Disease relevance of OCM

• RNA from a rat liver tumor (Morris hepatoma 5123tc) was used to construct cDNAs together comprising the complete coding sequence of rat oncomodulin mRNA [1].
• Oncomodulin (OM) is a small, acidic calcium-binding protein first discovered in a rat hepatoma and later found in placental cytotrophoblasts, the pre-implantation embryo, and in a wide variety of neoplastic tissues [2].
• Proliferation, expression of androgen-regulated genes, and transactivation of the androgen receptor (AR) were monitored in LNCaP human prostate cancer cells in response to OCM using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Northern blot analysis, and reporter gene constructs [3].
• In 18 cases (50%) intestinal metaplasia was present in CM/OCM; pancreatic metaplasia was found in 22 cases (61%) [4].
• In the OAM group, six patients had overgrowth of resistant enterobacteriaceae during treatment compared with none in the OCM group, in the gastric microflora [5].

High impact information on OCM

• MATERIALS AND METHODS: We performed an overview using the data from two large analyses, the Advanced Ovarian Cancer Trialists Group (AOCTG [Br Med J 303:884-893, 1991] and Williams et al [Seminars in Oncol 19:120-128, 1992 (suppl 2)]) and the Ovarian Cancer Meta-Analysis Project (OCMP [J Clin Oncol 9:1668-1674, 1991]) [6].
• Excitation spectra of Y57F, F102W, Y65W oncomodulin, and Cod III parvalbumin revealed that the principal Tb3+ luminescence donor residues were phenylalanine or tyrosine located in position 7 of a loop, despite the presence of other nearby donors, including tryptophan [7].
• Tryptophan in binding loop position 7 best enhanced Tb3+ luminescence in the oncomodulin mutant Y57W, as well as VU-9 (F99W) and VU-32 (T26W) calmodulin [7].
• An alternate binding loop, based on Tb3+ binding to model peptides, was inserted into the CD loop of oncomodulin by cassette mutagenesis [7].
• Results obtained with the site-specific variant of oncomodulin known as D59E, in which glutamate replaces the aspartate naturally present at position 59, have necessitated substantial revision of these ideas [8].

Chemical compound and disease context of OCM

• The total anaerobic microflora was strongly suppressed in both treatment groups, although most pronounced in the OCM group, where the frequency of clarithromycin-resistant bacteroides strains increased from 2 to 76% during treatment, and remained at 59% 4 weeks post-treatment [5].
• METHODS: Three hundred and forty-five patients with current or previously active peptic ulcer and a positive H. pylori urease test were randomly assigned to receive RCA, OCA, RCM or OCM twice daily for 7 days (R, rabeprazole 20 mg; O, omeprazole 20 mg; C, clarithromycin 500 mg; A, amoxicillin 1000 mg; M, metronidazole 400 mg) [9].
• Hematoxylin and eosin-stained slides were evaluated by two pathologists for the following histologic details: minimal and maximal length of cardiac mucosa (CM) and oxyntocardiac mucosa (OCM, mixture of cardiac and fundic glands), degree of inflammation in CM and OCM, and presence of intestinal metaplasia or pancreatic metaplasia [4].
• METHODS: Four melanoma cell lines originally isolated from melanotic tumors (B16F10, RPMI 1846, OCM 1, and IIB) were used to establish choroidal melanomas in 105 rabbits; 88 animals were immunosuppressed with cyclosporine [10].

Biological context of OCM

• Oncomodulin is a parvalbumin-like calcium binding protein of Mr 11,700 from rodent tumours [11].
• The interaction of these proteins could also be indirectly demonstrated by monitoring glutathione reductase activity since oncomodulin was shown to inhibit the enzyme in a dose-dependent manner with an apparent IC50 of approximately 5 microM [12].
• The Eu(III) (7)F(0) --> (5)D(0) excitation spectra are pH-dependent, as reported for several EF-hand proteins (oncomodulin, parvalbumin) [13].
• Our results suggest that the integration of the IAP particle genome within the rat oncomodulin gene occurred after the rat and the mouse became distinct species [14].
• Sequencing of 16S rRNA genes and phylogenetic analysis of Methanogenium tationis DSM 2702T (OCM 43T) (T = type strain) and Methanogenium liminatans GKZPZT (= DSM 4140T) as well as other members of the family Methanomicrobiaceae revealed that both species belong to a separate line of descent within this family [15].

Anatomical context of OCM

• The widely-distributed tumour protein, oncomodulin, is a normal constituent of human and rodent placentas [16].
• Glutathione reductase (EC 1.6.4.2) isolated from either the bovine intestinal mucosa or the rat liver was bound in a Ca2(+)-dependent manner to oncomodulin which was covalently attached to Sepharose [12].
• EXPERIMENTAL DESIGN: Primary cultures of human osteoblasts were used as a source of conditioned medium (OCM) [3].
• Locations of CM/OCM over submucosal esophageal glands or squamous epithelium-lined ducts, both indicating a location in the esophagus, were found in eight cases (22%) and in four cases (11%), respectively [4].
• Because of the short length and incomplete circumferential extension of CM/OCM, future endoscopic-bioptic investigations will probably have to be based on more extensive sampling of the gastroesophageal junction [4].

Associations of OCM with chemical compounds

• Oncomodulin, an oncofetal Ca2+-binding protein, contains a single Cys residue in position 18 of its primary structure [17].
• As in other parvalbumins, the liganding residues in the CD and EF sites of oncomodulin differ at the +z and -x coordination positions: serine and aspartate, respectively, in the CD site; aspartate and glycine in the EF site [18].
• Synergistic increases in the activities of PSA (6.1 kb)- and pARR(3)-tk-luciferase reporters were measured in cells cotreated with both OCM and androgen [3].
• Of the strains isolated following treatment failure with OAC, OBC or OCM, 84% were clarithromycin resistant [19].
• CONCLUSION: Our results show that the RCM regimen was more effective than that based on OCM and that the antisecretory drugs affected metronidazole availability, increasing the efficacy of ranitidine-based regimens [20].

Other interactions of OCM

• OCM targeted the NH(2)-terminal domain of the AR [3].
• RESULTS: OCM increased the proliferation and expression of PSA at both the protein and RNA levels in LNCaP cells [3].
• Neutralizing antibodies to IL-6 blocked proliferation and expression of PSA by OCM [3].
• The pattern of staining for desmin in HCM cats was not the same as that reported in humans, but was weaker than in OCM cats and controls [21].
• The I: and C: values derived from original data for forward and retro mutations in aspartate and tyrosine aminotransferase, from literature data for quasi domain exchange in oncomodulin and for the interaction of Tat with bovine and human TAR are evaluated [22].

Analytical, diagnostic and therapeutic context of OCM

• These antigenic sites appeared to differ from the calcium-binding site since immunoblotting against other calcium-binding proteins sharing this site (calmodulin, carp parvalbumin, oncomodulin) was negative [23].
• As native oncomodulin is devoid of tryptophan, site-specific mutagenesis was performed to create a mutant protein in which tryptophan was placed in the identical position (residue 102) as the single tryptophan residue in cod III parvalbumin [24].
• Seven and 13 patients in the OA and OCM groups, respectively, refused a second endoscopy (p = 0.25) [25].
• Even if the treatment outcome was better in the OCM group (100%) than in the OAM group (71%), the amoxycillin-based treatment might be preferable from an ecological point of view, since the qualitative alterations in terms of emergence and persistence of resistant strains seemed to be most pronounced in the clarithromycin-treated group [5].
• METHODS: Sixty five adult patients with histologically confirmed H. pylori infection were randomly assigned in this open cohort study to 2 wk, low dose, twice daily treatment with omeprazole 20 mg and clarithromycin 250 mg (OC) (n = 31) or OC plus metronidazole 500 mg (OCM) (n = 34) [26].

References