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[A histological and immunohistological study of vascular and inflammatory changes in rosacea].

BACKGROUND: Rosacea has a number of pathophysiological components, chief of which are vascular abnormalities and inflammation. The morpholog … bodies, anti-CD68 (histiocytic) antibodies, anti-CD31 (endothelial cell) antibodies and anti-D2-40 (podoplanin, a marker for lymphatic endothelial cells) antibodies. RESULTS: In 88% of cases of rosacea, large superficial dermal vessels of geometrical or bizarre configuration were noted, and turgescent cells and dermal edema were frequently seen. Over 75% of …

Doxycycline treatment attenuates acute lung injury in mice infected with virulent influenza H3N2 virus: involvement of matrix metalloproteinases.

Acute respiratory distress syndrome, a severe form of acute lung injury (ALI), is a major cause of death during influenza pneumonia. We have provided evidence for the involvement of recruited neutrophils, their toxic enzymes such as myeloperoxidase and matrix metalloproteinases (MMPs), and neutrophil extracellular traps in aggravating alveolar-capillary damage. In this study, we investigated the effects of doxycycline (DOX), an inhibitor of MMPs, on influenza-induced ALI. BALB/c mice were infected with a sublethal dose of mouse-adapted virulent influenza A/Aichi/2/68 (H3N2) virus, and administ

Mesothelin/Mucin 16 Signaling in Activated Portal Fibroblasts Drives the Development of Cholestatic Fibrosis and Hepatocellular Carcinoma in Aged Female Multidrug Resistance Protein 2 Knockout Mice.

BACKGROUND & AIMS: The contribution of activated hepatic stellate cells (aHSCs) to cholestatic fibrosis and cancer is well-documented, but the role of portal fibroblasts (PFs), and especially mesothelin (Msln)-mucin 16 (Muc16)- Thy-1 cell surface antigen (Thy-1) signaling in activated portal fibroblasts (aPFs), is unknown. METHODS: The role of aPFs/mesenchymal cells in the pathogenesis of cholestatic fibrosis and hepatocellular carcinoma (HCC) was studied in aged (16 months old) multidrug resistance protein 2 knockout (Mdr2-/-) mice, which mimic primary biliary cholangitis with biliary fibros

An immunohistochemical study of lymphatic elements in the human brain.

Almost 150 papers about brain lymphatics have been published in the last 150 years. Recently, the information in these papers has been synthesized into a picture of central nervous system (CNS) "glymphatics," but the fine structure of lymphatic elements in the human brain based on imaging specific markers of lymphatic endothelium has not been described. We used LYVE1 and PDPN antibodies to visualize lymphatic marker-positive cells (LMPCs) in postmortem human brain samples, meninges, cavernous sinus (cavum trigeminale), and cranial nerves and bolstered our findings with a VEGFR3 antibody. LMPCs

The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors.

OBJECTIVE: Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the numb

Effect of alveolar epithelial cell plasticity on the regulation of GM-CSF expression.

Local pulmonary expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) is critically important for defense of the pulmonary alveolar space. It is required for surfactant homeostasis and pulmonary innate immune responses and is protective against lung injury and aberrant repair. Alveolar epithelial cells (AEC) are a major source of GM-CSF; however, the control of homeostatic expression of GM-CSF is incompletely characterized. Increasing evidence suggests considerable plasticity of expression of AEC phenotypic characteristics. We tested the hypothesis that this plasticity extend

Cutaneous digital papillary adenocarcinoma: a clinicopathologic study of 31 cases of a rare neoplasm with new observations.

Aggressive digital papillary adenocarcinoma is a rare tumor predominantly involving the distal end of digits. We examined 31 cases of this d … f 6) highlighted a myoepithelial layer around tubular/glandular structures, as did p63 (2 of 2) and podoplanin (5 of 5). Follow-up after excision or amputation (n=23; range, 2 mo- to 21 y) revealed local recurrence (n=5) and metastatic disease (n=6; lymph node in 1, lungs in 4, and both lymph node and lung in 1). Metastases were noted at presentation in 2 ca …

Evaluating organ preservation outcome as treatment endpoint for T1aN0 glottic cancer.

OBJECTIVES/HYPOTHESIS: Common endpoints in reporting the outcomes for early glottic cancer do not highlight the importance of organ preservation. We evaluated the treatment outcomes among patients with T1aN0 laryngeal cancer with laryngectomy-free disease-specific survival (LFS-DSS), which is defined as time to total laryngectomy or time to death from cancer cause, against all other endpoints. STUDY DESIGN: Outcome research on an institutional database. METHODS: A retrospective review covered all consecutive patients from 2003 to 2013. Patients with T1a laryngeal squamous cell carcinoma (SCC

Deciphering Mesenchymal Drivers of Human Dupuytren's Disease at Single-Cell Level.

Dupuytren's disease (DD) is a common, progressive fibroproliferative disease affecting the palmar fascia of the hands, causing fingers to irreversibly flex toward the palm with significant loss of function. Surgical treatments are limited; therefore, effective new therapies for DD are urgently required. To identify the key cellular and molecular pathways driving DD, we employed single-cell RNA sequencing, profiling the transcriptomes of 35,250 human single cells from DD, nonpathogenic fascia, and healthy dermis. We identify a DD-specific population of pathogenic PDPN+/FAP+ mesenchymal cells di

Heterocellular N-cadherin junctions enable nontransformed cells to inhibit the growth of adjacent transformed cells.

BACKGROUND: The Src tyrosine kinase phosphorylates effector proteins to induce expression of the podoplanin (PDPN) receptor in order to promote tumor progression. However, nontransformed cells can normalize the growth and morphology of neighboring transformed cells. Transformed cells must escape this process, called "contact normalization", to become invasive and malignant. Contact normalization requires junctional communication between transformed and nontransformed cells. However, specific junctions that mediate this process have not been defined. This study aimed to identify junctional prot…

Effect of insulin-like growth factors on lung development in a nitrofen-induced CDH rat model.

PURPOSE: Both the mortality and morbidity associated with congenital diaphragmatic hernia (CDH) are mainly caused by pulmonary hypoplasia and persistent pulmonary hypertension. A previous study revealed that insulin-like growth factors (IGFs) play important roles in fetal lung development. The aim of this study was to investigate the effect of IGF-1 and IGF-2 on tissue cultures of fetal hypoplastic lungs obtained from nitrofen-induced CDH model rats. METHODS: Pregnant rats were exposed to nitrofen on day 9 of gestation (D9). Fetuses were harvested on D18 by caesarian section. Lung specimens o

Vasculogenic Mesenchymal Tumor: A Clinicopathologic and Molecular Study of 55 Cases of a Distinctive Neoplasm Originating From Mediastinal Yolk Sac Tumor and an Occasional Precursor to Angiosarcoma.

We report 55 postchemotherapy resections of primary nonseminomatous mediastinal germ cell tumors with prominent vasculogenic features showin … ls from the tumor stroma, most commonly by the development of stromal clefts showing reactivity for podoplanin, CD34, and occasionally ERG, followed by the gradual development from the clefts of thin-walled vessels that later became encircled by stromal cells showing smooth muscle differentiation by immunohistochemistry. Occasionally, round collections of st …

[Clinicopathological study on the follicular dendritic cell sarcoma].

OBJECTIVE: To investigate the clinicopathologic features and differential diagnostic methods for follicular dendritic cell sarcoma. METHODS: Histological and immunohistochemical examinations and EBER in situ hybridization were used to investigate the pathological features of 5 cases of follicular dendritic cell sarcoma, and related literature was reviewed. RESULTS: There were 3 males and 2 females with a median age of 54 years (range, 28 - 75 years). The location of lesions included lymph node (2 cases), tonsil (1 case), stomach (1 case), and liver (1 case). The growth patterns were fascicul

Therapeutic Apheresis Using a β2-Microglobulin Removal Column Reduces Circulating Tumor Cell Count.

An elevated serum β2-microglobulin (β2M) level is indicative of impaired glomerular filtration and prerenal diseases, such as malignant tumors, autoimmune disorders, and liver diseases. An elevated serum β2M level has been shown to promote metastasis via the induction of epithelial-mesenchymal transition (EMT) in cancer cells. However, the therapeutic potential of targeting β2M remains unclear. Here, we aimed to investigate the efficacy of Filtor, a small polymethyl methacrylate fiber-based β2M removal column, in reducing the β2M level and suppressing cancer cell-induced EMT and metastasis. We

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… Podoplanin (PDPN) is an important platelet aggregation-promoting factor expressed on the cell surface of highly metastatic cancer cells [ 18 , 19 ]. … Roles of podoplanin in malignant progression of tumor Cells 2022 11 575 10.3390/cells11030575 35159384 PMC8834262 20. Ikoma Y. Kijima H. Masuda R. Tanaka M. Inokuchi S. Iwazaki M. Podoplanin expression is correlated with the prognosis of lung squamous cell carcinoma Biomed. …

Development of a Novel Anti-CD44 Variant 7/8 Monoclonal Antibody, C44Mab-34, for Multiple Applications against Oral Carcinomas.

Cluster of differentiation 44 (CD44) has been investigated as a cancer stem cell (CSC) marker as it plays critical roles in tumor malignant progression. The splicing variants are overexpressed in many carcinomas, especially squamous cell carcinomas, and play critical roles in the promotion of tumor metastasis, the acquisition of CSC properties, and resistance to treatments. Therefore, each CD44 variant (CD44v) function and distribution in carcinomas should be clarified for the establishment of novel tumor diagnosis and therapy. In this study, we immunized mouse with a CD44 variant (CD44v3-10)

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… Establishment of a monoclonal antibody PMab-233 for immunohistochemical analysis against Tasmanian devil podoplanin. Biochem. Biophys. Rep. 2019;18:100631. doi: 10.1016/j.bbrep.2019.100631. 38. … Antitumor effect of novel anti-podoplanin antibody NZ-12 against malignant pleural mesothelioma in an orthotopic xenograft model. Cancer Sci. 2016;107:1198–1205. doi: 10.1111/cas.12985. 45. …

Establishment of a Novel Anti-CD44 Variant 10 Monoclonal Antibody C44Mab-18 for Immunohistochemical Analysis against Oral Squamous Cell Carcinomas.

Head and neck squamous cell carcinoma (HNSCC) is the most common type of head and neck cancer, and has been revealed as the second-highest expression of CD44 in cancers. CD44 has been investigated as a cancer stem cell marker of HNSCC and plays a critical role in tumor malignant progression. Especially, splicing variant isoforms of CD44 (CD44v) are overexpressed in cancers and considered a promising target for cancer diagnosis and therapy. We developed monoclonal antibodies (mAbs) against CD44 by immunizing mice with CD44v3-10-overexpressed PANC-1 cells. Among the established clones, C44Mab-18

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… The PA16 tag can be detected by NZ-1 mAb, which was originally developed as an anti-human podoplanin (PDPN) mAb [ 32 ]. … A cancer-specific monoclonal antibody recognizes the aberrantly glycosylated podoplanin. Sci. Rep. 2014;4:5924. doi: 10.1038/srep05924. 47. Suzuki H., Kaneko M.K., Kato Y. Roles of Podoplanin in Malignant Progression of Tumor. Cells. 2022;11:575. doi: 10.3390/cells11030575. 48. …

Extravillous trophoblast invasion of venous as well as lymphatic vessels is altered in idiopathic, recurrent, spontaneous abortions.

STUDY QUESTION: Do extravillous trophoblasts (EVTs) invade non-arterial decidual vessels in healthy and pathological pregnancies? SUMMARY A … staining with antibodies against CD31, CD34, ephrin B2 (EFNB2), ephrin receptor B4 (EPHB4), HLA-G, podoplanin, prospero-related homeobox 1 (Prox-1), alpha-smooth muscle actin 2 (ATCTA2), von willebrand factor (vWF) and proteoglycan 2 (PRG2). Arterial, venous and lymphatic-associated EVTs were further characterized according to their position in the vascular …

Research progress on venous thrombosis development in patients with malignant tumors.

The coexistence of venous thromboembolism (VTE) within patients with cancer, known as cancer-associated thrombosis (CAT), stands as a prominent cause of mortality in this population. Over recent years, the incidence of VTE has demonstrated a steady increase across diverse tumor types, influenced by several factors such as patient management, tumor-specific risks, and treatment-related aspects. Furthermore, mutations in specific genes have been identified as potential contributors to increased CAT occurrence in particular cancer subtypes. We conducted an extensive review encompassing pivotal hi

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… Cancer-associated fibroblasts promote venous thrombosis through podoplanin/CLEC-2 interaction in podoplanin-negative lung cancer mouse model. J Thromb Haemost. 2023;21:3153–3165. doi: 10.1016/j.jtha.2023.07.005. 18. … Platelets and cancer-associated thrombosis: focusing on the platelet activation receptor CLEC-2 and podoplanin. Blood. 2019;134:1912–1918. doi: 10.1182/blood.2019001388. 40. Herre M, Cedervall J, Mackman N, Olsson AK. …

Isolation and characterization of lymphatic microvascular endothelial cells from human tonsils.

Human lymphatic endothelial cells (LECs) have isolated prevalently from human derma and tumors. As specialized lymphatic organs within the oropharynx, palatine tonsils are easily obtained and rich in lymphatic venules. Using a two-step purification method based on the sorting of endothelial cells with Ulex Europaeus Agglutinin 1 (UEA-1)-coated beads, followed by purification with monoclonal antibody D2-40, we successfully purified LECs from human palatine tonsils. The LECs were expanded on flasks coated with collagen type 1 and fibronectin for up to 8-10 passages and then analyzed for phenotyp

Thrombotic complications in patients with cancer: Advances in pathogenesis, prevention, and treatment-A report from ICTHIC 2021.

Venous thromboembolism (VTE) is a common complication in cancer patients, resulting in deep vein thrombosis (DVT) or pulmonary embolism (PE), and is responsible for high morbidity and mortality. This article discusses evidence and future perspectives on pathogenesis and prevention and treatment of thrombotic complications in patients with cancer. In April 2021, international basic researchers and clinicians met for the virtual edition of the 10th International Conference on Thrombosis & Hemostasis Issues in Cancer. Pathogenic mechanisms, markers and scores for risk assessment, diagnosis and th

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… Glioblastoma cell populations with distinct oncogenic programs release podoplanin as procoagulant extracellular vesicles, and podoplanin expression in primary brain tumors induces platelet aggregation and increased risk of thromboembolism. 18 , 19 The study of coagulome provides the opportunity to understand … Podoplanin expression in primary brain tumors induces platelet aggregation and increases risk of venous thromboembolism. Blood. 2017;129(13):1831–1839. doi: 10.1182/blood-2016-06-720714 20. Rothmeier AS, Liu E, Chakrabarty S, et al. …