Osteoporotic fracture risk in women with breast cancer treated with aromatase inhibitors: a health insurance claims database study in Japan.

BACKGROUND: Hormone therapy with aromatase inhibitors (AIs) for estrogen receptor-dependent breast cancer may expose patients to an increased osteoporosis risk. This study was performed to estimate fracture risk in women with breast cancer to whom AIs were prescribed in Japan. METHODS: This retrospective study used data from the Japanese Medical Data Vision database. Women with breast cancer prescribed AIs over a 12-month period were identified and matched to women not prescribed AIs using a propensity score. Fracture rates were estimated by a cumulative incidence function and compared using a cause-specific Cox hazard model. The proportion of women undergoing bone density tests was retrieved. RESULTS: For all fractures sites combined, cumulative fracture incidence at 10 years was 0.19 [95%CI: 0.16-0.22] in women prescribed AIs and 0.18 [95%CI: 0.15-0.21] without AIs. AI prescription was not associated with any changes in risk (adjusted hazard ratio: 1.08 [95%CI: 0.99-1.17] p = 0.08). Women prescribed AI more frequently underwent bone density testing (31.9% [95% CI: 31.2%; 32.6%] versus 2.2% [95% CI: 2.0%; 2.4%]). CONCLUSIONS: The anticipated association between AI exposure and osteoporotic fracture risk in Japanese women with breast cancer was not seen clearly.

Long-Term Outcomes of Self-Expandable Metallic Stents as a Bridge to Surgery for Obstructive and Symptomatic Primary Tumors of Stage IV Colorectal Cancer: A Propensity-Score Analysis.

Background: Self-expandable metallic stent (SEMS) was introduced for the treatment of obstructive colorectal cancer (CRC) a few decades ago. However, its long-term outcomes remain controversial, especially for stage IV CRC. The aim of this study was to clarify the outcomes of SEMS as a "bridge to surgery" (BTS) for obstructive and symptomatic primary tumors in stage IV CRC by one-to-one propensity-score matching. Materials and Methods: This retrospective cohort study was conducted at a single center from January 2007 to December 2017. Patients with obstructive and symptomatic primary tumors of stage IV CRC underwent primary resection (PR) or placement of a SEMS as a BTS. They were divided into SEMS and PR groups, and their short- and long-term outcomes were compared. Results: In total, 52 patients were reviewed (SEMS group, 21; PR group, 31). Sixteen patients in both groups were matched using propensity scores. Patients in the SEMS group more frequently underwent laparoscopic surgery than those in the PR group (75% versus 19%, P = .004). The two groups showed no significant differences in perioperative and pathological outcomes. The 5-year overall survival was not significantly different between groups (29% versus 20%, P = .53). Conclusions: As a BTS, the use of SEMS for obstructive and symptomatic primary tumors in CRC stage IV can be a comparable option to PR in terms of short- and long-term outcomes, and would be less invasive with respect to surgical procedures.

How do magnetic resonance cholangiopancreatography findings predict conversion from laparoscopic cholecystectomy for acute cholecystitis to bailout procedures?

BACKGROUND: Acute cholecystitis is one of the most prevalent surgical abdominal conditions. The Tokyo Guidelines describe the management of acute cholecystitis and recommend bailout procedures for "difficult" cholecystitis cases. This study aimed to identify risk factors for conversion from laparoscopic cholecystectomy to bailout procedures in patients with acute cholecystitis. METHODS: This retrospective cohort study was conducted at a single center between January 2017 and December 2021. Patients who underwent laparoscopic cholecystectomy for acute cholecystitis were enrolled and classified into bailout and non-bailout groups. The patients' characteristics and perioperative data were compared between the 2 groups. RESULTS: In total, 161 patients who underwent laparoscopic cholecystectomy for acute cholecystitis were reviewed. Fourteen were excluded because of a lack of preoperative magnetic resonance cholangiopancreatography; thus, 147 patients were enrolled (bailout group, 21; non-bailout group, 126). Age (74 vs 67 years old; P = .048), days from onset to surgery (3 vs 2 days; P = .02), or defect of cystic duct in magnetic resonance cholangiopancreatography (57% vs 29%; P = .02) were significantly associated with conversion to bailout procedures. In the logistic regression analysis, a defect of the cystic duct in magnetic resonance cholangiopancreatography was an independent predictor for bailout procedures (odds ratio, 2.793; P = .04). CONCLUSION: In this study, defect of the cystic duct in the magnetic resonance cholangiopancreatography can predict conversion to bailout procedures. To the best of our knowledge, this is the first report to describe magnetic resonance cholangiopancreatography finding of the cystic duct as a predictor of surgical difficulty in patients with acute cholecystitis.

A Rare Case of Severe Post-operative Pyoderma Gangrenosum After Surgery for Perforated Diverticulitis at the Sigmoid Colon.

Pyoderma gangrenosum (PG) is a nonbacterial ulcerating skin condition. It is typically associated with other systemic disorders. However, approximately 20%-30% of cases are idiopathic. Post-operative PG (PPG) is a rare type of PG with a rapidly expanding cutaneous ulcer at a surgical site and is often misdiagnosed as a wound infection. The difficulty in diagnosis can lead to unnecessary surgical interventions and delay in the treatment of PG. Herein, we present the case of a 68-year-old patient with severe PPG with no underlying diseases. He underwent an emergency laparotomy (Hartmann's procedure) for perforated diverticulitis. After the operation, systemic inflammatory response syndrome (SIRS) developed and the skin around the incisional wound, stoma, injection venous lines, and electrocardiogram monitoring pads gradually became erythematous. Skin biopsy and the absence of a source of infection confirmed the diagnosis of PG. Drug therapy for PG with steroids, and tumor necrosis factor-α inhibitors improved SIRS and the patient recovered.

Comparison of Minimally Invasive Surgery with Open Surgery for Remnant Gastric Cancer: A Multi-institutional Cohort Study.

BACKGROUND: Despite growing evidence of the effectiveness of minimally invasive surgery (MIS) for primary gastric cancer, MIS for remnant gastric cancer (RGC) remains controversial due to the rarity of the disease. This study aimed to evaluate the surgical and oncological outcomes of MIS for radical resection of RGC. PATIENTS AND METHODS: Patients with RGC who underwent surgery between 2005 and 2020 at 17 institutions were included, and a propensity score matching analysis was performed to compare the short- and long-term outcomes of MIS with open surgery. RESULTS: A total of 327 patients were included in this study and 186 patients were analyzed after matching. The risk ratios for overall and severe complications were 0.76 [95% confidence interval (CI): 0.45, 1.27] and 0.65 (95% CI: 0.32, 1.29), respectively. The MIS group had significantly less blood loss [mean difference (MD), -409 mL; 95% CI: -538, -281] and a shorter hospital stay (MD, -6.5 days; 95% CI: -13.1, 0.1) than the open surgery group. The median follow-up duration of this cohort was 4.6 years, and the 3-year overall survival were 77.9% and 76.2% in the MIS and open surgery groups, respectively [hazard ratio (HR), 0.78; 95% CI: 0.45, 1.36]. The 3-year relapse-free survival were 71.9% and 62.2% in the MIS and open surgery groups, respectively (HR, 0.71; 95% CI: 0.44, 1.16). CONCLUSIONS: MIS for RGC showed favorable short- and long-term outcomes compared to open surgery. MIS is a promising option for radical surgery for RGC.

A Rare Case of the Coexistence of Pancreaticobiliary Maljunction and Gastrointestinal Tumor in Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a congenital condition characterized by "café au lait" spots and subcutaneous fibromas. There are various combined diseases, such as malignant tumors in the abdominal organs or brain tumors. Here, we present a case of a 35-year-old patient with a rare combination of NF1 with a gastrointestinal stromal tumor (GIST) and pancreaticobiliary maljunction (PBM). At the first visit, her main symptom was right upper abdominal pain. Radiological investigations revealed a common bile duct stone, submucosal tumor in the duodenum, PBM, and abnormal findings in the intrahepatic bile ducts. After the common bile duct stone was removed by endoscopic intervention, the patient underwent laparoscopic cholecystectomy, resection of the duodenal submucosal tumor, and liver biopsy. Pathological examination revealed chronic cholecystitis, GIST of the duodenum, and chronic inflammation of the intrahepatic bile ducts. This is the first case report of the rare coexistence of GIST and PBM in a patient with NF1.

Re-pancreaticojejunostomy for Necrosis of the Roux-en-Y Limb Tip 14 Years After Partington-Rochelle Procedure.

Longitudinal pancreaticojejunostomy for chronic pancreatitis, the Partington-Rochelle (PR) procedure, is a good option to control pain caused by dilation of the main pancreatic duct. However, long-term complications related to anastomosis are still unclear. Here, we present a case of a 78-year-old patient with sudden necrosis of the Roux-en-Y limb tip in a PR procedure performed 14 years ago. During emergent laparotomy, we resected the necrotic limb and re-anastomosed the remaining Roux-en-Y limb to the main pancreatic duct. Postoperatively, we managed the inflammation caused by the pancreatic fistula and successfully saved the patient by long-term drainage. Although the cause of necrosis is still unclear, mild kinking and stenosis of the Roux-en-Y limb might be associated with this situation.

Activities to support individual dosimetry of children in Kawamata Town.

This paper does not necessarily reflect the views of the International Commission on Radiological Protection.Kawamata Town in Date District, Fukushima Prefecture is located more than 30 km north-west of Fukushima Daiichi nuclear power plant, but on 22 April 2011, part of the Yamakiya District of Kawamata Town was designated as a planned evacuation area. The exposure of children was a concern in Kawamata Town. Based on the proposal of Kindai University, Kawamata Town Board of Education took the initiative to measure individual radiation doses with an integrated dosimeter (glass badge) for all kindergarten children, nursery school children, elementary school students, and junior high school students in the town. These measurements were continued for nearly 3 years from June 2011 until the end of March 2014. The total number of measurements was approximately 16,800 across 11-cycle measurement, with 3 months' accumulation taken as one-cycle measurement. Kindai University provided financial support for the glass badge measurement service, and cooperated in the analysis of measured values and the development of advice based on the results. The main body implementing the measurements was Kawamata Town Board of Education, and the data obtained belong to Kawamata Town. When measurements were starting to be taken, schools got involved in the collection and distribution of dosimeters after explanations were provided to principals and school nurses who were in charge of risk communication. Thanks to the efforts of the schools, the recovery rate exceeded 90%, increasing the reliability of the measurements. It was clear who needed the information - the children and their parents. Kawamata Town Board of Education summarised the cumulative dose results for each measurement and notified parents via personal reports. These were sent to parents with advice on measurement results prepared by Kindai University, and care was taken to ensure that people could understand the measured results. Further briefing sessions were held as appropriate. At the briefing sessions, at the request of Kawamata Town Board of Education, the faculty members of Kindai University explained the measurement results from a professional point of view, and a professor from the Faculty of Medicine provided individual health consultations. Kawamata Town took the lead in using specialists to gain peace of mind, and this was key to the project's success. The situation was managed by taking measurements by dosimetry, and asking experts to interpret the data and provide advice to help reassure the residents.

Oestrogen receptor α in T cells controls the T cell immune profile and glucose metabolism in mouse models of gestational diabetes mellitus.

AIMS/HYPOTHESIS: The imbalance between maternal insulin resistance and a relative lack of insulin secretion underlies the pathogenesis of gestational diabetes mellitus (GDM). Alterations in T cell subtypes and increased levels of circulating proinflammatory cytokines have been proposed as potential mechanisms underlying the pathophysiology of insulin resistance in GDM. Since oestrogen modulates T cell immunity, we hypothesised that oestrogen plays a homeostatic role in visceral adipose tissue by coordinating T cell immunity through oestrogen receptor α (ERα) in T cells to prevent GDM. METHODS: Female CD4-cre ERαfl/fl (KO) mice on a C57BL/6 background with ERα ablation specifically in T cells, and ERαfl/fl (ERα-floxed [FL]) mice were fed 60 kJ% high-fat diet (HFD) for 4 weeks. Female mice mated with male BALB/c mice to achieve allogenic pregnancy and were maintained on an HFD to generate the GDM model. Mice were divided into four experimental groups: non-pregnant FL, non-pregnant KO, pregnant FL (FL-GDM) and pregnant KO (KO-GDM). GTTs and ITTs were performed on day 12.5 or 13.5 and 16.5 after breeding, respectively. On day 18.5 after breeding, mice were killed and T cell subsets in the gonadal white adipose tissue (gWAT) and spleen were analysed using flow cytometry. Histological examination was also conducted and proinflammatory gene expression in gWAT and the liver was evaluated. RESULTS: KO mice that mated with BALB/c mice showed normal fertility rates and fetal weights as compared with FL mice. Body and tissue weights were similar between FL and KO mice. When compared with FL-GDM mice, KO-GDM mice showed decreased insulin secretion (serum insulin concentration 15 min after glucose loading: 137.3 ± 18.3 pmol/l and 40.1 ± 36.5 pmol/l, respectively; p < 0.05), impaired glucose tolerance (glucose AUC in GTT: 2308.3 ± 54.0 mmol/l × min and 2620.9 ± 122.1 mmol/l × min, respectively; p < 0.05) and increased numbers of T helper (Th)17 cells in gWAT (0.4 ± 0.0% vs 0.8 ± 0.1%; p < 0.05). However, the contents of Th1 and regulatory T cells (Tregs) in gWAT remained similar between FL-GDM and KO-GDM. Glucose-stimulated insulin secretion was similar between isolated islets derived from FL and KO mice, but was reduced by IL-17A treatment. Moreover, the levels of proinflammatory gene expression, including expression of Emr1 and Tnfa in gWAT, were significantly higher in KO-GDM mice than in FL-GDM mice (5.1-fold and 2.7-fold, respectively; p < 0.01 for both). Furthermore, KO-GDM mice showed increased expression of genes encoding hepatokines, Ahsg and Fgf21 (both were 2.4-fold higher vs FL-GDM mice; p < 0.05 and p = 0.09, respectively), with no changes in inflammatory gene expression (e.g., Tnfa and Ifng) in the liver compared with FL-GDM mice. CONCLUSIONS/INTERPRETATION: Deletion of ERα in T cells caused impaired maternal adaptation of insulin secretion, changes in hepatokine profiles, and enhanced chronic inflammation in gWAT alongside an abnormal increase in Th17 cells. These results suggest that the ERα-mediated oestrogen signalling effects in T cells regulate T cell immunity and contribute to glucose homeostasis in pregnancy.

Estrogen regulates sex-specific localization of regulatory T cells in adipose tissue of obese female mice.

Regulatory T cells (Treg) play essential roles in maintaining immune homeostasis. Resident Treg in visceral adipose tissue (VAT-Treg) decrease in male obese mice, which leads to the development of obesity-associated chronic inflammations and insulin resistance. Although gender differences in immune responses have been reported, the effects of the difference in metabolic environment on VAT-Treg are unclear. We investigated the localization of VAT-Treg in female mice in comparison with that in male mice. On a high-fat diet (HFD), VAT-Treg decreased in male mice but increased in female mice. The increase was abolished in ovariectomized and HFD-fed mice, but was restored by estrogen supplementation. The IL33 receptor ST2, which is important for the localization and maturation of VAT-Treg in males, was reduced in CD4+CD25+ T cells isolated from gonadal fat of obese mice of both genders, suggesting that a different system exists for VAT-Treg localization in females. Extensive analysis of chemokine expression in gonadal fat and adipose CD4+CD25+T cells revealed several chemokine signals related to female-specific VAT-Treg accumulation such as CCL24, CCR6, and CXCR3. Taken together, the current study demonstrated sexual dimorphism in VAT-Treg localization in obese mice. Estrogen may attenuate obesity-associated chronic inflammation partly through altering chemokine-related VAT-Treg localization in females.

Usefulness of transanal tube placement for prevention of anastomotic leakage following laparoscopic low anterior resection.

INTRODUCTION: Anastomotic leakage (AL) is a major complication of laparoscopic low anterior resection (LLAR) for rectal cancer. Although several recent reports have suggested that transanal tube placement can prevent AL, this practice is still controversial. Additionally, the mechanism by which a transanal tube prevents AL is unknown. The aim of this study was to evaluate the efficacy of transanal tube placement for prevention of AL following LLAR. METHODS: This was a retrospective study that included 69 patients who underwent LLAR between February 2012 and January 2016. After an anastomosis using a double stapling technique, a transanal tube was placed in 28 patients. A diverting stoma was created in 26 patients. Univariate and multivariate analyses of clinicopathological characteristics were performed. RESULTS: The overall incidence of AL was 15.9% (11/69). Univariate analysis showed that transanal tube placement (P = 0.022) and early postoperative diarrhea (P < 0.001) were associated with AL. The duration of the postoperative hospital stay for patients with transanal tube placement (13.1 ± 4.1 days) was significantly shorter than for patients without a transanal tube (22.7 ± 12.3 days; P < 0.001). However, transanal tube placement did not reduce postoperative diarrhea. Creation of a diverting stoma did not affect the incidence of AL. Multivariate analysis revealed that the absence of a transanal tube (odds ratio = 33.5, P = 0.018) and the occurrence of postoperative diarrhea (odds ratio = 86.3, P = 0.001) were independent risk factors for AL. CONCLUSION: Transanal tube placement prevents AL after LLAR. Furthermore, this protective effect may be due to a reduction in the unfavorable incidence of early postoperative diarrhea.

Teneligliptin improves metabolic abnormalities in a mouse model of postmenopausal obesity.

A decrease in serum estrogen levels in menopause is closely associated with the development of visceral obesity and the onset of type 2 diabetes in women. In the present study, we demonstrated the therapeutic effects of the novel DPP4 inhibitor, teneligliptin, on the features of postmenopausal obesity in mice. In the control group, female C57BL/6 mice were sham-operated and maintained on a standard diet. In the postmenopausal obese group, ovariectomized (OVX) mice were maintained on a high-fat diet, and were referred to as OVX-HF. In the treated group, teneligliptin at 60 mg/kg per day was administrated to OVX-HF, and were referred to as Tene. After a 12-week food challenge, the metabolic phenotypes of these mice were analyzed. Body weight, fat accumulation, and glucose intolerance were greater in OVX-HF than in control, while these abnormalities were markedly improved without alterations in calorie intake in Tene. Teneligliptin effectively ameliorated the characteristics of metabolic abnormalities associated with postmenopausal obesity. Regarding chronic inflammation in visceral adipose tissue, the numbers of F4/80(+)CD11c(+)CD206(-) M1-macrophages in flow cytometry, crown-like structure formation in immunohistochemistry, and proinflammatory cytokine expression were significantly attenuated in Tene. Hepatic steatosis was also markedly improved. Furthermore, decreased energy consumption in the dark and light phases, reduced locomotor activity in the dark phase, and lowered core body temperature in OVX-HF were ameliorated in Tene. Since obesity and reduced energy metabolism are a common physiology of menopause, teneligliptin appears to be beneficial as a treatment for type 2 diabetes in postmenopausal obesity.

K+ excretion: the other purpose for puddling behavior in Japanese Papilio butterflies.

To elucidate the purpose of butterfly puddling, we measured the amounts of Na+, K+, Ca2+, and Mg2+ that were absorbed or excreted during puddling by male Japanese Papilio butterflies through a urine test. All of the butterflies that sipped water with a Na+ concentration of 13 mM absorbed Na+ and excreted K+, although certain butterflies that sipped solutions with high concentrations of Na+ excreted Na+. According to the Na+ concentrations observed in naturally occurring water sources, water with a Na+ concentration of up to 10 mM appears to be optimal for the health of male Japanese Papilio butterflies. The molar ratio of K+ to Na+ observed in leaves was 43.94 and that observed in flower nectars was 10.93. The Na+ amount in 100 g of host plant leaves ranged from 2.11 to 16.40 mg, and the amount in 100 g of flower nectar ranged from 1.24 to 108.21 mg. Differences in host plants did not explain the differences in the frequency of puddling observed for different Japanese Papilio species. The amounts of Na+, K+, Ca2+, and Mg2+ in the meconium of both male and female butterflies were also measured, and both males and females excreted more K+ than the other three ions. Thus, the fluid that was excreted by butterflies at emergence also had a role in the excretion of the excessive K+ in their bodies. The quantities of Na+ and K+ observed in butterfly eggs were approximately 0.50 µg and 4.15 µg, respectively; thus, female butterflies required more K+ than male butterflies. Therefore, female butterflies did not puddle to excrete K+. In conclusion, the purpose of puddling for male Papilio butterflies is not only to absorb Na+ to correct deficiencies but also to excrete excessive K+.

Suspected panosteitis in a crossbred calf.

A male crossbred calf developed a limp and pain upon deep pressure on the right hind limb and the right forelimb. The radiographic findings of affected limbs and pathological findings of bone biopsy were similar to those observed in canine panosteitis. This is the first case of suspected panosteitis reported in cattle.

Panostéite suspectée chez un veau de race croisée. Un veau mâle de race croisée a développé une boiterie et de la douleur à l'application d'une pression profonde sur la jambe arrière droite et la jambe avant droite. Les résultats de la radiographie des membres touchés et les résultats pathologiques d'une biopsie osseuse étaient semblables à ceux observés dans la panostéite canine. Il s'agit du premier cas de panostéite suspectée chez le bétail.(Traduit par Isabelle Vallières).

A case of primary adenocarcinoma of the third portion of the duodenum resected by laparoscopic and endoscopic cooperating surgery.

INTRODUCTION: We report a case of primary adenocarcinoma in the third portion of the duodenum (D3) curatively resected by laparoscopic and endoscopic cooperating surgery (LECS). PRESENTATION OF CASE: A 65-year-old woman had a routine visit to our hospital for a follow-up of rectal cancer resected curatively 2 years ago. A routine screening gastroduodenal endoscopy revealed an elevated lesion of 20mm in diameter in the D3. The preoperative diagnosis was adenoma with high-grade dysplasia; however, suspicion about potential adenocarcinoma was undeniable. Curative resection was performed by LECS. Pathological examination revealed intramucosal adenocarcinoma arising from normal duodenal mucosa. The tumor was stage I (T1/N0/M0) in terms of the tumor, nodes, metastasis (TNM) classification. LECS for duodenal tumor has seldom been reported previously, and this is the first report of LECS for primary adenocarcinoma in the D3. The transverse mesocolon was removed from the head of pancreas to expose the duodenum, and the accessory right colic vein was cut; this was followed by the Kocher maneuver for mobilization of the lesion site. DISCUSSION: LECS enabled en bloc resection with adequate surgical margins and secure intra-abdominal suturing. Thorough mobilization of the mesocolon and pancreas head is essential for this procedure because it facilitates correct resection and suturing. CONCLUSION: LECS is a feasible treatment option for duodenal neoplasms, including intramucosal adenocarcinoma, even though it exists in the D3.

A novel immunochromatographic system for easy-to-use detection of group 1 avian influenza viruses with acquired human-type receptor binding specificity.

A switch of viral hemagglutinin receptor binding specificity from bird-type α2,3- to human-type α2,6-linked sialic acid is necessary for an avian influenza virus to become a pandemic virus. In this study, an easy-to-use strip test to detect receptor binding specificity of influenza virus was developed. A biotinylated anti-hemagglutinin antibody that bound a broad range of group 1 influenza A viruses and latex-conjugated α2,3 (blue) and α2,6 (red) sialylglycopolymers were used in an immunochromatographic strip test, with avidin and lectin immobilized on a nitrocellulose membrane at test and control lines, respectively. Accumulation of a sialylglycopolymer-virus-antibody complex at the test line was visualized by eye. The strip test could be completed in 30min and did not require special equipment or skills, thereby avoiding some disadvantages of current methods for analyzing receptor binding specificity of influenza virus. The strip test could detect the receptor binding specificity of a wide range of influenza viruses, as well as small increases in the binding affinity of variant H5N1 viruses to α2,6 sialylglycans at viral titers >128 hemagglutination units. The strip test results were in agreement with those of ELISA virus binding assays, with correlations >0.95. In conclusion, the immunochromatographic strip test developed in this study should be useful for monitoring potential changes in the receptor binding specificity of group 1 influenza A viruses in the field.

Japanese Papilio butterflies puddle using Na+ detected by contact chemosensilla in the proboscis.

Many butterflies acquire nutrients from non-nectar sources such as puddles. To better understand how male Papilio butterflies identify suitable sites for puddling, we used behavioral and electrophysiological methods to examine the responses of Japanese Papilio butterflies to Na(+), K(+), Ca(2+), and Mg(2+). Based on behavioral analyses, these butterflies preferred a 10-mM Na(+) solution to K(+), Ca(2+), and Mg(2+) solutions of the same concentration and among a tested range of 1 mM to 1 M NaCl. We also measured the ion concentrations of solutions sampled from puddling sites in the field. Na(+) concentrations of the samples were up to 6 mM, slightly lower than that preferred by butterflies in the behavioral experiments. Butterflies that sipped the 10 mM Na(+) solution from the experimental trays did not continue to puddle on the ground. Additionally, butterflies puddled at sites where the concentrations of K(+), Ca(2+), and/or Mg(2+) were higher than that of Na(+). This suggests that K(+), Ca(2+), and Mg(2+) do not interfere with the detection of Na(+) by the Papilio butterfly. Using an electrophysiological method, tip recordings, receptor neurons in contact chemosensilla inside the proboscis evoked regularly firing impulses to 1, 10, and 100 mM NaCl solutions but not to CaCl(2) or MgCl(2). The dose-response patterns to the NaCl solutions were different among the neurons, which were classified into three types. These results showed that Japanese Papilio butterflies puddle using Na(+) detected by the contact chemosensilla in the proboscis, which measure its concentration.

Polo-like kinase 1 regulates cell proliferation and is targeted by miR-593* in esophageal cancer.

Polo-like kinase 1 (PLK1) is overexpressed in various human cancers. However, the biological functions and the post-transcriptional regulations of PLK1 in esophageal cancer (EC) are still unknown. The purposes of our study are to determine whether PLK1 can be a molecular target of EC therapy and to identify a microRNA (miRNA) targeting PLK1. We performed loss-of-function and gain-of-function experiments regarding cell proliferation, cell cycle, apoptosis, in vivo tumor formation and luciferase reporter assays, using siRNAs against PLK1 and miRNA. PLK1 protein was expressed in all 11 EC cell lines, but not in normal esophageal epithelial cells (HEEpiC). Knockdown of PLK1 in EC cells induced G2/M arrest (p < 0.001) in cell cycle assay and reduced cell proliferation (p = 0.019) and tumor formation ability in vivo (p < 0.0001). MiR-593*, identified as a miRNA targeting PLK1 by a database search, was less expressed especially in six EC cell lines than HEEpiC cells. Moreover, miR-593* expression level was inversely correlated with PLK1 mRNA level in 48 clinical tissue specimens of EC (p = 0.006). Introduction of synthetic miR-593* suppressed PLK1 expression by 69-73%, reduced cell proliferation (p = 0.008) and increased cell proportion of G2/M phase (p = 0.01) in HSA/c (an EC cells), whereas a miR-593* inhibitor upregulated PLK1 expression by 11-55%. Additionally, luciferase assay demonstrated that miR-593* interacted two binding sites in the PLK1 3'-UTR and reduced 56.8-71.5% of luciferase activity by degrading luciferase mRNA in HSA/c cells. In conclusion, PLK1 is post-transcriptionally regulated by miR-593* and could be a promising molecular target for EC treatment.

Effects of small interfering RNAs targeting fascin on human esophageal squamous cell carcinoma cell lines.

BACKGROUND: Fascin induces membrane protrusions and cell motility. Fascin overexpression was associated with poor prognosis, and its downregulation reduces cell motility and invasiveness in esophageal squamous cell carcinoma (ESCC). Using a stable knockdown cell line, we revealed the effect of fascin on cell growth, cell adhesion and tumor formation. METHODS: We examined whether fascin is a potential target in ESCC using in vitro and in vivo studies utilizing a specific siRNA. We established a stable transfectant with downregulated fascin from KYSE170 cell line. RESULTS: The fascin downregulated cell lines showed a slower growth pattern by 40.3% (p < 0.01) and detachment from collagen-coated plates by 53.6% (p < 0.01), compared to mock cells, suggesting that fascin plays a role in cell growth by maintaining cell adhesion to the extracellular matrix. In vivo, the tumor size was significantly smaller in the tumor with fascin knockdown cells than in mock cells by 95% at 30 days after inoculation. CONCLUSIONS: These findings suggest that fascin overexpression plays a role in tumor growth and progression in ESCC and that cell death caused by its downregulation might be induced by cell adhesion loss. This indicates that targeting fascin pathway could be a novel therapeutic strategy for the human ESCC.