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PubMed1994

Polyamine requirements in nicotinamide-stimulated beta-cell differentiation in fetal porcine islet-like cell clusters.

The impact of nicotinamide on regulation of cell replication and hormone production by fetal porcine islet-like cell clusters (ICCs) containing a low fraction of beta-cells was investigated. For this purpose, ICCs were produced in tissue culture for 4 days in the presence or absence of nicotinamide (10 mM). ICCs formed in the presence of nicotinamide showed increased rates of (pro)insulin biosynthesis, contained more insulin, and displayed elevated contents of polyamines when compared with untreated ICCs. Immunocytochemical analyses of autoradiographed ICCs disclosed that nicotinamide expanded the relative size of the beta-cell population, and that the vitamin increased DNA synthesis of non-beta-cells only. The possibility that the effects of nicotinamide were conveyed by the increased polyamine content was explored by giving nicotinamide together with inhibitors of rate-limiting enzymes of polyamine biosynthesis, a maneuver that precluded the increases in polyamines of whole ICCs. Although this treatment prevented the increases in beta-cell population size, insulin production, and insulin content evoked by nicotinamide, the elevated cell replication nonetheless persisted. We conclude that the stimulatory effects of nicotinamide on insulin production and content by fetal porcine ICCs result from neoformation of beta-cells through differentiation. Since these effects were prevented by blocking the increased polyamine content, it is suggested that a stimulated synthesis of polyamines may be an important event in mediating the differentiating action of nicotinamide.

Animals↗
PubMed1996

Permissive role of polyamines in the cooperative action of estrogens and insulin or insulin-like growth factor I on human breast cancer cell growth.

Polyamines have been proposed as specific mediators of estrogen action in breast cancer cells, but their exact role in this process is still controversial. As estrogens cooperatively interact with peptide growth factors in several hormonal responses, the involvement of polyamines in the synergistic effect of 17 beta-estradiol (E2) and insulin or insulin-like-growth factor I (IGF-I) on cell growth, polyamine pools, specific gene induction, and cell cycle progression was examined in estrogen-responsive MCF-7 and ZR-75-1 human breast cancer cells. Spermidine depletion induced by the ornithine decarboxylase inhibitor, alpha-difluoromethylornithine (DFMO), resulted in complete cytostasis and loss of mitogenic response to either E2 or insulin (or IGF-I). In contrast, a steroidal antiestrogen blocked the mitogenic effect of E2, but only partly interfered with the synergistic stimulation of estrogen action by insulin. Whereas antiestrogen-resistant growth in insulin-treated cells was halted by DFMO, the antiestrogen did not further inhibit growth upon prior polyamine depletion. E2 and either IGF-I or insulin induced early increases in putrescine and spermidine, but not spermine, contents in both MCF-7 and ZR-75-1 cells. Moreover, spermidine depletion and decarboxylated S-adenosylmethionine accumulation induced by DFMO required prior mitogenic stimulation by E2 and/or IGF-I. The antiestrogen alone had only a limited effect on polyamine and nucleoside pools. DFMO did not interfere with the coordinate induction of the estrogen- and growth factor-inducible pS2 messenger ribonucleic acid by E2 and insulin even after a 5-day treatment with the drug. On the other hand, DFMO depressed the cycling fraction of E2/IGF-I-stimulated MCF-7 cell population far more dramatically than the antiestrogen and to less than that noted in mitogen-deprived cells. However, in ZR-75-1 cells, which have a much lower spermidine/spermine ratio than MCF-7 cells, specific inhibition of spermine synthase selectively antagonized the effect of E2 compared with that of insulin. These data indicate that spermidine has a permissive role for macromolecular synthesis and cell cycle traverse, but does not qualify as a limiting factor in estrogen receptor-mediated events per se in breast cancer cells. Moreover, polyamine depletion is an efficient complementary strategy to block the mitogenic action of peptide growth factors, which is only partly antagonized by antiestrogens.

Base Sequence↗
PubMed1992

Effect of captopril on isoproterenol-induced cardiac hypertrophy and polyamine contents.

It is well known that isoproterenol (ISO) a nonselective beta adrenoceptor agonist induces cardiac hypertrophy. It can be assumed that, in addition to its direct cardiac effect, ISO has a cardiac trophic effect via stimulation of the renin angiotensin system. Synthesis of polyamines is facilitated in cardiac hypertrophy and polyamine levels are rapidly elevated prior to an increase in heart weight. In the present study, we investigated whether captopril (30 mg/kg body weight, daily) could attenuate cardiac hypertrophy and elevation of cardiac polyamine levels in rats, which effects were elicited by a chronic (1- or 2-weeks) and repeated administration of a small dose (0.5 mg/kg body weight) of ISO. Cardiac hypertrophy was assessed by an increase in the wet weight and RNA content of the heart. Polyamines were analyzed by HPLC. Captopril alone did not affect either heart weight/body weight ratio or cardiac contents of polyamines and nucleic acids at the end of the second week. In isoproterenol-treated rats, the above parameters, except for putrescine content on day 14, were significantly increased on both day 7 and day 14. Captopril slightly attenuated ISO-induced cardiac hypertrophy and significantly prevented the ISO-evoked increase in the contents of RNA, spermidine, and spermine at the end of the second week. These results suggest that the ISO-evoked increase in cardiac polyamines was mediated, at least in part, by the renin angiotensin system, which was stimulated by ISO.

Animals↗
PubMed1981

[A potential role of polyamines in goiter formation (author's transl)].

Changes in polyamine contents and in the activity of polyamine biosynthetic enzymes were studied in the rat thyroid. Both exogenous and endogenous TSH promptly stimulated the activity of thyroid ornithine decarboxylase (ODC) and S-adenosyl-L-methionine decarboxylase. Treatment of the animals with antithyroid drugs resulted in an increase in circulating TSH level, the activities of the enzymes and thyroidal contents of putrescine, spermidine and spermine. Theophylline, which stimulated methylthiouracil (MTU)-induced goitrogenesis without increasing circulating TSH level, increased the thyroid ODC activity. In contrast, treatment with excess iodine (KI) which induced thyroid involution without affecting circulating levels of TSH, T4 and T3, resulted in a rapid reduction in the thyroid ODC activity. The MTU-induced goiter involuted after MTU withdrawal and the thyroid ODC and polyamine contents decreased within a few days after its withdrawal. The activity of thyroid arginase was increased by MTU and decreased by T4 injection. The enzyme may have some regulatory role in polyamine biosynthesis by controlling ornithine supply. Polyamine levels were elevated in both papillary and follicular adenocarcinomas of the human thyroid. The results suggest that the measurement of thyroid polyamines may be useful for the diagnosis of carcinomas.

Adenosylmethionine Decarboxylase↗
PubMed1981

A possible role of cadaverine in the biosynthesis of polyamines in the Japanese newt testis.

Polyamine content in testes of various vertebrates was studied extensively. Putrescine, spermidine and spermine were detected in all the animals examined, although the distribution pattern varied greatly from animal to animal. Cadaverine was detected only in amphibian testes; sym-homospermidine was found not only in testes but also in various other tissues of amphibians and of some reptiles. In the newt testis the concentration of cadaverine was lower than that of any other polyamines in summer, but there was a great increase in cadaverine content from autumn to winter. The testicular content of cadaverine was greater than that of other polyamines in winter. There was a gradual decrease in the cadaverine content in spring. The spermidine and spermine levels, which were rather low in winter, increased in spring and reached a peak in summer when spermatogenesis was active. The testicular concentration of putrescine that was much higher than that of spermidine or spermine throughout the year, increased only a little in summer. There was a significant negative correlation between the cadaverine levels and four other polyamine levels. Exogenous cadaverine decreased the testicular levels of putrescine. Mammalian gonadotropins decreased the cadaverine levels and increased the levels of other polyamines. A partially purified LH fraction from pituitaries of bullfrog, Rana catesbeiana, was also potent in depleting cadaverine of the testes of newts kept at 8 degrees C. These results suggest that testicular cadaverine suppresses the biosynthesis of polyamines, especially spermidine and spermine which are closely associated with spermatogenesis.

Animals↗
PubMed2006

The effects of exogenous polyamines on some biochemical changes during drought stress in Ctenanthe setosa (Rosc.) Eichler.

Morphological and biochemical changes in plant cells are known as important events for adaptation to stress. In this study, in Ctenanthe setosa leaves to which polyamines were applied during drought stress, changes in the activity of peroxidase, reducing sugar, proline and soluble protein levels were investigated. The three common polyamines, putrescine, spermidine and spermine were exogenously treated through the leaves. The polyamines were sprayed onto the leaves at 5 x 10(-5) M. In the leaves to which polyamines were applied the peroxidase activity decreased, soluble protein increased. Also, it was determined that putrescine and spermidine caused an increase in the amount of proline and in reducing sugar. However, increase was not observed in the leaves to which spermine was applied. In addition, we observed an increase in the activity of peroxidase, proline and reducing sugar levels, and a decrease in soluble protein level in the control ones and the leaves to which polyamines were applied during drought stress. As a result, the effect of polyamine on leaf rolling may be explained through the contribution to osmotic adjustment of the increase in proline, reducing sugar and soluble protein contents.

Adaptation, Biological↗
PubMed2006

Agmatine suppresses mesangial cell proliferation by modulating polyamine metabolism.

Polyamines play an essential role in the growth and differentiation of mammalian cells. The depletion of intracellular polyamines results in the suppression of growth. Proliferation of glomerular mesangial cells (MC) is the most common pathologic change in many forms of glomerulonephritis. Agmatine is a metabolite of arginine via arginine decarboxylase (ADC), highly expressed in the kidney, and unique in its capacity to suppress intracellular polyamine levels required for proliferation. As agmatine enters mammalian cells via the polyamine transport system, its antiproliferative effects may preferentially target cells with increased proliferative kinetics. In the present study, we evaluated the antiproliferative effects of agmatine on human MC in vitro. MC proliferation was stimulated with 20% fetal bovine serum (FBS) or platelet-derived growth factor (PDGF-BB, 20 ng/ml). Cell proliferation was measured using the (4.3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) (MTT) proliferation assay. Intracellular polyamine levels were assayed by high performance liquid chromatography, and cell death was assessed by cellular DNA fragmentation enzyme-linked immunosorbent assay. The MTT proliferation assay showed that agmatine significantly suppressed proliferation of human MC treated with 20% FBS or 5% FBS + PDGF as compared to human MC treated with 5% FBS. Polyamine levels were markedly lower in cells treated with agmatine, and proliferation was rescued by administration of putrescine. The fragmented DNA was hardly detected in agmatine-treated human MC. In summary, human MC stimulated to increase their proliferative kinetics are significantly more sensitive to the antiproliferative effects of agmatine than normally cultured cells. Suppressed proliferation of the agmatine-treated human MC is not due to increased cell death. These results suggest that agmatine is a promising drug candidate for the treatment of human mesangial proliferative glomerulonephritis.

Agmatine↗
PubMed2005

Polyamine depletion reduces TNFalpha/MG132-induced apoptosis in bone marrow stromal cells.

Polyamines are powerful modulators of both growth and survival in mammalian cells. In this study, we investigated the possibility of attenuating the process of apoptosis in bone marrow stromal cells (BMSCs), which comprise mesenchymal stem cells, by reducing the intracellular levels of polyamines. BMSCs were isolated from rat femurs and expanded for 12 days. At this time, BMSCs were CD34neg, CD45neg, and mostly CD90pos. BMSCs were grown for an additional 2 days in the presence of 1 mM alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, which reduced the content of both putrescine and spermidine by nearly 90%. DFMO treatment progressively slowed down BMSC proliferation, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay, without arresting their growth completely. The effect of polyamine depletion on caspase-3 activity was evaluated in BMSCs after treatment with 500 U/ml tumor necrosis factor-alpha (TNFalpha) and 5 microM MG132, an inhibitor of proteasome. Caspase-3 activity increased linearly over a period of 24-hour stimulation (p<.01), but this augmentation was blunted by 50% after DFMO administration (p<.05). The effect of DFMO on TNFalpha/MG132-induced upregulation of caspase-3 activity was reversed by the addition of 100 microM putrescine, confirming that polyamines were really involved in the apoptotic process. Also, the number of apoptotic BMSCs after TNFalpha/MG132 treatment, as determined by terminal transferase-mediated dUTP nick end-labeling (TUNEL) assay, were threefold reduced after polyamine depletion (p<.05). On the contrary, DFMO did not affect the MG132-mediated increase in p53 abundance, nor its translocation to the nucleus. Thus, polyamine depletion can be considered a useful tool for counteracting programmed cell death in BMSCs without involving the p53 proapoptotic protein.

Animals↗
PubMed1985

Ornithine decarboxylase activity and polyamines in the anterior pituitary gland during the rat oestrous cycle.

The biosynthesis of polyamines, an ubiquitous group of amines shown to be essential for normal cellular growth and differentiation, was studied in the rat anterior pituitary gland during the different stages of the oestrous cycle. The activity of ornithine decarboxylase (ODC), which catalyses the rate-limiting step in the biosynthesis of polyamines, was low during oestrus, metoestrus and dioestrus. However, a marked transitory rise in ODC activity was found in the pituitary gland on the evening of pro-oestrus. The rise in ODC activity was accompanied by an increase in the pituitary content of the polyamines putrescine and spermidine. Ovariectomy did not significantly change the basal ODC activity in the pituitary gland. Oestrogen treatment of ovariectomized rats resulted in a marked stimulation of pituitary polyamine biosynthesis. The largest effects were observed when oestrogen was given as two injections 72 h apart, which gave rise to levels of ODC activity comparable to those observed on the evening of pro-oestrus. The increase in polyamine synthesis in the anterior pituitary gland during pro-oestrus appeared not to be related to the preovulatory secretion of LH or prolactin, since neither LH-releasing hormone nor thyrotrophin-releasing hormone (which induces a secretion of prolactin) affected pituitary ODC activity. The observed biosynthesis of polyamines may be associated with the cellular proliferation which occurs in the anterior pituitary gland at oestrus.

Animals↗
PubMed1985

Concentrations of polyamines in umbilical blood.

Red blood cell and plasma polyamines in umbilical and maternal blood at delivery were measured using high performance liquid chromatography. The concentration of each polyamine in red blood cells and plasma of umbilical blood was significantly higher than in maternal blood. Spermidine and spermine concentrations in fetal red blood cells decreased markedly with the progress of pregnancy. In addition, younger red blood cells contained more polyamines than older cells. Red blood cell polyamines are closely associated with the cell membrane. Plasma polyamine in umbilical blood reflect active fetal metabolism, whereas red blood cell polyamines mainly reflect alterations in erythropoiesis in bone marrow and may indicate the proliferation of the bone marrow.

Embryonic and Fetal Development↗
PubMed1983

Clinical relevance of polyamines.

The polyamines, putrescine, spermidine, and spermine have been established as biochemical markers of normal and pathological growth. In malignancy, the urinary concentrations of spermidine reflect the tumor cell loss and the urinary level of putrescine is related both to the number of tumor cells in cell cycle and to the tumor cell loss factor. A greater than twofold increase in urinary spermidine within 72 hr of chemotherapy predicts a complete or a partial response with a high degree of accuracy. Urinary putrescine may be valuable, not only in assessing the early response to therapy but also in determining whether the chemotherapy promotes a later burst of cell proliferation. Erythrocyte spermidine concentrations also appear to track alterations in tumor kinetics. Alterations in intracellular and extracellular polyamines in other pathologies such as psoriasis, muscular dystrophy, and cystic fibrosis also accurately reflect the disease activity and, in those cases studied, response to therapy. Therefore, the determination of polyamine concentrations in extracellular fluids and in erythrocytes allows for (1) the early assessment of response to multimodality therapy, (2) disease or tumor staging, and (3) assessment of disease activity including long-term monitoring of polyamine concentrations to pinpoint remission and relapse in adjuvant patients. Information obtained by the monitoring of polyamines could result in prolongation of survival time of patients as well as assist in the design of the most effective therapy regimen for the pathology. Since other such specific kinetic markers are not available, polyamines should be clinically utilized to track tumor evolution and tumor response to therapy in those patients at high risk, in which such measurements could be translated into therapeutic efficacy.

Animals↗
PubMed1994

Eflornithine treatment in SHR: potential role of vascular polyamines and ornithine decarboxylase in hypertension.

This study was performed to assess the potential role of polyamines in the alterations in vascular structure and function in spontaneously hypertensive rats (SHR). The effects of chronic administration of eflornithine (alpha-difluoromethylornithine; DFMO), a highly specific inhibitor of ornithine decarboxylase (the rate limiting enzyme in polyamine biosynthesis), on vascular polyamine contents, vascular structure and function, and blood pressure was studied. Male SHR (16-17 weeks of age) with an average systolic blood pressure (SBP) of 161 +/- 3 mmHg were used. The rats were divided into two groups and received either tap water or a 1% DFMO solution to drink for 6 weeks. SBP and body weight were recorded prior to and once-a-week during the experiment. Standard in vitro vascular reactivity studies on ring segments of aorta and tail artery were performed. Ring segment weight, arterial medial thickness, and vascular polyamine contents were also determined. Body weights were not significantly affected by the DFMO treatment. SBP in control SHR rose progressively to an average value of 185 +/- 5 mmHg by the sixth experimental week. Although DFMO treatment did not cause a significant decrease in SBP compared to pretreatment values, it did prevent a further increase in SBP. Aortic and tail artery responsiveness to norepinephrine and electrical stimulation, respectively, ring segment weight, arterial medial thickness, and vascular polyamine contents were all significantly less in SHR receiving the DFMO treatment. These data are the first to demonstrate the effectiveness of DFMO to lower polyamine contents in the vasculature of hypertensive SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Some properties of the polyamine deprivation-inducible uptake system for methylglyoxal bis(guanylhydrazone) in tumor cells.

Intracellular polyamine deprivation, produced by DL-alpha-difluoromethylornithine (DFMO), resulted in a striking enhancement of cellular transport of the natural polyamines and methylglyoxal bis(guanylhydrazone) (MGBG). In addition to the natural polyamines and MGBG, the uptake of other diamines and triamines was likewise enhanced in response to DFMO, although longer than three-carbon backbone was required for about 10-fold stimulation to occur. Intracellular deprivation of polyamines did not increase the affinity of the transport system for MGBG but greatly enhanced the maximum velocity of the drug transport. The uptake process of MGBG was temperature dependent and the activation energy (Ea = 67.5 kJ) for the uptake system was the same for both the polyamine-depleted tumour cells and for the untreated cells. The uptake of the drug appeared to be more dependent on the Na+-linked uptake, as indicated by the inhibitory effect of ouabain, than on energy production. Deprivation of putrescine and spermidine changed the intracellular distribution of MGBG since a major portion of the drug was concentrated in the microsomal fraction in polyamine-depleted cells.

Animals↗
PubMed1998

Polyamine metabolism as target for cancer chemoprevention (review).

The natural polyamines putrescine, spermidine and spermine are intimately involved in growth-related processes. More and more evidence indicates that the excessive accumulation of putrescine and spermidine favors malignant transformation of cells. Selective depletion of putrescine has been shown to restore in some transformed cells the normal phenotype. Inhibition of polyamine formation appears, therefore, a rational target in chemoprevention. Clinical trials with 2-(difluoromethyl)ornithine, a selective inactivator of ornithine decarboxylase, a key enzyme of polyamine biosynthesis, are promising. Structural analogs of the polyamines with polyamine-mimetic or antagonist properties, and calmodulin antagonists are other types of drugs which affect several key reactions of polyamine metabolism, and appear to be candidates for the prevention of carcinogenesis especially of the gastrointestinal tract.

Antineoplastic Agents↗
PubMed1998

[Changes in blood polyamine levels following chemotherapy in patients with invasive urinary bladder carcinoma].

BACKGROUND: Polyamines are recognized as cell growth factors. We attempted to determine whether blood polyamines are useful biochemical makers for monitoring the efficacy of the chemotherapy on bladder tumors. METHODS: The blood concentrations of three polyamines, diamine, spermidine and spermine, were determined in 31 patients with invasive urinary bladder carcinoma, following chemotherapy with cisplatin, methotrexate and pirarubicin. Clinical response was evaluated by CT after 3 weeks. In 26 patients who underwent subsequent surgical therapy, the effectiveness of the chemotherapy were histopathologically evaluated by a pathologist according to the response criteria for bladder cancer treatment. RESULTS: Mean regression rate in the size of the tumor after the chemotherapy was 40.8%. Of 31 patients, clinical CR was observed in 2, PR in 11, and NC in 18. Of 26 patients who were histopathologically evaluated, grade 3 was observed in 5, grade 2 in 4, grade 1b in 4, grade 1a in 12, and grade 0 in 1. One week after chemotherapy, the levels of spermine and total polyamine in the patients with CR and PR were significantly lower than those in the patients with NC. Similarly one week after chemotherapy, the levels of spermine and total polyamine in the patients with grade 3 and grade 2 were significantly lower than those in the patients with grade 1b, grade 1a and grade 0. CONCLUSION: The study suggested that the levels of blood polyamines could be used as biochemical markers for monitoring the efficacy of the chemotherapy on bladder tumors.

Adenocarcinoma↗
PubMed1999

Overexpression of spermidine/spermine N1-acetyltransferase under the control of mouse metallothionein I promoter in transgenic mice: evidence for a striking post-transcriptional regulation of transgene expression by a polyamine analogue.

We recently generated a transgenic mouse line overexpressing spermidine/spermine N1-acetyltransferase (SSAT) gene under its own promoter. The tissue polyamine pools of these animals were profoundly affected and the mice were hairless from early age. We have now generated another transgenic-mouse line overexpressing the SSAT gene under the control of a heavy-metal-inducible mouse metallothionein I (MT) promoter. Even in the absence of heavy metals, changes in the tissue polyamine pools indicated that a marked activation of polyamine catabolism had occurred in the transgenic animals. As with the SSAT transgenic mice generated previously, the mice of the new line (MT-SSAT) suffered permanent hair loss, but this occurred considerably later than in the previous SSAT transgenic animals. Liver was the most affected tissue in the MT-SSAT transgenic animals, revealed by putrescine overaccumulation, significant decrease in spermidine concentration and >90% reduction in the spermine pool. Even though hepatic SSAT mRNA accumulated to massive levels in non-induced transgenic animals, SSAT activity was only moderately elevated. Administration of ZnSO4 further elevated the level of hepatic SSAT message and induced enzyme activity, but not more than 2- to 3-fold. Treatment of the transgenic animals with the polyamine analogue N1,N11-diethylnorspermine (DENSPM) resulted in an immense induction, more than 40000-fold, of enzyme activity in the liver of transgenic animals, and minor changes in the SSAT mRNA level. Liver spermidine and spermine pools were virtually depleted within 1-2 days in response to the treatment with the analogue. The treatment also resulted in a marked mortality (up to 60%) among the transgenic animals which showed ultrastructural changes in the liver, most notably mitochondrial swelling, one of the earliest signs of cell injury. These results indicated that, even without its own promoter, SSAT is powerfully induced by the polyamine analogue through a mechanism that appears to involve a direct translational and/or heterogenous nuclear RNA processing control. It is likewise significant that overexpression of SSAT renders the animals extremely sensitive to polyamine analogues.

Acetyltransferases↗
PubMed1999

Prognostic value of ornithine decarboxylase and polyamines in human breast cancer: correlation with clinicopathologic parameters.

The polyamines putrescine, spermidine, and spermine and ornithine decarboxylase (ODC), the rate-limiting enzyme in their biosynthetic pathway, play an important role in cell proliferation, differentiation, and transformation. In the present study, we have analyzed polyamine concentrations and ODC activity in samples from benign breast diseases (n = 36), benign breast tissue adjacent to the primary carcinoma (n = 19), and breast carcinoma (n = 104). ODC activity in primary carcinoma was significantly higher (2.42 +/- 0.22 nmol CO2/h g; P < 0.001) than that found in benign breast (0.62 +/- 0.15 nmol CO2/h g) or in breast tissue adjacent to the primary carcinoma (0.52 +/- 0.16 nmol CO2/h g). The total polyamine content of breast cancer tissues was higher than in benign breast diseases (704.3 +/- 38.3 nmol/g wet weight versus 295.8 +/- 27.4 nmol/g wet weight) and correlated well with ODC activity (Pearson, r = 0.42; P < 0.001). ODC activity correlated with histological grade, peritumoral lymphatic or blood vessel invasion, S-phase fraction, and cathepsin D. Total polyamine concentration increased with S-phase fraction, cathepsin D, and aneuploidy. No significant correlation was found between ODC or polyamines and tumor size, lymph node involvement, or steroid receptor status. A major finding in our study was that ODC activity was an independent prognostic factor for recurrence and death. The results indicate that the estimation of ODC activity and polyamines in human breast carcinoma might be useful to determine tumor aggressiveness and suggest that ODC may have a potential value as both a prognostic factor and a chemoprevention target in human breast cancer.

Adolescent↗
PubMed1999

Novel polyamine derivatives as neuroprotective agents.

The induction of an early increase in polyamine metabolism, termed "the polyamine response," is now recognized to have a critical role in the reaction of neurons to injury. Several studies in experimental animals have demonstrated that treatment with the naturally occurring polyamines spermine, spermidine, and putrescine can protect neurons from dying after the infliction of various types of neurotrauma, including mechanical injuries, neurotoxic insults, and ischemia. These findings led us to synthesize a series of polyamine derivatives of 1-aminoindan and 1-aminotetralin and to determine their effects in several in vitro and in vivo models of neurotrauma. Some of the novel compounds proved to be potent neuroprotective in these models, and one of them, N, N-di-(4-aminobutyl)-1-aminoindan, was superior to the others and to the natural polyamines themselves. We conclude that compounds based on the novel polyamine-based structures we synthesized have therapeutic potential as neuroprotective agents.

Animals↗