Evaluating the use of three-dimensional reconstruction visualization technology for precise laparoscopic resection in gastroesophageal junction cancer

BACKGROUND Laparoscopic gastrectomy for esophagogastric junction(EGJ)carcinoma enables the removal of the carcinoma at the junction between the stomach and esophagus while preserving the gastric function,thereby providing patients with better treatment outcomes and quality of life.Nonetheless,this surgical technique also presents some challenges and limitations.Therefore,three-dimensional reconstruction visualization technology(3D RVT)has been introduced into the procedure,providing doctors with more comprehensive and intuitive anatomical information that helps with surgical planning,navigation,and outcome evaluation.AIM To discuss the application and advantages of 3D RVT in precise laparoscopic resection of EGJ carcinomas.METHODS Data were obtained from the electronic or paper-based medical records at The First Affiliated Hospital of Hebei North University from January 2020 to June 2022.A total of 120 patients diagnosed with EGJ carcinoma were included in the study.Of these,68 underwent laparoscopic resection after computed tomography(CT)-enhanced scanning and were categorized into the 2D group,whereas 52 underwent laparoscopic resection after CT-enhanced scanning and 3D RVT and were categorized into the 3D group.This study had two outcome measures:the deviation between tumor-related factors(such as maximum tumor diameter and infiltration length)in 3D RVT and clinical reality,and surgical outcome indicators(such as operative time,intraoperative blood loss,number of lymph node dissections,R0 resection rate,postoperative hospital stay,postoperative gas discharge time,drainage tube removal time,and related complications)between the 2D and 3D groups.RESULTS Among patients included in the 3D group,27 had a maximum tumor diameter of less than 3 cm,whereas 25 had a diameter of 3 cm or more.In actual surgical observations,24 had a diameter of less than 3 cm,whereas 28 had a diameter of 3 cm or more.The findings were consistent between the two methods(χ^(2)=0.346,P=0.556),with a kappa consistency coefficient of 0.808.With respect to infiltration length,in the 3D group,23 patients had a length of less than 5 cm,whereas 29 had a length of 5 cm or more.In actual surgical observations,20 cases had a length of less than 5 cm,whereas 32 had a length of 5 cm or more.The findings were consistent between the two methods(χ^(2)=0.357,P=0.550),with a kappa consistency coefficient of 0.486.Pearson correlation analysis showed that the maximum tumor diameter and infiltration length measured using 3D RVT were positively correlated with clinical observations during surgery(r=0.814 and 0.490,both P<0.05).The 3D group had a shorter operative time(157.02±8.38 vs 183.16±23.87),less intraoperative blood loss(83.65±14.22 vs 110.94±22.05),and higher number of lymph node dissections(28.98±2.82 vs 23.56±2.77)and R0 resection rate(80.77%vs 61.64%)than the 2D group.Furthermore,the 3D group had shorter hospital stay[8(8,9)vs 13(14,16)],time to gas passage[3(3,4)vs 4(5,5)],and drainage tube removal time[4(4,5)vs 6(6,7)]than the 2D group.The complication rate was lower in the 3D group(11.54%)than in the 2D group(26.47%)(χ^(2)=4.106,P<0.05).CONCLUSION Using 3D RVT,doctors can gain a more comprehensive and intuitive understanding of the anatomy and related lesions of EGJ carcinomas,thus enabling more accurate surgical planning.

Three-dimensional printed talar prosthesis with biological function for giant cell tumor of the talus:A case report and review of the literature

BACKGROUND Giant cell tumors(GCT)are most commonly seen in the distal femur.These tumors are uncommon in the small bones of the hand and feet,and a very few cases have been reported.A giant cell tumor of the talus is rarely seen clinically and could be a challenge to physicians.CASE SUMMARY We report a rare case of GCT of the talus in one patient who underwent a new reconstructive surgery technique using a three-dimensional(3D)printing talar prosthesis.The prosthesis shape was designed by tomographic image processing and segmentation using technology to match the intact side by mirror symmetry with 3D post-processing technologies.The patient recovered nearly full range of motion of the ankle after 6 mo.The visual analogue scale and American Orthopaedic Foot and Ankle Society scores were 1 and 89 points,respectively.CONCLUSION We demonstrated that 3D printing of a talar prosthesis is a beneficial option for GCT of the talus.

Central nervous system tumors and three-dimensional cell biology: Current and future perspectives in modeling

Central nervous system(CNS)tumors are a variety of distinct neoplasms that present multiple challenges in terms of treatment and prognosis.Glioblastoma,the most common primary tumor in adults,is associated with poor survival and remains one of the least treatable neoplasms.These tumors are highly heterogenous and complex in their nature.Due to this complexity,traditional cell culturing techniques and methods do not provide an ideal recapitulating model for the study of these tumors’behavior in vivo.Two-dimensional models lack the spatial arrangement,the heterogeneity in cell types,and the microenvironment that play a large role in tumor cell behavior and response to treatment.Recently,scientists have turned towards three-dimensional culturing methods,namely spheroids and organoids,as they have been shown to recapitulate tumors in a more faithful manner to their in vivo counterparts.Moreover,tumor-on-a-chip systems have lately been employed in CNS tumor modeling and have shown great potential in both studying the pathophysiology and therapeutic testing.In this review,we will discuss the current available literature on in vitro threedimensional culturing models in CNS tumors,in addition to presenting their advantages and current limitations.We will also elaborate on the future implications of these models and their benefit in the clinical setting.

THE THREE-DIMENSIONAL FUNDAMENTAL SOLUTION TO STOKES FLOW IN THE OBLATE SPHEROIDAL COORDINATES WITH APPLICATIONS TO MULTIPLES SPHEROID PROBLEMS

A new three-dimensional fundamental solution to the Stokes flow was proposed by transforming the solid harmonic functions in Lamb's solution into expressions in terms Of the oblate spheroidal coordinates. These fundamental solutions are advantageous in treating flows past an arbitrary number of arbitrarily positioned and oriented oblate spheroids. The least squares technique was adopted herein so that the convergence difficulties often encountered in solving three-dimensional problems were completely avoided. The examples demonstrate that present approach is highly accurate, consistently stable and computationally efficient. The oblate spheroid may be used to model a variety of particle shapes between a circular disk and a sphere. For the first time, the effect of various geometric factors on the forces and torques exerted on two oblate spheroids were systematically studied by using the proposed fundamental solutions. The generality of this approach was illustrated by two problems of three spheroids.

Digital measurement of bone tumor volume by CT three-dimensional reconstruction technology

Objective To discuss the measurement of bone tumor volume on the basis of three dimensional images segmentation technology. Methods Twenty patients with lacunar bone tumor from Tianjin Hospital and Tongji Hospital were included in the

Three-Dimensional Conformal Radiotherapy for Rectal Cancer and the Changes in Cancer Multi-biomarkers

OBJECTIVE To investigate the clinical efficacy of three-dimensional conformal radiotherapy （3D-CRT） for locally advanced or postoperatively relapsed rectal cancer, and to examine the changes in cancer multi-biomarkers. METHODS Sixty patients with locally advanced or postoperatively relapsed rectal cancer were randomly divided into two groups after 40 Gy external radiation, namely a late-course 3D-CRT group and a conventional radiotherapy group that served as the control. There were 30 patients in each group. For patients in the 3D-CRT group, multi-biomarkers were measured before and after radiotherapy and after relapse. RESULTS Response rates in the 3D-CRT and the control groups were 86.7% （26/30） and 70% （21/30） respectively, without a significant difference （P〉0.05）. The 1-, 2- and 3-year survival rates were 80%, 53.3% and 36.7% in the 3D-CRT group; in the control group the rates were 56.7%, 40% and 13.3% respectively, with a significant difference （P=0.0213）. CEA, CA19-9, CA242 and FER decreased after radiotherapy in the 3D-CRT group, P〈0.01, indicating a significant difference. The values after relapse were higher than those without relapse, P〈0.01, indicating a significant difference. CONCLUSION Conventional radiotherapy with a 3D-CRT boost gives better therapeutic effect to patients with locally advanced or postoperatively locally relapsed rectal cancer. A multi-biomarker protein chip diagnosis system can be utilized as an effective tool to determine the therapeutic effect and prognosis.

Three-dimensional image simulation of primary diaphragmatic hemangioma: A case report

BACKGROUND Fewer than 200 cases of diaphragmatic tumors have been reported in the past century. Diaphragmatic hemangiomas are extremely rare. Only nine cases have been reported in English literature to date. We report a case of cavernous hemangioma arising from the diaphragm. Pre-operative three-dimensional(3D)simulation and minimal invasive thoracoscopic excision were performed successfully, and we describe the radiologic findings and the surgical procedure in the following article.CASE SUMMARY A 40-year-old man was referred for further examination of a mass over the right basal lung without specific symptoms. Contrast-enhanced computed tomography revealed a poorly-enhanced lesion in the right basal lung, abutting to the diaphragm, measuring 3.1 cm × 1.5 cm in size. The mediastinum showed a clear appearance without evidence of abnormal mass or lymphadenopathy. A preoperative 3D image was reconstructed, which revealed a diaphragmatic lesion. Video-assisted thoracic surgery was performed, and a red papillary tumor was found, originating from the right diaphragm. The tumor was resected, and the pathological diagnosis was cavernous hemangioma.CONCLUSION In this rare case of diaphragmatic hemangioma, 3D image simulation was helpful for the preoperative evaluation and surgical decision making.

Analysis of the efficacy and safety of conventional radiotherapy of chest wall and clavicular field and three-dimensional conformal radiotherapy in patients after modified radical mastectomy

Objective:To explore the efficacy and safety of conventional radiotherapy of chest wall and clavicular field and three-dimensional conformal radiotherapy in patients after modified radical mastectomy.Methods: A total of 84 patients who were admitted in our hospital after modified radical mastectomy were included in the study and divided into the conventional radiotherapy group (n=42) and the three-dimensional conformal radiotherapy group (n=42) according to different radiotherapy methods. The patients in the conventional radiotherapy group were given conventional radiotherapy of chest wall and clavicular field, while the patients in the three-dimensional conformal radiotherapy group were given three-dimensional conformal radiotherapy. The serum tumor markers and peripheral blood T lymphocyte subsets 6-8 weeks after treatment in the two groups were detected. The clinical efficacy, and toxic and side effects in the two groups were evaluated.Results: The serum CA15-3, CA125, CEA, and CK19 levels after treatment in the two groups were significantly reduced when compared with before treatment, CD3+,CD4+, and CD4+/CD8+ were significantly elevated, while CD8+ was significantly reduced when compared with before treatment, but the comparison of the above indicators between the two groups was not statistically significant. The occurrence rate of radioactive skin damage and pneumonia after treatment in the conventional radiotherapy group was significantly higher than that in the three-dimensional conformal radiotherapy group. Conclusions:The two kinds of radiotherapy schemes have an equal efficacy, but the toxic and side effects of three-dimensional conformal radiotherapy are significantly lower than those by the conventional radiotherapy, with a certain advantage.

Construction and application of a three-dimensional vascular variation-based nephrometry scoring system for completely endophytic renal tumors

Background:Completely endophytic renal tumors(CERT)pose significant challenges due to their anatomical complexity and loss of visual clues about tumor location.A facile scoring model based on three-dimensional(3D)reconstructed images will assist in better assessing tumor location and vascular variations.Methods:In this retrospective study,80 patients diagnosed with CERT were included.Forty cases underwent preoperative assessment using 3D reconstructed imaging(3D-Cohort),while the remaining 40 cases were assessed using two-dimensional imaging(2D-Cohort).Vascular variations were evaluated by ascertaining the presence of renal arteries>1,prehilar branching arteries,and arteries anterior to veins.The proposed scoring system,termed RAL,encompassed three critical components:(R)adius(maximal tumor diameter in cm),(A)rtery(occurrence of arterial variations),and(L)ocation relative to the polar line.Comparison of the RAL scoring system was made with established nephrometry scoring systems.Results:A total of 48(60%)patients exhibited at least one vascular variation.In the 2D-Cohort,patients with vascular variations experienced significantly prolonged operation time,increased bleeding volume,and extended warm ischemia time compared with those without vascular variations.Conversely,the presence of vascular vari-ations did not significantly affect operative parameters in the 3D-Cohort.Furthermore,the 2D-Cohort demon-strated a notable decline in both short-and long-term estimated glomerular filtration rate(eGFR)changes com-pared with the 3D-Cohort,a trend consistent across patients with warm ischemia time≥25 min and those with vascular variations.Notably,the 2D-Cohort exhibited a larger margin of normal renal tissue compared with the 3D-Cohort.Elevated RAL scores correlated with larger tumor size,prolonged operation time,extended warm is-chemia time,and substantial postoperative eGFR decrease.The RAL scoring system displayed superior predictive capabilities in assessing postoperative eGFR changes compared with conventional nephrometry scoring systems.Conclusions:Our proposed 3D vascular variation-based nephrometry scoring system offers heightened proficiency in preoperative assessment,precise prediction of surgical complexity,and more accurate evaluation of postoper-ative renal function in CERT patients.

Multicellular tumor spheroids bridge the gap between two-dimensional cancer cells and solid tumors: The role of lipid metabolism and distribution

Previous studies demonstrated that three-dimensional(3D) multicellular tumor spheroids(MCTS) could more closely mimic solid tumors than two-dimensional(2D) cancer cells in terms of the spatial structure, extracellular matrix-cell interaction, and gene expression pattern. However, no study has been reported on the differences in lipid metabolism and distribution among 2D cancer cells, MCTS, and solid tumors. Here, we used Hep G2 liver cancer cell lines to establish these three cancer models. The variations of lipid profiles and spatial distribution among them were explored by using mass spectrometry-based lipidomics and matrix-assisted laser desorption/ionization mass spectrometry imaging(MSI). The results revealed that MCTS, relative to 2D cells, had more shared lipid species with solid tumors. Furthermore,MCTS contained more comparable characteristics than 2D cells to solid tumors with respect to the relative abundance of most lipid classes and mass spectra patterns. MSI data showed that 46 of 71 lipids had similar spatial distribution between solid tumors and MCTS, while lipids in 2D cells had no specific spatial distribution. Interestingly, most of detected lipid species in sphingolipids and glycerolipids preferred locating in the necrotic region to the proliferative region of solid tumors and MCTS. Taken together, our study provides the evidence of lipid metabolism and distribution demonstrating that MCTS are a more suitable in vitro model to mimic solid tumors, which may offer insights into tumor metabolism and microenvironment.

Volumetric measurement techniques for assessment of cutaneous neurofibromas:A review

Cutaneous neurofibroma(cNF)is a prevalent clinical manifestation of neurofibromatosis type 1,significantly affecting the well-being and quality of life of the affected individuals.The adoption of reliable and reproducible volumetric measurement techniques is essential for precisely evaluating tumor burden and plays a critical role in the development of effective treatments for cNF.This study focuses on widely used volumetric measurement techniques,including vernier calipers,ultrasound,computed tomography,magnetic resonance imaging,and three-dimensional scanning imaging.It outlines the merits and drawbacks of each technique in assessing the cNF load,providing an overview of their current applications and ongoing research advancements in this domain.

Three-dimensional digital technology-assisted precise tumor resection and reconstruction of the femoral trochanter and postoperative functional recovery:a retrospective study

Background The trochanter of the femur is a common site for bone tumors.However,locating the specificboundary of bone tumor infiltration and determining the surgical method can be challenging.The objective of thisstudy was to review the diagnosis,treatment,and surgical outcomes of patients with tumors or tumor-like changesin the femoral trochanter after computer-assisted precise tumor resection and hip-preserving reconstruction ofthe trochanter.Methods From January 2005 to September 2020,11 patients with trochanteric tumors(aged:18–53 years;sixmales and five females)were treated in Guangzhou First People’s Hospital.The cases included aneurysmal bonecyst(n=1),giant cell tumor of bone(n=2),fibrous histiocytoma of bone(n=1),endochondroma(n=1),andfibrous dysplasia of bone(n=6).For patients with trochanteric tumors,computed tomography and magnetic resonance imaging scanning were performed before operation to obtain two-dimensional image data of the lesion.Athree-dimensional digital model of bilateral lower limbs was reconstructed by computer technology,the boundary of tumor growth was determined by computer simulation,the process of tumor resection and reconstructionwas simulated,and the personalized guide template was designed.During the operation,the personalized guideplate guided the precise resection of the tumor,and the allogeneic bone was trimmed to match the shape of thebone defect.Results All 11 patients underwent accurate resection of the tumor or tumor-like lesion and reconstruction ofthe hip.In eight cases,the lesion was confined to the trochanter,which was fixed with large segment allogeneicbone,autologous iliac bone,and proximal femoral anatomic plate.In three cases,allogeneic bone,autologousiliac bone,and femoral reconstruction nail were used to fix the tumor under the trochanter.Postoperative Xray examination showed that the repair and reconstruction of the bone defect was effective,and callus bridgingbetween the allogenic bone and autogenous bone was observed 6 months after operation.All patients recoveredtheir walking function 3–6 months after operation.The duration of the follow-up period ranged from 6 monthsto 6 years.A patient experienced recurrence of endochondroma;pathological examination revealed chondrocyticsarcoma.The remaining 10 patients were treated with segmental resection and reconstruction.The operationtime ranged 2.5–4.5 h(average:3.2 h).Intraoperative blood loss ranged from 300 to 500 ml(average:368 ml).The local recurrence rate was 9.1%,and the overall survival rate was 100%.The average Musculoskeletal TumorSociety score was 27(excellent and good for eight and three patients,respectively).Conclusions Three-dimensional computer skeleton modeling and simulation-assisted resection and reconstruction of femoral trochanteric tumor is a new surgical technique,which might markedly improve the surgical effect,shorten the surgical time,increase the overall survival rate of patients with tumors,reduce the local recurrencerate,assist in the digitization and programming of femoral trochanteric tumor surgery,and improve surgicalaccuracy.

Malignant peritoneal effusion acting as a tumor environment in ovarian cancer progression: Impact and significance

Until recently, ovarian cancer research has mainly focused on the tumor cells themselves ignoring for the most part the surrounding tumor environment which includes malignant peritoneal effusions. However, one of the major conceptual advances in oncology over the last few years has been the appreciation that cancer progression cannot be explained by aberrations in cancer cells themselves and is strongly influenced by the surrounding tumor environment. The mechanisms of ovarian cancer progression differ from that of other solid tumors because ovarian cancer cells primarily disseminate within the peritoneal cavity.Malignant peritoneal effusion accumulates in the peritoneal cavity during ovarian cancer progression. These exudative fluids act as a unique tumor environment providing a framework that orchestrates cellular and molecular changes contributing to aggressiveness and disease progression. The composition of ascites, which includes cellular and acellular components, constantly adapts during the course of the disease in response to various cellular cues originating from both tumor and stromal cells. The tumor environment that represents peritoneal effusions closely constitute an ecosystem, with specific cell types and signaling molecules increasing and decreasing during the course of the disease progression creating a single complex network. Although recent advances aiming to understand the ovarian tumor environment have focused one at a time on components, the net impact of the whole environment cannot be understood simply from its parts or outside is environmental context.

3D tumor model biofabrication

Animal models have been extensively used in cancer pathology studies and drug discovery.These models,however,fail to reflect the complex human tumor microenvironment and do not allow for high-throughput drug screening in more human-like physiological conditions.Three-dimensional(3D)cancer models present an alternative to automated high-throughput cancer drug discovery and oncology.In this review,we highlight recent technology innovations in building 3D tumor models that simulate the complex human tumor microenvironment and responses of patients to treatment.We discussed various biofabrication technologies,including 3D bioprinting techniques developed for characterizing tumor progression,metastasis,and response to treatment.

Controlled generation of cell–laden hydrogel microspheres with core–shell scaffold mimicking microenvironment of tumor

Development of an in vitro three-dimensional(3D) model that closely mimics actual environment of tissue has become extraordinarily important for anti-cancer study. In recent years, various 3D cell culture systems have been developed,with multicellular tumor spheroids being the most popular and effective model. In this work, we present a microfluidic device used as a robust platform for generating core–shell hydrogel microspheres with precisely controlled sizes and varied components of hydrogel matrix. To gain a better understanding of the governing mechanism of microsphere formation,computational models based on multiphase flow were developed to numerically model the droplet generation and velocity field evolution process with COMSOL Multiphysics software. Our modeling results show good agreement with experiments in size dependence on flow rate as well as effect of vortex flow on microsphere formation. With real-time tuning of the flow rates of aqueous phase and oil phase, tumor cells were encapsulated into the microspheres with controllable core–shell structure and different volume ratios of core(comprised of alginate, Matrigel, and/or Collagen) and shell(comprised of alginate). Viability of cells in four different hydrogel matrices were evaluated by standard acridine orange(AO) and propidium iodide(PI) staining. The proposed microfluidic system can play an important role in engineering the in vitro micro-environment of tumor spheroids to better mimic the actual in vivo 3D spatial structure of a tumor and perfect the 3D tumor models for more effective clinical therapies.

Late course shrinking gross tumor volume (GTV) and boost radiotherapy for a special left lung cancer patient whose right lung was resected: a case report

We reported a special case of a locally advanced squamous cell carcinoma of the left lung. Due to pulmonary tuberculosis, the patient had underwent a complete right-side pulmonary lobectomy 20 years ago. Left lung supports his life, he is unable to carry on an operation treatment, so he accepted radiotherapy. Firstly, we defined gross tumor volume (GTV1) by CT simulation location, three-dimensional conformal radiotherapy (3D-CRT) was used until tumor dose reached 50 Gy/25 f. Secondly, by repeating the planning CT scan, defined GTV2, continued to radiotherapy by 2.5 Gy/f until the dose was 65 Gy/31 f. Using the same method for third CT scan, defined GTV3, continued to radiotherapy by 3 Gy/f until the total dose was 74 Gy/34 f. After radiotherapy, the patient acquired complete response and he had no obvious side-effect of radiotherapy. There has been no recurrence for 5 years now.

Folate and cell penetrating peptide modification effects on penetration behavior of nanostructured lipid carriers using multicellular tumor spheroids

Surface modification may have important influences on the penetration behavior of nanoscale drug delivery system. In the present study, we mainly focused on whether cell targeting or cell penetration could affect penetration abilities of nanostructured lipid carriers（NLC）. Real--time penetration of folate--or cell penetrating peptide（CPP）-modified NLC was evaluated using a multicellular tumor spheroid（MTS） established by stacking culture method as an in vitro testing platform. The results suggested that CPP modification had a better penetration behavior both on penetration depth and intensity compared with folate-modified NLC at the early stage of penetration process.

无血清悬浮球状培养方法在人源前列腺癌干细胞富集纯化中的应用

目的:通过无血清悬浮球状培养方法富集纯化人源前列腺癌干细胞并进行小鼠体内外实验验证。方法:采用前列腺癌DU145细胞系,通过无血清悬浮球状培养的方法分离富集、培养纯化出肿瘤干细胞微球(Tumor spheres)。通过流式细胞仪鉴定干细胞表型,并采用动物成瘤实验,将不同数量级的DU145细胞和Tumor spheres细胞接种到NOD/SCID小鼠双侧腋下,观察成瘤率和成瘤速度。对分离富集、培养纯化的Tumor spheres进行诱导分化、增殖水平、活性氧簇、细胞周期检测。为进一步明确Tumor spheres的肿瘤干细胞特性,采用Western blot法检测特异性蛋白的表达,RT-PCR法检测相关mRNA表达。结果:采用无血清悬浮球状培养的方法可使对数生长期DU145细胞分离富集形成Tumor spheres,培养3代可达到纯化的目的,流式细胞技术鉴定其表达前列腺癌干细胞表型CD44(+)CD24(-/low)比例为(63±1)%,明显高于DU145细胞[(33±4)%](P<0.05)。动物成瘤实验显示,接种Tumor spheres侧肿瘤成瘤速度和成瘤率均高于接种DU145细胞侧。Tumor spheres具有更强的自我更新能力和分化潜能,细胞周期检测发现Tumor spheres中(81.67±0.68)%处于细胞周期的G_(0)/G_(1)期(P<0.05),同时Tumor spheres具有更低水平的活性氧簇ROS水平(P<0.05)。Tumor spheres高表达肿瘤干细胞HES1蛋白(P<0.05),Tumor spheres高表达肿瘤干细胞相关Notch1、HES1、HIF-1α、Sox2、Jagged1的mRNA(P<0.05)。结论:无血清悬浮球培养分离纯化DU145肿瘤干细胞的方法简便易行、获取量大、成瘤率高,Tumor spheres具有明确的肿瘤干细胞特性,可作为前列腺癌肿瘤干细胞研究的良好实验模型。

脂质质谱成像揭示三氯生促进三维肝癌肿瘤细胞球增长的相关机理

三氯生(triclosan,TCS)作为一种广谱抗菌剂被广泛应用于多种日常消费品中。当前研究表明,TCS暴露可以促进肝癌肿瘤增长,但涉及的相关脂质代谢机理尚不完全清楚。基于此,本研究建立了TCS暴露的肝癌肿瘤细胞球模型,利用质谱成像技术分析对照组和暴露组间脂质小分子在肿瘤细胞球内丰度和分布的差异。结果表明,6μmol/L TCS暴露可以显著促进肝癌肿瘤细胞球的增长,并引起脂质代谢的变化。27种脂质代谢小分子(含19种甘油磷脂、3种甘油酯和5种鞘脂)的丰度在对照组和暴露组的肿瘤细胞球内发生了显著性的变化。在暴露组的19种甘油磷脂中,16种在肿瘤细胞球外围增殖区发生了显著性上调;在3种甘油酯中,1种在外围增殖区发生了显著性上调,2种在内部凋亡区发生了显著性下调;5种鞘脂在肿瘤细胞球内部凋亡区均发生了显著性下调。可见,TCS可能是通过促进肿瘤细胞球外围细胞的增殖以及抑制内层细胞的凋亡来促进三维肿瘤细胞球的增长。该结果可为进一步探讨环境污染物对肿瘤发展影响的分子机制提供参考。

Co-culture of tumor spheroids and monocytes in a collagen matrix-embedded microfluidic device to study the migration of breast cancer cells

Recapitulating the tumor microenvironment is a major challenge in the development of in vitro tumor model for the study of cancer biology and therapeutic treatments. 3D multicellular tumor spheroids (MCTS) have been used as reliable models of mimicking in vivo solid tumors. Macrophages and extracellular matrix (ECM), regarded as two key factors of the tumor microenvironment, play significant roles in tumor progression and drug resistance. In order to investigate their effects on tumor cell migration, a microfluidic chip-based 3D breast cancer model was developed by co-culturing monodisperse MCTS with monocytes in 3 D collagen matrix. A reversible bonding technique was employed for the fabrication of the microfluidic chip, which made it easier for MCTS formation and tailoring the MCTS co-culture conditions. When co-culturing monocytes with low invasive T47D spheroids or high invasive MD-MBA-231 spheroids, we found that T47 D cells with the stimulation of macrophage colony-stimulating factor (M-CSF) and MD-MBA-231 cells could polarize monocytes into tumor-associated macrophages (TAMs). The increased stiffness via increasing collagen concentration decreased tumor cell migration, whereas the presence of TAMs enhanced the migration ability of cells.Moreover, M-CSF-activated TAMs promoted the migration of T47 D tumor cells via the regulation of TGFβ1. Overall, this 3D co-culture microfluidic model may be useful for studying tumor progress and may offer a reliable and low-cost method for evaluation of drug efficiency.