Therapeutic strategies for targeting the ovarian tumor stroma

Epithelial ovarian cancer is the most lethal type of gynecologic malignancy. Sixty percent of women who are diagnosed with ovarian cancer present with advancedstage disease that involves the peritoneal cavity and these patients have a 5-year survival rate of less than 30%. For more than two decades, tumor-debulking surgery followed by platinum-taxane combination chemotherapy has remained the conventional first-line treatment of ovarian cancer. Although the initial response rate is 70%-80%, most patients with advancedstage ovarian cancer eventually relapse and succumb to recurrent chemoresistant disease. A number of molecular aberrations that drive tumor progression have been identified in ovarian cancer cells and intensive efforts have focused on developing therapeutic agents that target these aberrations. However, increasing evidence indicates that reciprocal interactions between tumor cells and various types of stromal cells also play important roles in driving ovarian tumor progression and that these stromal cells represent attractive therapeutic targets. Unlike tumor cells, stromal cells within the tumor microenvironment are in general geneticallystable and are therefore less likely to become resistant to therapy. This concise review discusses the biological significance of the cross-talk between ovarian cancer cells and three major types of stromal cells(endothelial cells, fibroblasts, macrophages) and the development of new-generation therapies that target the ovarian tumor microenvironment.

Spatiotemporal transformable nano-assembly for on-demand drug delivery to enhance anti-tumor immunotherapy

Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.

Correlation of tumor-associated macrophage density and proportion of M2 subtypes with the pathological stage of colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a prevalent global malignancy with complex prognostic factors.Tumor-associated macrophages(TAMs)have shown paradoxical associations with CRC survival,particularly concerning the M2 subset.AIM We aimed to establish a simplified protocol for quantifying M2-like TAMs and explore their correlation with clinicopathological factors.METHODS A cross-sectional study included histopathological assessment of paraffinembedded tissue blocks obtained from 43 CRC patients.Using CD68 and CD163 immunohistochemistry,we quantified TAMs in tumor stroma and front,focusing on M2 proportion.Demographic,histopathological,and clinical parameters were collected.RESULTS TAM density was significantly higher at the tumor front,with the M2 proportion three times greater in both zones.The tumor front had a higher M2 proportion,which correlated significantly with advanced tumor stage(P=0.04),pathological nodal involvement(P=0.04),and lymphovascular invasion(LVI,P=0.01).However,no significant association was found between the M2 proportion in the tumor stroma and clinicopathological factors.CONCLUSION Our study introduces a simplified protocol for quantifying M2-like TAMs in CRC tissue samples.We demonstrated a significant correlation between an increased M2 proportion at the tumor front and advanced tumor stage,nodal involvement,and LVI.This suggests that M2-like TAMs might serve as potential indicators of disease progression in CRC,warranting further investigation and potential clinical application.

Different types of tumor microvessels in stageⅠ-ⅢA squamous cell lung cancer and their clinical significance

BACKGROUND Lung cancer(LC)is the leading cause of morbidity and mortality among malignant neoplasms.Improving the diagnosis and treatment of LC remains an urgent task of modern oncology.Previously,we established that in gastric,breast and cervical cancer,tumor microvessels(MVs)differ in morphology and have different prognostic significance.The connection between different types of tumor MVs and the progression of LC is not well understood.AIM To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma(LUSC).METHODS A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts,respectively.All patients underwent radical surgery(R0)at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021.Tumor sections were routinely processed,and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34(CD34),podoplanin,Snail and hypoxia-inducible factor-1 alpha were performed.The morphological features of different types of tumor MVs,tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis.Statistical analysis was performed using Statistica 10.0 software.Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes(RLNs)and disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence.The effectiveness of the predictive models was assessed by the area under the curve.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.A value of P<0.05 was considered to indicate statistical significance.RESULTS Depending on the morphology,we classified tumor vessels into the following types:normal MVs,dilated capillaries(DCs),atypical DCs,DCs with weak expression of CD34,"contact-type"DCs,structures with partial endothelial linings,capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates.We also evaluated the presence of loose,fine fibrous connective tissue(LFFCT)and retraction clefts in the tumor stroma,tumor spread into the alveolar air spaces(AASs)and fragmentation of the tumor solid component.According to multivariate analysis,the independent predictors of LUSC metastasis in RLNs were central tumor location(P<0.00001),the presence of retraction clefts(P=0.003),capillaries in the tumor solid component(P=0.023)and fragmentation in the tumor solid component(P=0.009),whereas the independent predictors of LUSC recurrence were tumor grade 3(G3)(P=0.001),stage N2(P=0.016),the presence of LFFCT in the tumor stroma(P<0.00001),fragmentation of the tumor solid component(P=0.0001),and the absence of tumor spread through the AASs(P=0.0083).CONCLUSION The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.

How the interplay among the tumor microenvironment and the gut microbiota influences the stemness of colorectal cancer cells

Colorectal cancer(CRC)remains the third most prevalent cancer disease and involves a multi-step process in which intestinal cells acquire malignant characteristics.It is well established that the appearance of distal metastasis in CRC patients is the cause of a poor prognosis and treatment failure.Nevertheless,in the last decades,CRC aggressiveness and progression have been attributed to a specific cell population called CRC stem cells(CCSC)with features like tumor initiation capacity,self-renewal capacity,and acquired multidrug resistance.Emerging data highlight the concept of this cell subtype as a plastic entity that has a dynamic status and can be originated from different types of cells through genetic and epigenetic changes.These alterations are modulated by complex and dynamic crosstalk with environmental factors by paracrine signaling.It is known that in the tumor niche,different cell types,structures,and biomolecules coexist and interact with cancer cells favoring cancer growth and development.Together,these components constitute the tumor microenvironment(TME).Most recently,researchers have also deepened the influence of the complex variety of microorganisms that inhabit the intestinal mucosa,collectively known as gut microbiota,on CRC.Both TME and microorganisms participate in inflammatory processes that can drive the initiation and evolution of CRC.Since in the last decade,crucial advances have been made concerning to the synergistic interaction among the TME and gut microorganisms that condition the identity of CCSC,the data exposed in this review could provide valuable insights into the biology of CRC and the development of new targeted therapies.

Tumor-stroma crosstalk对肝细胞癌中肝星状细胞氨基酸代谢水平的影响

目的探讨tumor-stroma crosstalk对肝星状细胞(HSC)氨基酸代谢的影响。方法分别培养人肝癌细胞系HepG2、Hep3B、Huh7,以及LX-2 HSC。分别使用LX-2 HSC条件培养基(LX2-CM)和HepG2、Hep3B、Huh7肝癌细胞混合条件培养基(Hep-CM)培养HSC,并收集细胞上清,应用氨基酸分析仪检测细胞上清氨基酸谱变化。计量资料组间比较采用t检验。结果HSC氨基酸代谢水平改变情况,与对照组(LX2-CM)相比,实验组(Hep-CM)上清中瓜氨酸(t=3. 426,P=0. 027)、缬氨酸(t=2. 892,P=0. 045)、异亮氨酸(t=4. 224,P=0. 013)、亮氨酸(t=4. 150,P=0. 014)、酪氨酸(t=3. 556,P=0. 024)、苯丙氨酸(t=4. 023,P=0. 016)、赖氨酸(t=3. 369,P=0. 028)水平降低,差异均有统计学意义。结论肿瘤微环境中,tumor-stroma crosstalk可以影响HSC的氨基酸代谢水平,这种改变可能反过来促使肝癌细胞更加适应低氧微环境。

Tumor-stroma ratio as prognostic factor for survival in rectal adenocarcinoma: A retrospective cohort study

AIM To evaluate the prognostic value of the tumor-stroma ratio(TSR) in rectal cancer.METHODS TSR was determined on hematoxylin and eosin stained histological sections of 154 patients treated for rectal adenocarcinoma without prior neoadjuvant treatment in the period 1996-2006 by two observers to assessreproducibility. Patients were categorized into three categories: TSR-high [carcinoma percentage(CP) ≥ 70%], TSR-intermediate(CP 40%, 50% and 60%) and TSR-low(CP ≤ 30%). The relation between categorized TSR and survival was analyzed using Cox proportional hazards model.RESULTS Thirty-six(23.4%) patients were scored as TSR-low, 70(45.4%) as TSR-intermediate and 48(31.2%) as TSRhigh. TSR had a good interobserver agreement(κ = 0.724, concordance 82.5%). Overall survival(OS) and disease free survival(DFS) were significantly better for patients with a high TSR(P = 0.01 and P = 0.02, respectively). A similar association existed for disease specific survival(P = 0.06). In multivariate analysis, patients without lymph node metastasis and an intermediate TSR had a higher risk of dying from rectal cancer(HR = 5.27, 95%CI: 1.54-18.10), compared to lymph node metastasis negative patients with a high TSR. This group also had a worse DFS(HR = 6.41, 95%CI: 1.84-22.28). An identical association was seen for OS. These relations were not seen in lymph node metastasis positive patients. CONCLUSION The TSR has potential as a prognostic factor for survival in surgically treated rectal cancer patients, especially in lymph node negative cases.

Micronodular thymic tumor with lymphoid stroma: A case report and review of the literature

BACKGROUND Micronodular thymic tumors with lymphoid stroma include micronodular thymoma with lymphoid stroma(MNT)and micronodular thymic carcinoma with lymphoid hyperplasia(MNC),whose micromorphological features are lymphoid stromal hyperplasia and nodular arrangement of tumor epithelial cells.This type of tumor is rare;therefore,the corresponding clinical guidelines,histopathological diagnostic criteria,prognostic factors,and therapeutic regimens have not been established.CASE SUMMARY This study covers a novel presentation of MNC in a patient and summarizes the clinicopathological characteristics of this type of tumor by using pooled-analysis methods.Morphologically,this tumor type is a series of benign to malignant pedigrees.We establish the following criteria for the classification of micronodular thymic tumors with lymphoid stroma:(1)Tumor cells with moderate-to-severe dysplasia;(2)Tumor cell mitotic figures>2/10 high-power fields;(3)Appearance of neoplastic necrosis;(4)No terminal deoxynucleotidyl transferase-positive immature T lymphocytes within the tumor;(5)Tumor cells with a Ki-67 index≥10%;and(6)Tumor cells express CD5.Cases that fall into the borders of two categories in terms of morphology are attributed to atypical MNT.It is proposed that the diagnosis of MNT should be established on the diagnostic criteria mentioned above.CONCLUSION Our diagnostic algorithm can effectively distinguish malignant tumors from benign tumors and provides a potent basis for predicting a prognosis,which offers a practical reference for oncologists and pathologists.

Tumor–stromal cross-talk modulating the therapeutic response in pancreatic cancer

Background: Pancreatic ductal adenocarcinoma(PDAC) is a highly malignant solid tumor with a dismal prognosis. The stroma component makes up to 90% of the tumor mass and is thought to be one of the main reasons for the tumor’s high chemoresistance. Cancer associated fibroblasts(CAFs) have previously been identified to be the key stromal players. This is the first time we provide detailed in vitro experiments investigating tumor–stromal interactions when exposed to three well-known chemotherapeutic agents. Methods: Monocultures, indirect and direct co-cultures of two PDAC cell lines(AsPC and Panc-1) and six primary patients derived CAFs were treated with gemcitabine, nab-paclitaxel and the γ-secretaseinhibitor(GSI) DAPT. The cell viability of each component was measured with XTT. Finally, IL-6 concentrations of the supernatants were analyzed. Results: On the contrary to PDAC cell lines, CAF monocultures hardly responded to any treatment which suggested that stroma(CAFs) itself is more resistant to standard chemo-treatments than the epithelial cancer cells. Moreover, only a weak chemotherapeutic response was observed in direct co-cultures of cancer cells with CAFs. A change in the morphology of direct co-cultures was accompanied with the chemoresistance. CAFs were observed to build cage-like structures around agglomerates of tumor cells. High levels of IL-6 were also associated with a reduced response to therapy. Indirect co-cultures make the tumor–stromal interaction more complex. Conclusions: CAFs are highly chemoresistant. Direct cell–cell contact and high levels of IL-6 correlate with a high chemoresistance.

肿瘤间质比在口腔鳞状细胞癌患者预后评估中的价值分析

目的:分析肿瘤间质比(tumor-stroma ratio,TSR)在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)患者预后中的价值。方法:收集2015年1月~2017年12月在蚌埠医学院第一附属医院接受根治性切除术的OSCC患者为研究对象,并收集临床及病理资料。TSR以50%为界限,将其分为高间质比组(≥50%)及低间质比组(<50%)。分析TSR和OSCC患者的无病生存期及总生存期之间的关系。结果:术后随访及临床资料完整的98例患者中,高间质比患者42例,低间质比患者56例。高间质比组OSCC患者的5年总生存率以及5年无病生存率分别为31.0%(13/42)、26.2%(11/42);低间质比组OSCC患者的5年总生存率以及5年无病生存率分别为73.2%(41/56)、67.9%(38/56)。肿瘤发病部位与患者的5年总生存率(χ^(2)=1.327,P=0.932)及5年无病生存率(χ^(2)=3.113,P=0.683)无关;肿瘤临床分期、TSR与患者的5年总生存率5年无病生存率显著相关(P<0.001)。单因素COX分析结果显示,年龄、肿瘤T分期、淋巴结转移、TSR与OSCC患者总体生存率以及无病生存率有关。而通过多因素COX研究显示,肿瘤T分期、淋巴结转移以及TSR是影响OSCC患者总生存率与无病生存率的独立危险因素(P<0.05)。结论:TSR可作为OSCC患者术后预后的影响因素,可为OSCC患者术后辅助治疗方法的选择提供参考依据。

Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway:Providing understanding of the complex mechanisms of chemoresistance

Colorectal cancer(CRC)continues to be one of the main causes of death from cancer because patients progress unfavorably due to resistance to current therapies.Dysregulation of the Wnt/β-catenin pathway plays a fundamental role in the genesis and progression of several types of cancer,including CRC.In many subtypes of CRC,hyperactivation of theβ-catenin pathway is associated with mutations of the adenomatous polyposis coli gene.However,it can also be associated with other causes.In recent years,studies of the tumor microenvironment(TME)have demonstrated its importance in the development and progression of CRC.In this tumor nest,several cell types,structures,and biomolecules interact with neoplastic cells to pave the way for the spread of the disease.Cross-communications between tumor cells and the TME are then established primarily through paracrine factors,which trigger the activation of numerous signaling pathways.Crucial advances in the field of oncology have been made in the last decade.This Minireview aims to actualize what is known about the central role of the Wnt/β-catenin pathway in CRC chemoresistance and aggressiveness,focusing on crosscommunication between CRC cells and the TME.Through this analysis,our main objective was to increase the understanding of this complex disease considering a more global context.Since many treatments for advanced CRC fail due to mechanisms involving chemoresistance,the data here exposed and analyzed are of great interest for the development of novel and effective therapies.

Tumor stem cell, or its niche, which plays a primary role in tumorigenesis?

Cancer research over the past decades has focused on neoplastic cells, or a fraction of them, i.e. tumor stem cells, as the ultimate causes of tumorigenesis. However, during recent years, scientists have come to realize that tumorigenesis is not a solo act of neoplastic cells, but rather a cooperative process in which the roles of numerous types of non-neoplastic cells should be recognized. These tumor-residing non-neoplastic cells constitute the so-called tumor-associated stroma, which in certain cases even greatly surpasses the neoplastic cellular compartment that was previously thought of as a sole determiner leading to a seemingly autonomous growth pattern. In this review, we summarize several recent research highlights that have unveiled many previously unappreciated roles for microenvironmental factors, especially during the initiation stage of tumorigenesis. It is becoming increasingly clear that the stroma’s regulatory effects constitute not only an essential force for maintaining tumor growth, but also primary causes initiating tumorigenesis.

Pancreatic cancer stroma:understanding biology leads to new therapeutic strategies

Pancreatic ductal adenocarcinoma(PDA)is among the deadliest cancers in the United States and in the world.Late diagnosis,early metastasis and lack of effective therapy are among the reasons why only 6%of patients diagnosed with PDA survive past 5 years.Despite development of targeted therapy against other cancers,little progression has been made in the treatment of PDA.Therefore,there is an urgent need for the development of new treatments.However,in order to proceed with treatments,the complicated biology of PDA needs to be understood first.Interestingly,majority of the tumor volume is not made of malignant epithelial cells but of stroma.In recent years,it has become evident that there is an important interaction between the stromal compartment and the less prevalent malignant cells,leading to cancer progression.The stroma not only serves as a growth promoting source of signals but it is also a physical barrier to drug delivery.Understanding the tumor-stroma signaling leading to development of desmoplastic reaction and tumor progression can lead to the development of therapies to decrease stromal activity and improve drug delivery.In this review,we focus on how the current understanding of biology of the pancreatic tumor microenvironment can be translated into the development of targeted therapy.

自动量化的肿瘤-间质比预测胃癌新辅助化疗疗效

目的:探讨通过深度学习的方法来全自动定量评估术前活检标本的肿瘤-间质比(tumor-stroma ratio,TSR)是否可以预测胃癌患者新辅助化疗(neoadjuvant chemotherapy,NAC)疗效。方法:选取2013年3月至2020年3月在云南省肿瘤医院接受NAC治疗的胃癌患者的术前活检切片148张和手术切除切片43张。构建肿瘤区域分割模型和上皮-间质分割模型,使用手术切除切片训练和评估模型,在活检切片上预测,取二者预测结果的交集,根据TSR的定义得到TSR值。根据术后病理学肿瘤退缩分级(tumor regression grade,TRG)将所有患者分为反应良好者(TRG 0~1)和反应不良者(TRG 2~3)。采用单因素和多因素回归分析TSR与胃癌新辅助化疗疗效的相关性。结果:肿瘤组织分割模型的IOU(intersection over union)为0.94,上皮-间质分割模型的IOU为0.88。以44.93%和70.22%作为TSR的临界值,将患者分为低、中、高间质比组,三组之间反应良好者比例具有显著性差异(P<0.05)。多因素分析显示,TSR是治疗前对胃癌NAC反应的独立预测因子(OR=0.10,95%CI:0.03~0.32)。使用常规临床信息预测治疗响应的基础上,加入TSR三分类等级作为治疗响应的预测变量时,曲线下面积(area under curve,AUC)可从0.71提升至0.85。结论:该模型能够在病理切片上自动分割肿瘤区域、上皮区域和间质区域,并能够自动、准确的计算出TSR,同时发现基于此方法自动计算的TSR可以预测NAC疗效。

肿瘤微环境在肝细胞癌中的研究进展

肝癌是世界上常见的恶性肿瘤,早期肝癌症状无特异性。越来越多的研究表明,肿瘤微环境是导致肝脏细胞发生恶性转变的重要原因之一。有大量研究报道了肝癌微环境的作用,本文主要从肝癌肿瘤微环境的主要组成、肿瘤微环境在肝癌中的作用以及针对肝癌微环境的靶向治疗等几个方面进行总结,以期有助于改善肝癌的诊断、治疗和预后,提高肝癌患者的生存率。

胰岛素样生长因子-1、肝细胞生长因子、肿瘤间质比值诊断乳腺癌患者淋巴结转移的价值及与预后的关系

目的:探讨血清胰岛素样生长因子-1(IGF-1)、肝细胞生长因子(HGF)、肿瘤间质比值(TSR)诊断乳腺癌发生淋巴结转移的价值及与患者预后的关系。方法:采取回顾性研究方法,选取2015年6月—2017年8月北京市通州区妇幼保健院乳腺科收治的120例乳腺癌患者作为研究对象,根据手术后病理学结果患者是否发生淋巴结转移将其分为复发转移组24例、未复发转移组96例,对比两组患者的血清IGF-1、HGF、TSR值,采用受试者工作特组(ROC)曲线分析三项指标诊断乳腺癌患者发生淋巴结转移的价值;采用Logistic回归模型分析乳腺癌病理学特征、治疗方法及IGF-1、HGF、TSR与乳腺癌患者预后结局的关系。结果:乳腺癌淋巴结转移组患者的IGF-1、HGF测定值高于未转移组,TSR水平低于未转移组,差异均有统计学意义(P<0.05);IGF-1、HGF、TSR测定值诊断乳腺癌发生淋巴结转移的ROC曲线下面积值分别为0.837(0.766~0.907)、0.842(0.773~0.911)、0.880(0.821~0.938);Logistic回归分析结果显示:TNM分期≥Ⅱ期、发生淋巴结转移、IGF-1水平增高、HGF水平增高、TSR低水平会增加乳腺癌患者手术治疗后复发转移的风险(P<0.05)。结论:IGF-1、HGF水平增高及TSR降低会增加乳腺癌患者发生手术后复发的风险,术前检查IGF-1、HGF及TSR可以评估是否发生淋巴结转移,对手术方案制定有一定的参考价值。

结直肠癌患者淋巴结转移与间质病理特征的关系

目的 分析结直肠癌患者淋巴结转移与间质病理特征的关系。方法 选取100例结直肠癌患者,依据淋巴结转移情况分为转移组(n=42)和未转移组(n=58),收集患者的临床特征及间质病理特征[肿瘤间质比(TSR)、肿瘤出芽(TB)情况、肿瘤相关成纤维细胞(CAF)形态、促结缔组织反应(DR)情况、成纤维细胞活化蛋白(FAP)表达情况及E-钙黏蛋白(E-cadherin)表达情况]。结直肠癌患者淋巴结转移的影响因素采用Logistic回归分析。结果 两组患者性别、年龄、肿瘤部位、饮酒史及吸烟史比较,差异均无统计学意义(P﹥0.05)。转移组患者TSR﹤1、TB为2~3级、非成熟CAF形态、E-cadherin表达阴性、FAP表达强阳性比例均高于非转移组,差异均有统计学意义(P﹤0.05);多因素Logistic回归分析结果显示,TSR﹤1、FAP表达强阳性均是结直肠癌患者淋巴结转移的独立危险因素(P﹤0.05)。结论 间质病理特征如TSR﹤1与FAP表达强阳性均是结直肠癌患者淋巴结转移的独立危险因素,临床应早期采取措施以改善预后。

伴淋巴样间质的微结节型胸腺瘤7例临床病理分析

目的探讨伴淋巴样间质的微结节型胸腺瘤(MNT)的临床病理特征、诊断及鉴别诊断。方法回顾性分析7例MNT患者的临床资料、病理学特征、免疫表型、治疗及预后,并复习相关文献。结果7例MNT患者中,男性4例,女性3例;年龄44~71岁,平均年龄58岁。病灶均位于前纵隔,其中3例位于前上纵隔,1例位于左前中纵隔。2例为重症肌无力,4例无症状者胸部CT显示纵隔占位,1例因尿频尿急行前列腺穿刺示高级别上皮内瘤变(HGPIN),同时全身检查示纵隔占位。镜下2例为单纯MNT,1例合并胸腺囊肿,4例合并其他类型胸腺瘤(2例为AB型胸腺瘤,1例为B2型胸腺瘤,1例为A型胸腺瘤);7例均包膜完整,1例局灶包膜侵犯,其余6例包膜无肿瘤侵犯。镜下MNT示多灶分散或融合的小上皮样结节被大量淋巴细胞间质分隔,微结节由短梭形或卵圆形细胞组成,核染色质均匀,核仁不明显,未见核分裂和坏死。上皮细胞PCK、CK19、CK5/6表达阳性,且CD20、CD5、CD117表达阴性。淋巴间质细胞主要为CD20^(+)/CD79a^(+)B细胞,混有部分CD3^(+)/CD5^(+)/TdT-T细胞。7例MNT均行胸腔镜下纵隔肿物切除术,随访4~55个月,患者均存活且无复发和转移。结论MNT较罕见,无特殊性临床表现,易与其他类型胸腺瘤合并,经病理形态学并结合免疫表型可明确诊断。治疗以手术切除为主,患者预后较好。

中医胃癌痰证理论与细胞间质相关性探讨

痰是津液的变异和转化,细胞间质是肿瘤细胞赖以生存的微环境、物质代谢和信号交换的场所,是津液转化的桥梁和痰液生成的枢纽。这种病理生理学特征与中医“痰证理论”存在相关性。对肿瘤细胞间质成分和代谢过程的认识,是中胃癌痰本质研究新的切入点,有助于阐明中医胃癌痰病因的特性、特点,为研究中医肿瘤“痰本质”奠定基础。

乳腺癌淋巴管生成与肿瘤转移的关系

目的:探讨乳腺癌肿瘤淋巴管生成与肿瘤转移的关系。方法:免疫组织化学SP法进行VEGFR-3染色标记89例原发性乳腺癌肿瘤淋巴管。结果:所有病例均有不同程度淋巴管生成,但以肿瘤间质组织中淋巴管生成为主,癌巢中未见明显的成形淋巴管。肿瘤淋巴管密度与乳腺癌临床分期和腋淋巴结转移呈正相关,临床分期越晚,肿瘤淋巴管密度越高(P<0.05);腋淋巴结转移组的肿瘤淋巴管密度比无淋巴结转移组高(P<0.05)。结论:乳腺癌淋巴管密度与腋淋巴结转移呈正相关,淋巴管生成主要发生在肿瘤间质组织中。