首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 51 毫秒
1.
Introduction: Despite aggressive multimodality treatment of glioblastoma, outcome remains poor and patients mostly die of local recurrences. Besides reoperation and occasionally reirradiation, systemic treatment of recurrent glioblastoma consists of alkylating chemotherapy (lomustine, temozolomide), bevacizumab and combinations thereof. Unfortunately, antiangiogenic agents failed to improve survival either as a monotherapy or in combination treatments. This review provides current insights into tumor-derived escape mechanisms and other areas of treatment failure of antiangiogenic agents in glioblastoma.

Areas covered: We summarize the current literature on antiangiogenic agents in the treatment of glioblastoma, with a focus on recurrent disease. A literature search was performed using the terms ‘glioblastoma’, ‘bevacizumab’, ‘antiangiogenic’, ‘angiogenesis’, ‘resistance’, ‘radiotherapy’, ‘chemotherapy’ and derivations thereof.

Expert commentary: New insights in glioma neoangiogenesis, increasing understanding of vascular pathway escape mechanisms, and upcoming immunotherapy approaches might revitalize the therapeutic potential of antiangiogenic agents against glioblastoma, although with a different treatment intention. The combination of antiangiogenic approaches with or without radiotherapy might still hold promise to complement the therapeutic armamentarium of fighting glioblastoma.  相似文献   


2.
3.
Introduction: The mainstays of brain tumor therapy are surgery, radiotherapy and chemotherapy. Cancer immunotherapy is explored as an additional treatment modality. However, emerging evidence indicates that also radio- and chemotherapy have immunological effects in addition to their cytotoxic and cytostatic activities.

Area covered: We summarize the literature on radio- and chemotherapy-mediated immunological effects in primary and secondary brain tumors and outline open questions within the field. To this end, a literature search was performed using the terms ‘brain tumor’, ‘immune system’, ‘immunogenic cell death’, ‘vaccination’, ‘checkpoint inhibition’, ‘radiotherapy’, ‘chemotherapy’ and derivations thereof.

Expert commentary: Immunological effects of chemo- and radiotherapy in brain tumors involve direct immunogenic modulations of tumor cells, changes of the microenvironment and functional alterations of innate and adaptive immune cells. Each treatment modality can exert various effects that comprise both immune-stimulatory and immunosuppressive mechanisms. A detailed knowledge of these mechanisms is indispensable for an optimal combination of conventional anti-tumor treatments and novel immunotherapeutic approaches.  相似文献   


4.
Introduction: In the era of minimally-invasive surgery, urinary incontinence (UI) after radical prostatectomy (RP) still represents a troublesome issue for a considerable rate of patients. Factors associated with the risk of post-RP UI, need to be carefully assessed throughout the overall clinical management process thus including the pre-operative, intra-operative and post-operative setting.

Areas covered: This review analyses current published evidences regarding clinical and surgical aspects associated with urinary continence (UC) recovery after RP. A careful evaluation of patient’s clinical characteristics should be carried out before surgery in order to properly counsel the patients regarding the risk of UI. In the last two decades, the advent of robotic surgery has led to an overall improvement of functional outcomes after RP, thanks to the development of different surgical strategies based on either the ‘preservation’ or the ‘reconstruction’ of the anatomical elements responsible for urinary continence.

Finally, several therapeutic strategies including either a conservative approach, or pharmacological and surgical treatments, should be carefully considered for the post-operative management of UI.

Expert commentary: A comprehensive pre-operative patient’s clinical assessment, along with a proper and well-conducted surgical procedure and an effective post-operative care management are essential element to achieve a high probability of UC recovery.  相似文献   


5.
Introduction: Prostatic small cell carcinoma (PSCC) is a rare, aggressive form of prostate cancer associated with poor clinical outcomes. It can arise de novo or in the setting of castrate resistant adenocarcinoma of the prostate. Current therapeutic interventions are based upon observations the PSCC responds similarly to small cell carcinoma of the lung. Standard treatment includes chemotherapy with cisplatin and etoposide, radiation therapy, and occasional extirpative management. Ongoing research into the molecular pathway behind the development of PSCC and potential interventions is resulting in the identification of multiple novel therapeutic targets.

Areas covered: A review of contemporary literature was undertaken to evaluate the histology, pathogenesis, evolution, current and novel treatment regimens, and upcoming methods of diagnosis of PSCC. To this end a literature search using terms, ‘prostate small cell carcinoma’, ‘neuroendocrine prostate cancer’, and derivations thereof was performed with a thorough review of the current literature.

Expert commentary: Among current studies, AURKA inhibitors and PAPR1 inhibitors are exciting potential targets with early studies suggesting significant benefit. Continued research into the molecular underpinnings of PSCC is necessary to identify novel targets for early identification of patients with PSCC and to develop optimal treatment regimens.  相似文献   


6.
Introduction: Non-visible hematuria, also referred to as ‘microscopic hematuria’ or ‘dipstick positive hematuria’ is a common reason for urology referrals with prevalence rates that range from 13% to 20%. The main concern for investigating non-visible hematuria, especially in the absence of lower urinary tract symptoms, is its potential relation to urinary tract malignancy, which however does not exceed 5%.

The pathway of investigation of non-visible hematuria is impeded by the lack of clarity over definitions, diagnosis and specialist referral criteria. Towards that goal guidelines have been introduced by different societies. In this review we aim to discuss differences in current guideline regarding the investigation, management and follow up of non-visible hematuria.

Areas covered: Guidelines, recommendations, algorithms and original articles on hematuria published in the English literature were retrieved using the following PubMed search terms ‘microscopic hematuria’, ‘dipstick hematuria’, ‘non-visible hematuria’ and ‘guidelines’.

Expert commentary: Available guidelines for investigation of microscopic hematuria actually differ both in the extent and the intensity of the proposed imaging and invasive tests. There is evidence that guidelines are not adhered to and this reflects the necessity for introducing selection criteria and maybe variable levels of investigation for microscopic hematuria depending on the individual patient.  相似文献   


7.
Introduction: Hormone receptor positive (HR+) breast cancer represents the most common subtype of breast cancer. Metastatic HR+ breast cancer may develop resistance to standard hormone therapies, arising from genomic alterations in the estrogen receptor and/or upregulation of other signal transduction pathways.

Areas covered: In this review, we discuss hormone resistance and strategies to overcome it, from the pre-clinical and clinical perspectives. This review includes a discussion of inhibition of the PI3K/AKT/mTOR, CDK 4/6, histone deacetylation, fibroblast growth factor receptor, and immune pathways, based on review of relevant literature.

Expert commentary: Several emerging novel therapies to improve the response to hormone therapy are approved or are in development. The most promising agents at present are inhibitors of CDK 4/6 and mTOR, which have already been incorporated into treatment in the advanced stage setting and are under study for early stage disease.  相似文献   


8.
Introduction: Since 2007 Sorafenib has represented the only approved drug for first-line treatment of advanced hepatocellular carcinoma (HCC). Lenvatinib, an orally active inhibitor of multiple receptor tyrosine kinases (VEGFR 1–3, FGFR 1–4, PDGFRa, RET and KIT), showed preclinical and clinical activity in the treatment of solid tumors, including HCC.

Areas covered: In this review, we summarize the current therapeutic paradigm for the systemic treatment of advanced HCC, focusing on Lenvatinib pre-clinical and clinical development. Keywords ‘Lenvatinib’, ‘ Target therapy’, ‘REFLECT trial’, ‘Hepatocellular carcinoma’, ‘HCC’, ‘Sorafenib’ were used for literature search on PubMed.

Expert commentary: In Phase-III multicentric REFLECT trial Lenvatinib demonstrated a non-inferior overall survival (OS) compared to Sorafenib in the first-line treatment of advanced HCC, with a manageable toxicity profile, becoming a valid alternative option in the therapeutic repertoire of this disease. Nevertheless, the potential role of Lenvatinib in real-life clinical practice has still to be defined, especially in the light of the positive results that have been achieved with other new therapeutic agents (e.g. immunotherapy).  相似文献   


9.
Introduction: Current therapeutic approaches for high-risk neuroblastoma (HR-NB) include high-dose chemotherapy, surgery and radiotherapy; interventions that are associated with long and short-term toxicities. Effective immunotherapy holds particular promise for improving survival and quality of life by reducing exposure to cytotoxic agents. GD2, a surface glycolipid is the most common target for immunotherapy.

Areas covered: We review the status of anti-GD2 immunotherapies currently in clinical use for neuroblastomas and novel GD2-targeted strategies in preclinical development.

Expert commentary: Anti-GD2 monoclonal antibodies are associated with improved survival in patients in their first remission and are increasingly being used for chemorefractory and relapsed neuroblastoma. As protein engineering technology has become more accessible, newer antibody constructs are being tested. GD2 is also being targeted by natural killer cells and T-cells. Active immunity can be elicited by anti-GD2 vaccines. The rational combination of currently available and soon-to-emerge immunotherapeutic approaches, and their integration into conventional multimodality therapies will require further investigation to optimize their use for HR-NB.  相似文献   


10.
Introduction: Chemotherapy-induced peripheral neuropathy (CIPN), a common adverse effect of several chemotherapeutic agents, has a significant impact on quality of life and may even compromise treatment efficacy, requiring chemotherapy dose reduction or discontinuation. CIPN is predominantly related with sensory rather than motor symptoms and the most common related cytotoxic agents are platinum compounds, taxanes and vinca alkaloids. CIPN symptoms may resolve after treatment cessation, but they can also be permanent and continue for years.

Areas covered: We present an overview of CIPN pathophysiology, clinical assessment, prevention and treatment identified through a Pubmed search.

Expert commentary: No substantial progress has been made in the last few years within the field of prevention and/or treatment of CIPN, in spite of remarkable efforts. Continuous research could expand our knowledge about chemotherapeutic-specific neuropathic pathways and eventually lead to the conception of innovative and targeted agents for the prevention and/or treatment of this debilitating chemotherapy adverse effect.  相似文献   


11.
Introduction: Knowledge of the molecular subtypes of bladder cancer enables powerful generalizations involving the distinctive biology and pathways driving different disease subsets.

Areas covered: In this review, we summarize the findings of a number of published studies exploring the molecular landscape of bladder cancer by analysis of genomic data from The Cancer Genome Atlas (TCGA). TCGA project has provided a comprehensive data resource of 412 muscle-invasive bladder cancers as characterized by multiple molecular analytical platforms. These data have been and will continue to be utilized in numerous subsequent studies aimed at better understanding the molecular basis of bladder cancer. The catalog of DNA-level alterations can greatly inform personalized and precision medicine approaches. Molecular subtypes of bladder cancer include distinct ‘basal/squamous’ and ‘luminal’ subtypes, cancers with papillary histology, disease subsets with prominent leukocyte infiltration and immune checkpoint marker expression, and a ‘neuronal’ subtype lacking small cell or neuroendocrine histology. The gene-level alterations and subtypes as revealed by TCGA data are relevant from the standpoint of both basic biology and clinical trial studies.

Expert commentary: Multiple studies analyzing TCGA muscle-invasive bladder cancer cases point to the existence of five major expression-based molecular subtypes of the disease, with these subtypes having therapeutic implications.  相似文献   


12.
Introduction: Recent advances in prognostication as well as management of Follicular Lymphoma (FL) are moving to personalized approach.

Areas covered: Prognostic scores as well as consolidated and innovative therapeutic approaches are evaluated according to the various presentation modalities. For asymptomatic, low-tumor burden FL, a ‘watch and wait’ policy is currently the first-choice approach, although possible alternatives are discussed. Early stage FL may be treated with local radiotherapy although the role of minimal residual disease in possible additional agents should be determined. The first line treatment for symptomatic FL is chemo-immunotherapy followed by two years maintenance therapy with anti-CD20 monoclonal antibodies. A deeper knowledge of FL biology has opened new perspectives regarding the timing of therapy and has offered new targets for the development of novel agents that aim to change the therapeutic scenario of FL management.

Expert commentary: The introduction of novel agents could question the incurability of FL and change the therapeutic goal from prolonging the complete remission state to eradicating the disease in young/fit patients, as well as improving quality of life in elderly/unfit patients. In the near future, combining new biologic agents and adoptive cell therapies could help in achieving these aims.  相似文献   


13.
Introduction: Current treatment of osteosarcoma includes surgical resection of all gross disease in conjunction with systemic chemotherapy to control micro-metastatic disease. This yields a 5-year event free survival (EFS) of approximately 70% for patients with localized osteosarcoma while patients with metastatic or recurrent disease fare poorly with overall survival rates of less than 20%.

Areas covered: This review outlines the current and future approach towards the treatment of osteosarcoma. A literature search was performed utilizing PubMed. Several recent clinical trials are reviewed in detail, as is innovative research evaluating novel agents and surgical techniques which hold promise.

Expert commentary: The outcome for patients with osteosarcoma has not changed in several decades. This plateau in survival rates highlights the need for a novel approach towards research. There remains a great deal of interest in utilizing the very high risk population of recurrent osteosarcoma patients to rapidly and sequentially evaluate novel agents to determine if any of these agents hold promise. Several phase II studies are ongoing or in development that offer hope based on intriguing preclinical data. Furthermore, initiatives in obtaining specimens to further explore the genetic and immunological profile behind osteosarcoma will be essential towards identifying novel pathways and targets to exploit.  相似文献   


14.
Introduction: Extended adjuvant (5–10 years) therapy targeted to the estrogen receptor (ER) has

significantly decreased mortality from breast cancer (BC).

Areas covered: Translational research advanced clinical testing of extended adjuvant therapy with tamoxifen or aromatase inhibitors (AIs). Short term therapy or non-compliance increase

recurrence, but surprisingly recurrence and death does not increase dramatically after 5 years of adjuvant therapy stops.

Expert commentary: Compliance ensures optimal benefit from extended antihormone adjuvant therapy.Retarding acquired resistance using CDK4/6 or mTOR inhibitors is discussed. Preventing acquired resistance from mutations of ER could be achieved with Selective ER Downregulators (SERDs), eg fulvestrant. Fulvestrant is a depot injectable so oral SERDs are sought for extended use. In reality, a ‘super SERD’ which destroys ER but improves women’s health like a Selective ER Modulator (SERM), would aid compliance to prevent recurrence and death. Estrogen-induced apoptosis occurs in 30% of BC with antihormone resistance. The ‘one in three’ rule that dictates that one in three unselected patients respond to either hormonal or antihormonal therapy in BC occurs with estrogen or antiestrogen therapy and must be improved. The goal is to maintain patients for their natural lives by blocking cancer cell survival through precision medicine using short cycles of estrogen apoptotic salvage therapy, and further extended antihormone maintenance.  相似文献   


15.
Introduction: The majority of gastrointestinal stromal tumors (GIST) are driven by an abnormal receptor tyrosine kinase (RTK) signaling, occurring mainly due to somatic mutations in KIT or platelet derived growth factor receptor alpha (PDGFRA). Although the introduction of tyrosine kinase inhibitors (TKIs) has revolutionized therapy for GIST patients, with time the vast majority of them develop TKI resistance. Advances in understanding the molecular background of GIST resistance allows for the identification of new targets and the development of novel strategies to overcome or delay its occurrence.

Areas covered: The focus of this review is on novel, promising therapeutic approaches to overcome heterogeneous resistance to registered TKIs. These approaches involve new TKIs, including drugs specific for a mutated form of KIT/PDGFRA, drugs with inhibitory effect against multiple RTKs, compounds targeting dysregulated downstream signaling pathways, drugs affecting KIT expression and degradation, inhibitors of cell cycle, and immunotherapeutics.

Expert commentary: As the resistance to standard TKI treatment can be heterogeneous, a combinational approach for refractory GIST could be beneficial. Moreover, the understanding of the molecular background of resistant disease would allow development of a more personalized approach for these patients and their response to targeted therapy could be monitored closely using ‘liquid biopsy’.  相似文献   


16.
It appears from empirical studies that the problem-solving ability of patients is associated with the experience of distress and the patients’ mental state. The goals of this study were the (1) conception and (2) associated evaluation of the psychological short-time intervention “problem-solving training” (PST) for patients hospitalized for hematopoietic stem cell transplantation (HSCT).

(1) The conception of the PST comprised a multi-stage development phase. An existing manual for outpatients diagnosed with cancer was adapted to the specific situation of a HSCT. This was followed by development of a manual, definition of the general framework, instruction of coaches, and implementation in a hospital setting.

(2) The associated evaluation of PST was conducted from the patients’ and the coaches’ point of view. A total of 22 patients and five coaches evaluated the training.

The training was evaluated by both patients and coaches as being well achievable with the exception of a limited time frame for the first module. The manual explanations were judged to be intelligible by all participants. Regarding on-topic alertness, patients were, on average, rated as “rather “to “very attentive.” The patients evaluated the response to their needs as “good.” They further assessed their overall condition due to the training as “good.”

This study provides preliminary evidence for the feasibility of PST by using the developed manual (Psychological Short-Term Intervention PST for Patients During HSCT). Based on this, it is conceivable to implement this intervention in similar situations to the advantage of a different patient clientele.  相似文献   


17.
Background: Radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) are important treatments for patients with hepatocellular carcinoma (HCC) who are not eligible for resection and liver transplantation. Therefore, it is important to establish comparisons between RFA, PEI and the two therapies in combination.

Aims: To evaluate the clinical efficacy and safety of combined RFA-PEI versus monotherapy with either RFA or PEI for HCC to provide references for clinical practice and further research.

Methods: We searched all eligible studies published before September 2015 in the Cochrane Library, PubMed, Embase, Web of Science and Chinese databases, such as CBM, CNKI, VIP and WanFang and also retrieved papers from other sources. All relevant controlled trials were collected. Meta-analyses were performed using RevMan version 5.3 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark).

Results: Thirteen trials with 1621 patients were identified. Compared with PEI, RFA was associated with significant improvement in overall survival (OS) rate at 1, 2, 3 and 4 years, cancer-free survival (CFS) rate at 1, 2 and 3 years and complete tumour necrosis. RFA was associated with a significant reduction in the local recurrence rate at 1, 2 and 3 years. However, RFA was also associated with a higher total risk of complications. Compared with RFA alone, combined RFA-PEI was associated with a significant improvement in the OS rate at 1.5, 2 and 3 years and a significant reduction in the local recurrence rate. However, combined RFA-PEI was also associated with a higher risk of fever.

Conclusion: The combination of RFA and PEI appears to be the optimal treatment strategy when considering combined RFA-PEI or either RFA or PEI alone. Combined RFA-PEI significantly improves OS and reduces the risk of local recurrence without increasing major complications. Further large-scale studies are needed to assess economic outcomes and quality of life.  相似文献   


18.
Purpose: To test the accuracy and efficacy of the multimodality imaging-compatible insertion robot with a respiratory motion calibration module designed for ablation of liver tumors in phantom and animal models. To evaluate and compare the influences of intervention experience on robot-assisted and ultrasound-controlled ablation procedures.

Methods: Accuracy tests on rigid body/phantom model with a respiratory movement simulation device and microwave ablation tests on porcine liver tumor/rabbit liver cancer were performed with the robot we designed or with the traditional ultrasound-guidance by physicians with or without intervention experience.

Results: In the accuracy tests performed by the physicians without intervention experience, the insertion accuracy and efficiency of robot-assisted group was higher than those of ultrasound-guided group with statistically significant differences. In the microwave ablation tests performed by the physicians without intervention experience, better complete ablation rate was achieved when applying the robot. In the microwave ablation tests performed by the physicians with intervention experience, there was no statistically significant difference of the insertion number and total ablation time between the robot-assisted group and the ultrasound-controlled group. The evaluation by the NASA-TLX suggested that the robot-assisted insertion and microwave ablation process performed by physicians with or without experience were more comfortable.

Conclusion: The multimodality imaging-compatible insertion robot with a respiratory motion calibration module designed for ablation of liver tumors could increase the insertion accuracy and ablation efficacy, and minimize the influence of the physicians’ experience. The ablation procedure could be more comfortable with less stress with the application of the robot.  相似文献   


19.
Background: Non-Hodgkin’s lymphoma (NHL) survivors are at a higher risk of cardiovascular diseases (CVDs).

Methods: A population-based study was conducted to investigate the cardiovascular mortality trends to identify NHL survivors at the highest risk.

Results: The CVDs mortality was the second most common cause of death (13.07%) after NHL. There were more patients ≥ 60 years old in the cardiovascular group (87.2%), P < 0.001. Patients who died from CVDs had the best survival while patients who died from NHL had a significantly lower mean survival. The overall survival rate was 92.4%. Consistently, older age, unmarried, male patients, not recently diagnosed with NHL and not receiving radiation and/or surgery were associated with a worse survival across all models. The black race and stage IV only had a worse cardiovascular specific survival (CVSS).

Conclusions: Although the CVSS improved over time, the mortality from the CVDs is still the second most common cause of death after NHL. Older age, not married, black, male patients, not recently diagnosed with NHL, with an advanced stage and not receiving radiation and/or surgery were associated with a worse survival. Risk factor modification along with CVDs screening should be intensified in NHL patients with these mortality predictors.  相似文献   


20.
Introduction: Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor (VEGF). (Avastin; Genetech, Inc, San Francisco, CA) Angiogenesis is blocked by the binding of bevacizumab to VEGF, inhibiting the binding of this ligand to the VEGF receptor. On 14 August 2014 the Food and Drug Administration (FDA) approved use of bevacizumab in persistent, recurrent, or metastatic cervical cancer.

Areas covered: Herein we review pharmacodynamics and kinetics, clinical data and treatment-related toxicities of bevacizumab in the treatment of metastatic, recurrent or persistent cervical cancer. Additionally, future areas of development are reviewed.

Expert commentary: Anti-angiogenesis therapy with bevacizumab is central to metastatic, persistent, and recurrent cervical cancer treatment. Additional anti-angiogenesis drugs are in development. Future studies will need to establish if the addition of multiple anti-angiogenesis agents or anti-angiogenesis in combination with immunotherapy is more effective than bevacizumab with chemotherapy.  相似文献   


设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号