Background/Aims: Heart failure (HF) is a main cause of mortality of hemodialysis (HD) patients. While HF with reduced ejection fraction (HFrEF) is known to only a

/pdf/heart-failure-with-preserved-and-reduced-ejection-fraction-x6ohbcir7v.pdf

Heart Failure with Preserved and Reduced Ejection Fraction in Hemodialysis Patients: Prevalence, Disease Prediction and Prognosis

Tumor-associated macrophages (TAMs) are major innate immune cells that constitute up to 50% of the cell mass of human tumors. TAMs are highly heterogeneous cells that originate from resident tissue-specific macrophages and from newly recruited monocytes. TAMs' variability strongly depends on cancer type, stage, and intratumor heterogeneity. Majority of TAMs are programmed by tumor microenvironment to support primary tumor growth and metastatic spread. However, TAMs can also restrict tumor growth and metastasis. In this review, we summarized the knowledge about the role of TAMs in tumor growth, metastasis and in the response to cancer therapy in patients with five aggressive types of cancer: breast, colorectal, lung, ovarian, and prostate cancers that are frequently metastasize into distant organs resulting in high mortality of the patients. Two major TAM parameters are applied for the evaluation of TAM correlation with the cancer progression: total amount of TAMs and specific phenotype of TAMs identified by functional biomarkers. We summarized the data generated in the wide range of international patient cohorts on the correlation of TAMs with clinical and pathological parameters of tumor progression including lymphatic and hematogenous metastasis, recurrence, survival, therapy efficiency. We described currently available biomarkers for TAMs that can be measured in patients' samples (tumor tissue and blood). CD68 is the major biomarker for the quantification of total TAM amounts, while transmembrane receptors (stabilin-1, CD163, CD206, CD204, MARCO) and secreted chitinase-like proteins (YKL-39, YKL-40) are used as biomarkers for the functional TAM polarization. We also considered that specific role of TAMs in tumor progression can depend on the localization in the intratumoral compartments. We have made the conclusion for the role of TAMs in primary tumor growth, metastasis, and therapy sensitivity for breast, colorectal, lung, ovarian, and prostate cancers. In contrast to other cancer types, majority of clinical studies indicate that TAMs in colorectal cancer have protective role for the patient and interfere with primary tumor growth and metastasis. The accumulated data are essential for using TAMs as biomarkers and therapeutic targets to develop cancer-specific immunotherapy and to design efficient combinations of traditional therapy and new immunomodulatory approaches.

/pdf/tumor-associated-macrophages-in-human-breast-colorectal-lung-55u30ctebp.pdf

Tumor-Associated Macrophages in Human Breast, Colorectal, Lung, Ovarian and Prostate Cancers

Prostate cancer stem cells (PCSCs) play a critical role in prostate cancer progression and metastasis, which remains an obstacle for successful prostate cancer treatment. Tumor-associated macrophages (TAMs) are the most abundant immune cell population within the tumor microenvironment (TME). Systematic investigation of the interaction and network signaling between PCSCs and TAMs may help in searching for the critical target to suppress PCSCs and metastasis. Herein, we demonstrated that TAMs-secreted CCL5 could significantly promote the migration, invasion, epithelial–mesenchymal transition (EMT) of prostate cancer cells as well as the self-renewal of PCSCs in vitro. QPCR screening validated STAT3 as the most significant response gene in prostate cancer cells following CCL5 treatment. RNA-sequencing and mechanistic explorations further revealed that CCL5 could promote PCSCs self-renewal and prostate cancer metastasis via activating the β-catenin/STAT3 signaling. Notably, CCL5 knockdown in TAMs not only significantly suppressed prostate cancer xenografts growth and bone metastasis but also inhibited the self-renewal and tumorigenicity of PCSCs in vivo. Finally, clinical investigations and bioinformatic analysis suggested that high CCL5 expression was significantly correlated with high Gleason grade, poor prognosis, metastasis as well as increased PCSCs activity in prostate cancer patients. Taken together, TAMs/CCL5 could promote PCSCs self-renewal and prostate cancer metastasis via activating β-catenin/STAT3 signaling. This study provides a novel rationale for developing TAMs/CCL5 as a potential molecular target for PCSCs elimination and metastatic prostate cancer prevention.

/pdf/ccl5-derived-from-tumor-associated-macrophages-promotes-3ntvaru4re.pdf

CCL5 derived from tumor-associated macrophages promotes prostate cancer stem cells and metastasis via activating β-catenin/STAT3 signaling.

Tumor-associated macrophages (TAMs), the most abundant infiltrating immune cells in tumor microenvironment, have distinct functions in hepatocellular carcinoma (HCC) progression. CD68⁺ TAMs represent multiple polarized immune cells mainly containing CD86⁺ antitumoral M1 macrophages and CD206⁺ protumoral M2 macrophages. TAMs expression and density were assessed by immunohistochemical staining of CD68, CD86, and CD206 in tissue microarrays from 253 HCC patients. Clinicopathologic features and prognostic value of these markers were evaluated. We found that CD68⁺ TAMs were not associated with clinicopathologic characteristics and prognosis in HCC. Low presence of CD86⁺ TAMs and high presence of CD206⁺ TAMs were markedly correlated with aggressive tumor phenotypes, such as multiple tumor number and advanced tumor-node-metastasis (TNM) stage; and were associated with poor overall survival (OS) (p = 0.027 and p = 0.024, respectively) and increased time to recurrence (TTR) (p = 0.037 and p = 0.031, respectively). In addition, combined analysis of CD86 and CD206 provided a better indicator for OS (p = 0.011) and TTR (p = 0.024) in HCC than individual analysis of CD86 and CD206. Moreover, CD86⁺/CD206⁺ TAMs predictive model also had significant prognosis value in α-fetoprotein (AFP)-negative patients (OS: p = 0.002, TTR: p = 0.005). Thus, these results suggest that combined analysis of immune biomarkers CD86 and CD206 could be a promising HCC prognostic biomarker.

/pdf/cd86-cd206-diametrically-polarized-tumor-associated-2mmni1nc8s.pdf

CD86⁺/CD206⁺, Diametrically Polarized Tumor-Associated Macrophages, Predict Hepatocellular Carcinoma Patient Prognosis.

Background: Prostate cancer (PCa) is one of the most frequently diagnosed cancers in the world. Emerging evidence suggests that inflammatory cells such as M2 macrophages and regulatory T cells (Tre ...

https://onlinelibrary.wiley.com/doi/pdf/10.1002/pros.23742

M2 macrophages and regulatory T cells in lethal prostate cancer

Recent studies have revealed that alternatively activated macrophages (AAMs) are involved in tumor progression. However, the effect of AAMs on the metastasis of prostate cancer is poorly understood. In the present study, the prostate tissues of 42 patients with prostate adenocarcinoma (PCa) were used in the analysis of tumor associated macrophages (TAMs) and AAMs by immunofluorescence. The patients were followed up for 5 years. The associations of TAMs and AAMs with the clinicopathological features and outcome in these cases were evaluated. Immunofluorescent analysis indicated that the mean number of TAMs (CD68-positive cells) in the prostate tissues of PCa patients with metastasis [45.29±7.25 cells/high-power field (HPF)] was significantly higher compared with that of PCa patients without metastasis (33.57±5.25 cells/HPF; P<0.01). The mean numbers of AAMs (CD68- and CD206-positive cells) in the tissues of PCa patients with and without metastasis were 29.43±5.68 and 9.14±5.29 cells/HPF, respectively. In addition, the percentage of AAMs (number of AAMs/number of TAMs) was 65.11±9.68 and 27.32±7.85% in patients with and without metastasis, respectively. The differences in the number and percentage of AAMs between the two groups were statistically significant (P<0.01). The number and percentage of AAMs was positively correlated with tumor grade and serum prostate-specific antigen (PSA) level. Univariate analysis indicated that the level of PSA, Gleason score, metastatic status, T grade, number of TAMs, number of AAMs and percentage of AAMs were predictors of the overall survival. Furthermore, multivariate analyses revealed that Gleason score, level of PSA and number of TAMs were predictors for overall survival rate. These results indicate that TAMs and AAMs may be important in the metastasis of PCa, and that TAMs and AAMs may be used as potential biomarkers of poor prognosis in late-stage PCa patients.

/pdf/alternatively-activated-macrophages-are-associated-with-3igpe2c02i.pdf

Alternatively activated macrophages are associated with metastasis and poor prognosis in prostate adenocarcinoma

Chronic kidney disease accounts for much of the increased mortality, especially in the elder population. The prevalence of this disease is expected to increase significantly as the society ages. Our aim was to evaluate the kidney function and risk factors of reduced renal function among elderly Chinese patients. This study retrospectively collected clinical data from a total of 1062 inpatients aged 65 years or over. Estimated glomerular filtration rate (eGFR) was calculated with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Renal function and risk factors were also analyzed. For all 1062 subjects, the mean eGFR was 71.0 ± 24.8 mL/min/1.73 m2, and the incidence rates of reduced renal function, proteinuria, hematuria and leukocyturia were 31.1%, 11.8%, 6.6% and 8.7%, respectively. The eGFR values were 83.4 ± 28.4, 72.2 ± 22.9, 67.8 ± 24.3 and 58.8 ± 29.1 mL/min/1.73 m2 in the groups of 60–69, 70–79, 80–89 and ≥90 years age group (F = 15.101, p = 0.000), respectively; whil...

A retrospective analysis of kidney function and risk factors by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in elderly Chinese patients

Aim This study was purposed to figure out the contribution of Numb-induced Notch signaling to the development of diabetic nephropathy (DN). Methods Two hundred and twenty six DN patients were included, and human glomerular endothelial cells (RGEC) were cultured. MSCV-Numb-IRES-GFP, MSCV-Notch1-IRES-GFP and MSCV-Hes1-IRES-GFP were transfected to construct the recombinant retroviral vectors. Result The over-expressed Numb and Notch1, as well as the under-expressed Hes-1 were correlated with the undesirable prognosis of DN patients (P  Conclusion Numb negatively regulated Notch signaling pathway in EMT of DN, implying that they had great potentials to serve as therapeutic targets or diagnostic biomarkers for DN.

The implication of Numb-induced Notch signaling in endothelial-mesenchymal transition of diabetic nephropathy

Statement of Retraction We, the Editors and Publisher of the journal Cell Cycle, have retracted the following article: Feng Yu, Ying Lin, Guojie Tan, Maomao Ai, Huicheng Gong, Wei Liu, Jiali Huang and Zirou Zou. Tumor-derived exosomal microRNA-15b-5p augments laryngeal cancer by targeting TXNIP. Cell Cycle. 2020;21(7):730-740. doi: 10.1080/15384101.2021.2022845 Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors did not provide their original data or any necessary supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. The authors agree/do not agree with the retraction. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

RETRACTED ARTICLE: Tumor-derived exosomal microRNA-15b-5p augments laryngeal cancer by targeting TXNIP

BACKGROUND Recent studies show that alternatively activated macrophages (AAMs) are involved in tissue remodeling and fibrosis. However, the relationship between AAMs and the development of benign prostate hyperplasia (BPH) is unclear. The aim of this study is to investigate the correlation among AAMs, prostate volume, and lower urinary tract symptoms (LUTS) severity of benign prostate hyperplasia (BPH) patients. METHODS Patients who underwent transurethral incision of the prostate (TUIP) for BPH were recruited and international prostatic symptom scores (IPSS) were assessed before the operations. Patients were divided into two groups: small (< 40  mL) and large prostate (≥ 40 mL) groups. Total macrophages (CD68) and AAMs (co-localization of CD68 and CD206) were analyzed by immunofluorescence. Prostate volume, post-voided residual volume (PVR), maximal (Qmax) and average (Qave) urinary flow rate were measured. We compared AAMs and clinical features between groups and analyzed the relationship of AAMs and these clinical parameters. RESULTS A total of 42 patients diagnosed with BPH were recruited. The numbers of AAMs in prostate tissues of BPH patients with small prostate (n = 20) (5.15 ± 2.32 cells/HP) were significantly lower than those of large prostate (n = 22) (7.73 ± 2.83 cells/HP) (p < 0.05). Moreover, percentages of AAMs (AAMs/total macrophages) of small prostate patients (17.28 ± 6.62%) were lower than those of large prostate patients (23.30 ± 8.66%) (p < 0.05). Pearson's correlation analysis showed the numbers of AAMs were significantly positively correlated with prostate volume (r = 0.509, p < 0.01) and international prostatic symptom score (r = 0.344, p < 0.05). Percentages of AAMs were positively correlated with prostate volume (r = 0.447, p < 0.01). CONCLUSIONS AAMs are associated the degree of BPH and the severity of LUTS, which indicates that AAMs may play an important role in development of BPH.

Alternatively Activated Macrophages are Associated with Prostate Volume and Lower Urinary Tract Symptoms Severity of Patients with Benign Prostate Hyperplasia.

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