Non-Small Cell Lung Cancer-Tumor Biology.

Lung cancer is one of the leading causes of cancer-related mortality worldwide among men and women [...

TIMP-1 Dependent Modulation of Metabolic Profiles Impacts Chemoresistance in NSCLC.

The development of chemoresistance remains a significant barrier to treating NSCLC. Alteration of cancer cell metabolism is an important mechanism for chemoresistance. This study explored the role of aberrant metabolism in TIMP-1-mediated chemoresistance.

Natural Killer Cells and Dendritic Cells: Expanding Clinical Relevance in the Non-Small Cell Lung Cancer (NSCLC) Tumor Microenvironment.

Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer that accounts for almost 85% of lung cancer cases worldwide. Although recent advances in chemotherapy, radiotherapy, and immunotherapy have helped in the clinical management of these patients, the survival rate in advanced stages remains dismal. Furthermore, there is a critical lack of accurate prognostic and stratification markers for emerging immunotherapies.

Prognostic and therapeutic implications of extracellular matrix associated gene signature in renal clear cell carcinoma.

Complex interactions in tumor microenvironment between ECM (extra-cellular matrix) and cancer cell plays a central role in the generation of tumor supportive microenvironment. In this study, the expression of ECM-related genes was explored for prognostic and immunological implication in clear cell renal clear cell carcinoma (ccRCC). Out of 964 ECM genes, higher expression (z-score > 2) of 35 genes showed significant association with overall survival (OS), progression-free survival (PFS) and disease-specific survival (DSS).

Immunogenomic Gene Signature of Cell-Death Associated Genes with Prognostic Implications in Lung Cancer.

Lung cancer is one of the leading causes of death worldwide. Cell death pathways such as autophagy, apoptosis, and necrosis can provide useful clinical and immunological insights that can assist in the design of personalized therapeutics. In this study, variations in the expression of genes involved in cell death pathways and resulting infiltration of immune cells were explored in lung adenocarcinoma (The Cancer Genome Atlas: TCGA, lung adenocarcinoma (LUAD), 510 patients).

TIMP-1-Mediated Chemoresistance via Induction of IL-6 in NSCLC.

Elevated tissue inhibitor of metalloproteinase-1 (TIMP-1) is a negative prognosticator in non-small cell lung carcinoma NSCLC patients. This study sought to identify mechanisms whereby TIMP-1 impacts anticancer therapy. Using NSCLC cells and their TIMP-1 knockdown clones, we examined the chemoresistance against two chemotherapeutic agents, Gemcitabine and Cisplatin, as identified by increased apoptosis in the knockdown clones.

Multifocal Necrotizing Leukoencephalopathy: Expanding the Clinicopathologic Spectrum.

Multifocal necrotizing leukoencephalopathy (MNL) is a rare condition typically described in patients undergoing chemotherapy or with HIV/AIDS. As a pathologic entity, it is characterized by multiple small foci of necrosis typically within white matter of the pons and occasionally in other areas. Herein we describe findings in 6 patients with MNL, 5 diagnosed at postmortem examination and 1 by surgical biopsy.

TIMP-1 downregulation modulates miR-125a-5p expression and triggers the apoptotic pathway.

Matrix metalloproteinases and their natural inhibitors (TIMPs) are important elements in a wide range of oncology settings. Elevated levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) have often been associated with increased tumorigenesis. This has been demonstrated in a number of clinical and experimental models which include breast, gastric, colorectal and non-small cell lung carcinoma (NSCLC).

Suprasellar Ganglioglioma: Expanding the Differential Diagnosis.

This case study describes a young man with symptoms suggestive of the presence of a space-occupying lesion within the cranial cavity. Imaging studies confirmed a lesion in the suprasellar region and surgical intervention to remove the tumor yielded an unexpected diagnosis. Neuroimaging characteristics and histopathology including immunohistochemistry are described.

Morphologic and Elemental Analysis of Primary Melanosis of the Dentate Nucleus: Review and Correlation With Neuromelanin.

Primary melanosis of the dentate nucleus is a rarely described entity with neither known cause nor definitive clinicopathologic correlation. We revisit this previously reported phenomenon by presenting one such case with a review of the pathology as well as additional investigations including elemental analysis by energy-dispersive X-ray, immunohistochemistry and electron microscopy. The lesion presented macroscopically as a sharply defined, black pigmentation that was restricted to the dentate nucleus of the cerebellum.

Gender-specific differential expression of exosomal miRNA in synovial fluid of patients with osteoarthritis.

The pathogenesis of osteoarthritis (OA) is poorly understood, and therapeutic approaches are limited to preventing progression of the disease. Recent studies have shown that exosomes play a vital role in cell-to-cell communication, and pathogenesis of many age-related diseases. Molecular profiling of synovial fluid derived exosomal miRNAs may increase our understanding of OA progression and may lead to the discovery of novel biomarkers and therapeutic targets.

Vessel morphometric parameters-correlation with histologic grade and VEGF expression in oligodendroglioma.

The contributions of histologic features including microvascular proliferation to the determination of malignancy in oligodendrogliomas remain uncertain. We have retrospectively performed morphometric assessments in 20 tumors histologically classified as well-differentiated (WHO Grade II, n=8) or anaplastic (WHO Grade III, n=12) oligodendrogliomas (WDO or AO). Quantitative studies utilized image analysis of double immunolabeled vasculature with anti CD34 with VIP chromogen (purple) and proliferating nuclei with anti MIB-1, using DAB (brown).

TIMP-1 Inhibits Apoptosis in Lung Adenocarcinoma Cells via Interaction with Bcl-2.

Tissue inhibitors of metalloproteinases (TIMPs) are multifaceted molecules that exhibit properties beyond their classical proteinase inhibitory function. Although TIMP-1 is a known inhibitor of apoptosis in mammalian cells, the mechanisms by which it exerts its effects are not well-established. Our earlier studies using H2009 lung adenocarcinoma cells, implanted in the CNS, showed that TIMP-1 overexpressing H2009 cells (HB-1), resulted in more aggressive tumor kinetics and increased vasculature.

TIMP-1 overexpression in lung carcinoma enhances tumor kinetics and angiogenesis in brain metastasis.

Tissue inhibitors of matrix metalloproteinase (TIMP) orchestrate many biologic activities, including inhibition of matrix metalloproteinase activity, activation of pro-matrix metalloproteinases, and regulation of cell proliferation, angiogenesis, and apoptosis induction. Tissue inhibitors of matrix metalloproteinase can play a protective role during tumor invasion and metastasis, but elevated TIMP messenger RNA levels have also been associated with aggressive cancers and poor clinical outcome. We examined the potential roles of TIMP-1 in H2009 lung adenocarcinoma cells and in cells transfected with a human TIMP-1-overexpressing vector (HB-6 and HB-1).

Vascular alterations in schwannoma.

Schwannomas or neurilemmoma are benign peripheral nerve sheath tumors, which most frequently occur at the cerebellopontine angle. This morphologic study examines vascular alterations in these tumors, comparing them to other benign spindle cell neoplasms of the nervous system, while correlating these findings with evidence of vascular permeability. Thirty-four nervous system spindle cell neoplasms, sixteen schwannomas, nine fibroblastic/transitional meningiomas and nine peripheral neurofibromas were stained with H&E, Prussian-blue stain, and immunoreacted for factor VIII-related antigen and interstitial albumin.

Expression of MMP-2 correlates with increased angiogenesis in CNS metastasis of lung carcinoma.

Matrix metalloproteinases (MMP) have been implicated in increased invasive and metastatic potential of tumors, possibly via interactions with the extracellular matrix and angiogenesis. This study investigates the relationship between MMP-2 immunoexpression and angiogenesis in a series of lung carcinomas metastatic to the central nervous system (CNS). Twenty eight metastatic carcinoma cases with adequate brain-tumor interface were identified from the archives at the Moffitt Cancer Center.

CD44 and p53 immunoexpression patterns in NF1 neoplasms - indicators of malignancy and infiltration.

Neurofibromatosis type 1 (NF1) provides a unique system to evaluate the complete range of neoplastic expressions, from encapsulated benignity to invasiveness and malignancy. This study was aimed at determining whether CD44 and p53 may serve as indicators of malignant progression of neurofibroma. CD44, a transmembrane glycoprotein receptor for hyaluronic acid, and participates in cell-extracellular matrix interactions and migration.

Cell proliferation index determination by immunohistochemical detection of hCDC47 protein.

A member of the human minichromosome maintenance complex protein family, hCDC47 (alias MCM7) has been identified as a component of the regulatory mechanism in cell proliferation. The expression of this protein, as determined by immunohistochemistry, was investigated to determine its application as a proliferation marker. A mouse monoclonal antibody (Clone 47DC141, NeoMarkers, Fremont CA) raised against recombinant hCDC47 protein was tested against a wide range of tissues.