Respiratory complex I regulates dendritic cell maturation in explant model of human tumor immune microenvironment.

Background: Combining cytotoxic chemotherapy or novel anticancer drugs with T-cell modulators holds great promise in treating advanced cancers. However, the response varies depending on the tumor immune microenvironment (TIME). Therefore, there is a clear need for pharmacologically tractable models of the TIME to dissect its influence on mono- and combination treatment response at the individual level.

Hepsin promotes breast tumor growth signaling via the TGFβ-EGFR axis.

Hepsin, a type II transmembrane serine protease, is commonly overexpressed in prostate and breast cancer. The hepsin protein is stabilized by the Ras-MAPK pathway, and, downstream, this protease regulates the degradation of extracellular matrix components and activates growth factor pathways, such as the hepatocyte growth factor (HGF) and transforming growth factor beta (TGFβ) pathway. However, how exactly active hepsin promotes cell proliferation machinery to sustain tumor growth is not fully understood.

A deep convolutional neural network for efficient microglia detection.

Microglial cells are a type of glial cells that make up 10-15% of all brain cells, and they play a significant role in neurodegenerative disorders and cardiovascular diseases. Despite their vital role in these diseases, developing fully automated microglia counting methods from immunohistological images is challenging. Current image analysis methods are inefficient and lack accuracy in detecting microglia due to their morphological heterogeneity.

miR-22 and miR-205 Drive Tumor Aggressiveness of Mucoepidermoid Carcinomas of Salivary Glands.

Objectives: To integrate mRNA and miRNA expression profiles of mucoepidermoid carcinomas (MECs) and normal salivary gland (NSGs) tissue samples and identify potential drivers.

Material And Methods: Gene and miRNA expression arrays were performed in 35 MECs and six NSGs.

Results: We found 46 differentially expressed (DE) miRNAs and 3,162 DE mRNAs.

Hepsin regulates TGFβ signaling via fibronectin proteolysis.

Transforming growth factor-beta (TGFβ) is a multifunctional cytokine with a well-established role in mammary gland development and both oncogenic and tumor-suppressive functions. The extracellular matrix (ECM) indirectly regulates TGFβ activity by acting as a storage compartment of latent-TGFβ, but how TGFβ is released from the ECM via proteolytic mechanisms remains largely unknown. In this study, we demonstrate that hepsin, a type II transmembrane protease overexpressed in 70% of breast tumors, promotes canonical TGFβ signaling through the release of latent-TGFβ from the ECM storage compartment.

Biopsy quality is essential for preoperative prognostication in oral tongue cancer.

A role for incisional biopsy in preoperative prognostication is increasingly being advocated in oral tongue squamous cell carcinomas (OTSCC). Biopsies at two locations were compared, and prognostic factors in biopsies and their corresponding resections were evaluated. A total of 138 OTSCC biopsy slides from Finland and Saudi Arabia were compared for size (horizontal and vertical) and invasive front.

Effect of Sex Steroid Hormones on Tongue Cancer Cells .

Background: Tongue cancer is more common in men than in women. Yet the effects of sex steroid hormones on the behaviour of oral tongue squamous cell carcinoma (OTSCC) are not well known. Matrix metalloproteinase 8 (MMP8) is expressed in OTSCC and can degrade estrogen receptors (ERs).

Morphine-3-glucuronide causes antinociceptive cross-tolerance to morphine and increases spinal substance P expression.

Morphine-3-glucuronide (M3G), the main metabolite of morphine, has been implicated in the development of tolerance and of opioid-induced hyperalgesia, both limiting the analgesic use of morphine. We evaluated the acute and chronic effects of M3G and morphine as well as development of antinociceptive cross-tolerance between morphine and M3G after intrathecal administration and assessed the expression of pain-associated neurotransmitter substance P in the spinal cord. Sprague-Dawley rats received intrathecal M3G or morphine twice daily for 6 days.

The critical effects of matrices on cultured carcinoma cells: Human tumor-derived matrix promotes cell invasive properties.

The interaction between squamous cell carcinoma (SCC) cells and the tumor microenvironment (TME) plays a major role in cancer progression. Therefore, understanding the TME is essential for the development of cancer therapies. We used four (primary and metastatic) head and neck (HN) SCC cell lines and cultured them on top of or within 5 matrices (mouse sarcoma-derived Matrigel®, rat collagen, human leiomyoma-derived Myogel, human fibronectin and human fibrin).

In vitro humanized 3D microfluidic chip for testing personalized immunotherapeutics for head and neck cancer patients.

Objectives: Immunotherapy and personalized medicine therapeutics are emerging as promising approaches in the management of head and neck squamous cell carcinoma (HNSCC). In spite of that, there is yet no assay that could predict individual response to immunotherapy.

Methods: We manufactured an in vitro 3D microfluidic chip to test the efficacy of immunotherapy.

Fully Human Tumor-based Matrix in Three-dimensional Spheroid Invasion Assay.

Two-dimensional cell culture-based assays are commonly used in in vitro cancer research. However, they lack several basic elements that form the tumor microenvironment. To obtain more reliable in vitro results, several three-dimensional (3D) cell culture assays have been introduced.

A deep convolutional neural network approach for astrocyte detection.

Astrocytes are involved in various brain pathologies including trauma, stroke, neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, or chronic pain. Determining cell density in a complex tissue environment in microscopy images and elucidating the temporal characteristics of morphological and biochemical changes is essential to understand the role of astrocytes in physiological and pathological conditions. Nowadays, manual stereological cell counting or semi-automatic segmentation techniques are widely used for the quantitative analysis of microscopy images.

Differential Spinal and Supraspinal Activation of Glia in a Rat Model of Morphine Tolerance.

Development of tolerance is a well known pharmacological characteristic of opioids and a major clinical problem. In addition to the known neuronal mechanisms of opioid tolerance, activation of glia has emerged as a potentially significant new mechanism. We studied activation of microglia and astrocytes in morphine tolerance and opioid-induced hyperalgesia in rats using immunohistochemistry, flow cytometry and RNA sequencing in spinal- and supraspinal regions.

A Novel Small Molecule GDNF Receptor RET Agonist, BT13, Promotes Neurite Growth from Sensory Neurons and Attenuates Experimental Neuropathy in the Rat.

Neuropathic pain caused by nerve damage is a common and severe class of chronic pain. Disease-modifying clinical therapies are needed as current treatments typically provide only symptomatic relief; show varying clinical efficacy; and most have significant adverse effects. One approach is targeting either neurotrophic factors or their receptors that normalize sensory neuron function and stimulate regeneration after nerve damage.