Splenic cord capillary hemangioma with non-islet cell tumor hypoglycemia: a case report.

BACKGROUND: Splenic cord capillary hemangioma is a rare benign vascular lesion classified as a splenic hamartoma. On the other hand, non-islet cell tumor hypoglycemia (NICTH) is one of the rare causes of spontaneous hypoglycemia and is considered to be one of the paraneoplastic syndromes. To the best of our knowledge, this is the first reported case of a splenic cord capillary hemangioma with NICTH. CASE PRESENTATION: A 25-year-old male was referred to our hospital with hypoglycemia. Except for his low blood sugar, there were no abnormal findings from laboratory tests, which included an endocrinological examination. Enhanced computed tomography confirmed the presence of a solid mass measuring about 6 cm in the retroperitoneum, and a tumorectomy was performed. During this operation, it became clear that the tumor turned out to be a splenic parenchyma, and as a result, a total splenectomy was performed. Microscopically, we diagnosed this as a cord capillary hemangioma, and through immunohistochemistry, we found that some tumor cells were positive for insulin-like growth factor -II. Fortunately, the hypoglycemia-related symptoms disappeared after surgical resection was performed. The patient is still alive and well without evidence of local tumor recurrence 15 years after the operation. CONCLUSIONS: Splenic cord capillary hemangioma, one of the types of splenic hamartomas, is a very rare benign vascular lesion and might be associated with hypoglycemia thought to be NICTH.

Alternative splicing variant of vascular endothelial growth factor-A is a critical prognostic factor in non-small cell lung cancer.

Lung cancer is one of the most common malignant diseases in the world, and its prognosis is generally poor. Cancer and metastasis involve numerous biological steps, including angiogenesis in both the primary and metastatic sites. Although various molecules that are involved in both tumor neovascularization (angiogenesis) and invasion have been identified, little is known about how these molecules interact in cancerous microenvironments. We previously reported that the gene expressions of some factors associated with vascularization correlated with the prognosis of non-small cell lung cancer (NSCLC). In this study, we performed multivariate analysis of the mRNA levels of 10 selected genes [VEGF-A, VEGF121, VEGF165, VEGF189, S100A4, E-cadherin, Thrombospondin (TSP)-1, TSP-2, matrix metalloproteinase (MMP)-2, and MMP-9] in 130 NSCLC specimens using the real-time quantitative reverse transcription-polymerase chain reaction. Spearman's rank correlation test was used to determine the co-expression patterns. The analysis demonstrated highly significant co-expressions (P<0.0001) among the VEGF isoforms (VEGF-A, VEGF121, VEGF165, and VEGF189). We also analyzed the correlations among the prognosis, gene expressions, clinical factors (age and gender), and pathological features (histological types, TNM status, stages, lymphatic involvement, and venous involvement) using the Cox proportional hazards model. Multivariate analyses showed that only VEGF189 expression was an independent prognostic indicator (P=0.0252). The alternative splicing variant VEGF189, the cell binding isoform, plays a leading role in the progression of NSCLC.

Cancerous, but not stromal, thrombospondin-2 contributes prognosis in pulmonary adenocarcinoma.

Thrombospondin (TSP)-2 is known to be an endogenous negative regulator of vascularization in human cancer. However, it is unclear whether TSP-2 expression is related to neovascularization and prognosis in non-small cell lung cancer. In this study, we quantitatively examined the expression of TSP-2 mRNA by real-time reverse transcription-polymerase chain reaction (RT-PCR) in 102 pulmonary adenocarcinomas. All 102 carcinoma specimens expressed TSP-2 mRNA. The expression of TSP-2 mRNA in carcinoma was significantly higher than normal lung tissues (p<0.0001, Kruskal-Wallis test). Sizes of tumors were significantly correlated with TSP-2 gene expression (p=0.0179, Kruskal-Wallis test). The TSP-2 expression levels of the stage II/III pulmonary carcinomas were significantly increased as compared to those of stage I (p=0.0136, Kruskal-Wallis test). Thirty-five patients with high TSP-2 mRNA expression showed poor prognosis in survival (p=0.0139, log-rank test). We examined TSP-2 protein localizations in the pulmonary adenocarcinoma overexpressing TSP-2 mRNA. The TSP-2 localizations were categorized in two patterns: cancerous TSP-2 expression pattern (TSP-2 expression in the cancerous cells) and non-cancerous TSP-2 expression pattern (TSP-2 expression in the stromal lymphoid cells). Pulmonary adenocarcinoma patients with cancerous TSP-2 expression pattern showed good prognosis (p=0.0322; Fisher's probability exact test). Pulmonary adenocarcinoma patients with non-cancerous TSP-2 expression pattern showed poor prognosis (p=0.0220; Fisher's probability exact test). Non-cancerous TSP-2 expressions may reflect secondary reactions in the cancerous stroma. The stromal TSP-2 expression is not enough to suppress growth of pulmonary adenocarcinoma, while the cancerous TSP-2 expression directly inhibits growth of the carcinoma.

Thrombospondin 2 inhibits metastasis of human malignant melanoma through microenvironment-modification in NOD/SCID/gammaCnull (NOG) mice.

Thrombospondin (TSP) 2 interacts with matrix metalloproteinases (MMPs) and matrix serine proteases such as plasminogen activator (PA). Malignant melanoma is an aggressive human neoplasm showing aggressive metastatic features. We examined the effects of TSP2 gene introduction in the human malignant melanoma cell line A375. We established three clones transfected with human TSP2 (A375/TSP2). The in vitro invasiveness was remarkably suppressed (42-61%) in the TSP2-transfectants, while growth properties were preserved. The A375/TSP2 showed significantly decreased liver metastatic potential (liver weight: 3.88+/-0.30 g in A375/TSP2, 7.07+/-0.67 g in vector-transfectant (A375/V), p<0.01, Mann-Whitney U test) in super immuno-deficient mice (NOD/SCID/gammacnull, NOG). The PA inhibitor-1 (PAI-1) and PAI-2 mRNAs were significantly overexpressed in A375/TSP2. The increased activities of PAI-1 and PAI-2 were confirmed by reverse zymography. The vascularity of metastatic lesions was significantly decreased in A375/TSP2 (vascular density: 0.62+/-0.15% in A375/TSP2, 4.96+/-0.61% in A375/V, p<0.01, Welch test). These results suggest that TSP2 suppresses hematogenous metastasis through microenvironment-modification including PAI up-regulation and anti-vascularization in human malignant melanoma.

In vivo chemotherapeutic profile of human gallbladder small cell carcinoma.

Small cell carcinoma of the gallbladder is very rare, but shows high malignant potential with frequent metastasis. Chemotherapeutic regimens for the treatment of gallbladder small cell carcinoma have not yet been established. In this study, we examined in vivo chemosensitivity tests for the GB-04-JCK human gallbladder small cell carcinoma, which were previously established as a serial-transplantable xenograft in nude mice. We used four anticancer drugs: docetaxel, irinotecan, nedaplatine and gemcitabine. Docetaxel maximally suppressed xenograft tumor growth in mice (P<0.01), and showed complete tumor regression after chemotherapy day 35. Irinotecan and nedaplatine suppressed tumor growth without complete regression (P<0.01). Gemcitabine did not affect tumor growth significantly. This in vivo experimental study proposed chemotherapeutic regimens for human gallbladder small cell carcinoma.

Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) correlates with cisplatin resistance in human non-small cell lung cancer xenografts.

Copper-transporting P-type adenosine triphosphatase (ATP7B) is reportedly associated with platinum drug resistance in various solid carcinomas. However, the impact of ATP7B on platinum drug resistance in non-small cell lung cancer (NSCLC) remains unknown. We investigated ATP7B expression in nine human NSCLC xenografts using real-time polymerase chain reaction (PCR) and immunohistochemistry, and examined the relationship between the expression level of ATP7B and in vivo cisplatin (CDDP) sensitivity. ATP7B mRNA expression was significantly correlated with in vivo cisplatin sensitivity [coefficient of determination (R(2))=0.949, p=0.005]. ATP7B protein was detected in the nine xenografts. The ATP7B protein expression level was comparable to that of ATP7B mRNA. ATP7B mRNA and protein expression levels in the CDDP-resistant xenografts were significantly higher than those in the CDDP-sensitive xenografts (p=0.0389 and p=0.0357, respectively, Mann-Whitney U test). These results suggest that ATP7B is a CDDP-resistance marker in human NSCLC xenografts in vivo.

An Efficient reproductive method for Irs2-/- mice with C57BL/6JJcl genetic background.

Efficient reproduction using natural mating and reproduction technology [in vitro fertilization (IVF) and embryo transfer (ET)] was investigated in IRS2 deficient mice with C57BL/6JJcl genetic background (Irs2(-/-) mice) as a typical type 2 diabetes model. From the results using various combinations of Irs2(-/-) and Irs2(-/+) mice, the combination of female Irs2(-/+) x male Irs2(-/-) was found to be more efficient than other combinations. In applications of reproduction technology using IVF and ET, the combination of female Irs2(-/+) x male Irs2(-/-) involves the possibility of Irs2(-/-) production by repeats using female Irs2(-/+) mice. However, reproductive continuity using this combination is difficult because of dependence on human technique and the cost of ET. Therefore, we concluded that Irs2(-/-) mice should be produced by embryo transfer using Irs2(-/-) mice from a colony consisting of female Irs2(-/+) x male Irs2(-/-).

Thrombospondin-2 inhibits tumor cell invasion through the modulation of MMP-9 and uPA in pancreatic cancer cells.

The extracellular matrix protein thrombospondin (TSP) plays an important role in a variety of biological processes, including cell-cell and cell-matrix interactions. The biological role of TSP-2 in invasion and metastasis is poorly understood, while it is known that TSP-1 regulates a proteolytic cascade that allows tumor cells to invade and metastasize. In this study, we examined the role of TSP-2 in tumor cell invasion and its association with proteolytic proteins, matrix metalloproteinase (MMP) and the plasminogen/plasmin system, including urokinase-type plasminogen activator (uPA), in the human pancreatic cancer cell line PANC-1. PANC-1 cells expressed a low level of TSP-2, but significant levels of TSP-1. We isolated three clones of PANC-1 transformants stably overexpressing human TSP-2 (PANC-T). PANC-T highly expressed the TSP-2 gene and protein, while TSP-1 expression was not altered. In vitro invasion assays demonstrated that the invasiveness of PANC-T clones was significantly suppressed (p<0.05; Welch test). Zymography revealed that restoration of TSP-2 synthesis in the PANC-T clones significantly inhibited MMP-9 activity (p<0.05; Welch test). uPA activity in the PANC-T clones was significantly suppressed (p<0.05; Welch test). We concluded that restoration of TSP-2 can inhibit cell invasion through the down-regulation of MMP-9 and uPA activity in pancreatic cancer cell lines. Thus, TSP-2 may be a potent inhibitor of metastasis in pancreatic cancer.

Phenotypes of IRS-2 deficient mice produced by reproductive technology are stable.

We studied the impact of "IVF - ET" on the glucose tolerance test (GTT), insulin tolerance test (ITT) and adiponectin to investigate differences in the phenotypes of B6J- Irs2(-/-) mice. The B6J-Irs2(-/-) mice (KO-Nat group) were prepared by natural mating. Other mice were produced by IVF-ET used ICR strain recipients and surrogate mothers (KO-IVF group). Measurement of body weight, GTT, ITT and blood sampling were performed at the ages of 6, 14 and 24 weeks after birth. Body weights, impaired glucose tolerance, insulin resistance and plasma adiponectin concentrations did not differ for each gender between the KO-IVF and KO-Nat groups. Therefore, we concluded that phenotypes of Irs2(-/-) mice produced by reproductive technology are stable.

Increased S100A4 expression combined with decreased E-cadherin expression predicts a poor outcome of patients with pancreatic cancer.

The calcium-binding protein, S100A4, with an inverse association of E-cadherin, is known to correlate with prognosis in various cancers. In this study, we investigated the expression of the S100A4 and E-cadherin status in relation to the clinicopathological parameters of pancreatic cancer. The expression status of these two proteins was examined in 72 specimens of primary pancreatic carcinoma with immunohistochemistry. Fifty-six of 72 (78%) surgical specimens of primary pancreatic cancer were positive for S100A4 according to immunohistochemistry. Thirty-one (43%) specimens of pancreatic cancer showed positive expression of E-cadherin. The inverse association of S100A4 and E-cadherin expression was significant in the cancers (p < 0.0001). The S100A4 expression correlated significantly with the pathological T stage and poorer prognosis (p = 0.024). The 41 E-cadherin-negative cases showed poorer prognoses and a higher incidence of liver metastasis (p = 0.0344, p = 0.027). The 10 cases with S100A4-negative/E-cadherin-positive cancers showed a significantly better prognosis than the others (p < 0.05). The histological grade (p = 0.004), nodal status (p < 0.0001) and S100A4-positive status (p = 0.048) were highly significant independent prognostic predictors (p < 0.05). These results suggest that S100A4 overexpression combined with reduced E-cadherin expression play important roles in tumor progression and metastasis in pancreatic cancer. The combined examination of these two molecules is useful in evaluating the outcome of pancreatic cancer patient.

Ontogenetic characteristics of enzyme activities and plasma metabolites in C57BL/6J:Jcl mice deficient in insulin receptor substrate 2.

We have established an inbred line of mice deficient in insulin receptor substrate 2 (IRS2) on a C57BL/6J Jcl genetic background (B6J-IRS2(-/-) mice) as an animal model for typical type 2 diabetes mellitus (DM). We investigated the effect of age and sex on glucose tolerance and insulin resistance and on the activities of enzymes related to lipid metabolism in the liver and skeletal muscle of B6J-IRS2( -/-) mice. Glucose tolerance tests (GTT), insulin tolerance tests (ITT), and sampling for chemical analysis were performed at ages of 6,14, and 24 wk. GTT showed that both genders of B6J-IRs2(-/-) mice had impaired glucose tolerance at the ages of 6 and 14 wk, whereas 24-wk-old female B6J-IRs2(-/-) mice showed glucose tolerance almost comparable to that of wild-type mice; 24-wk-old male B6J-IRs2(-/-) mice still showed impaired glucose tolerance. ITT revealed that both male and female B6J-IRS2(-/-) mice remained insulin-resistant at all time points. Hepatic lipogenetic enzyme activities were higher in B6J-IRS2(-/-) mice than in wild-type mice at 6, 14 and 24 wk of age. In addition, plasma glucose, triglyceride, free fatty acid, total cholesterol, and insulin concentrations in B6J-IRS2(-/-) mice were significantly higher than those in wild-type mice at most time points; plasma triglycerides in 14-wk-old B6J-IRS2(-/-) mice were lower than those of wild-type mice. These findings suggest that young B6J-IRS2(-/-) mice are useful as type 2 DM models.

Poor outcome of patients with pulmonary adenocarcinoma showing decreased E-cadherin combined with increased S100A4 expression.

A loss or reduced expression of E-cadherin, the main cell-to-cell adhesion molecule, correlates with distant metastasis in various cancers. Recent studies have reported a close correlation between the expression of E-cadherin and that of S100A4, calcium-binding protein. In this study, we investigated the expression of E-cadherin and S100A4 status in relation to the clinicopathological parameters of pulmonary adenocarcinoma. We finely and quantitatively examined the expression of E-cadherin and S100A4 using real-time polymerase chain reaction (PCR) in a total of 92 pulmonary adenocarcinomas obtained by surgical resection. All of the pulmonary adenocarcinomas showed significant expression of E-cadherin and S100A4. Real-time PCR showed lower E-cadherin expression in 21 adenocarcinomas, while 71 adenocarcinomas expressed a higher expression of E-cadherin. Of 21 adenocarcinomas with lower-expressing E-cadherin, 12 showed a higher expression of S100A4. These 12 cases significantly showed a poorer prognosis than others (p=0.047, Kaplan-Meier, log-rank test) and significantly showed more frequent venous involvement than others (p=0.042, chi2 test). These results suggested that reduced E-cadherin expression combined with higher S100A4 expression is related to a poor prognosis through hematogenous metastasis in pulmonary adenocarcinoma.

Gallbladder small cell carcinoma Xenograft established by serial transplantation in nude mice.

The GB-04-JCK xenograft line of human gallbladder small cell carcinoma was established in nude mice by serial transplantation. The xenotransplantability has been maintained for more than 20 years. The carcinoma cells grew in a solid-sheet pattern and were found to have hyperchromatic nuclei, finely dispersed chromatin and inconspicuous nucleoli in the primary gallbladder tumor, as well as in the established xenograft GB-04-JCK The carcinoma cells also had Grimelius argyrophil granules, electron-dense neuroendocrine granules bounded by a single membrane. The xenograft line retained histological and immunohistochemical characteristics of the primary gallbladder tumor and is the first reported xenotransplantable tumor of human gallbladder small cell carcinoma.

The preserved expression of neuropilin (NRP) 1 contributes to a better prognosis in colon cancer.

Vascular endothelial growth factor A (VEGF-A) plays an essential role in tumor progression through stromal neovascularization in malignant solid tumors. Neuropilin (NRP) is considered to be the specific receptor for limited types of VEGF-A isoform, VEGF165. The clinicopathological implications of NRP are not well understood in colon cancer, while almost all colon cancers overexpressed VEGF-A. We examined the expression levels of NRP1 and NRP2 genes in 54 colon cancer cases and paired extraneoplastic tissue with quantitative real-time polymerase chain reaction. The gene expression levels of NRP1 in the tumor (0.431+/-0.583) were significantly decreased compared to those in the extraneoplastic tissue (0.754+/-0.799) (paired t-test, p=0.0208). On the other hand, the gene expression levels of NRP2 in the tumor (0.763+/-0.791) were not decreased compared to those in the extraneoplastic tissue (0.508+/-0.386) (paired t-test, p=0.0511). Twenty cases, with preserved expression of the NRP1 gene in the tumor, showed a better prognosis as compared to the 34 cases with decreased NRP1 expression (p=0.0258, log-rank test). No significant relationship was noted between NRP2 gene expression and prognosis. The results suggested that preserved NRP1 expression provides colon cancer patients with a better prognosis.

S100A4 expression with reduced E-cadherin expression predicts distant metastasis of human malignant melanoma cell lines in the NOD/SCID/gammaCnull (NOG) mouse model.

Tumor xenografts in immune-deficient mice (athymic nude mice and SCID mice) are well-established animal models for the study of human cancer. Several human melanoma cell lines were reported to metastasize in the immune-deficient mice models. However, metastatic rates were extremely low in spite of large numbers of injections of cancer cells, more than 1 x 10(6) cells/mouse. The NOD/SCID/gamma(C)(null) (NOG) mouse shows multiple immunological dysfunctions, including cytokine production capability, in addition to the functional incompetence of T, B and natural killer (NK) cells. However, the immune-deficient mice, with preserved NK cell activity, might interfere with engraftment efficiency. We examined the distant metastasis of the human melanoma cell lines (A2058, A375, G361 and HMY-1, 1 x 10(4) cells/mouse) in the 6 weeks after intravenous inoculation. All four melanoma cell lines showed metastasis in the NOG mice, while no metastatic lesions were observed in the NOD/SCID mice. Metastatic lesions were noted in the liver and lung of 6/6 (100%) mice at A2058, 8/9 (89%) at A375, 2/6 (33%) at G361 and 2/8 (25%) at HMY-1. A2058 and A375 cell lines with high metastatic potentials show increased gene expression of S100A4. Western blot assay confirmed the increased protein levels of S100A4 in the A2058 and A375 cell lines. E-cadherin gene expression was conversely inhibited in these cell lines. The increased expression of S100A4 combined with inhibited E-cadherin expression resulted in high metastatic potentials of the human melanoma cell lines in vivo.

The modifier subunit of glutamate cysteine ligase relates to cisplatin resistance in human small cell lung cancer xenografts in vivo.

Glutamate cysteine ligase (GCL) plays an important role in the intracellular detoxification of cisplatin (CDDP). GCL is composed of a modifier or light chain subunit (GCLM) and a catalytic or heavy chain subunit (GCLC). Previously, we showed that the GCL subunits enhanced CDDP-resistance in non-small cell lung cancer (NSCLC) xenografts. In small cell lung cancer (SCLC), it is unclear whether the GCL subunits are essential to CDDP-resistance. We examined the gene expression of GCLM and GCLC in four human SCLC xenografts with the real-time polymerase chain reaction (PCR). An in vivo drug sensitivity test with CDDP was performed on the SCLC xenografts. CDDP-resistance was examined as the growth ratio of the relative volume of the treated xenografts to the controls (T/C%). The expression level of GCLM gene in SCLC was significantly lower than that in NSCLC (p=0.0026, Welch's t-test). One of four SCLC xenografts showed 62% of T/C and this was evaluated as CDDP-resistance, while the other three xenografts were sensitive to CDDP in vivo (Mann-Whitney U-test, p<0.01, one-sided). The expression level of the GCLM gene was significantly correlated to T/C% (Fisher's test, p=0.0289, correlations = 0.975), while the GCLC gene expression level was not associated with T/C%. These results suggest that the overexpression of GCLM is correlated with CDDP-resistance in SCLC xenografts in vivo.

Cell binding isoforms of vascular endothelial growth factor-A (VEGF189) contribute to blood flow-distant metastasis of pulmonary adenocarcinoma.

Vascular endothelial growth factor A (VEGF-A) has two kinds of isoforms depending on cellular binding domains. VEGF189 is the largest molecule with the strongest cellular binding ability, and is thought to be most potent for vascularization in various cancers. This study aims to clear the clinicopathological characteristics of VEGF189 in the pulmonary adenocarcinoma. We finely and quantitatively examined the expression of VEGF-A isoforms (VEGF121, VEGF165 and VEGF189) by real-time polymerase chain reaction in a total of 100 pulmonary adenocarcinomas resected by surgical operation. The VEGF isoform expression status was analyzed on clinicopathological features including stromal vascularization, vascular involvement, distant metastasis, lymph nodal metastasis, postoperative relapse time and prognosis of long-term observation periods. All the pulmonary adenocarcinomas showed significant expression of VEGF-A. Twenty-two cases with the adenocarcinomas overexpressing VEGF-A significantly showed earlier postoperative relapse and poorer prognosis between 5- to 15-year periods (p = 0.0093 and p = 0.0240, Kaplan Meier, log-rank test). The expression levels of VEGF189 increased in 13% of the pulmonary adenocarcinoma. These 13 cases with increased VEGF189 expression significantly showed higher distant metastases, earlier postoperative relapse, and poorer prognosis (p = 0.0006, Fisher's test; p = 0.0016 and p = 0.0084, Kaplan Meier, log-rank test) than the other 87 cases. The 13 lung cancers with VEGF189 overexpression also showed increased vessel counts, areas (p = 0.0091 and p < 0.0001, Mann-Whitney U test) and enhanced venous involvement (p = 0.0056, Fisher's test). The cellular binding isoform VEGF189 confers pulmonary adenocarcinoma patients with poorer prognosis with distant metastasis via blood flow.

Aberrant expression of the gastric mucin MUC6 in human pulmonary adenocarcinoma xenografts.

Certain pulmonary adenocarcinomas show gastrointestinal differentiation with the expression of various mucins. The CDX homeobox gene, an intestine-specific transcription factor, is related to gastric carcinogenesis with MUC2 and MUC6 expression. The intestinal mucin MUC2 is expressed in the normal lung, while the gastric mucin MUC6 is not. Previously, we have reported that the expressions of MUC2 and MUC6 were related to a poor prognosis in small adenocarcinomas of the lung. We estimated the expressions of the mucin (MUC2 and MUC6) and CDX (CDX1 and CDX2) to examine how CDX relates to the gastrointestinal mucin production in the pulmonary adenocarcinoma. Thirty-nine human non-small cell lung cancer (NSCLC) xenografts were examined (13 adenocarcinoma, 18 squamous cell carcinoma and 8 large cell carcinoma). Significant expression of the MUC6 gene was observed in 7 out of 39 (17.9%) NSCLC xenografts. The expressions of the MUC6 genes were noted in 6 out of 13 (46.2%) adenocarcinoma xenografts, but only in 1 of 18 (0.06%) squamous cell carcinoma xenografts. The adenocarcinoma xenografts significantly showed higher expression of the MUC6 gene than squamous cell carcinoma xenografts (t-test, p=0.0343). Four adenocarcinoma-xenografts co-expressed both the MUC2 and MUC6 genes, and the residual 2 adenocarcinoma-xenografts expressed only the MUC6 gene. One MUC6 overexpressing squamous cell carcinoma focally contained an adenocarcinoma component. The expression patterns of the gastrointestinal mucins were analogous to gastric cancer. The cellular morphology of these carcinoma xenografts was of the gastric cancer type. The proteins of the MUC2 and MUC6 were immunohistochemically confirmed in the xenografts. The expression of the MUC6 gene was significantly correlated with the expressions of the CDX1 and CDX2 genes in the xenografts (Fisher's test, p<0.0001 and p=0.0005, respectively), while there was no significant association between the expression of the MUC2 and CDX genes. These results suggest that the expression of CDX molecules in the pulmonary carcinogenesis pathway relates to gastric cancerous features of aberrant MUC6 expression.

A case of epidermal cyst with pilomatrical differentiation.

A 20-year-old Japanese woman with an epidermal cyst on the back is described. Physical examination revealed a deep blue and round shaped cystic lesion measuring 10 min in diameter. A comedo-like keratotic plug also could be seen at the center. Histologically, the inner surface of the cyst was clearly separated of two types of the cells. The one was layers of epidermal keratinocytes and the other looked like a basal layer of epidermis, which immunohistochemically stained by S-100, HMB-45, cytokeratin (CK19) and Fontana-Masson staining. We diagnosed this case as epidermal cyst with pilomatrical differentiation.

An anti-K-ras ribozyme suppresses oncogene expression and cell growth of human pancreatic cancer.

Hammerhead ribozymes are effective modulators of gene expression due to their simple structure, site-specific cleavage activity and catalytic potential. The K-ras oncogene is thought to play an important role in the growth of pancreatic cancer, because an activated (mutated) ras gene is found in approximately 90% of human pancreatic cancers. In this study, we designed a hammerhead ribozyme directed against K-ras mRNA at codon 25 [K-ras Rz (25)], and investigated its efficacy in a cultured human pancreatic carcinoma cell line, MIA PaCa-2. K-ras Rz (25) significantly reduced the cellular K-ras mRNA level when introduced into the MIA PaCa-2 cells. The ribozyme suppressed cell growth. K-ras Rz (25) appears capable of reversing the malignant phenotype in human pancreatic carcinoma cells.