Global Study on the Accuracy of Human Epidermal Growth Factor Receptor 2-Low Diagnosis in Breast Cancer.

Context.—: Recently, a new type of antibody-drug conjugate, trastuzumab-deruxtecan (T-DXd), has been approved for the treatment of metastatic breast cancer with low level of human epidermal growth factor receptor 2 (HER2) gene expression. Thereby, eligibility relies on an accurate diagnosis of HER2-low status defined by immunohistochemistry IHC 1+/2+ with no gene amplification.

Implementing an integrated molecular classification for gastric cancer from endoscopic biopsies using on-slide tests.

The availability of more effective biological therapy can improve outcomes of gastric cancer (GC), but most patients do not have access to personalized treatment. GC molecular classification helps identify patients suitable for specific therapies and provides useful prognostic information. To date, only a small number of patients have access to molecular classification.

Degradation of a poly(3-hydroxybutyrate--3-hydroxyvalerate) (PHBV) compound in different environments.

Poly(3-hydroxybutyrate--3-hydroxyvalerate) (PHBV) is a promising biodegradable bio-based material, which is designed for a vast range of applications, depending on its composite. This study aims to assess the degradability of PHBV-based compound under different conditions. The research group followed different methodological approaches and assessed visual and mass changes, mechanical and morphological properties, spectroscopic and structural characterisation, along with thermal behaviour.

Implementing an On-Slide Molecular Classification of Gastric Cancer: A Tissue Microarray Study.

Gastric cancer (GC) is one of the most commonly diagnosed cancers and the fourth cause of cancer death worldwide. Personalised treatment improves GC outcomes. A molecular classification is needed to choose the appropriate therapy.

A consolidated working classification of gastric cancer for histopathologists (Review).

Gastric cancer (GC) remains a disease with poor prognosis despite increasing availability of more effective targeted treatment. This may be in part due to the difficulty in selecting patients for appropriate treatment. Conventional taxonomic classifications of GC are ill-suited to make full use of recent advances in personalised therapy.

Use of Prospective Multiplex Immunohistochemistry to Redefine Tissue Pathways of Diagnostic Core Biopsy of Prostate.

The incidence of prostatic cancer in the United Kingdom has increased over 40% in the past 30 years. The majority of these cancers are diagnosed by core biopsy, posing a considerable strain on a service that struggles to recruit sufficient histopathologists. The current methodology for tissue diagnosis has a significant false-negative rate, small false-positive rate, and a proportion of indeterminate diagnoses.

Tissue Selection for PD-L1 Testing in Triple Negative Breast Cancer (TNBC).

Atezolizumab in combination with nab-paclitaxel has been introduced for the treatment of locally advanced or recurrent triple negative breast cancer (TNBC). Patient selection relies on the use of immunohistochemistry using a specific monoclonal PD-L1 antibody (clone SP142) in a tightly controlled companion diagnostic test (CDx) with a defined interpretative algorithm. Currently there are no standardized recommendations for selecting the optimal tissue to be tested and there is limited data to support decision making, raising the possibility that tissue selection may bias test results.

2,5-Diisopropenylthiophene by Suzuki-Miyaura cross-coupling reaction and its exploitation in inverse vulcanization: a case study.

A novel thiophene derivative, namely 2,5-diisopropenylthiophene (DIT) was synthetized by Suzuki-Miyaura cross-coupling reaction (SMCCR). The influence of reaction parameters, such as temperature, solvent, stoichiometry of reagents, role of the base and reaction medium were thoroughly discussed in view of yield optimization and environmental impact minimization. Basic design of experiment (DoE) and multiple linear regression (MLR) modeling methods were used to interpret the obtained results.

Lysyl-Oxidase Dependent Extracellular Matrix Stiffness in Hodgkin Lymphomas: Mechanical and Topographical Evidence.

Purpose: The biochemical composition and architecture of the extracellular matrix (ECM) is known to condition development and invasiveness of neoplasms. To clarify this point, we analyzed ECM stiffness, collagen cross-linking and anisotropy in lymph nodes (LN) of Hodgkin lymphomas (HL), follicular lymphomas (FL) and diffuse large B-cell lymphomas (DLBCL), compared with non-neoplastic LN (LDN).

Methods And Results: We found increased elastic (Young's) modulus in HL and advanced FL (grade 3A) over LDN, FL grade 1-2 and DLBCL.

Determining PD-L1 Status in Patients With Triple-Negative Breast Cancer: Lessons Learned From IMpassion130.

Triple-negative breast cancer (TNBC) accounts for approximately 12% to 17% of all breast cancers and has an aggressive clinical behavior. Increased tumor-infiltrating lymphocyte counts are prognostic for survival in TNBC, making this disease a potential target for cancer immunotherapy. Research on immunophenotyping of tumor-infiltrating lymphocytes is revealing molecular and structural organization in the tumor microenvironment that may predict patient prognosis.

Inhibitors of ADAM10 reduce Hodgkin lymphoma cell growth in 3D microenvironments and enhance brentuximab-vedotin effect.

Shedding of ADAM10 substrates, like TNFa or CD30, can affect both anti-tumor immune response and antibody-drug-conjugate (ADC)-based immunotherapy. We have published two new ADAM10 inhibitors, LT4 and MN8 able to prevent such shedding in Hodgkin lymphoma (HL). Since tumor tissue architecture deeply influences the outcome of anti-cancer treatments, we set up a new threedimensional (3D) culture systems to verify whether ADAM10 inhibitors can contribute to, or enhance, the anti-lymphoma effects of the ADC brentuximab-vedotin (BtxVed).

LANCL1 binds abscisic acid and stimulates glucose transport and mitochondrial respiration in muscle cells via the AMPK/PGC-1α/Sirt1 pathway.

Objective: Abscisic acid (ABA) is a plant hormone also present and active in animals. In mammals, ABA regulates blood glucose levels by stimulating insulin-independent glucose uptake and metabolism in adipocytes and myocytes through its receptor LANCL2. The objective of this study was to investigate whether another member of the LANCL protein family, LANCL1, also behaves as an ABA receptor and, if so, which functional effects are mediated by LANCL1.

Is dual cup mobility better than hemiarthroplasty in patients with dementia and femoral neck fracture? A randomized controlled trial.

Purpose: Treatment of patients with dementia and hip fracture is challenging. Total hip arthroplasty (THA) with dual mobility cup (DMC) has been designed to reduce the rate of dislocation by increasing the stability of the implant. This study aimed to compare the dislocation rates of DMC THA with hemiarthroplasty (HA) in elderly patients with displaced femoral neck fracture (FNF) and a diagnosis of dementia.

Biophysical and in Vivo Studies Identify a New Natural-Based Polyphenol, Counteracting Aβ Oligomerization in Vitro and Aβ Oligomer-Mediated Memory Impairment and Neuroinflammation in an Acute Mouse Model of Alzheimer's Disease.

In this study natural-based complex polyphenols, obtained through a smart synthetic approach, have been evaluated for their ability to inhibit the formation of Aβ oligomers, the most toxic species causing synaptic dysfunction, neuroinflammation, and neuronal death leading to the onset and progression of Alzheimer's disease. In vitro neurotoxicity tests on primary hippocampal neurons have been employed to select nontoxic candidates. Solution NMR and molecular docking studies have been performed to clarify the interaction mechanism of Aβ with the synthesized polyphenol derivatives, and highlight the sterical and chemical requirements important for their antiaggregating activity.

Multicomponent Synthesis of Polyphenols and their in vitro Evaluation as Potential β-Amyloid Aggregation Inhibitors.

While plant polyphenols possess a variety of biological properties, exploration of chemical diversity around them is still problematic. Here, an example of application of the Ugi multicomponent reaction to the combinatorial assembly of artificial, yet "natural-like", polyphenols is presented. The synthesized compounds represent a second-generation library directed to the inhibition of β-amyloid protein aggregation.

A Survey on Pituitary Surgery in Italy.

Background: Pituitary tumors are a heterogeneous group of lesions that are usually benign. Therefore, a proper understanding of the anatomy, physiology, and pathology is mandatory to achieve favorable outcomes. Accordingly, diagnostic tests and treatment guidelines should be determined and implemented.

Brain Mapping as Helpful Tool in Brain Glioma Surgical Treatment-Toward the "Perfect Surgery"?

Gliomas are the most common primary malignant brain tumours in adults, representing nearly 80%, with poor prognosis in their high-grade forms. Several variables positively affect the prognosis of patients with high-grade glioma: young age, tumour location, radiological features, recurrence, and the opportunity to perform post-operative adjuvant therapy. Low-grade gliomas are slow-growing brain neoplasms of adolescence and young-adulthood, preferentially involving functional areas, particularly the eloquent ones.

Synthesis and in vitro Evaluation of ADAM10 and ADAM17 Highly Selective Bioimaging Probes.

A disintegrin and metalloproteinase (ADAMs) are membrane-bound metalloproteases responsible for the ectodomain shedding of various transmembrane proteins and play important roles in multiple relevant biological processes. Their altered expression is involved in several pathological conditions, and in particular ADAM10 or ADAM17 overexpression is found in various forms of cancer. To better understand how they are regulated in the cellular context, it is useful to visualize the specific ADAMs pathway by means of molecular imaging techniques.

Colorectal Cancer Stratification in the Routine Clinical Pathway: A District General Hospital Experience.

Colorectal cancer (CRC) has many subtypes with different prognoses and response to treatment. Patients must be characterized to access the most appropriate treatment and improve outcomes. An increasing number of biomarkers are required for characterization but are not in routine use.

Effects of Prion Protein on Aβ42 and Pyroglutamate-Modified AβpΕ3-42 Oligomerization and Toxicity.

Soluble Aβ oligomers are widely recognized as the toxic forms responsible for triggering AD, and Aβ receptors are hypothesized to represent the first step in a neuronal cascade leading to dementia. Cellular prion protein (PrP) has been reported as a high-affinity binder of Aβ oligomers. The interactions of PrP with both Aβ42 and the highly toxic N-truncated pyroglutamylated species (AβpE3-42) are here investigated, at a molecular level, by means of ThT fluorescence, NMR and TEM.

Optimization and validation of PD-L1 immunohistochemistry staining protocols using the antibody clone 28-8 on different staining platforms.

Several immunohistochemistry (IHC) assays have been developed to assess tumor programmed death-ligand 1 (PD-L1) expression levels in patients who are candidates for programmed death-1 (PD-1)/PD-L1 inhibitor therapy. The PD-L1 IHC 28-8 pharmDx kit is FDA-approved as a complementary diagnostic and CE-marked as an in vitro diagnostic device for nivolumab therapy in melanoma and specific lung cancer subtypes (and for squamous cell carcinoma of the head and neck/urothelial carcinoma in Europe only). Kit availability is limited outside the United States, and its use requires the Dako Autostainer Link 48 platform, which is unavailable in many laboratories.

Effect of ferric citrate on amyloid-beta peptides behavior.

Amyloid beta (Aβ) aggregation and oxidative stress are two of the central events in Alzheimer's Disease (AD). Both these phenomena can be caused by the interaction of Aβ with metal ions. In the last years the interaction between Zn , Cu , and Aβ was much studied, but between iron and Aβ it is still little known.

Specific ADAM10 inhibitors localize in exosome-like vesicles released by Hodgkin lymphoma and stromal cells and prevent sheddase activity carried to bystander cells.

Shedding of ADAM10 substrates, like TNFα, MICA or CD30, is reported to affect both anti-tumor immune response and antibody-drug-conjugate (ADC)-based immunotherapy. Soluble forms of these molecules and ADAM10 can be carried and spread in the microenvironment by exosomes released by tumor cells. We reported new ADAM10 inhibitors able to prevent MICA shedding in Hodgkin lymphoma (HL), leading to recognition of HL cells by cytotoxic lymphocytes.