Prognostic significance of tumor budding,desmoplastic reaction,and lymphocytic infiltration in patients with gastric adenocarcinoma

BACKGROUND Recent studies have shown that the tumor microenvironment significantly influences the behavior of solid tumors.In this context,Accumulated data suggests that pathological evaluation of tumor budding(TB),desmoplastic reaction(DR),and tumor-infiltrating lymphocytes(TILs)may be crucial in determining tumor behavior in the gastrointestinal tract.Regarding gastric adenocarcinoma(GAC),although some results suggest that TB and TILs may be effective in determining the course of the disease,the data do not agree.Moreover,very few studies have investigated the relationship between DR and survival.At present,the associations between tumor TB,DR and TILs in GAC patients have not been determined.AIM To establish the relationships between TB,DR,and TILs in patients with GAC and to assess their influence on prognosis.METHODS Our study group comprised 130 patients diagnosed with GAC.The definition of TB was established based on the International TB Consensus Conference.The DR was categorized into three groups according to the level of tumor stroma maturation.The assessment of TILs was conducted using a semiquantitative approach,employing a cutoff value of 5%.The statistical analysis of the whole group and 100 patients with an intestinal subtype of GAC was performed using SPSS version 27.RESULTS A significant correlation between peritumoral budding(PTB)and intratumoral budding(ITB)was noted(r=0.943).Tumors with high PTBs and ITBs had a greater incidence of immature DRs and low TILs(P<0.01).PTB and ITB were associated with histological subtype,lymph node metastasis(LNM),and stage(P<0.01).ITB,PTB,LNM,DR,and stage were significant risk factors associated with poor prognosis.The multivariate Cox regression analysis identified ITB,PTB,and LNM as independent prognostic variables(P<0.05).In intestinal-type adenocarcinomas,a positive correlation between PTB and ITB was noted(r=0.972).While univariate analysis revealed that LNM,stage,PTB,ITB,and DR were strong parameters for predicting survival(P<0.05),only PTB and ITB were found to be independent prognostic factors(P<0.001).CONCLUSION TB may be a potential prognostic marker in GAC.However,further studies are needed to delineate its role in pathology reporting protocols and the predictive effects of DR and TILs.

Small-diameter acellular porcine corneal stroma for peripheral corneal ulceration treatment

AIM:To evaluate the clinical efficacy of small-diameter acellular porcine corneal stroma(SAPS)for the treatment of peripheral corneal ulceration(PCU).METHODS:This retrospective clinical study included 18 patients(18 eyes)with PCU between April 2018 and December 2020.All patients had PCU and underwent lamellar keratoplasty with SAPS.Observation indicators included preoperative and postoperative best-corrected visual acuity(BCVA)and transparency of SAPS.The infection control rate in the surgical eye-lesion area was also calculated.RESULTS:Eighteen patients underwent lamellar keratoplasty with SAPS to treat PCU.None of the patients experienced rejection after 6mo(18/18)and 12mo(16/16)of follow-up.The BCVA(0.47±0.30)at the 6mo followup after operation was significantly improved compared with the baseline(0.99±0.80),and the difference was statistically significant(Z=-3.415,P<0.05).The BCVA at the 12mo follow-up after operation was not statistically significant compared to the 6mo(Z=0,P=1).With time,the SAPS graft gradually became transparent.At the 6mo(18/18)and 12mo(16/16)follow-up,none of the patients had recurrent corneal infection.CONCLUSION:SAPS is clinically effective in the treatment of PCU,improving the patient’s BCVA and reducing the incidence of rejection after keratoplasty.

T cells in pancreatic cancer stroma:Tryptophan metabolism plays an important role in immunoregulation

Several studies have shown that the immune system is highly regulated by tryptophan metabolism,which serves as an immunomodulatory factor.The indoleamine 2,3-dioxygenase 1(IDO1),as an intracellular enzyme that participates in metabolism of the essential amino acid tryptophan in the kynurenine pathway,is an independent prognostic marker for pancreatic cancer(PC).First,overexpression of IDO1 inhibits the maturation of dendritic cells and T-cell proliferation in the liver and spleen.Second,the high expression of kynurenine induces and activates the aryl hydrocarbon receptor,resulting in upregulated programmed cell death protein 1 expression.Third,the induction of IDO1 can lead to loss of the T helper 17 cell/regulatory T cell balance,mediated by the proximal tryptophan catabolite from IDO metabolism.In our study,we found that overexpression of IDO1 upregulated CD8+T cells and reduced natural killer T cells in pancreatic carcinoma in mice.Hence,it may be essential to pay more attention to tryptophan metabolism in patients,especially those who are tolerant to immunotherapy for PC.

Stromal inflammation,fibrosis and cancer:An old intuition with promising potential

It is now well established that the biology of cancer is influenced by not only malignant cells but also other components of the tumour microenvironment.Chronic inflammation and fibrosis have long been postulated to be involved in carcinogenesis.Chronic inflammation can promote tumorigenesis via growth factor/cytokine-mediated cellular proliferation,apoptotic resistance,immunosuppression;and free-radical-induced oxidative deoxyribonucleic acid damage.Fibrosis could cause a perturbation in the dynamics of the tumour microenvironment,potentially damaging the genome surveillance machinery of normal epithelial cells.In this review,we will provide an in-depth discussion of various diseases characterised by inflammation and fibrosis that have been associated with an increased risk of malignancy.In particular,we will present a comprehensive overview of the impact of alterations in stromal composition on tumorigenesis,induced as a consequence of inflammation and/or fibrosis.Strategies including the application of various therapeutic agents with stromal manipulation potential and targeted cancer screening for certain inflammatory diseases which can reduce the risk of cancer will also be discussed.

Papillary thyroid carcinoma with nodular fasciitis-like stroma-an unusual variant with distinctive histopathology:A case report

BACKGROUND Papillary thyroid carcinoma(PTC)is regarded as a fairly common endocrine malignancy,which can be divided into different multiple variants due to wide morphologic differences.The majority of PTC variants have been reported,but PTC with nodular fasciitis-like stroma(NFS)is a rare pathological variant and has been infrequently reported in the relevant literature.This condition involves abundant reactive stromal components rich in spindle cells,which may account for 60%-80%of the tumor along with a typical papillary carcinoma.CASE SUMMARY A 44-year-old man presented with a 4-mo history of a palpable mass over the anterior aspect of the left neck,the tumor demonstrated gradual enlargement but was painless during the 4 mo prior to discovery.Thyroid function test results were normal.Physical examination showed an enormous and firm nodular mass in the left lobe of the thyroid gland extending to the level of the hyoid bone.Ultrasonography of the neck revealed a well-defined heterogeneous lesion measuring around 5.0 cm×4.0 cm with a hypoechoic complex nodule,decreased vascularity and speckles of microcalcification.The patient underwent left thyroidectomy with central compartment lymph node dissection.Final histopathological examination confirmed the diagnosis of PTC with extensive fibromatosis-like stroma combined with typical PTC.The patient was asymptomatic at the 3-mo follow-up.CONCLUSION PTC-NFS is a rare pathological variant and its diagnosis and prognosis may be similar to typical papillary carcinoma.

脱细胞猪角膜基质深板层移植治疗感染性角膜炎的疗效观察

目的:评价脱细胞猪角膜基质深板层移植治疗感染性角膜炎的有效性、安全性。方法:前瞻性研究。收集2017-02/2020-10在我院经药物保守治疗无效的感染性角膜炎患者17例17眼,应用脱细胞猪角膜基质进行深板层角膜移植手术。术后随访6 mo,观察BCVA、角膜上皮愈合情况、角膜透明情况,并记录有无感染复发以及植片排斥。结果:所有患者中均顺利完成深板层角膜移植手术,均未发生术中并发症,无失访病例,术后角膜感染均得到有效控制。术后BCVA均较术前改善(P<0.05)。17眼中16眼术后1 mo上皮完全覆盖角膜植片,仅1眼上皮未完全愈合,为病毒性角膜炎的反复发作。术后1.5 mo所有患者上皮均完全愈合。术后1 mo角膜水肿开始改善,其中1眼角膜植片轻度混浊,16眼中重度混浊;术后3-6 mo角膜透明度稳定,至术后6 mo时4眼完全透明,6眼轻度混浊,6眼中度混浊,1眼重度混浊。随访过程中,无感染复发,有1眼发生眼压升高现象,经治疗后眼压恢复正常。结论:脱细胞猪角膜基质深板层移植治疗感染性角膜炎,不仅能有效控制感染,缓解患者角膜刺激症状,恢复角膜的解剖与功能,而且能维持良好的透明性,提高患者视力,可作为替代同种异体人角膜。

辐射合成的温敏材料上兔角膜基质细胞的培养

目的:探索以电子加速器合成具有温度敏感特性的聚异丙基丙烯酰胺凝胶(PNIPAAm)及接枝有PNIPAAm水凝胶的培养皿的方法,及兔角膜基质细胞在温敏材料PNIPAAm水凝胶上的生长条件及特性,以及利用PNIPAAm水凝胶获得的细胞片。方法:55%N-异丙基丙烯酰胺(NIPAAm)单体和0.5%的N,N’-亚甲基双丙烯酰胺的异丙醇溶液70μL,加入到35 mm培养皿上,电子加速器下辐射合成温敏材料(PNIPAAm),后续处理后,接种兔角膜基质细胞体外培养。结果:按本实验中的单体配方以及辐射合成方案,能够在培养皿表面合成PNIPAAm,角膜基质细胞能在部分接枝了PNIPAAm的培养皿上生长,并能成片脱离。结论:使用辐射合成温敏培养皿能够获得单层及多层无载体的角膜基质细胞片。

结直肠癌中CD66b^(+)肿瘤相关中性粒细胞和促纤维间质反应与临床病理学特征及预后的关系

目的分析结直肠癌(colorectal cancer,CRC)中CD66b^(+)肿瘤相关中性粒细胞(tumor-associated neutrophils,TANs)和促纤维间质反应(desmoplastic reaction,DR)分类情况,探讨CD66b^(+)TANs和DR在CRC中的临床病理学意义及预后价值。方法采用免疫组化法检测240例CRC中CD66b^(+)TANs的表达数量,应用HE染色切片观察肿瘤间质DR的分类,并分析CD66b^(+)TANs和DR分类与CRC临床病理特征的关系;利用Kaplan-Meier生存曲线分析CD66b^(+)TANs和DR分类与CRC患者预后的关系。结果240例CRC中,CD66b^(+)TANs丰富型(NR)组29例,CD66b^(+)TANs中间型(NI)/缺乏型(NP)组211例;DR分类中,成熟型92例,中间型63例,不成熟型85例。CD66b^(+)TANs NR组与较高的组织学分级(P=0.034)、更晚的TNM分期(P=0.006)和脉管侵犯(P=0.002)均有关。CRC中DR分类与肿瘤分化程度、神经侵犯、淋巴结转移和pTNM分期均密切相关(P<0.05),DR不成熟型CRC分化程度低、有神经侵犯和淋巴结转移、更晚的pTNM分期。Kaplan-Meier生存分析显示,与CD66b^(+)TANs NI/NP CRC患者相比,CD66b^(+)TANs NR CRC患者的3年总生存率明显降低(P<0.05);多因素分析显示:高TANs是CRC的独立预后因素(P<0.05)。DR不成熟型CRC患者的3年总生存率明显低于中间型和成熟型CRC患者(P<0.05)。结论CD66b^(+)TANs和肿瘤间质DR程度均可影响CRC的临床生物学行为,评估CRC中CD66b^(+)TANs和DR有助于预测CRC患者的预后。

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。

超声检查SA/TA及卵巢间质血流动力学指标联合AMH在多囊卵巢综合征诊疗中的应用分析

目的:研究超声检查卵巢间质面积/卵巢总面积比(SA/TA)及卵巢间质血流动力学指标联合抗苗勒管激素(AMH)在多囊卵巢综合征(PCOS)诊疗中的应用。方法:选取本院2020年8月至2022年1月临床诊断的PCOS患者50例作为PCOS组,单纯多囊性卵巢(PCO)患者50例作为PCO组,以及正常女性50例作为对照组。对所有受试者均开展超声检查,对比三组SA/TA及卵巢间质血流动力学指标水平,血清AMH及生化指标水平,以Pearson相关性分析明确各项指标相关性。通过受试者工作特征曲线(ROC)分析明确SA/TA及卵巢间质血流动力学指标水平与实验室生化指标的相关性。结果:PCOS组及PCO组SA/TA、PSV、EDV水平均高于对照组,PCOS组上述指标水平均高于PCO组;PCOS组及PCO组PI、RI均低于对照组,且PCOS组PI、RI均低于PCO组(均P<0.05)。PCOS组、PCO组FPG、TG、FINS以及血清AMH水平均高于对照组,且PCOS组高于PCO组(均P<0.05)。经Pearson相关性分析发现:SA/TA、PSV、EDV水平与FPG、TG、FINS、血清AMH水平均呈正相关,而PI、RI与FPG、TG、FINS、血清AMH水平均呈负相关(均P<0.05)。经ROC曲线分析发现,SA/TA及卵巢间质血流动力学指标与血清AMH水平联合诊断PCOS的效能优于上述指标单独检测(均P<0.05)。结论:超声检查SA/TA及卵巢间质血流动力学指标联合AMH在PCOS诊疗中的应用效果较好。

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.

角膜基质再生与修复的研究进展

角膜在眼球屈光系统中起着重要作用,角膜基质是角膜的主要组成部分,角膜基质的损伤可能导致永久性的视力损害,角膜移植术是目前治疗角膜基质疾病最有效的方法,但供体缺乏,长期免疫抑制治疗以防止排斥反应,以及移植物存活的限制阻碍了其进一步发展。此外,还可利用角膜基质内源性再生能力使角膜基质的胶原细胞外基质在合适的条件下能自我更新。然而,角膜基质复杂的超微结构难以在体外模拟。因此,再生医学被应用来克服这些挑战。这些方法涉及多个领域,包括干细胞诱导分化、组织工程技术、基因编辑等。本文就相关的角膜基质再生与修复技术、研究进展和存在的问题进行了归纳总结,并为未来角膜基质再生与修复的临床应用提供可能的途径。

白兰的嫁接繁殖技术

为探究白兰(Michelia × alba)嫁接苗不同砧穗组合的亲和力差异和影响白兰嫁接苗生长的相关因素,以醉香含笑(Michelia macclurei Dandy)、黄兰(Michelia champaca Linn.)、乐昌含笑(Michelia chapensis Dandy)、深山含笑(Michelia maudiae Dunn)、山玉兰(Magnolia delavayi Franch.)、白兰自根砧6种类型砧木以切接方式嫁接白兰,并探究不同嫁接时间、砧木径级、基质类型的白兰嫁接苗生长差异表现。结果表明,12月左右最适宜白兰嫁接;砧木类型对嫁接苗生长及开花产生影响。白兰自根砧嫁接苗和醉香含笑嫁接苗成活率较其他4种砧木高,达94.0%以上,但以醉香含笑为砧木的嫁接苗生长最快;不同砧木类型白兰嫁接苗现蕾期不同,以山玉兰为砧木的白兰嫁接苗现蕾最早,嫁接满4个月现蕾,现蕾率达68.2%,白兰自根砧现蕾率最低,仅为12.7%;砧木径级对嫁接苗成活率有影响,当砧木地径大于等于0.8 cm时嫁接成活率最高,达94.1%,当砧木地径小于0.5 cm时,嫁接成活率明显降低;苗木培育基质对嫁接苗的成活率和生长都有影响,选用70.0%黄心土∶25.0%泥炭土∶4.5%稻糠和95.0%黄心土∶4.5%稻糠搭配0.5%长效控释肥配比的基质苗木成活率和生长量均优于其他组合。影响嫁接苗品质的因素有多种,研究结果显示砧木类型影响嫁接苗的成活率和花期特性;嫁接时间、砧木径级、基质类型均对苗木成活率和生长产生作用。

Key players in pancreatic cancer-stroma interaction: cancer-associated fibroblasts, endothelial and inflammatory cells

Pancreatic cancer(PC) is the most aggressive type of common cancers, and in 2014, nearly 40000 patients died from the disease in the United States. Pancreatic ductal adenocarcinoma, which accounts for the majority of PC cases, is characterized by an intense stromal desmoplastic reaction surrounding the cancer cells. Cancer-associated fibroblasts(CAFs) are the main effector cells in the desmoplastic reaction, and pancreatic stellate cells are the most important source of CAFs. However, other important components of the PC stroma are inflammatory cells and endothelial cells. The aim of this review is to describe the complex interplay between PC cells and the cellular and noncellular components of the tumour stroma. Published data have indicated that the desmoplastic stroma protects PC cells against chemotherapy and radiation therapy and that it might promote the proliferation and migration of PC cells. However, in animal studies, experimental depletion of the desmoplastic stroma and CAFs has led to more aggressive cancers. Hence, the precise role of the tumour stroma in PC remains to be elucidated. However, it is likely that a contextdependent therapeutic modification, rather than pure depletion, of the PC stroma holds potential for the development of new treatment strategies for PC patients.

Adipose-derived stromal cells: Their identity and uses in clinical trials, an update

In adults, adipose tissue is abundant and can be easily sampled using liposuction. Largely involved in obesity and associated metabolic disorders, it is now described as a reservoir of immature stromal cells. These cells, called adipose-derived stromal cells (ADSCs) must be distinguished from the crude stromal vascular fraction (SVF) obtained after digestion of adipose tissue. ADSCs share many features with mesenchymal stem cells derived from bone marrow, including paracrine activity, but they also display some specific features, including a greater angiogenic potential. Their angiogenic properties as well as their paracrine activity suggest a putative tumor-promoting role for ADSCs although contradictory data have been published on this issue. Both SVF cells and ADSCs are currently being investigated in clinical trials in several fields (chronic inflammation, ischemic diseases, etc. ). Apart from a phase Ⅲ trial on the treatment of fistula,most of these are in phaseⅠand use autologous cells. In the near future, the end results of these trials should provide a great deal of data on the safety of ADSC use.

Stroma-epithelium crosstalk in prostate cancer

The critical role played by stroma-epithelium crosstalk in carcinogenesis and progression of prostate cancer has been increasingly recognized. These interactions are mediated by a variety of paracrine factors secreted by cancer cells and/or stromal cells. In human prostate cancer, reactive stroma is characterized by an increase in myofibroblasts and a corresponding amplification of extracellular matrix production and angiogenesis. Permanent genetic mutations have been reported in stromal cells as well as in tumour cells. Transforming growth factor-J3, vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor signalling pathways are involved in the process of angiogenesis, whereas hepatocyte growth factor, insulin-like growth factor-l, epidermal growth factor, CXC12 and Interleukin-6 play active roles in the progression, androgen-independent conversion and distal metastasis of prostate cancer. Some soluble factors have reciprocal interactions with androgens and the androgen receptor （AR）, and can even activate AR in the absence of the androgen ligand. In this article, we review the complex interactions between cancer cells and the surrounding microenvironment, and discuss the potential therapeutic targets in the stromal compartment of prostate cancer.

Androgen and prostatic stroma

<abstract>Aim: To investigate the effect of androgen on the proliferation, differentiation and regression of canine prostatic stromal cells in vivo and human stromal cells in vitro. Methods: Twenty-two dogs, including 15 normal prostate dogs and 7 prostatic hyperplasia dogs, had their serum concentration of testosterone and estrodiol determined by radioimmunoassay before and after castration. The expression of androgen receptor (AR) and estrogen receptor (ER) in the prostate were analysed by immunohistochemistry and semi-quantitative RT-PCR before and after castration. Light microscopy, transmission electron microscopy and TUNEL assay were carried out successively before and after castration to evaluate the prostatic histomorphology. In vitro serum-free cell cultures from human prostatic stroma were established and exposed to dihydrotestosterone (DHT). The proliferation of the cell culture was detected by MTT assay. The expression of TGFβ, bFGF, AR, and smooth muscle cell (SMC) specific proteins (myosin and/or smoothelin) were detected using immunohistochemistry and RT-PCR. The differentiation from fibroblasts to smooth muscle cells was deduced by measuring the expression of SMC specific proteins. Results: Before castration, the serum concentrations of testosterone and estrodiol were not statistically different between normal and hyperplasia groups. Following castration, the serum concentration of testosterone decreased rapidly in 2 days, and the concentration of estrodiol had no significant change compared with the pre-castration data. In the prostate, AR was presented in both the epithelial and stromal cells and the AR mRNA level was higher in hyperplasia than in normal prostate tissues (P<0.05). While ER predominantly existed in the prostate stromal cells and the ER mRNA had no difference between the hyperplasia and the normal group. Within the early phase of castration (<d7), the expression of AR was increased rapidly. Then it gradually dropped to a lower level than that of the pre-castration by the end of d90. The expression of ER remained unchanged in the whole course. The prostatic stromal cells, including SMCs and fibroblasts, diminished and underwent serial pathological changes of atrophy and apoptosis after castration. The atrophic cells were filled with huge intracellular lipofuscin. The expression of SMC myosin declined after castration, coincident with the increase in TGFβ mRNA level and decline in bFGF mRNA level. In vitro, DHT caused a weak increase in the proliferation and expression of SMC-specific proteins (P<0.05). However, DHT and bFGF together stimulated the proliferation of stromal cells significantly more than either agent alone (P<0.01). The combination of DHT and TGFβ greatly enhanced the expression of SMC-specific proteins (P<0.01) more strongly than either alone (P<0.01). Conclusions: The whole prostate gland is an androgen-sensitive organ with both the epithelium and stroma under the control of androgen. Androgen may direct the proliferation, differentiation and regression of stromal cells by regulating the expression of TGFβ, bFGF, AR and smooth muscle cell specific proteins.

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.