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Background: Breast implants are biomaterials eliciting a physiological and mandatory foreign body response.Objectives: We designed an animal study to investigate the impact of different implant surfaces on the formation of the perirprosthetic capsule, the inflammatory response and the cellular composition.Methods: We implanted 1 scaled-down version of breast implants by different manufactures on 70 female Sprague Dawley rats. Animals were divided into five groups of 14 animals. Group A received a smooth implant (Ra≈0.5µm) according to the ISO 14607-2018 classification, Group B smooth implant (Ra≈3.2µm), Group C smooth implant (Ra≈5µm), Group D macrotextured implant (Ra≈62µm) and Group E macrotextured implant (Ra≈75µm). At 60 days, all animals received a magnetic resonance imaging (MRI) and 35 animals were sacrificed and their capsules sent for histology (capsule thickness, inflammatory infiltrate) and immunohistochemistry analysis (cellular characterization). The remaining animals repeated the MRI at 120 days and were sacrificed following the same protocol.Results: MRI showed a thinner capsule in the smooth implants (Group A, B, C) at 60 days (p < 0.001) but not at 120 days (p = 0.039), confirmed with histology both at 60 days (p = 0.005) and 120 days (p < 0.001). Smooth implants (Group A, B, C) presented a mild inflammatory response at 60 days that was maintained at 120 days and a high M2-Macrophage concentration (anti-inflammatory).Conclusions: Our study confirms that smooth implants form a thinner capsule, inferior inflammatory infiltrate and a cellular composition that indicates a mild host inflammatory response. A new host inflammatory response classification is elaborated classifying breast implants into mild, moderate, and high. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the role of the lipid peak derived from 1H magnetic resonance (MR) spectroscopy in assessing cervical cancer prognosis, particularly in assessing response to neoadjuvant chemotherapy (NACT) of locally advanced cervical cancer (LACC). Methods: We enrolled 17 patients with histologically proven cervical cancer who underwent 3-T MR imaging at baseline. In addition to conventional imaging sequences for pelvic assessment, the protocol included a single-voxel point-resolved spectroscopy (PRESS) sequence, with repetition time of 1,500 ms and echo times of 28 and 144 ms. Spectra were analysed using the LCModel fitting routine, thus extracting multiple metabolites, including lipids (Lip) and total choline (tCho). Patients with LACC were treated with NACT and reassessed by MRI at term. Based on tumour volume reduction, patients were classified as good responder (GR; tumour volume reduction > 50%) and poor responder or nonresponder (PR-or-NR; tumour volume reduction ≤ 50%). Results: Of 17 patients, 11 were LACC. Of these 11, only 6 had both completed NACT and had good-quality 1H-MR spectra; 3 GR and 3 PR-or-NR. A significant difference in lipid values was observed in the two groups of patients, particularly with higher Lip values and higher Lip/tCho ratio in PR-NR patients (p =0.040). A significant difference was also observed in choline distribution (tCho), with higher values in GR patients (p = 0.040). Conclusions: Assessment of lipid peak at 1H-MR spectroscopy could be an additional quantitative parameter in predicting the response to NACT in patients with LACC. [ABSTRACT FROM AUTHOR]

We aimed at the further characterization of rats in which SERT gene silencing was achieved by hippocampal injection of a lentiviral vector, carrying three si‐RNA to block SERT mRNA at 66% of normal levels. Improved self‐control and reduced restlessness were already demonstrated in these rats. Present further studies consisted of male adult rats, bilaterally inoculated within the hippocampus; control rats received lentivirus particles inactivated with heat. Both groups were maintained in isolation for 5 months, starting from inoculation. Neurochemical changes were studied by proton magnetic resonance spectroscopy (1H‐MRS): we found increased hippocampal viability and bioenergetic potential; however, rats showed a behaviorally depressive pattern, also characterized by enhanced affiliation. Based on the extent of such effects, the whole lenti‐SERT group was divided into two subgroups, termed intermediate‐ and extreme‐ phenotype profiles. While all rats had a widespread modification within dorsal/ventral striatum, amygdala, and hypothalamus, only the former subgroup showed an involvement of Raphé medialis, while, for the latter subgroup, an increase of SERT within hippocampus was unexpectedly caused. Within the less‐affected "intermediate" rats, hippocampal 5‐HT7 receptors were down‐modulated, and also similarly within substantia nigra, septum, and neocortex. This picture demonstrates that additional rather than fewer neurobiological changes accompany a lower phenotypic expression. Overall, tapping hippocampal SERT affected the balance between habits versus strategies of coping by promoting morphogenetic processes indicative of a serotonergic fiber plasticity. Supplementary studies about serotonergic dynamics and neurogenesis within fronto‐striatal circuits are needed. [ABSTRACT FROM AUTHOR]

Despite different molecular tumor profiles indicate that human epidermal growth factor receptor 2 (HER2) messenger RNA (mRNA) levels mirror HER2 addiction and trastuzumab benefit in HER2‐positive breast cancer (BC), the identification of noninvasive clinical predictors of trastuzumab sensitivity remains an unmet clinical need. In the current study, we investigated whether intratumor lactate levels reflect HER2 addiction and, in turn, trastuzumab susceptibility. Accordingly, the gene expression profiles of transgenic murine BC cell lines expressing the human d16HER2 variant (HER2‐addicted) or human full‐length HER2 (WTHER2; HER2‐nonaddicted) revealed a significant enrichment of glycolysis‐related gene pathways in HER2‐addicted cells. We studied the metabolic content of 22 human HER2‐positive BC by quantitative nuclear magnetic resonance spectroscopy and found that those cases with higher lactate levels were characterized by higher HER2 transcript levels. Moreover, gene expression analyses of HER2‐positive BC samples from a TCGA data set revealed a significant enrichment in glycolysis‐related pathways in high/HER2‐addicted tumors. These data were confirmed by metabolic analyses of human HER2‐positive BC cell lines with high or low HER2 transcript levels, which revealed significantly more active glycolytic metabolism in high HER2 transcript than in low HER2 transcript cells. Overall, our results provide evidence for noninvasive intratumor lactate detection as a potential metabolic biomarker of HER2 addiction and trastuzumab response suggesting the possibility to use in vivo imaging to assess lactate levels and, in turn, select HER2‐positive BC patients who are more likely to benefit from anti‐HER2 treatments. The purpose of this study was to identify a reliable, noninvasive, and novel biomarker associated with HER2 addiction that reflects the susceptibility to HER2‐specific therapy. Our results provide experimental and relevant support for the preclinical and clinical association between HER2 addiction/trastuzumab susceptibility and intratumor levels of lactate, a key metabolic player in cancer progression that is upregulated early in the development of malignancies. Through molecular and metabolic analyses, we found a statistically significant association among HER2 transcript levels, intratumor lactate levels and response to therapy, thus paving the way for the utilization of Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy as a powerful and independent tool to better tailor anti‐HER2 therapies and improve the outcomes of all patients with HER2‐positive BC. [ABSTRACT FROM AUTHOR]