Home VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
Article Open Access

VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature

  • Ran Ren , Xin Chang , Cong Chen , Hao Yu and Lu Han EMAIL logo
Published/Copyright: December 11, 2023

Abstract

V-domain Ig suppressor of T cell activation (VISTA), encoded by the human VSIR gene, is a B7 family checkpoint homologous to the programmed death-Ligand 1 sequence. In gynecologic malignancies, VISTA is abnormally expressed and regulates the tumor immune microenvironment, causing a high upregulation of VISTA expression in T-cells and myeloid cells in the tumor microenvironment and promoting tumor proliferation, progression, and immune tolerance. Here, we review the research progress of VISTA in ovarian, cervical, and endometrial cancers through its structure and immunomodulatory mechanism. The comprehensive study of VISTA is expected to improve the current problem of poor immunotherapeutic effects and provide new ideas for immune therapy in patients with gynecologic tumors.

1 Introduction

V-domain Ig suppressor of T cell activation (VISTA), also known as programmed death-1homolog (PD-1H) [1,2], is a type I transmembrane protein domain encoded by the human VSIR gene encoding a type I transmembrane protein subunit, a recently identified B7 family checkpoint with sequence homology to programmed death-Ligand 1 (PD-L1), and the highest similarity to PD-L1 [3,4]. Similar to PD-1 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) immune checkpoints, VISTA decreases T cell activation and proliferation. VISTA is believed to exert significant immunological effects because of its specific structure, which can be both a ligand and a receptor. As a ligand, VISTA is expressed on antigen-presenting cells (APCs) and binds to receptors on T cells to inhibit downstream T cell activation. As a receptor, VISTA is expressed on T cells and transduces intracellular inhibitory signals on ligand binding to suppress T-cell activity [5]. In this review, we summarize the structure, expression, and immunomodulatory mechanism of VISTA, and suggest the feasibility of VISTA as a new immune checkpoint for the immunotherapy of gynecological tumors, to improve the treatment status and prognosis of gynecologic oncology patients.

2 Structure and expression of VISTA

The human VSIR gene encodes the VISTA protein. It is 279 amino acids in length, including a 162 amino acid extracellular structural domain, a 21 amino acid transmembrane structural domain, and a 96 amino acid cytoplasmic structural domain. The cytoplasmic structural domain lacks immunoreceptor tyrosine-based signal transduction sequences but contains multiple casein kinase two and phosphokinase C phosphorylation sites that play a significant role in signal transduction. VISTA gene sequence analysis revealed surprisingly high conservation, with 76% homology between mice and humans, especially in the cytoplasmic structural domain, making mice the most suitable experimental subjects for studying VISTA. The analysis of VISTA protein sequences revealed that VISTA is similar to the B7 family group of ligands (CD80, CD86, PD-L1, PD-L2, ICOSL, and CD276), all of which contain a conserved immunoglobulin variable-like fold. PD-L1 in the B7 family shares 23% sequence homology with VISTA [6]. However, unlike traditional B7 family members, the intracytoplasmic structural domain of VISTA does not contain ITAM, ITMM, or ITSM sequences. In contrast, the intracellular tail of VISTA contains two potential protein kinase C binding sites and a proline residue that may serve as a docking site and includes an Ig-V structural domain. Thus, VISTA may act as both a receptor and a ligand [2].

At the cellular level, VISTA is mainly found in the hematopoietic tissue of human peripheral blood mononuclear cells (PBMCs). VISTA was expressed at high levels on the CD11CloCD123+HLA-DR+lymphoid lineage and CD11C+CD123LOHLA-DR+ myeloid subpopulation of monocytes and dendritic cells, at moderate levels on CD4+T, CD8+T, and FOXP3+CD4+Tregs expressing cells, at low levels on thymocytes, CD56loNK cells, and completely absent on CD56hiNK cells and CD19+ B cells [79]. However, Bharaj has found that in human PBMCs, there was VISTA expression in CD3+ T cells and CD19+ B cells, which was considered as a different result of different antibody types [10]. In addition, the expression of VISTA gradually decreased with time in vitro culture.

At the tissues and organs, transcription of Vsir genes in adult individuals under normal conditions occurs mainly in lymphoid tissues such as the spleen, thymus, and bone marrow [11]. In non-hematopoietic organs, VISTA expression is usually highest in the brain, stomach, and thyroid, while it is expressed at intermediate levels in the spleen and liver and rarely in bone and heart [12]. Lower levels of VISTA-mRNA were detected in the lung, muscle, testis, kidney, and placenta.

A series of studies have examined VISTA expression in human tumors, including acute myeloid leukemia, prostate cancer, cutaneous melanoma, hepatocellular carcinoma, gestational trophoblastic tumors, and breast cancer [1318]. Increased expression of VISTA in different tumors is usually accompanied by tumor progression and recurrence, and predicts low patient survival [19,20].

3 Immunomodulatory mechanisms of VISTA

When VISTA acts as a ligand, it negatively regulates T-cell activation [21]. The extracellular structural domain of VISTA interacts with coinhibitory receptors on T cells to inhibit T cell proliferation and cytokine (IL-2 and IFN-γ) production, and naïve T cells and memory T-cells are sensitive to Vista-mediated suppression by inhibiting phosphorylation of T cell receptor proximal signaling molecules (LAT, PLC-γ1, and SLP76) and upregulation of early activation markers (CD69, CD44, and CD25) [22]. In the presence of exogenous TGF-β, VISTA promotes the conversion of FOXP3-CD4+ T cells to FOXP3+ adaptive regulatory T cells. This effect contributes to the overall T-cell suppressive effect of VISTA.

When VISTA acts as a receptor, its expression on the surface of CD4+ T cells is independent of acting APCs on T cells. When CD4+ T cells were exposed to Vista–/–APCs, it resulted in increased cell proliferation and promoted the production of IFNγ, TNF-α, and IL-17A. It suggests that VISTA can act as a suppressor receptor for CD4+ T cells. Recently, Shahbaz et al. showed that Vista+ CD71+ red lineage cells produce more TGF-β and promote the production of Tregs from primitive CD4+ T cells by inhibiting p-Akt and p-mTOR [23].

Abnormal VISTA expression can cause sustained tumor growth acceleration; conversely, blocking VISTA expression enhances the T-cell antitumor response and slows tumor progression. A VISTA/PD-1 double knockout mouse model found that VISTA inhibits T cell activation through a pathway different from PD-1 to achieve immune escape of tumor cells (TCs) [22]. VISTA acts as a ligand on TCs and mediates negative immune regulation by inhibiting the activity of CD4+ and CD8+ T cells and suppressing immune cell (IC) activity. When VISTA molecules act as receptors, they are highly expressed in bone marrow-derived suppressor cells (MDSCs) and significantly inhibit IC responses in the tumor microenvironment (TME). VISTA expression is upregulated on MDSCs in various human tumor types, exerting a powerful tumor-infiltrating lymphocyte suppressing function and promoting their immunosuppression [24].

4 Association of VISTA with gynecologic tumors

As a close relative of PD-1/PD-L1, VISTA is also aberrantly expressed in gynecologic malignancies and regulates ICs and related cytokines in the TME, which promotes tumor proliferation, progression, and immune tolerance. VISTA expression has been demonstrated in tumor-associated ICs and/or TCs in different types of cancer. However, in contrast with its negative regulatory role in T-cell responses, increasing evidence suggests that VISTA expression on TCs or ICs correlates with improved survival among patients with ovarian, cervical cancer, and endometrial cancer.

4.1 Ovarian cancer and VISTA

Ovarian cancer has the highest mortality rate among the three primary female reproductive system tumors [25], and the current first-line treatment with surgery and postoperative platinum-based chemotherapy is ineffectual, with most patients experiencing postoperative recurrence and platinum resistance, which significantly affects the prognosis of ovarian cancer patients [26]. Recent immunotherapeutic approaches to kill ovarian cancer cells through CTLA-4, PD-1/PD-L1, and other immune target inhibitors such as Pembrolizumab and Nivolumab to interfere with immune modulation in ovarian cancer TME have shown initial success, and immunotherapy with VISTA and ovarian cancer is in full swing [2729].

Mulati et al. have found that VISTA is expressed more often in ovarian cancer TCs than in normal cells. In mice with ovarian cancer cells expressing high levels of VISTA, a significant decrease in the abundance of CD8+ T cells in the TME, infiltration of IFN-γ-producing T cells, and upregulation of MDSC accumulation were observed [30]. This dynamic immunological alteration in the TME reflects accelerated migration of MDSCs to the tumor site and increased infiltration of immature myeloid cells that may differentiate into MDSCs at the tumor site. However, VISTA antibodies blocked the expression of VISTA on both TCs and ICs. However, the inhibitory effect of VISTA on tumors was much stronger than that on ICs. In a retrospective analysis of 65 ovarian cancer patients, the positive expression of VISTA was 30.8% in TCs and 44.6% in ICs. High expression of VISTA on TCs and ICs was correlated with advanced ovarian cancer and lymph node metastasis, probably because VISTA molecules can protect related TCs and ICs to achieve an immune escape effect [31].

Zong found by immunohistochemistry in 146 ovarian cancers that VISTA expression was associated with pathological type and PD-L1 expression. VISTA was frequently expressed in PD-L1-negative ovarian cancer tissues, and VISTA expression in TCs represented longer progression-free survival and a high survival rate [32]. This situation may be related to VISTA regulation of C10orf54 gene expression for tumor immune escape, but further in-depth study is needed.

In ovarian cancer mice animal experiments, the survival of mice added with anti-VISTA antibody was significantly prolonged. The expression of VISTA in TCs not only inhibited cytotoxic T lymphocytes (CTLs) from lysing antigen-specific cells but also considerably suppressed T cell proliferation. In addition, Mulati also found that VISTA treatment may be effective in ovarian cancer resistant to anti-PD-1 therapy expressing VISTA, which is expected to be a strategy to address PD-1 resistance in the future [30].

4.2 Cervical cancer and VISTA

Cervical cancer, one of the three major malignant tumors of the female reproductive system, has been greatly reduced by early screening, diagnosis, and treatment [33]. With the rapid development of surgery, radiotherapy, and chemotherapy, the treatment of cervical cancer has achieved specific achievements. However, the 5-year survival rate is still unsatisfactory, about 68%, and the recurrence rate for patients with advanced cervical cancer is about 40% [34]. Immunotherapy has a good prospect in the treatment of cervical cancer. Specific progress has been made through the treatment of PD-L1, CTLA-4, PARP, and other immune checkpoint inhibitors. However, it still has a limited role in advanced and recurrent cervical cancer, with high drug resistance, and usually requires combination therapy to be effective [35].

Human papillomavirus (HPV) positivity is a high-risk factor for the development of cervical cancer, and HPV positivity and viral load are independent risk factors for the recurrence of cervical cancer, which affects the outcome of cervical cancer treatment [36]. The disruption of the immune system partly leads to the inability of HPV to be cleared in time and the progression to cervical intraepithelial neoplasia or even cervical cancer. VISTA blocks the response of T cells to tumor antigens. It inhibits the differentiation of T cells to Treg cells, which reduces Foxp3 protein, causing the body to develop immune tolerance to TCs, leading to the immune escape of cancer cells.

Currently, there are fewer studies on VISTA in cervical cancer. Li et al. found differences in VISTA expression in 130 cervical cancer specimens in cervical chronic inflammation, cervical intraepithelial neoplasia, and cervical cancer. There was a correlation between VISTA and cervical cancer pathological stage, and VISTA expression was higher in patients with stage II cervical cancer [37]. The risk of death with positive VISTA expression was as high as 3.184 times that of VISTA negative, suggesting that VISTA is closely associated with the development of cervical cancer. Therefore, VISTA can be used as an auxiliary indicator for cervical cancer screening, preoperative disease severity assessment, and postoperative treatment outcome monitoring.

Kuang and He systematically researched the expression of VISTA in cervical cancer by using immunohistochemistry on 104 cervical cancer specimens [38]. It was found that the high expression of VISTA on ICs was 43.27%, correlated with advanced cervical cancer and lymph node metastasis, and greatly affected the median survival of cervical cancer patients. These suggest that VISTA is a potential predictor of cervical cancer progression. Therefore, VISTA could be a candidate biomarker for cervical cancer progression and lymph node status. In addition, cervical cancer is extensively infiltrated by ICs because of long-term HPV infection. VISTA could be used in the future as a potential immunotherapy target for cervical cancer to reduce “immune escape” by treating cervical cancer patients alone or in combination with other immunotherapy strategies.

4.3 Endometrial cancer and VISTA

Endometrial cancer is a common malignant tumor of the female reproductive tract, and its incidence has been increasing yearly in recent years, with an average annual increase of 1.9% [39]. Although immunotherapy based on immune checkpoint inhibitors such as CTLA-4 and PD-1/PD-L1 has significantly improved the objective remission rate and overall survival of patients with advanced malignancies, there are problems such as low efficiency of monotherapy, more immune-related adverse effects, and limited benefit audience [4042]. A retrospective analysis showed that VISTA expression was present in all endometrial cancer specimens under regulating promoter methylation status and that VISTA expressing in TCs inhibited CTLs against antigen-specific cytolysis and significantly suppressed T cell proliferation. In contrast, T cell proliferation and secretion of cytokines (IFN-γ, TNF-α) were restored when silencing the expression of VISTA [30].

Zong et al. studied 839 endometrial cancer patient tissues and found that 76.6% of ICs and 6.8% of TCs expressed VISTA, and that IC VISTA positivity was more common in FIGO stage I–III, PD-L1-positive, and DNA polymerase epsilon mutated (POLEmut) and mismatch repair-deficient types of endometrial cancer, and also positively correlated with recurrence-free survival in endometrial cancer patients [43]. VISTA is a predictor of improved prognosis independent of FIGO stage, molecular subtype, and mismatch repair functional status, and predicts improved survival in patients with endometrial cancer. However, the regulatory mechanism of VISTA in endometrial cancer is still unclear, and further studies are needed to enlighten the immunomodulatory mechanism of VISTA, as well as the prognostic impact and mechanism of anti-VISTA antibodies, to verify that VISTA can be used as a new biomarker and provide a new direction for immunotherapy of endometrial cancer.

5 Immunotherapy study of VISTA

Immunotherapy research on VISTA is currently underway, and several VISTA inhibitors and related antibodies are in the research phase. CA-170 is an oral small molecule antagonist targeting PD-L1 and VISTA that induces T cell proliferation and INF-γ production. In vitro studies have shown that CA-170 presents antagonistic effects on the PD-1/PD-L1/VISTA signaling pathway, promoting tumor infiltration and peripheral T-cell viability in a dose-dependent manner. In multiple tumor models in vivo, CA-170 also exhibited antitumor effects similar to those of anti-PD-1 or anti-VISTA antibodies [44]. Curis et al. investigated the efficacy of CA-170 in the treatment of patients with advanced solid tumors and lymphomas (NCT02812875).

Two VISTA-inhibitory monoclonal antibodies, CI-8993 and W0180, are currently entering clinical trials to study the therapeutic efficacy of solid tumors. Curis initiated CI-8993 in 2020 in a Phase I trial (NCT04475523) to evaluate the effectiveness, safety, and tolerability of CI8993 in treating patients with relapsed and refractory solid tumors. As well, CI-8993 was found to bind specifically to human-derived VISTA in vivo. WO180 was developed by Pierre Fabre as an IgG1 kappa-type antibody. The antibody is being tested in clinical trials for its antitumor effects and combination with PD-1 inhibitory monoclonal antibody (NCT04564417).

6 Conclusions

VISTA is closely associated with the development of gynecologic malignancies. Its unique protein structure as a “close neighbor” of B7 family PD-L1 makes it a new immunological research hotspot and promising for immunotherapy of gynecologic tumors. Research on VISTA in gynecologic tumors is continuing, and the biological role of VISTA in gynecologic tumors and the mechanisms of immune regulation in the TME still need further clarification. It is recommended to further explore the role of VISTA in the tumor immune microenvironment and patient prognosis. In the context of tumor immunotherapy, preclinical studies have shown a clear role of VISTA in anti-tumor immunity. Monoclonal antibodies and small molecules targeting human VISTA have been developed and are in early clinical trials for cancer treatment. Intensive research on VISTA is expected to improve the current problem of ineffective immunotherapy and provide new ideas for immunotherapy of gynecologic oncology patients.

  1. Funding information: None.

  2. Author contributions: The manuscript has been read and approved by all the authors, all journal requirements for authorship have been met, and each author believes that the manuscript represents honest work.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

References

[1] Flies DB, Han X, Higuchi T, Zheng L, Sun J, Ye JJ, et al. Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell-mediated immunity. J Clin Invest. 2014;124(5):1966–75.10.1172/JCI74589Search in Google Scholar PubMed PubMed Central

[2] Flies DB, Wang S, Xu H, Chen L. Cutting edge: a monoclonal antibody specific for the programmed death-1 homolog prevents graft-versus-host disease in mouse models. J Immunol Baltim Md. 1950 2011;187(4):1537–41.10.4049/jimmunol.1100660Search in Google Scholar PubMed PubMed Central

[3] Flies DB, Higuchi T, Chen L. Mechanistic assessment of PD-1H coinhibitory receptor-induced T cell tolerance to allogeneic antigens. J Immunol Baltim Md. 1950 2015;194(11):5294–304.10.4049/jimmunol.1402648Search in Google Scholar PubMed PubMed Central

[4] Mehta N, Maddineni S, Mathews II, Sperberg RAP, Huang P-S, Cochran JR. Structure and functional binding epitope of V-domain Ig suppressor of T cell activation. Cell Rep. 2019;28(10):2509–16.e5.10.1016/j.celrep.2019.07.073Search in Google Scholar PubMed

[5] Wang J, Wu G, Manick B, Hernandez V, Renelt M, Erickson C, et al. VSIG-3 as a ligand of VISTA inhibits human T-cell function. Immunology. 2019;156(1):74–85.10.1111/imm.13001Search in Google Scholar PubMed PubMed Central

[6] Oliveira P, Carvalho J, Rocha S, Azevedo M, Reis I, Camilo V, et al. Dies1/VISTA expression loss is a recurrent event in gastric cancer due to epigenetic regulation. Sci Rep. 2016;6:34860.10.1038/srep34860Search in Google Scholar PubMed PubMed Central

[7] Xu W, Hiếu T, Malarkannan S, Wang L. The structure, expression, and multifaceted role of immune-checkpoint protein VISTA as a critical regulator of anti-tumor immunity, autoimmunity, and inflammation. Cell Mol Immunol. 2018;15(5):438–46.10.1038/cmi.2017.148Search in Google Scholar PubMed PubMed Central

[8] Bharaj P, Chahar HS, Alozie OK, Rodarte L, Bansal A, Goepfert PA, et al. Characterization of programmed death-1 homologue-1 (PD-1H) expression and function in normal and HIV infected individuals. PLoS One. 2014;9(10):e109103.10.1371/journal.pone.0109103Search in Google Scholar PubMed PubMed Central

[9] Borggrewe M, Grit C, Den Dunnen WFA, Burm SM, Bajramovic JJ, Noelle RJ, et al. VISTA expression by microglia decreases during inflammation and is differentially regulated in CNS diseases. Glia. 2018;66(12):2645–58.10.1002/glia.23517Search in Google Scholar PubMed PubMed Central

[10] ElTanbouly MA, Croteau W, Noelle RJ, Lines JL. VISTA: a novel immunotherapy target for normalizing innate and adaptive immunity. Semin Immunol. 2019;42:101308.10.1016/j.smim.2019.101308Search in Google Scholar PubMed PubMed Central

[11] Wang L, Rubinstein R, Lines JL, Wasiuk A, Ahonen C, Guo Y, et al. VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses. J Exp Med. 2011;208(3):577–92.10.1084/jem.20100619Search in Google Scholar PubMed PubMed Central

[12] Wang G, Tai R, Wu Y, Yang S, Wang J, Yu X, et al. The expression and immunoregulation of immune checkpoint molecule VISTA in autoimmune diseases and cancers. Cytokine Growth Factor Rev. 2020;52:1–14.10.1016/j.cytogfr.2020.02.002Search in Google Scholar PubMed

[13] Pagliuca S, Gurnari C, Kewan T, Bahaj W, Zhang K, Mori M, et al. Transcriptomic profile identifies early signatures of immunoediting and a potential role for VISTA as a molecular target in acute myeloid leukemia. Blood. 2021;138:4467.10.1182/blood-2021-151834Search in Google Scholar

[14] Jindal V. Immunotherapy: a glimmer of hope for metastatic prostate cancer. Chin Clin Oncol. 2018;7(6):61.10.21037/cco.2018.02.01Search in Google Scholar PubMed

[15] Choi JW, Kim YJ, Yun KA, Won CH, Lee MW, Choi JH, et al. The prognostic significance of VISTA and CD33-positive myeloid cells in cutaneous melanoma and their relationship with PD-1 expression. Sci Rep. 2020;10(1):14372.10.1038/s41598-020-71216-2Search in Google Scholar PubMed PubMed Central

[16] Shrestha R, Prithviraj P, Anaka M, Bridle KR, Crawford DHG, Dhungel B, et al. Monitoring immune checkpoint regulators as predictive biomarkers in hepatocellular carcinoma. Front Oncol. 2018;8:269.10.3389/fonc.2018.00269Search in Google Scholar PubMed PubMed Central

[17] Zong L, Zhang M, Wang W, Wan X, Yang J, Xiang Y. PD-L1, B7-H3 and VISTA are highly expressed in gestational trophoblastic neoplasia. Histopathology. 2019;75(3):421–30.10.1111/his.13882Search in Google Scholar PubMed

[18] Kang J, Pilones KA, Daviaud C, Kraynak J, Rodriguez-Ruiz ME, Demaria S, et al. VISTA blockade immunotherapy in a MULTI-modal approach to triple negative breast cancer (TNBC) in MICE and IMPACT on microbiome. Int J Radiat Oncol. 2019;105:S88–9.10.1016/j.ijrobp.2019.06.561Search in Google Scholar

[19] Kuklinski LF, Yan S, Li Z, Fisher JL, Cheng C, Noelle RJ, et al. VISTA expression on tumor-infiltrating inflammatory cells in primary cutaneous melanoma correlates with poor disease-specific survival. Cancer Immunol Immunother J. 2018;67(7):1113–21.10.1007/s00262-018-2169-1Search in Google Scholar PubMed

[20] Deng J, Li J, Sarde A, Lines JL, Lee Y-C, Qian DC, et al. Hypoxia-induced VISTA promotes the suppressive function of myeloid-derived suppressor cells in the tumor microenvironment. Cancer Immunol Res. 2019;7(7):1079–90.10.1158/2326-6066.CIR-18-0507Search in Google Scholar PubMed PubMed Central

[21] Blando J, Sharma A, Higa MG, Zhao H, Vence L, Yadav SS, et al. Comparison of immune infiltrates in melanoma and pancreatic cancer highlights VISTA as a potential target in pancreatic cancer. Proc Natl Acad Sci U S A. 2019;116(5):1692–7.10.1073/pnas.1811067116Search in Google Scholar PubMed PubMed Central

[22] Liu J, Yuan Y, Chen W, Putra J, Suriawinata AA, Schenk AD, et al. Immune-checkpoint proteins VISTA and PD-1 nonredundantly regulate murine T-cell responses. Proc Natl Acad Sci U S A. 2015;112(21):6682–7.10.1073/pnas.1420370112Search in Google Scholar PubMed PubMed Central

[23] Shahbaz S, Bozorgmehr N, Koleva P, Namdar A, Jovel J, Fava RA, et al. CD71+ VISTA+ erythroid cells promote the development and function of regulatory T cells through TGF-β. PLoS Biol. 2018;16(12):e2006649.10.1371/journal.pbio.2006649Search in Google Scholar PubMed PubMed Central

[24] Wang L, Jia B, Claxton DF, Ehmann WC, Rybka WB, Mineishi S, et al. VISTA is highly expressed on MDSCs and mediates an inhibition of T cell response in patients with AML. Oncoimmunology. 2018;7(9):e1469594.10.1080/2162402X.2018.1469594Search in Google Scholar PubMed PubMed Central

[25] Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49.10.3322/caac.21660Search in Google Scholar PubMed

[26] Buechel M, Herzog TJ, Westin SN, Coleman RL, Monk BJ, Moore KN. Treatment of patients with recurrent epithelial ovarian cancer for whom platinum is still an option. Ann Oncol. 2019;30(5):721–32.10.1093/annonc/mdz104Search in Google Scholar PubMed PubMed Central

[27] Pujade-Lauraine E, Fujiwara K, Dychter SS, Devgan G, Monk BJ. Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN ovarian 200 phase III study design. Future Oncol Lond Engl. 2018;14(21):2103–13.10.2217/fon-2018-0070Search in Google Scholar PubMed

[28] Disis ML, Taylor MH, Kelly K, Beck JT, Gordon M, Moore KM, et al. Efficacy and safety of avelumab for patients with recurrent or refractory ovarian cancer: phase 1b results from the JAVELIN solid tumor trial. JAMA Oncol. 2019;5(3):393–401.10.1001/jamaoncol.2018.6258Search in Google Scholar PubMed PubMed Central

[29] Zamarin D, Burger RA, Sill MW, Powell DJ, Lankes HA, Feldman MD, et al. Randomized phase II trial of nivolumab versus nivolumab and ipilimumab for recurrent or persistent ovarian cancer: an NRG oncology study. J Clin Oncol J Am Soc Clin Oncol. 2020;38(16):1814–23.10.1200/JCO.19.02059Search in Google Scholar PubMed PubMed Central

[30] Mulati K, Hamanishi J, Matsumura N, Chamoto K, Abiko K, Baba T, et al. VISTA expressed in tumour cells regulates T cell function. Br J Cancer. 2019;120(1):115–27.10.1038/s41416-018-0313-5Search in Google Scholar PubMed PubMed Central

[31] Liao H, Zhu H, Liu S, Wang H. Expression of V-domain immunoglobulin suppressor of T cell activation is associated with the advanced stage and presence of lymph node metastasis in ovarian cancer. Oncol Lett. 2018;16(3):3465–72.10.3892/ol.2018.9059Search in Google Scholar PubMed PubMed Central

[32] Zong L, Zhou Y, Zhang M, Chen J, Xiang Y. VISTA expression is associated with a favorable prognosis in patients with high-grade serous ovarian cancer. Cancer Immunol Immunother. 2020;69(1):33–42.10.1007/s00262-019-02434-5Search in Google Scholar PubMed PubMed Central

[33] Enokida T, Moreira A, Bhardwaj N. Vaccines for immunoprevention of cancer. J Clin Invest. 2021;131(9):146956.10.1172/JCI146956Search in Google Scholar PubMed PubMed Central

[34] Orbegoso C, Murali K, Banerjee S. The current status of immunotherapy for cervical cancer. Rep Pract Oncol Radiother. 2018;23(6):580–8.10.1016/j.rpor.2018.05.001Search in Google Scholar PubMed PubMed Central

[35] Sherer MV, Kotha NV, Williamson C, Mayadev J. Advances in immunotherapy for cervical cancer: recent developments and future directions. Int J Gynecol Cancer. 2022;32(3):281–7.10.1136/ijgc-2021-002492Search in Google Scholar PubMed

[36] Yu MC, Austin RM, Lin JF, Beck TL, Beriwal S, Comerci JT, et al. The diagnostic utility of HR-HPV as a predictor of cervical cancer recurrence. Gynecol Oncol. 2014;133:64.10.1016/j.ygyno.2014.03.173Search in Google Scholar

[37] Li L, Xu X-T, Wang L-L, Qin S-B, Zhou J-Y. Expression and clinicopathological significance of Foxp3 and VISTA in cervical cancer. Am J Transl Res. 2021;13(9):10428–38.Search in Google Scholar

[38] Kuang L, He Y. Potential value of V-domain Ig suppressor of T-cell activation for assessing prognosis in cervical cancer and as a target for therapy. Int J Clin Exp Pathol. 2020;13(1):26–37.Search in Google Scholar

[39] Liu L, Habeshian TS, Zhang J, Peeri NC, Du M, De Vivo I, et al. Differential trends in rising endometrial cancer incidence by age and race and ethnicity. JNCI Cancer Spectr. 2023;7(1):pkad001.10.1093/jncics/pkad001Search in Google Scholar PubMed PubMed Central

[40] Fontenot VE, Tewari K. The current status of immunotherapy in the treatment of primary advanced and recurrent endometrial cancer. Curr Opin Obstet Gynecol. 2023;35(1):34–42.10.1097/GCO.0000000000000839Search in Google Scholar PubMed

[41] Zheng M, Hu Y, Gou R, Li S, Nie X, Li X, et al. Development of a seven-gene tumor immune microenvironment prognostic signature for high-risk grade III endometrial cancer. Mol Ther – Oncolytics. 2021;22:294–306.10.1016/j.omto.2021.07.002Search in Google Scholar PubMed PubMed Central

[42] Amarin JZ, Mansour R, Al-Ghnimat S, Al-Hussaini M. Differential characteristics and prognosis of PD-L1-positive endometrial carcinomas: a retrospective chart review. Life. 2021;11(10):1047.10.3390/life11101047Search in Google Scholar PubMed PubMed Central

[43] Zong L, Mo S, Sun Z, Lu Z, Yu S, Chen J, et al. Analysis of the immune checkpoint V-domain Ig-containing suppressor of T-cell activation (VISTA) in endometrial cancer. Mod Pathol. 2022;35(2):266–73.10.1038/s41379-021-00901-ySearch in Google Scholar PubMed

[44] Li K, Tian H. Development of small-molecule immune checkpoint inhibitors of PD-1/PD-L1 as a new therapeutic strategy for tumour immunotherapy. J Drug Target. 2019;27(3):244–56.10.1080/1061186X.2018.1440400Search in Google Scholar PubMed

Received: 2023-01-28
Revised: 2023-10-10
Accepted: 2023-11-16
Published Online: 2023-12-11

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Research Articles
  2. Exosomes derived from mesenchymal stem cells overexpressing miR-210 inhibits neuronal inflammation and contribute to neurite outgrowth through modulating microglia polarization
  3. Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
  4. circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
  5. circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
  6. WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4
  7. Up-regulation of collagen type V alpha 2 (COL5A2) promotes malignant phenotypes in gastric cancer cell via inducing epithelial–mesenchymal transition (EMT)
  8. Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
  9. 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
  10. Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
  11. PVT1/miR-16/CCND1 axis regulates gastric cancer progression
  12. Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
  13. Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
  14. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
  15. Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder’s lung
  16. lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
  17. SIRT1/APE1 promotes the viability of gastric cancer cells by inhibiting p53 to suppress ferroptosis
  18. Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation
  19. Treatments for brain metastases from EGFR/ALK-negative/unselected NSCLC: A network meta-analysis
  20. Association of osteoporosis and skeletal muscle loss with serum type I collagen carboxyl-terminal peptide β glypeptide: A cross-sectional study in elder Chinese population
  21. circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway
  22. Delivery in a vertical birth chair supported by freedom of movement during labor: A randomized control trial
  23. UBE2J1 knockdown promotes cell apoptosis in endometrial cancer via regulating PI3K/AKT and MDM2/p53 signaling
  24. Metabolic resuscitation therapy in critically ill patients with sepsis and septic shock: A pilot prospective randomized controlled trial
  25. Lycopene ameliorates locomotor activity and urinary frequency induced by pelvic venous congestion in rats
  26. UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats
  27. LINC00511 promotes melanoma progression by targeting miR-610/NUCB2
  28. Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of serum metabolomic characteristics in people with different vitamin D levels
  29. Role of Jumonji domain-containing protein D3 and its inhibitor GSK-J4 in Hashimoto’s thyroiditis
  30. circ_0014736 induces GPR4 to regulate the biological behaviors of human placental trophoblast cells through miR-942-5p in preeclampsia
  31. Monitoring of sirolimus in the whole blood samples from pediatric patients with lymphatic anomalies
  32. Effects of osteogenic growth peptide C-terminal pentapeptide and its analogue on bone remodeling in an osteoporosis rat model
  33. A novel autophagy-related long non-coding RNAs signature predicting progression-free interval and I-131 therapy benefits in papillary thyroid carcinoma
  34. WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients
  35. Radiomics model using preoperative computed tomography angiography images to differentiate new from old emboli of acute lower limb arterial embolism
  36. Dysregulated lncRNAs are involved in the progress of myocardial infarction by constructing regulatory networks
  37. Single-arm trial to evaluate the efficacy and safety of baclofen in treatment of intractable hiccup caused by malignant tumor chemotherapy
  38. Genetic polymorphisms of MRPS30-DT and NINJ2 may influence lung cancer risk
  39. Efficacy of immune checkpoint inhibitors in patients with KRAS-mutant advanced non-small cell lung cancer: A retrospective analysis
  40. Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma
  41. Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
  42. CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
  43. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
  44. Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells
  45. HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway
  46. The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study
  47. Myostatin silencing inhibits podocyte apoptosis in membranous nephropathy through Smad3/PKA/NOX4 signaling pathway
  48. A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis
  49. Impact of omicron wave and associated control measures in Shanghai on health management and psychosocial well-being of patients with chronic conditions
  50. Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer
  51. TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia
  52. The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life
  53. miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
  54. Long non-coding RNA AL137789.1 promoted malignant biological behaviors and immune escape of pancreatic carcinoma cells
  55. IRF6 and FGF1 polymorphisms in non-syndromic cleft lip with or without cleft palate in the Polish population
  56. Comprehensive analysis of the role of SFXN family in breast cancer
  57. Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy
  58. Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
  59. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
  60. Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial–mesenchymal transition
  61. Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
  62. Inhibition of glycolysis represses the growth and alleviates the endoplasmic reticulum stress of breast cancer cells by regulating TMTC3
  63. The function of lncRNA EMX2OS/miR-653-5p and its regulatory mechanism in lung adenocarcinoma
  64. Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6
  65. Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer
  66. F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
  69. Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
  70. Cholesterol induces inflammation and reduces glucose utilization
  71. circ_0004904 regulates the trophoblast cell in preeclampsia via miR-19b-3p/ARRDC3 axis
  72. NECAB3 promotes the migration and invasion of liver cancer cells through HIF-1α/RIT1 signaling pathway
  73. The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk
  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
  75. Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis
  76. α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice
  77. Changes of microbiota level in urinary tract infections: A meta-analysis
  78. Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
  79. Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study
  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
  89. miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
  90. lncRNA OIP5-AS1 attenuates the osteoarthritis progression in IL-1β-stimulated chondrocytes
  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
  95. Bladder cancer screening: The new selection and prediction model
  96. circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
  97. Prone position effect in intensive care patients with SARS-COV-2 pneumonia
  98. Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children
  99. Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
  101. Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
  102. Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study
  103. Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
  104. Clinical significance of serum MBD3 detection in girls with central precocious puberty
  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
  109. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy
  110. A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
  115. Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
Downloaded on 9.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/med-2023-0866/html
Scroll to top button