A case of breast squamous cell carcinoma following breast augmentation with liquid silicone injection after 16 years.

BACKGROUND: Breast augmentation has been linked to various complications, including cancerous tumors. The majority type of breast cancer associated with breast augmentation is adenocarcinoma. Primary squamous cell carcinoma (SCC) of the breast is extremely rare in both augmented and non-augmented women. Due to the low incidence, the possible origin and the mechanism of carcinogenesis of the breast SCC are not well understood. Here, we report a rare case of pure SCC 16 years after breast augmentation with liquid silicone injection. CASE PRESENTATION: A 51-year-old Japanese woman was suffered from prolonged breast fluid retention in her left breast. Multiple unknown foreign bodies caused difficulties to investigate the inflammatory focus with ultrasonography. After unsuccessful surgical drainage and antibiotics treatments, the long-standing fluid retention was surgically removed and pathologically investigated. SCC was found in the removed tissue, and the patient underwent a total left mastectomy followed by postoperative chemotherapy. Pathological analysis revealed multiple cystic structures with a hard shell which enclosed high viscous liquid. A qualitative analysis using a Fourier transform infrared spectroscope defined the liquid as pure silicon, which possibly caused the squamous cell carcinogenesis. CONCLUSIONS: Although liquid silicone injection is not a current option for breast augmentation, the injected silicone could result in cancerous tumor generation after years. This case revealed that unphysiological substances could lead to unexpected biological reactions, which caused difficulties in diagnosis with our routine examination. It will be required that accumulate information from more cases and develop novel diagnostic equipment and biomarkers to address these artificial substance-derived tumors.

[A case of the breast cancer metastases to skin treated with local radiotherapy was effective].

A case was a 78-year-old woman. We detected a precordial tumor by palpation in January 2007. The patient left it untreated for a while. She then came to see us as the tumor had grown enlarged. In local findings, the precordium midline showed a non-elastic tumor of 2 cm in size. Biopsy revealed a possibility of breast cancer metastases. Mammography and the breast echography did not show any anomalies. Histopathology specific immune-staining was CK7, CEA positive, ER (+), PgR (+). The diagnosis was latent breast metastasis. Radiotherapy was performed and irradiated a total dose of 66 Gy. Our judgment was cCR in the post irradiation. After 2 years from the radiotherapy, there was no recurrence or metastases confirmed until today. In a breast cancer treatment, radiotherapy will be performed for the purpose of local control. However, we report here our experience with an unusual cCR judgment of more than 1 year for reference.

Modulation of bile acid metabolism by 1alpha-hydroxyvitamin D3 administration in mice.

The vitamin D receptor (VDR) is a nuclear receptor for the active form of vitamin D(3) and mediates regulation of calcium homeostasis. Bile acids, such as lithocholic acid, have been identified as additional endogenous VDR ligands. The in vivo role of VDR in bile acid metabolism has not been elucidated. We investigated potential effects of in vivo VDR activation on bile acid metabolism by feeding mice bile acid-supplemented chow and then treating them with 1alpha-hydroxyvitamin D(3) [1alpha(OH)D(3)]. We administered 1alpha(OH)D(3) via gavage to mice fed chow supplemented with 0.4% cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), or lithocholic acid (LCA) and examined liver and plasma bile acid composition with gas chromatography-mass spectrometry analysis. 1alpha(OH)D(3) treatment reduced hepatic bile acids in mice fed CDCA- and DCA-supplemented chow but was less effective in mice fed chow supplemented with LCA or CA. 1alpha(OH)D(3) administration also decreased plasma bile acids in mice fed bile acids, such as DCA. The effect of 1alpha(OH)D(3) administration in decreasing liver bile acid composition was observed in mice under fasting conditions and was associated with increased urinary excretion and increased expression of bile acid transporters, such as renal multidrug resistance-associated protein 4. These findings indicate that pharmacological activation of VDR enhances metabolism of bile acids, especially urinary excretion. The results confirm that VDR acts a regulator of bile acid metabolism in vivo.

Enhanced transcription of pancreatic peptide YY by 1α-hydroxyvitamin D3 administration in streptozotocin-induced diabetic mice.

Peptide YY (PYY) is a peptide hormone secreted from L cells in the intestine in response to food intake that regulates appetite and gastrointestinal function. PYY is also produced in the pancreatic islets. The vitamin D receptor (VDR) is a nuclear receptor for the active form of vitamin D3 that regulates numerous physiological processes. VDR is expressed in the pancreatic islets and pharmacological VDR activation increases PYY expression in mouse peripheral islet cells. Although VDR is present in insulin-producing ß cells as well as non-ß cells, the role of ß cell VDR in Pyy transcription remains unknown. We treated mice with streptozotocin to ablate ß cells in the pancreas. Pancreatic Vdr mRNA expression was decreased in streptozotocin-induced diabetic mice. Interestingly, streptozotocin-treated mice exhibited increased basal Pyy expression and 1α-hydroxyvitamin D3 treatment further increased expression. Moreover, 1α-hydroxyvitamin D3 increased mRNA expression of pancreatic polypeptide and decreased that of neuropeptide Y in streptozotocin-induced diabetic mice but not in control mice. 1α-Hydroxyvitamin D3 slightly increased mRNA expression of insulin but transcript levels were nearly undetectable in the pancreas of streptozotocin-treated mice. Thus, VDR in non-ß islet cells is involved in Pyy expression in the mouse pancreas. The findings from this ß cell ablation study suggest a hormone transcription regulatory network composed of ß cells and non-ß cells.

Vitamin D receptor activation induces peptide YY transcription in pancreatic islets.

Peptide YY (PYY) is a peptide hormone secreted from L cells in the intestine after food intake and regulates appetite and intestinal function. PYY is also expressed in the pancreas, but the mechanisms of regulation of pancreatic PYY expression have not been elucidated. The vitamin D receptor (VDR) is a nuclear receptor for the active form of vitamin D(3) and regulates numerous physiological processes. Because VDR is expressed in the pancreas, we investigated the role of pancreatic VDR activation and found that Pyy is a VDR target gene in the mouse pancreas. Treatment of mice with 1α-hydroxyvitamin D(3) increased plasma PYY levels. VDR activation increased mRNA and protein expression of PYY in the pancreatic islets of mice and pancreatic endocrine cell lines but did not change intestinal PYY expression. 1α-Hydroxyvitamin D(3)-dependent induction of pancreatic and plasma PYY was abolished in VDR-null mice. We identified a functional vitamin D-responsive element in the mouse Pyy promoter using chromatin immunoprecipitation assay, EMSA, and luciferase promoter assay. Thus, Pyy is a tissue-specific VDR target gene. The pancreatic VDR-PYY pathway may mediate a regulatory function of vitamin D in the neuroendocrine system.

Aryl hydrocarbon receptor ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin enhances liver damage in bile duct-ligated mice.

The environmental pollutant 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) is known to cause a wide variety of toxic effects, including hepatotoxicity, by way of the aryl hydrocarbon receptor (AHR). Although inducible expression of cytochrome P450 (CYP) 1A1 and CYP1A2 is associated with liver injury caused by high-dose TCDD, the specific role of the AHR-CYP1 cascade in hepatotoxicity remains unclear. We investigated the effects of AHR activation under conditions of cholestasis. We administered oral TCDD to mice at a dose that can effectively induce Cyp1 gene expression without overt liver toxicity and then ligated their bile ducts. TCDD pretreatment enhanced bile duct ligation (BDL)-induced increases in liver and plasma bile acids, bilirubin, and aminotransferases. Histology of TCDD-pretreated BDL mice revealed massive hepatic necrosis without any increase in number of apoptotic cells. Whereas induction of AHR-target genes by TCDD was observed similarly in sham-operated as well as in BDL mice, TCDD pretreatment of BDL mice altered the expression of hepatic genes involved in bile acid synthesis and transport. Increased plasma proinflammatory cytokines, tumor necrosis factor and interleukin-1ß, in BDL mice were further elevated by TCDD pretreatment. Liver injury by TCDD plus BDL, such as increased plasma bile acids, bilirubin and aminotransferases, liver necrosis, and increased tumor necrosis factor production, was exaggerated in Cyp1a1/1a2(-/-) double knockout mice. These findings indicate that TCDD aggravates cholestatic liver damage and that the presence of CYP1A1 and CYP1A2 plays a protective role in liver damage caused by TCDD and BDL.