surgery. We calculated the rate of upgrade of DCIS identified on VABB upon excision for patients with post‐biopsy complete lesion removal and for those showing residual lesion. Results: We observed 2173 cases of DCIS: 408 classified as low‐grade, 1262 as intermediate‐grade, and 503 as high‐grade. The overall upgrading rate to invasive carcinoma was 15.2% (330/2173). The upgrade rate was 8.2% in patients showing mammographically documented complete removal of the lesion and 19% in patients without complete removal. Conclusion: The absence of mammographically documented residual lesion following VABB was found to be associated with a lower upgrading rate of DCIS to invasive carcinoma on surgical excision and should be considered when deciding the proper management DCIS diagnosis

PARP-1 modulates amyloid beta peptide-induced neuronal damage.

Amyloid beta peptide (A beta) causes neurodegeneration by several mechanisms including oxidative stress, which is known to induce DNA damage with the consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were treated with A beta(25-35) fragment in the presence or absence of MC2050, a new PARP-1 inhibitor. A beta(25-35) induces an enhancement of PARP activity which is prevented by cell pre-treatment with MC2050. These data were confirmed by measuring PARP-1 activity in CHO cells transfected with amylod precursor protein and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the amyloid peptide. Following A beta(25-35) exposure a significant increase in intracellular ROS was observed. These data were supported by the finding that A beta(25-35) induces DNA damage which in turn activates PARP-1. Challenge with A beta(25-35) is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB impairment upon MC2050 treatment. Moreover, A beta(25-35) via PARP-1 induces a significant increase in the p53 protein level and a parallel decrease in the anti-apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1 involvment in cellular responses induced by A beta and hence a possible rationale for the implication of PARP-1 in neurodegeneration is discussed

90Y-DOTA-nimotuzumab: synthesis of a promising β⁻ radiopharmaceutical

BACKGROUND: Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody, nowadays used for tumour immunochemotherapy. This study aimed to label the conjugate DOTA-nimotuzumab with yttrium-90, in order to provide a beta- emitting radioimmunoconjugate (90Y-DOTA-nimotuzumab) potentially useful to assess the feasibility of a new radio-guided surgery approach.METHODS: The synthesis of 90Y-DOTA-nimotuzumab was performed in two days. Nimotuzumab was conjugated with a 50 fold excess of DOTA and then labelled with 90Y3+. The 90Y-DOTA-nimotuzumab preparation was optimized considering several parameters such as pH, temperature and reaction volume. Moreover, the 90Y-DOTA-nimotuzumab stability was evaluated in human plasma.RESULTS: The radioimmunoconjugate 90Y-DOTA-nimotuzumab was obtained with a radiochemical purity greater than 96%, and showed a good stability at 20°C as well as at 37°C in human plasma.CONCLUSIONS: The optimized conditions for a mild and easy preparation of 90Y-DOTA-nimotuzumab joined to a promising stability under physiological conditions suggest to propose this radioimmunoconjugate as a potential diagnostic radiopharmaceutical for beta- radio-guided surgery

"Shock and kill" effects of class I-selective histone deacetylase inhibitors in combination with the glutathione synthesis inhibitor buthionine sulfoximine in cell line models for HIV-1 quiescence

Latently infected, resting memory CD4+ T cells and macrophages represent a major obstacle to the eradication of HIV-1. For this purpose, "shock and kill" strategies have been proposed (activation of HIV-1 followed by stimuli leading to cell death). Histone deacetylase inhibitors (HDACIs) induce HIV-1 activation from quiescence, yet class/isoform-selective HDACIs are needed to specifically target HIV-1 latency. We tested 32 small molecule HDACIs for their ability to induce HIV-1 activation in the ACH-2 and U1 cell line models. In general, potent activators of HIV-1 replication were found among non-class selective and class I-selective HDACIs. However, class I selectivity did not reduce the toxicity of most of the molecules for uninfected cells, which is a major concern for possible HDACI-based therapies. To overcome this problem, complementary strategies using lower HDACI concentrations have been explored. We added to class I HDACIs the glutathione-synthesis inhibitor buthionine sulfoximine (BSO), in an attempt to create an intracellular environment that would facilitate HIV-1 activation. The basis for this strategy was that HIV-1 replication decreases the intracellular levels of reduced glutathione, creating a pro-oxidant environment which in turn stimulates HIV-1 transcription. We found that BSO increased the ability of class I HDACIs to activate HIV-1. This interaction allowed the use of both types of drugs at concentrations that were non-toxic for uninfected cells, whereas the infected cell cultures succumbed more readily to the drug combination. These effects were associated with BSO-induced recruitment of HDACI-insensitive cells into the responding cell population, as shown in Jurkat cell models for HIV-1 quiescence. The results of the present study may contribute to the future design of class I HDACIs for treating HIV-1. Moreover, the combined effects of class I-selective HDACIs and the glutathione synthesis inhibitor BSO suggest the existence of an Achilles' heel that could be manipulated in order to facilitate the "kill" phase of experimental HIV-1 eradication strategies

Kinetin and nitrogen in agronomic characteristics of soybean.

The objective of this work was to evaluate the application of kinetin associated with nitrogen in coverage on the agronomic characteristics and soybean yield. In the 2016/2017 harvest, a 6x2 factorial scheme was used, six doses of kinetin (0; 0.30; 0.60; 0.90; 1.20; 1.50 g ha&#8722;1) and two doses of N (20 and 40 kg ha&#8722;1) and in the 2017/2018 harvest, factorial scheme 5x2 was used, five doses of kinetin (0; 0.25; 0.75; 1.00; 1.25 g ha&#8722;1) and two doses of N (20 and 40 kg ha&#8722;1). Agronomic plant height characteristics, first pod insertion height, number of grains per plant, number of pods per plant, number of grains per pod, number of grains per pod, hundred-grain mass and grain yield were evaluated. The use of N alone and associated with kinetin increased the number of pods and grains in the 2016/2017 harvest. In the 2017/2018 crop, kinetin caused a reduction of 8.9% at plant height and N caused an increase in plant height and first pod insertion and reduced the number of pods and grains per plant, grains per pods and productivity