Lung adenocarcinoma is a leading cause of cancer-related mortality despite recent therapeutic advances. Cancer stem cells have gained increasing attention due to their ability to induce cancer cell proliferation through self-renewal and differentiation into multiple cell lineages. OCT4 and LIN28 (and their homologs A and B) have been identified as key regulators of pluripotency in mammalian embryonic (ES) and induced stem (IS) cells, and they are the crucial regulators of cancer progression.
View Article and Find Full Text PDFNovel data report a "cross-talk" between Heat-Shock Factor 1 (HSF1) and the transient receptor potential vanilloid 1 cation channel (TRPV1) located in the cell membrane, introducing these channels as possible drug targets for the regulation of HSF1 activation. This study aims to investigate the co-expression of TRPV1 and HSF1 in human brain tumors. Additionally, the expression of the transient receptor potential ankyrin 1 channel (TRPA1), which is co-operated with TRPV1 in a plethora of cells, was studied.
View Article and Find Full Text PDFBackground: Genetic events cannot account for the complexity of human carcinogenesis alone. Mutations of epigenetic regulators and aberrations of their expression patterns have been detected in various human malignancies. Methylation of histone H3 at lysine 4 (H3K4me), is an evolutionarily conserved histone modification that marks regions of active transcription and regulates cell growth, migration, and invasion.
View Article and Find Full Text PDFThe TRPV1-4 members of TRPV cation channel subfamily are mainly regarded as polymodal receptors that may be activated by diverse changes in cellular microenvironment and endogenous and exogenous agents. Abnormal expression of these channels has been reported in various tumors but not in meningiomas. Meningioma cells are thought to originate from arachnoid cap cells due to cytological and functional similarities between the two types of cells.
View Article and Find Full Text PDFPhyllodes tumors (PTs) of the breast constitute an uncommon group of mammary fibroepithelial lesions with ambiguous biologic behavior. Recent evidence suggests that epithelial mesenchymal transition (EMT), a driving force of cancer progression is implicated in PTs pathogenesis. Integrin-linked kinase (ILK), a focal adhesion kinase, has been implicated in cancer and EMT and represents a novel cancer therapeutic target.
View Article and Find Full Text PDFBackground/aim: Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) are critically implicated in cancer metastasis and chemoresistance. Herein, we investigated integrin-linked kinase (ILK)'s role in human colon cancer (CRC) progression and chemoresistance in relation to EMT and CSC markers.
Patients And Methods: Expression of ILK, EMT and CSC markers were evaluated by immunohistochemistry in 149 CRC samples.
Breast cancer is the most common malignancy, affecting one in eight women in North America and Europe. The human epidermal growth factor receptor (EGFR) protein comprises a major determinant of normal development but also cancer. RANK receptor (Receptor Activator of Nuclear factor-κB) is a tumor necrosis superfamily member and a binding partner for RANKL, which was recently implicated in breast cancer initiation, progression and metastasis.
View Article and Find Full Text PDFObjectives: Several aquaporins (AQPs) are present in the salivary glands, likely contributing to their secretions. AQP dysfunction may contribute to the salivary gland dysfunction in SS. Antibodies to AQP4 and AQP1 are detected in neuromyelitis optica and are believed to play a pathogenic role.
View Article and Find Full Text PDFActa Neurochir (Wien)
February 2017
Syphilis has plagued humanity for thousands of years. Despite the measures of precaution against its transmission and the advancement of modern pharmacology, late-stage phenomena like intracerebral gumma are not uncommon even today. We present a complex case, which has misled the physicians twice.
View Article and Find Full Text PDFHorner's syndrome is characterized by a combination of ipsilateral miosis, blepharoptosis, enophthalmos, facial anhidrosis, and iris heterochromia in existence of congenital lesions. The syndrome results from a disruption of the ipsilateral sympathetic innervation of the eye and ocular adnexa at different levels. Though rare, thyroid and neck surgery could be considered as possible causes of this clinical entity.
View Article and Find Full Text PDFThe pathogenesis of many tumors, including brain tumors, has been associated with hypoxia, which induces the transcriptional activity of hypoxia-inducible Factor-1α (HIF-1α). HIF-1α is normally degradated by the von Hippel-Lindau protein (pVHL) but, in hypoxia, pVHL/HIF-1α interaction is inhibited resulting in the nuclear accumulation of HIF-1α. Hsp90 (Heat shock protein 90), as a chaperone protein, plays a critical role for both stabilization of HIF-1α and degradation of pVHL.
View Article and Find Full Text PDFCurr Mol Pharmacol
September 2015
Breast carcinoma is currently considered as a group of diseases, differing not only in histopathologic phenotype, as indicated by histologic type and grade, but also in their protein, genetic and epigenetic molecular profile. The standard of care indicates that the core information for patient management includes data on Estrogen Receptor (ER), Progesterone Receptor (PgR) and Human Epidermal Growth Factor Receptor 2 (HER2), while there is an emerging role for the proliferation marker Ki67. These indices can be provided even in low resource settings and are indispensable for prognostication and therapeutic patient management.
View Article and Find Full Text PDFThe Ki67 labelling index (LI - proportion of staining cells) is widely used to reflect proliferation in breast carcinomas. Several cut-off values have been suggested to distinguish between tumours with low and high proliferative activity. The aim of the current study was to evaluate the distribution of Ki67 LIs in breast carcinomas diagnosed at different institutions by different pathologists using the method reflecting their daily practice.
View Article and Find Full Text PDFTissue granulomas formation in adult-onset Still's disease (AOSD) is extremely rare. We describe a case of AOSD associated with formation of granulomatous lesions in lymph nodes, liver and presumably spleen. The high dose steroid-dependent nature of our patient's illness, characterized by disease relapses when methylprednisolone dose was reduced below 10 mg/d, was overwhelmed with institution of anakinra (100 mg/d).
View Article and Find Full Text PDFIntroduction: Lymphadenopathy is found in about 65% of patients with adult-onset Still's disease and is histologically characterized by an intense, paracortical immunoblastic hyperplasia. Adult-onset Still's disease has not been previously described as an etiology of suppurative necrotizing granulomatous lymphadenitis.
Case Presentation: We describe a 27-year-old Greek man who manifested prolonged fever, abdominal pain, increased inflammatory markers, episodic skin rash and mesenteric lymphadenopathy histologically characterized by necrotizing granulomatous adenitis with central suppuration.
Background: Extranodal nasal-type natural killer (NK)/T-cell lymphoma represents a rare entity, typically originating in the nasal cavity, palate or midfacial region. Signs and symptoms include non-specific rhinitis and/or sinusitis, nasal obstruction, epistaxis, facial swelling and development of deep necrotic ulceration in the midline of the palate, causing an oronasal defect. Differential diagnosis includes fungal infections, Wegener's granulomatosis, tertiary syphilis, other non-Hodgkin's lymphomas and malignant epithelial midline tumors.
View Article and Find Full Text PDFBackground: The importance of definitive histological subclassification has increased as drug trials have shown benefit associated with histology in nonsmall-cell lung cancer (NSCLC). The acuity of this problem is further exacerbated by the use of minimally invasive cytology samples. Here we describe the development and validation of a 4-protein classifier that differentiates primary lung adenocarcinomas (AC) from squamous cell carcinomas (SCC).
View Article and Find Full Text PDFEstrogen receptors alpha (ERα) and beta (ERβ) and their co-regulatory proteins are key components of complex signaling networks that specifically regulate the growth and development of various tissues and tumors. Still, their protein expression profiles and possible role in the pathogenesis of astrocytic tumors remain largely unknown. The purpose of the present study is to evaluate the differential protein expression of ΕRα, ERβ, and their co-activators, AIB1, TIF2, and PELP1 in astrocytic tumors of World Health Organization (WHO) grade II-IV, using immunohistochemistry.
View Article and Find Full Text PDFChallenges in measurement of epidermal growth factor receptor (EGFR) protein expression have led to conflicting data on its prognostic value and discontinuation of its use for prediction of response. Herein is described a quantitative standardized assay for EGFR and its use in a series of retrospective cohorts of patients with non-small cell lung cancer (NSCLC). The AQUA technology of quantitative immunofluorescence was used in conjunction with Western blot analysis to calculate the absolute concentration of EGFR in two independent NSCLC cohorts (170 from Yale New Haven Hospital and 335 from Sotiria and Patras Hospitals in Greece).
View Article and Find Full Text PDFPhosphorylation of p27(Kip1) at threonine 187 (pThr187-p27(Kip1)) occurs frequently in the development of human tumors, directing protein polyubiquitination and subsequent proteasomal degradation. We investigated the immunoexpression of p27(Kip1) and pThr187-p27(Kip1) in 126 B-cell lymphomas and their relation to proliferative activity and clinical parameters. Increased levels of p27(Kip1) and pThr187-p27(Kip1) were significantly correlated with indolent and aggressive lymphomas, respectively (p < 0.
View Article and Find Full Text PDFObjective: The aim of this study was to assess the antitumour effect of an anti-VEGFR (sunitinib) and the anti-EGFR multi-targeted agent (lapatinib), applied either alone or in combination on the migration capacity of two glioma cell lines. Furthermore, this study sought to evaluate the effect of lapatinib in the formation of EGFR-integrin β(1) complex, as well as the effect of sunitinib in the VEGFR-integrin β(3) and PDGFR-integrin β(3) complexes formation.
Materials And Methods: U87 and M059K cells were cultured as recommended by the American Type Culture Collection (ATCC).
Background: Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results.
Methods: Here, we quantitatively assessed Bcl-2 expression in two large and independent cohorts to investigate the impact of Bcl-2 on survival.
Background: Thymomas are the most common tumor arising in the anterior mediastinum. Surgery is the cornerstone for the management of these tumors. The role of postoperative radiotherapy in Masaoka stage II thymomas remains controversial, but it is well established in the advanced stages.
View Article and Find Full Text PDFBackground: Lung cancer is the most lethal type of cancer in humans. Cell cycle alterations have commonly been encountered in lung cancer and may have prognostic value.
Materials And Methods: This study investigates the immunohistochemical expression of the important cell cycle regulators phosphatase and tensin homolog deleted on chromosome 10 (PTEN), p27, Cks1, and Skp2 in 128 non-small cell lung carcinomas (64 adenocarcinomas, 46 squamous cell carcinomas, and 18 large cell undifferentiated carcinomas) and adjacent non-neoplastic lung tissue.
Several studies have implicated leptin in the pathophysiology of neoplasias. We investigated the direct effect of leptin on malignant hematopoietic tissue that included: primary acute myeloid leukemia (AML) cells, leukemic cell lines and bone marrow biopsies from multiple myeloma (MM) patients. PBMC, T-cells, B-cells and monocytes from healthy subjects served as controls.
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