Tumor suppressive function of Matrin 3 in the basal-like breast cancer

BACKGROUND: Basal-like breast cancer (BLBC) or triple-negative breast cancer (TNBC) is an aggressive and highly metastatic subtype of human breast cancer. The present study aimed to elucidate the potential tumor-suppressive function of MATR3, an abundant nuclear protein, in BLBC/TNBC, whose cancer-relevance has not been characterized. METHODS: We analyzed in vitro tumorigenecity by cell proliferation and soft agar colony formation assays, apoptotic cell death by flow cytometry and Poly (ADP-ribose) polymerase (PARP) cleavage, epithelial-mesenchymal transition (EMT) by checking specific EMT markers with real-time quantitative PCR and in vitro migration and invasion by Boyden Chamber assays. To elucidate the underlying mechanism by which MATR3 functions as a tumor suppressor, we performed Tandem affinity purification followed by mass spectrometry (TAP-MS) and pathway analysis. We also scrutinized MATR3 expression levels in the different subtypes of human breast cancer and the correlation between MATR3 expression and patient survival by bioinformatic analyses of publicly available transcriptome datasets. RESULTS: MATR3 suppressed in vitro tumorigenecity, promoted apoptotic cell death and inhibited EMT, migration, and invasion in BLBC/TNBC cells. Various proteins regulating apoptosis were identified as MATR3-binding proteins, and YAP/TAZ pathway was suppressed by MATR3. MATR3 expression was inversely correlated with the aggressive and metastatic nature of breast cancer. Moreover, high expression levels of MATR3 were associated with a good prognosis of breast cancer patients. CONCLUSIONS: Our data demonstrate that MATR3 functions as a putative tumor suppressor in BLBC/TNBC cells. Also, MATR3 potentially plays a role as a biomarker in predicting chemotherapy-sensitivity and patient survival in breast cancer patients.

Long-Term (Postnatal Day 70) Outcome and Safety of Intratracheal Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Neonatal Hyperoxic Lung Injury

PURPOSE: This study was performed to evaluate the long-term effects and safety of intratracheal (IT) transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in neonatal hyperoxic lung injury at postnatal day (P)70 in a rat model. MATERIALS AND METHODS: Newborn Sprague Dawley rat pups were subjected to 14 days of hyperoxia (90% oxygen) within 10 hours after birth and allowed to recover at room air until sacrificed at P70. In the transplantation groups, hUCB-MSCs (5x10(5)) were administered intratracheally at P5. At P70, various organs including the heart, lung, liver, and spleen were histologically examined, and the harvested lungs were assessed for morphometric analyses of alveolarization. ED-1, von Willebrand factor, and human-specific nuclear mitotic apparatus protein (NuMA) staining in the lungs and the hematologic profile of blood were evaluated. RESULTS: Impaired alveolar and vascular growth, which evidenced by an increased mean linear intercept and decreased amount of von Willebrand factor, respectively, and the hyperoxia-induced inflammatory responses, as evidenced by inflammatory foci and ED-1 positive alveolar macrophages, were attenuated in the P70 rat lungs by IT transplantation of hUCB-MSCs. Although rare, donor cells with human specific NuMA staining were persistently present in the P70 rat lungs. There were no gross or microscopic abnormal findings in the heart, liver, or spleen, related to the MSCs transplantation. CONCLUSION: The protective and beneficial effects of IT transplantation of hUCB-MSCs in neonatal hyperoxic lung injuries were sustained for a prolonged recovery period without any long-term adverse effects up to P70.

Nuclear matrix proteins differentially expressed in human prostate cancer cell lines and benign prostatic hyperplasia epithelial cell line / 中华男科学杂志

<p><b>OBJECTIVE</b>To compare the expression of nuclear matrix proteins (NMPs) in benign prostatic hyperplasia (BPH) epithelial cell line BPH-1 versus those in androgen-dependent human prostate cancer cell line LNCap and androgen-independent prostate cancer cell line PC-3.</p><p><b>METHODS</b>We isolated NMPs from the BPH-1, LNCap and PC-3 cell lines by 2-dimensional electrophoresis (2-DE), analyzed the differentially expressed proteins by matrix-assisted laser desorption / ionization time of flight mass spectrometry (MALDI-TOF-MS), and identified them by peptide mass fingerprint and database searching.</p><p><b>RESULTS</b>We successfully obtained well-resolved reproducible 2-DE patterns of NMPs in human prostate cancer cell lines, identified 12 differentially expressed NMPs including enzymes, regulatory proteins, RNA-binding protein and various other factors, 3 up-regulated and 9 down-regulated in prostate cancer cell lines.</p><p><b>CONCLUSION</b>There are obvious differences in the expressions of NMPs between human prostate cancer cell lines and benign prostatic hyperplasia epithelial cell line.</p>

Identification and characterization of nuclear matrix protein[s] and assessment of its usefullness for early diagnosis of bladder cancer

The highest incidence rates of bladder cancer are generally found in industrially developed countries, particularly North America and Western Europe, and areas associated with endemic schistosomiasis, including parts of Africa and the Middle East. The appropriate treatment of patients with bladder cancer mandates early detection and regular follow up for recurrences. Currently, cystoscopy is the standard method for diagnosing and monitoring bladder cancer recurrence, but it is an invasive and relatively costly technique, and may sometimes be inconclusive, particularly in cases of cystitis. Western blot and specific immunoglobulin-G antibody were used to identify the urinary NMP marker. Urine samples from 123 patients with bladder cancer and 50 controls were evaluated using the developed SDS-PAGE, Western blot and ELISA. The NMP marker was identified in the urine of patients with bladder cancer at 52 kDa [NMP- 52] by SDS-PAGE, Western blot and ELISA. In addition, the NMP-52 tumor marker was not detected in the urine of patients. Detecting the urinary NMP-52 marker using SDS-PAGE, Western blot and ELISA, would be helpful in the rapid diagnosis of bladder cancer

Nuclear matrix protein [NMP 22] as a diagnostic tool in urinary bladder cancer

To evaluate the role of urinary nuclear matrix protein NMP22 in urinary bladder cancer diagnosis. From August 2003 to January 2007, 373 patients, were enrolled in this study in Al Noor Specialist Hospital K.S.A and Urology Department in Benha Faculty of Medicine, patients were complaining of hematuria, LUTS, and bladder mass suspected On U/S examination, after clinical evaluation including complete history, general and local examination especially D.R.E, 50 ml of midstream morning urine samples was taken from all patients and examined for complete urine analysis and for detection of urine level of NMP 22 assay, cystoscopy, and TUR resection was done for all the patients and comparative analysis was done for the results of the cystoscopy, histopathology and NMP22 assay results. The results of the present study revealed that there was decreased overall sensitivity [28.2%] and specificity was [75%] ofNMP 22 in diagnosing transitional cell carcinoma of the bladder in comparison with confirmed cystoscopic positive results [98.8%] but the specificity and sensitivity increases in large invasive tumors to be [56.7%], and specificity [75%]. NMP22 could be considered a diagnostic or screening tool only in high grade transitional cell carcinoma, invasive or large advancing tumor, but NMP22 could not replace cystoscopy as the gold standard for cancer bladder diagnosis

Effects of NKG2D and its ligands RAE-1 and H60 on graft-versus-tumor response / 中国实验血液学杂志

The study was purposed to explore the effects of NKG2D receptor and its ligands RAE-1 and H60 on graft-versus-tumor (GVT) response induced by MHC haploidentical bone marrow/spleen cell transplantation. Female (BALB/c x C57BL/6) F1 mice (CB6F1, H-2K(b/d)) inoculated with H22 cells to develop a solid tumor model were the recipients, and bone marrow mixed with spleen cells of the healthy male C57BL/6 (H-2K(b)) mice were the donor cells. GVT response was observed after transplantation that from donor cells T and NK cells were purged with anti-CD3 and anti-NK monoclonal antibody, and the NKG2D receptor was blocked with anti-NKG2D monoclonal antibody, the expression levels of RAE-1 and H60 mRNA in tumor tissue were measured by means of semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) at different time points after transplantation. The results showed that the GVT response of transplantation was reduced after in vitro depletion of T and NK cells or blocking NKG2D receptor in donor cells of the graft, the expression levels of RAE-1 and H60 mRNA in tumor tissue increased after transplantation of haploidential bone marrow mixed with spleen cells. It is concluded that NKG2D and its ligands RAE-1 and H60 may play important roles in GVT response.

Usefulness of NMP22 BladderChek for the Diagnosis and Monitoring of Bladder Cancer / 대한진단검사의학회지

BACKGROUND: As bladder cancer is a superficial tumor with frequent recurrences, early detection and confirmation of recurrence are important. We evaluated the usefulness of NMP22 BladderChek (NMP22BC) for the diagnosis and monitoring of bladder cancer. METHODS: From July to December 2004, we enrolled in the study 670 patients who visited the urology clinic in Ewha Womans University, Dongdaemun Hospital with hematuria or dysuria and were tested with NMP22BC. We also performed the NMP22BC and BTA stat tests simultaneously in 21 patients and interference test in 10 patients. RESULTS: NMP22BC tests were negative in 97% of the patients who had been cured of bladder cancer and were positive in 95% of the patients with recurred bladder cancer. The diagnostic sensitivity, specificity, positive and negative predictive value, and efficiency were 95.0%, 91.5%, 25.7%, 99.8%, and 91.6%, respectively, with 8.5% false positive and 5% false negative rates. Fifty-five patients showed false positive in the NMP22BC test, the main cause of which was the presence of WBCs in urine. There was a good agreement between the NMP22BC and BTA stat tests (kappa agreement value, 0.5; P=0.008). According to the interference test, two patients with more than 3+ in leukocyte esterase results showed false positive in the NMP22BC test. CONCLUSIONS: NMP22BC test was simple to perform, rapid to produce the results, and useful in diagnosing a bladder cancer recurrence; the test shows a high efficiency with a high sensitivity, specificity, negative predictive value, and low false negative rate.

Proteomic analysis of nuclear matrix proteins during arsenic trioxide induced apoptosis in leukemia K562 cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Arsenic trioxide (As2O3) has been identified as a very potent anti-acute leukemic agent. However its role in apoptosis needs to be elucidated. As2O3 interferes with the proliferation and survival of tumor cells via a variety of mechanisms. Drug-target interactions at the level of nuclear matrix (NM) may be critical events in the induction of cell death by As2O3. This study dealt with As2O3-target interactions at the level of NM in chronic myelogenous leukemia cell line K562 by proteomics.</p><p><b>METHODS</b>K562 cells were cultured in MEM and treated with different concentrations of As2O3. The nuclear matrix proteins were analyzed by high-resolution two-dimensional gel electrophoresis and computer-assisted image analysis.</p><p><b>RESULTS</b>As2O3 significantly inhibited the growth of chronic myelogenous leukemia cell line K562 at low concentrations. While more than 200 protein spots were shared among the nuclear matrices, about 18 distinct spots in the nuclear matrices were found characteristic for As2O3 treated cells.</p><p><b>CONCLUSIONS</b>As2O3 induces apoptosis in K562 cells in a dose and time-dependent manner. Our results demonstrated that for the detection of the onset of apoptosis, the alteration in the composition of nuclear matrix proteins was a more sensitive indicator than nucleosomal DNA fragmentation test. These results indicated that As2O3 might be clinically useful in the treatment of chronic myelogenous leukemia. The changes of nuclear matrix proteins in the treated cells can be used as a useful indicator for this treatment.</p>