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1.
J Surg Case Rep ; 2024(4): rjae184, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572276

RESUMO

Mesenchymal hamartoma of the liver (MHL) is rare. Less than 50 adult cases have been described. Due to their potential degeneration or recurrence, a complete surgical resection must be performed. We describe a case of a 26-year-old with a palpable solid lesion, which displaced abdominal organs. Percutaneous needle biopsies suggested the diagnosis of MHL. A right hemi-hepatectomy without segment 1 was performed; the post-operative course was uneventful. The mesenchymal component of the tumour was reactive to desmin and smooth muscle actin. Low proliferation index was confirmed (MIB1). Genetic counselling: the sequencing analysis of DICER1 and CDKN1C gene was negative, DNA methylation analysis on the chromosome 11p15 region was normal. After 42 months, there was no recurrence. In conclusion, clinicians should consider MHL in the differential diagnosis. The dimension and the need of radicality impose major liver resections or liver transplantations, which should be performed in referral centres.

2.
Cancers (Basel) ; 16(8)2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38672554

RESUMO

Proton beam therapy is considered a step forward with respect to electromagnetic radiation, thanks to the reduction in the dose delivered. Among unwanted effects to healthy tissue, cardiovascular complications are a known long-term radiotherapy complication. The transcriptional response of cardiac tissue from xenografted BALB/c nude mice obtained at 3 and 10 days after proton irradiation covering both the tumor region and the underlying healthy tissue was analyzed as a function of dose and time. Three doses were used: 2 Gy, 6 Gy, and 9 Gy. The intermediate dose had caused the greatest impact at 3 days after irradiation: at 2 Gy, 219 genes were differently expressed, many of them represented by zinc finger proteins; at 6 Gy, there were 1109, with a predominance of genes involved in energy metabolism and responses to stimuli; and at 9 Gy, there were 105, mainly represented by zinc finger proteins and molecules involved in the regulation of cardiac function. After 10 days, no significant effects were detected, suggesting that cellular repair mechanisms had defused the potential alterations in gene expression. The nonlinear dose-response curve indicates a need to update the models built on photons to improve accuracy in health risk prediction. Our data also suggest a possible role for zinc finger protein genes as markers of proton therapy efficacy.

3.
Life (Basel) ; 14(3)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38541733

RESUMO

The aim of the present study consists of the evaluation of the biodistribution of a novel 68Ga-labeled radiopharmaceutical, [68Ga]Ga-NODAGA-Z360, injected into Balb/c nude mice through histopathological analysis on bioptic samples and radiomics analysis of positron emission tomography/computed tomography (PET/CT) images. The 68Ga-labeled radiopharmaceutical was designed to specifically bind to the cholecystokinin receptor (CCK2R). This receptor, naturally present in healthy tissues such as the stomach, is a biomarker for numerous tumors when overexpressed. In this experiment, Balb/c nude mice were xenografted with a human epidermoid carcinoma A431 cell line (A431 WT) and overexpressing CCK2R (A431 CCK2R+), while controls received a wild-type cell line. PET images were processed, segmented after atlas-based co-registration and, consequently, 112 radiomics features were extracted for each investigated organ / tissue. To confirm the histopathology at the tissue level and correlate it with the degree of PET uptake, the studies were supported by digital pathology. As a result of the analyses, the differences in radiomics features in different body districts confirmed the correct targeting of the radiopharmaceutical. In preclinical imaging, the methodology confirms the importance of a decision-support system based on artificial intelligence algorithms for the assessment of radiopharmaceutical biodistribution.

4.
Cell Prolif ; 57(6): e13606, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38454614

RESUMO

Glioblastoma (GBM), a WHO grade IV glioma, is a malignant primary brain tumour for which combination of surgery, chemotherapy and radiotherapy is the first-line approach despite adverse effects. Tumour microenvironment (TME) is characterized by an interplay of cells and soluble factors holding a critical role in neoplastic development. Significant pathophysiological changes have been found in GBM TME, such as glia activation and oxidative stress. Microglia play a crucial role in favouring GBM growth, representing target cells of immune escape mechanisms. Our study aims at analysing radiation-induced effects in modulating intercellular communication and identifying the basis of protective mechanisms in radiation-naïve GBM cells. Tumour cells were treated with conditioned media (CM) derived from 0, 2 or 15 Gy irradiated GBM cells or 0, 2 or 15 Gy irradiated human microglia. We demonstrated that irradiated microglia promote an increase of GBM cell lines proliferation through paracrine signalling. On the contrary, irradiated GBM-derived CM affect viability, triggering cell death mechanisms. In addition, we investigated whether these processes involve mitochondrial mass, fitness and oxidative phosphorylation and how GBM cells respond at these induced alterations. Our study suggests that off-target radiotherapy modulates microglia to support GBM proliferation and induce metabolic modifications.


Assuntos
Neoplasias Encefálicas , Proliferação de Células , Glioblastoma , Microglia , Microambiente Tumoral , Humanos , Glioblastoma/radioterapia , Glioblastoma/patologia , Glioblastoma/metabolismo , Microglia/metabolismo , Microglia/patologia , Microglia/efeitos da radiação , Proliferação de Células/efeitos da radiação , Linhagem Celular Tumoral , Meios de Cultivo Condicionados/farmacologia , Microambiente Tumoral/efeitos da radiação , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/metabolismo , Sobrevivência Celular/efeitos da radiação , Mitocôndrias/metabolismo , Mitocôndrias/efeitos da radiação
5.
Int J Mol Sci ; 25(4)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38396757

RESUMO

The hypoxic pattern of glioblastoma (GBM) is known to be a primary cause of radioresistance. Our study explored the possibility of using gene knockdown of key factors involved in the molecular response to hypoxia, to overcome GBM radioresistance. We used the U87 cell line subjected to chemical hypoxia generated by CoCl2 and exposed to 2 Gy of X-rays, as single or combined treatments, and evaluated gene expression changes of biomarkers involved in the Warburg effect, cell cycle control, and survival to identify the best molecular targets to be knocked-down, among those directly activated by the HIF-1α transcription factor. By this approach, glut-3 and pdk-1 genes were chosen, and the effects of their morpholino-induced gene silencing were evaluated by exploring the proliferative rates and the molecular modifications of the above-mentioned biomarkers. We found that, after combined treatments, glut-3 gene knockdown induced a greater decrease in cell proliferation, compared to pdk-1 gene knockdown and strong upregulation of glut-1 and ldha, as a sign of cell response to restore the anaerobic glycolysis pathway. Overall, glut-3 gene knockdown offered a better chance of controlling the anaerobic use of pyruvate and a better proliferation rate reduction, suggesting it is a suitable silencing target to overcome radioresistance.


Assuntos
Glioblastoma , Transportador de Glucose Tipo 3 , Humanos , Biomarcadores/metabolismo , Hipóxia Celular/genética , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Glioblastoma/genética , Glioblastoma/radioterapia , Glioblastoma/metabolismo , Hipóxia , Transportador de Glucose Tipo 3/genética , Transportador de Glucose Tipo 3/metabolismo
6.
Diagnostics (Basel) ; 13(20)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37892077

RESUMO

Idiopathic acute pancreatitis (IAP) presents a diagnostic challenge and refers to cases where the cause of acute pancreatitis remains uncertain despite a comprehensive diagnostic evaluation. Endoscopic ultrasound (EUS) has emerged as a valuable tool in the diagnostic workup of IAP. This review explores the pivotal role of EUS in detecting the actual cause of IAP and assessing its accuracy, timing, safety, and future technological improvement. In this review, we investigate the role of EUS in identifying the actual cause of IAP by examining the available literature. We aim to assess possible existing evidence regarding EUS accuracy, timing, and safety and explore potential trends of future technological improvements in EUS for diagnostic purposes. Following PRISMA guidelines, 60 pertinent studies were selected and analysed. EUS emerges as a crucial diagnostic tool, particularly when conventional imaging fails. It can offer intricate visualization of the pancreas, biliary system, and adjacent structures. Microlithiasis, biliary sludge, chronic pancreatitis, and small pancreatic tumors seem to be much more accurately identified with EUS in the setting of IAP. The optimal timing for EUS is post-resolution of the acute phase of the disease. With a low rate of complications, EUS poses minimal safety concerns. EUS-guided interventions, including fine-needle aspiration, collection drainage, and biopsies, aid in the cytological analysis. With high diagnostic accuracy, safety, and therapeutic potential, EUS is able to improve patient outcomes when managing IAP. Further refinement of EUS techniques and cost-effectiveness assessment of EUS-guided approaches need to be explored in multicentre prospective studies. This review underscores EUS as a transformative tool in unraveling IAP's enigma and advancing diagnostic and therapeutic strategies.

7.
Diagnostics (Basel) ; 13(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37046428

RESUMO

Radionuclides are unstable isotopes that mainly emit alpha (α), beta (ß) or gamma (γ) radiation through radiation decay. Therefore, they are used in the biomedical field to label biomolecules or drugs for diagnostic imaging applications, such as positron emission tomography (PET) and/or single-photon emission computed tomography (SPECT). A growing field of research is the development of new radiopharmaceuticals for use in cancer treatments. Preclinical studies are the gold standard for translational research. Specifically, in vitro radiopharmaceutical studies are based on the use of radiopharmaceuticals directly on cells. To date, radiometric ß- and γ-counters are the only tools able to assess a preclinical in vitro assay with the aim of estimating uptake, retention, and release parameters, including time- and dose-dependent cytotoxicity and kinetic parameters. This review has been designed for researchers, such as biologists and biotechnologists, who would like to approach the radiobiology field and conduct in vitro assays for cellular radioactivity evaluations using radiometric counters. To demonstrate the importance of in vitro radiopharmaceutical assays using radiometric counters with a view to radiogenomics, many studies based on 64Cu-, 68Ga-, 125I-, and 99mTc-labeled radiopharmaceuticals have been revised and summarized in this manuscript.

8.
Commun Biol ; 6(1): 388, 2023 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-37031346

RESUMO

Despite aggressive therapeutic regimens, glioblastoma (GBM) represents a deadly brain tumor with significant aggressiveness, radioresistance and chemoresistance, leading to dismal prognosis. Hypoxic microenvironment, which characterizes GBM, is associated with reduced therapeutic effectiveness. Moreover, current irradiation approaches are limited by uncertain tumor delineation and severe side effects that comprehensively lead to unsuccessful treatment and to a worsening of the quality of life of GBM patients. Proton beam offers the opportunity of reduced side effects and a depth-dose profile, which, unfortunately, are coupled with low relative biological effectiveness (RBE). The use of radiosensitizing agents, such as boron-containing molecules, enhances proton RBE and increases the effectiveness on proton beam-hit targets. We report a first preclinical evaluation of proton boron capture therapy (PBCT) in a preclinical model of GBM analyzed via µ-positron emission tomography/computed tomography (µPET-CT) assisted live imaging, finding a significant increased therapeutic effectiveness of PBCT versus proton coupled with an increased cell death and mitophagy. Our work supports PBCT and radiosensitizing agents as a scalable strategy to treat GBM exploiting ballistic advances of proton beam and increasing therapeutic effectiveness and quality of life in GBM patients.


Assuntos
Glioblastoma , Radiossensibilizantes , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Glioblastoma/patologia , Prótons , Boro , Mitofagia , Qualidade de Vida , Radiossensibilizantes/farmacologia , Morte Celular , Microambiente Tumoral
9.
Molecules ; 27(13)2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35807404

RESUMO

Copper radioisotopes are generally employed for cancer imaging and therapy when firmly coordinated via a chelating agent coupled to a tumor-seeking vector. However, the biologically triggered Cu2+-Cu+ redox switching may constrain the in vivo integrity of the resulting complex, leading to demetallation processes. This unsought pathway is expected to be hindered by chelators bearing N, O, and S donors which appropriately complements the borderline-hard and soft nature of Cu2+ and Cu+. In this work, the labelling performances of a series of S-rich polyazamacrocyclic chelators with [64Cu]Cu2+ and the stability of the [64Cu]Cu-complexes thereof were evaluated. Among the chelators considered, the best results were obtained with 1,7-bis [2-(methylsulfanyl)ethyl]-4,10,diacetic acid-1,4,7,10-tetraazacyclododecane (DO2A2S). DO2A2S was labelled at high molar activities in mild reaction conditions, and its [64Cu]Cu2+ complex showed excellent integrity in human serum over 24 h. Biodistribution studies in BALB/c nude mice performed with [64Cu][Cu(DO2A2S)] revealed a behavior similar to other [64Cu]Cu-labelled cyclen derivatives characterized by high liver and kidney uptake, which could either be ascribed to transchelation phenomena or metabolic processing of the intact complex.


Assuntos
Radioisótopos de Cobre , Medicina de Precisão , Animais , Quelantes , Camundongos , Camundongos Nus , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/metabolismo , Distribuição Tecidual
10.
J Surg Case Rep ; 2022(6): rjac305, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35755016

RESUMO

Intestinal tuberculosis (ITB) represents an important diagnostic challenge in the clinical setting, as it generally can occur as a chronic condition often mimicking other diseases such as Crohn's disease (CD), and can present itself with acute onset, which can be life-threatening. A 29-years-old Chinese woman coming to ER with abdominal pain, fever and weight loss. Computed tomography and colonoscopy images were not diagnostic. Despite medical therapy, the patient progressively worsened developing sepsis requiring emergency surgery. Pathological and microbiological examination of the colon both pointed towards gastrointestinal tuberculosis involvement. Although ITB is generally a chronic-wasting condition, it can also occur as acute abdomen representing an absolute surgical emergency. Although caseation and necrosis in granulomas can be used for diagnosis of ITB, preoperative diagnosis is still challenging. Endoscopic biopsies targeted to ulcerous lesions could be an essential diagnostic tool, contrary to those targeted to the ulcers' edges as performed in CD.

11.
Biomedicines ; 10(4)2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35453557

RESUMO

In 2021 the World Health Organization published the fifth and latest version of the Central Nervous System tumors classification, which incorporates and summarizes a long list of updates from the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy work. Among the adult-type diffuse gliomas, glioblastoma represents most primary brain tumors in the neuro-oncology practice of adults. Despite massive efforts in the field of neuro-oncology diagnostics to ensure a proper taxonomy, the identification of glioblastoma-tumor subtypes is not accompanied by personalized therapies, and no improvements in terms of overall survival have been achieved so far, confirming the existence of open and unresolved issues. The aim of this review is to illustrate and elucidate the state of art regarding the foremost biological and molecular mechanisms that guide the beginning and the progression of this cancer, showing the salient features of tumor hallmarks in glioblastoma. Pathophysiology processes are discussed on molecular and cellular levels, highlighting the critical overlaps that are involved into the creation of a complex tumor microenvironment. The description of glioblastoma hallmarks shows how tumoral processes can be linked together, finding their involvement within distinct areas that are engaged for cancer-malignancy establishment and maintenance. The evidence presented provides the promising view that glioblastoma represents interconnected hallmarks that may led to a better understanding of tumor pathophysiology, therefore driving the development of new therapeutic strategies and approaches.

12.
J Imaging ; 8(4)2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35448219

RESUMO

The 64Cu-labeled chelator was analyzed in vivo by positron emission tomography (PET) imaging to evaluate its biodistribution in a murine model at different acquisition times. For this purpose, nine 6-week-old female Balb/C nude strain mice underwent micro-PET imaging at three different time points after 64Cu-labeled chelator injection. Specifically, the mice were divided into group 1 (acquisition 1 h after [64Cu] chelator administration, n = 3 mice), group 2 (acquisition 4 h after [64Cu]chelator administration, n = 3 mice), and group 3 (acquisition 24 h after [64Cu] chelator administration, n = 3 mice). Successively, all PET studies were segmented by means of registration with a standard template space (3D whole-body Digimouse atlas), and 108 radiomics features were extracted from seven organs (namely, heart, bladder, stomach, liver, spleen, kidney, and lung) to investigate possible changes over time in [64Cu]chelator biodistribution. The one-way analysis of variance and post hoc Tukey Honestly Significant Difference test revealed that, while heart, stomach, spleen, kidney, and lung districts showed a very low percentage of radiomics features with significant variations (p-value < 0.05) among the three groups of mice, a large number of features (greater than 60% and 50%, respectively) that varied significantly between groups were observed in bladder and liver, indicating a different in vivo uptake of the 64Cu-labeled chelator over time. The proposed methodology may improve the method of calculating the [64Cu]chelator biodistribution and open the way towards a decision support system in the field of new radiopharmaceuticals used in preclinical imaging trials.

13.
Radiat Oncol ; 17(1): 77, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428301

RESUMO

BACKGROUND: There is currently significant interest in assessing the role of oxygen in the radiobiological effects at ultra-high dose rates. Oxygen modulation is postulated to play a role in the enhanced sparing effect observed in FLASH radiotherapy, where particles are delivered at 40-1000 Gy/s. Furthermore, the development of laser-driven accelerators now enables radiobiology experiments in extreme regimes where dose rates can exceed 109 Gy/s, and predicted oxygen depletion effects on cellular response can be tested. Access to appropriate experimental enviroments, allowing measurements under controlled oxygenation conditions, is a key requirement for these studies. We report on the development and application of a bespoke portable hypoxia chamber specifically designed for experiments employing laser-driven sources, but also suitable for comparator studies under FLASH and conventional irradiation conditions. MATERIALS AND METHODS: We used oxygen concentration measurements to test the induction of hypoxia and the maintenance capacity of the chambers. Cellular hypoxia induction was verified using hypoxia inducible factor-1α immunostaining. Calibrated radiochromic films and GEANT-4 simulations verified the dosimetry variations inside and outside the chambers. We irradiated hypoxic human skin fibroblasts (AG01522B) cells with laser-driven protons, conventional protons and reference 225 kVp X-rays to quantify DNA DSB damage and repair under hypoxia. We further measured the oxygen enhancement ratio for cell survival after X-ray exposure in normal fibroblast and radioresistant patient- derived GBM stem cells. RESULTS: Oxygen measurements showed that our chambers maintained a radiobiological hypoxic environment for at least 45 min and pathological hypoxia for up to 24 h after disconnecting the chambers from the gas supply. We observed a significant reduction in the 53BP1 foci induced by laser-driven protons, conventional protons and X-rays in the hypoxic cells compared to normoxic cells at 30 min post-irradiation. Under hypoxic irradiations, the Laser-driven protons induced significant residual DNA DSB damage in hypoxic AG01522B cells compared to the conventional dose rate protons suggesting an important impact of these extremely high dose-rate exposures. We obtained an oxygen enhancement ratio (OER) of 2.1 ± 0.1 and 2.5 ± 0.1 respectively for the AG01522B and patient-derived GBM stem cells for X-ray irradiation using our hypoxia chambers. CONCLUSION: We demonstrated the design and application of portable hypoxia chambers for studying cellular radiobiological endpoints after exposure to laser-driven protons at ultra-high dose, conventional protons and X-rays. Suitable levels of reduced oxygen concentration could be maintained in the absence of external gassing to quantify hypoxic effects. The data obtained provided indication of an enhanced residual DNA DSB damage under hypoxic conditions at ultra-high dose rate compared to the conventional protons or X-rays.


Assuntos
Prótons , Radiobiologia , DNA/efeitos da radiação , Humanos , Hipóxia , Lasers , Oxigênio
14.
Updates Surg ; 74(5): 1763-1771, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35304900

RESUMO

Multi-drug resistant organisms (MDR-Os) are emerging as a significant cause of surgical site infections (SSI), but clinical outcomes and risk factors associated to MDR-Os-SSI have been poorly investigated in general surgery. Aims were to investigate risk factors, clinical outcomes and costs of care of multi-drug resistant organisms (MDR-Os-SSI) in general surgery. From January 2018 to December 2019, all the consecutive, unselected patients affected by MDR-O SSI were prospectively evaluated. In the same period, patients with non-MDR-O SSI and without SSI, matched for clinical and surgical data were used as control groups. Risk factors for infection, clinical outcome, and costs of care were compared by univariate and multivariate analysis. Among 3494 patients operated on during the study period, 47 presented an MDR-O SSI. Two control groups of 47 patients with non-MDR-O SSI and without SSI were identified. MDR-Os SSI were caused by poly-microbial etiology, meanly related to Gram negative Enterobacteriales. MDR-Os-SSI were related to major postoperative complications. At univariate analysis, iterative surgery, open abdomen, intensive care, hospital stay, and use of aggressive and expensive therapies were associated to MDR-Os-SSI. At multivariate analysis, only iterative surgery and the need of total parenteral and immune-nutrition were significantly associated to MDR-Os-SSI. The extra-cost of MDR-Os-SSI treatment was 150% in comparison to uncomplicated patients. MDR-Os SSI seems to be associated with major postoperative complications and reoperative surgery, they are demanding in terms of clinical workload and costs of care, they are rare but increasing, and difficult to prevent with current strategies.


Assuntos
Abdome , Complicações Pós-Operatórias , Infecção da Ferida Cirúrgica , Abdome/cirurgia , Estudos de Casos e Controles , Resistência a Múltiplos Medicamentos , Humanos , Tempo de Internação , Fatores de Risco , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle
15.
J Pers Med ; 12(2)2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35207800

RESUMO

Despite all the recent pharmacological advances and the introduction of targeted therapies in clinical practice, cancer still remains one of the leading cause of death, accounting for 10 million deaths per year, based on the most recent reports [...].

16.
Front Surg ; 9: 834870, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35198598

RESUMO

From 30 to 70% of patients with Crohn's disease (CD) may develop perianal fistulas during their lifetime. The medical and surgical management of this complication is challenging, and its treatment still gives unsatisfactory results. However, recent studies on adipose-derived mesenchymal stem cells have proven their anti-inflammatory and immuno-modulatory potential, representing a new promising tool in the treatment of such stubborn disease. We report our initial experience with three patients who had recurrent perianal CD treated with local infiltration of stem cell darvadstrocel (Alofisel). All the patients had a long history of perianal disease refractory to multiple medical and surgical treatments. The preoperative workup included transperineal ultrasound (TP-US), pelvic MRI, and colonoscopy that ruled out active proctitis in all the patients. The post-treatment follow-up included clinical assessment at 1, 3, and 6 months with repeated MRI and TP-US at 6 months. At 6 months, 2 patients had a clinical response despite radiological persistence of fistula tracts, while one patient presented perianal fistula recurrence complicated by perianal abscess. Although our experience is limited to 3 patients and a short follow-up, our results confirm that darvadstrocel injection is a safe procedure, with a good clinical response in most of the patients, but that it apparently had no effect on the anatomical modification of the fistula tracts. Long-term results, with a rigorous assessment of anatomical lesions, are still needed to support the promising data of the literature.

18.
Life (Basel) ; 11(11)2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34833068

RESUMO

The rapid improvement of space technologies is leading to the continuous increase of space missions that will soon bring humans back to the Moon and, in the coming future, toward longer interplanetary missions such as the one to Mars. The idea of living in space is charming and fascinating; however, the space environment is a harsh place to host human life and exposes the crew to many physical challenges. The absence of gravity experienced in space affects many aspects of human biology and can be reproduced in vitro with the help of microgravity simulators. Simulated microgravity (s-µg) is applied in many fields of research, ranging from cell biology to physics, including cancer biology. In our study, we aimed to characterize, at the biological and mechanical level, a Random Positioning Machine in order to simulate microgravity in an in vitro model of Triple-Negative Breast Cancer (TNBC). We investigated the effects played by s-µg by analyzing the change of expression of some genes that drive proliferation, survival, cell death, cancer stemness, and metastasis in the human MDA-MB-231 cell line. Besides the mechanical verification of the RPM used in our studies, our biological findings highlighted the impact of s-µg and its putative involvement in cancer progression.

19.
Front Oncol ; 11: 682647, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262867

RESUMO

Protontherapy is a rapidly expanding radiotherapy modality where accelerated proton beams are used to precisely deliver the dose to the tumor target but is generally considered ineffective against radioresistant tumors. Proton-Boron Capture Therapy (PBCT) is a novel approach aimed at enhancing proton biological effectiveness. PBCT exploits a nuclear fusion reaction between low-energy protons and 11B atoms, i.e. p+11B→ 3α (p-B), which is supposed to produce highly-DNA damaging α-particles exclusively across the tumor-conformed Spread-Out Bragg Peak (SOBP), without harming healthy tissues in the beam entrance channel. To confirm previous work on PBCT, here we report new in-vitro data obtained at the 62-MeV ocular melanoma-dedicated proton beamline of the INFN-Laboratori Nazionali del Sud (LNS), Catania, Italy. For the first time, we also tested PBCT at the 250-MeV proton beamline used for deep-seated cancers at the Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, Italy. We used Sodium Mercaptododecaborate (BSH) as 11B carrier, DU145 prostate cancer cells to assess cell killing and non-cancer epithelial breast MCF-10A cells for quantifying chromosome aberrations (CAs) by FISH painting and DNA repair pathway protein expression by western blotting. Cells were exposed at various depths along the two clinical SOBPs. Compared to exposure in the absence of boron, proton irradiation in the presence of BSH significantly reduced DU145 clonogenic survival and increased both frequency and complexity of CAs in MCF-10A cells at the mid- and distal SOBP positions, but not at the beam entrance. BSH-mediated enhancement of DNA damage response was also found at mid-SOBP. These results corroborate PBCT as a strategy to render protontherapy amenable towards radiotherapy-resilient tumor. If coupled with emerging proton FLASH radiotherapy modalities, PBCT could thus widen the protontherapy therapeutic index.

20.
J Surg Case Rep ; 2021(7): rjab308, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34316347

RESUMO

Parathyroid lipoadenoma is a very rare cause of primary hyperparathyroidism. Preoperative imaging techniques often fail to detect such lesions, and even during surgery they can be misinterpreted just as fat tissue. A 62-year-old woman clinically monitored for primary hyperparathyroidism, with hypertension and a left nephrectomy for hydrouretheronephrosis caused by recurrent kidney stones. A neck ultrasound showed a nodule consistent with left parathyroid of 9 × 5 mm, which was not confirmed on single-photon-emission computed tomography/computed tomography (CT) scan. On surgery, a voluminous lesion with adipose appearance and texture was removed. Frozen sections and intraoperative parathyroid hormone (PTH) confirmed such lesion to be a parathyroid lipoadenoma. Parathyroid lipoadenomas are difficult to localize preoperatively. Sometimes they can be seen by ultrasound scan as hyperechoich lesion, but scintigraphy and CT often fail to identify them. Only the awareness of such lesions and the use of intraoperative PTH can avoid unnecessary extensive cervical exploration.

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