Plasma Prostaglandin E in Patients with Cancer with and Without Hypercalcemia

Robertson, R. P.; Baylink, D J; Sa, Metz; Kb, Cummings

doi:10.1210/jcem-43-6-1330

Cited by 71 publications

(9 citation statements)

References 16 publications

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“…Hypercalcemia is attributed to the production by the tumor of a humoral substance that induces resorption of calcium from bone [33, 34,441. Rapid decline of serum calcium levels following tumor removal and the recurrence of hypercalcemia with tumor regrowth in man [3,41,43], in mice with fibrosarcoma [48], and in rabbits with VX2 carcinoma [49]. Osteoclast-activating factor has been identified in the medium from cultured myeloma and lymphosarcoma cells obtained from people with hypercalcemia [30].…”

Section: Discussionmentioning

confidence: 99%

Hypercalcemia Associated with an Adenocarcinoma Derived from the Apocrine Glands of the Anal Sac

et al. 1981

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Abstract. Clinical, gross. and light microscopic findings are described for 36 dogs, 33 females and three males. with adenocarcinomas arising from the apocrine glands of the anal sac. All tumors had light microscopic features of malignancy and 22 of 23 metastasized to iliac and lumbar lymph nodes. Nine dogs had disseminated metastases, but bone metastases were found in only one dog. Differentiated neoplasms formed secretory acini and tubules lined by tall columnar or cuboidal epithelium. Most neoplasms were histologically bimorphic. with glandular areas and solid nests. Parathyroid glands were atrophic. Hypercalcemia (mean = 16.1 mg/dl) was present in 20 of 22 dogs (90%) and hypophosphatemia (mean = 3.2 mg/dl) in 12 of 17 (7 1%). Remission of hypercalcemia by tumor ablation and recurrence of hypercalcemia with tumor regrowth suggested that the tumor produced a substance that caused hypercalcemia. This unique clinicopathologic syndrome is characterized by hypercalcemia in old. predominantly female, dogs with an adenocarcinoma arising from the apocrine glands of the anal sac.Neoplasms occur frequently in the perineum of the dog, with adenomas derived from the circumanal gland the most common [13,32,50]. Other glands in the perineum that may undergo neoplastic transformation include dermal sebaceous and apocrine glands, merocrine anal glands. and the apocrine glands of the anal sac [ 1,8,12,24,25, 27, 281. We describe a tumor that originated from the apocrine glands of the anal sac. In the most complete description of this unique syndrome, only females were reported to have developed this neoplasm, the tumors were malignant, and all dogs had hypercalcemia [40].A syndrome of hypercalcemia associated with malignancy has been seen in dogs [23, 34,401, mice [48], rabbits [49], rats [39]. and infrequently in the horse [26] and cat [6]. Lymphosarcoma [34] is the tumor most frequently associated with hypercalcemia in dogs, although there are isolated reports implicating other neoplasms [ 18, 23, 3 I, 541. Malignant neoplasms with metastasis to bone are the most common cause of hypercalcemia in hospitalized people [29, 531. Many hypercalcemic people, however, have neoplasms without evidence of osteolysis due to bone metastases 454

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Section: Discussionmentioning

confidence: 99%

Hypercalcemia Associated with an Adenocarcinoma Derived from the Apocrine Glands of the Anal Sac

et al. 1981

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“…Thus, indomethacin has been shown both to decrease plasma or urinary levels of PGs and to restore normal blood calcium levels both in patients with solid tumours and hypercalcemia (Seyberth et al, 1975;Robertson et al, 1976) and in hypercalcaemic mice bearing a prostaglandin-producing fibrosarcoma (Tashjian et al, 1973). Immunosuppressive mouse tumours treated in vivo or in vitro with non-steroidal anti-inflammatory drugs lost their capacity to suppress antibody production (Plescia et al, 1975;Grinwich & Plescia, 1977).…”

Section: Methodsmentioning

confidence: 99%

Elevated levels of prostaglandin E2 in Yoshida hepatoma and the inhibition of tumour growth by non-steroidal anti-inflammatory drugs

Trevisani¹,

Ferretti²,

Capuzzo³

et al. 1980

Br J Cancer

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Summary.-Prostaglandin (PG) E2 biosynthesis in Yoshida hepatoma (AH 130) was evaluated by radioimmunoassay. When hepatoma cells were incubated in vitro, the levels of PGE2 in the medium were similar to those found in hepatocytes for the first 2 h; this was followed by a rapid increase in PGE2 formation, and the 6h incubation levels were 4-fold higher than in hepatocytes.Addition of sodium arachidonate markedly and dose-dependently stimulated PGE2 synthesis; the increase was largely prevented by the addition of indomethacin (1 um) or L 8027, a prostaglandin synthetase inhibitor.Experiments in vivo indicated that indomethacin treatment of tumour-bearing rats significantly reduced the tumour mass. When rats were injected with PGE2 after receiving the drug, the number of tumour cells was very similar to that of untreated animals. This, as well as the inhibition of tumour growth by acetylsalicylic acid, strongly suggests that the inhibition of PG biosynthesis by antiinflammatory drugs and the inhibition of tumour proliferation may be closely associated events. It was also found that injections of indomethacin very significantly prolonged survival of hepatoma-bearing rats. Since PGE2 does not appear to affect the cyclic AMP levels of hepatoma cells, it is possible that hepatoma may use PGE2 to subvert the immune system. This could help to explain the effectiveness of anti-inflammatory drugs in the control of tumour growth.

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“…The nature of the factor or factors responsible for this humorally mediated hypercalcemia remains elusive. Although vitamin D metabolites, prostaglandins of the E series, and parathyroid hormone (PTH) have in the past been suggested as causative agents (1)(2)(3)(4)(5)(6), the available evidence suggests that these agents can account for at best a minority of instances of HHM (1,2,(7)(8)(9). Thus, an as yet unidentified humoral substance appears to be'responsible for the majority of instances of this syndrome (10).…”

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confidence: 99%

Identification of adenylate cyclase-stimulating activity and cytochemical glucose-6-phosphate dehydrogenase-stimulating activity in extracts of tumors from patients with humoral hypercalcemia of malignancy.

Stewart¹,

Insogna²,

Goltzman³

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

158

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Humoral hypercalcemia of malignancy (HHM) most commonly results from secretion by tumors of an unidentified circulating calcemic factor that appears in clinical studies to stimulate both a parathyroid hormone (PTH)-sensitive proximal tubular adenylate cyclase and a distinct PTH-sensitive renal tubular glucose-6-phosphate dehydrogenase complex. In the present study, 8 M urea extracts of tumors from patients with HHM.have been shown to contain both in vitro adenylate cyclase-stimulating activity and glucose-6-phosphate dehydrogenase-stimulating activity as detected in a sensitive cytochemical bioassay. Both the adenylate cyclase-stimulating activity and cytochemical bioactivity are due to specific binding of a substance in the tumor extracts to renal PTH receptors, as demonstrated by competitive inhibition studies using the bovine PTH fragment analogue [Nle8"8, Tyr4]bPTH-(3-34) amides Preincubation with an antiserum to PTH results in no loss of activity in the tumor extract, and the activity appears both on gel filtration and ultrafiltration to be far larger than PTH (estimated Mr 70,000). These studies demonstrate that extracts of tumors from patients with HHM contain a substance that binids to the PTH receptors in the nephron responsible for activation of both the PTH-sensitive glucose-6-phosphate dehydrogenase and the PTH-sensitive adenylate cyclase. This substance is chromatographically and immunologically distinct from PTH. Its role in the genesis of HHM requires further study.Humoral hypercalcemia of malignancy (HHM) results from the secretion by tumors remote from bone of a circulating, calcemic factor (or factors) that stimulates bone resorption (1, 2). The nature of the factor or factors responsible for this humorally mediated hypercalcemia remains elusive. Although vitamin D metabolites, prostaglandins of the E series, and parathyroid hormone (PTH) have in the past been suggested as causative agents (1-6), the available evidence suggests that these agents can account for at best a minority of instances of HHM (1, 2, 7-9). Thus, an as yet unidentified humoral substance appears to be'responsible for the majority of instances of this syndrome (10).Of the calcemic hormones listed above, the humoral factor responsible for HHM most closely resembles PTH. Both patients with HHM and those with primary hyperparathyroidism, the prototype of humorally mediated hypercalcemia, display (i) increased osteoclastic activity in bone (11), (ii) increased nephrogenous cAMP excretion (2, 12, 13), and (iii) increased plasma cytochemical bioactivity in a PTH-sensitive cytochemical bioassay (14). However, there are also a number ofdistinctive points of pathophysiological difference between these two humoral syndromes, in that, unlike primary hyperparathroidism, HHM is associated with: (i) markedly increased fractional calcium-excretion (2, 3), (ii) strikingly decreased plasma concentrations of 1,25-dihydroxyvitamin. D (2), (iii) decreased to absent osteoblastic activity in bone (11), (iv) low to undetectable circulatin...

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Plasma Prostaglandin E in Patients with Cancer with and Without Hypercalcemia

Cited by 71 publications

References 16 publications

Hypercalcemia Associated with an Adenocarcinoma Derived from the Apocrine Glands of the Anal Sac

Hypercalcemia Associated with an Adenocarcinoma Derived from the Apocrine Glands of the Anal Sac

Elevated levels of prostaglandin E2 in Yoshida hepatoma and the inhibition of tumour growth by non-steroidal anti-inflammatory drugs

Identification of adenylate cyclase-stimulating activity and cytochemical glucose-6-phosphate dehydrogenase-stimulating activity in extracts of tumors from patients with humoral hypercalcemia of malignancy.

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