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PubMed2004

[Adiponecrosis subcutanea neonatorum in congenital pneumonia].

In the course of a connatal pneumonia, a 7-day-old female newborn developed symmetrical subcutaneous nodules on her back, shoulders, and upper arms. These skin lesions were accompanied by hypercalcemia. Histological examination confirmed the putative clinical diagnosis of subcutaneous fat necrosis of the newborn. We discuss the differential diagnoses, therapeutic strategies, and prognosis of this uncommon disorder of the fat tissue.

Biopsy↗

PubMed2005

Insufficient ability of omental milky spots to prevent peritoneal tumor outgrowth supports omentectomy in minimal residual disease.

BACKGROUND: The greater omentum is frequently involved in the course of gastrointestinal and ovarian tumors. Therefore, common practice in surgical treatment for especially gastric and ovarian cancer includes removal of the greater omentum. Paradoxically, many immune cells, such as macrophages that accumulate in so-called milky spots, reside within the omentum and are cytotoxic against tumor cells ex vivo. Consequently, omental macrophages might play an important role in killing tumor cells, and may hereby prevent development into local peritoneal recurrences. In the present study, we therefore evaluated the role of the omentum and the clinical relevance of omentectomy in minimal residual disease (MRD). METHODS: Tumor cell dissemination patterns on the omentum in a rat model were examined using DiI-labelled CC531s tumor cells. Additionally, intra peritoneal (i.p.) tumor load was investigated in rats that underwent omentectomy or sham laparotomy followed by i.p. injection of CC531s cells on day 21, which represented MRD. RESULTS: At 4 h post injection, tumor cells predominantly adhered on milky spots. Number of cells thereafter declined rapidly suggesting initial tumor killing functions in these specific immune aggregates. Despite initial reduction observed in milky spots, numbers of tumor cells however increased at fatty tissue stripes that border the omentum. This indicated proliferation at these locations, which corresponded to macroscopic observations of the omenta on day 21 after tumor cell injection. Omentectomy resulted in reduced intra-abdominal tumor load, which was completely attributable to the absence of the omentum, as tumor development did not differ on other sites. Even in the MRD group microscopic clusters of tumor cells located in the omentum eventually developed into macroscopic nodules. CONCLUSION: Since the ability of omental milky spots is, even in MRD, insufficient to prevent intra abdominal tumor outgrowth, omentectomy, which reduces tumor load, is recommended in surgical treatment of intra abdominal tumors that are prone to disseminate intraperitoneally.

Adenocarcinoma↗

PubMed2001

The multistep process of hepatocarcinogenesis in cirrhosis with imaging correlation.

Hepatocarcinogenesis in the cirrhotic liver has recently become a subject of intense investigation. The development of hepatocellular nodules demonstrating varying degrees of cellular and architectural atypia suggests that these nodular lesions represent a pathway of carcinogenesis in cirrhosis of different etiologies. This pathway involves processes, such as capillarization and neoangiogenesis, leading to a gradual change in blood supply from portal to arterial, as a dysplastic nodule becomes hepatocellular carcinoma. These changes in intranodular blood supply create different enhancement patterns in the two phases of liver circulation after an intravenous contrast injection on multi-phase helical CT or dynamic gadolinium-enhanced MRI. This article reviews the current concepts regarding the vascular changes occurring in dysplastic nodules in the multistep process of hepatocarcinogenesis, along with the associated imaging manifestations. Some practical issues and dilemmas regarding the follow-up and biopsy of these lesions are also discussed.

Carcinoma, Hepatocellular↗

PubMed2002

Angiomyoid proliferative lesion: an unusual stroma-rich variant of Castleman's disease of hyaline-vascular type.

The stroma-rich variant of Castleman's disease of hyaline-vascular type (CDHV) is a newly identified entity that shows overgrowth of a variety of stromal cells. Six CDHV patients showed proliferation of vasculature and actin-positive myoid cells in the expanded interfollicular (IF) area. There were three women and three men, and the median age was 29.5 years. Of the six lesions, four were located in the retroperitoneum, one in the neck, and one in the mediastinum. All patients were asymptomatic. Microscopically, the degree of widening of the IF area varied from slight overgrowth of the IF area (approximately 55% of the lymph node area) to vague nodularity and finally to the formation of prominent nodules. In the nodular lesions, lymph follicles were compressed and attenuated. In the IF area, there were numerous vessels and proliferation of spindle cells that possessed blunt nuclei. The long, slender, dendritic cytoplasms of the spindle cells were stained by alpha smooth muscle actin. The spindle cells were negative for desmin, CD34, factor VIII-related antigen, S-100, CD21, and CD68. No patient has had recurrence after simple excision. We maintain that these angiomyoid proliferative lesions in CDHV are of a hyperplastic nature. This condition encompasses proliferation of small vessels and myoid cells. Its characteristics include an asymptomatic, solitary nodule that predominantly develops in the retroperitoneum.

Actins↗

PubMed2026

Endoscopic ultrasound-guided biopsy of left and right adrenal metastases enabling pathological diagnosis and genomic profiling after nondiagnostic conventional biopsies: two case reports.

Obtaining adequate tissue for histologic diagnoses and genomic testing can be challenging in metastatic lung cancer, particularly when conventional biopsy approaches are nondiagnostic. The study reports an effective salvage strategy using endoscopic ultrasound (EUS)-guided adrenal tissue acquisition in two cases. A 66-year-old woman (case 1) developed recurrent lung adenocarcinoma with progressive metastases to the left adrenal, liver, and lungs following multiple lines of systemic therapy. A percutaneous biopsy of a suspected liver metastasis proved nondiagnostic. Subsequently, transgastric EUS-guided biopsy was performed, which confirmed metastatic adenocarcinoma originating in the lung. Oncomine-based genomic testing detected a human epidermal growth factor receptor 2 exon 20 insertion. Trastuzumab deruxtecan was subsequently introduced, resulting in disease stabilization for 6 months. A 75-year-old man (case 2) developed bilateral pulmonary nodules and a right adrenal mass detected on positron emission tomography. Bronchoscopy failed to yield diagnostic tissue. Following careful review of cross-sectional anatomy, EUS-guided biopsy of the right adrenal gland was safely performed via the duodenal bulb, confirming metastatic squamous cell carcinoma and yielding adequate tissue for genomic testing. EUS-guided adrenal biopsy, including transduodenal sampling of the right adrenal gland, may provide tissue for histopathologic and precision oncology testing, facilitating definitive diagnoses.

Adrenal metastasis↗

PubMed1992

Polyionic regulation of cartilage development: promotion of chondrogenesis in vitro by polylysine is associated with altered glycosaminoglycan biosynthesis and distribution.

The development of cartilage nodules in cultures of chick limb bud mesenchyme (Hamburger-Hamilton stages 23/24) is significantly promoted when the culture medium is supplemented with (poly-L-lysine (PL) (M(r) greater than or equal to 14K) (San Antonio and Tuan, 1986. Dev. Biol. 115: 313). Here we present findings consistent with the hypothesis that PL may promote chondrogenesis by interacting electrostatically with sulfated glycosaminoglycans (GAGs): (1) poly-L-ornithine, poly-L-histidine, poly-D,L-lysine, and lysine-containing heteropolypeptides stimulate chondrogenesis in proportion to their contents of cationic residues; (2) the effects of PL are diminished when limb mesenchyme cultures are supplemented with exogenous GAGs, including heparin, dermatan sulfate, and chondroitin sulfate; (3) in high density cultures of limb bud mesenchyme, the release of sulfated macromolecules, but not of proteins in general, into the culture medium was significantly inhibited by PL (398K M(r)) treatment, and a net increase in total GAG content of the PL-treated cultures was observed; and (4) in monolayer cultures of cells derived from other chick embryonic tissues, including liver, skeletal muscle, and calvaria, PL treatment promoted the cell layer-associated retention of sulfated GAG. These effects were not observed using the nonstimulatory, low M(r) PL (4K). Based on the above findings and those from previous studies, it is proposed that PL may promote chondrogenesis by interacting electrostatically with cartilage GAGs, thus trapping the extracellular matrix around the newly emerging cartilage nodules and thereby stabilizing their growth and differentiation.

Animals↗

PubMed1987

Cutaneous histiocytoma in a heifer.

A young Friesian heifer developed multiple skin nodules. Histologically, the tumours appeared similar to the canine cutaneous histiocytoma. Over the next few weeks, the tumours underwent regression. These findings are considered to be consistent with a case of hitherto unreported bovine cutaneous histiocytoma. The only previously reported cases have been in dogs.

Animals↗

PubMed1988

Pathological effects of carbadox in pigs with special emphasis on the adrenal.

Weaned pigs, 4-weeks-old, were divided into 6 groups of 13 animals each, which received 0, 25, 50, 100, 150 and 200 ppm (mg per kg) of carbadox medicated feed, respectively. After 5 and 10 weeks of carbadox administration, three and two pigs, respectively, of each group were necropsied. After 5 weeks treatment, gross lesions were seen in pigs receiving 50 ppm or more. The main features were retarded growth, dehydration with dry contents in the intestine, especially in the colon and findings suggestive of pica. The severity of lesions increased with higher dosages. After 10 weeks, the same changes, though much more pronounced, were observed at 100 ppm or higher dosages. After 5 weeks histological changes in the adrenals were found at 50 ppm treatment and upwards. The common feature was a hydropic appearance of the glomerular zone. In the 50 ppm group one out of three and, in the higher dosed groups, all pigs showed these changes. There was a dose-response effect. At 100 ppm or more an enlargement of the glomerular zone was observed, resulting in narrowing of the fascicular layer. The adrenal capsule was slightly thickened and contained cells with PAS-positive granules. After 10 weeks, changes were found at 25 ppm dosage and higher. In the 25 and 50 ppm group half of the pigs had hydropic changes of the glomerular zone. In the higher dosed groups there were also chronic lesions. The outer part of the glomerular zone had become fibrotic. With 150 ppm or more the hydropic changes had extended into the fascicular layer, with development of hyperplastic nodules. This led to disappearance of zonal differentiation. From 100 ppm dosage, many richly granulated PAS-positive cells were present in the thickened capsule, more numerous and more granulated than after 5 weeks treatment. From this study, it can be concluded that carbadox may induce adverse effects on the adrenal in growing pigs at therapeutic (100 to 150 ppm) and feed-additive doses (50 ppm). Even at lower doses (25 ppm), mild lesions were found. The grade of lesions was positively correlated with the duration of exposure to this growth promoter.

Adrenal Glands↗

PubMed1981

The effect of 13-cis-retinoic acid on hamster buccal pouch carcinogenesis.

In order to determine whether 13-cis-retinoic acid, an analog of vitamin A, has antitumor activity in an oral cancer model system, the following study was undertaken. Fifty-three adult hamsters were divided into four groups. Group 1 was tested with a 0.5 percent solution of 9,10-dimethyl-1,2-benzanthracene (DMBA) in heavy mineral oil, which was painted on the right buccal pouch three times per week for 12 weeks. Group 2 received DMBA plus 13-cis-retinoic acid (RA) incorporated into gelatinized beadlets and mixed with a powdered commercial diet (dosage, 300 mg per kilogram of diet). Group 3 received only RA; Group 4 received a placebo. The animals were killed at 6, 12, and 18 weeks and tissues were studied clinically and histologically in a routine manner. Results show that all groups receiving DMBA developed epidermoid carcinomas. However, there were several other changes. In the RA-treated animals, particularly those treated with DMBA, there was an ingrowth of surface epithelium with development of ductal structures in the buccal pouch. There were changes in surface epithelium, and there were dense aggregates of lymphoid tissue with development of exophytic nodules suggestive of lymphoma. Animals fed RA showed a relative weight loss. The findings suggest that there was a hypervitaminosis A state yielding prominent epithelial metaplastic changes but not affecting the progression or production of carcinoma.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1982

Experimental leprosy with Mycobacterium lepraemurium in hairless mice (Mus musculus).

Forty-three homozygous albino hairless mice (Mus musculus) were inoculated intradermally on the head, back, sides and base of the tail with suspensions of lepromatous tissue containing numerous Mycobacterium lepraemurium (Hawaiian strain). Visible nodules were noted in all mice. These lepromatous nodules enlarged slowly and often merged with each other, covering up to two thirds of the dorsum. Several mice became blind during the course of the infection. All of the mice died or were killed 68 to 287 days following inoculation. Post-mortem examinations on representative mice showed, in addition to observed cutaneous lesions, generalized systemic murine leprosy. Smears and histological sections from nodules, skin, lymph nodes, spleen, liver, kidney, heart and lung were positive for acid-fast bacilli. The cysts in the skin (which are degenerated hair follicles filled with keratin-like material and which are one of the characteristics of hairless mice) contained scattered acid-fast bacilli, but no acid-fast globi. Ten mice with hair (M. musculus) which were used as controls did not reveal noticeable cutaneous nodules; however, all developed generalized visceral leprosy similar to that of the hairless M. musculus. Thus, hairless mice (with thymus) can be looked upon as a model for studying experimental cutaneous leprosy.

Animals↗

PubMed1990

Calcifying panniculitis associated with polycystic kidney disease and chronic renal failure.

Tender erythematous nodules and plaques developed on the abdomen and legs of two women, 45 and 48 years of age, with hyperparathyroidism as a result of chronic renal failure caused by polycystic kidney disease. The histopathologic findings of these lesions were characterized by a calcifying panniculitis. Laboratory tests disclosed normal calcium levels and hyperphosphatemia with an elevated level of calcium phosphate product. Calciphylaxis appeared to be the mechanism of soft tissue calcification in these patients.

Calcinosis↗

PubMed1989

Intraperitoneal tumor growth and chemotherapy in a rat model.

Animal models are important to evaluate new treatment modalities. In the present paper a new animal model is described, in which the effects of intraperitoneal (i.p.) administration of cytostatic drugs on cancers restricted to the peritoneal cavity can be studied. The tumor cell line used is a chemically induced carcinoma (CC531), sensitive in vitro to cisplatin (cDDP), carboplatin (CBDCA), 5-fluorouracil (5-FU), doxorubicin and mitoxantrone. Three to 5 weeks after i.p. inoculation of 2 x 10(6) CC531 cells, 80% of Wag/Rij rats develop small tumor nodules on peritoneal surfaces. Both tumor size and localization at this time are comparable to the human situation, especially to cases of minimal residual disease ovarian carcinoma. The model has been used to determine the usefulness of i.p. treatment in comparison to i.v. Changing the route of administration of cDDP from i.v. to i.p. increases tumor platinum concentrations and prolongs survival. The model offers the possibility to study drug pharmacokinetics and tumor drug penetration related to i.p. drug administration.

Animals↗

PubMed1993

Structure-activity relationships of fumonisins in short-term carcinogenesis and cytotoxicity assays.

A short-term rat liver cancer initiation/promotion model was used to monitor the cancer-initiating activity of the mycotoxins fumonisin B1 (FB1), fumonisin B2 (FB2) and fumonisin B3 (FB3) as well as the N-acetyl derivatives of FB1 and FB2, and their respective hydrolysis products the aminopolyols. The induction of resistant hepatocytes, which develop into hepatocyte nodules on selection by the 2-acetylaminofluorene-partial hepatectomy promoting treatment, was taken as the endpoint for cancer initiation. When fed at a level of 1000 mg/kg diet for 21 days, only the fumonisins B were found to initiate cancer. In addition, these mycotoxins caused a marked reduction in the rat body weight during the initiating treatment. Comparative cytotoxicity studies in primary rat hepatocytes indicated that FB2 exhibited the highest cytotoxic effect followed by FB3 and FB1. In general, the fumonisin B mycotoxins exhibited a low cytotoxic effect in hepatocyte cultures, and the concentrations of FB1 and FB2 that caused a 50% (CD50) release of the total lactate dehydrogenase (LDH) were in the order of 2000 and 1000 microM, respectively. The N-acetyl derivatives also exhibited a cytotoxic effect, but were not as cytotoxic as the parent molecules at high concentrations. The respective aminopolyols exhibited a higher cytotoxicity than did the parent compounds, while tricarballylic acid (TCA) exhibited no dose-response effect despite the fact that it had a higher background cytotoxicity compared with the control. The apparent inability of the aminopolyols to act as cancer initiators could be related to a lack in absorption from the gut.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1981

Carcinogenic activity of 3-amino-1-methyl-5H-pyrido [4,3-b]indole (Trp-P-2), a pyrolysis product of tryptophan.

The carcinogenic activity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), a pyrolysis product of tryptophan, was studied in inbred strain ACI rats. Twenty rats received a diet containing 0.01% Trp-P-2 for 870 days. Nineteen rats survived for more than 400 days after the start of feeding, 1 rat developed a hemangioendothelial sarcoma of the liver, and 6 rats developed neoplastic liver nodules. These liver tumors were found only in female rats that died 666--870 days after the start of feeding. No liver tumors were found in control animals.

Animals↗

PubMed1993

Effects of carbon tetrachloride, ethanol and acetaldehyde on diethylnitrosamine-induced hepatocarcinogenesis in rats.

The modifying action of experimentally induced chronic liver injury on diethylnitrosamine (DEN) hepatocarcinogenesis was investigated using a minimal treatment protocol. A single dose of DEN (15 mg/kg b.w.) was administered as a carcinogen to 1-day-old Sprague-Dawley rats. From 3 weeks of age rats received repeated intraperitoneal injections of carbon tetrachloride (CCl4), or 10% ethanol or 5% acetaldehyde in the drinking water for 9 weeks. Combinations of CCl4 and ethanol or acetaldehyde were also tested. Morphology, immunohistochemistry for glutathione S-transferase-placental form, and incidence and quantity of preneoplastic lesions of the livers were studied. The chronic CCl4 administration produced complete or incomplete liver cirrhosis and exerted a strong promoting effect on the development of neoplastic nodules. Ethanol alone revealed no cirrhogenous or tumor-promoting effect, but enhanced both actions of CCl4. Acetaldehyde increased only the cirrhogenous effect of CCl4.

Acetaldehyde↗

PubMed1995

Effect of dietary fat on diethylnitrosamine induced hepatocarcinogenesis in Wistar rats.

In a diethylnitrosamine (DEN) induced hepatoma model, the effect of fish oil, a rich source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and ground nut oil, a rich source of oleic acid (OA) and linoleic acid (LA), was studied. Both 20% fish oil and ground nut oil inhibited DEN-induced hepatocarcinogenesis in rats. Contrary to general belief, an inverse correlation was observed between the development of neoplastic nodules and the amount of lipid peroxides formed in the high fat (20% fish oil and ground nut oil) diet groups, indicating that the higher the lipid peroxides formed, the lower the incidence of liver tumours in DEN-treated animals. Results of the analysis of liver fatty acid composition of the phospholipid fraction suggested that DEN and fish oil treatment can inhibit the activity of the delta-6 and 5-desaturases. It is concluded from the results of the present study that a 'high fat' diet and lipid peroxidation can modulate DEN-induced hepatocarcinogenesis in rats.

Animals↗

PubMed1994

Kinetics of cell labeling and thymidine replacement after continuous infusion of halogenated pyrimidines in vivo.

PURPOSE: Iododeoxyuridine (IdUrd) is a halogenated pyrimidine which has been recognized as a clinical radiosensitizer. It is generally agreed that the extent of radiosensitization correlates with the degree of thymidine substitution in DNA. Controversy exists regarding the optimal administration schedule to achieve maximum radiosensitization. To obtain more information relating to this problem, we present experiments on an in vivo human tumor xenograft continuously exposed to a fixed serum concentration of halogenated pyrimidines so as to study the kinetics of cell labeling and thymidine replacement. METHODS AND MATERIALS: Human colon tumor (HCT-116) cells were injected subcutaneously into nude mice. After 10 days, most animals (> 90%) developed measurable tumor nodules with a volume doubling time of 5 +/- 1 days. Once the tumors reached a cross-sectional area of 0.25-0.30 cm2, miniosmotic pumps were implanted to deliver a dose of 100 mg/kg/day of IdUrd by continuous infusion. After an IdUrd exposure time of 1-7 days, blood and tumor tissue were collected. RESULTS: The steady state serum IdUrd concentration was 0.95 +/- 0.1 microM, which is a clinically relevant concentration for a prolonged continuous intravenous infusion. The tumor cell potential doubling time (Tpot) was 25 +/- 2 h. The percent IdUrd thymidine replacement and the fraction of cells labeled, followed exponential saturation kinetics with a halflife of 33 +/- 9 and 27 +/- 2 h, respectively. After 5 days of exposure (congruent to 5 x Tpot), the thymidine replacement in tumor cells was 2.0 +/- 0.2% and the fraction of tumor cells labeled was 94 +/- 1%. Immunohistochemical staining of IdUrd labeled tumor tissues showed an exposure dependent gradient of cellular labeling that was initially highest in regions close to blood vessels. After 4 days of exposure at 100 mg/kg/day, there was an increase in the fraction of cells in G(0) + G1 and a decrease in the S phase population, suggesting a block between G1 and S phase. CONCLUSION: We conclude that the in vivo kinetics of IdUrd thymidine replacement and fraction of cells labeled after continuous exposure followed exponential saturation kinetics with a halflife of approximately the potential doubling time of the tumor cell population. Simple modeling suggests that some form of prolonged, or briefly interrupted, continuous infusion should be considered for clinical administration because such schedules would leave fewer cells unsensitized than shorter infusions would. Even 10% of unlabeled clonogenic cells could explain the lack of dramatic clinical successes with IdUrd or BrdUrd sensitization.

Animals↗

PubMed2005

Bisphosphonate (YM529) delays the repair of cortical bone defect after drill-hole injury by reducing terminal differentiation of osteoblasts in the mouse femur.

We evaluated the effects of YM529, a nitrogen-containing bisphosphonate, on the repair of cortical bone after drill-hole injury at the tissue-, cell- and gene-levels in the femur of mice. Eight-week-old male C57BL/6N mice were treated with an intravenous injection of 0.01, 0.05 and 0.1 mg/kg body weight (BW) of YM529, or the vehicle (VC) once a week from 8 weeks of age until sacrifice. At 10 weeks of age (day 0), a drill-hole was made in the diaphysis of bilateral femurs. Femoral specimens were obtained at days 3, 5, 7, 10, 14, 21 and 28 after surgery. Histology and histomorphometry confirmed the early woven bone formation in 7 days after injury in all four groups, but the following lamellar bone repair in the cortical tissue area delayed only in the YM529-treated groups. Since the findings were not dose-dependent, following evaluations were performed in VC and YM529 0.1 mg/kg BW dose groups. Calcein-labeled surface of regenerated bone decreased at day 21 in the YM529 group. At day 0, CFU-f number and mineralized nodule area that developed from marrow cells were significantly smaller in YM529 group than in VC group. At day 5, however, these values increased to levels similar to those in VC group. The mRNA expression levels of BMP-2, cbfa1, osterix, type I collagen, and osteocalcin in the injured bone and marrow cells at days 3 and 5 were similar in the two groups, but were higher in YM529 group at day 7 compared with that in the VC group. At day 14, the levels of these mRNAs were still high, while that of osteocalcin was significantly reduced compared to the VC group. These data indicate that the action of YM529 on bone formation is bimodal, stimulatory on the developments of osteogenic cells for the woven bone regeneration and inhibitory on the terminal differentiation of osteoblasts for the later remodeling, consequently leading to a delay in the lamellar bone healing in the cortical tissue area.

Animals↗