Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immune adjuvants have been shown to induce tumor growth control in many experimental tumor-host models. The beneficial effect depends on tumor size and type and dose of the adjuvants in question, but few experimental data elucidate, which immunological mechanisms--if any--that are directly involved in the tumor destructive processes induced by immuno-adjuvants. The importance of non-specific tumor immunity is discussed with emphasize on the importance of immuno-competent cells that react non-specifically, and that may include "self-directed" cells. Non-immunological mechanisms are proposed also to be of importance, underlining the possible role of the phenomenon of spontaneous reversion of malignant cells to a non-malignant state. It is finally stressed that both immunologic and non-immunologic properties of immunoadjuvant induced tumor growth control must be analysed before therapy with immunoadjuvants can be optimally applicated in the cancer patient.
 ...
PMID:Experimental induction of tumor growth control by immune adjuvants: current status and some theories to be explored. 66 79

Macrophages require a plasma component, designated "recognition factor" (RF), for the expression of optimal function. The RF activity was profoundly depleted in plasma from patients with malignant disease, and the degree of depletion and the severity of the malignant state seemed to be related. Since experiments demonstrated that an active RF significantly inhibited tumor growth, clinical studies were initiated to investigate the influence of intratumor administration of an active RF fraction. Glucan, a potent macrophage activator, was also employed alone or combined with RF. These studies were undertaken to enhance the recognition of malignant cells by macrophages and to mobilize and activate macrophages intralesionally. The initial 9 patients studied had malignant melanoma, adenosquamous carcinoma of the lung, or carcinoma of the breast. Control and experimental lesions were injected; subsequently biopsies were performed at varying intervals for histologic evaluation. Always when glucan or glucan and RF fraction were administered intralesionally, the size of the lesion was strikingly reduced in as short a period as 5 days. This reduction was associated with necrosis of the tumor and a monocytic infiltrate. In small lesions, resolution was complete, whereas in large lesions, resolution was partial. The amount of glucan injected and the quantity of residual tumor appeared to be related. The induced necrosis of the tumor nodule was associated with an increase in plasma levels of circulating RF activity.
 ...
PMID:Macrophage-mediated destruction of human malignant cells in vivo. 112 50

The production of plasminogen activator by the human breast cancer cell line MCF-7 was stimulated by physiological concentrations of estradiol under conditions where the growth of the cells was neither dependent on nor stimulated by estradiol. Stimulation was measurable within 8 hr after the addition of estradiol and was evident in both the level of plasminogen activator released into the culture medium and the level within the cells. The level of production varied with cell density, but production was stimulated by estradiol at all densities tested. The antiestrogen tamoxifen inhibited estrogen stimulation, and this inhibition could be overcome by increased concentrations of estradiol. Production was also stimulated by progesterone and could be stimulated by lower levels of progesterone in cells pretreated with estradiol or tamoxifen, both of which have been reported to increase the level of progesterone receptor in these cells. It has been reported that estrogen is essential and that progesterone is stimulatory for the formation of tumors by MCF-7 cells in athymic mice. The ability of these same two hormones to stimulate the production of plasminogen activator by these cells, under conditions where they have no effect on cell growth, raises the possibility that estrogen may not play a mitogenic role in the growth of these tumors. Rather, it may support tumor growth by inducing the cells to produce products, such as plasminogen activator, and possibly take on other characteristics essential to the malignant state.
 ...
PMID:Steroid stimulation of plasminogen activator production in a human breast cancer cell line (MCF-7). 668 6

Prostate cancer is one of the most commonly diagnosed cancers and is a major cause of cancer death in men. Although the majority of the diagnosed prostate cancers will remain localized and never produce clinical symptoms during the lifetime of the host, a subset of these cancers will progress to a more malignant state requiring therapeutic intervention. Acquisition of metastatic ability by prostatic cancer cells is the most lethal aspect of prostatic cancer progression. Once this has occurred, definitive therapy is required before the initially localized metastatic cells escape from the prostate. At present, metastatic prostate cancer is incurable. Therefore, there is an urgent need to develop molecular markers that can be used to predict the metastatic potential of prostate cancers. Using somatic cell hybridization, we have demonstrated that acquisition of metastatic ability requires both the loss of metastasis-suppressor function(s) and the activation of oncogenes. In further studies using micro-cell-mediated chromosomal transfer, we located genes on human chromosome, 8, 10cen-q23, 11p11.2-13, and 17pter-q23, which, when introduced into rat prostatic cancer cells, are capable of suppressing their metastatic ability without affecting their tumorigenicity or growth rate in vivo. Initially we focused upon the human chromosome 11p11.2-13 region to clone metastasis-suppressor gene(s) positionally. One such gene, termed KAI-1, encodes a membrane glycoprotein. KAI-1 has been mapped to the p11.2 region of human chromosome 11 by fluorescence in-situ hybridization analysis. Expression of KAI-1 has been detected in all normal human tissues thus far tested, including prostate tissue. When introduced into rat metastatic prostatic cancer cells, KAI-1 significantly suppressed the metastasis without affecting the tumor growth rate. KAI-1 expression is high in human normal prostate and benign prostatic hyperplasia but is dramatically lower in cancer cell lines derived from metastatic prostate tumors.
 ...
PMID:Prostate cancer--biology of metastasis and its clinical implications. 880 97

In this study, we demonstrate insulin-like growth factor binding protein (IGFBP) acid proteolysis in conditioned media (CM) from normal and malignant primary cultures of prostatic epithelial cells, prostatic cell lines, and in seminal plasma. We further demonstrate the absence of such activity in CM from prostatic stromal cells. Radio-labeled IGFBPs (1-6) were incubated with various acidified CM and seminal plasma. None of these media showed IGFBP proteolytic activity at neutral pH, but all CM from prostatic epithelial cells (PC-E) demonstrated strong IGFBP proteolysis at acidic pH. No acid-activated proteolysis was observed in the CM from stromal cell cultures. In order to ascertain the role of cathepsin D, anti-cathepsin antibodies were used to immunodeplete the media of the selected enzymes prior to incubation with IGFBPs. Depletion of cathepsin D greatly reduced the proteolytic activity of the PC-E CM. Additionally, purified cathepsin D yielded a digestion pattern identical to that produced by prostatic cell CM and seminal plasma, following acidic incubation with IGFBP-3. Remarkably, the proteolytic pattern generated by seminal plasma, when incubated with IGFBP-3 at neutral pH, corresponded to that produced by prostate-specific antigen (PSA), demonstrating the interpolation of both neutral and acid proteases from prostate cells into seminal plasma. In conclusion, prostatic epithelial cells secrete acid-specific IGFBP protease(s) related to cathepsin D. Although no significant statistical difference was observed in the degree of acid-specific proteolysis in the media from normal versus malignant primary epithelial cell cultures, physiological characteristics of the malignant state might facilitate increased cathepsin D activity. We suspect this proteolysis may play a role in prostatic cell proliferation and invasive tumor growth.
 ...
PMID:Acid-activated insulin-like growth factor binding protein protease activity of cathepsin D in normal and malignant prostatic epithelial cells and seminal plasma. 913 Apr 67

Although its precise function has not yet been established, galectin-1 seems to play a role in tumor progression. In this study, we investigated galectin-1 mRNA expression in human glioma specimens and glioma cell lines. Northern blot analysis showed higher galectin-1 mRNA levels in glioma tissues. The 0.7-kb galectin-1 mRNA transcript was detected, and the expression level correlated with the malignant state, from low-grade astrocytoma to glioblastoma. In several human glioma specimens, immunohistochemical examination with antiserum against a synthetic peptide corresponding to the predicted C-terminal sequence of the protein showed high levels of galectin-1 expression. To clarify the correlation between the expression of galectin-1 and the malignancy of gliomas, we examined whether expression of antisense galectin-1 would suppress tumor growth in rat 9L cells that express high levels of galectin-1. The cells were transfected with a plasmid DNA that produces antisense galectin-1 mRNA under the control of the metallothionein promoter, and stable clones expressing low levels of galectin-1 protein in comparison with control clones were isolated. Cells with low levels of galectin-1 displayed dramatic phenotypic changes in their morphology and growth properties compared with vector-transfected control 9L cells. Our data suggest that decreased expression of galectin-1 may arrest the growth of rat 9L cells.
 ...
PMID:Expression of galectin-1 mRNA correlates with the malignant potential of human gliomas and expression of antisense galectin-1 inhibits the growth of 9 glioma cells. 1070 9

Primary corneal myxoma is extremely rare. It has only been reported on 2 previous occasions. Secondary corneal myxomas are more common, arising from corneal diseases such as infective keratitis, keratoconus, and bullous keratopathy. Myxomas occur commonly in other soft tissues such as the heart, paranasal sinuses, and muscles but can rarely present in periocular structures including the conjunctiva, orbit, and eyelid. Ours is only the third case of primary corneal myxoma reported in the literature and illustrates several unusual features. These include an inferonasal location between the corneal epithelium and Bowman layer and with no relationship to the corneal stroma, rapid tumor growth over a 3-month period, and no previous ocular trauma or conjunctival pathology. The histology of this lesion has an important part to play in the management of this condition as it determines the cellular origin, establishes a benign or malignant state, and helps with treatment and prognosis. One reported case of primary corneal myxoma recurred within 2 months after local resection. This was treated with bandage soft contact lens, and no recurrence had been reported since. Our case is now 12 months post op and has had no recurrence.
 ...
PMID:Primary corneal myxoma. 1903 39

Glioblastoma multiforme (GBM) is the most frequent and incurable type of brain tumor of adults. Hypoxia has been shown to direct GBM toward a more aggressive and malignant state. Here we show that hypoxia increases Notch1 activation, which in turn induces the expression of transient receptor potential 6 (TRPC6) in primary samples and cell lines derived from GBM. TRPC6 is required for the development of the aggressive phenotype because knockdown of TRPC6 expression inhibits glioma growth, invasion, and angiogenesis. Functionally, TRPC6 causes a sustained elevation of intracellular calcium that is coupled to the activation of the calcineurin-nuclear factor of activated T-cell (NFAT) pathway. Pharmacologic inhibition of the calcineurin-NFAT pathway substantially reduces the development of the malignant GBM phenotypes under hypoxia. Clinically, expression of TRPC6 was elevated in GBM specimens in comparison with normal tissues. Collectively, our studies indicate that TRPC6 is a key mediator of tumor growth of GBM in vitro and in vivo and that TRPC6 may be a promising therapeutic target in the treatment of human GBM.
 ...
PMID:Receptor channel TRPC6 is a key mediator of Notch-driven glioblastoma growth and invasiveness. 2002 70

Overexpression of the human epidermal growth factor receptor-2 (HER2) in breast cancer strongly correlates with aggressive tumors and poor prognosis. Recently, a positive correlation between HER2 and MIF (macrophage migration inhibitory factor, a tumor-promoting protein and heat-shock protein 90 (HSP90) client) protein levels was shown in cancer cells. However, the underlying mechanistic link remained unknown. Here we show that overexpressed HER2 constitutively activates heat-shock factor 1 (HSF1), the master transcriptional regulator of the inducible proteotoxic stress response of heat-shock chaperones, including HSP90, and a crucial factor in initiation and maintenance of the malignant state. Inhibiting HER2 pharmacologically by Lapatinib (a dual HER2/epidermal growth factor receptor inhibitor) or CP724.714 (a specific HER2 inhibitor), or by knockdown via siRNA leads to inhibition of phosphoactivated Ser326 HSF1, and subsequently blocks the activity of the HSP90 chaperone machinery in HER2-overexpressing breast cancer lines. Consequently, HSP90 clients, including MIF, AKT, mutant p53 and HSF1 itself, become destabilized, which in turn inhibits tumor proliferation. Mechanistically, HER2 signals via the phosphoinositide-3-kinase (PI3K)-AKT- mammalian target of rapamycin (mTOR) axis to induce activated pSer326 HSF1. Heat-shock stress experiments confirm this functional link between HER2 and HSF1, as HER2 (and PI3K) inhibition attenuate the HSF1-mediated heat-shock response. Importantly, we confirmed this axis in vivo. In the mouse model of HER2-driven breast cancer, ErbB2 inhibition by Lapatinib strongly suppresses tumor progression, and this is associated with inactivation of the HSF1 pathway. Moreover, ErbB2-overexpressing cancer cells derived from a primary mouse ErbB2 tumor also show HSF1 inactivation and HSP90 client destabilization in response to ErbB2 inhibition. Furthermore, in HER2-positive human breast cancers HER2 levels strongly correlate with pSer326 HSF1 activity. Our results show for the first time that HER2/ErbB2 overexpression controls HSF1 activity, with subsequent stabilization of numerous tumor-promoting HSP90 clients such as MIF, AKT and HSF1 itself, thereby causing a robust promotion in tumor growth in HER2-positive breast cancer.
...
PMID:HER2/ErbB2 activates HSF1 and thereby controls HSP90 clients including MIF in HER2-overexpressing breast cancer. 2438 23

Chaperone dependency of cancer cells is an emerging trait that relates to the need of transformed cells to cope with the various stresses associated with the malignant state. URI1 (unconventional prefoldin RPB5 interactor 1) encodes a member of the prefoldin (PFD) family of molecular chaperones that acts as part of a heterohexameric PFD complex, the URI1 complex (URI1C), to promote assembly of multiprotein complexes involved in cell signaling and transcription processes. Here, we report that human colorectal cancer (CRCs) cell lines demonstrate differential dependency on URI1 and on the URI1 partner PFD STAP1 for survival, suggesting that this differential vulnerability of CRC cells is directly linked to URI1C chaperone function. Interestingly, in URI1-dependent CRC cells, URI1 deficiency is associated with non-genotoxic p53 activation and p53-dependent apoptosis. URI1-independent CRC cells do not exhibit such effects even in the context of wildtype p53. Lastly, in tumor xenografts, the conditional depletion of URI1 in URI1-dependent CRC cells was, after tumor establishment, associated with severe inhibition of subsequent tumor growth and activation of p53 target genes. Thus, a subset of CRC cells has acquired a dependency on the URI1 chaperone system for survival, providing an example of 'non-oncogene addiction' and vulnerability for therapeutic targeting.
...
PMID:Colorectal cancer cells display chaperone dependency for the unconventional prefoldin URI1. 2710 89


1 2 Next >>