死亡结构域相关蛋白及其在宫颈病变中的研究进展

宫颈癌对妇女健康构成严重威胁,人乳头瘤病毒感染与宫颈病变及宫颈癌的发生密切相关。关于宫颈癌发生发展的机制仍在研究中。近年研究发现一种多功能核蛋白,即死亡结构域相关蛋白(death domain associated protein,Daxx),其与细胞内蛋白或病毒蛋白相互作用,参与调节细胞凋亡、转录调控、抗病毒等细胞活动,在不同途径中发挥不同的生理或病理作用。通过对Daxx功能及其作用机制的研究有助于进一步阐明宫颈癌发生发展的机制,有助于发现新的预防和治疗方法。综述Daxx的一般特性和研究现况及其在宫颈病变的研究进展。     

Nidogen 1 regulates proliferation and migration/invasion in murine claudin-low mammary tumor cells

Nidogen 1 (NID1) is a glycoprotein found in basement membranes involved in cross-linking collagen IV and laminin. The role of NID in breast cancer has only been evaluated in a small number of studies and the findings of these studies have been inconsistent. Our previous work revealed that highly tumorigenic murine mammary tumor cells express high levels of Nid1 while weakly tumorigenic mammary tumor cells express low levels of Nid1. To investigate Nid1, two stable knockdown lines were created, and Nid1 knockdown was confirmed at both the mRNA and protein level. Nid1 knockdown significantly reduced cell proliferation and migration/invasion and these reductions in proliferation and migration/invasion could be rescued by conditioned media containing NID1 protein. The reduced migration/invasion observed in the Nid1 knockdown cells was not associated with significant alterations in the epithelial gene Cdh1 or the mesenchymal genes Snai1, Snai2, Twist1, Twist2, Zeb1 and Zeb2. Therefore, suppression of Nid1 expression reduces proliferation and migration/invasion in claudin-low murine mammary tumor cells.     

Information autour du dépistage organisé du cancer du sein. L’INCa et Cancer Rose répondent-ils aux critères des outils d’aide à la décision ?

BackgroundControversies around organized breast cancer screening emphasize the need for information for women. In France, the institute of cancer (INCa) is in charge of conveying this information. Cancer Rose's website (CR) provides complementary information considering INCa's incomplete. The objective of this study was to identify if these informations meet criteria for decision aid.MethodsInformation documents were selected and analyzed using International Patient Decision Aid Standards (IPDAS). Each item was noted A (absent), P (present) or I (present but incomplete).ResultsInformation booklet and press kit for INCa and studies section for CR were the document meeting most criteria. The document meeting fewer criteria were the INCa's video and information leaflet for CR. Videos are more accessible tools for people with lower levels of health literacy. INCa's video did not present the risks of screening and CR's emphasized the risks.ConclusionThese documents have not been evaluated for intelligibility, clarity and readability. Addressing these criteria limits social inequities and improves health literacy.     

¿Es el intervalo libre de docetaxel un factor predictivo para el cáncer de próstata resistente a la castración?

ObjectiveProstate cancer (PCa) is the second most common solid tumor in men and the fifth leading cause of cancer-related death. In advanced stage, palliative treatments are used instead of curative therapies. Therefore, finding predictive indicators seems crucial. Patients with castration-resistant prostate cancer (CRPC) that received Dx chemotherapy have been retrospectively reviewed. The aim of this study was to investigate whether docetaxel (Dx)-free interval could have a predictive value for PCa and influence other sequential therapies.Material and methodsThis clinical trial study was performed on 104 patients at Medeniyet University Oncology Clinic in 2018-2020. All CRPC patients had metastases, received Dx as first-line treatment and underwent androgen receptor axis targeted (ARAT) therapy after disease progression. We analyzed patients’ progression time after Dx therapy and the effects on sequential treatment.ResultsAfter Dx therapy, all patients received ARAT (abiraterone (ABI) n: 49 (47.1%) and enzalutamide (ENZ) n: 54 (51.9%)) as a second-line treatment, except for one patient who received cabazitaxel. There was a statistically significant relationship between the Dx-free interval and duration of response to ARAT (P<.001). The response time of ARAT treatment was <10.5 months in all patients whose Dx-free interval period was <9 months.ConclusionsOur findings support the theory that Dx-free interval can be a predictive factor for CRPC. CRPC disease can be classified as Dx-sensitive disease or Dx-resistance disease, based on the Dx-free interval. Decision on subsequent treatments could be made considering this information.     

Deep learning with biopsy whole slide images for pretreatment prediction of pathological complete response to neoadjuvant chemotherapy in breast cancer：A multicenter study

IntroductionPredicting pathological complete response (pCR) for patients receiving neoadjuvant chemotherapy (NAC) is crucial in establishing individualized treatment. Whole-slide images (WSIs) of tumor tissues reflect the histopathologic information of the tumor, which is important for therapeutic response effectiveness. In this study, we aimed to investigate whether predictive information for pCR could be detected from WSIs.Materials and methodsWe retrospectively collected data from four cohorts of 874 patients diagnosed with biopsy-proven breast cancer. A deep learning pathological model (DLPM) was constructed to predict pCR using biopsy WSIs in the primary cohort, and it was then validated in three external cohorts. The DLPM could generate a deep learning pathological score (DLPs) for each patient; stromal tumor-infiltrating lymphocytes (TILs) were selected for comparison with DLPs.ResultsThe WSI feature-based DLPM showed good predictive performance with the highest area under the curve (AUC) of 0.72 among the cohorts. Alternatively, the combination of the DLPM and clinical characteristics offered a better prediction performance (AUC >0.70) in all cohorts. We also evaluated the performance of DLPM in three different breast subtypes with the best prediction for the triple-negative breast cancer (TNBC) subtype (AUC: 0.73). Moreover, DLPM combined with clinical characteristics and stromal TILs achieved the highest AUC in the primary cohort (AUC: 0.82) and validation cohort 1 (AUC: 0.80).ConclusionOur study suggested that WSIs integrated with deep learning could potentially predict pCR to NAC in breast cancer. The predictive performance will be improved by combining clinical characteristics. DLPs from DLPM can provide more information compared to stromal TILs for pCR prediction.     

Dry eye signs and symptoms in aromatase inhibitor treatment and the relationship with pain

PurposeAromatase inhibitors (AIs) limit the synthesis of oestrogen in peripheral tissues thus lowering levels of oestrogen. The primary aim was to evaluate whether women treated with AIs have altered dry eye symptoms and signs. A sub-aim was to investigate whether symptoms of dry eye in postmenopausal women were associated with symptoms of non-eye pain, ocular pain and self-rated pain perception.MethodsThis cross-sectional, observational, single visit study recruited 56 postmenopausal women (mean age 64.1 + 7.9 years) and 52 undergoing AI treatment (mean age 66.6 + 9.0). Ocular symptoms (OSDI, MGD14) and pain questionnaires (PSQ, OPAS) were administered and signs of dry eye and meibomian gland dysfunction were evaluated.ResultsAlmost half of each group reported dry eye symptoms, defined as OSDI>12 (48% control, 46% AI). The PSQ score was significantly higher in the AI group (p = 0.04). Neither frequency or severity of dry eye (or MGD) symptoms scores were significantly different between groups. In the AI group, meibomian gland expressibility score was worse (p = 0.003); there were no differences in any other signs. Higher OSDI scores were associated with higher OPAS eye-pain scores (r = 0.49, p < 0.001), but not OPAS non-eye pain (r = 0.09, p = 0.35). Pain perception (PSQ) showed a moderate positive association with OPAS eye-pain (r = 0.30, p = 0.003).ConclusionsIn this study elevated ocular symptoms were observed in both the AI treated and the untreated groups, with no difference between the groups. Women undergoing AI treatment for early stage breast cancer had worse meibum expressibility score and increased pain perception compared to an untreated group of women.     

Patient preferences and predicted relative uptake for targeted therapies in metastatic colorectal cancer: a discrete choice experiment

Abstract

Objective

Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients’ preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies.     

El papel de la resonancia magnética multiparamétrica en el diagnóstico de la recidiva local tras la prostatectomía radical y antes de la radioterapia de rescate

PurposeAssess multiparametric-MRI (mp-MRI) diagnostic accuracy in the detection of local recurrence of prostate cancer (PCa) after radical prostatectomy (PR) and before radiation therapy (RT).Materials and methodsA total of 188 patients underwent 1.5-T mp-MRI after RP before RT. Patients were divided into 2 groups: with biochemical recurrence (group A) and without but with high risk of local recurrence (group B). Continuous variables were compared between 2 groups using Student-t test; categoric variables were analyzed using Pearson chi-square. ROC analysis was performed considering PSA before RT, ISUP, pT and pN as grouping variables.ResultsPCa recurrence (reduction of PSA levels after RT) was 89.8% in group A and 80.3% in group B. Comparing patients with and without PCa recurrence, there was a significant difference in PSA values before RT for group A and for PSA values before RT and after RT for group B. In group A, there was a significant correlation between PSA before RT and diameter of recurrence and between PSA before RT and time spent before recurrence. The mp-MRI diagnostic accuracy in detecting PCa local recurrence after RP is of 62.2% in group A and 38% in group B. Diffusion weighted imaging is the most specific MRI-sequence and dynamic contrast enhanced the most sensitive. For PSA = 0.5 ng/ml, the AUC decreases while sensitivity and accuracy increase for each MRI-sequence. For PSA = 0.9 ng/ml, dynamic contrast enhanced-AUC increases significantly.Conclusionmp-MRI should always be performed before RT when a recurrence is suspected. New scenarios can be opened considering the role of diffusion weighted imaging for PSA ≤ 0.5 ng/ml.     

电视辅助胸腔镜下解剖性肺切除治疗I期肺癌的临床效果

目的 探讨电视辅助胸腔镜下解剖性肺切除治疗Ⅰ期肺癌的临床效果。方法 采用回顾性研究方法,选取2015年5月至2017年1月广西医科大学附属肿瘤医院收治的I期肺癌患者84例,按照手术方法不同将患者分为两组:观察组和对照组,每组各42例。观察组患者实施电视辅助胸腔镜下解剖性肺切除术治疗,对照组患者给予传统开胸肺叶切除术治疗。比较两组患者的住院时间、切口长度、术中出血量、手术时间、1年和3年生存情况及生活质量评分(SF-36生活量表)变化。结果 观察组患者的住院时间短于对照组(6. 13±1. 46 vs. 10. 39±2. 41 d),切口长度小于对照组(4. 38±1. 09 vs. 11. 84±3. 25 cm),术中出血量少于对照组(284. 62±54. 21 vs. 397. 57±61. 49 ml),差异均具有统计学意义(P <0. 05);而两组手术时间比较(165. 28±33. 24 vs. 156. 39±30. 92 min),差异无统计学意义(P> 0. 05)。观察组患者的1、3年生存率[97. 62%(41/42)、90. 48%(38/42)]均高于对照组[88. 10%(37/42)、76. 19%(32/42)],但差异无统计学意义(P> 0. 05)。观察组患者的各项生活质量评分[精神健康(75. 42±6. 87 vs 61. 30±4. 15分)、情感职能(81. 38±7. 15 vs. 73. 49±5. 76分)、社会功能(82. 67±5. 78 vs. 75. 42±4. 35分)、一般健康状况(79. 49±6. 17 vs.70. 31±5. 04分)、精力(84. 37±5. 45 vs. 74. 13±6. 07分)、生理职能(86. 52±6. 88 vs. 76. 93±6. 42分)、躯体疼痛(83. 46±7. 49 vs. 74. 33±5. 79分)、生理功能(70. 39±4. 31 vs. 61. 38±3. 56分)]均高于对照组,且差异具有统计学意义(P <0. 05)。结论 与传统开胸肺叶切除术相比,电视辅助胸腔镜下解剖性肺切除治疗I期肺癌手术损伤更小、短期生存率更高,且有助于提高患者术后生活质量水平,这对改善患者预后有重要意义,值得临床推广应用。