• Cerebrovascular disease
• Dipeptidyl peptidase-IV
• Long coronavirus disease 2019 (long COVID)
• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
• Stroke

• Humans
• Dipeptidyl Peptidase 4/metabolism
• COVID-19/complications
• Cerebrovascular Disorders
• SARS-CoV-2/pathogenicity
• Post-Acute COVID-19 Syndrome
• Animals

• dpp4
• integrated analysis
• gi cancer
• gastroesophageal cancer
• gastroesophageal junction
• prognosis

• Humans
• Dipeptidyl Peptidase 4/genetics
• Dipeptidyl Peptidase 4/metabolism
• Esophageal Neoplasms/genetics
• Esophageal Neoplasms/metabolism
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Macrophages/metabolism

• R01 CA204552 NCI NIH HHS
• R01 CA206069 NCI NIH HHS
• R01 CA210192 NCI NIH HHS
• SC1 GM139727 NIGMS NIH HHS

• Brain metastases
• cancer-associated fibroblasts
• fibroblast activation protein
• theranostics
• tumour stroma

• Humans
• Membrane Proteins/metabolism
• Precision Medicine
• Quality of Life
• Fibroblasts/pathology
• Serine Endopeptidases/metabolism
• Carcinoma, Renal Cell/pathology
• Brain Neoplasms/pathology
• Kidney Neoplasms/pathology
• Tumor Microenvironment

• ACE inhibitors
• DPP-4 inhibitors
• bradykinin
• lung cancer
• substance P

There is growing interest in identifying the effects of antidiabetic agents on cancer risk, progression, and anti-cancer treatment due to the long-term use of these medications and the inherently increased risk of malignancies in diabetic patients. Tumor development and progression are affected by multiple mediators in the tumor microenvironment, several of which may be proteolytically modified by the multifunctional protease dipeptidyl peptidase-IV (DPP-IV, CD26). Currently, low-molecular-weight DPP-IV inhibitors (gliptins) are used in patients with type 2 diabetes based on the observation that DPP-IV inhibition enhances insulin secretion by increasing the bioavailability of incretins. However, the DPP-IV-mediated cleavage of other biopeptides and chemokines is also prevented by gliptins. The potential utility of gliptins in other areas of medicine, including cancer, is therefore being evaluated. Here, we critically review the existing evidence on the role of DPP-IV inhibitors in cancer pathogenesis, their potential to be used in anti-cancer treatment, and the possible perils associated with this approach.

Dipeptidyl peptidase IV (DPP-IV, CD26) is frequently dysregulated in cancer and plays an important role in regulating multiple bioactive peptides with the potential to influence cancer progression and the recruitment of immune cells. Therefore, it represents a potential contributing factor to cancer pathogenesis and an attractive therapeutic target. Specific DPP-IV inhibitors (gliptins) are currently used in patients with type 2 diabetes mellitus to promote insulin secretion by prolonging the activity of the incretins glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Nevertheless, the modulation of the bioavailability and function of other DPP-IV substrates, including chemokines, raises the possibility that the use of these orally administered drugs with favorable side-effect profiles might be extended beyond the treatment of hyperglycemia. In this review, we critically examine the possible utilization of DPP-IV inhibition in cancer prevention and various aspects of cancer treatment and discuss the potential perils associated with the inhibition of DPP-IV in cancer. The current literature is summarized regarding the possible chemopreventive and cytotoxic effects of gliptins and their potential utility in modulating the anti-tumor immune response, enhancing hematopoietic stem cell transplantation, preventing acute graft-versus-host disease, and alleviating the side-effects of conventional anti-tumor treatments.

Background: The role of cancer stem cells in esophageal squamous cell carcinoma (ESCC) remains unclear. Methods: The mRNA stemness index (mRNAsi) of 179 ESCC patients (GSE53625) was calculated using a machine learning algorithm based on their mRNA expression. Stemness-related genes were identified by weighted correlation network analysis (WGCNA) and LASSO regression, whose associations with mutation status, immune cell infiltrations, and potential compounds were also analyzed. The role of these genes in proliferation and their expressions was assessed in ESCC cell lines and 112 samples from our center. Results: The ESCC samples had significantly higher mRNAsi than the normal tissues. Patients with high mRNAsi exhibited higher worse OS. Seven stemness-related genes were identified by WGCNA and LASSO regression, based on which a risk-predicted score model was constructed. Among them, CST1, CILP, PITX2, F2RL2, and RIOX1 were favorable for OS, which were adverse for DPP4 and ZFHX4 in the GSE53625 dataset. However, RIOX1 was unfavorable for OS in patients from our center. In vitro assays showed that CST1, CILP, PITX2, F2RL2, and RIOX1 were pro-proliferated, which were opposite for DDP4 and ZFHX4. In addition, SMARCA4, NOTCH3, DNAH5, and KALRN were more mutated in the low-score group. The low-score group had significantly more memory B cells, monocytes, activated NK cells, and Tregs and less macrophages M2, resting mast cells, and resting dendritic cells. Conclusions: Seven stemness-related genes are significantly related to the prognosis, gene mutations, and immune cell infiltration of ESCC. Some potential anticancer compounds may be favorable for OS.

• GEO database
• TCGA database
• WGCNA
• connectivity map database
• esophageal squamous cell carcinoma

• COVID-19
• DPP4 inhibitors
• dipeptidyl peptidase 4 (DPP4)
• infectious lung disease
• non-infectious disease
• pulmonary fibrosis

The transmembrane serine protease CD26/Dipeptidylpeptidase 4 modulates T-cell activation, proliferation, and effector function. Due to their remarkable tumoricidal properties CD26-positive T cells are considered promising candidates for T cell-based immunotherapies while in cutaneous T cell lymphoma CD26/DPP4 expression patterns are established markers for diagnosis and possibly prognosis. With a focus on T cells, we review current knowledge on the regulation of CD26/DPP4 expression and release, its implication in T-cell effector function and the suitability CD26/DPP4 as a diagnostic and/or prognostic factor in T-cell malignancies.

CD26/Dipeptidylpeptidase 4 is a transmembrane serine protease that cleaves off N-terminal dipeptides. CD26/DPP4 is expressed on several immune cell types including T and NK cells, dendritic cells, and activated B cells. A catalytically active soluble form of CD26/DPP4 can be released from the plasma membrane. Given its wide array of substrates and interaction partners CD26/DPP4 has been implicated in numerous biological processes and effects can be dependent or independent of its enzymatic activity and are exerted by the transmembrane protein and/or the soluble form. CD26/DPP4 has been implicated in the modulation of T-cell activation and proliferation and CD26/DPP4-positive T cells are characterized by remarkable anti-tumor properties rendering them interesting candidates for T cell-based immunotherapies. Moreover, especially in cutaneous T-cell lymphoma CD26/DPP4 expression patterns emerged as an established marker for diagnosis and treatment monitoring. Surprisingly, besides a profound knowledge on substrates, interaction partners, and associated signal transduction pathways, the precise role of CD26/DPP4 for T cell-based immune responses is only partially understood.

• CD26
• DPP4
• Sézary syndrome
• T cells
• cutaneous T-cell lymphoma
• cytotoxic granules
• dipeptidyl peptidase 4
• mycosis fungoides

• CD26
• chemokines
• modification
• post-translational
• truncation
• tumor

Dipeptidyl peptidase (DPP)-4 inhibitor is widely used for type 2 diabetes. Although DPP-4/CD26 has been recognized as both a suppressor and inducer in tumor biology due to its various functions, how DPP-4 inhibitor affects cancer progression in diabetic patients is still unknown. The aim of this review is to summarize one unfavorable aspect of DPP-4 inhibitor in cancer-bearing diabetic patients.

DPP-4/CD26, a membrane-bound glycoprotein, is ubiquitously expressed and has diverse biological functions. Because of its enzymatic action, such as the degradation of incretin hormones, DPP-4/CD26 is recognized as the significant therapeutic target for type 2 diabetes (T2DM); DPP-4 inhibitors have been used as an anti-diabetic agent for a decade. The safety profile of DPP-4 inhibitors for a cardiovascular event in T2DM patients has been widely analyzed; however, a clear association between DPP-4 inhibitors and tumor biology is not yet established. Previous preclinical studies reported that DPP-4 suppression would impact tumor progression processes. With regard to this finding, we have shown that the DPP-4 inhibitor induces breast cancer metastasis and chemoresistance via an increase in its substrate C-X-C motif chemokine 12, and the consequent induction of epithelial-mesenchymal transition in the tumor. DPP-4/CD26 plays diverse pivotal roles beyond blood glucose control; thus, DPP-4 inhibitors can potentially impact cancer-bearing T2DM patients either favorably or unfavorably. In this review, we primarily focus on the possible undesirable effect of DPP-4 inhibition on tumor biology. Clinicians should note that the safety of DPP-4 inhibitors for diabetic patients with an existing cancer is an unresolved issue, and further mechanistic analysis is essential in this field.

• CXCL12
• DPP-4
• epithelial-mesenchymal transition
• metformin
• type 2 diabetes

• CD26
• Sitagliptin
• aggregation
• collagen
• colorectal cancer
• dipeptidyl peptidase 4
• invasion
• metastasis
• motility

Avian reovirus p17 (ARV p17) is a non-structural protein known to activate autophagy, interfere with gene transcription and induce a significant tumor cell growth inhibition in vitro and in vivo. In this study, we show that ARV p17 is capable of exerting potent antiangiogenic properties. The viral protein significantly inhibited the physiological angiogenesis of human endothelial cells (ECs) by affecting migration, capillary-like structure and new vessel formation. ARV p17 was not only able to suppress the EC physiological angiogenesis but also rendered ECs insensitive to two different potent proangiogenic inducers, such as VEGF-A and FGF-2 in the three-dimensional (3D) Matrigel and spheroid assay. ARV p17 was found to exert its antiangiogenic activity by upregulating transcription and release of the well-known tumor suppressor molecule dipeptidyl peptidase 4 (DPP4). The ability of ARV p17 to impact on angiogenesis is completely new and highlights the “two compartments” activity of the viral protein that is expected to hamper the tumor parenchymal/stromal crosstalk. The complex antitumor activities of ARV p17 open the way to a new promising field of research aimed to develop new therapeutic approaches for treating tumor and cancer metastasis.

• ARV p17
• DPP4
• FGF-2
• VEGF-A
• angiogenesis
• antiangiogenic activity

• Angiogenesis Inhibitors/pharmacology
• Animals
• Cell Movement/drug effects
• Chickens
• Dipeptidyl Peptidase 4/metabolism
• Fibroblast Growth Factor 2/pharmacology
• Human Umbilical Vein Endothelial Cells
• Humans
• Microvessels/cytology
• Morphogenesis/drug effects
• Neovascularization, Pathologic/metabolism
• Orthoreovirus, Avian/metabolism
• Recombinant Proteins/pharmacology
• Transduction, Genetic
• Up-Regulation/drug effects
• Viral Nonstructural Proteins/pharmacology

• 1-OHP
• CD26
• ICAM-1
• Immune-regulation
• Toxic metals
• p53

• Air Pollution
• Biomarkers
• Humans
• Neoplasms/chemically induced
• Occupational Exposure/adverse effects
• Occupational Exposure/analysis
• Oxidative Stress
• Polycyclic Aromatic Hydrocarbons
• Pyrenes/analysis

Dipeptidyl peptidase (DPP)-4, a molecular target of DPP-4 inhibitors, which are type 2 diabetes drugs, is expressed in a variety of cell types, tissues and organs. DPP-4 has been shown to be involved in cancer biology, and we have recently shown that a DPP-4 inhibitor promoted the epithelial mesenchymal transition (EMT) in breast cancer cells. The EMT is known to associate with chemotherapy resistance via the induction of ATP-binding cassette (ABC) transporters in cancer cells. Here, we demonstrated that deficiency in DPP-4 promoted chemotherapy resistance via the CXCL12/CXCR4/mTOR axis, activating the TGFβ signaling pathway via the expression of ABC transporters. DPP-4 inhibition enhanced ABC transporters in vivo and in vitro. Doxorubicin (DOX) further induced ABC transporters in DPP-4-deficient 4T1 cells, and the induction of ABC transporters was suppressed by either the CXCR4 inhibitor AMD3100, the mTOR inhibitor rapamycin or a neutralizing TGFβ (1, 2 and 3) antibody(N-TGFβ). Knockdown of snail, an EMT-inducible transcription factor, suppressed ABC transporter levels in DOX-treated DPP-4-deficient 4T1 cells. In an allograft mouse model, however, the effects of DOX in either primary tumor or metastasis were not statistically different between control and DPP-4-kd 4T1. Taken together, our findings suggest that DPP-4 inhibitors potentiate chemotherapy resistance via the induction of ABC transporters by the CXCL12/CXCR4/mTOR/TGFβ signaling pathway in breast cancer cells.

• ABC transporters
• DPP-4
• EMT
• apoptosis
• breast cancer
• chemoresistance

Oncogene-induced senescence (OIS), provoked in response to oncogenic activation, is considered an important tumor suppressor mechanism. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nt without a protein-coding capacity. Functional studies showed that deregulated lncRNA expression promote tumorigenesis and metastasis and that lncRNAs may exhibit tumor-suppressive and oncogenic function. Here, we first identified lncRNAs that were differentially expressed between senescent and non-senescent human fibroblast cells. Using RNA interference, we performed a loss-function screen targeting the differentially expressed lncRNAs, and identified lncRNA-OIS1 (lncRNA#32, AC008063.3 or ENSG00000233397) as a lncRNA required for OIS. Knockdown of lncRNA-OIS1 triggered bypass of senescence, higher proliferation rate, lower abundance of the cell-cycle inhibitor CDKN1A and high expression of cell-cycle-associated genes. Subcellular inspection of lncRNA-OIS1 indicated nuclear and cytosolic localization in both normal culture conditions as well as following oncogene induction. Interestingly, silencing lncRNA-OIS1 diminished the senescent-associated induction of a nearby gene (Dipeptidyl Peptidase 4, DPP4) with established role in tumor suppression. Intriguingly, similar to lncRNA-OIS1, silencing DPP4 caused senescence bypass, and ectopic expression of DPP4 in lncRNA-OIS1 knockdown cells restored the senescent phenotype. Thus, our data indicate that lncRNA-OIS1 links oncogenic induction and senescence with the activation of the tumor suppressor DPP4.

Asthma is a heterogeneous and chronic inflammatory family of disorders of the airways with increasing prevalence that results in recurrent and reversible bronchial obstruction and expiratory airflow limitation. These diseases arise from the interaction between environmental and genetic factors, which collaborate to cause increased susceptibility and severity. Many asthma susceptibility genes are linked to the immune system or encode enzymes like metalloproteases (e.g., ADAM-33) or serine proteases. The S9 family of serine proteases (prolyl oligopeptidases) is capable to process peptide bonds adjacent to proline, a kind of cleavage-resistant peptide bonds present in many growth factors, chemokines or cytokines that are important for asthma. Curiously, two serine proteases within the S9 family encoded by genes located on chromosome 2 appear to have a role in asthma: CD26/dipeptidyl peptidase 4 (DPP4) and DPP10. The aim of this review is to summarize the current knowledge about CD26 and to provide a structured overview of the numerous functions and implications that this versatile enzyme could have in this disease, especially after the detection of some secondary effects (e.g., viral nasopharyngitis) in type II diabetes mellitus patients (a subset with a certain risk of developing obesity-related asthma) upon CD26 inhibitory therapy.

• Asthma
• CD26
• CD26 inhibitors
• Cytokines and chemokines
• DPP4
• sCD26

• Animals
• Asthma/diagnosis
• Asthma/etiology
• Asthma/metabolism
• Asthma/therapy
• Biomarkers
• Body Fluids/metabolism
• CD4-Positive T-Lymphocytes/immunology
• CD4-Positive T-Lymphocytes/metabolism
• Chemokines/metabolism
• Cytokines/metabolism
• Dipeptidyl Peptidase 4/chemistry
• Dipeptidyl Peptidase 4/genetics
• Dipeptidyl Peptidase 4/metabolism
• Disease Models, Animal
• Genetic Predisposition to Disease
• Humans
• Multigene Family
• Phenotype
• Prolyl Oligopeptidases
• Serine Endopeptidases/genetics
• Serine Endopeptidases/metabolism
• Severity of Illness Index
• Structure-Activity Relationship
• T-Lymphocyte Subsets/immunology
• T-Lymphocyte Subsets/metabolism

• Instituto de Salud Carlos III
• Sociedad Española de Neumología y Cirugía Torácica

• CD26
• DPP4
• biomarker
• cancer
• metastasis
• therapy

• CD26
• Dipeptidyl peptidase IV
• Rheumatoid arthritis

• Adult
• Arthritis, Rheumatoid/physiopathology
• Bone and Bones/physiopathology
• Case-Control Studies
• Connective Tissue Diseases/metabolism
• Cytokines/metabolism
• Dipeptidyl Peptidase 4/metabolism
• Female
• Hand/diagnostic imaging
• Humans
• Inflammation
• Leukocytes, Mononuclear/enzymology
• Male
• Middle Aged
• Wrist/diagnostic imaging

TMPRSS4 is a novel type II transmembrane serine protease found at the cell surface that is highly expressed in pancreatic, colon, and other cancer tissues. Previously, we demonstrated that TMPRSS4 mediates tumor cell invasion, migration, and metastasis. We also found that TMPRSS4 activates the transcription factor activating protein-1 (AP-1) to induce cancer cell invasion. Here, we explored TMPRSS4-mediated cellular functions and the underlying mechanisms. TMPRSS4 induced Slug, an epithelial-mesenchymal transition (EMT)-inducing transcription factor, and cyclin D1 through activation of AP-1, composed of c-Jun and activating transcription factor (ATF)-2, which resulted in enhanced invasion and proliferation of PC3 prostate cancer cells. In PC3 cells, not only c-Jun but also Slug was required for TMPRSS4-mediated proliferation and invasion. Interestingly, Slug induced phosphorylation of c-Jun and ATF-2 to activate AP-1 through upregulation of Axl, establishing a positive feedback loop between Slug and AP-1, and thus induced cyclin D1, leading to enhanced proliferation. Using data from The Cancer Genome Atlas, we found that Slug expression positively correlated with that of c-Jun and cyclin D1 in human prostate cancers. Expression of Slug was positively correlated with that of cyclin D1 in various cancer cell lines, whereas expression of other EMT-inducing transcription factors was not. This study demonstrates that TMPRSS4 modulates both invasion and proliferation via Slug and cyclin D1, which is a previously unrecognized pathway that may regulate metastasis and cancer progression.

• Slug
• TMPRSS4
• invasion
• proliferation
• prostate cancer

Sézary syndrome (SS) is a leukemic variant of cutaneous T cell lymphoma (CTCL), and the neoplastic CD4+ T cells of SS patients undergo intense clonal proliferation. Although Sézary cells have been studied extensively, studies on adaptive immunity regarding CD8+T cells are scarce. This study aimed to investigate activation marker expression in CD8+ T cells according to the differentiation stages and IL-7/IL7Rα axis responses of patients with SS. Moreover, this study aimed to verify the soluble forms of CD38, sCD127 and IL-7 in serum. Although the SS patients of our cohort had reduced numbers of CD8+ T cells, they exhibited higher percentages of CD8+CD38+ T cells, mainly effector/memory CD8+ T cells, than the control group. In contrast, down-regulated expression of the activation markers CD127/IL-7R and CD26 was found in the CD8+ T cells of SS patients. High serum levels of sCD38 and sCD127 and scarce serum levels of IL-7 were detected, emphasizing the immune activation status of SS patients. Moreover, CD8+ T cells from SS patients exhibited IL-7 unresponsiveness to STAT5 phosphorylation and Bcl-2 expression, and IL-7 priming partially restored IFNγ production. Our findings showed a chronic activation profile of CD8+ T cells, as an attenuated cytotoxic profile and impaired IL-7 responsiveness was observed, suggesting chronic activation status of CD8+ T cells in SS patients.

• CD8+ T cells
• Sézary syndrome
• chronic activation markers
• sCD127
• sCD38

• Dipeptidyl peptidase 4 (DPP4)
• dipeptidyl peptidase 8 (DPP8)
• dipeptidyl peptidase 9 (DPP9)
• fibroblast activation protein α (FAP)
• lung
• prolyl oligopeptidase (PREP)

• CD26
• Dipeptidyl peptidase IV
• Growth
• Metastasis
• Pancreatic cancer

To elucidate the profile of the salivary proteome.

Unstimulated whole mouth saliva was collected from 30 volunteers [15 proliferative verrucous leukoplakia (PVL) patients and 15 controls] and proteins were submitted for mass spectrometry-based proteomics using the discovery approach, followed by analyses of variance and logistic regression tests.

A total of two hundred and eighty-three proteins were confidently identified in saliva. By combining two low abundance proteins from the PVL group, angiotensinogen (AGT) and dipeptidyl peptidase 1 (DPP1), a model for group differentiation was built with a concordance index of 94.2%, identifying both proteins as potential etiologic biomarkers for PVL.

This study suggests that both AGT and DPP1 may be involved in developmental mechanisms of PVL.

• Saliva
• Angiotensinogen
• Dipeptidyl peptidase 1
• Biomarkers
• Proliferative verrucous leukoplakia
• LC-MS/MS

• cancer
• cancer metabolism
• hallmarks of cancer
• lysosome function

• Angiogenesis
• Dipeptidyl peptidase IV
• Ischemic brain injury
• Migration
• Neural progenitor cells
• Stromal-derived factor

• Animals
• Brain/metabolism
• Brain Ischemia/enzymology
• Brain Ischemia/pathology
• Cell Movement/drug effects
• Cell Movement/physiology
• Dipeptidyl Peptidase 4/metabolism
• Endothelial Cells/metabolism
• Male
• Neovascularization, Pathologic/metabolism
• Neural Stem Cells/enzymology
• Neurogenesis/physiology
• Rats
• Stroke/enzymology
• Stroke/therapy

• R03 NS077087 NINDS NIH HHS

• Cell Line, Tumor
• Energy Metabolism/drug effects
• Extracellular Space/drug effects
• Extracellular Space/metabolism
• Glycolysis/drug effects
• Humans
• Isoflavones/pharmacology
• Lung Neoplasms/pathology
• Mitochondria/drug effects
• Mitochondria/metabolism
• Oxidation-Reduction/drug effects
• Oxidative Stress/drug effects
• Signal Transduction/drug effects

• C06 RR015455 NCRR NIH HHS
• P20 RR024485 NCRR NIH HHS
• R41 CA117259 NCI NIH HHS
• R43 CA086604 NCI NIH HHS

• Apoptosis
• Autophagy
• CD26/DPP4
• Lung metastases

Dipeptidyl peptidase IV (DPPIV/CD26) is a transmembrane glycoprotein that inactivates or degrades some bioactive peptides and chemokines. For this reason, it regulates cell proliferation, migration and adhesion, showing its role in cancer processes. This enzyme is found mainly anchored onto the cell membrane, although it also has a soluble form, an enzymatically active isoform. In the present study, we investigated DPPIV/CD26 activity and expression in cervical cancer cell lines (SiHa, HeLa and C33A) and non-tumorigenic HaCaT cells. The effect of the DPPIV/CD26 inhibitor (sitagliptin phosphate) on cell migration and adhesion was also evaluated. Cervical cancer cells and keratinocytes exhibited DPPIV/CD26 enzymatic activity both membrane-bound and in soluble form. DPPIV/CD26 expression was observed in HaCaT, SiHa and C33A, while in HeLa cells it was almost undetectable. We observed higher migratory capacity of HeLa, when compared to SiHa. But in the presence of sitagliptin SiHa showed an increase in migration, indicating that, at least in part, cell migration is regulated by DPPIV/CD26 activity. Furthermore, in the presence of sitagliptin phosphate, SiHa and HeLa cells exhibited a significant reduction in adhesion. However this mechanism seems to be mediated independent of DPPIV/CD26. This study demonstrates, for the first time, the activity and expression of DPPIV/CD26 in cervical cancer cells and the effect of sitagliptin phosphate on cell migration and adhesion.

• Carcinoma/metabolism
• Carcinoma/pathology
• Cell Adhesion/drug effects
• Cell Adhesion/physiology
• Cell Line, Tumor
• Cell Membrane/drug effects
• Cell Membrane/metabolism
• Cell Movement/drug effects
• Cell Movement/physiology
• Dipeptidyl Peptidase 4/metabolism
• Dipeptidyl-Peptidase IV Inhibitors/pharmacology
• Female
• HeLa Cells
• Humans
• Keratinocytes/drug effects
• Keratinocytes/metabolism
• Membrane Glycoproteins/metabolism
• Sitagliptin Phosphate/pharmacology
• Uterine Cervical Neoplasms/metabolism
• Uterine Cervical Neoplasms/pathology

• Cell surface proteins
• Dimethyl labeling
• LC–MS/MS
• Oviduct epithelial cells
• Quantitation
• Semen

• adverse events
• dipeptidyl peptidase-4 inhibitor
• hypoglycaemia
• incretin
• saxagliptin
• type 2 diabetes mellitus

• Adamantane/adverse effects
• Adamantane/analogs & derivatives
• Adamantane/therapeutic use
• Adult
• Aged
• Aged, 80 and over
• Diabetes Mellitus, Type 2/drug therapy
• Dipeptides/adverse effects
• Dipeptides/therapeutic use
• Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
• Dose-Response Relationship, Drug
• Female
• Humans
• Incretins/adverse effects
• Incretins/therapeutic use
• Male
• Middle Aged
• Randomized Controlled Trials as Topic
• Risk Assessment
• Treatment Outcome

• CD26/DPPIV
• Triuret
• Uric acid

• Neurology adverse events
• antidiabetic drug
• antithyroid drug
• endocrine drug
• hypothalamic hormone
• insulin
• oral antidiabetic
• parathyroid drug
• pituitary hormone
• thyroid hormone

• anti-inflammatory
• cardiovascular protection
• dipeptidyl peptidase-4 inhibitors
• immunomodulatory
• 抗炎，心血管保护，DPP-4抑制剂，免疫调节

• Cardiovascular Diseases/prevention & control
• Diabetes Mellitus, Type 2/drug therapy
• Dipeptidyl-Peptidase IV Inhibitors/therapeutic use
• Humans
• Hypoglycemic Agents/therapeutic use
• Immunologic Factors/therapeutic use
• Inflammation/drug therapy

• Colorectal cancer
• dipeptidyl peptidase 10
• prognosis
• progression

• Biomarkers, Tumor/metabolism
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/pathology
• Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/metabolism
• Disease Progression
• Female
• Humans
• Immunohistochemistry
• Male
• Prognosis

• Animals
• Cell Proliferation/drug effects
• Diabetes Mellitus, Type 2/drug therapy
• Diabetes Mellitus, Type 2/metabolism
• Drug-Related Side Effects and Adverse Reactions/etiology
• Drug-Related Side Effects and Adverse Reactions/metabolism
• Drug-Related Side Effects and Adverse Reactions/prevention & control
• Gastric Inhibitory Polypeptide/metabolism
• Gastric Inhibitory Polypeptide/pharmacology
• Gastrointestinal Agents/metabolism
• Gastrointestinal Agents/pharmacology
• Glucagon-Like Peptide 1/metabolism
• Glucagon-Like Peptide 1/pharmacology
• Humans
• Incretins/metabolism
• Incretins/pharmacology
• Insulin/metabolism
• Models, Animal
• Neoplasms/chemically induced
• Neoplasms/classification
• Neoplasms/metabolism
• Neoplasms/prevention & control
• Outcome Assessment, Health Care
• Pancreas/drug effects
• Pancreas/metabolism
• Pancreas/physiopathology
• Pancreatic Diseases/chemically induced
• Pancreatic Diseases/classification
• Pancreatic Diseases/epidemiology
• Pancreatic Diseases/metabolism
• Pancreatic Diseases/prevention & control
• Randomized Controlled Trials as Topic
• Rats
• Risk Factors