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An in vitro model of pancreatic carcinoma. Morphology and in vivo growth.

Pancreas rudiments from 13-day rat embryos were cultured in the presence of dimethylnitrosamine (DMN) for up to 10 weeks. Pancreas morphogenesis and differentiation occurred during the first week of culture. Acinar cell degeneration and necrosis began on the fifth day of culture and resulted in almost complete loss of acinar cells, islet cells, and fibroblasts by the end of the third week. This was associated with proliferation of cells without zymogen granules (centroacinar, ductal, or undifferentiated?). Theses cells formed glandular structures which extended to the surface of the explant. By the end of the fourth week, explants resembled ductal hyperplasia with foci of carcinoma in situ. The distribution pattern of neoplasia in 343 explants examined after 10 weeks of DMN treatment was as follows: 79% resembled ductal cell carcinoma; 9%, ductal hyperplasia; and 3%, acinar cell carcinoma. Nude mice injected with cell suspensions prepared from 10-week-old culture developed subcutaneous nodules. These nodules resembled duct cell carcinoma with desmoplastic reaction.

Animals↗

Human focal nodular hyperplasia-like lesion in the liver of a cat.

A young cat clinically displaying marked ascites had multiple nodule hyperplasia in the liver. One of the nodules sampled at exploratory laparotomy was studied histopathologically. The nodule consisted mainly of hyperplastic hepatocytes with a central stellate scarlike connective tissue. The connective tissue had thick-walled blood vessels and radiating bands of fibrous connective tissue extending peripherally, dividing the nodule into pseudolobules. The lesions resembled focal nodular hyperplasia (FNH) in man. Serial section revealed a single large artery with the splitting of the internal elastic lamina running into the central connective tissue and branching to connect with the main vessels. The arterial branchings formed a spider-like structure. From these findings, it was suggested that the nodule had developed from a hepatic response to pre-existing vascular anomalies as had been reported in human FNH.

Animals↗

[Idiopathic tumoral calcinosis. A clinical case].

A 25-year-old Chilean woman of Jewish ancestry developed subcutaneous nodules at the thighs, axillae, elbows and coccygeal areas. X rays disclosed heavily calcified lesions at these levels. The patient's father had Whipple's disease, her mother and one brother had early hip osteoarthrosis and one son had idiopathic pancreatitis. Laboratory studies ruled out hyper or hypoparathyroidism. Electromyogram showed evidence of mild myopathy and inflammatory elements were present on muscle biopsy. However, the diagnosis of polymyositis associated to calcinosis was ruled out. Skin biopsy disclosed calcifications and fat necrosis. After 20 years of follow up, an increase in calcification specially at the pelvis and periarticular regions has been observed. Etiology, differential diagnosis and treatment are discussed.

Arthrography↗

Dietary fructose enhances the development of atypical acinar cell nodules in the pancreas of rats pretreated with N-nitrosomorpholine.

Dietary influences on carcinogenesis have been shown in various tissues on the basis of epidemiological and experimental approaches. The present paper demonstrates that the oral application of fructose over long periods to rats previously treated with N-nitrosomorpholine increases the incidence of atypical acinar cell nodules (AACN) in the pancreas. Whereas an increase in AACN was statistically significant (P less than 0.005), no effect on ductule-like structures was detectable. AACN have been regarded as precursor lesions of the acinar cell carcinoma. Although the AACN observed frequently exhibited severe atypia and numerous mitotic figures, no clearcut evidence for malignancy could be detected under our experimental conditions.

Animals↗

31P-nuclear magnetic resonance analysis of interferon-induced alterations of phospholipid metabolites in interferon-sensitive and interferon-resistant Friend leukemia cell tumors in mice.

Adult DBA/2 mice were given injections s.c. with either interferon-sensitive (745) or -resistant (3Cl-8) Friend erythroleukemia cells (FLC). After tumor nodules had developed, mouse interferon-alpha/beta was injected daily into the tumor. 31P-Nuclear magnetic resonance (NMR) spectroscopy examinations were undertaken on freshly dissected tumors at different days of treatment with either interferon or control preparations. Analysis of 745 FLC tumors in untreated mice at different days of tumor growth (day 8 to 13 after tumor implantation) showed marked increases in the levels of phosphorylcholine (PCho), glycerophosphorylethanolamine (GroPEtn) and glycerophosphorylcholine (GroPCho). In contrast high levels of PCho, GroPEtn and GroPCho were already detectable in the 3Cl-8 FLC tumors on day 8, and no significant changes were observed during subsequent tumor growth. The intracellular pH value remained practically constant in both FLC tumors. Daily intratumoral administration of either partially purified (10(7) IU/mg of protein) or highly purified (10(9) IU/mg of protein) mouse interferon-alpha/beta to both cell tumors resulted in decreases in the levels of PCho, GroPEtn and GroPCho and in increases in the intracellular pH with respect to tumors treated with control preparations or left untreated. Two days of daily treatment of mice with interferon sufficed to induce these metabolic changes which preceded the appearance of necrosis in the tumors. Treatment of FLC tumors with X-rays on day 12 of tumor growth did not result in any comparable metabolic changes 2 days after irradiation. Changes in the levels of phospholipid metabolites were not observed when 745 or 3Cl-8 cells were cultivated in the presence of interferon. As interferon induced these changes in both interferon-sensitive and -resistant tumors we conclude that interferon treatment results in host-mediated effects on the biosynthesis and/or catabolism of tumor cell phospholipids.

Animals↗

Disseminated cat-scratch disease in a patient with AIDS.

A patient with AIDS developed subcutaneous nodules and associated osteolytic lesions with negative stains and cultures for bacteria, fungi and parasites. Flucloxacillin was not effective but treatment with vancomycin was associated with improvement. Six months later the patient became severely ill, with fever, malaise and multiple skin and laryngeal papules. Cat-scratch disease was diagnosed from the typical epithelioid angiomatosis seen in skin biopsies with bacterium-like structures in the Warthin-Starry stain. Retrospectively these typical structures were also seen in earlier biopsies. All lesions improved after therapy with erythromycin had been instituted.

Acquired Immunodeficiency Syndrome↗

Sarcoidal reaction to lymphoma presenting as granulomatous rosacea.

A patient with poorly differentiated lymphocytic lymphoma had rosacealike facial lesions noted at the time of diagnosis of the lymphoma. The skin lesions followed the course of exacerbations and remissions of the systemic lymphoma. A biopsy specimen showed a sarcoidal granulomatous inflammation in the skin, and later in subcutaneous nodules that developed on the face. This case is consistent with a sarcoidal tissue reaction to lymphoma, and is unique in its clinical presentation as granulomatous rosacea.

Humans↗

Intravascular death of disseminated cancer cells mediated by superoxide anion.

The release of radiolabelled Lewis lung carcinoma cells arrested in the vasculature of the major organs of mice after intravenous injection was significantly inhibited in animals treated with the oxygen radical scavenger, superoxide dismutase. There was a parallel increase in the numbers of tumor nodules which developed after injection of non-radiolabelled cells into superoxide dismutase-treated mice. The results indicate that superoxide anion plays an important role in the lethal release of arrested cancer cells, either directly since the radical is cytotoxic or possibly indirectly since its metabolites are also highly toxic. It is suggested that a major source of toxic oxygen species is the polymorphonuclear leukocyte.

Animals↗

Lymphocutaneous nocardiosis caused by Nocardia asteroides. Case report and literature review.

A 22-year-old man developed erythematous nodules and an ulcer mimicking sporotrichosis on his right hand and forearm, which was subsequently diagnosed as lymphocutaneous nocardiosis caused by Nocardia asteroides. To our knowledge, 21 cases of lymphocutaneous nocardiosis have been reported, with the majority of those cases, except for a few that remain uncertain, being due to Nocardia brasiliensis. The case reported herein, the first known definitive case caused by N asteroides (to our knowledge), showed a more chronic course and less inflammatory manifestation compared with that caused by N brasiliensis. This is probably because N brasiliensis has a stronger virulence than N asteroides.

Adult↗

Painful orbital inflammatory lesions and mastocytosis.

A 15-year-old female patient developed painful nodules in an anophthalmic socket that were exacerbated by treatment with steroids and narcotics. Although orbit biopsy showed chronic inflammation, the diagnosis of mastocytosis was confirmed with skin biopsy and urinary levels of histamine. The patient responded to excision of nodules and treatment for mastocytosis. Painful orbital lesions associated with mastocytosis have not been reported previously.

Adolescent↗

Nuclear magnetic resonance analysis of tumor necrosis factor-induced alterations of phospholipid metabolites and pH in Friend leukemia cell tumors and fibrosarcomas in mice.

The alterations induced on the pool sizes of five phospholipid metabolites, glycerol 3-phosphorycholine, glycerol 3-phosphorylethanolamine, phosphorylcholine, sn-glycerol 3-phosphate, and choline were studied by nuclear magnetic resonance (NMR) spectroscopy in murine tumors injected with recombinant murine tumor necrosis factor (TNF). Solid tumors were obtained by s.c. injection of either Friend leukemia cells (clones 3C1-8 and 745) in DBA/2 mice or murine fibrosarcoma cells (HeN4) in C3H/HeN mice. After tumor nodules had developed, TNF or bovine serum albumin was injected intratumorally. Treatment of both tumors with TNF resulted in a marked inhibition of tumor growth. 31P-NMR analyses of Friend leukemia cell tumors (and tissue extracts), 6 h after injection of TNF, showed: (a) a 1.5- to 3.5-fold decrease in the pool sizes of glycerol 3-phosphorylcholine and glycerol 3-phosphorylethanolamine; (b) a 7- to 8-fold increase of sn-glycerol 3-phosphate; (c) a 2- to 3.5-fold decrease of phosphorylcholine; (d) an alkaline shift (0.2 units) in intratumoral pH. Similar metabolic alterations occurred in TNF-treated HeN4 fibrosarcoma. 1H-NMR analyses of Friend leukemia cell tumor extracts also indicated, 6 h after tumor injection with TNF: (a) elevated choline levels (9X); (b) a 19-fold increase in the ratio [choline]/[phosporylcholine]; (c) elevated (1.4X) levels of lactic acid; and (d) a 1.6-fold decrease in the [taurine]/[glycine] ratio. The results are interpreted in the light of possible alterations in the activity of enzymes controlling the de novo biosynthesis and catabolism of phospholipids. We concluded that NMR spectroscopy can be a useful means to monitor the level of some phospholipid precursors and/or derivatives as early markers of therapeutic efficacy in intact neoplastic tissues.

Animals↗

Posttraumatic occurrence of infantile digital fibromatosis. A histologic and electron microscopic study.

We encountered a patient with infantile digital fibromatosis. The representative lesion was a firm, indurated nodule, which developed in the scar of a previous injury on the skin of the left thigh of an 11-year-old girl. Electron microscopy revealed tumor cells that were strongly reminiscent of myofibroblasts. Histopathologically, the cytoplasmic inclusion bodies in the tumor cells stained positively or negatively with hematoxylin-eosin. Electron microscopically, they were either well-defined dense bodies that often showed a doughnutlike appearance or ill-demarcated dense bodies. Spotty calcified foci were seen in the central area of the tumor mass.

Child↗

Overexpression of a novel anionic glutathione transferase in multidrug-resistant human breast cancer cells.

Adriamycin-resistant (AdrR) human breast cancer cells have been selected which exhibit cross-resistance to a wide range of anti-cancer drugs. This multidrug-resistant phenotype is associated with increases in the activities of glutathione peroxidase and glutathione transferase. The 45-fold increase in glutathione transferase activity is associated with the appearance of a new anionic isozyme in AdrR cells which is immunologically related to the anionic glutathione transferase present in human placenta. The increase in transferase and the level of drug resistance is relatively stable during passage of AdrR cells in the absence of adriamycin for over 10 months. A similar anionic glutathione transferase isozyme is also found in rat hyperplastic liver nodules, a preneoplastic state resulting from exposure to carcinogens. A rat cDNA which codes for the anionic glutathione transferase in rat hyperplastic nodules hybridizes to a 1.1-kilobase pair mRNA which is overexpressed in the AdrR MCF-7 cells. The anionic transferase has been purified from the AdrR cells and found to have characteristics which distinguish it from other anionic human glutathione transferases, including high levels of intrinsic peroxidase activity. The overexpression of a similar anionic glutathione transferase in human breast cancer cells selected for multidrug resistance and in rat hyperplastic liver nodules, which develop resistance to various hepatotoxins, suggests a possible role for this drug-conjugating enzyme in the mechanism of resistance in both of these states.

Animals↗

The relationship of terminal duct hyperplasia to mammary carcinoma in 7,12-dimethylbenz(alpha)anthracene-treated LEW/Mai rats.

The evolution of dysplasias and carcinomas in the inguinal mammary glands of LEW/Mai rats given 7,12-dimethylbenz(alpha)anthracene (DMBA) by gastric gavage was studied with the use of stained whole mounts. Two major dysplasias, hyperplastic terminal end buds (HEBs) and hyperplastic alveolar nodules (HANs), developed prior to mammary carcinomas. HEBs were present in the mammary glands of approximately 70% of the rats within 1 week following DMBA. The percentage of rats with these lesions and the incidence of HEBs in the mammary gland decreased prior to the appearance of palpable and microscopic tumors. During the time when tumors first became evident (40-80 days), the percentage of rats with HEBs (11%) paralleled the percentage of rats with mammary tumors (12%). The initial percentage of rats with HEBs ( approximately 70%) paralleled the final tumor incidence (71%) observed in DMBA-treated rats that were allowed to live until they developed tumors. The histologic features of HEBs resembled those of the carcinomas, and HEBs were present in the immediate vicinity of some of the microscopic and palpable tumors. With only one exception, the location of microscopic tumors in the mammary gland was consistent with their derivation from small terminal ducts. These data are compatible with a developmental relationship between HEBs and mammary carcinoma. HANs, on the other hand, developed relatively late (ie, 30 days) following DMBA administration and became more numerous with the passage of time. Over the period of time when mammary carcinomas first became evident, the percentage of rats with HANs (73%) was inconsistent with a developmental relationship between HANs and mammary carcinoma. This conclusion was supported by the absence of HANs in the vicinity of microscopic tumors, by the dissimilarity between the histologic features of HANs and mammary carcinomas, and by their absence from the mammary gland during the time when at least some of the mammary tumors must have arisen. The results implicate terminal duct hyperplasia in the histopathogenesis of rat mammary carcinomas.

9,10-Dimethyl-1,2-benzanthracene↗

Tumor cells carried through autotransfusion. Are these cells still malignant?

A suspension of 3 X 10(7) cells of longterm carcinoma cell lines--HLaC 78 and 79 from human laryngeal carcinoma, CaKi 1 derived from renal cell carcinoma and PC 3 from prostatic carcinoma,--was pumped with maximum pressure up to 5 times through the filters of the Bentley autotransfusion device. Following filter passage after centrifugation the untrapped cells were recovered, counted and brought in culture under appropriate conditions. As soon as monolayers were obtained 3 X 10(6) cells were transferred subcutaneously into athymic mice. The time intervals of growth in culture and of developing tumor nodules in nude mice were measured. The histological pattern of the daughter tumors in nude mice was compared with the genuine tumor. After the first filter passage 12.3% respectively 18.2% untrapped cells were found. This number dropped to 3% after the 5th passage. After the 5th passage in only 3 out of 5 experiments there were enough cells to start a culture. After the first passage cell proliferation in the culture as well as yielding tumor nodules in nude mice was markedly reduced. HLaC78 died. After the 5th passage cell growth in the culture as well as tumor growth in nude mice was reduced the more while using HLaC79. Taking CaKi 1 and PC 3 both parameters showed identical growth behaviour as compared with the original not-filter-passaged cells. The histological findings were identical with the pattern of the genuine tumors.

Animals↗

Strobiloestrus sp. larvae in Merino sheep.

Seventeen Merino sheep in the Springbokfontein region of the Orange Free State were found to harbour Strobiloestrus sp. larvae in cutaneous nodules in the flank and rump regions of their bodies. The life cycle, however, could apparently not be completed in the sheep as the larvae left the nodules without developing further. Mountain reedbuck, running with the sheep, were also infested and were a probable source of infestation for the sheep.

Animals↗