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1.
In Vivo ; 19(4): 787-92, 2005.
Article in English | MEDLINE | ID: mdl-15999550

ABSTRACT

Androgen ablation is palliative and does not cure advanced prostate cancer. The hormone-sensitive cells die and the hormone-resistant cells overgrow, resulting in disease progression. The drug of choice for secondary treatment is estramustine (Estracyt). The success of the therapy is followed by changes of the prostate-specific antigen level and Karnofsky scale. In the present study, the results of estramustine treatment of 79 patients with advanced prostate cancer in 12 hospitals were evaluated. The mean prostate-specific antigen level improved for 6 months, but rose from the ninth month on. The improvement in the subjective condition of the patients paralleled the change in the prostate-specific antigen level. The short time of improvement was a consequence of the very high prostate-specific antigen level and the poor general condition. Estramustine administration is recommended when the prostate-specific antigen level becomes more than doubled following primary treatment. At a starting prostate-specific antigen level of > 100 ng/ml, the treatment leads to total androgen blockade. If the prostate-specific antigen level has not decreased after treatment for 3 months, the secondary strategy is to apply chemotherapy.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents, Alkylating/therapeutic use , Estramustine/therapeutic use , Karnofsky Performance Status , Prostate-Specific Antigen/blood , Prostatic Neoplasms/drug therapy , Adenocarcinoma/blood , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Aged , Humans , Male , Middle Aged , Prostatic Neoplasms/blood , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Retrospective Studies , Survival Rate
2.
Orv Hetil ; 146(12): 553-7, 2005 Mar 20.
Article in Hungarian | MEDLINE | ID: mdl-15853064

ABSTRACT

INTRODUCTION/AIMS: Prostate cancer is a dynamic disease. Androgen ablation is palliative, and does not cure advanced prostate cancer. The hormone-sensitive cells die, and the hormone-resistant cells come into excess; the disease then progresses, which results in a deterioration of the condition of the patient. The theoretical basis of the curing strategy is the fact that the prostate tumour itself changes during the progression; the molecular determinants of the resistance are present in the varying stages of the disease. The treatment of advanced prostate cancer remains unsolved; it is a well-known fact that a hormone-resistant state develops after the primary treatment forms (androgen withdrawal). The drug of choice for the secondary treatment is estramustine. This can be utilized as monotherapy or in combination. METHODS: In the present study, the results of estramustine treatment of 79 patients with advanced prostate cancer were evaluated. The preparation, known and clinically applied for more than 20 years, was studied in 12 centres. RESULTS: The mean prostate-specific antigen level improved for 6 months, but rose from the 9th month on. The improvement in the subjective condition of the patients paralleled the change in the prostate-specific antigen level. The shortness of the improvement was a consequence of the very high prostate-specific antigen level and the poor general condition. CONCLUSIONS: Estramustine administration is recommended when the prostate-specific antigen level becomes more than doubled following the primary treatment. At a starting prostate-specific antigen level of >100 ng/ml, the treatment leads to total androgen blockade. If the prostate-specific antigen level has not decreased after treatment for 3 months, the secondary strategy is to apply chemotherapy.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Estramustine/therapeutic use , Prostatic Neoplasms/drug therapy , Aged , Humans , Male , Middle Aged , Prostate-Specific Antigen/blood , Prostatic Neoplasms/immunology , Prostatic Neoplasms/mortality , Survival Analysis , Treatment Outcome
3.
In Vivo ; 19(1): 253-9, 2005.
Article in English | MEDLINE | ID: mdl-15796183

ABSTRACT

The treatment of prostate cancer in an advanced state is still unsatisfactory. In the event of the ineffectiveness of total androgen blockade (TAB) therapy, cytostatic administration may be attempted. In this study, we modelled the drugs used in practice on human prostate cancer cell lines. Studies aimed at decreasing multidrug resistance were performed on PC-3 cells. With the use of various cytostatics, the cell proliferation-inhibiting effects were measured under in vitro conditions on human prostate cancer cell lines LNCaP-FGC and PC-3. Under the given experimental conditions, the examined cytostatics exhibited antiproliferative effects on each of the investigated cell lines. Our results indicate that it is not necessary to wait until the development of a hormone-resistant state. In the studies on the PC-3 cell line, we did not find a multidrug-resistant efflux activity responsible for the resistance of the tumour.


Subject(s)
Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cell Proliferation/drug effects , Drug Resistance, Multiple/genetics , Drug Resistance, Neoplasm/genetics , Prostatic Neoplasms/drug therapy , Antineoplastic Agents/metabolism , Cell Culture Techniques , Cell Line, Tumor , Dose-Response Relationship, Drug , Humans , Male , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology
4.
In Vivo ; 18(6): 809-12, 2004.
Article in English | MEDLINE | ID: mdl-15646825

ABSTRACT

Under normal conditions, androgen receptors function via ligand binding and other coactivators in prostate cancer cells. The effects of the currently applied therapy are achieved through inhibition of the formation of the testosterone-receptor complex. With the advance of research at a cellular level, it is now known that tumorigenesis is much more complicated, and that tumour cell growth regulated by androgens is a complex process. The aim of our work was to utilize literature data in a search for a correlation between the number of androgen receptors and the clinical course of the disease. Transperineal ultrasound-guided biopsies were performed on 82 (otherwise unselected) patients with suspected prostate cancer, and the numbers of androgen receptors in the tissue samples were determined by a receptor-analytical method. Prostate cancer was confirmed in 43 cases. Rebiopsy was scheduled for 1 year later. We were able to carry out repeated biopsies in 18 cases, and to determine the number of receptors by the earlier method. The patients were followed clinically, and the efficacy of their medication was measured via improvement in their general condition and study of the prostate-specific antigen level. The investigation demonstrated that determination of the number of receptors itself is not of prognostic value, but it does provide information to supplement the other parameters relating to the state.


Subject(s)
Carcinoma/metabolism , Prostate/metabolism , Prostatic Neoplasms/metabolism , Receptors, Androgen/metabolism , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Biopsy , Carcinoma/mortality , Carcinoma/pathology , Humans , Male , Prognosis , Prostate/pathology , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Radioligand Assay , Receptors, Androgen/analysis , Survival Rate
5.
In Vivo ; 17(2): 145-9, 2003.
Article in English | MEDLINE | ID: mdl-12792975

ABSTRACT

Various compounds were tested with regard to their reversal of multidrug resistance (MDR) in mouse tumor cells transfected with the human MDR1 gene. Phenothiazines containing aromatic moieties were bound through stacking interaction involving the polarization of the aromatic aminoacid substituents at the target site of p-glycoprotein (Pgp) 170, as a consequence of their large dipoles (as in the binding of phenothiazine to calmodulin-like structures). Acting as a calcium channel blocker, verapamil may induce conformational changes in the calcium channel-like structures of the transmembrane regions of Pgp. Most probably the tyrosine moieties of Pgp are involved in the action of verapamil and phenothiazines. Tomato lectin specifically binds to the polylactosamine moiety of Pgp170 at the first loop of Pgp. Other targets in the membrane may exist in close proximity to Pgp170, such as conA-reactive glycoproteins with terminal mannosyl residues. WGA-reactive N-acetyl glucosamine residues can also be modified resulting in conformational changes in trans-membrane regions of the ABC transporter. Our results demonstrate that MDR can be reversed by interaction of various compounds with Pgp or by modification of the membrane structure around the Pgp.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1 , Drug Resistance, Multiple/drug effects , Leukemia L5178/drug therapy , Phenothiazines/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Animals , Antineoplastic Agents/pharmacology , Calcium Channel Blockers/pharmacology , Drug Therapy, Combination , Flow Cytometry , Leukemia L5178/metabolism , Mice , Verapamil/pharmacology
6.
J Cataract Refract Surg ; 29(1): 217-9, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12551693

ABSTRACT

Three years after uneventful excimer laser photorefractive keratectomy in both eyes, a 34-year-old man sustained a perforating injury in the left eye. The severe injury, followed by endophthalmitis and retinal detachment, necessitated vitrectomy, lensectomy, and an internal tamponade with silicone oil. One month after the accident and operations, disk-shaped corneal edema corresponding to the laser treatment zone appeared. The edematous region showed a circular, ring-like epithelial thickening at the borders and central corneal epithelial erosion. The anterior stroma developed a central opacity that was separated by a clear rim from the developing silicone-oil keratopathy with the typical band shape.


Subject(s)
Corneal Diseases/etiology , Eye Diseases/surgery , Eye Injuries/complications , Photorefractive Keratectomy/adverse effects , Silicone Oils/adverse effects , Vitrectomy , Wounds, Stab/complications , Adult , Cornea/pathology , Endophthalmitis/etiology , Endophthalmitis/surgery , Eye Diseases/etiology , Eye Injuries/surgery , Humans , Lasers, Excimer , Lens, Crystalline/surgery , Male , Retinal Detachment/etiology , Retinal Detachment/surgery , Wounds, Stab/surgery
7.
Ophthalmology ; 109(5): 909-13, 2002 May.
Article in English | MEDLINE | ID: mdl-11986096

ABSTRACT

OBJECTIVE: To investigate the incidence and clinical findings of radiation retinopathy after single-fraction high-dose gamma knife radiosurgery for choroidal melanoma. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: Thirty-two patients with choroidal melanoma. METHODS: Review of charts, color fundus photographs, and fluorescein angiograms of 32 choroidal melanoma patients after radiosurgery. All patients were treated with the Leksell gamma knife in one fraction with a marginal dose between 40 and 80 Gy (median, 50 Gy) and were followed for at least 24 months (or until enucleation because of complications secondary to radiation). MAIN OUTCOME MEASURES: Any clinical feature of radiation retinopathy and neovascular glaucoma. RESULTS: During a mean follow-up of 38 months (range, 6-81 months) we found radiation retinopathy in 84% of our patients. The most common findings in these patients were intraretinal hemorrhages with an incidence of 70%, macular edema and capillary nonperfusion in 63%, and hard exudates in 52% of the patients. Less common were microaneurysms in 30% and retinal neovascularization in 22%. The time of onset of the various radiation-associated retinal findings ranged between 1 and 22 months. Forty-seven percent of all patients developed neovascular glaucoma. In our study there was no correlation between radiation dosage applied and clinical findings. CONCLUSIONS: Single-fraction high-dose Leksell gamma knife radiosurgery of choroidal melanomas with a median marginal dose of 50 Gy is highly associated with early radiation retinopathy and with neovascular glaucoma.


Subject(s)
Choroid Neoplasms/surgery , Melanoma/surgery , Radiation Injuries/etiology , Radiosurgery/adverse effects , Retina/radiation effects , Retinal Diseases/etiology , Adult , Aged , Aged, 80 and over , Female , Fluorescein Angiography , Follow-Up Studies , Glaucoma, Neovascular/epidemiology , Glaucoma, Neovascular/etiology , Humans , Incidence , Male , Middle Aged , Radiation Injuries/epidemiology , Retinal Diseases/epidemiology , Retrospective Studies
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