Cancer Translational Medicine

Review | Open Access

Vol.7 (2021) | Issue-1 | Page No: 13-23

DOI: https://doi-ds.org/doilink/01.2022-46449534/CTM/01.2022-11557263/2021.V7/I1/A2

Research Progress of Cytokines and Their Receptors in Ovarian Cancer

Yuanwen Zhang1, Zhouman He1, Shiyun Liang1, Jian Yuan1, Huihui Ti1 *

 

 

Affiliations  

1 School of Clinical Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China

*Corresponding Author

Address for correspondence: Prof. Huihui Ti, School of Clinical Pharmacy, Guangdong Pharmaceutical University, No. 280, University Town, Panyu District, Guangzhou 510006, Guangdong, China. E-mail: tihuihui@126.com


Important Dates  

Date of Submission:   26-Oct-2021

Date of Acceptance:   29-Nov-2021

Date of Publication:   29-Dec-2021

ABSTRACT

Ovarian cancer is characterized by its high occurrence rate, poor prognosis, high recurrence rate, and increasing incidence rate year by year. The cause of the disease is not clear, probably related to heredity, hormones, lifestyle, and environment. Many studies have shown that cytokines such as interleukins not only play a key role in the abnormal proliferation, differentiation, apoptosis, carcinogenesis, metastasis, and multidrug resistance (MDR) of ovarian cancer cells, but also play an important role in the diagnosis, prevention and prognosis of ovarian cancer. In this review, we expound the influence and therapeutic effects of cytokines on ovarian cancer by referring the relevant research studies. This will help us understand the expression levels of cytokines in ovarian cancer and provide evidences for immunologic diagnosis and prognosis as well as new therapeutic targets for cancer immunotherapy.


INTRODUCTION

Often known as the silent killer, ovarian cancer is frequently not diagnosed until it is at an advanced stage because of its generally vague symptoms, making it hard to treat on a curative basis.[1] Thus, ovarian cancer is the deadliest gynecological cancer with Case Fatality Ratio (CFR) of nearly three times that of breast cancer, which is ranked fifth within the main causes of cancer deaths in women.[2],[3] According to the statistics released by the International Cancer Research Center (IARC) in 2020, there are 310,000 new cases and 210,000 deaths due to ovarian cancer around the world.[3] Specially, epithelial ovarian cancer, the most common among ovarian malignant tumors, account for about 50% to 70% of ovarian tumors. The second most common is malignant germ cell tumor, including immature teratoma, endodermal sinus tumor, dysgerminoma, mixed type, embryonal carcinoma and polyembryoma.[4] The last type of ovarian cancer is a specialized stromal cell tumor. High-grade serous ovarian carcinoma (HGSOC) is the most common subtype of ovarian cancer. Besides, the 5-year survival rate of ovarian cancer is less than 40% due to extremely poor prognosis.[5],[6] Also, the mortality rate is highest in all kinds of gynecological tumors, which poses a serious threat to the lives of women.

Cytokine is a class of small-molecular soluble polypeptides secreted by immune cells and tissue cells with mutual regulation. They play an important role in the development and differentiation of immune cells, immune response, and immune regulation by binding to corresponding receptors to regulate the activities of themselves or other cells. As targeted biological agents, cytokines have certain clinical value in the treatment of tumors, autoimmune diseases, immunodeficiency, infection and so on. This review focuses on recent research developments on common cytokines and ovarian cancer due to their critical involvement in the onset and progression of the disease.


CYTOKINES

INTERLEUKIN (IL)

Interleukin is a group of soluble proteins secreted by leukocytes and can regulate the function of other leukocytes and histiocytes. They are participants in the activation and regulation of immune cells as well as proliferation, differentiation of T and B cells, and inflammation.

Interleukin-6

Interleukin-6 (IL-6) is a pleiotropic pro-inflammatory cytokine, a core participant in chronic inflammatory diseases including cancer, as well as one of the main immunomodulatory cytokines in tumor micro-environment. Studies have shown that IL-6 regulates tumor progression including anti-apoptosis, inducing proliferation, promoting metabolism, enhancing tissue invasiveness, metastasis, etc.[7] It has been found that the over-expression and dysfunction of IL-6 are related to ovarian cancer, multiple myeloma, and breast cancer.[8],[9],[10] For example, high levels of IL-6 promoted the progression of malignant ascites in ovarian cancer,[11]1 and also promoted the enrichment of ovarian cancer stem cells after platinum-based chemotherapeutic treatment.[12] In addition, leukemia inhibitory factor (LIF) in parallel with IL-6  promote the progression of ovarian cancer, hence simultaneous blocking of both can improve survival.[13] The STAT3 signaling pathway is highly regulated and instantaneous in normal cells, while it is constantly activated by IL-6 in cancer cells, which is related to the invasion and poor prognosis of ovarian cancer.[14],[15] In fact, activated STAT3 is more common in epithelial ovarian cancer diagnosed at a late stage. The activation of JAK/STAT signaling pathway correlated with aggressiveness of ovarian cancer, survival and proliferation of cells, which suggest that STAT3 is necessary for cell migration in ovarian cancer.[16]

Interleukin-8

Interleukin-8 (IL-8), also named as CXCL8, is a pro-inflammatory chemokine secreted by multiple cell types, such as monocytes, mesothelial cells, endothelial cells, tumor cells etc. It has been confirmed that the elevated levels of IL-8 in ovarian cyst fluid, ascites, serum and tumor tissues of patients with ovarian cancer are associated with poor prognosis and survival.[17] IL-8 may cause the malignant behavior such as excessive proliferation of cancer cells by inducing relevant molecular signaling pathways in cells. Specifically, cell proliferation stimulated by IL-8 and increased cell cycle-regulated Cyclin D1 and B1 promote the activation of PI3K/Akt and Raf/MEK/ERK.[18] Meanwhile, the invasiveness of epithelial ovarian cancer cells enhanced by IL-8 is closely related to the expression of MMP-2 and MMP-9.[18] IL-8 can also promote human ovarian cancer cell mobility by inducing epithelial-mesenchymal transformation (EMT) in-vitro.[19] In addition, neurobehavioral stress leads to the increase of FosB drive in IL8, which plays a role in promoting the growth and metastasis of ovarian cancer.[20] In epithelial ovarian cancer cells, histone deacetylase (DHAC) inhibitors may induce IL-8/CXCL8 expression in a dependent manner through IκB kinase (IKK). IKK inhibitors may work synergistically with DHAC inhibitors when treating solid tumor-ovarian cancer and other cancers characterized by increased expression of IL-8/CXCL8.[21] Current studies have described that osteopontin, macrophage migration inhibitory factor and anti-IL-8 antibody can be used as markers for early detection of ovarian cancer as well as in combination with CA125.[22]

Others

Natural killer (NK) cells belong to the first group of innate lymphocytes, which have the ability to kill malignant cells and inhibit the metastasis and spread of cancer.[23] NK cells with high spontaneous cytotoxicity are associated with a reduction in the incidence of human cancer.[24] Cytokines bind to receptor complexes in cell membrane and activate intracellular signaling pathways based on phosphorylation of signal transducing and transcription-activating protein kinases. For example, IL-10 and other cytokines present in the tumor environment affected the JAK/STAT5 pathway by reducing the phosphorylation status of STAT5 protein, and enhanced the expression of VEGF in NK cells at the same time.[25] IL-15 can significantly enhance NK cell’s Anti-tumor response.[26],[27]

Most of the cell types in the ascites of ovarian cancer patients are lymphocytes (37%) and macrophages (32%), which contribute to the progression and metastasis of ovarian cancer.[28] Interleukin 20 receptor subunit alpha (IL20RA), as a key receptor in regulating the polarization of peritoneal macrophages, is silenced in disseminated ovarian cancer cells for the accumulation of M2-subtype macrophages in the peritoneal cavity for a successful metastatic growth.[29] However, the administration of recombinant IL-18 significantly suppresses the metastasis of IL20RA-deficient ovarian cancer cells. When ovarian cancer cells spread to the abdominal cavity, it greatly induces the expression of IL-20 and IL-24 in peritoneal mesothelial cells, activating the downstream signal of IL20RA in ovarian cancer cells to produce mature IL-18, ultimately leading to the polarization of macrophages to M1-like subtype to eliminate cancer cells.[29]

COLONY-STIMULATING FACTOR (CSF)

Colony-stimulating factor (CSF) is a group of glycoproteins, including granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF) and multi-potential colony-stimulating factor (Multi-CSF), which regulate the proliferation and differentiation of granulocytes, mononuclear macrophages and some correlative hematopoietic stem and progenitor cells.

M-CSF is a homodimer formed by hydrolysis of precursor protein, also known as colony stimulating factor 1 (CSF-1). It plays an important role in regulating the proliferation and differentiation of mononuclear macrophages.[30] Secreting large amounts of CSF-1 is a distinctive feature of many human epithelial ovarian cancers.[31] In epithelial ovarian cancer, the overexpression of CSF-1R and CSF-1/CSF-1R activated by CSF-1 enhances invasiveness and promotes metastasis, and is thus associated with poor prognosis.[32],[33] CSF-1 not only play a role in converting macrophages into M2 phenotype,[34] but also increases the ascites of patients, which indicates that the CSF-1/CSF1R axis may directly promote carcinogenic effects on tumor cells.[31] Previous research has found that CSF-1R is up-regulated in cisplatin-resistant cells in which inhibiting the expression of CSF-1R is able to reduce the polarization of M2 macrophages, therefore delay the growth of tumor cells. It suggests that the expression of genes and proteins related to M-CSF can be used as novel therapeutic targets for ovarian cancer.[35] Another research detected the expression G-CSFR in advanced serous ovarian epithelial cancers and some ovarian cancer cell lines. Mediated by signaling via the downstream JAK2/STAT3 pathway, stimulation of G-CSFR-expressing ovarian epithelial cancer cells with G-CSF led to increased migration and survival against chemotherapy-induced apoptosis in these cells.[36] Experimental results in mice have shown that targeting the GM-CSF contributes to overcoming the anti-VEGF therapy resistance in ovarian cancers, because both anti-VEGF therapy and recruiting and suppressing tumor immunity were inducing tumor hypoxia and the expression of GM-CSF.[37]

INTERFERON (IFN)

Interferon is the first cytokine discovered. According to its origin and physicochemical properties, interferon can be divided into type Ⅰ (IFN- α, IFN- β), type Ⅱ (IFN- γ) and type Ⅲ (IFN- λ) interferon. IL-28/IL29 reported recently is classified into type Ⅲ.[38] Type I interferon is mainly produced by virally infected cells, while IFN-γ is a glycoprotein primarily secreted by activated Th1 cells, CTLs and NK cells. Many studies have investigated the characteristics and biological activities of type II interferon (IFN- γ), suggesting that it has similar features to type I IFN, such as anti-proliferation, anti-virus, immunomodulatory, anti-tumor effects and so on.[39]

The view that IFN-γ has anti-tumor effects on cancer patients is widely recognized. However, Zaidi et al.[40] believed that IFN-γ has both immune-activation/immunoregulatory and antitumor/tumor-promoting effects and that the inhibition of FN-γ/IFN-γ receptor pathway might be a feasible new therapeutic target for some malignant tumors. Because of the difference in the cancer microenvironment, IFN-γ secreted by CD8-positive lymphocytes upregulates Programmed death-ligand 1 (PD-L1) on ovarian cancer cells and promotes tumor growth.[41] A previous study has shown that interferon signal transduction in tumor-associated macrophages (TAMs) in ascites of patients with ovarian cancer is closely related to the good clinical prognosis of the patient subgroup.[42] The increase in tumor-infiltrating lymphocytes (TIL) infiltration is associated with the increase in cytokine IFN- γ levels, which is a prognostic factor for prolonging survival as observed in clinical trials for the treatment of ovarian cancer.[43] Cytokine immunotherapy with IFN-α and IFN-γ is mainly used in the intraperitoneal treatment of ovarian cancer. Previously, studies suggested that autologous monocytes injected into the peritoneum have anti-tumor properties. Recent research studies have shown that combination of monocyte and cytokine immunotherapy is more effective than monotherapy in treating cancer.[44],[45] In addition, bone marrow monocytes derived from pluripotent stem cells can produce IFN-β. IFN-β reduces the patient's ascites retention by reducing the production of VEGF and maintaining vascular integrity, thereby controlling severe malignant ascites, which can be used as a new therapeutic strategy for advanced ovarian cancer.[46] New polyethylene glycol IFN-β, as a strong inhibitor of malignant ascites in human peritoneal metastasis model, has the potential to maintain vascular integrity.[47] Some studies have also shown that recombinant IFN-γ gene expressed and reorganized in mammalian cells increases the death of drug-resistant SKOV3 cells. Fas-associating protein with a novel death domain (FADD) may inhibit apoptosis through the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Therefore, FADD in SKOV3 can be used as a new therapeutic target.[48] At the same time, interferon regulators are also used to overcome the drug resistance of human ovarian cancer to VSV-GP oncolytic virus therapy.[49]

TUMOR NECROSIS FACTOR (TNF)

Tumor Necrosis Factor (TNF) was originally identified because of its antitumoral activity in vivo and its selective cytotoxic/cytostatic activity on some transformed cell lines in 1975.[50] It is a soluble multifunctional cytokine mainly synthesized by activated macrophages. It can participate in inflammation and cellular immune responses and play a critical role in the pathology of many diseases, such as rheumatoid arthritis, crohn's disease and so on.[51],[52] TNF gene family includes TNF-α and lymphotoxin (LT).

It is well known that TNF-α is a key cytokine in inflammation and was initially considered to be anti-tumor. However, recent studies have emphasized the role of TNF-α in immunosuppression and its ability to enhance tumor growth.[53] TNF-α released from TAM stimulated the expression of PD-L1 on the surface of the cancer cells.[54] In ovarian cancer, the expression of TNF-α is related to different histologic subtype.[55] TNF-α self-expression in ovarian tumor cells can increase the synthesis of MCP-1, SDF-1, IL-6, MIF and VEGF which enhance angiogenesis and peritoneal diffusion of tumor.[56] Besides, the production of TNF-α also enhances the synthesis of IL-17, which can cause recruitment of myeloid cells and eventually lead to the progression of ovarian tumor.[57] In advanced epithelial ovarian cancer, TNF-α in ascites interacts with IL-6, driving tumor progression and chemotherapy resistance and increase the potential of these cytokines as prognostic biomarkers to treat ascites leves.[58] Previous studies have shown that overexpression of tumor necrosis factor receptor-associated protein 1 (TRAP1) is associated with poor prognosis of epithelial ovarian cancer.[59] A recent research has found that spermatogenesis associated 2 (SPATA2) is identified as TNF receptor modulator, which is necessary for TNF-induced inflammation and apoptosis. The expression of SPATA2 regulated by TNF-α and IL-1β has been found to independently affect the clinical outcome of patients with ovarian cancer.[60] In addition, the decreased expression of tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) is a predictive biomarker for neoadjuvant chemotherapy drug-resistance. TNFAIP8 may be involved in chemoresistance induced by cisplatin through interaction with autophagy-related proteins in which it is expected to become an important target for ovarian cancer therapy.[61]


GROWTH FACTORS

Vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) is a cytokine that promotes angiogenesis and can be synthesized by a variety of cells, such as endothelial cells, macrophages, tumor cells, etc. VEGF, especially VEGF-A, is a key angiogenic factor, which plays an important role in inducing neovascularization, progression, and metastasis of many human cancers.[62] It is up-regulated by oncogene expression, a variety of growth factors and also hypoxia.[63] The production of VEGF and other growth factors by the tumor results in the 'angiogenic switch', where new vasculature is formed in and around the tumor, allowing it to grow exponentially.[64] This core role makes it a reasonable target for anti-cancer treatment. For example, during ovarian tumor progression, the imprinted tumor suppressor NOEY2 dramatically downregulated VEGF and hypoxia-inducible factor-1α (HIF-1α) via direct binding to vascular endothelial growth factor receptor-2 (VEGFR-2).[65] F-box and WD repeat domain containing 7 (FBXW7) inhibited invasion, migration and angiogenesis of ovarian cancer cells by suppressing VEGF expression through inactivation of β-catenin signaling.[66] Compared to women with benign tumors or healthy ovaries, the distribution of VEGF genotypes in patients with epithelial ovarian cancer is different, which indicated that CGTCT and CGTGT haplotypes have a poorer prognosis.[67] VEGF genotype may predict prognosis in patients with epithelial ovarian cancer. High levels of VEGF were found in primary ovarian cancer tumors and ascites, which was related to poor survival. Therefore, Bevacizumab, a monoclonal antibody that targets VEGF, has been approved for treatment of advanced and recurrent ovarian cancer which is shown to prolong the non-progressive survival period.[68] Studies have shown that the expression of VEGF in ovarian cancer suppresses tumor immunity by inducing myeloid-derived suppressor cells.[69] VEGF also promotes the metastasis of ovarian cancer by promoting angiogenesis and vascular permeability by acting on the peritoneum. The inhibition of VEGF completely suppressed the formation of ascites, with partial inhibition of the ovarian tumor growth in peritoneum. It is suggested that the pathology of tumor aggressiveness in advanced ovarian cancer may be related to ascites caused by early vascular permeability disorder.[70] In addition, studies have shown that the combined use of anti-VEGF, anti-IL-8 and anti-IGFR antibodies can inhibit tumor growth and improve the survival of preclinical models.[71] Not only that, with the growth of tumor, the concentration of VEGF-A becomes more localized so that a decrease in concentration of VEGF-A in serum can be easily observed.[72] Thus, serum VEGF-A can be used as a strong diagnostic biomarker in the early stages of ovarian cancer and has inverse relation in terms of concentration with the advancement of the disease.[73]

 

Transforming growth factor-β

Transforming growth factor-β (TGF-β) can act as a tumor suppressor and tumor promoter. Signal transduction of TGF-β plays an important role in occurrence, development and metastasis of tumor. As with most aspects of tumor progression, there are multiple potential mechanisms for this switch, including both cell autonomous (i.e. EMT) and non-cell autonomous (i.e. angiogenesis and immune system) mechanisms.[74] Studies have shown that the dysregulation of TGF-β signal conduction may contribute to occurrence of ovarian cancer. TGF-β can promote migration of ovarian cancer cells, which may be associated with up-regulation of junction protein 43 through Smad2/3 signal pathway.[75] On one hand, TGF-β is an effective cell growth inhibitor, and on the other hand a malfunction of its pathway in tumor microenvironment leads to uncontrolled cell growth and proliferation, which can progress to the occurrence and development of tumor.[76] Tumor progression occurs when cancer cells can escape the inhibitory effects of TGF-β and instead begin to overexpress TGF-β thus promoteing EMT, resulting in increased cell proliferation, invasiveness and enhanced metastatic potential. This will generate a more aggressive tumor phenotype.[77] Recent studies have shown that LY2157299 monohydrate, a TGF-β R1 inhibitor, can suppress tumor growth and the development of ascites in ovarian cancer.[78]

Epidermal growth factor (EGF)

Epidermal growth factor (EGF) is reported to be associated with a variety of cancers, especially ovarian cancer. EGF can stimulate the ovarian cancer cell line Caov-3 to enter EMT and then participate in cell cycle regulation.[79] In recurrent ovarian cancer, activity of spleen tyrosine kinase (SYK) positively regulates the EGF receptor (EGFR) pathway, providing a biological basis for the co-targeting of SYK and EGFR.[80] Increased expression of EGFR on ovarian cancer cells is associated with poor prognosis. Not only that, the activation of EGFR can activate the IL-6/STAT3 pathway, increasing the migration of epithelial ovarian cancer cells. Therefore, high EGFR and IL-6/STAT3 expression predicts poor survival in patients with ovarian cancer, which indicates that the high expression of EGFR/IL-6/STAT3 pathway components may be positively correlated with the progression of ovarian cancer.[81] Phase III clinical studies have also shown that an increase in EGFR gene copy number is associated with the deterioration in overall survival and progression-free survival (PFS) of patients with ovarian cancer.[82] EGFR has become a new therapeutic target for ovarian cancer.[83],[84]

In more than 30% of ovarian cancer cases, human epidermal growth factor receptor 2 (HER2) is overexpressed and plays an important role in tumorigenesis and metastasis.[85] However, the treatment results of clinical trials using HER2 antibody targeted therapy have shown poor to modest therapeutic responses.[86],[87]

Peritoneal metastatic tumors cannot be completely removed through Debulking Surgery and have developed chemoresistance, which are the main clinical challenges for the treatment of ovarian cancer. Further study has found that in the ovarian cancer xenograft model in nude mice, the systemic delivery of HER2-targeted magnetic iron oxide nanoparticles carrying cisplatin significantly inhibited the growth of primary tumor and peritoneal and lung metastases.[88] This targeted cancer therapy has the potential to effectively treat metastatic ovarian cancer.

In serous ovarian cancer, the expression of fibroblast growth factor 18 (FGF18) is significantly correlated with micro-vessel density and tumor-associated macrophage infiltration. Signal of FGF18 regulates the aggressiveness and microenvironment of ovarian tumors, thereby promoting tumor progression. It increases the production of carcinogenic factors and chemokines by activating NF-κB to control the migration, invasion and tumorigenicity of ovarian cancer cells. This leads to a tumor microenvironment characterized by enhanced angiogenesis and augmented tumor-associated macrophage infiltration and M2 polarization.[89]


CHEMOKINES

Chemokines, a superfamily of inducible, secreted, heparin-binding proteins, are structurally homologous and are involved in tumor growth and metastasis.[90] Besides, chemokines were first studied as mediators of inflammation.[91] They have the following functions and characteristics: binding with chemokine receptors to induce chemotaxis of cells, inducing Chemotactic migration of target cells, rebuilding the cytoskeleton, enhancing the adhesion of target cells and endothelial cells etc. Besides, they have a variety of physiological functions, such as widely participating in cell growth, development, differentiation and apoptosis. Not only can they chemotactically direct inflammatory cells, but also play an important role in growth and metastasis of tumor.[92]

CC-chemokine ligand 18 (CCL18) is mainly produced by TAM. The level of CCL18 in ascites is positively correlated with the ability of ascites in promoting cell migration. The CCL18 blocking antibody significantly reduces cancer cell metastasis induced by ascites. Ascites and CCL18 stimulate the phosphorylation of proline-rich tyrosine kinase 2 (PYK2) in human ovarian cell line. However, the expression of phosphorylated Pyk2 in serous ovarian cancer tumors is associated with short PFS.[93] CCL18 levels in serum have been used as a potential biomarker to distinguish ovarian cancer with gynecological benign diseases in patients.[94] Infiltration of CD8+ T lymphocyte is an indicator of good prognosis for ovarian cancer. The homeodomain transcription factor MEIS1 triggers the expression of chemokines CCL18, CCL4, CXCL7, CCL5, CXCL1 and IL8, and participates in infiltration of CD8+ T lymphocyte in early ovarian cancer.[95] Studies have shown that CXCR7 plays a key role in the invasion of ovarian cancer cells. Under the control of the estrogen receptor α (ERα), the activation of the CXCR7/CXCL11 axis may promote a feedforward mechanism to induce remodel of ECM, EMT, and metastasis of ovarian cancer cells.[96] In addition, in ovarian cancer cells, the overexpression of scaffold protein Gab2 promotes tumor growth and angiogenesis by up regulating the expression of some chemokines depended by IKKβ, such as CXCL1, CXCL2, and CXCL8. Co-targeting IKKβ and PI3K pathways, the downstream of Gab2, may be a promising therapeutic strategy to treat the ovarian cancer that overexpress Gab2.[97]

In addition, chemokines such as CXCL8, CXCL1 and CCL2 bind to CXCR1 and CXCR2 expressed by endothelial cells as well as lead to the proliferation, migration of endothelial cells and blood vessel formation.[98] For example, under hypoxic conditions, the interaction of CXCL12 produced by cancer cells and CXCR4 expressed by endothelial cells may enhance angiogenesis in ovarian cancer. Regulating the immune system via the CCR4/CCL22 axis and CCL2/CCR2 axis, they respectively determine the degree of T cell and macrophage infiltration in ovarian cancer. In addition, the CX3CL1/CX3CR1 axis supports the adhesion and proliferation of ovarian cancer cells, and plays a potentially key role in the occurrence and progression of ovarian cancer metastasis. Therefore, according to the actual patient's condition and the different effects of chemokine receptor axes, chemotherapy combined with immunotherapy is used to pursue the greatest anti-tumor effects.


CONCLUSION

Cytokines are mutually promoted or restricted in the body. They form a particularly complex network system. Thus, cytokines play a double-edged role in the occurrence and development of ovarian cancer. On one hand, certain cytokines have anti-tumor effects, such as IFN. On the other hand, certain cytokines promote occurrence and development of tumor, such as IL-6, IL-8, and VEGF. However, some cytokines play a dual role, such as TNF-α, GM-CSF, and TGF-β. The mechanisms and applications of cytokines to tumor therapeutics remain unclear. Therefore, understanding the expression levels of cytokines in ovarian cancer tissues may provide a basis for the immunological diagnosis and prognosis assessment of tumors, at the same time, provide new therapeutic targets for tumor immunotherapy.

 

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.


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Demeng Chen1, Caifeng Dai2, Yizhou Jiang3


Genetic Characteristics of Glioblastoma: Clinical Implications of Heterogeneity

Qian Li1, Yanyang Tu1,2


Acute Lymphoblastic Leukemia with Normal Platelet Count

Khushboo Dewan, Kiran Agarwal


Galanin is a Novel Epigenetic Silenced Functional Tumor Suppressor in Renal Cell Carcinoma

Shengkun Sun1*, Axiang Xu1*, Guoqiang Yang1, Yingduan Cheng2

 


Selenium Dioxide Induced Apoptosis in Cervical Cancer Cells via Regulating Apoptosis-related Let-7a MicroRNA and Proteins

Sisun Liu1, Jieqi Xiong2, Ling Guo3, Min Xiu1,4, Feng He1,4, Yuanlei Lou5, Fei Guo6,7


Low Expression of Polo‑like Kinase 1 is Associated with Poor Prognosis in Liver Cancer

Weixia Li1, Kunpeng Liu1, Dechen Lin2, Xin Xu2, Haizhen Lu3, Xinyu Bi4, Mingrong Wang2


Extracorporeal Photopheresis for Steroid‑refractory Chronic Graft‑versus‑host Disease After Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta‑Analysis

Runzhe Chen1, Baoan Chen1, Peter Dreger2, Michael Schmitt2, Anita Schmitt2


Glucans and Cancer: Historical Perspective

Petr Sima1, Luca Vannucci1, Vaclav Vetvicka2


Implications of Circadian Rhythm Regulation by microRNAs in Colorectal Cancer

Song Wu1, Andrew Fesler2, Jingfang Ju2


BCL2 Family, Mitochondrial Apoptosis, and Beyond

Haiming Dai1, X. Wei Meng2, Scott H. Kaufmann2


Quantum Dot‑based Immunohistochemistry for Pathological Applications

Li Zhou1, Jingzhe Yan2, Lingxia Tong3, Xuezhe Han4, Xuefeng Wu5, Peng Guo6


CD24 as a Molecular Marker in Ovarian Cancer: A Literature Review

Lu Huang1, Weiguo Lv2, Xiaofeng Zhao1


Etiological Trends in Oral Squamous Cell Carcinoma: A Retrospective Institutional Study

Varsha Salian, Chethana Dinakar, Pushparaja Shetty, Vidya Ajila


Effect of Irinotecan Combined with Cetuximab on Liver Function in Patients with Advanced Colorectal Cancer with Liver Metastases

Yan Liang1, Yang Li2, Xin Li3, Jianfu Zhao4


The Role of Precision Medicine in Pancreatic Cancer: Challenges for Targeted Therapy, Immune Modulating Treatment, Early Detection, and Less Invasive Operations

Khaled Kyle Wong1, Zhirong Qian2, Yi Le3


Targeting Signal Transducer and Activator of Transcription 3 for Colorectal Cancer Prevention and Treatment with Natural Products

Weidong Li1,2*, Cihui Chen3*, Zheng Liu2, Baojin Hua1


The Potential of Wnt Signaling Pathway in Cancer: A Focus on Breast Cancer

Mahnaz M. Kazi, Trupti I. Trivedi, Toral P. Kobawala, Nandita R. Ghosh


Imaging‑driven Digital Biomarkers

Enrico Capobianco


Target‑Matching Accuracy in Stereotactic Body Radiation Therapy of Lung Cancer: An Investigation Based on Four‑Dimensional Digital Human Phantom

Jing Cai1,2, Kate Turner2, Xiao Liang2, W. Paul Segars2,3, Chris R. Kelsey1, David Yoo1, Lei Ren1,2, Fang‑Fang Yin1,2


Downregulation of Death‑associated Protein Kinase 3 and Caspase‑3 Correlate to the Progression and Poor Prognosis of Gliomas

Ye Song, Tianshi Que, Hao Long, Xi’an Zhang, Luxiong Fang, Zhiyong Li, Songtao Qi


Hyaluronic Acid in Normal and Neoplastic Colorectal Tissue: Electrospray Ionization Mass Spectrometric and Fluor Metric Analysis

Ana Paula Cleto Marolla1, Jaques Waisberg2, Gabriela Tognini Saba2, Demétrius Eduardo Germini2, Maria Aparecida da Silva Pinhal1


Melanoma Antigen Gene Family in the Cancer Immunotherapy

Fengyu Zhu1, Yu Liang1, Demeng Chen2, Yang Li1


Combined Chronic Lymphocytic Leukemia and Pancreatic Neuroendocrine Carcinoma: A Collision Tumor Variation

Kaijun Huang1, Panagiotis J. Vlachostergios1, Wanhua Yang2, Rajeev L. Balmiki3


Antiproliferative and Apoptotic Effect of Pleurotus ostreatus on Human Mammary Carcinoma Cell Line (Michigan Cancer Foundation‑7)

Krishnamoorthy Deepalakshmi, Sankaran Mirunalini


Impact of Age on the Biochemical Failure and Androgen Suppression after Radical Prostatectomy for Prostate Cancer in Chilean Men

Nigel P. Murray1,2, Eduardo Reyes1,3, Nelson Orellana1, Cynthia Fuentealba1, Omar Jacob1


Carcinoma of Unknown Primary: 35 Years of a Single Institution’s Experience

Rana I. Mahmood1,2, Mohammed Aldehaim1,3, Fazal Hussain4, Tusneem A. Elhassan4,
Zubeir A. Khan5, Muhammad A. Memon6


Metformin in Ovarian Cancer Therapy: A Discussion

Yeling Ouyang1, Xi Chen2, Chunyun Zhang1, Vichitra Bunyamanop1, Jianfeng Guo3


The Progress in Molecular Biomarkers of Gliomas

Jing Qi1, Hongwei Yang2, Xin Wang2, Yanyang Tu1


Correlation between Paclitaxel Tc > 0.05 and its Therapeutic Efficacy and Severe Toxicities in Ovarian Cancer Patients

Shuyao Zhang1*, Muyin Sun2*, Yun Yuan3*, Miaojun Wang4*, Yuqi She1*, Li Zhou5, Congzhu Li5, Chen Chen1, Shengqi Zhang4


Identifying Gaps and Relative Opportunities for Discovering Membrane Proteomic Biomarkers of Triple‑negative Breast Cancer as a Translational Priority

Bhooma Venkatraman


The Molecular Mechanism and Regulatory Pathways of Cancer Stem Cells

Zhen Wang1, Hongwei Yang2, Xin Wang2, Liang Wang3, Yingduan Cheng4, Yongsheng Zhang5, Yanyang Tu1,2


Nanoparticle Drug Delivery Systems and Three‑dimensional Cell Cultures in Cancer Treatments and Research

Wenjin Shi1, Ding Weng2,3, Wanting Niu2,3


Choline Kinase Inhibitors Synergize with TRAIL in the Treatment of Colorectal Tumors and Overcomes TRAIL Resistance

Juan Carlos Lacal1, Ladislav Andera2


MicroRNA Regulating Metabolic Reprogramming in Tumor Cells: New Tumor Markers

Daniel Otero‑Albiol, Blanca Felipe‑Abrio


Biomarkers of Colorectal Cancer: A Genome‑wide Perspective

José M. Santos‑Pereira1, Sandra Muñoz‑Galván2


Nicotinamide Adenine Dinucleotide+ Metabolism Biomarkers in Malignant Gliomas

Manuel P. Jiménez‑García, Eva M. Verdugo‑Sivianes, Antonio Lucena‑Cacace


Patient-derived Xenografts as Models for Personalized Medicine Research in Cancer

Marco Perez, Lola Navas, Amancio Carnero


Genome‑wide Transcriptome Analysis of Prostate Cancer Tissue Identified Overexpression of Specific Members of the Human Endogenous Retrovirus‑K Family

Behnam Sayanjali1,2


Clinical Utility of Interleukin‑18 in Breast Cancer Patients: A Pilot Study

Reecha A. Parikh, Toral P. Kobawala, Trupti I. Trivedi, Mahnaz M. Kazi, Nandita R. Ghosh


Current and Future Systemic Treatment Options for Advanced Soft‑tissue Sarcoma beyond Anthracyclines and Ifosfamide

Nadia Hindi1,2, Javier Martin‑Broto1,2


The Genomic Organization and Function of IRX1 in Tumorigenesis and Development

Pengxing Zhang1, Hongwei Yang2, Xin Wang2, Liang Wang3, Yingduan Cheng4, Yongsheng Zhang5, Yanyang Tu1,2


Stem Cell‑based Approach in Diabetes and Pancreatic Cancer Management

Yi‑Zhou Jiang1, Demeng Chen2


Mutation Detection with a Liquid Biopsy 96 Mutation Assay in Cancer Patients and Healthy Donors

Aaron Yun Chen, Glenn D. Braunstein, Megan S. Anselmo, Jair A. Jaboni, Fernando Troy Viloria, Julie A. Neidich, Xiang Li, Anja Kammesheidt


The Application of Estrogen Receptor‑1 Mutations’ Detection through Circulating Tumor DNA in Breast Cancer

Binliang Liu, Yalan Yang, Zongbi Yi, Xiuwen Guan, Fei Ma


Circulating MicroRNAs and Long Noncoding RNAs: Liquid Biomarkers in Thoracic Cancers

Pablo Reclusa1, Anna Valentino1, Rafael Sirera1,2, Martin Frederik Dietrich3, Luis Estuardo Raez3, Christian Rolfo1


Exosomes Biology: Function and Clinical Implications in Lung Cancer

Martin Frederik Dietrich1, Christian Rolfo2, Pablo Reclusa2, Marco Giallombardo2, Anna Valentino2, Luis E. Raez1


Circulating Tumor DNA: A Potential Biomarker from Solid Tumors’ Monitor to Anticancer Therapies

Ting Chen1,2, Rongzhang He1,3, Xinglin Hu1,3,4, Weihao Luo1, Zheng Hu1,3, Jia Li1, Lili Duan1, Yali Xie1,2, Wenna Luo1,2, Tan Tan1,2, Di‑Xian Luo1,2


Novel Molecular Multilevel Targeted Antitumor Agents

Poonam Sonawane1, Young A. Choi1, Hetal Pandya2, Denise M. Herpai1, Izabela Fokt3,
Waldemar Priebe3, Waldemar Debinski1


Fish Oil and Prostate Cancer: Effects and Clinical Relevance

Pei Liang, Michael Gao Jr.


Stemness‑related Markers in Cancer

Wenxiu Zhao1, Yvonne Li2, Xun Zhang1


Autophagy Regulated by miRNAs in Colorectal Cancer Progression and Resistance

Andrew Fesler1, Hua Liu1, Ning Wu1,2, Fei Liu3, Peixue Ling3, Jingfang Ju1,3


Gastric Metastases Mimicking Primary Gastric Cancer: A Brief Literature Review

Simona Gurzu1,2,3, Marius Alexandru Beleaua1, Laura Banias2, Ioan Jung1


Possibility of Specific Expression of the Protein Toxins at the Tumor Site with Tumor‑specialized Promoter

Liyuan Zhou1,2, Yujun Li1,2, Changchen Hu3, Binquan Wang1,2


SKI‑178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models

Jeremy A. Hengst1,2, Taryn E. Dick1,2, Arati Sharma1, Kenichiro Doi3, Shailaja Hegde4, Su‑Fern Tan5, Laura M. Geffert1,2, Todd E. Fox5, Arun K. Sharma1, Dhimant Desai1, Shantu Amin1, Mark Kester5, Thomas P. Loughran5, Robert F. Paulson4, David F. Claxton6, Hong‑Gang Wang3, Jong K. Yun1,2


A T‑cell Engager‑armed Oncolytic Vaccinia Virus to Target the Tumor Stroma

Feng Yu1, Bangxing Hong1, Xiao‑Tong Song1,2,3


Real‑world Experience with Abiraterone in Metastatic Castration‑resistant Prostate Cancer

Yasar Ahmed1, Nemer Osman1, Rizwan Sheikh2, Sarah Picardo1, Geoffrey Watson1


Combination of Interleukin‑11Rα Chimeric Antigen Receptor T‑cells and Programmed Death‑1 Blockade as an Approach to Targeting Osteosarcoma Cells In vitro

Hatel Rana Moonat, Gangxiong Huang, Pooja Dhupkar, Keri Schadler, Nancy Gordon,
Eugenie Kleinerman


Efficacy and Safety of Paclitaxel‑based Therapy and Nonpaclitaxel‑based Therapy in Advanced Gastric Cancer

Tongwei Wu, Xiao Yang, Min An, Wenqin Luo, Danxian Cai, Xiaolong Qi


Motion Estimation of the Liver Based on Deformable Image Registration: A Comparison Between Four‑Dimensional‑Computed Tomography and Four‑Dimensional-Magnetic Resonance Imaging

Xiao Liang1, Fang‑Fang Yin1,2, Yilin Liu1, Brian Czito2, Manisha Palta2, Mustafa Bashir3, Jing Cai1,2


A Feasibility Study of Applying Thermal Imaging to Assist Quality Assurance of High‑Dose Rate Brachytherapy

Xiaofeng Zhu1, Yu Lei1, Dandan Zheng1, Sicong Li1, Vivek Verma1, Mutian Zhang1, Qinghui Zhang1, Xiaoli Tang2, Jun Lian2, Sha X. Chang2, Haijun Song3, Sumin Zhou1, Charles A. Enke1


Role of Exosome microRNA in Breast Cancer

Wang Qu, Ma Fei, Binghe Xu


Recent Progress in Technological Improvement and Biomedical Applications of the Clustered Regularly Interspaced Short Palindromic Repeats/Cas System

Yanlan Li1,2*, Zheng Hu1*, Yufang Yin3, Rongzhang He1, Jian Hu1, Weihao Luo1, Jia Li1, Gebo Wen2, Li Xiao1, Kai Li1, Duanfang Liao4, Di-Xian Luo1,5


The Significance of Nuclear Factor‑Kappa B Signaling Pathway in Glioma: A Review

Xiaoshan Xu1, Hongwei Yang2, Xin Wang2, Yanyang Tu1


Markerless Four‑Dimensional‑Cone Beam Computed Tomography Projection‑Phase Sorting Using Prior Knowledge and Patient Motion Modeling: A Feasibility Study

Lei Zhang1,2, Yawei Zhang2, You Zhang1,2,3, Wendy B. Harris1,2, Fang‑Fang Yin1,2,4, Jing Cai1,4,5, Lei Ren1,2


The Producing Capabilities of Interferon‑g and Interleukin‑10 of Spleen Cells in Primary and Metastasized Oral Squamous Cell Carcinoma Cells-implanted Mice

Yasuka Azuma1,2, Masako Mizuno‑Kamiya3, Eiji Takayama1, Harumi Kawaki1, Toshihiro Inagaki4, Eiichi Chihara2, Yasunori Muramatsu5, Nobuo Kondoh1


“Eating” Cancer Cells by Blocking CD47 Signaling: Cancer Therapy by Targeting the Innate Immune Checkpoint

Yi‑Rong Xiang, Li Liu


Glycosylation is Involved in Malignant Properties of Cancer Cells

Kazunori Hamamura1, Koichi Furukawa2


Biomarkers in Molecular Epidemiology Study of Oral Squamous Cell Carcinoma in the Era of Precision Medicine

Qing‑Hao Zhu1*, Qing‑Chao Shang1*, Zhi‑Hao Hu1*, Yuan Liu2, Bo Li1, Bo Wang1, An‑Hui Wang1


I‑Kappa‑B Kinase‑epsilon Activates Nuclear Factor‑kappa B and STAT5B and Supports Glioblastoma Growth but Amlexanox Shows Little Therapeutic Potential in These Tumors

Nadège Dubois1, Sharon Berendsen2, Aurélie Henry1,2, Minh Nguyen1, Vincent Bours1,
Pierre Alain Robe1,2


Suppressive Effect of Mesenchymal Stromal Cells on Interferon‑g‑Producing Capability of Spleen Cells was Specifically Enhanced through Humoral Mediator(s) from Mouse Oral Squamous Cell Carcinoma Sq‑1979 Cells In Vitro

Toshihiro Inagaki1,2, Masako Mizuno‑Kamiya3, Eiji Takayama1, Harumi Kawaki1, Eiichi Chihara4, Yasunori Muramatsu5, Shinichiro Sumitomo5, Nobuo Kondoh1


An Interplay Between MicroRNA and SOX4 in the Regulation of Epithelial–Mesenchymal Transition and Cancer Progression

Anjali Geethadevi1, Ansul Sharma2, Manish Kumar Sharma3, Deepak Parashar1


MicroRNAs Differentially Expressed in Prostate Cancer of African‑American and European‑American Men

Ernest K. Amankwah


The Role of Reactive Oxygen Species in Screening Anticancer Agents

Xiaohui Xu1, Zilong Dang2, Taoli Sun3, Shengping Zhang1, Hongyan Zhang1


Panobinostat and Its Combination with 3‑Deazaneplanocin‑A Induce Apoptosis and Inhibit In vitro Tumorigenesis and Metastasis in GOS‑3 Glioblastoma Cell Lines

Javier de la Rosa*, Alejandro Urdiciain*, Juan Jesús Aznar‑Morales, Bárbara Meléndez1,
Juan A. Rey2, Miguel A. Idoate3, Javier S. Castresana


Cancer Stem‑Like Cells Have Cisplatin Resistance and miR‑93 Regulate p21 Expression in Breast Cancer

Akiko Sasaki1, Yuko Tsunoda2, Kanji Furuya3, Hideto Oyamada1, Mayumi Tsuji1, Yuko Udaka1, Masahiro Hosonuma1, Haruna Shirako1, Nana Ichimura1, Yuji Kiuchi1


The Contribution of Hexokinase 2 in Glioma

Hui Liu1, Hongwei Yang2, Xin Wang3, Yanyang Tu1


The Mechanism of BMI1 in Regulating Cancer Stemness Maintenance, Metastasis, Chemo‑ and Radiation Resistance

Xiaoshan Xu, Zhen Wang, Nan Liu, Pengxing Zhang, Hui Liu, Jing Qi, Yanyang Tu


A Multisource Adaptive Magnetic Resonance Image Fusion Technique for Versatile Contrast Magnetic Resonance Imaging

Lei Zhang1,2, Fang‑Fang Yin1,2,3, Brittany Moore1,2, Silu Han1,2, Jing Cai1,2,4


Senescence and Cancer

Sulin Zeng1,2, Wen H. Shen2, Li Liu1


The “Wild”‑type Gastrointestinal Stromal Tumors: Heterogeneity on Molecule Characteristics and Clinical Features

Yanhua Mou1, Quan Wang1, Bin Li1,2


Retreatment with Cabazitaxel in a Long‑Surviving Patient with Castration‑Resistant Prostate Cancer and Visceral Metastasis

Raquel Luque Caro, Carmen Sánchez Toro, Lucia Ochoa Vallejo


Therapy‑Induced Histopathological Changes in Breast Cancers: The Changing Role of Pathology in Breast Cancer Diagnosis and Treatment

Shazima Sheereen1, Flora D. Lobo1, Waseemoddin Patel2, Shamama Sheereen3,
Abhishek Singh Nayyar4, Mubeen Khan5


Glioma Research in the Era of Medical Big Data

Feiyifan Wang1, Christopher J. Pirozzi2, Xuejun Li1


Transarterial Embolization for Hepatocellular Adenomas: Case Report and Literature Review

Jian‑Hong Zhong1,2, Kang Chen1, Bhavesh K. Ahir3, Qi Huang4, Ye Wu4, Cheng‑Cheng Liao1, Rong‑Rong Jia1, Bang‑De Xiang1,2, Le‑Qun Li1,2


Nicotinamide Phosphoribosyltransferase: Biology, Role in Cancer, and Novel Drug Target

Antonio Lucena‑Cacace1,2,3, Amancio Carnero1,2


Enhanced Anticancer Effect by Combination of Proteoglucan and Vitamin K3 on Bladder Cancer Cells

Michael Zhang, Kelvin Zheng, Muhammad Choudhury, John Phillips, Sensuke Konno


Molecular Insights Turning Game for Management of Ependymoma: A Review of Literature

Ajay Sasidharan, Rahul Krishnatry


IDH Gene Mutation in Glioma

Leping Liu1, Xuejun Li1,2


Challenges and Advances in the Management of Pediatric Intracranial Germ Cell Tumors: A Case Report and Literature Review

Gerard Cathal Millen1, Karen A. Manias1,2, Andrew C. Peet1,2, Jenny K. Adamski1


Assessing the Feasibility of Using Deformable Registration for Onboard Multimodality‑Based Target Localization in Radiation Therapy

Ge Ren1,2,3, Yawei Zhang1,2, Lei Ren1,2


Research Advancement in the Tumor Biomarker of Hepatocellular Carcinoma

Qing Du1, Xiaoying Ji2, Guangjing Yin3, Dengxian Wei3, Pengcheng Lin1, Yongchang Lu1,
Yugui Li3, Qiaohong Yang4, Shizhu Liu5, Jinliang Ku5, Wenbin Guan6, Yuanzhi Lu7


Novel Insights into the Role of Bacterial Gut Microbiota in Hepatocellular Carcinoma

Lei Zhang1, Guoyu Qiu2, Xiaohui Xu2, Yufeng Zhou3, Ruiming Chang4


Central Odontogenic Fibroma with Unusual Presenting Symptoms

Aanchal Tandon, Bharadwaj Bordoloi, Safia Siddiqui, Rohit Jaiswal


The Prognostic Role of Lactate in Patients Who Achieved Return of Spontaneous Circulation after Cardiac Arrest: A Systematic Review and Meta‑analysis

Dongni Ren1, Xin Wang2, Yanyang Tu1,2


Inhibitory Effect of Hyaluronidase‑4 in a Rat Spinal Cord Hemisection Model

Xipeng Wang1,2, Mitsuteru Yokoyama2, Ping Liu3


Research and Development of Anticancer Agents under the Guidance of Biomarkers

Xiaohui Xu1, Guoyu Qiu1, Lupeng Ji2, Ruiping Ma3, Zilong Dang4, Ruling Jia1, Bo Zhao1


Idiopathic Hypereosinophilic Syndrome and Disseminated Intravascular Coagulation

Mansoor C. Abdulla


Phosphorylation of BRCA1‑Associated Protein 1 as an Important Mechanism in the Evasion of Tumorigenesis: A Perspective

Guru Prasad Sharma1, Anjali Geethadevi2, Jyotsna Mishra3, G. Anupa4, Kapilesh Jadhav5,
K. S. Vikramdeo6, Deepak Parashar2


Progress in Diagnosis and Treatment of Mixed Adenoneuroendocrine Carcinoma of Biliary‑Pancreatic System

Ge Zengzheng1, Huang-Sheng Ling2, Ming-Feng Li2, Xu Xiaoyan1, Yao Kai1, Xu Tongzhen3,
Ge Zengyu4, Li Zhou5


Surface-Enhanced Raman Spectroscopy to Study the Biological Activity of Anticancer Agent

Guoyu Qiu1, Xiaohui Xu1, Lupeng Ji2, Ruiping Ma3, Zilong Dang4, Huan Yang5


Alzheimer’s Disease Susceptibility Genes in Malignant Breast Tumors

Steven Lehrer1, Peter H. Rheinstein2


OSMCC: An Online Survival Analysis Tool for Merkel Cell Carcinoma

Umair Ali Khan Saddozai1, Qiang Wang1, Xiaoxiao Sun1, Yifang Dang1, JiaJia Lv1,2, Junfang Xin1, Wan Zhu3, Yongqiang Li1, Xinying Ji1, Xiangqian Guo1


Protective Activity of Selenium against 5‑Fluorouracil‑Induced Nephrotoxicity in Rats

Elias Adikwu, Nelson Clemente Ebinyo, Beauty Tokoni Amgbare


Advances on the Components of Fibrinolytic System in Malignant Tumors

Zengzheng Ge1, Xiaoyan Xu1, Zengyu Ge2, Shaopeng Zhou3, Xiulin Li1, Kai Yao1, Lan Deng4


A Patient with Persistent Foot Swelling after Ankle Sprain: B‑Cell Lymphoblastic Lymphoma Mimicking Soft‑tissue Sarcoma

Crystal R. Montgomery‑Goecker1, Andrew A. Martin2, Charles F. Timmons3, Dinesh Rakheja3, Veena Rajaram3, Hung S. Luu3


Coenzyme Q10 and Resveratrol Abrogate Paclitaxel‑Induced Hepatotoxicity in Rats

Elias Adikwu, Nelson Clemente Ebinyo, Loritta Wasini Harris


Progress in Clinical Follow‑up Study of Dendritic Cells Combined with Cytokine‑Induced Killer for Stomach Cancer

Ling Wang1,2, Run Wan1,2, Cong Chen1,2, Ruiliang Su1,2, Yumin Li1,2


Supraclavicular Lymphadenopathy as the Initial Manifestation in Carcinoma of Cervix

Priyanka Priyaarshini1, Tapan Kumar Sahoo2


ABO Typing Error Resolution and Transfusion Support in a Case of an Acute Leukemia Patient Showing Loss of Antigen Expression

Debasish Mishra1, Gopal Krushna Ray1, Smita Mahapatra2, Pankaj Parida2


Protein Disulfide Isomerase A3: A Potential Regulatory Factor of Colon Epithelial Cells

Yang Li1, Zhenfan Huang2, Haiping Jiang3


Clinicopathological Association of p16 and its Impact on Outcome of Chemoradiation in Head‑and‑Neck Squamous Cell Cancer Patients in North‑East India

Srigopal Mohanty1, Yumkhaibam Sobita Devi2, Nithin Raj Daniel3, Dulasi Raman Ponna4,
Ph. Madhubala Devi5, Laishram Jaichand Singh2


Potential Inhibitor for 2019‑Novel Coronaviruses in Drug Development

Xiaohui Xu1, Zilong Dang2, Lei Zhang3, Lingxue Zhuang4, Wutang Jing5, Lupeng Ji6, Guoyu Qiu1


Best‑Match Blood Transfusion in Pediatric Patients with Mixed Autoantibodies

Debasish Mishra1, Dibyajyoti Sahoo1, Smita Mahapatra2, Ashutosh Panigrahi3


Characteristics and Outcome of Patients with Pheochromocytoma

Nadeema Rafiq1, Tauseef Nabi2, Sajad Ahmad Dar3, Shahnawaz Rasool4


Comparison of Histopathological Grading and Staging of Breast Cancer with p53‑Positive and Transforming Growth Factor‑Beta Receptor 2‑Negative Immunohistochemical Marker Expression Cases

Palash Kumar Mandal1, Anindya Adhikari2, Subir Biswas3, Amita Giri4, Arnab Gupta5,
Arindam Bhattacharya6


Chemical Compositions and Antiproliferative Effect of Essential Oil of Asafoetida on MCF7 Human Breast Cancer Cell Line and Female Wistar Rats

Seyyed Majid Bagheri1,2, Davood Javidmehr3, Mohammad Ghaffari1, Ehsan Ghoderti‑Shatori4


Cyclooxygenase‑2 Contributes to Mutant Epidermal Growth Factor Receptor Lung Tumorigenesis by Promoting an Immunosuppressive Environment

Mun Kyoung Kim1, Aidin Iravani2, Matthew K. Topham2,3


Potential role of CircMET as A Novel Diagnostic Biomarker of Papillary Thyroid Cancer

Yan Liu1,2,3,4#, Chen Cui1,2,3,4#, Jidong Liu1,2,3,4, Peng Lin1,2,3,4,Kai Liang1,2,3,4, Peng Su5, Xinguo Hou1,2,3,4, Chuan Wang1,2,3,4, Jinbo Liu1,2,3,4, Bo Chen6, Hong Lai1,2,3,4, Yujing Sun1,2,3,4* and Li Chen 1,2,3,4*


Cuproptosis-related Genes in Glioblastoma as Potential Therapeutic Targets

Zhiyu Xia1,2, Haotian Tian1, Lei Shu1,2, Guozhang Tang3, Zhenyu Han4, Yangchun Hu1*, Xingliang Dai1*


Cancer Diagnosis and Treatments by Porous Inorganic Nanocarriers

Jianfeng Xu1,2, Hanwen Zhang1,2, Xiaohui Song1,2, Yangong Zheng3, Qingning Li1,2,4*


Delayed (20 Years) post-surgical Esophageal Metastasis of Breast Cancer - A Case Report

Bowen Hu1#, Lingyu Du2#, Hongya Xie1, Jun Ma1, Yong Yang1*, Jie Tan2*


Subtyping of Undifferentiated Pleomorphic Sarcoma and Its Clinical Meaning

Umair Ali Khan Saddozai, Zhendong Lu, Fengling Wang, Muhammad Usman Akbar, Saadullah Khattak, Muhammad Badar, Nazeer Hussain Khan, Longxiang Xie, Yongqiang Li, Xinying Ji, Xiangqian Guo


Construction of Glioma Prognosis Model and Exploration of Related Regulatory Mechanism of Model Gene

Suxia Hu, Abdusemer Reyimu, Wubi Zhou, Xiang Wang, Ying Zheng, Xia Chen, Weiqiang Li, Jingjing Dai


ESRP2 as a Non-independent Potential Biomarker-Current Progress in Tumors

Yuting Chen, Yuzhen Rao, Zhiyu Zeng, Jiajie Luo, Chengkuan Zhao, Shuyao Zhang


Resection of Bladder Tumors at the Ureteral Orifice Using a Hook Plasma Electrode: A Case Report

Jun Li, Ziyong Wang, Qilin Wang


Structural Characterization and Bioactivity for Lycium Barbarum Polysaccharides

Jinghua Qi1,2,  Hangping Chen3,Huaqing Lin2,4,Hongyuan Chen1,2,5* and Wen Rui2,3,5,6*


The Role of IL-22 in the Prevention of Inflammatory Bowel Disease and Liver Injury

Xingli Qi1,2, Huaqing Lin2,3, Wen Rui2,3,4,5 and Hongyuan Chen1,2,3


RBM15 and YTHDF3 as Positive Prognostic Predictors in ESCC: A Bioinformatic Analysis Based on The Cancer Genome Atlas (TCGA)

Yulou Luo1, Lan Chen2, Ximing Qu3, Na Yi3, Jihua Ran4, Yan Chen3,5*


Mining and Analysis of Adverse Drug Reaction Signals Induced by Anaplastic Lymphoma Kinase-Tyrosine Kinase Inhibitors Based on the FAERS Database

Xiumin Zhang1,2#, Xinyue Lin1,3#, Siman Su1,3#, Wei He3, Yuying Huang4, Chengkuan Zhao3, Xiaoshan Chen3, Jialin Zhong3, Chong Liu3, Wang Chen3, Chengcheng Xu3, Ping Yang5, Man Zhang5, Yanli Lei5*, Shuyao Zhang1,3*


Advancements in Immunotherapy for Advanced Gastric Cancer

Min Jiang1#, Rui Zheng1#, Ling Shao1, Ning Yao2, Zhengmao Lu1*


Tumor Regression after COVID-19 Infection in Metastatic Adrenocortical Carcinoma Treated with Immune Checkpoint Blockade: A Case Report

Qiaoxin Lin1, Bin Liang1, Yangyang Li2, Ling Tian3*, Dianna Gu1*


Mining and Analysis of Adverse Events of BRAF Inhibitors Based on FDA Reporting System

Silan Peng1,2#, Danling Zheng1,3#, Yanli Lei4#, Wang Chen3, Chengkuan Zhao3, Xinyue Lin1, Xiaoshan Chen3, Wei He3, Li Li3, Qiuzhen Zhang5*, Shuyao Zhang1,3*


Malignant Phyllodes Tumor with Fever, Anemia, Hypoproteinemia: A Rare and Strange Case Report and Literature Review

Zhenghang Li1, Yuxian Wei1*


Construction of Cuproptosis-Related LncRNA Signature as a Prognostic Model Associated with Immune Microenvironment for Clear-Cell Renal Cell Carcinoma

Jiyao Yu1#, Shukai Zhang2#, Qingwen Ran3, Xuemei Li4,5,6*


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