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Does old-to-young kidney transplantation rejuvenate old donor kidneys? 老肾移植是否能让捐献者的老肾焕发青春?
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-10-07 DOI: 10.14670/HH-18-829
Mayumi Takahashi-Kobayashi, Kunio Kawanishi, Joichi Usui, Satoshi Yamazaki, Surya V Seshan, Kunihiro Yamagata

Background: The number of older organ donors is increasing due to the aging population. Aged kidneys often face problems such as delayed graft function but previous murine experiments suggested the possibilities of rejuvenation, for example, in a parabiosis setting between old and young mice. To investigate kidney-graft rejuvenation, we compared an old-to-young (O-Y) patient transplantation group and a transplantation group with donors/recipients of approx. the same age (SA) with the renal senescence marker p16 in kidney biopsy samples at baseline and one year post-transplantation.

Methods: We retrospectively analyzed our hospital's 32 cases of living-donor ABO-compatible transplants performed between 2013-2020. Both the baseline and one-year biopsy (n=9) or only the baseline biopsy (n=32) were analyzed. We divided the nine cases into an O-Y group (donors' median age 68 yrs, recipients 41, difference -27) and an SA group (donors' median age 53 yrs, recipients 51.5, difference -3.5). p16 was stained with the clones JC8 and E6H4 to determine the precise p16-positive rate.

Results: The 32 baseline biopsies' p16-positive rate was weakly related to donor age, suggesting that the p16-positive rate can help evaluate kidney senescence. The (n=5) O-Y group's p16-positive rates were at baseline 0.08 and one year 0.12; the (n=4) SA group's rate was 0.03 at both baseline and one year.

Conclusions: No kidney rejuvenation was observed, even when old donor kidneys went to young recipients.

背景:由于人口老龄化,器官捐献者的年龄越来越大。衰老的肾脏经常面临移植功能延迟等问题,但以前的小鼠实验表明,例如在老年小鼠和年轻小鼠之间的同种异体移植中,存在肾脏再生的可能性。为了研究肾移植的年轻化问题,我们比较了从老到年轻(O-Y)移植组和年龄大致相同(SA)的供体/受体移植组在基线和移植后一年肾活检样本中肾脏衰老标志物 p16 的情况:我们对本院在 2013-2020 年间进行的 32 例 ABO 相容活体供体移植进行了回顾性分析。我们分析了基线活检和一年活检(9 例),或仅分析了基线活检(32 例)。我们将这9个病例分为O-Y组(捐献者中位年龄68岁,受者41岁,差异-27)和SA组(捐献者中位年龄53岁,受者51.5岁,差异-3.5),用克隆JC8和E6H4对p16进行染色,以确定精确的p16阳性率:结果:32 例基线活检的 p16 阳性率与供体年龄关系不大,这表明 p16 阳性率有助于评估肾脏衰老情况。O-Y组(n=5)的p16阳性率基线为0.08,一年后为0.12;SA组(n=4)的p16阳性率基线和一年后均为0.03:结论:即使高龄捐献者的肾脏给了年轻的受者,也没有观察到肾脏年轻化的现象。
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引用次数: 0
Clinicopathological diagnosis of axillary signet-ring cell-like/histiocytoid carcinoma: a case report and literature review. 腋窝标志环细胞样癌/组织细胞样癌的临床病理诊断:病例报告和文献综述。
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-10-04 DOI: 10.14670/HH-18-828
Ling Zhang, Li Li, Yun Wang, Xiao Ling Wang

Objective: To explore the clinicopathological and morphological characteristics, diagnosis, differential diagnosis, treatment, and prognosis of primary signet-ring cell/histiocytoid carcinoma (SRCHC) of the axilla.

Methods: The clinical manifestations, pathomorphological characteristics, and immunohistochemical staining results of a case of primary SRCHC in the axilla were retrospectively analyzed, and the relevant literature was reviewed.

Results: The patient was a 69-year-old male. Subcutaneous gray-white nodules with unclear boundaries were visible. Microscopic examination: The tumor was located in the dermis and subcutaneous tissue. The tumor cells were arranged in a cord-like, soldier-like, or nest-like shape, with mild to moderate atypia. Some cells had obvious nucleoli. The tumor cytoplasm was eosinophilic, and mucoid material inside and outside the cells could be seen, showing a signet-ring-like or histiocytoid appearance. Immunohistochemical staining was positive for GCDFP-15, CK7, E-cadherin, AR, P120, GATA3 and negative for Villin, S-100, CK20, SMA, P63, CD68, TTF-1, NapsinA, ER, PR, and Ki-67 proliferation index (8%), HER2(2+) and FISH(-). The special staining AB-PAS (AB+,PAS-).

Conclusion: Cutaneous axillary primary SRCHC is extremely rare and highly invasive and needs to be differentiated from a variety of metastatic tumors (breast, digestive system, lung, etc.).

目的探讨腋窝原发性标志环细胞/组织细胞癌(SRCHC)的临床病理形态学特征、诊断、鉴别诊断、治疗和预后:方法:回顾性分析一例腋窝原发性标志环细胞癌(SRCHC)的临床表现、病理形态学特征和免疫组化染色结果,并查阅相关文献:患者为一名69岁的男性。皮下可见边界不清的灰白色结节。显微镜检查:肿瘤位于真皮和皮下组织。肿瘤细胞呈条索状、士兵状或巢状排列,有轻度至中度不典型性。一些细胞有明显的核仁。肿瘤细胞质呈嗜酸性,细胞内外可见粘液状物质,呈标志环状或组织细胞样外观。免疫组化染色结果显示,GCDFP-15、CK7、E-cadherin、AR、P120、GATA3阳性,Villin、S-100、CK20、SMA、P63、CD68、TTF-1、NapsinA、ER、PR、Ki-67增殖指数(8%)、HER2(2+)和FISH(-)阴性。特殊染色AB-PAS(AB+,PAS-):皮肤腋窝原发性 SRCHC 极其罕见,具有高度侵袭性,需要与各种转移性肿瘤(乳腺癌、消化系统肿瘤、肺癌等)相鉴别。
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引用次数: 0
STAT3/p-STAT3 expression is correlated with clinicopathological characteristics and prognosis in non-small cell lung cancer. STAT3/p-STAT3的表达与非小细胞肺癌的临床病理特征和预后相关。
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-10-03 DOI: 10.14670/HH-18-827
Jili Li, Yingying Zhu, Jianyue Peng, Lan Yang, Li Zhang, Lei Li

Signal transducer and activator of transcription factor 3 (STAT3)/phosphorylated STAT3 (p-STAT) play a critical role in tumorigenesis, however, there is limited information on its prognostic value in non-small cell lung cancer (NSCLC). To address this question, 239 lung cancer and 71 normal lung tissue samples were obtained in this study. Immunohistochemistry was applied to detect STAT3/p-STAT3 expression. Pearson's Chi-squared test and the Kaplan-Meier method were conducted to evaluate associations with patients' clinical characteristics and survival. According to our results, STAT3/p-STAT3 was significantly upregulated in lung cancer tissue (p<0.001). Moreover, p-STAT3 expression was significantly correlated with age (p=0.046) and pathological types (p=0.037). In survival analysis, STAT3 positivity was negatively associated with survival in patients older than 60 years (p=0.043) but failed to be an independent prognostic factor in multivariate analysis (p=0.083). Therefore, STAT3/p-STAT3 may serve as a critical biomarker in NSCLC.

信号转导和激活转录因子 3(STAT3)/磷酸化 STAT3(p-STAT)在肿瘤发生过程中起着至关重要的作用,但有关其在非小细胞肺癌(NSCLC)中的预后价值的信息却很有限。为解决这一问题,本研究采集了 239 例肺癌和 71 例正常肺组织样本。研究采用免疫组化方法检测 STAT3/p-STAT3 的表达。采用皮尔逊卡方检验和 Kaplan-Meier 法评估了 STAT3/p-STAT3 表达与患者临床特征和生存期的关系。结果显示,STAT3/p-STAT3在肺癌组织(pp=0.046)和病理类型(pp=0.037)中显著上调。在生存率分析中,STAT3 阳性与 60 岁以上患者的生存率呈负相关(p=0.043),但在多变量分析中未能成为独立的预后因素(p=0.083)。因此,STAT3/p-STAT3可作为NSCLC的重要生物标志物。
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引用次数: 0
Cancer-associated fibroblast-secreted exosomes promote prostate cancer cell migration and invasion by the FGL1/SOX5 axis. 癌症相关成纤维细胞分泌的外泌体通过FGL1/SOX5轴促进前列腺癌细胞迁移和侵袭
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-10-02 DOI: 10.14670/HH-18-826
Lingquan Kong, Xing Wang, Yu Li, Xiansheng Zhang

Exosomes secreted by cancer-associated fibroblasts (CAFs) play a critical role in cancer progression. This study aimed to explore the effects of CAF exosomes on prostate cancer (PC) cell metastasis. PC cells were treated with these exosomes, and their processes were evaluated using cell-counting kit-8 and Transwell assays. Exosome-regulated mRNAs were explored using quantitative real-time PCR. The relationship between FGL1 and SOX5 was analyzed using co-immunoprecipitation and fluorescence in situ hybridization (FISH) assays. The results of this study showed that exosomes derived from CAFs promoted PC cell viability, migration, and invasion. CAFs promoted PC cell viability and metastasis by releasing exosomes. Exosome treatment increased the levels of FGL1, which interacted with SOX5 and negatively regulated its expression. Rescue experiments demonstrated that CAF exosomes promoted the biological behaviors of PC cells by upregulating FGL1 and downregulating SOX5. Moreover, exosomes accelerated tumor growth by regulating the FGL1 level. In conclusion, CAF-derived exosomes promoted PC cell viability, migration, and invasion by elevating the FGL1/SOX5 axis, suggesting a novel strategy for the treatment of metastatic PC.

癌症相关成纤维细胞(CAF)分泌的外泌体在癌症进展中起着关键作用。本研究旨在探讨CAF外泌体对前列腺癌(PC)细胞转移的影响。用这些外泌体处理 PC 细胞,并用细胞计数试剂盒-8 和 Transwell 试验评估它们的作用过程。利用实时定量 PCR 技术研究了外泌体调控的 mRNA。使用共免疫共沉淀和荧光原位杂交(FISH)方法分析了FGL1和SOX5之间的关系。研究结果表明,来自CAFs的外泌体促进了PC细胞的活力、迁移和侵袭。CAF通过释放外泌体促进了PC细胞的活力和转移。外泌体处理增加了FGL1的水平,FGL1与SOX5相互作用并负向调节其表达。拯救实验表明,CAF外泌体通过上调FGL1和下调SOX5促进了PC细胞的生物学行为。此外,外泌体还通过调节 FGL1 水平加速肿瘤生长。总之,CAF衍生的外泌体通过提高FGL1/SOX5轴促进了PC细胞的活力、迁移和侵袭,为治疗转移性PC提供了一种新策略。
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引用次数: 0
Colorectal cancer histopathology image analysis: A comparative study of prognostic values of automatically extracted morphometric nuclear features in multispectral and red-blue-green imagery. 结直肠癌组织病理学图像分析:多光谱和红蓝绿图像中自动提取的核形态特征预后价值比较研究。
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-01-23 DOI: 10.14670/HH-18-715
Wenlou Liu, Aiping Qu, Jingping Yuan, Linwei Wang, Jiamei Chen, Xiuli Zhang, Hongmei Wang, Zhengxiang Han, Yan Li

Objectives: Multispectral imaging (MSI) has been utilized to predict the prognosis of colorectal cancer (CRC) patients, however, our understanding of the prognostic value of nuclear morphological parameters of bright-field MSI in CRC is still limited. This study was designed to compare the efficiency of MSI and standard red-green-blue (RGB) images in predicting the prognosis of CRC.

Methods: We compared the efficiency of MS and conventional RGB images on the quantitative assessment of hematoxylin-eosin (HE) stained histopathology images. A pipeline was developed using a pixel-wise support vector machine (SVM) classifier for gland-stroma segmentation, and a marker-controlled watershed algorithm was used for nuclei segmentation. The correlation between extracted morphological parameters and the five-year disease-free survival (5-DFS) was analyzed.

Results: Forty-seven nuclear morphological parameters were extracted in total. Based on Kaplan-Meier analysis, eight features derived from MS images and seven featured derived from RGB images were significantly associated with 5-DFS, respectively. Compared with RGB images, MSI showed higher accuracy, precision, and Dice index in nuclei segmentation. Multivariate analysis indicated that both integrated parameters 1 (factors negatively correlated with CRC prognosis including nuclear number, circularity, eccentricity, major axis length) and 2 (factors positively correlated with CRC prognosis including nuclear average area, area perimeter, total area/total perimeter ratio, average area/perimeter ratio) in MS images were independent prognostic factors of 5-DFS, in contrast with only integrated parameter 1 (P<0.001) in RGB images. More importantly, the quantification of HE-stained MS images displayed higher accuracy in predicting 5-DFS compared with RGB images (76.9% vs 70.9%).

Conclusions: Quantitative evaluation of HE-stained MS images could yield more information and better predictive performance for CRC prognosis than conventional RGB images, thereby contributing to precision oncology.

目的:多光谱成像(MSI)已被用于预测结直肠癌(CRC)患者的预后,然而,我们对明视野MSI的核形态学参数在CRC中的预后价值的了解仍然有限。本研究旨在比较 MSI 和标准红-绿-蓝(RGB)图像在预测 CRC 预后方面的效率:我们比较了 MSI 和传统 RGB 图像在定量评估苏木精-伊红(HE)染色组织病理学图像方面的效率。我们使用像素支持向量机(SVM)分类器开发了腺体-基质分割流水线,并使用标记控制的分水岭算法进行细胞核分割。分析了提取的形态学参数与五年无病生存率(5-DFS)之间的相关性:结果:共提取了47个核形态学参数。根据 Kaplan-Meier 分析,从 MS 图像中提取的 8 个特征和从 RGB 图像中提取的 7 个特征分别与 5-DFS 显著相关。与 RGB 图像相比,MSI 在细胞核分割方面表现出更高的准确度、精确度和 Dice 指数。多变量分析表明,MS图像中的综合参数1(与CRC预后呈负相关的因素,包括核数目、圆度、偏心率、主轴长度)和综合参数2(与CRC预后呈正相关的因素,包括核平均面积、周长面积、总面积/总周长比、平均面积/周长比)都是5-DFS的独立预后因素,而只有综合参数1(PConclusions:与传统的RGB图像相比,HE染色MS图像的定量评估可为CRC预后提供更多信息和更好的预测性,从而为精准肿瘤学做出贡献。
{"title":"Colorectal cancer histopathology image analysis: A comparative study of prognostic values of automatically extracted morphometric nuclear features in multispectral and red-blue-green imagery.","authors":"Wenlou Liu, Aiping Qu, Jingping Yuan, Linwei Wang, Jiamei Chen, Xiuli Zhang, Hongmei Wang, Zhengxiang Han, Yan Li","doi":"10.14670/HH-18-715","DOIUrl":"10.14670/HH-18-715","url":null,"abstract":"<p><strong>Objectives: </strong>Multispectral imaging (MSI) has been utilized to predict the prognosis of colorectal cancer (CRC) patients, however, our understanding of the prognostic value of nuclear morphological parameters of bright-field MSI in CRC is still limited. This study was designed to compare the efficiency of MSI and standard red-green-blue (RGB) images in predicting the prognosis of CRC.</p><p><strong>Methods: </strong>We compared the efficiency of MS and conventional RGB images on the quantitative assessment of hematoxylin-eosin (HE) stained histopathology images. A pipeline was developed using a pixel-wise support vector machine (SVM) classifier for gland-stroma segmentation, and a marker-controlled watershed algorithm was used for nuclei segmentation. The correlation between extracted morphological parameters and the five-year disease-free survival (5-DFS) was analyzed.</p><p><strong>Results: </strong>Forty-seven nuclear morphological parameters were extracted in total. Based on Kaplan-Meier analysis, eight features derived from MS images and seven featured derived from RGB images were significantly associated with 5-DFS, respectively. Compared with RGB images, MSI showed higher accuracy, precision, and Dice index in nuclei segmentation. Multivariate analysis indicated that both integrated parameters 1 (factors negatively correlated with CRC prognosis including nuclear number, circularity, eccentricity, major axis length) and 2 (factors positively correlated with CRC prognosis including nuclear average area, area perimeter, total area/total perimeter ratio, average area/perimeter ratio) in MS images were independent prognostic factors of 5-DFS, in contrast with only integrated parameter 1 (<i>P</i><0.001) in RGB images. More importantly, the quantification of HE-stained MS images displayed higher accuracy in predicting 5-DFS compared with RGB images (76.9% vs 70.9%).</p><p><strong>Conclusions: </strong>Quantitative evaluation of HE-stained MS images could yield more information and better predictive performance for CRC prognosis than conventional RGB images, thereby contributing to precision oncology.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Histological and morphometrical evaluation of the urethral wall after bioresorbable stent implantation in male New Zealand White Rabbits: A preliminary study. 雄性新西兰白兔植入生物可吸收支架后尿道壁的组织学和形态学评估:初步研究。
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-02-19 DOI: 10.14670/HH-18-722
Joanna Skonieczna-Kurpiel, Jan P Madej, Tomasz Klekiel, Agnieszka Mackiewicz, Romuald Będziński, Agnieszka Noszczyk-Nowak, Tomasz Piasecki, Cassandra Ceccopieri

The aim of the study was the histological and morphometrical evaluation of the urethral wall at three time points after bioresorbable stent implantation in male New Zealand White Rabbits. The research was performed on 26 male New Zealand White rabbits aged 3-4 months and weighing 2.1-3.0 kg. Two models of bioresorbable sodium alginate-based stents were developed and implanted into the urethral lumen for one (T1), three (T3), and six weeks (T6). Sections of 5 µm thickness were cut from the urethra at intervals of 2 mm. The sliced sections were stained with hematoxylin-eosin (H&E), Van Gieson's (VG), Von Kossa, and Movat-Russell modified pentachrome (MOVAT) staining methods. The study provided valuable information for future models of urethral stents. The first model of the stent failed to fit the requirements due to inadequate mechanical properties. It curled up on itself losing the ability to adhere to the animals' urethra and was bioresorbed three weeks after implantation. The more rigid no. 2 stent was effective in widening the urethral lumen but did not biodegrade during the experiment. A comprehensive assessment of the second model's properties of biosorption and biointegration requires an extended observation of at least 12 months for an in depth morphological analysis. Stent migration is not likely to be caused solely by the mechanical properties of the urethra or urinary flow but mainly by muscle contraction of the organ wall.

该研究的目的是对雄性新西兰白兔植入生物可吸收支架后三个时间点的尿道壁进行组织学和形态学评估。研究对象为 26 只雄性新西兰白兔,年龄 3-4 个月,体重 2.1-3.0 千克。研究人员开发了两种基于藻酸钠的生物可吸收支架模型,并将其分别植入尿道腔内一周(T1)、三周(T3)和六周(T6)。每隔 2 毫米从尿道上切下厚度为 5 微米的切片。切片采用苏木精-伊红(H&E)、范吉森(VG)、冯-科萨(Von Kossa)和 Movat-Russell 改良五色染色法(MOVAT)染色。这项研究为今后的尿道支架模型提供了宝贵的信息。由于机械性能不足,第一个尿道支架模型未能达到要求。它自行卷曲,失去了附着在动物尿道上的能力,并在植入三周后被生物吸收。硬度更高的 2 号支架能有效拓宽尿道管腔,但在实验过程中没有发生生物降解。要全面评估第二个模型的生物吸附和生物整合特性,需要进行至少 12 个月的长期观察,以进行深入的形态分析。支架移位的原因可能不仅仅是尿道或尿流的机械特性,而主要是器官壁的肌肉收缩。
{"title":"Histological and morphometrical evaluation of the urethral wall after bioresorbable stent implantation in male New Zealand White Rabbits: A preliminary study.","authors":"Joanna Skonieczna-Kurpiel, Jan P Madej, Tomasz Klekiel, Agnieszka Mackiewicz, Romuald Będziński, Agnieszka Noszczyk-Nowak, Tomasz Piasecki, Cassandra Ceccopieri","doi":"10.14670/HH-18-722","DOIUrl":"10.14670/HH-18-722","url":null,"abstract":"<p><p>The aim of the study was the histological and morphometrical evaluation of the urethral wall at three time points after bioresorbable stent implantation in male New Zealand White Rabbits. The research was performed on 26 male New Zealand White rabbits aged 3-4 months and weighing 2.1-3.0 kg. Two models of bioresorbable sodium alginate-based stents were developed and implanted into the urethral lumen for one (T1), three (T3), and six weeks (T6). Sections of 5 µm thickness were cut from the urethra at intervals of 2 mm. The sliced sections were stained with hematoxylin-eosin (H&E), Van Gieson's (VG), Von Kossa, and Movat-Russell modified pentachrome (MOVAT) staining methods. The study provided valuable information for future models of urethral stents. The first model of the stent failed to fit the requirements due to inadequate mechanical properties. It curled up on itself losing the ability to adhere to the animals' urethra and was bioresorbed three weeks after implantation. The more rigid no. 2 stent was effective in widening the urethral lumen but did not biodegrade during the experiment. A comprehensive assessment of the second model's properties of biosorption and biointegration requires an extended observation of at least 12 months for an in depth morphological analysis. Stent migration is not likely to be caused solely by the mechanical properties of the urethra or urinary flow but mainly by muscle contraction of the organ wall.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The immune microenvironment of cancer of the uterine cervix. 子宫颈癌的免疫微环境。
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-03-01 DOI: 10.14670/HH-18-727
Michail Mastrogeorgiou, Elena Chatzikalil, Stamatios Theocharis, Alexandra Papoudou-Bai, Michel Péoc'h, Mousa Mobarki, Georgia Karpathiou

While several treatment choices exist for cervical cancer, such as surgical therapy, chemotherapy, and radiotherapy, some patients will still show poor prognosis. HPV infection is a principal factor for cervical cancer development, from early inflammation to proliferation, angiogenesis, and neoplastic growth. While HPV T-cell responses exist, the tumor seems to evade the immune system upon its tolerance. The latter suggests the existence of a confluent tumor microenvironment responsible for the evasion tactics employed by the neoplasm. Therefore, novel biomarkers governing prognosis and treatment planning must be developed, with several studies tackling the significance of the tumor microenvironment in the genesis, development, proliferation, and overall response of cervical cancer during neoplastic processes. This review aims to analyze and contemplate the characteristics of the tumor microenvironment and its role in prognosis, progression, evasion, and invasion, including therapeutic outcome and overall survival.

虽然宫颈癌有多种治疗方法可供选择,如手术治疗、化疗和放疗,但仍有一些患者预后不佳。从早期炎症到增殖、血管生成和肿瘤生长,HPV 感染是宫颈癌发展的主要因素。虽然存在 HPV T 细胞反应,但肿瘤在耐受后似乎会躲避免疫系统。后者表明存在一个汇合的肿瘤微环境,负责肿瘤所采用的逃避策略。因此,必须开发新的生物标志物来预测预后和制定治疗计划,目前已有多项研究探讨了肿瘤微环境在宫颈癌的发生、发展、增殖和肿瘤过程中的整体反应中的重要作用。本综述旨在分析和思考肿瘤微环境的特点及其在预后、进展、逃避和侵袭中的作用,包括治疗效果和总生存期。
{"title":"The immune microenvironment of cancer of the uterine cervix.","authors":"Michail Mastrogeorgiou, Elena Chatzikalil, Stamatios Theocharis, Alexandra Papoudou-Bai, Michel Péoc'h, Mousa Mobarki, Georgia Karpathiou","doi":"10.14670/HH-18-727","DOIUrl":"10.14670/HH-18-727","url":null,"abstract":"<p><p>While several treatment choices exist for cervical cancer, such as surgical therapy, chemotherapy, and radiotherapy, some patients will still show poor prognosis. HPV infection is a principal factor for cervical cancer development, from early inflammation to proliferation, angiogenesis, and neoplastic growth. While HPV T-cell responses exist, the tumor seems to evade the immune system upon its tolerance. The latter suggests the existence of a confluent tumor microenvironment responsible for the evasion tactics employed by the neoplasm. Therefore, novel biomarkers governing prognosis and treatment planning must be developed, with several studies tackling the significance of the tumor microenvironment in the genesis, development, proliferation, and overall response of cervical cancer during neoplastic processes. This review aims to analyze and contemplate the characteristics of the tumor microenvironment and its role in prognosis, progression, evasion, and invasion, including therapeutic outcome and overall survival.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140119285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The potential of EZH2 expression to facilitate treatment choice in stage II colorectal adenocarcinoma. EZH2 表达促进 II 期结直肠腺癌治疗选择的潜力。
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-03-08 DOI: 10.14670/HH-18-732
Xiaoqun Zhu, Lu He, Zhong Zheng, Ya Wang, Jun Yang, Biao Zhang, Chaoshan Wang, Zhiwen Li

Background: The current selection criteria of patients with stage II colorectal carcinoma (CRC) suitable for adjuvant therapy are not satisfactory. Enhancer of zeste homolog 2 (EZH2) has been demonstrated to be over-expressed in CRC. However, data regarding the role of EZH2 in CRC survival remains controversial, and little is known about it in stage II CRC. Thus, we conducted this study to investigate the clinical significance of EZH2 expression in stage II CRC.

Methods: Cases with stage II CRC resected between 2015 and 2018 were retrospectively reviewed. EZH2 expression was analyzed by immunohistochemistry using tissue microarrays. The relationship between EZH2 expression and clinicopathological variables was analyzed. Survival curves were estimated by the Kaplan-Meier approach.

Results: We found high EZH2 expression in 134 of 221 analyzable stage II tumors (60.63%). No significant associations were observed between EZH2 expression and common clinicopathological factors. Survival analyses showed that cases receiving surgery alone had inferior overall survival (OS) than those receiving surgery and chemotherapy (P=0.0075) in stage II CRC with high EZH2 expression, however, metastasis-free survival (MFS) was similar between these two subgroups. Treatment choice had no impact on the survival of stage II CRC with low EZH2 expression.

Conclusion: The OS of stage II CRC with high EZH2 expression improved more strikingly with surgery and adjuvant chemotherapy than with surgery alone, which suggests the potential of EZH2 expression as a biomarker to help identify a subgroup of early-stage CRC benefiting from surgery and adjuvant chemotherapy. More large-scale studies are warranted to corroborate this finding and to further evaluate the predictive nature of EZH2.

背景:目前,适合辅助治疗的 II 期结直肠癌(CRC)患者的选择标准并不令人满意。泽斯特同源增强子 2(EZH2)已被证实在 CRC 中过度表达。然而,有关 EZH2 在 CRC 存活率中的作用的数据仍存在争议,而且人们对其在 II 期 CRC 中的作用知之甚少。因此,我们开展了这项研究,以探讨 EZH2 表达在 II 期 CRC 中的临床意义:回顾性回顾2015年至2018年间切除的II期CRC病例。使用组织芯片通过免疫组化分析EZH2的表达。分析了EZH2表达与临床病理变量之间的关系。采用Kaplan-Meier方法估计了生存曲线:在221例可分析的II期肿瘤中,我们发现134例(60.63%)存在EZH2高表达。EZH2的表达与常见的临床病理因素无明显关联。生存期分析表明,在EZH2高表达的II期CRC中,单纯接受手术治疗的病例的总生存期(OS)低于接受手术和化疗的病例(P=0.0075),但这两个亚组的无转移生存期(MFS)相似。治疗选择对EZH2低表达的II期CRC的生存率没有影响:结论:EZH2高表达的II期CRC患者接受手术和辅助化疗后的OS比单纯手术有更显著的改善,这表明EZH2表达作为一种生物标记物,可以帮助识别早期CRC中受益于手术和辅助化疗的亚组。我们需要进行更大规模的研究来证实这一发现,并进一步评估EZH2的预测性。
{"title":"The potential of EZH2 expression to facilitate treatment choice in stage II colorectal adenocarcinoma.","authors":"Xiaoqun Zhu, Lu He, Zhong Zheng, Ya Wang, Jun Yang, Biao Zhang, Chaoshan Wang, Zhiwen Li","doi":"10.14670/HH-18-732","DOIUrl":"10.14670/HH-18-732","url":null,"abstract":"<p><strong>Background: </strong>The current selection criteria of patients with stage II colorectal carcinoma (CRC) suitable for adjuvant therapy are not satisfactory. Enhancer of zeste homolog 2 (EZH2) has been demonstrated to be over-expressed in CRC. However, data regarding the role of EZH2 in CRC survival remains controversial, and little is known about it in stage II CRC. Thus, we conducted this study to investigate the clinical significance of EZH2 expression in stage II CRC.</p><p><strong>Methods: </strong>Cases with stage II CRC resected between 2015 and 2018 were retrospectively reviewed. EZH2 expression was analyzed by immunohistochemistry using tissue microarrays. The relationship between EZH2 expression and clinicopathological variables was analyzed. Survival curves were estimated by the Kaplan-Meier approach.</p><p><strong>Results: </strong>We found high EZH2 expression in 134 of 221 analyzable stage II tumors (60.63%). No significant associations were observed between EZH2 expression and common clinicopathological factors. Survival analyses showed that cases receiving surgery alone had inferior overall survival (OS) than those receiving surgery and chemotherapy (<i>P=0.0075</i>) in stage II CRC with high EZH2 expression, however, metastasis-free survival (MFS) was similar between these two subgroups. Treatment choice had no impact on the survival of stage II CRC with low EZH2 expression.</p><p><strong>Conclusion: </strong>The OS of stage II CRC with high EZH2 expression improved more strikingly with surgery and adjuvant chemotherapy than with surgery alone, which suggests the potential of EZH2 expression as a biomarker to help identify a subgroup of early-stage CRC benefiting from surgery and adjuvant chemotherapy. More large-scale studies are warranted to corroborate this finding and to further evaluate the predictive nature of EZH2.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neoastilbin ameliorates sepsis-induced liver and kidney injury by blocking the TLR4/NF-κB pathway. Neoastilbin 通过阻断 TLR4/NF-κB 通路改善败血症诱发的肝肾损伤
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-02-02 DOI: 10.14670/HH-18-719
Ruiming Xu, Dawei Wang, Zhengyi Shao, Xiangbo Li, Qiumei Cao

Sepsis frequently causes systemic inflammatory response syndrome and multiple organ failure in patients. Neoastilbin (NAS) is a flavonoid that plays vital functions in inflammation. This work aims to investigate the protective effects of NAS against sepsis-induced liver and kidney injury and elucidate its underlying mechanisms. The mouse model was established using cecal ligation puncture (CLP) induction. NAS was given to mice by gavage for 7 consecutive days before surgery. Liver and kidney function, oxidative stress, and inflammatory factors in serum or tissues were examined by ELISA or related kits. The expression of relevant proteins was assessed by Western blot. Hematoxylin and eosin and/or periodic acid-Schiff staining revealed that NAS ameliorated the pathological damage in liver and kidney tissues of CLP-induced mice. NAS improved liver and kidney functions, as evidenced by elevated levels of blood urea nitrogen, Creatinine, ALT, and AST in the serum of septic mice. TUNEL assay and the expression of Bcl-2 and Bax showed that NAS dramatically reduced apoptosis in liver and renal tissues. NAS treatment lowered the levels of myeloperoxidase and malondialdehyde, while elevated the superoxide dismutase content in liver and kidney tissues of CLP-induced mice. The levels of inflammatory cytokines (IL-6, TNF-α, and IL-1β) in the serum and both tissues of CLP-injured mice were markedly decreased by NAS. Mechanically, NAS downregulated TLR4 expression and inhibited NF-κB activation, and overexpression of TLR4 reversed the protective effects of NAS against liver and kidney injury. Collectively, NAS attenuated CLP-induced apoptosis, oxidative stress, inflammation, and dysfunction in the liver and kidney by restraining the TLR4/NF-κB pathway.

败血症经常导致患者出现全身炎症反应综合征和多器官功能衰竭。新橙皮甙(NAS)是一种类黄酮,在炎症反应中发挥着重要作用。本研究旨在探讨NAS对败血症所致肝肾损伤的保护作用,并阐明其潜在机制。小鼠模型是利用盲肠结扎术(CLP)诱导建立的。小鼠在手术前连续7天灌胃NAS。用ELISA或相关试剂盒检测血清或组织中的肝肾功能、氧化应激和炎症因子。用 Western 印迹法评估相关蛋白质的表达。血色素和伊红及/或周期性酸-Schiff染色显示,NAS可改善CLP诱导小鼠肝脏和肾脏组织的病理损伤。脓毒症小鼠血清中的血尿素氮、肌酐、谷丙转氨酶和谷草转氨酶水平升高,证明NAS改善了肝肾功能。TUNEL检测和Bcl-2和Bax的表达表明,NAS显著减少了肝脏和肾脏组织的细胞凋亡。NAS治疗降低了CLP诱导小鼠肝脏和肾脏组织中髓过氧化物酶和丙二醛的水平,同时提高了超氧化物歧化酶的含量。NAS能显著降低CLP损伤小鼠血清和两个组织中的炎症细胞因子(IL-6、TNF-α和IL-1β)水平。从机制上讲,NAS可下调TLR4的表达并抑制NF-κB的活化,而过表达TLR4可逆转NAS对肝脏和肾脏损伤的保护作用。总之,NAS通过抑制TLR4/NF-κB途径,减轻了CLP诱导的肝脏和肾脏凋亡、氧化应激、炎症和功能障碍。
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引用次数: 0
Female fertility and the mammalian egg's zona pellucida. 雌性生育能力与哺乳动物卵子的透明带。
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-10-01 Epub Date: 2024-03-04 DOI: 10.14670/HH-18-728
Paul M Wassarman, Eveline S Litscher

All mammalian eggs are surrounded by a relatively thick extracellular matrix (ECM) or zona pellucida (ZP) to which free-swimming sperm bind in a species-restricted manner during fertilization. The ZP consists of either three (e.g., Mus musculus) or four (e.g., Homo sapiens) glycosylated proteins, called ZP1-4. These proteins are unlike those found in somatic cell ECM, are encoded by single-copy genes on different chromosomes, and are well conserved among different mammals. Mammalian ZP proteins are synthesized as polypeptide precursors by growing oocytes that will become ovulated, unfertilized eggs. These precursors are processed to remove a signal-sequence and carboxy-terminal propeptide and are secreted into the extracellular space. Secreted ZP proteins assemble into long, crosslinked fibrils that exhibit a structural repeat due to the presence of ZP2-ZP3 dimers every 140 Å or so along fibrils. Fibrils are crosslinked by ZP1 and are oriented either perpendicular, parallel, or randomly to the plasma membrane of eggs depending on their position in the ZP. Free-swimming mouse sperm recognize and bind to ZP2 or ZP3 that serve as sperm receptors. Acrosome-intact sperm bind to ZP3 oligosaccharides and acrosome-reacted sperm bind to ZP2 polypeptide. ZP fibrils fail to assemble in the absence of either nascent ZP2 or ZP3 and results in mouse eggs that lack a ZP and female infertility. Gene sequence variations due to point, missense, or frameshift mutations in genes encoding ZP1-4 result in human eggs that lack a ZP or have an abnormal ZP and female infertility. These and other features of the mouse and human egg's ZP are discussed here.

所有哺乳动物的卵子周围都有一个相对较厚的细胞外基质(ECM)或透明带(ZP),在受精过程中,自由游动的精子以物种限制的方式与透明带结合。透明带由三种(如麝)或四种(如智人)糖基化蛋白质组成,称为 ZP1-4。这些蛋白与体细胞 ECM 中的蛋白不同,由不同染色体上的单拷贝基因编码,在不同哺乳动物中非常一致。哺乳动物的 ZP 蛋白是由生长中的卵母细胞合成的多肽前体,这些卵母细胞将成为排卵的未受精卵。这些前体经过处理,去除信号序列和羧基末端前肽,然后分泌到细胞外空间。分泌的 ZP 蛋白组装成交联的长丝,由于沿长丝每隔 140 Å 左右就有一个 ZP2-ZP3 二聚体,因此这些长丝会出现结构重复。细丝由 ZP1 交联,并根据其在 ZP 中的位置垂直、平行或随机地指向卵子的质膜。自由游动的小鼠精子能识别并与作为精子受体的 ZP2 或 ZP3 结合。顶体接触的精子与 ZP3 低聚糖结合,顶体反应的精子与 ZP2 多肽结合。在缺乏新生 ZP2 或 ZP3 的情况下,ZP 丝无法组装,导致小鼠卵子中缺乏 ZP 和雌性不孕。由于编码 ZP1-4 的基因发生点突变、错义突变或框架移位突变,导致人类卵子中缺乏 ZP 或 ZP 异常,并造成女性不孕。本文将讨论小鼠和人类卵子 ZP 的这些特征和其他特征。
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Histology and histopathology
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