SEARCH · PubMed Health

Results for “cellular proliferation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed1995

Cellular proliferation in prostatic adenocarcinoma as assessed by bromodeoxyuridine uptake and Ki-67 and PCNA expression.

Prostatic carcinomas vary in their biological potential, even when stratified by grade and stage. Measurement of cellular proliferation by various methods has been shown to correlate with outcome for several human cancers, including prostatic carcinoma. Uptake of bromodeoxyuridine (BrdUrd), a thymidine analogue, has been accepted as a measure of cellular proliferative rate. However, the technique is somewhat complex, requiring incubation with fresh tissue. We compared cellular proliferation as measured by BrdUrd uptake with two more simple immunohistochemical methods in 44 prostatic adenocarcinoma specimens and correlated the results with standard clinical parameters. The tissue was obtained via needle biopsy, channel transurethral resection, and radical prostatectomy. Specimens were incubated in vitro with BrdUrd and then fixed and paraffin embedded. Sections were immunohistochemically stained with antibodies to BrdUrd, proliferating cell nuclear antigen (PCNA), and Ki-67. At least 1,000 cells were scored, and a labeling index (LI) was calculated (number of positive cells/total number of cells). The mean LI determined by all three indices was low (BrdUrd = 3.0, PCNA = 7.0, Ki-67 = 3.4), consistent with the knowledge that prostatic tumors grow slowly. In 36 patients who had not been treated at the time of analysis, the LI as determined by all three methods correlated well with clinical stage and pathological grade. Furthermore, the LIs discriminated between those with tumor confined to the prostate and those with extension to the seminal vesicles, lymph nodes, or bone (P = 0.003, 0.004, 0.008 for BrdUrd, PCNA, and Ki-67, respectively). The LIs for PCNA and Ki-67 correlated well with that for BrdUrd (r = 0.84; r = 0.85), while the LIs for Ki-67 and PCNA correlated slightly less well with each other (r = 0.78). PCNA and Ki-67 expression appear to reflect essentially the same biological process as BrdUrd uptake. Either can substitute for BrdUrd as a measure of cellular proliferation, and Ki-67 seems to offer the fewest technical problems.

Adenocarcinoma↗

PubMed1994

Sepsis in rats stimulates cellular proliferation in the mucosa of the small intestine.

BACKGROUND/AIMS: Increased protein synthesis in intestinal mucosa during sepsis may reflect increased cell turnover. The influence of sepsis and endotoxemia on cellular proliferation in the mucosa of the small intestine was studied. METHODS: Sepsis was induced in rats by cecal ligation and puncture. Control rats were sham-operated. Other rats were treated with endotoxin (total dose, 2 mg/kg), human recombinant tumor necrosis factor alpha, or human recombinant interleukin 1 alpha at a dose of 100 micrograms/kg each. Villus height and crypt depth in the jejunum were measured as the number of cells along the side of the villus and crypt, respectively. Cellular proliferation was assessed by measuring the rate of [3H]thymidine incorporation into DNA of the jejunal mucosa and performing autoradiographic studies after intravenous administration of [3H]thymidine. RESULTS: Sepsis resulted in reduced villus height, increased crypt depth, and increased incorporation of [3H]thymidine into DNA in the jejunal mucosa. Autoradiography after administration of [3H]thymidine showed labeled cells almost exclusively in the crypts; the number of labeled cells per crpt was higher in septic than in control rats. Administration of endotoxin or recombinant interleukin 1 alpha, but not recombinant tumor necrosis factor alpha, stimulated the incorporation of [3H]-thymidine into DNA in the jejunal mucosa. CONCLUSION: Sepsis and endotoxemia stimulate cellular proliferation in the mucosa of the small intestine. This response to sepsis and endotoxemia may be partly mediated by interleukin 1.

Animals↗

PubMed1980

Cytogenetic effects of inhaled benzene in murine bone marrow: induction of sister chromatid exchanges, chromosomal aberrations, and cellular proliferation inhibition in DBA/2 mice.

Exposure of adult male and female DBA/2 mice to 3100 ppm benzene for 4 hr significantly increased the frequency of sister chromatid exchanges in bone marrow cells of both sexes, inhibited marrow cellular proliferation (but only in male mice), and did not significantly increase the frequency of chromosomal aberrations in either sex. Phenobarbital pretreatment synergistically interacted with benzene exposure to further increase sister chromatid exchanges in female mice, induce greater inhibition of cellular proliferation in male mice, and induce a significant level of chromatid-type chromosomal aberrations in both sexes. During the second day after exposure to benzene there was increased inhibition of cellular proliferation in male mice and both new DNA damage and persistance of old DNA damage in female mice. The differences in both the type and magnitude of the response of bone marrow cellular populations, as determined by different cytogenetic end points in male and female DBA/2 mice exposed to benzene or to phenobarbital and benzene, suggest not only that a metabolite of benzene is responsible for the observed effects, but that different metabolites may be involved in different end points.

Animals↗

PubMed2001

Inhibition of cellular proliferation through IkappaB kinase-independent and peroxisome proliferator-activated receptor gamma-dependent repression of cyclin D1.

The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-regulated nuclear receptor superfamily member. Liganded PPARgamma exerts diverse biological effects, promoting adipocyte differentiation, inhibiting tumor cellular proliferation, and regulating monocyte/macrophage and anti-inflammatory activities in vitro. In vivo studies with PPARgamma ligands showed enhancement of tumor growth, raising the possibility that reduced immune function and tumor surveillance may outweigh the direct inhibitory effects of PPARgamma ligands on cellular proliferation. Recent findings that PPARgamma ligands convey PPARgamma-independent activities through IkappaB kinase (IKK) raises important questions about the specific mechanisms through which PPARgamma ligands inhibit cellular proliferation. We investigated the mechanisms regulating the antiproliferative effect of PPARgamma. Herein PPARgamma, liganded by either natural (15d-PGJ(2) and PGD(2)) or synthetic ligands (BRL49653 and troglitazone), selectively inhibited expression of the cyclin D1 gene. The inhibition of S-phase entry and activity of the cyclin D1-dependent serine-threonine kinase (Cdk) by 15d-PGJ(2) was not observed in PPARgamma-deficient cells. Cyclin D1 overexpression reversed the S-phase inhibition by 15d-PGJ(2). Cyclin D1 repression was independent of IKK, as prostaglandins (PGs) which bound PPARgamma but lacked the IKK interactive cyclopentone ring carbonyl group repressed cyclin D1. Cyclin D1 repression by PPARgamma involved competition for limiting abundance of p300, directed through a c-Fos binding site of the cyclin D1 promoter. 15d-PGJ(2) enhanced recruitment of p300 to PPARgamma but reduced binding to c-Fos. The identification of distinct pathways through which eicosanoids regulate anti-inflammatory and antiproliferative effects may improve the utility of COX2 inhibitors.

Binding Sites↗

PubMed1990

Do AgNOR counts reflect cellular ploidy or cellular proliferation? A study of trophoblastic tissue.

There is considerable debate as to whether AgNOR counts reflect cellular ploidy or cellular proliferation. Trophoblastic tissue from hydropic abortions and from hydatidiform moles offers an excellent model for analysing this problem. Thus, complete moles show considerable cell proliferation but are diploid, whilst partial moles show markedly less cell proliferation but are triploid: hydropic abortuses are diploid and show no cellular proliferation. AgNOR counts in villous cytotrophoblastic cells from hydropic abortions and from complete hydatidiform moles are similar, but those in partial hydatidiform moles are 50 per cent higher than in either hydropic abortions or complete moles. Thus, in non-neoplastic trophoblastic tissue AgNOR counts are clearly a reflection of ploidy rather than of cell proliferation.

Abortion, Spontaneous↗

PubMed2001

[Expression of P21 WAF1/CIP1 in human astrocytomas in correlating with P53, MDM2, and cellular proliferation index].

OBJECTIVE: To study the correlation between the expression of p21, p53, MDM2 gene products and the initiation and progression of human astrocytomas. METHODS: The expression of P21, P53, MDM2, and proliferative cell nuclear antigen (PCNA) labeling index using immunohistochemistry in 41 paraffin embedded human astrocytoma samples. As well as the expression of p21 mRNA using mRNA in situ hybridization in 24 fresh human astrocytoma samples stored at -70 degrees C were investigated. In immunohistochemistry, we divided whole tumor cells by positive tumor cell nuclei to obtain labeling index (LI), in this way we could understand the protein product expression of gene in astrocytoma in different patients. In mRNA in situ hybridization, the expression of p21 mRNA was scored according to the rough percentage of positive cells. RESULTS: In p21 mRNA in situ hybridization, the positive staining was present in 87.5%. In immunohistochemistry, positive P21, P53, MDM2, and PCNA staining were presented in 75.6%, 68.3%, 65.9%, 100% respectively. Higher levels of P21 protein expression were seen in higher histological grade (P = 0.001). The association between P21 expression positively correlated with proliferation index. But not with P53 expression and MDM2 expression. The association between P53 expression and proliferation indices were statistically significant, but the expression of P53 was not related to tumor grade. There was no association between MDM2 expression and grade, or cellular proliferation index. Linear stepwise regression analysis showed the parameters affecting tumor grade were PCNA LI (P = 0.000) and P21 LI (P = 0.001). CONCLUSIONS: (1) Both p21 mRNA and P21 protein were overexpressed in human astrocytomas, the overexpression was related to cellular proliferation index, but was not related to P53 expression, suggesting there could be P53-independent pathway to induce the P21 expression, in addition, the overexpression of P21 alone appeared insufficient to suppress tumor growth, provided the participation of PCNA. (2) The expression of P53 protein was associated with proliferation indices, but was not with the tumor malignancy, this indicated that the inactivation of P53 might be the early event in the growth of human astrocytomas. (3) P21 labeling index and cellular proliferation index influenced the tumor histological grade, our data indicated that p21 gene might play a role in the progression of human astrocytomas.

Adolescent↗

PubMed2001

A comparison of four stent designs on arterial injury, cellular proliferation, neointima formation, and arterial dimensions in an experimental porcine model.

The stent-artery interactions of different stent designs have implications for their clinical effects. We studied four different stent designs to compare their effects on arterial injury, cellular proliferation, neointima formation, and arterial dimensions. Eighteen nonatherosclerotic miniswine underwent random placement of 52 coronary stents (3.0 mm), including self-expanding nitinol stents (no postdilation; Radius, n = 13) and balloon-expandable stents (8 atm x 45 sec; Palmaz-Schatz, n = 13; BX, n = 12; and Multilink, n = 14). Cellular proliferation was determined by S-phase labeling with BrdU at 7, 14, and 28 days. Proliferation, injury scores, and arterial morphometry were blindly evaluated. All four stent designs had similar injury scores, cellular proliferation indexes (neointimal and medial), and adventitial areas. Nitinol stents resulted in a twofold increase in neointimal area and thickness in 28-day vessels (P = 0.002). However, lumen area was similar for all stent designs because of an offsetting expansion in vessel area in nitinol stents (20% greater than balloon-expandable stents) occurring between 7 and 14 days after stent deployment (P = 0.03). Reduced neointimal cell density in nitinol stents (20% less than balloon-expandable stents, P = 0.012) suggests that extracellular matrix expansion accounts for the larger neointima in nitinol stents. Self-expansion of nitinol stents within normal porcine arteries results in a similar degree of arterial injury compared to balloon-expandable stent designs. Progressive enlargement of nitinol stents between 7 and 14 days after deployment is associated with the development of a larger, matrix-rich neointima, with a preserved lumen area. Cathet Cardiovasc Intervent 2001;53:420-425. Published 2001 Wiley-Liss, Inc.

Alloys↗

PubMed1998

Cellular proliferation, estrogen receptor, progesterone receptor, and bcl-2 expression in GnRH agonist-treated uterine leiomyomas.

Gonadotropin-releasing hormone (GnRH) agonists are commonly used in the treatment of uterine leiomyomas, but little is known about their histological and cellular effects on these neoplasms. We examined a cellular proliferation index as determined by the nuclear antigen Ki-67 and proliferating cell nuclear antigen (PCNA) expression, estrogen receptor (ER), and progesterone receptor (PR) expression in 27 leiomyomas from patients treated with the GnRH agonist leuprolide acetate (LA) and compared them with 33 untreated controls. All leiomyomas were removed by myomectomies from premenopausal woman after 2 to 6 months of LA treatment or in the follicular phase of the menstrual cycle in the untreated controls. Histological features examined included cellularity, nuclear atypia, vascular changes (dilated, thickened, or thrombosed vessels), edema, calcification, hemorrhage, necrosis, hyalinization, and mitotic activity. Although no difference was found between GnRH-treated and nontreated groups with respect to most histological features examined, immunohistochemical studies showed a significant decrease in the cellular proliferation index, ER, and PR expression in the LA-treated cases compared with nontreated controls. The cellular proliferation index, ER, and PR expression decreased by 85%, 49%, and 36%, respectively, in the LA-treated group as compared with controls (P < .001). A subset of cases from the LA-treated and nontreated groups were also analyzed with respect to bcl-2 (an inhibitor of apoptosis) expression, and no significant difference between the LA-treated and nontreated groups was observed with both groups showing a strong (> 75% of cells) cytoplasmic staining pattern. Results of this study show that LA treatment of leiomyomas results in a decrease in number of cycling cells.

Adult↗

PubMed2006

Short interfering RNA-mediated gene silencing of vascular endothelial growth factor: effects on cellular proliferation in colon cancer cells.

HYPOTHESIS: By using short interfering RNA (siRNA) to inhibit the in vitro expression of vascular endothelial growth factor (VEGF) A, we hope to further investigate the presence of an autocrine loop in colon cancer cells. We hypothesize that VEGF inhibition will result in decreased cellular proliferation. DESIGN: Human colon cancer cells were evaluated for the expression of VEGF and VEGF receptor 2 (VEGFR-2). In vitro assessments were then made of the ability of anti-VEGF siRNA to knock down expression of VEGF and the subsequent effect this decreased expression had on colon cancer cell proliferation. SETTING: Surgical oncology research laboratory. INTERVENTIONS: Human colon cancer cells from the RKO cell line were transfected with siRNA targeting the coding region of VEGF. MAIN OUTCOME MEASURES: Enzyme-linked immunosorbent assay, Northern blot analysis, and real-time quantitative polymerase chain reaction were performed to establish the ability of siRNA to decrease VEGF production. Proliferation assays were run on transfected and wild-type cells to establish concomitant decrease in VEGF expression and cellular proliferation. RESULTS: The RKO colon cancer cells expressed both VEGF and VEGFR-2. Those cells transfected with siRNA targeting VEGF showed a 94% knockdown in VEGF expression and a 67% decrease in cellular proliferation. CONCLUSION: Colon cancer cells expressing VEGF and VEGFR-2 may possess an autocrine growth pathway that can be effectively targeted using RNA interference as an antiangiogenic therapy.

Apoptosis↗

PubMed1983

2',5'-Oligoadenylates and related 2',5'-oligonucleotide analogues. 2. Effect on cellular proliferation, protein synthesis, and endoribonuclease activity.

A number of the new enzymatically synthesized 2',5'-oligonucleotide trimers, namely, those containing the nucleosides 8-azaadenosine, toyocamycin, sangivamycin, formycin, 8-bromoadenosine, tubercidin, and guanosine, were found to inhibit protein synthesis and cellular proliferation after uptake into intact L and HeLa cells. 2',5'-Oligonucleotide trimers containing cytidine, inosine, uridine, and 1,N6-ethenoadenosine had some effect while those containing 2-chloroadenosine, 3-ribosyladenine, ribavirin, and 2-beta-D-ribofuranosylthiazole-4-carboxamide had no detectable effect on protein synthesis or cellular proliferation after uptake into L or HeLa cells. All of these 2',5'-oligonucleotide analogues inhibited protein synthesis in the in vitro rabbit reticulocyte lysate system except for the trimer containing ribavirin. Such nucleoside substitutions have further defined the substrate-specificity requirements for the endoribonuclease and/or the inhibitors for the 2',5'-phosphodiesterase. Most of the 2',5'-analogues were degraded in L-cell extracts so the endogenous nucleases are not very specific. The 2',5'-trimers containing tubercidin and 2-beta-D-ribofuranosylthiazole-4-carboxamide were quite stable in comparison to the 2',5'-A trimer. The inhibition of protein synthesis and cellular proliferation observed correlated well with the degradation of rRNA and polyadenylated mRNA observed after uptake of the 2',5'-analogues into intact L cells. The degradation of the polyadenylated mRNA appeared to be a more sensitive test than inhibition of cellular protein synthesis for determining biological activities of the 2',5'-oligonucleotide analogues.

Adenine Nucleotides↗

PubMed1975

Cellular proliferation and renewal in the various zones of the hamster epididymis after colchicine administration.

Cellular proliferation was examined in the various regions of the excurrent ducts of the reproductive system of the male golden hamster after colchicine administration. Each of the two zones of the ductuli efferentes displayed only infrequent mitotic figures. Similarly, the basal cell population of the epididymis as well as the epithelium of the vas deferens exhibited too few mitotic figures to allow meaningful evaluation of cellular proliferation. The following observations were reported. 1. The principal cells of the entire epididymis are characterized by a singular diurnal cycle of proliferative activity reaching its maximum about 3 P.M. and its nadir about 9 A.M. 2. A circadian rhythm of cell division is also found in the principal cells of each of the six zones of the epididymis, although the time of maximal activity may vary from zone to zone. 3. The most actively proliferating region of the excurrent duct system is zone 3 of the epididymis, whereas the least active region is the ductuli efferentes. 4. The renewal rates of the principal cells vary considerably at various points along the excurrent duct system, ranging from cells which renew themselves as many as 10 times to cells which fail to renew themselves at all during the normal life-span of the animal.

Animals↗

PubMed1997

Glutathione and the rate of cellular proliferation determine tumour cell sensitivity to tumour necrosis factor in vivo.

Low rates of cellular proliferation are associated with low GSH content and enhanced sensitivity of Ehrlich ascites-tumour (EAT) cells to the cytotoxic effects of recombinant human tumour necrosis factor (rhTNF-alpha). Buthionine sulphoximine, a selective inhibitor of GSH synthesis, inhibited tumour growth and increased rhTNF-alpha cytoxicity in vitro. Administration of sublethal doses (10(6)units/kg per day) of rhTNF-alpha to EAT-bearing mice promoted oxidative stress (as measured by increases in intracellular peroxide levels, O2(-); generation and mitochondrial GSSG) and resulted in a slight reduction (19%) in tumour cell number when controls showed the highest rate of cellular proliferation. ATP (1mmol/kg per day)-induced selective GSH depletion, when combined with rhTNF-alpha administration, afforded a 61% inhibition of tumour growth and resulted in a significant extension of host survival. Administration of N-acetylcysteine (1mmol/kg per day) or GSH ester (5mmol/kg per day) abolished the rhTNF-alpha- and ATP-induced effects on tumour growth by maintaining high GSH levels in the cancer cells. Our results demonstrate that the sensitivity of tumour cells to rhTNF-alpha in vivo depends on their GSH content and their rate of proliferation.

Animals↗

PubMed1992

Effects of high glucose on cellular proliferation and fibronectin production by cultured human mesangial cells.

Diabetic glomerulosclerosis is characterized by the accumulation of the matrix protein fibronectin in the glomerular mesangium and could result from increased mesangial cell fibronectin synthesis induced by hyperglycemia. To test this hypothesis, we cultured human mesangial cells for up to 14 days in media containing normal (5 mM) or high glucose (20 to 115 mM) concentrations and assessed cellular proliferation and fibronectin synthesis. When compared to 5 mM glucose, high glucose levels significantly inhibited cellular proliferation in a dose dependent fashion, as assessed by direct cell counting and thymidine incorporation. After eight days in culture, tissue culture supernatant fibronectin levels, as assessed by ELISA, were significantly higher from cells cultured under high glucose conditions than cells exposed to normal glucose levels. After 14 days and when compared to 5 mM glucose, matrix fibronectin levels and fibronectin mRNA expression (by Northern analysis) were also increased by 20 mM glucose. To control for the osmotic effects of high glucose, mesangial cells were also cultured in the presence of 20 mM or 50 mM mannitol. Mannitol had no effect on cellular proliferation but significantly increased tissue culture supernatant fibronectin levels and fibronectin gene expression. These studies demonstrate that, in vitro, high glucose suppresses human mesangial cell proliferation and stimulates fibronectin synthesis. The increase in fibronectin synthesis may in part result from changes in osmolality induced by high glucose. These data suggest that increased mesangial cell fibronectin synthesis may play a role in the accumulation of glomerular fibronectin common to diabetic glomerulosclerosis.

Cell Division↗

PubMed1988

Quantification of cellular proliferation in experimental proliferative vitreoretinopathy.

Proliferation of host cells from around the optic nerve head has recently been implicated in the development of experimental proliferative vitreoretinopathy in rabbit eyes injected with homologous fibroblasts. We used liquid scintillation spectrometry to quantitate the tritiated thymidine incorporation into cells in the vitreous, retina, and optic nerve head following intravitreal injection of 250,000 homologous dermal fibroblasts. Cellular proliferation peaked three days after injection of the fibroblasts. The amount of tritiated thymidine incorporation that occurred three days following injection of irradiated homologous fibroblasts (incapable of cellular division) was not significantly different than that following injection of normal homologous fibroblasts, indicating that host cells were responsible for most of the cellular proliferation. Treatment with fluorouracil or triamcinolone acetonide completely arrested cellular proliferation following injection of normal fibroblasts.

Animals↗

PubMed1996

Inhibition of cellular proliferation and modulation of insulin-like growth factor binding proteins by retinoids in a bovine mammary epithelial cell line.

Retinoids are potent inhibitors of growth and tumor progression in many mammary carcinoma cell lines, though regulation of growth in nontumorigenic mammary epithelial cells by retinoids is less clear. Here, we have characterized the inhibition of MAC-T (a nontransformed bovine mammary epithelial cell line) cellular proliferation by retinoids and their role in regulating insulin-like growth factor binding proteins (IGFBPs). Retinoic acid (RA) (100 nM) was a potent inhibitor of MAC-T cell proliferation. Retinol was 10-100 times less effective. Neither retinoid could completely arrest growth at noncytotoxic concentrations. Retinoic acid inhibited cellular proliferation by 1 h (P < .05), but inhibition was fivefold greater by 24 h (P < .01). This second stage of growth inhibition (after 12 h) was dependent upon protein synthesis. However, RA-induced inhibition of cellular proliferation did not persist, with thymidine incorporation increasing toward control levels by 4 days in culture. Retinoic acid was less effective in inhibiting thymidine incorporation when cells were stimulated with insulin, des(1-3) IGF-I, or Long(R3) IGF-I when compared to cells stimulated with native IGF-I or serum. Inhibition of proliferation by RA was associated with increased levels of IGFBP-2 in conditioned media and in plasma membrane preparations. Treatment with insulin or des(1-3) IGF-I resulted in the appearance of IGFBP-3 in conditioned media and on the cell surface. However, RA significantly reduced IGFBP-3 levels in conditioned media and eliminated IGFBP-3 associated with the plasma membrane. Thus, RA is a potent but transient inhibitor of bovine mammary epithelial cell proliferation, and this growth inhibition is correlated with increased IGFBP-2 accumulation and inhibition of IGF-I stimulated IGFBP-3 protein secretion.

Animals↗

PubMed2004

Proteasome inhibitors and their combination with antiandrogens: effects on apoptosis, cellular proliferation and viability of prostatic adenocarcinoma cell cultures.

The 26S proteasome is a ubiquitin-dependent proteolytic system that has been implicated in the regulation of cell cycle progression and apoptosis. We investigated the effects of the proteasome inhibitors MG115 and PSI alone or in combination with different concentrations of the antiandrogen hydroxyflutamide on the cellular proliferation, apoptosis and viability of 10 prostatic adenocarcinoma cell cultures. Treatment with both proteasome inhibitors resulted in apoptosis induction, whereas the combinations with hydroxyflutamide generally did not, with the exception of MG115 combined with 10(-7) M hydroxyflutamide. MG115 caused a significant decrease in cellular proliferation, as did the combinations of both proteasome inhibitors with hydroxyflutamide, whereas hydroxyflutamide alone was only effective at a concentration of 10(-5) M. Cellular viability was significantly reduced when both proteasome inhibitors were combined with 10(-5) M hydroxyflutamide. Although the results varied among different cell lines, we conclude that proteasome inhibitors are able to induce apoptosis and reduce cellular proliferation. They might prove effective as antineoplastic substances in prostatic adenocarcinoma alone or in combination with antiandrogens.

Adenocarcinoma↗

PubMed2004

JNK2: a negative regulator of cellular proliferation.

The three different c-Jun N-terminal kinases (JNKs) are activated in multiple cell types by both apoptotic and mitogenic signals, and in turn regulate the activity of transcription factors such as c-Jun. Being highly homologous and ubiquitously expressed, the JNK1 and JNK2 proteins have been thought to perform redundant functions in many physiological process. However, our data from Jnk1-/- or Jnk2-/- cells and mice suggest that both JNK isozymes perform distinct functions in regulating cellular proliferation via differential regulation of c-Jun, which is a critical regulator of cell-cycle progression. Absence of JNK1, the positive regulator of c-Jun, leads to decreased fibroblast proliferation. In contrast, JNK2 deficiency leads to reduced c-Jun degradation, thereby augmenting c-Jun levels and cellular proliferation. Various cell types including fibroblasts, erythroblasts and hepatocytes from Jnk2-/- mice exhibit increased proliferation rates compared to their wild-type counterparts. These data therefore suggests that JNK2, in contrast to JNK1, is a negative regulator of cellular proliferation in multiple cell types.

Animals↗

PubMed2003

In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography.

BACKGROUND: and aims: Positron emission tomography (PET) using (18)F labelled 2-fluoro-2-deoxy-D-glucose ((18)FDG) is an established imaging tool, although the recent development of a biologically stable thymidine analogue [18F] 3'-deoxy-3-fluorothymidine ((18)FLT) has allowed PET to image cellular proliferation by utilising the salvage pathway of DNA synthesis. In this study, we have compared uptake of (18)FLT and (18)FDG with MIB-1 immunohistochemistry to evaluate the role of PET in quantifying in vivo cellular proliferation in colorectal cancer (CRC). PATIENTS AND METHODS: Patients with resectable, primary, or recurrent CRC were prospectively studied. Thirteen lesions from 10 patients (five males, five females), median age 68 years (range 54-87), were evaluated. Patients underwent (18)FDG and (18)FLT PET scanning. Tracer uptake within lesions was quantified using standardised uptake values (SUVs). Histopathological examination and MIB-1 immunohistochemistry were performed on all lesions, and proliferation quantified by calculating a labelling index (% of MIB-1 positively stained nuclei within 1500 tumour cells). RESULTS: Histology confirmed adenocarcinoma in 12 of 13 lesions; the remaining lesion was reactive. All eight extrahepatic lesions were visualised using both (18)FLT and (18)FDG. Three of the five resected liver metastases were also avid for (18)FLT and showed high proliferation, while the remaining two lesions which demonstrated no uptake of (18)FLT had correspondingly very low proliferation. There was a statistically significant positive correlation (r =0.8, p<0.01) between SUVs of the tumours visualised with (18)FLT and the corresponding MIB-1 labelling indices. No such correlation was demonstrated with (18)FDG avid lesions (r =0.4). CONCLUSIONS: (18)FLT PET correlates with cellular proliferation markers in both primary and metastatic CRC. This technique could provide a mechanism for in vivo grading of malignancy and early prediction of response to adjuvant chemotherapy.

Adenocarcinoma↗