Expression of phosphatase and tensin homolog and programmed cell death ligand 1 in adenosquamous carcinoma of the lung.

BACKGROUND: Lung adenosquamous carcinoma (ASC) is a rare variant of non-small cell lung cancer (NSCLC) with poor prognosis. Certain biological differences may exist between these tumors and other common histological types of NSCLC, including adenocarcinoma (ADC) and squamous cell carcinoma (SCC). The phosphoinositide 3-kinase (PI3K) pathway, which links oncogenes and multiple receptor classes to essential cellular functions, is activated by phosphatase and tensin homolog (PTEN) loss. The PTEN loss has been suggested to induce programmed cell death ligand 1 (PD-L1) expression in various cancer types. OBJECTIVE: Here, we sought to determine the relationships between the expression of PTEN and PD-L1 in each component of ASC with ADC and SCC, and clinical parameters. MATERIAL AND METHODS: Tissue microarrays of 148 cases of surgically resected lung ADC and 102 cases of SCC, as well as full sections from 28 ASC cases, were analyzed immunohistochemically for the expression of PTEN and PD-L1. RESULTS: PD-L1 expression was similar between the adenocarcinoma component of ASC vs. lung ADC and between the squamous component of ASC vs. lung SCC. PTEN loss was higher in lung ADC than in the adenocarcinoma component of ASC and significantly higher in lung SCC than in the squamous component of ASC. PD-L1 expression was higher in the squamous component than in the glandular component of the 28 ASC cases, but PTEN loss was similar. Overall, PTEN loss was higher in lung SCC than in lung ADC and both components of ASC. In lung SCC and glandular portions of ASC, PD-L1 expression levels were significantly associated with those of PTEN. The loss of PTEN correlated with smoking status in patients with lung ADC. CONCLUSIONS: Our results implied that both squamous and glandular components of ASC may share the same oncogenic driver pathway for carcinogenesis. However, the squamous cell components of ASC likely escape the immune surveillance better than the glandular components due to higher PD-L1 expression.

Maspin mRNA expression in sentinel lymph nodes predicts non-SLN metastasis in breast cancer patients with SLN metastasis.

AIMS: Maspin is known to be a tumour suppressor protein, but its prognostic significance in breast cancer patients is controversial. There is no report focusing on maspin expression in metastatic carcinoma of sentinel lymph nodes (SLNs); we thus investigated maspin mRNA expression in SLNs using the remaining specimens after the one-step nucleic acid amplification (OSNA) assay. METHODS AND RESULTS: Ninety-three breast cancer patients with SLNs metastasis detected by the OSNA assay were enrolled. All patients experienced additional axillary lymph nodes (LNs) dissection and all dissected LNs were examined histopathologically. Maspin mRNA expression in SLNs was detected in 49.5% (46 of 93) and was correlated significantly with the presence of non-SLN metastasis (P < 0.0001) and ≥4 LN metastases (P = 0.029). In a multivariate logistic analysis, maspin mRNA expression in SLNs (P = 0.0015) had the most significant effect on predicting non-SLN metastasis, followed by pathological tumour size (P = 0.0039) and lymphovascular invasion (P = 0.009). The status of maspin mRNA expression in SLNs was correlated significantly with that of maspin protein expression in the primary carcinoma (P < 0.0001). CONCLUSIONS: This is the first study, to our knowledge, demonstrating that maspin mRNA expression in SLNs is an independent predictor of non-SLN metastasis and the presence of ≥4 LN metastases in breast cancer patients with SLN metastasis. The investigation of maspin mRNA expression in SLNs using the remaining specimens after the OSNA assay may be useful for predicting the further progression of metastatic carcinoma in breast cancer patients with SLNs metastasis.

The administration of ghrelin improved hepatocellular injury following parenteral feeding in a rat model of short bowel syndrome.

PURPOSE: Long-term parenteral nutrition following massive bowel resection causes liver dysfunction, such as intestinal failure-associated liver disease (IFALD). IFALD includes two different states, cholestasis and steatosis, which represents a life-threatening complication. The previous reports have shown the protective role of ghrelin in the liver. The aim of this study was to evaluate the effects of the administration of ghrelin in the liver in a parenterally fed rat model of short bowel syndrome (SBS). METHODS: Rats underwent jugular vein catheterization, and were divided into three groups: 90 % small bowel resection (90 % SBR) and TPN (SBS/TPN group), 90 % SBR and TPN plus ghrelin (SBS/TPN/ghrelin group), and sham operation with normal chow (sham group). Ghrelin was administered continuously at a dose of 10 µg/kg/day. On day 13, all rats were euthanized. The serum chemistry was analyzed, the lipid content of the liver was measured, and the liver tissue was histologically analyzed. RESULT: The AST and LDH levels significantly increased, and the accumulation of lipids in the liver was observed in the TPN/SBS group. The accumulation of lipids in the liver of the rats in the SBS/TPN group was attenuated by the administration of ghrelin. CONCLUSION: The administration of ghrelin has a therapeutic potential for IFALD.

Age-dependent sex difference of non-alcoholic fatty liver disease in TSOD and db/db mice.

According to previous clinical studies, the prevalence of non-alcoholic fatty liver disease (NAFLD) is higher in men than women only during the reproductive age. Animal models of NAFLD that reflect sex differences in humans have not been established. In this study, we examined sex differences in the hepatic lesions of Tsumura Suzuki obese diabetes (TSOD) and db/db mice, which are representative genetic models of NAFLD. Male and female TSOD and db/db mice were fed with a normal diet and tap water ad libitum. Six male and female mice of each strain were sacrificed at the ages of 3 and 9 months, respectively, and serum biochemical, pathological, and molecular analyses were performed. Serum aspartate aminotransferase (AST) levels were significantly higher in male than female mice of both strains at the age of 3 months; however, at 9 months, significant sex differences were not observed. Similarly, alanine aminotransferase (ALT) levels were significantly higher in male mice than in female TSOD mice at the age of 3 months; however, at 9 months, significant sex differences were not observed. Image analysis of histological slides revealed that the frequency of the steatotic area was significantly higher in male than female db/db mice at the age of 3 months; however, significant sex differences were not observed at 9 months. The frequency of Sirius red-positive fibrotic area was significantly higher in male than female mice in both strains at the age of 3 months; however, significant sex differences were not observed at 9 months. Serum AST and ALT levels and hepatic steatosis and fibrosis in TSOD and db/db mice showed age-dependent sex differences consistent with those observed in human NAFLD. These mice may be suitable for studying sex differences of the disease.

Aldehyde dehydrogenase 1 expression predicts poor prognosis in triple-negative breast cancer.

AIMS: Aldehyde dehydrogenase 1 (ALDH1) has been identified as a reliable marker of breast cancer stem cells, and its clinical significance as a prognostic indicator of breast cancer has been reported by several investigators. However, the clinical significance of ALDH1 expression in triple-negative (TN) breast cancer, a high-risk breast cancer lacking the benefit of specific therapy, remains to be solved. METHODS AND RESULTS: We performed immunohistochemical analyses of 106 TN breast cancers, using paraffin-embedded sections. The basal-like phenotype was also investigated with the use of basal cytokeratin 5/6 and epidermal growth factor receptor. ALDH1 expression in carcinoma cells was found in 59% of cases and was correlated with high histological grade alone (P < 0.006), whereas ALDH1 expression in stromal cells was found in 49% of cases but was not correlated with any clinicopathological parameter. Patients with ALDH1 expression in carcinoma cells had a shorter relapse-free survival (RFS) according to the log-rank test (P = 0.015). According to Cox multivariate analysis, ALDH1 expression in carcinoma cells was an independent prognostic indicator of RFS (P = 0.025). The log-rank test revealed that stromal expression of ALDH1 had no effect on RFS. CONCLUSIONS: ALDH1 expression in carcinoma cells is an independent prognostic factor in TN breast cancer patients.

Aldehyde dehydrogenase 1 expression is a predictor of poor prognosis in node-positive breast cancers: a long-term follow-up study.

AIMS: Aldehyde dehydrogenase 1 (ALDH1) has been identified as a reliable marker of breast cancer stem cells. The aim was to determine the prognostic significance of ALDH1 expression in a long-term follow-up study. METHODS AND RESULTS: Immunohistochemical analyses were performed on 257 invasive ductal carcinomas (IDCs), 109 matched lymph node metastases and 190 ductal carcinomas in situ (DCISs), using paraffin-embedded sections. ALDH1 expression was found in 26% of IDCs, and correlated with larger tumour size (P=0.007), high histological grade (P<0.001), HER2 overexpression (P<0.001) and negative hormone receptor status (P<0.001). ALDH1 expression was observed in 14% of DCISs but was not correlated with any clinicopathological parameter. The IDC patients were followed up for 7-190 months (median: 120 months), and groups with ALDH1 expression had shorter relapse-free survival (P=0.0013) and overall survival (OS) (P=0.0005) by log-rank test. By Cox's multivariate analysis, it had a weak effect on OS (P=0.047), and its most significant effect on OS was observed in node-positive groups (P=0.013). No significant differences in OS stratified by ALDH1 expression status in lymph node metastases were noted. CONCLUSIONS: ALDH1 expression in primary cancer is an independent prognostic factor in node-positive breast cancer patients.

Effects of fetal exposure to 4-n-octylphenol on mammary tumorigenesis in rats.

BACKGROUND: The aim of this study was to investigate the effect of fetal exposure to 4-n-octylphenol (OP) on the induction of mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) in rats. MATERIALS AND METHODS: All rats which showed vaginal plugs or sperm by vaginal smear test after mating were fed a normal diet only, or a diet mixed with 10, 100, 1000 ppm OP throughout the pregnancy period and from day 13 of pregnancy to the end of the pregnancy. No abnormal pregnancy was seen in any of the rats. Pups were given 10 mg DMBA by gastric intubation 50 days after birth. RESULTS: Uterine weight decrease was observed in pups with fetal exposure to 1000 ppm OP throughout the pregnancy period. No endocrine disrupting conditions, such as persistent estrus, anovulatory ovaries or abnormal lactation in the mammary glands were seen in pups with fetal exposure to OP. However, fetal exposure to 100 and 1000 ppm OP throughout pregnancy period enhanced the early incidence and number of mammary carcinomas (MCs) while it did not enhance the incidence and number of benign proliferative lesions (PLs) which consisted of solid masses (fibroadenoma and lobular hyperplasia) and gross cysts. CONCLUSION: These results suggest that fetal exposure to the very weak estrogenicity of OP could enhance the induction of MCs but not affect the induction of PLs.

Gene expression profiling during rat mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthracene.

7,12-Dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinoma is a well-recognized model; however, the genetic alterations during its carcinogenesis have yet to be determined. We used laser capture microdissection to specifically isolate cells from terminal end buds (TEBs), the origin of carcinoma, at 2 weeks after sesame oil treatment (control) or DMBA treatment (DMBA-TEBs), ductal carcinoma in situ (DCIS) and invasive mammary carcinoma (MC). Using an oligonucleotide microarray representing 20,600 rat probe sequences, we analyzed gene expression profiles and validated mRNA and protein levels of genes of interest by real-time quantitative PCR and immunohistochemistry. The number of differentially expressed genes dramatically increased from DMBA-TEBs (63) to DCIS (798) and MC (981). Only the expression of PEP-19, an anti-apoptotic gene, showed significant increases in DMBA-TEBs (4-fold), DCIS (10-fold) and MC (16-fold). MMP-13 expression was increased markedly in DCIS (19-fold) and MC (61-fold) while OPN expression was increased 6-fold in DCIS and 8-fold in MC. MMP-7 expression was increased 4-fold in MC. Nidogen-1; a participant in the assembly of basement membranes, TSP-2; an inhibitor of angiogenesis and COUP-TFI; a transcription repressor showed significant decreases in DCIS (4-, 9- and 17-fold, respectively) and MC (10-, 37- and 100-fold). Network analyses with IPA software revealed that the most significant network included Akt groups in DCIS and ERK groups in MC. The present findings provide us with a better understanding of the molecular alteration that occur during mammary carcinogenesis and suggest the importance of PEP-19 overexpression in the very early stage of mammary carcinogenesis.

Effects of fetal exposure to diethylstilbestrol on mammary tumorigenesis in rats.

The aim of this study was to investigate the effect of fetal exposure to diethylstilbestrol (DES) on the induction of mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female rats. Pregnant rats were fed only normal diet, diet mixed with 0.1 ppm DES throughout pregnancy period or diet mixed with 0.1, 1 or 10 ppm DES from day 13 of pregnancy till the end of pregnancy. Delivered pups were given 10 mg DMBA by gastric intubation at 50 days after birth and observed till 336 days after birth. Some rats exposed to DES throughout pregnancy and those from day 13 till the end of pregnancy showed endocrine disrupting effects such as absence of CL and active lactation in mammary glands at necropsy, while no abnormal estrus cycle such as persistent estrus was seen during the observation period until 88 days after birth. Fetal exposure to 0.1 ppm DES throughout pregnancy period, 0.1 and 1 ppm DES from day 13 of pregnancy increased the incidence and number of mammary carcinomas (MCs) at the earlier period while exposure to 0.1 ppm DES throughout pregnancy period enhanced the incidence and number of benign proliferative lesions (PLs) at the later period. MCs appeared earlier than benign PLs. These results suggest that exposure to DES throughout pregnancy and from day 13 of pregnancy could induce endocrine disrupting conditions and enhance the induction of MCs and that exposure to DES throughout pregnancy enhance PLs.

Effects of exposure period and dose of diethylstilbestrol on pregnancy in rats.

The aim of this study was to investigate the effect of exposure period and dose of diethylstilbestrol (DES), which has strong estrogenic activity, on pregnancy in rats. All rats with observed vaginal plugs or sperm in vaginal smear tests after mating were divided into 3 groups: those fed a normal diet, a diet mixed with DES throughout pregnancy and a diet mixed with DES from day 13 of pregnancy. DES was mixed into the diet at 0.1, 1, 10 and 100 ppm. All bred rats fed the normal diet and 0.1 ppm DES from day 13 of pregnancy delivered pups, while none of the rats treated with 1-100 ppm DES during pregnancy and 100 ppm DES from day 13 of pregnancy delivered any pups. The number of male and female pups born decreased in rats treated with 10 ppm DES from day 13 of pregnancy. These results suggest that DES could affect pregnancy and that the exposure period and dose may result in sterility, abortion, poor fetal growth and reduced number of pups born.

Effects of 4-tert-Octylphenol on the incubation of eggs in Japanese brown frogs (Rana japonica).

4-tert-Octylphenol (OP), is an endocrine disruptor or surfactant widely used in herbicides. Its effects (0, 1 and 10 mg/l) on the incubation of eggs were examined using wild Japanese brown frogs (Rana japonica). In 10 mg/l OP, all the eggs were corrupted and no eggs developed. In 1 mg/l OP, 9.8% eggs developed and systemic edema, malformations such as crooked vertebrae and atrophy of the systemic muscles were observed in all the surviving tadpoles. These results suggested that OP use in paddy fields may affect the survival rate of wild frogs and induce malformation.

Effects of neonatal administration of diethylstilbestrol on aberrant crypt foci induced by 7,12-dimethylbenz[alpha] anthracene in rats.

Gastrointestinal carcinoma is affected environmental factors, however, it remains to be determined whether neonatal administration of an estrogenic endocrine disruptor, such as diethylstilbestrol (DES), affects gastrointestinal carcinogenesis. The effects of neonatally administered DES on gastrointestinal tumorigenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) were investigated in male and female rats. Male and female rats in group I were daily administered oil alone from 0-14 days after birth. Male and female rats in groups II and III were daily administered DES at 1 and 10 microg/rat, respectively. The administration periods of DES in subgroups a (IIa and IIIa), b (IIb and IIIb) and c (IIc and IIIc) were from 0-14, 0-5 and 6-14 days after birth, respectively. At 28, 42 and 56 days after birth, all male rats were given 10 mg of DMBA. At 50 days after birth, all female rats were given 10 mg of DMBA. In the digestive tracts of male rats, forestomach masses (FMs) in all groups (13-58%), small intestine masses in group IIIa (17%), and colon masses (CMs) in groups IIIa (8%) and IIIb (33%) were observed, although there were no significant changes in the incidence and number. In the digestive tracts of female rats, FMs in groups I (10%), IIa (13%), IIb (33%), IIc (25%) and IIIc (33%), CMs in groups IIa (6%) and IIIa (6%) were seen, although there were no significant changes in the incidence. Aberrant crypt foci (ACF) in the colon and rectum were seen in all male and female rats. The neonatal administration of DES in male rats increased the number of ACF while that in female rats did not. These results suggest that neonatal administration of DES may affect male colorectal carcinogenesis.

Effects of neonatally administered low-dose diethylstilbestrol on the induction of mammary carcinomas and dysplasias induced by 7,12-dimethylbenz [a] anthracene in female rats.

The aim of this study was to investigate the effects of neonatal administration of diethylstilbestrol (DES) on the induction of mammary carcinomas (MCs) and dysplasias (MDs) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female rats. Three different methods of continuous administration of DES (1 microg) were used: 0-14, 0-5 and 6-14 days after birth, and all rats were given DMBA (10 mg) at 50 days after birth. All rats administered DES showed persistent estrus and anovulatory ovaries. In rats administered DES from 0-14 days after birth, neither MCs nor MDs were observed, and serum levels of both estrogen and progesterone were significantly lower than in controls at 100 days after birth. In rats administered DES from 0-5 days after birth, the incidence and number of MCs were significantly lower while the number ofMDs was slightly higher than in controls. In rats administered DES from 6-14 days after birth, the incidence of MCs was equal to that of the controls while the incidence and number ofMDs were significantly higher. These results suggest that neonatal periods of exposure and doses of endocrine disruptors, such as DES, could affect the incidence and progression of MCs and MDs.

Ghrelin stimulates intestinal adaptation following massive small bowel resection in parenterally fed rats.

BACKGROUND: Since short bowel syndrome (SBS) patients face life-threatening conditions, the development of therapeutic strategies to induce intestinal adaptation has been investigated. Ghrelin, a ligand of growth hormone (GH) secretagogue-receptor that stimulates the release of GH and insulin like growth factor-1 (IGF-1), has several pleiotropic effects. We investigated whether ghrelin induces intestinal adaptation in parenterally fed rats with SBS. METHODS: Sprague-Dawley rats underwent venous catheterization and were divided into 3 groups: those receiving 90% small bowel resection while leaving the proximal jejunum and distal ileum (90% SBR) with TPN (SBS/TPN group), those receiving 90% SBR with TPN + ghrelin (SBS/TPN/ghrelin group), and those receiving sham operation and fed chow (sham group). Ghrelin was administered intravenously at 10 µg/kg/day. On Day 13, the rats were euthanized and the small intestine harvested, and the histology and crypt cell proliferation rates (CCPR), apoptosis, and nutrient transporter protein levels were analyzed and the plasma hormones were measured. RESULTS: The villus height and crypt depth of the ileum in the SBS/TPN/ghrelin group were significantly higher than in the SBS/TPN group. The CCPR of the jejunum and the ileum significantly increased by the administration of ghrelin; however, the apoptosis rates did not significantly differ between the SBS/TPN and SBS/TPN/ghrelin groups. Significant differences did not exist in the plasma IGF-1 and nutrient transporter protein levels among three groups. CONCLUSIONS: The intravenous administration of ghrelin stimulated the morphological intestinal adaptation of the ileum to a greater degree than the jejunum due to the direct effect of ghrelin.

Increased bone mineral density in aged rats with spontaneous mammary dysplasia.

Spontaneous mammary tumors were seen in seven of the 12 breeding female rats aged 2 years. All mammary tumors were diagnosed as mammary dysplasia (MD). Bone mineral contents (BMC) and bone mineral density (BMD) of their lumbar vertebrae and femur were determined using dual energy X-ray absorptiometry (DXA). In rats with MD, body weight (BW), BMD of the lumbar vertebrae and BMC of the femur were significantly higher than in the rats without MD. Although corpus luteum (CL) and follicles were seen in the ovaries of all animals, the number of CL in rats with MD was significantly lower than the rats without MD. It was suggested that high BMD, BW and decreased CL promoted mammary tumors.

Expression of estrogen receptor-alpha protein in the rat digestive tract.

The current study evaluates the expression of estrogen receptor-alpha (ER-alpha) protein in the digestive tract and other organs using immunohistochemistry in male and female intact rats. As a result, the expression of ER-alpha protein was intensively immunoreactive in the nuclei of squamous epithelium of the forestomach connected to the limiting ridge and the anus connected to the anorectal junction. Rat ER-alpha mRNA signals were also detected in the epithelium of the limiting ridge using in situ hybridization. The incidence of ER-alpha protein in the limiting ridge decreased with age in both males and females. The incidence of ER-alpha protein in the anorectal junction strongly decreased with age in males, although the incidence did not decrease with age in females. In conclusion, it was suggested that estrogen may be involved in the proliferation and differentiation of these cells in the limiting ridge of the stomach and anorectal junction of rats.

Expression of estrogen receptor alpha and progesterone receptor in normal human breast epithelium.

BACKGROUND: Recently, the immunohistochemical detection of estrogen receptor alpha (ERalpha) expression in breast cancer has become a prerequisite for therapeutic decision-making, however, it remains unknown whether ERalpha or progesterone receptor (PgR) expression in histologically normal breast epithelium (NBE) adjacent to carcinoma can be a reliable internal positive control. PATIENTS AND METHODS: Tissues from a total of 220 breast cancer patients were investigated by immunohistochemistry of ERalpha and PgR expression in NBE adjacent to carcinoma, as well as in carcinoma. The expression pattern was divided into three groups: singular, one or two positive cells; scattered, scattered positive cells surrounded by negative cells; contiguous, ten or more positive cells in contact with each other. RESULTS: In NBE adjacent to carcinoma, the positivity of ERalpha and PgR was 99% (217 out of 220) and 89% (195 out of 220), respectively. The expression pattern of ERalpha and PgR was as follows: singular - 13 and 42 patients, scattered - 116 and 100 patients, and contiguous - 88 and 53 patients, respectively. The contiguous expression pattern of PgR was more frequently noted in premenopausal patients in contrast with ERalpha (p=0.0004). PgR expression was more frequently seen in premenopausal than postmenopausal patients (p=0.0034). PgR expression in carcinoma was more frequently seen in premenopausal than postmenopausal patients (p= 0.009). There was statistically significant correlation between PgR expression in carcinoma and NBE adjacent to carcinoma (p=0.0019). CONCLUSION: These findings suggest that more frequent PgR expression in NBE adjacent to carcinoma might be correlated with carcinogenesis in premenopausal breast cancer patients and that ERalpha expression, not PgR, in NBE adjacent to carcinoma could be a reliable internal positive control.

Expression of maspin in colorectal cancer.

BACKGROUND: Maspin, a member of the serpin family of protease inhibitors, is known to be a tumor suppressor. Although the relationship between its expression and biological significance has been investigated in several types of cancer, the clinicopathological significance of maspin expression in colorectal cancer has not been fully elucidated. MATERIALS AND METHODS: The expression of maspin in colorectal adenocarcinomas from 104 patients (Ti, T2: 20 patients, T3, T4: 84 patients) was investigated using immunohistochemical methods and the extent of tumor budding was evaluated. RESULTS: The expression of maspin was observed in 66% (69 of 104) of colorectal adenocarcinomas and was significantly correlated with the depth of invasion (p < 0.0001), higher Dukes' classification (p < 0.0001) and high-grade tumor budding (>9 foci in a field) (p = 0.0001); however, no significant correlation was noted concerning lymph node metastases, vascular invasion and tumor differentiation. The intensity of immunostaining was most strongly observed at the invasion front, especially at the site of tumor budding. CONCLUSION: These results suggest that the expression of maspin may correlate with the aggressiveness of colorectal adenocarcinomas.

PCP4/PEP19 promotes migration, invasion and adhesion in human breast cancer MCF-7 and T47D cells.

Purkinje cell protein (PCP) 4/peptide (PEP) 19 is expressed in Purkinje cells where it has a calmodulin-binding, anti-apoptotic function. We recently demonstrated that PCP4/PEP19 is expressed and inhibit apoptosis in human breast cancer cell lines. In the present study we investigated the role of PCP4/PEP19 in cell morphology, adhesion, migration, and invasion in MCF-7 and T47D human breast cancer cell lines. Knockdown of PCP4/PEP19 reduced the formation of filopodia-like cytoplasmic structures and vinculin expression, and enhanced E-cadherin expression. Activities of migration, invasion, and cell adhesion were also decreased after the knockdown of PCP4/PEP19 in MCF-7 and T47D cells. These results suggested that PCP4/PEP19 promotes cancer cell adhesion, migration, and invasion and that PCP4/PEP19 may be a potential target for therapeutic agents in breast cancer treatment which act by inhibiting epithelial-mesenchymal transition and enhancing apoptotic cell death.

Ghrelin improves intestinal mucosal atrophy during parenteral nutrition: An experimental study.

BACKGROUND/PURPOSE: Total parenteral nutrition (TPN) has been reported to be associated with mucosal atrophy of the small intestine. Ghrelin has hormonal, orexigenic, and metabolic activities. We investigated whether ghrelin improved intestinal mucosal atrophy using a TPN-supported rat model. METHODS: Rats underwent jugular vein catheterization and were divided into four groups: TPN alone (TPN), TPN plus low-dose ghrelin (TPNLG), TPN plus high-dose ghrelin (TPNHG), and oral feeding with normal chow (OF). Ghrelin was administered continuously at dosages of 10 or 50 µg/kg/day. On day 6 rats were euthanized, and the small intestine was harvested and divided into the jejunum and ileum. Then the villus height (VH) and crypt depth (CD) were evaluated. RESULTS: The jejunal and ileal VH and CD in the TPN group were significantly decreased compared with those in the OF group. TPNHG improved only VH of the jejunum. TPNLG improved VH and CD of the jejunum and CD of the ileum. The improvement of TPNLG was significantly stronger than that in CD of the jejunum and ileum. CONCLUSIONS: TPN was more strongly associated with mucosal atrophy in the jejunum than in the ileum. Low-dose intravenous administration of ghrelin improved TPN-associated intestinal mucosal atrophy more effectively than high-dose administration.