management of one patient with oligoprogressive thyroid cancer during treatment with lenvatinib

Recent thyroid cancer guidelines found it reasonable to use local therapies during treatment with tyrosine kinase inhibitors (TKIs) in selected patients with oligoprogressive disease, namely, in the presence of a single progressing lesion in an otherwise TKI-responsive metastatic cancer. However, there is a lack of experience in the management of oligoprogressive thyroid cancers. This report illustrates the case of one patient with oligoprogressive thyroid cancer during therapy with lenvatinib. We found that the application of local ablative therapy in oligoprogressive disease prolonged the progression-free survival and thus extended the time to therapy interruption. However, the optimal care for TKI-treated oligoprogressive cancers remains unclear and needs to be investigated in prospective trials

A Trifunctional ATRP Initiator Bearing Adaptable Bonds

Atom Transfer Radical Polymerization (ATRP) allows for the production of polymers with precise control over molecular weight, dispersity, topology, composition, and functionality. Functional groups can be introduced into the polymer through post-functionalization of chain ends, or on the alkyl residue of the initiator, or by introducing functionalized (co)monomers, greatly greatly enhancing the targetable applications. In addition, the desired functional group can also be carried by the ATRP initiator. Some researchers have explored initiators with hydrolysis- or heat-sensitive functionalities to impart self-healing properties to the final polymer. However, the commonly used aliphatic halide ester initiators have shown poor thermal stability. To address this issue, we recently developed a novel bifunctional benzamide-containing initiator employed in ARGET ATRP of styrene, demonstrating enhanced thermal stability. Covalent Adaptable Networks (CANs) have emerged as a solution for improving the recyclability of thermoset materials. CANs can reorganize connectivity between chains upon thermal treatment, enabling reprocessing. Our goal is to modify the structure of the benzamide-containing initiator to develop a trifunctional initiator bearing adaptable bonds

Aleurocanthus spiniferus, an alien invasive threat to Europe. AssociatEd bacterial community and natural enemies

Aleurocanthus spiniferus also known as orange spiny whitefly (OSW), is a pest native to tropical Asia that in the last century has spread throughout Asia, reaching Africa, Australia, and Pacific islands. In 2008 the first European OSW population was recorded in Apulia region (South East Italy) and allowed EPPO to add the species as a quarantine threat to Europe now in the A2 list. In the following years OSW spread and invaded new territories of Italy, Croatia and Montenegro. Although OSW polyphagy is already well-known, new associations with autochthonous and allochthonous plants have been reported showing its host-shifting ability. To counteract an upcoming pan-Mediterranean invasion updated bio-ethological information of the pest and the role of possible natural enemies are essential to implement a correct IPM strategy. Field samplings have been aimed at the identification of natural enemies and the evaluation of their efficacy. Furthermore, through insect small-RNA sequencing and by Denaturing Gradient Gel Electrophoresis (DGGE) technique coupled with 16S-rRNA gene sequencing, the primary symbiotic bacteria of OSW have been identified. Sampling on natural enemies highlighted the presence of predatory species belonging to the Coccinellidae family. Besides to the almost ineffective populations of Oenopia conglobata and Clithostetus arcuatus, new findings detected scattered Delphastus sp. populations along the western coast of Italy. Both adult and larvae of this ladybird species preyed OSW developmental stages. The evaluation of the role of Delphastus sp. as biocontrol agent is underway. The first study on OSW microbiota allowed to find symbiotic bacteria commonly associated with the genus Aleurocanthus: Portiera sp., Serratia sp., Wolbachia sp., Rickettsia sp. and, although sporadically, other species. Further studies will target the functional role of these symbionts to develop an effective IPM tailored for Countries at risk

Trematocine, a Novel Antimicrobial Peptide from the Antarctic Fish Trematomus bernacchii: Identification and Biological Activity

Antimicrobial peptides (AMPs) are short peptides active against a wide range of pathogens and, therefore, they are considered a useful alternative to conventional antibiotics. We have identified a new AMP in a transcriptome derived from the Antarctic fish Trematomus bernacchii. This peptide, named Trematocine, has been investigated for its expression both at the basal level and after in vivo immunization with an endemic Antarctic bacterium (Psychrobacter sp. TAD1). Results agree with the expected behavior of a fish innate immune component, therefore we decided to synthesize the putative mature sequence of Trematocine to determine the structure, the interaction with biological membranes, and the biological activity. We showed that Trematocine folds into a \u3b1-helical structure in the presence of both zwitterionic and anionic charged vesicles. We demonstrated that Trematocine has a highly specific interaction with anionic charged vesicles and that it can kill Gram-negative bacteria, possibly via a carpet like mechanism. Moreover, Trematocine showed minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against selected Gram-positive and Gram-negative bacteria similar to other AMPs isolated from Antarctic fishes. The peptide is a possible candidate for a new drug as it does not show any haemolytic or cytotoxic activity against mammalian cells at the concentration needed to kill the tested bacteria

Outer Membrane Vesicles Derived from Klebsiella pneumoniae Influence the miRNA Expression Profile in Human Bronchial Epithelial BEAS-2B Cells

: Klebsiella pneumoniae is an opportunistic pathogen that causes nosocomial and community-acquired infections. The spread of resistant strains of K. pneumoniae represents a growing threat to human health, due to the exhaustion of effective treatments. K. pneumoniae releases outer membrane vesicles (OMVs). OMVs are a vehicle for the transport of virulence factors to host cells, causing cell injury. Previous studies have shown changes of gene expression in human bronchial epithelial cells after treatment with K. pneumoniae OMVs. These variations in gene expression could be regulated through microRNAs (miRNAs), which participate in several biological mechanisms. Thereafter, miRNA expression profiles in human bronchial epithelial cells were evaluated during infection with standard and clinical K. pneumoniae strains. Microarray analysis and RT-qPCR identified the dysregulation of miR-223, hsa-miR-21, hsa-miR-25 and hsa-let-7g miRNA sequences. Target gene prediction revealed the essential role of these miRNAs in the regulation of host immune responses involving NF-ĸB (miR-223), TLR4 (hsa-miR-21), cytokine (hsa-miR-25) and IL-6 (hsa-let-7g miRNA) signalling pathways. The current study provides the first large scale expression profile of miRNAs from lung cells and predicted gene targets, following exposure to K. pneumoniae OMVs. Our results suggest the importance of OMVs in the inflammatory response

The Interaction between Reactive Peritoneal Mesothelial Cells and Tumor Cells via Extracellular Vesicles Facilitates Colorectal Cancer Dissemination

Simple SummaryEmerging evidence has suggested that cancer-derived extracellular vesicles (EVs) have a crucial role in mediating directional metastasis to the peritoneal surface in colorectal cancer (CRC). We investigated the EV-mediated crosstalk between tumor and mesothelial cells which may drive remodeling of the premetastatic niche to allow tumor spread to the peritoneal surface. Our findings demonstrated that cancer-derived EVs triggered apoptosis and reduced mesothelial cell invasiveness and mesothelial-to-mesenchymal transition. On the other hand, mesothelial cells actively supported tumor invasion by releasing EVs, which induced upregulation of the major pro-invasive system in tumor cells. For the first time, we provide evidence of EV-driven mechanisms of CRC progression in patient-derived models, highlighting the crucial role of EVs in the reprogramming of mesothelial and tumor cells to establish the metastatic process.Advanced colorectal cancer (CRC) is highly metastatic and often results in peritoneal dissemination. The extracellular vesicles (EVs) released by cancer cells in the microenvironment are important mediators of tumor metastasis. We investigated the contribution of EV-mediated interaction between peritoneal mesothelial cells (MCs) and CRC cells in generating a pro-metastatic environment in the peritoneal cavity. Peritoneal MCs isolated from peritoneal lavage fluids displayed high CD44 expression, substantial mesothelial-to-mesenchymal transition (MMT) and released EVs that both directed tumor invasion and caused reprogramming of secretory profiles by increasing TGF-beta 1 and uPA/uPAR expression and MMP-2/9 activation in tumor cells. Notably, the EVs released by tumor cells induced apoptosis by activating caspase-3, peritoneal MC senescence, and MMT, thereby augmenting the tumor-promoting potential of these cells in the peritoneal cavity. By using pantoprazole, we reduced the biogenesis of EVs and their pro-tumor functions. In conclusion, our findings provided evidence of underlying mechanisms of CRC dissemination driven by the interaction of peritoneal MCs and tumor cells via the EVs released in the peritoneal cavity, which may have important implications for the clinical management of patients

Electrochemotherapy in Vulvar Cancer and Cisplatin Combined with Electroporation. Systematic Review and In Vitro Studies

Electrochemotherapy (ECT) is an emerging treatment for solid tumors and an attractive research field due to its clinical results. This therapy represents an alternative local treatment to the standard ones and is based on the tumor-directed delivery of non-ablative electrical pulses to maximize the action of specific cytotoxic drugs such as cisplatin (CSP) and bleomycin (BLM) and to promote cancer cell death. Nowadays, ECT is mainly recommended as palliative treatment. However, it can be applied to a wide range of superficial cancers, having an impact in preventing or delaying tumor progression and therefore in improving quality of life. In addition, during the natural history of the tumor, early ECT may improve patient outcomes. Our group has extensive clinical and research experience on ECT in vulvar tumors in the palliative setting, with 70% overall response rate. So far, in most studies, ECT was based on BLM. However, the potential of CSP in this setting seems interesting due to some theoretical advantages. The purpose of this report is to: (i) compare the efficacy of CSP and BLM-based ECT through a systematic literature review; (ii) report the results of our studies on CSP-resistant squamous cell tumors cell lines and the possibility to overcome chemoresistance using ECT; (iii) discuss the future ECT role in gynecological tumors and in particular in vulvar carcinoma

Cervical cancer benefits from trabectedin combination with the β-blocker propranolol: in vitro and ex vivo evaluations in patient-derived organoids

Background: Cervical cancer (CC) is characterized by genomic alterations in DNA repair genes, which could favor treatment with agents causing DNA double-strand breaks (DSBs), such as trabectedin. Hence, we evaluated the capability of trabectedin to inhibit CC viability and used ovarian cancer (OC) models as a reference. Since chronic stress may promote gynecological cancer and may hinder the efficacy of therapy, we investigated the potential of targeting β-adrenergic receptors with propranolol to enhance trabectedin efficacy and change tumor immunogenicity.Methods: OC cell lines, Caov-3 and SK-OV-3, CC cell lines, HeLa and OV2008, and patient-derived organoids were used as study models. MTT and 3D cell viability assays were used for drug(s) IC50 determination. The analysis of apoptosis, JC-1 mitochondrial membrane depolarization, cell cycle, and protein expression was performed by flow cytometry. Cell target modulation analyses were carried out by gene expression, Western blotting, immunofluorescence, and immunocytochemistry.Results: Trabectedin reduced the proliferation of both CC and OC cell lines and notably of CC patient-derived organoids. Mechanistically, trabectedin caused DNA DSBs and S-phase cell cycle arrest. Despite DNA DSBs, cells failed the formation of nuclear RAD51 foci and underwent apoptosis. Under norepinephrine stimulation, propranolol enhanced trabectedin efficacy, further inducing apoptosis through the involvement of mitochondria, Erk1/2 activation, and the increase of inducible COX-2. Notably, trabectedin and propranolol affected the expression of PD1 in both CC and OC cell lines.Conclusion: Overall, our results show that CC is responsive to trabectedin and provide translational evidence that could benefit CC treatment options. Our study pointed out that combined treatment offset trabectedin resistance caused by β-adrenergic receptor activation in both ovarian and cervical cancer models

“Ectomosphere”: Insects and Microorganism Interactions

This study focuses on interacting with insects and their ectosymbiont (lato sensu) microorganisms for environmentally safe plant production and protection. Some cases help compare insect-bearing, -driving, or -spreading relevant ectosymbiont microorganisms to endosymbionts’ behaviour. Ectosymbiotic bacteria can interact with insects by allowing them to improve the value of their pabula. In addition, some bacteria are essential for creating ecological niches that can host the development of pests. Insect-borne plant pathogens include bacteria, viruses, and fungi. These pathogens interact with their vectors to enhance reciprocal fitness. Knowing vector-phoront interaction could considerably increase chances for outbreak management, notably when sustained by quarantine vector ectosymbiont pathogens, such as the actual Xylella fastidiosa Mediterranean invasion episode. Insect pathogenic viruses have a close evolutionary relationship with their hosts, also being highly specific and obligate parasites. Sixteen virus families have been reported to infect insects and may be involved in the biological control of specific pests, including some economic weevils. Insects and fungi are among the most widespread organisms in nature and interact with each other, establishing symbiotic relationships ranging from mutualism to antagonism. The associations can influence the extent to which interacting organisms can exert their effects on plants and the proper management practices. Sustainable pest management also relies on entomopathogenic fungi; research on these species starts from their isolation from insect carcasses, followed by identification using conventional light or electron microscopy techniques. Thanks to the development of omics sciences, it is possible to identify entomopathogenic fungi with evolutionary histories that are less-shared with the target insect and can be proposed as pest antagonists. Many interesting omics can help detect the presence of entomopathogens in different natural matrices, such as soil or plants. The same techniques will help localize ectosymbionts, localization of recesses, or specialized morphological adaptation, greatly supporting the robust interpretation of the symbiont role. The manipulation and modulation of ectosymbionts could be a more promising way to counteract pests and borne pathogens, mitigating the impact of formulates and reducing food insecurity due to the lesser impact of direct damage and diseases. The promise has a preventive intent for more manageable and broader implications for pests, comparing what we can obtain using simpler, less-specific techniques and a less comprehensive approach to Integrated Pest Management (IPM).The present work acknowledges the support from: European Union’s Horizon 2020 research and innovation programme under Grant Agreements No. 635646-POnTE “Pest Organisms Threatening Europe”, No. 727987-XF-ACTORS “Xylella Fastidiosa Active Containment Through a multidisciplinary-Oriented Research Strategy”, Grant number 952337-MycoTWIN “Enhancing Research and Innovation Capacity of Tubitak MAM Food Institute on Management of Mycotoxigenic Fungi and Mycotoxins”, and CURE-Xf, H2020-Marie Sklodowska-Curie Actions—Research and Innovation Staff Exchange. Reference number: 634353, coordinated by CIHEAM Bari. The EU Funding Agency is not responsible for any use that may be made of the information it contains. European Union’s StopMedWaste “Innovative Sustainable technologies TO extend the shelf-life of Perishable MEDiterranean fresh fruit, vegetables and aromatic plants and to reduce WASTE” a PRIMA project ID: 1556. European Union’s Euphresco BasicS “Basic substances as an environmentally friendly alternative to synthetic pesticides for plant protection” project ID: 2020-C-353. The work was partially carried out in the framework of the National Projects: RIGENERA, granted by MASAF n. 207631, 9 May 2022, and GENFORAGRIS, granted by MASAF n. 207631, 9 May 2022; and regional projects “Laboratory network for the selection, characterisation and conservation of germplasm and for preventing the spread of economically-relevant and quarantine pests (SELGE) No. 14”, founded by the Apulia Region, PO FESR 2007–2013—Axis I, Line of intervention 1.2., Action 1.2.1; Research for Innovation (REFIN) POR Puglia 2014–2020 Project: 8C6E699D, and PON AIM, COD. AIM 1809249-Attività 1 Linea 1