Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review focuses on the promising roles of prostate secretory protein of 94 amino acids (PSP-94) and one of its derived peptides (PCK3145) as potential therapeutic modalities for prostate cancer and its associated complications. Evaluation of these compounds was carried out in vitro and in vivo using syngeneic models of rat prostate cancer. Overproduction of parathyroid hormone-related protein (PTHrP) results in the development of hypercalcemia of malignancy in several malignancies including prostate cancer. In order to evaluate the effect of PSP-94 and PCK3145 on prostate cancer progression, the rat Dunning R3227 MatLyLu cell line transfected with full-length cDNA encoding PTHrP (MatLyLu-PTHrP) was used. As the main pathogenetic factor of hypercalcemia of malignancy, overexpression of PTHrP was aimed at mimicking the hypercalcemic nature seen in patients suffering from late-stage cancer. In vitro studies showed that PSP-94 and PCK3145 can cause a dose-dependent inhibition in the growth of MatLyLu-PTHrP cells. For in vivo studies, male Copenhagen rats were inoculated either s.c. into the right flank or directly into the left ventricle via intracardiac (i.c.) inoculation with MatLyLu-PTHrP cells. In these models, s.c. injection of MatLyLu cells results in the development of primary tumor growth, whereas i.c. inoculation routinely results in the development of experimental skeletal metastases in the lumbar vertebrae causing hind-limb paralysis. Administration of PSP-94 and PCK3145 into tumor-bearing animals resulted in a dose-dependent inhibition of primary tumor growth, and tumoral and plasma PTHrP levels, and in the reduction of plasma calcium levels. Additionally, treatment with PSP-94 or PCK3145 caused an inhibition of skeletal metastases resulting in a significant delay in the development of hind-limb paralysis. Interestingly, equimolar concentrations of PCK3145 were shown to be more effective in delaying the development of experimental skeletal metastases as compared to PSP-94. One of the possible mechanisms of action of these modalities is through the induction of apoptosis which was observed by both in-vitro and in-vivo analyses of MatLyLu-PTHrP cells and tumors. Several intracellular mechanisms can also be involved in inhibiting PTHrP production and anti-tumor effects of PSP-94 and PCK3145. Collectively, these studies warrant the continued clinical development of these agents as therapeutic agents for patients with hormone-refractory prostate cancer.
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PMID:Prostate secretory protein of 94 amino acids (PSP-94) and its peptide (PCK3145) as potential therapeutic modalities for prostate cancer. 1622 45

Hypercalcemia of malignancy carries an extremely grim prognosis. The most common mechanism underlying hypercalcemia of malignancy is production by the tumor cells of cytokines responsible for osteoclastic differentiation and, therefore, lysis of the bone adjacent to the tumor. A minority of cases are attributable to increased renal reabsorption of calcium caused by a humoral factor, termed parathyroid hormone-related peptide, which is produced by some primary tumors. These two mechanisms can be involved in conjunction, particularly in patients with breast cancer. The development of osteolytic metastases initiates a vicious cycle in which bone degradation products, especially growth factors, stimulate the growth of the tumor cells located at the bone-tumor interface. Parathyroid hormone-related peptide is produced by many malignant tumors, most notably those of the breast. In addition to its endocrine effect on the kidney, it may have a paracrine effect consisting of enhancement of osteoclastic differentiation with osteolysis of the bone adjacent to the tumor. Other factors produced by primary tumor cells, such as proteases, intercellular adhesion molecules, or bone matrix proteins, may influence the propensity for the tumor to produce bone metastases. Bisphosphonates are usually effective in inducing a remission of hypercalcemia of malignancy and in improving the clinical manifestations of osteolytic metastases. Elucidation of the factors that influence the propensity for malignancies to metastasize to bone would improve our ability to use bisphosphonates optimally as adjuncts to tumor therapy.
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PMID:Role of Parathyroid Hormone Related Peptide (PTHrP) in Hypercalcemia of Malignancy and the Development of Osteolytic Metastases. 1907 66

A 9 yr old neutered male mixed-breed dog was presented for an anal sac apocrine gland adenocarcinoma with regional nodal metastases. At presentation, ionized calcium was 1.91 mmol/L (NOVA Stat reference range, 1.1-1.3 mmol/L). Surgical excision of the primary tumor and metastatic lymph nodes was performed. Following surgery, symptomatic hypocalcemia was noted. Repeated ionized calcium measurements confirmed hypocalcemia, and hypercalcemia of malignancy panels suggested parathyroid gland suppression as the cause. The calcium normalized with parenteral calcium administration, but calcium later became elevated with tumor recurrence and an increase in the parathormone-related peptide. Disrupted calcium homeostasis is a potential complication following the treatment of long-standing humoral hypercalcemia of malignancy.
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PMID:Hypocalcemia following surgical treatment of metastatic anal sac adenocarcinoma in a dog. 2205 67

The most common cause of hypercalcemia in hospitalized patients is malignancy. Primary hyperparathyroidism most commonly causes hypercalcemia in the outpatient setting. These two account for over 90% of all cases of hypercalcemia. Hypercalcemia can be divided into PTH-mediated and PTH-independent variants. Primary hyperparathyroidism, familial hypocalciuric hypercalcemia, familial hyperparathyroidism, and secondary hyperparathyroidism are PTH mediated. The most common PTH-independent type of hypercalcemia is malignancy related. Several mechanisms lead to hypercalcemia in malignancy-direct osteolysis by metastatic disease or, more commonly, production of humoral factors by the primary tumor also known as humoral hypercalcemia of malignancy that accounts for about 80% of malignancy-related hypercalcemia. The majority of HHM is caused by tumor-produced parathyroid hormone-related protein and less frequently production of 1,25-dihydroxyvitamin D or parathyroid hormone by the tumor. We report the rare case of a patient with hypercalcemia and diagnosed primary hyperparathyroidism. The patient had persistent hypercalcemia after surgical removal of parathyroid adenoma with recorded significant decrease in PTH level. After continued investigation it was found that the patient also had elevated 1,25-dihydroxyvitamin D and further studies confirmed a large spleen mass that was later confirmed to be a lymphoma. This is a rare example of two concomitant causes of hypercalcemia requiring therapy.
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PMID:Multifactorial hypercalcemia and literature review on primary hyperparathyroidism associated with lymphoma. 2471 7