Can serum endoglin be used to improve the diagnostic performance in prostate cancer?

PURPOSE: New biomarkers may contribute to avoid unnecessary biopsies resulting from the suboptimal performance of prostate-specific antigen (PSA) testing. This study aimed to assess serum endoglin as a prostate cancer (PCa) diagnostic tool among biopsy candidates. METHODS: A total of 262 consecutive patients referred for prostate biopsy based on abnormal digital rectal examination and/or elevated total PSA (tPSA) who had serum endoglin assessed by solid-phase enzyme-linked immunosorbent assay were selected. Receiver operating characteristic curves were used to compare the predictive accuracy of different combinations of biomarkers to distinguish between PCa and benign prostatic conditions, and to identify cut-offs that maximize the ability of endoglin to rule out patients for biopsy (highest sensitivities). RESULTS: Serum endoglin levels were higher in patients with PCa (median: 7.86 vs. 5.88 pg/mL, P < 0.001). Among patients with baseline tPSA ≤ 10 ng/mL the area under the curve was 0.69 for endoglin. Approximately one-quarter of the patients had serum endoglin < 4.92 ng/mL (sensitivity: 90.3%; specificity: 32.8%), and the probability of PCa varied from 37.7% before testing to 15.2% among those with low endoglin levels [negative predictive value (NPV) = 84.8%]. When restricting the analyses to patients with free/total PSA ratio > 0.25, the probability of cancer was less than 5% among those with serum endoglin < 6.04 ng/mL (sensitivity: 93.8%; specificity: 56.1%), corresponding to a NPV of 95.8%; this could allow sparing approximately 40% of patients from biopsy. CONCLUSIONS: Serum endoglin may be useful in clinical practice to distinguish between PCa and non-cancer patients among prostatic biopsy candidates.

Life cycle of Amblyomma mixtum (Acari: Ixodidae) parasitizing different hosts under laboratory conditions.

Amblyomma mixtum is a tick species in the Amblyomma cajennense complex. The known geographic range of A. mixtum extends from Texas in the USA to western Ecuador and some islands in the Caribbean. Amblyomma mixtum is a vector of disease agents of veterinary and public health importance. The objective of this study was to describe the life cycle of A. mixtum under laboratory conditions. Bovines, rabbits and sheep were infested with larvae, nymphs, and adult ticks under controlled conditions to assess several biological parameters. Eggs, larvae, nymphs and adults were kept in an incubator (27 °C temperature and 80% relative humidity) when they were off the host. The average life cycle of A. mixtum was 88 and 79 days when fed on rabbits and cattle, respectively. Sheep were found to be unsuitable because no ticks attached. The rabbit is a more practical host to maintain a colony of A. mixtum under laboratory conditions. The data from this study can be considered as an example for the life cycle of A. mixtum. However, caution must be exercised when making comparisons to the biology of A. mixtum in its natural habitat.

Reticulons bind sphingolipids to activate the endoplasmic reticulum cell cycle checkpoint, the ER surveillance pathway.

The inheritance of a functional endoplasmic reticulum (ER) is ensured by the ER stress surveillance (ERSU) pathway. Here, we made the unexpected discovery that reticulon 1 (Rtn1) and Yop1, well-known ER-curvature-generating proteins, each possess two sphingolipid-binding motifs within their transmembrane domains and that these motifs recognize the ER-stress-induced sphingolipid phytosphingosine (PHS), resulting in an ER inheritance block. Upon binding PHS, Rtn1/Yop1 accumulate on the ER tubule, poised to enter the emerging daughter cell, and cause its misdirection to the bud scars (i.e., previous cell division sites). Amino acid changes in the conserved PHS-binding motifs preclude Rtn1 or Yop1 from binding PHS and diminish their enrichment on the tubular ER, ultimately preventing the ER-stress-induced inheritance block. Conservation of these sphingolipid-binding motifs in human reticulons suggests that sphingolipid binding to Rtn1 and Yop1 represents an evolutionarily conserved mechanism that enables cells to respond to ER stress.

Prostate cancer treatment in Portugal: a nationwide analysis.

Different treatment options exist for localized prostate cancer. Treatments performed in high-volume hospitals are associated with better results. Our objective was to describe time trends in prostate cancer treatments in Portugal and case volume per hospital. We used the national database of diagnosis-related group of the Portuguese Central Administration of the Health System to describe the number of radical prostatectomy (RP), brachytherapy (BT) and external radiotherapy (eRT) treatments performed in all National Health System hospitals. There was a rapid increase in the annual number of RP until 2006 and then a deceleration; BT treatments augmented significantly until 2011. The utilization of eRT also increased, surpassing RP after 2010. From the 46 hospitals performing RP, only eight had a case-volume > 50 treatments/year, and from the nine hospitals performing BT, only four accomplished > 15 treatments/year. In the 11 hospitals with eRT, nine performed > 50/year. Regarding RP, there was negative correlation between the hospital volume and length of stay (r = - 0.303; p = 0.041). In the Portuguese National Health Service there was a steep increase in the number of prostate cancer treatments, and there is an ample margin for concentration of RP and BT treatments, for improvement of the hospitals case volume.

Synergy between highly dispersed Ni nanocrystals and graphitized carbon derived from a single source as a strategy for high performance Lithium-Sulfur batteries.

Due to their higher energy density, lower prices, and more environmentally friendly active components, Li-S batteries will soon compete with the current Li-ion batteries. However, issues persist that hinder this implementation, such as the poor conductivity of S and sluggish kinetics due to the polysulfide shuttle, among others. Herein, Ni nanocrystals encapsulated in a C matrix are obtained by a novel strategy based on the thermal decomposition of a Ni oleate-oleic acid complex at low-to-moderate temperatures: 500 and 700 °C. The two C/Ni composites were employed as hosts in Li-S batteries. Although the C matrix is amorphous at 500 °C, it is highly graphitized at 700 °C. At this moderate temperature, the simultaneous generation of Ni nanocrystals and the carbon matrix enhances the catalytic activity of Ni toward the graphitization process, which is negligible if starting from a mixture of a Ni salt and carbon source, even when calcined at temperatures as high as 1000 °C. The electrode made from the C/Ni composite obtained at 700 °C exhibits a high reversible capacity and an enhanced rate capability, much better not only than the C/Ni composite obtained at 500 °C but than others based on amorphous C calcined at very high temperatures, around 1000 °C. These properties are attributed to an increase in the electrical conductivity parallel to the ordering of the layers. We believe this work provides a new strategy to design C-based composites capable of combining the formation of nanocrystalline phases and the control of the C structure with superior electrochemical properties for Li-S batteries.

Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue.

BACKGROUND: Periprostatic (PP) adipose tissue surrounds the prostate, an organ with a high predisposition to become malignant. Frequently, growing prostatic tumor cells extend beyond the prostatic organ towards this fat depot. This study aimed to determine the genome-wide expression of genes in PP adipose tissue in obesity/overweight (OB/OW) and prostate cancer patients. METHODS: Differentially expressed genes in human PP adipose tissue were identified using microarrays. Analyses were conducted according to the donors' body mass index characteristics (OB/OW versus lean) and prostate disease (extra prostatic cancer versus organ confined prostate cancer versus benign prostatic hyperplasia). Selected genes with altered expression were validated by real-time PCR. Ingenuity Pathway Analysis (IPA) was used to investigate gene ontology, canonical pathways and functional networks. RESULTS: In the PP adipose tissue of OB/OW subjects, we found altered expression of genes encoding molecules involved in adipogenic/anti-lipolytic, proliferative/anti-apoptotic, and mild immunoinflammatory processes (for example, FADS1, down-regulated, and LEP and ANGPT1, both up-regulated). Conversely, in the PP adipose tissue of subjects with prostate cancer, altered genes were related to adipose tissue cellular activity (increased cell proliferation/differentiation, cell cycle activation and anti-apoptosis), whereas a downward impact on immunity and inflammation was also observed, mostly related to the complement (down-regulation of CFH). Interestingly, we found that the microRNA MIRLET7A2 was overexpressed in the PP adipose tissue of prostate cancer patients. CONCLUSIONS: Obesity and excess adiposity modified the expression of PP adipose tissue genes to ultimately foster fat mass growth. In patients with prostate cancer the expression profile of PP adipose tissue accounted for hypercellularity and reduced immunosurveillance. Both findings may be liable to promote a favorable environment for prostate cancer progression.

Hph1 and Hph2 are novel components of the Sec63/Sec62 posttranslational translocation complex that aid in vacuolar proton ATPase biogenesis.

Hph1 and Hph2 are homologous integral endoplasmic reticulum (ER) membrane proteins required for Saccharomyces cerevisiae survival under environmental stress conditions. To investigate the molecular functions of Hph1 and Hph2, we carried out a split-ubiquitin-membrane-based yeast two-hybrid screen and identified their interactions with Sec71, a subunit of the Sec63/Sec62 complex, which mediates posttranslational translocation of proteins into the ER. Hph1 and Hph2 likely function in posttranslational translocation, as they interact with other Sec63/Sec62 complex subunits, i.e., Sec72, Sec62, and Sec63. hph1Δ hph2Δ cells display reduced vacuole acidification; increased instability of Vph1, a subunit of vacuolar proton ATPase (V-ATPase); and growth defects similar to those of mutants lacking V-ATPase activity. sec71Δ cells exhibit similar phenotypes, indicating that Hph1/Hph2 and the Sec63/Sec62 complex function during V-ATPase biogenesis. Hph1/Hph2 and the Sec63/Sec62 complex may act together in this process, as vacuolar acidification and Vph1 stability are compromised to the same extent in hph1Δ hph2Δ and hph1Δ hph2Δ sec71Δ cells. In contrast, loss of Pkr1, an ER protein that promotes posttranslocation assembly of Vph1 with V-ATPase subunits, further exacerbates hph1Δ hph2Δ phenotypes, suggesting that Hph1 and Hph2 function independently of Pkr1-mediated V-ATPase assembly. We propose that Hph1 and Hph2 aid Sec63/Sec62-mediated translocation of specific proteins, including factors that promote efficient biogenesis of V-ATPase, to support yeast cell survival during environmental stress.

Tick fauna in non-anthropogenic areas in Mato Grosso do Sul, Brazil, with the presence of the Rickettsia parkeri strain Atlantic rainforest in Amblyomma ovale.

The aim of this study was to evaluate tick fauna and identify the possible presence of Rickettsia spp. in ticks of the genus Amblyomma from two environmental preservation areas in different regions of Mato Grosso do Sul state, Brazil. CO2 traps, visual observation and cloth dragging were used to capture ticks. Three hundred ticks were submitted to the hemolymph test, and samples that showed organisms morphologically compatible with Rickettsia were used for rickettsial DNA detection by PCR. DNA was extracted using guanidine-phenol isothiocyanate, and the primers CS78 and CS323 were used for PCR, which amplified a 401-base pair fragment of the citrate synthase (gltA) gene. If positive, the DNA sample was tested by primers Rr190.70p and Rr190.602n that produce a 530 bp amplicon of the ompA gene that is present only in rickettsiae of the spotted fever group. A total of 1,745 adult ticks were collected, including 1,673 specimens of Amblyomma sculptum, 63 of Amblyomma coelebs, five of Amblyomma naponense and four of Amblyomma ovale. Thirteen ticks of the species A. ovale, A. coelebs and A. sculptum showed structures compatible with Rickettsia inside the hemocytes; after DNA extraction, the presence of Rickettsia spp. in a sample of A. ovale was confirmed by PCR in both analyzed fragments. In the sequencing analysis, 100% identity for the Rickettsia parkeri strain Atlantic rainforest was obtained according to GenBank. The two environmental preservation areas showed A. sculptum as the predominant species, as well as the presence of marked seasonality for this species. This paper is the first report of the R. parkeri strain Atlantic rainforest in A. ovale ticks in the state of Mato Grosso do Sul, Brazil.

Regulation of the early stages of endoplasmic reticulum inheritance during ER stress.

The endoplasmic reticulum (ER) is one of the largest cytoplasmic organelles in eukaryotic cells and plays a role in many cellular processes, such as the production and quality control of secretory protein, lipid synthesis, and calcium homeostasis. The ER cannot be generated de novo, and thus its proper inheritance during cell division is paramount to the health and survival of the daughter cells. Although previous work has uncovered the cytoskeletal components involved, we still lack a comprehensive understanding of the intricate steps of and the cytoplasmic and membrane-bound components involved in ER inheritance. To directly address these issues, we utilized microfluidics and genetic analyses to show that before nuclear migration, early ER inheritance can be further divided into three distinctive steps. Moreover, we demonstrated that perturbing each of these steps affects the cell's ability to mitigate ER stress. Thus, proper ER inheritance is essential to ensuring a healthy, functional cell.

Horse welfare at slaughter: A novel approach to analyse bruised carcasses based on severity, damage patterns and their association with pre-slaughter risk factors.

The study presents a novel veterinary forensic approach to analyse the bruising of horse carcasses, based on the nature of the bruises and how they are grouped in certain anatomical areas. Data on pre-slaughter logistics was obtained for 113 journeys with horses that travelled from Mexico and the USA to a Mexican abattoir. We found that carcass bruising was a highly prevalent problem (79% of carcasses had bruising) and was especially problematic in journeys lasting longer than 12 h, independently of the animal's country of origin, sex, age, lairage time or vehicle type. Multivariable logistic regression showed that the most severe bruises were not dispersed randomly on the carcass and that their distribution was associated with the presence of medium-sized bruises on the abdominal wall, front and rear limb. Cluster analysis suggested four damage patterns based on bruise location: severe and concentrated bruising, as well as non-severe bruises on the rear limb, thoracic-wall or more dispersed throughout the carcass.

Vascular endothelial growth factor (VEGF) and prostate pathology.

PURPOSE: Previous studies suggest that vascular endothelial growth factor (VEGF) circulating levels might improve identification of patients with prostate cancer but results are conflicting. Our aim was to compare serum VEGF levels across different prostate pathologies (including benign prostatic hyperplasia, prostatitis, high grade prostate intraepithelial neoplasia and prostate cancer) in patients at high risk of prostate cancer. MATERIALS AND METHODS: We consecutively enrolled 186 subjects with abnormal digital rectal examination and/or total PSA (tPSA) > or = 2.5 ng/mL. Blood was collected before diagnostic ultrasound guided trans-rectal prostate biopsy, or any prostate oncology treatment, to measure PSA isoforms and VEGF. Unconditional logistic regression was used to compute age-, tPSA- and free/total PSA-adjusted odds ratios (OR) and respective 95% confidence intervals (95% CI) for the association between serum VEGF and different prostatic pathologies. RESULTS: Prostate biopsy main diagnoses were normal or benign prostatic hyperplasia (27.3%), prostatitis (16.6%), and prostatic cancer (55.0%). The median VEGF levels (ng/mL) in these groups were 178.2, 261.3 and 266.4 (p = 0.029), respectively, but no significant differences were observed for benign vs. malignant pathologies (215.2 vs. 266.4, p = 0.551). No independent association was observed between VEGF (3rd vs. 1st third) and prostate cancer, when compared to benign conditions (adjusted OR = 1.44; CI 95%: 0.64-3.26). CONCLUSIONS: In patients at high risk of prostate cancer, circulating VEGF levels have no clinical role in deciding which patients should be submitted to prostate biopsy. Prostatitis patients, often with higher PSA levels, also present high serum levels of VEGF, and their inclusion in control groups might explain the heterogeneous results in previous studies.

Prostate cancer screening in Portugal: prevalence and perception of potential benefits and adverse effects.

INTRODUCTION: Opportunistic screening for prostate cancer has been widely used, though organized programs are not recommended. We aimed to estimate the prevalence of prostate cancer screening and the perception of potential benefits and harms of screening, among the Portuguese general population. METHODS: A representative sample of Portuguese-speaking inhabitants in mainland Portugal was selected, using a stratified probabilistic sampling procedure; men above 40 were considered for analysis (n = 414). Data on sociodemographic characteristics, lifetime use and usual frequency of prostate cancer screening (prostate-specific antigen test or digital rectal examination) and perception of potential benefits and adverse effects of cancer screening were assessed using face-to-face interviews, by structured questionnaire. RESULTS: The proportion of participants who reported having been submitted to prostate cancer screening at least once in their lifetime was 44.2% (95% confidence interval: 37.5-51.0; 13.8% only digital rectal examination, 12.2% only prostate-specific antigen test, and 18.2% digital rectal examination and prostate-specific antigen test). As potential benefits of cancer screening, the options "knowledge of not having the disease", "earlier detection" and "more effective treatment" were selected by 55.8%, 12.9% and 31.3% of the participants, respectively. Regarding potential adverse effects, the most and least frequently identified were 'anxiety while waiting for the results' (55.1%) and 'false negatives' (38.0%), respectively. CONCLUSIONS: Almost half of the men between 40 and 79 years old declared that they have been screened for prostate cancer. Nearly one-third of the participants considered that reassurance of a negative result was the main potential benefit of screening, whereas most failed to identify the most frequent adverse effects.

Evidence of acaricide resistance in different life stages of Amblyomma mixtum and Rhipicephalus microplus (Acari: Ixodidae) collected from the same farm in the state of Veracruz, Mexico.

The objectives of this study were to evaluate the resistance of Amblyomma mixtum and Rhipicephalus microplus ticks from co-infested bovines from the Veracruz region in Mexico to different acaricide families and to demonstrate the viability of the packet test on different A. mixtum instars. The following acaricide families were used: a combination (cypermethrin 15 g + chlorpyrifos 25 g + citronella 1 g + butoxide piperonyl 15 g), amidine (formamidine 12.5 g), pyrethroid (cypermethrin 15 g), and organophosphate (dichlorvos 60 g + chlorpyrifos 20 g). Regarding the packet test in both species, resistance was found for the pyrethroid and amidine families in A. mixtum and R. microplus, as efficacy did not surpass 40 %, including in immature instars; regarding the adult immersion test in R. microplus, the efficacy was 93.3 % for the amidine family and 26.2 % for the pyrethroid family. The proposed methodology is an alternative technique to optimize resistance detection in immature ticks with a heteroxenous life cycle.

Welfare of horses from Mexico and the United States of America transported for slaughter in Mexico: Fitness profiles for transport and pre-slaughter logistics.

Every year thousands of horses from Mexico and the United States of America (USA) are transported to slaughter in Mexico, but little is known about their welfare or pre-slaughter logistics. In this study, we recorded the origin, sex, age and condition of horses (121 journeys, 2648 animals) upon arrival to an abattoir in northern Mexico, including transport details. Horse welfare was measured indirectly via individual scores for body condition, coat quality, lameness, ocular and nasal discharge, as well as reactivity to a chute restraint test, all performed shortly after unloading. The average journey duration was 9.69 (±7.6) hours for horses from Mexico and 16.77 (±4.51) hours for horses from the USA (77 % of all journeys). The prevalence of ocular discharge, nasal discharge, skin wounds, lameness and diarrhoea, were 23 %, 12 %, 11 %, 9 %, 1 % (respectively) of all the horses observed, with no significant differences between Mexican and American horses (P ≥ 0.05). During the chute test the American horses were calmer than the Mexican ones (P < 0.001), who were more restless and aggressive (P = 0.001). Likewise, vocalizations in their three variants during the restraint, neigh/whinny (P = 0.018), nicker (P < 0.001), and snort (P = 0.018), were more common in horses from Mexico. In order to help characterize fitness for transport, a two-step cluster analysis was applied using the welfare indicators, suggesting the existence of four clusters (C) evaluated on arrival at the abattoir (from good to very poor fitness): good (profile C4, n = 769, 29.1 %), average (profile C1, n = 799 horses, 30.2 %), poor (profile C3, n = 586, 22.1 %) and very poor (profile C2, n = 494, 18.6 %). In fact, the C4 best welfare group had 0% lame, 0% nasal discharge, 16.4 % ocular discharge, 7.9 % skin wounds. Instead, the C2 poorest welfare group had 45.8 % lame, 61.1 % nasal discharge, 42.8 % ocular discharge, and 19.9 % skin wounds. Results show potential for using nasal discharge, lameness and ocular discharge as key indicators of horse fitness and welfare on abattoir. The study provides detailed scientific data to help establish strategies regarding optimal days of recovery post-transport and fattening for homogenization of weights between animals of different origins, logistic planning, and optimization of logistic resources to minimize the biological cost of long-distance transport.

Intermediate-term results, up to 4 years, of a bone-anchored male perineal sling for treating male stress urinary incontinence after prostate surgery.

OBJECTIVE: To examine the intermediate-term outcome (up to 4 years) of a bone-anchored perineal sling (InVance(TM), American Medical Systems, Minnetonka, MN, USA) in men with stress urinary incontinence (SUI) after prostate surgery. PATIENTS AND METHODS: In all, 62 men with SUI were implanted with the InVance sling. SUI was diagnosed after radical prostatectomy in 58 patients and after benign prostatic hyperplasia (BPH) prostatectomy in four patients. Implantation of the InVance bone-anchored bulbourethral sling was conducted primarily under spinal anaesthesia. Patients were considered cured, if they stopped wearing continence pads and improved if the daily number of pads used decreased by at least half. The Incontinence Quality of Life questionnaire and a simple verbal question about patient satisfaction with the surgery were also used and complications were measured. RESULTS: In all, 40 patients (65%) were cured and 14 (23%) were improved after a mean follow-up of 28 months. The UI cure rates at 3 and 4 years follow-up were 70% and 66%, respectively. The most common side-effect was transient scrotal or perineal pain or numbness, which affected 12 patients (19%). There was a prolonged postvoid residual urine volume of >100 mL in six patients (10%), which resolved within 2 weeks of indwelling catheterization. Explantation of the sling was required in two cases (3%) because of infection. In one patient (2%), revision was required for bone-anchor dislodgement. CONCLUSION: The InVance sling offers good intermediate-term cure and improvement rates for SUI after prostatectomy. The procedure has an acceptably low rate of minor complications, and should be considered for treating men with less severe forms (< or =5 pads per day) of SUI.

Genetic polymorphism in EGF is associated with prostate cancer aggressiveness and progression-free interval in androgen blockade-treated patients.

PURPOSE: Most prostate cancer patients develop resistance to androgen deprivation treatment, resulting in hormone resistance. Epidermal growth factor (EGF) activates several pro-oncogenic intracellular pathways inducing proliferation, differentiation, and tumorigenesis in epithelial cells. The EGF-EGF receptor pathway seems to be especially relevant in hormone-resistant prostate cancer stage. A single nucleotide polymorphism G>A in +61 locus of EGF gene has been described, in which A homozygous carriers express significantly less EGF protein compared with G allele carriers. Our purpose was to investigate the potential prognostic and predictive role of EGF functional genetic variant +61 G>A in prostate cancer patients submitted to androgen blockade therapy (ABT). EXPERIMENTAL DESIGN: We conducted a case-control study in prostate cancer patients treated with ABT (n = 123) and in healthy controls without evidence of cancer (n = 152). Cumulatively, a follow-up study (median follow-up, 37 months) was undertaken to evaluate response to ABT therapy in prostate cancer patients. EGF +61 G>A genotypes were detected by PCR-RFLP. RESULTS: We found increased risk in G carriers, after age-adjusted regression analysis, for being diagnosed with Gleason > or =7 and with metastatic disease compared with control group (CG; age-adjusted odds ratio, 3.37, P = 0.004 and age-adjusted odds ratio, 2.61, P = 0.043, respectively). Kaplan-Meier survival analysis and log-rank test showed an influence of EGF +61 G>A polymorphism in time to relapse during ABT (P = 0.018). CONCLUSIONS: EGF functional polymorphism may contribute to earlier relapse in ABT patients, supporting the involvement of EGF as an alternative pathway in hormone-resistant prostatic tumors. Furthermore, our results lend support to EGF-EGF receptor pathway as an additional therapeutic target during hormonal treatment.

Hepatoid adenocarcinoma of the stomach - a different histology for not so different gastric adenocarcinoma: a case report.

Hepatoid adenocarcinoma is an extrahepatic tumor characterized by morphological similarities to hepatocellular carcinoma. Hepatoid adenocarcinoma of the stomach is a cancer with an extremely poor prognosis with few cases reported. Here, we describe a 75-year-old Spanish man referred to our hospital with a history of abdominal pain, general fatigue, anorexia and sickness. Initial study revealed anemia, and computed tomography scan and abdominal ultrasonography showed multiple metastases to the liver with hepatocellular carcinoma characteristics in a liver with no cirrhotic change. Further study included a serum level of alpha-fetoprotein (AFP), which resulted markedly elevated, and a conclusive esophagogastroduodenoscopy describing an elevated tumour growing through the cardia and gastroesophageal junction with foci of necrosis and haemorrhage. Gastric biopsies of the tumor revealed poorly differenciated adenocarcinoma, with hepatoid differentiation. After a diagnosis of AFP-producing hepatoid adenocarcinoma of the stomach with multiple liver metastases was made, pallitive total gastrectomy, without liver resection, was performed. Patient recovered well after surgery, and entered into a palliative systemich chemotherapy protocol. Although this illness is recognized as having poor prognosis, the patient remains alive 8 months after the operation. Accurate diagnosis of hepatoid adenocarcinoma of the stomach is important, and should be suspected under certain circumstances. We describe this rare case of hepatoid adenocarcinoma of the stomach, and review the literature concerning the clinicopathological aspects.

Transfer of the Septin Ring to Cytokinetic Remnants in ER Stress Directs Age-Sensitive Cell-Cycle Re-entry.

During cell division, the inheritance of a functional endoplasmic reticulum (ER) is ensured by the endoplasmic reticulum stress surveillance (ERSU) pathway. Activation of ERSU causes the septin ring to mislocalize, which blocks ER inheritance and cytokinesis. Here, we uncover that the septin ring in fact translocates to previously utilized cell division sites called cytokinetic remnants (CRMs). This unconventional translocation requires Nba1, a negative polarity regulator that normally prevents repolarization and re-budding at CRMs. Furthermore, septin ring translocation relies on the recruitment and activation of a key ERSU component Slt2 by Bem1, without activating Cdc42. Failure to transfer all septin subunits to CRMs delays the cell's ability to re-enter the cell cycle when ER homeostasis is restored and hinders cell growth after ER stress recovery. Thus, these deliberate but unprecedented rearrangements of cell polarity factors during ER stress safeguard cell survival and the timely cell-cycle re-entry upon ER stress recovery.

Early distant relapse after optimal local control in locally advanced rectal cancer.

We present a case of locally advanced rectal cancer with initial optimal local control after neoadjuvant concurrent chemoradiotherapy followed by surgery; early liver recurrence then occurred and was treated again with curative intent with neoadjuvant combination chemotherapy followed by liver surgery. We reflect on this difficult problem and discuss relevant topics to this case report.