B-36 Needle Bearing

[Mertie Oldow]

DrawnCup Needle Roller Bearings have a thin-walled outer ring. They are designed for applications where the housing bore cannot be used as a raceway for a needle roller and cage assembly. Drawn cup needle roller bearings generally run directly on a shaft, if the shaft cannot be hardened and ground they can be combined with an inner ring.

Franke FDE linear guides are equipped with lubricant-free, high-quality needle bearings and are made almost entirely of lightweight aluminum. They are suitable for linear motion tasks in almost all industries, especially for use in food production or in clean rooms. Rail elements can be manufactured in a length of 200 mm to 4000 mm and, on request, can also be linked endlessly.

Needle bearings give the universal joints at an inclination angle from 3 to 5 a considerably higher degree of efficiency than those fitted with friction bearings. The needle bearings have permanent lubrication and thus do not require servicing.

Cross holes in universal joint shafts and in universal shafts are suitable for making shaft-hub connections using a pin or a grub screw. For bores with keyway or square, they serve to secure the axial position of the universal joint and shaft. The d2 pin hole with H11 tolerance is intended for use with spiral spring pins.

The position of the cross holes / cross threads in relation to the keyway / square or the universal joints is shown in the overview.

To order cross hole GN 110.1, please call our sales team:

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Prostate cancer is the second most frequent cancer type among men globally. Herein, the roles of exosomes in prostate cancer tumorigenesis, progress along with metastasis were reviewed. Exosomes are small extracellular vesicles originated from the endosomal system then released to surrounding body fluids. They carry cargo comprising nucleic acids and proteins and deliver then to recipient cells and are implicated in cell-to-cell communications. They regulate the activities of recipient cells by modulating several physiological and pathological processes, such as remodeling the properties of the tumor microenvironment, modulating cancer metabolism and metastases, and regulating drug resistance. Tumor derived exosomes are present in various body fluids and their molecular profile can reflect the real-time status of the cancer cell. These characteristics make them prospective biologic signatures for diagnosis along with prognosis of different cancer types. Besides, exosomes have good biophysical properties, for instance high stability in the lipid bilayer membrane, as well as low immunogenicity which are key parameters for development of novel drug delivery approach.

Exosomes are small extracellular vesicles (EVs) enclosed by a lipid bilayer membrane and are secreted by most eukaryotic cells. The size of EVs range from 50 nm to 1000 nm in diameter, and the size of exosomes range from 30 to 120 nm in diameter (7). Exosomes are present in various biological fluids, for instance blood, urine, milk, semen as well as saliva, and can be purified from cell growth medium. Previous investigations document that exosomes have pivotal roles in diseases through inter-cellular communication and modulation of biological processes. The biological function of an exosome depends on the contents of the cargo, for instance miRNAs, viral particles, mRNAs, proteins, or lipids (8). Exosomes and their cargos play roles as mediators in short- or long-distance communication, as observed in tumor-derived EVs (TDEs). Tumor cells have been documented to be generating, releasing, and utilizing exosomes to enhance tumor growth. Therefore, have an indispensable role in tumorigenesis, proliferation, migration and drug resistance and are prospective signatures for diagnosis along with prognosis and can be used as drug-delivering systems (9, 10).

Tumor cells from various origins constitutively release exosomes, which play indispensable roles in malignant transformation and progress of tumors. Effects of exosomes are mediated through transfer of cargo that comprises various proteins, RNA (including miRNAs), and DNA. A previous study reports that a favorable prostatic tumoral niche is established through the CXCR1 chemokine receptor present in the exosome membrane derived from the cancer cell in prostate cancer. Tumor derived exosomes activate fibroblasts by upregulating expression of metalloprotein 9 (MMP-9). MMPs are implicated in degrading the extracellular matrix and promote cancer cell invasion. MMP-9 upregulation increases cell motility and promotes increased exosome secretion from activated fibroblasts which ultimately increases cancer cell migration (Figure 2). This cancer-to-fibroblast cell communication mediated by exosomes provides a favorable environment for cancer development (19). Besides, miR-139, miR-21 along with miR-100 trigger migrations of fibroblasts via upregulating expressions of MMP-2, RANKL, MMP-9, as well as MMP-13 (20).

Multiple roles of cancer originated exosomes in PCa. Tumor exosomes can modulate cancer metastasis by forming the niche of pre-metastasis via miRNA regulation of MMP9 expression. TGF-β can induce differentiation of stromal fibroblasts to myofibroblast-like phenotype and promote tumor progression. Tumor exosomes downregulate NKG2D-triggered cytotoxic response in individuals with PC, resulting in immune repression and tumor escape. Cross-talk between tumor originated exosome proteins Src and IGF-1R promotes angiogenesis.

A hallmark of cancer development is transition of the normal stroma cells to reactive stroma cells promoting cancer cell growth along with metastasis. The influenced stromal cells then use exosomes to modulate the tumor microenvironment, as well as enhance tumor growth along with metastasis. A sustained interplay ensues between tumor cells and neighboring stromal cells (21). TGF-β bearing cancer exosomes have pivotal roles in generating tumor-promoting stroma by promoting differentiation of fibroblast to a myofibroblast-like phenotype that induces angiogenesis and tumor growth. This effect is achieved via activating the TGF-β/SMAD3 cascade (Figure 2). Exosomes generated by PCa cells highly express latent TGF-β which bind the exosome surface through proteoglycans thus promote activation of SMAD3 dependent signaling pathways (18).

Metastasis is reported in most advanced PCa patients and is linked to high incidence of death. Pre-metastatic niche (PMN) is a key determinant priming distal site for metastasis. Studies report that exosomes have an indispensable role in triggering tumor cell metastasis via establishing the PMN by acting as cellular communicators. Different populations of PCa cells (bulk and cancer stem cells, CSCs) generate exosomes that harbor miRNAs which modify the pre-metastatic niche. Two miRNA types derived from PCa exosomes including miRNA-21 along with miRNA-139, upregulate protein expressions of MMP-2, MMP-9 coupled with MMP -13, and RANKL in fibroblasts. The balance between RANKL and OPG level at the niche of pre-metastasis can modify tumor microenvironment and promote cell migration. In addition, miRNA-21 upregulates expression of MMPs in normal fibroblasts and triggers cellular alterations involved in activating fibroblast such as alterations in cell shape along with elavated cell migration (22).

Bone metastasis is the most common type of metastasis from of advanced prostate cancer (PCa). Pyruvate kinase M2 (PKM2) is transported through exosomes from PCa cells into BMSCs (bone marrow stromal cells). This feature is a novel mechanism via which primary tumor-originated exosomes enhance pre-metastatic niche formation (8). PCa-derived exosomes upregulate PKM2 expression, which ultimately upregulates CXCL12 expression (C-X-C motif chemokine ligand-12) in BMSCs thus inducing a pre-metastatic niche. Targeting the exosome-triggered CXCL12 axis abrogates exosome-stimulated bone metastasis indicating the therapeutic potential of targeting exosome derived PKM2.

Tumor microenvironment has an indispensable role in cancer development mainly resulting in formation of vascular tumors (13). Angiogenesis constitutes a multistep process for generation of new blood vessels from the already-existing vasculature and is the main cause of tumor metastasis, as well as malignancy (23, 24). Prostate cancer cells generate EVs for transporting sphingomyelin along with CD147 into endothelial cells, and enhance migration coupled with proangiogenic activity of endothelial cells (25, 26). Proteins such as c-Src tyrosine kinase, IGF-R (insulin-like growth factor 1 receptor) as well as FAK (focal adhesion kinase) play pivotal roles in prostate tumor growth along with progression (27). Prostate cancer exosomes have high levels of these proteins. Cross-talk between Src and IGF-1R promotes angiogenesis (28). Src coupled with c-Src are highly expressed in plasma exosomes of prostate tumor-bearing mice, indicating that Src-rich exosomes can enhance angiogenesis in vivo (Figure 2). In addition, Src and IGF1-R modulate angiogenesis by inducing VEGF and VEGF-C, respectively (29, 30). Exosomes derived from menstrual stem cells block prostate tumor-induced angiogenesis through inhibition of reactive oxygen species. Notably, exosomes with anti-angiogenic effect are only derived from menstrual cells (31). These findings indicate that prostate cancer exosomes can stimulate or block angiogenic activity within the tumor microenvironment.

Markers can be determine in liquid biopsies (such as biofluids) thus avoiding use of invasive approaches and can reflect heterogeneity of the tumor effectively compared with prostate needle biopsies (40). Studies are currently exploring biomarkers for PCa that can supplement PSA and improve efficacy of diagnosis. Biologic signatures for early diagnosis, as well as risk stratification should be explored for timely diagnosis and aid in designing more effective therapies. Exosomes generated by cancer cells into biological fluids harbor biomolecules that exhibit the disease condition, and are currently referred as a new kind of liquid biopsies (6, 41).

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