Hypofractionated three-dimensional conformal radiation therapy (3D-CRT) is a treatment option for patients with early-stage non-small cell lung cancer (NSCLC) who are medically unable to tolerate surgery and w...
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Δευτέρα 18 Ιανουαρίου 2016
Patient outcomes of monotherapy with hypofractionated three-dimensional conformal radiation therapy for stage T2 or T3 non-small cell lung cancer: a retrospective study
The Barrett-associated variants at GDF7 and TBX5 also increase esophageal adenocarcinoma risk
Abstract
Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) represent two stages within the esophagitis-metaplasia-dysplasia-adenocarcinoma sequence. Previously genetic risk factors have been identified that confer risk to BE and EAC development. However, to which extent the genetic variants confer risk to different stages of the BE/EAC sequence remains mainly unknown. In this study we analyzed three most recently identified BE variants at the genes GDF7 (rs3072), TBX5 (rs2701108), and ALDH1A2 (rs3784262) separately in BE and EAC samples in order to determine their risk effects during BE/EAC sequence. Our data show that rs3072 at GDF7 and rs2701108 at TBX5 are also associated with EAC and conclude that both loci confer disease risk also at later stages of the BE/EAC sequence. In contrast, rs3784262 at ALDH1A2 was highly significantly associated with BE, but showed no association with EAC. Our data do not provide evidence that the ALDH1A2 locus confers equal risk in early and late stages of BE/EAC sequence.
The authors followed up SNPs at GDF7, TBX5, and ALDH1A2 that showed association with Barrett's esophagus (BE) in a previous study. The sample comprised 542 BE and 1106 esophageal adenocarcinoma (EAC) cases as well as 1602 controls. SNPs at GDF7 and TBX5 are also associated with EAC and thereby risk-conferring also to later stages of the BE/EAC sequence. The variant at ALDH1A2 is associated with BE only, which indicates that this locus plays a more prominent role in early stages of the BE/EAC sequence.
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Colorectal clinical trials: what is on the horizon?
Future Oncology Ahead of Print.
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Putative role of SUMOylation in controlling the activity of deubiquitinating enzymes in cancer
Future Oncology Ahead of Print.
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Immunotherapy with checkpoint inhibitors for lung cancer: novel agents, biomarkers and paradigms
Future Oncology Ahead of Print.
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National Cancer Center Singapore: the way forward
Future Oncology Ahead of Print.
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Unknown primary tumors: is there a future therapeutic role for immune checkpoint inhibitors?
Future Oncology Ahead of Print.
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Clinical outcomes in octogenarians treated with docetaxel as first-line chemotherapy for castration-resistant prostate cancer
Future Oncology Ahead of Print.
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Effective targeting of colorectal cancer cells using TORC1/2 kinase inhibitors in vitro and in vivo
Future Oncology Ahead of Print.
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The calm before the storm: a report from the International Liver Cancer Association Congress 2015 – part 2
Future Oncology Ahead of Print.
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The calm before the storm: a report from the International Liver Cancer Association congress 2015 – part 1
Future Oncology Ahead of Print.
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The effect of the gastrectomy on survival in patients with metastatic gastric cancer: a study of ASMO
Future Oncology Ahead of Print.
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Risk of endocrine complications in cancer patients treated with immune check point inhibitors: a meta-analysis
Future Oncology Ahead of Print.
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A Phase I Study of the AKT Inhibitor MK-2206 in Combination with Hormonal Therapy in Postmenopausal Women with Estrogen Receptor Positive Metastatic Breast Cancer
Purpose:Phosphatidylinositol-3-kinase (PI3K)/AKT pathway activation is an important endocrine resistance mechanism in estrogen receptor positive (ER+) breast cancer. After promising preclinical modeling of MK-2206, an allosteric pan-AKT inhibitor, with either estrogen-deprivation or fulvestrant, we conducted a Phase 1 trial in patients with metastatic ER+HER2- breast cancer to determine the recommended phase II treatment dose (RPTD) of MK-2206 when combined with either anastrozole, fulvestrant, or anastrozole/fulvestrant. Experimental Design:ER+ breast cancer cell lines were exposed in vitro to MK-2206 plus estrogen-deprivation with or without fulvestrant and monitored for apoptosis. A standard 3+3 design was employed to first determine the maximum tolerated dose (MTD) of MK-2206 plus anastrozole based on cycle 1 toxicity. Each cycle was 28 days. The RPTD was determined based on toxicities observed at MTD level during the first 3 cycles. Subsequent patients received MK-2206, at the RPTD determined above, and fulvestrant or anastrozole/fulvestrant to define RPTD for these additional regimens. Results:MK-2206 induced apoptosis in parental ER+ but not in long term estrogen deprived cell lines, for which fulvestrant was required for apoptosis induction. Thirty one patients enrolled. The RPTD was defined as MK-2206 150 mg PO weekly with prednisone prophylaxis for each combination. Grade 3 rash was dose limiting. 42% (95% CI: 23%-63%) patients derived clinical benefit without progression within 6 months. Response was not associated with tumor PIK3CA mutation. Conclusions: MK-2206 plus endocrine treatments were tolerable. MK-2206 in combination with anastrozole is being further evaluated in a phase II neoadjuvant trial for newly diagnosed ER+HER2- breast cancer.
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The Majority of Expedited Investigational New Drug Safety Reports Are Uninformative
Sponsors of human drug and biological products subject to an investigational new drug application (IND) are required to distribute expedited safety reports of serious and unexpected suspected adverse reactions to participating investigators and FDA to assure the protection of human subjects participating in clinical trials. On September 29, 2010, FDA issued a final rule amending its regulations governing expedited IND safety reporting requirements that revised the definitions used for reporting and clarified when to submit relevant and useful information in order to reduce the number of uninformative reports distributed by sponsors. From January 1, 2006 to December 31, 2014, FDA's Office of Hematology and Oncology Products received an average of 17,686 expedited safety reports per year. An analysis of the FDA submissions by commercial sponsors covering this time period suggested a slight increase in the number of expedited safety reports per IND per year after publication of the final rule. An audit of 160 randomly selected expedited safety reports submitted to FDA's Office of Hematology and Oncology Products in 2015 revealed that only 22 (14%) were informative. Submission of uninformative expedited safety reports by commercial sponsors of INDs continues to be a significant problem that can compromise detection of valid safety signals.
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Inflammatory Marker Testing Identifies CD74 Expression in Melanoma Tumor Cells, and its Expression Associates with Favorable Survival for Stage III Melanoma
Purpose Inflammatory marker expression in stage III melanoma tumors was evaluated for association with outcome, using two independent cohorts of stage III melanoma patients' tumor tissues. Experimental Design Fifteen markers of interest were selected for analysis, and their expression in melanoma tissues was determined by immunohistochemistry. Proteins associating with either overall survival (OS) or relapse-free survival (RFS) in the retrospective discovery tissue microarray (TMA) (n = 158) were subsequently evaluated in an independent validation TMA (n = 114). Cox proportional hazards regression models were used to assess the association between survival parameters and covariates, the Kaplan-Meier method to estimate the distribution of survival, and the log-rank test to compare distributions. Results Expression of CD74 on melanoma cells was unique, and in the discovery TMA it associated with favorable patient outcome (OS: HR, 0.53, P = 0.01 and RFS: HR, 0.56; P = 0.01). The validation dataset confirmed the CD74 prognostic significance and revealed that the absence of MIF and iNOS was also associated with poor survival parameters. Consistent with the protein observation, tumor CD74 mRNA expression also correlated positively (p = 0.003) with OS in the melanoma TCGA data set. Conclusions Our data validate CD74 as a useful prognostic tumor cell protein marker associated with favorable RFS and OS in stage III melanoma. Low or negative expression of MIF in both TMAs, and of iNOS in the validation set also provided useful prognostic data. A disease-specific investigation of CD74's functional significance is warranted, and other markers appear intriguing to pursue.
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Role of NADH Dehydrogenase (Ubiquinone) 1 alpha subcomplex 4-like 2 in clear cell renal cell carcinoma
Purpose: We delineated the functions of the HIF1α target NADH Dehydrogenase (Ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) in ccRCC and characterized NDUFA4L2 as a novel molecular target for ccRCC treatment. Experimental Design: We evaluated normal kidney and ccRCC patient microarray and RNAseq data from Oncomine and The Cancer Genome Atlas (TCGA) for NDUFA4L2 mRNA levels and the clinical implications of high NDUFA4L2 expression. Additionally, we examined normal kidney and ccRCC patient tissue samples, human ccRCC cell lines, and murine models of ccRCC for NDUFA4L2 mRNA and protein expression. Utilizing shRNA, we performed NDUFA4L2 knockdown experiments and analyzed the proliferation, clonogenicity, metabolite levels, cell structure, and autophagy in ccRCC cell lines in culture. Results: We found that NDUFA4L2 mRNA and protein are highly expressed in ccRCC samples but undetectable in normal kidney tissue samples, and that NDUFA4L2 mRNA expression correlates with tumor stage and lower overall survival. Additionally, we demonstrated that NDUFA4L2 is a HIF1α target in ccRCC and that NDUFA4L2 knockdown has a profound anti-proliferative effect, alters metabolic pathways, and causes major stress in cultured RCC cells. Conclusions: Collectively, our data show that NDUFA4L2 is a novel molecular target for ccRCC treatment.
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Colorectal clinical trials: what is on the horizon?
Future Oncology Ahead of Print.
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Putative role of SUMOylation in controlling the activity of deubiquitinating enzymes in cancer
Future Oncology Ahead of Print.
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Immunotherapy with checkpoint inhibitors for lung cancer: novel agents, biomarkers and paradigms
Future Oncology Ahead of Print.
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National Cancer Center Singapore: the way forward
Future Oncology Ahead of Print.
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Limited thoracotomy for segmentectomy: a comparison of postoperative pain with thoracoscopic lobectomy
Abstract
Purposes
To assess whether a video-assisted thoracoscopic surgery (VATS) procedure is superior to limited thoracotomy (LT) for segmentectomy; postoperative pain was compared between VATS-lobectomy (VATS-L) and LT-segmentectomy (LT-S). Widely opened anterolateral thoracotomy segmentectomy (WT-S) was used as a control.
Methods
This study was a retrospective analysis of prospectively collected data for 220 consecutive patients with stage I NSCLC treated between 2012 and 2015 at a single institute using VATS-L (n = 58), LT-S (n = 93), or WT-S (n = 69). Pain scores from postoperative days (POD) 1–4 were measured using a visual analog scale three times a day. Chronic pain was assessed by the need for analgesics at 1, 2, and 3 months postoperatively.
Results
No significant differences in pain from POD 1 to 4 were observed between VATS-L and LT-S, whereas WT-S showed significantly higher pain scores than these two procedures (p = 0.0001–0.02). Chronic pain did not differ significantly among the procedures.
Conclusion
Postoperative pain does not differ significantly between VATS-L and LT-S. LT may be preferable to VATS for segmentectomy to identify the anatomy, dissect the hilar nodes, and establish surgical margins.
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Genetic heterogeneity of actionable genes between primary and metastatic tumor in lung adenocarcinoma
Abstract
Background
Biopsy for lung cancer diagnosis is usually done at a single site. But it is unclear that genetic information at one biopsy site represents that of other lesions and is sufficient for therapeutic decision making.
Methods
Non-synonymous mutations and insertions/deletions of 16 genes containing actionable mutations, and intron 2 deletion polymorphism of Bcl2-like11 were analyzed in 41 primary tumor and metastatic lymph node (L/N) matched, pStage IIA ~ IIIA non-small cell lung cancer (NSCLC) samples using a next generation sequencing based technique.
Results
A total of 249 mutations, including 213 non-synonymous mutations, 32 deletions, and four insertions were discovered. There was a higher chance of discovering non-synonymous mutations in the primary tumors than in the metastatic L/N (138 (64.8%) vs. 75 (35.2%)). In the primary tumors, 106 G > A:C > T transitions (76.8%) of 138 non-synonymous mutations were detected, whereas in the metastatic L/N, 44 (58.7%) of 75 were discovered. A total 24 (11.3%) out of 213 non-synonymous mutations were developed in the context of APOBEC signature. Of those, 21 (87.5%) was detected in the primary tumors and 4 (16.7%) was detected in the metastatic L/N. When the mutation profiles between primary tumor and metastatic L/N were compared, 13 (31.7%) of 41 cases showed discrepant mutation profile. There were no statistically significant differences in disease free survival and overall survival between groups showing identical mutation profiles and those with discrepancy between primary and metastatic L/N.
Conclusions
Genetic heterogeneity between the primary and L/N metastatic lesions is not infrequent finding to consider when interpreting genomic data based on the result of one site inspection. A large prospective study may be needed to evaluate the impact of genetic heterogeneity on the clinical outcomes of NSCLC patients.
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Elevated growth differentiation factor 15 expression predicts poor prognosis in epithelial ovarian cancer patients
Abstract
The purpose of this study was to determine the expression of growth differentiation factor 15 (GDF15) and explore its clinical significance in epithelial ovarian cancer (EOC) patients. The expression of GDF15 in EOC tissues and serum samples was evaluated using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), respectively. The association of GDF15 expression with clinicopathologic parameters was analyzed. Survival time was assessed using the Kaplan–Meier technique and Cox regression model. Both in EOC tissues and serum, high GDF15 levels were obviously related with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, ascites, and chemoresistance. Kaplan–Meier analysis indicated that EOC patients with high GDF15 expression showed poorer progression-free survival (PFS) and overall survival (OS). Multivariate analysis demonstrated that GDF15 expression was an independent predictor of PFS in EOC patients. Our study shows that elevated GDF15 expression was associated with poor prognosis in EOC patients. We suggest that GDF15 is a novel biomarker for the early detection of EOC, prediction of the response to chemotherapy, and screening for recurrence in EOC patients.
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Gastric cardia adenocarcinoma microRNA profiling in Chinese patients
Abstract
Gastric cardia adenocarcinoma (GCA), which occurs at the gastroesophageal boundary, is one of the most malignant types of cancer. Over the past 30 years, the incidence of GCA has increased by approximately sevenfold, which has a more substantial increase than that of many other malignancies. However, as previous studies mainly focus on non-cardia gastric cancer, until now, the mechanisms behind GCA remain largely unknown. MicroRNAs (miRNAs) have been shown to play pivotal roles in carcinogenesis. To gain insight into the molecular mechanisms regulated by miRNAs in GCA development, we investigated miRNA expression profiles using 81 pairs of primary GCAs and corresponding non-tumorigenic tissues. First, 21 pairs of samples were used for microarray analysis, and then another 60 pairs of samples were used for further analysis. Our results showed that 464 miRNAs (237 upregulated, 227 downregulated, false discovery rate FDR <0.05) were differently expressed between GCA and non-tumor tissues. Pearson test and pathway analysis revealed that these dysregulated miRNA correlated coding RNAs may have effects on several cancer-related pathways. Four miRNAs (miR-1244, miR-135b-5p, miR-3196, and miR-628-3p) were found to be associated with GCA differentiation. One miRNA, miR-196a-5p, was found to be associated with age of GCA onset. Further, survival analysis showed that the expression level of miR-135b-5p was associated with GCA survival. Taken together, our study first provided the genome-wide expression profiles of miRNA in GCA and will be good help for further functional studies.
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Effect of major lifestyle risk factors, independent and jointly, on life expectancy with and without cardiovascular disease: results from the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES)
Abstract
Seldom have studies taken account of changes in lifestyle habits in the elderly, or investigated their impact on disease-free life expectancy (LE) and LE with cardiovascular disease (CVD). Using data on subjects aged 50+ years from three European cohorts (RCPH, ESTHER and Tromsø), we used multi-state Markov models to calculate the independent and joint effects of smoking, physical activity, obesity and alcohol consumption on LE with and without CVD. Men and women aged 50 years who have a favourable lifestyle (overweight but not obese, light/moderate drinker, non-smoker and participates in vigorous physical activity) lived between 7.4 (in Tromsø men) and 15.7 (in ESTHER women) years longer than those with an unfavourable lifestyle (overweight but not obese, light/moderate drinker, smoker and does not participate in physical activity). The greater part of the extra life years was in terms of "disease-free" years, though a healthy lifestyle was also associated with extra years lived after a CVD event. There are sizeable benefits to LE without CVD and also for survival after CVD onset when people favour a lifestyle characterized by salutary behaviours. Remaining a non-smoker yielded the greatest extra years in overall LE, when compared to the effects of routinely taking physical activity, being overweight but not obese, and drinking in moderation. The majority of the overall LE benefit is in disease free years. Therefore, it is important for policy makers and the public to know that prevention through maintaining a favourable lifestyle is "never too late".
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Effect of Cadmium on Trophoblast Cell Proliferation and Apoptosis in Different Gestation Periods of Rat Placenta
Abstract
In this study, we aimed to show how cadmium (Cd) affects the trophoblast proliferation and differentiation in the placenta and the apoptotic activity in different gestational days and, hence, its effects of placental development with immunohistochemical and TUNEL techniques. Experimental model of our study consisted of placental development of control and Cd groups on 15, 17, 19, and 21th days of the gestation. Female rats in Cd groups were subcutaneously administered a single dose of 0.5 mg Cd/kg/day dissolved in sodium chloride as 2 mL/kg Cd chloride until the day they sacrificed. Embryo and placenta of female rats were separately removed on 15, 17, 19, and 21th days of the gestation in which the placental development takes place and placentas were processed for microscopic examinations. In the placentas of the control group, all layers were observed to be formed on the 15th gestational day and thereafter a continuous growth was monitored. In the Cd group also all layers existed from the 15th gestational day. However, they were smaller in size than control groups. Frequency of proliferating cell nuclear antigen (PCNA)-positive cells was decreased and the number of apoptotic cells was increased in all the gestational days related to Cd. In conclusion, Cd administered during the pregnancy was observed to cause abnormal placental development by disrupting the normal structure of the placenta, inhibiting the proliferation of trophoblast and increasing the number of apoptotic trophoblast cells.
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The Effects of Lithium Administration on Oxidant/Antioxidant Status in Rats: Biochemical and Histomorphological Evaluations
Abstract
Present study was planned to determine possible dose-dependent effects of lithium (Li) on oxidant-antioxidant status and histomorphological changes in liver and kidney tissues. For this purpose, twenty-four Wistar male rats were equally divided into three groups: the rats in group I served as controls, drinking tap water without lithium. Groups II and III received 0.1 and 0.2 % lithium carbonate (Li2CO3) through their drinking water, respectively, for 30 days. At the end of the experimental period, lithium concentrations, levels of malondialdehyde (MDA) and glutathione (GSH) and superoxide dismutase (SOD) activities were measured in considered tissues. Histomorphological study was also performed on liver and kidney tissues. Compared to controls, MDA was significantly higher but GSH level lower in groups II and III. SOD activity was higher in group III, but no difference was determined in group II in liver tissue. In kidney tissue, there was no difference determined in MDA and GSH levels between control and experimental groups but SOD activity in groups II and III was significantly higher. In histologic sections of both experimental liver and kidney tissues, specific degenerations were observed. The results of the present study show that treatment with lithium carbonate may result in liver and kidney tissue abnormalities and oxidative damage.
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The Content of Copper and Molybdenum in the Liver, Kidneys, and Skeletal Muscles of Elk ( Alces alces ) from North-Eastern Poland
Abstract
The aim of the study was to evaluate the content of Cu and Mo in the liver, kidneys, and skeletal muscles of elks from north-eastern Poland. The investigation material comprised samples obtained in 2010 from 35 animals. Animals were grouped according to age (elks up to 2 years and over than 3 years). The metal concentrations were determined using coupled plasma-mass spectrometry (ICP-MS) method. The mean Cu concentrations in the liver, kidneys, and skeletal muscles were 23.08, 5.03, and 2.36 mg∙kg−1 wet weight, respectively. The mean Mo content in the examined samples was as follows: 0.92, 0.42, and 0.05 mg∙kg−1 wet weight (w.w.) in the liver, kidneys, and muscles. In the analysis of correlation between the Cu and Mo levels in particular organs, the presence of significant dependence (p ≤ 0.05) was observed in the liver of animals studied. The mean Cu content in the liver of animals studied is lower compared with data reported from Sweden, Russia, and North America. Concentrations of Cu and Mo in the kidneys and skeletal muscles of Polish elks are similar to data noted in healthy animals from Scandinavian region. The results suggest that elks from north-eastern Poland may be threatened by primary Cu deficiency.
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Effects of Selenium on Morphological Changes in Candida utilis ATCC 9950 Yeast Cells
Abstract
This paper presents the results of microscopic examinations of the yeast cells cultured in yeast extract–peptone–dextrose (YPD) media supplemented with sodium selenite(IV). The analysis of the morphological changes in yeast cells aimed to determine whether the selected selenium doses and culturing time may affect this element accumulation in yeast cell structures in a form of inorganic or organic compounds, as a result of detoxification processes. The range of characteristic morphological changes in yeasts cultivated in experimental media with sodium selenite(IV) was observed, including cell shrinkage and cytoplasm thickening of the changes within vacuole structure. The processes of vacuole disintegration were observed in aging yeast cells in culturing medium, which may indicate the presence of so-called ghost cells lacking intracellular organelles The changes occurring in the morphology of yeasts cultured in media supplemented with sodium selenite were typical for stationary phase of yeast growth. From detailed microscopic observations, larger surface area of the cell (6.03 μm2) and yeast vacuole (2.17 μm2) were noticed after 24-h culturing in the medium with selenium of 20 mg Se4+/L. The coefficient of shape of the yeast cells cultured in media enriched with sodium selenite as well as in the control YPD medium ranged from 1.02 to 1.22. Elongation of cultivation time (up to 48 and 72 h) in the media supplemented with sodium selenite caused a reduction in the surface area of the yeast cell and vacuole due to detoxification processes.
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Effect of major lifestyle risk factors, independent and jointly, on life expectancy with and without cardiovascular disease: results from the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES)
Abstract
Seldom have studies taken account of changes in lifestyle habits in the elderly, or investigated their impact on disease-free life expectancy (LE) and LE with cardiovascular disease (CVD). Using data on subjects aged 50+ years from three European cohorts (RCPH, ESTHER and Tromsø), we used multi-state Markov models to calculate the independent and joint effects of smoking, physical activity, obesity and alcohol consumption on LE with and without CVD. Men and women aged 50 years who have a favourable lifestyle (overweight but not obese, light/moderate drinker, non-smoker and participates in vigorous physical activity) lived between 7.4 (in Tromsø men) and 15.7 (in ESTHER women) years longer than those with an unfavourable lifestyle (overweight but not obese, light/moderate drinker, smoker and does not participate in physical activity). The greater part of the extra life years was in terms of "disease-free" years, though a healthy lifestyle was also associated with extra years lived after a CVD event. There are sizeable benefits to LE without CVD and also for survival after CVD onset when people favour a lifestyle characterized by salutary behaviours. Remaining a non-smoker yielded the greatest extra years in overall LE, when compared to the effects of routinely taking physical activity, being overweight but not obese, and drinking in moderation. The majority of the overall LE benefit is in disease free years. Therefore, it is important for policy makers and the public to know that prevention through maintaining a favourable lifestyle is "never too late".
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Creating Quality Online Materials for Specialty Nurse Practitioner Content: Filling a Need for the Graduate Nurse Practitioner
Abstract
Nurse practitioners are entering specialized areas of practice immediately after graduation from nurse practitioner (NP) education and certification and are finding employment in specialized areas such as oncology. Rapidly achieving a knowledge base in this highly specialized area of medicine coupled with the stress of the new nurse practitioner role can lead to a very difficult orientation and transition period. There are several methods to provide specialized education to NPs during their orientation period. Unfortunately, limitations such as a lack of motivated mentors, limited opportunities to practice the desired skill set or a lack of structure in regards to curriculum quality, and the learning needs of the new nurse hinder the NP's transition to practice. In response to either inadequate or non-standardized orientation to the specialty role of the oncology NP (ONP), a web-enhanced educational tool, funded through the National Cancer Institute, was developed for use in the USA: Oncology Nurse Practitioner Web Education Resource (ONc-PoWER). The development of ONc-PoWER was based upon essential education for NPs new to cancer care, adult learning theory, Bloom's Taxonomy, and foundations of quality online education. The five interactive web-based modules provide specialized education for the nurse practitioner new to oncology along with an on-site mentor to assist the NP in applying the course content to clinical practice.
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Adolescents’ Attitudes to Sun Exposure and Sun Protection
Abstract
Adolescents are considered a risk group for the development of skin cancer in later life due to their high rates of sunburn. The aim of this study is to evaluate the association between attitudes to sun exposure and the sociodemographic characteristics of adolescents, their habits, practices and knowledge. As a secondary goal, we describe the magnitude and sign of the correlations between these attitudes. Cross-sectional study of adolescent students from 12 secondary schools in southern Spain, the subjects were asked to complete the 'Beach Questionnaire'. This instrument examines four dimensions of attitudes, with standardised scores of 0–100, related to the sun, sun tanning, sun protection and sun cream. The higher the score, the more positive the attitude. The study population was composed of 270 adolescents. The highest scores were obtained for attitudes towards sun protection practices (mean 66.2; SD 18.6) and towards sun tanning (mean 64.2; SD 21.1). The lowest scores were obtained for attitudes towards using sun cream (mean 50.1; SD 24.6). Significant differences were found for all four attitudes, with a positive sign for the relationship between the number of days of sun exposure and a higher score for attitudes towards sunbathing (27.3 points difference between response extremes) and for attitudes towards suntanning (20 points difference). Favourable attitudes towards sunbathing and sun tanning have most influence on inadequate habits of sun exposure and deficient measures of sun protection. Adolescents should be considered a priority group for targeted interventions to improve sun protection behaviour.
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National and regional breast cancer incidence and mortality trends in Mexico 2001–2011: Analysis of a population-based database
Publication date: April 2016
Source:Cancer Epidemiology, Volume 41
Author(s): Enrique Soto-Perez-de-Celis, Yanin Chavarri-Guerra
IntroductionBreast cancer is the most common malignancy in Mexican women since 2006. However, due to a lack of cancer registries, data is scarce. We sought to describe breast cancer trends in Mexico using population-based data from a national database and to analyze geographical and age-related differences in incidence and mortality rates.MethodsAll incident breast cancer cases reported to the National Epidemiological Surveillance System and all breast cancer deaths registered by the National Institute of Statistics and Geography in Mexico from 2001 to 2011 were included. Incidence and mortality rates were calculated for each age group and for 3 geographic regions of the country. Joinpoint regression analysis was performed to examine trends in BC incidence and mortality. We estimated annual percentage change (APC) using weighted least squares log-linear regression.ResultsWe found an increase in the reported national incidence, with an APC of 5.9% (95% CI 4.1–7.7, p<0.05). Women aged 60–65 had the highest increase in incidence (APC 7.89%; 95% CI 5.5 −10.3, p<0.05). Reported incidence rates were significantly increased in the Center and in the South of the country, while in the North they remained stable. Mortality rates also showed a significant increase, with an APC of 0.4% (95% CI 0.1–0.7, p<0.05). Women 85 and older had the highest increase in mortality (APC 2.99%, 95% CI 1.9–4.1; p<0.05).ConclusionsThe reporting of breast cancer cases in Mexico had a continuous increase, which could reflect population aging, increased availability of screening, an improvement in the number of clinical facilities and better reporting of cases. Although an improvement in the detection of cases is the most likely explanation for our findings, our results point towards an epidemiological transition in Mexico and should help in guiding national policy in developing countries.
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Post-sampling mortality and non-response patterns in the English Cancer Patient Experience Survey: Implications for epidemiological studies based on surveys of cancer patients
Publication date: April 2016
Source:Cancer Epidemiology, Volume 41
Author(s): Gary A. Abel, Catherine L. Saunders, Georgios Lyratzopoulos
BackgroundSurveys of the experience of cancer patients are increasingly being introduced in different countries and used in cancer epidemiology research. Sampling processes, post-sampling mortality and survey non-response can influence the representativeness of cancer patient surveys.MethodsWe examined predictors of post-sampling mortality and non-response among patients initially included in the sampling frame of the English Cancer Patient Experience Survey. We also compared the respondents' diagnostic case-mix to other relevant populations of cancer patients, including incident and prevalent cases.ResultsOf 109,477 initially sampled cancer patients, 6273 (5.7%) died between sampling and survey mail-out. Older age and diagnosis of brain, lung and pancreatic cancer were associated with higher risk of post-sampling mortality. The overall response rate was 67% (67,713 respondents), being >70% for the most affluent patients and those diagnosed with colon or breast cancer and <50% for Asian or Black patients, those under 35 and those diagnosed with brain cancer. The diagnostic case-mix of respondents varied substantially from incident or prevalent cancer cases.ConclusionsRespondents to the English Cancer Patient Experience Survey represent a population of recently treated cancer survivors. Although patient survey data can provide unique insights for improving cancer care quality, features of survey populations need to be acknowledged when analysing and interpreting findings from studies using such data.
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Chronic combined stress induces selective and long-lasting inflammatory response evoked by changes in corticosterone accumulation and signaling in rat hippocampus
Abstract
Hippocampus is believed to be selectively vulnerable to stress. We hypothesized that this phenomenon may be mediated by relatively high vulnerability to neuroinflammation related to impairments of local glucocorticoid metabolism and signaling. We have evaluated inflammatory responses induced by acute or chronic combined stress in the cerebral cortex and hippocampus as well as circulating and brain corticosterone (CS) levels as well as expression of corticosterone target genes. The hippocampus showed higher stress-induced expression of the proinflammatory cytokine IL-1β as compared to the cerebral cortex. A month after the termination of the chronic stress, IL-1β mRNA in the cerebral cortex reached control level, while in the hippocampus it remained significantly increased. Under chronic stress, the maladaptive inflammatory response in hippocampus was accompanied by a significant increase in local CS levels, as compared to cerebral cortex. Under acute stress, the increased CS level induced changes in CS-regulated genes expression (CRF and IGF1), while this phenomenon was not observed after chronic stress. Thus, the hippocampus appears to be more vulnerable to stress-induced inflammation as compared to the neocortex and demonstrates persistent inflammatory response induced by chronic stress. Stress-induced maladaptive inflammatory response is associated with a selective increase in hippocampal CS accumulation and changes in CS signaling.
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Elevated growth differentiation factor 15 expression predicts poor prognosis in epithelial ovarian cancer patients
Abstract
The purpose of this study was to determine the expression of growth differentiation factor 15 (GDF15) and explore its clinical significance in epithelial ovarian cancer (EOC) patients. The expression of GDF15 in EOC tissues and serum samples was evaluated using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), respectively. The association of GDF15 expression with clinicopathologic parameters was analyzed. Survival time was assessed using the Kaplan–Meier technique and Cox regression model. Both in EOC tissues and serum, high GDF15 levels were obviously related with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, ascites, and chemoresistance. Kaplan–Meier analysis indicated that EOC patients with high GDF15 expression showed poorer progression-free survival (PFS) and overall survival (OS). Multivariate analysis demonstrated that GDF15 expression was an independent predictor of PFS in EOC patients. Our study shows that elevated GDF15 expression was associated with poor prognosis in EOC patients. We suggest that GDF15 is a novel biomarker for the early detection of EOC, prediction of the response to chemotherapy, and screening for recurrence in EOC patients.
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Gastric cardia adenocarcinoma microRNA profiling in Chinese patients
Abstract
Gastric cardia adenocarcinoma (GCA), which occurs at the gastroesophageal boundary, is one of the most malignant types of cancer. Over the past 30 years, the incidence of GCA has increased by approximately sevenfold, which has a more substantial increase than that of many other malignancies. However, as previous studies mainly focus on non-cardia gastric cancer, until now, the mechanisms behind GCA remain largely unknown. MicroRNAs (miRNAs) have been shown to play pivotal roles in carcinogenesis. To gain insight into the molecular mechanisms regulated by miRNAs in GCA development, we investigated miRNA expression profiles using 81 pairs of primary GCAs and corresponding non-tumorigenic tissues. First, 21 pairs of samples were used for microarray analysis, and then another 60 pairs of samples were used for further analysis. Our results showed that 464 miRNAs (237 upregulated, 227 downregulated, false discovery rate FDR <0.05) were differently expressed between GCA and non-tumor tissues. Pearson test and pathway analysis revealed that these dysregulated miRNA correlated coding RNAs may have effects on several cancer-related pathways. Four miRNAs (miR-1244, miR-135b-5p, miR-3196, and miR-628-3p) were found to be associated with GCA differentiation. One miRNA, miR-196a-5p, was found to be associated with age of GCA onset. Further, survival analysis showed that the expression level of miR-135b-5p was associated with GCA survival. Taken together, our study first provided the genome-wide expression profiles of miRNA in GCA and will be good help for further functional studies.
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Modal variety of microsatellite instability in human endometrial carcinomas
Abstract
Purpose
Microsatellite instability (MSI) in human endometrial cancer (EC) was analysed using a unique fluorescent technique. MSI is associated with various human neoplasms. However, the reported frequency of MSI differs widely in each malignancy. Methodological difficulties have in fact been pointed out in its assay techniques.
Methods
We previously established a sensitive fluorescent technique in which the major methodological problems are overcome. Application of this technique has revealed two distinct modes of microsatellite alterations, i.e. Type A and Type B. In the present study, we have applied this technique to 94 ECs.
Results
Significant microsatellite alterations were observed in 38 (40.4 %) tumours of the panel. The two modes, Type A and Type B, were indeed observed in this malignancy. More importantly, we found that the modes more closely correlated with the molecular and clinicopathological backgrounds of the tumours than the established and widely used MSI grades, MSI-H and MSI-L. Type B MSI widely correlated with family history of hereditary non-polyposis colorectal cancer-associated cancers, whereas MSI-H only did with that of colorectal cancer. Furthermore, mutation in the KRAS oncogene, which has been regarded as generally infrequent in microsatellite-unstable tumours, was clearly associated with Type A MSI.
Conclusions
Our observations may suggest a biological relevance and a potential utility of the modal classification of MSI and, furthermore, added complexities to genomic instability underlying tumourigenesis in human endometrium.
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Prevalence of depression, anxiety and their risk factors in German women with breast cancer in general and gynecological practices
Abstract
Aims
To analyze the prevalence of depression, anxiety and their risk factors in German women with breast cancer (BC) in general and gynecological practices (GP, GYP).
Methods
Women initially diagnosed with BC between 2009 and 2013 were identified by 1202 general practitioners and 244 gynecologists in the IMS Disease Analyzer database. They were included only if they had not suffered from depression or an anxiety disorder within the 12 months prior to the index date. The main outcome was the first diagnosis of depression or an anxiety disorder within 5 years after index date. A multivariate Cox regression model was used to predict these diagnoses on the basis of patient characteristics.
Results
A total of 24,537 patients in GP were available for the study, as well as 20,018 patients in GYP. The mean age was 65.8 and 62.5 years in GP and GYP, respectively (p value <0.0001). The proportions of depressive or anxiety episodes in the past and the proportion of metastases were higher in GP than in GYP (7.9 vs. 3.6 %, and 10.1 vs. 8.6 %, p values <0.0001). Within 5 years of follow-up, 36.9 % of GP patients and 35.1 % of GYP patients had been diagnosed with depression or anxiety. There was a significantly higher risk of depression and/or anxiety in women in the age groups 51–60, 61–70 and >70 years than in women = <50 years (OR between 1.05 and 1.27, all p values lower than 0.0359). Patients with metastases or with previous episodes of depression/anxiety had a higher risk of depression/anxiety (OR = 1.21 and 1.97, p values <0.0001). Finally, women with private health insurance had a lower risk of depression and anxiety (OR = 0.45, p value <0.0001).
Conclusion
The present study indicates that levels of depression and anxiety increase in German women after diagnosis of BC and may be predicted on the basis of several demographic and clinical characteristics.
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Vorinostat, a histone deacetylase (HDAC) inhibitor, promotes cell cycle arrest and re-sensitizes rituximab- and chemo-resistant lymphoma cells to chemotherapy agents
Abstract
Purpose
Preclinical models of chemotherapy resistance and clinical observations derived from the prospective multicenter phase III collaborative trial in relapsed aggressive lymphoma (CORAL) study demonstrated that primary refractory/relapsed B cell diffuse large B cell lymphoma has a poor clinical outcome with current available second-line treatments. Preclinically, we found that rituximab resistance is associated with a deregulation on the mitochondrial potential rendering lymphoma cells resistant to chemotherapy-induced apoptotic stimuli. There is a dire need to develop agents capable to execute alternative pathways of cell death in an attempt to overcome chemotherapy resistance. Posttranscriptional histone modification plays an important role in regulating gene transcription and is altered by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs regulate several key cellular functions, including cell proliferation, cell cycle, apoptosis, angiogenesis, migration, antigen presentation, and/or immune regulation. Given their influence in multiple regulatory pathways, HDAC inhibition is an attractive strategy to evaluate its anti-proliferation activity in cancer cells. To this end, we studied the anti-proliferation activity and mechanisms of action of suberoylanilide hydroxamic acid (SAHA, vorinostat) in rituximab–chemotherapy-resistant preclinical models.
Methods
A panel of rituximab–chemotherapy-sensitive (RSCL) and rituximab–chemotherapy-resistant cell lines (RRCL) and primary tumor cells isolated from relapsed/refractory B cell lymphoma patients were exposed to escalating doses of vorinostat. Changes in mitochondrial potential, ATP synthesis, and cell cycle distribution were determined by Alamar blue reduction, Titer-Glo luminescent assays, and flow cytometric, respectively. Protein lysates were isolated from vorinostat-exposed cells, and changes in members of Bcl-2 family, cell cycle regulatory proteins, and the acetylation status of histone H3 were evaluated by Western blotting. Finally, cell lines were pre-exposed to vorinostat for 48 h and subsequently exposed to several chemotherapy agents (cisplatin, etoposide, or gemcitabine); changes in cell viability were determined by CellTiter-Glo® luminescence assay (Promega, Fitchburg, WI), and synergistic activity was evaluated using the CalcuSyn software.
Results
Vorinostat induced dose-dependent cell death in RRCL and in primary tumor cells. In addition, in vitro exposure of RRCL to vorinostat resulted in an increase in p21 and acetylation of histone H3 leading to G1 cell cycle arrest. Vorinostat exposure resulted in apoptosis in RSCL cell lines but not in RRCL. This finding suggests that in RRCL, vorinostat induces cell death by alternative pathways (i.e., irreversible cell cycle arrest). Of interest, vorinostat was found to reverse acquired chemotherapy resistance in RRCL.
Conclusions
Our data suggest that vorinostat is active in RRCL with a known defective apoptotic machinery, it can active alternative cell death pathways. Given the multiple pathways affected by HDAC inhibition, vorinostat can potentially be used to overcome acquired resistant to chemotherapy in aggressive B cell lymphoma.
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Cancer cell invasion driven by extracellular matrix remodeling is dependent on the properties of cancer-associated fibroblasts
Abstract
Purpose
As one form of tumor invasion, cancer cells can invade the extracellular matrix (ECM) through tracks that have been physically remodeled by cancer-associated fibroblasts (CAFs). However, CAFs are a heterogeneous population with diverse matrix-remodeling capacities. The purpose of this study was to investigate how CAFs with various matrix-remodeling capacities influence cancer cell invasion.
Methods
We established single-cell-derived clones from three primary cultures of CAFs from lung adenocarcinoma patients (Case 1, 5 clones; Case 2, 5 clones; and Case 3, 7 clones). Using a co-culture model, we evaluated the correlations between the number of invaded cancer cells and the remodeling areas generated by CAF clones in each case.
Results
When A549 lung adenocarcinoma cells and CAF clones were co-cultured, both the numbers of invaded cancer cells and the remodeling areas generated by the CAF clones varied greatly. The number of invaded cancer cells was moderately and strongly correlated with the remodeling areas generated by each CAF clone originating from Cases 1 and 2 (R 2 value = 0.53 and 0.68, respectively), suggesting that the remodeling areas in the ECM may determine the number of invaded cancer cells. In contrast, the number of invaded cancer cells was not correlated with the remodeling areas generated by CAF clones originating from Case 3, suggesting that factors other than the remodeling areas might determine the number of invading cancer cells.
Conclusions
These findings showed two types of fibroblast-dependent cancer cell invasion that are dependent on and independent of the remodeling areas generated by CAFs.
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The effects of percutaneous ethanol injection followed by 20-kHz ultrasound and microbubbles on rabbit hepatic tumors
Abstract
Objective
Low-frequency ultrasound (US) in combination with microbubbles (MBs) is able to inhibit the growth of VX2 rabbit liver tumors. In this study, we investigated the feasibility of using percutaneous ethanol injection (PEI) followed by low-frequency ultrasound and microbubbles (USMB) to inhibit VX2 tumor growth.
Methods
Eighteen New Zealand rabbits with hepatic VX2 tumors were divided into three groups: PEI, low-frequency ultrasound and MBs followed by PEI (USMB + PEI), and PEI followed by USMB (PEI + USMB). PEI was performed by ultrasound-guided injection of 95 % anhydrous alcohol into internal liver tumors in rabbits twice a week for 2 weeks. The US parameters were 20 kHz, 2 W/cm2, 40 % duty cycle, 5 min, and once every other day for 2 weeks. Magnetic resonance imaging (MRI) was used to observe tumors before and after treatment, to examine changes in the tumors, and to measure the diameters of the tumors. All animals were followed up for 180 days after tumor implantation. Autopsy was performed at the end of the scheduled follow-up or immediately after death. Anatomically observed metastatic sites included the liver, lung, abdomen, and pelvic cavity. The survival time of all rabbits was recorded.
Results
After 4 weeks of treatment, on MRI, the tumor diameters in the PEI, USMB + PEI, and PEI + USMB groups were 8.33 ± 1.83, 19 ± 2.61, and 4.5 ± 1.22 mm, respectively. There was a significant difference in tumor size indicated by MRI in the three groups. Tumor size was smaller in the PEI + USMB group than in the PEI and USMB + PEI groups, with t = 4.54, p = 0.0062, and t = 16.38, p < .0001, respectively. The PEI + USMB group showed the fewest metastasis sites (χ 2 = 11.7333, p = 0.0194) and the longest survival period (χ 2 = 7.448, p = 0.0241).
Conclusion
Percutaneous ethanol injection followed by low-frequency ultrasound and microbubbles can be effective in inhibiting rabbit liver tumors and prolonging survival time.
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Early detection of colorectal cancer: from conventional methods to novel biomarkers
Abstract
Purpose
Colorectal cancer (CRC) is one of the major health problems worldwide and is often diagnosed at late stage. There is growing body of evidence in early detection of this disease with novel screening modalities to reduce compliance and increase specificity of available methods. The aim of current review is to give an overview on currently available screening methods (e.g., fecal occult blood testing (FOBT), flexible sigmoidoscopy, and colonoscopy), with their own merits and disadvantages, and new genetic/epigenetic/protein markers, as novel screening modalities.
Result
There are several serum and fecal biomarkers that can predict CRC and polyps. Overall sensitivities for detection by fecal DNA markers ranged from 53 to 87 %, while a panel of serum protein markers provides a sensitivity/specificity up to 85 % for CRC. In particular, DNA methylation markers (e.g., SEPT9, SFRP2, and ALX4), circulating microRNAs (e.g., microRNA21), SNPs in microRNAs binding site (e.g., rs4596 located within a target region of the predicted miR-518a-5p and miR-527), protein markers (e.g., carcinoembryonic antigen, N-methyltransferase), or microsatellites instability in tumors with deficient mismatch repair of some genes are among the most interesting and promising biomarkers.
Conclusion
Increasing evidence supports the use of combined fecal and serum biomarkers with sigmoidoscopy and colonoscopy screening in order to maximize the benefits and reduce the number of false-positive tests and patients undergoing invasive methods, which in turn could overcome the limitations of the current screening methods for early detection of CRC and adenomas.
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Incidence of metachronous contralateral breast cancer in the Canton of Zurich: a population-based study of the cancer registry
Abstract
Purpose
To examine the incidence and characteristics of metachronous contralateral breast cancer (CBC) among women in the Canton of Zurich, Switzerland.
Methods
For 1980–2006, patients with unilateral invasive breast cancer (UBC) were analysed for metachronous CBC. Poisson's regression was used to estimate incidence rates of metachronous CBC according to age, year of diagnosis, follow-up period since first breast cancer and morphology.
Results
Of 16,323 patients with UBC, 700 (4.3 %) developed a second malignant tumour of the opposite breast. Median age at first breast cancer was lower in the CBC group than in the full cohort. Median interval time between first and second breast cancer was 5.5 (interquartile range 2.6–10.1) years. Incidence rate at age 20–29 was 1006 (95 % confidence interval, CI, 452–2238) cases per 100,000 person-years and decreased to 299 (199–450) at 80–84. Age-adjusted incidence rates according to period of diagnosis decreased from 618 (530–721) for 1980–1984 to 329 (217–500) cases per 100,000 person-years for 2005–2006. Incidence rate ratio of CBC for lobular carcinoma was 1.28 (95 % CI 0.99–1.67) adjusted by age group and period of diagnosis compared to ductal carcinoma.
Conclusions
In our study, incidence rates for CBC are comparable with findings from the literature. A reduction in the incidence of metachronous CBC, thought to be due to adjuvant therapies, is seen in our data. In our cohort, younger age and lobular carcinoma were associated with an increased risk of CBC.
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Amplified HMGA2 promotes cell growth by regulating Akt pathway in AML
Abstract
Purpose
The aim of this study was to investigate how the amplification of HMGA2 contributes to acute myeloid leukemia (AML) cell proliferation.
Methods
The amplification and expression of HMGA2 were examined by FISH, qRT-PCR and Western blot in AML cases. The effect of HMGA2 knockdown on cell proliferation was analyzed with XTT, colony-forming assays and BrdUrd incorporation assays. The effects of HMGA2 knockdown on cell cycle were studied by flow cytometry analysis. The progression of AML cells in vivo was examined by the xenografted tumor model. The interaction between Akt pathway and HMGA2 was examined by Western blot.
Results
HMGA2 is amplified in AML, and the levels of HMGA2 messenger RNA (mRNA) and protein expressed in AML cells were significantly higher than those in normal cells, which may be related to NR and prognosis of AML patients. Reduction in HMGA2 expression in AML cells inhibited cell proliferation through a decrease in the protein expression of pAkt and pmTOR, compared with control cells.
Conclusions
HMGA2 is predominantly amplified and expressed in AML cells, and that aberrant expression of HMGA2 induces AML cell proliferation through the PI3K/Akt/mTOR signaling pathway. Inhibition of HMGA2 expression represents an attractive target for AML therapy.
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Analysis of outcomes of percutaneous coronary intervention in metastatic cancer patients with acute coronary syndrome over a 10-year period
Abstract
Background
Early medical palliative care has been shown to improve overall survival of patients with metastatic cancer, but the role of cardiac surgical interventions in such patients is not clear. The limited life expectancy of these patients often poses a dilemma to clinicians and involves a detailed analysis of the risks and benefits of such interventions. This study examines the outcomes of percutaneous coronary intervention (PCI) in patients with metastatic cancer.
Methods
The National Inpatient Database of USA was used to identify patients aged ≥18 years who had a diagnosis of metastatic cancer and acute coronary syndrome (ACS) between 2000 and 2009 using ICD-9-CM codes. These were categorized into ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI). The utilization of PCI was also identified using ICD-9-CM codes. The outcomes studied were in-hospital mortality, length of hospital stay and discharge disposition. The association between various outcomes and use of cardiac catheterization was assessed using multivariate regression models.
Results
There were 49,515 patients with metastatic disease who were discharged with a diagnosis of ACS. Of these, 15,964 had STEMI and 33,551 had NSTEMI. 3981 patients (24.9 %) with STEMI and 3209 patients (9.6 %) with NSTEMI received percutaneous coronary intervention. Caucasian male patients under age 65 years were more likely to receive PCI in the setting of an ACS. The hospital characteristics associated with higher use of PCI included academic affiliation, large bedsize, private for-profit hospitals and Midwestern and Western regions of USA. The adjusted odds of receiving PCI in this group of patient have gradually increased by 1.14 every year in last decade (95 % CI 1.11–1.16). The beneficial effect of PCI on in-hospital mortality has declined in NSTEMI such that by 2009, there was no significant difference between patients who received PCI and those who did not receive PCI. This has remained unchanged for STEMI patients.
Conclusions
In metastatic cancer patients with ACS, the rate of PCI has increased over the last decade. In the current era, metastatic cancer patients with NSTEMI may perform equally well without PCI in terms of in-hospital mortality. The decision to provide such care may be considered on an individual basis based on the extent of their medical comorbidity and tumor burden.
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The recent progress of the mechanism and regulation of tumor necrosis in colorectal cancer
Abstract
In colorectal cancer (CRC), despite the complex inducing and regulating mechanism in necrosis progress, the prognostic value of tumor necrosis has been reported. It is generally recognized that necrosis is associated with many process involving severe hypoxia, inflammatory responses and angiogenesis, all of which contribute to promote tumor growth and poor prognosis. In addition to local hypoxia, regulation by RIP kinase and the conversion from apoptosis to necrosis can result in necrosis also. Recent studies showed necrosis can be a histopathologic characteristic for special molecular phenotype of CRC. A novel and attractive complementary treatment, tumor necrosis therapy, using radiolabelled compounds avid for necrosis has emerged. However, the complicated regulatory mechanisms of tumor necrosis were rarely reported in CRC, and we collected and reviewed these effect and relevance in CRC.
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Utility of endometrial sampling prior to risk-reducing hysterectomy in a patient with Lynch syndrome
Melissa K Frey, Gizelka David-West, Khushbakhat R Mittal, Franco M Muggia and Bhavana Pothuri
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Biological evaluation of 2-arylidene-4, 7-dimethyl indan-1-one (FXY-1): a novel Akt inhibitor with potent activity in lung cancer
Abstract
Purpose
Human lung cancer is contributed to be a major mortality factor in the cancer-related deaths. Arylidene indan-ones constitute a new class of potential anti-tumor compounds. Herein, we report the biological efficacy of the 2-arylidene-4, 7-dimethyl indan-1-one (FXY-1), a potential lead molecule of arylidene indan-ones in lung cancer models. We previously described anticancer activity of FXY-1 against human breast adenocarcinoma.
Methods
FXY-1 efficacy was assessed by standard anticancer screening in NCI-H 460, A549, NCI-H 1975 and NCI-H 2170 cells. Initial molecular docking analysis was performed to check the interaction of compound to Akt enzyme. Anti-proliferation, anti-metastatic and transendothelial cell migration were performed to check efficacy of the drug. Western blot analysis was performed to understand the regulation of pro-apoptotic and anti-apoptotic proteins by the compound. The effect of FXY-1 on caspase induction and Akt phosphorylation were checked using Western blot analysis. Flow cytometry was used to reveal the cell cycle changes and apoptosis-inducing properties of FXY-1 in the lung cancer cells. In-vitro Akt inhibition property of the compound was studied using a fluorescence-based, coupled-enzyme reaction. The in-vivo efficacy of the compound was determined using a mouse xenograft model.
Results
Our molecular docking analysis reveals higher interaction of FXY-1 with Akt. FXY-1 depicted anti-proliferative and pro-apoptotic activity with higher therapeutic window in-vitro in NCI-H 460 and A549 cells. The compound treatment to lung cancer cells resulted in induction of DNA fragmentation, inhibition of transendothelial migration, caspase activation and poly (ADP-ribose) polymerase (PARP) cleavage. FXY-1 treatment resulted in G 0/G 1 arrest in both cell lines at lower concentrations, but led to apoptosis at higher doses. Western blot analysis revealed dephosphorylation of Akt (Ser 473) with activation of p53, Bax, Bak, Bid and reduction in Bcl-2 and Bcl-xL levels. Further mechanistic investigation showed that FXY-1 activity was facilitated through an allosteric inhibition of Akt enzyme. FXY-1 treatment significantly reduced the tumor growth and pAkt levels in mouse xenograft exhibiting the in-vivo efficacy in the compound.
Conclusion
Collectively, our results suggest DNA damage-mediated activation by FXY-1 in lung cancer cells leading to extensive apoptosis through the mitochondrial pathway.
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Development of anti-angiogenic tyrosine kinases inhibitors: molecular structures and binding modes
Abstract
Purpose
Since the hypothesis that solid tumors cause angiogenesis by secreting pro-angiogenic factors was introduced, research on angiogenesis has proceeded continuously. Development of inhibitors targeting the angiogenic tyrosine kinases, to block downstream signal transduction pathways, has become an important approach to cancer therapy. Our goal was to study the development and mechanism of anti-angiogenic tyrosine kinases inhibitors.
Methods
We researched data on discovery of the inhibitors and their binding modes using the PubMed, Web of Science, Food and Drug Administration (FDA), and Clinical Trials Web sites.
Results
In the last decade, many small molecule inhibitors targeting angiogenesis have been designed and synthesized with many now entering the clinic or gaining FDA approval. Advances in understanding regulatory mechanisms of angiogenesis have enabled development of these drugs. The development of inhibitors up to Phase 3 clinical trials and, for many, FDA approval has helped leading to the discovery of additional compounds. The structures, activities, and binding modes of these inhibitors are discussed in this review.
Conclusions
Though the angiogenesis inhibitors have different chemical structures, they share similar binding modes. Their interactions with the hinge region of receptor tyrosine kinases (RTKs) are critical to their effectiveness as inhibitors. In addition, as we review here, different drugs, when bound, induce different conformations of RTKs.
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Energy disruptors: rising stars in anticancer therapy?
Energy disruptors: rising stars in anticancer therapy?
Oncogenesis 5, e188 (January 2016). doi:10.1038/oncsis.2015.46
Authors: F Bost, A-G Decoux-Poullot, J F Tanti & S Clavel
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Uncoupling of EGFR–RAS signaling and nuclear localization of YBX1 in colorectal cancer
Uncoupling of EGFR–RAS signaling and nuclear localization of YBX1 in colorectal cancer
Oncogenesis 5, e187 (January 2016). doi:10.1038/oncsis.2015.51
Authors: F Roßner, C Gieseler, M Morkel, H-D Royer, M Rivera, H Bläker, M Dietel, R Schäfer & C Sers
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Mucin 1-mediated chemo-resistance in lung cancer cells
Mucin 1-mediated chemo-resistance in lung cancer cells
Oncogenesis 5, e185 (January 2016). doi:10.1038/oncsis.2015.47
Authors: S Y Ham, T Kwon, Y Bak, J-H Yu, J Hong, S K Lee, D-Y Yu & D-Y Yoon
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[Synovial sarcoma in children and adolescents].
[Synovial sarcoma in children and adolescents].
Bull Cancer. 2016 Jan 7;
Authors: Mansuy L, Bernier V, Ranchère-Vince D, Mainard L, Orbach D, Corradini N
Abstract
Synovial sarcoma (SS) is a rare high-grade malignant mesenchymal tumor affecting children, adolescents, and young adults. Cytogenetically, more than 90% of SS is characterized by the t(X;18)(p11.2;q11.2), translocation resulting in two chimeric fusion genes SYT-SSX1 and SYT-SSX2, confirming histological diagnosis. Pediatric SS arises most often in soft tissues of the extremities (66% of cases), and is a localized tumor without spreading to regional lymph nodes (96% of cases) nor to metastatic sites (94% of cases). Although clinical and radiologic presentation, histologic analysis and tumor biology appear similar in pediatric and adolescent SS, outcome seems better in children than in adolescents, respectively 84% vs 60% of 5years overall survival (OS). If complete resection is the gold standard in SS, other therapeutic modalities differ between pediatric and adult populations, considering SS as an intermediate chemosensitive tumor more frequently by pediatric oncologists. Prognostic factors evaluation (tumor size, site of primary and IRS group) is necessary to establish optimal treatment strategies, with multimodal therapeutic approach in children and adolescents. Thus, recent results about the European prospective EpSSG NRSTS 05 study for children and adolescent patients with localized SS showed a 5years OS >90%. Moreover, recent somatic genetic data about SS open the debate on an appropriate strategy based and stratified on tumor genomic. Multinational prospective pediatric, adolescent and young adult study is necessary to improve optimal and appropriate approach in this rare tumor.
PMID: 26774699 [PubMed - as supplied by publisher]
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Acute empathy decline among resident physician trainees on a hematology–oncology ward: an exploratory analysis of house staff empathy, distress, and patient death exposure
Abstract
Objective
A reason for empathy decline during medical training has not been fully elucidated. Empathy may decrease acutely during an inpatient hematology–oncology rotation because of the acuity of death exposures. This study aimed to explore physician trainee empathy, distress, death exposures, and their attributed meaning for the trainee.
Methods
Internal medicine interns and residents at a single academic center were evaluated before and after hematology–oncology ward rotations using Interpersonal Reactivity Index for empathy, previously cited reasons for empathy decline, Impact of Event Scale-Revised for distress, death exposures (no. of dying patients cared for) and attributed sense of meaning (yes/no) (post-rotation).
Results
Fifty-six trainees completed both pre-rotation and post-rotation questionnaires (58% response). Empathy averaged 58.9 (SD 12.0) before and 56.8 (SD 11.1) after the rotation (2.1 point decrease) (p = 0.018). Distress was elevated but did not change significantly during the rotation. Residents cared for 4.28 dying patients. Seventy-three percent reported that death was the most stressful event during the rotation, yet 68% reported that they derived a sense of meaning from caring for dying patients. Empathy and distress scales were positively correlated before the rotation (r = 0.277, p = 0.041) but not after (r = .059, p = 0.69).
Conclusion
This study suggests that an acute drop in empathy can occur over several weeks in residents rotating through inpatient hematology–oncology, similar to empathy decline associated with years of training in other studies. Empathy decline may be associated with elevated distress and death exposures on the hematology–oncology ward and should be explored further in other medical training environments. Copyright © 2016 John Wiley & Sons, Ltd.
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Completion thyroidectomy and total thyroidectomy for differentiated thyroid cancer: Comparison and prediction of postoperative hypoparathyroidism
Background
Consensus regarding the difference of postoperative hypoparathyroidism following completion thyroidectomy (CT) and total thyroidectomy (TT) has yet to be reached. We compare the occurrence of postoperative hypoparathyroidism between CT and TT for differentiated thyroid cancer (DTC), and explore the predictive factors for postoperative hypoparathyroidism.
Methods
We retrospectively reviewed 221 consecutive patients underwent CT or TT for DTC between February 2012 and March 2014. Patients' demographic and clinical data of the two groups were analyzed.
Results
There were 57 CTs and 164 TTs. Temporary hypoparathyroidism occurred in 12.3% (7 of 57) and 28.0% (46 of 164) of patients in the CT and TT groups, respectively. In univariate analysis, type of surgical procedure (CT or TT) and extent of central lymph node dissection (CND) (unilateral or bilateral) were significantly associated with the postoperative temporary hypoparathyroidism (P < 0.05). Multivariate analysis showed that only the extent of CND was an independent risk factor for temporary hypoparathyroidism.
Conclusions
Although temporary hypoparathyroidism was lower in the CT group, our analysis indicates the difference is due to the extent of CND rather than type of surgical procedure (CT vs. TT). Only bilateral CND is an independent risk factor for temporary hypoparathyroidism after thyroidectomy. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.
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The true prognosis of resected distal cholangiocarcinoma
Background
Prognosis of distal cholangiocarcinoma (DCC) after pancreaticoduodenectomy (PD) remains poorly assessed. The aims of this study were to describe the oncological results of PD in DCC and to compare its prognosis to pancreatic ductal adenocarcinoma (PDAC).
Methods
All PD for periampullary carcinoma performed between January 2000 and March 2013 were extracted from a prospective database. Risk factors likely to influence overall (OS) and disease-free (DFS) survivals of DCC were assessed by multivariable analyses. The DCC and PDAC prognoses were compared after matching using propensity score (nearest neighbor matching).
Results
Of the 290 patients analyzed, 56 had DCC, with a mean age of 65 ± 15 years. The median OS was 36.9 months. Recurrence occurred in 35 patients (67%), mostly in the liver (37%). The median DFS was 14.6 months. Combined organ resection was an independent risk factor for worse OS and DFS (P = 0.01 and P = 0.001, respectively). Matching analysis found no significant difference between DCC and PDAC in terms of OS (P = 0.284) or DFS (P = 0.438).
Conclusion
This first propensity analysis demonstrated that DCC and PDAC have the same prognosis, linked to the high rate of early recurrence, particularly associated with the need for combined organ resection. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.
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Extended right hepatectomy with caudate lobe resection using the hilar “en bloc” resection technique with a modified hanging maneuver
The hanging liver maneuver is a useful technique to guide the transection of liver parenchyma by lifting a tape passed between the anterior surface of the inferior vena cava and the liver. Modified hanging liver maneuvers have been described in different types of liver resection. Surgical resection of hilar cholangiocarcinoma can involve the portal vein and the caudate lobe for margin clearance. However, hilar dissection and resection of the caudate lobe can be a challenging during the hanging maneuver once the tape is positioned.
Herein, we describe a modified hanging liver maneuver for a hilar "en bloc" extended right hepatectomy with portal vein resection for the treatment of hilar cholangiocarcinoma including the caudate lobe. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.
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Assessment of extent of surgical resection of primary high-grade osteosarcoma by treating institutions: A report from the Children's Oncology Group
Background
Complete surgical resection of primary tumors is critical for long-term control of high-grade osteosarcoma. Uniform assessment of the extent of surgical resection is important in clinical trials, though the accuracy of this reporting has been poorly studied.
Methods
We conducted a retrospective cohort study of patients 5–40 years of age with newly diagnosed high-grade resectable osteosarcoma treated as part of the AOST0331 clinical trial at Children's Oncology Group institutions. The extent of surgical resection of the primary tumor was graded as wide or radical by the treating institution. Central assessment of the extent of resection by two orthopedic oncologists was compared with institutional assessment by reviewing pathology and operative reports.
Results
We included 956 patients who had data available for central review. The extent of resection reported by treating institutions was 536/956 (56%) radical and 420/956 (44%) wide. The extent of resection assessed by central review was 162/956 (17%) radical and 794/956 (83%) wide. The overall discordance rate for the cohort was 43%.
Conclusions
Institutional reports of radical resection in high-grade osteosarcoma significantly over-estimate the proportion of patients undergoing radical resection. This highlights the need for centralized review and improved accuracy of reporting of the extent of resection. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.
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