Quantitative Longitudinal Imaging Reveals that Inhibiting Hedgehog Activity Alleviates the Hypoxic Tumor Landscape.

Metastases account for the majority of mortalities related to breast cancer. The onset and sustained presence of hypoxia strongly correlates with increased incidence of metastasis and unfavorable prognosis in patients with breast cancer. The Hedgehog (Hh) signaling pathway is dysregulated in breast cancer, and its abnormal activity enables tumor progression and metastasis.

Gold Nanoparticles sensitize pancreatic cancer cells to gemcitabine.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid cancers with dismal prognosis. Several mechanisms that are mainly responsible for aggressiveness and therapy resistance of PDAC cells include epithelial to mesenchymal transition (EMT), stemness and Mitogen Activated Protein Kinase (MAPK) signaling. Strategies that inhibit these mechanisms are critically important to improve therapeutic outcome in PDAC.

Neurofibromin (NF1) genetic variant structure-function analyses using a full-length mouse cDNA.

Neurofibromatosis type 1 (NF1) is caused by pathogenic variants or mutations in the NF1 gene that encodes neurofibromin. We describe here a new approach to determining the functional consequences of NF1 genetic variants. We established a heterologous cell culture expression system using a full-length mouse Nf1 cDNA (mNf1) and human cell lines.

Loss of Merlin induces metabolomic adaptation that engages dependence on Hedgehog signaling.

The tumor suppressor protein Merlin is proteasomally degraded in breast cancer. We undertook an untargeted metabolomics approach to discern the global metabolomics profile impacted by Merlin in breast cancer cells. We discerned specific changes in glutathione metabolites that uncovered novel facets of Merlin in impacting the cancer cell metabolome.

Loss of tumor suppressor Merlin results in aberrant activation of Wnt/β-catenin signaling in cancer.

The expression of the tumor suppressor Merlin is compromised in nervous system malignancies due to genomic aberrations. We demonstrated for the first time, that in breast cancer, Merlin protein expression is lost due to proteasome-mediated elimination. Immunohistochemical analysis of tumor tissues from patients with metastatic breast cancer revealed characteristically reduced Merlin expression.

Nanowire nanocomputer as a finite-state machine.

Implementation of complex computer circuits assembled from the bottom up and integrated on the nanometer scale has long been a goal of electronics research. It requires a design and fabrication strategy that can address individual nanometer-scale electronic devices, while enabling large-scale assembly of those devices into highly organized, integrated computational circuits. We describe how such a strategy has led to the design, construction, and demonstration of a nanoelectronic finite-state machine.

Nonclassical activation of Hedgehog signaling enhances multidrug resistance and makes cancer cells refractory to Smoothened-targeting Hedgehog inhibition.

The Hedgehog (Hh) pathway is critical in normal development. However, it has been reported to be up-regulated in numerous cancers and implicated in tumorigenicity and metastasis. Classical activation of Hh signaling initiated by Hh ligands results in activation of Smoothened (SMOH) and culminates in the activation of the GLI transcription factors.

Hedgehog signaling in tumor cells facilitates osteoblast-enhanced osteolytic metastases.

The remodeling process in bone yields numerous cytokines and chemokines that mediate crosstalk between osteoblasts and osteoclasts and also serve to attract and support metastatic tumor cells. The metastatic tumor cells disturb the equilibrium in bone that manifests as skeletal complications. The Hedgehog (Hh) pathway plays an important role in skeletogenesis.

The hedgehog pathway conditions the bone microenvironment for osteolytic metastasis of breast cancer.

The microenvironment at the site of tumor metastasis plays a key role in determining the fate of the metastasizing tumor cells. This ultimately has a direct impact on the progression of cancer. Bone is the preferred site of metastasis of breast cancer.

Loss of tumor suppressor Merlin in advanced breast cancer is due to post-translational regulation.

Unlike malignancies of the nervous system, there have been no mutations identified in Merlin in breast cancer. As such, the role of the tumor suppressor, Merlin, has not been investigated in breast cancer. We assessed Merlin expression in breast cancer tissues by immunohistochemistry and by real-time PCR.

Programmable nanowire circuits for nanoprocessors.

A nanoprocessor constructed from intrinsically nanometre-scale building blocks is an essential component for controlling memory, nanosensors and other functions proposed for nanosystems assembled from the bottom up. Important steps towards this goal over the past fifteen years include the realization of simple logic gates with individually assembled semiconductor nanowires and carbon nanotubes, but with only 16 devices or fewer and a single function for each circuit. Recently, logic circuits also have been demonstrated that use two or three elements of a one-dimensional memristor array, although such passive devices without gain are difficult to cascade.

Hedgehog signaling induced by breast cancer cells promotes osteoclastogenesis and osteolysis.

Bone integrity is maintained by a dynamic equilibrium between the activities of bone-forming osteoblasts and bone-resorbing osteoclasts. Osteolytic lesions are a painful consequence of metastasis of breast cancer cells to bone in an overwhelming majority of breast cancer patients. Factors secreted by breast cancer cells propel a cascade of events that trigger osteoclastogenesis and elevated bone resorption.

Studies on Multifunctional Effect of All-Trans Retinoic Acid (ATRA) on Matrix Metalloproteinase-2 (MMP-2) and Its Regulatory Molecules in Human Breast Cancer Cells (MCF-7).

Background. Vitamin A derivative all-trans retinoic acid (ATRA) is considered as a potent chemotherapeutic drug for its capability of regulating cell growth and differentiation. We studied the effect of ATRA on MMP-2 in MCF-7, human breast cancer cells, and the probable signaling pathways which are affected by ATRA on regulating pro-MMP-2 activity and expression.

The hedgehog pathway transcription factor GLI1 promotes malignant behavior of cancer cells by up-regulating osteopontin.

The role of Hedgehog (Hh) signaling as a developmental pathway is well established. Several recent studies have implicated a role for this pathway in multiple cancers. In this study we report that expression of GLI1 and osteopontin (OPN) increase progressively with the progression of melanoma from primary cutaneous cancer to metastatic melanoma in clinically derived specimens.

Performance simulation and analysis of a CMOS/nano hybrid nanoprocessor system.

This paper provides detailed simulation results and analysis of the prospective performance of hybrid CMOS/nanoelectronic processor systems based upon the field-programmable nanowire interconnect (FPNI) architecture. To evaluate this architecture, a complete design was developed for an FPNI implementation using 90 nm CMOS with 15 nm wide nanowire interconnects. Detailed simulations of this design illustrate that critical design choices and tradeoffs exist beyond those specified by the architecture.

Multifunctional effect of epigallocatechin-3-gallate (EGCG) in downregulation of gelatinase-A (MMP-2) in human breast cancer cell line MCF-7.

Aims: The tumor inhibiting property of green tea polyphenol epigallocatechin-3-gallate (EGCG) is well documented. Studies reveal that matrix-metalloproteinases (MMPs) play pivotal roles in tumor invasion through degradation of basement membranes and extracellular matrix (ECM). We studied the effect of EGCG on matrixmetalloproteinases-2 (MMP-2), the factors involved in activation, secretion and signaling molecules that might be involved in the regulation of MMP-2 in human breast cancer cell line, MCF-7.

Culture of human A375 melanoma cells in the presence of fibronectin causes expression of MMP-9 and activation of MMP-2 in culture supernatants.

Unlabelled: Interactions between tumor cell surface integrin receptors and extracellular matrix (ECM) ligands play an important role in tumor development, affecting cell survival, proliferation, and migration. Integrin-ECM ligand interaction leads to phosphorylation of focal adhesion kinase (FAK) and activation of mitogen-activated protein kinase (MAPK) pathways. It has been reported that integrins also regulate expression and function of matrix metalloproteinases (MMPs).

Rapid expression and activation of MMP-2 and MMP-9 upon exposure of human breast cancer cells (MCF-7) to fibronectin in serum free medium.

Interactions between tumour cells and the extracellular matrix (ECM) strongly influence tumour development, affecting cell survival, proliferation and migration. Many of these interactions are mediated through a family of cell surface receptors named integrins. Fibronectin and its integrin receptors play important roles in tumour development.

Cutting Edge: Stimulation of dopamine D4 receptors induce T cell quiescence by up-regulating Kruppel-like factor-2 expression through inhibition of ERK1/ERK2 phosphorylation.

The neurotransmitter dopamine (DA) is an important regulator of human T cell functions. Although it has been observed that DA, by acting through the D1/D5, D2, and D3 receptors, can activate resting T cells by stimulating the release of cytokines and the expression of surface integrins and also inhibit the proliferation of activated T cells by down-regulating nonreceptor tyrosine kinases, there is not yet a report indicating the functional significance of the D4 DA receptors present in these cells. The present work, for the first time, demonstrates that the stimulation of D4 DA receptors in human T cells induces T cell quiescence by up-regulating lung Krüppel-like factor-2 expression through the inhibition of ERK1/ERK2 phosphorylation.

Culture of human cervical cancer cells, SiHa, in the presence of fibronectin activates MMP-2.

Purpose: Several studies indicate that integrin receptors are involved in the regulation of matrix metalloproteinase (MMP) expression. Integrin-ECM ligand interaction leads to phosphorylation of focal adhesion kinase (FAK) and activation of mitogen activated protein kinase pathways. In this present communication, we cultured human cervical cancer cells, SiHa, in the presence of fibronectin to study fibronectin-integrin mediated modulation of MMP activity.

Oxygen uptake and filtration rate as animal health biomarker in Lamellidens marginalis (Lamarck).

The freshwater bivalve, L. marginalis was experimentally exposed to 10 and 30 ppm concentrations of CdCl2 to examine filtration rate, oxygen uptake and glycogen level of liver and gills for health assessment for their reuse in the reclamation of cadmium intoxicated environments. In situ experiment was also performed for better appraisal of the filtration rate in the lake.

Distribution pattern of ambient cadmium in wetland ponds distributed along an industrial complex.

Water and sediment samples collected from 18 wetland ponds within and outside industrial areas were examined for cadmium concentration and water quality parameters during the period of January to July 1996. The Cd contents in gill, liver, mantle and shell of freshwater mussel (Lamellidens marginalis) as well as leaves and roots of water hyacinth Eichhornia those occurred in these ponds were also estimated. Cd concentration ranged from 0.

In situ cadmium reclamation by freshwater bivalve Lamellidens marginalis from an industrial pollutant-fed river canal.

The biofilter potential of the freshwater bivalve, Lamellidens marginalis was examined in cage experiments conducted in a river canal (Ichhapore, 24-Parganas, West Bengal, India) receiving industrial effluents from steel and metal factories as well as from an ordinance factory. Cadmium is one of the major contaminants in this river canal. Lamellidens collected from pollution free natural ponds, were sorted into three size groups (large: 59+/-3.