癌因性疲乏相关治疗研究进展

癌因性疲乏是临床上癌症患者最为常见的伴随症状,它不仅严重影响患者的生活质量,并可导致患者癌症治疗中断,危及患者的生命安全。CRF的病因及机制较为复杂,国外许多学者认为,CRF的发生可能与贫血、肥胖、肿瘤类型、失眠、炎性细胞因子,下丘脑-垂体-肾上腺轴等有关。针对CRF患者应采取有效措施进行干预,本文对CRF的相关治疗进展进行综述,为临床提供指导。     

Review old bone,new tricks

Despite the significant progress made over the past decade with combination of molecular profiling data and the development of new clinical strategies, our understanding of metastasis remains elusive. Bone metastasis is a complex process and a major cause of mortality in breast and prostate cancer patients, for which there is no effective treatment to-date. The current review summarizes the routes taken by the metastatic cells and the interactions between them and the bone microenvironment. We emphasize the role of the specified niches and cues that promote cellular adhesion, colonization, prolonged dormancy, and reactivation. Understanding these mechanisms will provide better insights for future studies and treatment strategies for bone metastatic conditions.

     

Tumor dormancy of primary and secondary cancers

Tumor dormancy is a phenomenon whereby cancer cells persist below the threshold of diagnostic detection for months to decades. This condition may arise due to either cell cycle arrest or a dynamic equilibrium state in which cell proliferation is in balance with cells undergoing apoptosis. Tumor dormancy is usually a reference to occult cancer cells that persist for an extended period of time after treatment, but primary cancers can also exhibit extended growth plateaus below the limits of detection. For example, autopsies of individuals who died of trauma reveal that most individuals harbor microscopic primary cancers. Mechanisms that operate independently or successively may restrict tumor expansion throughout tumor progression from incipiency to late-stage cancer. Proposed mechanisms include cell cycle withdrawal, immune surveillance, and blocked angiogenesis. The precise mechanisms underlying dormancy remain to be established, and relevant models will have an important impact on diagnostic and therapeutic strategies for treating cancer. This review summarizes the phenomenon of tumor dormancy, experimental models, and potential mechanisms.     

Prevalence of Fatigue Among Cancer Patients Receiving Various Anticancer Therapies and its Impact on Quality of Life: A Cross-Sectional Study

Background:

Fatigue is disabling and continuous phenomenon in cancer patients during and after various anticancer treatments which can continue for many years after treatment and definitely it has profound effect on Quality of Life (QOL). However, determining its severity is still underestimated among the cancer patients and also very few studies in the literature exist reporting on Cancer-Related Fatigue (CRF) among Indian population.

Aims:

To find out the prevalence of rate of fatigue in cancer patient receiving various anti cancer therapies. To find out the relative impact of fatigue on QOL.

Materials and Methods:

This cross-sectional observational study included a total 121 cancer patients receiving radiotherapy, chemotherapy, and concurrent chemo-radiation with the age group of above 15 years who fulfilled the inclusion and exclusion criteria. All the patients were assessed for severity of fatigue using Brief Fatigue Inventory (BFI) and for QOL using FACT-G scale while they were receiving the anticancer therapies as an in-patient in the regional cancer centers in Madhya Pradesh, India.

Results:

The severe fatigue was more prevalent in chemotherapy [58/59 (98.30%)], and concurrent chemo-radiation (33/42 (78.57%)) as compared to radiotherapy (Moderate-9/20 (45%) and Severe-9/20 (45%)). Moderate correlations were exhibited between fatigue due to radiotherapy and QOL (r = -0.71, P < 0.01), whereas weak correlation was found between fatigue due to chemotherapy and concurrent chemo-radiation (r = -0.361, P < 0.01 and r = -0.453, P < 0.01, respectively).

Conclusion:

Severity of fatigue was found more after chemotherapy and concurrent chemo-radiation therapy while impact on QOL was more after the radiotherapy.     

Analgésie placebo et sommeil

The placebo response is a psychobiological phenomenon for clinical benefits following the administration of an inert substance whatever its form. This phenomenon can be attributed to a wide range of neurobiological processes, such as expectations of relief, the Pavlovian conditioning and learning, emotional regulation, and reward mechanisms, which are themselves under the influence of processes that take place during sleep. The study of placebo analgesia in healthy from a placebo conditioning associated with analgesic suggestions has highlighted a relationship between sleep, expectations of relief and placebo analgesia: when the induction is persuasive before sleep, expectations of relief modulate placebo response the next morning and paradoxical sleep correlates negatively with both expectations and the placebo response. When the analgesic experience before sleep is less persuasive, expectations of relief are still present but no longer interact with placebo analgesia while paradoxical sleep no longer correlates with the analgesic placebo response. Sleep-processes especially during paradoxical sleep seem to influence the relationship between expectations of relief and placebo analgesia. In this review, we describe the relationship between sleep and placebo analgesia, the mechanisms involved in the placebo response (e.g., conditioning, learning, memory, reward) and their potential link with sleep that could make it a special time for the building placebo response.     

Psychosocial functioning in pediatric cancer

OBJECTIVE: To describe the emergence of pediatric psycho-oncology and to summarize research on psychosocial aspects of childhood cancer and survivorship. METHODS: To review research into illness communication and informed consent, procedural pain, late effects, psychological distress, coping and adjustment, and special risk populations. Methodological challenges, appropriate methodology, and directions for future research are discussed. RESULTS: The past 30 years have seen change from avoidance of communication about cancer to an emphasis on straightforward discussion of diagnosis and prognosis. Behavioral research has led to interventions to reduce procedural distress. Late effects have been observed in social functioning. Although average levels of distress in survivors of pediatric cancer are typical, subsets of more vulnerable patients and family members exist. Factors predicting positive and negative coping have been identified. CONCLUSIONS: As the numbers of pediatric cancer survivors increase, psychosocial researchers will be better able to conduct longitudinal studies not only of adjustment and its predictors but also of the impact of the emerging medical treatments and interventions to ameliorate late effects of treatment. Additional funding, improving methodology, and multi-institutional cooperation will aid future pediatric psycho-oncology investigators.     

Evaluation and management of fatigue in oncology: a multidimensional approach

Fatigue, one of the most common symptoms experienced by cancer patients, is multidimensional and is associated with significant impairment in functioning and overall quality of life. Although the precise pathophysiology of cancer-related fatigue (CRF) is not well understood, a number of metabolic, cytokine, neurophysiologic, and endocrine changes have been described in these patients. A better understanding of these abnormalities is likely to lead to novel therapeutic interventions. Clinically, all patients presenting with significant fatigue should be evaluated for treatable conditions that might contribute to this symptom. Exercise and treatment of anemia are the two most established interventions for CRF. Psychostimulants seem promising based on early studies. Several complementary medicine treatments that showed efficacy in preliminary studies merit further testing.     

Resistance to TRAIL and how to surmount it

Development of resistance to TRAIL-induced toxicity is one of the strategies used from tumor cells to escape destruction from the immune system. This process may occur through aberrant expression of functional receptors, overexpression of decoy receptors on tumor cell membrane, or malfunctioning of downstream signals triggered by specific ligation of TRAIL. Numerous cytostatic, but also noncytostatic, drugs like protease inhibitors and NO-hybridized molecules have been shown to revert sensitivity of neoplastic cells to TRAIL by means of different mechanisms. This paper will review the possible routes of reconstitution of sensitivity to TRAIL-mediated immune response by specific modulation of different signals responsible for the development of resistance at both the membrane and the intracellular levels. Moreover, we will review and suggest novel strategies, aimed at resetting immune cell efficiency in cancer treatment.     

Immunological mechanisms of specific immunotherapy with pollen vaccines: implications for diagnostics and the development of improved vaccination strategies

This review deals with specific immunotherapy performed with pollen vaccines. Pollen allergens, the immunological mechanism of allergic inflammation and the mechanisms behind successful specific immunotherapy treatment of seasonal pollen allergy shall be discussed. The different approaches to develop improved regimes for specific immunotherapy based on new diagnostic tools, improved pollen vaccines and alternative routes for administration of the vaccines will be highlighted. Diagnostic tools to select patients for specific immunotherapy and for monitoring the treatment are quantitative measurements of allergen-specific immunoglobulin E, G and G4 antibodies and component-resolved diagnostics based on immunoglobulin E binding to individual allergenic components. Future pollen vaccines may consist of hypoallergenic recombinant allergens and T-helper cell type 1-inducing immunostimulatory adjuvants. Both sublingual and nasal administration of pollen vaccines for specific immunotherapy may be used more in future.     

Pitfalls And Hopes in Down Syndrome Therapeutic Approaches: In the Search for Evidence-Based Treatments

Trisomy 21 or Down syndrome (DS) is a complex syndrome, of genetic origin with multiple and variable neurobiological and neuropsychological manifestations. DS patients have consistent signs of brain damage along their lives, but understanding the biology of DS is complicated due to the extraordinary heterogeneity of the phenotypic signs. Thus, treatment of DS mental retardation poses significant challenges for clinicians and scientists. The review addresses the classical pharmacological and environmental treatments and also critically reviews the new possibilities that are emerging from the exciting advances in gene or cell therapy. We describe some of the most recent developments in the field and give a sense of the prospects for future prevention and therapy.     

Progress Review of the Psychosocial Treatment of Child Conduct Problems

I assess current methods for reviewing advances in psychotherapy research and describe a new method for evaluating such work—the progress review. The need for progress reviews is highlighted and the usefulness of this technique is demonstrated via an evaluation of the extant literature on the psychosocial treatment of child conduct problems. Overall, an impressive body of research has amassed in support of the efficacy of several different treatment approaches for child conduct problems. However, information about which treatment components are responsible for therapeutic change, which mechanisms are involved, and which factors influence therapeutic change is lacking for each of the treatment approaches discussed. A theoretically based plan for future research is outlined for each treatment approach, in accordance with the results of this review. The continued use of progress reviews in all areas of psychotherapy research will help ensure that all of the goals of such research are attended to and will increase our ability to develop more effective and efficient psychotherapeutic interventions.     

Biological changes associated with healthy versus pathological aging: A symposium review

The Douglas Mental Health University Institute, in collaboration with the McGill Centre for Studies in Aging, organized a 2-day symposium entitled “Biological Changes Associated with Healthy Versus Pathological Aging” that was held in 13 and 14 December 2007 on the Douglas campus. The symposium involved presentations on current trends in aging and dementia research across several sub-disciplines: genetics, neurochemistry, structural and functional neuroimaging and clinical treatment and rehabilitation. The goal of this symposium was to provide a forum for knowledge-transfer between scientists and clinicians with different specializations in order to promote cross-fertilization of research ideas that would lead to future collaborative neuroscience research in aging and dementia. In this review article, we summarize the presentations made by the 13 international scientists at the symposium and highlight: (i) past research, and future research trends in neuroscience of aging and dementia and (ii) links across levels of analysis that can lead to fruitful transdisciplinary research programs that will advance knowledge about the neurobiological changes associated with healthy aging and dementia.     

Combined dexamethasone/CRF test in remitted outpatients with recurrent major depressive disorder

BACKGROUND: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is a prominent neurobiological finding during a major depressive episode, reflecting a state dependent factor. An issue under investigation is whether the dysfunction of the HPA axis has also a role to play as a state-independent or trait factor for major depressive disorder (MDD). In relation to this, it is important to examine HPA axis function in patients who are clinically remitted from depression. METHODS: Twenty-three remitted outpatients with recurrent MDD and 23 age- and gender-matched control individuals without a history of MDD participated in the sensitive combined dexamethasone/corticotropin-releasing factor (DEX/CRF) test. RESULTS: Free salivary cortisol responses were not significantly different between the two groups, although three patients (13%) displayed extremely elevated cortisol responses after CRF. LIMITATIONS: Limited sample size. All but one patient were under treatment with an antidepressant. CONCLUSIONS: This study shows no evidence for a disturbed DEX/CRF test as a state-independent factor in recurrent MDD on a group level. However, MDD is a complex and heterogenic disorder. Probably, there is a subgroup of patients who show a disturbed DEX/CRF test due to an inherited and/or acquired predisposition or as a biological scar after previous depressive episodes.     

Viral based gene therapy for prostate cancer

In the last few years, significant advances in gene therapy have been made as a result of advances in many areas of molecular and cell biology, including the improvement of both viral and nonviral gene delivery systems, discovery of new therapeutic genes, better understanding of mechanism of disease progression, exploration of tissue specific promoter, receptor- and antibody-mediated targeting delivery, and development of better prodrug enzyme/prodrug systems. In this article, viral based gene therapy for prostate cancer will be reviewed and discussed. The areas of emphasis in this review are: choice of viral vectors, comparison of delivery routes, development of prostate-targeted viruses, choice of therapeutic genes and strategies including corrective gene therapy (tumor suppressor gene and anti-oncogene gene approaches), suicide gene therapy, programmed cell death therapy, immunomodulation therapy, and conditional oncolytic virus approach. Among them, several examples will be discussed in detail for the scientific basis and therapeutic applications. In addition, prostate cancer gene therapy clinical trials, unresolved problems and future directions in this field will also be described.     

Immune checkpoint inhibitors: new strategies to checkmate cancer

Immune checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte‐associated protein‐4 (CTLA‐4) or programmed cell death protein 1 (PD‐1) receptors have demonstrated remarkable efficacy in subsets of patients with malignant disease. This emerging treatment modality holds great promise for future cancer treatment and has engaged pharmaceutical research interests in tumour immunology. While ICIs can induce rapid and durable responses in some patients, identifying predictive factors for effective clinical responses has proved challenging. This review summarizes the mechanisms of action of ICIs and outlines important preclinical work that contributed to their development. We explore clinical data that has led to disease‐specific drug licensing, and highlight key clinical trials that have revealed ICI efficacy across a range of malignancies. We describe how ICIs have been used as part of combination therapies, and explore their future prospects in this area. We conclude by discussing the incorporation of these new immunotherapeutics into precision approaches to cancer therapy.     

The oral allergy syndrome: improved diagnostic and treatment methods

PURPOSE OF REVIEW: The aim of this article is to review recent clinical and molecular findings related to the oral allergy syndrome in order to define its relevance in the field of food allergy, describe current diagnostic approaches and discuss attempts to use specific immunotherapy for treatment. RECENT FINDINGS: New allergenic sources causing the oral allergy syndrome have been reported. Their allergenic molecules have been identified. In most of those studies oral allergy syndrome is reported as a clinical manifestation among more severe ones. Some of the molecules generally considered not to be at risk for severe reactions have been demonstrated to pose a threat for inducing generalized reactions. Some studies tried to assess the usefulness of immunotherapy with birch pollen extract by either subcutaneous or sublingual routes for the treatment of associated food allergies. In most of the cases, a well defined study design and a molecular approach at different study levels are lacking and thus the value of the obtained results is limited. To date, no final conclusion can be drawn on the basis of reported results. SUMMARY: The knowledge about the highly prevalent phenomenon of oral allergy syndrome is still incomplete, in respect to both, epidemiology and foods inducing symptoms. It is very important to reach consensus on several aspects of this food-induced allergic disease. Further studies are required to highlight whether immunotherapy using co-recognized inhalant allergens is an effective way of curative treatment, or if co-treatment with purified pollen-related food allergens will be required to obtain a long-lasting effect.     

调控癌干细胞凋亡的外来因素

背景：目前收集的证据表明癌干细胞或肿瘤原始细胞是肿瘤形成和进展的关键驱动程序,这些细胞的高抵抗特性使常规治疗模式被阻碍。迄今为止,只有少量的研究发表癌干细胞死亡定向凋亡疗法的潜能。 目的：综述癌干细胞调节其凋亡的外来因素。 方法：由第一作者采用电子检索的方式在PubMed数据及万方数据库中检索1990年1月至2011年12月有关肿瘤干细胞和干细胞凋亡的研究。英文检索词为“cancer stem  cells,apoptosis,extrinsic factors”,中文关键词为“癌干细胞,凋亡,外来因素”。计算机初检得到120篇文献,阅读标题和摘要进行初筛,排除与研究目的相关性差及内容陈旧、重复的文献70篇,纳入50篇符合标准的文献进行综述。 结果与结论：癌干细胞理论在癌症的研究中有重要意义。它不仅在理解恶性肿瘤行为上有重要突破,而且有能力发展新的治疗方法。调节癌干细胞凋亡的外在因素包括微环境提供的外源性因子如分泌存活因子,黏附介导的凋亡抵抗和缺氧条件。潜在调节癌干细胞肿瘤微环境是非常关键的研究领域,并且这领域仍然进一步研究。通过各种已成型的各种机制解释癌干细胞的调控将一定会成为未来的研究趋势。     

Exploiting viral properties for the rational design of modern vaccines

A major challenge for the future is the development of effective vaccines against chronic infections and the application of therapeutic immunization to the treatment of noninfectious diseases, such as cancer, allergy and autoimmune disorders. In recent years, many of the immunological principles governing the immune response to infectious agents have been clarified and can now be exploited for the rational design of new and better vaccines. As an elucidative example, this review will describe the key immunogenic determinants of viruses and discuss how they can be harnessed for the development of tailor-made vaccines against a wide array of human diseases.     

Lobular Breast Cancer: Pathology, Biology, and Options for Clinical Intervention

Lobular carcinoma is a breast cancer subtype comprising approximately 15 % of all breast cancer cases. Clinical diagnosis of this subtype is difficult due to a characteristic growth pattern that inhibits detection using palpation or standard X-ray mammography. While clinical intervention based on hormone antagonists has proven an effective strategy, hormone receptor negative or nonresponsive disease cannot be treated successfully, indicating the need for alternative curative approaches. In contrast to its well-defined histopathological characteristics that were first recognized a century ago, the surface of the underlying biology has only recently been scratched. Progress was made in understanding the biology of the disease, which will hopefully have its impact on future treatment modalities and initiate development of novel intervention strategies. Here, we review the pathological and molecular features of lobular breast cancer and report on the currently known mechanisms that control disease development and progression. Finally we will reflect on past, present, and future treatment options.     

Overcoming Challenges of Ovarian Cancer Stem Cells: Novel Therapeutic Approaches

Understanding the genetic and molecular mechanisms of ovarian cancer has been the focus of research efforts working toward the greater goal of improving cancer therapy for patients with residual disease after initial treatment with conventional surgery and neoadjuvant chemotherapy. The focus of this review will be centered on new therapeutic strategies based on Cancer Stem Cells studies of chemoresistant subpopulations, the prevention of metastasis, and individualized therapy in order to find the most successful combination of treatments to effectively treat human ovarian cancer. We reviewed recent literature (1993-2011) of novel treatment approaches to ovarian cancer stem cells. As the focus of ovarian cancer investigation has centered on the cancer stem cell model and the complexities that it presents in the development of effective treatments, the future of treating ovarian cancer lies in utilizing individualized treatment systems that include enhancing existing treatments, aiming for novel therapy targets, managing the plasticity of stem cells to induce cellular differentiation, and regulating oncogenic signaling pathways.