A Review of Parathyroid Surgery for Primary Hyperparathyroidism from the United Kingdom Registry of Endocrine and Thyroid Surgery (UKRETS).

BACKGROUND: The United Kingdom Registry of Endocrine and Thyroid Surgeons is a national database holding details on > 28,000 parathyroidectomies. METHODS: An extract (2004-2017) of the database was analysed to investigate the reported efficacy, safety and use of intra-operative surgical adjuncts in targeted parathyroidectomy (tPTx) and bilateral neck exploration (BNE) for adult, first-time primary hyperparathyroidism (PHPT). RESULTS: 50.9% of 21,738 cases underwent tPTx. Excellent short-term (median follow-up 35 days) post-operative normocalcaemia rates were reported overall (tPTx 96.6%, BNE 94.5%, p < 0.05) and in image-positive cases (tPTx 96.7%, BNE 96%, p < 0.05). Intra-operative PTH improved overall normocalcaemia rates (tPTx 97.8% vs 96.3%, BNE 95% vs 94.4%: both p < 0.05). Intra-operative nerve monitoring reduced vocal cord (VC) dysfunction in image-positive tPTx, but not in BNE (97.8% vs 93.2%, p < 0.05). Complications were higher following BNE (7.4% vs 3.8%, p < 0.05), especially hypocalcaemia (5.3% vs 2%, p < 0.05). There was no difference in rates of subjective dysphonia following tPTx or BNE (2.4% vs 2.3%, p > 0.05), nor any difference in VC dysfunction when formally examined (4.9% vs 4.1%, p > 0.05). CONCLUSIONS: In image-positive, first time, adult PHPT cases, tPTx is as safe and effective as BNE, with both achieving excellent short-term results with minimal complications.

Kondo-Induced Giant Isotropic Negative Thermal Expansion.

Negative thermal expansion is an unusual phenomenon appearing in only a handful of materials, but pursuit and mastery of the phenomenon holds great promise for applications across disciplines and industries. Here we report use of x-ray spectroscopy and diffraction to investigate the 4f-electronic properties in Y-doped SmS and employ the Kondo volume collapse model to interpret the results. Our measurements reveal an unparalleled decrease of the bulk Sm valence by over 20% at low temperatures in the mixed-valent golden phase, which we show is caused by a strong coupling between an emergent Kondo lattice state and a large isotropic volume change. The amplitude and temperature range of the negative thermal expansion appear strongly dependent on the Y concentration and the associated chemical disorder, providing control over the observed effect. This finding opens avenues for the design of Kondo lattice materials with tunable, giant, and isotropic negative thermal expansion.

Effects of preceding endoscopic treatment on laparoscopic surgery for early rectal cancer.

AIM: Endoscopic treatment for rectal cancer, such as endoscopic mucosal resection and endoscopic submucosal dissection, causes inflammation, oedema and fibrosis in the surrounding tissue. However, little is known about the effect of these endoscopic therapies on salvage laparoscopic rectal surgery. The objective of this retrospective cohort study was to analyse the effect of preceding endoscopic treatment on the outcomes of laparoscopic surgery for rectal cancer. METHOD: We analysed 53 patients who underwent laparoscopic surgery for rectal cancer with clinical Tis or T1 at our department between May 2011 and June 2019. Data from 30 patients who underwent laparoscopic surgery after preceding endoscopic treatment (Group E + S) were compared with those of 23 patients who underwent laparoscopic surgery alone (Group S). RESULTS: There was no significant difference between the groups with respect to preoperative details. The mean operative time tended to be longer in Group E + S, and the volume of intra-operative blood loss was greater in Group E + S than in Group S (median 63 ml vs 10 ml, P = 0.049). There were no significant differences between the groups in other surgical parameters or oncological outcomes. CONCLUSION: Laparoscopic surgery after endoscopic treatment for rectal cancer may be difficult due to an increased risk of intra-operative bleeding. Long-term prognosis after surgery was not affected by preceding endoscopic treatment in rectal cancer.

Vascular anatomy of the splenic flexure, focusing on the accessory middle colic artery and vein.

AIM: Recently, the accessory middle colic artery (AMCA) has been recognized as the vessel that supplies blood to the splenic flexure. However, the positional relationship between the AMCA and inferior mesenteric vein (IMV) has not been evaluated. Herein, we aimed to evaluate the anatomy of the AMCA and the splenic flexure vein (SFV). METHOD: Two hundred and five patients with colorectal cancer who underwent enhanced CT preoperatively were enrolled in the present study. The locations of the AMCA and IMV were evaluated, focusing on the positional relationship between the vessels and pancreas - below the pancreas or to the dorsal side of the pancreas. RESULTS: The AMCA was observed in 74 (36.1%) patients whereas the SFV was found in 177 (86.3%) patients. The left colic artery (LCA) was the major artery accompanying the SFV in 87 (42.4%) of patients. The AMCA accompanied the SFV in 65 (32.7%) patients. In 15 (7.8%) patients, no artery accompanied the SFV. The origin of the AMCA was located on the dorsal side of the pancreas in 15 (20.3%) of these 74 patients. Similarly, the destination of the IMV was located on the dorsal side of the pancreas in 65 (31.7%) of patients. CONCLUSION: The SFV was observed in most patients, and the LCA or AMCA was the common accompanying artery. In some patients these vessels were located on the dorsal side of the pancreas and not below it. Preoperative evaluation of this anatomy may be beneficial for lymph node dissection during left-sided hemicolectomy.

Utility of computed tomography and 18 F-fluorodeoxyglucose with positron emission tomography/computed tomography for distinguishing appendiceal mucocele caused by mucinous adenocarcinoma from other pathologies.

AIM: Differentiating appendiceal mucocele with mucinous adenocarcinoma from other pathologies before surgery is difficult. The objective of this study was to evaluate the utility of CT and 18 F-fluorodeoxyglucose (FDG) with positron emission tomography (PET)/CT for differentiating mucinous adenocarcinoma of appendiceal mucocele from other pathologies. METHOD: The study included 25 patients who underwent surgery for clinically diagnosed appendiceal mucoceles detected on CT at the University of Tokyo Hospital. Among these patients, 19 underwent FDG-PET/CT preoperatively. We compared features of the CT imaging findings and maximum standard uptake values (SUVmax ) detected by FDG-PET/CT between mucocele with mucinous adenocarcinoma and other pathologies. RESULTS: A total of 13 men (52%) and 12 women (48%) were included in this study, with a median age of 65 years (range 34-83). There were six patients (24%) with pathologically confirmed mucinous adenocarcinoma, 15 patients (60%) with appendiceal mucinous neoplasm and four patients (16%) with simple mucocele caused by chronic inflammation. On the CT findings, wall irregularity was the only significant feature for the two groups in this study (83.3% vs 0.0%, P < 0.01). There was a significant difference in the SUVmax levels on PET/CT between the two groups (100.0% vs 20.0%, P < 0.01). CONCLUSION: Distinguishing between mucocele with mucinous adenocarcinoma and other pathologies using imaging modalities is challenging. Our results suggest that wall irregularity on CT and elevated SUVmax on PET/CT are useful factors that can be employed for such discrimination.

Transitions to slow or fast diffusions provide a general property for in-phase or anti-phase polarity in a cell.

Cell polarity is an important cellular process that cells use for various cellular functions such as asymmetric division, cell migration, and directionality determination. In asymmetric cell division, a mother cell creates multiple polarities of various proteins simultaneously within her membrane and cytosol to generate two different daughter cells. The formation of multiple polarities in asymmetric cell division has been found to be controlled via the regulatory system by upstream polarity of the membrane to downstream polarity of the cytosol, which is involved in not only polarity establishment but also polarity positioning. However, the mechanism for polarity positioning remains unclear. In this study, we found a general mechanism and mathematical structure for the multiple streams of polarities to determine their relative position via conceptional models based on the biological example of the asymmetric cell division process of C. elegans embryo. Using conceptional modeling and model reductions, we show that the positional relation of polarities is determined by a contrasting role of regulation by upstream polarity proteins on the transition process of diffusion dynamics of downstream proteins. We analytically prove that our findings hold under the general mathematical conditions, suggesting that the mechanism of relative position between upstream and downstream dynamics could be understood without depending on a specific type of bio-chemical reaction, and it could be the universal mechanism in multiple streams of polarity dynamics of the cell.

Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial.

BACKGROUND: Gemcitabine plus cisplatin (GC) is the standard treatment of advanced biliary tract cancer (BTC); however, it causes nausea, vomiting, and anorexia, and requires hydration. Gemcitabine plus S-1 (GS) reportedly has equal to, or better, efficacy and an acceptable toxicity profile. We aimed to confirm the non-inferiority of GS to GC for patients with advanced/recurrent BTC in terms of overall survival (OS). PATIENTS AND METHODS: We undertook a phase III randomized trial in 33 institutions in Japan. Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable BTC, an Eastern Cooperative Oncology Group Performance Status of 0 - 1, and adequate organ function. The calculated sample size was 350 with a one-sided α of 5%, a power of 80%, and non-inferiority margin hazard ratio (HR) of 1.155. The primary end point was OS, while the secondary end points included progression-free survival (PFS), response rate (RR), adverse events (AEs), and clinically significant AEs defined as grade ≥2 fatigue, anorexia, nausea, vomiting, oral mucositis, or diarrhea. RESULTS: Between May 2013 and March 2016, 354 patients were enrolled. GS was found to be non-inferior to GC [median OS: 13.4 months with GC and 15.1 months with GS, HR, 0.945; 90% confidence interval (CI), 0.78-1.15; P = 0.046 for non-inferiority]. The median PFS was 5.8 months with GC and 6.8 months with GS (HR 0.86; 95% CI 0.70-1.07). The RR was 32.4% with GC and 29.8% with GS. Both treatments were generally well-tolerated. Clinically significant AEs were observed in 35.1% of patients in the GC arm and 29.9% in the GS arm. CONCLUSIONS: GS, which does not require hydration, should be considered a new, convenient standard of care option for patients with advanced/recurrent BTC. CLINICAL TRIAL NUMBER: This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index.htm), number UMIN000010667.

Height-related variations of leaf traits reflect strategies for maintaining photosynthetic and hydraulic homeostasis in mature and old Pinus densiflora trees.

Because tree size and age co-vary, it is difficult to separate their effects on growth and physiological function. To infer causes for age-related height-growth decline, we compared various leaf traits between mature (ca. 100 years) and old (ca. 300 years) trees of Pinus densiflora, having similar heights (ca. 30 m) and growing in the same stand. For many leaf traits, mature and old trees showed similar height-related trends reflecting acclimation to height-related hydraulic limitation for maintaining photosynthetic and hydraulic homeostasis. Photosynthetic capacity was constant within crowns of both age-classes, though 4.9-5.4 µmol CO2 m-2 s-1 lower for old than for mature trees. Biochemical acclimation of photosynthesis, allocating more nitrogen to treetop leaves, was observed only for mature trees. Leaf turgor loss point was also constant within crowns of both age-classes with no significant effect of age on leaf hydraulic traits. In mature trees, leaf capacitance increased, while bulk tissue elastic modulus decreased with height, whereas opposite height-related trends were observed for old trees. For both age-classes, leaf mass per area (LMA), transfusion-tissue area, and xylem area all increased with height, but LMA was ca. 30 g m-2 greater for old than for mature trees. In old trees, mesophyll area decreased with height, suggesting anatomical acclimation to height may negatively affect photosynthetic capacity. We inferred that old trees rely more on morphological than biochemical acclimation and that such post-maturational shift in resource allocation could underlie height-growth decline of P. densiflora after reproductive maturity.

Medial and lateral laxity in knees with advanced medial osteoarthritis.

OBJECTIVE: An increase in coronal laxity is recognized as a risk factor for progression of knee osteoarthritis (OA). The purpose of this study was to evaluate coronal laxity, which was defined as the angular motion from the neutral, unloaded (baseline) position to the loaded position, in patients with advanced medial knee OA. METHOD: Preoperative coronal laxity was assessed using radiographs in patients with medial knee OA undergoing total knee arthroplasty by applying a force of 150 N with an arthrometer. A consecutive series of 211 knees with OA and 40 normal control knees were examined. A knee with OA was defined as clinically "balanced" when the difference between medial and lateral laxity was 3° or less. Values are expressed as median [25th, 75th percentile]. RESULTS: The laxity was 4° [3, 5] from the baseline on the medial side and 3° [2, 4] on the lateral side. The distribution of medial and lateral laxity indicated that 90% (189/211) of patients fell within 3°. The equivalence test showed that the medial and lateral laxity was similar, with an equivalence margin of 3° (P < 0.001). In the control knees, the laxity was 3° [2, 4] from the baseline on the medial side and 2° [2, 4] on the lateral side. The differences between the knees with advanced OA and the controls were significant (P = 0.005, medial; P = 0.006, lateral). CONCLUSION: This study showed that a clinically balanced knee was maintained even in patients with advanced medial knee OA.

Report from the fifth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12-14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon.

The plasmonic properties of gold nanoparticle clusters formed via applying an AC electric field.

An external electric AC field with a field strength ranging from 10 V mm-1 to 30 V mm-1 and a frequency ranging from 0.1 kHz to 1 MHz was applied to suspensions of gold nanoparticles (Au NPs) to control their plasmonic properties. Apparent differences in the UV-vis spectra of the Au NPs were observed between the spectra with and without the field application. The characteristic red color of the Au NP suspension darkened; this suggested that the application of the AC field caused the aggregation of the Au NPs. In addition, the sizes of the Au NP clusters in suspension formed by the AC field application depended on the frequency of the applied field. The surface-enhanced Raman scattering (SERS) effects of Au NP clusters were examined by comparing the difference in Raman intensities obtained at 30 V mm-1 and in a frequency range of 0.1 kHz to 1 MHz. The application of a low-frequency field at 0.1 kHz caused a rapid aggregation of the Au NPs, resulting in low Raman intensities of the probe molecules. Conversely, high-frequency applications between 1 kHz and 1 MHz successfully enhanced the Raman intensities of the molecules in suspension. The strong correlation of the optical/sensing properties with the Au NP clustering states reveals that the application of an AC electric field is a powerful tool for control over the plasmonic properties.

Decision tree analysis for factors associated with dental caries in school-aged children in Japan.

OBJECTIVE: Our study aimed to elucidate the interactive relationship between factors associated with dental caries in school children using decision tree analysis. RESEARCH DESIGN: Cross-sectional study Methods: Participants were recruited from public primary schools (9-12 years, 4th to 6th grade) and junior high schools (12-13 years, 1st grade) in Japan. A total of 1775 students (928 boys and 847 girls) were analyzed. Questionnaire survey, oral examination, and saliva test were performed. Multiple logistic regression and decision tree analysis were performed. RESULTS: Multiple logistic regression showed an association between dental caries and toothpaste use, dental attendance and the presence of Streptococcus mutans. Decision tree analysis showed that students with non-regular dental attendance were at a significantly higher risk of dental caries at the late stage of primary school. At the early stage of primary school, high levels of Streptococcus mutans and male sex were factors associated with dental caries. In students with low levels of Streptococcus mutans, using toothpaste occasionally was associated with a high risk of dental caries. CONCLUSIONS: In early primary school years, S. mutans may be a useful screening and diagnostic tool for dental caries. In students with high levels of S. mutans, sex may be associated with dental caries. Furthermore, in students with low levels of S. mutans, regular use of toothpaste should be encouraged, and in late primary school years, regular dental attendance should be encouraged to prevent dental caries.

Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: randomized phase II trial.

BACKGROUND: Sorafenib (Sor) is acknowledged as a standard therapy for advanced hepatocellular carcinoma (HCC). This trial was conducted to evaluate the effect of addition of hepatic arterial infusion chemotherapy with cisplatin (SorCDDP) to Sor for the treatment of advanced HCC. PATIENTS AND METHODS: We conducted a multicenter open-labeled randomized phase II trial in chemo-naïve patients with advanced HCC with Child-Pugh scores of 5-7. Eligible patients were randomly assigned 2:1 to receive SorCDDP (sorafenib: 400 mg bid; cisplatin: 65 mg/m2, day 1, every 4-6 weeks) or Sor (400 mg bid). The primary end point was overall survival. RESULTS: A total of 108 patients were randomized (Sor, n = 42; SorCDDP, n = 66). The median survival in the Sor and SorCDDP arms were 8.7 and 10.6 months, respectively [stratified hazard ratio (95% confidence interval), 0.60 (0.38-0.96), P = 0.031]. The median time to progression and the response rate were, respectively, 2.8 months and 7.3% in the Sor arm and 3.1 months and 21.7% in the SorCDDP arm. The adverse events were more frequent in the SorCDDP arm than in the Sor arm, but well-tolerated. CONCLUSION: SorCDDP yielded favorable overall survival when compared with Sor in patients with advanced HCC. CLINICAL TRIAL REGISTRATION: UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703.

Ericaceous plant-fungus network in a harsh alpine-subalpine environment.

In terrestrial ecosystems, plant species and diverse root-associated fungi form complex networks of host-symbiont associations. Recent studies have revealed that structures of those below-ground plant-fungus networks differ between arbuscular mycorrhizal and ectomycorrhizal symbioses. Nonetheless, we still remain ignorant of how ericaceous plant species, which dominate arctic and alpine tundra, constitute networks with their root-associated fungi. Based on a high-throughput DNA sequencing data set, we characterized the statistical properties of a network involving 16 ericaceous plant species and more than 500 fungal taxa in the alpine-subalpine region of Mt. Tateyama, central Japan. While all the 16 ericaceous species were associated mainly with fungi in the order Helotiales, they varied remarkably in association with fungi in other orders such as Sebacinales, Atheliales, Agaricales, Russulales and Thelephorales. The ericaceous plant-fungus network was characterized by high symbiont/host preferences. Moreover, the network had a characteristic structure called 'anti-nestedness', which has been previously reported in ectomycorrhizal plant-fungus networks. The results lead to the hypothesis that ericaceous plants in harsh environments can host unexpectedly diverse root-associated fungal taxa, constituting networks whose structures are similar to those of previously reported ectomycorrhizal networks but not to those of arbuscular mycorrhizal ones.

Report from the fourth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmö, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.

Appendiceal orifice inflammation is associated with proximal extension of disease in patients with ulcerative colitis.

AIM: Ulcerative colitis (UC) is considered to be a disease of continuous mucosal inflammation extending proximally from the rectum. However, appendiceal orifice inflammation (AOI) is a skip lesion with segments of continuous involvement from the rectum. The aim of this study was to examine the clinical characteristics and clinical course, particularly focused on proximal extension, of UC in patients with AOI. METHOD: A retrospective evaluation of patients with UC who underwent total colonoscopy at the Department of Surgical Oncology, The University of Tokyo, from 2004 to 2014. The degree of AOI was graded endoscopically as follows: 0 (no inflammation); 1 (slight oedema); 2 (moderate inflammation); and 3 (marked inflammation). A total of 189 patient records were reviewed retrospectively. The presence of AOI was analysed with regard to the clinical information of each patient, and its association with proximal extension of proctitis or left-sided colitis was evaluated. RESULTS: Of 189 patients with UC who underwent total colonoscopy at our institution, 92 were diagnosed with pancolitis, 50 with left-sided colitis and 47 with proctitis. Endoscopic findings of AOI were observed in 26 patients, including 11 (12.0%) with pancolitis, six (12.0%) with left-sided colitis and nine (19.1%) with proctitis. During follow up, proximal extension of the disease occurred in all nine patients with proctitis AOI. CONCLUSION: AOI is more frequently observed in patients with proctitis. Our results showed correlations between AOI and subsequent proximal extension of mucosal inflammation in patients with proctitis.

Clinical pattern and progression of ulcerative proctitis in the Japanese population: a retrospective study of incidence and risk factors influencing progression.

AIM: The rate of extension of proctitis in Western countries has been reported, but no data regarding long-term follow-up have been described for the Japanese population. Additionally, patients with long-standing or extensive ulcerative colitis have an increased risk for developing colorectal cancer. This study evaluated both the rate of extension of the disease and the development of neoplasia among patients with an initial diagnosis of ulcerative proctitis. METHOD: We retrospectively investigated the medical charts of patients with proctitis from 1979 to 2014. The primary focus of this research was the extension of the inflammatory area. The secondary focus included risk factors for disease extension and the development of neoplasia. RESULTS: Sixty-six patients satisfied the inclusion criteria. Proximal extension of the disease occurred in 34 patients: 19 patients had left-sided colitis and 15 had pancolitis. According to a multivariate analysis, disease extension was significantly higher in patients with disease onset before 25 years of age (P-value = 0.043). The cumulative rates of disease extension at 10 and 20 years were 33.8% and 52.2%, respectively. Three patients were diagnosed with dysplasia during follow-up, all of whom experienced disease extension before the development of dysplasia. CONCLUSION: The rate of extension of ulcerative colitis in the Japanese population was comparable to that in Western countries. A younger age of disease onset was associated with disease extension. Extension of proctitis may be associated with an increased risk of colorectal cancer.

Intestinal epithelial culture under an air-liquid interface: a tool for studying human and mouse esophagi.

This study investigated whether an intestinal epithelial culture method can be applied to mouse and human esophageal cultures. The esophagi harvested from 1-day-old mice and adult humans were maintained in collagen gels. A commercially available culture medium for human embryonic stem cells was used for the human esophageal culture. We discovered that the intestinal epithelial culture method can be successfully applied to both mouse and human esophageal cultures. The long-term cultured esophageal organoids were rod-like luminal structures lined with myofibroblasts. We discovered that regeneration of the esophageal mucosal surface can be almost completely achieved in vitro, and the advantage of this method is that organoid cultures may be generated using host-derived fibroblasts as a niche. This method is a promising tool for mouse and human research in intestinal biology, carcinogenesis, and regenerative medicine.

Tumour-suppressive function of SIRT4 in human colorectal cancer.

BACKGROUND: SIRT4, which is localised in the mitochondria, is one of the least characterised members of the sirtuin family of nicotinamide adenine dinucleotide-dependent enzymes that play key roles in multiple cellular processes such as metabolism, stress response and longevity. There are only a few studies that have characterised its function and assessed its clinical significance in human cancers. METHODS: We established colorectal cancer cell lines (SW480, HCT116, and HT29) overexpressing SIRT4 and investigated their effects on proliferation, migration and invasion, as well as E-cadherin expression, that negatively regulates tumour invasion and metastases. The associations between SIRT4 expression in colorectal cancer specimens and clinicopathological features including prognosis were assessed by immunohistochemistry. RESULTS: SIRT4 upregulated E-cadherin expression and suppressed proliferation, migration and invasion through inhibition of glutamine metabolism in colorectal cancer cells. Moreover, SIRT4 expression in colorectal cancer decreased with the progression of invasion and metastasis, and a low expression level of SIRT4 was correlated with a worse prognosis. CONCLUSIONS: SIRT4 has a tumour-suppressive function and may serve as a novel therapeutic target in colorectal cancer.