Biomedical subjects

M Abdul

Publications and source records attributed to M Abdul.

11 recordsLinked to original sources

PubMed2006

Results obtained with various antifungal susceptibility testing methods do not predict early clinical outcome in patients with cryptococcosis.

The in vitro susceptibilities of Cryptococcus neoformans isolates from consecutive human immunodeficiency virus-positive and -negative patients to the antifungal agents fluconazole, amphotericin B, and flucytosine were determined by different techniques, including the CLSI method, Etest, and broth microdilution in yeast nitrogen base (YNB) medium, during a multicenter prospective study in France. The relationship between the in vitro data and the clinical outcome 2 weeks after the initiation of antifungal therapy was assessed. In addition, the correlation between the strain serotype and the in vitro activities of the antifungals was determined, and the susceptibility results obtained with the different techniques were also compared. Thirty-seven patients received a combination of amphotericin B with flucytosine as first-line therapy, 22 were treated with amphotericin B alone, and 15 received fluconazole alone. Whatever the antifungal tested, there was no trend toward higher MICs for strains isolated from patients who failed to respond to a given therapy compared to those from patients who did not with either the CLSI method, Etest, or broth microdilution in YNB medium. The MICs obtained by the CLSI or Etest method were significantly lower for serotype D strains than for serotype A strains for both fluconazole and amphotericin B, while flucytosine MICs were not different according to serotype. These findings suggest that the in vitro antifungal susceptibility of C. neoformans, as determined with the techniques used, is not able to predict the early clinical outcome in patients with cryptococcosis.

AIDS-Related Opportunistic Infections↗

PubMed2005

N-methyl-D-aspartate receptor in human prostate cancer.

Expression of the N-methyl-D-aspartate receptor (NMDAr) and its involvement in cellular proliferation is well-known in tumors of neuronal tissue, such as glioma and neuroblastoma. We have investigated NMDAr expression in the normal, hyperplastic and neoplastic human prostate by immunohistochemistry. Low stromal NMDAr immunostaining was observed in 2 of 12 (17%) normal prostate specimens, but epithelial NMDAr staining was not seen. Of 18 benign prostatic hyperplasia (BPH) specimens, none had stromal NMDAr staining, but 2 had low and 1 had high epithelial NMDAr immunoreactivity. Moderate to high NMDAr immunostaining was observed in the stroma of 60 of 145 (41%) prostate cancer (PCa) specimens. Epithelial NMDAr staining was low in 26 (18%) and moderate to high in 36 (25%) of 145 PCa specimens. We have also examined the effects of the NMDAr antagonist memantine on the growth of ten human cancer cell lines: four prostate, two breast and four colon. The NMDAr antagonist memantine inhibited in-vitro growth of all ten cell lines, with half-maximal growth-inhibition at 5 to 20 microg/ml (23 to 92 microM) memantine. An NMDA agonist, L-cysteinesulfinic acid, stimulated cellular proliferation of all ten cell lines, with maximal growth-stimulation (30% to 75%, depending on the cell line) observed between doses of 33 to 66 microM. Our data provide evidence for the expression and activity of NMDAr in prostate cancer.

Breast↗

PubMed2000

Changes in beta-2 microglobulin expression in prostate cancer.

Increased shedding of beta-2 microglobulin (B2m, 11.8 kDa), a component of the major histocompatibility complex class I (MHC I), by tumor cells has significance with regard to escape from immune-surveillance, cellular proliferation, and tumor development and progression. Aberrant expression of MHC I is known to occur in prostate cancer (PCa) but not in benign prostatic hyperplasia. We have determined B2m released by PCa cells in culture and in the urine of 101 patients with advanced PCa by Western blotting and radioimmunoassay. B2m levels in the conditioned medium of human PCa cell lines and primary cultures derived from distant metastasis as well as in the urine of patients with bone and visceral metastasis were higher than normal and also higher than those from patients with local/regional extensions of the disease. In the group of patients with bone metastasis (66 patients), high urine B2m was associated with significantly shortened survival. In addition to the 11.8 kDa B2m, a high molecular weight B2m immunoreactivity of approximately 38 kDa was found in highly tumorigenic PC-3 cell line, but not in the relatively indolent DU-145 and LNCaP human PCa cell lines. The approximately 38 kDa B2m was found in the urine of several PCa patients but not of healthy controls examined by Western analysis. The conditioned medium of a prostatic small cell carcinoma cell line, NCI-H660, had high levels of chromogranin A and B2m, but prostate specific antigen was absent. In conclusion, increased B2m shedding was associated with distant metastasis of PCa and an abnormal B2m immunoreactivity was found in PCa.

Journal Article↗

PubMed2000

Differences in the expression and effects of interleukin-1 and -2 on androgen-sensitive and -insensitive human prostate cancer cell lines.

The presence of interleukin-1 (IL-1) and IL-2 mRNA in five human prostate cancer (PCa) cell lines and their effects on cellular proliferation and prostate-specific antigen (PSA) levels were examined. IL-1 was found in androgen-unresponsive PC-3 and DU-145 but not in the androgen-responsive LNCaP, MDA-PCA-2a and MDA-PCA-2b cell lines. IL-2 message was absent while that of GAPDH (positive control) was present in all five cell lines. IL-1 decreased while IL-2 increased PSA levels of near-confluent LNCaP cells after 24 h of treatment. IL-1 inhibited whereas IL-2 stimulated the growth of sub-confluent LNCaP cells (72 h). Neither cytokine affected the proliferation of DU-145 or PC-3 cells.

Androgens↗

PubMed1998

Modulation of neuroendocrine differentiation in prostate cancer by interleukin-1 and -2.

Neuroendocrine differentiation in prostate cancer has received much attention recently because it has been found to be associated with androgen independence and shortened patient survival in some studies. We have investigated the effect of the cytokines interleukin-1 (IL-1), IL-2, and IL-6 on the expression of the neuroendocrine marker chromogranin A in human prostate cancer cell lines. Chromogranin A was measured by fluorescence-immunoassay, as well as by immunoblotting. We find that IL-1beta and IL-6 increase the cellular content and chromogranin A secretion by LNCaP and DU-145 cells. By contrast, IL-2 decreases the cellular and secreted chromogranin A levels in the two cell lines. Our results suggest that these proinflammatory cytokines can influence neuroendocrine differentiation in prostate cancer and be involved in disease progression.

Cell Differentiation↗

PubMed1995

Gammopathy associated with advanced prostate carcinoma.

As proteinuria was found to be common in patients with prostate cancer, the possible presence of elevated urinary immunoglobulin (Ig) levels was investigated. First morning urine samples from 30 patients with androgen-dependent (AD) and 43 patients with androgen-independent (AI) prostate cancer were tested. A sensitive, solid-phase radioimmunoassay and polyclonal antibody interacting with IgG, IgA and IgM was used to screen urine samples. Compared with 15 normal, age-matched, healthy subjects, urinary Ig levels were elevated in 10 of 30 (33%) patients with AD prostate cancer and in 24 of 43 (56%) patients with AI prostate cancer. In the latter group, five of seven (71%) patients with prostatic SCC had elevated urinary Igs. Further analysis of ten urine samples containing increased urinary Ig levels, using antibodies specific for each heavy chain (gamma, alpha and mu) as well as each light chain (kappa and lambda), indicated that patients with a high or moderate elevation in Ig levels had polyclonal gammopathy, whereas those with a low increase in urinary Igs had monoclonal gammopathy of the IgG class. These results indicate, for the first time, a high frequency of an abnormal increase in Ig levels in patients with advanced prostatic carcinoma.

Androgens↗

PubMed1995

Growth-inhibitory effects of serotonin uptake inhibitors on human prostate carcinoma cell lines.

Growth stimulation of a variety of cell types by the neurotransmitter serotonin has been reported. We have examined the effects of three serotonin-uptake inhibitors, 6-nitroquipazine, zimelidine and fluoxetine (Prozac, Eli Lilly Co., Indianapolis, Indiana) on human prostate carcinoma cell lines. In vitro, all 3 of these compounds inhibited the proliferation of PC-3, DU-145 and LNCaP cells in a dose-dependent manner. Also, all 3 compounds blocked the uptake of a radiolabeled analog of serotonin by the prostate carcinoma cell lines. The order of potency for inhibition of growth as well as for serotonin uptake was fluoxetine > zimelidine > 6-nitroquipazine. The growth of subcutaneous, PC-3 xenografts in athymic nude mice was significantly inhibited by fluoxetine. These results implicate biogenic amines such as serotonin in the growth of prostate carcinoma cells and indicate the potential use of serotonin-uptake inhibitors for the treatment of prostate cancer.

Animals↗

PubMed1990

[The morphological changes in the seminal vesicles in prostatic sclerosis].

A study is presented of morphological changes of the seminal vesicles removed during prostatectomy in 51 patients with sclerosis of the prostate and histological findings of the seminal vesicles were compared with roentgenological signs on the vesiculograms and clinical manifestations of the disease. Results indicate that the seminal vesicles undergo significant pathological changes in the development of sclerosis of the seminal vesicles requiring in some cases their surgical removal for restoration of the urodynamics in cystic-urethral segment.

Adult↗

PubMedDate not supplied

Inhibition by anticonvulsants of prostate-specific antigen and interleukin-6 secretion by human prostate cancer cells.

BACKGROUND: Anticonvulsants/antiepileptics inhibit high-frequency firing of action potentials that occur during an epileptic seizure, by mechanisms such as blocking sodium and calcium ion conductances. High sodium channel expression has been previously associated with aggressive behavior of prostate cancer (PCa) cell lines. The anticonvulsant phenytoin is known to inhibit the secretory activity and growth of human osteoblastic cells. MATERIALS AND METHODS: The effect of four anticonvulsants on the secretion of prostate-specific antigen (PSA) and interleukin-6 (IL-6) by human PCa cell lines (LNCaP, DU-145 and PC-3) was studied using immunoanalysis. RESULTS: Phenytoin and carbamazepine, which inactivate voltage-gated sodium channels, inhibited the secretion of PSA by LNCaP and IL-6 by DU-145 and PC-3 cell lines. Valproate and ethosuximide, which block calcium channels, had somewhat lower antisecretory effects. The growth of the three PCa cell lines in Matrigel was inhibited by all four anticonvulsants, at clinically-relevant doses. CONCLUSION: Further study of the usefulness of anticonvulsants in PCa therapy is warranted.

Anticonvulsants↗

PubMedDate not supplied

Antiproliferative effects of cyclocreatine on human prostatic carcinoma cells.

Creatine kinase (CK; EC 2.7.3.2) isoenzymes and their substrates have an important function in cellular energy generation and utilization. The brain isoform (CK-BB) has been implicated in cellular transformation processes involving the oncogenic products of the Ela virus and the p53 tumor suppressor gene. Cyclocreatine, an analogue of creatine, has been previously shown to inhibit the growth of a broad spectrum of cancer cells derived from solid tumors. Results reported herein indicate an increased level of creatine kinase activity in human prostate carcinoma cell lines and inhibitory effects of cyclocreatine alone and in combination with adriamycin on the growth of these cells in vitro and in vivo, in immune-deprived mice. Our results suggest the possible use of cyclocreatine in the treatment of prostatic carcinoma.

Animals↗

PubMedDate not supplied

Growth inhibition of human prostatic carcinoma cell lines by serotonin antagonists.

Neuroendocrine (NE) differentiation within the primary prostate tumor has been correlated with tumor progression and shortened patient survival. Serotonin (5-hydroxytryptamine, 5-HT), a known mitogen, is found in most neuroendocrine cells of the human prostate. We have previously found that human prostatic carcinoma cell lines, PC-3, DU-145 and LNCaP, display certain NE characteristics. In this study, we have examined the effects of several subtype-selective 5-HT receptor antagonists on the growth of the three lines. Of these, the 5-HT1A antagonist pindobind had the most marked antiproliferative effect in vitro. Pindobind also had marked growth-inhibitory effects on the aggressive PC-3 cell line in vivo, in athymic nude mice. Radioligand binding studies indicated the presence of 5-HT binding sites on all three cell lines. Our results suggest that 5-HT is involved in the growth of prostate tumor cells and may serve as a target for treatment.

Cell Division↗