Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dolastatin-10 is a natural, cytotoxic peptide with microtubule-inhibitory and apoptotic effects. It has demonstrated in vitro and in vivo efficacy in the DU-145 human prostate cancer model. A Phase II clinical trial was designed in patients with hormone-refractory prostate cancer. Dolastatin-10 was administered at a dose of 400 microg/m2 i.v. every 3 weeks. Dose escalation to 450 microg/m2 was permitted. Toxicity evaluation was conducted every 2 weeks, and assessment of response was done at the end of every two cycles. Sixteen patients were enrolled between October 1998 to December 1999. The median age was 71 years (range, 59-79 years). Median prostate-specific antigen value was 108 ng/ml (range, 15.3-1672 ng/ml). Of the 15 eligible patients, 7 were Caucasian and 8 were African-American. Eight patients had bone-only metastases, and seven had measurable disease with or without bone metastases. A total of 56 cycles have been administered. Only 2 patients required dose adjustment because of toxicity, and in 5 patients, dose escalation was feasible to 450 microg/m2. The major toxicities observed were grade 3 and 4 neutropenia in 8 patients and grade 3 neuropathy in 1 patient. All 15 patients are evaluable for response. Three patients demonstrated stable disease; 2 of these had bone disease, and 1 had nodal metastasis. All others had disease progression. Dolastatin-10 is very well tolerated in this elderly, pretreated population but lacks significant clinical activity as a single agent.
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PMID:Phase II study of dolastatin-10 in patients with hormone-refractory metastatic prostate adenocarcinoma. 1110 33

Atypical cribriform lesions on prostate needle biopsy specimens are rare and difficult to diagnose. Of 574 high-grade prostatic intraepithelial neoplasia (PIN) lesions on needle biopsy seen at our institution over 75 months, we identified 23 consult cases in which the differential diagnosis was cribriform high-grade PIN versus infiltrating cribriform carcinoma. Prebiopsy prostate-specific antigen (PSA) averaged 6.5 ng/mL (range, 0.3 to 37.3). A positive digital rectal examination (DRE) was present in 12 of 22 (55%) patients for whom information was available. Ordinary high-grade PIN was present elsewhere in the biopsy specimens in 32% of cases. The following architectural features of cribriform glands were evaluated: number (mean, 5; range, 1 to 21); largest size (mean, 0.5 mm; range, 0.1 to 1 mm); necrosis (14%); detached cribriform fragments (18%); stromal fibrosis (18%); and bilaterality (22%). Cytologically, there was cellular maturation toward the center of the cribriform glands (45%); identifiable basal cells on hematoxylin and eosin sections (36%); marked nuclear atypia (9%); and mitoses (23%). Nucleoli were not visible in 18% of cases, small in 36%, and prominent in 45%. With a mean follow-up of 13.8 months for those without progression (25.9 months' overall follow-up), a repeat biopsy diagnosis of cancer was seen in 10 of 22 men [by report: Gleason score (Gs) 4 (n = 1); Gs 6 (n = 3); Gs 7 (n = 4); Gs 9 (n = 2); three biopsy specimens showed ductal features]. An additional two men developed bone metastases without biopsy. Overall, 12 of 22 (55%) patients had cancer on follow-up (one patient lost to follow-up). Four clinicopathologic findings predicted carcinoma on follow-up: positive DRE (p = 0.02); positive transrectal ultrasound (p = 0.02); bilateral atypical cribriform glands (p = 0.02); and detached cribriform glands (p = 0.04).
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PMID:Atypical cribriform lesions on prostate biopsy. 1117 63

A review of 50 patients treated with strontium-89 for prostate cancer bone metastases from January 1993-1997 at the Wellington Cancer Centre was undertaken to determine if there was any correlation between changes in prostate-specific antigen (PSA) following treatment and subsequent survival. Thirty cases were evaluable for PSA response. Of these, 14 had a fall in PSA following strontium-89 treatment, and their mean survival was 641 days. The remaining 16 patients did not demonstrate a post-treatment fall in PSA and their mean survival was 275 days. A difference between these two groups in the time to development of new bone symptoms following treatment was also observed. No significant correlation between pretreatment PSA and PSA response was observed. In conclusion, a PSA response following strontium-89 treatment appears to predict for improved survival in patients with bone metastases from carcinoma of the prostate. Further prospective studies are indicated.
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PMID:Strontium-89 treatment for prostate cancer bone metastases: does a prostate-specific antigen response predict for improved survival? 1125 71

We previously reported cases of advanced prostate cancer (PCa) in which serum alpha2-macroglobulin (alpha2M) levels were markedly decreased to less than approximately 50 mg/dl whereas serum prostate-specific antigen (PSA) levels were remarkably increased. These cases were not complicated with disseminated intravascular coagulation (DIC). In this study, we measured serum PSA and alpha2M in 108 patients with either benign prostatic hyperplasia (BPH) or PCa to elucidate the relationship between PSA, i.e. the serum protease derived from the prostatic tissue, and alpha2M, i.e. the protease inhibitor that was the most abundantly contained in serum. alpha2M was determined by ELISA, total PSA and PSA-alpha1-antichymotrypsin (PSA-ACT) by EIA, and free-PSA by RIA in 44 patients with untreated BPH and 64 patients with untreated PCa. The ready association of alpha2M and PSA was assessed using Western blotting to identify complexes of the two. Levels of total serum PSA correlated positively with those of PSA-ACT in PCa (r = 0.99, p < 0.001), and both levels increased with advancing stage of disease. In contrast, the serum-free PSA/total PSA ratio (free/total PSA) and alpha2M levels decreased as the disease progressed. However, only the free/total PSA ratio attained significant difference for localized cancer in stage T1,2 versus BPH (p < 0.05). In stage M1b PCa, in which serum PSA levels were very high, there was a negative correlation between the total PSA and alpha2M values (r = -0.57, p < 0.05). In addition, serum alpha2M levels tended to decrease with progression of PCa. Serum total PSA levels correlated tightly with serum PSA-ACT levels. It is suggested that PSA is usually complexed with ACT in the serum. Free/total PSA was useful for differential diagnosis between early cancer and BPH. Levels of serum alpha2M of less than 50 mg/dl in PCa patients may indicate a possibility of bone metastases.
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PMID:Progression of prostate cancer: diagnostic and prognostic utility of prostate-specific antigen, alpha2-macroglobulin, and their complexes. 1129 72

We report the clinical evolution of a prostate cancer, metastasizing to lungs and bones, recurring locally, and escaping from anti-androgen therapy. Key event of biological progression of the patient's tumor was the coincidence of allelic imbalance accumulation and of bone metastases occurrence. The recurrent tumor was established as the transplantable xenograft PAC120 in nude mice, where it grew locally. PAC120 displayed the same immunophenotype of the original tumor (positive for keratin, vimentin, prostatic acid phosphatase, and Leu-7) and expressed human HOXB9, HOXA4, HER-2/neu, and prostate-specific antigen genes, as detected by reverse transcriptase-polymerase chain reaction. It formed lung micrometastases detected by mRNA expression of human genes. Cytogenetic analysis demonstrated numerous alterations reflecting the tumor evolution. PAC120 was still hormone-dependent; its growth was strongly inhibited by the new gonadotropin-releasing hormone antagonist FE 200486 but weakly by gonadotropin-releasing hormone superagonist D-Trp(6)-luteinizing-hormone releasing hormone (decapeptyl). Tumor growth inhibition induced by anti-hormone therapy was linked to the hormone deprivation degree, more important and more stable with FE 200486 than with D-Trp(6)-luteinizing-hormone releasing hormone. Surgical castration of mice led to tumor regressions but did not prevent late recurrences. Transition to hormone-independent tumors was frequently associated with a mucoid differentiation or with a neuroendocrine-like pattern. Independent variations of mRNA expression of HER-2/neu and prostate-specific antigen were observed in hormone-independent tumors whereas HOXB9 gene expression was constant. In conclusion, PAC120 xenograft, a new model of hormone-dependent prostate cancer retained the progression potential of the original tumor, opening the opportunity to study the hormone dependence escape mechanism.
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PMID:Clinical and experimental progression of a new model of human prostate cancer and therapeutic approach. 1148 33

Patients presenting with metastatic prostatic cancer can be categorized into 3 groups. At present, most patients seen with metastases are those identified as having lymph-node disease when being assessed for curative therapy. The second group consists of patients with a high level of prostate-specific antigen, without symptoms, who are found incidentally to have asymptomatic bone metastases or metastases in soft tissue. The third group, who previously comprised about half of patients presenting with metastatic prostate cancer, are those presenting with painful metastases. There can be little doubt that most urologists will treat the second and third group of patients with hormone therapy at the outset. The question is whether the mere presence of lymph-node metastases or painless bony or soft tissue metastases justifies the side effects of long-term hormone therapy. A number of studies have shown a benefit in progression-free survival in the treatment of patients with lymph-node disease. Only 1 study has shown an advantage in overall survival. All studies of hormone therapy in asymptomatic and symptomatic metastatic disease have shown that serious complications of the disease can be avoided by offering hormonal therapy when the diagnosis is established. With the new generation of antiandrogens, differentiation therapies, and possibly alpha-reductase inhibitors, hormone therapy causes many fewer side effects than in the past and can be tolerated for longer periods of time. An aim of early hormonal therapy and its justification is a possible improvement in the quality of life of patients with metastatic prostate carcinoma, whose quantity of life cannot be lengthened.
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PMID:Early versus late androgen deprivation therapy in metastatic disease. 1150 48

PTH and ionized calcium levels were measured in 131 patients with advanced prostate cancer, all of whom had received at least first-line hormone therapy. Patients were classified into those in remission, those with stable disease, or those with progressive disease according to their prostate-specific antigen response and their clinical status. Thirty-four percent of all patients had PTH levels above the upper level of normal for controls of similar age (7.0 pmol/liter), and in 44% of these patients this was associated with a normal ionized calcium. Patients with proven bone metastases had significantly higher PTH levels than those without. (7.3 +/- 0.5 vs. 4.3 +/- 0.4 pmol/liter, P < 0.0005). There was evidence for a difference in the PTH levels between the three response groups. The PTH levels tended to be higher in patients with progressive disease. Thirty-seven of 65 patients (57%) with both progressive disease and proven bone metastases had elevated PTH levels. Mean levels of urinary deoxypyridinoline and cAMP were significantly greater in patients with high PTH than in those with a normal PTH. Treatment with oral calcium supplements in 32 patients with a high PTH seemed to have only a transient effect on elevated PTH or low ionized calcium levels. These data show that secondary hyperparathyroidism occurs frequently in patients with advanced prostate cancer, particularly in those with both progressive disease and bone metastases. The increased PTH levels are associated with an increase in bone resorption markers. These findings raise important questions about the role of PTH in progression of prostatic cancer in bone and the potential limitations of the use of bisphosphonates in patients with a raised PTH or low serum calcium.
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PMID:Hypocalcemic and normocalcemic hyperparathyroidism in patients with advanced prostatic cancer. 1193 46

Nuclear medicine techniques play an important role in (re)staging and treatment of prostate carcinoma patients. These techniques are reviewed in this paper. For many years, bone scanning has been a valuable tool for the evaluation of bone metastases. Although utilized in a more refined way since the introduction of serum prostate-specific antigen (PSA) measurement, it is still the procedure of choice in patients with higher-grade or higher-stage tumors and elevated or rising PSA levels. Labeled monoclonal antibodies have been found to have some utility in the clinic for the evaluation of disseminated malignant prostate disease and position emission tomography holds promise for the metabolic characterization of prostate cancer. Several agents are available for radionuclide therapy for bone pain palliation in patients with metastasis, improving pain with minimal side effects or discomfort to the patient. Nuclear medicine techniques in prostate carcinoma are far from obsolete. On the contrary, they are evolving and offer unique opportunities for the management of these patients. The bone scan remains useful in well-defined stages of disease, and palliative therapeutic options are evolving. At present, monoclonal antibodies and PET are not very useful in daily clinical practice.
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PMID:Nuclear medicine techniques for the diagnosis and therapy of prostate carcinoma. 1168 45

Prostate cancer is a common disease among older men. Androgen suppression by either orchiectomy or administration of luteinising hormone-releasing hormone (LHRH) analogues is the mainstay of treatment. Since the use of prostate-specific antigen (PSA) serum testing has become widespread, however, the timing of endocrine therapy has expanded considerably to include patients with limited involvement of extraprostatic sites and patients presenting an isolated elevation of PSA after radical treatments. These patients are expected to be treated for a long time, since they have a rather low risk of disease progression and there is no recommended time limit for LHRH analogue therapy. The long-term adverse effects of androgen deprivation therapy, therefore, deserve more attention than they have received in the past. Osteoporosis represents a special concern for men with prostate cancer receiving androgen deprivation therapy. The rate of bone loss in these men seems to markedly exceed that associated with menopause in women, and fractures occur more frequently than in the healthy elderly male population. Serial bone mineral density (BMD) evaluation could allow the detection of patients with prostate cancer who are at greater risk of osteoporosis and adverse skeletal events after androgen deprivation therapy, such as patients already osteopenic or osteoporotic at baseline and men with rapid bone loss during treatment. BMD evaluated during treatment could also be a potential surrogate parameter of antiosteoporotic therapeutic efficacy. Treatment of bone loss induced by androgen deprivation comprises general prevention measures, antiosteoporotic drugs and the use of alternative endocrine therapies. Optimising lifestyle and diet is important, although it cannot completely prevent bone loss. Patients with nonsevere bone disease may benefit from calcium and vitamin D supplements. Men who are osteoporotic before androgen deprivation or men becoming osteoporotic during treatment and/or experiencing adverse skeletal events may also require bisphosphonates. The effectiveness of these drugs in preventing fractures has been shown in a single randomised study involving patients with osteoporosis, but it has not yet been established in a prostatic cancer population without bone metastases given androgen deprivation therapy. Different forms of endocrine therapy such as low-dose estrogens, antiandrogens and intermittent androgen ablation are under investigation. They could offer the advantage of avoiding (or limiting) treatment-related bone loss. In our opinion, however, the data available so far are not robust enough to recommend these alternative endocrine therapies instead of standard androgen deprivation in routine clinical practice.
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PMID:Background to and management of treatment-related bone loss in prostate cancer. 1249 66

Many types of chemotherapy are now being attempted all over the world for hormone-refractory prostate cancer (HRPC) patients, and prostate-specific antigen (PSA) reduction in almost half of the treated patients has been reported. However, only a few studies have reported the response of bone metastasis. The authors report a patient with HRPC who obtained complete regression of bone metastases on super bone scan by biochemical modulation (BM), dexamethasone, and endocrine therapy.
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PMID:Complete regression of bone metastases on super bone scan, by low-dose cisplatin, UFT, diethylstilbestrol diphosphate, and dexamethasone in a patient with hormone-refractory prostate cancer. 1272 Jan 6


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