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)

The decrease of the level of serum prostate specific antigen (PSA) after discontinuation of estramustine phosphate (EMP) has rarely been reported. We report 2 cases in whom EMP withdrawal syndrome was encountered. Case 1 was a 68-year-old man with a complaint of paresis of lower limbs. He was diagnosed with prostate cancer with multiple bone metastases. The serum PSA level was 9,300 ng/ml. He was treated with luteinizing hormone-releasing hormone agonist (LH-RHa) and bicalutamide (BCL). Six months later, EMP was started against PSA failure. During the 3-year treatment with EMP, PSA decreased to the nadir of 0.7 ng/ml and gradually increased to 14 ng/ml. After withdrawal of EMP, PSA decreased to 0.3 ng/ml (97.9% decline) and remained at this level for 4 months. Case 2 was a 61-year-old man who visited our hospital with gross hematuria. Transurethral bladder biopsy and transrectal prostate biopsy were performed. The diagnosis was moderately differentiated adenocarcinoma of the prostate that invaded to the bladder. Computed tomography (CT) showed a lymph node metastasis. He was treated with LH-RHa and BCL. The treatment was changed to EMP after PSA failure. EMP was withdrawn when PSA was 30 ng/ml. Then PSA decreased to less than 0.2 ng/ml (99% decline) and remained at this level for 9 months. We consider that in patients with EMP-resistant progression, EMP withdrawal syndrome should be checked.
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PMID:[Estramustine phosphate withdrawal syndrome in relapsed prostate cancer: two case reports]. 1863 39

Five cases of small-cell carcinoma (SCC) of prostate were identified, at the Rhode Island Hospital and the Miriam Hospital from 1984 to 2006, with an average age of 71 years at the time of diagnosis. Three of these patients had a prior diagnosis of prostatic adenocarcinoma, with all of the five patients receiving anti-androgen treatment. The average time between the diagnosis of adenocarcinoma and of SCC in these patients was 6.7 years. The PSA levels varied greatly, with two patients possessing markedly elevated levels and the remaining patients with normal levels. Approximately 3/5 patients developed liver metastases, 2/5 patients had bone metastases, and 1/5 patients developed carcinomatous meningitis. Of the four patients who expired, the median survival time after diagnosis of SCC was 3.6 months (0.5-12 months).
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PMID:Small-cell prostate carcinoma: A retrospective analysis of five newly reported cases. 1967 63

Poly(ethylene glycol) (PEG) is the most popular polymer for protein conjugation, but its potential as carrier of low molecular weight drugs has been limited by the intrinsic low loading, owing to its chemical structure. In fact, only the two end chain groups of PEG can be modified and exploited for drug coupling. We have demonstrated that by synthesizing a dendrimer structure at the polymer end chains, it is possible to increase the drug payload and overcome this limitation. Furthermore, this approach can be improved by using heterobifunctional PEG. These polymers allow the precise linking of two different drugs, or a drug and a targeting agent, on the same polymeric chain. Heterobifunctional PEG-dendrimers have been obtained with defined chemical structures leading to their attractive use as drug delivery systems. In fact, they offer a double benefit; first, the possibility to choose the best drug/targeting agent ratio, and second, the separation of the two functions, activity and targeting, which are coupled at the opposite polymer end chains. In this study, we investigated the role of a PEG-dendrimer, H(2)N-PEG-dendrimer-(COOH)(4), as carrier for a combination of paclitaxel (PTX) and alendronate (ALN). PTX is a potent anticancer drug that is affected by severe side effects originating from both the drug itself and its solubilizing formulation, Cremophor EL. ALN is an aminobiphosphonate used for the treatment of osteoporosis and bone metastases as well as a bone-targeting moiety. The PTX-PEG-ALN conjugate was designed to exploit active targeting by the ALN molecule and passive targeting through the enhanced permeability and retention (EPR) effect. Our conjugate demonstrated a great binding affinity to the bone mineral hydroxyapatite in vitro and an IC(50) comparable to that of the free drugs combination in human adenocarcinoma of the prostate (PC3) cells. The PTX-PEG-ALN conjugate exhibited an improved pharmacokinetic profile compared with the free drugs owed to the marked increase in their half-life. In addition, PTX-PEG-ALN could be solubilized directly in physiological solutions without the need for Cremophor EL. The data presented in this manuscript encourage further investigations on the potential of PTX-PEG-ALN as treatment for cancer bone metastases.
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PMID:Dendritic poly(ethylene glycol) bearing paclitaxel and alendronate for targeting bone neoplasms. 2160 27

Prostate-specific antigen (PSA) has been used for over two decades as a serum marker for adenocarcinoma of the prostate. Although PSA screening remains an important part of disease screening and monitoring in early prostate cancer (PC), its utility in monitoring disease progression in advanced PC is undetermined. Furthermore, the role of PSA monitoring in the management of patients with PC and bone metastases appears limited. The purpose of this review is to evaluate the role of circulating tumor cells (CTCs) as potential novel biomarkers in advanced PC. We present a review of CTC testing and the clinical data supporting the prognostic potential of CTCs in this setting. We propose that combination of CTCs and PSA velocity or doubling-time assessments may offer insights into the prognosis and management of advanced PC.
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PMID:The current role of circulating tumor cells in the diagnosis and management of bone metastases in advanced prostate cancer. 2240 67

In the present study, we describe an 80-year-old patient who developed prostatic small cell carcinoma (SCC) following high-dose-rate brachytherapy (HDR-BT) for low-risk prostatic adenocarcinoma. The patient received one implant of Ir-192 and 7 fractions of 6.5 Gy within 3.5 days, for a total prescribed dose of 45.5 Gy. A total of 27 months after HDR-BT, the patient complained of difficulty in urinating. His serum prostate-specific antigen (PSA) levels were 3.2 ng/ml. Systemic examination revealed an enlargement of the prostate, urethral stenosis, pelvic lymph node swelling and multiple lung and bone lesions. His serum neuron-specific enolase (NSE) levels were elevated to 120 ng/ml. A prostate needle biopsy was performed for pathological examination. Histologically, there were tumor cells with hyperchromatic nuclei and scant cytoplasm showing a solid or trabecular growth pattern. Immunohistochemically, they were positive for AE1/AE3, CD56 and synaptophysin, and negative for PSA, PAP and CD57. These findings are consistent with SCC of the prostate. A review of the prostate needle biopsy specimen prior to HDR-BT did not reveal any tumor cells positive for chromogranin A, nor synaptophysin. The final diagnosis was SCC of the prostate with local progression, with lung, lymph node and bone metastases. Three cycles of etoposide/cisplatin (EP) were administered. A greater than 50% decrease in the serum NSE levels was observed. However, there was no objective response. Due to the deterioration of the patient's general condition, EP was discontinued. One month later, his serum NSE showed a rapid increase to 210 ng/ml with aggressive local progression and the patient succumbed to the disease 5.5 months after the start of EP therapy.
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PMID:Small cell carcinoma of the prostate after high-dose-rate brachytherapy for low-risk prostatic adenocarcinoma. 2325 93

Bone metastases in prostate cancer constitute the most frequent cause of systemic failure in treatment, which results in numerous complications and finally leads to patient's death. Pain is one of the first and most important clinical symptoms of bone metastases and can be found among more than 80% of patients. Therefore, the most analgetic effective and simultaneously the least toxic treatment is an important point of therapeutic management in this group of patients. The aim of this prospective clinical trial was a comparison of analgetic effectiveness and toxicity of monotherapy with 153Sm isotope to combined therapy (153Sm + EBRT) among patients diagnosed with multiple painful bone metastases due to CRPC (mCRPC). 177 patients with mCRPC were included into the prospective randomised clinical trial in which 89 patients were assigned to the 153Sm isotope monotherapy, while 88 patients were assigned to the combined therapy including 153Sm isotope therapy and EBRT. All patients were diagnosed (bone scan and X-ray or/and CT or/and MRI) with painful bone metastases (bone pain intensity >= 6 according to VAS classification). The following additional inclusion criteria were established: histologically confirmed adenocarcinoma of prostate, multifocal bone metastases, no prior chemotherapy or palliative radiotherapy to bone. All patients signed informed consent.The combination of the isotope therapy with EBRT was more effective analgetic treatment than isotope therapy alone. The highest pain decline was noticed in the first weeks after treatment termination. In the whole group, a total or partial analgesic effect was observed among 154 (87%) patients while among 23 (13%) patients there was a lack of analgesic effect or even pain intensification. The results of this clinical trial demonstrated that for patients with multiple mCRPC it is recommended to combine the 153Sm isotope therapy with local EBRT because of a greater analgetic effect. It is important to note that combined therapy did not intensify the toxicity of treatment.
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PMID:A prospective randomized trial: a comparison of the analgesic effect and toxicity of 153Sm radioisotope treatment in monotherapy and combined therapy including local external beam radiotherapy (EBRT) among metastatic castrate resistance prostate cancer (mCRPC) patients with painful bone metastases. 2337 4

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 62-year-old construction site manager experienced 6 weeks of back pain that was not responsive to over-the-counter nonsteroidal anti-inflammatory medications. He visited his wife's primary care physician for evaluation. He denied neurologic symptoms or worsening of pain while lying down. He smoked (30 pack-years, quit 4 years ago), and drinks 3 beers each evening and more on weekends (up to a six-pack). He has had two lower extremity fractures from falls at construction sites. At the time of the physical examination, he was 5 feet 11 inches tall and weighed 194 pounds. He was alert, oriented, and in mild distress. He had no percussion tenderness of his spine, and a neurologic examination was negative. A digital rectal examination revealed an enlarged prostate with an area of induration of the left, normal rectal tone, and guaiac-negative stool. Laboratory studies included normal blood counts, electrolytes, and renal and liver function tests (including lactic acid dehydrogenase and total protein). The prostate-specific antigen (PSA) was 114 ng/mL; he had no prior PSA test. A bone scan showed diffuse bony involvement including the T7 vertebral body and left pedicle, ribs, pelvis, and calvarium. Magnetic resonance imaging of his spine confirmed bone metastases but showed no evidence of extension into the epidural space or spinal cord compromise. A prostate biopsy revealed Gleason 4+4 adenocarcinoma of the prostate. Androgen deprivation therapy with leuprolide acetate was initiated, and the addition of a bone-targeted agent was considered.
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PMID:To treat or not to treat, that is the question: the role of bone-targeted therapy in metastatic prostate cancer. 2459 Jun 51

Adenosquamous carcinoma (ASC) and sarcomatoid carcinoma (SC) of the prostate are rare, but highly aggressive tumors. The occurrence of mixed carcinomas in the prostate is even more rarely reported. The present study reports the case of a 62-year-old male who was diagnosed with prostatic adenocarcinoma accompanied by multiple bone metastases, as shown by a needle biopsy and skeletal computed tomography scan. The patient was treated with hormonal therapy, but thereafter, specimens from a transurethral resection of the prostate (TURP) were found to be composed of three histologically distinct elements: ASC, SC and adenocarcinoma. The level of p53 was evaluated by immunohistochemistry in detail, and it was found that this was significantly increased in the TURP samples compared with the needle biopsy samples. The abnormal level of p53 was likely associated with the prognosis of the patient; the patient succumbed to prostate carcinoma two months after the confirmation of the diagnosis.
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PMID:Mixed adenocarcinoma, sarcomatoid carcinoma and adenosquamous carcinoma of the prostate: A case report. 2529 18

Brain metastasis in prostate cancer is rare and not expected at initial presentation especially when the patient is asymptomatic for the same. A 45-year-old male patient undergoing initial evaluation for newly diagnosed prostatic adenocarcinoma was referred to our department for 99mTc-MDP bone scintigraphy. As part of the study protocol, he also underwent Glu-NH-CO-NH-Lys-(Ahx)-[Ga-68(HBED-CC)] (68Ga-PSMA) PET/CT, which revealed tracer accumulation in brain lesions, apart from localization in the primary, lymph node, and bone metastases. A subsequent MR evaluation confirmed brain metastases.
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PMID:Detection of brain metastasis with 68Ga-labeled PSMA ligand PET/CT: a novel radiotracer for imaging of prostate carcinoma. 2567 61

Prostate adenocarcinoma and hepatocellular carcinoma (HCC) are common cancer types. Both may present with bone metastases, and both are known to be CK7/CK20 negative. Thus, diagnosis of less well-differentiated tumors at metastatic sites essentially relies on immunohistochemical confirmation. However, insufficient data exist on the expression status of the main 2 hepatocyte markers hepatocyte paraffin 1 (HepPar-1) and arginase-1 (Arg-1) in prostatic adenocarcinoma. We screened 557 prostate carcinoma cases for expression of these 2 markers using tissue microarrays. Sixty-four of 557 (11.5%) cases showed highly variable expression of HepPar-1 in 1% to 75% of tumor cells with a characteristically strong granular "mitochondrial" pattern. Only 13 cases (2.3%) expressed HepPar-1 in greater than 10% of the tumor cells. No correlation was seen with Gleason grade. On the other hand, 19 (3.4%) of 557 cases showed variable nonspecific cytoplasmic expression of Arg-1 distinct from the specific combined nucleocytoplasmic staining seen in normal liver and in HCC. Specifically, this Arg-1 pattern was seen only using one antibody lot and not another suggesting cross-reactivity. Only a single case showed specific nucleocytoplasmic expression of Arg-1 in the tumor cells. In conclusion, specific granular cytoplasmic staining for HepPar-1 is frequent in prostatic adenocarcinomas (11.5%) but usually focal and limited to less than 5% of tumor cells. This should not be misinterpreted as evidence of HCC, particularly in solid-pattern neoplasms. On the other hand, specific Arg-1 expression is very rare (0.18%), highlighting the value of Arg-1 in distinguishing HepPar-1-positive prostatic carcinoma from HCC at metastatic sites or in cases of liver metastasis from prostate carcinoma.
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PMID:Hepatocyte differentiation markers in adenocarcinoma of the prostate: hepatocyte paraffin 1 but not arginase-1 is specifically expressed in a subset of prostatic adenocarcinoma. 2718 83


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