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  • apoptosis  (3)
  • Anal pain  (1)
  • 1
    ISSN: 1573-4919
    Keywords: antisense oligonucleotide ; apoptosis ; cAMP-dependent protein kinase ; cancer cells ; growth inhibition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract The enhanced expression of the RIα subunit of cyclic AMP-dependent protein kinase type 1 (PKA-I) has been correlated with cancer cell growth. We have investigated the effects of sequence-specific inhibition of RIα gene expression on the growth of MCF-7 human breast cancer cells. We report that RIα antisense treatment results in a reduction in RIα expression at both mRNA and protein levels and inhibition of cell growth. The growth inhibition was accompanied by changes in cell morphology, cleavage of poly(ADP-ribose) polymerase (PARP) and appearance of apoptotic nuclei. In addition, bcl-2 protein level was reduced and p53 expression increased in growth arrested cells. Interestingly, RIα antisense inhibited cell viability and induced apoptosis in the absence of p53, suggesting that these actions of RIα antisense are exerted independent of p53. In contrast, two- and four-base mismatched control oligonucleotides had no effect on either cell growth or morphology. These results demonstrate that the RIα antisense, which efficiently depletes the growth stimulatory molecule RIα, induces cell differentiation and apoptosis, providing a new approach to combat breast cancer cell growth.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-4919
    Keywords: retinoic acid ; RARβ ; protein kinase A ; apoptosis ; caspase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Both cAMP and retinoids play a role in cell differentiation and the control of cell growth. A site-selective cAMP analog, 8-Cl-cAMP and retinoic acid synergistically inhibit growth and induce apoptosis in certain cancer cells. In advanced or recurrent malignant diseases, retinoic acid (RA) is not effective even at doses that are toxic to the host. The objective of our present study was to examine the mechanism(s) of synergistic effects of retinoic acid (9-cis, 13-cis or all-trans RA) and 8-Cl-cAMP on apoptosis in human ovarian cancer NIH: OVCAR-3 and OVCAR-8 cells. RA induced growth inhibition and apoptosis in OVCAR-3 and OVCAR-8 cells. 8-Cl-cAMP acted synergistically with RA in inducing and activating retinoic acid receptor β (RARβ) which correlates with growth inhibition and apoptosis in both cell types. In addition, induction of apoptosis by RA plus 8-Cl-cAMP requires caspase-3 activation followed by cleavage of anti-poly(ADP-ribose) polymerase. Furthermore, mutations in CRE-related motif within the RARβ promoter resulted in loss of both transcriptional activation of RARβ and synergy between RA and 8-Cl-cAMP. RARβ expression appears to be associated with induction of apoptosis. Introduction of the RARβ gene into OVCAR-3 cells resulted in gain of RA sensitivity. Loss of RARβ expression, therefore, may contribute to the tumorigenicity of human ovarian cancer cells. Thus, combined treatment with RA and 8-Cl-cAMP may provide an effective means for inducing RARβ expression leading to apoptosis in ovarian cancer cells.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1530-0358
    Keywords: Levator syndrome ; Anal pain ; Triamcinolone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract PURPOSE: Several treatments are used for the treatment of levator syndrome, such as rectal massage, biofeedback, and galvanic stimulation. But their effects are inconsistent, and multiple treatment sessions are usually required. Triamcinolone acetonide and lidocaine mixture was injected locally into the tenderest point in levator syndrome under the hypothesis that levator syndrome is caused by tendinitis of pelvic floor musculature. METHODS: A mixture of 40 mg of triamcinolone acetonide and 1 ml of 2 percent lidocaine was injected into the tenderest point transanally in 104 patients (33 males; mean age, 51 years) with levator syndrome from December 1996 to May 1998 at Daehang Clinic. Additional injections were repeated at two-week intervals to a maximum of three injections in cases of poor response. Follow-up was performed prospectively concerning patient's perception of pain level using a visual analog scale. Depending on the response, the patients were classified into four groups: pain-free, good, fair, and no response. More than 50 percent pain reduction was classified as “good,” and less than 49 percent reduction as “fair.” RESULTS: The injection regions, where the tenderest points were identified on digital rectal compression, were left anterior anal canal in 71.2 percent of patients, right anterior in 3.8 percent of patients, and posterior in 25 percent of patients. The results of treatment were as follows: at three months after injection, response was classified as pain-free in 36.8 percent of patients, good in 35 percent of patients, fair in 19.5 percent of patients, and no response in 8.7 percent of patients; at six months the response was pain-free in 30.1 percent of patients, good in 46.5 percent of patients, fair in 18.2 percent of patients, and no response in 5.2 percent of patients. Most patients, except 8.7 percent at three months and 5.2 percent at six months, experienced treatment benefits. There were no complications during the follow-up periods. CONCLUSION: Transanal injection of triamcinolone acetonide and lidocaine mixture into the tenderest point is such a simple, safe, and very effective modality that it can be recommended as a primary therapy for levator syndrome.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7217
    Keywords: antisense ; protein kinase A ; apoptosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In recent years, several laboratories have explored the possibility of using antisense oligodeoxynucleotides for specific manipulation of gene expression leading to cancer treatment. The enhanced expression of the RIα subunit of cyclic AMP-dependent protein kinase type I (PKA-I) has been correlated with cancer cell growth. In the present study, the effects of an antisense oligodeoxynucleotide targeted against RIα subunit of PKA-I on growth inhibition and apoptosis in MDA-MB-231 human breast cancer cells were investigated. The growth inhibitory effects of RIα antisense oligodeoxynucleotide correlated with a decrease in the RIα mRNA and protein levels. The growth inhibition was accompanied by changes in the cell cycle phase distribution, cell morpbology, cleavage of poly (ADP-ribose) polymerase (PARP), and appearance of apoptotic nuclei. By comparison, mismatched control oligodeoxynucleotide had no effect. On the basis of these results, it can be suggested that the RIα antisense oligodeoxynucleotide, which efficiently depletes the growth stimulatory RIα and induces apoptosis/differentiation, could be used as a therapeutic agent for breast cancer treatment.
    Type of Medium: Electronic Resource
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