Disease relevance of C18orf8

• In low-grade localized prostate cancer (Gleason sum score < or = 6), the level of MIC-1 stromal stores was the best predictor of future relapse when compared with all other clinicopathologic variables [1].
• However, MIC-1 did not significantly suppress the proliferation of gastric cancer cell lines [2].
• Carcinomas commonly overexpress macrophage inhibitory cytokine 1 (MIC-1), a proapoptotic and antitumorigenic transforming growth factor-beta superfamily cytokine [1].
• CONCLUSION: In the differentiation of patients with resectable pancreatic cancer from controls, serum MIC-1 outperforms other markers including CA19-9 [3].
• Based on receiver operator curve analysis, the best predictor for the presence of baseline bone metastasis was MIC-1, which was significantly better than carboxy-terminal telopeptide of type I collagen, prostate-specific antigen, and PINP [4].

High impact information on C18orf8

• Single deletion of the MIC1 gene decreased invasion in fibroblasts, whereas MIC3 deletion had no effect either alone or in the mic1KO context [5].
• Individual disruption of MIC1 or MIC3 genes slightly reduced virulence in the mouse, whereas doubly depleted parasites were severely impaired in virulence and conferred protection against subsequent challenge [5].
• Although generally considered to be part of the cell's antitumorigenic repertoire, MIC-1 secretion, processing, and latent storage suggest a complex, dynamic variability in MIC-1 bioavailability in the tumor microenvironment, potentially modulating tumor progression and invasiveness [6].
• Stromal MIC-1 levels are linked to prostate cancer outcome following radical prostatectomy, with decreasing stromal levels providing an important independent predictor of disease relapse [1].
• Stable transfection of MIC-1 into SNU-216, a human gastric cancer cell line, significantly increased its invasiveness [2].

Chemical compound and disease context of C18orf8

• A clinical isolate of Streptococcus pyogenes UCN1 intermediate to erythromycin (MIC 1 mg/L) and susceptible to clindamycin (MIC 0.03 mg/L) harboured an inducible erm(TR) gene encoding a ribosomal methylase [7].
• Sixty recent Streptococcus pneumoniae isolates with different susceptibilities to ciprofloxacin (14 with MIC 0.5 mg/L, 10 with MIC 1 mg/L, eight with MIC 2 mg/L, 11 with MIC 4 mg/L and 17 with MIC > or =8 mg/L) were tested against five new quinolones using Todd-Hewitt broth with and without 80% serum [8].
• In the first, Staphylococcus aureus NCTC 6571 (vancomycin MIC 1 mg/L), was tested against a human serum containing vancomycin 38 mg/L plus gentamicin 0.5 mg/L [9].
• Collectively, 62% of all Bacteroides strains were susceptible to erythromycin (MIC 1 mg/1) and 74% were susceptible to azithromycin [10].
• The conventional nonsteroidal anti-inflammatory drug sulindac sulfide arrests ovarian cancer cell growth via the expression of NAG-1/MIC-1/GDF-15 [11].

Biological context of C18orf8

• Since there are no sister human chromosomes in AL cells, deletions which extend beyond the MIC1 locus may be conveniently and unambiguously mapped [12].
• Our results indicate that MIC-1 may contribute to the malignant progression of gastric cancer cells by inducing tumor cell invasion through the up-regulation of the uPA activation system via extracellular signal-regulated kinase-1/2-dependent pathway [2].
• MIC-1 is a novel TGF-beta superfamily cytokine associated with macrophage activation [13].
• The antifungal effects of the drugs alone and in combination on the fungal biomass as well as on the metabolic activity of fungi were measured using a spectrophotometric method and two colorimetric methods, based on the lowest drug concentrations showed 75 and 50% growth inhibition (MIC-1 and MIC-2, respectively) [14].
• CONCLUSIONS: Down-regulation of MIC-1 may play a role in the development of BPH [15].

Anatomical context of C18orf8

• MIC-1 is not expressed in resting macrophages but is induced by a number of different activation agents, including phorbol myristate acetate, interleukin 1, tumor necrosis factor alpha, and macrophage colony-stimulating factor but not by lipopolysaccharide or interferon-gamma [13].
• Tissue Northern blots show that MIC-1 transcripts are only found abundantly in placenta, although smaller amounts are seen in a limited number of other adult and fetal tissues [13].
• The presence of antibody to either parasite-excreted proteins (MIC-1 and MIC-2) or surface proteins (SAG-1 and SAG-2) during infection neutralized the marked decrease seen in mitogen-induced lymphoproliferation in the presence of infected monocytes [16].
• Both NPY and MIC-1 showed higher proportional immunostaining in HGPIN and prostate cancer compared with benign epithelium (P < 0.0001) [17].
• RESULTS: In contrast to normal prostates, MIC-1 gene was down-regulated in BPH samples with symptoms and histological BPH obtained from cystoprostatectomy specimens (P < 0.005 and P < 0.01, respectively) [15].

Associations of C18orf8 with chemical compounds

• PATIENTS AND METHODS: Ambulatory patients with NSCLC, aged 75 years or younger, with localized disease, were randomized in MIC1 to receive up to four cycles of chemotherapy (CT: mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2)) every 21 days, followed by radical radiotherapy (CT + RT) or radiotherapy (RT) alone [18].
• Expression level of MIC-1 in androgen-sensitive LNCaP cells was high and enhanced by androgens, whereas in the androgen-insensitive PC-3 and DU-145 cells the expression level was low [15].
• Two strains showed intermediate susceptibility to erythromycin (MIC 1 mg/L) and 27 required greater than or equal to 32 mg/L of sulphamethoxazole for inhibition [19].
• A further 100 strains with a reduced zone (less than 20 mm) to a 2 micrograms ampicillin disc showed a definite (MIC greater than or equal to 4 mg/l) or intermediate (MIC 1 or 2 mg/l) degree of intrinsic resistance to ampicillin [20].
• Using RT-PCR, doxycycline and tetracycline were the most active agents (MIC 1 mg/L), followed by erythromycin (1.6 mg/L), and ciprofloxacin (16 mg/L) [21].

Analytical, diagnostic and therapeutic context of C18orf8

• Xenograft models bearing tumors secreting various engineered forms of MIC-1 show that the propeptide regulates the balance between ECM stores and circulating serum levels of mature MIC-1 in vivo [1].
• EXPERIMENTAL DESIGN: Using immunoassay determination of serum MIC-1 concentration in 1,000 men, 538 of whom had PCa, we defined the relationship of MIC-1 to disease variables [22].
• MIC-1 mRNA was assessed quantitatively by real-time reverse transcriptase-polymerase chain reaction [23].
• NPY and MIC-1 protein expression was determined by immunohistochemistry on tissue microarrays containing 1,626 cores of benign, low-grade prostatic intraepithelial neoplasia (PIN), high-grade PIN (HGPIN), and prostate cancer tissue from 243 radical prostatectomy patients [17].
• PURPOSE: Our previous DNA microarray analyses revealed that the macrophage inhibitory cytokine-1 (MIC-1) gene was significantly down-regulated in symptomatic benign prostatic hyperplasia (BPH) samples [23].

References