OBJECTIVE: The activation of Janus kinase (JAK) and signal transducers and activators of transcription (STAT) plays an important role in the prognosis and targeted therapy of ovarian high-grade serous carcinoma (HGSC). Utilizing simple and practicable technique, this study aimed to evaluate the activation of JAK/STAT signaling pathway in ovarian HGSC patients, and investigated the correlation between the activation of JAK/STAT signaling pathway and the prognosis of the HGSC patients. METHODS: We performed immunohistochemistry of phosphorylated STAT3 (pSTAT3) and phosphorylated STAT5 (pSTAT5) on paraffin imbedded slides of 73 ovarian HGSC patients, and evaluated the expression level and range of both markers. According to the grading score of the immunostaining of pSTAT3 and pSTAT5, we divided the 73 ovarian HGSC cases into STAT3 low/high expression and STAT5 low/high expression groups, and analyzed the prognosis of the patients in different groups, in order to explore the relationship between the expression of pSTAT3 and pSTAT5 proteins and the prognosis of the HGSC patients. RESULTS: Some of the ovarian HGSC cases showed high expression of pSTAT3 and pSTAT5 protein level, which was related to the poorer prognosis of the HGSC patients. There was a significant difference in the expression level of pSTAT3 and pSTAT5 between the patients with better prognosis (survival time ≥3 years) and poorer prognosis (survival time < 3 years). The patients with higher protein expression of pSTAT3, pSTAT5 or both markers might have poorer prognosis, with significant shorter progression-free survival time and overall survival time (P < 0.001). CONCLUSION Immunostaining of pSTAT3 and pSTAT5 proteins might be helpful to evaluate and predict the prognosis of the ovarian HGSC patients, and to identify the patients who might have higher chances to respond to the STAT inhibitors and anti-angiogenesis therapy.
Humans ; Prognosis ; STAT5 Transcription Factor/metabolism* ; Neoplasms ; Signal Transduction ; Immunohistochemistry

OBJECTIVETo study on effects of different manipulation methods of acupuncture on the binding ability of signal transducers and activators of transcription (STAT5) in human peripheral blood mononuclear cells (PBMC) with DNA.

METHODSThirty healthy volunteers were randomly divided into 3 groups; reinforcing method group, reducing method group, normal control group, 10 cases in each group. The expression of STAT5 mRNA and the activation of STAT5 in the human PBMC were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA).

RESULTSIn the reinforcing method group, the basic transcription level of STATS mRNA in human PBMC and the binding ability of STAT5 with DNA significantly increased (P<0.01), but in the reducing method group, they did not significantly change as compared with those in the normal control group (P>0.05).

CONCLUSIONCytokines and JAK/STAT signal transduction pathway are in volved in immunoregulative actions of acupuncture of the reinforcing method, but the reasons of influencing the transcription level of STAT5 mRNA and the binding ability of STAT5 with DNA are unclear.

Acupuncture Therapy ; Humans ; Leukocytes, Mononuclear ; RNA, Messenger ; STAT5 Transcription Factor ; Signal Transduction

Signal transducer and activator of transcription 5 (STAT5) is an important transcription factor existing in the cytoplasm of various types of cells. Once activated, STAT5 dimers translocate into nucleus and bind to the corresponding DNA sequence to regulate the transcription of its target genes. There are two isoforms of STAT5: STAT5A and STAT5B with 96% sequence homology and are encoded by two closely related but different genes. Studies have shown that STAT5 can regulate the survival, proliferation, differentiation and death of hematopoietic cells. Furthermore, elevated activation of STAT5 was found in many malignant hematologic diseases and therefore raised the possibility that STAT5 may be used as a new therapeutic target for blood related diseases. This review discusses the regulatory role of STAT5 in hematopoietic cells and its effect on the occurrence and development of blood diseases.
Animals ; Hematologic Diseases ; genetics ; metabolism ; Hematopoietic System ; metabolism ; Humans ; STAT5 Transcription Factor ; genetics ; metabolism

OBJECTIVE: To study the effects of iron metabolism abnormality on EPO-STAT5 signaling pathway in anemia patients. METHODS: According to diseases, the patients were divided into 3 groups: lower risk myelodysplastic syndrome (MDS) group (30 cases) including 14 cases of non-iron over load and 16 cases of iron over load, 12 cases of them were treated by iron chelation therapy; anemia of chronic disease (ACD) group (12 cases) and iron deficiency anemia (IDA) group (12 cases). In addition, the healthy control group was selected. The iron metaloslism index (SF, SI, TIBC), serum level of EPO, plasma level of P-STAT5 and STAT-5 mRNA expression in peripheral blood cells were detected and compared in different groups. Moreover, the effects of iron metabolism abnormality on the expression of EPO and STAT5 in anemia patients were analyzed. RESULTS: compared with non-iron over load group, the EPO level in iron over load group significantly increased (P<0.05), the expression of STAT5 mRNA and P-STAT5 significantly decreased (P<0.05). After iron chelation therapy, the EPO level in serum significantly decreased (P<0.05), the expression of STAT5 mRNA and P-STAT5 was up-regulated significantly (P<0.05). Compared with healthy control group, the expression of EPO in ACD group was down-regulated significantly, while the expression of STAT5 mRNA was not different, but the P-STAT5 expression was down-regulated significantly (P<0.05). Compared with the healtly control group, the EPO expression in IDA group was enhanced significantly (P<0.05), the expression of STAT5 mRNA and P-STAT5 were also significantly enhanced (P<0.05). CONCLUSION The excessive iron load or chronic inflammation may inhibit the activation of EPO-STAT5 signaling pathway and aggravate the anemia.
Anemia ; Anemia, Iron-Deficiency ; Erythropoietin ; Humans ; Iron ; STAT5 Transcription Factor ; Signal Transduction

Signal transducer and activator of transcription 5 (STAT5) can be involved in the processes such as cell proliferation, differentiation, apoptosis, and hematopoiesis, and its dysregulation is closely associated with the development and progression of malignant tumors including leukemia and may affect the treatment outcome and prognosis of pediatric patients. Identification of STAT5 can facilitate targeted therapy to improve the response rate of children with acute lymphoblastic leukemia. This article reviews the impact of STAT5 on the development/progression, targeted therapy strategies and the prognosis of childhood acute lymphoblastic leukemia.
Apoptosis ; Cell Proliferation ; Child ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; STAT5 Transcription Factor ; Signal Transduction

To explore the effectiveness and safety of a Chinese medicinal decoction Wuwei Xiaodu Drink (WWXDD) in inhibiting chronic osteomyelitis via regulatory T cells signaling. The effective constitutes of WWXDD and osteomyelitis related genes were screened. Target proteins were cross-validated using the Venny database. GO function and KEGG pathway analysis were performed for target proteins, while pharmacological network was constructed. The bone properties were analyzed by HE staining and the concentrations of immune factors were measured by ELISA. The expression of CTLA-4 and Foxp3 mRNA and STAT5, p-STAT5, CTLA-4 and Foxp3 protein were detected using Real-time PCR and Western blot, respectively. FACS was used to analyze the percentages of cells. A total of 117 genes overlapped between 785 target genes of the active compounds of WWXDD and 912 osteomyelitis related genes. Inflammation-related genes, including IL-6, TNFα, IL-1β and IL-2 showed high connection degree in the drug-compound-disease-target network. GO function and KEGG pathway analysis revealed that 117 intersection genes mainly enriched in virus infection related pathways, immune related pathways and chemokine signaling pathway. Furthermore, the development of chronic osteomyelitis was suppressed in model rats after treatment with WWXDD. Meanwhile, the concentrations of IL-2 and CD4⁺CD25⁺Foxp3 Treg percentages together with the levels of p-STAT5, CTLA-4 and Foxp3 were also down-regulated. Furthermore, IL-2 and WWXDD drug-containing serum exhibited opposite effects on regulating IL-2, IL-10, TGF-β1, Foxp3, CTLA4 and STAT5. In addition, a STAT5 phosphorylation inhibitor suppressed the expression of Foxp3 and CTLA-4. WWXDD can treat chronic osteomyelitis through suppressing the main regulating factors of Tregs and interfere its immunodepression. Our results bring a new solution for chronic osteomyelitis.
Animals ; Forkhead Transcription Factors/metabolism* ; Interleukin-2/metabolism* ; Osteomyelitis/metabolism* ; Rats ; STAT5 Transcription Factor/metabolism* ; Signal Transduction ; T-Lymphocytes, Regulatory

This study was aimed to explore the effect of homoharringtonine in combination with AG490 on JAK2-STAT5 associated signal pathway in HEL cells, and analyze its mechanism so as to provide theoretical basis for therapy of chronic myeloproliferative neoplasma by new program. The cell survival rates were tested by MTT, apoptosis was tested by flow cytometry after HEL cells were treated by 20 ng/ml HHT, 100 µmol/L AG490 and 20 ng/ml HHT in combination with 100 µmol/L AG490, while the signal proteins such as P-JAK2, P-STAT5 and BCL-xL activated by abnormal activated JAK2 were tested by Western blot. The results showed that both HHT and AG490 could inhabit the HEL cell proliferation after being treated for 24 hours, and Annexin V-PI double staining confirmed early apoptosis while HHT effect was more obvious, Western blot showed that the expressions of P-JAK2 and P-STAT5 were down-regulated, while the total protein levels of JAK2 and STAT5 were stable. It is concluded that HHT combined with AG490 can obviously inhibit the proliferation and induce early apoptosis of HEL cells, and there is synergistic effect between the two drugs. HHT possibly acts as a broad-spectrum PTK inhibitor and synergistically with AG490 inhibits the phosphorylation of signal proteins caused by JAK2V617F, thus down-regulating the transcription of STAT5.
Cell Line, Tumor ; Harringtonines ; pharmacology ; Humans ; Janus Kinase 2 ; metabolism ; STAT5 Transcription Factor ; metabolism ; Signal Transduction ; drug effects ; Tyrphostins ; pharmacology

PURPOSE: Cytokines, hormones and growth factors use signal transducers and activators of transcription (STAT) signaling pathways to control various biological responses, including development, differentiation, cell proliferation and survival. STAT3 and 5 help promote cell cycle progression and cellular transformation and prevent apoptosis. In this research, the presence of STAT3 and STAT5 activation and their association with pathological features and clinical outcome in renal cell carcinoma cases were studied. MATERIALS AND METHODS: Using immunohistochemistry with rabbit polyclonal anti-STAT3 and STAT5 antibodies, forty-eight paraffin-embedded renal cell carcinoma specimens were examined for the activation status of STAT3 and STAT5. Cells of which 10% or more were left with a dark brown stains in the nucleus were regarded as positive tumor cells. The activation status of STAT3 and STAT5 were compared with the clinicopathological variables. RESULTS: Significant associations of STAT3 activation with tumor size, T-stage, distant metastases and low survival rate were observed (p<0.05); and in STAT5, significant associations with distant metastases and low survival rate were observed (p<0.05). CONCLUSIONS: The results of this study strongly suggest that the activation of STAT3 and STAT5 contribute to the development and progression of the renal cell carcinoma.
Antibodies ; Apoptosis ; Carcinoma, Renal Cell* ; Cell Cycle ; Cell Differentiation ; Coloring Agents ; Cytokines ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; Neoplasm Metastasis ; STAT3 Transcription Factor ; STAT5 Transcription Factor ; Survival Rate ; Transducers

OBJECTIVETo investigate the frequency of JAK2 V617F mutation in 145 myeloproliferative disorders (MPDs) patients, analyze the correlation between JAK2 V617F mutation and clinical features.

METHODSThe JAK2 V617F mutation was detected by direct DNA sequencing of PCR product and allele-specific PCR respectively. The expression of JAK2, phospho-JAK2 and phospho-STAT5 proteins was determined by Western blot. The clinical data of MPDs patients with or without JAK2 V617F mutation was collected and analyzed for evaluating the clinical significance of JAK2 V617F mutation.

RESULTS1) The frequency of JAK2 V617F mutation for PV, IMF, ET was 92%, 58%, 50% respectively. Compared with conventional DNA sequencing (PV 84%, IMF 44%, ET 39%, respectively), allele-specific PCR exhibited a higher sensitivity in JAK2 V617F mutation detection. 2) The expression levels of phospho-JAK2 and phospho-STAT5 in peripheral blood mononuclear cells (PBMNCs) were upregulated significantly in JAK2 V617F-positive patients than in JAK2 V617F negative patients. 3) Compared with the patients with no JAK2 V617F mutation, the JAK2 V 617F-positive patients' features were as follows: older age of onset, higher mean leukocyte counts, lower platelet counts and smaller spleen volume. Frequency of thrombosis events in PT, ET, IMF was 17%, 32%, 16% respectively for JAK2 V617F positive group, and 0% (PV), 16% (ET), 5% (IMF) for JAK2 V617F negative group.

CONCLUSIONSMPDs patients display higher frequency of JAK2 V617F mutation. JAK2 V617F mutation positive patients predispose to a thrombosis tendency.

Female ; Humans ; Janus Kinase 2 ; genetics ; metabolism ; Male ; Mutation ; Myeloproliferative Disorders ; genetics ; metabolism ; Phosphorylation ; STAT5 Transcription Factor ; metabolism ; Sequence Analysis, DNA

Humans ; Leukemia, Promyelocytic, Acute ; genetics ; Oncogene Proteins, Fusion ; genetics ; Receptors, Retinoic Acid ; genetics ; Retinoic Acid Receptor alpha ; STAT5 Transcription Factor ; genetics