Anti-metastatic Pharmacology Based on Tumor Microenvironment Regulation： A Review / 中国实验方剂学杂志

Tumor metastasis is the major cause of death for tumor patients and the key bottleneck of clinical treatment. In recent years， basic and clinical studies have recognized that tumor microenvironment （TME） is highly correlated with tumor metastasis， which provides hope for anti-metastatic drug development and clinical treatment. At present， the mainstream studies on TME represented by immune checkpoint inhibitors （ICIs） mainly focus on the rectification of immune function of T cells and B cells. However， a large number of studies have shown that the significance of other members of TME for tumor metastasis cannot be ignored， which greatly reflects the progress of anti-metastatic research based on TME regulation. This review focused on tumor metastasis， summarized the mechanism of action of non-T and non-B immune cells ［tumor-associated macrophages （TAMs） and tumor-associated neutrophils （TANs）］ and non-immune members ［vascular endothelial cells （ECs）， tumor-associated fibroblasts （CAFs）， and blood platelet］ in the process of tumor metastasis in TME based on the literature over the recent five years， and explored their key value in the treatment of metastasis. At the treatment level， this review focused on the perspective of the integration of frontier and traditional methods and took the functional homeostasis remodeling of TME as the entry point to summarize the activity and mechanism of traditional Chinese medicine （TCM） regulation of non-T and non-B immune cells and non-immune members and highlight its advantages and characteristics in clinical intervention of metastasis. This review helps to break through the limitations of over-reliance on T and B immune cells in anti-metastatic research， make the research rely on a wider range of cell groups， explore the potential value of TME in anti-metastatic drug intervention， and enrich the idea and strategy of understanding the anti-metastatic pharmacological activity. The review is also expected to provide a broader vision for the research and development of new anti-metastatic drugs.

Recent progress on the effects of structured lipids and fluidity of plasma membrane on tumor metastasis / 药学学报

The lipid composition of cell plasma membranes of aggressive tumors is significantly altered from normal, affecting the membrane fluidity and function. Plasma membrane fluidity involves multiple steps in tumor invasion and metastasis, including cell movement, adhesion, lateral diffusion of membrane molecules, signal transduction, material exchange and so on. This review highlights the difference in plasma membrane lipid composition and fluidity between normal and cancer cells, as well as the correlation with the invasion and metastasis potential of cancer. We also point out that the proliferation, invasion and metastasis of tumors can be inhibited by improving membrane fluidity or interfering with the membrane structured lipid composition, this focusing more on changing the biophysical properties of cancer cell membranes, and providing a novel strategy that works for treatment of tumor metastasis.

Research progress on the role of glutamine metabolism-related proteins in tumor metastasis / 中国癌症杂志

Tumor metastasis is closely related to high mortality rate of cancer.It is well known that glutamine plays an important role in the malignant progression of cancer.Notably,as an important carbon and nitrogen donor,glutamine has been found to be closely related to tumor metastasis in recent years.Glutamine is not only involved in regulating the proliferation of tumor cells,but is also closely related to the migration and invasion of tumor cells.Furthermore,various enzymes along with transporters in the metabolism of glutamine are involved in the process of tumor metastasis through different signaling pathways.This review provided a summary of the role of glutamine in tumor metastasis in recent years and proposed therapeutic targets to provide new strategies for the clinical treatment of tumor metastases.

Mechanism of TFF3-dependent TWIST1 Upregulating TRIB3 to Promote Colorectal Cancer Metastasis / 肿瘤防治研究

Objective To investigate the effects of TFF3 overexpression on the proliferation, migration, and invasion ability of colorectal cancer HT29 cells and the mechanisms involved in cancer metastasis. Methods HT29 cells were transfected with pIRES2-TFF3, and the expression levels of mRNAs and proteins related to TFF3 gene, TWIST1/TRIB3 signaling pathway, and epithelial-mesenchymal transition (EMT) were detected by qRT-PCR and Western blot. The proliferation, migration, and invasion ability of HT29 cells were detected by the CCK-8, cell scratch, and Transwell assays. Changes in cell morphology after TFF3 overexpression were observed through transmission electron microscopy. Results After the HT29 cells were transfected with pIRES2-TFF3, the expression levels of TFF3 mRNA and protein significantly increased (P<0.01); cell proliferation, migration, and invasion were significantly enhanced (P<0.01); and the expression of related genes, such as TWIST1, TRIB3, Vimentin, and Snail were significantly upregulated. By contrast, the expression of E-cadherin significantly decreased (P<0.05). Various changes in cell morphology were observed after TFF3 overexpression, such as decrease in cell junctions, loss of cilia, formation of pseudopodia, and increase in fusiform cells. Conclusion TFF3 overexpression may promote EMT in colorectal cancer cells through the Twist1/TRIB3 signaling pathway, increase their metastatic potential, and accelerate the malignant progression of colorectal cancer.

Research progress on role of angiopoietin-like 4 in tumor progression / 中国生物制品学杂志

@#Angiopoietin-like 4(ANGPTL4)is one of the angiopoietin family members and plays a regulatory role in lipid metabolism,glucose homeostasis,inflammatory signal transduction,angiogenesis and vascular permeability.Inflammatory reaction in tumor microenvironment regulates tumor progression,and tumor angiogenesis plays a vital role in tumor growth and metastasis,so ANGPTL4 is closely related to tumor occurrence and development.Many studies have shown that ANGPTL4 plays an important regulatory role in tumor growth,anoikis resistance,tumor angiogenesis and tumor metastasis.This paper reviews the role of ANGPTL4 in tumor progression.

Expression level of miR-199b in human colorectal cancer tissues and its correlation with clinicopathological features and prognosis of patients / 中华肿瘤杂志

Objective: To investigate the relationship between miR-199b and clinicopathologic features and prognosis of patients with colorectal cancer. Methods: Cancer tissues and adjacent normal tissues of 202 patients with colorectal cancer treated in Cancer Hospital of Chinese Academy of Medical Sciences from March to December 2011 were collected. Reverse transcription-quantitative real-time polymerase chain reaction was used to detect the expression level of miR-199b in colorectal cancer tissues and corresponding adjacent normal tissues. Kaplan-Meier method and Log rank test were used for survival analysis, and receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of miR-199b in colorectal cancer patients. Results: The relative expression level of miR-199b in colorectal cancer tissues (-7.88±0.11) was lower than that in adjacent normal tissues (-6.49±0.12, P<0.001). The expression level of miR-199b in colorectal cancer tissues with lymph node metastasis (-7.51±0.14) was higher than that in colorectal cancer tissues without lymph node metastasis (-8.23±0.17, P<0.001). The relative expression levels of miR-199b in stage Ⅰ/Ⅱ, Ⅲ and Ⅳ colorectal cancer tissues were gradually increased, which were -8.26±0.17, -7.70±0.16 and -6.57±0.27, respectively, and the difference was statistically significant (P<0.001). The 5-year survival rates of patients with high and low expressions of miR-199b were 75.6% and 84.6%(P=0.045) respectively. ROC curve showed that when miR-199b was -7.965, the area under the curve was 0.578 (95% CI: 0.468, 0.688). Conclusion: The high expression of miR-199b in colorectal cancer tissues is associated with late TNM stage, lymph node metastasis and poor prognosis in colorectal cancer patients, and miR-199b may be used as a potential marker for postoperative progress and prognosis in colorectal cancer patients.

Role and Mechanism of Super-enhancers in Tumor Metastasis / 肿瘤防治研究

Super-enhancers (SEs) are large clusters of enhancers located near the promoter and are necessary to determine the identity of cancer cells. The alterations of super-enhancers can cause dysregulation of the transcriptional program, which resulted in tumor cells being addicted to certain transcriptional programs. Tumor metastasis is the leading cause of death in cancer. Recently, SEs have been demonstrated to facilitate tumor metastasis by regulating lncRNA generation, tumor microenvironment, epithelial-mesenchymal transition, and cancer stem cells. In this review, the characteristics of SEs, the relationship between SEs and tumor metastasis, and inhibitors against SEs are summarized to provide a reference for the relevant mechanism of SEs regulating tumor metastasis and provide new perspectives for the diagnosis and treatment of patients with cancer metastasis.

The application of contrast-enhanced ultrasound guided radioactive 125I seed implantation for the treatment of metastatic liver cancer with Iso-echo imaging / 中华内分泌外科杂志

Radioactive 125I seed implantation has definite curative effect in the treatment of local liver cancer. Currently, percutaneous implantation guided by CT, nuclear magnetism or ultrasound can be adopted, which is safe and minimally invasive. However, the images of some patients with metastatic liver cancer show isodensity or iso-echo imaging under CT or ultrasound, which is easy to miss diagnosis and treatment, seriously affecting the quality of life of patients. A case of terminal cholangiocarcinoma of the biliary tract with metastasis to the liver was admitted to China-Japan Union Hospital of Jilin University. Ultrasound image showed iso-echo, and radio 125I seed implantation was performed under the guidance of contrast-enhanced ultrasound. The operation was completed according to the preoperative treatment plan.

Review of the role of collagen in tumorigenesis and development / 上海交通大学学报（医学版）

Collagen is one of the most abundant proteins in the body and is the main component of the extracellular matrix.Collagen regulates cellular behavior,and its dysregulation can cause a variety of diseases,including cancer.Collagen in tumors is mainly produced by fibroblasts and plays an important role in cancer progression and metastasis.Collagen can act as a prognostic predictor for cancer patients and may be an effective target for the treatment and prevention of tumor progression and metastasis.Anti-tumor drugs targeting collagen and its receptors may be developed in the future.This review focuses on the newly discovered role of collagen in cancer in recent years,specifically the role of collagen in tumor cell dormancy and immune evasion,and the participation of collagen in tumor cell metabolism.

Correlation between the Expression of Ang-2,LYVE-1 and the Biological Characteristics of Cutaneous Squamous Cell Carcinoma / 医学研究杂志

Objective To investigate the correlation between the expression of angiopoietin-2(Ang-2),lymphatic vessel endo-thelial hyaluronan receptor-1(LYVE-1)and the biological characteristics of cutaneous squamous cell carcinoma.Methods A total of 44 patients with primary cSCC admitted to the Affiliated Hospital of Jiangsu University from September 2013 and February 2021 were in-cluded.The expression levels of Ang-2 and LYVE-1 in their cSCC specimens was detected by immunohistochemistry(IHC).The ex-pression level of LYVE-1 was expressed by the microlymphatic vessel density(MLVD).Results The high expression rate of Ang-2 in cSCC group without lymph node metastasis was 44％(15/34),which was significantly lower than that in CSCC group(90％,9/10),and the difference was statistically significant(P＜0.05).The high expression rate of Ang-2 in the highly differentiated cSCC group was 35％(9/26),which was significantly lower than that in the medium and poorly differentiated CSCC group(83％,15/18),and the differ-ence was statistically significant(P＜0.05).The expression of LYVE-1 in cSCC group without lymph node metastasis was 8.49±4.26,which was significantly lower than that in cSCC group(13.48±5.91),and the difference was statistically significant(P＜0.05).The expression of LYVE-1 in highly differentiated cSCC group was 6.39±2.09,which was significantly lower than that in medium and poor-ly differentiated cSCC group(14.28±4.42),and the difference was statistically significant(P＜0.05).The expression of Ang-2 and LYVE-1 was not related to gender,age and tumor size(P＞0.05).The expression level of Ang-2 was positively correlated with LYVE-1(r=0.598,P＜0.01).Conclusion Ang-2 and LYVE-1 are involved in promoting the occurrence,development and lymph node metastasis of cSCC.

Analysis of survival factors and prediction of metastasis in patients with gallbladder carcinoma / 中国现代普通外科进展

Objective:To analyze the factors affecting the survival cycle of gallbladder cancer patients and to predict whether patients had lymph node metastasis or distant metastasis in early stage by tumor markers.Methods:We reviewed the clinical data of 73 gallbladder cancer patients with definite diagnosis admitted to our hospital from January 2017 to December 2021 in surgery and followed up their survival cycles,analyzed the influence of each clinical data on patients'survival,and predicted tumor metastasis by tumor markers.Results:The univariate and multivariate analysis showed that distant metastasis,the number of positive tumor markers and TNM stage were inde-pendent factors affecting the survival of patients with gallbladder carcinoma.According to the re-ceiveroperatingcharacteristic,ROC curve drawn by tumor markers,it can be inferred that there may be lymph node metastasis when the concentrations of CEA and CA125 are higher than 7.07 ng/mL and 38.875 U/mL respectively.Conclusion:The survival cycle of patients with gallbladder cancer is affected by many factors.Screening of patients with high risk factors should be strengthened and disease progression should be judged according to the expression level of tumor markers in order to carry out effective clinical intervention.

Thoughts and Analysis on Regulating Tumor Pre-Metastatic Niche by Regulating Qi and Detoxifying / 中医杂志

Based on the concept of “imbalance of qi movement with the latent cancer toxin”， it is believed that the development process of tumor pre-metastatic niche （PMN） could be summarized as tumor derived secretory factors， exosomes and other “cancer toxin”， which latent in the body， were diffusion-prone by means of meridians and membrane-sources. Besides， the latent toxin induced the imbalance of qi movement， especially the distant weakest qi， and the local sweat pore and collateral vessels were blocked， which resulted in phlegm and blood stasis， and the cross-aggregation of poison. We also proposed therapeutic principles of PMN as first regulating qi and then clearing and expelling toxin， and tried to discuss the theoretical model of traditional Chinese medicine for PMN based on the theory of qi regulation and detoxification， aimed at providing ideas for the future theory construction of traditional Chinese medicine prevention and treatment for malignant tumor metastasis.

pH and GSH dual-responsive silybin nano-micelles for inhibition of breast cancer activity and metastasis in vitro / 药学学报

The clinical tumor therapy was greatly challenged due to the complex characteristics of tumor microenvironment, however, which also provide arena for novel therapeutic strategies. In this study, poly(2-ethyl-2-oxazoline)-poly(lactic acid)-SS-poly(β-amino ester (PEOz-PLA-SS-PBAE) triblock copolymers with pH and GSH double response were synthesized, polymer micelles were prepared by thin film hydration method for loading of silybin to improve its antitumor activity. The critical micelle concentration was determined by pyrene fluorescence method as 1.8 μg·mL-1. The particle size was 155.30 ± 1.80 nm as determined by dynamic light scattering, with polydispersity index of 0.168 ± 0.004. The drug loading and entrapment efficiency of the micelles were determined by HPLC as (5.48 ± 0.04)% and (68.52 ± 0.48)%, respectively. The in vitro drug release profiles showed that the micelles have low pH sensitivity and high GSH responsiveness, and exhibited sustained release profiles. The good biocompatibility of the material was proved by measuring the hemolysis rate and cytotoxicity of the blank micelle. The cytotoxicity and apoptosis rate of tumor cells showed that the drug loaded PEOz-PLA-SS-PBAE micelles had significant inhibitory effect and apoptosis-inducing effect on MDA-MB-231 cells. The results of wounding healing assay and Transwell invasion test showed that the drug loaded PEOz-PLA-SS-PBAE micelles could significantly inhibit the metastasis of MDA-MB-231 cells. The PEOz-PLA-SS-PBAE drug-loaded micelles prepared in this study have good inhibitory effect on tumor growth and anti-tumor metastasis in vitro, which lays the foundation for the further application of silybin.

Discussion on the anti-tumor metastasis mechanism of Notoginseng Radix et Rhizoma based on internet pharmacology / 国际中医中药杂志

Objective:To analyze and explore the possible mechanism of anti-tumor metastasis of Notoginseng Radix et Rhizoma using Internet pharmacology. Methods:The active components and targets of Notoginseng Radix et Rhizoma were screened by retrieving Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). GeneCards database was used to screen the anti-tumor metastasis-related targets, and compounds and disease targets were under mapping analysis. Key targets of Notoginseng Radix et Rhizoma for anti-tumor metastasis were screened through Venn map. With the help of Cytoscape 3.7.2 software, a compound-disease network diagram was constructed. String platform was used to build a PPI network. Bioconductor was used to enrich the target genes for KEGG signaling pathway and GO biological process analysis. Results:Totally 119 active components were selected from Notoginseng Radix et Rhizoma. There were 8 eligible active components, corresponding to 162 related targets, 121 targets related to anti-tumor metastasis, and 30 key targets screened by PPI network, including AKT1, MAPK1, JUN, RELA, IL6, etc. GO enrichment analysis mainly involved biological processes such as cytokine receptor binding, heme binding, RNA polymerase Ⅱ transcription factor binding, ubiquitin protein ligase binding, and steroid hormone receptor activity. 149 signal pathways related to Notoginseng Radix et Rhizoma anti-tumor metastasis were obtained by KEGG enrichment analysis, mainly involving multiple signal pathways, such as AGE-RAGE and PI3K-Akt, and hepatitis B, Kaposi's sarcoma-associated herpes virus infection, human cytomegalovirus infection and other viral infections and various tumors. Conclusion:Notoginseng Radix et Rhizoma can pass multiple active components, such as ginsenoside f2, ginsenoside rh2 β-, sitosterol, stigmasterol and quercetin, and multiple targets, such as AKT1, MAPK1, JUN, RELA and IL6, acting on multiple pathways such as PI3K-Akt, thereby playing the role of anti-tumor metastasis.

Self-assembly of CXCR4 antagonist peptide-docetaxel conjugates for breast tumor multi-organ metastasis inhibition

As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.

Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy

Autologous cancer vaccine that stimulates tumor-specific immune responses for personalized immunotherapy holds great potential for tumor therapy. However, its efficacy is still suboptimal due to the immunosuppressive tumor microenvironment (ITM). Here, we report a new type of bacteria-based autologous cancer vaccine by employing calcium carbonate (CaCO3) biomineralized Salmonella (Sal) as an in-situ cancer vaccine producer and systematical ITM regulator. CaCO3 can be facilely coated on the Sal surface with calcium ionophore A23187 co-loading, and such biomineralization did not affect the bioactivities of the bacteria. Upon intratumoral accumulation, the CaCO3 shell was decomposed at an acidic microenvironment to attenuate tumor acidity, accompanied by the release of Sal and Ca2+/A23187. Specifically, Sal served as a cancer vaccine producer by inducing cancer cells' immunogenic cell death (ICD) and promoting the gap junction formation between tumor cells and dendritic cells (DCs) to promote antigen presentation. Ca2+, on the other hand, was internalized into various types of immune cells with the aid of A23187 and synergized with Sal to systematically regulate the immune system, including DCs maturation, macrophages polarization, and T cells activation. As a result, such bio-vaccine achieved remarkable efficacy against both primary and metastatic tumors by eliciting potent anti-tumor immunity with full biocompatibility. This work demonstrated the potential of bioengineered bacteria as bio-active vaccines for enhanced tumor immunotherapy.

Brain Metastasis is Associated with Tumor Size, Nodal Status, and c-erbB-2 Expression in Invasive Breast Carcinoma / A metástase cerebral está associada com tamanho tumoral, status nodal e expressão de c-erbB-2 no carcinoma invasivo de mama

Introduction According to the World Health Organization (WHO) classification, invasive breast carcinoma (IBC) of no special type (IBC-NST) is the second most common primary site of central nervous system metastases, affecting 15% to 30% of patients. Brain metastasis originating from IBC is associated with patient age, tumor size, and axillary lymph node status. Loss of expression of hormone receptors and cerbB-2 amplification are frequent findings in patients who develop brain metastasis. Radiological studies of the central nervous system are carried out only in patients presenting with neurological signs or symptoms during the clinical follow-up. Objective To evaluate the associations of clinical and pathological findings with brain metastasis in breast cancer. Materials and Methods The sample comprised 73 patients with breast cancer who underwent mastectomy with lymph node resection. The following variables were evaluated: tumor size, histological grade, nodal state, expression of estrogen and progesterone receptors and c-erbB-2, and presence of brain metastasis. Results The histopathological findings associated with brain metastasis in patients with IBC were tumor size (p » 0.03), presence of nodal metastasis (p » 0.045), and c erbB-2 expression (p » 0.012). Conclusion The assessment of specific pathological findings in breast carcinoma can help identify risk factors and/or clinical parameters associated with the development of brain metastasis.

Introdução O carcinoma invasivo de mama (CIM) de tipo não especial, segundo a classificação da Organização Mundial de Saúde, é o segundo sítio primário mais comum de metástases do sistema nervoso central, afetando de 15% a 30% das pacientes. A metástase cerebral originada de CIM está associada à idade do paciente, tamanho do tumor, estado nodal axilar e perfil imuno-histoquímico do local primário. A perda da expressão dos receptores hormonais e a amplificação do c-erbB-2 são achados frequentes em pacientes que desenvolvem metástase cerebral. Estudos radiológicos do sistema nervoso central são realizados apenas em pacientes que apresentam sinais ou sintomas neurológicos durante o acompanhamento clínico. Objetivo Este estudo teve como objetivo avaliar associações de achados clínicos e patológicos com metástase cerebral em IBC. Método: A amostra foi composta por 73 pacientes com CIM submetidas à mastectomia e ressecção nodal axilar. Foram avaliadas as seguintes variáveis: tamanho do tumor, grau histológico, estado nodal, expressão de receptores de estrogênio e progesterona e c-erbB-2 e presença de metástase cerebral tratada por ressecção cirúrgica. Resultados Os achados histopatológicos associados à metástase cerebral em pacientes com IBC foram tamanho do tumor (p » 0,03), presença de metástase nodal (p » 0,045) e expressão de c-erbB-2 (p » 0,012). Conclusão A avaliação de achados patológicos específicos no IBC pode ajudar a identificar fatores de risco e/ou parâmetros clínicos associados ao desenvolvimento de metástase cerebral.

Cordoma sacral metastático / Metastatic sacral chordoma

Os cordomas sacrais (CS) são tumores ósseos malignos primários da coluna vertebral de ocorrência rara, com incidência entre 0,000005-0,000027%. O objetivo deste estudo é relatar um caso de CS metastático. Homem de 41 anos, sem comorbidades, chega ao serviço de referência apresentando lesão sacral. Ressonância magnética mostrou tratar-se de tumor com 9,3 cm sugestivo de mieloma ou cordoma. Realizou-se biópsia e histopatológico, confirmando o diagnóstico de CS. O paciente submeteu-se à excisão cirúrgica do tumor. Seis meses após a cirurgia, evoluiu com recidiva e implantes metastáticos em coluna vertebral, partes moles da parede torácica, fígado e espa-ço pleural, evoluindo com paraplegia. Não havia indicação de radioterapia e/ou quimioterapia adjuvante. Não havia também possibilidade de liberação de imatinibe pelo Sistema Único de Saúde. Em cerca de 28 meses de seguimento clínico mensal, o paciente foi a óbito. O caso apresentado mostrou um CS sem sucesso cirúrgico, o que é associa-do a pior prognóstico. O paciente apresentou disseminação sistêmica do tumor e paraplegia poucos meses após a cirurgia, indo a óbito em 28 meses de seguimento. (AU)

Sacral chordomas (SC) are rare primary malignant bone tumors of the vertebral column, with an incidence between 0.000005-0.000027%. This study aims to describe a case of metastatic SC. A 42-year-old man without comorbid conditions, arrived at the referral center, presenting with a sacral lesion. MRI showed a tumor measuring 9.3 cm that was suggestive of myeloma or chordoma. A biopsy with histopathology study was performed, confirming the diagnosis of SC. The patient underwent surgical tumor excision. Six months after surgery, the tumor recurred with metastatic vertebral column implants, soft tissues of the chest wall, liver, and pleural space, and the patient developed paraplegia. There was no indication of adjuvant radiotherapy and/or chemotherapy. There was also no possibility that the Unified Health System would approve imatinib. At about 28 months of monthly clinical follow-up, the patient died. The case presented showed unsuccessful SC surgery, which is associated with a worse prognosis. The patient had systemic tumor dissemination and paraplegia a few months after surgery, dying at 28 months of follow-up. (AU)

Assessment of Role of Platelet Aggregation in Metastatic Breast Cancer Patients

Background: To assess role of platelet aggregation in metastatic breast cancer patients.Methods:40 cases (Group I) of metastatic breast cancer patients and equal number of healthy control (Group II) subjects were included. Platelet aggregation studies in vitro using ADP and Thrombin were performed using an optical aggregometer. Detection of platelet aggregation was done by Chrono log series 490 dual and four channel optical aggregometer systems.Results:There were 4 subjects in group I and 12 in group II having ADP <60, 26 subjects in group I and 28 in group II with ADP 61-72 and 10 subjects in group I with ADP >72. Low thrombin <58 was seen in 8 in group II, normal thrombin between 61-72 was seen among 11 in group I and 32 in group II and high thrombin >82 among 29 in group I respectively. Amongst patients with normal platelet count, 14 patients had platelet aggregation with ADP in the normal range and 4 patients had platelet aggregation with ADP in the lower range. In patients with high platelet count, 12 showed aggregation in the normal range, and 10 patients showed aggregation in the higher range which was statistically significant (P< 0.05) (Table III, Graph II).Conclusion: Platelet aggregation has an important part to play in the tumor metastasis of breast cancer patients.

Fucoidan-functionalized activated platelet-hitchhiking micelles simultaneously track tumor cells and remodel the immunosuppressive microenvironment for efficient metastatic cancer treatment

Tumor metastasis is responsible for most mortality in cancer patients, and remains a challenge in clinical cancer treatment. Platelets can be recruited and activated by tumor cells, then adhere to circulating tumor cells (CTCs) and assist tumor cells extravasate in distant organs. Therefore, nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor, CTCs and metastasis in distant organs. However, the activated tumor-homing platelets will release transforming growth factor-β (TGF-β), which promotes tumor metastasis and forms immunosuppressive microenvironment. Therefore, a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals. In this study, a fucoidan-functionalized micelle (FD/DOX) was constructed, which could efficiently adhere to activated platelets through P-selectin. Compared with the micelle without P-selectin targeting effect, FD/DOX had increased distribution in both tumor tissue and metastasis niche, and exhibited excellent anti-tumor and anti-metastasis efficacy on 4T1 spontaneous metastasis model. In addition, due to the contribution of fucoidan, FD/DOX treatment was confirmed to inhibit the expression of TGF-β, thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment. The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.