bluuebunny/crossref_metadata_2025 huggingface dataset:
The knowledge, attitude and behavior about public health emergencies and the response capacity of primary care medical staffs of Guangdong Province, China
Authors: Zhiheng Zhou , Caixia Wang , Jiaji Wang , Huajie Yang , Chao Wang , Wannian Liang
Published: September 2012

Background

Primary care medical staffs’ knowledge, attitude and behavior about health emergency and the response capacity are directly related to the control and prevention of public health emergencies. Therefore, it is of great significance for improving primary care to gain in-depth knowledge about knowledge, attitude and behavior and the response capacity of primary care medical staffs. The main objective of this study is to explore knowledge, attitude and behavior, and the response capacity of primary care medical staffs of Guangdong Province, China.

Methods

Stratified clustered sample method was used in the anonymous questionnaire investigation about knowledge, attitude and behavior, and the response capacity of 3410 primary care medical staffs in 15 cities of Guangdong Province, China from July, 2010 to October 2010. The emergency response capacity was evaluated by 33 questions. The highest score of the response capacity was 100 points (full score), score of 70 was a standard.

Results

62.4% primary care medical staffs believed that public health emergencies would happen. Influenza (3.86 ± 0.88), food poisoning (3.35 ± 0.75), and environmental pollution events (3.23 ± 0.80) (the total score was 5) were considered most likely to occur. Among the 7 public health emergency skills, the highest self-assessment score is “public health emergency prevention skills” (2.90 ± 0.68), the lowest is “public health emergency risk management (the total score was 5)” (1.81 ± 0.40). Attitude evaluation showed 66.1% of the medical staffs believed that the community awareness of risk management were ordinary. Evaluation of response capacity of health emergency showed that the score of primary care medical staffs was 67.23 ± 10.61, and the response capacity of senior physicians, public health physicians and physicians with relatively long-term practice were significantly better (P <0.05). Multiple linear stepwise regression analysis showed gender, title, position, type of work, work experience and whether to participate relative training were the main factors affecting the health emergency response capacity.

Conclusions

The knowledge, attitude and behavior about public health emergencies and the response capacity of primary care medical staffs of Guangdong Province (China) were poor. Health administrative departments should strengthen the training of health emergency knowledge and skills of the primary care medical staffs to enhance their health emergency response capabilities.
Proteomic identification of MYC2-dependent jasmonate-regulated proteins in Arabidopsis thaliana
Authors: Guo Jing , Pang Qiuying , Wang Lihua , Yu Ping , Li Nan , Yan Xiufeng
Published: September 2012

Background

MYC2, a basic helix-loop-helix (bHLH) domain-containing transcription factor, participates in the jasmonate (JA) signaling pathway and is involved in the modulation of diverse JA functions. However, a comprehensive list of MYC2-dependent JA-responsive proteins has yet to be defined.

Results

In this paper, we report the comparative proteomics of wild-type (WT) plants and jin1-9, a MYC2 mutant plant, in response to methyl jasmonate (MeJA) treatment. Proteins from mock/MeJA-treated jin1-9 and WT samples were extracted and separated by two-dimensional gel electrophoresis. Twenty-seven JA-mediated proteins demonstrated differential expression modulated by MYC2. We observed that MYC2 negatively regulates the accumulation of JA-dependent indolic glucosinolate-related proteins and exhibits opposite effects on the biosynthetic enzymes involved aliphatic glucosinolate pathways. In addition, proteins involved in the tricarboxylic acid cycle and a majority of the MeJA-inducible proteins that are involved in multiple protective systems against oxidative stress were reduced in jin1-9/myc2 sample compared to the WT sample. These results support a positive role for MYC2 in regulating JA-mediated carbohydrate metabolism and oxidative stress tolerance.

Conclusions

We have identified MYC2-dependent jasmonate-regulated proteins in Arabidopsis thaliana by performing two-dimensional gel electrophoresis and MALDI-TOF/TOF MS analysis. The observed pattern of protein expression suggests that MYC2 has opposite effects on the biosynthetic enzymes of indolic and aliphatic glucosinolate pathways and positively regulates JA-mediated carbohydrate metabolism and oxidative stress tolerance-related proteins. Furthermore, it is very interesting to note that MYC2 plays opposite roles in the modulation of a subset of JA-regulated photosynthetic proteins during short-term and long-term JA signaling. This study will enhance our understanding of the function of MYC2 in JA signaling in Arabidopsis thaliana.
6th Golden Helix Pharmacogenomics Day: pharmacogenomics and individualized therapy
Authors: Stojiljkovic Maja , Fazlagic Amira , Dokmanovic-Krivokapic Lidija , Nikcevic Gordana , Patrinos George P , Pavlovic Sonja , Zukic Branka
Published: September 2012

The Golden Helix Pharmacogenomics Days are international scientific meetings aiming to educate healthcare professionals and biomedical scientists about pharmacogenomics and personalized medicine. In this meeting report, we provide an overview of the scientific lectures and the topics discussed during the 6th Golden Helix Pharmacogenomics Day that was held in Belgrade, Serbia last June 5, 2012. The scientific program included lectures by the local and international speakers from Europe and the United States.
Toxic epidermal necrolysis, DRESS, AGEP: Do overlap cases exist?
Authors: Bouvresse Sophie , Valeyrie-Allanore Laurence , Ortonne Nicolas , Konstantinou Marie Pauline , Kardaun Sylvia H , Bagot Martine , Wolkenstein Pierre , Roujeau Jean-Claude
Published: September 2012

Background

Severe cutaneous adverse reactions to drugs (SCARs) include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) and epidermal necrolysis (Stevens-Johnson syndrome–toxic epidermal necrolysis [SJS-TEN]). Because of the varied initial presentation of such adverse drug reactions, diagnosis may be difficult and suggests overlap among SCARs. Overlapping SCARs are defined as cases fulfilling the criteria for definite or probable diagnosis of at least 2 ADRs according to scoring systems for AGEP, DRESS and SJS-TEN. We aimed to evaluate the prevalence of overlap among SCARs among cases in the referral hospital in France.

Methods

We retrospectively analyzed data for 216 patients hospitalized in the referral centre over 7 years with a discharge diagnosis of AGEP (n = 45), DRESS (n = 47), SJS-TEN (n = 80) or “drug rash” (n = 44). Each case with detailed clinical data and a skin biopsy specimen was scored for AGEP, DRESS and SJS-TEN by use of diagnostic scores elaborated by the RegiSCAR group.

Results

In total, 45 of 216 cases (21%) had at least 2 possible diagnoses: 35 had a single predominant diagnosis (definite or probable), 7 had several possible diagnoses and 3 (2.1% of 145 confirmed SCARs) were overlap SCARs.

Conclusions

Despite ambiguities among SCARs, confirmed overlap cases are rare. This study did not avoid pitfalls linked to its retrospective nature and selection bias. In the acute stage of disease, early identification of severe ADRs can be difficult because of clinical or biologic overlapping features and missing data on histology, biology and evolution. Retrospectively analyzing cases by use of diagnostic algorithms can lead to reliable discrimination among AGEP, DRESS and SJS-TEN.
Heat degradation of eukaryotic and bacterial DNA: an experimental model for paleomicrobiology
Authors: Nguyen-Hieu Tung , Aboudharam Gérard , Drancourt Michel
Published: September 2012

Background

Theoretical models suggest that DNA degradation would sharply limit the PCR-based detection of both eukaryotic and prokaryotic DNA within ancient specimens. However, the relative extent of decay of eukaryote and prokaryote DNA over time is a matter of debate. In this study, the murine macrophage cell line J774, alone or infected with Mycobacterium smegmatis bacteria, were killed after exposure to 90°C dry heat for intervals ranging from 1 to 48 h in order to compare eukaryotic cells, extracellular bacteria and intracellular bacteria. The sizes of the resulting mycobacterial rpo B and murine rpb 2 homologous gene fragments were then determined by real-time PCR and fluorescent probing.

Findings

The cycle threshold (Ct) values of PCR-amplified DNA fragments from J774 cells and the M. smegmatis negative controls (without heat exposure) varied from 26–33 for the J774 rpb 2 gene fragments and from 24–29 for M. smegmatis rpo B fragments. After 90°C dry heat incubation for up to 48 h, the Ct values of test samples increased relative to those of the controls for each amplicon size. For each dry heat exposure time, the Ct values of the 146-149-bp fragments were lower than those of 746-747-bp fragments. During the 4- to 24-h dry heat incubation, the non-infected J774 cell DNA was degraded into 597-bp rpb 2 fragments. After 48 h, however, only 450-bp rpb 2 fragments of both non-infected and infected J774 cells could be amplified. In contrast, the 746-bp rpo B fragments of M. smegmatis DNA could be amplified after the 48-h dry heat exposure in all experiments. Infected and non-infected J774 cell DNA was degraded more rapidly than M. smegmatis DNA after dry heat exposure (ANOVA test, p < 0.05).

Conclusion

In this study, mycobacterial DNA was more resistant to dry-heat stress than eukaryotic DNA. Therefore, the detection of large, experimental, ancient mycobacterial DNA fragments is a suitable approach for paleomicrobiological studies.
Structural attributes for the recognition of weak and anomalous regions in coiled-coils of myosins and other motor proteins
Authors: Sunitha Margaret S , Nair Anu G , Charya Amol , Jadhav Kamalakar , Mukhopadhyay Sami , Sowdhamini Ramanathan
Published: September 2012

Background

Coiled-coils are found in different proteins like transcription factors, myosin tail domain, tropomyosin, leucine zippers and kinesins. Analysis of various structures containing coiled-coils has revealed the importance of electrostatic and hydrophobic interactions. In such domains, regions of different strength of interactions need to be identified since they could be biologically relevant.

Findings

We have updated our coiled-coil validation webserver, now called COILCHECK+, where new features were added to efficiently identify the strength of interaction at the interface region and measure the density of charged residues and hydrophobic residues. We have examined charged residues and hydrophobic ladders, using a new algorithm called CHAHO, which is incorporated within COILCHECK + server. CHAHO permits the identification of spatial charged residue patches and the continuity of hydrophobic ladder which stabilizes and destabilizes the coiled-coil structure.

Conclusions

The availability of such computational tools should be useful to understand the importance of spatial clustering of charged residues and the continuity of hydrophobic residues at the interface region of coiled-coil dimers. COILCHECK + is a structure based tool to validate coiled-coil stability; it can be accessed athttp://caps.ncbs.res.in/coilcheckplus.
Species diversity and biting activity of Anopheles dirus and Anopheles baimaii (Diptera: Culicidae) in a malaria prone area of western Thailand
Authors: Tananchai Chatchai , Tisgratog Rungarun , Juntarajumnong Waraporn , Grieco John P , Manguin Sylvie , Prabaripai Atchariya , Chareonviriyaphap Theeraphap
Published: September 2012

Background

A survey of adult anopheline mosquito diversities, collected from September 2009 to August 2010, was conducted in a malaria endemic area of western Thailand. Two anopheline species complexes, Dirus and Minimus, along with the Maculatus group were observed. Of several species documented from within each complex and group, four important malaria vectors were identified, including An. dirus, An. baimaii, An. minimus, and An. sawadwongporni. Information on biting activity and host preference for any single species within the Dirus complex has never been assessed. Using specific molecular identification assays, the trophic behavior and biting activity of each sibling species within the Dirus complex were observed and analyzed for the Kanchanaburi Province, Thailand.

Methods

Adult female mosquitoes were collected for two consecutive nights each month during a one year period. Three collection methods, human landing indoor (HLI), human landing outdoor (HLO), and cattle baited collections (CBC) were applied. Each team of collectors captured mosquitoes between 1800 and 0600 h.

Results

From a total of 9,824 specimens, 656 belong to the Dirus complex (An. dirus 6.09% and An. baimaii 0.59%), 8,802 to the Minimus complex (An. minimus 4.95% and An. harrisoni 84.65%) and 366 to the Maculatus group (An. maculatus 2.43% and An. sawadwongporni 1.29%). Both An. dirus and An. baimaii demonstrated exophagic and zoophilic behaviors. Significantly greater numbers of An. dirus and An. baimaii were collected from cattle as compared to humans (P = 0.003 for An. dirus and P = 0.048 for An. baimaii).

Conclusions

Significantly greater numbers of An. dirus and An. baimaii were collected from cattle baited traps as compared to human landing collections (P < 0.05), demonstrating that both species show a strong zoophilic behavior. Knowledge of host-seeking behavior helps to define a species' capacity to acquire and transmit malaria and its contribution to the overall risk for disease transmission in the human population, as well as, assisting in the design and implementation of appropriate vector prevention and control strategies.
DNA Methylation status of Wnt antagonist SFRP5 can predict the response to the EGFR-tyrosine kinase inhibitor therapy in non-small cell lung cancer
Authors: Zhu Jian , Wang Yuyan , Duan Jianchun , Bai Hua , Wang Zhijie , Wei Lai , Zhao Jun , Zhuo Minglei , Wang Shuhang , Yang Lu , An Tongtong , Wu Meina , Wang Jie
Published: September 2012

Background

It is well known that genetic alternation of epidermal growth factor receptor (EGFR) plays critical roles in tumorgenesis of lung cancer and can predict outcome of non-small-cell lung cancer treatment, especially the EGFR tyrosine-kinase inhibitors (EGFR-TKIs) therapy. However, it is unclear whether epigenetic changes such as DNA methylation involve in the response to the EGFR-TKI therapy.

Methods

Tumor samples from 155 patients with stages IIIB to IV NSCLC who received EGFR-TKI therapy were analyzed for DNA methylation status of Wnt antagonist genes, including SFRP1, SFRP2, SFRP5, DKK3, WIF1, and APC, using methylation specific PCR (MSP) method. EGFR mutations detections were performed in the same tissues samples using Denaturing High Performance Liquid Chromatography (DHPLC).

Results

We found that Wnt antagonists tend to methylate simultaneously. Methylation of sFRP1 and sFRP5 are reversely correlated with EGFR mutation (P = 0.005, P = 0.011). However, no correlations of methylations of other Wnt antagonist genes with EGFR mutation were found. The patients with methylated SFRP5 have a significant shorter progression free survival than those with unmethylated SFRP5 in response to EGFR-TKI treatment (P = 0.002), which is independent of EGFR genotype.

Conclusions

Patients with unmethylated SFRP5 are more likely to benefit from EGFR-TKI therapy.
Immunoreactivities of androgen receptor, estrogen receptors, p450arom, p450c17 proteins in wild ground squirrels ovaries during the nonbreeding and breeding seasons
Authors: Li Xiaonan , Zhang Haolin , Sheng Xia , Li Ben , Zhou Jiao , Xu Meiyu , Weng Qiang , Watanabe Gen , Taya Kazuyoshi
Published: September 2012

The aim of this study was to elucidate the regulatory role of androgen in the follicular development of wild female ground squirrels. Immunohistochemical staining of FSHR, LHR, P450c17, P450arom, androgen receptor (AR), estrogen receptors (ERa and ERb) were executed in ovaries of female ground squirrels from both breeding and nonbreeding seasons. In addition, total ovarian proteins were extracted from the ovaries of squirrels from breeding and nonbreeding seasons, and Western blot analysis were performed in order to probe for FSHR, LHR, P450c17, P450arom, AR, ERa and ERb. The results of immunohistochemical staining and Western blotting of P450c17 showed that there was no significant difference between the breeding and nonbreeding seasons. It was found that granulosa cells expressed P450arom during the breeding season. In contrast, there was no positive staining of P450arom in the nonbreeding season. There was no significant difference in immunoreactivity of AR between the breeding and nonbreeding seasons. However, the immunoreactivities of ERa and ERb were both significantly reduced in the nonbreeding season compared to the breeding season. The positive stains of FSHR and LHR were found in the granulosa cells and theca cells of the ovaries of the breeding and nonbreeding seasons. In addition, the Western blotting results of FSHR and LHR showed a significant reduction in the nonbreeding season compared with the breeding season. These findings suggested that androgen might be predominantly converted into estrogen in order to regulate the follicular development via binding of estrogen receptors during the breeding season, whereas androgen might predominantly directly bind androgen receptor to regulate the follicular development during the nonbreeding season in the ovaries of wild female ground squirrels.
The antifungal effect of cellobiose lipid on the cells of Saccharomyces cerevisiae depends on carbon source
Authors: Trilisenko Ludmila V , Kulakovskaya Ekaterina V , Kulakovskaya Tatiana V , Ivanov Alexander Yu , Penkov Nikita V , Vagabov Vladimir M , Kulaev Igor S
Published: September 2012

The cellobiose lipid of Cryptococcus humicola, 16-(tetra-O-acetyl-β-cellobiosyloxy)-2-hydroxyhexadecanoic acid, is a natural fungicide. Sensitivity of the cells of Saccharomyces cerevisiae to the fungicide depends on a carbon source. Cellobiose lipid concentrations inducing the leakage of potassium ions and ATP were similar for the cells grown in the medium with glucose and ethanol. However, the cells grown on glucose and ethanol died at 0.05 mg ml-1 and 0.2 mg ml-1 cellobiose lipid, respectively. Inorganic polyphosphate (PolyP) synthesis was 65% of the control with 0.05 mg ml-1 cellobiose lipid during cultivation on ethanol. PolyP synthesis was not observed during the cultivation on glucose at the same cellobiose lipid concentration. The content of longer-chain polyP was higher during cultivation on ethanol. We speculate the long-chained polyP participate in the viability restoring of ethanol-grown cells after treatment with the cellobiose lipid.
Watchful Waiting in Low–Tumor Burden Follicular Lymphoma in the Rituximab Era: Results of an F2-Study Database
Authors: Solal-Céligny Philippe , Bellei Monica , Marcheselli Luigi , Pesce Emanuela Anna , Pileri Stefano , McLaughlin Peter , Luminari Stefano , Pro Barbara , Montoto Silvia , Ferreri Andrés J.M. , Deconinck Eric , Milpied Noël , Gordon Leo I. , Federico Massimo
Published: September 2012

Purpose

Patients with follicular lymphoma (FL) registered in the F2-study and initially managed without treatment were analyzed to describe the presentation and outcome of a watch and wait (W&W) strategy in the rituximab era, to identify parameters for initiating treatment, and to evaluate whether initial W&W could have deleterious effects on treatment efficacy after progression or relapse.

Patients and Methods

Between 2003 and 2005, 120 patients selected from the 1,093 treatment-naive patients with FL in the F2-study cohort were initially managed expectantly (W&W), and 107 patients were assessed. Most of these patients (80%) had disseminated disease with a low tumor burden according to Groupe d'Etudes des Lymphomes Folliculaires criteria.

Results

After a median follow-up of 64 months, treatment was initiated in 54 patients (50%), with a median delay of 55 months for the entire cohort. In a univariate analysis, involvement of more than four nodal areas (hazard ratio [HR], 2.26) and serum albumin less than 3.5 g/dL (HR, 3.51) were predictive of a shorter time to lymphoma treatment initiation. In a multivariate analysis, only involvement of more than four nodal areas remained significant (HR, 2.32). The 4-year freedom from treatment failure (FFTF) rate of W&W patients (79%; 95% CI, 69% to 85%) was not inferior to that of a subgroup of 242 patients from the F2-study cohort with good prognosis characteristics who were initially treated with a rituximab-based regimen (69%; 95% CI, 61% to 76%; P = .103).

Conclusion

In the rituximab era, patients with FL in a selected prognostically favorable group can still be managed with W&W. W&W does not seem to have detrimental effects on FFTF and overall survival rates after treatment.
Open-Label, Multicenter, Randomized Phase III Trial of Adjuvant Chemoradiation Plus Interferon Alfa-2b Versus Fluorouracil and Folinic Acid for Patients With Resected Pancreatic Adenocarcinoma
Authors: Schmidt Jan , Abel Ulrich , Debus Jürgen , Harig Sabine , Hoffmann Katrin , Herrmann Thomas , Bartsch Detlef , Klein Justus , Mansmann Ulrich , Jäger Dirk , Capussotti Lorenzo , Kunz Reiner , Büchler Markus W.
Published: September 2012

Purpose

Adjuvant chemotherapy prolongs survival in patients with pancreatic cancer, but its benefit is limited. Long-term survival times of up to 44 months after adjuvant chemoradioimmunotherapy in phase II trials motivated the present study.

Patients and Methods

Between 2004 and 2007, 132 R0/R1 resected patients received either fluorouracil (FU), cisplatin, and interferon alfa-2b (IFN α-2b) plus radiotherapy followed by two cycles of FU (arm A, n = 64) or six cycles of FU monotherapy (arm B, n = 68). One hundred ten patients (arm A, n = 53; arm B, n = 57) received at least one dose of the study medication, and these patients composed the per-protocol (PP) population. Biomarkers were analyzed longitudinally for their predictive value.

Results

Median survival for all randomly assigned patients was 26.5 months (95% CI, 21.6 to 39.5 months) in arm A and 28.5 months (95% CI, 20.4 to 38.6 months) in arm B. The hazard ratio was 1.04 (arm A v arm B: 95% CI, 0.66 to 1.53; P = .99). Median survival for the PP population was 32.1 months (95% CI, 22.8 to 42.2 months) in arm A and 28.5 months (95% CI, 19.5 to 38.6 months) in arm B (P = .49). Eighty-five percent of patients in arm A and 16% of patients in arm B experienced grade 3 or 4 toxicity. The quality of life was temporarily negatively affected in arm A.

Conclusion

The FU, cisplatin, and IFN α-2b plus radiotherapy regimen did not improve the survival compared with FU monotherapy. Given the substantial adverse effects, this treatment can currently not be recommended. Nevertheless, the outcome in both arms represents the best survival, to our knowledge, ever reported for patients with resected pancreatic cancer in randomized controlled trials. Future studies will demonstrate whether immune response to IFN α-2b challenge has a predictive value.
Long-Term Results of the Randomized Phase III Trial EORTC 18991 of Adjuvant Therapy With Pegylated Interferon Alfa-2b Versus Observation in Resected Stage III Melanoma
Authors: Eggermont Alexander M.M. , Suciu Stefan , Testori Alessandro , Santinami Mario , Kruit Wim H.J. , Marsden Jeremy , Punt Cornelis J.A. , Salès François , Dummer Reinhard , Robert Caroline , Schadendorf Dirk , Patel Poulam M. , de Schaetzen Gaetan , Spatz Alan , Keilholz Ulrich
Published: September 2012

Purpose

Adjuvant pegylated interferon alfa-2b (PEG-IFN-α-2b) was approved for treatment of resected stage III melanoma in 2011. Here, we present long-term follow-up results of this pivotal trial.

Patients and Methods

In all, 1,256 patients with resected stage III melanoma were randomly assigned to observation (n = 629) or PEG-IFN-α-2b (n = 627) for an intended duration of 5 years. Stratification factors were microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumor thickness, sex, and center. Recurrence-free survival (RFS; primary end point), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed for the intent-to-treat population.

Results

At 7.6 years median follow-up, 384 recurrences or deaths had occurred with PEG-IFN-α-2b versus 406 in the observation group (hazard ratio [HR], 0.87; 95% CI, 0.76 to 1.00; P = .055); 7-year RFS rate was 39.1% versus 34.6%. There was no difference in OS (P = .57). In stage III-N1 ulcerated melanoma, RFS (HR, 0.72; 99% CI, 0.46 to 1.13; P = .06), DMFS (HR, 0.65; 99% CI, 0.41 to 1.04; P = .02), and OS (HR, 0.59; 99% CI, 0.35 to 0.97; P = .006) were prolonged with PEG-IFN-α-2b. PEG-IFN-α-2b was discontinued for toxicity in 37% of patients.

Conclusion

Adjuvant PEG-IFN-α-2b for stage III melanoma had a positive impact on RFS, which was marginally significant and slightly diminished versus the benefit seen at prior follow-up (median, 3.8 years). No significant increase in DMFS or OS was noted in the overall population. Patients with ulcerated melanoma and lower disease burden had the greatest benefit.
Troublesome Symptoms in Cancer Survivors: Fatigue, Insomnia, Neuropathy, and Pain
Authors: Pachman Deirdre R. , Barton Debra L. , Swetz Keith M. , Loprinzi Charles L.
Published: September 2012

Patients with cancer suffer from a variety of symptoms associated with both cancer and its treatment. These symptoms may lead to a decreased quality of life for patients and can affect compliance with cancer therapies. The importance of adequately treating cancer-related symptoms is gaining more attention but, overall, many symptoms remain underdiagnosed and undertreated. Fatigue, insomnia, neuropathy, and pain are among the most common troublesome symptoms experienced by cancer survivors. This article will focus on the management of these symptoms, including an assessment of the current research and proposed best- management practices.
Sexuality in Adult Cancer Survivors: Challenges and Intervention
Authors: Bober Sharon L. , Varela Veronica Sanchez
Published: September 2012

Sexual dysfunction is one of the most common and distressing consequences of cancer treatment. Although some treatment-related sexual adverse effects are short-term, many survivors face long-term effects such as treatment-induced menopause, altered gonadal function, and significant surgical disfigurement. Profound sexual dysfunction has been shown to have a significant negative effect on quality of life. Although these problems have been well documented and there are a range of intervention strategies that can help patients cope with treatment-related sexual problems, many survivors do not feel prepared for potential sexual changes and often do not receive adequate support to manage sexual dysfunction. Numerous barriers contribute to this underprovided aspect of survivorship care, including lack of provider training and access to readily available resources. In addition, psychological, relational, and cultural factors significantly influence sexuality but are often not taken into consideration in research and clinical practice. By taking an integrative approach and providing survivors with appropriate screening, information, and support, sexual dysfunction and accompanying distress can be significantly alleviated. In this article, we aim to provide a concise review of the most common sexual problems experienced by survivors and highlight some of the most promising evidence-based practices for assessment and intervention. We also address limitations encountered in research and practice and explore future directions, including suggestions for adopting an integrative treatment model to address sexual dysfunction in a cancer survivorship treatment setting.
Nomogram Predicting Long-Term Survival After D2 Gastrectomy for Gastric Cancer
Authors: Han Dong-Seok , Suh Yun-Suhk , Kong Seong-Ho , Lee Hyuk-Joon , Choi Yunhee , Aikou Susumu , Sano Takeshi , Park Byung-Joo , Kim Woo-Ho , Yang Han-Kwang
Published: September 2012

Purpose

The aim of this study was to combine clinicopathologic variables associated with overall survival after gastric resection with D2 lymphadenectomy (D2 gastrectomy) for gastric cancer into a prediction nomogram.

Patients and Methods

We retrospectively analyzed 7,954 patients who underwent D2 gastrectomy for gastric cancer at Seoul National University Hospital (SNUH) in Seoul, Korea. Two thirds of the patients were randomly assigned to the training set (n = 5,300), and one third were assigned to the validation set (n = 2,654). Multivariate analysis by Cox proportional hazards regression was performed using the training set, and the nomogram was constructed. Discrimination and calibration were performed using the SNUH validation set. Additional external validation was performed using the data set (n = 2,500) from Cancer Institute Ariake Hospital (CIAH) in Tokyo, Japan.

Results

The multivariate Cox model identified age at diagnosis, sex, location, depth of invasion, number of metastatic lymph nodes, and number of examined lymph nodes as covariates associated with survival. In the SNUH validation set, the nomogram exhibited superior discrimination power compared with the seventh American Joint Committee on Cancer TNM classification (Harrell's C-index, 0.78 v 0.69, respectively; P < .001). Calibration of the nomogram predicted survival corresponding closely with the actual survival. In the CIAH validation set, discrimination was good (C-index, 0.79), and the predicted survival was within a 10% margin of ideal nomogram.

Conclusion

We developed a nomogram predicting 5- and 10-year overall survival after D2 gastrectomy for gastric cancer. Validation using the SNUH and CIAH data sets revealed good discrimination and calibration, suggesting good clinical utility. The nomogram improved individualized predictions of survival.
Sexuality and Intimacy After Definitive Treatment and Subsequent Androgen Deprivation Therapy for Prostate Cancer
Authors: Higano Celestia S.
Published: September 2012

There are more than 2 million prostate cancer survivors in the United States. Primary therapy with surgery or radiation results in permanent changes in sexual function. More than half of these men are subsequently treated with androgen deprivation therapy (ADT) at some point. The addition of ADT further compromises sexuality, intimacy, and a couple's relationship. This review will highlight the challenges faced by patients and couples and reveal the tremendous need for better education of physicians, patients, and couples as well as for more research in sexuality and intimacy with the goal of improving quality of life for this large population of survivors. Suggestions for clinicians to better help patients and their partners regarding sexuality and intimacy are offered.
Cancer-Related Lymphedema Risk Factors, Diagnosis, Treatment, and Impact: A Review
Authors: Paskett Electra D. , Dean Julie A. , Oliveri Jill M. , Harrop J. Phil
Published: September 2012

Purpose

Cancer-related lymphedema (LE) is an incurable condition associated with lymph-involved cancer treatments and is an increasing health, quality of life (QOL), and cost burden on a growing cancer survivor population. This review examines the evidence for causes, risk, prevention, diagnosis, treatment, and impact of this largely unexamined survivorship concern.

Methods

PubMed and Medline were searched for cancer-related LE literature published since 1990 in English. The resulting references (N = 726) were evaluated for strength of design, methods, sample size, and recent publication and sorted into categories (ie, causes/prevention, diagnosis, treatment, and QOL). Sixty studies were included.

Results

Exercise and physical activity and sentinel lymph node biopsy reduce risk, and overweight and obesity increase risk. Evidence that physiotherapy reduces risk and that lymph node status and number of malignant nodes increase risk is less strong. Perometry and bioimpedence emerged as attractive diagnostic technologies, replacing the use of water displacement in clinical practice. Swelling can also be assessed by measuring arm circumference and relying on self-report. Symptoms can be managed, not cured, with complex physical therapy, low-level laser therapy, pharmacotherapy, and surgery. Sequelae of LE negatively affect physical and mental QOL and range in severity. However, the majority of reviewed studies involved patients with breast cancer; therefore, results may not be applicable to all cancers.

Conclusion

Research into causes, prevention, and effect on QOL of LE and information on LE in cancers other than breast is needed. Consensus on definitions and measurement, increased patient and provider awareness of signs and symptoms, and proper and prompt treatment/access, including psychosocial support, are needed to better understand, prevent, and treat LE.
Second Malignant Neoplasms: Assessment and Strategies for Risk Reduction
Authors: Wood Marie E. , Vogel Victor , Ng Andrea , Foxhall Lewis , Goodwin Pamela , Travis Lois B.
Published: September 2012

Improvements in early detection, supportive care, and treatment have resulted in an increasing number of cancer survivors, with a current 5-year relative survival rate for all cancers combined of approximately 66.1%. For some patients, these survival advances have been offset by the long-term late effects of cancer and its treatment, with second malignant neoplasms (SMNs) comprising one of the most potentially life-threatening sequelae. The number of patients with SMNs is growing, with new SMNs now representing about one in six of all cancers reported to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. SMNs reflect not only the late effects of therapy but also the influence of shared etiologic factors (in particular, tobacco and excessive alcohol intake), genetic susceptibility, environmental exposures, host effects, and combinations of factors, including gene-environment interactions. For selected SMNs, risk is also modified by age at exposure and attained age. SMNs can be categorized into three major groups according to the predominant etiologic factor(s): (1) treatment-related, (2) syndromic, and (3) those due to shared etiologic exposures, although the nonexclusivity of these groups should be underscored. Here we provide an overview of SMNs in survivors of adult-onset cancer, summarizing the current, albeit limited, clinical evidence with regard to screening and prevention, with a focus on the provision of guidance for health care providers. The growing number of patients with second (and higher-order) cancers mandates that we also further probe etiologic influences and genetic variants that heighten risk, and that we better define high-risk groups for targeted preventive and interventional clinical strategies.
Resistance and Escape From Antiangiogenesis Therapy: Clinical Implications and Future Strategies
Authors: Bottsford-Miller Justin N. , Coleman Robert L. , Sood Anil K.
Published: September 2012

Angiogenesis has long been considered an important target for cancer therapy. Initial efforts have primarily focused on targeting of endothelial and tumor-derived vascular endothelial growth factor signaling. As evidence emerges that angiogenesis has significant mechanistic complexity, therapeutic resistance and escape have become practical limitations to drug development. Here, we review the mechanisms by which dynamic changes occur in the tumor microenvironment in response to antiangiogenic therapy, leading to drug resistance. These mechanisms include direct selection of clonal cell populations with the capacity to rapidly upregulate alternative proangiogenic pathways, increased invasive capacity, and intrinsic resistance to hypoxia. The implications of normalization of vasculature with subsequently improved vascular function as a result of antiangiogenic therapy are explored, as are the implications of the ability to incorporate and co-opt otherwise normal vasculature. Finally, we consider the extent to which a better understanding of the biology of hypoxia and reoxygenation, as well as the depth and breadth of systems invested in angiogenesis, may offer putative biomarkers and novel therapeutic targets. Insights gained through this work may offer solutions for personalizing antiangiogenesis approaches and improving the outcome of patients with cancer.
Lifestyle Factors in Cancer Survivorship
Authors: Ligibel Jennifer
Published: September 2012

Lifestyle factors have been linked to the risk of developing many common malignancies and, increasingly, to prognosis. Observational evidence has shown a relationship between so-called energy balance factors (ie, diet, physical activity, and body weight) and risk of cancer recurrence and mortality in cancers of the breast, prostate, colon and, perhaps, other cancers. Interventional work has shown that individuals who make favorable changes in these lifestyle factors after cancer diagnosis feel better, experience less fatigue, and may possibly even decrease risk of cancer recurrence. Other lifestyle behaviors, such as smoking and alcohol consumption, have also been linked to the development of common cancers and may have important health consequences for cancer survivors. This article reviews the evidence that links lifestyle factors to cancer outcomes, provides clinical recommendations for cancer survivors, and describes future directions for lifestyle research in cancer survivors.
Randomized Trial of Short-Course Radiotherapy Versus Long-Course Chemoradiation Comparing Rates of Local Recurrence in Patients With T3 Rectal Cancer: Trans-Tasman Radiation Oncology Group Trial 01.04
Authors: Ngan Samuel Y. , Burmeister Bryan , Fisher Richard J. , Solomon Michael , Goldstein David , Joseph David , Ackland Stephen P. , Schache David , McClure Bev , McLachlan Sue-Anne , McKendrick Joseph , Leong Trevor , Hartopeanu Cris , Zalcberg John , Mackay John
Published: September 2012

Purpose

To compare the local recurrence (LR) rate between short-course (SC) and long-course (LC) neoadjuvant radiotherapy for rectal cancer.

Patients and Methods

Eligible patients had ultrasound- or magnetic resonance imaging–staged T3N0-2M0 rectal adenocarcinoma within 12 cm from anal verge. SC consisted of pelvic radiotherapy 5 × 5 Gy in 1 week, early surgery, and six courses of adjuvant chemotherapy. LC was 50.4 Gy, 1.8 Gy/fraction, in 5.5 weeks, with continuous infusional fluorouracil 225 mg/m2 per day, surgery in 4 to 6 weeks, and four courses of chemotherapy.

Results

Three hundred twenty-six patients were randomly assigned; 163 patients to SC and 163 to LC. Median potential follow-up time was 5.9 years (range, 3.0 to 7.8 years). Three-year LR rates (cumulative incidence) were 7.5% for SC and 4.4% for LC (difference, 3.1%; 95% CI, −2.1 to 8.3; P = .24). For distal tumors (< 5 cm), six of 48 SC patients and one of 31 LC patients experienced local recurrence (P = .21). Five-year distant recurrence rates were 27% for SC and 30% for LC (log-rank P = 0.92; hazard ratio [HR] for LC:SC, 1.04; 95% CI, 0.69 to 1.56). Overall survival rates at 5 years were 74% for SC and 70% for LC (log-rank P = 0.62; HR, 1.12; 95% CI, 0.76 to 1.67). Late toxicity rates were not substantially different (Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer G3-4: SC, 5.8%; LC, 8.2%; P = .53).

Conclusion

Three-year LR rates between SC and LC were not statistically significantly different; the CI for the difference is consistent with either no clinically important difference or differences in favor of LC. LC may be more effective in reducing LR for distal tumors. No differences in rates of distant recurrence, relapse-free survival, overall survival, or late toxicity were detected.
Long-Term and Late Effects of Germ Cell Testicular Cancer Treatment and Implications for Follow-Up
Authors: Haugnes Hege S. , Bosl George J. , Boer Hink , Gietema Jourik A. , Brydøy Marianne , Oldenburg Jan , Dahl Alv A. , Bremnes Roy M. , Fosså Sophie D.
Published: September 2012

Germ cell testicular cancer (TC) represents a malignancy with high cure rates. Since the introduction of cisplatin-based chemotherapy in the late 1970s, the 5-year survival rate has increased considerably, and it is currently above 95%. Because TC is usually diagnosed before the age of 40 years, these men can expect to live for another 40 to 50 years after being successfully treated. This success, however, is hampered by an increased risk of long-term and late effects of treatment. Secondary malignant neoplasms and cardiovascular disease represent the most common potentially life-threatening late effects, typically occurring more than 10 years after treatment. Other long-term effects include pulmonary toxicity, nephrotoxicity, neurotoxicity, decreased fertility, hypogonadism, and psychosocial problems. The incidence and time to onset of these various adverse effects vary according to treatment type and intensity. There is still little knowledge about underlying mechanisms and genetic susceptibility of the various adverse effects. Apart from treatment burden, it is not yet possible to identify patients who are at high risk for certain late effects after TC treatment. In this clinical review, we present the current status regarding different somatic and psychosocial long-term late effects after treatment for TC, based on Medline searches and our own research. Moreover, we postulate recommendations for general medical evaluations that should begin after treatment is completed and continue during follow-up.
RNA Interference-Based Silencing Reveals the Regulatory Role of Fatty Acid-Binding Protein 4 in the Production of IL-6 and Vascular Endothelial Growth Factor in 3T3-L1 Adipocytes
Authors: Kajimoto Kazuaki , Takayanagi Shiharu , Sasaki Shun , Akita Hidetaka , Harashima Hideyoshi
Published: September 2012

The fatty acid-binding protein 4 (FABP4) is believed to play an important role in maintaining glucose and lipid homeostasis. However, the physiological functions of FABP4 in adipocytes have not been fully elucidated because of difficulties associated with the effective transfection of small interfering RNA (siRNA) to differentiated adipocytes. The aim of this study was to clarify the physiological roles of FABP4 in adipocytes by establishing an efficient, universal technique for endogenous gene silencing in fully differentiated 3T3-L1 cells. Confocal-based three-dimensional observations demonstrated that, in traditionally cultured 3T3-L1 cells, multilayers of undifferentiated cells were formed. As a result, small interfering RNA failed to reach many of the differentiated cells. To solve this problem, we developed a reliable method, denoted as density-based separation followed by replating of enriched adipocytes in a monolayer (DREAM) and, using the developed method, succeeded in a significant knockdown of FABP4. Loss-of-function analyses revealed that FABP4 regulates the expression of IL-6 and vascular endothelial growth factor (VEGF) mediated by the protease-activated receptor 1 (PAR1), a thrombin receptor, in adipocytes. In addition, the basal IL-6 production was partially suppressed by PAR1 knockdown. Moreover, we also demonstrated that IL-6 stimulates the proliferation of primary endothelial cells isolated from murine adipose tissue. These findings indicate that FABP4 may have a crucial role in modulating IL-6 and vascular endothelial growth factor as angiogenesis inducers stimulated by the cellular action of thrombin on adipocytes via PAR1. These findings promise to be helpful for developing an understanding of physiological counterparts with respect to the inflammatory and angiogenic properties of adipose tissue.
Rhesus Monkey Cumulus Cells Revert to a Mural Granulosa Cell State After an Ovulatory Stimulus
Authors: Chaffin Charles L. , Lee Young S. , VandeVoort Catherine A. , Patel Bela G. , Latham Keith E.
Published: September 2012

Follicular somatic cells (mural granulosa cells and cumulus cells) and the oocyte communicate through paracrine interactions and through direct gap junctions between oocyte and cumulus cells. Considering that mural and cumulus cells arise through a common developmental pathway and that their differentiation is essential to reproductive success, understanding how these cells differ is a key aspect to understanding their critical functions. Changes in global gene expression before and after an ovulatory stimulus were compared between cumulus and mural granulosa cells to test the hypothesis that mural and cumulus cells are highly differentiated at the time of an ovulatory stimulus and further differentiate during the periovulatory interval. The transcriptomes of the two cell types were markedly different (>1500 genes) before an ovulatory hCG bolus but converged after ovulation to become completely overlapping. The predominant transition was for the cumulus cells to become more like mural cells after hCG. This indicates that the differentiated phenotype of the cumulus cell is not stable and irreversibly established but may rather be an ongoing physiological response to the oocyte.
Congenital adrenal hyperplasia in pregnancy: approach depends on who is the ‘patient’
Authors: Keely Erin , Malcolm Janine
Published: September 2012

Congenital adrenal hyperplasia (CAH) is a group of autosomal-recessive disorders caused by a reduced or absent enzymatic activity at one of the stages of adrenal steroid biosynthesis. Prenatal exposure to androgens leads to external genital masculinization of the affected female child. In pregnancy, the provider may be optimizing care for the woman with CAH or targeting treatment to reduce virilization in the affected unborn child. For the affected adult woman the goals of therapy in pregnancy are to prevent adrenal insufficiency, reduce fetal exposure to androgens and glucocorticoids and to avoid damage to reconstructed genitalia. For prenatal therapy for prevention of virilization of possibly affected female children, dexamethasone is used. However, questions remain about the efficacy and safety of exposing 7/8 unaffected children in the first trimester. Prenatal treatment should only be undertaken after careful discussion with the parents of the risks and benefits in an experienced centre or as part of a research protocol.
A noncoding RNA produced by arthropod-borne flaviviruses inhibits the cellular exoribonuclease XRN1 and alters host mRNA stability
Authors: Moon Stephanie L. , Anderson John R. , Kumagai Yutaro , Wilusz Carol J. , Akira Shizuo , Khromykh Alexander A. , Wilusz Jeffrey
Published: September 2012

All arthropod-borne flaviviruses generate a short noncoding RNA (sfRNA) from the viral 3′ untranslated region during infection due to stalling of the cellular 5′-to-3′ exonuclease XRN1. We show here that formation of sfRNA also inhibits XRN1 activity. Cells infected with Dengue or Kunjin viruses accumulate uncapped mRNAs, decay intermediates normally targeted by XRN1. XRN1 repression also resulted in the increased overall stability of cellular mRNAs in flavivirus-infected cells. Importantly, a mutant Kunjin virus that cannot form sfRNA but replicates to normal levels failed to affect host mRNA stability or XRN1 activity. Expression of sfRNA in the absence of viral infection demonstrated that sfRNA formation was directly responsible for the stabilization of cellular mRNAs. Finally, numerous cellular mRNAs were differentially expressed in an sfRNA-dependent fashion in a Kunjin virus infection. We conclude that flaviviruses incapacitate XRN1 during infection and dysregulate host mRNA stability as a result of sfRNA formation.