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

Parathyroid hormone-related peptide (PTHrP) is a major factor in the pathophysiology of hypercalcaemia of malignancy. Recent evidence suggests that PTHrP may play an important role in the growth and differentiation of neoplastic as well as non-neoplastic cells. PTHrP was originally detected in normal fetal, but not adult, liver. We have used immunocytochemistry to show that reactive human bile ductules expressing a neuroendocrine phenotype contain immunoreactive PTHrP. These observations raised the possibility that PTHrP immunoreactivity may be useful in the differential diagnosis of primary liver tumours and metastases of adenocarcinoma. A total of 24 primary liver tumours and 22 metastases of adenocarcinoma were studied. All cholangiocarcinomas showed immunopositivity for PTHrP and chromogranin A, while all hepatocellular carcinomas were negative for PTHrP and showed only focal and weak positivity for chromogranin A. Mixed types of primary liver tumour contained PTHrP immunoreactivity only in the areas of cholangiocellular differentiation. Moreover, all metastatic adenocarcinomas were negative for PTHrP and chromogranin A except for two out of five metastatic breast adenocarcinomas. These two patients had bone metastases and hypercalcaemia and thus did not yield differential diagnostic problems with cholangiocarcinoma. None of the patients with cholangiocarcinoma and hepatocellular carcinoma had hypercalcaemia. We conclude that PTHrP is a useful marker for primary cholangiocarcinoma, especially in the differential diagnosis of hepatocellular carcinoma and metastatic adenocarcinoma.
 ...
PMID:Parathyroid hormone-related peptide expression in primary and metastatic liver tumours. 831 35

An autopsy case of ACTH-producing thymic carcinoid with Cushing's syndrome is reported. The patient was a 63-yr-old man with multiple bone metastases from an undetermined primary site. Hyperpigmentation was observed at the terminal stage. The plasma levels of ACTH, cortisol, chromogranin A, and urinary 17-hydroxy-corticosteroids were extremely high, and ectopic ACTH-producing neuroendocrine tumor was diagnosed. In addition, plasma CRH was high. Autopsy revealed that the patient had primary thymic carcinoid with extensive metastases. Remarkable hyperplasia of the adrenal cortexes and Crooke's hyaline degeneration of the pituitary gland were consistent with Cushing's syndrome by ectopic ACTH production. There were multiple CRH-producing cells without degenerative changes in the hypothalamus. The tumor cells were immunoreactive to ACTH, CRH, and the cleavage enzyme PC2. POMC messenger ribonucleic acid and PC2 messenger ribonucleic acid were detected in the tumor cells by an in situ hybridization method. Expression of PC2 was considered to induce hyperpigmentation by producing alpha MSH. Despite hypercortisolism and ectopic production of CRH by the tumor cells, hypothalamic CRH cells were not atrophic. This case is a good example to demonstrate the correlation between CRH and the hypothalamo-pituitary-adrenal axis as well as hyperpigmentation in Cushing's syndrome.
 ...
PMID:Expression of prohormone convertase, PC2, in adrenocorticotropin-producing thymic carcinoid with elevated plasma corticotropin-releasing hormone. 855 Jul 83

In this exploratory study, our objectives were to correlate the serum and bone marrow concentrations of putative markers of prostate cancer progression in patients with advanced androgen-independent prostate cancer (AIPC), to assess the frequency and quantity of relative expression of these markers, and to correlate the expression of the markers with extent of disease (EOD) and overall survival. In a cohort of 50 patients with AIPC with bone metastases, we obtained serum and bone marrow samples and measured prostate specific antigen (PSA), serum interleukin-6 (sIL-6), bone marrow interleukin-6, serum chromogranin A (sCgA), bone marrow chromogranin A, and prostate specific membrane antigen (PSMA) by immunoassays. EOD was determined by quantifying identifiable bone lesions on radionuclide bone scans. Each variable was categorized into two groups (low and high) based on the median found in this cohort or on the cutoff based on normal limits when available. Analyses were performed in two subsets of patients with EOD either <20 or >/=20. Results showed that: (1) PSA is associated with EOD but not with outcome; (2) sIL-6 and sCgA may be intermediate markers of early progression in AIPC, because they are predictive of outcome only in patients with EOD <20; (3) elevated PSMA is associated with elevated sIL-6 but not with PSA, suggesting that PSMA may be a useful marker in AIPC; and (4) the ratio of PSA to putative markers of progression may reflect the complex clonal progression of prostate cancer. We conclude that patients with advanced AIPC exhibit one of two patterns of serologic marker expression: in some patients the disease status is reflected by PSA, and in others it is reflected by other markers. If these data are prospectively confirmed, this would help group patients with advanced AIPC into clinically relevant categories.
 ...
PMID:The pattern of serum markers in patients with androgen-independent adenocarcinoma of the prostate. 1076 15

Small cell carcinoma of the prostate (SCCP), although relatively rare, is the most aggressive variant of prostate cancer, currently with no successful treatment. It was therefore tempting to evaluate the response of this violent malignancy and its bone lesions to Pd-Bacteriopheophorbide (TOOKAD)-based photodynamic therapy (PDT), already proven by us to efficiently eradicate other aggressive non-epithelial solid tumors. TOOKAD is a novel bacteriochlorophyll-derived, second-generation photosensitizer recently, developed by us for the treatment of bulky tumors. This photosensitizer is endowed with strong light absorbance (epsilon(0) approximately 10(5) mol(-1) cm(-1)) in the near infrared region (lambda=763nm), allowing deep tissue penetration. The TOOKAD-PDT protocol targets the tumor vasculature leading to inflammation, hypoxia, necrosis and tumor eradication. The sensitizer clears rapidly from the circulation within a few hours and does not accumulate in tissues, which is compatible with the treatment of localized tumor and isolated metastases. Briefly, male CD1-nude mice were grafted with the human SCCP (WISH-PC2) in 3 relevant anatomic locations: subcutaneous (representing tumor mass), intraosseous (representing bone metastases) and orthotopically within the murine prostate microenvironment. The PDT protocol consisted of i.v. administration of TOOKAD (4 mg/kg), followed by immediate illumination (650-800 nm) from a xenon light source or a diode laser emitting at 770 nm. Controls included untreated animals or animals treated with light or TOOKAD alone. Tumor volume, human plasma chromogranin A levels, animal well being and survival were used as end points. In addition, histopathology and immunohistochemistry were used to define the tumor response. Subcutaneous tumors exhibited complete healing within 28-40 days, reaching an overall long-term cure rate of 69%, followed for 90 days after PDT. Intratibial WISH-PC2 lesions responded with complete tumor elimination in 50% of the treated mice at 70-90 days after PDT as documented histologically. The response of the orthotopic model was also analyzed histologically with similar results. The study with this model suggests that TOOKAD-based PDT can reach large tumors and is a feasible, efficient and well-tolerated approach for minimally invasive treatment of local and disseminated SCCP.
 ...
PMID:Photodynamic therapy with Pd-Bacteriopheophorbide (TOOKAD): successful in vivo treatment of human prostatic small cell carcinoma xenografts. 1264 Jun 88

To better understand the clinical and pathologic features of end-stage, androgen-independent carcinoma of the prostate (CaP), we performed rapid autopsies on 14 men who died of progressive CaP and recorded relevant clinical data. The timing of tumor progression varied widely. The median time to androgen independence was 2 years (range, 4 months to 13.6 years). The median survival after androgen independence was 1 year (range, 1 month to 3.6 years). Because osseous metastases are prevalent in progressive CaP, up to 20 bone sites were systematically sampled in each patient. Bone metastases were widespread; tumor filled the marrow in an average of 14 bone sites. Tumor histology and expression of prostate-specific antigen (PSA) and chromogranin A (CGA) were examined in all metastases and were compared with the primary tumor. Five histological patterns of metastatic tumor were observed: solid (10 patients), macroacinar (1 patient), microacinar (1 patient), clear cell (1 patient), and comedocarcinoma (1 patient). Gleason grade of the primary tumor did not predict the histological pattern of the metastases. Although >70% of tumor cells expressed PSA, the fraction of PSA-positive cells varied widely in separate metastases in some patients (standard deviation >25). Likewise, the fraction of neuroendocrine (NE) (CGA-positive) tumor cells in different metastases varied widely. For example, between 0 and 95% of tumor cells in different metastases in 1 patient had a NE phenotype. The present study highlights the heterogeneity--histologically and immunophenotypically--of metastatic CaP. Consequently, therapy directed to the phenotype of 1 metastasis may have no effect on other metastases in the same patient because of phenotypic heterogeneity.
 ...
PMID:Phenotypic heterogeneity of end-stage prostate carcinoma metastatic to bone. 1287 59

Paragangliomas are indolent tumors that arise from the chief cells of the paraganglia in the head and neck, mediastinum, and retroperitoneal regions. Less than 10% of paragangliomas metastasize. Paragangliomas are known to regress slowly and usually partially after radiation therapy, which has been attributed to the development of fibrosis within the abundant vascular elements of the tumor. Positron emission tomography (PET) scanning was used to monitor a 33-year-old woman with recurrent paraganglioma of the carotid body with lung and bone metastases before and after chemotherapy with cyclophosphamide, doxorubicin (Adriamycin), and dacarbazine. The patient derived clinical benefit from chemotherapy, with marked improvement of her systemic and respiratory symptoms, improvement of cancer-related anemia, and normalization of chromogranin A levels. A response was demonstrated on PET scan with decreased [18F] fluoro-2-deoxy-d-glucose uptake after chemotherapy, but no significant changes were detected on serial computed tomography (CT) scans. The patient has remained free of disease progression 24 months after chemotherapy completion. It is suggested that metabolic imaging with PET scans is superior to anatomical imaging with CT scans for the monitoring of patients with paragangliomas.
 ...
PMID:PET scan assessment of chemotherapy response in metastatic paraganglioma. 1466 72

Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion is rarely observed in breast carcinoma and only four cases have been previously published. We report here the case of a 50-year-old woman who presented with a history of diffuse bone pain associated with multiple hepatic, pulmonary, and bone metastases. A core needle biopsy specimen revealed an invasive ductal carcinoma in the right breast. The patient subsequently developed an ACTH-dependent paraneoplastic Cushing's syndrome and she died of arrhythmia and heart failure, despite treatment. At autopsy, immunohistochemical staining showed chromogranin A and ACTH positivity in the breast tumor and a lung metastasis. The mRNA expression of the pro-opiomelanocortin (POMC) gene was detected in tumoral cells by reverse transcriptase polymerase chain reaction (RT-PCR). This is the first case of Cushing's syndrome secondary to ectopic ACTH secretion where the presence of ACTH by immunohistochemistry and the expression of the POMC gene by RT-PCR have both been demonstrated in a breast carcinoma with metastases. The clinical history and the pathologic findings are presented with the methods and results of the molecular analysis. This case illustrates an example of ectopic ACTH syndrome in a breast carcinoma with neuroendocrine (NE) differentiation. This NE phenotype is directly related to the synthesis of ACTH by the tumoral cells. It should be kept in mind that an ectopic ACTH syndrome may be produced not only by small cell carcinoma or endocrine tumors but also by breast cancer. No relationship has been established between NE features and prognostic factors or patient outcome for this peculiar type of breast carcinoma. The demonstration of mRNA POMC in breast carcinoma with NE features suggests a depression and/or an activation of the POMC gene linked to the NE differentiation.
 ...
PMID:Pro-opiomelanocortin expression in a metastatic breast carcinoma with ectopic ACTH secretion. 1523 95

Carcinoids are neuroendocrine tumours derived from enterochromaffin cells which are widely distributed in the body and may, therefore, arise from any site. They are traditionally described as originating from the foregut, midgut and hindgut. Localisation in the gastrointestinal tract is the most frequent, among which the appendiceal involvement is often found at laparoscopy for appendicitis and the small bowel is known for the liver metastases with the production of serotonin causing the characteristic carcinoid syndrome with diarrhoea and flushes. The overall incidence of carcinoid disease has increased in the past decades, but whether this is a true increase or due to early detection or better recognition at pathology is not known. The prognosis of metastatic carcinoid tumours has improved during the last decade resulting in a 5 year survival of approximately 50% in the Netherlands. Due to a longer survival, complications such as carcinoid heart disease and new metastatic patterns like skin and bone metastases may become a more important feature in carcinoid disease. New developments are in the field of diagnostics (fine-tuning of the pathology, videocapsule endoscopy to find the primary tumour, positron emission tomography [PET] scanning) and treatment options (radiofrequency ablation, radioactive octreotide, meta-iodobenzylguanidine combinations). The new serum marker of carcinoid, chromogranin A, may play an important role in the follow-up and NT-proBNP for the detection of heart problems. Combining new diagnostic and treatment modalities in metastatic carcinoid patients may result in a better quality of life and a longer survival. The increasing number of therapeutic options and diagnostic procedures requires a multidisciplinary approach focused on tailor-made therapy based on patients' specific conditions preferably in specialised centres and in clinical studies.
 ...
PMID:Developments in diagnosis and treatment of metastatic midgut carcinoid tumors. A review. 1628 61

We report a rare case of basaloid squamous cell carcinoma of the lung in a young Japanese woman. An 18-year-old woman presented with productive cough. Chest radiogram and computed tomography (CT) revealed a tumor in the left hilum accompanied by partial atelectasis of the left upper lobe and pleural effusion. Transbronchial fine-needle aspiration cytology supported a tentative diagnosis of primary squamous-cell carcinoma of the lung. The clinical stage was T4N2M1, with multiple bone metastases. Despite a transient response to chemotherapy consisting of carboplatin and paclitaxel, the patient died because of tumor progression 2 months after the start of the chemotherapy. Necropsy established the diagnosis of basaloid squamous-cell carcinoma of the lung. Immunohistochemical studies of the necropsy specimen indicated that the tumor was positive for keratin, vimentin, and S100, and negative for chromogranin A, cytokeratin CAM5.2, and bcl-2. Besides the rarity of the disease itself, the present case seemed to have additional uniqueness in that the patient was 18 years old and female. This is the youngest patient with a case of basaloid squamous cell carcinoma of the lung ever reported.
 ...
PMID:Basaloid squamous-cell carcinoma of the lung in a young woman. 1650 33

We report a recurrent case of gastric endocrine cell cancer that showed a remarkable response to systemic chemotherapy. A 70-year-old male who underwent gastroscopy at our hospital showed a 0-IIa-like lesion, but no abnormal CT findings. He was diagnosed with gastric cancer, and underwent a proximal gastrectomy. The resected specimen showed endocrine cell cancer. The tumor was Grimelius-positive histologically and chromogranin A-and NSE-positive immunohistochemically. About 2 years after surgery, liver, lymph node, and bone metastases were detected. Systemic chemotherapy with TS-1 and CDDP was started, and the lesions progressed. Then, by approximately 1 year after CDDP and CPT-11 treatments, the recurrent lesions had diminished remarkably and were no longer seen on CT or FDG-PET.
 ...
PMID:[A recurrent endocrine cell cancer of the stomach showing almost complete remission after chemotherapy for 1 year]. 1719 57


1 2 3 Next >>