The role of stromal immune microenvironment in the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer

Abstract Aim The first aim of the study was to compare the scores and types of stromal immune cells in 30 patients with primary DCIS and in the same patients after invasive breast recurrence in order to assess possible differences in both during tumor progression. The second aim was to evaluate possible differences in stromal cells of 30 patients with primary DCIS before progression and in the control group of 11 DCIS patients without recurrence during long-term follow-up. Material and methods Evaluation of tumor-infiltrating lymphocytes (TILs) and immunohistochemical stains for immune cell markers CD4, CD8, CD20, CD138, FOXP3, CD163 and TGF beta was performed on the stroma of primary DCIS before progression, invasive breast cancer of the same patients after progression and DCIS without progression. Results The comparison of stromal cells in 30 patients with initial DCIS and its invasive recurrence revealed an increased level of CD20 + immune cells (median score 5% vs. 17%, respectively, p < 0.001) and CD163 + cells (median score 1% vs. 5%, respectively, p < 0.001) in invasive breast cancer. The comparison of stromal cells in 30 patients with initial DCIS before recurrence and the control group of 11 patients with DCIS without recurrence showed statistically significant difference for CD138 + cells, which were more prevalent in patients with worse prognosis (median score 0 vs. 2%, respectively, p < 0.001). No similar relationship was found for the other tested cells as well as for TGF-beta. Conclusions CD138 + immune cells that were more prevalent in patients with a worse prognosis should be explored in further studies to confirm or exclude their role as a potential biological marker of DCIS invasive recurrence.

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Comparative Expression Analysis of Innate Immune Markers and Phagocytic Activity in Peripheral Blood of Dogs with Mammary Tumors

Animals ◽

10.3390/ani11082398 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2398

Author(s):

Urszula Lisiecka ◽

Piotr Brodzki ◽

Anna Śmiech ◽

Janusz Kocki ◽

Marcin Czop ◽

...

Keyword(s):

Immune Cells ◽

Immune Cell ◽

Mammary Tumors ◽

Innate Immune ◽

Control Group ◽

Detailed Knowledge ◽

Innate Immune Cells ◽

Immune Mechanisms ◽

Significant Difference ◽

Epithelial Origin

Canine innate immune system role in cancer prevention and progression remains poorly understood. It has been revealed that innate immune cells could play a dual role in cancer immunology promoting or inhibiting tumor development and growth. Current immunotherapies target mainly the adaptive anti-tumor response and that may be a reason why they remain ineffective in a majority of patients. It is important to acquire detailed knowledge about innate immune mechanisms to broaden the diagnostic and therapeutic options and employ innate immune cells in anti-cancer therapies. In the present study, 21 female dogs of different breeds and types of spontaneous mammary tumors were investigated. The study aimed to find simple and cheap markers that can be used for preliminary diagnosis, prior to the surgical resection of the tumor. The differences in innate immune cell quantity and function were investigated between female dogs with malignant mammary tumors of epithelial and mesenchymal origin. Flow cytometry was used to evaluate the percentages of CD5+ lymphocytes including CD5low lymphocytes, CD11b integrin expression on leukocytes, phagocytosis, and oxidative burst. The number of CD11b lymphocytes was increased in tumors with epithelial origin compared to the control group. No significant differences were found between the percentages of phagocytic cells neither for granulocytes nor for monocytes. However, the phagocytes of canine patients with tumors of epithelial origin showed increased phagocytosis compared to the control group. The percentages of granulocytes that produced reactive oxygen species (ROS) in response to E.coli and PMA were not altered in patients with malignant tumors compared to control. A statistically significant difference between the number of ROS produced by the single granulocyte was demonstrated only between the group of bitches with epithelial tumors and the control group in case of E. coli stimulation. The obtained results suggest that some innate immune cells may be involved in anti-tumor immune mechanisms and have the potential to be supportive diagnostic markers in canine mammary tumors.

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Identification of Hub Genes and Immune Cell Infiltration Characteristics in Alzheimer’s Disease

Journal of Healthcare Engineering ◽

10.1155/2021/7036194 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Ming Hu ◽

Jianhua Wang

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Immune Cells ◽

Immune Cell ◽

Differential Expression Analysis ◽

Cell Infiltration ◽

Control Group ◽

Immune Cell Infiltration ◽

Hub Genes ◽

Significant Difference

The purpose of this study was to identify hub genes closely correlated with Alzheimer's disease (AD) and their association with immune cell infiltration. In this work, 119 overlapping differentially expressed genes (DEGs) were obtained from GSE5281 and GSE122063 datasets through differential expression analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the 119 DEGs, revealing some important biological functions and key pathways. AD immune cell infiltration analysis revealed a significant difference in the proportion of immune cells between the AD group and the control group. Finally, correlation analysis between target hub genes and immune cells indicated that GFAP had a positive or negative correlation with some specific immune cells. Our results provided useful clues, which will help to explain the molecular mechanism of AD and search for precise prognostic markers and potential therapeutic targets.

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COMPARISON OF THE QUALITY OF LIFE OF PATIENTS IN THE LOCALY ADVANCED BREAST CANCER FORMS AFTER SYSTEM AND INTRALYMPHATIC POLYCHEMOTHERAPY

EUREKA Health Sciences ◽

10.21303/2504-5679.2018.00693 ◽

2018 ◽

Vol 4 ◽

pp. 3-13

Author(s):

Yuriy Dumanskiy ◽

Oleksandr Bondar ◽

Oleksandr Tkachenko ◽

Evhenii Stoliachuk ◽

Vasilii Ermakov

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Locally Advanced ◽

Developed Countries ◽

Control Group ◽

Preoperative Treatment ◽

Discrete Elements ◽

Important Indicator ◽

Significant Difference

In recent years, breast cancer (BC) is the most common cancer pathology and the most common cause of disability among women in developed countries. Finding the most effective ways of interaction between the patient and the doctor creates the preconditions for the necessary analysis of the treatment process from an objective and subjective point of view. Therefore, an important indicator to be taken into account is the quality of life of a patient. To compare the indicators of a comprehensive assessment of the quality of life of patients to the adverse locally advanced forms (LA) of breast cancer before and after systemic intravenous polychemotherapy (SPCTx) and selective endolymphatic polychemotherapy (ELPCTx) in neoadjuvant mode. The study was conducted on the basis of a random analysis of outpatient cards from 112 patients with LA BC T4A-DN0-3M0 who received a comprehensive antitumor treatment on the basis of the Donetsk regional antitumor center and the University Clinic of the Odessa National Medical University from 2000 to 2017, which was proposed a questionnaire at various stages of preoperative treatment. The first (control) group consisted of 65 patients (58 %) with inoperable forms of LA BC, which was performed in neoadjuvant mode by SPCTx. The second (study group) included 47 patients (42 %) with inoperable forms of LA BC, which was performed as a neoadjuvant course ELPCTx. According to the integral indicators of quality of life and quality of health between patients in the control and study groups, there was no statistically significant difference. In a detailed analysis of the indicators of symptomatic scales, the difference between the groups did not exceed the critical. Based on the results of a study conducted among patients receiving endolymphatic chemotherapy in a neoadjuvant mode, the subjective evaluations of treatment in absolute numbers have better reference values without statistical superiority. The study of the integrative indicator of quality of life and its discrete elements is an ergonomic and economical means of heuristic assessment of the health of patients in order to further develop more rational and convenient ways of solving urgent issues of modern oncology by increasing compliance and finding a compromise between the physician and the patient.

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The clinical efficacy of arthroscopic therapy with knee infrapatellar fat pad cell concentrates in treating knee cartilage lesion: a prospective, randomized, and controlled study

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02224-9 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Yiqin Zhou ◽

Haobo Li ◽

Dong Xiang ◽

Jiahua Shao ◽

Qiwei Fu ◽

...

Keyword(s):

Clinical Efficacy ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Knee Arthroscopy ◽

Infrapatellar Fat Pad ◽

Control Group ◽

Knee Cartilage ◽

Fat Pad ◽

Group 12 ◽

Significant Difference

Abstract Introduction To evaluate the clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesions, we conducted a prospective randomized single-blind clinical study of controlled method. Methods Sixty cases from Shanghai Changzheng Hospital from April 2018 to December 2019 were chosen and randomly divided into 2 groups equally. Patients in the experiment group were treated through knee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stromal cells, while patients in the control group were treated through regular knee arthroscopic therapy. VAS and WOMAC scores were assessed at pre-operation, and 6 weeks, 12 weeks, 6 months, and 12 months after intervention. MORCART scores were assessed at pre-operation and 12 months after intervention. Results Twenty-nine cases in the experiment group and 28 cases in the control group were followed up. No significant difference in VAS, WOMAC, and MOCART scores were found between the two groups before surgery (P > 0.05). The WOMAC total and WOMAC function scores of the experiment group were significantly lower than those of the control group 6 months and 12 months after surgery (P < 0.05). The VAS rest and VAS motion scores of the experiment group were found significantly lower than those of the control group 12 months after surgery (P < 0.05). The MOCART scores of the experiment group were found significantly higher compared with the control group 12 months after surgery (P < 0.05). No significant difference in WOMAC stiffness scores were found between the two groups. Conclusions The short-term results of our study are encouraging and demonstrate that knee arthroscopy with infrapatellar fat pad cell concentrates containing mesenchymal stromal cells is safe and provides assistance in reducing pain and improving function in patients with knee cartilage lesions. Trial registration ChiCTR1800015379. Registered on 27 March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25901.

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VWCE as a potential biomarker associated with immune infiltrates in breast cancer

Cancer Cell International ◽

10.1186/s12935-021-01955-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Qin Huo ◽

Zhenwei Li ◽

Siqi Chen ◽

Juan Wang ◽

Jiaying Li ◽

...

Keyword(s):

Breast Cancer ◽

Immune Cell ◽

Her2 Status ◽

Cancer Tissue ◽

M2 Macrophage ◽

Breast Cancer Patients ◽

Immune Infiltration ◽

Potential Biomarker ◽

Significant Difference ◽

Factor C

Abstract Purpose Von Willebrand Factor C and EGF Domains (VWCE) is an important gene that regulates cell adhesion, migration, and interaction. However, the correlation between VWCE expression and immune infiltrating in breast cancer remain unclear. In this study, we investigated the correlation between VWCE expression and immune infiltration levels in breast cancer. Methods The expression of VWCE was analyzed by the tumor immune estimation resource (TIMER) and DriverDB databases. Furthermore, genes co-expressed with VWCE and gene ontology (GO) enrichment analysis were investigated by the STRING and Enrichr web servers. Also, we performed the single nucleotide variation (SNV), copy number variation (CNV), and pathway activity analysis through GSCALite. Subsequently, the relationship between VWCE expression and tumor immunity was analyzed by TIMER and TISIDB databases, and further verified the results using Quantitative Real-Time PCR (RT-PCR), Western blotting, and immunohistochemistry. Results The results showed that the expression of VWCE mRNA in breast cancer tissue was significantly lower than that in normal tissues. We found that the expression level of VWCE was associated with subtypes, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status of breast cancer patients, but there was no significant difference in the expression of VWCE was found in age and nodal status. Further analyses indicated that VWCE was correlated with the activation or inhibition of multiple oncogenic pathways. Additionally, VWCE expression was negatively correlated with the expression of STAT1 (Th1 marker, r = − 0.12, p = 6e−05), but positively correlated with the expression of MS4A4A (r = 0.28, p = 0). These results suggested that the expression of VWCE was correlated with immune infiltration levels of Th1 and M2 macrophage in breast cancer. Conclusions In our study, VWCE expression was associated with a better prognosis and was immune infiltration in breast cancer. These findings demonstrate that VWCE is a potential prognostic biomarker and correlated with tumor immune cell infiltration, and maybe a promising therapeutic target in breast cancer.

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A novel 3-D bio-microfluidic system mimicking in vivo heterogeneous tumour microstructures reveals complex tumour–stroma interactions

Lab on a Chip ◽

10.1039/c7lc00191f ◽

2017 ◽

Vol 17 (16) ◽

pp. 2852-2860 ◽

Cited By ~ 15

Author(s):

Qihui Fan ◽

Ruchuan Liu ◽

Yang Jiao ◽

Chunxiu Tian ◽

James D. Farrell ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Invasive Breast Cancer ◽

Stromal Cells ◽

Breast Cancer Cells ◽

Microfluidic System ◽

Tumour Stroma ◽

Collagen Hydrogel

A 3-D microfluidic system consisting of microchamber arrays embedded in a collagen hydrogel with tunable biochemical gradients was constructed for investigating interactions between invasive breast cancer cells and stromal cells.

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Early assessment of shear wave elastography parameters foresees the response to neoadjuvant chemotherapy in patients with invasive breast cancer

Breast Cancer Research ◽

10.1186/s13058-021-01429-4 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Juanjuan Gu ◽

Eric C. Polley ◽

Max Denis ◽

Jodi M. Carter ◽

Sandhya Pruthi ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Shear Wave ◽

Invasive Breast Cancer ◽

Shear Wave Elastography ◽

Early Prediction ◽

Early Assessment ◽

Significant Difference ◽

Mass Size ◽

Response To Neoadjuvant Chemotherapy

Abstract Background Early prediction of tumor response to neoadjuvant chemotherapy (NACT) is crucial for optimal treatment and improved outcome in breast cancer patients. The purpose of this study is to investigate the role of shear wave elastography (SWE) for early assessment of response to NACT in patients with invasive breast cancer. Methods In a prospective study, 62 patients with biopsy-proven invasive breast cancer were enrolled. Three SWE studies were conducted on each patient: before, at mid-course, and after NACT but before surgery. A new parameter, mass characteristic frequency (fmass), along with SWE measurements and mass size was obtained from each SWE study visit. The clinical biomarkers were acquired from the pre-NACT core-needle biopsy. The efficacy of different models, generated with the leave-one-out cross-validation, in predicting response to NACT was shown by the area under the receiver operating characteristic curve and the corresponding sensitivity and specificity. Results A significant difference was found for SWE parameters measured before, at mid-course, and after NACT between the responders and non-responders. The combination of Emean2 and mass size (s2) gave an AUC of 0.75 (0.95 CI 0.62–0.88). For the ER+ tumors, the combination of Emean_ratio1, s1, and Ki-67 index gave an improved AUC of 0.84 (0.95 CI 0.65–0.96). For responders, fmass was significantly higher during the third visit. Conclusions Our study findings highlight the value of SWE estimation in the mid-course of NACT for the early prediction of treatment response. For ER+ tumors, the addition of Ki-67improves the predictive power of SWE. Moreover, fmass is presented as a new marker in predicting the endpoint of NACT in responders.

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Effect of Rapid Rehabilitation Concepts on Quality of Life and Pain in Patients Undergoing Radical Breast Cancer Surgery in Perioperative Period

Tobacco Regulatory Science ◽

10.18001/trs.7.5.74 ◽

2021 ◽

Vol 7 (5) ◽

pp. 1538-1544

Author(s):

Xin Li ◽

Hai-yan An ◽

Yi Zhao ◽

Mingli Ji ◽

Jing An ◽

...

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Perioperative Period ◽

Nursing Intervention ◽

Cancer Surgery ◽

Breast Cancer Surgery ◽

Control Group ◽

T Lymphocyte Subsets ◽

Significant Difference

To study the effect of rapid rehabilitation nursing on patients’ quality of life and pain level during the perioperative period of radical breast cancer surgery. Methods: 126 patients who were hospitalized in our hospital from January 2018 to February 2020 and underwent radical breast cancer surgery were divided into control group and rapid rehabilitation group according to the perioperative period intervention method. Routine nursing intervention and rapid rehabilitation nursing intervention were used respectively. The general conditions of the two groups were recorded, and the differences of T cell subsets before operation and 3 days after operation were detected. Visual analogue pain (VAS) score was used to evaluate the changes of pain degree at 1 day, 3 days and 5 days after operation and on the day of discharge. Postoperative complications and satisfaction were compared between the two groups. Quality of life (QOL) was assessed at 1 month and 3 months after operation using the CARES-SF score. Results: Anesthesia waking time (26.12 ± 5.77) min, off-bed activity time (14.25 ± 2.87) h and hospital stay (7.82 ± 2.15) d in the rapid rehabilitation group were shorter than those in the control group (P < 0.05). The operation time (92.02 ± 14.78) min and intraoperative blood loss (57.96 ± 13.96) mL in the rapid rehabilitation group were not significantly different from those in the control group (P > 0.05). In the control group, 3d after operation, T lymphocyte subsets were decreased gradually than that before operation (P < 0.05), CD3+ was decreased 3d after operation than that before operation in the rapid rehabilitation group (P < 0.05), but CD4+, CD8+, CD4+ / CD8 + 3d after operation had no significant difference than that before operation (P > 0.05). In rapid rehabilitation group, T lymphocyte subsets at 3d after operation were higher than those in the control group (P < 0.05). The postoperative complication rate of the rapid rehabilitation group was lower than that of the control group, and the satisfaction degree was higher than that of the control group, with significant difference (P < 0.05). After follow-up, it was found that the scores of qualities of life, such as physiology, psychosocial, marriage, sexual life and relationship with medical staff in the rapid rehabilitation group were lower than those in the control group at 1 month and 3 months after operation (P < 0.05). Conclusion: The concept of rapid rehabilitation nursing can stabilize the immune function of patients after radical breast cancer surgery, promote the postoperative rehabilitation and improve the quality of life after operation.

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Exploring The Clinical Significance of Serum Angiopoietin-2 In Breast Cancer Patients

QJM ◽

10.1093/qjmed/hcab091.014 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Abeer I Abd Elmagid ◽

Hala Abdel Al ◽

Wessam El Sayed Saad ◽

Seham Kamal Mohamed

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Serum Levels ◽

Tnm Staging ◽

Control Group ◽

Healthy Controls ◽

Breast Cancer Patients ◽

Female Patients ◽

Significant Difference ◽

Angiopoietin 2

Abstract Background Breast cancer is the most common cancer among women and one of the most important causes of death among them.Angiogenesis is an important step for primary tumor growth, invasiveness, and metastases. Angiopoietins are well-recognized endothelial growth factors that are involved in angiogenesis associated with tumors. Aim To explore the diagnostic significance of serum angiopoietin-2 (Ang-2) in breast cancer and to evaluate its prognostic efficacy through studying the degree of its association with the TNM staging of the disease. Patients and Methods This study was conducted on (35) Egyptian female patients who were diagnosed as breast cancer according to histopathological examination of breast biopsy (Group 1, Breast Cancer Patients) and (25) female patients with benign breast diseases (Group II, Pathological Control Patients), in addition to (20) age - matched apparently healthy, free mammogram, females serving as healthy controls (Group III, Healthy Controls). For all participants, measurement of serum Ang-2 was done using enzyme linked immunosorbent assay (ELISA) technique. Results A highly significant increased levels of Ang-2 was observed in breast cancer patients when compared to healthy control group (Z = 4.95, p < 0.01). However, no significant difference was observed in Ang-2 levels between breast cancer patients group and pathological control group (Z = 3.37, p > 0.05). No significant difference was detected in Ang-2 levels in relation to TNM stage and histological grade. No significant correlation was found between Ang-2 levels and serum levels of CA15-3, hormone receptors, HER2/new receptor status (p > 0.05, respectively). Conclusion This study revealed that Ang-2 serum levels were significantly increased in patient with breast cancer compared with healthy controls, indicating that high Ang-2 level is a promising non invasive biomarker for breast cancer diagnosis. However, no significant difference of Ang-2 levels was detected in relation of breast TNM staging in the population studied.

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Re-Excision Rates in Breast-Conserving Surgery for Invasive Breast Cancer after Neoadjuvant Chemotherapy with and without the Use of a Radiopaque Tissue Transfer and X-ray System

Breast Care ◽

10.1159/000493017 ◽

2018 ◽

Vol 14 (5) ◽

pp. 302-307

Author(s):

Suniza Jamaris ◽

Leyla Akpolat-Basci ◽

Miltiades Stephanou ◽

Sarah Wetzig ◽

Yueksel Cubuk ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Invasive Breast Cancer ◽

Breast Conserving Surgery ◽

Control Group ◽

Study Group ◽

Transfer System ◽

Tissue Transfer ◽

Resected Tissue ◽

Specimen Radiography

Background: Significant re-excision rates in breast-conserving surgery (BCS) after neoadjuvant systemic chemotherapy may result from difficulties in defining the surgical target particularly in cases with excellent treatment response. Devices allowing an exact topographic localisation of the lesion in the resected tissue could reduce re-excision rates by optimising the intraoperative detection of involved margins. Methods: 80 patients with invasive breast cancer receiving BCS after neoadjuvant chemotherapy were included in this non-randomized case-control study. 40 patients with specimen radiography performed in a standard approach (control group) were compared to 40 patients with use of a radiopaque tissue transfer system (study group). Results: 19/80 (23.75%) patients required re-excision because of involved margins; among those, 14/40 (35%) were in the control group and 5/40 (12.5%) in the study group. The association between the use of the radiopaque tissue transfer system and the lower re-excision rate was statistically significant (p = 0.023). Conclusion: Our analysis provides a rationale for the routine use of a radiopaque tissue transfer system for specimen radiography in BCS after neoadjuvant chemotherapy for invasive breast cancer in order to reduce re-excision rates.

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