BACKGROUND: Tumor associated macrophages (TAMs) and CXC chemokine receptor 4 (CXCR4) have emerged as potential biomarkers in various human cancers. The aims of this study were to investigate the clinical characteristics of anaplastic thyroid cancer (ATC) patients according to the TAM numbers in the tumor tissue, and to evaluate the associations between CXCR4 expressions and macrophage densities in ATC tumor microenvironment. METHODS: Total 14 ATC samples from thyroid tissue microarray were used. Immunohistochemical staining was performed using anti-CD163 and anti-CXCR4 antibodies. According to the immunoreactivity of CD163, all subjects were divided into two groups: low-CD163 (n=8) and high-CD163 (n=6) groups. RESULTS: The mean diagnostic age was 65±7 years and the median tumor size was 4.3 cm, ranging 2.5 to 15 cm. Clinicopathological characteristics were not significantly different between low-CD163 and high-CD163 groups, while age of diagnosis was younger in high-CD163 group than that of low-CD163 group with marginal significance (56.9±5.5 years vs. 67.5±6.8 years, P=0.09). However, overall survival was significantly reduced in high-CD163 group (5.5 months [range, 1 to 10]) compared with low-CD163 groups (8.8 months [range, 6 to 121); log-rank test, P=0.0443). Moreover, high-CD163 group showed strong CXCR4 expressions in both cancer and stromal compartments, while low-CD163 group showed relatively weak, stromal-dominant CXCR4 expressions. Additionally, CD163 and CXCR4 expressions showed a strong positive correlation (γ²=0.432, P=0.013). CONCLUSION: Increased number of TAMs showed poor overall survival in ATC, suggesting TAMs are potentially a prognostic biomarker for ATC. CXCR4 expression was significantly correlated with CD163-positive TAM densities, which suggest the possible role of CXCR4 in TAM recruitments.
Antibodies ; Biomarkers ; Diagnosis ; Humans ; Macrophages* ; Receptors, CXCR* ; Receptors, CXCR4* ; Thyroid Carcinoma, Anaplastic* ; Thyroid Gland ; Tumor Microenvironment

BACKGROUND AND OBJECTIVES: Follicular tumors can present a difficult diagnostic challenge for cytological evaluation and ultrasound findings. Therefore, new methods which could help distinguish follicular adenoma from follicular carcinoma simply and accurately are greatly desired. This study investigated the usefulness of immnunohistochemical expression of CXC chemokine receptor 4 (CXCR4) and galectin-3 as marker of differentiated thyroid carcinomas. MATERIALS AND METHODS: Expression of CXCR4 and galectin-3 were examined immunohistochemically in the 60 paraffin embedded tissues which were already diagnosed as follicular adenoma (n=20), follicullar carcinoma (n=20), and papillary carcinoma (n=20) of thyroid. RESULTS: Galatin-3 was expressed significantly high in follicular carcinoma than follicular adenoma (p=0.022). CXCR4 was also expressed significantly high in follicular carcinoma than follicular adenoma (p=0.027). The sensitivity of CXCR4 and galectin-3 was 70% and 80% and specificity, 65% and 60% for differential diagnosis of follicular tumors. CONCLUSION: An immunohistochemical panel, including galatin-3 and CXCR4, could be useful in the differential diagnosis between follicular adenoma from follicular carcinoma.
Adenoma ; Carcinoma, Papillary ; Diagnosis, Differential ; Galectin 3 ; Paraffin ; Receptors, CXCR ; Receptors, CXCR4 ; Sensitivity and Specificity ; Thyroid Gland

OBJECTIVETo investigate the expression status of CXCR7 in gastric cancer tissues and cell lines.

METHODSThe expression status of CXCR7 was detected in 35 primary gastric cancer tissues and matched adjacent tissues by immunohistochemistry and RT-PCR. The correlation of CXCR7 expression with the clinicopathological parameters and risk factors of gastric cancer was analyzed. The expression of CXCR7 in gastric cell lines (HGC-27, MGC-803, BGC-823, SGC-7901 and MKN-28) was also detected by immunofluorescence assay.

RESULTSThe expression of CXCR7 was significantly higher in gastric cancer tissues than in adjacent tissues (P<0.01). CXCR7 expression was not correlated with age, gender, smoking history, Helicobacter pylori infection, tumor location or the pathological type, but showed a higher expression level in patients with a alcohol-drinking history than in those without (P<0.05). CXCR7 was expressed with variable intensities in the 5 gastric cancer cell lines without correlation with the degrees of cell differentiation; its expression was the highest in SGC-7901 cells, a moderately differentiated human gastric adenocarcinoma cell line.

CONCLUSIONSCXCR7 is highly expressed in gastric cancer tissues with variable intensities in 5 gastric cancer cell lines, suggesting its important role in gastric cancer progression.

Cell Differentiation ; Cell Line, Tumor ; Disease Progression ; Helicobacter Infections ; Humans ; Immunohistochemistry ; Receptors, CXCR ; metabolism ; Signal Transduction ; Stomach Neoplasms ; diagnosis ; metabolism

OBJECTIVE: To investigate the enhancement of macrophage chemotaxis in patients with knee osteoarthritis (KOA) and its correlation with the disease severity. METHODS: Eighty patients with KOA admitted from July 2019 to June 2022 were enrolled as the observation group and divided into 29 cases of moderate group, 30 cases of severe group and 21 cases of extremely severe group. At the same time, 30 healthy subjects were included as the control group. The gene expressions of NF-κB, CXC chemokine receptor 7 (CXCR7) and CXC chemokine ligand 12 (CXCL12) in macrophages of each group were analyzed. Visual analogue scale(VAS) was used to evaluate the degree of joint pain. Joint function was evaluated by knee Joint Society Scoring system(KSS). Finally, data analysis was carried out. RESULTS: The expression levels of NF-κB, CXCR7 and CXCL12 in moderate group, severe group and extreme recombination group were higher than those in control group. The VAS, the expression of NF-κB, CXCR7 and CXCL12 in the severe group and the extreme recombination group were higher than those in the moderate group, whereas KSS was lower than that in the moderate group. The VAS, expression levels of NF-κB, CXCR7 and CXCL12 in the extremely severe group were higher than those in the severe group, and KSS was lower than that in the severe group (all P<0.01). The expression levels of NF-κB, CXCR7 and CXCL12 in macrophages were positively correlated with VAS score, but negatively correlated with KSS(all P<0.01). The expression levels of NF-κB, CXCR7 and CXCL12 in macrophages were positively correlated with the severity of disease. After excluding the influence of traditional factors (gender, age and disease duration), multiple linear regression analysis further showed that the expression levels of NF-κB, CXCR7 and CXCL12 were still positively correlated with the severity of disease(all P<0.01). CONCLUSION The chemotaxis of macrophages in patients with KOA increased with the aggravation of the disease, and was related to the degree of pain and function impairment.
Humans ; Osteoarthritis, Knee/genetics* ; Chemotaxis/genetics* ; NF-kappa B/metabolism* ; Macrophages/metabolism* ; Receptors, CXCR/metabolism* ; Patient Acuity

OBJECTIVETo construct a soluble prokaryotic expression vector of the CXCR7-specific antagonist SDF-1/54R and evaluate its activity.

METHODSSDF-1/54r gene amplified by PCR was inserted into the soluble expression vector pET-41a+ engineered with GST fusion tag, and the recombinant vector was transformed into E. coli strain BL21 (DE3). After IPTG induction of E. coli, the expressed recombinant protein was purified with GST affinity chromatography purification system and confirmed by SDS-PAGE and Western blotting assay. The target protein SDF-1/54R was obtained after digestion of the purified product with enterokinase. Breast cancer MCF-7 cells with high expression of CXCR7 was treated with SDF-1/54R and the cell proliferation and metastasis was evaluated with MTT and chemotaxis assays.

RESULTSThe target protein SDF-1/54R obtained showed an obvious inhibitory effect on the proliferation and metastasis of MCF-7 cells as confirmed by MTT and chemotaxis assays.

CONCLUSIONSDF-1/54R is a good antagonist of CXCR7 and shows a potential value as an effective anti-cancer agent.

Blotting, Western ; Chemokine CXCL12 ; metabolism ; Chromatography, Affinity ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli ; Genetic Vectors ; Humans ; Polymerase Chain Reaction ; Receptors, CXCR ; antagonists & inhibitors ; Recombinant Proteins ; biosynthesis

OBJECTIVETo explore the effects of CXCR7 knock-down by CXCR7-shRNA lentiviral vector on the proliferation and invasion of human hepatoma carcinoma cells in vitro.

METHODSCXCR7-shRNA lentiviral vector was transfected into hepatocellular carcinoma HCCLM3 cells. The changes in mRNA and protein expression of CXCR7 in the transfected cells were investigated using real-time PCR and Western blotting, respectively, and MTT assay was employed to assess the cell proliferation changes. In vitro adhesion assay and transwell chamber test were used to observe the adhesion and invasiveness of HCCLM3 cells, respectively.

RESULTSTransfection of HCCLM3 cells with CXCR7-shRNA lentiviral vector resulted in a significantly decreased expression of CXCR7 at both mRNA and protein levels (P<0.01) and obvious suppression of the cell proliferative activity (P<0.05). CXCR7-shRNA also significantly suppressed the invasiveness and adhesion of HCCLM3 cells (P<0.01).

CONCLUSIONCXCR7 knock-down can significantly inhibit the proliferation and invasiveness of human hepatoma carcinoma cells in vitro, suggesting the value of CXCR7 as a potential target for hepatoma carcinoma therapy.

Carcinoma, Hepatocellular ; genetics ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Genetic Vectors ; Humans ; Lentivirus ; genetics ; Liver Neoplasms ; genetics ; pathology ; RNA, Small Interfering ; genetics ; Receptors, CXCR ; genetics ; Transfection

Acute kidney injury is a serious global health problem and determinant of morbidity and mortality. Recent advancements in the field of stem cell research raise hopes for stem cell-based regenerative approaches to treat acute kidney diseases. In this review, the authors summarized the latest research advances of the adult resident renal progenitor cells (ARPCs) on kidney repair, the role of ARPCs on tubular regeneration after acute kidney injury, the current understanding of the mechanisms related to ARPC activation and modulation, as well as the challenges that remain to be faced.
Acute Kidney Injury ; physiopathology ; Antigens, CD ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Kidney ; physiopathology ; Kidney Tubules ; physiopathology ; Receptors, CXCR ; metabolism ; Regeneration ; physiology ; Reperfusion Injury ; physiopathology ; Stem Cells ; physiology

BACKGROUND: Chemokine receptor CXC chemokine receptor type 4 (CXCR4) and its ligand CXC motif chemokine 12 (CXCL12; stromal cell-derived factor-1) are implicated in tumor growth, metastasis, and tumor cell-microenvironment interaction. A number of studies have reported that increased CXCR4 expression is associated with worse prognosis in triple-negative breast cancer (TNBC), but its prognostic significance has not been studied in TNBC patients treated with adjuvant chemotherapy. METHODS: Two hundred eighty-three TNBC patients who received adjuvant chemotherapy were retrospectively analyzed. Tissue microarray was constructed from formalin-fixed, paraffin-embedded tumor tissue and immunohistochemistry for CXCR4 and CXCL12 was performed. Expression of each marker was compared with clinicopathologic characteristics and outcome. RESULTS: High cytoplasmic CXCR4 expression was associated with younger age (p = .008), higher histologic grade (p = .007) and lower pathologic stage (p = .045), while high CXCL12 expression was related to larger tumor size (p = .045), positive lymph node metastasis (p = .005), and higher pathologic stage (p = .017). The patients with high cytoplasmic CXCR4 experienced lower distant recurrence (p = .006) and better recurrence-free survival (RFS) (log-rank p = .020) after adjuvant chemotherapy. Cytoplasmic CXCR4 expression remained an independent factor of distant recurrence (p = .019) and RFS (p = .038) after multivariate analysis. CONCLUSIONS: High cytoplasmic CXCR4 expression was associated with lower distant recurrence and better RFS in TNBC patients treated with adjuvant chemotherapy. This is the first study to correlate high CXCR4 expression to better TNBC prognosis, and the underlying mechanism needs to be elucidated in further studies.
Chemotherapy, Adjuvant ; Cytoplasm ; Humans ; Immunohistochemistry ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Receptors, CXCR ; Recurrence ; Retrospective Studies ; Triple Negative Breast Neoplasms

Adenocarcinoma ; metabolism ; pathology ; surgery ; Adenoma ; metabolism ; pathology ; surgery ; Adult ; Aged ; Colorectal Neoplasms ; metabolism ; pathology ; surgery ; Female ; Humans ; Intestinal Mucosa ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Receptors, CXCR ; metabolism ; Young Adult

INTRODUCTIONC-X-C chemokine receptor type 7 (CXCR7) has recently been characterised as a novel receptor for the C-X-C motif chemokine 12 (CXCL12)/stromal cell-derived factor 1-alpha. CXCR7 has been thought to play an important role in the pathogenesis of chronic rhinosinusitis, angiogenesis and tumour metastasis. The present study aimed to examine the expression of CXCR7 in tissue samples of laryngeal cancer and maxillary sinus carcinoma to determine its role in the development of otorhinolaryngologic neoplasms.

METHODSSamples of otorhinolaryngologic neoplasms were obtained from 17 patients with either nasal polyps (n = 7), laryngeal cancer (n = 5) or maxillary sinus carcinoma (n = 5), and who underwent surgical resection at West China Hospital of Sichuan University. Total RNA was isolated and CXCR7 mRNA expression was examined and quantified by relative real-time reverse transcription polymerase chain reaction. A one-way analysis of variance was performed using SPSS Statistics version 11.0 (SPSS Inc, Chicago, IL, USA) to compare the CXCR7 mRNA levels among the three groups of patients.

RESULTSAll samples tested positive for CXCR7 mRNA. The quantitative results showed that the CXCR7 mRNA levels were highest in laryngeal cancer and lowest in maxillary sinus carcinoma neoplasms, although there was no significant difference among the three samples.

CONCLUSIONCXCL12 and its receptor CXCR7 may contribute to eosinophilic inflammation in patients with chronic sinusitis and nasal polyps. Our results also suggest that CXCR7 may play a role in the progression, metastasis and angiogenesis of otorhinolaryngologic tumours.

Aged ; Biomarkers, Tumor ; biosynthesis ; genetics ; Carcinoma, Squamous Cell ; genetics ; metabolism ; pathology ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Middle Aged ; Otorhinolaryngologic Neoplasms ; genetics ; metabolism ; pathology ; RNA, Neoplasm ; genetics ; Real-Time Polymerase Chain Reaction ; Receptors, CXCR ; biosynthesis ; genetics