Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to elucidate the effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) in experimental rodent tumors. EHDP had no antitumor activity against the L1210 leukemia implanted i.p. and against sarcoma 180, Lewis lung carcinoma (3LL) and Walker 256/B carcinoma injected i.p., s.c. or i.m. respectively. EHDP did not interfere with the antitumor activity of commonly used conventional chemotherapeutic agents (adriamycin, cyclophosphamide, 5-fluorouracil, bis-chloroethylnitrosourea) in the L1210 and 3LL models. EHDP reduced proportionally to the dose the hypercalcemia and hypercalciuria due to the Walker 256/B carcinoma growth. In an effort to evaluate whether EHDP-treated osseous tissues were more refractory to tumor growth, cells from sarcoma 180 and 3LL carcinoma were implanted intratibially (i.t.). Growth of 3LL cells was not consistently affected by EHDP, whereas a modest, but significant, growth inhibition was consistently observed with sarcoma 180 injected i.t. Growth of sarcoma 180 implanted i.p. or s.c. was not reduced by this drug, thus suggesting that inhibition of i.t. sarcoma 180 was in fact related to alterations of osseous tissues by EHDP. Inoculation of Walker 256/B carcinoma intra-aortically resulted in osteolytic bone lesions in the hind limbs. EHDP inhibited the formation of bone metastasis under these conditions.
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PMID:Effects of disodium etidronate in murine tumor models. 642 94

Walker carcinoma 256 (W256) was reported to induce hypercalcemia dependent on bone metastasis and/or parathyroid hormone-related protein (PTHrP) in the rat, providing a model of the humoral hypercalcemia of malignancy. In this study, after the subcutaneous inoculation of cells of the W256/S line, which is maintained in this laboratory, into young female Wistar Imamichi rats (6 weeks old), serum calcium and phosphorus levels changed only within the control range, whereas serum alkaline phosphatase activity and urinary calcium level significantly increased and urinary phosphorus decreased during the tumor growth, resulting in hypercalciuria and hypophosphaturia. W256/S did not express PTHrP-mRNA, whereas LLC-W256 cells did express it. Serum PTHrP level was not changed in W256/S-bearing rats. Osteoporosis-like changes, bone weight loss, low contents of bone calcium and phosphorus, and a decrease in the bone mineral density (BMD), were observed in the femur 14 days after the tumor inoculation. There was a pronounced decrease in the serum 17 beta-estradiol level during the tumor growth. The reduction of BMD of femurs in W256/S-bearing rats was significantly inhibited by treatment with salmon calcitonin or 17 beta-estradiol. On the basis of these results, W256/S carcinoma-bearing rats seem to be a useful model for osteoporosis of hypoovarianism.
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PMID:Osteoporosis-like changes in Walker carcinoma 256-bearing rats, not accompanied with hypercalcemia or parathyroid hormone-related protein production. 754 Jun 9

We have shown that Walker 256/S mammary carcinoma caused osteoporosis-like changes in young female rats, accompanied by low serum estradiol and hypercalciuria without changes in the serum levels of calcium, phosphorus, and parathyroid hormone-related peptide. In this study, we investigated the cause of bone loss after Walker 256/S inoculation into female 6-week-old Wistar Imamichi rats, focusing on the sex hormone balance in the host animal. Walker 256/S-bearing rats showed characteristic osteoporosis, with a significant increase in spleen weight and a significant decrease in uterine weight by 14 days after s.c. tumor inoculation. In the in vitro bone marrow culture, mineralized nodule formation ability decreased according to the time after tumor inoculation, and tartrate-resistant acid phosphatase-positive multinucleated cell formation increased at 7 days after tumor inoculation, but it began to decrease at 14 days after tumor inoculation. This indicates that after inoculation with Walker 256/S tumor, the progenitors of osteoblasts and ostroclasts lost their balance in the bone turnover, resulting in bone resorption. On the other hand, Walker 256/S carcinoma expressed luteinizing hormone-releasing hormone (LH-RH) mRNA, and in Walker 256/S-bearing rats, the serum LH-RH level increased significantly from 3 days after tumor inoculation, whereas in the healthy control rats, this level was very low. Consequently, the serum levels of follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone were significantly lower in the tumor-bearing rats than in the healthy control rats. Because the LH-RH gene is located in the long prolactin release-inhibiting factor (PIF) gene and mRNA amplified by reverse transcription-PCR in this study contained whole LH-RH and a part of PIF, the Walker 256/S tumor is thought to express PIF. Indeed, the serum prolactin level decreased in tumor-bearing rats. The serum level of growth hormone, one of the other pituitary hormones, was not changed. Moreover, the level of an osteolytic cytokine, tumor necrosis factor alpha, increased in the serum of Walker 256/S-bearing rats, although this may be a result of the immune response of the host animal to tumor growth as well as an enlarged spleen. In conclusion, the Walker 256/S tumor lowers estrogen secretion through ectopical oversecretion of LH-RH, and then osteolytic cytokines, such as tumor necrosis factor alpha, increase in tumor-bearing rats, escape the control of estrogen, and activate osteoclasts, resulting in bone loss in a short period.
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PMID:Walker 256/S carcinosarcoma causes osteoporosis-like changes through ectopical secretion of luteinizing hormone-releasing hormone. 1009 51

Pancreatic cancer is ranked fifth among cancer-related deaths worldwide with a 5-year survival rate of less than 5%. Currently, surgery is the only effective therapy. However, most patients are diagnosed in the late stage and are not suitable for receiving curative surgery. Moreover, pancreatic cancer doesn't respond well to traditional chemotherapy and radiotherapy, leaving little effective treatment for advanced pancreatic cancer cases. 1alpha,25-dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], the biologically active form of vitamin D(3), was originally identified during studies of calcium and bone metabolism, though it is now recognized that it exerts biological effects in almost every tissue in the body. Abundant evidence has shown that 1alpha,25(OH)(2)D(3) has antiproliferative, apoptotic, pro-differentiation and antiangiogensis effects in many types of cancer cells in vivo and in vitro, including breast, prostate, and colon. Similarly, the antitumor growth effect of 1alpha,25(OH)(2)D(3) on pancreatic cells has been demonstrated. The clinical use of 1alpha,25(OH)(2)D(3) is impeded by the lethal side effects of hypercalcemia and hypercalciuria. Therefore, 1alpha,25(OH)(2)D(3) analogs, which are either equipotent or more potent than 1alpha,25(OH)(2)D(3) in inhibiting tumor cell growth but with fewer hypercalcemic and hypercalciuric side effects, have been developed for the treatment of different cancers. Recently, a pre-clinical study demonstrated that a less calcemic analog of 1alpha,25(OH)(2)D(3), 19-nor-1alpha,25(OH)(2)D(2) (Paricalcitol), is effective in inhibiting tumor growth in vitro and in vivo, via upregulation of p21 and p27 tumor suppressor genes. Studies on the anti-tumor effects of a more potent analog of Paricalcitol are underway. 1alpha,25(OH)(2)D(3) and its analogs are potentially attractive novel therapies for pancreatic cancer.
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PMID:Vitamin D for the prevention and treatment of pancreatic cancer. 1961 Jan 35