Expression of MUC5AC and MUC6 in invasive ductal carcinoma of the pancreas and relationship with prognosis

AIM/BACKGROUND: MUC5AC and MUC6 are two major types of mucin that are abundantly present in the stomach; both of them form a gel of high viscosity that provides protection and lubrication. Expressions of MUC5AC and MUC6 are seen in pancreatic neoplasms, whereas the relationships between MUC5AC/MUC6 expression and clinicopathological factors and patient prognosis in invasive ductal carcinoma (IDC) of the pancreas have not been investigated. The aim of this study was to investigate MUC5AC and MUC6 expressions in IDC with special reference to clinicopathological factors and patient prognosis. METHODS: Tissue samples were taken from 33 patients with IDC of the pancreas after radical surgical treatment. MUC5AC and MUC6 expressions were examined immunohistochemically. RESULTS: The expressions of MUC5AC and MUC6 were observed in the cytoplasm of the tumor cells. MUC5AC and MUC6 immunoreactivities in the cancer tissues were found in 21 (63.6%) and 15 (45.5%) of 33 cases of IDC of the pancreas, respectively. MUC5AC-negative expression was associated significantly with lymphatic invasion, venous invasion, lymph node metastasis, and MUC5AC-positive patients showed significant better survival than those MUC5AC-negative patients. MUC6 expression was significantly related to tumor location, whereas MUC6 expression did not show significant relationship with patient survival. CONCLUSION: The results indicate that MUC5AC expression plays an important role in impacting tumor progression in IDC of the pancreas. MUC5AC expression is a benefit to better survival of patients with IDC of the pancreas. MUC6 expression is not involved in tumor progression in IDC of the pancreas.     

Effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in hemodialysis patients

BACKGROUND: Orthostatic hypotension (OH) is a serious complication observed in hemodialysis (HD) patients after HD as well as during the interdialytic period. L-Threo-3,4-dihydroxyphenylserine (L-DOPS) is a nonphysiological neutral amino acid that is directly converted to the neurotransmitter norepinephrine by aromatic L-amino acid decarboxylase. METHODS: A placebo-controlled double-blind study for 4 consecutive weeks and a long-term study (24-52 weeks) were conducted to evaluate the efficacy of L-DOPS for OH after HD. The drug was administered orally 30 min before the start of each HD period in both studies. Doses of 400 mg of L-DOPS or placebo were given to HD patients with OH (45 and 41 patients, respectively) in the double-blind study, and doses of 200 or 400 mg of L-DOPS were given to 74 HD patients in the long-term study. RESULTS: In the double-blind study, L-DOPS significantly ameliorated subjective symptoms related to OH, including dizziness/light-headed feeling, and malaise, throughout the interdialytic period. For 19 patients with delayed-type OH, hypotension with the lowest blood pressure recorded 10 min after standing, the decrease in blood pressure was suppressed significantly after L-DOPS treatment (10 patients) as compared with the placebo-treated group (9 patients). In the long-term study, the efficacy of L-DOPS was not attenuated, and the marked fluctuations in the plasma L-DOPS and norepinephrine levels were not noted after long-term use, without increases in incidence or severity of adverse reactions. CONCLUSIONS: These results indicate that L-DOPS is effective for improving OH-related interdialytic subjective symptoms in HD patients after short-term as well as after long-term administration.     

Compartments in the lamprey embryonic brain as revealed by regulatory gene expression and the distribution of reticulospinal neurons

The vertebrate neural tube consists of a series of neuromeres along its anteroposterior axis. Between amphioxus that possesses no neuromeres and gnathostomes, the lamprey occupies a critical position in the phylogeny for the origin of the segmented brain. To clarify the rhombomeric configuration of the Japanese lamprey, Lampetra japonica, we injected rhodamine- and fluorescein-labeled dextrans into the larval spinal cord, and retrogradely labeled the reticulospinal neurons. We also isolated prosomere marker genes from the embryonic cDNA library of L. japonica, and performed in situ hybridization on the embryonic brain. Of the genes examined, LjOtxA, LjPax6, LjPax2/5/8, LjDlx1/6, and LjTTF-1 were expressed in clearly demarcated polygonal domains. In the telencephalon, LjDlx1/6, LjPax6, and a putative paralogue of LjEmx were expressed in different domains; the LjEmx paralogue was expressed in the dorsal region, and LjDlx1/6 and LjPax6 in a complimentary fashion of the middle part. These expression patterns implied existence of a tripartite configuration of the lamprey telencephalon similar to that in gnathostomes. All these evidences strongly suggest that the segmental and compartmental architecture of the vertebrate brain was already established before the divergence of agnathans and gnathostomes.     

Oral administration of leucine stimulates phosphorylation of 4E-bP1 and S6K 1 in skeletal muscle but not in liver of diabetic rats

Leucine performs a signaling role to enhance protein synthesis by phosphorylating eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and 70-kDa ribosomal protein S6 kinase (S6K1), two key regulatory proteins involved in the initiation of mRNA translation. The purpose of the current study was to assess whether the phosphorylation of 4E-BP1 and S6K1 was increased in skeletal muscle and liver by an oral administration of leucine to diabetic rats and to determine the in vivo contribution of insulin to a leucine-dependent induction of 4E-BP1 and S6K1 phosphorylation. Food-deprived (18 h) normal and diabetic rats were orally administered 135 mg/ 100 g body weight L-leucine and sacrificed at 1 h after administration. Leucine administration resulted in enhanced phosphorylation of 4E-BP1 and S6K1 in skeletal muscle and in liver of nondiabetic rats. The stimulatory action of leucine on the phosphorylation of 4E-BP1 and S6K1 in skeletal muscle was not abolished in rats with streptozotocin-induced diabetes. In contrast, leucine administration did not stimulate the phosphorylation of 4E-BP1 and S6K1 in the liver of diabetic rats. These findings suggest that in skeletal muscle, leucine functions as a nutritional signaling molecule that independently regulates the phosphorylation states of 4E-BP1 and S6K1. In contrast to skeletal muscle, insulin is essential in mediating the leucine-dependent induction of 4E-BP1 and S6K1 phosphorylation in liver. leucine, 4E-BP1, S6K1, translation initiation, diabetes     

Lymphatic absorption of docosahexaenoic acid given as monoglyceride,diglyceride, triglyceride,and ethyl ester in rats

Lymphatic absorption of docosahexaenoic acids (DHA) given as monoglyceride (MG), consisting of 1(or 3)-species (9 1.4%), 2-species (4.2%) and diglyceride (DG) consisting of 1,3-species (70.8%), 1(or 3),2-species (28.6%), were investigated in comparison with that of triglyceride (TG) and ethyl ester (EE). Rats were infused with a lipid emulsion containing 200 mg of DHA-MG, DG, TG, or EE via a gastric cannula. Lymph was collected through the thoracic lymph duct at 2 h intervals for 10 h and at a single collection from 10 to 30 h. Physiological saline containing glucose was infused (2 mL/h) throughout the lymph collection. The overall recovery of DHA at 30 h after its infusion was significantly higher in the rank order DHA-MG>DG>TG=EE. Moreover, time-dependent changes in recovery rates from 2 to 10 h of DHA given as MG were significantly higher than those of the corresponding DG, TG, and EE. These results indicate that DHA-MG and DG are absorbed and transported more effectively than TG and EE forms under restricted water supply, even if they mainly consist of 1(or 3)-species. Lymph lipids were mainly transported as TG, and a large amount of DHA was incorporated into a TG fraction in all fat types examined. Furthermore, the intramolecular distribution of DHA in lymph TG was similar in all groups. docosahexaenoic acid, monoglyceride, diglyceride triglyceride, ethyl ester     

Metastasis of breast cancer to intracranial meningioma: case report

Metastasis of systemic cancer to intracranial tumors is a rare event. The authors report a case of 49-year-old woman with such occurrence, whose breast cancer metastasized to a preexisting parasagittal meningioma at a postoperative interval of 1.5 years. She was admitted to our hospital because of progressive right hemiparesis. Magnetic resonance imaging revealed newly emerged perifocal edema and inhomogeneous contrast enhancement of the meningioma. High choline/creatine ratio and lactate/lipid peak on proton magnetic resonance spectroscopy suggested malignancy. She underwent a tumor resection, and pathologic examination revealed intratumoral metastasis of breast cancer in a transitional meningioma. Immunoreactivity of E-cadherin was detected in both meningioma and breast cancer cells. It is suggested that abrupt appearance of symptoms, inhomogeneous enhancement, and perifocal edema of meningioma is a sign of intratumoral metastasis from systemic cancers.     

Successive cultures of mature hepatocytes for hepatocyte autotransplantation to assist liver function after liver resection for cancer

We developed a method for the rapid successive cultures of adult rat mature hepatocytes on plastic dishes while avoiding viral transformation or co-culture with other cell lines. This method also allows for culturing adult human mature hepatocytes up to the secondary culture. These can be expected to provide a good source for hepatocyte autotransplantation, and, combined with the previously reported methods for the transplantation of hepatocytes into the spleen, a promising option for the support of liver function after liver resection for cancer without the need for immunosuppressive agents.     

TS-1/CDDP therapy for advanced gastric cancer as neoadjuvant chemotherapy

Five patients with inoperable advanced gastric cancer were treated with combination chemotherapy of TS-1 and cisplatin (CDDP). TS-1 of 80-120 mg/body/day was orally administered for 3 weeks followed by 2 drug-free weeks, and 60 mg/m2/day of CDDP was venally administered on Day 8. It was possible to evaluate all 5 patients for response and toxicity. Only low grade toxicities (Grade 1 or 2) of leukocytopenia, neutrocytopenia, anemia, nausea, diarrhea and stomatitis were seen. Four of 5 patients achieved a partial response, for a response rate of 80.0%. Stomach, liver, lymph node and peritoneal tumors responded to TS-1/CDDP. TS-1/CDDP therapy produces a high response in cases of gastric cancer, and it is useful as a neoadjuvant chemotherapy.