Previous
Aim:
Fragment crystallizable (Fc) glycans modulate
Methods:
Molecular dynamics simulations were used to generate con
Results:
Two important interaction patterns have been observed. The first is the strong but non-specific interactions between two carbohydrate chains in free antibody. Secondly, it has been found that N-glycans carbohydrate chains can directly interact with CH3 domain in free antibody, and that the distance distribution between carbohydrate chains and CH3 domain clearly differentiate the free antibody, antibody-antigen complex, antibody-hFcγRI complex, and final antibody-antigen-hFcγRI complex.
Conclusions:
N-glycans partially acts as allosteric sensor and respond to antigen and hFcγRI binding.
Aim:
Fragment crystallizable (Fc) glycans modulate
Methods:
Molecular dynamics simulations were used to generate con
Results:
Two important interaction patterns have been observed. The first is the strong but non-specific interactions between two carbohydrate chains in free antibody. Secondly, it has been found that N-glycans carbohydrate chains can directly interact with CH3 domain in free antibody, and that the distance distribution between carbohydrate chains and CH3 domain clearly differentiate the free antibody, antibody-antigen complex, antibody-hFcγRI complex, and final antibody-antigen-hFcγRI complex.
Conclusions:
N-glycans partially acts as allosteric sensor and respond to antigen and hFcγRI binding.
DOI: https://doi.org/10.37349/ei.2021.00004
Aim:
The present study aims to generate chimeric mouse single-chain variable fragment (scFv) and immunoglobulin G1 (IgG1) crystallizable fragment (Fc) antibody against disialoganglioside (GD2)
Methods:
Vector
Results:
Using plasmid fusion-human IgG1-Fc2 tag vector (pFUSE-hIgG1-Fc2), a plasmid vector encoding chimeric mouse scFv and hIgG1
Conclusions:
The results indicate that chimeric scFv-hIgG
Aim:
The present study aims to generate chimeric mouse single-chain variable fragment (scFv) and immunoglobulin G1 (IgG1) crystallizable fragment (Fc) antibody against disialoganglioside (GD2)
Methods:
Vector
Results:
Using plasmid fusion-human IgG1-Fc2 tag vector (pFUSE-hIgG1-Fc2), a plasmid vector encoding chimeric mouse scFv and hIgG1
Conclusions:
The results indicate that chimeric scFv-hIgG
DOI: https://doi.org/10.37349/etat.2023.00188
This article belongs to the special issue Novel Strategies and Targets for Immunotherapy of Cancer
Aim:
As the primary response antibody with increasing use as a therapeutic immunoglobulin (Ig)
Methods:
Through a panel of 14 recombinant complementarity determining regions (CDRs)-grafted trastuzumab and pertuzumab VH1-7 IgMs subjected to bio-layer interferometry measurements, the interactions with the antigen human epidermal growth factor receptor 2 (Her2), Fc-mu receptor (FcμR), and superantigen Protein L (PpL) were investigated.
Results:
Significant effects from the V-regions to mitigate FcμR binding and the IgM C-region bidirectional effect modulating Her2 antigen engagements at the V-regions were found. Additional modulatory effects from superantigen PpL binding on the V-region of the kappa chain (Vκ) mitigating antigen binding were also found, revealing possible novel mechanisms of antibody superantigens that can be moderated by the antibody VH frameworks.
Conclusions:
These findings show that the oligomerisation of IgMs plays a significant role in FcμR, antigen, and superantigen binding that made IgM distinct from the other antibody isotypes and how these features should be considered during further development and protein engineering of IgM therapeutics.
Aim:
As the primary response antibody with increasing use as a therapeutic immunoglobulin (Ig)
Methods:
Through a panel of 14 recombinant complementarity determining regions (CDRs)-grafted trastuzumab and pertuzumab VH1-7 IgMs subjected to bio-layer interferometry measurements, the interactions with the antigen human epidermal growth factor receptor 2 (Her2), Fc-mu receptor (FcμR), and superantigen Protein L (PpL) were investigated.
Results:
Significant effects from the V-regions to mitigate FcμR binding and the IgM C-region bidirectional effect modulating Her2 antigen engagements at the V-regions were found. Additional modulatory effects from superantigen PpL binding on the V-region of the kappa chain (Vκ) mitigating antigen binding were also found, revealing possible novel mechanisms of antibody superantigens that can be moderated by the antibody VH frameworks.
Conclusions:
These findings show that the oligomerisation of IgMs plays a significant role in FcμR, antigen, and superantigen binding that made IgM distinct from the other antibody isotypes and how these features should be considered during further development and protein engineering of IgM therapeutics.
DOI: https://doi.org/10.37349/ei.2022.00083
Aim:
In renal cell carcinoma (RCC), tumor heterogeneity generated challenges to biomarker development and therapeutic management, often becoming responsible
Methods:
The RIVELATOR study was a monocenter retrospective analysis of biological samples from 25 cases of primary RCC and their paired pulmonary metastases. The biomarkers analyzed included MET, mTOR, PD-1/PD-L1 pathways and the immune context.
Results:
High multi-level heterogeneity was demonstrated. MET was the most reliable biomarker, with the lowest intratumor heterogeneity: the positive mutual correlation between MET expression in primary tumors and their metastases had a significantly proportional intensity (P = 0.038). The intratumor heterogeneity grade was significantly higher
Conclusions:
In mRCC, multiple and multi-level assays of potentially predictive biomarkers are needed
Aim:
In renal cell carcinoma (RCC), tumor heterogeneity generated challenges to biomarker development and therapeutic management, often becoming responsible
Methods:
The RIVELATOR study was a monocenter retrospective analysis of biological samples from 25 cases of primary RCC and their paired pulmonary metastases. The biomarkers analyzed included MET, mTOR, PD-1/PD-L1 pathways and the immune context.
Results:
High multi-level heterogeneity was demonstrated. MET was the most reliable biomarker, with the lowest intratumor heterogeneity: the positive mutual correlation between MET expression in primary tumors and their metastases had a significantly proportional intensity (P = 0.038). The intratumor heterogeneity grade was significantly higher
Conclusions:
In mRCC, multiple and multi-level assays of potentially predictive biomarkers are needed
DOI: https://doi.org/10.37349/etat.2023.00165
Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline alterations in mismatch repair (MMR) genes leading to increased risk of colon cancer as well as other cancer types. Non-small cell lung cancer (NSCLC) is not among typical Lynch syndrome-associated tumors: pembrolizumab, an immune checkpoint inhibitor, is actually approved
Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline alterations in mismatch repair (MMR) genes leading to increased risk of colon cancer as well as other cancer types. Non-small cell lung cancer (NSCLC) is not among typical Lynch syndrome-associated tumors: pembrolizumab, an immune checkpoint inhibitor, is actually approved
DOI: https://doi.org/10.37349/etat.2021.00044
Aim:
Diagnostic laboratories are progressively introducing next-generation sequencing (NGS) technologies in the routine workflow to meet the increasing clinical need
Methods:
Herein, NGS data from 190 soft tissue tumors (STTs) and carcinoma cases, discussed in the context of the institutional Molecular Tumor Board, are reported and analyzed by FusionPlex© Solid tumor kit through the manufacturer’s pipeline and by two well-known fast and accurate open-source tools [Arriba (ARR) and spliced transcripts alignment to reference (STAR)-fusion (SFU)].
Results:
The combination of FusionPlex© Solid tumor with ArcherDX® Analysis suite (ADx) analysis package has been proven to be sensitive and specific in STT samples, while partial loss of sensitivity has been found in carcinoma specimens.
Conclusions:
Albeit ARR and SFU showed lower sensitivity, the use of additional fusion-detection tools can contribute to rein
Aim:
Diagnostic laboratories are progressively introducing next-generation sequencing (NGS) technologies in the routine workflow to meet the increasing clinical need
Methods:
Herein, NGS data from 190 soft tissue tumors (STTs) and carcinoma cases, discussed in the context of the institutional Molecular Tumor Board, are reported and analyzed by FusionPlex© Solid tumor kit through the manufacturer’s pipeline and by two well-known fast and accurate open-source tools [Arriba (ARR) and spliced transcripts alignment to reference (STAR)-fusion (SFU)].
Results:
The combination of FusionPlex© Solid tumor with ArcherDX® Analysis suite (ADx) analysis package has been proven to be sensitive and specific in STT samples, while partial loss of sensitivity has been found in carcinoma specimens.
Conclusions:
Albeit ARR and SFU showed lower sensitivity, the use of additional fusion-detection tools can contribute to rein
DOI: https://doi.org/10.37349/etat.2022.00102
This article belongs to the special issue Off-Label Drugs and -Omics Data in Cancer Treatment
Aims:
Reduced pre-operative cognitive functioning in older adults is a risk factor
Methods:
Results:
Above and beyond age, education, ASA physical status classification score, and frailty, only digitally-acquired CDT copy per
Conclusions:
Digital variables from clock copy condition provided predictive value over common demographic and comorbidity variables. We hypothesize this is due to the sensitivity of the copy condition to executive dysfunction, as has been shown in previous studies
Aims:
Reduced pre-operative cognitive functioning in older adults is a risk factor
Methods:
Results:
Above and beyond age, education, ASA physical status classification score, and frailty, only digitally-acquired CDT copy per
Conclusions:
Digital variables from clock copy condition provided predictive value over common demographic and comorbidity variables. We hypothesize this is due to the sensitivity of the copy condition to executive dysfunction, as has been shown in previous studies
DOI: https://doi.org/10.37349/emed.2021.00036
This article belongs to the special issue Digital Biomarkers: The New Frontier for Medicine and Research
B
B
DOI: https://doi.org/10.37349/emd.2023.00018
This article belongs to the special issue Diffuse Idiopathic Skeletal Hyperostosis- A common but neglected disease
Aim:
The clinical symptoms of autoantibody (AAb)-mediated autoimmune diseases (AID) usually correlate with the AAb-titer. Immunoglobulins (Igs) of the IgG type are actively recycled by the neonatal crystallizable fragment receptor (FcRn). The most common Ig type of AAb is IgG. This explorative study evaluates the safety and tolerability of a fully human anti-FcRn monoclonal antibody (mAb) in patients with thyroid autoimmunity (TA).
Methods:
Adverse events (AEs) and serious AEs (SAEs) were documented and coded according to the standardized Medical Dictionary
Results:
Of 31 patients with TA, 19 were administered the anti-FcRn mAb subcutaneously once weekly
Conclusions:
The anti-FcRn mAb is a safe and well-tolerated therapy
Aim:
The clinical symptoms of autoantibody (AAb)-mediated autoimmune diseases (AID) usually correlate with the AAb-titer. Immunoglobulins (Igs) of the IgG type are actively recycled by the neonatal crystallizable fragment receptor (FcRn). The most common Ig type of AAb is IgG. This explorative study evaluates the safety and tolerability of a fully human anti-FcRn monoclonal antibody (mAb) in patients with thyroid autoimmunity (TA).
Methods:
Adverse events (AEs) and serious AEs (SAEs) were documented and coded according to the standardized Medical Dictionary
Results:
Of 31 patients with TA, 19 were administered the anti-FcRn mAb subcutaneously once weekly
Conclusions:
The anti-FcRn mAb is a safe and well-tolerated therapy
DOI: https://doi.org/10.37349/ei.2024.00145
Aim:
The decellularization process aims to remove cellular comp
Methods:
Rabbit and rat b
Results:
Our method effectively removes cellular comp
Conclusions:
This study demonstrates that our novel decellularization method effectively develops biological b
Aim:
The decellularization process aims to remove cellular comp
Methods:
Rabbit and rat b
Results:
Our method effectively removes cellular comp
Conclusions:
This study demonstrates that our novel decellularization method effectively develops biological b
DOI: https://doi.org/10.37349/ebmx.2025.101345
This article belongs to the special issue Nature-Based Biomaterials for Biomedical Applications
Steroid use is a widely accepted practice
Steroid use is a widely accepted practice
DOI: https://doi.org/10.37349/etat.2022.00106
Aim:
Coronavirus disease 2019 (COVID-19) became pandemic on 11th March 2020 and it deeply stressed the healthcare system. Cancer patients represent a vulnerable population, so many recommendations have been approved to ensure optimal management. Clinical research was notably impacted by COVID too. This review aims to analyze the challenges occurred during a pandemic
Methods:
The studies included in the present review were selected from PubMed/Google Scholar/ScienceDirect databases.
Results:
During the first phase of pandemic many clinical trials were suspended in accrual and, as the pandemic progressed, recommendations were established to guarantee the safety and the continuity of care of enrolled patients. In addition, lot of new strategies was found during the pandemic to reduce the negative consequences on clinical trial per
Conclusions:
Among all modifiers, investigators would prefer to maintain the positive
Aim:
Coronavirus disease 2019 (COVID-19) became pandemic on 11th March 2020 and it deeply stressed the healthcare system. Cancer patients represent a vulnerable population, so many recommendations have been approved to ensure optimal management. Clinical research was notably impacted by COVID too. This review aims to analyze the challenges occurred during a pandemic
Methods:
The studies included in the present review were selected from PubMed/Google Scholar/ScienceDirect databases.
Results:
During the first phase of pandemic many clinical trials were suspended in accrual and, as the pandemic progressed, recommendations were established to guarantee the safety and the continuity of care of enrolled patients. In addition, lot of new strategies was found during the pandemic to reduce the negative consequences on clinical trial per
Conclusions:
Among all modifiers, investigators would prefer to maintain the positive
DOI: https://doi.org/10.37349/etat.2023.00183
This article belongs to the special issue COVID-19 and Cancer
Aim:
The role of tumor burden (TB)
Methods:
Sixty-five consecutive patients with advanced NSCLC treated with immunotherapy as first or second line therapy were retrospectively analyzed between August 2015 and February 2018. TB was recorded at baseline considering sites and number of metastases, thoracic vs. extrathoracic disease, measurable disease (MD) vs. not-MD (NMD) and evaluating dimensional aspects as maximum lesion diameter (cut-off = 6.3 cm), sum of the 5 major lesions diameters (cut-off = 14.3 cm), and number of sites of metastases (cut-off > 4). All cut-offs were calculated by receiver operating characteristic curves. Median overall survival (OS) was estimated using Kaplan-Meier method. A Cox regression model was carried out
Results:
Median age was 70 years and most patients (86.2%) had a good per
Conclusions:
This study underlines the negative prognostic impact of specific metastatic sites, presence of NMD and extrathoracic disease in advanced NSCLC patients treated with immunotherapy. However, TB does not appear to affect the outcome of these patients.
Aim:
The role of tumor burden (TB)
Methods:
Sixty-five consecutive patients with advanced NSCLC treated with immunotherapy as first or second line therapy were retrospectively analyzed between August 2015 and February 2018. TB was recorded at baseline considering sites and number of metastases, thoracic vs. extrathoracic disease, measurable disease (MD) vs. not-MD (NMD) and evaluating dimensional aspects as maximum lesion diameter (cut-off = 6.3 cm), sum of the 5 major lesions diameters (cut-off = 14.3 cm), and number of sites of metastases (cut-off > 4). All cut-offs were calculated by receiver operating characteristic curves. Median overall survival (OS) was estimated using Kaplan-Meier method. A Cox regression model was carried out
Results:
Median age was 70 years and most patients (86.2%) had a good per
Conclusions:
This study underlines the negative prognostic impact of specific metastatic sites, presence of NMD and extrathoracic disease in advanced NSCLC patients treated with immunotherapy. However, TB does not appear to affect the outcome of these patients.
DOI: https://doi.org/10.37349/etat.2021.00043
This article belongs to the special issue Immunotherapy in Cancer Patients
Aim:
Isolated specific glyc
Methods:
Considering the higher affinity
Results:
In silico molecular docking analyses have shown that flavonoids can bind strongly to the spike protein and main protease of the SARS-CoV-2 virus. Flavonoids also have anti-inflammatory and immune-modulating activity by inhibiting cytokines. Although flavonoids may be a treatment alternative
Conclusions:
It is found that the new
Aim:
Isolated specific glyc
Methods:
Considering the higher affinity
Results:
In silico molecular docking analyses have shown that flavonoids can bind strongly to the spike protein and main protease of the SARS-CoV-2 virus. Flavonoids also have anti-inflammatory and immune-modulating activity by inhibiting cytokines. Although flavonoids may be a treatment alternative
Conclusions:
It is found that the new
DOI: https://doi.org/10.37349/emed.2022.00071
Several preclinical studies suggested a potential benefit from combined treatment with inhibitors of epidermal growth factor receptor (EGFR) and angiogenesis, both effective in patients with advanced non-small-cell lung cancer (NSCLC). In pretreated patients with advanced EGFR wild type NSCLC, bevacizumab plus erlotinib improved progression-free survival as second-line therapy in the BeTa study and as maintenance therapy in the ATLAS trial, although the benefit was modest and did not translate into an advantage in overall survival. Disappointing results were reported with oral VEGF inhibitors plus erlotinib in pretreated patients with EGFR wild type NSCLC. On the contrary, erlotinib plus bevacizumab or ramucirumab showed a clinically relevant improvement of progression-free survival in naïve patients with EGFR mutations, leading to the approval of these two regimens as first-line treatment of NSCLC patients with EGFR mutant tumors. Several clinical studies are evaluating the feasibility and activity of osimertinib plus bevacizumab or ramucirumab. However, limits that could affect its use in clinical practice are the need of an intravenous infusion
Several preclinical studies suggested a potential benefit from combined treatment with inhibitors of epidermal growth factor receptor (EGFR) and angiogenesis, both effective in patients with advanced non-small-cell lung cancer (NSCLC). In pretreated patients with advanced EGFR wild type NSCLC, bevacizumab plus erlotinib improved progression-free survival as second-line therapy in the BeTa study and as maintenance therapy in the ATLAS trial, although the benefit was modest and did not translate into an advantage in overall survival. Disappointing results were reported with oral VEGF inhibitors plus erlotinib in pretreated patients with EGFR wild type NSCLC. On the contrary, erlotinib plus bevacizumab or ramucirumab showed a clinically relevant improvement of progression-free survival in naïve patients with EGFR mutations, leading to the approval of these two regimens as first-line treatment of NSCLC patients with EGFR mutant tumors. Several clinical studies are evaluating the feasibility and activity of osimertinib plus bevacizumab or ramucirumab. However, limits that could affect its use in clinical practice are the need of an intravenous infusion
DOI: https://doi.org/10.37349/etat.2020.00008
Aim:
From the start of the pandemic, several aspects of healthcare policies changed, not least the clinical trials management from recruiting capabilities to the protocol compliance in terms of schedule of procedures, follow-up
Methods:
Data from February to July of the years 2019, 2020 and 2021 were collected and three practical parameters of the trial unit were investigated: milest
Results:
The trials mean numbers were 18, 24, and 23, in 2019, 2020, and 2021 respectively. The pre-Site Initiation
Conclusions:
The growing number of remote Site Initiation
Aim:
From the start of the pandemic, several aspects of healthcare policies changed, not least the clinical trials management from recruiting capabilities to the protocol compliance in terms of schedule of procedures, follow-up
Methods:
Data from February to July of the years 2019, 2020 and 2021 were collected and three practical parameters of the trial unit were investigated: milest
Results:
The trials mean numbers were 18, 24, and 23, in 2019, 2020, and 2021 respectively. The pre-Site Initiation
Conclusions:
The growing number of remote Site Initiation
DOI: https://doi.org/10.37349/etat.2023.00168
This article belongs to the special issue COVID-19 and Cancer
International Guidelines as well as Cancer Associations recommend a multidisciplinary approach to lung cancer care. A multidisciplinary team (MDT) can significantly improve treatment decision-making and patient coordination by putting different physicians and other health professionals “in the same room”, who collectively decide upon the best possible treatment. However, this is not a panacea
International Guidelines as well as Cancer Associations recommend a multidisciplinary approach to lung cancer care. A multidisciplinary team (MDT) can significantly improve treatment decision-making and patient coordination by putting different physicians and other health professionals “in the same room”, who collectively decide upon the best possible treatment. However, this is not a panacea
DOI: https://doi.org/10.37349/etat.2024.00217
This article belongs to the special issue Integrated Approaches for Non-Small-Cell Lung Cancer
Alzheimer’s disease (AD), the term “dementia”, describes a specific neuropathology together with the development and progression of age-related cognitive and functional loss.
Alzheimer’s disease (AD), the term “dementia”, describes a specific neuropathology together with the development and progression of age-related cognitive and functional loss.
DOI: https://doi.org/10.37349/en.2025.100682
This article belongs to the special issue Medicinal Plants and Bioactive Phytochemicals in Neuroprotection
Hemangioblastoma are benign, vascularized cranial tumors caused by autosomal dominant inherited von Hippel-Lindau disease or can appear sporadically. This review will investigate current and emerging treatments
Hemangioblastoma are benign, vascularized cranial tumors caused by autosomal dominant inherited von Hippel-Lindau disease or can appear sporadically. This review will investigate current and emerging treatments
DOI: https://doi.org/10.37349/en.2023.00031
This article belongs to the special issue Cerebral Ischemia, Genetics, Comorbidities, Risk Factors and New Therapeutic Options for Neurorestoration
Primary biliary cholangitis (PBC) is an autoimmune cholangiopathy that affects mainly women and, if untreated, can evolve into biliary cirrhosis. Its prevalence varies worldwide, depending on race, and accounts
Primary biliary cholangitis (PBC) is an autoimmune cholangiopathy that affects mainly women and, if untreated, can evolve into biliary cirrhosis. Its prevalence varies worldwide, depending on race, and accounts
DOI: https://doi.org/10.37349/eds.2024.00033
This article belongs to the special issue Innovative Therapeutics in Hepato-Gastroenterology
