Serum kisspeptin levels in deep-infiltrating,ovarian, and superficial endometriosis: A prospective observational study

The diagnosis of endometriosis may delay for many years due to non-deterministic symptoms and avoiding surgical interventions. Kisspeptins are hormones that interact with endometrial tissue to limit invasions during placentation and various cancers and are suggested to be also associated with endometriosis. This study evaluated if serum kisspeptin levels are associated with the invasion depth in endometriosis. Forty patients between 18 and 45 years of age and admitted to a tertiary-care Obstetrics and Gynecology Department between 2020 and 2021 with a diagnosis of endometriosis, and 40 patients without endometrioma were included in the study. Demographic, obstetric, clinical, and biochemical characteristics were evaluated in patients with superficial (SE) and deep infiltrating (DIE) endometriosis and healthy controls. Twenty patients (50%) had SE, 14 (35%) had DIE, and 22 (55%) had endometrioma in the patient group. Fertility rates were higher among controls, but similar between patients with SE and DIE. CA125 levels were significantly higher in the DIE group. SE and DIE groups had similar kisspeptin values, significantly higher than controls. CA125 and kisspeptin levels were not correlated in study groups. Serum kisspeptin levels were significantly different between endometriosis patients and healthy controls. However, kisspeptin levels were unable to differentiate endometriosis severity. Our results suggest that kisspeptins might play a role in the pathogenesis of endometriosis, which needs further assessment in more comprehensive studies.     

Ⅳ期非小细胞肺癌预后因素分析

目的：回顾分析Ⅳ期非小细胞肺癌患者（NSCLC）的预后因素,指导临床个体规范化的治疗。方法：采用Kaplan Meier生存分析以及COX回归模型分析57例Ⅳ期初治NSCLC患者临床特征,如年龄、性别、吸烟指数、病理类型以及治疗前血浆中CEA和Cyfra21-1的水平等以及治疗相关因素与生存率的关系,筛选Ⅳ期NSCLC患者预后相关因素。结果：单因素分析表明,患者的年龄、吸烟指数、KPS评分、治疗前血浆Cyfra21-1水平以及化疗与否、化疗周期数与Ⅳ期NSCLC患者的生存率有关。多因素分析表明,Cyfra21-1、KPS评分、化疗周期是独立的预后因素。结论：治疗前血浆中Cyfra21-1的水平,KPS评分以及化疗周期数为Ⅳ期NSCLC患者的独立预后因素。无化疗禁忌症的Ⅳ期NSCLC患者积极规范合理的治疗能延长患者生存期,具有重要的临床意义。     

纤维蛋白原与肿瘤相关性及其机制

纤维蛋白原(Fib)是一种常见的凝血功能相关蛋白,除参与血凝外,还与肿瘤密切相关.研究发现多种恶性肿瘤术前血浆Fib可明显升高,并与肿瘤进展、转移及预后密切相关.尽管Fib与肿瘤的相互作用机制尚未完全明了,将Fib作为肿瘤标志物及肿瘤治疗新方向已成为肿瘤研究的新热点.     

Tumor’host interaction in the optimization of paclitaxel-based combination therapies with vascular targeting compounds

Targeting of the tumor stroma, including the tumor vasculature, represents a new frontier in the treatment of malignancy. Preclinical studies and clinical experiences have established that stroma-directed novel agents must be combined with conventional therapies in order to achieve relevant therapeutic efficacy. Here we review our preclinical experience on combinations of paclitaxel with a tyrosine kinase receptor inhibitor of angiogenesis (SU6668) and a vascular disrupting agent (VDA, ZD6126), and discuss the critical factors that determine the outcome of these treatments. We also analyze the relevance of the intrinsic sensitivity of the tumor to the drugs, as well as the possibility that the two combined agents synergistically affect the vasculature or independently target the host and the tumor compartments. Finally, we discuss the need to carefully optimize scheduling and sequencing, through the use of reliable end points, in order to avoid negative pharmacological interactions and to improve the antineoplastic efficacy of paclitaxel-based combination treatments.     

量化 DCE-MRI 技术对乳腺良恶性病变诊断价值分析

目的：探讨基于动态增强磁共振成像（dynamic contrast-enhanced MRI,DCE-MRI）及特定药物动力学模型所获得的量化参数对乳腺良恶性病变诊断价值。方法：收集我院2015年6月至2016年2月42例乳腺病变患者行 DCE-MRI 扫描,通过后处理软件测量如下量化参数,定量参数：容量转移常数（volume transfer constant, Ktrans ）、速率常数（rate constant,Kep ）、血浆分数（the plasma fraction,Vp ）;半定量参数：（1）增强后病灶达峰时间（time to peak,TTP）、（2）增强后病灶内造影剂最大浓度值（max concentration,MAX Conc）、（3）增强后时间信号曲线下面积（area under curve,AUC）、（4）增强后时间信号曲线最大斜率值（MAX Slope）。检查后1周内均经手术取得病理诊断,采用独立样本 t 检验或非参数检验比较良性组及恶性组间各量化参数的差异。绘制 ROC 曲线,并分析有价值量化参数对乳腺良、恶性病灶诊断价值。结果：恶性病灶组定量参数 Ktrans Max（t ＝2．228,P ＝0．033）、Ktrans Mean（t ＝4．092,P ＜0．001）、Kep Mean（Z ＝2．422,P ＝0．015）、Kep Max（t ＝2．240,P ＝0．031）及半定量参数 MAX Conc Max（t ＝3．256,P ＝0．002）、MAX Conc Mean（t ＝3．460,P ＝0．001）、AUC Max（t ＝2．250,P ＝0．034）、AUC Mean（t ＝2．861,P ＝0．007）、MAX Slope Max（t ＝2．478,P ＝0．018）、MAX Slope Mean（t ＝2．226,P ＝0．032）较良性病灶组值明显升高,而半定量参数 TTP Min（t ＝－5．145,P ＜0．001）、TTP Mean（t ＝－3．818,P ＜0．001）较良性病灶组明显缩短。经 ROC 曲线分析显示,Ktrans Mean、Kep Mean、TTP Min、MAX Conc Max、AUC Mean、MAX Slope Max 对乳腺良恶性病变具有诊断价值,根据最大约登指数计算最佳诊断阈值,分别以0．1137、0．0258、0．9065、0．1059、0．1640、0.1502为诊断阈值,其鉴别诊断乳腺病灶良恶性敏感度分别为73．33％、73．33％、91．67％、76．67％、80．00％、80.00％,特异性分别为100％、83．30％、70．00％、91．70％、66．70％、75．00％。结论：基于 DCE-MRI 技术及特定的药物动力学模型所获得的量化参数对乳腺良恶性病变鉴别诊断有临床价值,且有较高的诊断效能,有望成为无创性评价乳腺肿瘤微循环的新方法。     

Overview: Cellular plasticity,cancer stem cells and metastasis

Recently, a number of hypotheses have converged into a unified theoretical framework which addresses the most vexing aspects of cancer: metastasis, relapse and therapeutic resistance. The central component of this framework is the new paradigm of cellular differentiation, once viewed as a unidirectional process, but now recognized as a plastic process in which cancer cells can dedifferentiate into more primitive, stem-like phenotypes. This plasticity is controlled by both intrinsic biochemical processes and bi-directional environmental cues involving cancer-associated non-cancerous cells. Such plastic phenotypic shifts may influence the discontinuous behavior of cancers, in which some cancers remain dormant for months or years after therapy, only to relapse and wreak havoc. This Special Issue of Cancer Letters assembles a collection of mini-reviews describing the current knowledge of cellular plasticity and its relationship to cancer “stemness” and progression, illuminating how progress in this field may yield major benefits in overcoming resistance and thwarting metastasis.     

Heterogeneity of Proliferative Activity in Nodule-in-Nodule Lesions of Small Hepatocellular Carcinoma

Surgically resected small hepatocellular carcinomas showing "nodule-in-nodule'formation were analyzed in terms of cell proliferative activity. The analysis was achieved by successful immunohistochemical demonstration of proliferating cell nuclear antigen in formalin-fixed paraffin-embedded tissue sections. Eight nodules (up to 3 cm in diameter) examined were either atypical adenomatous hyperplasia or hepatocellular carcinoma of low histologic grade, containing a discrete inner nodular area composed of obvious hepatocellular carcinoma of higher histologic grade. In all cases, the proliferating cell nuclear antigen labeling index of the latter area was much higher than that of the former, which in turn was slightly higher than that of the non-cancerous liver of the patient in 6 cases. The data presented here provide supporting evidence that the successive emergence and expansion of a more rapidly proliferating subclone within a nodule result in the stepwise progression of malignancy of human hepatocellular carcinoma.     

Spontaneous xenogeneic GvHD in Wilms' tumor Patient‐Derived xenograft models and potential solutions

Severely immunocompromised NOD.Cg‐Prkdc ^scid Il2rg ^tm1Sug (NOG) mice are among the ideal animal recipients for generation of human cancer models. Transplantation of human solid tumors having abundant tumor‐infiltrating lymphocytes (TILs) can induce xenogeneic graft‐versus‐host disease (xGvHD) following engraftment and expansion of the TILs inside the animal body. Wilms'' tumor (WT) has not been recognized as a lymphocyte‐predominant tumor. However, 3 consecutive generations of NOG mice bearing WT patient‐derived xenografts (PDX) xenotransplanted from a single donor showed different degrees of inflammatory symptoms after transplantation before any therapeutic intervention. In the initial generation, dermatitis, auto‐amputation of digits, weight loss, lymphadenopathy, hepatitis, and interstitial pneumonitis were observed. Despite antibiotic treatment, no response was noticed, and thus the animals were prematurely euthanized (day 47 posttransplantation). Laboratory and histopathologic evaluations revealed lymphoid infiltrates positively immunostained with anti‐human CD3 and CD8 antibodies in the xenografts and primary tumor, whereas no microbial infection or lymphoproliferative disorder was found. Mice of the next generation that lived longer (91 days) developed sclerotic skin changes and more severe pneumonitis. Cutaneous symptoms were milder in the last generation. The xenografts of the last 2 generations also contained TILs, and lacked lymphoproliferative transformation. The systemic immunoinflammatory syndrome in the absence of microbial infection and posttransplant lymphoproliferative disorder was suggestive of xGvHD. While there are few reports of xGvHD in severely immunodeficient mice xenotransplanted from lymphodominant tumor xenografts, this report for the first time documented serial xGvHD in consecutive passages of WT PDX‐bearing models and discussed potential solutions to prevent such an undesired complication.     

五种抗衰老中药对小鼠T—淋巴细胞增殖与IL—2产生的影响

本文研究了当归、枸杞、党参、生地、甘草的免疫增强作用,结果表明,它们均可明显促进ConA活化的脾淋巴细胞DNA和蛋白质的生物合成,它们促进DNA合成的最适浓度分别为500,200,100,200,100μg/ml。DNA合成高峰在48 h,对白间素-2(IL-2)产生也有明显的增强作用,对DNA、蛋白质的生物合成及IL-2产生的影响基本上是相平行的。