Biomedical subjects

F Gao

Publications and source records attributed to F Gao.

At least 55 records · Page 3Linked to original sources

PubMed2002

Intracranial germ cell tumour: experience of a Singaporean institution over 11-year period.

BACKGROUND: Intracranial germ cell tumours (IGCT) are rare. We present our experience in Therapeutic Radiology Department, National Cancer Centre, Singapore. METHODS: A retrospective study was conducted through case notes review on 25 patients with IGCT referred between January 1988 and January 1999. RESULTS: The median age at diagnosis was 13 years (range 6-22). The tumours were mainly pineal germinoma (72%). Median follow-up for living patients was 2.57 years (range 0.12-10.8). Median radiotherapy (RT) dose to whole brain, primary site and spine was 35.3,54 and 30 Gys respectively. Four to six cycles of BEP or JEB chemotherapy (CM) were given in 10 patients. As for the whole study group, the seven-year overall survival (OS) and recurrence-free survival (RFS) were 86% (95% CI 72-100) and 78% (95% CI 60-100) respectively. The 10-year OS and RFS were 65% (95% CI 36-100) and 78% (95% CI 60-100) respectively. The germinoma group had 75% 10-year OS and 86% 10-year RFS. Mixed germinoma and non-germinoma germ cell tumours (NGGCT) group had 50% one-year RFS and 44% two-year OS. Acute side-effects of RT and CM were minimal. There was no statistically significant difference in side-effects when treatment modalities were compared. CONCLUSION: In the treatment of intracranial germinoma, we recommend biopsy and CSRT. Primary chemotherapy (+/- low-dose cranial RT) should be used in the protocol or clinical trial settings. Chemo-radiotherapy is recommended for mixed germinoma and NGGCT. A multicentre trial is needed to address various controversial issues.

Adolescent↗

PubMed2002

Angular regression and the detection of the seasonal onset of disease.

BACKGROUND: In examining the seasonality of onset of a disease over the year, investigators attempt to identify the peak of onset, and its magnitude. A second objective is to see if the day in which the disease manifests itself is related to subject-specific characteristics or environmental factors. METHOD: This paper describes appropriate statistical methodology for the situation where seasonality can be summarised by either a single peak or several peaks, possibly determined by patient characteristics or external influences. The circular, rather than linear, nature of the day of onset of a disease (irrespective of year) requires angular regression techniques to assess these relations, and the von Mises distribution replaces the normal distribution in this context. RESULTS: The methods outlined are illustrated by a national study of those experiencing an attack of acute primary angle-closure glaucoma in Singapore. CONCLUSIONS: We recommend re-analyses of already published work on seasonality of disease using this angular methodology. We anticipate that this may provide both useful further insight into aspects of aetiology and case studies for the methods themselves.

Acute Disease↗

PubMed2002

Delays in defibrillation: influence of different monitoring techniques.

BACKGROUND: Rapid defibrillation is the most important intervention required for a patient in cardiac arrest due to ventricular fibrillation or ventricular tachycardia. Isolated case reports of spurious asystole may have seen a change in practice, moving away from monitoring through defibrillator paddles and gel pads in favour of attaching electrocardiograph (ECG) leads for the initial monitoring of a collapsed patient. We surveyed current preferences for initial monitoring and estimated the difference in time taken to deliver the first shock with the following three monitoring techniques: defibrillator paddles and gel pads, ECG leads and hands-free adhesive pads. METHODS: Sixty Advanced Life Support (ALS) course directors, selected at random, were questioned to establish their current practice. Twenty ALS providers received 5 min revision in the three techniques for the initial monitoring of a collapsed patient and were then randomly tested to measure the time from confirmation of arrest to the first shock. RESULTS: Forty-two directors indicated their preferred methods for initial monitoring as 74% leads, 21% paddles and 5% hands-free adhesive pads. Before testing, 10 providers preferred paddles and 10 preferred leads. Monitoring through leads 54 (range 49-65) s was significantly slower than paddles 28 (24-31) s, P < 0.01 and adhesive pads 23 (19-27) s, P < 0.01. There was no significant difference in the time taken between paddles and adhesive pads. CONCLUSION: The current practice of monitoring through leads delays the time to deliver the first shock. We recommend that initial monitoring through leads be discontinued in favour of hands-free adhesive pads or defibrillator paddles/gel pads.

Electric Countershock↗

PubMed2002

Well-differentiated thyroid carcinoma: factors predicting recurrence and survival.

AIMS: 1) Determine the patient and tumour characteristics for well-differentiated thyroid carcinoma--towards developing a unique risk classification for our largely Chinese population. 2) Assess extent of thyroid surgery required. 3) Document prognostic value of UICC and AMES classification. METHODS: Retrospective review of 175 patients treated for primary thyroid epithelial malignancy by the Department of General Surgery at the Singapore General Hospital. RESULTS: There were 78% papillary carcinomas (PC) and 19% follicular carcinomas (FC). Female: male ratio was 3:1. Patient distribution in the UICC stages I, II, III, IV is respectively 56, 11, 31 and 2%. Twenty-six percent had hemithyroidectomy, and 74% total thyroidectomy. Neck dissections were required in 6% of FC compared to 34% of PC. Mean follow-up was 40 months. Extent of surgery did not affect PC/FC survival nor recurrence rates (p=0.53 and 0.06 respectively). Recurrences occurred in 15% FC and 9% PC. Death occurred in one FC and two PC. Survival correlated with UICC stage I/II and stage III/IV groups (p=0.04), and recurrence correlated with AMES High and Low Risk groups (p=0.004). No statistically significant difference was shown for survival between PC and FC or AMES groups and recurrence between PC and FC or UICC groups. CONCLUSIONS: Extent of thyroid surgery does not significantly affect local recurrences of PC/FC. The characterisation of thyroid carcinoma here is an important step towards developing a risk classification unique to our largely Chinese population.

Adenocarcinoma, Follicular↗

PubMed2001

Pattern of alloimmune response in second same donor allografts after induction of tolerance using CTLA4Ig.

BACKGROUND: The pattern of allograft acceptance in the presence of costimulatory blockade is manifested by the sequential appearance of Th1 cells, followed by Th2 cells. The aim of this study was to examine whether this phenomenon repeats itself after second same donor allotransplantation, hoping to determine whether acceptance in this setting provokes a predominance of the Th2 response. METHODS: Tolerance was achieved by transplantation of CTLA4Ig-transduced ACI liver allografts in Lewis recipients. Recipient long-term survivors received a second transplant, consisting of a cervical heterotopic heart from the same ACI donor strain. Animals were sacrificed at predetermined intervals following the second transplant and the heart and liver were processed for histology and cytokine mRNA expression. RESULTS: Recipients of CTLA4Ig-transduced livers survived indefinitely. Rechallenge with same donor strain second allograft was manifested by an anergic immune response in the second cardiac allograft, and a very mild transient infiltrate within the first accepted liver graft. Cardiac function was maintained with resolution of all infiltrates. The cytokine cascade was activated within the allografts; however, the pattern of acceptance was not associated with predominance of a specific Th subtype. CONCLUSIONS: The pattern of acceptance of an allograft following CTLA4Ig-mediated costimulatory blockade is not related to long-term predominance of Th2 cells, a phenomenon that may be unique to the setting of a tolerant liver. It may be likely that the infiltrating lymphocytes that are dominant in the second graft are suppressed by other memory mechanisms.

Abatacept↗

PubMed2001

Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease.

Parkinson's disease is a chronic neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction. We now report that minocycline, a semisynthetic tetracycline, recently shown to have neuroprotective effects in animal models of stroke/ischemic injury and Huntington's disease, prevents nigrostriatal dopaminergic neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Minocycline treatment also blocked dopamine depletion in the striatum as well as in the nucleus accumbens after MPTP administration. The neuroprotective effect of minocycline is associated with marked reductions in inducible NO synthase (iNOS) and caspase 1 expression. In vitro studies using primary cultures of mesencephalic and cerebellar granule neurons (CGN) and/or glia demonstrate that minocycline inhibits both 1-methyl-4-phenylpyridinium (MPP(+))-mediated iNOS expression and NO-induced neurotoxicity, but MPP(+)-induced neurotoxicity is inhibited only in the presence of glia. Further, minocycline also inhibits NO-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) in CGN and the p38 MAPK inhibitor, SB203580, blocks NO toxicity of CGN. Our results suggest that minocycline blocks MPTP neurotoxicity in vivo by indirectly inhibiting MPTP/MPP(+)-induced glial iNOS expression and/or directly inhibiting NO-induced neurotoxicity, most likely by inhibiting the phosphorylation of p38 MAPK. Thus, NO appears to play an important role in MPTP neurotoxicity. Neuroprotective tetracyclines may be effective in preventing or slowing the progression of Parkinson's and other neurodegenerative diseases.

Animals↗

PubMed2001

Beyond the hippocampus: MRI volumetry confirms widespread limbic atrophy in AD.

OBJECTIVE: To examine volumetric changes in limbic structures in patients with probable AD using planimetric measures on MRI. METHOD: Limbic structures (i.e., hippocampus, amygdala, anterior thalamus, hypothalamus, mamillary bodies, basal forebrain, septal area, fornix, and cingulate, orbitofrontal, and parahippocampal cortices) were traced on 3D T1-weighted MR images of 40 patients with mild to moderate AD and 40 age-, sex-, and education-matched normal control subjects. Limbic volumes were compared between groups and the predictive ability was assessed. RESULTS: Overall, limbic structures showed significant atrophy in AD patients compared with normal control subjects. Differences (p < 0.05) were found in all limbic regions except the anterior cingulate cortex. The greatest percentage volumetric losses occurred in the septal area (34%), hippocampus (28%), amygdala (21%), parahippocampal cortex (21%), and posterior cingulate cortex (20%). Combining volumetric measures of amygdala and septal area distinguished patients with AD from normal control subjects with 93% accuracy. CONCLUSIONS: These results verify that system-wide limbic degeneration occurs in patients with AD. In addition, atrophy in selected limbic structures was used to distinguish patients with AD from normal elderly individuals with over 90% accuracy in this select clinical sample. The measures require further exploration in samples more representative of those seen by primary care physicians before their utility can be accurately assessed.

Aged↗

PubMed2001

Allochimeric class I MHC molecules prevent chronic rejection and attenuate alloantibody responses.

BACKGROUND: We have shown that treatment with molecularly engineered, allochimeric [alpha1 hl/u]-RT1.Aa class I MHC antigens bearing donor-type Wistar-Furth (WF, RT1.Au) amino acid substitutions for host-type ACI (RTI.Aa) sequences in the alpha1-helical region induces donor-specific tolerance to cardiac allografts in rat recipients. This study examined the effect of allochimeric molecules on the development of chronic rejection. METHODS: Allochimeric [alpha1 hl/u]-RT1.Aa class I MHC antigenic extracts (1 mg) were administered via the portal vein into ACI recipients of WF hearts on the day of transplantation in conjunction with subtherapeutic oral cyclosporine (CsA, 10 mg/kg/day, days 0-2). Control groups included recipients of syngeneic grafts and ACI recipients of WF heart allografts treated with high-dose CsA (10 mg/kg/day, days 0-6). RESULTS: WF hearts in ACI rats receiving 7 days of CsA exhibited myocardial fibrosis, perivascular inflammation, and intimal hyperplasia at day 80. At day 120, these grafts displayed severe chronic rejection with global architectural disorganization, ventricular fibrosis, intimal hyperplasia, and progressive luminal narrowing. In contrast, WF hearts in rats treated with [alpha1 hl/u]-RT1.Aa molecules revealed only mild perivascular fibrosis, minimal intimal thickening, and preserved myocardial architecture. Alloantibody analysis demonstrated no IgM alloantibodies in all groups. An attenuated, but detectable, anti-WF IgG response was present in recipients receiving allochimeric molecules, with IgG1 and IgG2a subclasses predominating. Immunohistochemical analysis of allografts demonstrated minimal T cell infiltration and IgG binding to vascular endothelium. CONCLUSION: Treatment with allochimeric molecules prevents the development of chronic rejection. Such effect may be in part caused by deviation of host alloantibody responses.

Amino Acid Sequence↗

PubMed2001

Reduced levels of amyloid beta-peptide antibody in Alzheimer disease.

OBJECTIVE: To investigate whether it was possible to detect the presence and different levels of naturally occurring anti-beta-amyloid (Abeta) antibodies in the CSF of patients with AD and age-matched controls by employing a sensitive ELISA. BACKGROUND: Immunization with preaggregated amyloid beta-peptide (Abeta(1-42)) and administration of antibodies against Abeta into amyloid precursor protein APP(V717F)- transgenic mice (an animal model of AD) have recently been reported to dramatically reduce amyloid plaque deposition, neuritic dystrophy, and astrogliosis, most likely by enhancing Abeta clearance from brain. METHODS: A sensitive ELISA was performed to detect levels of naturally occurring anti-Abeta antibodies in the CSF of patients with AD and age-matched controls. Additionally, an immunoprecipitation assay was performed to confirm that naturally occurring anti-Abeta antibodies also exist in the human blood. RESULT: - Naturally occurring antibodies directed against Abeta were found in the CSF and plasma of patients with AD and healthy control subjects. Moreover, CSF anti-Abeta antibody titers are significantly lower in patients with AD compared with healthy control subjects. CONCLUSION: Naturally occurring antibodies directed against Abeta exist in human CSF and plasma. The CSF anti-Abeta antibody titers may be helpful in better understanding the effects of future immunologic therapies for AD.

Aged↗

PubMed2001

Molecular characterization of a highly divergent HIV type 1 isolate obtained early in the AIDS epidemic from the Democratic Republic of Congo.

Numerous complete human immunodeficiency virus type 1 (HIV-1) genomes have been characterized for contemporary viruses, but few isolates obtained early in the HIV-1 epidemic have been studied. In this article, we describe the molecular characterization of an HIV-1 isolate (83CD003) that was obtained from an AIDS patient in Kinshasa, Democratic Republic of Congo (DRC) in 1983. The complete 83CD003 genome was sequenced in its entirety and found to encode uninterrupted open reading frames for all viral genes. Phylogenetic analysis revealed 83CD003 was a member of the major (M) group of HIV -1, but did not group with any of the known subtypes. Rather, it formed an independent lineage in all regions of its genome that was roughly equidistant from representatives of all other subtypes. Similarly, 83CD003 also did not cluster with any of several unclassified group M sequences that have been reported more recently to circulate in the DRC, suggesting that it may represent an early group M lineage thai is either rare or has gone extinct. The molecular clone of 83CD003 yielded an infectious virus after transfection into mammalian cells and its biological properties can be further studied.

Cell Line↗

PubMed2001

ElogD(oct): a tool for lipophilicity determination in drug discovery. 2. Basic and neutral compounds.

We present an RP-HPLC method for the determination of the octanol-water distribution coefficients at pH 7.4, as log values, for neutral and basic drugs, which combines ease of operation with high accuracy. The method is shown to work for a training set of 90 molecules comprised largely of drugs, and it was also applied to a test set of 10 proprietary compounds. This work expands the applicability of the method presented in our earlier report, for the determination of logP(oct) for neutral compounds (J. Med. Chem. 2000, 43, 2922-2928), and it offers the same general features but widens the scope. Generally, the method (i) is compound sparing (< or =1 mL of a 50-100 microg/mL solution needed), (ii) is insensitive to concentration and phase ratio effects observed in some shake-flask determinations, (iii) is amenable to rapid determinations (< or = 20 min on average), (iv) is insensitive to impurities, (v) possesses a wide lipophilicity range (>7 log units), and (vi) offers a good accuracy, (vii) an excellent reproducibility, (viii) and an excellent potential for automation. To the best of our knowledge, a similar performance, on a set of noncongeneric drugs, has not been previously reported. We refer to the value generated via this method as ElogD(oct).

1-Octanol↗

PubMed2001

Hyaluronan synthase 3 overexpression promotes the growth of TSU prostate cancer cells.

Hyaluronan synthase 3 (HAS3) is responsible for the production of both secreted and cell-associated forms of hyaluronan and is the most active of the three isoforms of this enzyme in adults. In this study, the cDNA for human HAS3 was cloned and characterized. The open reading frame consisted of 1659 bp coding for 553 amino acids with a deduced molecular weight of about 63,000 and isoelectric pH of 8.70. The sequence of human HAS3 displayed a 53% identity to HAS1 and a 67% identity to HAS2. It also contained a signal peptide and six potential transmembrane domains, suggesting that it was associated with the plasma membrane. To evaluate the physiological role of human HAS3, expression vectors for this protein were transfected into TSU cells (a prostate cancer cell line), and the phenotypic changes in these cells were examined. The enhanced expression of hyaluronan in the transfected cells was demonstrated by dot blot analysis and ELISA. These cells were found to differ from their vector-transfected counterparts with respect to the following: (a) they grew at a faster rate in high (but not low) density cultures; (b) conditioned media from these cells stimulated the proliferation and migration of endothelial cells; (c) when placed on the chorioallantoic membrane of chicken embryos, these cells formed large, dispersed xenografts, whereas the control transfectants formed compact masses; and (d) when injected s.c. into nude mice, the xenografts formed by HAS3 transfectants were bigger than those formed by control transfectants. Histological examination of these xenografts revealed the presence of extracellular hyaluronan that could act as conduits for the diffusion of nutrients. In addition, they had a greater number of blood vessels. However, the HAS3-transfected TSU cells did not display increased metastatic properties as judged by their ability to form lung masses after i.v. injection. These results suggested that the HAS3-induced overexpression of hyaluronan enhanced tumor cell growth, extracellular matrix deposition, and angiogenesis but was not sufficient to induce metastatic behavior in TSU cells.

Allantois↗

PubMed2001

Evidence of two distinct subsubtypes within the HIV-1 subtype A radiation.

Members of HIV-1 group M are responsible for the vast majority of AIDS cases worldwide and have been classified on the basis of their phylogenetic relationships into nine roughly equidistant clades, termed subtypes. Although there are no known phenotypic correlates for these genotypes, the disproportionate spread of certain of these lineages has been taken to indicate that subtype-specific biological differences may exist. The subtype nomenclature thus remains an important molecular epidemiological tool with which to track the course of the group M pandemic. In this study, we have characterized HIV-1 strains described previously as unusual subtype A variants on the basis of partial sequence analysis. Six such strains from Cyprus (CY), South Korea (KR), and the Democratic Republic of Congo (CD) were PCR amplified from infected cell culture or patient PBMC DNA, cloned, and sequences in their entirety (94CY017, 97KR004, 97CDKTB48, and 97CDKP58) or as half genomes (97CDKS10 and 97CDKFE4). Distance and phylogenetic analyses showed that four of these viruses (94CY017, 97CDKTB48, 97CDKFE4, and 97CDKS10) were closely related to each other, but quite divergent from all other HIV-1 strains, except for subtype A viruses, which represented their closest relatives. In phylogenetic trees from gag, pol, env, and nef regions, the four newly characterized HIV-1 strains formed a distinct sister clade to subtype A, which was as closely related to subtype A as subsubtypes F1 and F2 are to each other. According to current nomenclature rules, this defines a subsubtype, which we have tentatively termed A2. The two other viruses, 97KR004 and 97CDKP58, as well as a full-length HIV-1 sequence from the sequence database (ZAM184), were found to represent complex A2/D, A2/G, and A2/C recombinants, respectively. These results indicate that HIV-1 subtype A is composed of two subsubtypes (A1 and A2), both of which appear to have a widespread geographic distribution. The A2 viruses described here represent the first reference reagents for this new group M lineage.

Cyprus↗

PubMed2001

Seasonal variation in breast cancer diagnosis in Singapore.

This study investigates seasonality in the diagnosis of 3219 female breast carcinoma cases reported between 1995-8 in Singapore. There is little evidence of marked seasonal variation. Angular regression suggested that observed differences in peak diagnosis with respect to menopausal status, tumour size, ER and PR status may be chance.

Adult↗

PubMed2001

Novel role for JNK as a stress-activated Bcl2 kinase.

Interleukin (IL)-3-induced Bcl2 phosphorylation at Ser(70) may be required for its full and potent antiapoptotic activity. However, in the absence of IL-3, increased expression of Bcl2 can also prolong cell survival. To determine how Bcl2 may be functionally phosphorylated following IL-3 withdrawal, a stress-activated Bcl2 kinase (SAK) was sought. Results indicate that anisomycin, a potent activator of the stress kinase JNK/SAPK, can induce Bcl2 phosphorylation at Ser(70) and that JNK1 can be latently activated following IL-3 withdrawal to mediate Bcl2 phosphorylation. JNK1 directly phosphorylates Bcl2 in vitro, co-localizes with Bcl2, and collaborates with Bcl-2 to mediate prolonged cell survival in the absence of IL-3 or following various stress applications. Dominant-negative (DN)-JNK1 can block both anisomycin and latent IL-3 withdrawal-induced Bcl2 phosphorylation (>90%) and potently enhances cell death. Furthermore, low dose okadaic acid (OA), a potent protein phosphatase 1 and 2A inhibitor, can activate the mitogen-activated protein kinases JNK1 and ERK1/2, but not p38 kinase, to induce Bcl2 phosphorylation and prolong cell survival in factor-deprived cells. Since PD98059, a specific MEK inhibitor, can only partially inhibit OA-induced Bcl2 phosphorylation but completely blocks OA-induced Bcl2 phosphorylation in cells expressing DN-JNK1, this supports the conclusion that OA may stimulate Bcl2 phosphorylation via a mechanism involving both JNK1 and ERK1/2. Collectively, these findings indicate a novel role for JNK1 as a SAK and may explain, at least in part, how functional phosphorylation of Bc12 can occur in the absence of growth factor.

Animals↗

PubMed2001

Marked suppression of the activity of some, but not all, antifolate compounds by augmentation of folate cofactor pools within tumor cells.

Folates have been co-administered with some antifolates to diminish host toxicity; however, the extent to which this will reduce antitumor activity is not known. To further clarify this issue, studies were undertaken to characterize and quantitate the impact of alterations in intracellular folate levels on the activities of a variety of antifolates in L1210 murine leukemia cells. Intracellular folate cofactor levels increased almost in proportion to the increase in extracellular 5-formyltetrahydrofolate (5-CHO-THF) over a concentration range that encompassed physiological levels of 5-methyltetrahydrofolate. This resulted in a spectrum of increases in the ic50 values of antifolates upon continuous exposure to drugs [Lometrexol (DDATHF) (70x) > trimetrexate (TMQ) (30x), multitargeted antifolate, LY231514 (ALIMTA) (30x) > Raltitrexed, Tomudex (ZD1694) (10x), 6R-2',5'-thienyl-5,10-dideazatetrahydrofolic acid (LY309887) (10x) > methotrexate (MTX) (6x) > (2S)-2-[o-fluoro-p-[N-(2,7-dimethyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl)-N-(prop-2-ynyl)amino]benzamido]-4-(tetrazol-5-yl) butyric acid (ZD9331) (3x), N(alpha)-(4-amino-4-deoxypteroyl)-N(delta)-hemiphthaloyl-l-ornithine (PT523) (3x)]. Upon a 4-hr pulse exposure to drug, the ic50 values for DDATHF and ALIMTA were increased > 180- and 5-fold, respectively, with only a 2.5-fold increase in the extracellular 5-CHO-THF level within the physiological range. The reductions in drug sensitivities could be attributed to decreases in accumulation of polyglutamate derivatives of ALIMTA and DDATHF. Hence, in these studies, natural folates diminished the activity of agents that undergo polyglutamation by suppression of the formation of these active congeners at the level of folylpolyglutamate synthetase. For inhibitors of dihydrofolate reductase, the suppressive effect of endogenous folates appears to be due to competition between the antifolate and dihydrofolate at the level of the target enzyme. These data should be carefully considered in the design of regimens with antifolates, which incorporate co-administration of folates.

Animals↗

PubMed2001

Rescue of embryonic lethality in reduced folate carrier-deficient mice by maternal folic acid supplementation reveals early neonatal failure of hematopoietic organs.

The reduced folate carrier (RFC1) is an important route by which the major blood folate, 5-methyltetrahydrofolate, is transported into mammalian cells. In this study we determined the consequences of inactivation of RFC1 in mice by homologous recombination. While RFC1-null embryos died in utero before embryonic day 9.5 (E9.5), near-normal development could be sustained in RFC1(-)/- embryos examined at E18.5 by supplementation of pregnant RFC1(+/-) dams with 1-mg daily subcutaneous doses of folic acid. About 10% of these animals went on to live birth but died within 12 days. These RFC1(-)/- mice showed a marked absence of erythropoiesis in bone marrow, spleen, and liver along with lymphoid depletion in the splenic white pulp and thymus. In addition, there was some impairment of renal and seminiferous tubule development. These data indicate that in the absence of RFC1 function, neonatal animals die due to failure of hematopoietic organs.

Alleles↗

PubMed2001

Metastatin: a hyaluronan-binding complex from cartilage that inhibits tumor growth.

In this study, a hyaluronan-binding complex, which we termed Metastatin, was isolated from bovine cartilage by affinity chromatography and found to have both antitumorigenic and antiangiogenic properties. Metastatin was able to block the formation of tumor nodules in the lungs of mice inoculated with B16BL6 melanoma or Lewis lung carcinoma cells. Single i.v. administration of Metastatin into chicken embryos inhibited the growth of both B16BL6 mouse melanoma and TSU human prostate cancer cells growing on the chorioallantoic membrane. The in vivo biological effect may be attributed to the antiangiogenic activity because Metastatin is able to inhibit the migration and proliferation of cultured endothelial cells as well as vascular endothelial growth factor-induced angiogenesis on the chorioallantoic membrane. In each case, the effect could be blocked by either heat denaturing the Metastatin or premixing it with hyaluronan, suggesting that its activity critically depends on its ability to bind hyaluronan on the target cells. Collectively, these results suggest that Metastatin is an effective antitumor agent that exhibits antiangiogenic activity.

Allantois↗