E-cadherin adhesion molecule and syndecan-1 expression in various thyroid pathologies

Cadherins and syndecans are transmembrane glycoproteins implicated in cell-cell and cell-matrix adhesion. Impairment of cadherin and syndecan mediated adhesion is likely to constitute one of the main factors leading to the reduced cell-cell and cell-matrix adhesion characteristics of tumor cells and play a pivotal role in the acquisition of invasive and metastatic proprieties by neoplastic epithelial cells. Aim: To elucidate the role and alterations of syndecan-1 expression in comparison with those of E-cadherin in normal and pathological thyroid glands (TG). Methods: A total of 55 TG carcinomas, 40 TG adenomas, 40 cases of hyperplastic TG disorders and 20 cases of normal TG autopsy samples, were evaluated by immunohistochemistry. The staining intensity, and localization of syndecan-1 and E-cadherin in sequential sections were examined, and semi-quantified. Results: Immunostaining of syndecan-1 and E-cadherin was strong in normal follicular TG epithelial cells, and located mainly in basolateral membrane. No significant change was seen in either molecule in hyperplastic TG disorders compared with TG adenomas. A significant reduction in expression of both syndecan-1 and E-cadherin was seen in well-differentiated TG carcinomas as compared with normal TG epithelium (p = 0.0001 and p = 0.032, respectively). Similarly, there was a significant reduction of both molecules expression in poorly differentiated and anaplastic TG carcinomas compared to well differentiated tumors (syndecan-1: p = 0.0037; and E-cadherin: p = 0.075). Conclusion: Decreased E-cadherin and syndecan-1 expression along with decreasing cellular differentiation may be involved in the complex mechanism of progression of TG pathology.Кадгерины и синдеканы — это трансмембранные гликопротеины, участвующие в межклеточной адгезии и адгезии клеток к матриксу. Изменения экспрессии этих молекул играют главную роль в приобретении инвазивного и метастатического потенциала злокачественно трансформированными эпителиальными клетками. Цель: оценка роли экспрессии синдекана-1 и Е-кадгерина в ткани щитовидной железы в норме и при патологии. Методы: образцы ткани для иммуногистохимического исследования взяли у 55 больных раком щитовидной железы (ЩЖ), 40 пациентов — с аденомой ЩЖ, 40 — с гиперпластическими процессами ЩЖ, контролем служили 20 образцов неизмененной ткани ЩЖ (аутопсия). Результаты: экспрессия синдекана-1 и Е-кадгерина в нормальных фолликулярных эпителиальных клетках ЩЖ выражена интенсивно, с преимущественной локализацией в базолатеральной мембране. Не отмечали существенных различий в экспрессии обеих молекул при гиперпластических процессах по сравнению с аденомами ЩЖ. Однако таковая значительно снижена в образцах высокодифференцированной карциномы по сравнению с нормальным эпителием ЩЖ (p = 0,0001 и p = 0,032 соответственно), а также при низкодифференцированном и анапластическом раке по сравнению с высокодифференцированными опухолями ЩЖ (p = 0,0037 для синдекана-1 и p = 0,075 для Е-кадгерина). Выводы: снижение экспрессии синдекана-1 и Е-кадгерина, сопровождающееся снижением способности клеток к дифференциации, может быть частью механизма прогрессирования заболеваний ЩЖ

Perinatal inflammation influences but does not arrest rapid immune development in preterm babies

Infection and infection-related complications are important causes of death and morbidity following preterm birth. Despite this risk, there is limited understanding of the development of the immune system in those born prematurely, and of how this development is influenced by perinatal factors. Here we prospectively and longitudinally follow a cohort of babies born before 32 weeks of gestation. We demonstrate that preterm babies, including those born extremely prematurely (<28 weeks), are capable of rapidly acquiring some adult levels of immune functionality, in which immune maturation occurs independently of the developing heterogeneous microbiome. By contrast, we observe a reduced percentage of CXCL8-producing T cells, but comparable levels of TNF-producing T cells, from babies exposed to in utero or postnatal infection, which precedes an unstable post-natal clinical course. These data show that rapid immune development is possible in preterm babies, but distinct identifiable differences in functionality may predict subsequent infection mediated outcomes

Transdiaphragmatic nephrectomy with synchronous pulmonary and anterior thoracic wall mass metastasectomy in a young male with metastatic renal cell carcinoma; A single-incision approach

Renal cell carcinoma represents approximately 3% of all cancers, with the highest incidence occurring in the western world. Around 33% of the patients experience metastatic disease at diagnosis. Since the approval of the first targeted therapy, the treatment of metastatic renal cell carcinoma (mRCC) has positively changed, but the surgical treatment of the primary tumor, and metastases if possible, is sometimes crucial in selected patients controlling the burden of cancer sites with the intention to improve survival. We, herein, report on a case of a young male patient presented in the emergency room with gross hematuria which underwent transdiaphragmatic nephrectomy with synchronous pulmonary and anterior thoracic wall mass metastasectomy with a single thoracic incision due to mRCC. Achieving a full response in patients with mRCC is extremely rare only with medical treatment. The role of complete surgical metastasectomy is questioned, but there are several studies that support its efficacy in achieving metastases free status prolonged overall survival and better quality of life. The therapeutic treatment plan for these patients should be discussed within dedicated multidisciplinary cancer centers and focus on each patient individually and they should be offered a closed follow-up strategy. © 2021 Wolters Kluwer Medknow Publications. All rights reserved

Syndecan-1, epithelial-mesenchymal transition markers (E-cadherin/β-catenin) and neoangiogenesis-related proteins (PCAM-1 and Endoglin) in colorectal cancer

The Syndecan-1 protein plays a crucial role in cell proliferation, cell adhesion, cell migration and angiogenesis and, at the same time, its co-expression with E-cadherin is regulated during epithelial-mesenchymal transition (EMT). In colorectal cancer (CRC), the expression of syndecan-1, E-cadherin/β-catenin complex is frequently disturbed. Angiogenesis is critical for the growth and metastatic spread of tumors. In the present study, we focused on the expression of these biological molecules and their prognostic significance in human CRC. Formalin-fixed paraffin-embedded surgical specimens from 69 patients with CRC were immunostained for syndecan-1, E-cadherin, β-catenin, endoglin (CD105) and CD31 (platelet cell adhesion molecule (PCAM-1)). A significant association was found between syndecan-1 with E-cadherin (p<0.0001), as well with β-catenin (p<0.0001). High β-catenin expression appeared to reduce the risk of poor outcome. Endoglin microvascular density (MVD) count was correlated significantly with Dukes' stage (p<0.0001), vessel invasion (p<0.0001), lymph node metastasis (p=0.039), liver metastasis (p<0.0001), recurrence of disease (p=0.010) and poor survival rate (p<0.0001). Endoglin tumor epithelial cell expression was associated with E-cadherin, β-catenin and syndecan-1 (p=0.001, p=0.068 and p=0.005, respectively). In conclusion, changes in the pattern of expression of syndecan-1, EMT markers, E-cadherin/β-catenin, in association with endoglin (CD105), may be involved in tumor progression and prognosis of CRC patients. Further studies are needed to clarify the interaction between these proteins and tumor initiation and progression

Proinflammatory cytokines in irritable bowel syndrome: A comparison with inflammatory bowel disease

Background/Aims: Irritable bowel syndrome (IBS) is a common disease often considered as a functional intestinal disorder. Inflammation in IBS is a quite intriguing theory. The aim of this study was to investigate tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 expression in inflammatory bowel disease (IBD) patients, IBS patients and normal controls. Methods: IBS and IBD patients along with normal controls were recruited in the study. In all groups, 2 pinch biopsies were taken at each of 3 anatomical sites (terminal ileum, cecum, and rectum). IBS patients were also subcategorized according to the syndrome clinical manifestations. Two monoclonal antibodies (mAb), TNF-α mAb and IL-6 mAb, and one polyclonal antibody IL-1β mAb were applied for immunohistochemical analysis. Results: In IBD patients intensity of TNF-α and IL-1β were lower than in IBS patients or controls, while IL-6 was significantly increased comparing to the aforementioned groups. In IBS patients TNF-α was increased comparing to IBD patients or controls, while IL-6 and IL-1β were similar to controls. In IBS subgroups, TNF-α was lower in diarrhea predominant IBS patients and higher constipation predominant IBS patients. Differences among IBS subgroups regarding IL-6 and IL-1β were nonsignificant. Conclusions: IL-6 seems to be the most important proinflammatory cytokine in IBD patients, while TNF-α could play a more significant role in IBS pathogenesis. © 2020. Korean Association for the Study of Intestinal Diseases

IFNs-signaling effects on lung cancer: an up-to-date pathways-specific review

IFNs have found important applications in clinical medicine, including the treatment of lung malignancies. The biological effect of the IFN-receptor signaling is regulated essentially by three factors: the expression profile of the IFN itself, the profile of the receptor, and the expression of target genes. IFNs initiate their signaling by binding to specific receptors. The activated IFNs can directly induce gene transcription and/or multiple downstream signaling that both induce diverse cellular responses including the cell cycle arrest and the apoptosis in tumor cells. We provided evidence that IFN-γ enhances the pro cell death effects of Fas/CD95 in human neoplastic alveolar epithelial cell line, A549. We also found that p27 protein plays a pivotal role in the inducing cell death of IFNγ-CH-11-treated A549 cells, since it is involved in the Ras/Raf signaling pathway. This article discusses recent insights into these possible additional functions of IFNs in lung cancer treatment. © 2016, Springer International Publishing Switzerland

Unusual abscess masquerading as poorly differentiated adenocarcinoma of the colon showing characteristics of choriocarcinoma

Extragonadal non-gestational choriocarcinoma (ENC) is an uncommon malignant tumor occasionally found in the gastrointestinal tract. ENC is characterized by a biphasic tumor growth with distinct areas of adenocarcinoma and choriocarcinoma differentiation. Primary choriocarcinoma of the colon is extremely rare, with only 21 cases reported in the literature. Most of the perforation of colorectal cancers occurs in the abdominal cavity, while abdominal wall abscess is rare; the psoas abscess associated with colon carcinoma is even less observed. Herein, we report the case of a 61-year-old female with poorly differentiated adenocarcinoma of the ascending colon and sigmoid, with choriocarcinomatous differentiation, masquerading a psoas abscess formation. Unfortunately, despite the aggressive therapy, the patient’s disease rapidly progressed, and she died within 2 months after the diagnosis. The typical morphological pattern, immunohistochemistry, and its correlation with serum β-human chorionic gonadotropin enabled a correct diagnosis. © 2020, Hospital Universitario da Universidade de Sao Paulo. All rights reserved

The role of apoptosis defects in malignant mesothelioma pathogenesis with an impact on prognosis and treatment

Malignant mesothelioma (MM) is a highly aggressive tumor that is strongly related to asbestos fiber exposure. The tumorigenesis procedure in MM is complex, and many pathogenetic mechanisms including chronic inflammation, deregulation of cell death, and the genomic copy-number losses and gains may contribute to carcinogenesis. MM cells are resistant to TRAIL-mediated apoptosis due to defects in extrinsic apoptotic pathway. CAPS, a regulator of cell cycle and death, may contribute to the MM development as well. BAP1 is the most frequently inactivated gene in MPM; BAP1 deficiency triggers malignant transformation via disruption of DNA repair, transcription regulation, cell metabolism, apoptosis, and ferroptosis. In addition, bcl-2 family proteins as well as abnormal activation of PI3 K/Akt/mTOR pathway and deregulation of the Wnt signaling pathway may result in MM tumorigenesis. Finally, the Hippo pathway plays a critical role in MPM development. Mutations of NF2 and LATS lead to YAP activation in MPM. Thus, inhibition of YAP activity by YAP inhibitors could be a potentially promising treatment option for MM. In conclusion, extensive genetic alterations exist in mesotheliomas associated with the signaling of apoptotic HM cells death. The comprehension of these pathways may contribute to enhancing survival via developing new effective therapeutic strategies. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature