Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer

1. Download : Download high-res image (207KB)
2. Download : Download full-size image

     

Nanotechnology for colorectal cancer detection and treatment

Colorectal cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer-related mortality in the United States. Across the globe, people in the age group older than 50 are at a higher risk of CRC. Genetic and environmental risk factors play a significant role in the development of CRC. If detected early, CRC is preventable and treatable. Currently, available screening methods and therapies for CRC treatment reduce the incidence rate among the population, but the micrometastasis of cancer may lead to recurrence. Therefore, the challenge is to develop an alternative therapy to overcome this complication. Nanotechnology plays a vital role in cancer treatment and offers targeted chemotherapies directly and selectively to cancer cells, with enhanced therapeutic efficacy. Additionally, nanotechnology elevates the chances of patient survival in comparison to traditional chemotherapies. The potential of nanoparticles includes that they may be used simultaneously for diagnosis and treatment. These exciting properties of nanoparticles have enticed researchers worldwide to unveil their use in early CRC detection and as effective treatment. This review discusses contemporary methods of CRC screening and therapies for CRC treatment, while the primary focus is on the theranostic approach of nanotechnology in CRC treatment and its prospects. In addition, this review aims to provide knowledge on the advancement of nanotechnology in CRC and as a starting point for researchers to think about new therapeutic approaches using nanotechnology.     

Synthesis and automated fluorine-18 radiolabeling of new PSMA-617 derivatives with a CuAAC radiosynthetic approach

In the last decade, the development of new radiopharmaceuticals for the imaging and therapy of prostate cancer has been a highly active and important area of research, especially focusing on the prostate-specific membrane antigen (PSMA), an antigen which is upregulated in prostate, as well as in other tumor cells. A large variety of PSMA ligands have been radiolabeled, to date. Among the various derivatives, PSMA-617 resulted to be one of the most interesting in terms of interaction with the antigen and clinical properties, and its lutetium-177 labeled version has recently been approved by regulatory agencies for therapeutic purposes. For this reasons, the radiolabeling with fluorine-18 of a PSMA-617 derivative might be of interest. Beside other methodologies to radiolabel macromolecules with fluorine-18, the “click-chemistry” approach resulted to be very useful, and the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is considered one of most efficient and reliable. This paper proposes the synthesis of a suitable precursor for the radiolabeling with fluorine-18 of a new PSMA-617 derivative. The whole radiosynthetic procedure has been fully automated, and the final product, which proved to be stable in plasma, has been obtained with radiochemical yield and purity suitable for subsequent preclinical studies.     

子野个数限值对宫颈癌固定野调强放疗计划的影响

目的:分析子野个数限值对宫颈癌固定野调强放疗（fixed-field intensity-modulated radiotherapy,ff-IMRT）计划的影响，寻求最优的子野个数限值。方法:选取10例接受ff-IMRT的宫颈癌患者，基于Monaco 5.11.03计划系统，以45 Gy/25 f处方剂量分别对同一患者设计8种ff-IMRT计划（ff-IMRT计划依据子野个数限值命名，子野个数限值分别为40、60、70、80、100、120、130、150），采用SPSS 20.0软件比较除plan100之外7个ff-IMRT计划与plan100剂量学参数、优化时间和治疗参数的差异。结果:8种ff-IMRT计划归一化后，plan40和plan60的D2%、Dmin、CI和HI均劣于plan100（P＜0.05）。8种ff-IMRT计划均能较好保护危及器官（organ at risk,OAR）和正常组织。plan40小肠V45;plan40和plan60小肠D2cc，直肠、膀胱V45、D40%，两侧股骨头V40和正常组织 V35、V40均高于plan100（P＜0.05）。plan40和plan60优化时间、治疗参数均优于plan100（P＜0.05）；plan120、plan130和plan150子野面积、子野个数（51~150 cm2和＞150 cm2）和出束时间均劣于plan100（P＜0.05）。结论:子野个数限值为70~100时，ff-IMRT计划能兼顾剂量学参数满足临床要求、优化时间和治疗参数最优化，建议在设计宫颈癌ff-IMRT计划时在该范围内设置子野个数限值。     

A systematic review of axillary nodal irradiation for the management of the axilla in patients with early-stage breast cancer

BackgroundGiven numerous publications and clinical trials regarding axillary management in breast cancer, we sought to summarize this complex literature to help clarify this field for clinicians. This systematic review focuses on the role of irradiation of the axillary nodes (locoregional nodal irradiation [LRNI]) in the management of the axilla in patients with early-stage breast cancer in various clinical settings.MethodsWe searched MEDLINE and EMBASE databases, the Cochrane library, the proceedings of the ASCO, the ASTRO, the ESMO, the ESTRO, and the San Antonio Breast Cancer Symposium (2016–2019) meetings. The quality of the studies was assessed with design-specific tools. The study was registered in PROSPERO.ResultsWe included one systematic review, one individual patient data (IPD) meta-analysis, and five randomized controlled trials (RCTs). After axillary lymph node dissection (ALND), LRNI resulted in small benefits in breast cancer specific mortality, locoregional recurrence, and distant metastases-free survival but not overall survival. After a positive sentinel node biopsy (SLNB), LRNI may provide equivalent locoregional control and disease-free survival (DFS) compared to ALND with a lower risk of lymphedema. No randomized data is available for the neoadjuvant setting.ConclusionsThe summary of the role of radiation, is relevant to radiation oncologists for choosing the correct cohort of patient requiring LRNI and to surgeons making clinical decisions regarding the timing and type of breast reconstruction offered to patients.     

Oral cancer prediction by noninvasive genetic screening

Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next-generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high-risk individuals. Noninvasive genetic screening can be employed to screen high-risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient.     

Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

Atrial fibrillation after cardiac surgery: A systematic review and meta-analysis

ObjectiveNew-onset postoperative atrial fibrillation (POAF) after cardiac surgery is common, with rates up to 60%. POAF has been associated with early and late stroke, but its association with other cardiovascular outcomes is less known. The objective was to perform a meta-analysis of the studies reporting the association of POAF with perioperative and long-term outcomes in patients with cardiac surgery.MethodsWe performed a systematic review and a meta-analysis of studies that presented outcomes for cardiac surgery on the basis of the presence or absence of POAF. MEDLINE, EMBASE, and the Cochrane Library were assessed; 57 studies (246,340 patients) were selected. Perioperative mortality was the primary outcome. Inverse variance method and random model were performed. Leave-one-out analysis, subgroup analyses, and metaregression were conducted.ResultsPOAF was associated with perioperative mortality (odds ratio [OR], 1.92; 95% confidence interval [CI], 1.58-2.33), perioperative stroke (OR, 2.17; 95% CI, 1.90-2.49), perioperative myocardial infarction (OR, 1.28; 95% CI, 1.06-1.54), perioperative acute renal failure (OR, 2.74; 95% CI, 2.42-3.11), hospital (standardized mean difference, 0.80; 95% CI, 0.53-1.07) and intensive care unit stay (standardized mean difference, 0.55; 95% CI, 0.24-0.86), long-term mortality (incidence rate ratio [IRR], 1.54; 95% CI, 1.40-1.69), long-term stroke (IRR, 1.33; 95% CI, 1.21-1.46), and longstanding persistent atrial fibrillation (IRR, 4.73; 95% CI, 3.36-6.66).ConclusionsThe results suggest that POAF after cardiac surgery is associated with an increased occurrence of most short- and long-term cardiovascular adverse events. However, the causality of this association remains to be established.