妊娠期乳腺癌相关基因的生物信息学分析

目的通过生物信息分析途径对妊娠期乳腺癌患者与正常人群的差异基因进行分析,从分子水平探讨妊娠期乳腺癌的发病机制。方法从公共数据库基因表达数据库(GEO)中下载妊娠期乳腺癌相关数据集,采用Qlucore Omics Explore(QOE)筛选差异表达基因,用DAIVID、STRING等在线分析工具对差异表达基因进行功能富集分析,信号转导通路分析以及预测蛋白质之间的关系。结果共筛选出148个差异表达基因,其中表达上调24个,下调124个,对其进行生物信息学分析发现,TAGLN、ACTG2、TPM2、TPM3、MYLK、ACTA2、MTH11等基因以及MAPK信号通路、黏着斑信号通路、血管平滑肌细胞收缩信号通路等在妊娠期乳腺癌的发生发展中可能起着重要作用。通过STRING分析发现,20个基因处于核心节点位置。结论利用生物信息学的方法能有效分析基因芯片数据并获取生物内在信息。     

Coping,catastrophizing and chronic pain in breast cancer

This cross-sectional study investigated the relationships between individual differences in coping and catastrophizing, and markers of adaptation to chronic pain associated with breast cancer. Sixty-eight breast cancer patients with chronic pain due to either cancer or cancer-treatment were administered self-report instruments that assess active and passive coping, catastrophizing, pain, disability, and mood disturbance. Regression analyses were performed to investigate the unique contribution of differences in coping and catastrophizing to the various markers of adaptation. Both active and passive coping explained unique variance in self-reported disability; active coping was associated with less disability while passive coping was associated with greater disability. Catastrophizing explained unique variance in anxiety and depression scores; higher levels of catastrophizing were associated with greater emotional distress. The results suggest that coping and catastrophizing may contribute to different outcomes in chronic pain in breast cancer patients and provides preliminary evidence that they may be important targets of psychological treatments.     

Aerobic and resistance exercise improve patient-reported sleep quality and is associated with cardiometabolic biomarkers in Hispanic and non-Hispanic breast cancer survivors who are overweight or obese: results from a secondary analysis

Study ObjectivesPoor sleep quality affects nearly one-third of breast cancer survivors and is associated with insulin resistance. The purpose of this secondary analysis was to examine the effects of a 16-week exercise intervention on patient-reported sleep quality among breast cancer survivors and assess whether changes in patient-reported sleep quality were associated with cardiometabolic biomarkers. We explored Hispanic ethnicity as a moderator of the effects of exercise on patient-reported sleep quality.MethodsBreast cancer survivors who were overweight or obese were randomized to exercise (n = 50) or usual care (n = 50). The 16-week intervention included aerobic and resistance exercise. Patient-reported sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and biomarkers of cardiometabolic health were assessed at baseline and post-intervention. Within- and between-group differences were assessed using general linear models repeated-measures analyses of variance and mixed-model repeated-measure analysis, respectively. Associations between changes in PSQI and cardiometabolic biomarkers were computed using Pearson correlations. Linear mixed-models were used to evaluate effect modification by ethnicity.ResultsParticipants were 52 ± 10.4 years old, and over half were of Hispanic ethnicity. As compared to usual care, PSQI global scores improved significantly in the exercise group (mean between-group difference −2.2; 95% CI −3.2 to −0.6). Change in PSQI was inversely associated with changes in all cardiometabolic biomarkers (p < 0.01) among the exercise group. Ethnicity was found to moderate the effects of exercise training on global sleep quality (p < 0.001).ConclusionsAn aerobic and resistance exercise intervention effectively improved patient-reported sleep quality in breast cancer survivors. Hispanic ethnicity as a moderator showed greater improvement in patient-reported sleep indicating Hispanic versus non-Hispanic breast cancer survivors may derive larger sleep benefits.Clinical Trail Information{"type":"clinical-trial","attrs":{"text":"NCT01140282","term_id":"NCT01140282"}}NCT01140282.     

Subjective insomnia symptoms and sleep duration are not related to hypothalamic–pituitary–adrenal axis activity in older adults

Insomnia symptoms are highly prevalent in depressed older adults. This study investigates the association between hypothalamic–pituitary–adrenal (HPA) axis activity and symptoms of insomnia, respectively, sleep duration among 294 depressed and 123 non‐depressed older adults of the Netherlands Study of Depression in Older people (NESDO) study. Insomnia symptoms were defined as clinically relevant when having a score ≥ 10 points on the Women's Health Initiative Insomnia Rating Scale (WHIIRS). Sleep duration was categorized in short (≤ 6 h per night), normal (7–8 h per night) and long (≥ 9 h per night) duration. Salivary cortisol levels were used to assess the following cortisol parameters for HPA axis activity: area under the curve with respect to the increase (AUCi) and to the ground (AUCg), diurnal slope, evening cortisol level and dexamethasone suppression ratio. Clinically relevant insomnia symptoms were present in 46% of the participants. Thirty‐two per cent of the participants were short sleepers, whereas 16% were long sleepers. However, univariate analyses showed no differences in any of the HPA axis parameters between people with and without insomnia symptoms or between the three groups with different sleep duration. In addition, no significant interaction was found between a diagnosis of depression or the severity of depressive symptoms and any of the cortisol parameters in relation to insomnia symptoms or sleep duration.     

Physical exercise and quality of life in breast cancer survivors

An important goal for cancer patients is to improve the quality of life (QOL) by maximising functions affected by the disease and its therapy. Preliminary research suggests that exercise may be an effective intervention for enhancing QOL in cancer survivors. Research has provided preliminary evidence for the safety, feasibility, and efficacy of exercise training in breast cancer survivors. The aim of this study was to assess the association between physical exercise and quality of life in a population of female breast cancer survivors, followed up from diagnosis to the off-treatment time period, and investigated about their exercise habits in pre-diagnosis.A total of 212 female breast cancer survivors consecutively registered from January 2002 to December 2006 at a Supportive Care Unit in an Italian Oncology Department were enrolled. Exercise behaviour was assessed by the Leisure Score Index (LSI) of the Godin Leisure-Time Exercise Questionnaire. Patients were asked to report their average weekly exercise for three cancer-related time periods, i.e. pre-diagnosis, during active treatment and off-treatment. Quality of life was assessed by the Italian version of the WHOQOL-BREF standardised instrument. Statistical analysis indicated significant differences across the cancer-relevant time-periods for all exercise behaviour outcomes: the exercise behaviour was significantly lower during both on- and off- treatment than during prediagnosis; exercise during active treatment was significantly lower than during off-treatment. QOL strongly decreases during active treatment. Significant correlations were found between total exercise on- and off-treatment and all QOL indicators. Strenuous exercise is strongly correlated with QOL. Absent/mild exercise seems to be inversely correlated with a positive perception of disease severity and with quality of life on all axes. Need clearly results for inclusion of physical activity programs in comprehensive, complementary treatment regimes for breast cancer patients in Italian oncology departments.     

Position of the Spanish Menopause Society regarding the management of menopausal symptoms in breast cancer patients

Breast cancer is the most common female cancer in Spain. Its high prevalence, its high survival rate, and its incidence are the reasons treatment is increasingly sought for common problems by young women who have survived it. Besides the contraception and fertility issues, many breast cancer survivors develop sexual disorders and menopausal symptoms, whether as a consequence of treatment-induced menopause or side effects of treatment. For such reasons, a panel of experts from the Spanish Menopause Society has met to develop usage recommendations for the relief of vasomotor symptoms and for sexual and reproductive health in patients with breast cancer based on the best evidence available.     

Duration of sleep and breast cancer risk in a large population-based case-control study

One important function of sleep may be its contribution to the maintenance of the immune system and regulation of the circadian rhythms by melatonin. Researchers have speculated that disruption of immune functions involving cortisol levels and natural killer cell activity may increase breast cancer risk whereas increased melatonin exposure may protect against breast cancer. We conducted a multistate population-based case-control study of 4,033 women with invasive breast cancer and 5,314 community women without breast cancer in which we inquired about women's sleep habits in the recent past and during adult lifetime. Relative to women who slept 7.0-7.9 h/night, the multivariate odds ratio for developing breast cancer among women who slept an average of 9 h or more per night approximately 2 years prior to interview was 1.13 (95% CI 0.93-1.37). The multivariate-adjusted odds ratio for the continuous term was 1.06 (95% CI 1.01-1.11), suggesting a 6% increase in risk for every additional hour of sleep. Similar patterns were observed for average lifetime adult sleep duration. We found little evidence that sleeping few hours per night was associated with breast cancer risk. The results of this study suggest that increasing sleep duration is modestly associated with an increased breast cancer risk. In contrast, short duration of sleep (<7 h/night) is not substantially associated with increased risk. Further research in this area is warranted.     

The management of menopausal symptoms in breast cancer survivors: A case-based approach

Introduction

The intensified treatment of breast cancer improves survival but has a price in terms of side-effects. The main side-effects, such as vasomotor symptoms and impaired sexual functioning, are related to premature menopause due to chemotherapy and/or anti-hormonal therapy. Though for some women these symptoms are bearable, for others they have a large impact on their quality of life. The paper discusses the menopausal symptoms most frequently reported by breast cancer survivors and current treatment options.

Methods

A literature review is presented of menopausal symptoms after breast cancer and management strategies, illustrated by two cases.

Summary

Vasomotor symptoms can be relieved by lifestyle adaptation, acupuncture and non-hormonal agents such as venlafaxine, gabapentin or clonidine. Impaired sexual functioning can be treated by couple-based sexual counselling or psycho-educational therapy. Painful intercourse due to vaginal dryness can be alleviated by vaginal lubricants and moisturizers, but is most effectively treated by vaginal estriol. Local estriol seems safe if used for a short period (less than six weeks). Because of proven increased risk of recurrence with hormone replacement therapy (HRT), it should not be prescribed for breast cancer survivors, although exceptions could be made of selected cases of fully informed BRCA mutation carriers after ER-negative breast cancer and with severe menopausal symptoms due to prophylactic oophorectomy at a young age and (preferably) after mastectomy.

Conclusion

The management of vasomotor symptoms and impaired sexual functioning in breast cancer survivors should focus on lifestyle and, if necessary, non-hormonal pharmacological interventions.     

Contribution of BRCA1 and BRCA2 germline mutations to the incidence of early-onset breast cancer in Cyprus

In Cyprus, the prevalence of breast cancer associated with BRCA1 and BRCA2 mutations in young women is unknown. In this study, we present the results of mutational analysis of the BRCA1 and BRCA2 genes in 26 Cypriot women diagnosed with breast cancer by the age of 40. The entire coding regions, including splice sites, of the BRCA1 and BRCA2 genes were sequenced using cycle sequencing. We identified four pathogenic mutations: two in BRCA1 [c.1840A>T (K614X), c.5310delG (5429delG)] and two in BRCA2 [c.3531-3534delCAGC (3758del4), c.8755delG (8984delG)] in six of 26 unrelated patients. The BRCA2 mutation c.3531-3534delCAGC (3758del4) is novel and the BRCA1 mutation c.1840A>T (K614X) is reported for the first time in Cypriot patients. The BRCA2 Cypriot founder mutation c.8755delG (8984delG) was detected in three unrelated patients. Additionally, we identified one novel BRCA1 missense mutation, two novel polymorphisms and three novel intronic variants of which BRCA1 c.4185+3A>G (IVS12+3A>G) may be pathogenic. Of the six BRCA1/2 mutation carriers, only four had a family history. These results show that the prevalence of BRCA1 and BRCA2 mutations in Cypriot women diagnosed with early-onset breast cancer is high. We conclude that Cypriot women with early-onset breast cancer should be offered BRCA1/2 testing irrespective of their family history.     

Impact of mindfulness-based stress reduction (MBSR) on sleep,mood, stress and fatigue symptoms in cancer outpatients

Sleep disturbance is a very common problem for cancer patients that has largely not been addressed in the clinical intervention literature. Mindfulness meditation has demonstrated clinical benefits for a variety of patient populations in other areas of functioning. This study examined the effects of an 8-week Mindfulness-Based Stress Reduction (MBSR) program on the sleep quality of a heterogeneous sample of 63 cancer patients. Overall sleep disturbance was significantly reduced (p < .001) and participants reported that their sleep quality had improved (p < .001). There was also a significant reduction in stress (p < .001), mood disturbance (p = .001), and fatigue (p < .001). The associations among these changes and implications for improving quality of life of cancer patients are discussed. Dr. Linda Carlson is funded by a Canadian Institutes of Health Research New Investigator Award. We would like to thank all of the participants in the MBSR program who have diligently completed questionnaires, and encourage their quest for healing and personal growth.     

Cognitive functioning and emotion processing in breast cancer survivors and controls: An ERP pilot study

Diagnosis and treatment of breast cancer is a very emotionally aversive and stressful life event, which can lead to impaired cognitive functioning and mental health. Breast cancer survivors responding with repressive emotion regulation strategies often show less adaptive coping and adverse outcomes. We investigated cognitive functioning and neural correlates of emotion processing using ERPs. Self‐report measures of depression, anxiety, and fatigue, as well as hair cortisol as an index of chronic stress, were assessed. Twenty breast cancer survivors (BCS) and 31 carefully matched healthy controls participated in the study. After neuropsychological testing and subjective assessments, participants viewed 30 neutral, 30 unpleasant, and 30 pleasant pictures, and ERPs were recorded. Recognition memory was tested 1 week later. BCS reported stronger complaints about cognitive impairments and more symptoms of depression, anxiety, and fatigue. Moreover, they showed elevated hair cortisol levels. Except for verbal memory, cognitive functioning was predominantly in the normative range. Recognition memory performance was decreased in cancer survivors, especially for emotional contents. In ERPs, survivors showed smaller late positive potential amplitudes for unpleasant pictures relative to controls in a later time window, which may indicate less elaborative processing of this material. Taken together, we found cognitive impairments in BCS in verbal memory, impaired emotional picture memory accuracy, and reduced neural activity when breast cancer survivors were confronted with unpleasant materials. Further studies and larger sample sizes, however, are needed to evaluate the relationship between altered emotion processing and reduced memory in BCS in order to develop new treatment strategies.     

Chiropractic intervention in the treatment of postmenopausal climacteric symptoms and insomnia: A review

Introduction

Insomnia is a frequent postmenopausal symptom and may be due to hormonal changes, depressive states related to this period of life, hot flashes or nocturia. Chiropractic care has been demonstrated to be effective in the treatment of these symptoms.

Objectives

The aim of this study was to review chiropractic interventions in postmenopausal women as a possible management approach to menopausal symptoms and insomnia.

Methods

A PubMed search was conducted by cross-referencing the key words insomnia, sleep, and menopause with chiropractic. The search used an end date of January 2014 and retrieved 17 articles.

Results

Three articles were eligible for the study. All epidemiological data from large surveys demonstrated a lack of evidence for chiropractic intervention as a complementary and alternative therapeutic method in the management of menopausal symptoms and insomnia.

Conclusions

There is no evidence for the effectiveness of chiropractic intervention as a complementary and alternative therapy for menopausal symptoms and insomnia. Further studies with proper methodological designs are warranted.     

肿瘤相关成纤维细胞在乳腺癌进程和治疗中作用研究进展

肿瘤相关成纤维细胞(cancer-associated fibroblasts,CAFs)是肿瘤微环境最重要的细胞成份之一,它不仅参与微环境血管和淋巴管形成、细胞外基质(extracellular matrix,ECM)重塑,而且促进乳腺癌的发生,癌细胞增殖、侵袭和转移,其标志分子也可作为乳腺癌临床诊断、靶向治疗和预后的生物标志。目前关于乳腺癌与CAFs的研究越来越多,本文将对近年来CAFs在乳腺癌的相关研究进展作综述。     

Perception of risk, anxiety, and health behaviors in women at high risk for breast cancer

Perception of risk, anxiety, psychological distress, and early detection behavior were investigated in 23 women with a family history of breast cancer who attended genetic counseling and 21 women without a family history of breast cancer. In addition to a breast cancer-specific questionnaire, the Symptom Checklist 90-Revised and the State-Trait Anxiety Inventory were used. Thirty-nine percent of the women with a family history of breast cancer correctly identified and 48% overestimated their own lifetime risk. Risk perception was independent of genetic counseling. Levels of general psychological morbidity were similar between women with a family history of breast cancer and controls. For controls, early detection behavior was related to lifetime risk estimate and was, in general, independent of level of anxiety. Despite genetic counseling, many women continued to perceive their own lifetime risk of breast cancer inaccurately. They might benefit from additional counseling on risk assessment.     

Normal breast stem cells, malignant breast stem cells, and the perinatal origin of breast cancer

Both experimental and epidemiological evidence support the concept that the in utero environment can influence an individual's risk of breast cancer in adult life. Recently identified breast stem cells may be the key to understanding the mechanism underlying this phenomenon. It has been theorized that breast cancers arise from breast stem cells. Our emerging view of the characteristics of normal breast stem cells and their link to malignant breast stem cells is reviewed here. It has also been postulated that factors that expand the normal breast stem cell pool in utero would increase the probability that one such cell might undergo an oncogenic mutation or epigenetic change. We dicuss how a number of proposed perinatal determinants of adult breast cancer risk, including (1) in utero estrogen and IGF-1 levels, (2) birthweight, (3) breast density, and (4) early-life mutagen exposure, can be tied together by this “breast stem cell burden” hypothesis.     

整数非线性规划模型在乳腺癌转移相关基因表达调控网络建立中的应用

利用乳腺癌转移基因表达数据的熵信息确定基因权重,建立以误差最小为目标函数的整数非线性规划模型推测基因之间的调控关系,并通过相关系数模型筛选调控基因.利用软件LING08.0和MATLAB7.0编程求解,得到27个乳腺癌转移相关基因的调控网络,其中25对基因存在调控关系,有11对存在相互促进的双向调控作用.整数非线性规划模型能较好地刻划乳腺癌转移相关基因调控关系,可用于更复杂的基因调控网络的研究.