This study analyzes the primary electrostatic interaction between the membrane-bound B-cell receptor and antigen peptide determinants, and identifies peptide frequency and hydrophobicity as the main factors that govern and shape immunotolerance versus immunoreactivity. Pathobiology

Pathobiology

Lymphovascular invasion (LVI) is associated with poor outcome in breast cancer (BC); however, its underlying mechanisms remain ill-defined. LVI in BC develops through complex molecular pathways involving not only the interplay with the surrounding microenvironment along with endothelial cells lining the lymphovascular spaces but also changes in the malignant epithelial cells with the acquisition of

Introduction: The severe acute respiratory syndrome coronavirus 2 caused a pandemic of coronavirus disease 2019 (COVID-19). Unprecedented public health actions were introduced, including social distancing, travel restrictions and quarantine. The Belgian government announced a national emergency plan, thereby postponing all non-urgent medical consultations and operations. This report analyses the impact

Background: NudC domain containing 1 (NudCD1) is an oncoprotein related to diverse cancers. This study aims to investigate the expression, role, and regulatory mechanism of NudCD1 in non-small cell lung cancer (NSCLC). Methods: qRT-PCR, Western blot, and immunohistochemistry were performed to detect the expressions of NudCD1 in NSCLC tissues and cell lines. The correlation between NudCD1 expression

Objectives: Esophageal cancer is the sixth most common malignancy worldwide. Signal peptidase complex 18 (SPC18) protein, which is encoded by the SEC11A gene, is one of the subunits of the signal peptidase complex and plays an important role in the secretion of proteins including transforming growth factor α (TGF-α). In this study, we investigated the significance of SPC18 expression in human esophageal

Objective: To study the structural and immunohistochemical features of placentas in women after assisted reproductive technology (ART) with allogeneic eggs (oocyte donation and surrogate motherhood). Study Design: The study involved 89 women whose pregnancy occurred as a result of in vitro fertilization (IVF) with a donor egg in a surrogate motherhood program (IVF-SM, n = 47 patients) or oocyte donation

Pathobiology 2020;87:51–54

Pathobiology 2020;87:159

Pathobiology 2020;87:160

Background: It has been reported that interferon-λ3 (IFNL3)might influence the pathogenesis and clearance of human papillomavirus (HPV) infection. The impact of IFNL3 single-nucleotide polymorphism (SNP) on HPV infection is currently unknown. The aim of this study was to investigate the association between variants in the IFNL3 region and HPV infection in women with human immunodeficiency virus (HIV)

Background: Malignant pleural mesothelioma (MPM) is a highly lethal disease comprising a heterogeneous group of tumors with challenging to predict biological behavior. The diagnosis is complex, and the histologic classification includes 2 major subtypes of MPM: epithelioid (∼60% of cases) and sarcomatous (∼20%). Its identification depends upon pathological investigation supported by clinical and radiological

Heterogeneity in breast carcinomas can be appreciated at various levels, from morphology to molecular alterations, and there are well-known genotypic-phenotypic correlations. Clinical decision-making is strictly focused on the evaluation of tumor cells and is based on the assessment of hormone receptors and of the HER2 status, by means of a combination of immunohistochemical and in situ hybridization

Transcriptome of papillary thyroid cancer (PTC) is well characterized and correlates with some prognostic and genotypic factors, but data addressing the interaction between PTC and tumor microenvironment (TME) are scarce. Therefore, in the present study, we aimed to assess the impact of TME on gene expression profile in PTC. We evaluated the gene expression profile in PTC and normal thyroid cells isolated

Pathobiology 2020;87:55–57

Pathobiology 2020;87:155–158

BACKGROUND/OBJECTIVE Clear cell renal cell carcinoma (ccRCC) is characterized by a high degree of functional intratumoral heterogeneity (ITH). This is highlighted by the finding that tumor cell proliferation and intracellular signaling occur preferentially in the tumor periphery. The driving forces for such a spatial organization are largely unknown. Herein, we investigate the role of the tumor microenvironment

OBJECTIVE Activin A is known to be highly expressed in rheumatoid synovium. In the present study, we investigated the effect of inflammatory cytokines on activin A production and its role in rheumatoid inflammation using freshly prepared rheumatoid synovial cells (fresh-RSC). METHODS Fresh-RSC from patients with rheumatoid arthritis were obtained and stimulated with multiple cytokines for activin A

OBJECTIVES B7-H3 and B7-H4 proteins are expressed in breast cancer tissues, but their relationships with respect to tumor immune surveillance and outcomes in breast cancer are not conclusive. METHODS We first examined B7-H3 and B7-H4 mRNA expression in the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. Next, mRNA and protein expression were assessed by RNAscope in situ

INTRODUCTION Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. It has distinct molecular features and primarily affects the KIT and PDGFRA genes. OBJECTIVE We wanted to assess the molecular profile of 68 GIST patients who were sequenced consecutively between 2014 and 2019 at our institute of pathology. METHODS Our cohort comprised 60 primary

The tumor microenvironment (TME) plays an essential role in the development and progression of neoplasms. TME consists of the extracellular matrix and numerous specialized cells interacting with cancer cells by paracrine and autocrine mechanisms. Tumor axonogenesis and neoneurogenesis constitute a developing area of investigation. Prostate cancer (PC) is one of the most common malignancies in men worldwide

INTRODUCTION Human papillomavirus with a high oncogenic potential (HR-HPV) is responsible for more than a half of squamous cell carcinomas of the oropharynx. The HR-HPV-dependent cases of this tumour have a better prognosis compared to the HR-HPV-negative cases, despite the usually more advanced disease at the time of diagnosis. In addition to genetic and epigenetic factors, the causes of this more

Echinoderm microtubule-associated protein-like 4 and anaplastic lymphoma kinase (ALK) fusion gene rearrangement is a key driver mutation in non-small cell lung cancer (NSCLC). Although Break-Apart ALK fluorescence in situ hybridization (FISH) is a reliable diagnostic method for detecting ALK gene rearrangement, it is also costly and time-consuming to use as a routine screening test. Our aim was to

The fallopian tube is thought to be the site of origin of most high-grade serous carcinomas (HGSCs). However, how often the tube is abnormal in the setting of other ovarian tumors is unknown. The aim of this study is to define the frequency of tubal abnormalities in the tumoral (n = 245) and nontumoral (n = 184) setting. We found that in ovarian tumors, 52.2% of the tubes were normal, while 39.2% were

Necrosis-inducing anticancer drugs enhance high-mobility group box 1 (HMGB1) release during cell necrosis, and HMGB1-induced autophagy in skeletal muscle induces muscle atrophy. We evaluated the efficacy of magnetic hyperthermia therapy (MHT) using a low-energy magnetic field and self-controlled heating elements in tumor treatment. MHT-induced apoptosis by heating mouse subcutaneous tumors at 43°C

The prognostic value of the immune cell infiltrate in the breast carcinoma microenvironment is still uncertain. We reviewed published articles analysing the infiltration of inflammatorycells in the microenvironment of breast carcinoma. Data revealed the importance of infiltration of these immune cells in the prognosis of breast carcinoma, particularly the triple-negative and HER2-positive phenotypes

INTRODUCTION Platycodin D (PD), a triterpenoid saponin isolated from Platycodon grandiflorum, has a well-known anti-tumor effect in multiple human cancers, including gastric cancer (GC). miR-34a plays an important role in the progression of GC. However, the relationship between miR-34a and the susceptibility of GC cells to PD is still unclear. The aim of our research was to investigate the functions

INTRODUCTION Triple-negative breast cancer (TNBC), which lacks expression of estrogen receptor (ER), progesterone receptor (PgR), and epidermal growth factor receptor 2 (HER2), currently has no effective hormonal or molecular target therapy. OBJECTIVE AND METHODS To elucidate the role of the mammalian target of rapamycin (mTOR) signaling pathway in TNBC, the expression of molecules involved in mTOR

Cachexia frequently occurs in cancer patients and is correlated with reduced therapeutic responsiveness and poor prognosis. Although skeletal muscle atrophy is an important factor related to cachexia, biomarkers for its early diagnosis are not yet definitive. In this study, weight loss, body mass index, skeletal muscle index (SMI), serum carcinoembryonic antigen, serum tumor necrosis factor (TNF)-α

OBJECTIVE To define the cross-reactivity potential and the consequent autoimmunity intrinsic to viral versus human peptide sharing. METHODS Using human papillomavirus (HPV) infection/active immunization as a research model, the experimentally validated HPV L1 epitopes catalogued at the Immune Epitope DataBase were analyzed for peptide sharing with the human proteome. RESULTS The final data show that

BACKGROUND Effective antiretroviral therapy extends the survival of patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome, but these patients remain at higher risk for heart diseases compared with the general population. Previous studies have suggested that HIV-1 glycoprotein 120 (gp120) may be associated with heart disease. However, the underlying mechanisms by which

It has become evident that the microenvironment - lymphocytes, macrophages, fibroblasts as well as the extracellular matrix, cytokines, chemokines, and a plethora of other cells, structures and substances residing in the vicinity of tumor cells - plays an important part in the maintenance of cancer growth and survival. This is also relevant in lymphomas. In this review, we give an outline on the importance

OBJECTIVE This study aimed to demonstrate that the cribriform-morular variant (CMV) of papillary thyroid carcinoma (PTC) has high Ki-67 labeling indices, despite its excellent prognosis. METHODS We examined 21 CMV-PTCs and 5 conventional PTCs (C-PTCs) resected at Kuma Hospital between 2008 and 2018. All of the patients with CMV-PTC were women. Their ages ranged from 17 to 35 years, with a mean of 25

Modes of tumor cell interaction include autocrine stimulation, secretion of paracrine growth factors and inhibitors, as well as interaction with the tumor macroenvironment. This evolving concept in tumor pathobiology describes the interaction of a malignant tumor with its host as an extension and addition to its local interaction with tumor cells and surrounding nontransformed cells, the tumor microenvironment

BACKGROUND Mitochondrial transcription factor A (TFAM) plays multiple pathophysiologic roles in mitochondrial DNA (mtDNA) maintenance. However, the role of TFAM in sepsis-induced acute kidney injury (AKI) remains largely unknown. METHODS Lipopolysaccharide (LPS) treatment of HK-2 cells mimics the in vitro model of AKI inflammation. pcDNA3.1 plasmid was used to construct pcDNA3.1-TFAM. sh-TFAM-543,

BACKGROUND Macrolides have anti-inflammatory and antioxidative stress function, but their pharmacological regulation remains unclear. Sirtuin 1 (SIRT1) is redox-sensitive protein belongs to class III histone/protein deacetylases, SIRT1 regulates the acetylation/expression of nuclear factor κB (NF-κB) and is involved in the airway inflammation of chronic obstructive pulmonary disease. OBJECTIVES The

OBJECTIVE This study aims to investigate the association of 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase reductase (MTRR A66G) gene polymorphisms with neural tube defects (NTDs) in a Tunisian population. METHODS Genotyping was performed by polymerase chain reaction with restriction fragment length polymorphisms (PCR-RFLPs) using the restriction enzymes.

BACKGROUND/AIMS Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder predisposing to tumorigenesis caused by abnormal expression or function of imprinted genes of the chromosome 11p15.5 imprinting gene cluster. This real-time PCR-based assay determines the methylation status of a selected CpG island and has been proposed for use in high-throughput methylation analysis. METHODS Here

OBJECTIVES Bladder cancer (BC) is a common malignancy worldwide. Signal peptidase complex 18 (SPC18) protein, which is encoded by the SEC11A gene, is one of the subunits of the signal peptidase complex and induces transforming growth factor-α secretion. In the present study, we analyzed the expression and function of SPC18 protein in human BC. METHODS Expression of SPC18 was analyzed by immunohistochemistry

CD47 activates signal regulatory protein alpha expressed on macrophages and suppresses its phagocytic ability; therefore, CD47 is drawing attention as an immune checkpoint in the innate immune system. Expression of CD47 in cancer is thought to allow cancer cells to escape antitumor immunity of the innate immune system. In this study, expression of CD47 was examined by immunostaining in colorectal cancer

BACKGROUND Collagenases are enzymes starting collagen degradation. The role of collagenases in renal carcinoma development is not well understood. OBJECTIVE Evaluation of collagen content and collagenase expression and activity in human kidney cancers. METHODS Collagen content was measured by the hydroxyproline assay. The expression and the content of collagenases were evaluated by Western blotting

BACKGROUND MicroRNAs (miRNAs), a class of small-regulatory RNA molecules, were closely involved in the pathogenesis of a broad-spectrum of colorectal cancer (CRC). But role of miR-147b in CRC still remains unclear. METHODS Real-time RT-PCR or Western blotting was utilized to detect the expressions of miR-147b and RAP2B in CRC cell lines and tissues. Luciferase reporter assays were conducted to detect

INTRODUCTION The interaction of K27M mutation in histone H3 (H3K27M mutation) with polycomb repressive complex 2 (PRC2) is facilitated by the enhancer of zeste homolog 2 (EZH2). Subsequently, this interaction leads to the global reduction level of H3K27me3. We analyzed the EZH2 expression level in H3K27M mutation-positive tumors and revealed the association of high EZH2 expression with poor survival

OBJECTIVE Helicobacter pylori eradication is expected to prevent gastric cancer. However, morphological alterations after eradication often hinder accurate diagnosis. Therefore, we evaluated endoscopic and histological changes in gastric tumors after eradication of H. pylori in a time-dependent manner. METHODS We classified 144 cases of endoscopic submucosal dissection (ESD) of early gastric cancer

OBJECTIVE Microsatellite instability (MSI) and a defective mismatch repair (MMR) system were described as beneficial tumor features for response to immune checkpoint therapy (PD-1 blockade). Meanwhile, the FDA approved PD-1/PD-L1 inhibition treatment for any solid tumor showing MSI and/or defects in the MMR system. For squamous cell carcinoma (SCC) of the penis, no data on the frequency of MSI and

OBJECTIVES Pituitary adenomas (PAs) may rarely occur in well-defined hereditary conditions, like multiple endocrine neoplasia type 1 (MEN1) syndrome and familial isolated pituitary adenoma (FIPA) associated with germline mutations in MEN1 and AIP, respectively. This study aimed to assess MEN1 genetic abnormalities in AIP mutation-negative FIPA patients, not associated with MEN1 components. METHODS

BACKGROUND To examine whether gastric carcinoma (GC) with chromosomal instability (CIN-type GC), the largest category in the Cancer Genome Atlas classification, consists of a single genetic lineage, we conducted a multisampling analysis of genomic DNA copy-number profile. METHODS We performed array-based comparative genomic hybridization using formalin-fixed paraffin-embedded tissues from 54 gland-forming

Extramedullary haematopoiesis (EMH) in the axillary lymph node of breast cancer patients is extremely rare but when encountered can represent a diagnostic challenge. We aim to highlight this incidental finding as a diagnostic pitfall which can be mistaken for metastatic carcinoma (particularly of the metaplastic type). We report the case of a 68-year-old Caucasian female with a family history of cancer

OBJECTIVES Exosomes are extracellular vesicles released from various inflammatory cells, such as T cells, B cells, dendritic cells (DCs), and mast cells, which have been implicated in the modulation of immune response in asthma. This study aimed to investigate whether exosomes from DCs activated by thymic stromal lymphopoietin (TSLP) play a role in T-helper cell differentiation through the OX40 ligand

OBJECTIVE To evaluate the potential beneficial effects of hawthorn leaf flavonoids (HLF) against polycystic ovary syndrome (PCOS) in a rat model of disease and elucidate the underlying molecular mechanism. METHODS The PCOS model was established by subcutaneous injection of dehydroepiandrosterone (DHEA, 60 mg/kg/day) for 21 consecutive days. HLF (200 mg/kg/day) were orally administered simultaneously

BACKGROUND RUNX1 is a crucial transcription factor for hematological stem cells and well-known for its association with acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML). Besides the translocation t(8; 21) that leads to the RUNX1-RUNX1T1 fusion, somatic mutations of RUNX1 have been discovered. METHODS Four bone marrow trephine biopsies of patients with CD79a-positive and/or PAX5-positive

BACKGROUND The American Joint Commission Cancer (AJCC) Cancer Staging Manual 8th edition introduced a breast cancer (BC) Prognostic Stage (PS) that combines tumour grade, oestrogen (ER), progesterone (PgR), and human epidermal growth factor-2 (HER2) receptor status with Anatomic TNM Stage (AS). In a further modification, patients with early BC and an Oncotype DX® Recurrence Score (RS) < 11 are assigned

BACKGROUND Ductal carcinoma in situ (DCIS) of the breast is heterogeneous in terms of the risk of progression to invasive ductal carcinoma (IDC). To treat DCIS appropriately for its progression risk, we classified individual DCIS by its profile of genomic changes into 2 groups and correlated them with clinicopathological progression factors. METHODS We used surgically resected, formalin-fixed, paraffin-embedded

BACKGROUND Papillary tumours of the breast are diagnostically challenging lesions and represent a wide spectrum of diseases from papilloma to invasive papillary carcinoma. A rare subtype of breast papillary tumour resembling the tall cell variant of thyroid papillary carcinoma (BTRTPC) has been described. The nomenclature of this entity, its relationship to other papillary tumours, and its nature,

BACKGROUND Malignant cells exhibit significant resistance to FAS-mediated cell death, through different processes, including FAS mutations, soluble FAS expression, or FAS transcriptional dysregulation by P53, eventually escaping from immune surveillance. Since thyroid carcinomas were shown to be resistant to FAS-mediated apoptosis, we investigated the above mechanisms in thyroid carcinoma samples.

Myelodysplastic syndromes (MDS) are a challenging group of diseases for clinicians and researchers, as both disease course and pathobiology are highly heterogeneous. In (suspected) MDS patients, multi-parameter flow cytometry can aid in establishing diagnosis, risk stratification and choice of therapy. This review addresses the developments and future directions of multi-parameter flow cytometry scores

OBJECTIVES Forkhead transcription factor, O subgroup, member 1 (FOXO1) is a regulatory protein that plays an essential role in cellular homeostasis. A biological function as a tumor suppressor has been proposed. Here, we examined FOXO1 expression in human pancreatic ductal adenocarcinoma (PDAC) and its precursor lesions. METHODS We immunohistochemically labeled tissue samples from 47 patients with

OBJECTIVE This study aims to investigate the mechanism of proliferation potential-related protein (PP-RP) in influencing the proliferation, migration, and apoptosis of esophageal cancer cells. METHODS Quantitative real-time PCR and western blotting were performed to analyze the expression of PP-RP gene, p53, and interleukin (IL)-17 in human normal tissues and tumor tissues, as well as the expression