ADAM10 and Neprilysin level decreases in immune cells of mice bearing metastatic breast carcinoma: Possible role in cancer inflammatory response.

Objective And Design: ADAM10 and Neprilysin, proteases, play critical role in inflammatory disease, however their role in cancer immune response is not clear. We here evaluated changes in immune response using an experimental model for breast cancer.

Material And Method: Highly metastatic breast cancer cells (4T1-derived) were injected orthotopically (mammary-pad of Balb-c mice) to induce tumors.

Carcinogenesis and Metastasis: Focus on TRPV1-Positive Neurons and Immune Cells.

Both sensory neurons and immune cells, albeit at markedly different levels, express the vanilloid (capsaicin) receptor, Transient Receptor Potential, Vanilloid-1 (TRPV1). Activation of TRPV1 channels in sensory afferent nerve fibers induces local effector functions by releasing neuropeptides (most notably, substance P) which, in turn, trigger neurogenic inflammation. There is good evidence that chronic activation or inactivation of this inflammatory pathway can modify tumor growth and metastasis.

Changes in TRPV1 Expression as Well as Substance P and Vasoactive Intestinal Peptide Levels Are Associated with Recurrence of Pterygium.

Pterygium, a disease of the ocular surface, is characterized by the proliferation and invasion of fibrovascular tissue. Chronic inflammation contributes to pterygium occurrence. Sensory neuropeptides of TRPV1-positive nerve fibers are involved in inflammation and corneal wound healing.

Regulation of Carcinogenesis by Sensory Neurons and Neuromediators.

Interactions between the immune system and the nervous system are crucial in maintaining homeostasis, and disturbances of these neuro-immune interactions may participate in carcinogenesis and metastasis. Nerve endings have been identified within solid tumors in humans and experimental animals. Although the involvement of the efferent sympathetic and parasympathetic innervation in carcinogenesis has been extensively investigated, the role of the afferent sensory neurons and the neuropeptides in tumor development, growth, and progression is recently appreciated.

Distribution of transient receptor potential vanilloid-1 channels in gastrointestinal tract of patients with morbid obesity.

Background: Transient receptor potential vanilloid-1 (TRPV1), a nonselective cation channel, is activated by capsaicin, a pungent ingredient of hot pepper. Previous studies have suggested a link between obesity and capsaicin-associated pathways, and activation of TRPV1 may provide an alternative approach for obesity treatment. However, data on the TRPV1 distribution in human gastric mucosa are limited, and the degree of TRPV1 distribution in the gastric and duodenal mucosal cells of obese people in comparison with normal-weight individuals is unknown.

Olvanil activates sensory nerve fibers, increases T cell response and decreases metastasis of breast carcinoma.

Background: Inactivation of sensory neurons expressing transient receptor potential vanilloid 1 (TRPV1) enhances breast cancer metastasis. Sensory neurons have profound effects on immune response to a wide range of diseases including cancer. Hence, activation of sensory nerves using feasible approaches such as specific TRPV1 agonists may inhibit breast cancer metastasis through neuroimmune pathways.

Effects of in-vitro modulation of TRPV1 activity on immune response of mice bearing metastatic breast carcinoma: Enhanced inflammatory response may hinder therapeutic potentials of TRPV1 agonists.

Aims: Activation of transient receptor potential vanilloid 1 (TRPV1) ion channels inhibits inflammation, enhance cytotoxic immune response, and may have therapeutic potential in treatment of cancer characterized by increased systemic inflammation. We here determined how activation of TRPV1 alters immune response of tumor-bearing mice.

Main Methods: Three different metastatic subset of 4 T1 breast carcinoma cells were used to induce tumors in Balb-c mice.

Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance.

The ability of tumor cells to evade apoptosis is established as one of the hallmarks of cancer. The deregulation of apoptotic pathways conveys a survival advantage enabling cancer cells to develop multi-drug resistance (MDR), a complex tumor phenotype referring to concurrent resistance toward agents with different function and/or structure. Proteins implicated in the intrinsic pathway of apoptosis, including the Bcl-2 superfamily and Inhibitors of Apoptosis (IAP) family members, as well as their regulator, tumor suppressor p53, have been implicated in the development of MDR in many cancer types.

Changes in ghrelin, substance P and vasoactive intestinal peptide levels in the gastroduodenal mucosa of patients with morbid obesity.

Aims: The aim of the study was to assess changes in levels of substance P (SP), vasoactive intestinal peptide (VIP) and ghrelin in the gastroduodenal mucosa of obese individuals, which has not been studied before.

Methods: Forty-six patients with a body mass index (BMI) of >40 kg/m and 20 patients with a BMI of 18-25 kg/m were included in the study. VIP and SP levels in the fundus, antrum and duodenal mucosa were measured in freshly frozen tissues using enzyme-linked immunosorbent assay (ELISA).

Rebound increases in chemokines by CXCR2 antagonist in breast cancer can be prevented by PKCδ and PKCε activators.

Activation of CXCR2 by chemokines such as CXCL1 and CXCL2 increases aggressiveness of breast cancer, inducing chemoresistance, hence CXCR2 antagonists are in clinical trials. We previously reported that inhibition of CXCR2 increases MIP-2 (CXCL2), which may inhibit anti-tumoral effects of CXCR2 antagonists. This seems to be due to inhibition of protein kinase C (PKC) by CXCR2 antagonist since specific inhibitor of PKC also enhances MIP-2 secretion.

Changes of HMGB-1 and sTLR4 levels in cerebrospinal fluid of patients with febrile seizures.

Purpose: Fever-induced inflammatory processes and pro-inflammatory cytokines have gained importance in recent years in the pathogenesis of febrile convulsion. Increased levels of HMGB1 (high mobility group box 1), one of the most important pro-inflammatory cytokines, are associated with prolongation of seizure duration, recurrence of seizures and the development of epilepsy. Changes in the sTLR4 level (soluble toll-like receptor 4) in the cerebrospinal fluid (CSF) are thought to be associated with memory and learning functions.

Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance.

It is well established that multifactorial drug resistance hinders successful cancer treatment. Tumor cell interactions with the tumor microenvironment (TME) are crucial in epithelial-mesenchymal transition (EMT) and multidrug resistance (MDR). TME-induced factors secreted by cancer cells and cancer-associated fibroblasts (CAFs) create an inflammatory microenvironment by recruiting immune cells.

NK1R antagonist decreases inflammation and metastasis of breast carcinoma cells metastasized to liver but not to brain; phenotype-dependent therapeutic and toxic consequences.

Substance P a neuro-immune mediator acts on Neurokinin-1 and -2 receptors (NK1R and NK2R). Inhibitors of NK1R are considered to be safe and effective approaches for cancer treatment since Aprepitant, a non-peptide antagonist of NK1R is widely used for chemotherapy-induced emesis and has cytotoxic and antitumor effects in various models for cancer. On the other hand, our previous findings demonstrated that systemic inhibition of NK1R may decrease cytotoxic anti-tumoral immune response.

Role of sensory neurons, neuroimmune pathways, and transient receptor potential vanilloid 1 (TRPV1) channels in a murine model of breast cancer metastasis.

Sensory nerves sensitive to capsaicin are afferent nerve fibers which contain TRPV1 channels. Activation of these channels induces release of neuropeptides which regulate local blood flow and immune response. Inactivation of sensory neurons either with high-dose capsaicin treatment or local ablation of vagal sensory nerve activity markedly increases metastasis of breast carcinoma formed by 4T1 derivative cells.

CD200 mimetic aptamer PEG-M49 markedly increases the therapeutic effects of pegylated liposomal doxorubicin in a mouse model of metastatic breast carcinoma: an effect independent of CD200 receptor 1.

We previously reported that CD200 overexpression in the host decreases progression and metastasis of the highly aggressive metastatic 4THM breast carcinoma. We have explored a possible synergistic interaction between the CD200 mimetic PEG-M49 and pegylated liposomal doxorubicin (Peg-Dox) in wild-type CD200 knockout (CD200) and CD200 Receptor 1 knockout (CD200R1) mice for the first time. A 4THM breast carcinoma model and three groups of BALB/c mice (wild type, CD200 and CD200R1) were used.

HSP90 inhibitor PU-H71 increases radiosensitivity of breast cancer cells metastasized to visceral organs and alters the levels of inflammatory mediators.

Heat shock protein 90 (HSP90) inhibitors are considered as new radiosensitizing agents. PU-H71, a novel HSP90 inhibitor, is under evaluation for the treatment of advanced cancer. It is however not known whether PU-H71 alters radiosensitivity of metastatic breast cancer.

Effect of Photobiomodulation on Secretion of IL-6 and IL-8 by Human Gingival Fibroblasts .

The aim of this study was to evaluate the effects of 940-nm diode laser irradiation on proinflammatory cytokine secretions [interleukin (IL)-6 and IL-8] by human gingival fibroblasts . Photobiomodulation has been routinely used in many dental procedures; however, the exact biological action mechanism of photobiomodulation and its therapeutic benefits have not been established. Cells derived from systemically healthy individuals were treated with three different laser parameters-6 J for 20 sec [0.

Examining the role of parasites in limiting unidirectional gene flow between lake and river sticklebacks.

Parasites are important selective agents with the potential to limit gene flow between host populations by shaping local host immunocompetence. We report on a contact zone between lake and river three-spined sticklebacks (Gasterosteus aculeatus) that offers the ideal biogeographic setting to explore the role of parasite-mediated selection on reproductive isolation. A waterfall acts as a natural barrier and enforces unidirectional migration from the upstream river stickleback population to the downstream river and lake populations.

Changes in substance P levels of inferior turbinate in patients with mucosal contact headache.

Introduction: Mucosal contact headache is a referred pain that arises from contact between the nasal septum and the lateral nasal wall. Evidence supports the role of substance P in a contact headache such that release of substance P from sensory nerve endings causes inflammation and allergy.

Objectives: This study aimed to determine possible differences in substance P levels in inferior turbinate hypertrophy creating a contact headache.

Differential consequences of neurokinin receptor 1 and 2 antagonists in metastatic breast carcinoma cells; Effects independent of Substance P.

Introduction: The biological action of Substance P (SP) is mediated mainly by NK-1 receptors (NK1R) followed by NK2 receptors (NK2R). Aberrant expression of NK1R and NK2R has been identified in various carcinomas. The role of Substance P and its receptors, especially NK2R in cancer progression is not entirely known and there are conflicting results in the literature demonstrating the need for further investigation.

Presence of S100A8/Gr1-Positive Myeloid-Derived Suppressor Cells in Primary Tumors and Visceral Organs Invaded by Breast Carcinoma Cells.

Background: Increased S100A8/A9 expression in Gr1-positive cells has been shown in myeloid-derived suppressor cells and may play a role in the formation of a metastatic milieu. We aimed to determine S100A8/A9 expression alone and with coexpression of Gr1 (a myeloid marker) in primary tumor and visceral tissues invaded by metastatic breast carcinoma.

Materials And Methods: Female BALB/c mice were injected with 4TLM, 4THM, and 67NR orthotopically.

CD200fc enhances anti-tumoral immune response and inhibits visceral metastasis of breast carcinoma.

CD200 is a widely expressed cell surface glycoprotein that inhibits excessive inflammation in autoimmunity, transplantation, and viral infections. We previously observed that visceral metastasis of highly aggressive and inflammatory 4THM breast carcinoma cells was markedly decreased in CD200 transgenic mice. The goal of this study was to determine whether exogenous exposure to CD200fc mimics the effects of endogenously over expressed CD200.

Correction to: Secretomes reveal several novel proteins as well as TGF-β1 as the top upstream regulator of metastatic process in breast cancer.

In the original publication of the article, Acknowledgement section was missed out and Table 1 was published incompletely. The Acknowledgment and complete table 1 are given in this correction. The original article has been corrected.

Secretomes reveal several novel proteins as well as TGF-β1 as the top upstream regulator of metastatic process in breast cancer.

Purpose: Metastatic breast cancer is resistant to many conventional treatments and novel therapeutic targets are needed. We previously isolated subsets of 4T1 murine breast cancer cells which metastasized to liver (4TLM), brain (4TBM), and heart (4THM). Among these cells, 4TLM is the most aggressive one, demonstrating mesenchymal phenotype.