bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Neuronal Nuclear and Perikaryal Size in the Medial Mamillary Nucleus of Vascular Dementia and Alzheimer’s Disease Patients: Relation to Nuclear Estrogen Receptor α
Authors: Ishunina Tatjana A. , Bogolepova Irina N. , Swaab Dick F.
Published: July 2019

Background: The hypothalamic medial mamillary (MMN) and the tuberomamillary (TMN) nuclei are important hubs in memory circuits. Previous studies determining the neuronal Golgi complex size showed decreased metabolic activity of the TMN neurons in both Alzhei­mer’s disease (AD) and vascular dementia (VD), and no obvious decline in the MMN of these patients. Objectives: In the present study, we aimed at determining whether other morphometric parameters that are informative about the neuronal metabolic activity are changed in the MMN of AD and VD patients and whether they can be related to the expression of the nuclear estrogen receptor α (ERα) that can mediate neurotrophic effects of estrogens in the brain. Method: The size of neuronal nuclei and perikarya was determined in AD, VD, and nondemented control patients, in relation to the expression of the nuclear ERα. Results: We found that neuronal nuclear and perikaryal sizes were significantly larger in the MMN in VD than in control patients (p < 0.01). Neuronal nuclei (p < 0.05), but not perikarya were larger in AD than in control patients. Neuronal nuclei and perikarya were larger if nuclear ERα staining was present. The intensity of ERα in the neuronal nuclei was significantly correlated with both nuclear and perikaryal sizes (p < 0.007). Conclusions: The human MMN shows a remarkable activation in aging and extra activation in dementias (AD and VD) that may be mediated by nuclear ERα. This makes it so far a unique brain area to study compensatory mechanisms that may prevent neurodegeneration.
Systemic Succinate, Hypoxia-Inducible Factor-1 Alpha, and IL-1β Gene Expression in Autosomal Dominant Polycystic Kidney Disease with and without Hypertension
Authors: Kocyigit Ismail , Taheri Serpil , Eroglu Eray , Sener Elif Funda , Zararsız Gokmen , Uzun Ilknur , Tufan Esra , Mehmetbeyoglu Ecmel , Korkmaz Bayramov Kezban , Sipahioglu Murat Hayri , Ozkul Yusuf , Tokgoz Bulent , Oymak Oktay , Axelsson Jonas
Published: July 2019

Background and Objectives: Cyst pressure induces renin-angiotensin-aldosterone system activation and kidney hypoxia in autosomal dominant polycystic kidney disease (ADPKD). Lipopolysaccharide-induced Toll-like receptor activation causes metabolic disturbances that are triggered by increased succinate levels and hypoxia inducible factors, which results in inflammation via IL-1β activation. Since we aimed to investigate the role of both inflammation and hypoxia in the clinical course of ADPKD, via succinate levels from sera samples, HIF-1α gene expression from whole blood and urine samples and IL-1βgene expression from whole blood were measured. Methods: One hundred ADPKD patients and 100 matched healthy controls were enrolled to this cross-sectional study. Twenty-four-hour ambulatory blood pressure monitoring was conducted in all participants. Blood, serum, and urine samples were taken after 12-h fasting for the measurement of biochemical parameters and succinate levels. Whole blood and urine samples were used for HIF-1α and IL-1β geneexpression by using quantitative real-time PCR. Results: There were significant differences in whole blood HIF-1α, IL-1β geneexpression, and serumsuccinate levels between the ADPKD patients and the control subjects. Whole blood HIF-1αgene expression, IL-1β geneexpression, and serumsuccinate levels were also significantly different in ADPKD patients with hypertension in comparison with normotensive ones (p < 0.05). Serum succinate levels and blood IL-1β geneexpression were increased in ADPKD patients with high levels of HIF-1α geneexpression (p = 0.018 and p = 0.029, respectively). Conclusions: Increased age,low eGFR, and HIF-1α and IL-1β geneexpressions were also independently associated with hypertension in ADPKD patients. Inflammation and hypoxia are both relevant factors that might be associated with hypertension in ADPKD.
Prognostic Value of Pretreatment Lymphocyte-to-Monocyte Ratio in Non-Small Cell Lung Cancer: A Meta-Analysis
Authors: Wang Yan , Huang Dong , Xu Wen-Ying , Wang Yan-Wen , Che Guo-Wei
Published: July 2019

Past evidence has shown that lymphocyte-to-monocyte ratio (LMR) could be considered as a potential prognostic factor in non-small cell lung cancer (NSCLC). We conducted the current meta-analysis based on published studies to elucidate the prognostic value of pretreatment LMR on survival outcomes in NSCLC. Comprehensive searches of available electronic databases were implemented to identify potentially related studies that focused on the role of pretreatment LMR in predicting the prognosis of NSCLC patients. The hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the association of pretreatment LMR with overall survival (OS) and progression-free survival (PFS). A total of 20 articles including 8,304 patients were analyzed. Compared with patients with higher LMR, patients with lower LMR had poorer OS (HR = 1.63, 95% CI: 1.44–1.85, p < 0.001) and PFS (HR = 1.49, 95% CI: 1.25–1.77, p < 0.001). The subgroup analysis outcomes were similar to the overall analysis. Pretreatment LMR may be a useful prognostic marker in patients with NSCLC. However, more well-designed studies are warranted to confirm our findings.
Impact of B-Cell–Targeted Therapies on Cardiovascular Disease
Authors: Porsch Florentina , Binder Christoph J.
Published: July 2019

Atherosclerosis is a lipid-driven chronic inflammatory disease that is modulated by many immune cell subsets, including B cells. Therefore, targeting the inflammatory component of cardiovascular disease represents a promising therapeutic strategy. In the past years, immunotherapy has revolutionized the treatment of autoimmunity and cancer. Many of these clinically used strategies target B cells. Given the multifaceted role of B cells in atherogenesis, it is conceivable that B-cell–directed therapies can modulate disease development. Here, we review clinically available B-cell–targeted therapies and the possible benefits or detrimental effects on cardiovascular disease.
Rheb (Ras Homolog Enriched in Brain 1) Deficiency in Mature Macrophages Prevents Atherosclerosis by Repressing Macrophage Proliferation, Inflammation, and Lipid Uptake
Authors: Zhang Qinghai , Hu Jie , Wu Yan , Luo Hairong , Meng Wen , Xiao Bo , Xiao Xianzhong , Zhou Zhiguang , Liu Feng
Published: July 2019

Objective:

Macrophage foam cell formation is an important process in atherosclerotic plaque development. The small GTPase Rheb (Ras homolog enriched in brain 1) regulates endocytic trafficking that is critical for foam cell formation. However, it is unclear whether and how macrophage Rheb regulates atherogenesis, which are the focuses of the current study.

Approach and Results:

Immunofluorescence study confirmed the colocalization of Rheb in F4/80 and Mac-2 (galectin-3)–labeled lesional macrophages. Western blot and fluorescence-activated cell sorting analysis showed that Rheb expression was significantly increased in atherosclerotic lesions of atherosclerosis-prone (apoE
−/−
[apolipoprotein E deficient]) mice fed with Western diet. Increased Rheb expression was also observed in oxidized LDL (low-density lipoprotein)–treated macrophages. To investigate the in vivo role of macrophage Rheb, we established mature Rheb
mKO
(macrophage-specific Rheb knockout) mice by crossing the Rheb floxed mice with
F4/80-cre
mice. Macrophage-specific knockout of Rheb in mice reduced Western diet–induced atherosclerotic lesion by 32%, accompanied with a decrease in macrophage content in plaque. Mechanistically, loss of Rheb in macrophages repressed oxidized LDL–induced lipid uptake, inflammation, and macrophage proliferation. On the contrary, lentivirus-mediated overexpression of Rheb in macrophages increased oxidized LDL–induced lipid uptake and inflammation, and the stimulatory effect of Rheb was suppressed by the mTOR (mammalian target of rapamycin) inhibitor rapamycin or the PKA (protein kinase A) activator forskolin.

Conclusions:

Macrophage Rheb plays important role in Western diet–induced atherosclerosis by promoting macrophage proliferation, inflammation, and lipid uptake. Inhibition of expression and function of Rheb in macrophages is beneficial to prevent diet-induced atherosclerosis.
Weibel-Palade Bodies Orchestrate Pericytes During Angiogenesis
Authors: Cossutta Mélissande , Darche Marie , Carpentier Gilles , Houppe Claire , Ponzo Matteo , Raineri Fabio , Vallée Benoit , Gilles Maud-Emmanuelle , Villain Delphine , Picard Emilie , Casari Caterina , Denis Cécile , Paques Michel , Courty José , Cascone Ilaria
Published: July 2019

Objective

Weibel-Palade bodies (WPBs) are endothelial cell (EC)-specific organelles formed by vWF (von Willebrand factor) polymerization and that contain the proangiogenic factor Ang-2 (angiopoietin-2). WPB exocytosis has been shown to be implicated for vascular repair and inflammatory responses. Here, we investigate the role of WPBs during angiogenesis and vessel stabilization.

Approach and Results

WPB density in ECs decreased at the angiogenic front of retinal vascular network during development and neovascularization compared with stable vessels. In vitro, VEGF (vascular endothelial growth factor) induced a VEGFR-2 (vascular endothelial growth factor receptor-2)-dependent exocytosis of WPBs that contain Ang-2 and consequently the secretion of vWF and Ang-2. Blocking VEGF-dependant WPB exocytosis and Ang-2 secretion promoted pericyte migration toward ECs. Pericyte migration was inhibited by adding recombinant Ang-2 or by silencing Ang-1 (angiopoietin-1) or Tie2 (angiopoietin-1 receptor) in pericytes. Consistently, in vivo anti-VEGF treatment induced accumulation of WPBs in retinal vessels because of the inhibition of WPB exocytosis and promoted the increase of pericyte coverage of retinal vessels during angiogenesis. In tumor angiogenesis, depletion of WPBs in vWF knockout tumor-bearing mice promoted an increase of tumor angiogenesis and a decrease of pericyte coverage of tumor vessels. By another approach, normalized tumor vessels had higher WPB density.

Conclusions

We demonstrate that WPB exocytosis and Ang-2 secretion are regulated during angiogenesis to limit pericyte coverage of remodeling vessels by disrupting Ang-1/Tie2 autocrine signaling in pericytes.
Free-living nematode assemblages in the rhizosphere of watermelon plants in Nigeria: a baseline study
Authors: Bello Tesleem T. , Coyne Danny L. , Fourie Hendrika
Published: July 2019

Watermelon is increasingly produced and consumed in Nigeria and sub-Saharan Africa. However, limited information exists regarding nematode pests and beneficial/free-living nematodes associated with the crop. The present study recorded the abundance and diversity of free-living nematodes from 50 watermelon fields across south-west Nigeria during 2016/2017. Of the 30 genera identified from soil samples, Cephalobus, followed by Rhabditis, Aphelenchus and Aporcelaimus, were predominant. Variation in nematode community structures across the 50 fields was apparent for mean maturity indices, metabolic footprints, feeding-type composition and coloniser-persister (c-p) structure. Faunal analyses characterised 52% of the fields as having stable and enriched soil food webs, which is beneficial for crop production. Significant correlations were apparent between some nematode genera and selected soil properties, and rainfall. This study provides the first information of free-living nematodes associated with watermelon from sub-Saharan Africa, offering novel and baseline information on their abundance and diversity in south-west Nigeria.
Herbiphantes Tanasevitch, 1992 and Labullinyphia van Helsdingen, 1985 (Araneae, Linyphiidae), two newly recorded spider genera from the Gaoligong Mountains in China with the description of two new species
Authors: IRFAN MUHAMMAD , PENG XIANJIN
Published: July 2019

Herbiphantes Tanasevitch, 1992 and Labullinyphia van Helsdingen, 1985 are two genera for the first time in China. Two new species,  Herbiphantes acutalis n. sp. (male, female) and Labullinyphia furcata n. sp. (male, female), are described from Gaoligong Mountains, Yunnan. Detailed morphological description of both new species, habitus photos, copulatory organs, line drawings of copulatory organs, as well as the locality map are provided.
Global Ocean Extreme Wave Heights from Spatial Ensemble Data
Authors: Takbash Alicia , Young Ian R.
Published: July 2019

A novel approach to estimation of extreme value ocean significant wave height is investigated, in which data from adjacent regions are pooled to form a spatial ensemble. The equivalent duration of this ensemble region is the sum of the durations of the data pooled to form the ensemble. To create such a spatial ensemble, data from regions to be pooled must be independent and identically distributed. ERA-Interim reanalysis data are used to investigate the requirement of independent and identically distributed data on a global basis. As a result, typical spatial ensembles are defined for a number of regions of the world and the 100-yr return period significant wave height is calculated for these regions. It is shown that the method can result in a reduction in the confidence interval for such extreme value estimates of between 30% and 60%. The method is demonstrated both with ERA-Interim data and altimeter data.
Advocacy Research on Homophobia in Education: Claims-Making, Trauma Construction and the Politics of Evidence
Authors: McCormack Mark
Published: July 2019

Sociology has an ambivalent relationship with advocacy research because the benefits of participation and engagement must be balanced with concerns about bias. The current study uses 10 recent research reports on homophobia in British educational settings, written and funded by campaigning charities, as a case study of contemporary advocacy research. Presenting a sociological analysis of these documents and adopting a social problems approach, claims-making processes in the reports are documented and significant methodological and analytical flaws are identified. Instead of objective research, these reports are campaigning documents that seek to gain media coverage and influence policy. Implications for how the reports should be used as resources for research and social policy are examined, and a more nuanced and sophisticated approach to engaging with advocacy research is called for.
Structural design and performance characterization of stable helical auxetic yarns based on the hollow-spindle covering system
Authors: Chen Junli , Du Zhaoqun
Published: July 2019

Helical auxetic yarns (HAYs) spun by ring spinning have a large residual torque, which restricts their application. To address this problem, the hollow-spindle covering system was adopted to prepare structurally stable HAYs consisting of the core yarn and the wrap yarn. Four types of HAYs were manufactured, and a self-designed automatic stretching device was prepared for recording the alteration of yarn diameter. These as-fabricated yarns were measured and characterized in terms of their deformation behavior and auxetic performance. The strain–stress curves of these HAYs have two peaks corresponding to their respective two component yarns during stretch until completely failure, and also it was found that the wrap component is always broken before the core yarn. By comparison, the maximum negative Poisson's ratio (NPR) of −2.55 was achieved with as-prepared HAYs composed of spandex and stainless steel monofilaments. Meanwhile, the structural stability of these yarns was discussed with respect to the residual torque, and the experimental results indicate that the residual torque of these HAYs is obviously smaller than that of conventional ring-spun yarns. These confirm the superiority of our proposed hollow-spindle method. Furthermore, the effects of the diameter of the core yarn and tensile modulus of the wrap yarn on the auxetic behavior were systematically investigated. It is found that a larger NPR can be obtained with a thicker diameter of core yarn and a higher tensile modulus of wrap yarn. It is also demonstrated that an appropriate combination of the component modulus and geometric parameters is essential to fabricate HAY with an obvious auxetic behavior.
Experiences from a Data-informed Approach to Configuring Online Assignments
Authors: Orchard Ryan K.
Published: July 2019

Learning management systems (LMS) allow for a variety of ways in which online multiple-choice assessments (“tests”) can be configured, including the ability to allow for multiple attempts and options for which of and how the attempts will count. These options are usually chosen according to the instinct of the instructor; however, LMS also provide an opportunity to make data-informed decisions based on data captured by the LMS itself. This article describes an experience with extracting and analyzing LMS data for determining online test option settings that encourage behaviors that promote learning (or discourage behaviors that do not). The data extraction and cleaning process was relatively straightforward, but not without some challenges, and required beyond-novice spreadsheet skills. It seems to have been worth the effort, though, as the insights gained led directly to a change in online test administration, and current option settings seem more appropriate and are supported by data.
Geochemical characteristics of fluorine in coal within Xiangning mining area, China, and associated mitigation countermeasures
Authors: Guohua Lin , Qiyan Feng , Xiaoli Deng , Yahong Cui , Wenbo Li , Hui Wang , Bo Gao , Lai Zhou , Xin Wang
Published: July 2019

The geochemical characteristics of fluorine in coal obtained from 534 borehole exploration data and mining test data from the Xiangning mining area were studied, and fluorine emissions were calculated. Results reveal that the fluorine content in Carboniferous-Permian coal in the mining area ranges from 2.00 to 911.00 mg/kg, and the Carboniferous coal seam contents are generally higher than those of the Permian system. The calculated average fluorine contents in Nos. 5 and 12 coal seams of the Carboniferous system are 203.42 and 308.00 mg/kg, respectively, and therefore, both are high-fluorine coal. In addition, the calculated mean fluorine contents of Nos. 2 and 10 coal seams are 168.58 and 187.02 mg/kg, respectively, which are higher than average value of Chinese and global coal values. The highest fluorine content of 896.00 mg/kg is found in medium- to high-fluorine coal. Fluorine in coal mainly exists in an inorganic bound state in forms such as fluorapatite and calcium fluoride. The Xiangning Coal Mine predominantly produces coal for coking and power, and the release of fluorine during coal combustion is harmful to the environment. According to the information obtained in relation to coal resource reserves and development planning, the amount of fluorine released from combustion is estimated at 2258.1 t/year and is estimated to reach 4862.9 t/year by 2020. Coal washing is an effective way of reducing fluorine emissions, and flotation experiments have shown that this can reduce the amount of fluorine by up to 30–47%. Different engineering measures, such as denitrification and desulfurization, can also significantly reduce the amount of fluorine released during coal combustion and can thus be employed to reduce the associated environmental impacts.
Assessing the Collective Impact of Community Health Programs Funded by Food and Beverage Companies: A New Community-Focused Methodology
Authors: Barata-Cavalcanti Olivia , Leung May May , Costa Sergio , Mateo Katrina F. , Guillermin Michelle , Palmedo P. C. , Crossley Rachel , Huang Terry T.-K.
Published: July 2019

Aims

We developed and pilot-tested a new methodology to evaluate the collective impact (CI) of food and beverage company-funded community-based programs aimed at improving nutrition and physical activity.

Methods

The Collective Impact Community Assessment Scale assesses programs across 14 dimensions. Five community programs funded by five companies participated in the testing of this tool. Qualitative data were collected through in-person key informant interviews, focus groups, and direct observations of program activities. Eight interviews/focus groups (representing program management, delivery staff, participants, and community champions) were selected in each program for review and analysis using a scoring system with preestablished anchors and algorithms. Raw scores ranged on a scale from 0 to 8 for each dimension and were standardized as percentages. Dimension scores were averaged to generate a total composite score.

Results

Total composite scores of CI for programs ranged from 63% to 89%. The CI dimensions that scored the highest were backbone infrastructure (median = 94%, range = 88%–100%) and common agenda (median = 91%, range = 59%–97%). All programs scored lower on dimensions related to their ability to impact funding flows (median = 47%, range = 34%–94%), cultural norms (median = 69%, range = 34%–88%), and advocacy and public policy (median = 56%, range = 25%–69%).

Conclusion

Variability in CI approach scores demonstrates the tool’s ability to differentiate the impact of a wide range of programs across multiple dimensions. The CI Community Assessment Scale provides a common metric platform to compare different community-based initiatives.
Participant Engagement and Ethical Digital Storytelling: The MOCHA Moving Forward Study
Authors: Gubrium Aline C. , Lowe Sarah , Douglas Henry , Scott Lamont , Buchanan David
Published: July 2019

African-American men continue to bear a disproportionate share of the burden of health disparities, in general, and chronic diseases, in particular. The Men of Color Health Awareness (MOCHA) Moving Forward study seeks to determine the effectiveness of an innovative, community-driven program to improve the health and quality of life of low-income African-American men between the ages of 35 to 70 years by reducing identified social risk factors for chronic disease for these men. The project uses digital storytelling (DST) to encourage African-American men to tell their stories, especially related to stress, gender role stereotypes, and mental and physical health and well-being. Thirty-six men were recruited to participate in one of four DST workshops, which resulted in each participant creating a 2- to 3-minute digital story. In this article, we describe and analyze three salient ethical dilemmas that arose in conducting the Men of Color Health Awareness Moving Forward study DST workshops with African-American men. The dilemmas can be traced to the distinct purposes for which DST can be used, data collection or intervention development, and the trade-offs between protecting and patronizing participants. We discuss potential ways to resolve or circumvent the identified issues.
Minimally invasive treatment of calcaneal fracture
Authors: Zhang Guangming , Ding Shenglong , Ruan Zhiyong
Published: July 2019

Objective

This study was performed to analyze the outcomes of calcaneal fractures using a minimally invasive internal fixation method with a thin plate and bone grafting.

Methods

This retrospective analysis included 21 patients treated using our minimally invasive approach. The outcome measures were the change in the Bohler and Gissane angles and the calcaneus width after fixation. The clinical outcomes were evaluated by the Maryland foot scoring system and assessment of soft tissue complications.

Results

The follow-up time was 12 to 18 months. The Bohler angle, Gissane angle, and width of the calcaneus were significantly different between the preoperative and postoperative periods. The rate of excellent and good outcomes was 85.7% according to the Maryland foot scoring system. The incidence of soft tissue complications was 14.3%.

Conclusion

Treatment of calcaneal fractures using a minimally invasive internal fixation method with a plate and bone grafting provides good to excellent clinical outcomes with few soft tissue complications.
Hepatic Arterial Infusion Chemotherapy in Sarcoma Liver Metastases: A Report of 6 Cases
Authors: Melichar Bohuslav , Vobořil Zbyněk , Nožička Jan , Cerman Jaroslav , Melicharová Karolina , Mergancová Jindřiška , Filip Stanislav , Krajina Antonín , Vobořil René , Jandík Pavel
Published: July 2019

Aims and background

Liver metastases in patients with sarcoma are rare and associated with a poor prognosis. The experience with liver-directed therapies, eg hepatic arterial infusion, in these patients is limited.

Methods

Six patients with sarcoma metastatic to the liver (4 patients with gastrointestinal stromal tumors and 2 patients with leiomyosarcoma) were treated by hepatic arterial infusion in our center over a 12-year period. Since the experience was limited, a pooled analysis of reports with data on survival of 22 individual patients was performed.

Results

None of the 5 assessable patients responded to the therapy, and liver metastases progressed in all patients. The median survival was 20 months. In the pooled analysis, partial response was observed in 10 of 21 assessable patients (48%) and median survival was 20 months. The survival was significantly longer in responding patients compared to nonresponders (35 vs 14 months; logrank test, P= 0.009).

Conclusions

Hepatic arterial infusion has little efficacy in the treatment of sarcoma metastatic to the liver. More promising results have been reported for chemoembolization. The survival of responding patients seems to be better compared to non-responders.
False Negative Bone Scintigraphy in a Patient with Primary Breast Cancer: A Possible Transient Phenomenon of Bisphosphonate (Alendronate) Treatment
Authors: Demirkan Binnaz , Başkan Zuhal , Alacacıoğlu Ahmet , Görken İknur Bilkay , Bekiş Recep , Ada Emel , Osma Emine , Alakavuklar Mehmet
Published: July 2019

Breast cancer is the most common cancer and the second leading cause of cancer deaths among women in developed countries. Bone is a frequent site of metastatic disease with a stage-dependent incidence. Most women with breast cancer are at risk of osteoporosis due to their age or their breast cancer treatment. Scintigraphy enables imaging of the entire skeleton with high sensitivity but limited specificity. The false positive rate varies from 1.6% to as high as 22%, while the false negative rate varies from 0.96% to 13%.

We observed a 70-year-old woman with a diagnosis of breast cancer and a false negative bone scan despite extensive bone metastases. She was under alendronate treatment for osteoporosis at the time. The false negative finding might be due to a transient phenomenon of alendronate, a bisphosphonate cleared from the plasma by uptake into bone and by renal excretion. 99mTc-MDP is eliminated via the same pathways, and therefore competition may occur between the two substances. Another possible explanation for the false negative bone scan could be that bone metastases, indicating hematogenous tumor spread, are detected earlier by CT scan or MRI than by bone scan. Breast cancer patients under bisphosphonate treatment for osteoporosis must be carefully evaluated for bone metastasis during radionuclide studies with 99mTc-MDP.
What is the Optimal Number of Lymph Nodes to be Dissected in Colorectal Cancer Surgery?
Authors: Gumus Mahmut , Yumuk Perran Fulden , Atalay Gul , Aliustaoglu Mehmet , Macunluoglu Beyza , Dane Faysal , Caglar Hale , Sengoz Meric , Turhal Serdar
Published: July 2019

Background

Regional lymph node (LN) involvement in colorectal cancer (CRC) identifies the stage and the subset of patients who would benefit from adjuvant chemotherapy. We performed a retrospective analysis to determine if the number of recovered LNs was associated with long-term outcome in patients operated on for stage II and III CRC.

Patients and methods

Hospital records of 179 patients with CRC followed in our unit from 1997 to April 2003 were reviewed.

Results

On average 11.68 ± 7.3 LNs were sampled per surgical specimen. Sampling of at least nine LNs appeared to be the minimum number required for accurately predicting LN involvement ( P = 0.002). Three-year rates of disease-free survival (DFS), local recurrence-free survival (LRFS) and overall survival (OS) were lower in patients with fewer than nine LNs sampled ( P = 0.032, P = 0.006 and P = 0.04, respectively). However, this had no impact on the three-year distant metastasis-free survival rate (DMFS) ( P = 0.472). In stage II disease, patients with nine or more LNs dissected had significantly higher three year DFS and LRFS rates than the subgroup with fewer than nine LNs dissected ( P = 0.024 and P = 0.015, respectively), but this did not have any effect on DMFS or OS ( P = 0.406 and P = 0.353, respectively).

Conclusion

Current protocols provide adjuvant treatment in stage III patients; the problem is to correctly determine stage by recovering as many LNs as possible.
Analysis of Metastatic Involvement of Interpectoral (Rotter's) Lymph Nodes Related to Tumor Location, Size, Grade and Hormone Receptor Status in Breast Cancer
Authors: Vrdoljak Danko Velimir , Ramljak Vesna , Mužina Dubravka , Šarčeviç Božena , Knežević Fabijan , Juzbašić Stjepan
Published: July 2019

Aims and background

This study was aimed at analyzing metastatic involvement in interpectoral (Rotter's) lymph nodes in relation to tumor location, size, grade and hormone receptor status in primary breast cancer.

Methods

The study included 172 female patients undergoing surgery for breast cancer at the University Hospital for Tumors, Zagreb, Croatia from November 2001 to August 2003. In addition to the standard surgical procedure, interpectoral (Rotter's) lymph nodes were removed in all of the patients. Serum levels of the tumor marker CA 15-3 were determined before surgery and hormone receptor status after surgery.

Results

Rotter's lymph nodes were identified in 67% of the patients, with metastatic involvement being found in 20% of the Rotter's nodes. Metastatic involvement of Rotter's nodes in patients with negative and positive axillary lymph nodes was 4% and 35%, respectively. When we looked at the location of the tumor in patients with metastatic involvement of Rotter's nodes, we found that tumors located in the upper quadrants were more prone to metastasis to Rotter's nodes; there was a significant positive correlation between tumor location and positive Rotter's nodes (r = 0.953, P = 0.012). As regards tumor size, Rotter's nodes were identified in 15%, 20% and 30% of stage T1 (<2 cm), T2 (2-5 cm) and T3 (>5 cm) tumors, respectively. Hormone receptor status showed no statistically significant difference in the expression of estrogen and progesterone receptors between patients with and those without positive Rotter's nodes. Of 35 Rotter's node-positive patients, 31.4% had elevated serum levels of CA 15-3; the level was significantly higher in Rotter's-positive patients compared to those with negative (or absent) Rotter's nodes.

Conclusions

The results show that one-fifth of breast cancer patients, or even one-third of those with positive axillary lymph nodes, are discharged with positive interpectoral lymph nodes that remain undiagnosed. As the nodes can be surgically removed without additional mutilation, exploration of Rotter's lymph nodes should be introduced into routine clinical practice.
Locally Advanced Breast Cancer in the Elderly: Curettage Mastectomy
Authors: Solej Mario , Ferronato Marco , Nano Mario
Published: July 2019

Aims and background

Locally advanced breast tumor represents 5–20% of new cases diagnosed every year. The purpose of this study was to report our experience and to compare it with the literature.

Methods

From 1998 to 2003 at the Molinette Hospital in the Turin University Third Division of General Surgery, there were 34 cases of breast cancer in older women (between 70 and 94 years of age), 14 of which (41.18%) were locally advanced breast tumor. We evaluated the type of surgical intervention and anesthesia used, muscular invasion, the presence of receptors positive to estrogens and progesterone, the operative mortality, the percentage of local-regional recurrence, and relapses after a period of time.

Results

Among the patients with locally advanced breast tumor, 21.43% (3/14) were at stage MIA and 78.57% (11/14) at stage IIIB. In 14.29% (2/14) of the cases, Patey's radical mastectomy was performed, in 57.14% (8/14) Halsted's radical mastectomy, and in 28.57% (4/14) a simple mastectomy with the removal of the fascia of the major pectoral muscle. Three (21.43%) patients underwent a second intervention for local-regional disease. None of the patients had distant metastasis in the first 2 years after the operation. Mortality after 2 years was 23.1% (3/13). None of the patients who underwent surgery had adjuvant therapy, usually because it was refused by the patients themselves or their families. All the negative and positive hormone receptor patients received tamoxifen.

Conclusions

Locally advanced breast tumors are frequent in elderly women. In the past, there has been a tendency to surgical under-treatment. As regards locally advanced breast tumor, curettage operations represent the only possibility to improve the quality of life of the elderly. These should be performed after carefully evaluating a series of variables in the general and local condition of the patient, the aggressiveness of the intervention and the life expectancy.
Potential Prognostic Significance of p185HER2 Overexpression with Loss of PTEN Expression in Gastric Carcinomas
Authors: lm Seock-Ah , Lee Kyung Eun , Nam Eunmi , Kim Do Yeun , Lee Joo-Ho , Han Ho-Seong , Seoh Ju-Young , Park Hae-Young , Cho Min-Sun , Han Woon Sup , Lee Soon Nam
Published: July 2019

Aims and Background

The HER2 gene encodes a 185-kd transmembrane glycoprotein receptor (p185HER2) that has partial homology with the epidermal growth factor receptor and shares intrinsic tyrosine kinase activity. The phosphatase and tensin homolog mutated on chromosome ten (PTEN) gene product is a protein tyrosine phosphatase that participates in modulating the phosphoinositide 3-kinase pathway which has antagonizing activity to protein tyrosine kinase. The authors investigated the correlation between clinicopathologic variables including survival and the overexpression of the p185HER2 with loss of PTEN expression in gastric adenocarcinoma patients.

Methods

The protein expression of p185HER2 and PTEN was examined by immunohistochemical stain in paraffin-embedded tissues of 94 (M:F, 52:42) gastric adenocarcinoma patients by using monoclonal antibody, and the results were related to clinicopathological variables and survival.

Results

p185HER2 overexpression correlated positively with lymph node metastasis, distant metastasis, AJCC classification, higher relapse rate. Patients with overexpression of p185HER2 were found to have significantly lower disease-free survival ( P = 0.003) and overall survival ( P = 0.0004). Loss of PTEN expression correlated positively with depth of invasion (T stage) and was more frequent in the advanced stage. The patient group with p185HER2 overexpression and loss of PTEN expression showed significantly shorter disease-free and overall survival ( P = 0.03, P = 0.01) than the other groups.

Conclusions

Our observations suggest potential prognostic significance of p185HER2 overexpression with PTEN loss in gastric adenocarcinoma patients. This opens up the possibility of considering p185HER2 and PTEN as a therapeutic target in gastric cancer.
Serum Markers and Prognosis in Locally Advanced Breast Cancer
Authors: Martínez-Trufero Javier , de Lobera Abigail Ruíz , Lao Juan , Puértolas Teresa , Artal-Cortés Angel , Zorrilla Mirian , Alonso Vicente , Pazo Roberto , Valero M. Ignacia , Ríos-Mitchell M. José , Calderero Verónica , Herrero Ana , Antón Antonio
Published: July 2019

Background

Locally advanced breast cancer (LABC) represents a heterogeneous subgroup of breast cancer with an often dismal outcome. Identifying prognostic factors has acquired great significance for the selection of optimal treatment in individual patients.

Methods

Between January 1993 and December 1997, 103 patients were treated in our institution with multimodality treatment consisting of neoadjuvant chemotherapy followed by surgery, adjuvant chemotherapy and radiotherapy; tamoxifen was added in hormone receptor-positive cases. In the search for prognostic factors well-established parameters (clinical, pathological and treatment-related) as well as new features with potential value (c-erbB-2, baseline serum levels of CA 15.3 and CEA) were included in the univariate and multivariate analysis.

Results

At a median follow-up of 92 months (range, 8-130), the estimated five-year cancer-specific overall survival (OS) and disease-free survival (DFS) were 71.34% and 57.7%, respectively. Among the 22 different variables studied, only 10 were significantly correlated with OS and DFS. In multivariate analysis five retained independent prognostic value for both OS and DFS: tumor grade, serum markers, features of inflammatory breast cancer (IBC), response to neoadjuvant chemotherapy and lymph node status. With cutoff values of 35 U/mL for CA 15.3 and 5 ng/mL for CEA, the probability of five-year OS (Cox hazard ratio 3.91, P = 0.0009) and DFS (Cox hazard ratio 2.40, P = 0.02) decreased from 78% to 52% and from 68% to 47%, respectively, when at least one of these markers was abnormal.

Conclusions

Baseline serum levels of CEA and CA 15.3 emerged from this study as strong independent predictors of outcome in LABC, whose value adds to other established prognostic factors such as postoperative nodal status, IBC, histological grade and response to neoadjuvant chemotherapy.
Adjuvant Treatment of High-risk Adult Soft Tissue Sarcomas: A Survey by the Italian Sarcoma Group
Authors: Frustaci Sergio , Berretta Massimiliano , Comandone Alessandro , Bidoli Ettore , De Paoli Antonino , Gherlinzoni Franco , De Pas Tommaso , Barbieri Enza , Pertici Maurizio , Apice Gaetano , Picei Piero
Published: July 2019

Aims and Background

After the first adjuvant study on adult soft tissue sarcomas was concluded, the participating institutions continued to select and treat patients according to that protocol. The aim of this study was to test the protocol reproducibility when applied as a standard practice.

Methods

A call for retrospective data was launched in June 1999 (self-referral of consecutive unregistered patients); thereafter, a prospective follow-up was performed. The treatment regimen consisted of epirubicin (60 mg/m2 days 1 and 2), ifosfamide (3 g/m2/die for 3 days) and equimolar doses of 6-mercapto-ethansulfonate (MESNA), with 300 μg G-CSF administered subcutaneously from day +8 until recovery, every 3 weeks for a total of 5 cycles.

Results

From November 1996 to June 1999, 55 high-risk, adult patients were treated. The average median dose intensity was 89% of the planned program. Grade 3-4 toxicities were leukopenia (49%), thrombocytopenia (14%), transfusion requiring anemia in 7 patients (16%), and alopecia in all patients (100%). After a median follow-up of 70 months, 23 patients (41.8%) relapsed and 19 died. Median disease-free, local disease-free and overall survival rates have not yet been reached. The disease-free survival rates at 2 and 4 years were 73% and 57%, respectively; the corresponding overall survival rates were 91% and 70%, respectively.

Conclusions

The feasibility and reproducibility of the original protocol were confirmed, since disease-specific overall survival and disease-free survival rates at the same period of observation and with the same prolonged follow-up did not differ.
Downregulation of Epstein-barr Virus-Encoded Latent Membrane Protein-1 by Arsenic Trioxide in Nasopharyngeal Carcinoma Cells
Authors: Du Caiwen , Wen Bogui , Li Derui , Lin Yingcheng , Zheng Yuwu , Peng Xun , Hong Chaoqun , Chen Jiongyu , Lin Wen , Hong Xi , Xie Liangxi , Wu Mingyao
Published: July 2019

Aims and Background

It was documented that nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) and that EBV-encoded latent membrane protein-1 expression (LMP1) plays an important role in the pathogenesis of NPC. In preclinical studies, arsenic trioxide (As2O3) has been identified as a promising anticancer agent for treatment of NPC. The purpose of this study is to investigate if this agent can inhibit the expression of LMP1 and therefore lead to growth inhibition of NPC cells in vitro.

Methods

LMP1-positive NPC cells, HNE1-LMP1, were treated with 3 umol/L of As2O3 for 96 hours. The LMP1 protein expression and mRNA level in HNE1-LMP1 cells were determined by western blot, confocal immunofluorescence staining and semiquantitative reverse transcriptase reaction (RT-PCR). Apoptosis was determined by light microscopy and the TUNEL method. Alterations in the cell cycle distribution were also investigated by flow cytometry. MTT assay and colony formation assay were used to detect the proliferation of the cells. The LMP1-negative parental cell lines HNE1 and HNE2 were used as control in an attempt to elucidate the role of LMP1 in the anticancer effect of As2O3 on NPC cells.

Results

The expression of LMP1 at the protein and mRNA level was reduced after exposure to 3 umol/L As2O3. This dose of As2O3 significantly induced apoptosis and growth retardation of HNE1-LMP1 cells. In addition, more HNE1-LMP1 cells were induced to G0/G1 and G2/M arrest. The same dose of As2O3 had a moderate effect on HNE1 and HNE2 cells.

Conclusion

Arsenic trioxide can inhibit LMP1 expression and dictate apoptosis and alterations of cell cycle distribution as well as growth retardation. LMP1-positive NPC cells are more sensitive to As2O3 treatment than LMP1-negative NPC cells.
Dna Methylation in Esophageal Diseases Including Cancer: Special Reference to hMLH1 Gene Promoter Status
Authors: Vasavi Mohan , Ponnala Shivani , Gujjari Kusumanjali , Boddu Prabhakar , Bharatula Ravi Shankar , Prasad Rupender , Ahuja Yog Raj , Hasan Qurratulain
Published: July 2019

Aims and Background

Chronic inflammation leading to malignancy in the esophagus may be due to errors in mismatch repair (MMR) genes such as hMLH1. Promoter hypermethylation has been suggested as the main cause of hMLH1 silencing. In this study we assessed hMLH1 promoter hypermethylation in a range of esophageal diseases. Further, we evaluated the role of factors affecting the methylation cycle: (1) methyt-enetetrahydrofolate reductase (MTHFR) C677T mutation and (2) serum homocysteine levels.

Methods

We endoscopically and histologically categorized 124 paired tissue and blood samples from patients into cancer, precancer, reflux esophagitis, other inflammatory esophagitis and controls (endoscopically normal). Restriction enzyme-based methylation analysis was carried out to assess hMLH1 promoter hypermethylation.

Results and Conclusions

hMLH1 promoter hypermethylation in tissue was seen in 63.5% of patients with cancer and 53.8% of those with precancer, which was significantly increased when compared with controls (P <0.001). There appears to be an increasing degree of hMLH1 hypermethylation with disease progression. Patients with gastroesophageal reflux disease (GERD) showed a high degree of hMLH1 hypermethylation (88.8%), indicating that local environment due to reflux may be promoting hypermethylation. We suggest that GERD is a progressive condition with an increased risk for developing into cancer. Only 14.5% of cases exhibited hypermethylation both in tissue and blood. Hence, we conclude that hMLH1 promoter hypermethylation is a tissue-specific change in the esophagus and blood testing cannot be used as a noninvasive tool to assess it. DNA methylation is dependent on the methylation cycle; MTHFR is a major enzyme in this pathway. MTHFR mutations did not correlate with hypermethylation or clinical pathology (P >0.5). Elevated homocysteine levels, independent of MTHFR mutation, correlated significantly with hMLH1 hypermethylation in tissue (P <0.005). Our study shows that hMLH1 hypermethylation in tissue may be the primary event caused by endogenous/exogenous factors in esophageal diseases, aiding disease progression.
Radioprotective Activity of Naturally Occurring Organosulfur Compounds
Authors: Chittezhath Manesh , Kuttan Girija
Published: July 2019

The radioprotective effects of naturally occurring sulfur compounds and isothiocyanates such as diallyl sulfide (DAS), diallyl disulfide (DADS), allyl methyl sulfide (AMS), allyl isothiocyanate (AITC) and phenyl isothiocyanate (PITC) have been investigated in whole body irradiated Swiss albino mice. Administration of these sulfur compounds could reduce the serum content of alkaline phosphatase (ALP), which was elevated after irradiation (23.9 ± 1.82 KA units). The elevated liver content of glutamate pyruvate transaminase (GPT) in control animals (76.2 ± 2.2 U/mL) after irradiation was significantly reduced in DAS (58.93 ± 4 U/mL) and AMS (55.7 ± 2.2 U/mL) treated animals. Elevated levels of lipid peroxides in serum and liver of irradiated control animals were also significantly reduced by treatment with these sulfur compounds. The glutathione (GSH) content in liver and intestinal mucosa was drastically reduced after irradiation. All the sulfur compounds and isothiocyanates could effectively enhance the GSH content of intestinal mucosa and liver. Findings at histopathological analysis of the intestine proved to be correlated with the above results.
Oxaliplatin with Raltitrexed and Preoperative Radiotherapy in T3-T4 Extraperitoneal Rectal Cancer. A Dose Finding Study
Authors: Lupattelli Marco , Bellavita Rita , Natalini Giovanni , Giovenali Paolo , Sidoni Angelo , Castagnoli Paolo , Corgna Enrichetta , Draghini Lorena , Trippolini Romano , Aristei Cynthia
Published: July 2019

Aims and background

The availability of new drugs offers the opportunity to improve the outcome of locally advanced rectal cancer. Raltitrexed and oxaliplatin are effective in advanced colorectal cancer with acceptable toxicity and can act as radiation enhancers as shown in phase 1-11 studies. The aim of the study was thus to determine the recommended dose of oxaliplatin concomitantly administered with raltitrexed and concurrent preoperative radiotherapy in patients with stage 11-111 extraperitoneal rectal cancer.

Methods

From September 2001 to September 2002, 18 consecutive patients with T3/T4 rectal cancer were treated at our Institution with preoperative chemoradiation followed by surgery after 6-8 weeks. Pelvic radiotherapy was delivered at a dose of 45 Gy in 25 fractions in 5 weeks followed by a 5.4 Gy boost at 1.8 Gy daily. Concomitant chemotherapy consisted of 3 mg/m2/iv of raltitrexed on days 1, 19, 38 of radiotherapy treatment with incremental doses of oxaliplatin according to dose finding rules (4 dose levels: 65, 85, 110, 130 mg/m2). Dose-limiting toxicity for oxaliplatin was defined as either grade 3-4 hematological or grade 3-4 gastrointestinal or neurological toxicity. We studied a minimum of 3 patients at each dose level.

Results

Three patients were treated at 65, 85, and 110 mg/m2/iv, respectively, while 9 patients were recruited at the last dose level. Neither grade 3-4 gastrointestinal nor neurological toxicity were documented. Dose-limiting toxicity was documented in 2/9 subjects at the 130 mg/m2 level consisting of grade 3 transient asymptomatic leukopenia. Thirteen patients developed transient increase of one or more liver enzymes (grade 3-4) and 2 patients developed grade 3 perineal dermatitis. All patients received the programmed dose of radiotherapy. The chemotherapy regimen was not completed in 4 cases due to grade 2 protracted leukopenia.

Conclusions

The maximum tolerated dose of oxaliplatin was not reached at the maximum dose level (IV); 130 mg/m2 can therefore be defined as the recommended dose. The combination of oxaliplatin with raltitrexed and radiotherapy can be considered feasible and well tolerated.