Tumors are diseases caused by abnormal cell division and growth, which can be life-threatening if not treated properly. Serpin inhibitors play a crucial role in regulating pathophysiological process and are promising drug targets. Kallistatin (SERPINA4) and Pigment Epithelium-Derived Factor (PEDF, SERPINF1) are two serpins that lack protease inhibitory activity but are abundant in blood. They exhibit anti-angiogenic effects and are involved in tumorigenesis. The pathogenic role and mechanism of Kallistatin and pigment epithelium-derived factor (PEDF) have been extensively studied for their potential use in cancer therapy. Kallistatin and PEDF play significant roles in controlling tumor growth and progression. While they share some common mechanisms of action, such as promoting apoptosis and inhibiting angiogenesis, they also have distinct differences in effectiveness and range of anti-tumor activities. This review compares and contrasts the expression patterns, structural features, expression regulation, disease roles, signaling pathways, and potential clinical value of Kallistatin and PEDF, aiming to provide a comprehensive understanding of their biomedical and clinical potential.

Due to systematic side effects, there is a growing interest in nanoparticle formulation of anticancer drugs. Here, we aimed to synthesize poly (styrene-alt-maleic anhydride) cross-linked by melamine (PSMA/Me) and coated with magnetite nanoparticles (MNPs) PSMA/Me/Fe3O4. In addition, we aimed to load paclitaxel (PTX) into PSMA/Me/Fe3O4 for drug delivery and anticancer investigations.

Novel PSMA/Me was synthesized via free radical copolymerization, coated with Fe3O4, and then used as a transporter for PTX delivery. Fabricated copolymer was characterized using SEM, TGA, and XRD techniques. Drug release rate and loading efficiency were investigated. Human ovarian cancer cells (Skov-3) and breast cancer cells (MCF-7 cells) were incubated with the serial concentration of either free PTX or PSMA/Me/Fe3O4/PTX for cell viability and IC50 analysis for 24 and 48 h.

Characterization methods confirmed PSMA/Me copolymer formation. The results showed a significant encapsulation efficiency of 83%. The drug release analysis exhibited that PSMA/Me/Fe3O4/PTX may be considered pH-sensitive nanocarriers. PSMA/Me/Fe3O4/PTX reduced cell viability both dose and time-dependently (p < 0.05). IC50 values of PSMA/Me/Fe3O4/PTX were low when compared to free PTX either 24 or 48 h post-treatment.

Our results indicated that PSMA/Me/Fe3O4/PTX was more cytotoxic than PTX in both cancer cells. Findings indicated the potential of PSMA/Me/Fe3O4/PTX as an anticancer nanocarrier system.

Gastrointestinal (GI) cancers are among the leading causes of mortality worldwide. Despite the emergence of new possibilities that offer hope regarding the successful treatment of these cancers, they still represent a significant global health burden. These cancers can arise from various cell types within the gastrointestinal tract and may exhibit different characteristics, behaviors, and treatment approaches. Both the prognosis and the outcomes of GI treatment remain problematic because these tumors are primarily diagnosed in advanced clinical stages. Current biomarkers exhibit limited sensitivity and specificity. Therefore, when developing strategies for the diagnosis and treatment of GI cancers, it is of fundamental importance to discover new biomarkers capable of addressing the challenges of early-stage diagnosis and the presence of lymph node metastases. Pigment epithelial-derived factor (PEDF) has garnered interest due to its inhibitory effects on the migration and proliferation of cancer cells. This protein has been suggested to be involved in various inflammation-related diseases, including cancer, through various mechanisms. It was also observed that reducing the level of PEDF is sufficient to trigger an inflammatory response. This suggests that PEDF is an endogenous anti-inflammatory factor. Overall, PEDF is a versatile protein with diverse biological functions that span across different tissues and organ systems. Its multifaceted activities make it an intriguing target for therapeutic interventions in various diseases, including cancer, neurodegeneration, and metabolic disorders. This review, for the first time, summarizes the role of PEDF in the pathogenesis of selected GI cancers and its potential utility in early diagnosis, prognosis, and therapeutic strategies for this malignancy.

Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD), that starts with atrophic lesions in the outer retina that expand to cover the macula and fovea, leading to severe vision loss over time. Pigment Epithelium-Derived Factor (PEDF) has a diverse-range of properties, including its ability to promote cell survival, reduce inflammation, inhibit angiogenesis, combat oxidative stress, regulate autophagy, and stimulate anti-apoptotic pathways, making it a promising therapeutic candidate for GA. However, the relatively short half-life of PEDF protein has precluded its potential as a clinical therapy for GA since it would require frequent injections. Therefore, we describe administration of a PEDF gene, comparing and contrasting delivery routes, viral and non-viral vectors, and consider the critical challenges for PEDF as a neuroprotectant for GA.

The incidence and mortality of colorectal cancer (CRC) are among the highest in the world, and its occurrence and development are closely related to tumor neovascularization. When the balance between pigment epithelium-derived factors (PEDF) that inhibit angiogenesis and vascular endothelial growth factors (VEGF) that stimulate angiogenesis is broken, angiogenesis is out of control, resulting in tumor development. Therefore, it is very necessary to find more therapeutic targets for CRC for early intervention and later treatment.

To investigate the expression and significance of PEDF, VEGF, and CD31-stained microvessel density values (CD31-MVD) in normal colorectal mucosa, adenoma, and CRC.

In this case-control study, we collected archived wax blocks of specimens from the Digestive Endoscopy Center and the General Surgery Department of Chengdu Second People's Hospital from April 2022 to October 2022. Fifty cases of specimen wax blocks were selected as normal intestinal mucosa confirmed by electronic colonoscopy and concurrent biopsy (normal control group), 50 cases of specimen wax blocks were selected as colorectal adenoma confirmed by electronic colonoscopy and pathological biopsy (adenoma group), and 50 cases of specimen wax blocks were selected as CRC confirmed by postoperative pathological biopsy after inpatient operation of general surgery (CRC group). An immunohistochemical staining experiment was carried out to detect PEDF and VEGF expression in three groups of specimens, analyze their differences, study the relationship between the two and clinicopathological factors in CRC group, record CD31-MVD in the three groups, and analyze the correlation of PEDF, VEGF, and CD31-MVD in the colorectal adenoma group and the CRC group. The F test or adjusted F test is used to analyze measurement data statistically. Kruskal-Wallis rank sum test was used between groups for ranked data. The chi-square test, adjusted chi-square test, or Fisher's exact test were used to compare the rates between groups. All differences between groups were compared using the Bonferroni method for multiple comparisons. Spearman correlation analysis was used to test the correlation of the data. The test level (α) was 0.05, and a two-sided P< 0.05 was considered statistically significant.

The positive expression rate and expression intensity of PEDF were gradually decreased in the normal control group, adenoma group, and CRC group (100% vs 78% vs 50%, χ2 = 34.430, P < 0.001; ++~++ vs +~++ vs -~+, H = 94.059, P < 0.001), while VEGF increased gradually (0% vs 68% vs 96%, χ2 = 98.35, P < 0.001; - vs -~+ vs ++~+++, H = 107.734, P < 0.001). In the CRC group, the positive expression rate of PEDF decreased with the increase of differentiation degree, invasion depth, lymph node metastasis, distant metastasis, and TNM stage (χ2 = 20.513, 4.160, 5.128, 6.349, 5.128, P < 0.05); the high expression rate of VEGF was the opposite (χ2 = 10.317, 13.134, 17.643, 21.844, 17.643, P < 0.05). In the colorectal adenoma group, the expression intensity of PEDF correlated negatively with CD31-MVD (r = -0.601, P < 0.001), whereas VEGF was not significantly different (r = 0.258, P = 0.07). In the CRC group, the expression intensity of PEDF correlated negatively with the expression intensity of CD31-MVD and VEGF (r = -0.297, P < 0.05; r = -0.548, P < 0.05), while VEGF expression intensity was positively related to CD31-MVD (r = 0.421, P = 0.002).

It is possible that PEDF can be used as a new treatment and prevention target for CRC by upregulating the expression of PEDF while inhibiting the expression of VEGF.